Patent Publication Number: US-6670367-B1

Title: Azinyloxy, and phenoxy-diaryl-carboxylic acid derivatives, their preparation and use as mixed ETA/ETB endothelin receptor antagonists

Description:
The present invention relates to novel carboxylic acid derivatives, their preparation and use. 
     Endothelin is a peptide which consists of 21 amino acids and is synthesized and released by vascular endothelium. Endothelin exists in three isoforms, ET-1, ET-2 and ET-3. “Endothelin” or “ET” hereinafter means one or all isoforms of endothelin. Endothelin is a potent vasoconstrictor and has a great effect on vessel tone. It is known that this vasoconstriction is caused by binding of endothelin to its receptor (Nature, 332, 1988, 411-415; FEBS Letters, 231, 1988, 440-444 and Biochem. Biophys. Res. Commun., 154, 1988, 868-875). 
     Increased or abnormal release of endothelin causes persistent vasoconstriction in peripheral, renal and cerebral vessels, which may lead to disorders. As reported in the literature, endothelin is involved in a number of disorders. These include: hypertension, acute myocardial infarct, pulmonary hypertension, Raynaud&#39;s syndrome, cerebral vasospasms, stroke, benign prostate hypertrophy, atherosclerosis and asthma (J. Vascular Med. Biology 2, (1990) 207, J. Am. Med. Association 264, (1990) 2868, Nature 344, (1990) 114, N. Engl. J. Med. 322, (1989) 205, N. Engl. J. Med. 328, (1993) 1732, Nephron 66, (1994) 373, Stroke 25, (1994) 904, Nature 365, (1993) 759, J. Mol. Cell. Cardiol. 27, (1995) A234; Cancer Research 56, (1996) 663). 
     At least two endothelin receptor subtypes, ET A  and ET B  receptors, have been described in the literature (Nature 348, (1990) 730, Nature 348, (1990) 732). Accordingly, substances which inhibit the binding of endothelin to the two receptors ought to antagonize the physiological effects of endothelin and therefore be valuable drugs. 
     WO 96/11914 describes carboxylic acid derivatives which, however, bind with high affinity to the ET A  receptor and with considerably less affinity to the ET B  receptor (called ET A -specific antagonists). 
     ET A -specific antagonists mean here those antagonists whose affinity for the ET A  receptor is at least twenty times higher than their affinity for the ET B  receptor. 
     It is an object of the present invention to provide endothelin receptor antagonists which bind with approximately the same affinity to the ET A  and ET B  receptors (called mixed antagonists). 
     Approximately the same affinity for the receptors means that the ET A :ET B  affinity ratio is greater than 0.1 and less than 20, preferably less than 10. 
     We have found that this object is achieved by carboxylic acid derivatives of the formula I                    
     where R 1  is tetrazole [sic] or a group                    
     where R has the following meaning: 
     a) a radical OR 7  where R 7  is: 
     hydrogen, the cation of an alkali metal, the cation of an alkaline earth metal, a physiologically tolerated organic ammonium ion such as C 1 -C 4 -alkylammonium or the ammonium ion; 
     C 3 -C 8 -cycloalkyl, C 1 -C 8 -alkyl, CH 2 -phenyl which can be substituted by one or more of the following radicals: halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, hydroxyl, C 1 -C 4 -alkoxy, mercapto, C 1 -C 4 -alkylthio, amino, carboxyl, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 ; 
     C 3 -C 6 -alkenyl or C 3 -C 6 -alkynyl, it being possible for these groups in turn to carry one to five halogen atoms; 
     R 7  can furthermore be a phenyl radical which may carry one to five halogen atoms and/or one to three of the following radicals, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, hydroxyl, C 1 -C 4 -alkoxy, mercapto, C 1 -C 4 -alkylthio, amino, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 ; 
     b) a 5-membered heteroaromatic system which is linked via a nitrogen atom, such as pyrrolyl, pyrazolyl, imidazolyl and triazolyl, which may carry one to two halogen atoms or one to two C 1 -C 4 -alkyl or one to two C 1 -C 4 -alkoxy groups; 
     c) a group                    
      where k is 0, 1 and 2, p is 1, 2, 3 and 4 and R 8  is 
     C 1 -C 4 -alkyl, C 3 -C 8 -cycloalkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl or phenyl which can be substituted by one or more, eg. one to three, of the following radicals: halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, hydroxyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, mercapto, amino, carboxyl, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 ; 
     d) a radical                    
      in which R 9  is: 
     C 1 -C 4 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, C 1 -C 4 -haloalkyl, it being possible for these radicals to carry a C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio and/or a phenyl radical as mentioned under c); 
     phenyl, unsubstituted or substituted, in particular as mentioned above, 
     e) R 1  can furthermore be                    
      where R 13  and R 14  can be identical or different and have the following meanings: 
     hydrogen, C 1 -C 8 -alkyl, C 3 -C 8 -cycloalkyl, C 3 -C 8 -alkenyl, C 3 -C 8 -alkynyl, benzyl, phenyl which may carry one to five halogen atoms and/or one to three of the following radicals: nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, hydroxyl, C 1 -C 4 -alkoxy, mercapto, C 1 -C 4 -alkylthio, amino, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , 
     or R 13  and R 14  together form a C 4 -C 7 -alkylene chain which is closed to form a ring and which may be substituted by C 1 -C 4 -alkyl and in which an alkylene group may be replaced by oxygen, sulfur or nitrogen, such as —(CH 2 ) 4 —, —(CH 2 ) 5 —, —(CH 2 ) 6 —, —(CH 2 ) 2 —O—(CH 2 ) 2 —, —(CH 2 ) 7 —, —CH 2 —S—(CH 2 ) 2 —, —CH 2 —NH—(CH 2 ) 2 —, —(CH 2 ) 2 —N—(CH 2 ) 2 —; 
     R 2  hydrogen, hydroxyl, NH 2 , NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , halogen, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio, or CR 2  is linked to CR 10  as indicated below to give a 5- or 6-membered ring. 
     X nitrogen or methine. 
     Y nitrogen or methine. 
     Z nitrogen or CR 10 , where R 10  is hydrogen or C 1 -C 4 -alkyl, or CR 10  forms together with CR 2  or CR 3  a 5- or 6-membered alkylene or alkenylene ring which may be substituted by one or two C 1 -C 4 -alkyl groups and in which in each case one or more methylene groups can be replaced by oxygen, sulfur, —NH or N(C 1 -C 4 -alkyl) 2 . 
     At least one of the ring members X, Y or Z is nitrogen. 
     R 3  hydrogen, hydroxyl, NH 2 , NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , halogen, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 1 -C 4 -hydroxyalkyl or C 1 -C 4 -alkylthio, or CR 3  is linked to CR 10  as indicated above to give a 5- or 6-membered ring. 
     R 4  and R 5  (which may be identical or different): 
     phenyl or naphthyl, which may be substituted by one or more of the following radicals: halogen, nitro, cyano, hydroxyl, mercapto, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 1 -C 4 -hydroxyalkyl, C 2 -C 4 -alkynyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, phenoxy, carboxyl, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylthio, amino, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2  or phenyl which can be substituted one or more times, eg. one to three times by halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio; or phenyl or naphthyl, which are linked together in the ortho positions by a direct linkage, a methylene, ethylene or ethenylene group, an oxygen or sulfur atom or an SO 2 , NH or N-alkyl group; 
     C 3 -C 8 -cycloalkyl. 
     R 6  C 3 -C 8 -Cycloalkyl, it being possible for these radicals in each case to be substituted one or more times by: halogen, hydroxyl, mercapto, carboxyl, nitro, cyano, C 1 -C 4 -alkoxy, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 6 -alkenyloxy, C 3 -C 6 -alkynyloxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 3 -C 8 -alkyl-carbonylalkyl, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , or phenyl which can be substituted one or more times, eg. one to three times, by halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio; 
     phenyl or naphthyl, each of which can be substituted by one or more of the following radicals: halogen, R 15 , nitro, mercapto, carboxyl, cyano, hydroxyl, amino, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 6 -alkenyloxy, C 1 -C 4 -haloalkyl, C 3 -C 6 -alkynyloxy, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, C 1 -C 4 -alkylthio, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , dioxomethylene [sic], dioxoethylene [sic] or phenyl which can be substituted one or more times, eg. one to three times, by halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio; 
     a five- or six-membered heteroaromatic system containing one to three nitrogen atoms and/or one sulfur or oxygen atom, which may carry one to four halogen atoms and/or one to two of the following radicals: C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylthio, phenyl or phenoxy it being possible for the phenyl radicals in turn to carry one to five halogen atoms and/or one to three of the following radicals: C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy and/or C 1 -C 4 -alkylthio; 
     R 15  is C 1 -C 4 -alkyl, C 1 -C 4 -alkylthio or C 1 -C 4 -alkoxy which carry one of the following radicals: hydroxyl, carboxyl, amino, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , carboxamide [sic] or CON(C 1 -C 4 -alkyl) 2 ; 
     W sulfur or oxygen. 
     Q a spacer whose length corresponds to that of a C 2 -C 4  chain. The function of Q is to produce a defined distance between the groups R 6  and W in the compounds of the formula I. The distance should correspond to the length of a C 2 -C 4 -alkyl chain. This can be achieved by a large number of chemical radicals, for example with C 2 -C 4 -alkyl, C 3 -C 4 -alkenyl, C 3 -C 4 -alkynyl, —S—CH 2 —CH 2 —, —O—CH 2 —CH 2 —, —N—CO—CH 2 —O—, it being possible for each of these radicals to be substituted one or more times by: halogen, hydroxyl, mercapto, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, carboxyl, nitro, cyano, C 1 -C 4 -alkoxy, C 3 -C 6 -alkenyloxy, C 3 -C 6 -alkynyloxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 3 -C 8 -alkylcarbonylalkyl, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , phenyl which can be substituted one or more times, eg. one to three times, by halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio. 
     Or the spacer Q is part of a 5-7-membered heterocyclic or carbocyclic ring to which R 6  is fused. 
     The following definitions apply thereto and hereinafter: 
     An alkali metal is, for example, lithium, sodium, potassium; 
     An alkaline earth metal is, for example, calcium, magnesium, barium; 
     C 3 -C 8 -cycloalkyl is, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; 
     C 1 -C 4 -haloalkyl can be linear or branched, such as, for example fluoromethyl, difluoromethyl, trifluoromethyl, chlorodifluoromethyl, dichlorofluoromethyl, trichloromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl or pentafluoroethyl; 
     C 1 -C 4 -haloalkoxy can be linear or branched, such as, for example, difluoromethoxy, trifluoromethoxy, chlorodifluoromethoxy, 1-fluoroethoxy, 2,2-difluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-1,1,2-trifluoroethoxy, 2-fluoroethoxy or pentafluoroethoxy; 
     C 1 -C 4 -alkyl can be linear or branched, such as, for example, methyl, ethyl, 1-propyl, 2-propyl, 2-methyl-2-propyl, 2-methyl-1-propyl, 1-butyl or 2-butyl; 
     C 2 -C 4 -alkenyl can be linear or branched, such as, for example, ethenyl, 1-propen-3-yl, 1-propen-2-yl, 1-propen-1-yl, 2-methyl-1-propenyl, 1-butenyl or 2-butenyl; 
     C 2 -C 4 -alkynyl can be linear or branched, such as, for example, ethynyl, 1-propyn-1-yl, 1-propyn-3-yl, 1-butyn-4-yl or 2-butyn-4-yl; 
     C 1 -C 4 -alkoxy can be linear or branched, such as, for example, methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy or 1,1-dimethylethoxy; 
     C 3 -C 6 -alkenyloxy can be linear or branched, such as, for example, allyloxy, 2-buten-1-yloxy or 3-buten-2-yloxy; 
     C 1 -C 4 -hydroxyalkyl can be linear or branched, such as, for example, hydroxymethyl, 1-hydroxyether-2-yl, 
     C 3 -C 6 -alkynyloxy can be linear or branched, such as, for example, 2-propyn-1-yloxy, 2-butyn-1-yloxy or 3-butyn-2-yloxy; 
     C 1 -C 4 -alkylthio can be linear or branched, such as, for example, methylthio, ethylthio, propylthio, 1-methylethylthio, butylthio, 1-methylpropylthio, 2-methylpropylthio or 1,1-dimethylethylthio; 
     C 1 -C 4 -alkylcarbonyl can be linear or branched, such as, for example, acetyl, ethylcarbonyl or 2-propylcarbonyl; 
     C 1 -C 4 -alkoxycarbonyl can be linear or branched, such as, for example, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, i-propoxycarbonyl or n-butoxycarbonyl; 
     C 3 -C 8 -alkylcarbonylalkyl can be linear or branched, such as, for example, 2-oxo-1-propyl, 3-oxo-1-butyl or 3-oxo-2-butyl 
     C 1 -C 8 -alkyl can be linear or branched, such as, for example, C 1 -C 4 -alkyl, pentyl, hexyl, heptyl or octyl; 
     halogen is, for example fluorine, chlorine, bromine, iodine. 
     The invention furthermore relates to those compounds from which compounds of the formula I can be liberated (called prodrugs). 
     Preferred prodrugs are those with which release takes place under conditions like those prevailing in certain compartments of the body, eg. in the stomach, intestine, bloodstream, liver. 
     The compounds, and the intermediates for preparing them, such as II, III and IV, may have one or more asymmetrically substituted carbon atoms. Such compounds can be in the form of pure enantiomers or pure diastereomers or mixture thereof. An enantiomerically pure compound is preferably used as active substance. 
     The invention furthermore relates to the use of the abovementioned carboxylic acid derivatives for producing drugs, in particular for producing inhibitors of ET A  and ET B  receptors. The compounds according to the invention are particularly suitable as mixed antagonists as defined at the outset. 
     Compounds of the formula IV where Z is sulfur or oxygen can be prepared as described in WO 96/11914, also in enantiomerically pure form.                    
     Compounds of the formula III are known or can be synthesized, for example, by reducing the corresponding carboxylic acids or esters thereof or by other conventional methods. 
     Carboxylic acid derivatives of the formula IV [sic] can also be prepared by reacting a compound of the formula IVa with an alcohol or thiol of the formula VII with acid catalysis.                    
     The indicated radicals have the following meanings: 
     R 1  has the meaning indicated for formula I 
     R 16  and R 17 , which may be identical or different, hydrogen or alkyl, alkenyl, alkynyl, phenyl, naphthyl, cycloalkyl, in each case unsubstituted or substituted, 
     R 18  hydrogen or alkyl, alkenyl, alkynyl, phenyl, naphthyl, cycloalkyl, in each case unsubstituted or substituted, 
     R 19  hydrogen or alkyl, alkenyl, alkynyl, phenyl, naphthyl, cycloalkyl, in each case unsubstituted or substituted, 
     and the radicals preferably have the following meanings: 
     R 1  COOR 7    
     R 16  and R 17 , which may be identical or different, alkyl, phenyl, naphthyl, cycloalkyl, in each case unsubstituted or substituted, 
     R 18  alkyl, phenyl, cycloalkyl, in each case unsubstituted or substituted, 
     R 19  alkyl, alkenyl, alkynyl, phenyl, cycloalkyl, in each case unsubstituted or substituted, 
     and the following radicals are particularly preferred: 
     R 1  COOCH 3    
     R 16  R 4    
     R 17  R 5    
     R 18  alkyl, unsubstituted or substituted, in particular methyl 
     R 19  R 6 —Q. 
     The carboxylic acid derivatives of the formula IV can be prepared by this process by reacting a compound of the formula IVa with an alcohol or thiol of the formula III with acid catalysis                    
     For this purpose, the compounds IVa and III are mixed without diluent or in a solvent which is inert for this reaction, and catalytic amounts of an acid such as p-toluenesulfonic acid are added. Examples of inert solvents are methylene chloride, benzene or toluene. Also suitable are those inert solvents which form an azeotrope with the alcohol R 18 OH. In the case of methanol (R 18 ═CH 3 ), examples of these are chloroform or methyl acetate. 
     The reaction mixture is then stirred at from room temperature to the boiling point of the solvent. The resulting alcohol R 18 OH is removed by distilling out or reducing the pressure. This method is also suitable for preparing enantiomerically pure IV if the IVa starting material is enantiomerically pure. 
     Compounds of the formula IVa are known and are described, for example, in WO 96/11914. 
     The compounds according to the invention in which the substituents have the meanings stated for formula I can be prepared, for example, by reacting the carboxylic acid derivatives of the formula IV in which the substituents have the stated meanings with compounds of the formula V.                    
     In formula V, R 11  is halogen or R 12 —SO 2 — where R 12  can be C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl or phenyl. In addition, at least one of the ring members X or Y or Z is nitrogen. The reaction preferably takes place in an inert solvent or diluent with the addition of a suitable base, ie. a base which deprotonates the intermediate IV, at a temperature in the range from room temperature to the boiling point of the solvent. 
     Compounds of type I with R 1 =COOH can furthermore be obtained directly by deprotonating the intermediate IV where R 1  is COOH with two equivalents of a suitable base, and reacting with compounds of the formula V. This reaction also takes place in an inert solvent and at a temperature in the range from room temperature to the boiling point of the solvent. 
     Examples of such solvents and diluents are aliphatic, alicyclic and aromatic hydrocarbons, each of which may be chlorinated, such as hexane, cyclohexane, petroleum ether, naphtha, benzene, toluene, xylene, methylene chloride, chloroform, carbon tetrachloride, ethyl chloride and trichloroethylene, ethers such as diisopropyl ether, dibutyl ether, methyl tert-butyl ether, propylene oxide, dioxane and tetrahydrofuran, nitriles such as acetonitrile and propionitrile, amides such as dimethylformamide, dimethylacetamide and N-methylpyrrolidone, sulfoxides and sulfones, for example dimethyl sulfoxide and sulfolane. 
     Compounds of the formula V are known, and in some cases can be bought or prepared in a conventional way. 
     The base which can be used is an alkali metal or alkaline earth metal hydride such as sodium hydride, potassium hydride or calcium hydride, a carbonate such as an alkali metal carbonate, eg. sodium or potassium carbonate, an alkali metal or alkaline earth metal hydroxide such as sodium or potassium hydroxide, an organometallic compound such as butyllithium or an alkali metal amide such as lithium diisopropylamide or lithium amide. 
     Compounds of the formula I can also be prepared by starting from the corresponding carboxylic acids, ie. compounds of the formula I where R 1  is COOH, and converting first them in a conventional way into an activated form, such as a halide, an anhydride or imidazolide, and then reacting the latter with an appropriate hydroxyl compound HOR 7 . This reaction can be carried out in conventional solvents and often requires the addition of a base, in which case those mentioned above are suitable. These two steps can also be simplified, for example, by allowing the carboxylic acid to act on the hydroxyl compound in the presence of a dehydrating agent such as a carbodiimide. 
     It is also possible to prepare compounds of the formula I by starting from the salts of the appropriate carboxylic acids, ie. from compounds of the formula I where R 1  is COR and R is OM [sic] where M can be an alkali metal cation or the equivalent of an alkaline earth metal cation. These salts can be reacted with many compounds of the formula R—A where A is a conventional nucleofugic leaving group, for example halogens such as chlorine, bromine, iodine, or aryl- or alkylsulfonyl which is unsubstituted or substituted by halogen, alkyl or haloalkyl, such as toluenesulfonyl and methylsulfonyl, or another equivalent leaving group. Compounds of the formula R—A with a reactive substituent A are known or can easily be obtained with general expert knowledge. This reaction can be carried out in conventional solvents and is advantageously undertaken with the addition of a base, in which case those mentioned above are suitable. 
     In some cases it is necessary to use generally known protective group techniques to prepare compounds I according to the invention. If, for example, R 6  is to be 4-hydroxyphenyl, it is possible first to protect the hydroxyl group as benzyl ether, which is then cleaved at a suitable stage in the reaction sequence. 
     Compounds of the formula I where R 1  is tetrazole [sic] can be prepared as described in WO 96/11914. 
     With a view to the biological effect, preferred carboxylic acid derivatives of the formula I, both as pure enantiomers or pure diastereomers or as mixture thereof, are those where the substituents have the following meanings: 
     R 2  hydrogen, hydroxyl, halogen, N(C 1 -C 4 -alkyl) 2 , C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy, or CR 2  is linked to CR 10  as indicated below to give a 5- or 6-membered ring; 
     X nitrogen or methine; 
     Y nitrogen or methine; 
     Z nitrogen or CR 10 , where R 10  is hydrogen or C 1 -C 4 -alkyl, or CR 10  forms together with CR 2  or CR 3  a 5- or 6-membered alkylene or alkenylene ring which can be substituted by one or two methyl groups and in which, in each case, one methylene group can be replaced by oxygen or sulfur, such as —CH 2 —CH 2 —O—, —CH 2 —CH 2 —CH 2 —O—, —CH═CH—O—, —CH═CH—CH 2 O—, —CH(CH 3 )—CH(CH 3 )—O—, —CH=C(CH 3 )—O—, —C(CH 3 )═C(CH 3 )—O—, or —C(CH 3 )═C(CH 3 )—S; 
     At least one of the ring members X, Y or Z is nitrogen. 
     R 3  hydrogen, hydroxyl, halogen, N(C 1 -C 4 -alkyl) 2 , C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy, or CR 3  is linked to CR 10  as indicated above to give a 5- or 6-membered ring; 
     R 4  and R 5  (which can be identical or different): 
     phenyl or naphthyl, which can be substituted by one or more of the following radicals: halogen, nitro, cyano, hydroxyl, mercapto, amino, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, carboxyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, C 1 -C 4 -alkylthio, NH(C 1 -C 4 -alkyl) or N(C 1 -C 4 -alkyl) 2  or phenyl which can be substituted one or more times, eg. one to three times, by halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio; or 
     phenyl or naphthyl, which are connected together in the ortho positions by a direct linkage, a methylene, ethylene or ethenylene group, an oxygen or sulfur atom or an SO 2 —, NH— or N-alkyl group, 
     C 3 -C 8 -cycloalkyl; 
     R 6  C 3 -C 8 -cycloalkyl, it being possible for these radicals in each case to be substituted one or more times by: halogen, hydroxyl, mercapto, carboxyl, nitro, cyano, C 1 -C 4 -alkoxy, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 6 -alkenyloxy, C 3 -C 6 -alkynyloxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2  or phenyl which can be substituted one or more times, eg. one to three times, by halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio; 
     phenyl or naphthyl, each of which can be substituted by one or more of the following radicals: halogen, R 15 , nitro, mercapto, carboxyl, cyano, hydroxyl, amino, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 6 -alkenyloxy, C 1 -C 4 -haloalkyl, C 3 -C 6 -alkynyloxy, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, C 1 -C 4 -alkylthio, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , dioxomethylene [sic], dioxoethylene [sic] or phenyl which can be substituted one or more times, eg. one to three times, by halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio; 
     a five- or six-membered heteroaromatic system containing one to three nitrogen atoms and/or one sulfur or oxygen atom, which can carry one to four halogen atoms and/or one to two of the following radicals: C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylthio, phenyl, phenoxy or phenylcarbonyl, where the phenyl radicals in turn can carry one to five halogen atoms and/or one to three of the following radicals: C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy and/or C 1 -C 4 -alkylthio; 
     R 15  methyl, ethyl, methoxy or ethoxy which carry one of the following radicals: hydroxyl, carboxyl, amino, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , carboxamide [sic] or CON(C 1 -C 4 -alkyl) 2 ; 
     W sulfur or oxygen; 
     Q C 2 -C 4 -alkyl, C 3 -C 4 -alkenyl, C 3 -C 4 -alkynyl, —S—CH 2 —CH 2 —, —O—CH 2 —CH 2 —, it being possible for each of these radicals to be substituted one or more times by: halogen, hydroxyl, mercapto, carboxyl, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkoxycarbonyl, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2  or phenyl which can be substituted one or more times, eg. one to three times, by halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio 
     or Q forms together with R 6  the following ring systems: 2-indanyl, 3-indanyl, 1,2,3,4-tetrahydro-2-naphthyl, 1,2,3,4-tetrahydro-3-naphthyl, it being possible for the phenyl rings in each case to be substituted by: halogen, hydroxyl, mercapto, carboxyl, nitro, cyano, C 1 -C 4 -alkoxy, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 6 -alkenyloxy, C 3 -C 6 -alkynyloxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, amino, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2  or phenyl. 
     Particularly preferred compounds of the formula I, both as pure enantiomers and pure diastereomers or mixtures thereof, are those where the substituents have the following meanings: 
     R 2  trifluoromethyl, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, or CR 2  is linked to CR 10  as indicated below to give a 5- or 6-membered ring; 
     X nitrogen or methine; 
     Y nitrogen or methine; 
     Z nitrogen or CR 10  where R 10  is hydrogen or C 1 -C 4 -alkyl, or CR 10  forms together with CR 2  or CR 3  a 5- or 6-membered alkylene or alkenylene ring which can be substituted by one or two methyl groups and in which in each case a methylene group can be replaced by oxygen or sulfur, such as —CH 2 —CH 2 —O—, —CH 2 —CH 2 —CH 2 —O—, —CH═CH—O—, —CH═CH—CH 2 O—, —CH(CH 3 )—CH(CH 3 )—O—, —CH=C(CH 3 )—O—, —C(CH 3 )═C(CH 3 )—O—, or —C(CH 3 )═C(CH 3 )—S; 
     At least one of the ring members X, Y or Z is nitrogen 
     R 3  trifluoromethyl, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, or CR 3  is linked to CR 10  as indicated above to give a 5- or 6-membered ring; 
     R 4  and R 5  (which can be identical or different): 
     phenyl or naphthyl, which can be substituted by one or more of the following radicals: halogen, nitro, cyano, hydroxyl, mercapto, amino, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, C 1 -C 4 -alkylthio, NH(C 1 -C 4 -alkyl) or N(C 1 -C 4 -alkyl) 2  or phenyl which can be substituted one or more times, eg. one to three times, by halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio; or 
     phenyl or naphthyl, which are connected together in the ortho positions by a direct linkage, a methylene, ethylene or ethenylene group, an oxygen or sulfur atom or an SO 2 —, NH— or N-alkyl group 
     C 5 -C 7 -cycloalkyl; 
     R 6  C 5 -C 7 -cycloalkyl, it being possible for these radicals in each case to be substituted one or more times by: C 1 -C 4 -alkoxy, 
     C 1 -C 4 -alkyl, C 1 -C 4 -alkylthio, halogen, hydroxyl, carboxyl, cyano, trifluoromethyl, acetyl, or phenyl which can be substituted one or more times, eg. one to three times, by halogen, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio; 
     phenyl or naphthyl, each of which can be substituted by one or more of the following radicals: halogen, R 15 , nitro, mercapto, carboxyl, cyano, hydroxyl, amino, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, acetyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, C 1 -C 4 -alkylthio, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , dioxomethylene [sic], dioxoethylene [sic] or 
     phenyl which can be substituted one or more times, eg. one to three times, by halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio; 
     a five- or six-membered heteroaromatic system containing one to three nitrogen atoms and/or one sulfur or oxygen atom, which can carry one to four halogen atoms and/or one to two of the following radicals: C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, trifluoromethoxy, C 1 -C 4 -alkylthio, phenyl or phenoxy, it being possible for the phenyl radicals in turn to carry one to five halogen atoms and/or one to three of the following radicals: C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy and/or C 1 -C 4 -alkylthio; 
     R 15  methoxy or ethoxy which carry one of the following radicals: hydroxyl, carboxyl, amino, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , carboxamide [sic] or CON(C 1 -C 4 -alkyl) 2 ; 
     W sulfur or oxygen; 
     Q C 2 -C 4 -alkyl, C 3 -C 4 -alkenyl, C 3 -C 4 -alkynyl, —S—CH 2 —CH 2 —, —O—CH 2 —CH 2 —, it being possible for each of these radicals to be substituted one or more times by: halogen, hydroxyl, mercapto, carboxyl, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, or phenyl which can be substituted one or more times, eg. one to three times, by halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio 
     or Q forms together with R 6  the following ring systems: 2-indanyl, 3-indanyl, 1,2,3,4-tetrahydro-2-naphthyl, 1,2,3,4-tetrahydro-3-naphthyl, it being possible for the phenyl rings in each case to be substituted by: halogen, hydroxyl, mercapto, carboxyl, cyano, C 1 -C 4 -alkoxy, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 6 -alkenyloxy, C 3 -C 6 -alkynyloxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkoxycarbonyl, NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2  or phenyl. 
     The compounds of the present invention offer a novel therapeutic potential for the treatment of hypertension, pulmonary hypertension, myocardial infarct, chronic heart failure, angina pectoris, acute/chronic kidney failure, renal insufficiency, cerebral vasospasms, cerebral ischemia, subarachnoid hemorrhages, migraine, asthma, atherosclerosis, endotoxic shock, endotoxin-induced organ failure, intravascular coagulation, restenosis after angioplasty, benign prostate hyperplasia, kidney failure and hypertension caused by ischemia and intoxication, metastasis and growth of mesenchymal tumors, kidney failure induced by contrast agents, pancreatitis, gastrointestinal ulcers. 
     The compounds according to the invention surprisingly also show in some cases an antagonistic action on the neurokinin receptor. 
     This is particularly true of compounds of the formula I where R 1  is                    
     The invention furthermore relates to combination products consisting of endothelin receptor antagonists of the formula I and inhibitors of the renin-angiotensin system. Inhibitors of the renin-angiotensin system are renin inhibitors, angiotensin II antagonists and, in particular, angiotensin converting enzyme (ACE) inhibitors. 
     The invention further relates to combination products of β blockers and the abovementioned endothelin receptor antagonists, and of mixed ACE/neutral endopeptidase (NEP) inhibitors and the abovementioned endothelin receptor antagonists. 
     The combination products can be administered in a single pharmaceutical form or else in spatially separate forms. Administration may take place simultaneously or sequentially. 
     The dosage of the combination may be up to the maximum single dose in each case. However, it is also possible to employ lower doses than in the single therapy in each case. 
     These combination products are particularly suitable for the treatment and prevention of hypertension and its sequelae, and for the treatment of heart failure. 
     The good effect of the compounds can be shown in the following tests: 
     Receptor Binding Studies 
     Cloned human ET A  or ET B  receptor-expressing CHO cells were employed for binding studies. 
     Membrane Preparation 
     The ET A  or ET B  receptor-expressing CHO cells were grown in DMEM NUT MIX F 12  medium (Gibco, No. 21331-020) with 10% fetal calf serum (PAA Laboratories GmbH, Linz, No. A15-022), 1 mM glutamine (Gibco No. 25030-024), 100 U/ml penicillin and 100 μg/ml streptomycin (Gibco, Sigma No. P-0781). After 48 hours, the cells were washed with PBS and incubated with 0.05% trypsin-containing PBS at 37° C. for 5 minutes. Neutralization with medium was then carried out, and the cells were collected by centrifugation at 300×g. 
     For the membrane preparation, the cells were adjusted to a concentration of 10 8  cells/ml of buffer (50 mM tris.HCL buffer, pH 7.4) and then disintegrated by ultrasound (Branson Sonifier 250, 40-70 seconds/constant/output 20). 
     Binding Assays 
     For the ET A  and ET B  receptor binding assays, the membranes were suspended in incubation buffer (50 mM tris-HCl, pH 7,4 with 5 mM MnCl 2 , 40 μg/ml bacitracin and 0.2% BSA) at a concentration of 50 μg of protein per assay mixture, and incubated with 25 pM  125 I-ET 1  (ET A  receptor assay) or 25 pM  125 I-ET 3  (ET B  receptor assay) in the presence and absence of test substance at 25° C. The nonspecific binding was determined with 10 −7  M ET 1 . Filtration was carried out after 30 min through GF/B glassfiber filters (Whatman, England) in a Skatron cell collector (Skatron, Lier, Norway) to separate free and bound radio ligands, and the filters were washed with ice-cold tris-HCl buffer, pH 7.4 with 0.2% BSA. The radioactivity collected on the filters was quantified using a 
     Packard 2200 CA liquid scintillation counter. 
     Testing of the ET antagonists in vivo: 
     Male SD rats weighing 250-300 g were anesthetized with amobarbital, artificially ventilated, vagotomized and pithed. The carotid artery and jugular vein were catheterized. 
     Intravenous administration of 1 μg/kg ET1 to control animals led to a marked rise in blood pressure, which persisted for a lengthy period. 
     The test animals received i.v. injections of the test compounds (1 ml/kg) 30 min before administration of ET1. To determine the ET-antagonistic properties, the changes in blood pressure in the test animals were compared with those in the control animals. 
     Oral testing of the mixed ET A  and ET B  antagonists: 
     Normotensive male rats (Sprague Dawley, Janvier) weighing 250-350 g are pretreated orally with the test substances. 80 minutes later, the animals are anesthetized with urethane, and the carotid artery (for measuring the blood pressure) and the jugular vein (administration of big endothelin/endothelin 1) are catheterized. 
     After a stabilization period, big endothelin (20 μg/kg, administration volume 0.5 ml/kg) or ET1 (0.3 μg/kg, administration volume 0.5 ml/kg) is given intravenously. The blood pressure and heartrate are recorded continuously for 30 minutes. The marked and long-lasting changes in blood pressure are calculated as area under the curve (AUC). To determine the antagonistic effect of the test substances, the AUC for the animals treated with the substance is compared with the AUC for the control animals. 
     The compounds according to the invention can be administered orally or parenterally (subcutaneously, intravenously, intramuscularly, intraperitoneally) in a conventional way. Administration may also take place with vapors or sprays through the nasopharyngeal space. 
     The dosage depends on the age, condition and weight of the patient and on the mode of administration. As a rule, the daily dose of active substance is about 0.5-50 mg/kg of bodyweight on oral administration and about 0.1-10 mg/kg of bodyweight on parenteral administration. 
     The novel compounds can be used in conventional solid or liquid pharmaceutical forms, eg. as uncoated or (film-)coated tablets, capsules, powders, granules, suppositories, solutions, ointments, creams or sprays. These are produced in a conventional way. For this purpose, the active substances can be processed with conventional pharmaceutical auxiliaries such as tablet binders, bulking agents, preservatives, tablet disintegrants, flow regulators, plasticizers, wetting agents, dispersants, emulsifiers, solvents, release-slowing agents, antioxidants and/or propellant gases (cf. H. Sucker et al.: Pharmazeutische Technologie, Thieme-Verlag, Stuttgart, 1991). The administration forms obtained in this way normally contain from 0.1 to 90% by weight of active substance. 
    
    
     SYNTHESIS EXAMPLES 
     Example 1 
     Methyl 2-Hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-diphenylpropionate 
     7 g (27.5 mmol) of methyl 3,3-diphenyl-2,3-epoxypropionate and 5.5 g (30.2 mmol) of 2-(3,4-dimethoxyphenyl)ethanol were dissolved in 20 ml of dichloromethane and, at room temperature, 5 drops of boron trifluoride etherate were added. The solution was stirred for 2 hours. The solvent was then distilled off, and the residue (10.7 g, 89%) was immediately reacted further. 
     Example 2 
     2-Hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid 
     12 g (27.5 mmol) of methyl 2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-diphenylpropionate were dissolved in 110 ml of dioxane, and 55 ml of 1 N NaOH solution were added. The mixture was stirred at 80° C. for 2 hours. Water was added to the mixture, and the aqueous phase was extracted twice with ether. The aqueous phase was acidified with 1 N aqueous HCl and extracted with ether, the organic phase was dried over magnesium sulfate, and the solvent was distilled off. The residue was recrystallized from ether/n-hexane, and 10.2 g (87%) of colorless crystals were isolated. 
     Melting point: 133-135° C. 
     Example 3 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-482) 
     1 g (2.3 mmol) of 2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-diphenylpropionic acid was introduced into 10 ml of DMF, and 340 mg of NaH (50% suspension) were added. After the mixture had been stirred for 15 minutes, 526 mg of 4-methoxy-6-methyl-2-methylsulfonylpyrimidine were added, and the mixture was stirred at room temperature for 3 hours. Water was added to the mixture, which was then extracted with ether. The aqueous phase was acidified with 1 N aqueous HCl, extracted with ether and dried over magnesium sulfate. The solvent was distilled off, the residue was purified by MPLC, and 655 mg (52%) of colorless powder were isolated after recrystallization from ether/n-hexane. 
       1 H-NMR (200 MHz): 7.2 ppm (10H, m), 6.8 (3H, m), 6.2 (1H, s), 6.18 (1H, s), 3.9 (9H, m), 3.8 (1H, m), 3.7 (1H, m), 2.85 (2H, tr), 2.2 (3H, s). EI-MS: M + =544. 
     Example 4 
     Methyl 3,3-di(4-Ethylphenyl)-2,3-epoxypropionate 
     A solution of 15 ml (168 mmol) of methyl chloroacetate and 20 g (84 mmol) of 4,4′-diethylbenzophenone in 20 ml of THF was added dropwise to a suspension of 9.1 g (168 mmol) of sodium ethanolate in 80 ml of THF at −10° C. The mixture was warmed to room temperature and stirred for 2 hours. The mixture was added to water and extracted with ether. The organic phase was washed with sodium bicarbonate solution and citric acid solution and dried over magnesium sulfate, and the solvent was distilled off. 15.4 g of a crude oil were isolated and were immediately employed further. 
     Example 5 
     Methyl 2-Hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-di-(4-ethyl-phenyl)propionate 
     6 g (19.3 mmol) of methyl 3,3-di(4-ethylphenyl)-2,3-epoxypropionate (crude) and 3.52 g (19.3 mmol) of 2-(3,4-dimethoxyphenyl)ethanol were dissolved in 20 ml of dichloromethane and, at room temperature, 5 drops of boron trifluoride etherate were added. The solution was stirred for 1.5 hours. The solvent was then distilled off, and the residue, a pale yellow oil (8.66 g, 91%), was immediately reacted further. 
     Example 6 
     2-Hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-di(4-ethylphenyl)propionic Acid 
     9.2 g (19.3 mmol) of methyl 2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-di(4-ethylphenyl)propionate were dissolved in 26 ml of dioxane, and 13 ml of 3 N NaOH solution were added. The mixture was stirred at 60° C. for 3 hours. Water was added to the mixture, and the aqueous phase was extracted twice with ether. The aqueous phase was acidified with 1 N aqueous HCl and extracted with ether, the organic phase was dried over magnesium sulfate, and the solvent was distilled off. 6.5 g (71%) of a yellowish oil were isolated and were immediately reacted further. 
     Example 7 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-di(4-ethylphenyl)propionic Acid (I-116) 
     1.8 g (3.8 mmol) of 2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-di(4-ethylphenyl)propionic acid were introduced into 20 ml of DMF, and 554 mg of NaH (50% suspension) were added. After the mixture had stirred for 15 minutes, 855 mg (4.2 mmol) of 4-methoxy-6-methyl-2-methylsulfonylpyrimidine were added, and the mixture was stirred at room temperature for 3 hours. Water was added to the mixture, which was then extracted with ether. The aqueous phase was acidified with 1 N aqueous HCl, extracted with ether and dried over magnesium sulfate. The solvent was distilled off and 540 mg (23%) of colorless powder were isolated after recrystallization from ether/n-hexane. 
       1 H-NMR (200 MHz): 7.0-7.4 ppm (10H, m), 6.8 (2H, d), 6.2 (1H, s), 6.15 (1H, s), 3.9 (3H, s), 3.8 (3H, s), 3.7 (1H, m), 3.5 (1H, m), 2.9 (2H, tr), 2.6 (4H, m), 2.3 (3H, s), 1.2 (6H, m). EI-MS: M + =600. 
     Example 8 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(3-phenyl-(2E)-propenoxy)-3,3-diphenylpropionic Acid (I-27) 
     1.12 g (3 mmol) of 2-hydroxy-3-(3-phenyl-(2E)-propenoxy)-3,3-diphenylpropionic acid were added to a suspension of 432 mg (9 mmol, 50%) of NaH in 20 ml of DMF, and the mixture was stirred at room temperature for 10 minutes. 614 mg (3.3 mmol) of 4,6-dimethyl-1-methylsulfonylpyrimidine were added, and the mixture was stirred for 16 hours, then diluted with 200 ml of water, acidified with 1 N hydrochloric acid and extracted with ether. The ether phase was extracted with 1 N sodium hydroxide solution, the aqueous phase was again acidified, and the product was extracted with ether. The organic phase was dried over magnesium sulfate and filtered, and the solvent was distilled off. The residue was recrystallized from ether/hexane, and 927 mg (65%) of crystalline product were isolated. 
     Melting point: 128-133° C.;  1 H-NMR (200 MHz): 7.3 ppm (15H, m), 6.74 (1H, s), 6.7 (1H, d), 6.3 (1H, s), 6.2 (1H, dtr, 4.3 (1H, dd), 4.1 (1H, dd), 2.3 (6H, s). EI-MS: M + =480. 
     Example 9 
     4,6-Dimethyl-1-methylthiopyrimidine 
     15 g (107 mmol) of 4,6-dimethyl-1-mercaptopyrimidine and 5.14 g of NaOH were dissolved in 175 ml of water. 12 ml (128 mmol) of dimethyl sulfate were added dropwise to this mixture at room temperature over the course of 10 minutes. After 1 hour, the aqueous phase was extracted 3 times with ether and dried over magnesium sulfate, and the solvent was distilled off. 15.9 g (97%) of crude product were isolated.  1 H-NMR (270 MHz): 6.7 ppm (1H, s), 2.5 (3H, s), 2.3 (6H, s). 
     Example 10 
     4,6-Dimethyl-1-methylsulfonylpyrimidine 
     15.9 g (103 mmol) of 4,6-dimethyl-1-methylthiopyrimidine were introduced into 120 ml of dichloromethane and 110 ml of water. Chlorine gas was passed into saturation (yellow coloration) at 0° C. After the conversion was complete, excess chlorine was driven out with nitrogen, the aqueous phase was extracted with dichloromethane, and the collected organic phases were dried over magnesium sulfate. The solution was concentrated, and the product (14 g, 73%) was crystallized by adding ether. 
     Melting point: 79-80° C.  1 H-NMR (270 MHz): 7.2 ppm (1H, s), 3.4 (3H, s), 2.6 (6H, s). 
     Example 11 
     Methyl (S)-2-Hydroxy-3-methoxy-3,3-diphenylpropionate 
     54.4 g (200 mmol) of (S)-2-hydroxy-3-methoxy-3,3-diphenylpropionic acid were introduced with 10.8 g (200 mmol) of sodium methoxide into 300 ml of DMF. 21 ml (210 mmol) of dimethylsulfate were added dropwise to this suspension over 15 minutes, during which the temperature rises to 50° C. and the suspension becomes mobile. The mixture was stirred overnight and then added to 1.5 l of water and ice. The aqueous phase was extracted twice with 500 ml of ether, and the ether phase was in turn washed with 200 ml of water twice. The organic phase was dried over magnesium sulfate, the desiccant was filtered off, and the solvent was distilled off. 55.8 g of an oil were isolated and were immediately processed further. 
     Example 12 
     Methyl (S)-2-Hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-diphenylpropionate 
     Variant A: 
     27.9 g of methyl (S)-2-hydroxy-3-methoxy-3,3-diphenylpropionate (100 mmol) were mixed with 1 g of p-toluenesulfonic acid and 18.2 g of 2-(3,4-dimethoxyphenyl)ethanol (100 mmol) in a flask and heated to 60° C. The pressure in the flask is reduced in order to distill out the methanol which is produced, and the mixture is stirred at 60° C. for a further 5 hours. For workup, the mixture is cooled and diluted with 300 ml of ether, and the organic phase is washed first with sodium bicarbonate solution and then several times with water. It is then dried with magnesium sulfate, and the desiccant is filtered off and the solvent is distilled off. A residue of 43 g of oil was isolated and could be employed immediately for the subsequent synthesis. 
     Variant B: 
     27.9 g of methyl (S)-2-hydroxy-3-methoxy-3,3-diphenylpropionate (100 mmol), 1 g of p-toluenesulfonic acid and 18.2 g (100 mmol) of 2-(3,4-dimethoxyphenyl)ethanol were dissolved in 75 ml of dichloromethane in a flask. The solution was heated and the dichloromethane was distilled out while simultaneously adding dichloromethane dropwise, in order to distill out the methanol which was produced, and the mixture was stirred at 60° C. for a further 5 hours. For workup, the mixture is cooled and diluted with 300 ml of ether, and the organic phase is washed first with sodium bicarbonate solution and then several times with water. It is then dried with magnesium sulfate, and the desiccant is filtered off and the solvent is distilled off. A residue of 43 g of oil was isolated and could be used immediately in the subsequent synthesis. 
     Example 13 
     (S)-2-Hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid 
     255 ml of 1 N sodium hydroxide solution were added to a solution of 74 g (170 mmol) of methyl (S)-2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy-3,3-diphenylpropionate in 510 ml of dioxane, and the suspension was stirred at 50° C. for two hours. The mixture was diluted with 2.5 l of water and neutralized with citric acid. The aqueous phase was extracted twice with 500 ml of ether. The organic phase was then washed with water, dried over magnesium sulfate and filtered, and then the ether was distilled off. The residue was purified by crystallization from ether/n-hexane, and 70 g of crystals were isolated. 
       1 H-NMR (200 MHz): 7.3 ppm (10H, m), 6.8 (1H, dbr), 6.7 (1H, dbr), 6.6 (1H, sbr), 5.0 (1H, s), 3.9 (3H, s), 3.85 (3H, s), 3.6 (1H, dt), 3.4 (1H, OH), 3.2 (1H, dt), 2.8 (2H, t). [α] 20 =8.3 (1; ethanol). 
     Example 14 
     2-(4,6-(Dimethylpyrimidin-2-yloxy)-3-(2-(3,4-dimethoxyphenyl)ethoxy-3,3-diphenylpropionic Acid (I-445) and 
     (S)-2-(4,6-Dimethylpyrimidin-2-yloxy)-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-445 (S) Enantiomer) 55 g (130 mmol) of 2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy-3,3-diphenylpropionic acid, dissolved in 150 ml of DMF, were added over the course of 15 minutes to 9 g (390 mmol) of lithium amide in 35 ml of DMF. 25 g (137 mmol) of 2-methylsulfone-4,6-dimethylpyrimidine [sic], dissolved in 75 ml of DMF, were slowly added dropwise to this, and the mixture was stirred at room temperature for 18 hours. For workup, the mixture was added to 2 l of ice-water and citric acid for neutralization. The crystals which separated out were filtered off with suction and washed with water. The moist crystals were dissolved in dichloromethane, the solution was dried over magnesium sulfate and filtered, and the solvent was distilled off. The oily residue was taken up in ether and extracted with 130 ml of 1 N sodium hydroxide solution, and the aqueous phase was neutralized with 130 ml of 1 N hydrochloric acid, whereupon crystals separated out. 64 g of product were isolated after drying. 
       1 H-NMR (200 MHz): 7.3 ppm (10H, m), 6.7 (4H, m), 6.3 (1H, s), 3.9 (3H, s), 3.85 (3H, s), 3.7 (1H, dt), 3.6 (1H, dt), 2.8 (2H, t), 2.3 (6H, s). 
     Melting point: 125-130° C. decomposition EI-MS: M + =528. 
     (S)-2-(4,6-dimethylpyrimidin-2-yloxy)-3-(2-(3,4-dimethoxyphenyl)ethoxy-3,3-diphenylpropionic acid was prepared in a similar way from (S)-2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-diphenylpropionic acid and 2-methylsulfone-4,6-dimethylpyrimidine [sic] in the presence of lithium amide. [α] 20 =111 (1; ethanol). 
     Example 15 
     The following compounds were prepared as in Example 8 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(4-methoxyphenyl)ethoxy)-3,3-di(4-ethylphenyl)propionic Acid (I-147) 
     Melting point: 150-155° C. EI-MS: M + =570. 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(2-(4-chlorophenyl)ethoxy)-3,3-diphenylpropionic Acid (I-651) 
     Melting point: 150-152° C. EI-MS: M + =546. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(2-(4-chlorophenyl)ethoxy)-3,3-diphenylpropionic Acid (I-713) 
     Melting point: 108° C. Decomposition EI-MS: M + =502. 
     2-(4,6-Dimethoxy-2-pyrimidinyloxy)-3-(2-(4-chlorophenyl)ethoxy)-3,3-diphenylpropionic Acid 
     Melting point: 165-167° C. EI-MS: M + =534. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(4-chlorophenyl)ethoxy)-3,3-diphenylpropionic Acid (I-746) 
     Melting point: 93-98° C. EI-MS: M + =518. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(2-(4-methoxyphenyl)ethoxy)-3,3-di(4-ethylphenyl)propionic Acid (I-148) 
     Melting point: 130-133° C. EI-MS: M + =554. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(4-methylphenyl)ethoxy)-3,3-di(4-chlorophenyl)propionic Acid (I-710) 
     Melting point: 90-100° C. EI-MS: M + =566. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(3,3-diphenylpropoxy)-3,3-di(4-chlorophenyl)propionic Acid 
       1 H-NMR(200 MHz): 7.3 ppm (18H, m), 6.25 (1H, s), 6.0 (1H, s), 4.0 (1H, tr), 3.8 (3H, s), 3.4 (2H, m), 2.2 (5H, m). EI-MS: M + =642. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-di(4-chlorophenyl)propionic Acid (I-699) 
     Melting point: 100-110° C. EI-MS: M + =612. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(2-methoxyphenyl)ethoxy)-3,3-di(4-chlorophenyl)propionic Acid (I-487) 
     Melting point: 85-90° C. EI-MS: M + =582. 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(2-(3-methoxyphenyl)ethoxy)-3,3-di(4-chlorophenyl)propionic Acid (I-486) 
     Melting point: 190-195° C. EI-MS: M + =610. 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(2-phenylethylthio)-3,3-di(4-chlorophenyl)propionic Acid 
     Melting point: 173-175° C.  1 H-NMR (200): 7.0-7.4 ppm (13H, m), 6.0 (1H, s), 4.7 (2H, tr), 3.8 (3H, s), 3.1 (2H, tr), 2.5 (4H, m). 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-di(4-chlorophenyl)propionic Acid (I-635) 
     Melting point: 100-110° C. EI-MS: M + =640. 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(2-(3,5-dimethoxyphenyl)ethoxy)-3,3-di(4-chlorophenyl)propionic Acid (1-593) 
     Melting point: 90-100° C. EI-MS: M + =640. 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(2-(2-methoxyphenyl)ethoxy)-3,3-di(4-chlorophenyl)propionic Acid (I-164) 
     Melting point: 135-145° C. EI-MS: M + =610. 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(3,3-diphenylpropoxy)-3,3-di(4-chlorophenyl)propionic Acid 
     Melting point: 125-127° C. EI-MS: M + =670. 
     2-(4-Methoxy-6,7-dihydro-5H-cyclopentapyrimidin-2-yloxy)-3-(3,3-diphenylpropoxy)-3,3-di(4-chlorophenyl)propionic Acid 
     Melting point: 135-140° C. EI-MS: M + =668. 
     2-(4-Methoxy-6,7-dihydro-5H-cyclopentapyrimidin-2-yloxy)-3-(2-phenylethylthio)-3,3-di(4-chlorophenyl)propionic Acid 
     Melting point: 135-140° C.  1 H-NMR (200): 7.0-7.5 ppm (13H, m), 5.9 (1H, s), 3.9 (3H, s), 2.6-2.8 (8H, m), 2.1 (2H, m). 
     2-(4-Methoxy-6,7-dihydro-5H-cyclopentapyrimidin-2-yloxy)-3-(2-(2-methoxyphenyl)ethoxy)-3,3-di(4-chlorophenyl)propionic Acid 
     Melting point: 105-115° C. EI-MS: M + =608. 
     2-(4-Methoxy-6,7-dihydro-5H-cyclopentapyrimidin-2-yloxy)-3-(2-(3-methoxyphenyl)ethoxy)-3,3-di(4-chlorophenyl)propionic Acid 
     Melting point: 110-120° C. EI-MS: M + =608. 
     2-(4-Methoxy-6,7-dihydro-5H-cyclopentapyrimidin-2-yloxy)-3-(2-(4-dimethylaminophenyl)ethoxy)-3,3-di(4-chlorophenyl)propionic Acid 
     Melting point: 135-140° C. EI-MS: M + =621. 
     2-(4-Methoxy-6,7-dihydro-5H-cyclopentapyrimidin-2-yloxy)-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-di(4-chlorophenyl)propionic Acid 
     Melting point: 125-130° C. EI-MS: M + =638. 
     2-(4-Methoxy-6,7-dihydro-5H-cyclopentapyrimidin-2-yloxy)-3-(2-(3,5-dimethoxyphenyl)ethoxy)-3,3-di(4-chlorophenyl)propionic Acid 
     Melting point: 125-130° C. EI-MS: M + =638. 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(2-(4-methylphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-370) 
     Melting point: 128-130° C. EI-MS: M + =526. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-phenylethoxy)-3,3-diphenylpropionic Acid (I-719) 
     Melting point: 155° C. Decomposition EI-MS: M + =484. 
     2-(4,6-Dimethoxy-2-pyrimidinyloxy)-3-(2-phenylethoxy)-3,3-diphenylpropionic Acid 
     Melting point: 203° C. Decomposition EI-MS: M + =500. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(2-phenylethoxy)-3,3-diphenyl propionic Acid (I-720) 
     Melting point: 130-133° C. EI-MS: M + =468. 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(2-phenylethoxy)-3,3-diphenylpropionic Acid (I-657) 
     Melting point: 138-142° C. EI-MS: M + =512. 
     2-(4,6-Dimethoxy-2-pyrimidinyloxy)-3-(2-(4-methylphenyl)ethoxy)-3,3-diphenylpropionic Acid 
     Melting point: 155-158° C. EI-MS: M + =514. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(4-methylphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-465) 
     Melting point: 145-147° C. EI-MS: M + =498. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(3-(4-methoxyphenyl)propoxy)-3,3-diphenylpropionic Acid (I-554) 
     Melting point: 160-165° C. EI-MS: M + =528. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(3-(4-methoxyphenyl)propoxy)-3,3-diphenylpropionic Acid (I-555) 
     Melting point: 165-170° C. EI-MS: M + =512. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(3-(3,4,5-trimethoxyphenyl)propoxy)-3,3-diphenylpropionic Acid (I-335) 
       1 H-NMR (200): 7.2-7.4 ppm (10H, m), 6.3 (2H, s), 6.2 (2H, s), 3.8 (3H, s), 3.75 (10H, s), 3.4 (2H, m), 2.6 (2H, m), 2.25 (3H, s), 1.9 (2H, m). EI-MS: M + =588. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(3-(3,4,5-trimethoxyphenyl)propoxy)-3,3-diphenylpropionic Acid (I-336) 
       1 H-NMR (200): 7.2-7.5 ppm (10H, m), 6.6 (1H, s), 6.3 (3H, S), 3.8 (9H, s), 3.4 (2H, m), 2.6 (2H, m), 2.3 (6H, s), 1.9 (2H, m). EI-MS: M + =572. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(3-(2-chlorophenyl)propoxy)-3,3-diphenylpropionic Acid (I-383) 
       1 H-NMR (200): 7.1-7.5 ppm (14H, m), 6.24 (1H, s), 6.23 (1H, s), 3.8 (3H, s), 3.4 (2H, m), 2.75 (2H, m), 2.25 (3H, s), 1.9 (2H, m). EI-MS: M + =532. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(3-(2-chlorophenyl)propoxy)-3,3-diphenylpropionic Acid (I-384) 
     Melting point: 172-178° C. EI-MS: M + =516. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(3-(4-chlorophenyl)propoxy)-3,3-diphenylpropionic Acid (I-251) 
       1 H-NMR (200): 7.0-7.4 ppm (14H, m), 6.6 (1H, s), 6.3 (1H, s), 3.5 (2H, m), 2.7 (2H, m), 2.3 (6H, s), 1.9 (2H, m). EI-MS: M + =516. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(3-(3,4-dimethoxyphenyl)propoxy)-3,3-diphenylpropionic Acid (I-490)) 
       1 H-NMR (200): 7.1-7.5 ppm (10H, m), 6.74 (1H, s), 6.7 (3H, S), 6.3 (1H, s), 3.8 (6H, s), 3.5 (2H, m), 2.7 (2H, m), 2.3 (6H, s), 1.9 (2H, m). EI-MS: M + =542. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(4-propoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-69) 
     Melting point: 115-119° C. EI-MS: M + =542. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(4-butoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-71) 
     Melting point: 118-122° C. EI-MS: M + =556. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(2-(4-butoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-70) 
     Melting point: 122-125° C. EI-MS: M + =540. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(3-phenyl-(2E)-propenoxy)-3,3-diphenylpropionic Acid (I-44) 
     Melting point: 171-174° C. EI-MS: M + =496. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(3-(2-methylphenyl)propoxy)-3,3-diphenylpropionic Acid (I-107) 
     Decomposition: 144-146° C. EI-MS: M + =512. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(3-(2-methylphenyl)propoxy)-3,3-diphenylpropionic Acid (I-90) 
     Decomposition: 173-176° C. EI-MS: M + =496. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(3-(4-methylphenyl)propoxy)-3,3-diphenylpropionic Acid (1-363) 
     Decomposition: 158-161° C. EI-MS: M + =512. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(3-(4-methylphenyl)propoxy)-3,3-diphenylpropionic Acid (I-346) 
     Decomposition: 163-167° C. EI-MS: M + =496. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(4-methylthiophenyl)ethoxy)-3,3-diphenylpropionic Acid (I-246) 
     Decomposition: 136-138° C. EI-MS: M + =530. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(2-(4-methylthiophenyl)ethoxy)-3,3-diphenylpropionic Acid (I-217) 
     Decomposition: 166-169° C. EI-MS: M + =514. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(4-ethoxy-3-methoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (1-145) 
     Decomposition: 141-145° C. EI-MS: M + =558. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(4-ethoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-510) 
     Decomposition: 131-135° C. EI-MS: M + =528. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(4-i-propylphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-705) 
       1 H-NMR (200 MHz, DMSO): 7.0-7.35 ppm (14H, m), 6.35 (1H, s), 6.1 (1H, s), 4.0 (1H, m), 3.9 (3H, s), 3.8 (3H, s), 3.7 (1H, m), 2.9 (3H, m), 2.2 (3H, s), 1.1 (6H, d). EI-MS: M + =526. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(3,4-methylenedioxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (1-568) 
     Decomposition: 146-148° C. EI-MS: M + =528. 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(2-(3,4-methylenedioxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-501) 
     Decomposition: 145-149° C. EI-MS: M + =556. 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(2-(4-ethoxy-3-methoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-735) 
       1 H-NMR (270 MHz, DMSO): 7.1-7.4 ppm (10H, m), 6.85 (2H, m), 6.7 (1H, d), 6.1 (1H, s), 4.6 (2H, tr), 4.0 (3H, m), 3.85 (3H, s), 3.75 (3H, s), 3.65 (1H, m), 3.05 (2H, tr), 2.8 (2H, m), 1.25 (3H, m). EI-MS: M + =586. 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(2-(4-ethoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-407) 
       1 H-NMR (270 MHz, DMSO): 7.1-7.4 ppm (12H, m), 6.8 (2H, d), 6.1 (1H, s), 4.65 (2H, tr), 3.95 (3H, m), 3.8 (3H, s), 3.65 (1H, m), 3.05 (2H, tr), 2.8 (2H, m), 1.25 (3H, m). EI-MS: M + =556. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(2-(4-ethoxy-3-methoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (1-146) 
     Decomposition: 129-134° C. EI-MS: M + =542. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(2-(3,4-methylenedioxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-569) 
       1 H-NMR (270 MHz, DMSO): 7.1-7.4 ppm (10H, m), 6.9 (1H, s), 6.8 (2H, m), 6.7 (1H, d), 6.2 (1H, s), 6.0 (2H, s), 3.95 (3H, m), 3.65 (1H, m), 2.8 (2H, m), 2.3 (6H, s). EI-MS: M + =512. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(2-(4-ethoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-473) 
     Decomposition: 145-148° C. EI-MS: M + =512. 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(2-(4-i-propylphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-604) 
       1 H-NMR (270 MHz, DMSO): 7.1-7.4 ppm (14H, m), 6.1 (1H, s), 4.6 (2H, tr), 3.9 (1H, m), 3.8 (3H, s), 3.6 (1H, m), 3.0 (2H, tr), 2.8 (3H, m), 1.1 (6H, d). EI-MS: M + =554. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(2-(4-i-propylphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-672) 
     Decomposition: 156-160° C. EI-MS: M + =510. 
     2-(4-Methoxy-5,6-dihydrofuro(2,3d)-2-pyrimidinyloxy)-3-(2-(4-methoxyphenyl)ethoxy)-3,3-di(4-methylphenyl)propionic Acid (I-517) 
       1 H-NMR (200 MHz, DMSO): 7.0-7.3 ppm (10H, m), 6.8 (2H, d), 6.0 (1H, s), 4.6 (2H, tr), 3.85 (3H, s), 3.8 (1H, m), 3.7 (3H, s), 3.6 (1H, m), 3.0 (2H, tr), 2.8 (2H, tr), 1.1 (6H, d). EI-MS: M + =570. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(2-(4-methoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-622) 
       1 H-NMR (270 MHz, DMSO): 7.1-7.4 ppm (12H, m), 6.8 (2H, d), 6.4 (1H, s), 6.1 (1H, s), 4.0 (1H, m), 3.7 (3H, s), 3.7 (1H, m), 2.8 (2H, tr), 2.3 (3H, s). EI-MS: M + =514. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(2-(4-methoxyphenyl)ethoxy)-3,3-diphenylpropionic Acid (I-585) 
       1 H-NMR (200 MHz, DMSO): 7.1-7.4 ppm (12H, m), 6.8 (3H, m), 6.1 (1H, s), 4.0 (1H, m), 3.7 (3H, s), 3.6 (1H, m), 2.8 (2H, r), 2.3 (6H, s). EI-MS: M + =498. 
     2-(4-Methoxy-6-methyl-2-pyrimidinyloxy)-3-(3-phenylpropoxy)-3,3-diphenylpropionic Acid (I-499) 
     Decomposition: 153-155° C. EI-MS: M + =498. 
     2-(4,6-Dimethyl-2-pyrimidinyloxy)-3-(3-phenylpropoxy)-3,3-diphenylpropionic Acid (I-500) 
     Decomposition: 148-151° C. EI-MS: M + =482. 
     The compounds listed in Table 1 can be prepared in a similar way or as described in the general part. 
     
       
         
           
               
               
             
               
                 TABLE I 
               
             
            
               
                   
               
               
                 [sic] 
                 I 
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 No. 
                 R 1   
                 R 4 , R 5   
                 Q 
                 R 6   
                 R 2   
                 R 3   
                 Z 
                 X 
                 Y 
                 W 
               
               
                   
               
               
                 I-1 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-2 
                 COOMe 
                 phenyl 
                 —CH 2 —CH 2 — 
                 phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-3 
                 COOH 
                 4-Br-phenyl 
                 —CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 OMe 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-4 
                 COOH 
                 phenyl 
                 —CH 2 —C(CH 3 ) 2 — 
                 phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-5 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-6 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-7 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-Cl-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-8 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-9 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-10 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-11 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-12 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-13 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 S 
               
               
                 I-14 
                 COOEt 
                 phenyl 
                 —CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-15 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-16 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-17 
                 COOMe 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-18 
                 COOEt 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-19 
                 tetrazole 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                   
                 [sic] 
               
               
                 I-20 
                 COOH 
                 phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-21 
                 COOH 
                 phenyl 
                 —CH 2 —C(CH 3 ) 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-22 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-23 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-24 
                 COOH 
                 4-Br-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 OMe 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-25 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-26 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-27 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-28 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-29 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-30 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 S 
               
               
                 I-31 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-32 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-33 
                 COOEt 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-34 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-35 
                 COOMe 
                 phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 N 
                 N 
                 CH 
                 S 
               
               
                 I-36 
                 COOH 
                 phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-37 
                 COOH 
                 4-Br-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-38 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-39 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-40 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-Me-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-41 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 SMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-42 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-43 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-44 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-45 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-46 
                 COOBzl 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-47 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-48 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-49 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-50 
                 COOH 
                 phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-51 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-Me-4-Et-phenyl 
                 OMe 
                 CF 3   
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-52 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-Me-4-Et-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-53 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 — 
                 4-Br-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-54 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-55 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-56 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Br-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-57 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-Br-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-58 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-Me-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-59 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-60 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-61 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 — 
                 3-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-62 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-Me-4-SMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-63 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-64 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-65 
                 tetrazole 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 OMe 
                 CH 
                 N 
                 N 
                 O 
               
               
                   
                 [sic] 
               
               
                 I-66 
                 COOH 
                 3-OMe-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-67 
                 COOH 
                 phenyl 
                 —O—CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-68 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-n-propoxy-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-69 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-n-propoxy-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-70 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-n-butoxy-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-71 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-n-butoxy-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-72 
                 COOH 
                 phenyl 
                 —O—CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 CH 
                 O 
               
               
                 I-73 
                 COOH 
                 phenyl 
                 —O—CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-74 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-75 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Me-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-76 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-Me-4-SMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-77 
                 COOH 
                 phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-78 
                 COOMe 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-79 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-80 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-81 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-(di-Me-amino)-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-82 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-83 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-84 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-85 
                 COOH 
                 3-OMe-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-86 
                 COOH 
                 phenyl 
                 —O—CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-87 
                 COOH 
                 phenyl 
                 —S—CH 2 —CH 2 — 
                 3-OMe-4-Cl-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-88 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-4-Cl-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-89 
                 COOH 
                 3-Me-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-4-Cl-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-90 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-91 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-92 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-93 
                 COOMe 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-94 
                 COOH 
                 2-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-F-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-95 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-96 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-97 
                 COOH 
                 2-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-98 
                 COOH 
                 phenyl 
                 —O—CH 2 —CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-99 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-100 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-101 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-(di-Me-amino)-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-102 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-(di-Me-amino)-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-103 
                 COOH 
                 2-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-104 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-105 
                 COOH 
                 phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 3-Cl-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-106 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Me-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-107 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Me-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-108 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 Me 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-109 
                 COOMe 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-110 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-111 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-iPr-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-112 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Me-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-113 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-114 
                 COOH 
                 phenyl 
                 —O—CH 2 —CH 2 — 
                 3,4-di-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-115 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-116 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-117 
                 COO- 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                   
                 i-Propyl 
               
               
                 I-118 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-119 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-(di-Me-amino)-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-120 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-(di-Me-amino)-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-121 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-122 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-123 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-124 
                 COOH 
                 phenyl 
                 —S—CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-125 
                 COOH 
                 phenyl 
                 —CH(OH)—CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-126 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-4-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-127 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-iPr-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-128 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-iPr-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-129 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-130 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-4-Me-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-131 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-132 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-133 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-134 
                 COOButyl 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-135 
                 COOH 
                 4-I-phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-136 
                 COOH 
                 phenyl 
                 —CH(OH)—CH 2 — 
                 4-Et-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-137 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-138 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-139 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-140 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-141 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-4-Et-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-142 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-143 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Cl-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-144 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-145 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-146 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-147 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-148 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-149 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-4-Et-phenyl 
                 OMe 
                 O—CH═CH—C 
                 N 
                 N 
                 O 
               
               
                 I-150 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-4-Et-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-151 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-152 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 OMe 
                 ethyl 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-153 
                 COOMe 
                 phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-154 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-155 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-156 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 Me 
                 Me 
                 CH 
                 N 
                 CH 
                 O 
               
               
                 I-157 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 Me 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-158 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-159 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Cl-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-160 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Cl-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-161 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-162 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-163 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-164 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-165 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-166 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 S 
               
               
                 I-167 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-168 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-169 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-Me-4-Cl-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-170 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-171 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-172 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-173 
                 COOH 
                 3-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-174 
                 COOH 
                 phenyl 
                 —O—CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-175 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Cl-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-176 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-177 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-Me-4-Cl-phenyl 
                 SMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-178 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-179 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-180 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-181 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-182 
                 COOBzl 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-183 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-Me-4-Cl-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-184 
                 COOH 
                 phenyl 
                 —CH(OH)—CH 2 — 
                 naphth-2-yl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-185 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-186 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-187 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-188 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-189 
                 COOH 
                 2-Me-phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-190 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-191 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-192 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-iPr-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-193 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-194 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-195 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-196 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-197 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 Me 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-198 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 1-Me-naphth-2-yl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-199 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 1-Me-naphth-2-yl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-200 
                 COOMe 
                 phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-201 
                 COOEt 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-202 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-203 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-204 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-205 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-206 
                 tetrazole 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                   
                 [sic] 
               
               
                 I-207 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-208 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-209 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OH-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-210 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OH-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-211 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-212 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-213 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-214 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-215 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-216 
                 COOH 
                 phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 4-OEt-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-217 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-218 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-219 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-220 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-221 
                 COOH 
                 phenyl 
                 —O—CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-222 
                 COOH 
                 4-Br-phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 CF 3   
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-223 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-224 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-225 
                 COOH 
                 4-I-phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-226 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 CH 
                 O 
               
               
                 I-227 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-228 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-229 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-230 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-231 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-232 
                 COOH 
                 phenyl 
                 —CH(OH)—CH 2 — 
                 3,5-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-233 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-4-Cl-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-234 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-235 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-236 
                 COOMe 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-237 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-238 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-239 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 3,4-di-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-240 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-241 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-Me-3-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-242 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-243 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-244 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-245 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 OMe 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-246 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-247 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 CH 
                 O 
               
               
                 I-248 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-249 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-250 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-251 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-252 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-253 
                 COOH 
                 phenyl 
                 —CH 2 —CH(CH 3 )— 
                 3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-254 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-255 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-256 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-257 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 OMe 
                 OMe 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-258 
                 tetrazole 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                   
                 [sic] 
               
               
                 I-259 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-260 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-261 
                 COOH 
                 phenyl 
                 —CH(2-OMe-phenyl)-CH 2 — 
                 2-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-262 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-4-Br-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-263 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-264 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-265 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-266 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-267 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-268 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-269 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-270 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-271 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-272 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-273 
                 COOH 
                 4-Br-phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-274 
                 COOH 
                 phenyl 
                 —CH(OH)—CH 2 — 
                 2-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-275 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-276 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-277 
                 COOH 
                 4-Cl-phenyl 
                 —CH(4-OMe-phenyl)—CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-278 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3-Me-4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-279 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-280 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-281 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-282 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-283 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-284 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-285 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-286 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-287 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-288 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-289 
                 COOH 
                 3,4-di-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-290 
                 COOEt 
                 4-Cl-phenyl 
                 —CH(OH)—CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-291 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-292 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-293 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-294 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-295 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 CH 
                 O 
               
               
                 I-296 
                 COOH 
                 4-Cl-phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-297 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-298 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-299 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-300 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-301 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-302 
                 COOH 
                 3,4-di-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-303 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-304 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-305 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3-Me-4-Et-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-306 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3-Me-4-Et-phenyl 
                 SMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-307 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-308 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-309 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-310 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-311 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Br-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-312 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-313 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-314 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-315 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-316 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Br-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-317 
                 COOH 
                 4-Cl-phenyl 
                 —CH(4-Br-phenyl)—CH 2 — 
                 4-Br-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-318 
                 COOH 
                 4-Cl-phenyl 
                 —CH(OH)—CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-319 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-320 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-321 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-322 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-323 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-324 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-325 
                 COOH 
                 4-Cl-phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 CH 
                 O 
               
               
                 I-326 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 S 
               
               
                 I-327 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-328 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-329 
                 COOH 
                 4-Cl-phenyl 
                 —O—CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-330 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-331 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-332 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 O—CH═CH—C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-333 
                 COOH 
                 4-Cl-phenyl 
                 —CH(OH)—CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-334 
                 COOH 
                 4-Cl-phenyl 
                 —CH(4-SMe-phenyl)—CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-335 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-336 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-337 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-338 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-339 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-340 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-341 
                 COOH 
                 3,4-di-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-342 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-343 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-344 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-345 
                 COOH 
                 4-Cl-phenyl 
                 —CH(4-Me-phenyl)—CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-346 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-347 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-348 
                 COOMe 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 CH 
                 O 
               
               
                 I-349 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-350 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-351 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Cl-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-352 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-353 
                 COOH 
                 4-Cl-phenyl 
                 —CH(OH)—CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-354 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-355 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-356 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-357 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 OMe 
                 OMe 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-358 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-359 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-360 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-361 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 CH 
                 O 
               
               
                 I-362 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-363 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-364 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-365 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-366 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-367 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Cl-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-368 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Cl-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-369 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 SMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-370 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-371 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-372 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-373 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-374 
                 COOH 
                 4-Cl-phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-375 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-376 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 1-Me-naphth-2-yl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-377 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-378 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-379 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-380 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-381 
                 COOH 
                 4-Cl-phenyl 
                 —CH(4-OEt-phenyl)—CH 2 — 
                 4-OEt-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-382 
                 COOH 
                 4-Cl-phenyl 
                 —CH(OH)—CH 2 — 
                 4-OEt-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-383 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Cl-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-384 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Cl-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-385 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-386 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-387 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-388 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-389 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-390 
                 COOH 
                 3,4-di-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-391 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-4-Cl-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-392 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-393 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-394 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-395 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-396 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-397 
                 COOH 
                 4-Cl-phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 3-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-398 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-399 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-400 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Cl-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-401 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-402 
                 COOH 
                 4-Cl-phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-403 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-404 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-405 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-406 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3-Me-4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-407 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-408 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-409 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3-Me-4-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-410 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-411 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-412 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 CH 
                 N 
                 O 
               
               
                 I-413 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-414 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-415 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-416 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-417 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 SMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-418 
                 COOMe 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-419 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-420 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-421 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 S 
               
               
                 I-422 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 CH 
                 N 
                 O 
               
               
                 I-423 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-424 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-425 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH═CH—C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-426 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-427 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-428 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-429 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-430 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 CF 3   
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-431 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-432 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-433 
                 COOH 
                 4-Et-phenyl 
                 —CH(3-OMe-phenyl)—CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-434 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-435 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-436 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-437 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-438 
                 COOH 
                 4-Et-phenyl 
                 —CH(OH)—CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-439 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-440 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-441 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 CH 
                 O 
               
               
                 I-442 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-443 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-444 
                 COOH 
                 4-Et-phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-445 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-446 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-447 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 —CH 2 —- 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-448 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-449 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-450 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-451 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-452 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-453 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-454 
                 COOBzl 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-455 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 CH 
                 N 
                 O 
               
               
                 I-456 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-457 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-458 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-459 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-460 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-461 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 CH 
                 N 
                 O 
               
               
                 I-462 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-463 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-464 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-465 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-466 
                 COOH 
                 4-CF 3 -phenyl 
                 —C(CH 3 ) 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-467 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-468 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-469 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 CH 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-470 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-471 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-472 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-473 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-474 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-475 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-476 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-477 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-478 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 2-Me-3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-479 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-480 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-481 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 OMe 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-482 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-483 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-484 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-485 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 3-Me-4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-486 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-487 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 2-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-488 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-489 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-490 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-491 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-492 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 cyclohexyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-493 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-494 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-495 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-496 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-497 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-498 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-499 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-500 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-501 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-502 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 CH 
                 N 
                 O 
               
               
                 I-503 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-504 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-505 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-506 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-507 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-508 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 cyclopentyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-509 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-510 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-511 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-512 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-513 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-514 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-515 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-516 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-517 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-518 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-519 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 CH 
                 N 
                 O 
               
               
                 I-520 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-521 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-522 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-523 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-524 
                 COOMe 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-525 
                 COOMe 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-526 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-527 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-528 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-529 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-530 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-531 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-532 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-533 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-F-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-534 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-535 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-536 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-537 
                 COOH 
                 4-Br-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-538 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-539 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-540 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-541 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-542 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-543 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-544 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-545 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-546 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-547 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-548 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-549 
                 COOMe 
                 phenyl 
                 —CH(phenyl)—CH 2 —CH 2 — 
                 phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-550 
                 COOH 
                 4-F-phenyl 
                 —CH(phenyl)—CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-551 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-552 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-553 
                 COOH 
                 phenyl 
                 —CH(phenyl)—CH 2 —CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 CH 
                 CH 
                 N 
                 O 
               
               
                 I-554 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-555 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-556 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-557 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-558 
                 COOH 
                 phenyl 
                 —CH(phenyl)—CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-559 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-560 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-561 
                 COOH 
                 phenyl 
                 —CH(phenyl)—CH 2 —CH 2 — 
                 phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-562 
                 COOMe 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-563 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-564 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-565 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-566 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-567 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-568 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-569 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-570 
                 COOH 
                 phenyl 
                 —CH(phenyl)—CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-571 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-572 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 CH 
                 O 
               
               
                 I-573 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-574 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-575 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-576 
                 COOH 
                 4-CF 3 -phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-577 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-578 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-Cl-4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-579 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-580 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-581 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-582 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-583 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-584 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-585 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-586 
                 COOH 
                 phenyl 
                 —CH(phenyl)—CH 2 —CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-587 
                 COOH 
                 phenyl 
                 —CH(phenyl)—CH 2 —CH 2 — 
                 phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-588 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-589 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-590 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-591 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-592 
                 COOH 
                 4- CF 3 -phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-593 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-594 
                 COOH 
                 phenyl 
                 —CH(OH)—CH(OH)—CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-595 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-596 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-597 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-598 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 CH 
                 N 
                 O 
               
               
                 I-599 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-600 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-601 
                 COOEt 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-602 
                 COOH 
                 phenyl 
                 —CH(phenyl)—CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-603 
                 COOH 
                 phenyl 
                 —CH(phenyl)—CH 2 —CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-604 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-605 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-606 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 S 
               
               
                 I-607 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-608 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-609 
                 COOH 
                 4-Br-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-610 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-611 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-612 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-613 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-614 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 N 
                 CH 
                 N 
                 O 
               
               
                 I-615 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-616 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-617 
                 COOH 
                 phenyl 
                 —CH(OH)—CH(OH)—CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-618 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-619 
                 COOH 
                 phenyl 
                 —CH(phenyl)—CH 2 —CH 2 — 
                 phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-620 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 CH 
                 O 
               
               
                 I-621 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 OMe 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-622 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-623 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-624 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-625 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-626 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-627 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-628 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-629 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-630 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-631 
                 COOH 
                 phenyl 
                 —CH(OH)—CH(OH)—CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-632 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-633 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-634 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-635 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-636 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-637 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-638 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4,5-tri-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-639 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-640 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-641 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-642 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-643 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-644 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-645 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-646 
                 COOH 
                 4-Me-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-647 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-648 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-649 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-650 
                 COOMe 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-651 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-652 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-653 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Et-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-654 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-655 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-Cl-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-656 
                 COOH 
                 4-F-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-657 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-658 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-659 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-660 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-661 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 S 
               
               
                 I-662 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-663 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-664 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 ethyl 
                 Me 
                 N 
                 CH 
                 N 
                 O 
               
               
                 I-665 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-666 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-667 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-668 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2,3-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-669 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-670 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-671 
                 COOH 
                 3,4-di-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-672 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-673 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-674 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-675 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-676 
                 COOH 
                 3,4-di-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-677 
                 COOH 
                 3,4-di-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-678 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-679 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-680 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-681 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-682 
                 COOH 
                 3,4-di-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-683 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-684 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-685 
                 COOH 
                 phenyl 
                 —CH(OH)—CH(OH)—CH 2 — 
                 2-Cl-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-686 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Cl-phenyl 
                 Me 
                 Me 
                 CH 
                 CH 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-687 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-688 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-689 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-690 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-691 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Cl-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 S 
               
               
                 I-692 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-693 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-694 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-695 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-696 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Cl-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-697 
                 COOMe 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 2-Cl-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-698 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,5-di-OMe-4-Cl-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-699 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-700 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-701 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-702 
                 COOH 
                 4-Et-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-703 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,5-di-OMe-4-Cl-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-704 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-705 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-706 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 S 
               
               
                 I-707 
                 COOMe 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-708 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OEt, 3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-709 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-iPr-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-710 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-711 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-712 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 CH 
                 N 
                 O 
               
               
                 I-713 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-714 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-715 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-716 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-717 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 3-Cl-4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-718 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 3-Cl-4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-719 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-720 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-721 
                 COOH 
                 4-F-phenyl 
                 —CH═CH—CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-722 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-723 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OEt, 3-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-724 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-725 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-726 
                 COOMe 
                 phenyl 
                 —CH═CH—CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-727 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 3,4-di-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 CH 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-728 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-729 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-730 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-731 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-732 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-733 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 cyclohexyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-734 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 OMe 
                 CH 2 —CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-735 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-736 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-737 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-738 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 cyclohexyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-739 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 4-Me-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 S 
               
               
                 I-740 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-741 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 3,4-methylenedioxyphenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-742 
                 COOH 
                 phenyl 
                 —C(phenyl)═CH—CH 2 — 
                 phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-743 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-744 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,5-di-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-745 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-746 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-Cl-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-747 
                 COOH 
                 4-F-phenyl 
                 —CH═CH—CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-748 
                 COOH 
                 4-F-phenyl 
                 —CH═CH—CH 2 — 
                 phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-749 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-750 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-751 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-SMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-752 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 — 
                 4-OEt-3-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-753 
                 COOH 
                 phenyl 
                 —C(phenyl)═CH—CH 2 — 
                 phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-754 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-755 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 naphth-2-yl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
               
                 I-756 
                 COOH 
                 phenyl 
                 —CH═CH—CH 2 — 
                 phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 S 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-757 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-758 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 l-759 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 CF 3   
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-760 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 OMe 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-761 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                 I-762 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 — 
                 4-OMe-phenyl 
                 Me 
                 Me 
                 N 
                 N 
                 N 
                 O 
               
               
                 I-763 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 ethyl 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 I-764 
                 COOH 
                 4-Cl-phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 3,4-di-OMe-phenyl 
                 OMe 
                 O—CH 2 —CH 2 —C 
                 N 
                 N 
                 O 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 I-765 
                 COOH 
                 phenyl 
                 —CH 2 —CH 2 —CH 2 — 
                 4-OEt-phenyl 
                 Me 
                 Me 
                 CH 
                 N 
                 N 
                 O 
               
               
                   
               
            
           
         
       
     
     Example 16 
     Receptor binding data were measured by the binding assay described above for the compounds listed hereinafter. 
     The results are shown in Table 2. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Receptor binding data (K i  values) 
               
            
           
           
               
               
               
               
            
               
                   
                 Compound 
                 ET A  [nM/l] [sic] 
                 ET B  [nM/l] [sic] 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 I-116 
                 35 
                 35 
               
               
                   
                 I-140 
                 575 
                 460 
               
               
                   
                 I-146 
                 4 
                 29 
               
               
                   
                 I-321 
                 340 
                 290 
               
               
                   
                 I-355 
                 132 
                 82 
               
               
                   
                 I-370 
                 11 
                 54 
               
               
                   
                 I-445 
                 3.5 
                 7.2 
               
               
                   
                 I-445 (S) enantiomer 
                 1.3 
                 4.1 
               
               
                   
                 I-445 (R) enantiomer 
                 65 
                 140 
               
               
                   
                 I-482 
                 2 
                 14 
               
               
                   
                 I-499 
                 31 
                 135 
               
               
                   
                 I-585 
                 6 
                 23 
               
               
                   
                 I-593 
                 300 
                 160 
               
               
                   
                 I-622 
                 3 
                 23 
               
               
                   
                 I-635 
                 210 
                 126 
               
               
                   
                 I-672 
                 60 
                 185 
               
               
                   
                 I-699 
                 230 
                 130 
               
               
                   
                 I-713 
                 20 
                 96