Patent Publication Number: US-2009227591-A1

Title: Cyclopentene compounds

Description:
This invention relates to cyclopentene compounds, to processes for their preparation, to pharmaceutical compositions containing them and to their use in medicine, in particular their use in the treatment of conditions mediated by the action of PGE 2  at EP 1  receptors. 
     The EP 1  receptor is a 7-transmembrane receptor and its natural ligand is the prostaglandin PGE 2 . PGE 2  also has affinity for the other EP receptors (types EP 2 , EP 3  and EP 4 ). The EP 1  receptor is associated with smooth muscle contraction, pain (in particular inflammatory, neuropathic and visceral), inflammation, allergic activities, renal regulation and gastric or enteric mucus secretion. We have now found a novel group of compounds which bind with high affinity to the EP 1  receptor. 
     A number of review articles describe the characterization and therapeutic relevance of the prostanoid receptors as well as the most commonly used selective agonists and antagonists:  Eicosanoids; From Biotechnology to Therapeutic Applications , Folco, Samuelsson, Madouf, and Velo eds, Plenum Press, New York, 1996, chap. 14, 137-154 and Journal of Lipid Mediators and Cell Signalling, 1996, 14, 83-87 and Prostanoid Receptors,  Structure, Properties and Function , S Narumiya et al, Physiological Reviews 1999, 79(4), 1193-126. An article from  The British Journal of Pharmacology,  1994, 112, 735-740 suggests that Prostaglandin E 2  (PGE 2 ) exerts allodynia through the EP 1  receptor subtype and hyperalgesia through EP 2  and EP 3  receptors in the mouse spinal cord. Furthermore an article from  The Journal of Clinical Investigation,  2001, 107 (3), 325 shows that in the EP 1  knock-out mouse pain-sensitivity responses are reduced by approximately 50%. Two papers from  Anesthesia and Analgesia  have shown that (2001, 93, 1012-7) an EP 1  receptor antagonist (ONO8711) reduces hyperalgesia and allodynia in a rat model of chronic constriction injury, and that (2001, 92, 233-238) the same antagonist inhibits mechanical hyperalgesia in a rodent model of post-operative pain. S. Sarkar et al in  Gastroenterology,  2003, 124(1), 18-25 demonstrate the efficacy of EP 1  receptor antagonists in the treatment of visceral pain in a human model of hypersensitivity. Thus, selective prostaglandin ligands, agonists or antagonists, depending on which prostaglandin E receptor subtype is being considered, have anti-inflammatory, antipyretic and analgesic properties similar to a conventional non-steroidal anti-inflammatory drug, and in addition, inhibit hormone-induced uterine contractions and have anti-cancer effects. These compounds have a diminished ability to induce some of the mechanism-based side effects of NSAIDs which are indiscriminate cyclooxygenase inhibitors. In particular, the compounds have a reduced potential for gastrointestinal toxicity, a reduced potential for renal side effects, a reduced effect on bleeding times and a lessened ability to induce asthma attacks in aspirin-sensitive asthmatic subjects. Moreover, by sparing potentially beneficial prostaglandin pathways, these agents may have enhanced efficacy over NSAIDS and/or COX-2 inhibitors. 
     In The American Physiological Society (1994, 267, R289-R-294), studies suggest that PGE 2 -induced hyperthermia in the rat is mediated predominantly through the EP 1  receptor. 
     WO 96/06822 (Mar. 7, 1996), WO 96/11902 (Apr. 25, 1996), EP 752421-A1 (Jan. 8, 1997), WO 01/19814 (22 Mar. 2001), WO 03/084917 (16 Oct. 2003), WO 03/101959 (11 Dec. 2003) and WO 2004/039753 (13 May 2004) disclose compounds as being useful in the treatment of prostaglandin mediated diseases. 
     It is now suggested that a novel group of cyclopentene derivatives surprisingly are selective for the EP 1  receptor over the EP 3  receptor, and are therefore indicated to be useful in treating conditions mediated by the action of PGE 2  at EP 1  receptors. Such conditions include pain, or inflammatory, immunological, bone, neurodegenerative or renal disorders. 
     Accordingly the present invention provides cyclopentene compounds of formula (I): 
     
       
         
         
             
             
         
       
     
     wherein:
 
A represents an optionally substituted aryl, or an optionally substituted 5- or 6-membered heterocyclyl ring, or an optionally substituted bicyclic heterocyclyl group;
 
B represents a phenyl or pyridyl ring;
 
Z represents O, S, SO, or SO 2 ;
 
R 1  represents CO 2 H, CN, CONR 5 R 6 , CH 2 CO 2 H, optionally substituted SO 2 alkyl, SO 2 NR 5 R 6 , NR 5 CONR 5 R 6 , COalkyl, 2H-tetrazol-5-yl-methyl, optionally substituted bicyclic heterocycle or optionally substituted heterocyclyl;
 
R 2a  and R 2b  each independently represents hydrogen, halo, optionally substituted alkyl, optionally substituted alkoxy, CN, SO 2 alkyl, SR 5 , NO 2 , optionally substituted aryl, CONR 5 R 6  or optionally substituted heteroaryl;
 
R x  represents optionally substituted alkyl wherein 1 or 2 of the non-terminal carbon atoms are optionally substituted by a group independently selected from NR 4 , O and SO n , wherein n is 0, 1 or 2; optionally substituted alkenyl; or optionally substituted alkynyl: or R x  represents optionally substituted alkenyl, optionally substituted CQ a Q b -heterocyclyl, optionally substituted CQ a Q b -bicyclic heterocyclyl or optionally substituted CQ a Q b -aryl;
 
R 4  represents hydrogen or an optionally substituted alkyl;
 
R 5  represents hydrogen or an optionally substituted alkyl;
 
R 6  represents hydrogen or optionally substituted alkyl, optionally substituted heteroaryl, optionally substituted SO 2 aryl, optionally substituted SO 2 alkyl, optionally substituted SO 2 heteroaryl, CN, optionally substituted CQ a Q b aryl, optionally substituted CQ a Q b heteroaryl or COR 7 ;
 
R 7  represents hydrogen, optionally substituted alkyl, optionally substituted heteroaryl or optionally substituted aryl;
 
R 8  and R 9  each independently represents hydrogen, chloro, fluoro, CF 3 , C 1-3 alkoxy or C 1-3 alkyl;
 
Q a  and Q b  are each independently selected from hydrogen and CH 3 ;
 
wherein when A is a 6-membered ring the R 1  substituent and cyclopentene ring are attached to carbon atoms 1,2-, 1,3- or 1,4-relative to each other, and when A is a five-membered ring or bicyclic heterocyclyl group the R 1  substituent and cyclopentene ring are attached to substitutable carbon atoms 1,2- or 1,3-relative to each other; and derivatives thereof.
 
     When A is a six membered ring, preferably R 1  is attached to the group A in the 3 position relative to the bond attaching A to the cyclopentene ring. 
     Suitable examples of A include phenyl, pyridyl, pyridazinyl, pyrimidinyl and pyrazinyl, all of which may be optionally substituted. 
     Optional substituents for A include up to four substituents, preferably 0 or 1 substituent, independently selected from halogen, optionally substituted C 1-4 alkyl e.g. CF 3 , CH 3 , and C 2 H 5 , NH 2 , NHC 1-4 alkyl, NHCOC 1-4 alkyl, and SCH 3 . 
     When B is pyridyl, in one aspect the pyridine N atom is situated adjacent to the ring carbon carrying the Z substituent. 
     Preferably Z is O, 
     Suitably R 1  includes CO 2 H and CONHSO 2 phenyl. 
     Particular examples of R 2a  and R 2b  include hydrogen, halogen, optionally substituted C 1-6 alkyl e.g. CF 3  or CH 3 , and optionally substituted C 1-6 alkoxy. 
     Preferably R 2a  is hydrogen or CH 3 . More preferably R 2a  is hydrogen. 
     Preferably R 2b  represents hydrogen, halogen, CF 3 , or CH 3 . 
     Preferably R 2b  is positioned 1,4-relative to the Z substituent and 1,3-relative to the cyclopentene ring. 
     Suitably R 4  includes hydrogen and C 1-4 alkyl. 
     Suitably R 5  includes hydrogen or C 1-4 alkyl. 
     Suitably R 6  includes hydrogen, C 1-4 alkyl or SO 2 phenyl. 
     Suitably R 7  include hydrogen or C 1-4 alkyl. 
     Suitably R 8  include CH 3  or hydrogen, in one aspect R 8  represents hydrogen. 
     An example of R 9  is hydrogen. 
     An example of Q a  is hydrogen. 
     An example of Q b  is hydrogen. 
     Suitably R x  includes optionally substituted C 1-8 alkyl, optionally substituted C 2-8 alkenyl and CH 2-8 phenyl optionally substituted by one, two or three substituents, selected from Cl, Br, F, CF 3 , OCF 3 , C 1-4 alkyl, and OC 1-4 alkyl. 
     In one aspect R x  is optionally substituted C 3-8 alkyl, optionally substituted C 3-8 alkenyl and CH 2 phenyl optionally substituted by one, two or three substituents, selected from Cl, Br, F, CF 3 , OCF 3 , C 1-4 alkyl, and OC 1-4 alkyl. 
     Suitably R x  when an optionally substituted C 3-8 alkyl includes e.g. isobutyl, CH 2 cyclopentene and CH 2 cyclohexene. 
     Suitably R x  when an optionally substituted C 2-8 alkenyl include e.g. CH 2 CH═CH 2  and CH 2 CH═CH-phenyl. 
     A certain group of compounds of formula (I) are compounds of formula (IA): 
     
       
         
         
             
             
         
       
     
     wherein:
 
W, X, and Y each represent CR 12  or N;
 
V represents CR 1 , CR 12  or N;
 
wherein at least two of W, X, Y and V is CR 12 , and R 12  is independently selected from hydrogen, halogen, CF 3 , CH 3 , NH 2 , NHC 1-6 alkyl, NHCOC 1-6 alkyl, and SCH 3 ;
 
Q 1  and Q 2  each represents CH, or one of Q 1  and Q 2  is N and the other is CH;
 
R 1  is CO 2 H, CONR 5 R 6 , CH 2 CO 2 H, SO 2 C 1-6 alkyl, SO 2 NR 5 R 6 , NR 5 CONR 6 R 6 , tetrazolyl or COSO 2 NR 5 R 6 ;
 
R 2a  and R 2b  are selected from hydrogen, halogen, optionally substituted C 1-6 alkyl, and optionally substituted C 1-6 alkoxy;
 
R x  represents optionally substituted C 1-6 alkyl, optionally substituted C 3-8 alkenyl, and optionally substituted CH 2 phenyl;
 
R 5  is hydrogen or C 1-4 alkyl;
 
R 6  is hydrogen, C 1-4 alkyl or SO 2 phenyl;
 
R 12  is selected from hydrogen, halogen, NR 5 R 6 , NR 5 COC 1-6 alkyl, NR 5 SO 2 C 1-6 alkyl, OR 5 , SR 5 , and optionally substituted C 1-6 alkyl;
 
or derivatives thereof.
 
     Suitably R 1  includes CO 2 H and CONHSO 2 phenyl. 
     Suitably R x  includes optionally substituted C 3-8 alkyl, optionally substituted C 3-8 alkenyl, and CH 2 phenyl optionally substituted by one, two or three substituents, selected from Cl, Br, F, CF 3 , OCF 3 , C 1-4 alkyl, and OC 1-4 alkyl. 
     In one aspect R 1  is positioned 1,3-relative to the cyclopentene ring. 
     In another aspect one or two of W, X, Y and V is N. 
     In yet another aspect one of Q 1  and Q 2  is N and the other is CH. 
     A particular set of compounds are those wherein one or two of W, X, Y and V is N and Q 1  and Q 2  are both CH. A further set of compounds are those where one of Q 1  and Q 2  is N and W, X, Y, and V are each CR 12 . 
     In one aspect Q 1  is N or CH and Q 2  is CH. 
     Suitably R 2a  is hydrogen. 
     Suitably R 2b  is positioned 1,4-relative to OR x  and 1,3-relative to the cyclopentene ring. 
     Suitably R 2b is selected from hydrogen, F, Br, Cl, CH 3  and CF 3 . 
     Suitably R 12  includes hydrogen, halogen e.g. F or C 1 , CF 3 , NH 2 , NHCOC 1-4 alkyl, SCH 3 , and C 1-4 alkyl, e.g. CH 3  and C 2 H 5 ; 
     Compounds of formula (I) include the compounds of Examples 1 to 417 and derivatives thereof. 
     A particular group of compounds of formula (I) include the compounds of Examples 145-148, 213-241, 342-368, and 388-417 and derivatives thereof. 
     The compounds of the invention are selective for EP 1  over EP 3 . The compounds of the examples are at least 20 fold selective. Preferred compounds are at least 100 fold selective for EP 1  over EP 3 . 
     Derivatives of the compounds of formula (I) include pharmaceutically acceptable derivatives. The term “pharmaceutically acceptable derivative” means any pharmaceutically acceptable salt, solvate, ester, or solvate of salt or ester of the compounds of formula (I), or any other compound which upon administration to the recipient is capable of providing (directly or indirectly) a compound of formula (I). 
     It will be appreciated by those skilled in the art that the compounds of formula (I) may be modified to provide pharmaceutically acceptable derivatives thereof at any of the functional groups in the compounds, and that the compounds of formula (I) may be derivatised at more than one position. 
     It will be appreciated that, for pharmaceutical use, the salts referred to above will be pharmaceutically acceptable salts, but other salts may find use, for example in the preparation of compounds of formula (I) and the pharmaceutically acceptable salts thereof. 
     Pharmaceutically acceptable salts include those described by Berge, Bighley and Monkhouse,  J. Pharm. Sci.,  1977, 66, 1-19. The term “pharmaceutically acceptable salts” refers to salts prepared from pharmaceutically acceptable bases including inorganic bases and organic bases. Salts derived from inorganic bases include aluminum, ammonium, calcium, copper, ferric, ferrous, lithium, magnesium, manganic salts, manganous, potassium, sodium, zinc, and the like. A particular salt is the sodium salt. Salts derived from pharmaceutically acceptable organic bases include salts of primary, secondary, and tertiary amines; substituted amines including naturally occurring substituted amines; and cyclic amines. Particular pharmaceutically acceptable organic bases include arginine, betaine, caffeine, choline, N,N′-dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethyl-morpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, lysine, methylglucamine, morpholine, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, tripropyl amine, tromethamine, and the like. Salts may also be formed from basic ion exchange resins, for example polyamine resins. When the compound of the present invention is basic, salts may be prepared from pharmaceutically acceptable acids, including inorganic and organic acids. Such acids include acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethanesulfonic, ethanedisulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic, malic, mandelic, methanesulfonic, mucic, pamoic, pantothenic, phosphoric, propionic, succinic, sulfuric, tartaric, p-toluenesulfonic acid, and the like. 
     The compounds of formula (I) may be prepared in crystalline or non-crystalline form, and if crystalline, may be optionally hydrated or solvated. This invention includes in its scope stoichiometric hydrates as well as compounds containing variable amounts of water. 
     Suitable solvates include pharmaceutically acceptable solvates, such as hydrates. 
     Solvates include stoichiometric solvates and non-stoichiometric solvates. 
     The terms “halogen” or “halo” are used to represent fluorine, chlorine, bromine or iodine. 
     The term “alkyl” as a group or part of a group means a straight, branched or cyclic chain alkyl group or combinations thereof. Unless hereinbefore defined, examples of alkyl include C 1-8 alkyl, for example methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, t-butyl, pentyl, hexyl, 1,1-dimethylethyl, cyclopentyl or cyclohexyl or combinations thereof such as cyclohexylmethyl and cyclopentylmethyl. 
     The term “alkoxy” as a group or as part of a group means a straight, branched or cyclic chain alkoxy group. Unless hereinbefore defined “alkoxy” includes C 1-8 alkoxy, e.g. methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, sec-butoxy, iso-butoxy, tert-butoxy, pentoxy, hexyloxy, cyclopentoxy or cyclohexyloxy. In one aspect “alkoxy” is C 1-6  alkoxy. 
     The term “alkenyl” means linear or branched structures and combinations thereof, of the indicated number of carbon atoms, having at least one carbon-to-carbon double bond, wherein hydrogen may be replaced by an additional carbon to carbon double bond. In one aspect “alkenyl” is C 2-6 alkenyl, for example ethenyl, propenyl, 1-methylethenyl, butenyl and the like. 
     The term “alkynyl” means linear or branched structures and combinations thereof, of the indicated number of carbon atoms, having at least one carbon-to-carbon triple bond. C 2-8 alkynyl, for example, includes ethynyl, propynyl, butynyl and the like. 
     The term “heterocyclyl” as a group or as part of a group means an aromatic or non-aromatic five or six membered ring which contains from 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and is unsubstituted or substituted by, for example, up to three substituents. Examples of 5-membered heterocyclyl groups include furyl, dioxalanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, triazolyl, triazinyl, isothiazolyl, isoxazolyl, thiophenyl, pyrazolyl or tetrazolyl. Examples of 6-membered heterocyclyl groups are pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl or tetrazinyl. 
     The term “aryl” as a group or part of a group means a 5- or 6-membered aromatic ring, for example phenyl, or a 7 to 12 membered bicyclic ring system where at least one of the rings is aromatic, for example naphthyl. An aryl group may be optionally substituted by one or more substituents, for example up to 4, 3 or 2 substituents. Preferably the aryl group is phenyl. 
     The term “heteroaryl” as a group or as part of a group means a monocyclic five or six membered aromatic ring, or a fused bicyclic aromatic ring system comprising two of such monocyclic five or six membered aromatic rings. These heteroaryl rings contain one or more heteroatoms selected from nitrogen, oxygen or sulfur, where N-oxides, sulfur oxides and sulfur dioxides are permissible heteroatom substitutions. A heteroaryl group may be optionally substituted by one or more substituents, for example up to 3 or up to 2 substituents. Examples of “heteroaryl” used herein include furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridinyl, pyrimidinyl, quinolinyl, isoquinolinyl, benzofuryl, benzothienyl, indolyl, and indazolyl. 
     The term “bicyclic heterocyclyl” when used herein means a fused bicyclic aromatic or non-aromatic bicyclic heterocyclyl ring system comprising up to four, preferably one or two, heteroatoms each selected from oxygen, nitrogen and sulphur. Each ring may have from 4 to 7, preferably 5 or 6, ring atoms. A bicyclic heteroaromatic ring system may include a carbocyclic ring. Examples of bicyclic heterocyclyl groups include quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, pyridopyrazinyl, benzoxazolyl, benzothiophenyl, benzimidazolyl, benzothiazolyl, benzoxadiazolyl, benzthiadiazolyl, indolyl, benztriazolyl or naphthyridinyl. 
     When the heteroatom nitrogen replaces a carbon atom in an alkyl group, or when nitrogen is present in a heteroaryl, heterocyclyl or bicyclic heterocyclyl group, the nitrogen atom will, where appropriate, be substituted by one or two substituents selected from hydrogen and C 1-8 alkyl, preferably hydrogen and C 1-6 alkyl, more preferably hydrogen. 
     Optional substituents for alkyl or alkenyl groups unless hereinbefore defined include phenyl or halo e.g. Cl, Br or F. An alkyl or alkenyl group may be substituted by one or more optional substituents, for example up to 5, 4, 3, or 2 optional substituents. Particular substituted alkyl groups include those substituted by one or more fluorines e.g. CH 2 F, CHF 2 , CF 3 , C 2 F 5  etc, especially CF 3 . 
     Optional substituents for alkoxy groups unless hereinbefore defined include halo e.g. Cl, Br or F. An alkoxy group may be substituted by one or more optional substituents, for example up to 5, 4, 3, or 2 optional substituents. Particular substituted alkoxy groups include those substituted by one or more fluorines e.g. OCH 2 F, OCHF 2 , OCF 3 , OC 2 F 5 etc. 
     Unless otherwise defined, optional substituents for aryl, heteroaryl or heterocycyl moieties as a group or part of a group are selected from C 1-6 alkyl, C 1-6 alkoxy and halogen. 
     Compounds of formula (I) can be prepared as set forth in the following schemes and in the examples. The following processes form another aspect of the present invention. 
     For example, compounds of formula (I) may be prepared by the general route below: 
     
       
         
         
             
             
         
       
     
     wherein L 1  and L 2  each represent a leaving group for example halo, or triflate; L 3  and L 4  each represent an activating group, for example boronic acid; P is an optional protecting group; and A, B, R 1 , R 2a , R 2b , R 8 , R 9 , Z and R x  are as defined for compounds of formula (I). L 1  can be converted to L 1a , and L 2  can be converted to L 2a  wherein L 1a  and L 2a  each represent an activating group for example a boronic acid, and in this situation L 3  and L 4  can be halo or triflate. 
     When R 1  is CO 2 H examples of P include methyl, ethyl or optionally substituted benzyl esters. 
     Suitable reaction conditions for the deprotection of a compound of formula (II) include heating in aqueous ethanolic sodium hydroxide solution. 
     Suitable reaction conditions for the reaction of a compound of formula (VI) with a boronic acid of formula (V) (wherein L 3  is —B(OH) 2 ) or a compound of formula (IV) with a boronic acid of formula (III) (wherein L 4  is —B(OH) 2 ) include heating with tetrakis(triphenylphosphine)palladium (0) and an inorganic base, for example potassium carbonate, in a solvent, e.g. ethylene glycol dimethyl ether (DME), toluene and ethanol, preferably in a ratio of 1:1. 
     Accordingly the present invention also provides a process for the preparation of a compound of formula (I) or a derivative thereof: 
     
       
         
         
             
             
         
       
     
     wherein:
 
A represents an optionally substituted aryl, or an optionally substituted 5- or 6-membered heterocyclyl ring, or an optionally substituted bicyclic heterocyclyl group;
 
B represents a phenyl or pyridyl ring;
 
Z represents O, S, SO, or SO 2 ;
 
R 1  represents CO 2 H, CN, CONR 5 R 6 , CH 2 CO 2 H, optionally substituted SO 2 alkyl, SO 2 NR 5 R 6 , NR 5 CONR 6 R 6 , COalkyl, 2H-tetrazol-5-yl-methyl, optionally substituted bicyclic heterocycle or optionally substituted heterocyclyl;
 
R 2a  and R 2b  each independently represents hydrogen, halo, optionally substituted alkyl, optionally substituted alkoxy, CN, SO 2 alkyl, SR 5 , NO 2 , optionally substituted aryl, CONR 5 R 6  or optionally substituted heteroaryl;
 
R x  represents optionally substituted alkyl wherein 1 or 2 of the non-terminal carbon atoms are optionally substituted by a group independently selected from NR 4 , O and SO n , wherein n is 0, 1 or 2; optionally substituted alkenyl; or optionally substituted alkynyl: or R x  represents optionally substituted alkenyl, optionally substituted CQ a Q b -heterocyclyl, optionally substituted CQ a Q b -bicyclic heterocyclyl or optionally substituted CQ a Q b -aryl;
 
R 4  represents hydrogen or an optionally substituted alkyl;
 
R 5  represents hydrogen or an optionally substituted alkyl;
 
R 6  represents hydrogen or optionally substituted alkyl, optionally substituted heteroaryl, optionally substituted SO 2 aryl, optionally substituted SO 2 alkyl, optionally substituted SO 2 heteroaryl, CN, optionally substituted CQ a Q b aryl, optionally substituted CQ a Q b heteroaryl or COR 7 ;
 
R 7  represents hydrogen, optionally substituted alkyl, optionally substituted heteroaryl or optionally substituted aryl;
 
R 8  and R 9  each independently represents hydrogen, chloro, fluoro, CF 3 , C 1-3 alkoxy or C 1-3 alkyl;
 
Q a  and Q b  are each independently selected from hydrogen and CH 3 ;
 
wherein when A is a 6-membered ring the R 1  substituent and cyclopentene ring are attached to carbon atoms 1,2-, 1,3- or 1,4-relative to each other, and when A is a five-membered ring or bicyclic heterocyclyl group the R 1  substituent and cyclopentene ring are attached to substitutable carbon atoms 1,2- or 1,3-relative to each other; comprising:
 
reacting a compound of formula (IV):
 
     
       
         
         
             
             
         
       
     
     wherein R 8 , R 9 , A, and R 1  are as hereinbefore defined above for a compound of formula (I),
 
L 1  is a leaving group and P is an optional protecting group;
 
with a compound of formula (III):
 
     
       
         
         
             
             
         
       
     
     wherein R 2a , R 2b , B, Z, and R x  are as hereinbefore defined above for a compound of formula (I) and L 4  is an activating group;
 
and where required converting:
 
one group A to another group A, and/or
 
one group R x  to another group R x ;
 
and where required carrying out the following optional steps in any order: effecting deprotection; and/or
 
converting one group R 1  to another group R 1 ; and/or
 
forming a derivative of the compound of formula (I) so formed.
 
     Alternatively compounds of formula (I) may be prepared according to the route described below: 
     
       
         
         
             
             
         
       
     
     wherein L 1 , L 2 , L 3 , L 4  and P are as defined above, and A, B, R 1 , R 2a , R 2b , R 8 , R 9 , Z, and R x  are as defined for compounds of formula (I). L 1  can be converted to L 1a , and L 2  can be converted to L 2a  wherein L 1a  and L 2a  each represent an activating group for example a boronic acid, and in this situation L 3  and L 4  can represent halo or triflate. 
     Accordingly the present invention also provides a process for the preparation of a compound of formula (I) or a derivative thereof: 
     
       
         
         
             
             
         
       
     
     wherein:
 
A represents an optionally substituted aryl, or an optionally substituted 5- or 6-membered heterocyclyl ring, or an optionally substituted bicyclic heterocyclyl group;
 
B represents a phenyl or pyridyl ring;
 
Z represents O, S, SO, or SO 2 ;
 
R 1  represents CO 2 H, CN, CONR 5 R 6 , CH 2 CO 2 H, optionally substituted SO 2 alkyl, SO 2 NR 5 R 6 , NR 5 CONR 5 R 6 , COalkyl, 2H-tetrazol-5-yl-methyl, optionally substituted bicyclic heterocycle or optionally substituted heterocyclyl;
 
R 2a  and R 2b  each independently represents hydrogen, halo, optionally substituted alkyl, optionally substituted alkoxy, CN, SO 2 alkyl, SR 5 , NO 2 , optionally substituted aryl, CONR 5 R 6  or optionally substituted heteroaryl;
 
R x  represents optionally substituted alkyl wherein 1 or 2 of the non-terminal carbon atoms are optionally substituted by a group Independently selected from NR 4 , O and SO n , wherein n is 0, 1 or 2; optionally substituted alkenyl; or optionally substituted alkynyl: or R x  represents optionally substituted alkenyl, optionally substituted CQ a Q b -heterocyclyl, optionally substituted CQ a Q b -bicyclic heterocyclyl or optionally substituted CQ a Q b -aryl;
 
R 4  represents hydrogen or an optionally substituted alkyl;
 
R 5  represents hydrogen or an optionally substituted alkyl;
 
R 6  represents hydrogen or optionally substituted alkyl, optionally substituted heteroaryl, optionally substituted SO 2 aryl, optionally substituted SO 2 alkyl, optionally substituted SO 2 heteroaryl, CN, optionally substituted CQ a Q b aryl, optionally substituted CQ a Q b heteroaryl or COR 7 ;
 
R 7  represents hydrogen, optionally substituted alkyl, optionally substituted heteroaryl or optionally substituted aryl;
 
R 8  and R 9  each independently represents hydrogen, chloro, fluoro, CF 3 , C 1-3 alkoxy or C 1-3 alkyl;
 
Q a  and Q b  are each independently selected from hydrogen and CH 3 ;
 
wherein when A is a 6-membered ring the R 1  substituent and cyclopentene ring are attached to carbon atoms 1,2-, 1,3- or 1,4-relative to each other, and when A is a five-membered ring or bicyclic heterocyclyl group the R 1  substituent and cyclopentene ring are attached to substitutable carbon atoms 1,2- or 1,3-relative to each other; comprising:
 
reacting a compound of formula (VII):
 
     
       
         
         
             
             
         
       
     
     wherein R 2a , R 2b , R 8 , R 9 , A, B, R x  and R 1  are as hereinbefore defined above for a compound of formula (I), and L 2  is a leaving group;
 
with a compound of formula (V):
 
     
       
         
         
             
             
         
       
     
     wherein R 1 , and A are as hereinbefore defined above for a compound of formula (I); L 3  is an activating group and P is an optional protecting group;
 
and where required converting:
 
one group A to another group A, and/or
 
one group R x  to another group R x ;
 
and where required carrying out the following optional steps in any order:
 
effecting deprotection; and/or
 
converting one group R 1  to another group R 1 ; and/or
 
forming a derivative of the compound of formula (I) so formed.
 
     It will be appreciated that certain substituents in intermediates and compounds of formula (I) may be converted to other substituents by conventional methods known to those skilled in the art. 
     A group R 1  may be converted to another group R 1  by use of conventional organic transformations known to those skilled in the art. For example R 1 ═CO 2 H may be converted to an amide, e.g. CONHCQ a Q b aryl or CONHCQ a Q b heteroaryl wherein Q a  and Q b  are selected from hydrogen and CH 3 , by conventional methods for the preparation of amides as described in, for example, Richard Larock,  Comprehensive Organic Transformations,  2nd edition, Wiley-VCH, ISBN 0-71-19031-4. 
     Cyclopentene derivatives of formula (VI), boronic acids of formula (III) and (V), and tetrakis(triphenylphosphine)palladium (0) are commercially available, or readily prepared by methods known to those skilled in the art. 
     The preparation and reactions of boronic acids of formula (III) and formula (V) is reviewed in Suzuki et al,  Synth. Commun.,  1981, 11, 513; Martin et al,  Acta. Chim. Scand.,  1993, 47, 221; and Miyaura et al,  Chem. Rev.,  1995, 95, 2457. For example, 2-benzyloxy-5-chlorophenylboronic acid may be prepared from 2-benzyloxy-5-chloro-iodobenzene. 2-Benzyloxy-5-chloro-iodobenzene may be prepared from 4-chloro-2-iodoanisole by demethylation followed by benzylation according to known methods. 
     Certain substituents in any of the reaction intermediates and compounds of formula (I) may be converted to other substituents by conventional methods known to those skilled in the art. Examples of substituents which may be converted include one group R x  to another group R x ; and one substituent on a group A to another substituent on a group A. Examples of such transformations include the reduction of a nitro group to give an amino group; alkylation and amidation of amino groups; hydrolysis of esters, alkylation of hydroxy and amino groups; and amidation and esterification of carboxylic acids. Such transformations are well known to those skilled in the art and are described in for example, Richard Larock,  Comprehensive Organic Transformations,  2nd edition, Wiley-VCH, ISBN 0-471-19031-4. 
     For example, when R x  is p-methoxybenzyl, cleavage of the ether to give the phenol or pyridinol is carried out using, for example, using acid e.g. HCl/dioxane or using sodium methanethiolate. When R x  is methyl, cleavage of the ether to give the phenol is carried out using, for example, sodium methanethiolate. Cleavage of the ether to give a pyridinol is carried out in the presence of, for example, trifluoroacetic acid. Conversion to another R x  group, for example a substituted benzyl group, may be effected by reaction of the phenol or pyridinol with a suitable substituted benzyl bromide. The skilled person will appreciate that conversion of the protecting group P to another protecting group P may also occur under the reaction conditions used. When R x  is benzyl, cleavage of the ether to give the phenol or pyridinol may be carried out by hydrogenation according to known methods e.g. H 2 —Pd/C or NH 4 CO 2 H—Pd/C. The resulting phenol or pyridinol can then be converted to another group R x  as described above. 
     It will be appreciated by those skilled in the art that it may be necessary to protect certain reactive substituents during some of the above procedures. The skilled person will recognise when a protecting group is required. Standard protection and deprotection techniques, such as those described in Greene T. W. ‘Protective groups in organic synthesis’, New York, Wiley (1981), can be used. For example, carboxylic acid groups can be protected as esters. Deprotection of such groups is achieved using conventional procedures known in the art. It will be appreciated that protecting groups may be interconverted by conventional means. 
     Cyclopentene intermediates of the formula (VI): 
     
       
         
         
             
             
         
       
     
     wherein L 1 , L 2  are as defined above, and R 8  and R 9  are as hereinbefore defined for compounds of formula (I) are commercially available or may be readily prepared according to known methods. 
     Compounds of the formula (III): 
     
       
         
         
             
             
         
       
     
     wherein L 4  is as hereinbefore defined, R 2a , R 2b , Z, B and R x  and are as defined for compounds of formula (I) are commercially available, or may readily be prepared by methods known to those skilled in the art, for example from suitable commercially available pyridinols, anisoles or phenols using methods as described in the examples. 
     Compounds of the formula (V): 
     
       
         
         
             
             
         
       
     
     wherein L 3  and P are as defined above and R 1  and A are as hereinbefore defined for compounds of formula (I) are commercially available or may readily be prepared, for example, from suitable halobenzoic acid esters according to known methods, for example using methods as described in the examples. 
     It is to be understood that the present invention encompasses all isomers of formula (I) and their pharmaceutically acceptable derivatives, including all geometric, tautomeric and optical forms, and mixtures thereof (e.g. racemic mixtures). Where additional chiral centres are present in compounds of formula (I), the present invention includes within its scope all possible diastereoismers, including mixtures thereof. The different isomeric forms may be separated or resolved one from the other by conventional methods, or any given isomer may be obtained by conventional synthetic methods or by stereospecific or asymmetric syntheses. 
     The compounds of the invention bind to the EP 1  receptor and they are therefore considered to be useful in treating conditions mediated by the action of PGE 2  at EP 1  receptors. 
     Conditions mediated by the action of PGE 2  at EP 1  receptors include pain; fever; inflammation; immunological diseases; abnormal platelet function diseases; impotence or erectile dysfunction; bone disease; hemodynamic side effects of non-steroidal anti-inflammatory drugs; cardiovascular diseases; neurodegenerative diseases and neurodegeneration; neurodegeneration following trauma; tinnitus; dependence on a dependence-inducing agent; complications of Type I diabetes; and kidney dysfunction. 
     The compounds of formula (I) are considered to be useful as analgesics. They are therefore considered useful in the treatment or prevention of pain. 
     The compounds of formula (I) are considered useful as analgesics to treat acute pain, chronic pain, neuropatic pain, inflammatory pain, visceral pain, pain associated with cancer and fibromyalgia, pain associated with migraine, tension headache and cluster headaches, and pain associated with functional bowel disorders, non-cardiac chest pain and non-ulcer dispepsia. 
     The compounds of formula (I) are considered useful in the treatment of chronic articular pain (e.g. rheumatoid arthritis, osteoarthritis, rheumatoid spondylitis, gouty arthritis and juvenile arthritis) including the property of disease modification and joint structure preservation; musculoskeletal pain; lower back and neck pain; sprains and strains; neuropathic pain; sympathetically maintained pain; myositis; pain associated with cancer and fibromyalgia; pain associated with migraine; pain associated with influenza or other viral infections, such as the common cold; rheumatic fever, pain associated with functional bowel disorders such as non-ulcer dyspepsia, non-cardiac chest pain and irritable bowel syndrome; pain associated with myocardial ischemia; post operative pain; headache; toothache; and dysmenorrhea. The compounds of this invention may also be useful in the treatment of visceral pain. 
     The compounds of the invention are considered to be particularly useful in the treatment of neuropathic pain. Neuropathic pain syndromes can develop following neuronal injury and the resulting pain may persist for months or years, even after the original injury has healed. Neuronal injury may occur in the peripheral nerves, dorsal roots, spinal cord or certain regions in the brain. Neuropathic pain syndromes are traditionally classified according to the disease or event that precipitated them. Neuropathic pain syndromes include: diabetic neuropathy; sciatica; non-specific lower back pain; multiple sclerosis pain; fibromyalgia; HIV-related neuropathy; post-herpetic neuralgia; trigeminal neuralgia; and pain resulting from physical trauma, amputation, cancer, toxins or chronic inflammatory conditions. These conditions are difficult to treat and although several drugs are known to have limited efficacy, complete pain control is rarely achieved. The symptoms of neuropathic pain are heterogeneous and are often described as spontaneous shooting and lancinating pain, or ongoing, burning pain. In addition, there is pain associated with normally non-painful sensations such as “pins and needles” (paraesthesias and dysesthesias), increased sensitivity to touch (hyperesthesia), painful sensation following innocuous stimulation (dynamic, static or thermal allodynia), increased sensitivity to noxious stimuli (thermal, cold, mechanical hyperalgesia), continuing pain sensation after 
     It is to be understood that reference to treatment includes both treatment of established symptoms and prophylactic treatment, unless explicitly stated otherwise. 
     According to a further aspect of the invention, we provide a compound of formula (I) or a pharmaceutically acceptable derivative thereof for use in human or veterinary medicine. 
     According to another aspect of the invention, we provide a compound of formula (I) or a pharmaceutically acceptable derivative thereof for use in the treatment of a condition which is mediated by the action of PGE 2  at EP 1  receptors. 
     According to a further aspect of the invention, we provide a method of treating a human or animal subject suffering from a condition which is mediated by the action of PGE 2  at EP 1  receptors which comprises administering to said subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable derivative thereof. 
     According to a further aspect of the invention we provide a method of treating a human or animal subject suffering from a pain, or an inflammatory, immunological, bone, neurodegenerative or renal disorder, which method comprises administering to said subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable derivative thereof. 
     According to a yet further aspect of the invention we provide a method of treating a human or animal subject suffering from inflammatory pain, neuropathic pain or visceral pain which method comprises administering to said subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable derivative thereof. 
     According to another aspect of the invention, we provide the use of a compound of formula (I) or a pharmaceutically acceptable derivative thereof for the manufacture of a medicament for the treatment of a condition which is mediated by the action of PGE 2  at EP 1  receptors. 
     According to another aspect of the invention we provide the use of a compound of formula (I) or a pharmaceutically acceptable derivative thereof for the manufacture of a medicament for the treatment or prevention of a condition such as a pain, or an inflammatory, immunological, bone, neurodegenerative or renal disorder. 
     According to another aspect of the invention we provide the use of a compound of formula (I) or a pharmaceutically acceptable derivative thereof for the manufacture of a medicament for the treatment or prevention of a condition such as inflammatory pain, neuropathic pain or visceral pain. 
     The compounds of formula (I) and their pharmaceutically acceptable derivatives are conveniently administered in the form of pharmaceutical compositions. Such compositions may conveniently be presented for use in conventional manner in admixture with one or more physiologically acceptable carriers or excipients. 
     Thus, in another aspect of the invention, we provide a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable derivative thereof adapted for use in human or veterinary medicine. 
     The compounds of formula (I) and their pharmaceutically acceptable derivatives may be formulated for administration in any suitable manner. They may be formulated for administration by inhalation or for oral, topical, transdermal or parenteral administration. The pharmaceutical composition may be in a form such that it can effect controlled release of the compounds of formula (I) and their pharmaceutically acceptable derivatives. 
     For oral administration, the pharmaceutical composition may take the form of, for example, tablets (including sub-lingual tablets), capsules, powders, solutions, syrups or suspensions prepared by conventional means with acceptable excipients. 
     For transdermal administration, the pharmaceutical composition may be given in the form of a transdermal patch, such as a transdermal iontophoretic patch. 
     For parenteral administration, the pharmaceutical composition may be given as an injection or a continuous infusion (e.g. intravenously, intravascularly or subcutaneously). The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles and may contain formulatory agents such as suspending, stabilising and/or dispersing agents. For administration by injection these may take the form of a unit dose presentation or as a multidose presentation preferably with an added preservative. Alternatively for parenteral administration the active ingredient may be in powder form for reconstitution with a suitable vehicle. 
     The compounds of the invention may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular Injection. Thus, for example, the compounds of the invention may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. 
     The EP 1  receptor compounds for use in the instant invention may be used in combination with other therapeutic agents, for example COX-2 inhibitors, such as celecoxib, deracoxib, rofecoxib, valdecoxib, parecoxib or COX-189; 5-lipoxygenase inhibitors; NSAID&#39;s, such as diclofenac, indomethacin, nabumetone or ibuprofen; leukotriene receptor antagonists; removal of the stimulation (hyperpathia) or an absence of or deficit in selective sensory pathways (hypoalgesia). 
     The compounds of formula (I) are also considered useful in the treatment of fever. 
     The compounds of formula (I) are also considered useful in the treatment of inflammation, for example in the treatment of skin conditions (e.g. sunburn, burns, eczema, dermatitis, psoriasis); ophthalmic diseases such as glaucoma, retinitis, refinopathies, uveitis and of acute injury to the eye tissue (e.g. conjunctivitis); lung disorders (e.g. asthma, bronchitis, emphysema, allergic rhinitis, respiratory distress syndrome, pigeon fancier&#39;s disease, farmer&#39;s lung, chronic obstructive pulmonary disease, (COPD); gastrointestinal tract disorders (e.g. aphthous ulcer, Crohn&#39;s disease, atopic gastritis, gastritis varialoforme, ulcerative colitis, coeliac disease, regional ileitis, irritable bowel syndrome, inflammatory bowel disease, gastrointestinal reflux disease); organ transplantation; other conditions with an inflammatory component such as vascular disease, migraine, periarteritis nodosa, thyroiditis, aplastic anaemia, Hodgkin&#39;s disease, scierodoma, myaesthenia gravis, multiple sclerosis, sorcoidosis, nephrotic syndrome, Bechet&#39;s syndrome, gingivitis, myocardial ischemia, pyrexia, systemic lupus erythematosus, polymyositis, tendinitis, bursitis, and Sjogren&#39;s syndrome. 
     The compounds of formula (I) are also considered useful in the treatment of immunological diseases such as autoimmune diseases, immunological deficiency diseases or organ transplantation. The compounds of formula (I) are also effective in increasing the latency of HIV infection. 
     The compounds of formula (I) are also considered useful in the treatment of diseases relating to abnormal platelet function (e.g. occlusive vascular diseases). 
     The compounds of formula (I) are also considered useful for the preparation of a drug with diuretic action. 
     The compounds of formula (I) are also considered useful in the treatment of impotence or erectile dysfunction. 
     The compounds of formula (I) are also considered useful in the treatment of bone disease characterised by abnormal bone metabolism or resorbtion such as osteoporosis (especially postmenopausal osteoporosis), hyper-calcemia, hyperparathyroidism, Paget&#39;s bone diseases, osteolysis, hypercalcemia of malignancy with or without bone metastases, rheumatoid arthritis, periodontitis, osteoarthritis, ostealgia, osteopenia, cancer cacchexia, calculosis, lithiasis (especially urolithiasis), solid carcinoma, gout and ankylosing spondylitis, tendinitis and bursitis. 
     The compounds of formula (I) are also considered useful for attenuating the hemodynamic side effects of non-steroidal anti-inflammatory drugs (NSAID&#39;s) and cyclooxygenase-2 (COX-2) inhibitors. 
     The compounds of formula (I) are also considered useful in the treatment of cardiovascular diseases such as hypertension or myocardiac ischemia; functional or organic venous insufficiency; varicose therapy; haemorrhoids; and shock states associated with a marked drop in arterial pressure (e.g. septic shock). 
     The compounds of formula (I) are also considered useful in the treatment of neurodegenerative diseases and neurodegeneration such as dementia, particularly degenerative dementia (including senile dementia, Alzheimer&#39;s disease, Pick&#39;s disease, Huntingdon&#39;s chorea, Parkinson&#39;s disease and Creutzfeldt-Jakob disease, ALS, motor neuron disease); vascular dementia (including multi-infarct dementia); as well as dementia associated with intracranial space occupying lesions; trauma; infections and related conditions (including HIV infection); metabolism; toxins; anoxia and vitamin deficiency; and mild cognitive impairment associated with ageing, particularly Age Associated Memory Impairment. 
     The compounds of formula (I) are also considered useful in the treatment of neuroprotection and in the treatment of neurodegeneration following trauma such as stroke, cardiac arrest, pulmonary bypass, traumatic brain injury, spinal cord injury or the like. 
     The compounds of formula (I) are also considered useful in the treatment of tinnitus. 
     The compounds of formula (I) are also considered useful in preventing or reducing dependence on, or preventing or reducing tolerance or reverse tolerance to, a dependence-inducing agent. Examples of dependence inducing agents include opioids (e.g. morphine), CNS depressants (e.g. ethanol), psychostimulants (e.g. cocaine) and nicotine. 
     The compounds of formula (I) are also considered useful in the treatment of complications of Type 1 diabetes (e.g. diabetic microangiopathy, diabetic retinopathy, diabetic nephropathy, macular degeneration, glaucoma), nephrotic syndrome, aplastic anaemia, uveitis, Kawasaki disease and sarcoidosis. 
     The compounds of formula (I) are also considered useful in the treatment of kidney dysfunction (nephritis, particularly mesangial proliferative glomerulonephritis, nephritic syndrome), liver dysfunction (hepatitis, cirrhosis), gastrointestinal dysfunction (diarrhoea) and colon cancer. 
     The compounds of formula (I) and pharmaceutically acceptable derivatives thereof are also useful in the treatment of overactive bladder and urge incontenance. 
     DMARD&#39;s such as methotrexate; adenosine A1 receptor agonists; sodium channel blockers, such as lamotrigine; NMDA receptor modulators, such as glycine receptor antagonists; gabapentin and related compounds; tricyclic antidepressants such as amitriptyline; neurone stabilising antiepileptic drugs; mono-aminergic uptake inhibitors such as venlafaxine; opioid analgesics; local anaesthetics; 5HT 1  agonists, such as triptans, for example sumatriptan, naratriptan, zolmitriptan, eletriptan, frovatriptan, almotriptan or rizatriptan; nicotinic acetyl choline (nACh) receptor modulators; glutamate receptor modulators, for example modulators of the NR2B subtype; EP 4  receptor ligands; EP 2  receptor ligands; EP 3  receptor ligands; EP 4  antagonists; EP 2  antagonists and EP 3  antagonists; cannabanoid receptor ligands; bradykinin receptor ligands and vanilloid receptor ligand. When the compounds are used in combination with other therapeutic agents, the compounds may be administered either sequentially or simultaneously by any convenient route. 
     Additional COX-2 inhibitors are disclosed in U.S. Pat. Nos. 5,474,995 5,633,272; 5,466,823, 6,310,099 and 6,291,523; and in WO 96/25405, WO 97/38986, WO 98/03484, WO 97/14691, WO99/12930, WO00/26216, WO00/52008, WO00/38311, WO01/58881 and WO02/18374. 
     The invention thus provides, in a further aspect, a combination comprising a compound of formula (I) or a pharmaceutically acceptable derivative thereof together with a further therapeutic agent or agents. 
     The combinations referred to above may conveniently be presented for use in the form of a pharmaceutical formulation and thus pharmaceutical formulations comprising a combination as defined above together with a pharmaceutically acceptable carrier or excipient comprise a further aspect of the invention. The individual components of such combinations may be administered either sequentially or simultaneously in separate or combined pharmaceutical formulations. 
     When a compound of formula (I) or a pharmaceutically acceptable derivative thereof is used in combination with a second therapeutic agent active against the same disease state the dose of each compound may differ from that when the compound is used alone. Appropriate doses will be readily appreciated by those skilled in the art. 
     A proposed daily dosage of compounds of formula (I) or their pharmaceutically acceptable derivatives for the treatment of man is from 0.01 to 30 mg/kg body weight per day and more particularly 0.1 to 10 mg/kg body weight per day, which may be administered as a single or divided dose, for example one to four times per day The dose range for adult human beings is generally from 8 to 2000 mg/day, such as from 20 to 1000 mg/day, preferably 35 to 200 mg/day. 
     The precise amount of the compounds of formula (I) administered to a host, particularly a human patient, will be the responsibility of the attendant physician. However, the dose employed will depend on a number of factors including the age and sex of the patient, the precise condition being treated and its severity, and the route of administration. 
     No unacceptable toxicological effects are expected with compounds of the invention when administered in accordance with the invention. 
     All publications, including but not limited to patents and patent applications, cited in this specification are herein incorporated by reference as if each individual publication were specifically and individually indicated to be incorporated by reference herein as though fully set forth. 
     The following non-limiting Examples illustrate the preparation of pharmacologically active compounds of the invention. 
    
    
     EXAMPLES 
     Abbreviations 
     Bn (benzyl), Bu, Pr, Me, Et (butyl, propyl, methyl ethyl), DMSO (dimethyl sulfoxide), DCM (dichloromethane), DME (ethylene glycol dimethyl ether), DMF (N,N-dimethylformamide), EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide), EDTA (ethylenediamine tetraacetic acid), EtOAc (ethyl acetate), EtOH (ethanol), HPLC (High pressure liquid chromatography), LCMS (Liquid chromatography/Mass spectroscopy), MDAP (Mass Directed Purification), MeCN (acetonitrile), MeOH (methanol), NMR (Nuclear Magnetic Resonance (spectrum)), Ph (phenyl), pTSA (para-toluene sulphonic acid), SPE (Solid Phase Extraction), TBAF (tetrabutylammonium fluoride), THF (tetrahydrofuran), s, d, t, q, m, br (singlet, doublet, triplet, quartet, multiplet, broad.) 
     LCMS 
     
         
         
           
             Column: 3.3 cm×4.6 mm ID, 3 um ABZ+PLUS 
             Flow Rate: 3 ml/min 
             Injection Volume: 5 μl 
             Temp: RT 
             UV Detection Range: 215 to 330 nm 
           
         
       
    
     
       
         
           
               
               
             
               
                   
               
             
            
               
                 Solvents: 
                 A: 0.1% Formic Acid + 10 mMolar Ammonium Acetate. 
               
               
                   
                 B: 95% Acetonitrile + 0.05% Formic Acid 
               
            
           
           
               
               
               
               
            
               
                 Gradient: 
                 Time 
                 A % 
                 B % 
               
               
                   
                 0.00 
                 100 
                 0 
               
               
                   
                 0.70 
                 100 
                 0 
               
               
                   
                 4.20 
                 0 
                 100 
               
               
                   
                 5.30 
                 0 
                 100 
               
               
                   
                 5.50 
                 100 
                 0 
               
               
                   
               
            
           
         
       
     
     Mass Directed Autopreparation 
     Hardware: 
     Waters 600 gradient pump
 
Waters 2767 inject/collector
 
     Waters Reagent Manager 
     Micromass ZMD mass spectrometer
 
Gilson Aspec—waste collector
 
Gilson 115 post-fraction UV detector
 
     Software: 
     Micromass Masslynx version 4.0 
     Column 
     The column used is typically a Supelco LCABZ++ column whose dimensions are 20 mm internal diameter by 100 mm in length. The stationary phase particle size is 5 μm. 
     Solvents: 
     A: Aqueous solvent=Water+0.1% Formic Acid
 
B: Organic solvent=MeCN:Water 95:5+0.05% Formic Acid
 
Make up solvent=MeOH:Water 80:20+50 mMol Ammonium Acetate
 
Needle rinse solvent=MeOH:Water:DMSO 80:10:10
 
     The method used depends on the analytical retention time of the compound of interest. 15-minute runtime, which comprises a 10-minute gradient followed by a 5-minute column flush and re-equilibration step. 
     MDP 1.5-2.2=0-30% B 
     MDP 2.0-2.8=5-30% B 
     MDP 2.5-3.0=15-55% B 
     MDP 2.84.0=30-80% B 
     MDP 3.8-5.5=50-90% B 
     Flow rate:
 
flow rate 20 ml/min.
 
     Preparation of Intermediates 
     1-[(Phenylmethyl)oxy]-4-(trifluoromethyl)benzene 
     A solution of 4-(trifluoromethyl)phenol (8.55 g, 52.78 mmol) in acetone (200 ml) was treated with benzyl bromide (9.87 g, 6.86 ml, 58.05 mmol) and potassium carbonate (10.94 g, 79.16 mmol). The mixture was stirred and heated to reflux under nitrogen for 3 h. After cooling, diethyl ether (400 ml) and water (400 ml) were added and the aqueous phase re-extracted with diethyl ether (100 ml). The combined organic layers were washed with water, dried (MgSO 4 ) and the solvent removed in vacuo to leave the title compound as a white solid. (12.71 g, 95%) 
       1 H NMR (CDCl 3 ) δ: 5.11 (2H, s), 7.03 (2H, d), 7.34-7.44 (5H, m), 7.55 (2H, d). 
     2-Iodo-1-[(phenylmethyl)oxy]-4-(trifluoromethyl)benzene 
     A solution of 1-[(phenylmethyl)oxy]-4-(trifluoromethyl)benzene (12.71 g, 50.4 mmol) In acetonitrile (300 ml) was stirred under nitrogen and 1-(chloromethyl)-4-fluoro-1,4 diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (17.75 g, 50.4 mmol) and iodine (6.4 g, 25.2 mmol) added. The mixture was stirred at room temperature for 88 h. The solvent was evaporated and the residue partitioned between ethyl acetate (400 ml) and water (400 ml). The organic layer was washed with water, dried (MgSO 4 ) and evaporated to an orange oil which was purified by flash chromatography (silica gel, 5% ethyl acetate: isohexane) to give the title compound as an orange oil (15.07 g, 79%) 
       1 H NMR (CDCl 3 ) δ: 5.21 (2H, s), 6.89 (1H, d J), 7.32-7.55 (6H, m), 8.04 (1H, d). 
     1-Chloro-5-iodo-2-methyl-4(methyloxy)benzene 
     A mixture of 1-chloro-5-iodo-2-methyl-4-(methyloxy)benzene (5.0 g, 32 mmol), 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (11.3 g, 32 mmol), and iodine (4.06 g, 16 mmol) in dry acetonitrile (100 ml) was stirred at room temperature for 6 hours. The solvent was evaporated at &lt;30° C. The residue was partitioned between ethyl acetate (50 ml) and water (50 ml). The organic phase was dried (MgSO 4 ) and evaporated to leave the the compound as a yellow gum (9.0 g). 
       1 H NMR (CDCl 3 ) δ: 2.31(3H, s), 3.83 (3H, s), 6.65 (1H, s), 7.68 (1H, s). 
     4,5-dichloro-2-iodophenyl methyl ether 
     The title compound was prepared in a similar manner to 1-Chloro-5iodo-2-methyl-4-(methyloxy)benzene using 4,5-dichlorophenyl methyl ether. 
       1 H NMR (CDCl 3 ) δ: 3.87(3H, s), 6.87 (1H, s), 7.82 (1H, s). 
     Ethyl 5-iodo-2-methylbenzoate 
     A solution of 5-amino-2-methylbenzoic acid ethyl ester (500 mg, 2.8 mmol) and iodine (425 mg, 1.68 mmol) in toluene (20 ml) was cooled to 0° C. and treated with t-butyl nitrite (303 mg, 2.94 mmol). The reaction mixture was stirred at 0° C. for 1 hour then at room temperature for 72 hours. The reaction mixture was washed with 10% aqueous sodium thiosulphate (20 ml), and brine (20 ml), dried (MgSO 4 ) and evaporated. Flash chromatography [silica, iso-hexane/EtOAc, 9:1] gave ethyl 5-iodo-2-methylbenzoate as a brown oil (510 mg). 
       1 H NMR (CDCl 3 ) δ: 1.39 (3H, t), 2.53 (3H, s), 4.36 (2H, q), 6.97 (1H, d), 7.37 (1H, d), 8.20 (1H, s). 
     Ethyl 2-fluoro-5-iodobenzoate 
     Ethyl 2-fluoro-5-aminobenzoate (6.5 g, 35.48 mmol) was stirred in 5N hydrochloric acid (60 ml) and cooled to 0° C. Sodium nitrite (2.7 g, 39.03 mmol) in water (5 ml) was added at 0-5° C. The resulting mixture was added to a solution of potassium iodide (7.07 g, 42.58 mmol) in water (50 ml) over 5 minutes. The reaction was stirred at room temperature for 1 hour, then extracted with diethyl ether. The organic solution was washed with water and 5% sodium thiosulphate solution, dried (MgSO 4 ) and evaporated. The residue was purified by flash chromatography, eluting with 5% ethyl acetate/isohexane to give the title compound as a colourless oil (7.8 g). 
       1 H NMR (CDCl 3 ) δ: 1.40 (3H, t), 4.39 (2H, q), 6.91 (1H, dd), 7.79 (1H, td), 8.22 (1H, dd). 
     Ethyl 3-fluoro-5-nitrobenzoate 
     5-Fluoro-3-nitrobenzoic acid (4.8 g, 25.92 mmol) was dissolved in ethanol (50 ml) and sulphuric acid (0.5 ml) added carefully. The mixture was heated to reflux for 16 hours. The solvent was evaporated and the residue dissolved in ethyl acetate and washed with water, 5% sodium bicarbonate solution and brine, dried (MgSO 4 ) and evaporated. The residue was purified by flash chromatography, eluting with 10% ethyl acetate/isohexane to give the title compound as a yellow oil (2.04 g) 
       1 H NMR (CDCl 3 ) δ: 1.44 (3H, t), 4.46 (2H, q), 8.07-8.14(2H, m), 8.69 (1H, s). 
     Ethyl 3-amino-5-fluorobenzoate 
     Ethyl 3-fluoro-5-nitrobenzoate (5.0 g, 23.46 mmol) was dissolved in ethanol (150 ml) and tin(II)chloride (44.24 g, 0.234 mol) added portionwise with stirring. The mixture was stirred at 80° C. for 1 hour. The solvent was evaporated and the residue partitioned between ethyl acetate and 2M sodium hydroxide solution. The resulting glutinous mixture was slowly filtered through a Kieselguhr bed, which was washed copiously with ethyl acetate. The organic phase was washed with water, dried (MgSO 4 ) and evaporated to give the title compound as a cream solid (3.98 g). 
       1 H NMR (CDCl 3 ) δ: 1.38 (3H, t), 3.94 (2H, br s), 4.35 (2H, q), 6.53 (1H, dd), 7.08 (1H, dd), 7.14 (1H, d). 
     Ethyl 3-fluoro-5iodobenzoate 
     Ethyl 3-fluoro-5-aminobenzoate (3.98 g, 21.73 mmol) was stirred in 5N hydrochloric acid (45 ml) and cooled to 0° C. Sodium nitrite (1.65 g, 23.91 mmol) in water (2 ml) was added at 0-5° C. The resulting mixture was added dropwise to a solution of potassium iodide (4.33 g, 26.09 mmol) in water (30 ml) over 20 minutes. The reaction was stirred at room temperature for 1 hour, then extracted with diethyl ether (×2). The organic solution was washed with water and 5% sodium-thiosulphate solution, dried (MgSO 4 ) and evaporated to give the title compound as an orange oil (5.0 g). 
       1 H NMR (CDCl 3 ) δ: 1.40 (3H, t), 4.39 (2H, q), 7.62 (1H, dd), 7.69 (1H, td), 8.17 (1H, s). 
     Ethyl 3-amino-5-nitrobenzoate 
     3-Amino-5-nitrobenzoic acid (10.0 g, 54.9 mmol) was dissolved in ethanol (100 ml) and treated with conc. sulphuric acid (5 ml). The mixture was heated at reflux overnight. After cooling the ethanol was removed in vacuo and the residue was dissolved in diethyl ether. The solution was basified with saturated aqueous sodium bicarbonate and the layers separated. The aqueous layer was further extracted with diethyl ether (×3) and the combined organic extracts were dried (Na 2 SO 4 ) and concentrated in vacuo to give the ester (6.5 g). 
       1 H NMR (CDCl 3 ) δ: 1.41 (3H, t), 4.15 (2H, br s), 4.40 (2H, q), 7.60-7.68 (2H, m), 8.20 (1H, s). 
     Ethyl 3-iodo-5-nitrobenzoate 
     Ethyl 3-amino-5-nitrobenzoate (6.5 g, 30.9mmol) was suspended in 5M aqueous HCl (50 ml), cooled to 0° C. and sodium nitrite (2.34 g, 33.9 mmol) in water (4 ml) was added slowly. The resulting solution of the diazonium salt was added slowly to a solution of potassium iodide (6.16 g, 37.1 mmol) in water (40 ml), and the resulting mixture was stirred at room temperature for 1 hour. The mixture was extracted with diethyl ether, and the extract was washed with water and aqueous sodium thiosulphate solution, dried (Na 2 SO 4 ) and concentrated in vacuo. The residue was purified by flash chromatography on silica (gradient elution, 10-20% ethyl acetate/cyclohexane) to give the title compound (5.46 g). 
       1 H NMR (CDCl 3 ) δ: 1.44 (3H, t), 4.46 (2H, q), 8.68 (1H, t), 8.73 (1H, t), 8.81 (1H, t). 
     Ethyl 3-amino-5-iodobenzoate 
     Ethyl 3-iodo-5-nitrobenzoate (4.45 g, 13.9 mmol) was dissolved in ethanol and tin (II) chloride (27 g, 146 mmol) was added. The mixture was heated to reflux for 2 hours. After cooling, the reaction was concentrated in vacuo. The residue was partitioned between ethyl acetate and aqueous sodium hydroxide solution, and the aqueous extracted with further ethyl acetate. The combined extracts were washed with water, dried (Na 2 SO 4 ) and concentrated in vacuo to give the title compound as a yellow oil which slowly crystallised (3.56 g). LC/MS Rt=3.23 min [MH + ] 292. 
       1 H NMR (CDCl 3 ) δ: 1.38 (3H, t), 3.80 (2H, br s), 4.45 (2H, q), 7.20 (1H, t), 7.30 (1H, t), 7.74 (1H, t). 
     3-Bromo-5-chloro-2(1H)-pyridinone 
     5-Chloro-2-pyridinol (5.18 g, 40 mmol) was dissolved in glacial acetic acid (50 ml) and bromine (7.51 g, 2.41 ml, 47 mmol) added dropwise. The mixture was stirred at room temperature for 48 hours. Ethyl acetate and water were added and the organic layer washed with water (×3), dried (MgSO 4 ) and evaporated. The residue was triturated with diethyl ether and the buff solid filtered and dried (5.59 g). 
       1 H NMR (CDCl 3 ) δ: 7.52 (1H, d), 7.87 (1H, d). 
     3-Bromo-5-chloro-2-[(phenylmethyl)oxy]pyridine 
     3-Bromo-5-chloro-2-pyridinol (7.0 g, 33.6 mmol) was stirred in toluene (160 ml) and silver carbonate (10.23 g, 36.9 mmol) added, followed by benzyl bromide (6.32 g, 4.39 ml, 36.9 mmol). The mixture was heated to reflux for 1 hour. After cooling, the mixture was filtered, washed with water (×2), dried (MgSO 4 ) and evaporated. The residue was triturated with isohexane and the pale yellow solid filtered and dried. (8.36 g). 
       1 H NMR (CDCl 3 ) δ: 5.43 (2H, s), 7.32-7.48 (5H, m), 7.82 (1H, d), 8.04 (1H, d). 
     5-Chloro-3-iodo-2-[(phenylmethyl)oxy]pyridine 
     5-Chloro-3-iodo-2(1H)-pyridinone (6.69 g, 26.18 mmol) was dissolved in toluene (125 ml) and silver carbonate (7.97 g, 28.8 mmol) added, followed by benzyl bromide (3.43 ml, 28.8 mmol). The mixture was stirred and heated to reflux for 2 hours. The mixture was cooled, filtered through a Kieselguhr pad and the solvent evaporated. The residue was triturated with isohexane containing a trace of diethyl ether and the title compound filtered and dried in vacuo (6.8 g). 
       1 H NMR (CDCl 3 ) δ: 5.41 (2H, s), 7.32-7.49 (5H, m), 8.03 (1H, d), 8.06 (1H, d). 
     3-Iodo-2-[(phenylmethyl)oxy]-5-(trifluoromethyl)pyridine 
     The title compound was prepared in a similar manner to 5-chloro-3-iodo-2-[(phenylmethyl)oxy]pyridine using 3-iodo-5-(trifluoromethyl)-2(1H)-pyridinone. 
       1 H NMR (CDCl 3 ) δ: 5.49 (2H, s), 7.33-7.50 (5H, m), 8.23 (1H, d), 8.39 (1H, d). 
     Ethyl 3-bromo-5-fluorobenzoate 
     3-Bromo-5-fluorobenzoic acid (ex. Fluorochem) (6.0 g, 22.8 mmol) was dissolved in ethanol (50 ml) and treated with conc. sulphuric acid (2.5 ml). The mixture was heated at reflux overnight. After cooling the ethanol was removed in vacuo and the residue was dissolved in diethyl ether. The solution was basified with saturated aqueous sodium bicarbonate, and the layers separated. The aqueous layer was further extracted with diethyl ether (×3), and the combined organic extracts were dried (Na 2 SO 4 ) and concentrated in vacuo to give the ester (6.17 g). 
       1 H NMR (CDCl 3 ) δ: 1.41 (3H, t), 4.40 (2H, q), 7.44 (1H, dt), 7.68 (1H, ddd), 7.99 (1H, s). 
     Ethyl 3-amino-5-nitrobenzoate 
     3-Amino-5-nitrobenzoic acid (ex Lancaster) (10.0 g, 54.9 mmol) was dissolved in ethanol (100 ml) and treated with conc. sulphuric acid (5 ml). The mixture was heated at reflux overnight. After cooling the ethanol was removed in vacuo and the residue was dissolved in diethyl ether. The solution was basified with saturated aqueous sodium bicarbonate, and the layers separated. The aqueous layer was further extracted with diethyl ether (×3), and the combined organic extracts were dried (Na 2 SO 4 ) and concentrated in vacuo to give the ester (6.5 g). 
       1 H NMR (CDCl 3 ) δ: 1.41 (3H, t), 4.15 (2H, br s), 4.40 (2H, q), 7.60-7.68 (2H, m), 8.20 (1H, s). 
     Ethyl 3-iodo-5-nitrobenzoate 
     Ethyl 3-amino-5-nitrobenzoate (6.5 g, 30.9 mmol) was suspended in 5M aqueous HCl (50 ml), cooled to 0° C., and treated with aqueous sodium nitrite (2.34 g 33.9 mmol in 4 ml water) added slowly. The resulting solution of the diazonium salt was added slowly to a solution of potassium iodide (6.16 g, 37.1 mmol) in water (40 ml), and the resulting mixture was stirred at room temperature for 1 hour. The mixture was extracted with diethyl ether, and the extract was washed with water, aqueous sodium thiosulphate solution, dried (Na 2 SO 4 ) and concentrated in vacuo. The residue was purified by flash chromatography on silica (gradient elution, 10-20% ethyl acetate/cyclohexane) to give the title compound (5.46 g). 
       1 H NMR (CDCl 3 ) δ: 1.44 (3H, t), 4.46 (2H, q), 8.68 (1H, t), 8.73 (1H, t), 8.81 (1H, t). 
     Ethyl 3-amino-5-iodobenzoate 
     Ethyl 3-iodo-5-nitrobenzoate (4.45 g, 13.9 mmol) was dissolved in ethanol and tin (II) chloride (27 g, 146 mmol) was added. The mixture was heated to reflux for 2 hours, by which time LC/MS analysis showed that reaction was complete. After cooling, the reaction was concentrated in vacuo. The residue was partitioned between ethyl acetate and aqueous sodium hydroxide solution, and the aqueous extracted with further ethyl acetate. The combined extracts were washed with water, dried (Na 2 SO 4 ) and concentrated in vacuo to give the title compound as a yellow oil which slowly crystallised (3.56 g). 
       1 H NMR (CDCl 3 ) δ: 1.38 (3H, t), 3.80 (2H, br s), 4.45 (2H, q), 7.20 (1H, t), 7.30 (1H, t), 7.74 (1H, t). LC/MS Rt=3.23 min [MH + ] 292. 
     Ethyl 3,6-dichloro-2-pyridinecarboxylate 
     3,6-Dichloro-2-pyridinecarboxylic acid (530 mg, 2.76 mmol) was dissolved in a mixture of ethanol (20 ml) and sulphuric acid (0.25 ml) and refluxed for 2 hours then left at room temperature for 3 days. The resulting solution was evaporated and the residue dissolved in diethyl ether/water and basified with potassium carbonate. The organic layer was dried (magnesium sulphate) and evaporated to give a colourless oil (602 mg). 
     LC/MS t=2.56, [MH+] 220.3 
     Ethyl 3-methyl-2-pyridinecarboxylate 1-oxide 
     A solution of ethyl 3-methyl-2-pyridinecarboxylate (12.1 g, 73 mmol) and 3-chloroperbenzoic acid (28 g, 50-55%, 80 mmol) in dichloromethane (200 ml) was left at room temperature for 16 hours then washed with sodium thiosulphate solution and sodium bicarbonate solution. The organic solution was dried (magnesium sulphate) and evaporated to give a light coloured oil (12.2 g). LC/MS Rt=1.39, [MH+] 182.3 
     Ethyl 6-chloro-3-methyl-2-pyridinecarboxylate 
     Ethyl 3-methyl-2-pyridinecarboxylate 1-oxide (12.1 g, 66.85 mmol) was added in portions with water bath cooling to phosphorus oxychloride (50 ml) and the resulting mixture stirred for 30 minutes and evaporated to dryness. The residue was dissolved in diethyl ether/water and basified with 2M sodium hydroxide solution. The organic layer was separated, dried (magnesium sulphate), evaporated and purified by chromatography on silica eluting with ethyl acetate/iso-hexane (1:9) to give a colourless oil (2.4 g). 
     LC/MS Rt=2.52, [MH+] 200.3, 202.3 
       1 H NMR (CDCl 3 ) δ: 1.43 (3H, t), 2.54 (3H, s), 4.44 (2H, q), 7.35 (1H, d), 7.57 (1H, d). 
     Methyl 5-chloro-2-ethyl-3-pyridinecarboxylate 
     Potassium-tert-butoxide (1.176 g, 10.5 mmol) was added slowly to a stirring solution of methyl 3-oxopentanoate (1.30 g, 10 mmol) in tetrahydrofuran (33 ml) and stirred for 45 minutes before adding 2-chloro-1,3-bis(dimethylamino)trimethinium hexafluorophosphate (4.6 g, 15.00 mmol) and 1,4-diazabicyclo(2.2.2) octane (1.12 g, 10 mmol) and stirring at 45° C. for 3 hours. Ammonium acetate (1.54 g, 20 mmols) was added and the reaction mixture was refluxed for 6 hours. The reaction mixture was cooled to room temperature and diluted with diethyl ether and water. The ether layer was separated, dried over magnesium sulphate and evaporated to dryness to give the title compound as a yellow oil. 1.24 g, 62%. LC/MS: Rt=2.65 min, [M+H] 200. 
     Methyl 5-bromo-2-(trifluoromethyl)-3-pyridinecarboxylate 
     (Trimethylsilyl)diazomethane (2M solution in hexanes, 5 ml, 10 mmol) was added to a solution of 5-bromo-2-(trifluoromethyl)-3-pyridinecarboxylic acid (Eur. J. Org. Chem. 2002, 327-330) (2.05 g, 7.59 mmol) in tetrahydrofuran (10 ml). The resulting solution was evaporated to dryness and the residue purified by chromatography on silica eluting with ethyl acetate/iso-hexane (1:19) to give 950 mg of pale coloured oil. 
       1 H NMR (CDCl 3 ) δ: 3.84 (3H, s), 8.12 (1H, d), 8.71 (1H, d). 
     Ethyl 6-chloro-4-(trifluoromethyl)-2-pyridinecarboxylate 
     A mixture of 6-chloro-4-(trifluoromethyl)-2-pyridinecarboxylic acid (5 g, 22.16 mmol) sulphuric acid (5 ml) and ethanol (80 ml) was stirred and refluxed for 14 hours then cooled and evaporated. The residue was dissolved in ether/water and basified with aqueous ammonia. The organic layer was dried (magnesium sulphate) and evaporated to give the title compound as a colourless oil (4.88 g). 
     LC/MS: [M+H] 254.3, 256.4, Rt=2.98 min 
     (2-Bromo-1-cyclopenten-1-yl)boronic acid 
     1,2-Dibromocyclopentene (10.1 g, 0.044 mol) was dissolved in 100 mL of tetrahydrofuran, cooled to −78° C. and n-butyllithium (1.6 M solution in hexanes; 28 mL, 0.044 mol), was added dropwise over 20 minutes under nitrogen. The mixture was stirred at −78° C. for 20 minutes, then triisopropylborate (20.8 mL, 0.089 mol) was added dropwise. The cooling bath was then removed and the reaction mixture was allowed to reach room temperature. The reaction mixture was then quenched with 1M HCl (40 mL) and stirred vigorously at room temperature for 15 minutes. The organic layer was separated, dried over magnesium sulphate and evaporated down. The residue was triturated with dichloromethane to yield the title compound as a white solid (2.2 g, 26%). 
       1 H NMR (CDCl 3 ) δ: 1.92-1.98 (2H, m), 2.50-2.55 (2H, m), 2.73-2.78 (2H, m), 5.02 (2H, s). 
     [2-(Methyloxy)-5-(trifluoromethyl)phenyl]boronic acid 
     2-Bromo-1-methoxy-4-(trifluoromethyl)benzene (20 g, 78 mmol) was dissolved in dry Et 2 O (300 ml) and cooled to −70° C., n-butyllithium (1.6M solution in hexanes; 53.4 ml, 86 mmol) was added slowly keeping the temperature at about −70° C. and the reaction stirred for 30 minutes. Tri-isopropyl borate (36.2 ml, 0.16 mol) was added slowly keeping the temperature at about −70° C. and the reaction allowed to warm to RT and stirred under nitrogen for 16 hours. 2N HCl (300 ml) was added and the reaction stirred vigorously for 3 hours. The reaction was diluted with EtOAc and the organics separated, the aqueous washed with 3×EtOAc. The combined organics were then washed with brine, dried over MgSO4, filtered and concentrated in vacuo to yield a yellow oil, this was triturated in iso-hexane to yield a white solid (14.6 g, 85%). LC/MS Rt=2.57. 
     {5-Chloro-2-[(Phenylmethyl)oxy]-3-pyridinyl}boronic acid 
     a) 3-Bromo-5-chloro-2-[(phenylmethyl)oxy]pyridine (3.65 g, 12.21 mmol) was dissolved in diethyl ether (80 ml) and added dropwise to a stirring solution of 1.6M n-butyllithium in hexanes (9.16 ml, 14.6 mmol) in diethyl ether (20 ml) at −78° C. under nitrogen over 30 minutes. The mixture was stirred at −78° C. for 1 hour. Triisopropyl borate (3.37 ml, 14.6 mmol) in diethyl ether (10 ml) was added dropwise over 10 minutes at −78° C. The reaction was allowed to warm to room temperature then stirred for 1 hour. 2M sodium hydroxide solution (100 ml) was added and the mixture stirred for 15 minutes. The layers were separated and the organic layer re-extracted with 2M sodium hydroxide solution (50 ml). The combined aqueous layers were acidified to pH6 with 2M hydrochloric acid solution at &lt;10° C. and extracted with ethyl acetate (×2). The combined organic phases were washed with water, dried (MgSO 4 ) and evaporated to a white solid (1.83 g). 
       1 H NMR (CDCl 3 ) δ: 5.45 (2H, s), 5.71 (2H, s), 7.36-7.45 (5H, m), 8.09 (1H, d), 8.20 (1H, d). 
     b) 5-Chloro-3-iodo-2-[(phenylmethyl)oxy]pyridine (3.35 g, 9.7 mmol) was dissolved in tetrahydrofuran (50 ml) under nitrogen and cooled to −40° C. 2M isopropyl magnesium chloride solution in diethyl ether (9.7 ml, 19.4 mmol) was added dropwise at 40° C. and the mixture stirred at 40° C. for 15 minutes, then cooled to −78° C. Trimethyl borate (2.02 g, 2.23 ml, 19.4 mmol) was added dropwise at −78° C. and the reaction was stirred and allowed to warm to room temperature over 2 hours. 2M sodium hydroxide solution (50 ml) was added and the mixture stirred for 15 minutes. The organic layer was re-extracted with 2M sodium hydroxide solution (20 ml) and the combined aqueous layers acidified with glacial acetic acid and extracted with diethyl ether (×2). The combined organic phases were washed with water, dried (MgSO 4 ) and evaporated. The residue was triturated with isohexane, filtered and dried in vacuo to give the title compound (2.13 g). 
       1 H NMR (CDCl 3 ) δ: 5.45 (2H, s), 5.71 (2H, s), 7.36-7.45 (5H, m), 8.09 (1H, d), 8.20 (1H, d). 
     [5-Bromo-2-(methyloxy)-3-pyridinyl]boronic acid 
     The title compound was prepared in a similar manner to {5-chloro-2-[(phenylmethyl)oxy]-3-pyridinyl}boronic acid using 3,5-dibromo-2-(methyloxy)pyridine. 
       1 H NMR (DMSOd 6 ) δ: 3.85 (3H, s), 7.92 (1H, d), 8.11 (2H, s), 8.29 (1H, d). 
     [2-[(Phenylmethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]boronic acid 
     3-Iodo-2-(phenylmethoxy)-5-(trifluoromethyl)pyridine (15.0 g, 39.5 mmol) was dissolved in tetrahydrofuran (90 mL) under nitrogen and cooled to −40° C. Isopropyl magnesium chloride solution in diethyl ether (2.0M, 39.5 mL, 79 mmol) was added dropwise at −40° C. and the mixture stirred at 40° C. for 15 minutes, then cooled to −78° C. Trimethyl borate (8.9 mL, 8.25 g, 79.4 mmol) was added dropwise at −78° C. and the reaction was stirred and allowed to warm to room temperature over 18 hours. 2M aqueous sodium hydroxide solution was added and the layers were separated. The organic phase was dried (MgSO 4 ) and concentrated in vacuo. The residue was triturated with dichloromethane, and the solid material was collected by filtration and dried in vacuo to give the title compound (10.53 g). 
     LC/MS Rt=3.45 min [MH + ] 298. 
     2-(2-Bromo-1-cyclopenten-1-yl)-4-chloro-1-(methyloxy)benzene 
     4-Chloro-2-iodoanisole (16.8 g, 0.062 mol), (2-bromo-1-cyclopenten-1-yl)boronic acid (12 g, 0.062 mol), potassium carbonate (35 g, 0.25 mol) and tetrakis(triphenylphosphine)palladium(0) (3.6 g, 0.003 mol) were dissolved in toluene-ethanol (1:1300 mL) and stirred at 90° C., under nitrogen, for 2 hrs. Upon cooling, the reaction mixture was poured into water and extracted with ethyl acetate (150 mL×3). The organic layers were dried (MgSO 4 ), filtered and concentrated. The residue was purified by flash chromatography using 2% ethyl acetate/iso-hexane to give a clear oil that was recrystallized from iso-hexane at 0-4° C. to give the required product as a white solid (7.55 g). 
       1 H NMR (CDCl 3 ) δ: 12.01-2.09 (2H, m), 2.65-2.69 (2H, m), 2.77-2.81 (2H, m), 3.79 (3H, s), 6.79-6.82 (1H, m), 7.2-7.25 (2H, m). 
     The following intermediates were prepared by a similar route to 2-(2-bromo-1-cyclopenten-1-yl)-4-chloro-1-(methoxy)benzene from the appropriate intermediates. 
     
       
         
           
               
               
             
               
                   
               
               
                 Name 
                 Data 
               
               
                   
               
             
            
               
                 1-(2-Bromo-1-cyclopenten-1-yl)-5-chloro-4- 
                   1 H NMR: CDCl 3  2.00-2.08(2H, m), 
               
               
                 methyl-2-(methyloxy)benzene 
                 2.34(3H, s), 2.65(2H, t), 2.78(2H, t), 
               
               
                   
                 3.78(3H, s), 6.74(1H, s), 7.21(1H, s). 
               
               
                 3-(2-Bromo-1-cyclopenten-1-yl)-2- 
                   1 H NMR: (CDCl 3 ) δ: 2.03-2.11(2H, m), 
               
               
                 (methyloxy)pyridine 
                 2.69-2.74(2H, m), 2.78-2.83(2H, m), 
               
               
                   
                 3.95(3H, s), 6.90(1H, dd), 7.58(1H, 
               
               
                   
                 dd), 8.12(1H, dd). 
               
               
                 2-(2-Bromo-1-cyclopenten-1-yl)-1- 
                   1 H NMR: CDCl 3  2.02-2.09(2H, m), 
               
               
                 [(phenylmethyl)oxy]-4- 
                 2.70-2.75(2H, t), 2.78-2.82(2H, t), 
               
               
                 (trifluoromethyl)benzene 
                 5.14(2H, s), 6.98(1H, d), 7.33- 
               
               
                   
                 7.40(5H, m), 7.48(1H, dd), 7.54(1H,d). 
               
               
                 2-(2-Bromo-1-cyclopenten-1-yl)-4-chloro-1- 
                   1 H NMR: CDCl 3  1.99-2.07(2H, m), 
               
               
                 [(phenylmethyl)oxy]benzene 
                 2.67-2.72(2H, t), 2.76-2.81(2H, t), 
               
               
                   
                 5.06(2H, s), 6.84(1H, d), 7.18(1H, dd), 
               
               
                   
                 7.24-7.38(6H, m). 
               
               
                 2-(2-bromo-1-cydopenten-1-yl)-4,5- 
                   1 H NMR: CDCl 3  2.01-2.09(2H, m), 
               
               
                 dichlorophenyl methyl ether 
                 2.63-2.65(2H, m), 2.77-2.80(2H, m), 
               
               
                   
                 3.79(3H, s), 6.95(1H, s), 7.31(1H, s). 
               
               
                   
               
            
           
         
       
     
     2-(2-Bromo-1-cyclopenten-1-yl)-1-(methyloxy)-4-(trifluoromethyl)benzene 
     [2-Methoxy-5-(trifluoromethyl)phenyl]boronic acid (20 g, 90.9 mmol), 1,2-dibromocyclopentene (32.5 ml, 0.27 mol), potassium carbonate (62.8 g, 0.45 mol) and tetrakis(triphenylphosphine)palladium(0) were refluxed in 1:1 ethanol/toluene (900 ml), in the dark, under a nitrogen atmosphere, for 2 hours. After cooling the reaction was filtered over celite and the solvent removed in vacuo, the residue was taken up in ethyl acetate and washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo to yield a dark oil. This was purified by column chromatography eluting with isohexane. This yielded the title compound as a yellow oil (26.79, 61%). LC/MS Rt=3.88. 
     2-(2-Bromo-1-cyclopenten-1-yl)-4-fluoro-1-(methyloxy)benzene 
     Procedure as for 2-(2-bromo-1-cyclopenten-1-yl)-1-(methyloxy)-4-(trifluoromethyl)benzene starting from [5-fluoro-2-(methyloxy)phenyl]boronic acid. LC/MS Rt=3.70, [MH] 270. 
     {2-[2-(Methyloxy)-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}boronic acid 
     2-(2-Bromo-1-cyclopenten-1-yl)-1-(methyloxy)-4-(trifluoromethyl)benzene (26 g, 81.3 mmol) was dissolved in dry THF (350 ml) and the solution cooled to −70° C. n-butyllithium (1.6M solution in hexanes; 101.6 ml, 0.16 mol) was added slowly keeping the temperature below −65° C. and the reaction allowed to stir for 45 minutes. Tri-isopropyl borate (37.5 ml, 0.16 mol) was added slowly keeping the temperature below 60° C. and the cooling removed and the reaction stirred under nitrogen at RT for a further 15 hours. 2N HCl (300 ml) was added and the reaction stirred at RT for a further 2 hours. The reaction was diluted with ethyl acetate and the organics separated, the aqueous washed with ethyl acetate (×3). The combined organics were then washed with brine, dried over MgSO4, filtered and concentrated in vacuo to yield a yellow oil. This was purified by column chromatography on a 75 L Biotage column eluting in 40% ethyl acetate/isohexane. This yielded the title compound as a white solid. LC/MS Rt=2.96. 
     The following intermediates were prepared by a similar route to {2-[2-(methyloxy)-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}boronic acid from the appropriate intermediates. 
     
       
         
           
               
               
             
               
                   
               
               
                 Name 
                 Data 
               
               
                   
               
             
            
               
                 {2-[2-(Methyloxy)phenyl]-1-cyclopenten-1- 
                 LC/MS Rt = 3.69 min. 
               
               
                 yl}boronic acid 
                 [2MH + ] 417.2 
               
               
                 {2-[5-Fluoro-2-(methyloxy)phenyl]-1- 
                 LC/MS Rt = 2.52 min. 
               
               
                 cyclopenten-1-yl}boronic acid 
               
               
                 {2-[5-Chloro-2-(methyloxy)phenyl]-1- 
                   1 H NMR (CDCl 3 ) δ: 1.91-1.98 (2H, 
               
               
                 cyclopenten-1-yl}boronic acid 
                 m), 2.66-2.73 (4H, m), 3.80 (3H, 
               
               
                   
                 s), 4.30 (2H, s), 6.85 (1H, s), 7.16 
               
               
                   
                 (1H, s), 7.21 (1H, dd). 
               
               
                 {2-[2-[(Phenylmethyl)oxy]-5- 
                 LC/MS: Rt = 3.44 min, [M + H 2 O] 
               
               
                 (trifluoromethyl)phenyl]-1-cyclopenten-1-yl} 
                 380, [2M] 724 
               
               
                 boronic acid 
               
               
                 {2-[5-Chloro-4-methyl-2-(methyloxy)phenyl]-1- 
                   1 H NMR (CDCl 3 ) δ: 1.90-1.97(2H, 
               
               
                 cyclopenten-1-yl}boronic acid 
                 m), 2.36(3H, s), 2.65-2.71(4H, m), 
               
               
                   
                 3.79(3H, s), 4.41(2H, s), 6.78(1H, 
               
               
                   
                 s), 7.14(1H, s). 
               
               
                 (2-{5-Chloro-2-[(phenylmethyl)oxy]phenyl}-1- 
                 LC/MS: Rt = 3.39 min, [2MH] 637 
               
               
                 cyclopenten-1-yl)boronic acid 
               
               
                 {2-[4,5-dichloro-2-(methyloxy)phenyl]-1- 
                 LCMS: Rt = 3.13 min 
               
               
                 cyclopenten-1-yl}boronic acid 
               
               
                   
               
            
           
         
       
     
     5-(2-Bromo-1-cyclopenten-1-yl)-N-(1,1-dimethylethyl)-3-pyridazinecarboxamide 
     (2-Bromo-1-cyclopenten-1-yl)boronic acid (0.6 g, 3.2 mmol), N-(1,1-dimethylethyl)-5-iodo-3-pyridazinecarboxamide (1.0 g, 3.2 mmol), tetrakis(triphenylphosphine)palladium(0) (200 mg, 0.172 mmol) and potassium carbonate (1.1 g, 8 mmol) in toluene/ethanol (1:1, 10 ml) were refluxed overnight under nitrogen in the dark. The reaction mixture was then filtered through celite, and chromatographed with diethyl ether/iso-hexane gradient giving (0.78 g, 71% yield). 
     LC/MS Rt=3.13 min [MH + ] 326, 327 
     Ethyl 6-(2bromo-1-cyclopenten-1-yl)-3-chloro-2pyridinecarboxylate 
     A mixture of ethyl 3,6-dichloro-2-pyridinecarboxylate (220 mg, 1 mmol), (2-bromo-1-cyclopenten-1-yl)boronic acid (191 mg, 1 mmol), potassium carbonate (552 mg, 4 mmol) and tetrakis(triphenylphosphine)palladium(0) (58 mg, 0.05 mmol) in 1:1 ethanol/toluene (4 ml) was stirred and heated at 90° C. under nitrogen for 2 hours after cooling the mixture was dissolved in diethyl ether/water and the organic phase dried (magnesium sulphate) evaporated and the residue purified by chromatography on silica eluting with ethyl acetate/iso-hexane (1:19) to give 110 mg of colourless oil. 
     LC/MS t=3.81, [MH+] 332.3. 
     The following compounds were prepared by a similar route to ethyl 6-(2-bromo-1-cyclopenten-1-yl)-3-chloro-2-pyridinecarboxylate from the appropriate intermediates. 
     
       
         
           
               
               
             
               
                   
               
               
                 Name 
                 Data 
               
               
                   
               
             
            
               
                 Ethyl 6-(2-bromo-1-cyclopenten-1-yl)-2- 
                 LC/MS: Rt = 3.07 min. [M + H] = 297, 
               
               
                 pyrazinecarboxylate 
                 299. 
               
               
                 Ethyl 6-(2-bromo-1-cyclopenten-1-yl)-2- 
                 LC/MS: Rt = 3.27 min. [M + H] = 
               
               
                 pyridinecarboxylate 
                 296, 298. 
               
               
                 Ethyl 3-(2-bromo-1-cyclopenten-1- 
                 Rt = 3.98 min. [MH + ] 295, 297. 
               
               
                 yl)benzoate 
               
               
                 Ethyl 5-(2-bromo-1-cyclopenten-1-yl)-2- 
                   1 H NMR (CDCl 3 ) δ: 1.39(3H, t), 2.01- 
               
               
                 methylbenzoate 
                 2.08(2H, m), 2.59(3H, s), 
               
               
                   
                 2.77(2H, m), 2.85(2H, m), 4.36(2H, 
               
               
                   
                 q), 7.24(1H, t), 7.65(1H, d), 8.12(1H, 
               
               
                   
                 s). 
               
               
                 Ethyl 5-(2-bromo-1-cyclopenten-1-yl)-2- 
                 Rt = 3.82 min. [MH + ] 313, 315. 
               
               
                 fluorobenzoate 
               
               
                 Ethyl 3-(2-bromo-1-cyclopenten-1-yl)-5- 
                 Rt = 3.91 min. [MH + ] 313, 315. 
               
               
                 fluorobenzoate 
               
               
                 Ethyl 3-amino-5-(2-bromocyclopent-1- 
                 LC/MS Rt = 3.51 min [MH + ] 310, 312. 
               
               
                 enyl)benzoate 
               
               
                 Ethyl 2-amino-5-(2-bromo-1-cyclopenten-1- 
                   1 H NMR (CDCl 3 ) δ: 1.39 (3H, t, 
               
               
                 yl)benzoate 
                 J = 7 Hz), 1.98-2.06 (2H, m), 2.71-2.76 
               
               
                   
                 (2H, m), 2.81-2.86 (2H, m) 4.33 (2H, 
               
               
                   
                 q, J = 7 Hz), 5.80 (2H, br s), 6.65 (1H, 
               
               
                   
                 d, J = 9 Hz), 7.65 (1H, dd, J = 9 Hz, 
               
               
                   
                 2 Hz), 8.14 (1H, d, J = 2 Hz). 
               
               
                   
               
            
           
         
       
     
     Ethyl 5-(2-bromocyclopent-1-enyl)-2-fluorobenzoate 
     Ethyl 2-fluoro-5-iodobenzoate (4.7 g, 16.0 mmol), 2-bromo-cyclopent-1-enylboronic acid (3.06 g, 16.0 mmol), potassium carbonate (15.5 g, 112 mmol) and Pd(PPh 3 ) 4  (0.925 g, 0.8 mmol) were dissolved in toluene-ethanol (1:1, 110 mL) and stirred at 100° C. under nitrogen for 1.5 hours. Upon cooling, the reaction mixture was diluted with diethyl ether, and washed with water. The aqueous layer was extracted with further diethyl ether, and the combined organic extracts were dried (MgSO 4 ), and concentrated in vacuo. The residue was purified by flash chromatography on silica (gradient elution, 1-5% ethyl acetate/cyclohexane) to give the required product as a yellow oil (3.84 g). 
     LC/MS Rt=3.80 min [MH + ] 313, 315. 
     Ethyl 3-(2-bromocyclopent-1-enyl)-5-fluorobenzoate 
     Ethyl 3-bromo-5-fluorobenzoate (5.17 g, 20.9 mmol), 2-bromo-cyclopent-1-enylboronic acid (3.99 g, 20.9 mmol), potassium carbonate (23 g, 167 mmol) and Pd(PPh 3 ) 4  (1.1 g, 1.0 mmol) were dissolved in toluene-ethanol (1:1, 150 mL) and heated to reflux for 1.5 hours under a nitrogen atmosphere. Upon cooling, the reaction mixture was diluted with diethyl ether, and washed with water. The aqueous layer was extracted with further diethyl ether, and the combined organic extracts were dried (Na 2 SO 4 ), and concentrated in vacuo. The residue was purified by flash chromatography on silica (gradient elution, 0-5% ethyl acetate/cyclohexane) to give the required product as a yellow oil (5.93 g). 
     LC/MS Rt=3.93 min [MH + ] 313, 315. 
     Ethyl 3-amino-5-(2bromocyclopent-1-enyl)benzoate 
     Ethyl 3-amino-5-iodobenzoate (3.66 g, 12.6 mmol), 2-bromo-cyclopent-1-enylboronic acid (2.41 g, 12.6 mmol), potassium carbonate (12.2 g, 88.2 mmol) and Pd(PPh 3 ) 4  (0.73 g, 0.63 mmol) were dissolved in toluene-ethanol (1:1, 50 mL) and heated to reflux for 1.75 hours under a nitrogen atmosphere. After cooling, the reaction mixture was diluted with diethyl ether, and washed with water. The aqueous layer was extracted with further diethyl ether, and the combined organic extracts were dried (Na 2 SO 4 ), and concentrated in vacuo. The residue was purified by flash chromatography on silica (gradient elution, 0-5% ethyl acetate/cyclohexane) to give the required product (4.21 g). 
     LC/MS Rt=3.51 min [MH + ] 310, 312. 
     Ethyl 6-{2-[5-chloro-2-(methyloxy)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     A mixture of ethyl 6-bromo-2-pyridinecarboxylate (4.1 g, 17.8 mmol), {2-[5-chloro-2-(methyloxy)phenyl]-1-cyclopenten-1-yl}boronic acid (4.1 g, 16 mmol), potassium carbonate (11.2 g, 81 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.88 g, 1.6 mmol) was stirred and heated in 1:1 toluene/ethanol (50 ml) at 90° C. under nitrogen for 2 hours. After cooling the mixture was diluted with ethyl acetate/water and the organic phase dried (magnesium sulphate), evaporated to dryness and the residue purified by chromatography (12% ethyl acetate in iso-hexane) to yield the title compound as a clear oil (4 g). 
     LC/MS: Rt 3.8 [MH+] 358, 361 
     The following compounds were prepared by a similar route to ethyl 6-{2-[5-chloro-2-(methyloxy)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylate from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Name 
                 Data 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-(methyloxy)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 LC/MS: Rt = 3.53 min, [M + H] 324. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-(methyloxy)phenyl]-1- cyclopenten-1-yl}-2- pyrazinecarboxylate 
                 LC/MS: Rt = 3.47 min, [M + H] 325. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[5-chloro-2- (methyloxy)phenyl]-1- cyclopenten-1- yl}-3-methyl-2-pyridinecarboxylate 
                 LC/MS: Rt = 3.98, [MH+] 372.4, 374.5 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-methyl-6-{2-[2- [(phenylmethyl)oxy]-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 LC/MS: Rt = 4.39 min, [M + H] 482. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-{2-[5-chloro-2- (methyloxy)phenyl]-1-cyclopenten-1- yl}-2-pyridinecarboxylate 
                 LC/MS Rt = 3.95, [MH+] 392.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-(2-{5-chloro-2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-2-(trifluoromethyl)- 3-pyridinecarboxylate 
                 LC/MS Rt = 4.20, [MH+] 488.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-{2-[2- [(phenylmethyl)oxy]-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 LC/MS Rt = 4.15, [MH+] 502.4, 504.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[5-chloro-2- (methyloxy)phenyl]-1-cyclopenten-1- yl}-3-pyridinecarboxylate 
                 LC/MS Rt = 3.84, [MH+] 358.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[5-chloro-4-methyl-2- methyloxy)phenyl]-1-cyclopenten-1- yl}-2-pyridinecarboxylate 
                 LC/MS: Rt = 3.77 min. [M + H] = 372. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-{2-[2-[(phenylmethyl)oxy]-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2-(trifluoromethyl)- 3-pyridinecarboxylate 
                 LC/MS: Rt = 3.91 min. [M + H] = 536 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 2-(2-{5-chloro-2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-3- pyridinecarboxylate 
                 LC/MS: Rt = 3.89 min. [M + H] = 434, 436 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-(2-{5-chloro-2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-4-(trifluoromethyl)- 2-pyridinecarboxylate 
                 LC/MS: [M + H] 502.4, 504.4, Rt = 4.58 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-(2-{5-chloro-2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-4- pyrimidinecarboxylate 
                 LC/MS: Rt = 3.74 min [M + H] 421, 423 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{5-Chloro-2- [(phenylmethyl)oxy]phenyl}-l- cyclopenten-1-yl)-N-(1,1- dimethylethyl)-3- pyridazinecarboxamide 
                 LC/MS: Rt = 3.98 min [M + H] 462, 464 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-{2-[4,5-dichloro-2- (methyloxy)phenyl]-1- cyclopenten-1- yl}-2-(trifluoromethyl)-3- pyridinecarboxylate 
                 LC/MS: Rt = 3.68 min [M + H] 392 
               
               
                   
               
            
           
         
       
     
     Methyl 5-{2-[5-chloro-2-(methyloxy)phenyl]-1-cyclopenten-1-yl}-2-ethyl-3-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     A mixture of {2-[5-chloro-2-(methyloxy)phenyl]-cyclopenten-1-yl}boronic acid (2.53 g, 10 mmol), methyl 5-chloro-2-ethyl-3-pyridinecarboxylate (1.995 g, 10 mmol), palladium acetate (22 mg, 0.0909 mmol), potassium fluoride on alumina (40%) (4.35 g, 30 mmol) and (di-tert-butylphosphino)biphenyl (60 mg, 0.20 mmol) In anhydrous tetrahydrofuran (25 ml) was heated at 50° C. under an atmosphere of nitrogen for 3 hours. The reaction mixture was cooled to room temperature and diluted with diethyl ether and water. The ether layer was separated, dried over magnesium sulphate and evaporated to dryness. The residue was purified using flash chromatography eluting with ethyl acetate/iso-hexane (15%) to give the title compound as a yellow oil. 1.93 g, 52%. 
       1 H NMR (CDCl 3 ) δ: 1.24 (3H, t), 2.06-2.14 (2H, m), 2.81-2.56 (2H, m), 2.91-2.95 (2H, m), 3.08 (2H, q), 3.63 (3H, s), 3.85 (3H, s), 6.79 (1H, d), 7.00 (1H, d), 7.18 (1H, dd), 7.91 (1H, d), 8.34 (1H, d). LC/MS: Rt=3.83 min, [M+H] 372. 
     The following intermediates were prepared by a similar route to methyl 5-{2-[5-chloro-2-(methyloxy)phenyl]-1-cyclopenten-1-yl}-2-ethyl-3-pyridinecarboxylate from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Name 
                 Data 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-{2-[5-chloro-2- (methyloxy)phenyl]-1- cyclopenten-1-yl)-2-methyl-3- pyridinecarboxylate 
                 LC/MS Rt = 3.64, [MH+] 358.4, 360.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-(2-{5-chloro-2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-2-methyl-3- pyridinecarboxylate 
                 LC/MS Rt = 4.06, [MH+] 334.4, 436.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 2-methyl-5-{2-[2- [(phenylmethyl)oxy]-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-3- pyridinecarboxylate 
                 LC/MS Rt = 4.04, [MH+] 468.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 2-ethyl-5-{2-[2- [(phenylmethyl)oxy]-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-3- pyridinecarboxylate 
                 LC/MS Rt = 4.17, [MH+] 482.5 
               
               
                   
               
            
           
         
       
     
     Ethyl 6-{2-[2-(methyloxy)-3-pyridinyl]-1-cyclopenten-1-yl}-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     {2-[2-(Methyloxy)-3-pyridinyl]-1-cyclopenten-1-yl}boronic acid (219 mg, 1 mmol) and ethyl 6-bromo-2-pyridinecarboxylate (230 mg, 1 mmol) were dissolved in toluene/ethanol (1:1, 10 ml) under nitrogen and tetrakis(triphenylphosphine)palladium(0) (58 mg, 0.05 mmol) and potassium carbonate (1.104 g, 8 mmol) added. The mixture was heated at 80° C. in a Smithcreator® microwave for 20 minutes. Diethyl ether and water were added and the organic layer washed with water, dried (MgSO 4 ) and evaporated. The brown oil was purified by flash chromatography, eluting with 5-20% ethyl acetate/isohexane to give the title compound (120 mg). 
       1 H NMR (CDCl 3 ) δ: 1.38 (3H, t), 2.07-2.15 (2H, m), 2.87-2.92 (2H, m), 3.09-3.14 (2H, m), 3.78 (3H, s), 4.38 (2H, q), 6.78 (1H, dd), 7.08 (1H, d), 7.33 (1H, dd), 7.54 (1H, t), 7.84 (1H, d), 8.07 (1H, dd). 
     6-{2-[2-(Methyloxy)-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylic acid 
     
       
         
         
             
             
         
       
     
     {2-[2-(Methyloxy)-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}boronic acid (5.5 g, 19.2 mmol), ethyl 6-bromopyridine-2-carboxylate (4.42 g, 19.2 mmol), potassium carbonate (13.29 g, 96.2 mmol) and tetrakis(triphenylphosphine)palladium(0) were refluxed in 1:1 ethanol/toluene (200 ml) under nitrogen in the dark for 16 hours. After cooling the reaction was filtered over celite and the solvent removed in vacuo, the residue was taken up in ethyl acetate and washed with water and brine, dried over MgSO 4 , filtered and concentrated in vacuo to yield a yellow solid. This was purified by column chromatography eluting in 50% ethyl acetate/isohexane. This yielded the title compound as a yellow solid (5.51 g, 79%). LC/MS Rt=3.22, [MH + ] 364. 
     The following compounds were prepared by a similar route to 6-{2-[2-(methyloxy)-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylic acid from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Name 
                 LC/MS 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-(Methyloxy)-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyrazinecarboxylic acid 
                 t = 3.66, [MH + ] 365 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[5-Fluoro-2- (methyloxy)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                 t = 2.70 min, [MH + ] 314 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[5-Fluoro-2- (methyloxy)phenyl]1- cyclopenten-1-yl}-2- pyrazinecarboxylic acid 
                 t = 3.59 min, [MH + ] 315 
               
               
                   
               
            
           
         
       
     
     5-{2-[5-Bromo-2-(methyloxy)phenyl]-1-cyclopenten-1-yl}-N-(1,1-dimethylethyl)-3-pyridazinecarboxamide 
     
       
         
         
             
             
         
       
     
     5-(2-Bromo-1-cyclopenten-1-yl)-N-(1,1-dimethylethyl)-3-pyridazinecarboxamide (8.3 g, 25.5 mmol), 5-bromo-2-(methyloxy)phenylboronic acid (6.9 g, 30 mmol), tetrakis(triphenylphosphine)palladium(0) (1.51 g, 1.3 mmol) and potassium carbonate (8.0 g, 57.97 mmol) in dimethoxyethane (60 ml) were refluxed overnight under nitrogen, in the dark. The reaction mixture was then filtered through celite and chromatographed giving the title compound (7.0 g, 65% yield). LC/MS Rt=3.71mins [MH + ] 432, 433. 
     Ethyl 6-{2-[5-bromo-2-(methyloxy)phenyl]-1-cyclopenten-1-yl}-chloro-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     A mixture of ethyl 6-(2-bromo-1-cyclopenten-1-yl)-3-chloro-2-pyridinecarboxylate (110 mg, 0.33 mmol), 5-bromo-2-(methyloxy)phenylboronic acid (77 mg, 0.33 mmol), potassium carbonate (276 mg, 2 mmol) and tetrakis(triphenylphosphine)palladium(0) (38 mg, 0.033 mmol) in 1,2-dimethoxyethane (4 ml) was stirred and heated at 70° C. under nitrogen for 2 hours when a further portion of 5-bromo-2-methoxyphenylboronic acid (77 mg, 0.33 mmol) was added. After heating for a further 2 hours the mixture was cooled, dissolved in diethyl ether/water and the organic phase dried (magnesium sulphate) evaporated and the residue purified by chromatography on silica eluting with ethyl acetate/iso-hexane (7:93) to give 110 mg of colourless oil. 
     LC/MS Rt=4.14, [MH+] 438.3. 
     The following compounds were prepared by a similar route to ethyl 6-{2-[5-bromo-2-(methyloxy)phenyl]-1-cyclopenten-1-yl}-3-chloro-2-pyridinecarboxylate from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Name 
                 Data 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[5-bromo-2- (methyloxy)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 LC/MS: Rt = 3.80 min. [M + H] = 402, 404. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[5-bromo-2- (methyloxy)phenyl]-1- cyclopenten-1-yl}-2- pyrazinecarboxylate 
                 LC/MS: Rt = 3.66 min. [M + H] = 403, 405. 
               
               
                   
               
            
           
         
       
     
     Ethyl 5-(2-{5-chloro-2-[(phenylmethyl)oxy]-3-Pyridinyl}-cyclopenten-1-yl)-2-methylbenzoate 
     
       
         
         
             
             
         
       
     
     {5-Chloro-2-[(phenylmethyl)oxy]-3-pyridinyl}boronic acid (247 mg, 0.938 mmol) and ethyl 5-(2-bromo-1-cyclopenten-1-yl)-2-methylbenzoate (290 mg, 0.938 mmol) were dissolved in toluene/ethanol (1:1, 4 ml) under nitrogen and tetrakis(triphenylphosphine)palladium(0) (54 mg, 0.047 mmol) and potassium carbonate (1.04 g, 7.5 mmol) added. The mixture was heated at 80° C. in a Smithcreator® microwave for 10 minutes. Diethyl ether and water were added and the organic layer washed with water, dried (MgSO 4 ) and evaporated. The brown oil was purified by flash chromatography, eluting with 3% ethyl acetate/isohexane to give the title compound (262 mg). LC/MS Rt=4.47 min [MH + ] 448, 450. 
     The following compounds were prepared by a similar route to ethyl 5-(2-{5-chloro-2-[(phenylmethyl)oxy]-3-pyridinyl}-1-cyclopenten-1-yl)-2-methylbenzoate from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 COMPOUND NAME 
                   1 H NMR/LCMS 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{5-chloro-2- [(phenylmethyl)oxy]-3- pyridinyl)-1-cyclopenten-1-yl}- 2-fluorobenzoate 
                 (CDCl 3 ) δ: 1.33 (3 H, t), 2.05-2.08 (2 H, m), 2.82- 2.91 (4 H, m), 4.31 (2 H, q), 5.27 (2 H, s), 6.84 (1 H, dd), 7.11 (1 H, m), 7.22- 7.29 (6 H, m), 7.66 (1 H, dd), 8.00 (1 H, d) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{5-chloro-2- [(phenylmethyl)oxy]-3- pyridinyl)-1-cyclopenten-1-yl}- 3-fluorobenzoate 
                 (CDCl 3 ) δ: 1.32 (3 H, t), 2.04-2.11 (2 H, m), 2.83- 2.92 (4 H, m), 4.29 (2 H, q), 5.26 (2 H, s), 6.89 (1 H, dd), 7.21-7.56 (8 H, m), 8.01 (1 H, d) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 2-fluoro-5-{2-[2- (methyloxy)-3-pyridinyl]-1- cyclopenten-1-yl}benzoate 
                 (CDCl 3 ) δ: 1.34 (3 H, t), 2.05-2.12 (2 H, m), 2.83- 2.87 (2 H, m), 2.89- 2.94 (2 H, m), 3.85 (3 H, s), 4.32 (2 H, q), 6.77 (1 H, dd), 6.88 (1 H, dd), 7.15 (1 H, td), 7.24 (1 H, dd), 7.69 (1 H, dd), 8.07 (1 H, dd). 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 2-fluoro-5-{2-[2- [(phenylmethyl)oxy]-5- (trifluoromethyl)-3-pyridinyl]-1- cyclopenten-1-yl}benzoate 
                 Rt = 4.42 min. [MH + ] 486 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-{2-[5-bromo-2- (methyloxy)-3-pyridinyl]-1- cyclopenten-1-yl}-2- fluorobenzoate 
                 Rt = 4.10 min. [MH + ] 420, 422. 
               
               
                   
               
            
           
         
       
     
     Ethyl 6-{2-[2-[(phenylmethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1-Cyclopenten-1-yl}-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     [2-[(Phenylmethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]boronic acid (3.71 g, 12.5 mmol) and 6-(2-bromocyclopent-1-enyl)-pyridine-2-carboxylic acid ethyl ester (1.85 g, 6.25 mmol) were dissolved in dioxane (75 mL) under nitrogen together with tris(dibenzylideneacetone)dipalladium(0) (86 mg, 0.094 mmol), tri(t-butyl)phosphonium tetrafluoroborate (82 mg, 0.28 mmol) and potassium fluoride (1.19 g, 20.5 mmol). The mixture was heated at 100° C. for 3 hours. After cooling, the dioxane was removed in vacuo and the residue was partitioned between diethyl ether and water. The aqueous was extracted with further ether, dried (Na 2 SO 4 ) and concentrated in vacuo. The resulting brown oil was purified by flash chromatography on silica (gradient elution, 0-3% ethyl acetate/cyclohexane) to give the title compound (871 mg). 
     LC/MS Rt=4.09 min [MH + ] 469. 
     Ethyl 3-amino-5-{2-[2-(phenylmethoxy)-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}benzoate 
     
       
         
         
             
             
         
       
     
     2-(Phenylmethoxy)-5-(trifluoromethyl)pyridine-3-boronic acid (6.0 g, 20.2 mmol) and ethyl 3-amino-5-(2-bromocyclopent-1-enyl)benzoate (3.16 g, 10.1 mmol) were dissolved in dimethoxyethane (50 mL) under nitrogen, and tetrakis(triphenylphosphine)palladium(0) (0.58 g, 0.5 mmol) and 2N aqueous sodium carbonate solution (10 ml) were added. The mixture was heated at 80° C. for 18 hours. After cooling, the solvents were removed in vacuo, and the residue was partitioned between diethyl ether and water. The aqueous was extracted with further ether (×2), and the combined organic layers were dried (Na 2 SO 4 ) and concentrated in vacuo. The resulting dark brown oil was purified using an acidic solid phase cartridge (Isolute® Flash SCX-2, 50 g), loading the crude material as a methanol solution and eluting with 10% aqueous ammonia in methanol. Concentration of the relevant fractions in vacuo gave the title compound (4.01 g). 
     LC/MS Rt=4.01 min [MH + ] 483. 
     Ethyl 3-{2-[5-bromo-2-(methyloxy)-3-pyridinyl]-1-cyclopenten-1-yl}benzoate 
     
       
         
         
             
             
         
       
     
     Ethyl 3-(2-bromo-1cyclopenten-1-yl)benzoate (0.5 g, 1.7 mmol), [5-bromo-2-(methyloxy)-3-pyridinyl]boronic acid (0.45 g, 1.7 mmol), potassium carbonate (1.2 g, 8.5 mmol) and 1,2-dimethoxyethane (10 ml) were combined and degassed for 15 minutes tetrakis(triphenylphosphine)palladium(0) (0.2 g, 0.17 mmol) was added and the reaction stirred under a nitrogen atmosphere in the dark at 80° C. for 3 hours. A further equivalent of [5-bromo-2-(methyloxy)-3-pyridinyl]boronic acid (0.45 g, 1.7 mmol) was added and the reaction continued under the above conditions for a further 14 hours. A further equivalent of [5-bromo-2-(methyloxy)-3-pyridinyl]boronic acid (0.45 g, 1.7 mmol) and a further equivalent of tetrakis(triphenylphosphine)palladium(0) (0.2 g, 0.17 mmol) was added and the reaction continued under the above conditions for a further 24 hours. The reaction was then filtered through celite and the solvent removed in vacuo. The residue was purified by column chromatography eluting with 10% diethyl ether/isohexane. This yielded the title compound as a clear oil (0.201 g, 30%). LC/MS Rt=4.30 [MH + ] 402/404. 
     6-[2-(5-Chloro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid 
     
       
         
         
             
             
         
       
     
     Ethyl 6-{2-[5-chloro-2-(methyloxy)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylate (3.9 g, 0.011 mol) and sodium methanethiolate (49, 0.055 mol) in dry DMF (40 ml) were heated at 100° C. under nitrogen for 5 h. After cooling the mixture was poured into water and washed with diethyl ether. The aqueous phase was then acidified with acetic acid and extracted with ethyl acetate (50 ml×3). The combined organic layers were dried (magnesium sulphate) and evaporated. The residue was redissolved in toluene and evaporated again to give a yellow solid that was triturated with diethyl ether to give the title compound as a yellow oil (2.6 g, 76%). LC/MS: Rt 2.85 [MH+] 316, 318. 
     The following intermediates were prepared by a similar route to 6-[2-(5-chloro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
               
               
                 Structure 
                 Name 
                 Data 
               
               
                   
               
             
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-Hydroxyphenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 2.20 min, [M + H] 282. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- hydroxyphenyl)-1- cyclopenten-1-yl]-2-ethyl-3- pyridinecarboxylic acid 
                 LC/MS: Rt = 2.99 min, [M + H] 344. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- hydroxyphenyl)-1- cyclopenten-1-yl]-2-methyl- 3-pyridinecarboxylic acid 
                 LC/MS Rt = 2.80 min, [MH+] 330.4, 332.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- hydroxyphenyl)-1- cyclopenten-1-yl]-3- pyridinecarboxylic acid 
                 LC/MS Rt = 3.70 min, [MH+] 316.3, 318.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2- hydroxyphenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                 LC/MS: Rt = 4.37 min. [M + H] = 361, 363. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-hydroxy-4- methylphenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 3.02 min. [M + H] = 330 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(4,5-dichloro-2- hydroxyphenyl)-1 cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylic acid 
                 LC/MS: Rt = 3.17 min. [M + H] = 418 
               
               
                   
               
            
           
         
       
     
     6-{2-[2-Hydroxy-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyrazinecarboxylic acid 
     
       
         
         
             
             
         
       
     
     6-{2-[2-(Methyloxy)-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyrazinecarboxylic acid (1.92 g, 5.27 mmol), sodium methanethiolate (1.87 g, 26.4 mmol) and DMF (40 ml) were heated to 75° C. for 4.5 hours. After cooling the reaction was diluted with ethyl acetate washed with water and brine. The organic layer was dried over MgSO 4 , filtered and concentrated in vacuo to yield a yellow solid (1.66 g). LC/MS Rt=3.57, [MH + ] 351. 
     6-[2-(5-Chloro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-(methylthio)-2-pyridinecarboxylic acid 
     
       
         
         
             
             
         
       
     
     A mixture of ethyl 3-chloro-6-{2-[5-chloro-2-(methyloxy)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylate (960 mg, 2.49 mmol) and sodium methanethiolate (857 mg, 12.25 mmol) in dimethylformamide (10 ml) was stirred and heated at 10° C. under nitrogen for 4 hours. After cooling the mixture was diluted with diethyl ether/water and the aqueous separated, acidified with acetic acid and extracted with ether which was washed three times with water then dried (magnesium sulphate) evaporated and triturated with ether to give an orange solid (695 mg). LC/MS Rt=3.46, [MH+] 362.4, 364.4. 
     6-{2-[2-Hydroxy-5-(trifluoromethyl)phenyl]cyclopent-1-en-1-yl}pyridine-2-carboxylic acid 
     
       
         
         
             
             
         
       
     
     6-{2-[2-Methoxy-5-(trifluoromethyl)phenyl]cyclopent-1-en-1-yl}pyridine-2-carboxylic acid (2 g, 5.5 mmol) was dissolved in anhydrous dichloromethane (80 ml) and cooled to −70° C. Boron tribromide (5 ml, 55 mmol) was added slowly and the reaction allowed to warm to −3° C. and stirred under nitrogen for 19 hours. The reaction was quenched with ice and then water and stirred vigorously for 30 minutes. The aqueous layer was washed with dichloromethane (×2), the combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to yield the title compound as a dark solid (2.13 g). LC/MS Rt=3.07 min, [MH + ] 350. 
     The following intermediates were prepared by a similar route to 6-{2-[2-hydroxy-5-(trifluoromethyl)phenyl]cyclopent-1-en-1-yl}pyridine-2-carboxylic acid from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Name 
                 LC/MS 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[5-Fluoro-2-hydroxyphenyl]- 1-cyclopenten-1-yl}2- pyridinecarboxylic acid 
                 Rt = 2.50 min [MH + ] 300. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[5-Fluoro-2-hydroxyphenyl]- 1-cyclopenten-1-yl}2- pyrazinecarboxylic acid 
                 Rt = 3.53 min [MH + ] 301. 
               
               
                   
               
            
           
         
       
     
     3-Chloro-6-[2-(5-chloro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid 
     
       
         
         
             
             
         
       
     
     A solution of ethyl 3-chloro-{2-[5-chloro-2-(methyloxy)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylate (2.35 g, 6 mmol) in dichloromethane (15 ml) was cooled to −50° C. and 1M boron tribromide in dichloromethane (20 ml) was added. 
     The mixture was allowed to warm to room temperature and after 3 hours was poured onto ice and basified with 2M sodium hydroxide solution then acidified with acetic acid. The organic layer was separated, dried (magnesium sulphate), toluene (30 ml) added and evaporated to give a yellow gum (2.16 g). LC/MS t=4.09, [MH+] 350.4 
     6-[2-(5-Chloro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-3-methyl-2-pyridinecarboxylic acid 
     
       
         
         
             
             
         
       
     
     Procedure as for 3-chloro-6-[2-(5-chloro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid. LC/MS t=3.05, [MH+] 330.4 
     Ethyl 6-[2-(5-bromo-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     1.0M boron tribromide in dichloromethane (9.95 ml, 9.95 mmol) was added to a solution of ethyl 6-[2-(5-bromo-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylate (2.0 g, 4.98 mmol) in dry dichloromethane (50 ml) at −78° C. The reaction mixture was allowed to warm to room temperature over 4 hours. The mixture was quenched with water (50 ml). The organic phase was separated, dried and evaporated to give the title compound as a yellow solid 2.0 g 100%. LC/MS: Rt=3.64 min. [M+H]=388, 390 (1 Br). 
     Ethyl 6-[2-(5-bromo-2-hydroxyphenyl)-cyclopenten-1-yl]-3-chloro-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     A solution of ethyl 6-{2-[5-bromo-2-(methyloxy)phenyl]-1-cyclopenten-1-yl}-chloro-2-pyridinecarboxylate (501 mg, 1.15 mmol) in dichloromethane (5 ml) was cooled to −50° C. and 1M boron tribromide in dichloromethane (5 ml) was added. 
     The mixture was allowed to warm to room temperature and after 2 hours was poured onto ice and basified with 2M sodium hydroxide solution then acidified with acetic acid. The organic layer was separated, dried (magnesium sulphate), toluene (10 ml) added and evaporated to dryness. The residue was dissolved in ethanol (25 ml) and sulphuric acid (2 ml) and refluxed for 5 hours then left at room temperature for 15 hours. After evaporation the residue was dissolved in ether/water, basified with potassium carbonate and the organic phase dried (magnesium sulphate), evaporated and purified by chromatography on silica eluting with ethyl acetate/iso-hexane (18:82) to give 415 mg of colourless gum. LC/MS t=3.97, [MH+] 424.3 
     Ethyl 5-[2(5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)-1-cyclopenten-1-yl]-2-methylbenzoate 
     
       
         
         
             
             
         
       
     
     Ethyl 5-(2-{5-chloro-2-[(phenylmethyl)oxy]-3-pyridinyl}-1-cyclopenten-1-yl)-2-methylbenzoate (200 mg, 0.447 mmol) was dissolved in glacial acetic acid (0.5 ml) and 45% hydrogen bromide in acetic acid (1 ml) added. The mixture was stirred at room temperature for 1.5 hours. 5% sodium bicarbonate solution was added carefully, followed by diethyl ether. The aqueous layer was reextracted with diethyl ether and the combined extracts washed with 5% sodium bicarbonate solution, dried (MgSO 4 ) and evaporated to leave the title compound (76 mg). LC/MS Rt=3.51 min [MH − ] 356, 358. 
     The following intermediates were prepared by a similar route to ethyl 5-[2-(5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)-1-cyclopenten-1-yl]-2-methylbenzoate from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Name 
                 Data 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 2-fluoro-5-{2-[2-oxo-5- (trifluoromethyl)-1,2-dihydro-3- pyridinyl]-1-cyclopenten-1- yl}benzoate 
                 LC/MS Rt = 3.54 min [MH + ] 396. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-oxo-5- (trifluoromethyl)-1,2-dihydro-3- pyridinyl]-1-cyclopenten-1-yl}-2- pyridinecarboxylate 
                 LC/MS Rt = 3.12 min [MH + ] 379. 
               
               
                   
               
            
           
         
       
     
     5-[2-(5-Bromo-2-oxo-1,2-dihydro-3-pyridinyl)-1-cyclopenten-1-yl]-2-fluorobenzoic acid 
     
       
         
         
             
             
         
       
     
     Ethyl 5-{2-[5bromo-2-(methyloxy)-3-pyridinyl]-1-cyclopenten-1-yl}-fluorobenzoate (127 mg, 0.302 mmol), was dissolved in glacial acetic acid (1 ml) and 48% aqueous hydrogen bromide (1 ml) added. The mixture was heated to reflux for 45 minutes. 5% Sodium bicarbonate solution was added carefully and the mixture extracted with ethyl acetate. The organic layer was washed with water, dried (MgSO 4 ) and evaporated to give the title compound (96 mg). LC/MS Rt=3.19 min [MH + ] 378, 380. 
     The following intermediates were prepared by a similar route to 5-[2-(5-bromo-2-oxo-1,2-dihydro-3pyridinyl)-cyclopenten-1-yl]-2-fluorobenzoic acid from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Name 
                 LC/MS 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-5-[2-(2-oxo-1,2-dihydro- 3-pyridinyl)-1-cyclopenten-1- yl]benzoic acid 
                 Rt = 2.66 min [MH + ] 300. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-Oxo-1,2-dihydro-3- pyridinyl)-1-cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 Rt = 1.48 min [MH + ] 283 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[2-(5-Bromo-2-oxo-1,2-dihydro- 3-pyridinyl)-1-cyclopenten-1- yl]benzoic acid 
                 Rt = 2.89 min [MH + ] 358, 360 
               
               
                   
               
            
           
         
       
     
     Ethyl 5-[2-(5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)-1-cyclopenten-1-yl]-2-fluorobenzoate 
     
       
         
         
             
             
         
       
     
     Ethyl 5-(2-{5-chloro-2-[(phenylmethyl)oxy]-3pyridnyl}-cyclopenten-1-yl)-2-fluorobenzoate (1.32 g, 2.93 mmol) was stirred in trifluoracetic acid (1 ml) at room temperature for 20 hours and at 50° C. for 12 hours. The mixture was poured carefully into 5% sodium bicarbonate solution and diethyl ether added. The organic layer was washed with 5% sodium bicarbonate solution, dried (MgSO 4 ) and evaporated to give the title compound as an orange oil which crystallised (1.06 g). 
     LC/MS Rt=3.25 min [MH + ] 362.5, 364.5. 
     Ethyl 6-[2-(5-chloro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridine carboxylate 
     
       
         
         
             
             
         
       
     
     6-[2-(5-chloro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid (2.6 g, 0.0082 mol) and concentrated sulphuric acid (1 ml) in 100 ml of ethanol were refluxed overnight. After cooling the mixture was quenched with ammonia, diluted with water and extracted with ethyl acetate (30 ml×3). The combined organic layers were washed with a saturated solution of sodium bicarbonate, dried (magnesium sulphate) and evaporated to dryness to give the title compound as a light yellow oil (2.5 g, 89%). 
     LC/MS: Rt 3.65 [MH + ] 344, 346 [MH−] 342, 344 
     The following intermediates were prepared by a similar route to ethyl 6-[2-(5-chloro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridine carboxylate from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Name 
                 Data 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2- hydroxyphenyl)-1-cyclopenten-1- yl]-2-methyl-3-pyridinecarboxylate 
                 LC/MS t = 3.62, [MH+] 358.4, 360.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2- hydroxyphenyl)-1-cyclopenten-1- yl]-3-(methylthio)-2- pyridinecarboxylate 
                 LC/MS t = 3.75, [MH+] 390.4, 392.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-[2-(5-chloro-2- hydroxyphenyl)-1-cyclopenten-1- yl]-2-pyridinecarboxylate 
                 LC/MS t = 3.93, [MH+] 378.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2- hydroxyphenyl)-1-cyclopenten-1- yl]-3-methyl-2-pyridinecarboxylate 
                 LC/MS t = 3.82, [MH+] 358.4, 360.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2- hydroxyphenyl)-1-cyclopenten-1- yl]-3-pyridinecarboxylate 
                 LC/MS t = 3.67, [MH+] 344.3, 346.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-bromo-2- hydroxyphenyl)-1-cyclopenten-1- yl]-2-pyrazinecarboxylate 
                 LC/MS: Rt = 3.48 min. [M + H] = 389, 391. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-hydroxy-4- methylphenyl)-1-cyclopenten-1-yl]- 2-pyridinecarboxylate 
                 LC/MS: Rt = 3.74 min. [M + H] = 358. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(4,5-dichloro-2- hydroxyphenyl)-1-cyclopenten-1- yl]-2-(trifluoromethyl)-3- pyridinecarboxylate 
                 LC/MS: Rt = 3.86 min. [M + H] = 378, 380. 
               
               
                   
               
            
           
         
       
     
     Ethyl 6-{2-[2-hydroxy-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-3-methyl-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     A mixture of ethyl 3-methyl-6-{2-[2-[(phenylmethyl)oxy]-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylate (2.21 g, 4.59 mmol) dissolved in acetic acid (5 ml) and 45% hydrogen bromide in acetic acid (10 ml) was stirred at room temperature for 3 hours. The reaction mixture was diluted with diethyl ether and water and basified with potassium carbonate. The ether layer was separated, dried over magnesium sulphate and evaporated to dryness. The residue was purified using flash chromatography eluting with ethyl acetate/iso-hexane (15%) to give 1.44 g of yellow solid. Sodium hydride (2 mg) was added to the product dissolved in ethanol and left at room temperature for 12 hours. The reaction mixture was diluted with diethyl ether and water, then acidified with acetic acid. The ether layer was washed with sodium hydrogen carbonate solution, dried over magnesium sulphate and evaporated to dryness. The residue was purified using flash chromatography eluting with 20% ethyl acetate/iso-hexane to give the title compound as a light coloured solid. 1.11 g, 62%. 
       1 H NMR (CDCl 3 ) δ: 1.48 (3H, t), 2.08-2.15 (2H, m), 2.50 (3H, s), 2.86-3.90 (2H, m), 3.01-3.05 (2H, m), 4.45 (2H, q), 7.08 (1H, d), 7.33-7.37 (2H, m), 7.39 (1H, dd), 7.61 (1H, d). 
     The following intermediates were prepared by a similar route to ethyl 6-{2-[2-hydroxy-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-3-methyl-2-pyridinecarboxylate from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Name 
                 Data 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-[2-(5-chloro-2- hydroxyphenyl)-1-cyclopenten- 1-yl]-2-methyl-3- pyridinecarboxylate 
                 LC/MS Rt = 3.45, [MH+] 344.3, 346.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-{2-[2-hydroxy-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2-methyl-3- pyridinecarboxylate 
                 LC/MS Rt = 3.49, [MH+] 378.5 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-{2-[2-hydroxy-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl)-2- pyridinecarboxylate 
                 LC/MS Rt = 3.90, [MH+] 412.5, 414.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-[2-(5-chloro-2- hydroxyphenyl)-1-cyclopenten- 1-yl]-2-(trifluoromethyl)-3- pyridinecarboxylate 
                 LC/MS Rt = 3.75, [MH+] 398.4, 400.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-{2-[2-hydroxy-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 LC/MS Rt = 4.02, [MH+] 446. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2- hydroxyphenyl)-1-cyclopenten- 1-yl]-4-(trifluoromethyl)-2- pyridinecarboxylate 
                 LC/MS Rt = 3.45, [MH+] 412. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-hydroxy-5- trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 LC/MS Rt = 4.09, [MH+] 446. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-bromo-2- hydroxyphenyl)-1-cyclopenten- 1-yl]-2-(trifluoromethyl)-3- pyridinecarboxylate 
                 LC/MS Rt = 3.17, [MH+] 457 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-[2-(5-chloro-2- hydroxyphenyl)-1-cyclopenten- 1-yl]-4-pyrimidinecarboxylate 
                 LC/MS Rt = 3.07, [MH+] 331, 333 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 2-[2-(5-chloro-2- hydroxyphenyl)-1-cyclopenten- 1-yl]-3-pyridinecarboxylate 
                 LC/MS Rt = 3.26, [MW+] 344.4, 346.3 
               
               
                   
               
            
           
         
       
     
     5-[2-(5-Bromo-2-hydroxyphenyl)-1-cyclopenten-1-yl]-N-(1,1-dimethylethyl)-3-pyridazinecarboxamide 
     
       
         
         
             
             
         
       
     
     5-{2-[5-Bromo-2-(methyloxy)phenyl]-1-cyclopenten-1-yl}-N-(1,1-dimethylethyl)-3pyridazinecarboxamide (5.3 g, 12.3 mmol) in dry dichloromethane (200 ml) was cooled to −75° C. under nitrogen and was treated slowly with boron tribromide (8.0 ml, 84.8 mmol). The reaction mixture was then heated to reflux for 1.5 hour. The reaction mixture was then quenched in ice-water (400 ml) and after stirring at room temperature for 2 hours the organic layer was dried and evaporated to a dark brown solid (6.0 g). 
     LC/MS Rt=3.55 min [MH + ] 418, 419. 
     Ethyl 5-[2-(5-bromo-2-hydroxyphenyl)-1-cyclopenten-1-yl]-3-pyridazinecarboxylate 
     
       
         
         
             
             
         
       
     
     5-[2-(5-Bromo-2-hydroxyphenyl)-1-cyclopenten-1-yl]-N-(1,1-dimethylethyl)-3-pyridazinecarboxamide (6.0 g, 13.95 mmol) in ethanol (75 ml) was treated with concentrated sulphuric acid/water (24/10 ml) and refluxed for two hours. The reaction was poured into water (200 ml) and extracted with ethyl acetate(3×30 ml). After drying the product was purified by chromatography giving the title compound (1.8 g, 32% yield). 
     LC/MS Rt=3.2 min [MH + ] 391, 392. 
     Ethyl 5-[2-(5-chloro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-3-pyridazinecarboxylate 
     
       
         
         
             
             
         
       
     
     5-(2-{5-Chloro-2-[(phenylmethyl)oxy]phenyl}-1-cyclopenten-1-yl)-N-(1,1-dimethylethyl)-3-pyridazinecarboxamide (970 mg, 2.1 mmol) in ethanol/sulphuric acid/water 2:2:1 (20 ml) was heated at 90° C. for 2 hours. After cooling the solution was diluted with water/ether and the organic layer dried (magnesium sulphate) evaporated and purified by chromatography on silica eluting with ethyl acetate/iso-hexane (1:1) to give the title compound as a white solid (260 mg). 
     LC/MS: [M+H] 345.3, 347.3, Rt=3.15 min 
     Methyl 6-{2-[2-hydroxy-5-trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     6-{2-[2-hydroxy-5-(trifluoromethyl)phenyl]cyclopent-1-en-1-yl}pyridine-2-carboxylic acid (2.49 g, 7.1 3 mmol) was dissolved in anhydrous methanol (100 ml) and cooled in an ice bath. 2M Trimethylsilyldiazomethane in hexanes (25 ml) was added slowly. Bubbles of nitrogen were observed after the addition of 5 ml; the addition was continued until no more bubbling was observed. The solvent was then removed in vacuo to yield a dark oil. This was purified by column chromatography eluting with 30% ethyl acetate/isohexane. This yielded the title compound as a yellow solid. LC/MS Rt=3.47 [MH + ] 364. 
     Methyl 6-{2-[2-hydroxy-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyrazinecarboxylate 
     
       
         
         
             
             
         
       
     
     Procedure as for methyl 6-{2-[2-hydroxy-5-trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylate. LC/MS t=3.47, [MH + ] 365. 
     Methyl 6-[2-(5-fluoro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     6-[2-(5-Fluoro-2-hydroxyphenyl]-cyclopenten-1-yl-2-pyridinecarboxylic acid (5.0 g, 16.72 mmol) in methanol (200 ml) and concentrated sulphuric acid (4 ml) were refluxed overnight under nitrogen. The reaction mixture was then cooled and treated with 0.880 ammonia (8 ml) and evaporated to an oil under reduced pressure. After partitioning between ethyl acetate and water, the resulting product was purified by flash chromatography with a gradient of diethyl ether/iso-hexane(10-30%) giving the title compound (3.5 g, 83%). LC/MS Rt=3.16 min. [MH + ] 314 
     Methyl 6-[2-(5-fluoro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyrazinecarboxylate 
     
       
         
         
             
             
         
       
     
     Procedure as for methyl 6-[2-(5-fluoro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylate. 
     LC/MS Rt=2.98min, [MH + ] 315. 
     Ethyl 2-fluoro-5-{2-[2-hydroxy-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}benzoate 
     
       
         
         
             
             
         
       
     
     Ethyl 2-fluoro-5{2-[2-(phenylmethoxy)-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}benzoate (6.77 g, 14.0 mmol) was dissolved in trifluoroacetic acid (50 ml). The solution was stirred at room temperature for 36 hours. The mixture was treated with 5% aqueous sodium bicarbonate solution, and extracted with diethyl ether (×2). The combined extracts were dried (Na 2 SO 4 ) and concentrated in vacuo. The residue was purified by flash chromatography on silica (gradient elution, 0-30% ethyl acetate/cyclohexane) to give the title compound (3.35 g). LC/MS Rt=3.46 min [MH + ] 396. 
     Ethyl 3-fluoro-5-{2-[2-hydroxy-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1yl}benzoate 
     
       
         
         
             
             
         
       
     
     Ethyl 3-fluoro-5-{2-[2-(phenylmethoxy)-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}benzoate (7.42 g, 15.3 mmol) was dissolved in trifluoroacetic acid (50 ml). The solution was stirred at room temperature for 18 hours. The mixture was treated with 5% aqueous sodium bicarbonate solution, and extracted with diethyl ether (×2). The combined extracts were dried (Na 2 SO 4 ) and concentrated in vacuo. The residue was purified by flash chromatography on silica (gradient elution, 0-30% ethyl acetate/cyclohexane) to give the title compound (3.3 g). LC/MS Rt=3.56 min [MH + ] 396. 
     Ethyl 5-{2-[2-(hydroxy)-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}-3-(trifluoroacetamido)benzoate 
     
       
         
         
             
             
         
       
     
     Ethyl 3-amino-5-{2-[2-(phenylmethoxy)-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}benzoate (4.5 g, 7.79 mmol) was dissolve in trifluoroacetic acid (50 ml) and stirred at room temperature for 20 hours. The mixture was neutralised with 5% aqueous sodium hydrogen carbonate, and extracted with water. The organic extracts were washed with further water, dried (Na 2 SO 4 ), and concentrated in vacuo. The residue was purified by flash chromatography on silica (gradient elution, 0-65% ethyl acetate/cyclohexane) to give the required product (1.99 g). LC/MS Rt=3.52 min [MH + ] 489. 
     (2,4-Dichlorophenyl)methyl 6-{2-[2-{[(2,4-dichlorophenyl)methyl]oxy}-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     6-{2-[2-Hydroxy-5-(trifluoromethyl)phenyl]cyclopent-1-en-1-yl}-pyridine-2-carboxylic acid (0.067 g, 0.19 mmol), potassium carbonate (0.079 g, 0.57 mmol), 2,4-dichlorobenzyl bromide (0.082 g, 0.42 mmol) and DMF (2 ml) were heated at 55° C. for 3 hours under a nitrogen atmosphere. After cooling the reaction was diluted with ethyl acetate and washed with water (×2). The aqueous layers were washed with ethyl acetate (×2). The combined organic layers were then washed with brine, dried over MgSO 4 , filtered and concentrated in vacuo to give a dark oil. This was purified by column chromatography eluting with 10% ethyl acetate/isohexane to yield the title compound as a brown oil (0.095 g, 74%). 
     LC/MS t=4.97, [MH + ] 668 
     (2,6-Difluorophenyl)methyl 6-{2-[2-{[(2,6-difluorophenyl)methyl]oxy}-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     Procedure as for (2,4-dichlorophenyl)methyl 6-{2-[2-{[(2,4-dichlorophenyl)methyl]oxy}-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylate. 
     LC/MS t=4.34, [MH + ] 602 
     Methyl 5-[2-(5-chloro-2-{[(4-fluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-methyl-3-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     A mixture of methyl 5-[2-(5-chloro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-methyl-3-pyridinecarboxylate (150 mg, 0.44 mmol), 4-fluorobenzyl bromide (95 mg, 0.50 mmol) and potassium carbonate (138 mg, 1 mmol) in acetone (5 ml) was stirred and refluxed for 3 hours then cooled, filtered, evaporated and purified by chromatography on silica eluting with ethyl acetate/iso-hexane (15:85) to give a colourless gum (191 mg). 
     LC/MS t=4.07, [MH+] 452.3 
     The following intermediates were prepared by a similar route to methyl 5-[2-(5-chloro-2-{[(4-fluorophenyl)methyl]oxy}phenyl)-cyclopenten-1-yl]-2-methyl-3-pyridinecarboxylate from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Name 
                 LC/MS 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-[2-(5-chloro-2-{[(2,4- difluorophenyl)methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2-methyl-3- pyridinecarboxylate 
                 Rt = 4.09, [MH+] 470.4, 472.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(4- chlorophenyl)methyl}oxy)-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.16, [MH + ] 488 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(2,3- difluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.08 [MH + ] 490 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-[2-(5-(trifluoromethyl)-2- {[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.02, [MH + ] 508 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(4-chloro-2- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.20, [MH + ] 506 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(2- fluorophenyl)methyloxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.02, [MH + ] 472 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(2- chlorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.19, [MH + ] 488. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(4- bromophenyl)methyl]oxy)-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.22, [MH + ] 532, 534 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(4-bromo-2- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.24, [MH + ] 550, 552 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(2-chloro-4- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.21, [MH + ] 506 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(2-chloro-6- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.09, [MH + ] 506 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-[2-(5-(trifluoromethyl)-2- {[(2,3,6- trifluorophenyl)methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.99, [MH + ] 508 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(2- bromophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.22, [MH + ] 534, 534 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-(2-{[(4- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyrazinecarboxylate 
                 Rt = 3.92, [MH + ] 473 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(2,4- difluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyrazinecarboxylate 
                 Rt = 3.95, [MH + ] 491 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(4- chlorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyrazinecarboxylate 
                 Rt = 4.21, [MH + ] 489 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(2- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyrazinecarboxylate 
                 Rt = 3.95, [MH + ] 473 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(4- bromophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyrazinecarboxylate 
                 Rt = 4.15, [MH + ] 533, 535 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(4-bromo-2- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyrazinecarboxylate 
                 Rt = 4.26, [MH + ] 551, 553 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-{2-[2-{[(2-chloro-4- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyazinecarboxylate 
                 Rt = 4.23, [MH + ] 507 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-{2-[2-{[(4- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2-methyl-3- pyridinecarboxylate 
                 Rt = 3.98, [MH+] 486.5 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-{2-[2-{[(2,4- difluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2-methyl-3- pyridinecarboxylate 
                 Rt = 4.03 [MH+] 504.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-{2-[2-{[(2,4,6- trifluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2-methyl-3- pyridinecarboxylate 
                 Rt = 4.06 [MH+] 522.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-{2-[2-{[(2-chloro-4- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1 cyclopenten-1-yl}-2-methyl-3- pyridinecarboxylate 
                 Rt = 4.22 [MH+] 520.4, 522.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-{2-[2-{[(4-chloro-2- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2-methyl-3- pyridinecarboxylate 
                 Rt = 4.23 [MH+] 520.4, 522.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-{2-[2-{[(2- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2-methyl-3- pyridinecarboxylate 
                 Rt = 4.41 [MH+] 500.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-{2-[2-{[(2,4,5- trifluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2-methyl-3- pyridinecarboxylate 
                 Rt = 4.57 [MH+] 536.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-[2-(5-chloro-2-{[(2- fluorophenyl)methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2-(trifluoromethyl)- 3-pyridinecarboxylate 
                 Rt = 3.95, [MH+] 506.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-[2-(5-chloro-2-{[(4- fluorophenyl)methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2-(trifluoromethyl)- 3-pyridinecarboxylate 
                 Rt = 3.96 [MH+] 506.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-[2-(5-chloro-2-{[(2,4- difluorophenyl)methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2-(trifluoromethyl)- 3-pyridinecarboxylate 
                 Rt = 3.95 [MH+] 524.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-[2-(5-chloro-2-{[(2-chloro-4- fluorophenyl)methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2-(trifluoromethyl)- 3-pyridinecarboxylate 
                 Rt = 4.06 [MH+] 540.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-[2-(5-chloro-2-{[(2,6- difluorophenyl)methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2-(trifluoromethyl)- 3-pyridinecarboxylate 
                 Rt = 3.93 [MH+] 524.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-[2-(5-chloro-2-{[(4-chloro-2- fluorophenyl)methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2-(trifluoromethyl)- 3-pyridinecarboxylate 
                 Rt = 4.11 [MH+] 540.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-[2-(5-chloro-2-{[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2-(trifluoromethyl)- 3-pyridinecarboxylate 
                 Rt = 4.02 [MH+] 542.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-[2-(5-chloro-2-{[(2,3,4- trifluorophenyl)methyl]oxylphenyl)-1- cyclopenten-1-yl]-2-(trifluoromethyl)- 3-pyridinecarboxylate 
                 Rt = 4.01 [MH+] 542.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 5-[2-(5-chloro-2-{[2,4,5- trifluorophenyl)methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2-(trifluoromethyl)- 3-pyridinecarboxylate 
                 Rt = 4.04 [MH+] 542.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl 6-[2-(5-chloro-2-{[(2,4- difluorophenyl)methyl]oxy}phenyl)-1- cyclopenten-1-yl-4- pyrimidinecarboxylate 
                 Rt = 4.10 [MH+] 457, 459 
               
               
                   
               
            
           
         
       
     
     Ethyl 6-[2-(5-chloro-2-{[(2-fluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     Ethyl 6-[2-(5-chloro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylate (100 mg, 0.29 mmol), 2-fluorobenzyl bromide (0.035 ml, 0.32 mmol) and potassium carbonate (100 mg, 0.73 mmol) in acetone (3 ml) were refluxed overnight under nitrogen. The reaction mixture was then filtered through hiflo and evaporated to give the title compound. 
     LC/MS: Rt=4.1 [MH + ] 452, 455 
     The following intermediates were prepared by a similar route to ethyl 6-[2-(5-chloro-2-{[(2-fluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylate from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Name 
                 LC/MS 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2-chloro- 6-fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.20, [MH+] 486, 489 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2- chlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.28, [MH+] 468, 471 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2- methylphenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.99, [MH+] 448, 451 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,6- dichlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl-2- pyridinecarboxylate 
                 Rt = 4.08, [MH+] 504, 506 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4- dimethylphenyl)methyl]oxy}phenyl)- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.09, [MH+] 462, 464 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,3,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.11, [MH+] 488, 490 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(4-bromo-2- fluorophenyl)methyl]oxy}-5- chlorophenyl)-1-cyclopenten-1-yl]- pyridinecarboxylate 
                 Rt = 4.11, [MH+] 532, 534 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,5- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.95, [MH+] 470, 473 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2- bromophenyl)methyl]oxy}-5- chlorophenyl)-1-cyclopenten-1-yl]- 2-pyridinecarboxylate 
                 Rt = 4.32, [MH+] 514, 516 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4- dichlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.45, [MH+] 504, 506 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2-bromo-4- fluorophenyl)methyl]oxy}-5- chlorophenyl)-1-cyclopenten-1-yl]- 2-pyridinecarboxylate 
                 Rt = 4.33, [MH+] 532, 534 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2- fluorophenyl)methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 3.81, [MH+] 453, 456 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2- chlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 3.96, [MH+] 469, 472 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2-chloro- 6-fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 3.88, [MH+] 487, 490 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,6- dichlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 4.19, [MH+] 505, 507 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4- dichlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 4.32, [MH+] 505, 507 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,6- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 3.97, [MH+] 473, 474 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2- bromophenyl)methyl]oxy}-5- chlorophenyl)-1-cyclopenten-1-yl]- 2-pyrazinecarboxylate 
                 Rt = 3.99, [MH+] 515, 517 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(4- bromophenyl)methyl]oxy}-5- chlorophenyl)-1-cyclopenten-1-yl]- 2-pyrazinecarboxylate 
                 Rt = 3.98, [MH+] 515, 517 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2-chloro- 4-fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 3.97, [MH+] 487, 490 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,5- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 3.83, [MH+] 471, 473 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(3,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 3.84, [MH+] 471, 473 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,3- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 3.82, [MH+] 471, 473 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2- methylphenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 4.34, [MH+] 449 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-(2-(5-chloro-2-{[(4- methylphenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl}-2- pyrazinecarboxylate 
                 Rt = 4.37, [MH+] 449, 451 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4- dimethylphenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 4.48, [MH+] 463 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(4-bromo-2- fluorophenyl)methyl]oxy}-5- chlorophenyl)-1-cyclopenten-1-yl]- 2-pyrazinecarboxylate 
                 Rt = 4.47, [MH+] 533, 535 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2-bromo-4- fluorophenyl)methyl]oxy}-5- chlorophenyl)-1-cyclopenten-1-yl]- 2-pyrazinecarboxylate 
                 Rt = 4.48, [MH+] 533 [MH−] 531 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[5-chloro-2-({[2-fluoro-4- (trifluoromethyl)phenyl]methyl}oxy) phenyl]-1-cyclopenten-1-yl}-2- pyrazinecarboxylate 
                 Rt = 4.46, [MH+] 521, 523 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 4.23, [MH+] 489, 491 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(4-chloro- 2-fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 4.23, [MH+] 487 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(4- chlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 4.23, [MH+] 469, 471 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-(2-(2-{[(4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.99 min, [M + H] 418. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(4- chlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.16 min, [M + H] 434. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(4- bromophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.21 min, [M + H] 480. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(4- methylphenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.11 min, [M + H] 414. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-({[4- (trifluoromethyl)phenyl]methyl}oxy) phenyl]-1-cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.17 min, [M + H] 486. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.99 min, [M + H] 418. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2- chlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.18 min, [M + H] 434. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2- bromophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.18 min, [M + H] 480. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2- methylphenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.06 min, [M + H] 414. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(4-chloro-2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.18 min, [M + H] 452. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(4-bromo-2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl-2- pyridinecarboxylate 
                 Rt = 4.21 min, [M + H] 498. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-({[2-fluoro-4- trifluoromethyl)phenyl]methyl}oxy) phenyl]-1-cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.22 min, [M + H] 486. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2-chloro-4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.21 min, [M + H] 452. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2,4- dichlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.43 min, [M + H] 468. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2-bromo-4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.26 min, [M + H] 498. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2,4- dimethylphenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.22 min, [M + H] 428. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-({[2,4- bis(trifluoromethyl)phenyl]methyl} oxy)phenyl]-1-cyclopenten-1-yl}- 2-pyridinecarboxylate 
                 Rt = 4.43 min, [M + H] 536. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(3,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.03 min, [M + H] 436. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.98 min, [M + H] 454. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2,4,6- trimethylphenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.31 min, [M + H] 442. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2,3,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.95 min, [M + H] 454. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2,4,5- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.08 min, [M + H] 454. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(3,4-5- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.12 min, [M + H] 454. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-(2-{2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-2- pyrazinecarboxylate 
                 Rt = 3.83 min, [M + H] 401. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl-2- pyrazinecarboxylate 
                 Rt = 3.86 min, [M + H] 419. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(4- chlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 3.75 min, [M + H] 437. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 4.03 min, [M + H] 435. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(4-chloro-2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 4.07 min, [M + H] 453. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2,4- dichlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 4.21 min, [M + H] 469. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2,5- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 3.89 min, [M + H] 437. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 3.85 min, [M + H] 419. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(2-{[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylate 
                 Rt = 3.84 min, [M + H] 455. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{5-chloro-2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-2-ethyl-3- pyridinecarboxylate 
                 Rt = 4.35 min, [M + H] 462. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2-ethyl-3- pyridinecarboxylate 
                 Rt = 4.34 min, [M + H] 480. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(4- chlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2-ethyl-3- pyridinecarboxylate 
                 Rt = 4.51 min, [M + H] 496. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-{2-[5-chloro-2-({[4- (trifluoromethyl)phenyl]methyl}oxy) phenyl]-1-cyclopenten-1-yl}-2- ethyl-3-pyridinecarboxylate 
                 Rt = 4.51 min, [M + H] 530. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5[2-(5-chloro-2-{[(2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2-ethyl-3- pyridinecarboxylate 
                 Rt = 4.35 min, [M + H] 480. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2-ethyl-3- pyridinecarboxylate 
                 Rt = 4.37 min, [M + H] 498. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,6- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2-ethyl-3- pyridinecarboxylate 
                 Rt = 4.29 min, [M + H] 498. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2- chloro-4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2-ethyl-3- pyridinecarboxylate 
                 Rt = 4.54 min, [M + H] 514. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,4,5- trifluorophenyl)methyl]oxy}pheny)- 1-cyclopenten-1-yl]-2-ethyl-3- pyridinecarboxylate 
                 Rt = 4.40 min, [M + H] 516. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2-ethyl-3- pyridinecarboxylate 
                 Rt = 4.33 min, [M + H] 516. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-methyl-6-{2-[2- [(phenylmethyl)oxy]-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.35 min, [M + H] 482. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{(4- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-3-methyl-2- pyridinecarboxylate 
                 Rt = 4.36 min, [M + H] 500. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(4- chlorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-3-methyl-2- pyridinecarboxylate 
                 Rt = 4.49 min, [M + H] 516. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2- fluorophenyl)methyl)oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-3-methyl-2- pyridinecarboxylate 
                 Rt = 4.39 min, [M + H] 500. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2,4- difluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-3-methyl-2- pyridinecarboxylate 
                 Rt = 4.43 min, [M + H] 518. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2-chloro-4- fluorophenyl)methyl]oxy]-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl)-3-methyl-2- pyridinecarboxylate 
                 Rt = 4.58 min, [M + H] 534. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2,6- difluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-3-methyl-2- pyridinecarboxylate 
                 Rt = 4.34 min, [M + H] 518. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2,3- difluorophenyl)methyl]oxy)-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-3-methyl-2- pyridinecarboxylate 
                 Rt = 4.39 min, [M + H] 518. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2-chloro-6- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-3-methyl-2- pyridinecarboxylate 
                 Rt = 4.44 min, [M + H] 534. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-methyl-6-[2-(5- (trifluoromethyl)-2-{[(2,4,5- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.30 min, [M + H] 536. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-methyl-6-[2-(5- (trifluoromethyl)-2-{[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.30 min, [M + H] 536. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,4,5- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- methyl-3-pyridinecarboxylate 
                 Rt = 4.24, [MH+] 502.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-{2-[5-chloro-2-({[4- (trifluoromethyl)phenyl]methyl} oxy)phenyl]-1-cyclopenten-1- yl}-2-methyl-3- pyridinecarboxylate 
                 Rt = 4.35 [MH+] 516.5, 518.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(4- chlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- methyl-3-pyridinecarboxylate 
                 Rt = 4.35 [MH+] 482.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,3,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- methyl-3-pyridinecarboxylate 
                 Rt = 4.13 [MH+] 502.4, 504.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2- chloro-4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- methyl-3-pyridinecarboxylate 
                 Rt = 4.38 [MH+] 500.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- methyl-3-pyridinecarboxylate 
                 Rt = 4.16 [MH+] 502.4, 504.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-{2-[5-chloro-2-({[2- fluoro-4- (trifluoromethyl)pheny]methyl} oxy)phenyl]-1-cyclopenten-1- yl}-2-methyl-3- pyridinecarboxylate 
                 Rt = 4.38 [MH+] 534.5, 536.5 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(2-{[(4- bromophenyl)methyl]oxy}-5- chlorophenyl)-1-cyclopenten- 1-yl]-2-methyl-3- pyridinecarboxylate 
                 Rt = 4.40 [MH+] 528.4, 530.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,6- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- methyl-3-pyridinecarboxylate 
                 Rt = 4.13 [MH+] 484.4, 486.5 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- methyl-3-pyridinecarboxylate 
                 Rt = 4.18 [MH+] 466.5, 468.5 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-(2-{5-chloro-2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-3- (methylthio)-2- pyridinecarboxylate 
                 Rt = 4.24, [MH+] 480.4, 482.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- (methylthio)-2- pyridinecarboxylate 
                 Rt = 4.27 [MH+] 498.4, 500.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- (methylthio)-2- pyridinecarboxylate 
                 Rt = 4.27 [MH+] 498.4, 500.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- (methylthio)-2- pyridinecarboxylate 
                 Rt = 4.31 [MH+] 516.4, 518.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- (methylthio)-2- pyridinecarboxylate 
                 Rt = 4.27 [MH+] 534.4, 536.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-(2-{5-chloro- 2-[(phenylmethyl)oxy]phenyl}- 1-cyclopenten-1-yl)-2- pyridinecarboxylate 
                 Rt = 4.50, [MH+] 468.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-[2-(5-chloro- 2-{[(4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.49 [MH+] 486.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-[2-(5-chloro- 2-{[(2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.45 [MH+] 486.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-[2-(5-chloro- 2-{[(2,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.52 [MH+] 504.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-[2-(5-chloro- 2-{[(2,6- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.46 [MH+] 504.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-[2-(5-chloro- 2-{[(2,3,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.46 [MH+] 522.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-[2-(5-chloro- 2-{[(2,4,5- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.55 [MH+] 522.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-[2-(5-chloro- 2-{[(4- chlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.65 [MH+] 502.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-[2-(5-chloro- 2-{[(2-chloro-4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.70 [MH+] 522.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-{2-[5-chloro- 2-({[4- (trifluoromethyl)phenyl]methyl} oxy)phenyl]-1-cyclopenten-1- yl}-2-pyridinecarboxylate 
                 Rt = 4.66 [MH+] 536.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-chloro-6-{2-[5-chloro- 2-({[2-fluoro-4- (trifluoromethyl)pheny]methyl} oxy)phenyl]-1-cyclopenten-1- yl}-2-pyridinecarboxylate 
                 Rt = 4.69 [MH+] 554.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-(2-{5-bromo-2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-3-chloro-2- pyridinecarboxylate 
                 Rt = 4.54, [MH+] 514.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-bromo-2-{[(4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3-chloro- 2-pyridinecarboxylate 
                 Rt = 4.10 [MH+] 532.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-bromo-2-{[(2,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- chloro-2-pyridinecarboxylate 
                 Rt = 4.57 [MH+] 550.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-bromo-2-{[(2,3,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- chloro-2-pyridinecarboxylate 
                 Rt = 4.35 [MH+] 568.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-bromo-2-{[(4- chloro-2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3-chloro- 2-pyridinecarboxylate 
                 Rt = 4.60 [MH+] 566.3, 568.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-bromo-2-{[(2,3,4- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- chloro-2-pyridinecarboxylate 
                 Rt = 4.52 [MH+] 568.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-(2-{5-chloro-2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-3-methyl-2- pyridinecarboxylate 
                 Rt = 4.40, [MH+] 448.5, 450.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- methyl-2-pyridinecarboxylate 
                 Rt = 4.42 [MH+] 466.5, 468.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- methyl-2-pyridinecarboxylate 
                 Rt = 4.26 [MH+] 466.4, 468.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- methyl-2-pyridinecarboxylate 
                 Rt = 4.09 [MH+] 484.4, 486.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4,5- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- methyl-2-pyridinecarboxylate 
                 Rt = 4.49 [MH+] 502.4, 504.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,3- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- methyl-2-pyridinecarboxylate 
                 Rt = 4.44 [MH+] 484.4, 486.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(3,4,5- trifluorophenyl)methyl]-oxy}phenyl)- 1-cyclopenten-1-yl]-3- methyl-2-pyridinecarboxylate 
                 Rt = 4.31 [MH+] 502.4, 504.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2- chloro-6- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl-3- methyl-2-pyridinecarboxylate 
                 Rt = 4.18 [MH+] 500.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyctopenten-1-yl]-3- methyl-2-pyridinecarboxylate 
                 Rt = 4.10 [MH+] 502.4, 504.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,6- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- methyl-2-pyridinecarboxylate 
                 Rt = 4.15 [MH+] 484.4, 486.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2- chloro-4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- methyl-2-pyridinecarboxylate 
                 Rt = 4.35 [MH+] 500.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(4- chlorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- methyl-2-pyridinecarboxylate 
                 Rt = 4.33 [MH+] 482.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-{2-[2-{[(2- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 Rt = 4.49 min [M + H] 554 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-{2-[2-{[(4- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 Rt = 4.49 min [MH] 554 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ethyl 5-{2-[2-{[(2,4- difluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 Rt = 3.88 min [M + H] 572 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ethyl 2-(trifluoromethyl)-5- [2-(5-trifluoromethyl)-2- {[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]- 3-pyridinecarboxylate 
                 Rt = 4.49 min [M + H] 590 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ethyl 5-{2-[2-{[(2-chloro-4- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 Rt = 4.62 min [M + H] 588 (1 Cl) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ethyl 6-{2-[2- [(phenylmethyl)oxy]-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.57 min [M + H] 536 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.54 min [M + H] 554 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(4- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-y[}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.26 min [M + H] 554 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2,4- difluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.58 min [M + H] 572 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 4-(trifluoromethyl)-6-[2- (5-(trifluoromethyl)-2-{[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.56 min [M + H] 590 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2-chloro-4- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.71 min [M + H] 588 (1 Cl) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(4-chloro-2- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.18 min [M + H] 588 (1 Cl) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(3,4- difluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.58 min [M + H] 572 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-(2-{[(4- bromophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.73 min [M + H] 614, 616 (1 Br) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 4-(trifluoromethyl)-6-{2- [5-(trifluoromethyl)-2-({[4- (trifluoromethyl)phenyl]methyl} oxy)phenyl]-1-cyclopenten-1- yl}-2-pyridinecarboxylate 
                 Rt = 4.60 min [M + H] 604 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2-chloro-4- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 599 Rt = 4.34 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-bromo-2-{[(2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 [M + H] 565 Rt = 4.21 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-bromo-2-{[(4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 [M + H] 565 Rt = 4.21 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ethyl 5-[2-(5-bromo-2-{[(2,4- difluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1-yl]- 2-(trifluoromethyl)-3- pyridinecarboxylate 
                 [M + H] 583 Rt = 4.37 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ethyl 5-[2-(5-bromo-2- {[(2,4,6- trifluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1-yl]- 2-(trifluoromethyl)-3- pyridinecarboxylate 
                 [M + H] 601 Rt = 4.39 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ethyl 5-[2-(5-bromo-2-{[(2- chloro-4- fluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 [M + H] 599 Rt = 4.31 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ethyl 5-[2-(5-bromo-2-{[(4- chlorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 [M + H] 581 Rt = 4.39 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-(2-{5-chloro-2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 502.4, 504.4 Rt = 4.58 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 520.4, 522.4 Rt = 4.55 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 520.4, 522.4 Rt = 4.57 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 538.4, 540.4 Rt = 4.59 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4,5- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 556.3, 558.4 Rt = 4.61 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(4- chloro-2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M = H] 554.3, 556.4 Rt = 4.73 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,3,4- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 556.3, 558.4 Rt = 4.61 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(3,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 538.4, 540.4 Rt = 4.59 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-(5-chloro-2-{[(3,4,5- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 556.3, 558.4 Rt = 4.65 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,3- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 538.4, 540.4 Rt = 4.57 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2- chloro-4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 554.3, 556.3 Rt = 4.75 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 556.3, 558.4 Rt = 4.56 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{5-chloro-2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-3- pyridazinecarboxylate 
                 [M + H] 435.2, 437.2, Rt = 3.76 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- pyridazinecarboxylate 
                 [M + H] 453.3, 455.3, Rt = 3.60 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- pyridazinecarboxylate 
                 [M + H] 471.3, 473.3, Rt = 3.61 min 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- pyridinecarboxylate 
                 Rt = 4.27, [MH+] 470.3, 472.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 2-[2-(5-chloro-2-{[(2,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- pyridinecarboxylate 
                 Rt = 3.94, [MH+] 470.3, 472.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 2-[2-(5-chloro-2-{[(4- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-3- pyridinecarboxylate 
                 Rt = 3.90, [MH+] 452.3, 454.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-chloro-2-{[(2,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.20 [MH+] 470.3, 472.3 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-{4,5-dichloro-2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-2- pyridinecarboxylate 
                 Rt = 4.33 [MH+] 468.4, 470.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(4,5-dichloro-2-{[(2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.35 [MH+] 486.4, 488.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(4,5-dichloro-2- {[(2,4- difluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.36 [MH+] 504.4, 506.4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(4,5-dichloro-2- {[(2,4,6- trifluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.34 [MH+] 522.4, 524.4 
               
               
                   
               
            
           
         
       
     
     Ethyl 6-(2-{5-chloro-2-[(cyclopentylmethyl)oxy]phenyl}-1-cyclopenten-1-yl)-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     A mixture of 6-[2-(5-chloro-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid (100 mg, 0.29 mmol), potassium carbonate (200 mg, 1.45 mmol) and cyclopentylmethyl 4-methylbenzenesulfonate (90 mg, 0.35 mmol) in DMF (3 ml) was heated at 90° C. under nitrogen for 2 hours. More cyclopentylmethyl 4-methylbenzenesulfonate (40 mg, 0.16 mmol) was added and the mixture heated for another 2 hours. After cooling the solution was diluted with water and extracted with ethyl acetate (3×10 ml). The combined extracts were dried (MgSO 4 ) and evaporated. Purification was carried out by flash chromatography (10% ethyl acetate:iso-hexane) to yield the title compound as a clear oil. 
     LC/MS: Rt=4.68, [MH+] 426, 428 
     Ethyl 6-(2-{5-chloro-2-[(2-methylpropyl)oxy]phenyl}-1-cyclopenten-1-yl)-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     Prepared in a similar manner to ethyl 6-(2-{5-chloro-2-[(cyclopentylmethyl)oxy]phenyl}-1-cyclopenten-1-yl)-2-pyridinecarboxylate using 1-bromo-2-methylpropane instead of cyclopentylmethyl 4-methylbenzenesulfonate. LC/MS: Rt=4.49 [MH+] 400, 402 
     Ethyl 6-(2-{5-bromo-2-[(1-methylethyl)oxy]phenyl}-1-cyclopenten-1-yl)-2-pyridinecarboxylate 
     
       
         
         
             
             
         
       
     
     A solution of ethyl 6-[2-(5bromo-2-hydroxyphenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylate (125 mg, 0.32 mmol) in dry THF (2 ml) was treated with diethyl azodicarboxylate (65 mg, 67 μl, 0.35 mmol), triphenylphosphine (84 mg, 0.35 mmol) and iso-butyl alcohol (22 mg, 27 μl, 0.3 mmol). The reaction mixture was stirred at room temperature overnight. The solvent was evaporated and the residue chromatographed using hexane/ethyl acetate 95:5 to give the title compound as a colourless oil. 
     LCMS: Rt=4.32 min. [M+H]=444, 446. 
     The following intermediates were prepared by a similar route to Ethyl 6-(2-{5-bromo-2-[(1-methylethyl)oxy]phenyl}-cyclopenten-1-yl)-2-pyridinecarboxylate from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
               
               
                 Structure 
                 Name 
                 LC/MS 
               
               
                   
               
             
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[5-bromo-2- (ethyloxy)phenyl]-1-cyclopenten- 1-yl}-2-pyridinecarboxylate 
                 Rt = 3.96 min. [M + H]= 416, 418 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-(2-{5-bromo-2- [(cyclopentylmethyl)oxy]phenyl}- 1-cyclopenten-1-yl)-2- pyridinecarboxylate 
                 Rt = 4.52 min. [M + H] = 470, 472 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-(2-{5-bromo-2- [(cyclohexylmethyl)oxy]phenyl}- 1-cyclopenten-1-yl)-2- pyridinecarboxylate 
                 Rt = 4.64 min [M + H] = 484, 486 
               
               
                   
               
            
           
         
       
     
     Ethyl 2-(acetylamino)-5-(2-{5-chloro-2-[(phenylmethyl)oxy]phenyl}-1-cyclopenten-1-yl)benzoate 
     
       
         
         
             
             
         
       
     
     A mixture of ethyl 2-amino-5-(2-{5-chloro-2-[(phenylmethyl)oxy]phenyl}-1-cyclopenten-1-yl)benzoate (75 mg, 0.17 mmol), acetyl chloride (21 mg, 0.3 mmol), and triethylamine (30 g, 42 μl, 0.3 mmol) in dichloromethane (3 ml) was stirred at room temperature for 30 mins. The solvent was evaporated and the residue was chromatographed eluting with ethyl acetate/hexane 1:4 to give the title compound as colourless glass. 
     Rt=4.08 min. [M+H]=490 
     The following intermediates were prepared by a similar route to ethyl 2-(acetylamino)-5-(2-{5-chloro-2-[(phenylmethyl)oxy]phenyl}-1-cyclopenten-1-yl)benzoate from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
               
               
                 Structure 
                 Name 
                 LC/MS 
               
               
                   
               
             
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 2-(acetylamino)-5-[2-(5-chloro-2- {[(4-fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]benzoate 
                 Rt = 4.09 min. [M + H] = 508 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 2-(acetylamino)-5-[2-(5-chloro-2- {[(2,4-difluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1-yl)benzoate 
                 Rt = 4.11 min. [M + H] = 526 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-(acetylamino)-5-(2-{5-chloro-2- [(phenylmethyl)oxy]-3-pyridinyl}-1- cyclopenten-1-yl)benzoate 
                 Rt = 4.04 min [M + H] = 491 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-(2-{5-chloro-2- [(phenylmethyl)oxy]-3-pyridinyl}-1- cyclopenten-1-yl)-5- (propanoylamino)benzoate 
                 Rt = 4.03 min. [M + H] = 505 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-(2-{5-chloro-2- [(phenylmethyl)oxy]-3-pyridinyl}-1- cyclopenten-1-yl)-5-[(2- methylpropanoyl)amino]benzoate 
                 Rt = 4.25 min. [M + H} = 519 
               
               
                   
               
            
           
         
       
     
     Ethyl 5-[2-(5-chloro-2-{[(4-fluorophenyl)methyl]oxy}-3-pyridinyl)-1-cyclopenten-1-yl]-2-methylbenzoate 
     
       
         
         
             
             
         
       
     
     Ethyl 5-[2-(5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)-1-cyclopenten-1-yl]-2-methylbenzoate (76 mg, 0.213 mmol) was dissolved in toluene (3 ml) and silver carbonate (65 mg, 0.234 mmol) and 4-fluorobenzyl bromide (29 □l, 0.234 mmol) added. The mixture was heated to reflux for 1 hour then stirred at room temperature for 16 hours. After filtration, the solution was washed with water, dried (MgSO 4 ) and evaporated. The residue was flash chromatographed eluting with 2% ethyl acetate/isohexane to give the title compound (47 mg). LC/MS Rt=4.47 min [MH + ] 466, 468. 
     The following intermediates were prepared by a similar route to ethyl 5-[2-(5-chloro-2-{[(4-fluorophenyl)methyl]oxy}-3-pyridinyl)-1-cyclopenten-1-yl]-2-methylbenzoate from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 COMPOUND NAME 
                 LC/MS 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,4- difluorophenyl) methyl]oxy}-3- pyridinyl)-1-cyclopenten-1-yl]-2- fluorobenzoate 
                 Rt = 4.46 min. [MH + ] 488, 490. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(4- fluorophenyl) methyl]oxy}-3-pyridinyl)- 1-cyolopenten-1-yl]-2-fluorobenzoate 
                 Rt = 4.42 min. [MH + ] 470, 472. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2- fluorophenyl) methyl]oxy}-3-pyridinyl)- 1-cyclopenten-1-yl]-2-fluorobenzoate 
                 Rt = 4.50 min. [MH + ] 470, 472. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,3- difluorophenyl)methyl]oxy}-3- pyridinyl)-1-cyclopenten-1-yl]-2- fluorobenzoate 
                 Rt = 4.40 min. [MH + ] 488, 490. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(3,4- difluorophenyl) methyl]oxy}-3- pyridinyl)-1-cyclopenten-1-yl]-2- fluorobenzoate 
                 Rt = 4.44 min. [MH + ] 488, 490. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,5- difluorophenyl)methyl]oxy}-3- pyridinyl)-1-cyclopenten-1-yl]-2- fluorobenzoate 
                 Rt = 4.43 min. [MH + ] 488, 490. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ethyl 5-{2-[5-chloro-2-({[2-fluoro-4- (trifluoromethyl)phenyl] methyl}oxy)- 3-pyridinyl]-1-cyclopenten-1-yl}-2- fluorobenzoate 
                 Rt = 4.32 min. [MH + ] 538, 540. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(4-chloro-2- fluorophenyl)methyl]oxy}-3-pyridinyl)- 1-cyclopenten-1-yl]-2-fluorobenzoate 
                 Rt = 4.32 min. [MH + ] 504, 506. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2-chloro-4- fluorophenyl)methyl]oxy}-3-pyridinyl)- 1-cyclopenten-1-yl]-2-fluorobenzoate 
                 Rt = 4.50 min. [MH + ] 504, 506. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,3,4- trifluorophenyl)methyl]oxy}-3- pyridinyl)-1-cyclopenten-1-yl]-2- fluorobenzoate 
                 Rt = 4.43 min. [MH + ] 506, 508. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,3,6- trifluorophenyl) methyl]oxy}-3- pyridinyl)-1-cyclopenten-1-yl]-2- fluorobenzoate 
                 Rt = 4.55 min. [MH + ] 506, 508. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,4,5- trifluorophenyl) methyl]oxy}-3- pyridinyl)-1-cyclopenten-1-yl]-2- fluorobenzoate 
                 Rt = 4.62 min. [MH + ] 506, 508. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(2,4,6- trifluorophenyl) methyl]oxy}-3- pyridinyl)-1-cyclopenten-1-yl]-2- fluorobenzoate 
                 Rt = 4.40 min. [MH + ] 506, 508. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-chloro-2-{[(3,4,5- trifluorophenyl) methyl]oxy}-3- pyridinyl)-1-cyclopenten-1-yl]-2- fluorobenzoate 
                 Rt = 4.49 min. [MH + ] 506, 508. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-[2-(5-chloro-2-{[(4- fluorophenyl) methyl]oxy}-3-pyridinyl)- 1-cyclopenten-1-yl]-5-fluorobenzoate 
                 Rt = 4.36 min. [MH + ] 470, 472. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-[2-(5-chloro-2-{[(2- fluorophenyl) methyl]oxy}-3-pyridinyl)- 1-cyclopenten-1-yl]-5-fluorobenzoate 
                 Rt = 4.38 min. [MH + ] 470, 472. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-[2-(5-chloro-2-{[(2,4- difluorophenyl) methyl]oxy}-3- fluorobenzoate 
                 Rt = 4.50 min. [MH + ] 488, 490. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-[2-(5-chloro-2-{[(2,6- difluorophenyl) methyl]oxy}-3- pyridinyl)-1-cyclopenten-1-yl]-5- fluorobenzoate 
                 Rt = 4.50 min. [MH + ] 488, 490. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-[2-(5-chloro-2-{[(2,4,6- trifluorophenyl) methyl]oxy}-3- pyridinyl)-1-cyclopenten-1-yl]-5- fluorobenzoate 
                 Rt = 4.53 min. [MH + ] 506, 508. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-[2-(5-chloro-2-{[(4-chloro-2- fluoro phenyl)methyl}oxy}-3-pyridinyl)- 1-cyclopenten-1-yl}-5-fluorobenzoate 
                 Rt = 4.72 min. [MH + ] 504, 506. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-{2-[5-chloro-2-({[2-fluoro-4- (trifluoromethyl)phenyl]methyl)oxy)-3- pyridinyl]-1-cyclopenten-1-yl)-5- fluorobenzoate 
                 Rt = 4.72 min. [MH + ] 538, 540. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-{2-[2-{[(2,4- difluorophenyl)methyl]oxy}-5- (trifluoromethyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2-fluorobenzoate 
                 Rt = 4.44 min. [MH + ] 522. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 2-fluoro-5-{2-[2-{[(4- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)-3-pyridinyl]-1- cyclopenten-1-yl}benzoate 
                 Rt = 4.41 min. [MH + ] 504. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 2-fluoro-5-(2-{2- [(phenylmethyl)oxy]-3-pyridinyl}-1- cyclopenten-1-yl)benzoate 
                 Rt = 4.14 min. [MH + ] 418. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-bromo-2-{[(4- fluorophenyl) methyl]oxy}-3-pyridinyl)- 1-cyclopenten-1-yl]-2-fluorobenzoate 
                 Rt = 4.36 min. [MH + ] 514, 516. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-bromo-2-{[(2-Chloro-4- fluoro phenyl)methyl]oxy}-3-pyridinyl)- 1-cyclopenten-1-yl]-2-fluorobenzoate 
                 Rt = 4.64 min. [MH + ] 548, 550. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-bromo-2-{[(2,4,6- trifluorophenyl) methyl]oxy}-3- pyridinyl)-1-cyclopenten-1-yl]-2- fluorobenzoate 
                 Rt = 4.44 min. [MH + ] 550, 552. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(5-bromo-2-{[(2- fluorophenyl) methyl]oxy}-3-pyridinyl)- 1-cyclopenten-1-yl]-2-fluorobenzoate 
                 Rt = 3.86 min. [MH + ] 514, 516. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-{2-[5-bromo-2-({[2-fluoro-4- (trifluoro methyl)phenyl]methyl}oxy)-3- pyridinyl]-1-cyclopenten-1-yl}-2- fluorobenzoate 
                 Rt = 4.61 min. [MH + ] 582, 584. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-(2-{2-[4- fluoro(phenylmethoxy)]-5- (trifluoromethyl)pyridin-3-yl}cyclopent- 1-en-1-yl)-pyridine-2-carboxylate 
                 LC/MS Rt = 4.11 min [MH + ] 487. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(4- chlorophenyl)methyl]oxy}-5- (trifluoromethyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.24 min [MH + ] 503 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2-chloro-4- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.28 min [MH + ] 521 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(4-chloro-2- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.28 min [MH + ] 521 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.11 min [MH + ] 487 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2,6- difluorophenyl)methyl]oxy}-5- (trifluoromethyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.08 min [MH + ] 505 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2-chloro-6- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.20 min [MH + ] 521 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(2,4- difluorophenyl)methyl]oxy}-5- (trifluoromethyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.13 min [MH + ] 505 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[5-(trifluoromethyl)-2-({[4- (trifluoromethyl)phenyl]methyl}oxy)-3- pyridinyl]-1-cyclopenten-1-yl}-2- pyrdininecarboxylate 
                 Rt = 4.25 min [MH + ] 537 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-{[(4-bromo-2- fluorophenyl)methyl]oxy}-5- (trifluoromethyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.31 min [MH + ] 565, 567 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-{2-[2-({[2-fluoro-4- (trifluoromethyl)phenyl]methyl}oxy)-5- (trifluoromethyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.29 min [MH + ] 555 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-(trifluoromethyl)-2- {[(2,4,5-trifluorophenyl)methyl]oxy}- 3-pyridinyl)-1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.17 min [MH + ] 523 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 6-[2-(5-(trifluoromethyl)-2- {[(2,3,6-trifluorophenyl)methyl]oxy}- 3-pyridinyl)-1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.10 min [MH + ] 523 
               
               
                   
               
            
           
         
       
     
     (4-Fluorophenyl)methyl 2-fluoro-5-[2-(2-{[(4-fluorophenyl)methyl]oxy}-3-pyridinyl)-1-cyclopenten-1-yl]benzoate 
     
       
         
         
             
             
         
       
     
     2-Fluoro-5-[2-(2-oxo-1,2-dihydro-3-pyridinyl)-1-cyclopenten-1-yl]benzoic acid (65 mg, 0.217 mmol) was dissolved in toluene (2 ml) and silver carbonate (1 32 mg, 0.478 mmol) and 4-fluorobenzyl bromide (60 μl, 0.478 mmol) added. The mixture was heated to reflux for 16 hours. After filtration and dilution with ethyl acetate, the solution was washed with water, dried (MgSO 4 ) and evaporated. The residue was flash chromatographed eluting with 3% ethyl acetate/isohexane to give the title compound (32 mg). 
     LC/MS Rt=4.40 min [MH + ] 516. 
     The following intermediates were prepared by a similar route to (4-fluorophenyl)methyl 2-fluoro-5-[2-(2-{[(4-fluorophenyl)methyl]oxy}-3-pyridinyl)-1-cyclopenten-1-yl]benzoate from the appropriate intermediates. 
     
       
         
           
               
               
               
             
               
                   
               
               
                 Structure 
                 COMPOUND NAME 
                 LCMS 
               
               
                   
               
             
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (2,4-Difluorophenyl) methyl 5-[2-(2- {[(2,4-difluorophenyl)methyl]oxy}-3- pyridinyl)-1-cyclopenten-1-yl]-2- fluorobenzoate 
                 Rt = 4.64 min [MH + ] 552. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (4-Fluorophenyl)methyl 2-fluoro-5- [2-(2-{[(4-fluorophenyl)methyl]oxy}- 3-pyridinyl)-1-cyclopenten-1- yl]benzoate 
                 Rt = 4.37 min [MH + ] 516. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Phenylmethyl 5-(2-{5-bromo-2- [(phenylmethyl)oxy]-3-pyridinyl}-1- cyclopenten-1-yl)-2-fluorobenzoate 
                 Rt = 4.64 min [MH + ] 558, 560. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (2,4-Difluorophenyl) methyl 5-[2-(5- bromo-2-{[(2,4-difluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2-fluorobenzoate 
                 Rt = 4.66 min [MH + ] 630, 632. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Phenylmethyl 6-(2-{2- [(phenylmethyl)oxy]-3-pyridinyl}-1- cyclopenten-1-yl)-2- pyridinecarboxylate 
                 Rt = 4.04 min [MH + ] 463. 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (4-Fluorophenyl)methyl 3-[2-(5- bromo-2-{[(4-fluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl]benzoate 
                 Rt = 4.63 min [MH + ] 576, 578 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (2,4-Difluorophenyl)methyl 3-[2-(5- bromo-2-{[(2,4-difluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl]benzoate 
                 Rt = 4.46 min [MH + ] 612, 614 
               
               
                   
               
            
           
         
       
     
     Ethyl 2-fluoro-5-{2-[2-(phenylmethoxy)-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}benzoate 
     
       
         
         
             
             
         
       
     
     2-(Phenylmethoxy)-5-(trifluoromethyl)pyridine-3-boronic acid (10.32 g, 34.7 mmol) and ethyl 5-(2-bromocyclopent-1-enyl)-2-fluorobenzoate (5.44 g, 17.4 mmol) were dissolved in dimethoxyethane (120 mL) under nitrogen, and Pd(PPh 3 ) 4  (1.00 g, 0.87 mmol) and 2N aqueous sodium carbonate solution (60 ml) were added. The mixture was heated at 80° C. for 18 hours, but TLC analysis showed incomplete reaction. Further Pd(PPh 3 ) 4  was added and heating was continued for 3 hours. After cooling, the solvents were removed in vacuo, and the residue was partitioned between diethyl ether and water. The aqueous was extracted with further ether, and the combined organic extracts were dried (Na 2 SO 4 ) and concentrated in vacuo. The resulting dark brown oil was purified by flash chromatography on silica (gradient elution, 0-6% ethyl acetate/cyclohexane) to give the title compound (7.02 g). LC/MS Rt=4.23 min [MH + ] 485. 
     Ethyl 2-fluoro-5-(2-{2-[(4-fluorophenyl)methoxy]-5-(trifluoromethyl)pyridin-3-yl}cyclopent-1-en-1-yl)-benzoate 
     
       
         
         
             
             
         
       
     
     Ethyl 2-fluoro-5-{2-[2-hydroxy-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}benzoate (250 mg, 0.633 mmol) was dissolved in toluene (4 ml), and silver carbonate (210 mg, 0.764 mmol) and 4-fluorobenzyl bromide (1 30 mg, 1.45 mmol) added. The mixture was heated to reflux for 5.5 hours. The mixture was concentrated in vacuo, and the residue was partitioned between water and dichloromethane. The organic extract was concentrated in vacuo. The residue was purified by flash chromatography on silica (gradient elution, 0-4% ethyl acetate/cyclohexane) to give the title compound. 
     LC/MS Rt=4.31 min [MH + ] 504. 
     The following compounds (table) were prepared by the same method from ethyl 2-fluoro-5-{2-[2-hydroxy-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}benzoate by reaction with appropriately substituted benzyl bromides. 
     
       
         
           
               
               
               
             
               
                   
               
               
                 STRUCTURE 
                 COMPOUND NAME 
                 LCMS 
               
               
                   
               
             
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{2-[(2,4- difluorophenyl) methoxy]-5- (trifluoromethyl) pyridin-3- yl}cyclopent-1-en-1-yl)-2- fluorobenzoate 
                 Rt = 4.33 min [MH + ] 522 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 2-fluoro-5-(2-{2-[(2- fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)- benzoate 
                 Rt = 4.32 min [MH + ] 504 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{2-[(2,6- difluorophenyl) methoxy]-5- (trifluoromethyl) pyridin-3- yl}cyclopent-1-en-1-yl)-2- fluorobenzoate 
                 Rt = 4.30 min [MH + ] 522 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{2-[(2-chloro-4- fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)-2- fluorobenzoate 
                 Rt = 4.45 min [MH + ] 539 
               
               
                   
               
            
           
         
       
     
     Ethyl 3-fluoro-5-{2-[2-(phenylmethoxy)-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}benzoate 
     
       
         
         
             
             
         
       
     
     2-(Phenylmethoxy)-5-(trifluoromethyl)pyridine-3-boronic acid (10.53 g, 33.6 mmol) and ethyl 5-(2-bromocyclopent-1-enyl)-3-fluorobenzoate (5.93 g, 20.0 mmol) were dissolved in dimethoxyethane (120 mL) under nitrogen, and Pd(PPh 3 ) 4  (1.15 g, 1.0 mmol) and 2N aqueous sodium carbonate solution (60 ml) were added. The mixture was heated at 80° C. for 18 hours. After cooling, the solvents were removed in vacuo, and the residue was partitioned between diethyl ether and water. The aqueous was extracted with further ether, and the combined organic layers were dried (Na 2 SO 4 ) and concentrated in vacuo. The resulting dark brown oil was purified by flash chromatography on silica (gradient elution, 0-4% ethyl acetate/cyclohexane) to give the title compound (7.42 g). 
     LC/MS Rt=4.32 min [MH + ] 485. 
     Ethyl 3-amino-5-{2-[2-(phenylmethoxy)-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}benzoate 
     
       
         
         
             
             
         
       
     
     2-(Phenylmethoxy)-5-(trifluoromethyl)pyridine-3-boronic acid (6.0 g, 20.2 mmol) and ethyl 3-amino-5-(2-bromocyclopent-1-enyl)benzoate (3.16 g, 10.1 mmol) were dissolved in dimethoxyethane (50 mL) under nitrogen, and Pd(PPh 3 ) 4  (0.58 g, 0.5 mmol) and 2N aqueous sodium carbonate solution (10 ml) were added. The mixture was heated at 80° C. for 18 hours. After cooling, the solvents were removed in vacuo, and the residue was partitioned between diethyl ether and water. The aqueous was extracted with further ether (×2), and the combined organic layers were dried (Na 2 SO 4 ) and concentrated in vacuo. The resulting dark brown oil was purified using an acidic solid phase cartridge (Isolute® Flash SCX-2, 50 g), loading the crude material as a methanol solution and eluting with 1 0% aqueous ammonia in methanol. Concentration of the relevant fractions in vacuo gave the title compound (4.01 g). LC/MS Rt=4.01 min [MH + ] 483. 
     General Procedure 
     
       
         
         
             
             
         
       
     
     Ethyl 5-{2-[2-(hydroxy)-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}-3-(trifluoroacetamido)benzoate (122 mg, 0.25 mmol) was dissolved in toluene (4 ml), together with silver carbonate (76 mg, 0.275 mmol) and a substituted benzyl bromide (1.1 equiv.), and this was heated to reflux for 18 hours. The mixture was filtered and concentrated in vacuo. The residue was-purified by flash chromatography on silica (gradient elution, 0-10% ethyl acetate/cyclohexane). 
     The following compounds were prepared by the above General Procedure from ethyl 2-fluoro-5-{2-[2-hydroxy-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}benzoate by reaction with appropriately substituted benzyl bromides. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 COMPOUND NAME 
                 LCMS 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{2-[(4- fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)-3- (trifluoroacetamido)benzoate 
                 Rt = 4.27 min [MH + ] 597 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{2-[(2,4- difluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)-3- (trifluoroacetamido)benzoate 
                 Rt = 4.29 min [MH + ] 615 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{2-[(2- fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)-3- (trifluoroacetamido)benzoate 
                 Rt = 4.28 min [MH + ] 597 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{2-[(2,6- difluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)-3- (trifluoroacetamido)benzoate 
                 Rt = 4.25 min [MH + ] 615 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{2-[(2-chloro-4- fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl-3- (trifluoroacetamido)benzoate 
                 Rt = 4.30 min [MH + ] 631 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{2-[(4-chloro-2- fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)-3- (trifluoroacetamido)benzoate 
                 Rt = 4.29 min [MH + ] 631 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-(trifluoroacetamido)-5-(2- {5-(trifluoromethyl)-2-[(2,4,6- trifluorophenyl) methoxy]pyridin- 3-yl}cyclopent-1-en-1-yl)- benzoate 
                 Rt = 4.17 min [MH + ] 633 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-(trifluoroacetamido)-5-(2- {5-(trifluoromethyl)-2-[(2,4,5- trifluorophenyl) methoxy]pyridin- 3-yl}cyclopent-1-en-1-yl)- benzoate 
                 Rt = 4.30 min [MH + ] 633 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-(trifluoroacetamido)-5-(2- {5-(trifluoromethyl)-2-[(2,3,6- trifluorophenyl) methoxy]pyridin- 3-yl}cyclopent-1-en-1-yl)- benzoate 
                 Rt = 4.26 min [MH + ] 633 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 3-(trifluoroacetamido)-5-[2- (5-[trifluoromethyl]-2-{[4- (trifluoromethyl)phenyl] methoxy}pyridin-3-yl)cyclopent- 1-en-1-yl]- benzoate 
                 Rt = 4.37 min [MH + ] 647 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-[2-(2-{[2-fluoro-4- (trifluoromethyl)phenyl]methoxy}- 5-[trifluoromethyl]pyridin-3- yl)cyclopent-1-en-1-yl]-3- (trifluoroacetamido)benzoate 
                 Rt = 4.40 min [MH + ] 665 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{2-[(2-chloro-6- fluorophenyl)methoxy}-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)-3- (trifluoroacetamido)benzoate 
                 Rt = 4.32 min [MH + ] 631 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Ethyl 5-(2-{2-[(4-bromo-2- fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)-3- (trifluoroacetamido)benzoate 
                 Rt = 4.39 min [MH + ] 675, 677 
               
               
                   
               
            
           
         
       
     
     PREPARATION OF EXAMPLES 
     Example 1 
     6-{2-[2-{[(2,4-Dichlorophenyl)methyl]oxy}-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylic acid 
     
       
         
         
             
             
         
       
     
     (2,4-Dichlorophenyl)methyl 6-{2-[2-{[(2,4-dichlorophenyl)methyl]oxy}-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylate (0.095 g), ethanol (2 ml) and 2M sodium hydroxide solution were heated in a Smithcreator® microwave to 120° C. for 3 minutes. After cooling the reaction was diluted with ethyl acetate and washed with dilute citric acid and brine, dried over MgSO 4 , filtered and concentrated in vacuo to yield a yellow oil which was freeze-dried from acetonitrile/H 2 O to give the title compound as an off-white solid. 
       1 H-NMR (CDCl 3 ) δ: 2.12-2.21 (2H, m), 2.91-2.98 (2H, m), 3.02-3.10 (2H, m), 5.03 (2H, s), 7.04 (1H, d), 7.08-7.16 (2H, m), 7.29 (1H, d), 7.35 (1H, d), 7.41 (1H, d), 7.58 (1H, dd), 7.72 (1H, t), 7.90 (1H, d). LC/MS Rt=4.50 min, [MH + ] 508, 510, 512. 
     Example 2 
     6-{2-[2-{[(2,6-Difluorophenyl)methyl]oxy}-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylic acid 
     
       
         
         
             
             
         
       
     
     Procedure as for 6-{2-[2-{[(2,4-dichlorophenyl)methyl]oxy}-5-(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylic acid. 
     LC/MS t=3.83, [MH + ] 476. 
     Example 3 
     6-[2-(5-(trifluoromethyl)-2-{[(2,4,6-trifluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyrazinecarboxylic acid 
     
       
         
         
             
             
         
       
     
     6-{2-[2-Hydroxy-5(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyrazinecarboxylic acid (0.15 g, 0.43 mmol), 2,4,6-trifluorobenzyl bromide (0.192 g, 0.86 mmol), potassium carbonate (0.13 g, 0.94 mmol) and potassium iodide (0.014 g, 0.086 mmol) were refluxed in methanol (10 ml) for 1 hour. The solvent was then removed in vacuo, the residue taken up in ethyl acetate and washed with acidified water (pH3). The aqueous layer was washed with ethyl acetate (×2). The combined organic layers were washed with brine, dried over MgSO 4 , filtered and concentrated in vacuo to yield a yellow oil. This was purified by preparative HPLC to yield the title compound as an off-white solid (0.075 g). 
       1 H-NMR (MeOD) δ: 2.02-2.11 (2H, m), 2.85-2.93 (2H, m), 3.01-3.09 (2H, m), 5.04 (2H, s), 6.82 (2H, t), 7.35 (1H, d), 7.44 (1H, s), 7.64 (1H, d), 8.10 (1H, s), 8.86 (1H, s). 
     LC/MS Rt=3.90 min, [MH + ] 495. 
     Example 4 
     6-{2-[2-{[(2,6-Difluorophenyl)methyl]oxy}-5(trifluoromethyl)phenyl]-1-cyclopenten-1-yl}-2-pyrazinecarboxylic acid 
     
       
         
         
             
             
         
       
     
     Procedure as for 6-[2-(5-(trifluoromethyl)-2-{[(2,4,6-trifluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyrazinecarboxylic acid. LC/MS Rt=3.92 min, [MH + ] 477. 
     Standard Hydrolysis Procedure A 
     
       
         
         
             
             
         
       
     
     The ester (0.5 mmol) was dissolved in methanol or ethanol (2 ml) and 2M sodium hydroxide (1 ml) added. The mixture was either stirred at from room temperature to reflux for from 30 minutes to 20 hours until the reaction was complete by tic or heated at 120° C. in a Smithcreator® microwave for 3 minutes. The solution was diluted with water then extracted with isohexane or diethyl ether and acidified to pH4 with either hydrochloric acid, citric acid or acetic acid. The mixture was extracted with diethyl ether or dichloromethane. The organic solution was dried over magnesium sulphate and evaporated to give the title compound. 
     Standard Hydrolysis Procedure B 
     
       
         
         
             
             
         
       
     
     The ester (0.5 mmol) was dissolved in methanol or ethanol (2 ml) and 2M sodium hydroxide (1 ml) added. The mixture was stirred at from room temperature to reflux for from 30 minutes to 20 hours until the reaction was complete by tic or heated at 120° C. in a Smithcreator® microwave for 3 minutes then evaporated to dryness. The residue was dissolved in water/ethyl acetate or dichloromethane and the organic phase dried (magnesium sulphate), evaporated and the residue either dissolved in a small volume of ether and iso-hexane added to precipitate the salt or dissolved in dioxan and water and freeze-dried. 
     The following Examples were prepared by Standard Hydrolysis Procedure A: 
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 Example 
                 Structure 
                 Name 
                 Data 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                 5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2,3- Difluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1- yl}-2-pyridinecarboxylic acid 
                 LC/MS Rt = 3.91, [MH + ] 476 
               
               
                   
               
               
                 6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(4- Chlorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1-yl}- 2-pyridinecarboxylic acid 
                 LC/MS Rt = 3.97, [MH+] 474, 476 
               
               
                   
               
               
                 7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-(Trifluoro- methyl)-2-{[(2,4,6- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 LC/MS Rt = 3.82, [MH + ] 494 
               
               
                   
               
               
                 8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(4-Chloro-2- fluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1- yl}-2-pyridinecarboxylic acid 
                 LC/MS Rt = 4.05, [MH + ] 492, 494 
               
               
                   
               
               
                 9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2- Fluorophenyl)methyl) oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1-yl}- 2-pyridinecarboxylic acid 
                 LC/MS Rt = 3.83, [MH + ] 458 
               
               
                   
               
               
                 10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2-Chloro- phenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}- 2-pyridinecarboxylic acid 
                 LC/MS Rt = 4.05, [MH + ] 474, 476 
               
               
                   
               
               
                 11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(4-Bromo- phenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}- 2-pyridinecarboxylic acid 
                 LC/MS Rt = 4.08, [MH + ] 518, 520. 
               
               
                   
               
               
                 12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(4-Bromo-2- fluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1-yl}- 2-pyridinecarboxylic acid 
                 LC/MS Rt = 4.13, [MH + ] 536, 538. 
               
               
                   
               
               
                 13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2-Chloro-4- fluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1-yl}- 2-pyridinecarboxylic acid 
                 LC/MS Rt = 4.07 [MH + ] 492, 494. 
               
               
                   
               
               
                 14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2-Chloro-6- fluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1-yl}- 2-pyridinecarboxylic acid 
                 LC/MS Rt = 3.93 [MH + ] 492, 494 
               
               
                   
               
               
                 15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-(Trifluoromethyl)- {[(2,3,6-trifluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 LC/MS Rt = 3.83 [MH + ] 494 
               
               
                   
               
               
                 16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2- Bromophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1-yl}- 2-pyridinecarboxylic acid 
                 LC/MS Rt = 4.10 [MH + ] 518, 520 
               
               
                   
               
               
                 17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(4- Fluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten]- 1-yl}-2-pyrazinecarboxylic acid 
                 LC/MS Rt = 3.93 [MH + ] 459. 
               
               
                   
               
               
                 18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2,4- Difluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1-yl}- 2-pyrazinecarboxylic acid 
                 LC/MS Rt = 4.00, [MH + ] 477. 
               
               
                   
               
               
                 19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(4- Chlorophenyl)methyl] oxy}-5-fluoromethyl) phenyl]-1-cyclopenten-1- yl}-2-pyrazinecarboxylic acid 
                 LC/MS Rt = 4.08, [MH + ] 475, 477 
               
               
                   
               
               
                 20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2- Fluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1-yl}- 2-pyrazinecarboxylic acid 
                 LC/MS Rt = 3.89, [MH + ] 459 
               
               
                   
               
               
                 21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(4- Bromophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1-yl}- 2-pyrazinecarboxylic acid 
                 LC/MS Rt = 4.09, [MH + ] 517, 519 
               
               
                   
               
               
                 22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(4-Bromo-2- fluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1-yl}- 2-pyrazinecarboxylic acid 
                 LC/MS Rt = 4.15, [MH + ] 537, 539 
               
               
                   
               
               
                 23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2-Chloro-4- fluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyctopenten-1-yl)- 2-pyrazinecarboxylic acid 
                 LC/MS Rt = 4.04, [MH + ] 493/495 
               
               
                   
               
               
                 24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.09- 2.15 (2H, m), 2.86-2.92 (2H, m), 2.98-3.04 (2H, m), 4.97 (2H, s), 6.93-7.02 (3H, m), 7.05-7.11 (2H, m), 7.23-7.27 (3H, m), 7.61-7.72 (1H, bs), 7.86- 7.93 (1H, bs). LC/MS Rt = 3.60, [MH+] 424, 426, 427 [MH−] 422, 424 
               
               
                   
               
               
                 25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2- chloro-6- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.02- 2.06 (2H, m), 2.78-2.84 (2H, m), 2.93-2.97 (2H, m), 5.05 (2H, s), 6.90 (1H, t), 7.07-7.09 (3H, m), 7.15-7.21 (2H, m), 7.21- 7.28 (1H, m), 7.63-7.67 (1H, m), 7.86 (1H, d). LC/MS Rt = 3.68, [MH+] 458, 461 [MH−] 456, 459 
               
               
                   
               
               
                 26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2- chlorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.11- 2.15 (2H, m), 2.90-2.94 (2H, m), 3.02-3.06 (2H, m), 5.00 (2H, s), 6.92 (1H, d), 7.12-7.18 (3H, m), 7.19-7.31 (4H, m), 7.69 (1H, t), 7.89 (1H, d). LC/MS Rt = 3.79, [MH+] 440, 443 [MH−] 438, 441 
               
               
                   
               
               
                 27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2- methylphenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.07- 2.1 (2H, m), 2.85-2.89 (2H, m), 2.98-3.02 (2H, m), 4.8 (2H, s), 6.94 (1H, d), 7.06-7.09 (4H, m), 7.14-7.18 (1H, m), 7.23- 7.26 (2H, m), 7.64-7.68 (1H, m), 7.87 (1H, d). LC/MS Rt = 3.68, [MH+] 420, 422 [MH−] 418, 420 
               
               
                   
               
               
                 28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- {[(2,6-dichlorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.01- 2.05 (2H, m), 2.85-2.87 (2H, m), 2.91-2.95 (2H, m), 5.24 (2H, s), 7.09-7.32 (7H, m), 7.63-7.67 (1H, m), 7.86 (1H, d). LC/MS Rt = 3.81, [MH+] 476, 478 [MH−] 474, 476 
               
               
                   
               
               
                 29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- {[(2,4-dimethylphenyl) methyl]oxy}phenyl)- 1-cyclopenten-1-yl]- 2-pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.05- 2.11 (2H, m), 2.14 (3H, s), 2.26 (3H, s), 2.85-2.89 (2H, m), 2.97-3.01 (2H, m), 4.85 (2H, s), 6.88 (1H, s), 6.92-6.96 (2H, m), 7.08 (1H, s), 7.22-7.26 (3H, m), 7.66 (1H, t), 7.87 (1H, d). LC/MS Rt = 3.81, [MH+] 434, 436 [MH−] 432, 434 
               
               
                   
               
               
                 30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- {[(2,3,6- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.03- 2.11 (2H, m), 2.81-2.85 (2H, m), 2.95-2.99 (2H, m), 5.0 (2H, s), 6.73-6.75 (1H, m), 7.03-7.09 (3H, m), 7.25-7.29 (2H, m), 7.68 (1H, t), 7.88 (1H, d). LC/MS Rt = 3.60, [MH+] 460, 463 
               
               
                   
               
               
                 31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4-Bromo-2- fluorophenyl)methyl] oxy}-5-chlorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.08- 2.13 (2H, m), 2.86-2.89 (2H, m), 2.99-3.03 (2H, m), 4.93 (2H, s), 6.93 (1H, d), 6.99 (1H, t), 7.01 (1H, s), 7.14-7.18 (2H, m), 7.25-7.27 (2H, m), 7.71 (1H, t), 7.91 (1H, d). LC/MS Rt = 3.86, [MH+] 504, 506 [MH−] 502, 503 
               
               
                   
               
               
                 32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- {[(2,5- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.13- 2.16 (2H, m), 2.89-2.93 (2H, m), 3.02-3.07 (2H, m), 4.94 (2H, s), 6.78-6.81 (1H, m), 6.90-6.96 (3H, m), 7.14 (1H, bs), 7.25- 7.27 (2H, m), 7.69-7.71 (1H, m), 7.86-7.89 (1H, m). LC/MS Rt = 3.86, [MH+] 504, 506 [MH−] 502, 503 
               
               
                   
               
               
                 33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.10- 2.18 (2H, m), 2.91-2.95 (2H, m), 3.02-3.06 (2H, m), 4.94 (2H, s), 6.96-7.29 (7H, m), 8.53 (1H, s), 9.04 (1H, s). LC/MS Rt = 4.32, [MH+] 425, 427 [MH−] 423, 425 
               
               
                   
               
               
                 34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2- chlorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.12- 2.20 (2H, m) 2.94-2.97 (2H, m), 3.05-3.08 (2H, m), 4.98 (2H, s), 6.95 (1H, d), 7.12-7.31 (6H, m), 8.55 (1H, s), 9.03 (1H, s). LC/MS Rt = 4.65, [MH+] 441, 444 [MH−] 439, 443 
               
               
                   
               
               
                 35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-chloro-2-{[(2- chloro-6- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.06- 2.10 (2H, m), 2.85-2.88 (2H, m), 2.96-2.99 (2H, m), 5.02 (2H, s), 6.90 (1H, t, J = 8.9 Hz), 7.06- 7.12 (2H, m), 7.16-7.2 (2H, m), 7.30 (1H, dd, J = 8.8 J = 2.6 Hz), 8.48 (1H, s), 9.03 (1H, s). LC/MS Rt = 4.40, [MH+] 459, 462 [MH−] 457, 460 
               
               
                   
               
               
                 36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- [[(2,6- dichlorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.05- 2.09 (2H, m), 2.85-2.89 (2H, m), 2.94-2.97 (2H, m), 5.11 (2H, s), 7.09 (1H, d, J = 8.8 Hz), 7.06- 7.12 (2H, m), 7.15-7.32 (5H, m), 8.48 (1H, s), 9.02 (1H, s). LC/MS Rt = 4.62, [MH+] 477, 479 [MH−] 475, 477 
               
               
                   
               
               
                 37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- {[(2,4- dichlorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.97- 2.03 (2H, m), 2.81-2.85 (2H, m), 2.95-2.98 (2H, m), 5.10 (2H, s), 7.06 (1H, d), 7.17 (1H, d), 7.26 (1H, d), 7.33 (1H, dd), 7.43 (1H, dd), 7.63 (1H, d), 7.80 (1H, s), 8.58 (1H, s). LC/MS Rt = 4.92, [MH+] 477, 479 [MH−] 475, 477 
               
               
                   
               
               
                 38 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- {[(2,6- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.89- 1.97 (2H, m), 2.75-2.79 (2H, m), 2.89-2.93 (2H, m), 5.06 (2H, s), 7.03- 7.11 (3H, m), 7.30 (1H, d), 7.38-7.47 (2H, m), 7.96 (1H, s), 8.75 (1H, s). LC/MS Rt = 4.65, [MH+] 443, 445 [MH−] 441, 443 
               
               
                   
               
               
                 39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2- Bromophenyl)methyl] oxy}-5-chlorophenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.14- 2.18 (2H, m), 2.94-2.98 (2H, m), 3.05-3.09 (2H, m), 4.95 (2H, s), 6.94 (1H, d), 7.11-7.19 (4H, m), 7.27-7.29 (1H, m), 7.48 (1H, d), 8.54 (1H, s), 9.03 (1H, s). LC/MS Rt = 4.75, [MH+] 487, 489 [MH−] 485, 487 
               
               
                   
               
               
                 40 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4- Bromophenyl)methyl] oxy}-5-chlorophenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.12- 2.16 (2H, m), 2.91-2.95 (2H, m), 3.05-3.09 (2H, m), 4.85 (2H, s), 6.88 (1H, d), 6.99 (2H, d), 7.11 (1H, bs), 7.23-7.25 (1H, m), 7.39 (2H), 8.51 (1H, s), 9.04 (1H, s). LC/MS Rt = 4.64, [MH+] 487, 488 [MH−] 485, 487 
               
               
                   
               
               
                 41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2- chloro-4- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.13- 2.17 (2H, m), 2.91-2.95 (2H, m), 3.05-3.08 (2H, m), 4.94 (2H, s), 6.89- 6.95 (2H, m), 7.07 (1H, dd), 7.11-7.15 (2H, m), 7.27-7.30 (1H, m), 8.55 (1H, s), 9.06 (1H, s). LC/MS Rt = 4.59, [MH+] 459, 462 [MH−] 457, 461 
               
               
                   
               
               
                 42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- {[(2,5- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.12- 2.21 (2H, m), 2.92-2.98 (2H, m), 3.03-3.11 (2H, m), 4.94 (2H, s), 6.78- 6.84 (1H, m), 6.91-6.98 (3H, m), 7.15 (1H, s), 7.26-7.31 (1H, m), 8.55 (1H, s), 9.06 (1H, s). LC/MS Rt = 4.29, [MH+] 443, 445 [MH−] 441, 443 
               
               
                   
               
               
                 43 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- {[(3,4- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.15- 2.21 (2H, m), 2.91-2.97 (2H, m), 3.08-3.11 (2H, m), 4.86 (2H, s), 6.81- 6.85 (1H, m), 6.89 (1H, d), 6.92-6.97 (1H, m), 7.03-7.12 (1H, m), 7.14 (1H, s), 7.26-7.31 (1H, m), 8.58 (1H, s), 9.08 (1H, s). LC/MS Rt = 4.29, [MH+] 443, 445 [MH−] 441, 443 
               
               
                   
               
               
                 44 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- {[(2,3- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.12- 2.19 (2H, m), 2.89-2.95 (2H, m), 3.03-3.10 (2H, m), 4.98 (2H, s), 6.81- 6.87 (1H, m), 6.92- 6.97 (2H, m), 7.04-7.14 (2H, m), 7.26-7.31 (1H, m), 8.56 (1H, s), 9.06 (1H, s). LC/MS Rt = 4.34, [MH+] 443, 445 [MH−] 441 
               
               
                   
               
               
                 45 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2- methylphenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.95- 2.03 (2H, m), 2.19 (3H, s), 2.83-2.86 (2H, m), 2.96- 3.0 (2H, m), 5.01 (2H, s), 7.08-7.18 (5H, m), 7.23 (1H, d), 7.36 (1H, dd), 8.03 (1H, s), 8.73 (1H, s). LC/MS Rt = 4.42, [MH+] 421, 423 [MH−] 419, 421 
               
               
                   
               
               
                 46 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-chloro-2-{[(4- methylphenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.96- 2.03 (2H, m), 2.25 (3H, s), 2.84-2.86 (2H, m), 2.95- 2.99 (2H, m), 4.97 (2H, s), 7.02-7.14 (6H, m), 7.31 (1H, dd, J = 8.8, 2.8 Hz), 7.95 (1H, s), 8.69 (1H, s). LC/MS Rt = 4.42, [MH+] 421 [MH−] 419, 421 
               
               
                   
               
               
                 47 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- {[(2,4-dimethylphenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.91- 1.99 (2H, m), 2.13 (3H, s), 2.21 (3H, s), 2.83-2.90 (2H, m), 2.96-3.0 (2H, m), 4.94 (2H, s), 6.95- 7.04 (3H, m), 7.18-7.24 (2H, m), 7.36-7.40 (1H, m), 8.10 (1H, s), 8.77 (1H, s), 13.65 (1H, s). LC/MS Rt = 4.64, [MH+] 435 [MH−] 433, 436 
               
               
                   
               
               
                 48 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4-Bromo-2- fluorophenyl)methyl] oxy}-5-chlorophenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.12- 2.16 (2H, m), 2.87- 2.91 (2H, m), 2.99-3.07 (2H, m), 4.91 (2H, s), 6.93-7.01 (2H, m), 7.12 (1H, bs), 7.18 (1H, d), 7.26-7.29 (1H, m), 8.53 (1H, s), 9.07 (1H, s). LC/MS Rt = 4.64, [MH+] 505, 507 [MH−] 502, 505 
               
               
                   
               
               
                 49 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2-Bromo-4- fluorophenyl)methyl] oxy}-5-chlorophenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.13- 2.17 (2H, m), 2.92- 2.96 (2H, m), 3.05-3.09 (2H, m), 4.92 (2H, s), 6.92-6.96 (2H, m), 7.10- 7.14 (2H, m), 7.24-7.30 (2H, m), 8.54 (1H, s), 9.06 (1H, s). LC/MS Rt = 4.67, [MH+] 505, 507 [MH−] 503, 505 
               
               
                   
               
               
                 50 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[5-Chloro-2-({[2- fluoro-4- (trifluoromethyl)phenyl] methyl}oxy)phenyl]- 1-cyclopenten-1-yl}-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.99- 2.03 (2H, m), 2.85- 2.88 (2H, m), 2.97-3.01 (2H, m), 5.15 (2H, s), 7.18 (1H, d), 7.23 (1H, d), 7.37 (1H, dd), 7.42 (1H, t), 7.54 (1H, d), 7.63 (1H, d), 8.06 (1H, s), 8.74 (1H, s). LC/MS Rt = 4.46, [MH+] 493, 495 [MH−] 491, 493 
               
               
                   
               
               
                 51 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- {[(2,4,6- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.91- 1.99 (2H, m), 2.78-2.81 (2H, m), 2.90-2.94 (2H, m), 4.96 (2H, s), 7.12 (2H, t), 7.21 (1H, d), 7.28 (1H, d), 7.39 (1H, dd), 8.07 (1H, s), 8.81 (1H, s), 13.65 (1H, s). LC/MS Rt = 4.20, [MH+] 461, 463 [MH−] 459, 461 
               
               
                   
               
               
                 52 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(4- chloro-2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.96- 2.04 (2H, m), 2.78-2.83 (2H, m), 2.90-2.98 (2H, m), 5.04 (2H, s), 7.12- 7.24 (4H, m), 7.32-7.40 (2H, m), 8.07 (1H, s), 8.79 (1H, s). LC/MS Rt = 4.55, [MH+] 459, 462 [MH−] 457, 460 
               
               
                   
               
               
                 53 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(4- chlorophenyl)methyl] oxy)phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.91- 2.05 (2H, m), 2.86-2.90 (2H, m), 2.98-3.01 (2H, m), 4.99 (2H, s), 7.12- 7.18 (4H, m), 7.33-7.46 (3H, m), 8.06 (1H, s), 8.74 (1H, s). LC/MS Rt = 4.51, [MH+] 441, 444 [MH−] 439, 442 
               
               
                   
               
               
                 54 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2- {[(2,4-dichlorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 LC/MS Rt = 4.01, [MH+] 476, 478 
               
               
                   
               
               
                 55 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2-Bromo-4- fluorophenyl)methyl] oxy}-5-chlorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 LC/MS Rt = 4.01, [MH+] 504, 506 [MH−] 502, 503 
               
               
                   
               
               
                 56 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Chloro-2-[(2- methylpropyl)oxy]phenyl}- 1-cyclopenten-1-yl)-2- pyridinecarboxylic acid 
                 LC/MS Rt = 3.96,  [MH+] 372, 374 
               
               
                   
               
               
                 57 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Chloro-2- [(cyclopentylmethyl)oxy] phenyl}-1-cyclopenten-1- yl)-2-pyridinecarboxylic acid 
                 LC/MS Rt = 4.26, [MH+] 398, 400 [MH−] 396, 398 
               
               
                   
               
               
                 58 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4- Fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.95-2.03 (2H, m), 2.83- 2.87 (2H, m), 2.99-3.33 (2H, m), 5.01 (2H, s), 6.90-6.92 (1H, m), 6.99 (1H, d), 7.04 (1H, dd), 7.09-7.13 (3H, m), 7.22- 7.28 (3H, m), 7.58-7.62 (1H, m), 7.74 (1H, d), 12.55-12.95 (1H, brs). LC/MS: Rt = 3.39 min, [M − H] 388, 390. 
               
               
                   
               
               
                 59 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4- Chlorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.95- 2.03 (2H, m), 2.83-2.87 (2H, m), 3.00-3.34 (2H, m), 5.03 (2H, s), 6.89-6.93 (1H, m), 7.00 (1H, d), 7.05 (1H, dd), 7.09 (1H, d), 7.20-7.22 (2H, m), 7.24-7.30 (1H, m), 7.34- 7.36 (2H, m), 7.55-7.59 (1H, m), 7.72 (1H, d). LC/MS: Rt = 3.68 min, [M + H] 406. 
               
               
                   
               
               
                 60 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4- Bromophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.96- 2.03 (2H, m), 2.83-2.87 (2H, m), 3.00-3.03 (2H, m), 5.01 (2H, s), 6.89-6.93 (1H, m), 6.96 (1H, d), 7.05 (1H, dd), 7.08 (1H, d), 7.15 (2H, d), 7.24-7.28 (1H, m), 7.48 (2H, d), 7.56-7.60 (1H, m), 7.73 (1H), 12.55-12.95 (1H, brs). LC/MS: Rt = 3.77 min, [M + H] 452. 
               
               
                   
               
               
                 61 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4- Methylphenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.94- 2.01 (2H, m), 2.26 (3H, s), 2.83-2.87 (2H, m), 2.98-3.02 (2H, m), 5.00 (2H, s), 6.86- 6.89 (1H, m), 6.92 (1H, d), 7.00 (1H, dd) 7.09-7.11 (5H, m), 7.22-7.26 (1H, m), 7.52- 7.55 (1H, m), 7.69 (1H, d, J = 7.5 Hz). LC/MS: Rt = 3.56 min, [M + H] 386. 
               
               
                   
               
               
                 62 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-({[4- (Trifluoromethyl)phenyl] methyl}oxy)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.97- 2.05 (2H, m), 2.86-2.89 (2H, m), 3.02-3.05 (2H, m), 5.14 (2H, s), 6.91-6.95 (1H, m), 6.98 (1H, d), 7.07-7.11 (2H, m), 7.25-7.28 (1H, m), 7.41 (2H, d), 7.56-7.60 (1H, m), 7.66 (2H, d), 7.71 (1H, d). LC/MS: Rt = 3.76 min, [M + H] 440. 
               
               
                   
               
               
                 63 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2- Chlorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.95- 2.02 (2H, m), 2.84-2.88 (2H, m), 3.00-3.03 (2H, m), 5.10 (2H, s), 6.91-6.95 (1H, m), 6.99 (1H, d), 7.04 (1H, dd), 7.14 (1H, d), 7.25-7.32 (4H, m), 7.45 (1H, d), 7.58-7.62 (1H, m), 7.73 (1H, d). LC/MS: Rt = 3.83 min, [M + H] 406. 
               
               
                   
               
               
                 64 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2- Bromophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.11- 2.18 (2H, m), 2.95-2.88 (2H, m), 3.03-3.08 (2H, m), 5.00 (2H, s), 6.99-7.04 (2H, m), 7.09-7.21 (4H, m), 7.28-7.35 (2H, m), 7.49 (1H, dd), 7.64- 7.68 (1H, m), 7.86 (1H, d). LC/MS: Rt = 3.77 min, [M + H] 450. 
               
               
                   
               
               
                 65 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2- Methylphenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.93- 2.01 (2H, m), 2.23 (3H, s), 2.81-2.84 (2H, m), 2.99-3.02 (2H, m), 5.05 (2H, s), 6.86- 6.90 (1H, m), 6.96 (1H, dd), 7.00 (1H, dd), 7.10-7.20 (5H, m), 7.56-7.60 (1H, m), 7.73 (1H, dd), 12.43-13.10 (1H, brs). LC/MS: Rt = 3.64 min, [M + H] 386. 
               
               
                   
               
               
                 66 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4-Chloro-2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.08- 2.16 (2H, m), 2.90-2.94 (2H, m), 3.00-3.04 (2H, m), 4.98 (2H, s), 6.99-7.03 (3H, m), 7.08-7.13 (2H, m), 7.28-7.31 (3H, m), 7.66-7.70 (1H, m), 7.87 (1H, d, J = 7.6 Hz). LC/MS: Rt = 3.75 min, [M + H] 424. 
               
               
                   
               
               
                 67 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4-Bromo-2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.93- 2.01 (2H, m), 2.80-2.84 (2H, m), 2.98-3.01 (2H, m), 5.05 (2H, s), 6.91-6.94 (2H, m), 7.03 (1H, dd), 7.18-7.23 (2H, m), 7.30-7.32 (1H, m), 7.38 (1H, dd), 7.53 (1H, dd), 7.56- 7.60 (1H, m), 7.72 (1H, d, J = 7.2 Hz), 12.56-13.05 (1H, br s). LC/MS: Rt = 3.96 min, [M + H] 470. 
               
               
                   
               
               
                 68 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-({[2-Fluoro-4- (trifluoromethyl)phenyl] methyl}oxy)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.96- 2.03 (2H, m), 2.83-2.87 (2H, m), 3.00-3.04 (2H, m), 5.16 (2H, s), 6.93-6.97 (2H, m), 7.07 (1H, d), 7.18 (1H, d), 7.28-7.32 (1H, m), 7.44-7.48 (1H, m), 7.52-7.59 (2H, m), 7.65 (1H, d), 7.70 (1H, d). LC/MS: Rt = 3.98 min, [M + H] 458. 
               
               
                   
               
               
                 69 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2-Chloro-4- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.10- 2.27 (2H, m), 2.92-2.96 (2H, m), 3.02-3.06 (2H, m), 5.00 (2H, s), 6.85-6.90 (1H, m), 6.99-7.07 (3H, m), 7.13 (1H, dd), 7.19-7.21 (1H, m), 7.28- 7.34 (2H, m), 7.66-7.70 (1H, m), 7.87 (1H, d). LC/MS: Rt = 3.76 min, [M + H] 424. 
               
               
                   
               
               
                 70 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2,4- Dichlorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.10- 2.18 (2H, m), 2.93-2.96 (2H, m), 3.02-3.06 (2H, m), 5.00 (2H, s), 6.98-7.04 (2H, m), 7.11-7.17 (3H, m), 7.28-7.34 (3H, m), 7.67-7.71 (1H, m), 7.87 (1H, d). LC/MS: Rt = 4.08 min, [M + H] 440. 
               
               
                   
               
               
                 71 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2-Bromo-4- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.94- 2.02 (2H, m), 2.83-2.87 (2H, m), 2.99-3.03 (2H, m), 5.02 (2H, s), 6.94-6.99 (2H, m), 7.05 (1H, dd), 7.14 (1H, d), 7.19-7.23 (1H, m), 7.30-7.37 (2H, m), 7.57-7.61 (2H, m), 7.72 (1H, d), 12.56-12.94 (1H, br s). LC/MS: Rt = 3.81 min, [M + H] 468. 
               
               
                   
               
               
                 72 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2,4- Dimethylphenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.92- 2.00 (2H, m), 2.18 (3H, s), 2.22 (3H, s), 2.79-2.83 (2H, m), 2.97-3.01 (2H, m), 5.00 (2H, s), 6.87-6.94 (4H, m), 6.98 (1H, dd), 7.06 (1H, d), 7.19 (1H, d), 7.28-7.30 (1H, m), 7.55-7.59 (1H, m), 7.72 (1H, dd), 12.52-12.87 (1H, br s). LC/MS: Rt = 3.70 min, [M − H] 398, 400. 
               
               
                   
               
               
                 73 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-({[2,4- Bis(trifluoromethyl) phenyl]methyl}oxy)phenyl]- 1-cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.97- 2.05 (2H, m), 2.85-2.89 (2H, m), 3.02-3.06 (2H, m), 5.20 (2H, s), 6.97-7.02 (2H, m), 7.08 (1H, d), 7.14 (1H, dd), 7.27-7.31 (1H, m), 7.58-7.62 (1H, m), 7.66-7.71 (2H, m), 8.02 (1H, d), 12.61-13.05 (1H, br s). LC/MS: Rt = 4.10 min [M + H] 508. 
               
               
                   
               
               
                 74 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(3,4- Difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.96- 2.04 (2H, m), 2.84-2.88 (2H, m), 3.01-3.04 (2H, m), 5.00 (2H, s), 6.92-6.95 (1H, m), 6.99 (1H, d), 7.07-7.11 (3H, m), 7.15-7.20 (1H, m), 7.26- 7.40 (2H, m), 7.58-7.62 (1H, m), 7.73 (1H, d), 12.41-12.98 (1H, br s). LC/MS: Rt = 3.52 min, [M − H] 408, 408. 
               
               
                   
               
               
                 75 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2,4,6- Trimethylphenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.84- 1.92 (2H, m), 2.18 (9H, s), 2.70-2.74 (2H, m), 2.90-2.94 (2H, m), 4.98 (2H, s), 6.81 (2H, s), 6.90-6.96 (3H, m), 7.31-7.33 (2H, m), 7.56-7.60 (1H, m), 7.71 (1H, dd). LC/MS: Rt = 3.76 min, [M − H] 412, 414. 
               
               
                   
               
               
                 76 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2,4,5- Trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.94- 2.02 (2H, m), 2.81-2.85 (2H, m), 2.98-3.02 (2H, m), 5.02 (2H, s), 6.95-6.97 (2H, m), 7.07 (1H, dd), 7.18 (1H, d), 7.24-7.33 (2H, m), 7.50-7.61 (2H, m), 7.72 (1H, dd), 12.57-12.87 (1H, br s). LC/MS: Rt = 3.58 min, [M + H] 426. 
               
               
                   
               
               
                 77 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(3,4,5- Trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.98- 2.05 (2H, m), 2.86-2.89 (2H, m), 3.02-3.06 (2H, m), 4.98 (2H, s), 6.97-7.00 (2H, m), 7.03-7.09 (3H, m), 7.13 (1H, dd), 7.27-7.29 (1H, m), 7.58- 7.61 (1H, m), 7.73 (1H, d). LC/MS: Rt = 3.68 min, [M − H] 424, 426. 
               
               
                   
               
               
                 78 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{2- [(Phenylmethyl)oxy] phenyl}-1-cyclopenten-1- yl)-2-pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.99- 2.06 (2H, m), 2.90-2.94 (2H, m), 2.99-3.02 (2H, m), 5.03 (2H, s), 6.92-6.96 (1H, m), 7.11 (1H, dd), 7.14-7.19 (3H, m), 7.25-7.34 (4H, m), 8.11 (1H, s), 8.80 (1H, s), 13.28- 13.89 (1H, br s). LC/MS: Rt = 4.18 min, [M + H] 373. 
               
               
                   
               
               
                 79 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4- Fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.98- 2.06 (2H, m), 2.89-2.93 (2H, m), 2.98-3.02 (2H, m), 4.99 (2H, s), 6.93-6.97 (1H, m), 7.08-7.17 (4H, m), 7.20-7.24 (2H, m), 7.30-7.34 (1H, m), 8.09 (1H, s), 8.79 (1H, s), 13.20-13.95 (1H, br s). LC/MS: Rt = 4.16 min, [M − H] 389, 391. 
               
               
                   
               
               
                 80 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4- Chlorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.99- 2.06 (2H, m), 2.89-2.93 (2H, m), 2.93-3.02 (2H, m), 5.01 (2H, s), 6.94-6.97 (1H, m), 7.11-7.15 (2H, m), 7.19 (2H, d), 7.30-7.35 (3H, m), 8.09 (1H, s), 8.80 (1H, s), 13.21- 13.89 (1H, br s). LC/MS: Rt = 4.50 min, [M − H] 405, 407. 
               
               
                   
               
               
                 81 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2,4- Difluorophenyl)methyl]- oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.96- 2.03 (2H, m), 2.85-2.89 (2H, m), 2.95-2.99 (2H, m), 5.02 (2H, s), 6.94-7.01 (2H, m), 7.11 (1H, dd), 7.16-77.23 (2H, m), 7.29-7.38 (2H, m), 8.05 (1H, s), 8.78 (1H, s), 13.19-13.78 (1H, br s). LC/MS: Rt = 4.20 min, [M − H] 407, 409. 
               
               
                   
               
               
                 82 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2,5- Difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.98- 2.05 (2H, m), 2.87-2.91 (2H, m), 2.98-3.01 (2H, m), 5.06 (2H, s), 6.97-7.02 (2H, m), 7.13 (1H, dd), 7.16-7.23 (3H, m), 7.33-7.37 (1H, m), 8.08 (1H, s), 8.78 (1H, s), 13.30- 13.78 (1H, br s). LC/MS: Rt = 4.22 min, [M + H] 409. 
               
               
                   
               
               
                 83 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2- Fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.96- 2.04 (2H, m), 2.86-2.90 (2H, m), 2.96-3.00 (2H, m), 5.01 (2H, s), 6.94-6.98 (1H, m), 7.08-7.28 (5H, m), 7.32-7.34 (2H, m), 8.08 (1H, s), 8.79 (1H, s), 13.20-13.88 (1H, br s). LC/MS: Rt = 4.14 min, [M − H] 389, 391. 
               
               
                   
               
               
                 84 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2,4,6- Trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.91- 1.99 (2H, m), 2.79-2.83 (2H, m), 2.91-2.94 (2H, m), 5.01 (2H, s), 6.97-7.00 (1H, m), 7.09-7.15 (3H, m), 7.28 (1H, d), 7.34-7.40 (1H, m), 7.99 (1H, s), 8.78 (1H, s), 13.31- 13.79 (1H, br s). 
               
               
                   
               
               
                 85 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{5-Chloro-2- [(phenylmethyl)oxy] phenyl)-1-cyclopenten-1- yl)-2-ethyl-3- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 1.27 (3H, t), 2.05-2.13 (2H, m), 2.86- 2.95 (4H, m), 3.15 (2H, q), 4.94 (2H, s), 6.84 (1H, d), 7.05 (1H, d), 7.14-7.19 (2H, m), 7.27-7.32 (4H, m), 8.00 (1H, d), 8.41 (1H, d). LC/MS: Rt = 3.95 min, [M − H] 432, 434. 
               
               
                   
               
               
                 86 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(4- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- ethyl-3- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 1.27 (3H, t), 2.05-2.12 (2H, m), 2.84-2.88 (2H, m), 2.90-2.94 (2H, m), 3.15 (2H, q), 4.87 (2H, s), 6.83 (1H, d), 6.96- 7.00 (2H, m), 7.07 (1H, d), 7.11-7.17 (3H, m), 7.99 (1H, d), 8.39 (1H, d). LC/MS: Rt = 3.99 min, [M − H] 450, 452. 
               
               
                   
               
               
                 87 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(4- chlorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- ethyl-3- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 1.27 (3H, t), 2.06-2.13 (2H, m), 2.84-2.88 (2H, m), 2.91-2.95 (2H, m), 3.15 (2H, q), 4.87 (2H, s), 6.81 (1H, d), 7.08- 7.10 (2H, m), 7.15 (1H, dd), 7.26-7.28 (3H, m), 7.99 (1H, d), 8.39 (1H, d). LC/MS: Rt = 4.24 min, [M − H] 466, 468. 
               
               
                   
               
               
                 88 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[5-Chloro-2-({[4- (trifluoromethyl)phenyl] methyl}oxy)phenyl]-1- cyclopenten-1-yl}-2- ethyl-3- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 1.25 (3H, t), 2.07-2.14 (2H, m), 2.86-2.89 (2H, m), 2.92-2.95 (2H, m), 3.12 (2H, q), 4.96 (2H, s), 6.81 (1H, d), 7.10 (1H, d), 7.16 (1H, dd), 7.26- 7.29 (2H, m), 7.55-7.57 (2H, m), 7.97 (1H, d), 8.39 (1H, d). LC/MS: Rt = 4.28 min, [M − H] 500, 502. 
               
               
                   
               
               
                 89 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- ethyl-3- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 1.13 (3H, t), 1.90-1.97 (2H, m), 2.70-2.80 (2H, m), 2.97-3.02 (2H, m) 4.97 (2H, s), 6.81 (1H, d), 6.93 (1H, d), 6.96- 7.03 (2H, m), 7.08 (1H, dd), 7.16-7.21 (2H, m), 7.24 (1H, d), 8.23 (1H, d). LC/MS: Rt = 3.98 min, [M − H] 450, 452. 
               
               
                   
               
               
                 90 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(2,4- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- ethyl-3- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 1.26 (3H, t), 2.05-2.12 (2H, m), 2.82-2.86 (2H, m), 2.90-2.94 (2H, m), 3.14 (2H, q), 4.93 (2H, s), 6.75-6.82 (2H, m), 6.87 (1H, d), 7.07 (1H, d), 7.11-7.15 (1H, m), 7.18 (1H, dd), 7.97 (1H, d), 8.38 (1H, d). LC/MS: Rt = 4.01 min, [M − H] 468, 470. 
               
               
                   
               
               
                 91 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(2,6- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl-2- ethyl-3- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 1.28 (3H, t), 1.99-2.06 (2H, m), 2.76-2.80 (2H, m), 2.84-2.88 (2H, m), 3.16 (2H, q), 5.02 (2H, s), 6.83-6.87 (2H, m), 6.99-7.01 (2H, m), 7.20 (1H, dd), 7.24-7.28 (1H, m), 7.95 (1H, d), 8.34 (1H, d). LC/MS: Rt = 3.90 min, [M − H] 468, 470. 
               
               
                   
               
               
                 92 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(2- chloro-4- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- ethyl-3- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 1.25 (3H, t), 2.07-2.14 (2H, m), 2.85-2.89 (2H, m), 2.93-2.96 (2H, m), 3.14 (2H, q), 4.95 (2H, s), 6.85 (1H, d), 6.90- 6.94 (1H, m), 7.07-7.10 (2H, m), 7.17-7.21 (2H, m), 7.99 (1H, d), 8.40 (1H, d). LC/MS: Rt = 4.30 min, [M − H] 484, 486. 
               
               
                   
               
               
                 93 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- {[(2,4,5- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- ethyl-3- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 1.25 (3H, t), 2.08-2.16 (2H, m), 2.84-2.88 (2H, m), 2.94-2.98 (2H, m), 3.14 (2H, q), 4.90 (2H, s), 6.84-6.92 (2H, m), 6.99-7.05 (1H, m), 7.11 (1H, d), 7.19 (1H, dd,), 7.99 (1H, d), 8.39 (1H, d). LC/MS: Rt = 4.13 min, [M − H] 486, 488. 
               
               
                   
               
               
                 94 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-chloro-2- {[(2,4,6- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- ethyl-3- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 1.28 (3H, t), 2.00-2.07 (2H, m), 2.76-2.80 (2H, m), 2.85-2.89 (2H, m), 3.16 (2H, q), 4.95 (2H, s), 6.60-6.64 (2H, m), 6.97 (1H, d), 7.03 (1H, d), 7.20 (1H, dd), 7.95 (1H, d), 8.35 (1H, d). LC/MS: Rt = 3.98 min, [M − H] 486, 488. 
               
               
                   
               
               
                 95 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Methyl-6-{2-[2- [(phenylmethyl)oxy]-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.10- 2.17 (2H, m), 2.65 (3H, s), 2.91-2.95 (2H, m), 3.00-3.05 (2H, m), 5.00 (2H, s), 7.03 (1H, d), 7.11-7.16 (3H, m), 2.27-2.28 (3H, m), 7.38 (1H, d), 7.44 (1H, d), 7.53 (1H, dd), 1075-11.23 (1H, br s). LC/MS: Rt = 4.10 min, [M − H] 452, 454. 
               
               
                   
               
               
                 96 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(4- Fluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-3- methyl-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.09- 2.16 (2H, m), 2.66 (3H, s), 2.89-2.93 (2H, m), 2.99-3.03 (2H, m), 4.97 (2H, s), 6.94- 6.98 (2H, m), 7.03 (1H, d), 7.09-7.13 (2H, m), 7.15 (1H, d), 7.37 (1H, d), 7.46 (1H, d), 7.54 (1H, dd), 10.42-11.20 (1H, br s). LC/MS: Rt = 4.06 min, [M − H] 470, 472. 
               
               
                   
               
               
                 97 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(4- Chlorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-3- methyl-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.10- 2.17 (2H, m), 2.66 (3H, s), 2.90-2.93 (2H, m), 3.00-3.04 (2H, m), 4.97 (2H, s), 7.02 (1H, d), 7.07 (2H, d), 7.16 (1H, d), 7.23-7.25 (2H, m), 7.37 (1H, d), 7.46 (1H, d), 7.54 (1H, dd), 10.50-10.98 (1H, br s). LC/MS: Rt = 4.22 min, [M − H] 486, 488. 
               
               
                   
               
               
                 98 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2- Fluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-3- methyl-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.09- 2.16 (2H, m), 2.65 (3H, s), 2.90-2.94 (2H, m), 3.00-3.04 (2H, m), 5.05 (2H, s), 6.97- 7.04 (2H, m), 7.07-7.09 (2H, m), 7.13 (1H, d), 7.25-7.28 (1H, m), 7.39 (1H, d), 7.43 (1H, d), 7.56 (1H, dd), 10.75- 11.09 (1H, br, s). LC/MS: Rt = 4.07 min, [M − H] 470, 472. 
               
               
                   
               
               
                 99 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2,4- Difluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl)-3- methyl-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.08- 2.16 (2H, m), 2.66 (3H, s), 2.88-2.91 (2H, m), 2.98-3.03 (2H, m), 5.01 (2H, s), 6.74- 6.79 (2H, m), 7.07-7.11 (2H, m), 7.14 (1H, d), 7.38 (1H, d), 7.46 (1H, d), 7.57 (1H, dd), 10.59-11.05 (1H, br s). LC/MS: Rt = 4.10 min, [M − H] 488, 490. 
               
               
                   
               
               
                 100 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2-Chloro-4- fluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-3- methyl-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.10- 2.18 (2H, m), 2.65 (3H, s), 2.90-2.94 (2H, m), 3.01-3.05 (2H, m), 5.04 (2H, s), 6.87- 6.91 (1H, m), 7.05-7.09 (2H, m), 7.14-7.18 (2H, m), 7.39 (1H, d), 7.46 (1H, d), 7.57 (1H, dd), 10.56-11.02 (1H, br s). LC/MS: Rt = 4.27 min, [M − H] 504, 506. 
               
               
                   
               
               
                 101 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2,6- Difluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-3- methyl-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.03- 2.10 (2H, m), 2.65 (3H, s), 2.83-2.87 (2H, m), 2.93-2.97 (2H, m), 5.05 (2H, s), 6.79- 6.83 (2H, m), 7.08 (1H, d), 7.17 (1H, d), 7.24-7.28 (1H, m), 7.37 (1H, d), 7.41 (1H, d), 7.58 (1H, dd). LC/MS: Rt = 4.03 min, [M − H] 488, 490. 
               
               
                   
               
               
                 102 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2,3- Difluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl)-3- methyl-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.09- 2.17 (2H, m), 2.65 (3H, s), 2.89-2.93 (2H, m), 3.00-3.04 (2H, m), 5.07 (2H, s), 6.88- 6.89 (1H, m), 6.95-7.0 (1H, m), 7.06-7.10 (2H, m), 7.14 (1H, d), 7.40 (1H, d), 7.44 (1H, d), 7.57 (1H, dd), 10.61- 10.99 (1H, br s). LC/MS: Rt = 4.10 min, [M − H] 488, 490. 
               
               
                   
               
               
                 103 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-{[(2-Chloro-6- fluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-3- methyl-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.01- 2.09 (2H, m), 2.65 (3H, s), 2.83-2.87 (2H, m), 2.92-2.96 (2H, m), 5.11 (1H, d), 6.91- 6.97 (1H, m), 7.07 (1H, d), 7.11 (1H, d), 7.19-7.24 (2H, m), 7.37-7.41 (2H, m), 7.59 (1H, dd). LC/MS: Rt = 4.14 min, [M − H] 504, 506. 
               
               
                   
               
               
                 104 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Methyl-6-[2-(5- (trifluoromethyl]-2- {[(2,4,5- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.12- 2.20 (2H, m), 2.65 (3H, s), 2.89-2.93 (2H, m), 3.02-3.06 (2H, m), 4.99 (2H, s), 6.86- 6.93 (2H, m), 7.05 (1H, d), 7.19 (1H, d), 7.41 (1H, d), 7.49 (1H, d), 7.58 (1H, dd), 10.56-10.90 (1H, br s). LC/MS: Rt = 4.15 min, [M − H] 506, 508. 
               
               
                   
               
               
                 105 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Methyl-6-[2-(5- (trifluoromethyl)-2- {[(2,4,6- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.03- 2.11 (2H, m), 2.66 (3H, s), 2.82-2.86 (2H, m), 2.93-2.98 (2H, m), 5.01 (2H, s), 6.56- 6.60 (2H, m), 7.10 (1H, d), 7.17 (1H, d), 7.36 (1H, d), 7.44 (1H, d), 7.58 (1H, dd), 10.56-11.00 (1H, br s). LC/MS: Rt = 4.07 min, [M − H] 506, 508. 
               
               
                   
               
               
                 106 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Methyl-6-[2-(5- (trifluoromethyl)-2- {[(3,4,5- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (CDCl 3 ) δ: 2.13- 2.21 (2H, m), 2.66 (3H, s), 2.90-2.94 (2H, m), 3.03-3.07 (2H, m), 4.93 (2H, s), 6.73- 6.76 (2H, m), 6.97 (1H, d), 7.22 (1H, d), 7.42 (1H, d), 7.51 (1H, d), 7.56 (1H, dd), 10.53-10.80 (1H, br s). LC/MS: Rt = 4.18 min, [M − H] 506, 508. 
               
               
                   
               
               
                 107 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- {[(2,4- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.00 min. [M + H] = 476 
               
               
                   
               
               
                 108 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(Acetylamino)-5-(2- {5-chloro-2- [(phenylmethyl)oxy] phenyl}-1- cyclopenten-1- yl)benzoic acid 
                 LC/MS: Rt = 4.05 min. [M + H]= 462 
               
               
                   
               
               
                 109 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(Acetylamino)-5-[2- (5-chloro-2-{[(4- fluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]benzoic acid 
                 LC/MS: Rt = 4.04 min. [M + H] = 480 
               
               
                   
               
               
                 110 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(Acetylamino)-5-[2- (5-chloro-2-{[(2,4- difluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]benzoic acid 
                 LC/MS: Rt = 4.06 min. [M + H] = 498 
               
               
                   
               
               
                 111 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Amino-5-[2-(5- chloro-2- [(phenylmethyl)oxy] phenyl}-1-cyclopenten- 1-yl)benzoic acid 
                 LC/MS: Rt = 3.87 min. [M + H] = 420 
               
               
                   
               
               
                 112 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Amino-5-[2-(5- chloro-2-{[(4- fluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]benzoic acid 
                 LC/MS: Rt = 3.87 min. [M + H]= 438 
               
               
                   
               
               
                 113 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Amino-5-[2-(5- chloro-2-{[(2,4- difluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]benzoic acid 
                 LC/MS: Rt = 3.91 min. [M + H] = 456 
               
               
                   
               
               
                 114 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6[2-(5-Bromo-2-{[(4- fluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-2-pyridinecarboxylic acid 
                 LC/MS: Rt = 3.66 min. [M + H] = 468, 470 
               
               
                   
               
               
                 115 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2- {[(2,4- difluorophenyl)methyl] oxy}phenyl)-1-cyclopenten-1- yl]-2-pyridinecarboxylic acid 
                 LC/MS: Rt = 3.69 min. [M + H] = 486, 488 
               
               
                   
               
               
                 116 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Bromo-2- [(phenylmethyl)oxy] phenyl}-1-cyclopenten-1- yl)-2-pyridinecarboxylic acid 
                 LC/MS: Rt = 3.65 min. [M + H] = 450, 452 
               
               
                   
               
               
                 117 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2-{[(4- methylphenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.10 min. [M + H] = 464, 466 
               
               
                   
               
               
                 118 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2-{[(4- chlorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-2-pyridinecarboxyic acid 
                 LC/MS: Rt = 4.20 min. [M + H] = 484, 486 
               
               
                   
               
               
                 119 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2- {[(2,4,6- trifluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-2-pyridinecarboxylic acid 
                 LC/MS: Rt = 4.07 min. [M + H] = 504, 506 
               
               
                   
               
               
                 120 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[5-Bromo-2-({[2- fluoro-4-(trifluoromethyl) phenyl]methyl}oxy)phenyl]- 1-cyclopenten-1-yl}- 2-pyridinecarboxylic acid 
                 LC/MS: Rt = 4.36 min. [M + H] = 536, 538 
               
               
                   
               
               
                 121 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2-{[(4- bromo-2-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.32 min. [M + H] = 546, 548, 550 
               
               
                   
               
               
                 122 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2-{[(4- chloro-2-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.25 min. [M + H] = 502, 504 
               
               
                   
               
               
                 123 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2-{[(4- bromophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-2-pyridinecarboxylic acid 
                 LC/MS: Rt = 4.26 min. [M + H] = 528, 530, 532 
               
               
                   
               
               
                 124 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2-{[(2- chloro-4-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.35 min. [M + H] = 502, 504 
               
               
                   
               
               
                 125 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2-{[(2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.08 min. [M + H] = 468, 470 
               
               
                   
               
               
                 126 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2- {[(2,3,6- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.05 min. [M + H] = 504, 506 
               
               
                   
               
               
                 127 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Bromo-2- [(phenylmethyl)oxy] phenyl}-1-cyclopenten- 1-yl)-2-pyrazinecarboxylic acid 
                 LC/MS: Rt = 4.15 min. [M + H] = 451, 453 
               
               
                   
               
               
                 128 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2-{[(4- fluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 LC/MS: Rt = 4.54 min. [M + H] = 469, 471 
               
               
                   
               
               
                 129 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2- {[(2,4-difluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                 LC/MS: Rt = 4.57 min. [M + H] 487, 489 
               
               
                   
               
               
                 130 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2- {[(2,4,6-trifluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                 LC/MS: Rt = 4.47 min. [M + H] 505, 507 
               
               
                   
               
               
                 131 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2-{[(2- chloro-4-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                 LC/MS: Rt = 4.94 min. [M + H] = 503, 505 
               
               
                   
               
               
                 132 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2-{[(4- chloro-2-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                 LC/MS: Rt = 4.87 min. [M + H] = 503, 505 
               
               
                   
               
               
                 133 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-bromo-2-{[(4- bromo-2-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                 LC/MS: Rt = 4.91 min. [M + H] = 547, 549, 551 
               
               
                   
               
               
                 134 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Bromo-2-[({4- [(trifluoromethyl)oxy] phenyl}methyl)oxy] phenyl}-1-cyclopenten-1- yl)-2-pyrazinecarboxylic acid 
                 LC/MS: Rt = 4.67 min. [M + H] = 535, 537 
               
               
                   
               
               
                 135 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2-{[(4- chlorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 LC/MS: Rt = 4.77 min. [M + H] = 485, 487 
               
               
                   
               
               
                 136 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[5-Bromo-2-({[2- fluoro-4-(trifluoromethyl) phenyl]methyl}oxy)phenyl]- 1-cyclopenten-1-yl}- 2-pyrazinecarboxylic acid 
                 LC/MS: Rt = 4.69 min. [M + H] = 537, 539 
               
               
                   
               
               
                 137 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[5-Bromo-2-({[4- (trifluoromethyl)phenyl] methyl}oxy)phenyl]-1- cyclopenten-1-yl}- 2-pyrazinecarboxylic acid 
                 LC/MS: Rt = 4.64 min. [M + H] = 519, 521 
               
               
                   
               
               
                 138 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-bromo-2-{[(4- bromophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 LC/MS: Rt = 4.90 min. [M + H] = 529, 531, 533 
               
               
                   
               
               
                 139 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2- {[(2E)-3-phenyl-2-propen- 1-yl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 2.00- 2.05 (2H, m), 2.67-3.02 (4H, br m), 4.50 (2H, s), 6.10-6.15 (1H, m), 6.5-6.7 (1H, m), 6.90-7.10 (3H, m), 7.15-7.35 (6H, m), 7.50-7.60 (1H, m), 7.65-7.70 (1H, m). 
               
               
                   
               
               
                 140 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[5-Bromo-2-(2- propen-1-yloxy)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO) δ: 1.98- 2.04 (2H, m), 2.70-2.75 (2H, m), 2.95-3.05 (2H, m), 4.40 (2H, m), 5.10-5.21 (2H, m), 5.73-5.76 (1H, m), 6.94-6.97 (1H, m), 7.05-7.15 (2H, m), 7.20-7.25 (1H, m), 7.60- 7.80 (2H, m). 
               
               
                   
               
               
                 141 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Bromo-2-[(2- methylpropyl)oxy] phenyl}-1-cyclopenten- 1-yl)-2-pyridinecarboxylic acid 
                 LC/MS: Rt = 3.95 min. [M + H] = 416, 418 
               
               
                   
               
               
                 142 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[5-Bromo-2- (ethyloxy)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 3.44 min. [M + H] = 388, 390 
               
               
                   
               
               
                 143 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Bromo-2- [(cyclohexylmethyl) oxy]phenyl}-1-cyclopenten- 1-yl)-2-pyridinecarboxylic acid 
                 LC/MS: Rt = 4.41 min. [M + H] = 456, 458 
               
               
                   
               
               
                 144 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Bromo-2- [(cyclopentylmethyl) oxy]phenyl}-1-cyclopenten- 1-yl)-2-pyridinecarboxylic acid 
                 LC/MS: Rt = 4.25 min. [M + H] = 442, 444 
               
               
                   
               
               
                 145 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-(2-{5- chloro-2-[(phenylmethyl) oxy]-3-pyridinyl)-1- cyclopenten-1-yl)benzoic acid 
                 LC/MS: Rt = 3.74 min. [M + H] = 421 
               
               
                   
               
               
                 146 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(Acetylamino)-5-(2- {5-chloro-2-[(phenylmethyl) oxy]-3-pyridinyl}-1- cyclopenten-1-yl)benzoic acid 
                 LC/MS: Rt = 3.74 min. [M + H] = 463 
               
               
                   
               
               
                 147 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(2-{5-Chloro-2- [(phenylmethyl)oxy]- 3-pyridinyl}-1-cyclopenten- 1-yl)-5-(propanoylamino) benzoic acid 
                 LC/MS: Rt = 3.90 min. [M + H] = 477 
               
               
                   
               
               
                 148 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(2-{5-Chloro-2- [(phenylmethyl)oxy]- 3-pyridinyl}-1-cyclopenten- 1-yl)-5-[(2-methylpropanoyl) amino]benzoic acid 
                 LC/MS: Rt = 4.02 min. [M + H] = 491 
               
               
                   
               
               
                 149 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-{2-[2-{[(2- fluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1- yl}-2-pyridinecarboxylic acid 
                 LC/MS: Rt = 4.33 min. [M + H] = 492 
               
               
                   
               
               
                 150 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-{2-[2- {[(2,4-difluorophenyl) methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.34 min. [M + H] = 510 
               
               
                   
               
               
                 151 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-[2-(5- (trifluoromethyl)-2- {[(2,4,6-trifluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.30 min. [M + H] = 528 
               
               
                   
               
               
                 152 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-{2-[2- {[(2,6-difluorophenyl) methyl]oxy}-5-(trifluoro- methyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.31 min. [M + H] = 510 
               
               
                   
               
               
                 153 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-chloro-6-{2-[2-{[(2- chloro-4-fluorophenyl) methyl]oxy}-5-(trifluoro- methyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.54 min. [M + H] = 526 
               
               
                   
               
               
                 154 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-{2-[2-{[(4- chloro-2-fluorophenyl) methyl]oxy}-5-(trifluoro- methyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.55 min. [M + H] = 526 
               
               
                   
               
               
                 155 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-{2-[2- {[(2,4-dichlorophenyl) methyl]oxy}-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.77 min. [M + H] = 542, 544 
               
               
                   
               
               
                 156 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-{2-[2-({[2- fluoro-4-(trifluoromethyl) phenyl]methyl}oxy)-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.41 min. [M + H] = 560 
               
               
                   
               
               
                 157 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-{2-[2- [(phenylmethyl)oxy]-5- (trifluoromethyl)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 4.31 min. [M + H] = 474 
               
               
                   
               
               
                 158 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Chloro-4- methyl-2-[(phenylmethyl) oxy]phenyl}-1- cyclopenten-1-yl)-2- pyridinecarboxylic acid 
                 LC/MS: Rt = 3.89 min. [M + H] = 420 
               
               
                   
               
               
                 159 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{5-Chloro-2- [(phenylmethyl)oxy]phenyl}- 1-cyclopenten-1-yl)-2- methyl-3-pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.98-2.05 (2H, m), 2.62 (3H, s), 2.79-2.83 (2H, m), 2.87- 2.90 (2H, m), 5.03 (2H, s), 7.09-7.33 (8H, m), 7.84 (1H, d), 8.21 (1H, d), 13.1 (1H, s) LC/MS: Rt = 3.81 [MH+] 420.4, 422.4 
               
               
                   
               
               
                 160 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(4- fluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1- yl]-2-methyl-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.99-2.06 (2H, m), 2.62 (3H, s), 2.78-2.82 (2H, m), 2.86- 2.90 (2H, m), 5.00 (2H, s), 7.10-7.14 (4H, m), 7.20-7.23 (2H, m), 7.31 (1H, dd), 7.81 (1H, d), 8.19 (1H, d), 13.1 (1H, s) LC/MS: Rt = 3.85 [MH+] 438.4, 440.4 
               
               
                   
               
               
                 161 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(2,4- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2-methyl- 3-pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.94-2.02 (2H, m), 2.61 (3H, s), 2.74-2.78 (2H, m), 2.83- 2.87 (2H, m), 5.01 (2H, s), 7.02 (1H, dt) 7.10 (1H, d), 7.18-7.35 (4H, m), 7.77 (1H, d), 8.14 (1H, d), 13.1 (1H, s) LC/MS: Rt = 3.89 [MH+] 456.3, 458.3 
               
               
                   
               
               
                 162 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(2,4,5- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2-methyl- 3-pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.96-2.02 (2H, m), 2.60 (3H, s), 2.77-2.80 (2H, m), 2.85- 2.88 (2H, m), 4.98 (2H, s), 7.16 (1H, d), 7.21 (1H, d) 7.21-7.26 (1H, m), 7.35 (1H, dd), 7.47-7.53 (1H, m), 7.75 (1H, d), 8.12 (1H, d), 13.0 (1H, s) LC/MS: Rt = 3.86 [MH+] 474.4, 476.4 
               
               
                   
               
               
                 163 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[5-Chloro-2-({[4- (trifluoromethyl)phenyl] methyl}oxy)phenyl]- 1-cyclopenten-1-yl}- 2-methyl-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.99-2.06 (2H, m), 2.60 (3H, s), 2.81-2.85 (2H, m), 2.89- 2.93 (2H, m), 5.13 (2H, s), 7.10 (1H, d), 7.14 (1H, d), 7.31-7.38 (3H, m), 7.83 (2H, d), 7.83 (1H, d), 8.21 (1H, d), 13.1 (1H, s) LC/MS: Rt = 4.02 [MH+] 488.4, 490.4 
               
               
                   
               
               
                 164 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(4- chlorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- methyl-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.96-2.04 (2H, m), 2.62 (3H, s), 2.79-2.82 (2H, m), 2.87-2.91 (2H, m), 5.01 (2H, s), 7.08-7.11 (2H, m), 7.18 (2H, d), 7.29-7.37 (3H, m), 7.82 (1H, d), 8.19 (1H, d), 13.1 (1H, s) LC/MS: Rt = 4.02 [MH+] 454.4 
               
               
                   
               
               
                 165 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- {[(2,3,6- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- methyl-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.91-2.01 (2H, m), 2.61 (3H, s), 2.68-2.72 (2H, m), 2.87- 2.91 (2H, m), 5.06 (2H, s), 7.07-7.12 (2H, m), 7.27 (1H, d), 7.37 (1H, dd), 7.44-7.53 (1H, m), 7.71 (1H, d), 8.07 (1H, d), 13.1 (1H, s) LC/MS: Rt = 3.68 [MH+] 474.6, 476.4 
               
               
                   
               
               
                 166 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-chloro-2-{[(2- chloro-4-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2-methyl-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.96-2.03 (2H, m), 2.60 (3H, s), 2.77-2.80 (2H, m), 2.85- 2.89 (2H, m), 5.01 (2H, s), 7.12-7.20 (3H, m), 7.31-7.35 (2H, m), 7.42 (1H, dd), 7.77 (1H, d), 8.14 (1H, d), 13.1 (1H, s) LC/MS: Rt = 4.05 [MH+] 472.4 
               
               
                   
               
               
                 167 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- {[(2,4,6-trifluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2-methyl- 3-pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.90-1.97 (2H, m), 2.61 (3H, s), 2.68-2.72 (2H, m), 2.79- 2.82 (2H, m), 4.99 (2H, s), 7.09-7.17 (3H, m), 7.26 (1H, d), 7.36 (1H, dd), 7.71 (1H, d), 8.07 (1H, d), 13.1 (1H, s) LC/MS: Rt = 3.72 [MH+] 474.4, 476.4 
               
               
                   
               
               
                 168 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[5-chloro-2-({[2- fluoro-4-(trifluoromethyl) phenyl]methyl}oxy)phenyl]- 1-cyclopenten-1-yl)-2-methyl- 3-pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.97-2.05 (2H, m), 2.59 (3H, s), 2.78-2.81 (2H, m), 2.87- 2.91 (2H, m), 5.14 (2H, s), 7.15 (1H, d), 7.20 (1H, d), 7.34 (1H, dd), 7.42 (1H, t), 7.53 (1H, d), 7.65 (1H, d), 7.78 (1H, d), 8.15 (1H, d), 13.1 (1H, s) LC/MS: Rt = 4.05 [MH+] 506.5, 508.4 
               
               
                   
               
               
                 169 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(4- bromophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- methyl-3-pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.97-2.05 (2H, m), 2.62 (3H, s), 2.79-2.82 (2H, m), 2.87-2.91 (2H, m), 5.00 (2H, s), 7.08-7.13 (4H, m), 7.31 (1H, dd), 7.49 (2H, d), 7.82 (1H, d), 8.19 (1H, d), 13.1 (1H, s) LC/MS: Rt = 4.09 [MH+] 500.3, 502.3 
               
               
                   
               
               
                 170 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(2,6- difluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-2-methyl-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.88-1.96 (2H, m), 2.62 (3H, s), 2.66-2.70 (2H, m), 2.78- 2.81 (2H, m), 5.05 (2H, s), 7.05-7.11 (3H, m), 7.26 (1H, d), 7.35 (1H, dd), 7.41-7.48 (1H, m), 7.74 (1H, d), 8.09 (1H, d), 13.1 (1H, s) LC/MS: Rt = 3.63 [MH+] 456.5, 458.4 
               
               
                   
               
               
                 171 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- methyl-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.95-2.02 (2H, m), 2.61 (3H, s), 2.75-2.79 (2H, m), 2.84- 2.88 (2H, m), 5.07 (2H, s), 7.08-7.24 (5H, m), 7.31-7.37 (2H, m), 7.80 (1H, d), 8.16 (1H, d), 13.1 (1H, s) LC/MS: Rt = 3.73 [MH+] 438.5, 440.4 
               
               
                   
               
               
                 172 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Methyl-5-{2-[2- [(phenylmethyl)oxy]-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.99-2.08 (2H, m), 2.61 (3H, s), 2.83-2.87 (2H, m), 2.89- 2.92 (2H, m), 5.14 (2H, s), 7.19-7.21 (2H, m), 7.26-7.34 (4H, m), 7.37 (1H, d), 7.63 (1H, dd), 7.82 (1H, d), 8.20 (1H, d), 13.0 (1H, s) LC/MS: Rt = 3.72 [MH+] 454.4 
               
               
                   
               
               
                 173 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[2-{[(4- Fluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1- yl}-2-methyl-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.99-2.07 (2H, m), 2.61 (3H, s), 2.82-2.86 (2H, m), 2.88- 2.91 (2H, m), 5.10 (2H, s), 7.11-7.16 (2H, m), 7.22-7.30 (3H, m), 7.38 (1H, d), 7.64 (1H, dd), 7.79 (1H, d), 8.18 (1H, d), 13.0 (1H, s) LC/MS: Rt = 3.74 [MH+] 472.4 
               
               
                   
               
               
                 174 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[2-{[(2,4- Difluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1- yl}-2-methyl-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.96-2.03 (2H, m), 2.60 (3H, s), 2.78-2.82 (2H, m), 2.85- 2.89 (2H, m), 5.12 (2H, s), 7.04 (1H, dt), 7.22 (1H, dt), 7.32-7.38 (3H, m), 7.65 (1H, dd), 7.74 (1H, d), 8.13 (1H, d), 13.1 (1H, s). LC/MS: Rt = 3.78 [MH+] 490.4 
               
               
                   
               
               
                 175 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[2-{[(2,4,6- Trifluorophenyl)methyl] yl]oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1- yl}-2-methyl-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.92-1.99 (2H, m), 2.61 (3H, s), 2.72-2.76 (2H, m), 2.80- 2.84 (2H, m), 5.09 (2H, s), 7.14-7.19 (2H, m), 7.37 (1H, d), 7.43 (1H, d), 7.67-7.69 (2H, m), 8.07 (1H, d), 13.1 (1H, s) LC/MS: Rt = 3.74 [MH+] 508.4 
               
               
                   
               
               
                 176 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[2-{[(2-Chloro-4- fluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1- yl}-2-methyl-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.97-2.04 (2H, m), 2.59 (3H, s), 2.80-2.84(2H, m), 2.87- 2.90 (2H, m), 5.12 (2H, s), 7.19 (1H, dt), 7.35-7.40 (3H, m), 7.45 (1H, dd), 7.66 (1H, dd), 7.75 (1H, d), 8.14 (1H, d), 13.1 (1H, s) LC/MS: Rt = 4.00 [MH+] 506.4, 508.4 
               
               
                   
               
               
                 177 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[2-{[(4-Chloro-2- fluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1- yl}-2-methyl-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.97-2.04 (2H, m), 2.60 (3H, s), 2.79-2.82 (2H, m), 2.86- 2.90 (2H, m), 5.14 (2H, s), 7.23-7.43 (5H, m), 7.66 (1H, dd), 7.75 (1H, d), 8.14 (1H, d), 13.1 (1H, br s) LC/MS: Rt = 3.99 [MH+] 506.4, 508.4 
               
               
                   
               
               
                 178 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[2-{[(2- Fluorophenyl)methyl]oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1- yl}-2-methyl-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.97-2.04 (2H, m), 2.61 (3H, s), 2.79-2.83 (2H, m), 2.86- 2.90 (2H, m), 5.18 (2H, s), 7.13-7.27 (3H, m), 7.35-7.39 (3H, m), 7.65 (1H, dd), 7.78 (1H, d), 8.16 (1H, d), 13.1 (1H, br s) LC/MS: Rt = 3.84 [MH+] 472.5 
               
               
                   
               
               
                 179 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Methyl-5-[2-(5- (trifluoromethyl)-2-{[(2,4,5- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.98-2.05 (2H, m), 2.59 (3H, s), 2.80-2.84 (2H, m), 2.87- 2.90 (2H, m), 5.09 (2H, s), 7.28-7.31 (1H, dt, m), 7.37 (1H, d), 7.43 (1H, d), 7.51- 7.54 (1H, m), 7.67 (1H, dd), 7.73 (1H, d), 8.12 (1H, d), 13.1 (1H, s) LC/MS: Rt = 3.95 [MH+] 508.4 
               
               
                   
               
               
                 180 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Chloro-2- [(phenylmethyl)oxy] phenyl}-1-cyclopenten-1- yl)-3-(methylthio)-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.95-2.02 (2H, m), 2.36 (3H, s), 2.82-2.85 (2H, m), 2.97- 3.01 (2H, m), 5.02 (2H, s), 7.03 (1H, d), 7.11-7.16 (4H, m), 7.25-7.33 (4H, m), 7.60 (1H, d), 12.6 (1H, s) LC/MS: Rt = 4.08 [MH+] 452.4, 454.4 
               
               
                   
               
               
                 181 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-3- (methylthio)-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.92- 2.00 (2H, m), 2.35 (3H, s), 2.78-2.82 (2H, m), 2.95-2.99 (2H, m), 5.07 (2H, s), 7.00 (1H, d), 7.09-7.21 (4H, m), 7.32-7.37 (2H, m), 7.58 (1H, d), 7.79 (1H, d), 12.5 (1H, s) LC/MS: Rt = 4.08 [MH+] 470.4, 472.4 
               
               
                   
               
               
                 182 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(4- fluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-3-(methylthio)-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.92- 2.00 (2H, m), 2.19 (3H, s), 2.74-2.80 (2H, m), 2.85-2.92 (2H, m), 5.08 (2H, s), 6.65 (1H, d), 7.08 (1H, d), 7.18- 7.23 (4H, m), 7.25-7.41 (3H, m). LC/MS: Rt = 4.05 [MH+] 470.4, 472.4 
               
               
                   
               
               
                 183 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2,4- difluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-3-(methylthio)-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.92- 1.99 (2H, m), 2.35 (3H, s), 2.77-2.81 (2H, m), 2.94-2.98 (2H, m), 5.02 (2H, s), 6.96- 7.01 (2H, m), 7.15-7.24 (4H, m), 7.34 (1H, dd), 7.57 (1H, d), 7.79 (1H, d), 12.5 (1H, s) LC/MS: Rt = 4.09 [MH+] 488.4, 490.4 
               
               
                   
               
               
                 184 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2,4,6- trifluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-3-(methylthio)-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.87- 1.95 (2H, m), 2.36 (3H, s), 2.71-2.74 (2H, m), 2.89-2.93 (2H, m), 5.02 (2H, s), 6.91 (1H, d), 7.10-7.14 (3H, m), 7.28 (1H, d), 7.37 (1H, dd), 7.56 (1H, d), 12.5 (1H, s) LC/MS: Rt = 4.06 [MH+] 506.3, 508.3 
               
               
                   
               
               
                 185 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-(2-{5-chloro-2- [(phenylmethyl)oxy] phenyl}-1-cyclopenten-1-yl)- 2-pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.94- 2.01 (2H, m), 2.82-2.86 (2H, m), 2.92-2.96 (2H, m), 5.01 (2H, s), 6.95 (1H, d), 7.10- 7.15 (4H, m), 7.26-7.33 (4H, m), 7.74 (1H, d), 13.6 (1H, s) LC/MS: Rt = 4.51 [MH+] 440.4 
               
               
                   
               
               
                 186 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-[2-(5- chloro-2-{[(4- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.93- 2.01 (2H, m), 2.81-2.84 (2H, m), 2.91-2.95 (2H, m), 4.97 (2H, s), 6.94 (1H, d), 7.09- 7.17 (6H, m), 7.32 (1H, dd), 7.74 (1H, d), 13.6 (1H, s) LC/MS: Rt = 4.50 [MH+] 458.4 
               
               
                   
               
               
                 187 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-[2-(5- chloro-2-{[(2-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.94- 1.99 (2H, m), 2.78-2.82 (2H, m), 2.90-2.94 (2H, m), 5.07 (2H, s), 6.92 (1H, d), 7.11- 7.20 (5H, m), 7.32-7.38 (2H, m), 7.73 (1H, d), 13.6 (1H, s) LC/MS: Rt = 4.51 [MH+] 458.4 
               
               
                   
               
               
                 188 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-[2-(5-chloro-2- {[(2,4-difluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.93- 1.99 (2H, m), 2.77-2.81 (2H, m), 2.89-2.93 2H, m), 5.02 (2H, s), 6.90 (1H, d), 7.01 (1H, dt), 7.14-7.26 (4H, m), 7.34 (1H, dd), 7.72 (1H, d), 13.6 (1H, br s) LC/MS: Rt = 4.55 [MH+] 476.4 
               
               
                   
               
               
                 189 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-[2-(5-chloro- 2-{[(2,6-difluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.85- 1.93 (2H, m), 2.70-2.73 (2H, m), 2.83-2.87 (2H, m), 5.07 (2H, s), 6.83 (1H, d), 7.05- 7.11 (3H, m), 7.27 (1H, d), 7.36-7.47 (2H, m), 7.70 (1H, d), 13.6 (1H, s) LC/MS: Rt = 4.43 [MH+] 476.4 
               
               
                   
               
               
                 190 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-[2-(5-chloro-2- {[(2,3,6-trifluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.87- 1.94 (2H, m), 2.70-2.74 (2H, m), 2.84-2.88 (2H, m), 5.09 (2H, s), 6.84 (1H, d), 7.10- 7.15 (2H, m), 7.27 (1H, d), 7.37 (1H, dd), 7.49 (1H, m), 7.71 (1H, d), 13.6 (1H, s) LC/MS: Rt = 4.38 [MH+] 494.4 
               
               
                   
               
               
                 191 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-[2-(5- chloro-2-{[(2,4,5- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.93- 2.01 (2H, m), 2.80-2.83 (2H, m), 2.91-2.94 (2H, m), 4.98 (2H, s), 6.92 (1H, d), 7.18- 7.28 (3H, m), 7.35 (1H, dd), 7.50 (1H, m), 7.72 (1H, d), 13.6 (1H, s) LC/MS: Rt = 4.48 [MH+] 494.4 
               
               
                   
               
               
                 192 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-[2-(5- chloro-2-{[(4- chlorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.94- 2.01 (2H, m), 2.81-2.85 (2H, m), 2.92-2.96 (2H, m), 4.99 (2H, s), 6.94 (1H, d), 7.08- 7.17 (4H, m), 7.30-7.36 (3H, m), 7.72 (1H, d), 13.7 (1H, s) LC/MS: Rt =0 4.78 [MH+] 476.4 
               
               
                   
               
               
                 193 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-[2-(5- chloro-2-{[(2-Chloro- 4-fluorophenyl)methyl] oxy}phenyl}-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.93- 2.00 (2H, m), 2.80-2.83 (2H, m), 2.91-2.95 (2H, m), 5.03 (2H, s), 6.92 (1H, d), 7.15- 7.19 (3H, m), 7.25 (1H, dd), 7.34 (1H, dd), 7.43 (1H, dd), 7.73 (1H, d), 13.6 (1H, s) LC/MS: Rt = 4.86 [MH+] 494.3 
               
               
                   
               
               
                 194 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-{2-[5-chloro-2- ({[4-(trifluoromethyl) phenyl]methyl}oxy)phenyl]- 1-cyclopenten-1-yl}- 2-pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.94- 2.03 (2H, m), 2.83-2.87 (2H, m), 2.94-2.98 (2H, m), 5.10 (2H, s), 6.97 (1H, d), 7.09 (1H, d), 7.20 (1H, d), 7.29- 7.35 (4H, m), 7.66 (1H, d), 7.73 (1H, d), 13.6 (1H, s) LC/MS: Rt = 4.58 [MH+] 508.4 
               
               
                   
               
               
                 195 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6-{2-[5- chloro-2-({[2-fluoro- 4-(trifluoromethyl)phenyl] methyl}oxy)phenyl]- 1-cyclopenten-1-yl}- 2-pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.94- 2.02 (2H, m), 2.81-2.84 (2H, m), 2.92-2.96 (2H, m), 5.14 (2H, s), 6.94 (1H, d), 7.17- 7.20 (2H, m), 7.32-7.36 (2H, m), 7.53 (1H, d), 7.65 (1H, d), 7.71 (1H, d), 13.6 (1H, s) LC/MS: Rt = 4.39 [MH+] 526.3 
               
               
                   
               
               
                 196 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Chloro-2- [(phenylmethyl)oxy]phenyl}- 1-cyclopenten-1-yl)-3-methyl- 2-pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.94- 2.02 (2H, m), 2.38 (3H, s), 2.82-2.85 (2H, m), 2.93-2.99 (2H, m), 5.02 (2H, s), 6.95 (1H, d), 7.10-7.16 (4H, m), 7.26-7.32 (4H, m), 7.50 (1H, d), 12.6 (1H, s) LC/MS: Rt = 4.02 [MH+] 420.4, 422.5 
               
               
                   
               
               
                 197 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2- fluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-3-methyl-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.92- 1.99 (2H, m), 2.37 (3H, s), 2.78-2.82 (2H, m), 2.93-2.97 (2H, m), 5.07 (2H, s), 6.92 (1H, d), 7.08-7.22 (5H, m), 7.31-7.36 (2H, m), 7.48 (1H, d), 12.6 (1H, s) LC/MS: Rt = 4.04 [MH+] 438.4, 440.4 
               
               
                   
               
               
                 198 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(4- fluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1- yl]-3-methyl-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.94- 2.01 (2H, m), 2.37 (3H, s), 2.80-2.84 (2H, m), 2.94-2.98 (2H, m), 4.99 (2H, s), 6.93 (1H, d), 7.08-7.19 (6H, m), 7.31, (1H, dd), 7.49 (1H, d), 12.6 (1H, s) LC/MS: Rt = 4.04 [MH+] 438.4, 440.4 
               
               
                   
               
               
                 199 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2,4- difluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-3-methyl-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.92- 1.99 (2H, m), 2.37 (3H, s), 2.77-2.80 (2H, m), 2.92-2.96 (2H, m), 5.02 (2H, s), 6.91 (1H, d), 7.00 (1H, dt), 7.10 (1H, d), 7.19-7.26 (4H, m), 7.33, (1H, dd), 7.48 (1H, d), 12.6 (1H, s) LC/MS: Rt = 4.09 [MH+] 456.4, 458.4 
               
               
                   
               
               
                 200 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2,4,5- trifluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-3-methyl-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.93- 2.00 (2H, m), 2.36 (3H, s), 2.79-2.82 (2H, m), 2.93-2.97 (2H, m), 4.99 (2H, s), 6.92 (1H, d), 7.15 (1H, d), 7.19- 7.24 (2H, m), 7.34, (1H, dd), 7.47-7.52 (2H, m), 12.6 (1H, s) LC/MS: Rt = 4.17 [MH+] 474.4, 476.4 
               
               
                   
               
               
                 201 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2,3- difluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-3-methyl-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.93- 2.00 (2H, m), 2.37 (3H, s), 2.78-2.82 (2H, m), 2.93-2.97 (2H, m), 5.11 (2H, s), 6.92 (1H, d), 7.01 (1H, t), 7.10- 7.15 (2H, m), 7.20 (1H, d), 7.32-7.37 (2H, m), 7.48 (1H, d), 12.6 (1H, s) LC/MS: Rt = 4.09 [MH+] 456.4, 458.4 
               
               
                   
               
               
                 202 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(3,4,5- trifluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-3-methyl-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.97- 2.04 (2H, m), 2.36 (3H, s), 2.83-2.86 (2H, m), 2.97-3.00 (2H, m), 4.96 (2H, s), 6.95- 7.09 (4H, m), 7.19 (1H, d), 7.33, (1H, dd), 7.50 (1H, d), 12.6 (1H, s) LC/MS: Rt = 4.24 [MH+] 474.4, 476.4 
               
               
                   
               
               
                 203 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2- chloro-6-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-3-methyl-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.85- 1.92 (2H, m), 2.38 (3H, s), 2.70-2.73 (2H, m), 2.86-2.89 (2H, m), 5.12 (2H, s), 6.85 (1H, d), 7.02 (1H, d), 7.21, (1H, t), 7.30-7.48 (5H, m), 12.5 (1H, s) LC/MS: Rt = 4.24 [MH+] 472.4 
               
               
                   
               
               
                 204 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2,4,6- trifluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-3-methyl-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.87- 1.95 (2H, m), 2.38 (3H, s), 2.70-2.74 (2H, m), 2.87-2.91 (2H, m), 5.02 (2H, s), 6.85 (1H, d), 7.07 (1H, d), 7.10- 7.16 (2H, m), 7.27 (1H, d), 7.36 (1H, dd), 7.47 (1H, d), 12.6 (1H, s) LC/MS: Rt = 4.06 [MH+] 474.4, 476.4 
               
               
                   
               
               
                 205 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2,6- difluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-3-methyl-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.86- 1.93 (2H, m), 2.38 (3H, s), 2.70-2.73 (2H, m), 2.87-2.90 (2H, m), 5.08 (2H, s), 6.85 (1H, d), 7.03-7.09 (3H, m), 7.28 (1H, d), 7.34-7.48 (3H, m), 12.6 (1H, s) LC/MS: Rt = 3.99 [MH+] 456.4, 458.4 
               
               
                   
               
               
                 206 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2- chloro-4-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-3-methyl- 2-pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.94- 2.00 (2H, m), 2.36 (3H, s), 2.79-2.83 (2H, m), 2.94-2.97 (2H, m), 5.03 (2H, s), 6.91 (1H, d), 7.12-7.20 (3H, m), 7.27-7.34 (2H, m), 7.41 (1H, dd), 7.48 (1H, d), 12.6 (1H, s) LC/MS: Rt = 4.31 [MH+] 472.4 
               
               
                   
               
               
                 207 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(4- chlorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-3-methyl-2- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.95- 2.01 (2H, m), 2.37 (3H, s), 2.81-2.84 (2H, m), 2.95-2.99 (2H, m), 5.00 (2H, s), 6.94 (1H, d), 7.10-7.15 (4H, m), 7.29-7.35 (3H, m), 7.49 (1H, d), 12.6 (1H, s) t = 4.26 [MH+] 454.4 
               
               
                   
               
               
                 208 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2,4- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.92- 2.00 (2H, m), 2.79-2.82 (2H, m), 2.94-2.98 (2H, m), 5.00 (2H, s), 6.94 (1H, d), 7.01 (1H, dt), 7.10 (1H, d), 7.15- 7.27 (3H, m), 7.34 (1H, dd), 7.92 (1H, dd), 8.86 (1H), 13.2 (1H, s) LC/MS: Rt = 4.25 [MH+] 442.3, 444.3 
               
               
                   
               
               
                 209 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-[2-(5-Chloro-2-{[(2,4- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.94- 2.02 (2H, m), 2.75-2.79 (4H, m), 5.01 (2H, s), 6.73 (1H, d), 6.97 (1H, d), 7.10-7.17 (2H, m), 7.28-7.33 (2H, m), 7.52 (1H, q), 7.98 (1H, dd), 8.56 (1H, dd), 13.0 (1H, s) LC/MS: Rt = 3.54 [MH+] 442.3, 444.3 
               
               
                   
               
               
                 210 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(2-{5-Chloro-2- [(phenylmethyl)oxy] phenyl}-1-cyclopenten- 1-yl)-3-pyridinecarboxylic acid 
                 LC/MS: Rt = 3.41 [MH+] 406.4, 408.4 
               
               
                   
               
               
                 211 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-[2-(5-Chloro-2-{[(4- fluorophenyl)methyl] oxy}phenyl)-1-cyclopenten- 1-yl]-3-pyridinecarboxylic acid 
                 LC/MS: Rt = 3.46 [MH+] 424.3, 426.3 
               
               
                   
               
               
                 212 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Ethyl-5-{2-[2- [(phenylmethyl)oxy]- 5-(trifluoromethyl)phenyl]- yl]-1-cyclopenten-1-yl}-3- pyridinecarboxylic acid 
                   1 H NMR (DMSO-d 6 ) δ: 1.12 (3H, t), 2.00-2.07 (2H, m), 2.83-2.92 (4H, m), 2.98 (2H, q), 5.13 (2H, s), 7.19 (2H, m), 7.27-7.36 (5H, m), 7.63 (1H, dd), 7.79 (1H, d), 8.24 (1H, d), 13.2 (1H, s) LC/MS: Rt = 3.87 [MH+] 468.4 
               
               
                   
               
               
                 213 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{5-Chloro-2- [(phenylmethyl)oxy]- 3-pyridinyl}-1- cyclopenten-1-yl)-2- methylbenzoic acid 
                 LC/MS: Rt = 4.04 min. [MH + ] 420, 422. 
               
               
                   
               
               
                 214 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(4- fluorophenyl)methyl] oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- methylbenzoic acid 
                 LC/MS: Rt = 4.04 min. [MH + ] 438, 440. 
               
               
                   
               
               
                 215 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{5-Chloro-2- [(phenylmethyl)oxy]- 3-pyridinyl}-1-cyclopenten- 1-yl)-2-fluorobenzoic acid 
                 LC/MS: Rt = 4.44 min. [MH + ] 424, 426. 
               
               
                   
               
               
                 216 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(4- fluorophenyl)methyl] oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.39 min. [MH + ] 442, 444. 
               
               
                   
               
               
                 217 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-chloro-2-{[(2- fluorophenyl)methyl] oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.32 min. [MH + ] 442, 444. 
               
               
                   
               
               
                 218 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- {[(2,3-difluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.26 min. [MH + ] 460, 462. 
               
               
                   
               
               
                 219 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- {[(3,4-difluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.31 min. [MH + ] 460, 462. 
               
               
                   
               
               
                 220 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- {[(2,5-difluorophenyl)methyl] oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzolc acid 
                 LC/MS: Rt = 4.32 min. [MH + ] 460, 462. 
               
               
                   
               
               
                 221 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[5-Chloro-2-({[2- fluoro-4-(trifluoromethyl) phenyl]methyl}oxy)-3- pyridinyl]-1-cyclopenten-1- yl}-2-fluorobenzoic acid 
                 LC/MS: Rt = 4.46 min. [MH + ] 510, 512. 
               
               
                   
               
               
                 222 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(4- chloro-2-fluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.53 min. [MH + ] 476, 477, 478, 479. 
               
               
                   
               
               
                 223 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-chloro-2-{[(2- chloro-4-fluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.54 min. [MH + ] 476, 477, 478, 479. 
               
               
                   
               
               
                 224 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- {[(2,3,4-trifluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.34 min. [MH + ] 478, 480. 
               
               
                   
               
               
                 225 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- {[(2,3,6-trifluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.26 min. [MH + ] 478, 480. 
               
               
                   
               
               
                 226 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- {[(2,4,5-trifluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.34 min. [MH + ] 478, 480. 
               
               
                   
               
               
                 227 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- {[(2,4,6-trifluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.28 min. [MH + ] 478, 480. 
               
               
                   
               
               
                 228 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-chloro-2- {[(3,4,5-trifluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.29 min. [MH + ] 478, 480. 
               
               
                   
               
               
                 229 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-5-(2-{2- [(phenylmethyl)oxy]- 3-pyridinyl}-1-cyclopenten- 1-yl)benzoic acid 
                 LC/MS: Rt = 4.04 min. [MH + ] 390. 
               
               
                   
               
               
                 230 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-5-[2-(2-{[(4- fluorophenyl)methyl] oxy}-3-pyridinyl)-1- cyclopenten-1-yl]benzoic acid 
                 LC/MS: Rt = 4.06 min [MH + ] 408. 
               
               
                   
               
               
                 231 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Bromo-2-{[(4- fluorophenyl)methyl]oxy}- 3-pyridinyl)-1-cyclopenten-1- yl]-2-fluorobenzoic acid 
                 LC/MS: Rt = 4.26 min. MH + ] 486, 488. 
               
               
                   
               
               
                 232 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Bromo-2-{[(2- chloro-4-fluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.25 min. [MH + ] 520, 522. 
               
               
                   
               
               
                 233 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Bromo-2-{[(2,4,6- trifluorophenyl)methyl] oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.23 min. [MH + ] 522, 524. 
               
               
                   
               
               
                 234 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Bromo-2-{[(2- fluorophenyl)methyl] oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.38 min. [MH + ] 486, 488. 
               
               
                   
               
               
                 235 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[5-Bromo-2-({[2- fluoro-4-(trifluoromethyl) phenyl]methyl}oxy)-3- pyridinyl]-1-cyclopenten-1- yl}-2-fluorobenzoic acid 
                 LC/MS: Rt = 4.54 min. [MH + ] 554, 556. 
               
               
                   
               
               
                 236 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{5-Bromo-2- [(phenylmethyl)oxy]- 3-pyridinyl}-1-cyclopenten- 1-yl)-2-fluorobenzoic acid 
                 LC/MS: Rt = 4.42 min [MH + ] 468, 470. 
               
               
                   
               
               
                 237 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Bromo-2- {[(2,4-difluorophenyl) methyl]oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoic acid 
                 LC/MS: Rt = 4.50 min [MH + ] 504, 506. 
               
               
                   
               
               
                 238 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{2-[(Phenylmethyl)oxy]- 3-pyridinyl}-1-cyclopenten- 1-yl)-2-pyridinecarboxylic acid 
                 LC/MS: Rt = 3.24 min [MH + ] 373. 
               
               
                   
               
               
                 239 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[2-(5-Bromo-2-{[(4- fluorophenyl)methyl]oxy}-3- pyridinyl)-1-cyclopenten-1- yl]benzoic acid 
                 LC/MS: Rt = 4.26 min [MH + ] 468, 470 
               
               
                   
               
               
                 240 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[2-(5-Bromo-2-{[(2,4- difluorophenyl)methyl] oxy}-3-pyridinyl)-1- cyclopenten-1-yl]benzoic acid 
                 LC/MS: Rt = 3.93 min [MH+] 486, 488 
               
               
                   
               
               
                 241 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[2-(Phenylmethoxy)- 5-(trifluoromethyl)pyridin- 3-yl]cyclopent-1-en-1-yl}- pyridine-2-carboxylic acid 
                 LC/MS Rt = 3.92 min [MH + ] 441. 
               
               
                   
               
               
                 242 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Chloro-2- [(phenylmethyl)oxy]phenyl}- 1-cyclopenten-1-yl)-4- pyrimidinecarboxylic acid 
                 LC/MS: Rt = 4.88 [MH+] 407.3, 409.3 
               
               
                   
               
               
                 243 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Chloro-2-{[(2,4- difluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1-yl]- 4-pyrimidinecarboxylic acid 
                 LC/MS: Rt = 5.13 [MH+] 443.3, 445.3 
               
               
                   
               
            
           
         
       
     
     Example 244 
     6-[2-(2-{[(4-Bromo-2-fluorophenyl)methyl]oxy}-5-fluorophenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid 
     
       
         
         
             
             
         
       
     
     Methyl 6-[2-(5-fluoro-2-hydroxyphenyl)1-cyclopenten-1-yl]-2-pyridinecarboxylate (104 mg, 0.333 mmol) was treated with 4-bromo-2-fluorobenzyl bromide (96 mg, 0.358 mmol) and potassium carbonate (140 mg, 1.0 mmol) in 2-butanone (4 ml). The reaction mixture was then refluxed overnight under nitrogen, filtered through celite and reduced under vacuum to an oil. The oil was dissolved in methanol (3 ml), 2M sodium hydroxide (2 ml) was added and the reaction mixture stirred at 65° C. for one hour. The reaction mixture was then reduced down to −1 ml under vacuum, diluted to 20 ml with water and 2M hydrochloric acid (1.6 ml) added as well as a couple of drops of acetic acid to pH-6, extracted with ethyl acetate (2×20 ml). The organic extract was then dried over magnesium sulphate, filtered and evaporated down to a solid (69 mg, 42%) 
     LC/MS Rt=3.94 min [MH + ] 488. 
     The following Examples were prepared by the procedure used for 6-[2-(2-{[(4bromo-2-fluorophenyl)methyl]oxy}-fluorophenyl)-cyclopenten-1-yl]-2-pyridinecarboxylic acid: 
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 Example 
                   
                 Name 
                 LC/MS 
               
               
                   
               
             
            
               
                 245 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2,4- Dichlorophenyl)methyl]oxy}- 5-fluorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylic acid 
                 Rt = 4.16, [MH + ] 458 
               
               
                   
               
               
                 246 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Fluoro-2-{[(4- methylphenyl)methyl]oxy} phenyl)-1-cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                 Rt = 3.75, [MH + ] 405 
               
               
                   
               
               
                 247 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4- Chlorophenyl)methyl]oxy}- 5-fluorophenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 Rt = 4.43, [MH + ] 425 
               
               
                   
               
               
                 248 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Fluoro-2-{[(2,4,6- trifluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                 Rt = 4.08, [MH + ] 445 
               
               
                   
               
               
                 249 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[5-Fluoro-2-({[2-fluoro-4- (trifluoromethyl)phenyl]methyl} oxy)phenyl]-1-cyclopenten-1- yl}-2-pyrazinecarboxylic acid 
                 Rt = 4.27, [MH + ] 475 
               
               
                   
               
               
                 250 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4-Bromo-2- fluorophenyl)methyl]oxy}-5- fluorophenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 Rt = 4.57, [MH + ] 489 
               
               
                   
               
               
                 251 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4-Chloro-2- fluorophenyl)methyl]oxy}-5- fluorophenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 Rt = 4.47, [MH + ] 443 
               
               
                   
               
               
                 252 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(4- Bromophenyl)methyl]oxy}-5- fluorophenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 Rt = 4.52, [MH + ] 471 
               
               
                   
               
               
                 253 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2-Chloro-4- fluorophenyl)methyl]oxy}-5- fluorophenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 Rt = 4.51, [MH + ] 443 
               
               
                   
               
               
                 254 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Fluoro-2-{[(2- fluorophenyl)methyl]oxy}phenyl)- 1-cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                 Rt = 4.20, [MH + ] 409 
               
               
                   
               
               
                 255 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2,3- Difluorophenyl)methyl]oxy)-5- fluorophenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 Rt = 4.21, [MH + ] 427 
               
               
                   
               
               
                 256 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2,4- Dichlorophenyl)methyl]oxy}- 5-fluorophenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                 Rt = 4.83, [MH + ] 459 
               
               
                   
               
               
                 257 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Fluoro-2- [(phenylmethyl)oxy]phenyl}-1- cyclopenten-1-yl)-2- pyrazinecarboxylic acid 
                 Rt = 4.14, [MH + ] 391 
               
               
                   
               
               
                 258 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Fluoro-2-{[(4- fluorophenyl)methyl]oxy} phenyl}-1-cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                 Rt = 4.12, [MH + ] 409 
               
               
                   
               
               
                 259 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2,4- Difluorophenyl)methyl]oxy}-5- fluorophenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 Rt = 4.15, [MH + ] 427 
               
               
                   
               
               
                 260 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2,5- Difluorophenyl)methyl]oxy}-5- fluorophenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 Rt = 4.13, [MH + ] 427 
               
               
                   
               
               
                 261 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(3,4- Difluorophenyl)methyl]oxy}-5- fluorophenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 Rt = 4.14, [MH + ] 427 
               
               
                   
               
               
                 262 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2- Chlorophenyl)methyl]oxy}-5- fluorophenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 Rt = 4.15, [MH + ] 425 
               
               
                   
               
               
                 263 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Fluoro-2-{[(2,3,6- trifluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1-yl]-2- pyrazinecarboxylic acid 
                 Rt = 4.03, [MH + ] 445 
               
               
                   
               
               
                 264 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2,6- Difluorophenyl)methyl]oxy}-5- fluorophenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 Rt = 5.15, [MH + ] 427 
               
               
                   
               
               
                 265 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2-Chloro-6- fluorophenyl)methyl]oxy}-5- fluorophenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 Rt = 4.19, [MH + ] 443 
               
               
                   
               
               
                 266 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(2-{[(2- Bromophenyl)methyl]oxy}-5- fluorophenyl)-1-cyclopenten- 1-yl]-2-pyrazinecarboxylic acid 
                 Rt = 4.51, [MH + ] 471 
               
               
                   
               
               
                 267 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-{2-[5-Fluoro-2-({[4- (trifluoromethyl)phenyl]methyl} oxy)phenyl]-1-cyclopenten-1- yl}-2-pyrazinecarboxylic acid 
                 Rt = 4.25, [MH + ] 459 
               
               
                   
               
            
           
         
       
     
     Example 268 
     5-[2-(5-Bromo-2{[(2,4-difluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-3-pyridazinecarboxylic acid 
     
       
         
         
             
             
         
       
     
     Ethyl 5-[2-(5-bromo-2-hydroxyphenyl)-1-cyclopenten-1-yl]-3-pyridazinecarboxylate (130 mg. 0.333 mmol) in dimethylformamide (4 ml) was treated with 2,4-difluorobenzyl bromide (80 mg, 0.386 mmol) and potassium carbonate (200 mg, 1.45 mmol). The reaction mixture was then stirred at room temperature for 5 hours, filtered through celite, and washed with ethyl acetate (3×15 ml). The filtrate was then washed with brine (2×50 ml), dried over magnesium sulphate and chromatographed, eluting with 1:1 diethyl ether/isohexane. The product was dissolved in 2M sodium hydroxide (2 ml) and methanol (3 ml) and heated with stirring for one hour at 70° C. The mixture was evaporated to ˜1 ml, diluted to 10 ml with water and treated with 2M hydrochloric acid (1.8 ml) and a couple of drops of acetic acid. The mixture was extracted with ethyl acetate (3×10 ml), dried over magnesium sulphate, filtered and evaporated to give the title compound (120 mg, 75% yield) 
     LC/MS Rt=4.25 min [MH + ] 489 
     The following Examples were prepared by the procedure used for 5-[2-(5-bromo-2-{[(2,4-difluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-3-pyridazinecarboxylic acid: 
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 Example 
                 Structure 
                 Name 
                   1 H NMR/LCMS 
               
               
                   
               
             
            
               
                 269 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Bromo-2-{[(4- fluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1- yl]-3-pyridazinecarboxylic acid 
                   1 H NMR (CD 3 OD) 2.05-2.15(2H, m) 2.85- 2.97(4H, m) 4.84(2H, s) 6.93-7.04(3H, m) 7.06- 7.13(2H, m) 7.25-7.29(1H, d) 7.40-7.45(1H, dd) 7.83(1H, s) 8.69(1H, s) 
               
               
                   
               
               
                 270 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Bromo-2-{[(2-6- difluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1- yl]-3-pyridazinecarboxylic acid 
                 Rt = 4.19, [MH + ] 489 
               
               
                   
               
               
                 271 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Bromo-2-{[(2- fluorophenyl)methyl]oxy} phenyl-1-cyclopenten-1-yl]- 3-pyridazinecarboxylic acid 
                 Rt = 4.29, [MH + ] 471 
               
               
                   
               
               
                 272 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Bromo-2-{[(2,4,6- trifluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1- yl]-3-pyridazinecarboxylic acid 
                 Rt = 4.19, [MH + ] 535 
               
               
                   
               
               
                 273 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Bromo-2-{[(2,4,5- trifluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1- yl]-3-pyridazinecarboxylic acid 
                 Rt = 4.30, [MH + ] 507 
               
               
                   
               
               
                 274 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Bromo-2-{[2,3-di- fluorophenyl)methyl[oxy} phenyl)-1-cyclopenten-1- yl]-3-pyridazinecaboxylic acid 
                 Rt = 4.27, [MH + ] 489 
               
               
                   
               
               
                 275 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Bromo-2-{[(2- chloro-4-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-3- pyridazinecarboxylic acid 
                 Rt = 4.61, [MH + ] 505 
               
               
                   
               
               
                 276 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Bromo-2- [(phenylmethyl)oxy]phenyl)- 1-cyclopenten-1-yl]-3- pyridazinecarboxylic acid 
                 Rt = 4.39, [MH + ] 453 
               
               
                   
               
            
           
         
       
     
     The following Examples were prepared by Standard Hydrolysis Procedure B: 
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 Example 
                 Structure 
                 Name 
                 Data 
               
               
                   
               
             
            
               
                 277 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(2- bromophenyl)methyl] oxy}-5-chlorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                   1 H NMR (DMSO) δ: 1.91-1.97 (2H, m), 2.79- 2.83 (2H, m), 2.93-2.98 (2H, m), 5.12 (2H, s), 6.63 (1H, d), 6.96 (1H, s), 7.12 (1H, d), 7.26- 7.38 (5H, m), 7.50 (1H, d), 7.64 (1H, d). 
               
               
                   
               
               
                 278 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                   1 H NMR (CDCl 3 ) δ: 1.91-1.98 (2H, m), 2.95- 2.98 (2H, m), 5.10 (2H, s), 6.66-6.72 (2H, m), 6.78- 6.80 (1H, m), 7.03 (1H, d), 7.08-7.16 (3H, m), 7.29- 7.32 (2H, m), 7.38-7.41 (1H, m), 7.60 (1H, d). LC/MS: Rt = 3.38 min, [M + H] 390. 
               
               
                   
               
               
                 279 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2- {[(2,4,6- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                   1 H NMR (DMSO, 50° C.) δ: 1.85-1.96 (2H, m), 2.67-2.93 (4H, m), 5.05 (2H, s), 6.69-6.75 (3H, m), 6.95- 7.00 (2H, m), 7.09 (1H, d), 7.14-7.18 (1H, m), 7.35- 7.40 (1H, m), 7.64 (1H, d). LC/MS: Rt = 3.40 min, [M + H] 426. 
               
               
                   
               
               
                 280 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2- {[(2,3,6- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                   1 H NMR (DMSO) δ: 1.86-1.94 (2H, m), 2.70- 2.73 (2H, m), 2.88-2.92 (2H, m), 5.24 (2H, s), 6.57 (1H, d), 6.85-6.86 (2H, m), 7.20-7.29 (3H, m), 7.32- 7.35 (1H, m), 7.51-7.58 (1H, m), 7.62 (1H, d). LC/MS: Rt = 3.38 min, [M + H] 426. 
               
               
                   
               
               
                 281 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(4- chloro-2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylate 
                   1 H NMR (DMSO) δ: 1.94-2.01 (2H, m), 2.80- 2.85 (2H, m), 2.95-2.98 (2H, m), 5.12 (2H, s), 6.89- 6.94 (1H, m), 6.98 (1H, dd), 7.18 (1H, d), 7.27-7.30 (2H, m), 7.44 (1H, dd), 7.74 (1H, s), 8.55 (1H, s). LC/MS: Rt = 4.48 min, [M − H] 423, 425. 
               
               
                   
               
               
                 282 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(2,4- dichlorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyrazinecarboxylate 
                   1 H NMR (DMSO) δ: 1.95-2.03 (2H, m), 2.83- 2.87 (2H, m), 2.95-2.99 (2H, m), 5.12 (2H, s), 6.91- 6.94 (1H, m), 7.01 (1H, dd), 7.15 (1H, d), 7.28-7.33 (2H, m), 7.43 (1H, dd), 7.63 (1H, d), 7.77 (1H, s), 8.56 (1H, s). LC/MS: Rt = 4.98 min, [M − H] 439, 441. 
               
               
                   
               
               
                 283 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2-{5-Bromo-2- [(phenylmethyl)oxy] phenyl}-1-cyclopenten-1- yl)-3-chloro-2- pyridinecarboxylic acid sodium salt 
                 LC/MS: Rt = 4.43, [MH+]486.3 
               
               
                   
               
               
                 284 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-[2-(5-Bromo-2-{[(4- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-3- chloro-2- pyridinecarboxylic acid sodium salt 
                 LC/MS: Rt = 4.38 [MH+] 504.3 
               
               
                   
               
               
                 285 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-bromo- 2-{[(2-4- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-3- chloro-2- pyridinecarboxylate 
                 LC/MS: Rt = 4.42 [MH+] 522.3 
               
               
                   
               
               
                 286 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-bromo- 2-{[(2,3,6- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-3- chloro-2- pyridinecarboxylate 
                 LC/MS: Rt = 4.27 [MH+] 540.3 
               
               
                   
               
               
                 287 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-bromo- 2-{[(4-chloro-2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-3- chloro-2- pyridinecarboxylate 
                 LC/MS: Rt = 4.65 [MH+] 538.3 
               
               
                   
               
               
                 288 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-bromo- 2-{[(2,3,4- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-3- chloro-2- pyridinecarboxylate 
                 LC/MS: Rt = 4.44 [MH+] 540.3 
               
               
                   
               
               
                 289 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-(2-{5-chloro- 2-[(phenylmethyl)oxy] phenyl}-1-cyclopenten-1- yl)-2-(trifluoromethyl)- 3-pyridinecarboxylate 
                 LC/MS: Rt = 3.37, [MH+] 474.4, 476.3 
               
               
                   
               
               
                 290 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-[2-(5-chloro- 2-{[(2-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 LC/MS: Rt = 4.30 [MH+] 492.3, 494.3 
               
               
                   
               
               
                 291 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-[2-(5-chloro- 2-{[(4-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 LC/MS: Rt = 3.83 [MH+] 492.3, 494.3 
               
               
                   
               
               
                 292 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-[2-(5-chloro- 2-{[(2,4- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 LC/MS: Rt = 4.02 [MH+] 510.3, 512.3 
               
               
                   
               
               
                 293 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-[2-(5-chloro- 2-{[(2-chloro-4- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 LC/MS: Rt = 4.25 [MH+] 526.3 
               
               
                   
               
               
                 294 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-[2-(5-chloro- 2-{[(2,6- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 LC/MS: Rt = 4.08 [MH+] 510.3, 512.3 
               
               
                   
               
               
                 295 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-[2-(5-chloro- 2-{[(4-chloro-2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 LC/MS: Rt = 4.37 [MH+] 526.3 
               
               
                   
               
               
                 296 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-[2-(5-chloro- 2-{[(2,4,6- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 LC/MS: Rt = 4.15 [MH+] 528.3, 530.3 
               
               
                   
               
               
                 297 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-[2-(5-chloro- 2-{[(2,4,5- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 LC/MS: Rt = 4.24 [MH+] 528.3, 530.3 
               
               
                   
               
               
                 298 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2- {[(2,4,5-trifluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylic acid sodium salt 
                 LC/MS: Rt = 4.17 [MH+] 528.3, 530.3 
               
               
                   
               
               
                 299 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-{2-[2- [(phenylmethyl)oxy]-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-2- (trifluoromethyl)-3- pyridinecarboxylate. 
                 LC/MS: Rt = 3.84 min. [M + H] = 508 
               
               
                   
               
               
                 300 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[2-{[(2- fluorophenyl)methyl] oxy}-5-(trifluoromethyl) phenyl]-1-cyclopenten-1- yl}-2-(trifluoromethyl)- 3-pyridinecarboxylic acid Sodium salt 
                 Rt = 4.23 min [M + H]526 
               
               
                   
               
               
                 301 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[2-{[(4- fluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-2- (trifluoromethyl)-3- pyridinecarboxylic acid sodium salt 
                 Rt = 3.77 min [M + H] 526 
               
               
                   
               
               
                 302 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[2-{[(2,4- difluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-2- (trifluoromethyl)-3- pyridinecarboxylic acid sodium salt 
                 Rt = 4.24 min [M + H] 544 
               
               
                   
               
               
                 303 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(trifluoromethyl)-5-[2- (5-(trifluoromethyl)-2- {[(2,4,6- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-3- pyridinecarboxylic acid sodium salt 
                 Rt = 4.16 min [M + H] 562 
               
               
                   
               
               
                 304 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-{2-[2-{[(2-chloro-4- fluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-2- (trifluoromethyl)-3- pyridinecarboxylic acid sodium salt 
                 Rt = 4.51 min [M + H] 560 (1Cl) 
               
               
                   
               
               
                 305 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-{2-[2-{[(4- chloro-2- fluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 Rt = 4.53 min [M + H] 560 (1Cl) 
               
               
                   
               
               
                 306 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 6-{2-[2- [(phenylmethyl)oxy]-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 3.77 min (M + H] 508 
               
               
                   
               
               
                 307 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 6-{2-[2-{[(2- fluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.46 min (M + H] 526 
               
               
                   
               
               
                 308 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 6-{2-[2-{[(4- fluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl)-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 3.74 min (M + H] 526 
               
               
                   
               
               
                 309 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 6-{2-[2-{[(2,4- difluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.43 min [M + H] 544 
               
               
                   
               
               
                 310 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 4- (trifluoromethyl)-6-[2- (5-(trifluoromethyl)-2- {[(2,4,6- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.36 min [M + H] 562 
               
               
                   
               
               
                 311 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 6-{2-[2-{[(2- chloro-4-fluorophenyl) methyl]oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.65 min [M + H] 560 (1Cl) 
               
               
                   
               
               
                 312 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 6-{2-[2-{[(4- chloro-2- fluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.23 min [M + H] 560 (1Cl) 
               
               
                   
               
               
                 313 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 6-{2-[2-{[(3,4- difluorophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.38 min [M + H] 544 
               
               
                   
               
               
                 314 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 6-{2-[2-{[(4- bromophenyl)methyl] oxy}-5- (trifluoromethyl)phenyl]- 1-cyclopenten-1-yl}-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 Rt = 4.50 min [M + H] 586, 588 (1Br) 
               
               
                   
               
               
                 315 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 4-(trifluoro- methyl)-6-{2-[5- (trifluoromethyl)-2- ({[4-(trifluoromethyl) phenyl]methyl}oxy) phenyl]-1-cyclopenten- 1-yl}-2- pyridinecarboxylate 
                 Rt = 4.55 min [M + H] 576 
               
               
                   
               
               
                 316 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-(2-{5-chloro- 2-[(phenylmethyl)oxy] phenyl}-1-cyclopenten-1- yl)-4-(trifluoromethyl)- 2-pyridinecarboxylate 
                 [M + H] 474.4, 476.4 Rt = 4.26 min 
               
               
                   
               
               
                 317 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-chloro- 2-{[(2-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 492.4, 494.4 Rt = 3.85 min 
               
               
                   
               
               
                 318 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-chloro- 2-{[(4-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 492.3, 494.3 Rt = 4.53 min 
               
               
                   
               
               
                 319 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-chloro- 2-{[(2,4-difluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 510.3, 512.3 Rt = 4.50 min 
               
               
                   
               
               
                 320 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-chloro- 2-{[(2,4,5- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 528.3, 530.3 Rt = 4.54 min 
               
               
                   
               
               
                 321 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-chloro- 2-{[(4-chloro-2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 526.3, 528.3 Rt = 4.78 min 
               
               
                   
               
               
                 322 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-chloro- 2-{[(2,3,4- trifluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 528.3, 530.3 Rt = 4.58 min 
               
               
                   
               
               
                 323 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-chloro- 2-{[(3,4-difluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 510.3, 512.3 Rt = 4.49 min 
               
               
                   
               
               
                 324 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-chloro- 2-{[(3,4,5-trifluoro- phenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 528.3, 530.3 Rt = 3.74 min 
               
               
                   
               
               
                 325 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-chloro- 2-{[(2,3-difluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 510.3, 512.3 Rt = 4.55 min 
               
               
                   
               
               
                 326 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-chloro- 2-{[(2-chloro-4- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-4- (trifluoromethyl)-2- pyridinecarboxylate 
                 [M + H] 526.3, 528.3 Rt = 4.82 min 
               
               
                   
               
               
                 327 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-chloro- 2-{[(2,4,6-trifluoro- phenyl)methyl]oxy} phenyl)-1-cyclopenten- 1-yl]-4-(trifluoro- methyl)-2- pyridinecarboxylate 
                 [M + H] 528.3, 530.3 Rt = 3.87 min 
               
               
                   
               
               
                 328 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 5-[2-(5-bromo- 2-{[(2-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 Rt = 4.0 min [M + H] 536, 539 (1Br) 
               
               
                   
               
               
                 329 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 5-[2-(5-bromo- 2-{[(4-fluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 Rt = 4.0 min [M + H] 536, 539 (1Br) 
               
               
                   
               
               
                 330 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 5-[2-(5-bromo- 2-{[(2,4-difluorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 Rt = 4.0 min [M + H] 556, 557 (1Br) 
               
               
                   
               
               
                 331 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 5-[2-(5-bromo- 2-{[2,4,6-trifluoro- phenyl)methyl]oxy} phenyl)-1-cyclopenten-1- yl]-2-(trifluoromethyl)-3- pyridinecarboxylate 
                 Rt = 3.9 min [M + H] 574, 575 (1Br) 
               
               
                   
               
               
                 332 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 5-[2-(5-bromo- 2-{[(2-chloro-4- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 Rt = 4.3 min [M + H] 572, 573 (1Br) 
               
               
                   
               
               
                 333 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 5-[2-(5-bromo- 2-{[(4-chlorophenyl) methyl]oxy}phenyl)-1- cyclopenten-1-yl]-2- (trifluoromethyl)-3- pyridinecarboxylate 
                 Rt = 4.2 min [M + H] 554, 556 (1 Br) 
               
               
                   
               
               
                 334 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 6-(2-{4,5- dichloro-2-[(phenylmethyl) oxy]phenyl}-1-cyclo- penten-1-yl)-2- pyridinecarboxylate 
                 Rt = 4.09 [MH+] 440.4, 442.4 
               
               
                   
               
               
                 335 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 6-[2-(4,5- dichloro-2-{[(2- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.11 [MH+] 458.4, 460.4 
               
               
                   
               
               
                 336 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 6-[2-(4,5- dichloro-2-{[(2,4- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.12 [MH+] 476.4, 478.4 
               
               
                   
               
               
                 337 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 6-[2-(4,5- dichloro-2-{[(2,4,6- trifluorophenyl)methyl] oxy)phenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 4.14 [MH+] 494.4, 496.4 
               
               
                   
               
               
                 338 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 sodium 3-chloro-6-{2- [5-(trifluoromethyl)-2-({[4- (trifluoromethyl)phenyl] methyl}oxy)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 4.41 min [M + H] 542 (1Cl) 
               
               
                   
               
               
                 339 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{5-Chloro-2- [(phenylmethyl)oxy] phenyl]-1-cyclopenten-1- yl)-3-pyridazinecarboxylic acid 
                 [M + H] 407.2, 409.2 Rt = 4.42 min 
               
               
                   
               
               
                 340 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(4- fluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-3- pyridazinecarboxylic acid 
                 [M + H] 425.1, 427.1 Rt = 4.30 min 
               
               
                   
               
               
                 341 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-[2-(5-Chloro-2-{[(2,4- difluorophenyl)methyl] oxy}phenyl)-1- cyclopenten-1-yl]-3- pyridazinecarboxylic acid 
                 [M + H] 443.1, 445.1 Rt = 4.30 min 
               
               
                   
               
               
                 342 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 2-fluoro-5-{2- [2-[(phenylmethyl)oxy]- 5-(trifluoromethyl)-3- pyridinyl]-1- cyclopenten-1- yl}benzoate 
                 LC/MS: Rt = 4.41 min. [MH + ] 458 
               
               
                   
               
               
                 343 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 3-(2-{5-chloro- 2-[(phenylmethyl)oxy]- 3-pyridinyl}-1- cyclopenten-1-yl)-5- fluorobenzoate 
                 LC/MS: Rt = 4.35 min. [MH + ] 424, 426. 
               
               
                   
               
               
                 344 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-[2-(5-chloro- 2-{[(2,4-difluorophenyl) methyl]oxy}-3-pyridinyl)- 1-cyclopenten-1-yl]-2- fluorobenzoate 
                 LC/MS: Rt = 4.42 min. [MH + ] 460, 462. 
               
               
                   
               
               
                 345 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 3-[2-(5-chloro- 2-{[(4-fluorophenyl) methyl]oxy}-3-pyridinyl)- 1-cyclopenten-1-yl]-5- fluorobenzoate 
                 LC/MS: Rt = 4.36 min. [MH + ] 442, 444. 
               
               
                   
               
               
                 346 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 3-[2-(5-chloro- 2-{[(2-fluorophenyl) methyl]oxy)-3-pyridinyl)- 1-cyclopenten-1-yl]-5- fluorobenzoate 
                 LC/MS: Rt = 4.41 min. [MH + ] 442, 444. 
               
               
                   
               
               
                 347 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 3-[2-(5-chloro- 2-{[(2,4-difluorophenyl) methyl]oxy}-3-pyridinyl)- 1-cyclopenten-1-yl]-5- fluorobenzoate 
                 LC/MS: Rt = 4.42 min. [MH + ] 460, 462. 
               
               
                   
               
               
                 348 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 3-[2-(5-chloro- 2-{[(2,6-difluorophenyl) methyl]oxy}-3- pyridinyl)-1- cyclopenten-1-yl]-5- fluorobenzoate 
                 LC/MS: Rt = 4.35 min. [MH + ] 460, 462. 
               
               
                   
               
               
                 349 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 3-[2-(5-chloro- 2-{[(2,4,6- trifluorophenyl)methyl] oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-5- fluorobenzoate 
                 LC/MS: Rt = 4.39 min. [MH + ] 478, 480. 
               
               
                   
               
               
                 350 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 3-[2-(5-chloro- 2-{[(4-chloro-2- fluorophenyl)methyl] oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-5- fluorobenzoate 
                 LC/MS: Rt = 4.62 min. [MH + ] 476, 477, 478, 479. 
               
               
                   
               
               
                 351 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 3-{2-[5-chloro- 2-({[2-fluoro-4- (trifluoromethyl)phenyl] methyl}oxy)-3-pyridinyl]- 1-cyclopenten-1-yl}-5- fluorobenzoate 
                 LC/MS: Rt = 4.56 min. [MH + ] 508, 510. 
               
               
                   
               
               
                 352 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-{2-[2-{[(2,4- difluorophenyl)methyl] oxy}-5-(trifluoromethyl)-3- pyridinyl]-1- cyclopenten-1-yl}-2- fluorobenzoate 
                 LC/MS: Rt = 4.43 min. [MH + ] 494. 
               
               
                   
               
               
                 353 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 2-fluoro-5-{2- [2-{[(4-fluorophenyl) methyl]oxy}-5-(trifluoro- methyl)-3-pyridinyl]-1- cyclopenten-1-yl}benzoate 
                 LC/MS: Rt = 4.30 min. [MH + ] 476. 
               
               
                   
               
               
                 354 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 5-[2-(2-{[(2,4- difluorophenyl)methyl] oxy}-3-pyridinyl)-1- cyclopenten-1-yl]-2- fluorobenzoate 
                 LC/MS: Rt = 4.20 min [MH + ] 426. 
               
               
                   
               
               
                 355 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 3-amino-5-{2- [2-[(phenylmethyl)oxy]- 5-(trifluoromethyl)-3- pyridinyl]-1- cyclopenten-1- yl}benzoate 
                   1 H NMR (MeOD) δ: 1.99-2.08 (2H, m), 2.80- 2.92 (4H, m), 5.35 (2H, s), 6.44 (1H, t), 7.15 (2H, dt), 7.23-7.35 (5H, m), 7.51 (1H, d), 8.27-8.29 (1H, m). LC/MS Rt = 3.71 min [MH + ] 455. 
               
               
                   
               
               
                 356 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-{2-[2-{[(4- fluorophenyl)methyl] oxy}-5-(trifluoromethyl)-3- pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                   1 H NMR (MeOD) δ: 2.03-2.11 (2H, m), 2.86- 2.91 (2H, m), 3.08-3.13 (2H, m), 5.31 (2H, s), 6.79 (1H, d), 7.03 (2H, t), 7.26- 7.30 (2H, m), 7.44 (1H, t), 7.61 (1H, d), 7.72 (1H, d), 8.34 (1H, s). LC/MS Rt = 3.88 min [MH + ] 459. 
               
               
                   
               
               
                 357 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-{2-[2-{[(2- chloro-4-fluorophenyl) methyl]oxy}-5-(trifluoro- methyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                   1 H NMR (MeOD) δ: 2.03-2.11 (2H, m), 2.85- 2.90 (2H, m), 3.08-3.13 (2H, m), 5.38 (2H, s), 6.81 (1H, d), 7.15-7.20 (2H, m), 7.25 (1H, t), 7.46 (1H, t), 7.63 (1H, d), 7.72 (1H, d), 8.35 (1H, s). LC/MS Rt = 4.07 min [MH + ] 493. 
               
               
                   
               
               
                 358 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-{2-[2-{[(4- chlorophenyl)methyl] oxy}-5-(trifluoromethyl)- 3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                   1 H NMR (MeOD) δ: 2.04-2.12 (2H, m), 2.87- 2.92 (2H, m), 3.09-3.14 (2H, m), 5.31 (2H, s), 6.80 (1H, d), 7.23 (2H, d), 7.29-7.34 (2H, m), 7.45 (1H, t), 7.63 (1H, d), 7.72 (1H, d), 8.34 (1H, s). LC/MS Rt = 4.04 min [MH + ] 475. 
               
               
                   
               
               
                 359 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-{2-[2-{[(4- chloro-2-fluorophenyl) methyl]oxy}-5-(trifluoro- methyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 LC/MS: Rt = 4.07 min [MH + ] 493 
               
               
                   
               
               
                 360 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-{2-[2-{[(2- fluorophenyl)methyl] oxy}-5-(trifluoromethyl)-3- pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 LC/MS: Rt = 3.88 min [MH + ] 459 
               
               
                   
               
               
                 361 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-{2-[2-{[(2,6- difluorophenyl)methyl] oxy}-5-(trifluoromethyl)-3- pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 LC/MS: Rt = 3.85 min [MH + ] 477 
               
               
                   
               
               
                 362 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-{2-[2-{[(2- chloro-6-fluorophenyl) methyl]oxy}-5-(trifluoro- methyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 LC/MS: Rt = 3.98 min [MH + ] 493 
               
               
                   
               
               
                 363 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-{2-[2-{[(2,4- difluorophenyl)methyl] oxy}-5-(trifluoromethyl)- 3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 LC/MS: Rt = 3.91 min [MH + ] 477 
               
               
                   
               
               
                 364 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-{2-[5- (trifluoromethyl)-2-({[4- (trifluoromethyl)phenyl] methyl}oxy)-3-pyridinyl]- 1-cyclopenten-1-yl}-2- pyridinecarboxylate 
                 LC/MS: Rt = 4.04 min [MH + ] 509 
               
               
                   
               
               
                 365 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-{2-[2-{[(4- bromo-2-fluorophenyl) methyl]oxy}-5-(trifluoro- methyl)-3-pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 LC/MS: Rt = 4.11 min [MH + ] 537, 539 
               
               
                   
               
               
                 366 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-{2-[2-({[2- fluoro-4-(trifluoromethyl) phenyl]methyl}oxy)-5- (trifluoromethyl)-3- pyridinyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 LC/MS: Rt = 4.07 min [MH + ] 527 
               
               
                   
               
               
                 367 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5- (trifluoromethyl)-2- {[(2,4,5-trifluorophenyl) methyl]oxy}-3-pyridinyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 LC/MS: Rt = 3.94 min [MH + ] 495 
               
               
                   
               
               
                 368 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5- (trifluoromethyl)-2- {[(2,3,6-trifluorophenyl) methyl]oxy}-3-pyridinyl)- 1-cyclopenten-1-yl]-2- pyridinecarboxylate 
                 LC/MS: Rt = 3.87 min [MH + ] 495 
               
               
                   
               
            
           
         
       
     
     Example 369 
     Sodium 6-[2-(5-fluoro-2-{[(4-methylphenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyridazinecarboxylate 
     
       
         
         
             
             
         
       
     
     6-{2-[5-Fluoro-2-hydroxyphenyl]-1-cyclopenten-1-yl}-2-pyridinecarboxylic acid methyl ester (104 mg, 0.333 mmol) in dimethyl/formamide (4 ml) was treated with 4-methylbenzyl bromide (66 mg, 0.356 mmol) and potassium carbonate (140 mg, 1.0 mmol). The reaction mixture was then refluxed overnight under nitrogen, filtered through celite and reduced under vacuum to an oil. The oil was dissolved in methanol (3 ml), 2M sodium hydroxide (2 ml) was added and the reaction mixture stirred at 65° C. for one hour. The reaction mixture was then reduced down to ˜0.1 ml under vacuum, diluted to 20 ml with water and extracted with ethyl acetate (2×20 ml). The organic extract was then washed with brine (20 ml), dried over sodium sulphate and evaporated down under reduced pressure to the required product (52 mg, 36%). LC/MS Rt=3.73 min [MH + ] 404. 
     The following Examples were prepared by the procedure used for sodium 6-[2-(5-fluoro-2-{[(4-methylphenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylate: 
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 Example 
                 Structure 
                 Name 
                 LC/MS 
               
               
                   
               
             
            
               
                 370 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(4- chlorophenyl)methyl]oxy}- 5-fluorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.83, [MH + ] 424 
               
               
                   
               
               
                 371 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-fluoro-2- {[(2,4,6- trifluorophenyl)methyl]oxy} phenyl)-1-cyclopenten-1- yl]-2-pyridinecarboxylate 
                 Rt = 3.58, [MH + ] 444 
               
               
                   
               
               
                 372 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-{2-[5-fluoro-2- ({[2-fluoro-4- (trifluoromethyl)phenyl] methyl}oxy)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 3.94, [MH + ] 476 
               
               
                   
               
               
                 373 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(4- chloro-2-fluorophenyl) methyl]oxy}-5- fluorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.89, [MH + ] 442 
               
               
                   
               
               
                 374 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(4- bromophenyl)methyl]oxy}- 5-fluorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.90, [MH + ] 470 
               
               
                   
               
               
                 375 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(2- chloro-4-fluorophenyl) methyl]oxy}- 5-fluorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.88, [MH + ] 442 
               
               
                   
               
               
                 376 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-fluoro-2- {[(2-fluorophenyl) methyl]oxy}phenyl)- 1-cyclopenten-1- yl]-2-pyridinecarboxylate 
                 Rt = 3.57, [MH + ] 408 
               
               
                   
               
               
                 377 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(2,3- difluorophenyl)methyl]oxy}- 5-fluorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.64, [MH + ] 426 
               
               
                   
               
               
                 378 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(2,5- difluorophenyl)methyl]oxy}- 5-fluorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.67, [MH + ] 426 
               
               
                   
               
               
                 379 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(3,4- difluorophenyl)methyl]oxy}- 5-fluorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.68, [MH + ] 426 
               
               
                   
               
               
                 380 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(2- chlorophenyl)methyl]oxy}- 5-fluorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.84, [MH + ] 424 
               
               
                   
               
               
                 381 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(5-fluoro-2- {[(2,3,6-trifluoro- phenyl)methyl]oxy} phenyl)-1-cyctopenten-1- yl]-2-pyridinecarboxylate 
                 Rt = 3.57, [MH + ] 444 
               
               
                   
               
               
                 382 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(2,6- difluorophenyl)methyl]oxy}- 5-fluorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.49, [MH + ] 426 
               
               
                   
               
               
                 383 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(2- chloro-6-fluorophenyl) methyl]oxy}-5- fluorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.66, [MH + ] 442 
               
               
                   
               
               
                 384 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-[2-(2-{[(2- bromophenyl)methyl]oxy}- 5-fluorophenyl)-1- cyclopenten-1-yl]-2- pyridinecarboxylate 
                 Rt = 3.90, [MH + ] 470 
               
               
                   
               
               
                 385 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 6-{2-[5-fluoro-2- ({[4-(trifluoromethyl) phenyl]methyl}oxy)phenyl]-1- cyclopenten-1-yl}-2- pyridinecarboxylate 
                 Rt = 3.88, [MH + ] 458 
               
               
                   
               
            
           
         
       
     
     Example 386 
     6-[2-(5-Chloro-2-{[(2,4-difluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-N-(phenylsulfonyl)-2-pyridinecarboxamide 
     
       
         
         
             
             
         
       
     
     a) Ethyl 6-[2-(5-chloro-2-{[(2,4-difluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylate (140 mg, 0.30 mmol) was dissolved in ethanol (5 ml) and 2M sodium hydroxide (1 ml) and heated to reflux then left to cool for 60 minutes. The solution was diluted with water then extracted with isohexane and acidified to pH4 with hydrochloric acid. The mixture was extracted with diethyl ether. The organic solution was dried over magnesium sulphate and evaporated to give 6-[2-(5-chloro-2-{[(2,-difluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid (110 mg). 
     LC/MS Rt=3.88 [MH + ] 442.3, 444.3. 
     b) A mixture of 6-[2-(5-chloro-2-{[(2,4-difluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid (110 mg, 0.25 mmol), benzenesulphonamide (58 mg, 0.3 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (58 mg, 0.3 mmol) and 4-dimethylaminopyridine (3 mg, 0.025 mmol) in 1:1 dichloromethane/tetrahydrofuran (4 ml) was stirred at room temperature for 2 hours and more benzenesulphonamide (16 mg, 0.1 mmol), 1-[3(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (19 mg, 0.1 mmol) and 4-dimethylaminopyridine (1 mg) was added. After a further 2 hours the mixture was diluted with ether/water and the organic layer dried (magnesium sulphate), evaporated and purified by chromatography on silica eluting with ethyl acetate/iso-hexane to give a white solid (85 mg). 
       1 H NMR (CDCl 3 ) δ 2.07-2.14 (2H, m), 2.84-2.88 (2H, m), 2.98-3.01 (2H, m), 5.04 (2H, s), 6.74-6.79 (2H, m), 6.99 (1H, d), 7.06 (1H, d), 7.16-7.32 (3H, m), 7.54 (2H, t), 7.63 (2H, q), 7.81 (1H, d), 8.08-8.10 (2H, m), 9.55 (1H, s). LC/MS t=4.30, [MH+] 581.3, 583.3. 
     Example 387 
     6-[2-(5-bromo-2-{[(2,4-difluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-N-phenylsulfonyl)-2-pyridinecarboxamide 
     
       
         
         
             
             
         
       
     
     A mixture of 6-[2-(5-bromo-2-{[(2,4-difluorophenyl)methyl]oxy}phenyl)-1cyclopenten-1-yl]-2-pyridinecarboxylic acid (10 mg, 0.23 mmol), benzenesulphonamide (45 mg, 0.29 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (55 mg, 0.29 mmol), and 4 dimethylaminopyridine (5 mg) in 1:1 dichloromethane/tetrahydrofuran (5 ml) was stirred at RT for 24 hours. The reaction mixture was diluted with diethyl ether (25 ml) and washed with saturated sodium bicarbonate solution, water and brine. The organic phase was separated, dried and evaporated. Chromatography of the residue eluting with 1:9 ethyl acetate/hexane gave the title compound as a colourless solid (52 mg). 
     LC/MS: Rt=4.33 min. [M+H]=625, 627. 
     Example 388 
     2-Fluoro-5-(2-{2-[(2-fluorophenyl)methoxy]-5-trifluoromethyl)pyridin-3-yl}cyclopent-1-en-1-yl)-benzoic acid, sodium salt 
     
       
         
         
             
             
         
       
     
     The corresponding ethyl ester was dissolved in ethanol (1 ml) and 2M aqueous sodium hydroxide (1 ml) was added. The mixture was heated to 120° C., by microwave, for 3mins. The reaction mixture was concentrated in vacuo, and the residue partitioned between ethyl acetate and water. The organic extract was dried (Na 2 SO 4 ) and concentrated in vacuo to give the title compound as the sodium salt. LC/MS Rt=4.07 min [MH + ] 477. 
     The following compounds were prepared as their sodium salts by the same method, starting from the appropriate ethyl esters. 
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 Example 
                 Structure 
                 COMPOUND NAME 
                 LCMS 
               
               
                   
               
             
            
               
                 389 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{2-[(2,6-Difluorophenyl) methoxy]-5-(trifluoromethyl) pyridin-3-yl}cyclopent-1-en-1- yl)-2-fluorobenzoic acid, sodium salt 
                 Rt = 4.03 min [MH + ] 495 
               
               
                   
               
               
                 390 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{2-[(2-Chloro-4- fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)-2- fluorobenzoic acid, sodium salt 
                 Rt = 4.25 min [MH + ] 512 
               
               
                   
               
            
           
         
       
     
     General Procedure C 
     
       
         
         
             
             
         
       
     
     Ethyl 2-fluoro-5-{2-[2-hydroxy-5(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-y}benzoate (250 mg, 0.63mmol) was dissolved in toluene (3 ml), together with silver carbonate (192 mg, 0.70 mmol) and a substituted benzyl bromide (1.1 equiv.). The mixture was heated to reflux for 4 hours, then concentrated in vacuo, and the product taken on without further purification. 
     Each residue was dissolved in a mixture of ethanol (2 ml) and 2N aqueous sodium hydroxide (2 ml), and this mixture was heated to 120° C., by microwave, for 3mins. The reaction mixture was filtered and concentrated in vacuo. The residue was dissolved in dichloromethane and treated with acetic acid, and then again concentrated in vacuo. The resulting material was purified using a basic solid phase extraction cartridge (Isolute® Flash NH2), loading the crude material as a methanol solution, and eluting with 10% aqueous HCl in methanol. The resulting adds were redissolved in dichloromethane and treated with aqueous 2N sodium hydroxide. The layers were separated, and the organic layer was concentrated in vacuo. The resulting sodium salt was redissolved in dioxane, which was removed by freeze-drying to give the product (sodium salt) as a solid. 
     The following compounds were prepared by General Procedure C: 
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 Examples 
                 Structure 
                 Compound Name 
                 LCMS 
               
               
                   
               
             
            
               
                 391 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-5-(2-{5- (trifluoromethyl)-2- [(2,4,6-trifluorophenyl) methoxy] pyridin-3- yl}cyclopent-1-en-1-yl)- benzoic acid, sodium salt 
                 Rt = 4.07 min [MH + ] 512 
               
               
                   
               
               
                 392 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-5-(2-{5- (trifluoromethyl)-2- [(2,4,5-trifluorophenyl) methoxy] pyridin-3- yl}cyclopent-1-en-1-yl)- benzoic acid, sodium salt 
                 Rt = 4.09 min [MH + ] 512 
               
               
                   
               
               
                 393 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-5-(2-{5- (trifluoromethyl)-2- [(2,3,6-trifluorophenyl) methoxy] pyridin-3- yl}cyclopent-1-en-1-yl)- benzoic acid, sodium salt 
                 Rt = 4.11 min [MH + ] 512 
               
               
                   
               
               
                 394 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-5-[2-(5- (trifluoromethyl)-2-{[4- (trifluoromethyl)phenyl] methoxy}pyridin-3- yl)cyclopent-1-en-1-yl]- benzoic acid, sodium salt 
                 Rt = 4.19 min [MH + ] 526 
               
               
                   
               
               
                 395 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-5-[2-(2-{(2- fluoro-4-(trifluoromethyl) phenyl]methoxy}-5- [trifluoromethyl] pyridin-3-yl)cyclopent- 1-en-1-yl]-benzoic acid, sodium salt 
                 Rt = 4.28 min [MH + ] 544 
               
               
                   
               
               
                 396 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{2-[(2-Chloro-6- fluorophenyl)methoxy]- 5-(trifluoromethyl)pyridin- 3-yl}cyclopent-1-en-1- yl)-2-fluorobenzoic acid, sodium salt 
                 Rt = 4.16 min [MH + ] 510 
               
               
                   
               
               
                 397 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{2-[(4-Bromo-2- fluorophenyl)methoxy]- 5-(trifluoromethyl)pyridin- 3-yl}cyclopent-1-en-1- yl)-2-fluorobenzoic acid, sodium salt 
                 Rt = 4.28 min [MH + ] 554, 556 
               
               
                   
               
            
           
         
       
     
     Example 398 
     3-Fluoro-5-{2-[2-(phenylmethoxy)-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1en-1-yl}benzoic acid, sodium salt 
     
       
         
         
             
             
         
       
     
     Ethyl 2-fluoro-5-{2-[2-(phenylmethoxy)-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}benzoate (150 mg, 0.31 mmol) was dissolved in ethanol (2 ml) and 2M sodium hydroxide (1.0 ml) was added. The mixture was heated to reflux for 1 hour, by which time TLC analysis indicated that the reaction was complete. The cooled reaction mixture was diluted with water, acidified to pH5 with acetic acid, and then extracted with diethyl ether (×2). The combined organic extracts were washed with water, dried (Na 2 SO 4 ) and concentrated in vacuo to give the crude acid, which was further purified by HPLC. The acid was treated with 2M aqueous sodium hydroxide, and this mixture extracted with dichloromethane. The organic extracts were concentrated in vacuo to give the title compound as the sodium salt. 
     LC/MS Rt=4.22 min [MH + ] 458. 
       1 H NMR (MeOD) δ: 2.06-2.14 (2H, m), 2.86-2.97 (4H, m), 5.31 (2H, s), 6.93 (1H, ddd), 7.17-7.21 (2H, m), 7.24-7.30 (3H, m), 7.43 (1H, ddd), 7.51 (1H, t), 7.68 (1H, d), 8.38 (1H, dd). 
     General Procedure D 
     
       
         
         
             
             
         
       
     
     Ethyl 3-fluoro-5-{2-[2-hydroxy-5-(trifluoromethyl)pyridin-3-yl]cyclopent-1-en-1-yl}benzoate (250 mg, 0.63 mmol) was dissolved in toluene (3 ml), together with silver carbonate (192 mg, 0.70 mmol) and a substituted benzyl bromide (1.1 equiv.). The mixture was heated to reflux for 4 hours, then concentrated in vacuo, and the product taken on without further purification. 
     Each residue was dissolved in a mixture of ethanol (2 ml) and 2N aqueous sodium hydroxide (2 ml), and this mixture was heated to 120° C., by microwave, for 3mins. The reaction mixture was filtered and concentrated in vacuo. The residue was dissolved in dichloromethane and treated with acetic acid, and then again concentrated in vacuo. The resulting material was purified using a basic solid phase extraction cartridge (Isolute® Flash NH2), loading the crude material as a methanol solution, and eluting with 10% aqueous HCl in methanol. The resulting acid was redissolved in dichloromethane and treated with aqueous 2N sodium hydroxide. The layers were separated, and the organic layer was concentrated in vacuo. This was followed by further purification by HPLC. The pure acid was treated with 2M aqueous sodium hydroxide, and the mixture extracted with dichloromethane. The organic extracts were concentrated in vacuo to give the title compound as the sodium salt. 
     The following Examples were prepared by General Procedure D: 
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 Example 
                 Structure 
                 Compound Name 
                 LCMS 
               
               
                   
               
             
            
               
                 399 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Fluoro-5-(2-{2-[(4- fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)- benzoic acid, sodium salt 
                 Rt = 4.15 min [MH + ] 476 
               
               
                   
               
               
                 400 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{2-[(2,4-Difluoro- phenyl)methoxy]-5- (trifluoromethyl) pyridin- 3-yl}cyclopent-1-en-1-yl)- 3-fluorobenzoic acid, sodium salt 
                 Rt = 4.17 min [MH + ] 494 
               
               
                   
               
               
                 401 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{2-[(4-Chloro-2- fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)-3- fluorobenzoic acid, sodium salt 
                 Rt = 4.31 min [MH + ] 510 
               
               
                   
               
               
                 402 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Fluoro-5-(2-{5- (trifluoromethyl)-2- [(2,4,6-trifluorophenyl) methoxy]pyridin-3-yl) cyclopent-1-en-1-yl)- benzoic acid, sodium salt 
                 Rt = 4.12 min [MH + ] 512 
               
               
                   
               
               
                 403 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(2-{2-[(4-Bromo-2- fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)-3- fluorobenzoic acid, sodium salt 
                 Rt = 4.40 min [MH + ] 554, 556 
               
               
                   
               
               
                 404 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Sodium 3-{2-[2-{[(2,6- difluorophenyl)methyl] oxy}-5-(trifluoromethyl)-3- pyridinyl]-1-cyclopenten- 1-yl)-5-fluorobenzoate 
                 Rt = 4.12 min [MH + ] 493 
               
               
                   
               
            
           
         
       
     
     General Procedure E 
     
       
         
         
             
             
         
       
     
     The ester was dissolved in ethanol (2 ml) and 2M aqueous sodium hydroxide (1 ml) was added. The mixture was heated to reflux for 2 hours. The reaction mixture was concentrated in vacuo, and treated according to procedure A or B. 
     Procedure A: The residue was triturated with aqueous sodium hydroxide to give the sodium salt as a solid, which was collected by filtration and washed with water.
 
Procedure B: The residue was partitioned between ethyl acetate and water. The organic layer was dried (Na 2 SO 4 ), and concentrated in vacuo, to give the sodium salt as a glassy solid.
 
     The following Examples were prepared as their sodium salts by General Procedure E, starting from the appropriate ethyl esters 
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 Example 
                 Structure 
                 Compound Name 
                 LCMS 
               
               
                   
               
             
            
               
                 405 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-(2-{2-[(4- fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)- benzoic acid, sodium salt 
                 Rt = 3.80 min [MH + ] 473 
               
               
                   
               
               
                 406 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-(2-{2-[(2,4- difluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)- benzoic acid, sodium salt 
                 Rt = 3.84 min [MH + ] 491 
               
               
                   
               
               
                 407 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-(2-{2-[(2- fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)- benzoic acid, sodium salt 
                 Rt = 3.80 min [MH + ] 473 
               
               
                   
               
               
                 408 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-(2-{2-[(2,6- difluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)- benzoic acid, sodium salt 
                 Rt = 3.77 min [MH + ] 491 
               
               
                   
               
               
                 409 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-(2-{2-[(2-chloro- 4-fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)- benzoic acid, sodium salt 
                 Rt = 3.98 min [MH + ] 507 
               
               
                   
               
               
                 410 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-(2-{2-[(4-chloro- 2-fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)- benzoic acid, sodium salt 
                 Rt = 3.98 min [MH + ] 507 
               
               
                   
               
               
                 411 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-(2-{5- (trifluoromethyl)-2-[(2,4,6- trifluorophenyl)methoxy]- pyridin-3-yl}cyclopent-1-en- 1-yl)-benzoic acid, sodium salt 
                 Rt = 3.84 min [MH + ] 509 
               
               
                   
               
               
                 412 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-(2-{5- (trifluoromethyl)-2-[(2,4,5- trifluorophenyl)methoxy]- pyridin-3-yl}cyclopent-1-en- 1-yl)-benzoic acid, sodium salt 
                 Rt = 3.87 min [MH + ] 509 
               
               
                   
               
               
                 413 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-(2-{5- (trifluoromethyl)-2-[(2,3,6- trifluorophenyl)methoxy]- pyridin-3-yl}cyclopent-1-en- 1-yl)-benzoic acid, sodium salt 
                 Rt = 3.85 min [MH + ] 509 
               
               
                   
               
               
                 414 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-[2-(5- {trifluoromethyl)-2-{[4- (trifluoromethyl)phenyl] methoxy}-pyridin-3-yl) cyclopent-1-en-1-yl]- benzoic acid, sodium salt 
                 Rt = 4.01 min [MH + ] 523 
               
               
                   
               
               
                 415 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-[2-(2-{[2-fluoro-4- (trifluoromethyl)phenyl] methoxy}-5-{trifluoro- methyl}pyridin-3- yl)cyclopent-1-en-1-yl]- benzoic acid, sodium salt 
                 Rt = 4.01 min [MH + ] 541 
               
               
                   
               
               
                 416 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-(2-{2-[(2-chloro- 6-fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)- benzoic acid, sodium salt 
                 Rt = 3.89 min [MH + ] 507 
               
               
                   
               
               
                 417 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-5-(2-{2-[(4-bromo- 2-fluorophenyl)methoxy]-5- (trifluoromethyl)pyridin-3- yl}cyclopent-1-en-1-yl)- benzoic acid, sodium salt 
                 Rt = 4.03 min [MH + ] 551, 553 
               
               
                   
               
            
           
         
       
     
     It is to be understood that the present invention covers all combinations of particular and preferred subgroups described herein above. 
     Assays for Determining Biological Activity 
     The compounds of formula (I) can be tested using the following assays to demonstrate their prostanoid antagonist or agonist activity in vitro and in vivo and their selectivity. The prostaglandin receptors investigated are DP, EP 1 , EP 2 , EP 3 , EP 4 , FP, IP and TP. 
     The ability of compounds to antagonise EP 1  &amp; EP 3  receptors may be demonstrated using a functional calcium mobilisation assay. Briefly, the antagonist properties of compounds are assessed by their ability to inhibit the mobilisation of intracellular calcium ([Ca 2+ ] 1 ) in response to activation of EP 1  or EP 3  receptors by the natural agonist hormone prostaglandin E 2  (PGE 2 ). Increasing concentrations of antagonist reduce the amount of calcium that a given concentration of PGE 2  can mobilise. The net effect is to displace the PGE 2  concentration-effect curve to higher concentrations of PGE 2 . The amount of calcium produced is assessed using a calcium-sensitive fluorescent dye such as Fluo-3, AM and a suitable instrument such as a Fluorimetric Imaging Plate Reader (FLIPR). Increasing amounts of [Ca 2+ ] produced by receptor activation increase the amount of fluorescence produced by the dye and give rise to an increasing signal. The signal may be detected using the FLIPR instrument and the data generated may be analysed with suitable curve-fitting software. 
     The human EP 1  or EP 3  calcium mobilisation assay (hereafter referred to as ‘the calcium assay’) utilises Chinese hamster ovary-K1 (CHO-K1) cells into which a stable vector containing either EP 1  or EP 3  cDNA has previously been transfected. Cells are cultured in suitable flasks containing culture medium such as DMEM:F-12 supplemented with 10% v/v foetal calf serum, 2 mM L-glutamine, 0.25 mg/ml geneticin and 10 μg/ml puromycin. 
     For assay, cells are harvested using a proprietary reagent that dislodges cells such as Versene. Cells are re-suspended in a suitable quantity of fresh culture media for introduction into a 384-well plate. Following incubation for 24 hours at 37° C. the culture media is replaced with a medium containing fluo-3 and the detergent pluronic acid, and a further incubation takes place. Concentrations of compounds are then added to the plate in order to construct concentration-effect curves. This may be performed on the FLIPR in order to assess the agonist properties of the compounds. Concentrations of PGE 2  are then added to the plate in order to assess the antagonist properties of the compounds. 
     The data so generated may be analysed by means of a computerised curve-fitting routine. 
     The concentration of compound that elicits a half-maximal inhibition of the calcium mobilisation induced by PGE 2  (pIC 50 ) may then be estimated. 
     Binding Assay for the Human Prostanoid EP 1  Receptor 
     Competition assay using [ 3 H]-PGE2. 
     Compound potencies are determined using a radioligand binding assay. In this assay compound potencies are determined from their ability to compete with tritiated prostaglandin E 2  ([ 3 H]-PGE 2 ) for binding to the human EP 1  receptor. 
     This assay utilises Chinese hamster ovary-K1 (CHO-K1) cells into which a stable vector containing the EP 1  cDNA has previously been transfected. Cells are cultured in suitable flasks containing culture medium such as DMEM:F-12 supplemented with 10% v/v foetal calf serum, 2 mM L-glutamine, 0.25 mg/ml geneticin, 10 μg/ml puromycin and 10 μM indomethacin. 
     Cells are detached from the culture flasks by incubation in calcium and magnesium free phosphate buffered saline containing 1 mM disodium ethylenediaminetetraacetic acid (Na 2 EDTA) and 10 μM Indomethacin for 5 min. The cells are isolated by centrifugation at 250×g for 5mins and suspended in an ice cold buffer such as 50 mM Tris, 1 mM Na 2 EDTA, 140 mM NaCl, 10 μM indomethacin (pH 7.4). The cells are homogenised using a Polytron tissue disrupter (2×10s burst at full setting), centrifuged at 48,000×g for 20mins and the pellet containing the membrane fraction is washed three times by suspension and centrifugation at 48,000×g for 20mins. The final membrane pellet is suspended in an assay buffer such as 10 mM 2-[N-morpholino]ethanesulphonic acid, 1 mM Na 2 EDTA, 10 mM MgCl 2  (pH 6). Aliquots are frozen at 80° C. until required. 
     For the binding assay the cell membranes, competing compounds and [ 3 H]-PGE 2  (3 nM final assay concentration) are incubated in a final volume of 100 μl for 30 min at 30° C. All reagents are prepared in assay buffer. Reactions are terminated by rapid vacuum filtration over GF/B filters using a Brandell cell harvester. The filters are washed with ice cold assay buffer, dried and the radioactivity retained on the filters is measured by liquid scintillation counting in Packard TopCount scintillation counter. 
     The data are analysed using non linear curve fitting techniques (GraphPad Prism 3) to determine the concentration of compound producing 50% inhibition of specific binding (IC 50 ). 
     By application of the binding assay technique, compounds of the examples had an antagonist pIC 50  value of 6.0 to 9.5 at EP 1  receptors. Compounds of the examples had a pIC50 value of &lt;6.0 at EP 3  receptors when measured by the calcium mobilisation assay. 
     No toxicological effects are indicated/expected when a compound (of the invention) is administered in the above mentioned dosage range. 
     The application of which this description and claims forms part may be used as a basis for priority in respect of any subsequent application. The claims of such subsequent application may be directed to any feature or combination of features described herein. They may take the form of product, composition, process, or use claims and may include, by way of example and without limitation the following claims: