CALCILYTIC COMPOUNDS

Abstract: Novel arylalkylamino compounds exhibiting calcilytic properties are provided.

Description: CALCILYTIC COMPOUNDS The present invention relates to novel arylalkylamine calcilytic compounds, pharmaceutical compositions containing these compounds and their use as calcium receptor antagonists. In mammals, extracellular Ca^ + is under rigid homeostatic control and regulates various processes such as blood clotting, nerve and muscle excitability, and proper bone formation. Extracellular Ca^ " * " inhibits the secretion of parathyroid hormone ("PTH") from parathyroid cells, inhibits bone resorption by osteoclasts, and stimulates secretion of calcitonin from C-cells. Calcium receptor proteins enable certain specialized cells to respond to changes in extracellular Csτ + concentration. PTH is the principal endocrine factor regulating Ca^ + homeostasis in the blood and extracellular fluids. PTH, by acting on bone and kidney cells, increases the level of Ca^+ in the blood. This increase in extracellular Ca^ + acts as a negative feedback signal, depressing PTH secretion. The reciprocal relationship between extracellular Ca^ + and PTH secretion forms an important mechanism maintaining bodily Ca^ + homeostasis. Extracellular Cd2 + acts directly on parathyroid cells to regulate PTH secretion. The existence of a parathyroid cell surface protein which detects changes in extracellular Ca^+ has been confirmed. See Brown et al., Nature 366:574, 1993. In parathyroid cells, this protein, the calcium receptor, acts as a receptor for extracellular Ca^ " * " , detects changes in the ion concentration of extracellular Ca^ + , and initiates a functional cellular response, PTH secretion. Extracellular Ca? + influences various cell functions, reviewed in Nemeth et αl., Cell Calcium 77:319, 1990. For example, extracellular Ca^ + plays a role in parafollicular (C-cells) and parathyroid cells. See Nemeth, Cell Calcium 77:323, 1990. The role of extracellular Ca^+ on bone osteoclasts has also been studied. See Zaidi, Bioscience Reports 70:493, 1990. Various compounds are known to mimic the effect of extra-cellular Ca^ + on a calcium receptor. Calcilytics are compounds able to inhibit calcium receptor activity, thereby causing a decrease in one or more calcium receptor activities evoked by extracellular Ca^+. Calcilytics are useful as lead molecules in the discovery, development, design, modification and/or construction of useful calcium modulators which are active at Ca^ + receptors. Such calcilytics are useful in the treatment of various disease states characterized by abnormal levels of one or more components, e.g.. polypeptides such as hormones, enzymes or growth factors, the expression and/or secretion of which is regulated or affected by activity at one or more Ca^ + receptors. Target diseases or disorders for calcilytic compounds include diseases involving abnormal bone and mineral homeostasis. Abnormal calcium homeostasis is characterized by one or more of the following activities: an abnormal increase or decrease in serum calcium; an abnormal increase or decrease in urinary excretion of calcium; an abnormal increase or decrease in bone calcium levels (for example, as assessed by bone mineral density measurements); an abnormal absorption of dietary calcium; an abnormal increase or decrease in the production and/or release of messengers which affect serum calcium levels such as PTH and calcitonin; and an abnormal change in the response elicited by messengers which affect serum calcium levels. Thus, calcium receptor antagonists offer a unique approach towards the pharmacotherapy of diseases associated with abnormal bone or mineral homeostasis, such as hypoparathyroidism, osteosarcoma, periodontal disease, fracture healing, osteoarthritis, rheumatoid arthritis, Paget's disease, humoral hypercalcemia associated with malignancy and fracture healing, and osteoporosis. SUMMARY OF THE INVENTION The present invention comprises arylalkylamine derivatives represented by Formula (I) and their use as calcium receptor antagonists which are useful in the treatment of a variety of diseases associated with abnormal bone or mineral homeostasis, including but not limited to hypoparathyroidism, osteosarcoma, periodontal disease, fracture healing, osteoarthritis, rheumatoid arthritis, Paget's disease, humoral hypercalcemia associated with malignancy and fracture healing, and osteoporosis. The present compounds maintain calcium receptor activity and selectivity while having minimal affinity for the beta adrenergic receptor. The present invention further provides a method for antagonizing calcium receptors in an animal, including humans, which comprises administering to an animal in need thereof an effective amount of a compound of Formula (I). DETAILED DESCRIPTION OF THE INVENTION The compounds of the present invention are represented by structural Formula (I): Formula (I) wherein: Y j is a covalent bond, alkylene or alkenylene of up to 4 carbon atoms, unsubstituted or substituted by Cj_4 alkyl; Y2 is methylene, unsubstituted or substituted by C 1 .4 alkyl or CF3. Z is selected from the group consisting of a covalent bond, O, S, NH, N-Cj_4 alkyl, 0(CH2) n> (CH 2 ) n O, NR'" C=0 and C=ONR"', where R"' is C μ 4 alkyl and n is an integer from 1 to 3, R3 and R4 are, independently, methyl or ethyl, or, together, form cyclopropyl; R5 is phenyl or naphthyl, unsubstituted or substituted with one or more substituents selected from the group consisting of OH, Cj^alkyl, halo, CH(CH3)2, halo C . alkyl, C _4 alkoxy, C3-6 cycloalkyl, OSO2R'\ CN, NO2, OCF3, CF3, and CH2CF3, wherein R ,v represents C1-.4 alkyl or C3-.6 cycloalkyl; G is a covalent bond or C-Rg wherein Rg is H, OH or O (forming a carbonyl moiety); R7 is H, OH, or O-C1-.4 alkyl; Rg is H or C1.4 alkyl; or R7 and Rg together form a carbonyl moiety; the -A-B- moiety is represented by CH2CH2, a covalent bond, -CH=CH- or -CΞC-; and X is selected from the group consisting of sub-formulae (Ia), (lb), (Ic) (Id) and (Ie) hereinbelow: (la) R (Ic) (Id) (le) wherein : in sub-formula (Ia): W is selected from the group consisting of R , SO2R1, C(O)R j , 802^^', C(0)NRιRι', C(0)OR j SO3Ri', wherein R\ and Rj' are independently selected from the group consisting of hydrogen, C1-.4 alkyl, C3_g cycloalkyl, C2-5 alkenyl, C2.5 alkynyl, heterocycloalkyl aryl and aryl C j _4 alkyl; or Rγ and Rj' together form a 3 to 7 membered optionally substituted heterocyclic ring; wherein any substituents are selected from the group consisting of CN, aryl, CO2R, C0 2 NHR, OH, OR, NH 2 , halo, CF3, OCF3 and N0 2 ; wherein R represents Cμ4 alkyl, or C3_g cycloalkyl; X ] is selected from the group consisting of CN, N0 2 , CI, F, Br, I, H, R', OR', CF3, OCF3 and OSO2R', wherein R' represents C1-4 alkyl, or C3_g cycloalkyl; X2 , X3 and X4 are, independently, selected from the group consisting of CN, NO2, CI, F, Br, I, H, R", OR", CF3, OCF3 and OS0 2 R", wherein R" is C^ alkyl or haloalkyl; or Xj and X2 together form an aryl or heteroaryl ring, substituted or unsubstituted; wherein the heteroatom is selected from N, S and O; and any substituents are selected from the group consisting of halo, C1.4 alkyl, OCF3, CF3, OMe, CN, OSO2R' and NO2; or X3 and X4 independently represent C(0)R j ; provided that when there are multiple halo substitutions in the haloalkyl, halo represents F; also provided that either X\ or X3 is hydrogen; and R2 is selected from the group consisting of hydrogen, C j .4 alkyl, C3.-6 cycloalkyl, C2-.5 alkenyl, C2.5 alkynyl, heterocycloalkyl aryl and aryl-C j --4 alkyl; in sub-formula (lb): X is selected from the group consisting of CN, N0 2 , CI, F, Br, I, H, R, OR, CF3, OCF3 and OSO2R, wherein R represents C1-.4 alkyl, or C3.6 cycloalkyl; X2", X3" and X4" are, independently, selected from the group consisting of CN, NO2, CI, F, Br, I, H, R', OR', CF3, OCF3 and OS0 2 R', wherein R" is Cι_ 4 alkyl or haloalkyl; provided that when there are multiple halo substitutions in the haloalkyl, halo represents F, or X\" and X2" together form an aryl or heteroaryl ring, substituted or unsubstituted; wherein the heteroatom is selected from N, S and O and any substituents are selected from the group consisting of halo, C1.4 alkyl, OCF3, CF 3 , OMe, CN, OS02-CJ.4 alkyl, OS0 2 -C 3 . 6 cycloalkyl and N0 2 ; or X3" and X4" independently represent C(0)Rj; provided that either X\" or X3" is hydrogen; and R " and R2" are, independently, selected from the group consisting of hydrogen, C j .4 alkyl, C3-.6 cycloalkyl, C2-5 alkenyl, C2-5 alkynyl, heterocycloalkyl and aryl; or R j " and R2" together form a 3 to 7 membered optionally substituted heterocyclic ring, optionally containing an additional heteroatom selected from O, S and N; wherein any substituents are selected from the group consisting of CN, aryl, CO 2 R", C0 2 NHR", OH, OR", NH 2 , halo, CF 3 , OCF3 and NO2; wherein R" represents Cj_4 alkyl, or C3_g cycloalkyl; in sub-formula (Ic): Xj'" is selected from the group consisting of CN, NO2, CI, F, Br, I, H, R, OR, CF3, OCF3 and OSO2R, wherein R represents C1-.4 alkyl, or C3_g cycloalkyl; X2'", X3'", and X4'" are, independently, selected from the group consisting of CN, NO2, CI, F, Br, I, H, R', OR', CF3, OCF3 and OS0 2 R', wherein R' is C1-.4 alkyl or haloalkyl; provided that when there are multiple halo substitutions in the haloalkyl, halo represents F; or X j '" and X2'" together form an aryl or heteroaryl ring, substituted or unsubstituted; wherein the heteroatom is selected from N, S and O and the substituents are selected from the group consisting of halo, C\_ 4 alkyl, OCF3, CF3, OMe, CN, OSO2-C1-4 alkyl, OS0 2 -C 3 . 6 cycloalkyl and N0 2 ; or X 3 '" and X4 '" independently represent C(0)R] ; provided that either Xj'" or X3"' represents hydrogen; and Rl"' and R2'" are, independently, selected from the group consisting of hydrogen, C 1 .4 alkyl, C3.6 cycloalkyl, C2-5 alkenyl, C2.5 alkynyl, heterocycloalkyl and aryl; or Rι"'and R2'" together form a 3 to 7 membered optionally substituted heterocyclic ring, optionally containing an additional heteroatom selected from O, S and N; wherein the substituents are selected from the group consisting of CN, aryl, C0 2 R", C0 2 NHR", OH, OR", NH 2 , halo, CF 3 , OCF3 pand NO2; wherem R" represents Cj_4 alkyl, or C3.6 cycloalkyl; in sub-formula (Id): D is selected from the group consisting of CN, NO2, CI, F, Br, I, R, OR, SR, CF3, OCF3 and OSO2R, wherein R represents C1-.4 alkyl, C3.6 cycloalkyl, or Cμjo ar yl or heteroaryl wherein the heteroatom is selected from N, S and O and substituents are selected from the group consisting of halo, C --4 alkyl, OCF3, CF3, OMe, CN, OSO2-C -.4 alkyl, OSO2-C3.6 cycloalkyl and N0 2 ; n is the integer 1 or 2; each E is independently C or N, provided that no more than two E moieties are N; further provided that when n is 2, each E is C; a and b are optionally present bonds; Rj ιv is selected from the group consisting of (CH 2 ) n C02R\ (CH 2 ) n C0 2 H, (CH 2 ) n CONR'2, (CH 2 )nCH 2 OR', OR', SR\ CN, N0 2 , CI, F, Br, I, CF3, OCF3, OSO 2 R\ R' and H; wherein R' represents C 1 .4 alkyl, or C3.6 cycloalkyl; or Ri IV is O, forming a ketone such that Y Ri IV represents -C=O; R 2 ' v is selected from the group consisting of hydrogen, CN, NO2 CI, F, Br, I, H, R", OR", CF3, OCF3, and OSO2R"; wherein R" represents C1-.4 alkyl, or C3.6 cycloalkyl. Y is selected from the group consisting of C, CH, O, N and S; provided that when Y is S, Ri 1V is O; further provided that when Y is O, R ιv is not present; X' is selected from the group consisting of CH2, NH, O and S; and attachment is at the carbon atom marked 3; in sub-formula (Ie): X j "" is selected from the group consisting of CN, NO 2 , CI, F, Br, I, H, R', OR', CF3, OCF3 and OSO2R', wherein R' represents C\.Λ alkyl, or C3-.6 cycloalkyl; X2"", X3"" and X4"" are, independently, selected from the group consisting of CN, NO2, CI, F, Br, I, H, R", OR", CF 3 , OCF3 and OS0 2 R", wherein R" is C^ alkyl or haloalkyl; or Xi"" and X2"" together form an aryl or heteroaryl ring, substituted or unsubstituted; wherein the heteroatom is selected from N, S and O; and any substituents are selected from the group consisting of halo, Cι_ 4 alkyl, OCF3, CF 3 , OMe, CN, OSO 2 R' and N0 2 ; or X 3 "" and X 4 "" independently represent C(0)Rι; provided that when there are multiple halo substitutions in the haloalkyl, halo represents F; also provided that either Xi"" or X3"" is hydrogen; and R9 is selected from the group consisting of 0-CH2-alkyl, O-CH2-aryl and O-aryl. Preferably, the compounds of the present invention are represented by Formula (II) hereinbelow: Formula (II) wherein: R9 is selected from the group consisting of H, OH, OCH3, CI, F, CH3, CH2CH3 and CH(CH 3 ) 2 ; Rl Q is selected from the group consisting of H, CI, F, CF3 and CH3; or R9 and RIQ form an optionally substituted fused phenyl ring; and Rl 1 is selected from methyl, H or F. More preferably, Rg is H, or OH. More preferably, R9 is selected from the group consisting of OCH3, CI, F, CH3, CH2CH3 and CH(CH3)2- More preferably, RIQ is selected from the group consisting of H, CI, F, and CH3; or R9 and RIQ form a fused aryl ring. More preferably, R is H or F. More preferably, the -A-B- moiety represents -CH=CH-. More preferably still, Rg is H. More preferably still, R9 is selected from the group consisting of OCH3, CI, CH3, CH 2 CH 3 , and CH(CH 3 ) 2 . More preferably still, RIQ is H; Ri 1 is H; or R9 and RIQ together form a fused aryl ring. Most preferably, R 9 is OCH3 or CH 2 CH 3 . In sub-formula (Ia), preferably, Xi is selected from the group consisting of CN, NO2, CI, F, Br, I and H. Preferably, X2, X3 and X4 are, independently, selected from the group consisting of CI, F, Br, I and H. Preferably, R\, Ri'and R2 are, independently, selected from the group consisting of Cj_4 alkyl, C3.6 cycloalkyl, heterocycloalkyl, aryl or arylC^alkyl. In sub-formula (Ia), more preferably, R\, Ri'and R2 are, independently, H, alkyl, or aryl. More preferably, X is selected from the group consisting of CN, NO2, CI, F, Br, I and H. More preferably, X , X3 and X4 are, independently, selected from the group consisting of CI, F, Br, I and H. . In sub-formula (Ia), more preferably still, R , Ri'and R2 are, independently, C1.4 alkyl, or aryl. More preferably still, X is CN, NO2, or CI. More preferably still, X2 is CI, or H. More preferably still, X3 and X4 are H. In sub-formula (Ia), most preferably, Xi is CN, or NO2. Most preferably, X2 is CI. In sub-formula (lb), preferably, Xi" is selected from the group consisting of CN, NO2, CI, F, Br, I and H. Preferably, X2", X3" and X4" are, independently, selected from the group consisting of CI, F, Br, I and H. Preferably, Ri" and R2" are, independently, selected from the group consisting of C .4 alkyl, C3_g cycloalkyl, heterocycloalkyl or aryl; or Ri" and R2" together form an optionally substituted 3-7 membered ring. In sub-formula (lb), more preferably, R " and R2" are, independently, H, C \,A alkyl, or aryl; or Ri" and R2" together form an optionally substituted 4-7 membered ring. More preferred substituents when the heteroatom is N include acyl, C\.A alkyl, and aryl. More preferably, Xi" is selected from the group consisting of CN, NO2, CI, F, Br, I and H. More preferably, X2" is selected from the group consisting of CI, F, Br, I and H. In sub-formula (lb), more preferably still, Ri'and R2" are, independently, C\_A alkyl, or aryl; or Ri " and R2" together form a 4-7 membered ring as described hereinabove. More preferably still, Xi" is CN, NO2, or CI. More preferably still, X " is CI, or H. In sub-formula (lb), most preferably, Ri" and R2" together form a 4-7 membered ring as described hereinabove. Most preferably, X " is CN, or N02- Most preferably, X2" is CI. In sub-formula (Ic), preferably, Xi'" is selected from the group consisting of CN, NO2, CI, F, Br, I and H. Preferably, X2'", X3'" and X4'" are, independently, selected from the group consisting of CI, F, Br, I and H. Preferably, Ri'" and R2'"are, independently, selected from the group consisting of C 1.4 alkyl, C3_g cycloalkyl, heterocycloalkyl or aryl; or Ri'" and R2'" together form an optionally substituted 3-7 membered ring. In sub-formula (Ic), more preferably, Ri'", and R2'" are, independently, H, C1--4 alkyl, or aryl; or Ri'" and R2'" together form an optionally substituted 4-7 membered ring, optionally containing a heteroatom selected from O, S, and N. More preferred substituents when the heteroatom is N include acyl, C \.A alkyl, and aryl. More preferably, Xi"' is selected from the group consisting of CN, N0 2 , CI, F, Br, I and H. More preferably, X 2 '", X3'" and X 4 * " are, independently, selected from the group consisting of CI, F, Br, I and H In sub-formula (Ic), more preferably still, Ri'and R2'" are, independently, C\.A alkyl, or aryl; or R '" and R2'" together form a 4-7 membered ring as described hereinabove. More preferably still, Xi'" is CN, NO2, or CI. More preferably still, X2"' is Cl or H. More preferably still, X 3 '" and X 4 '" are H. In sub-formula (Ic), most preferably, Ri'" and R2'" together form a 4-7 membered ring as described hereinabove. Most preferably, Xi'" is CN or NO2. Most preferably, X2 '" is CI. In sub-formula (Id), preferably, D is selected from the group consisting of Br, I, CI and F, R, OR, SR, and H. Preferably, Ri ιv is selected from the group consisting of (CH2) n Cθ2R', (CH 2 ) n C0 2 H, (CH 2 ) n CONR' 2 , (CH 2 ) n CH2OR', OR', SR', R' and H; wherein R' is Cμ alkyl or C3.6 cycloalkyl; or Ri ιv is O, forming a ketone such that Y R ιv represents -C=0. Preferably, R2 IV is selected from the group consisting of hydrogen, CN, NO2 CI, Br, F and I; In sub-formula (Id), more preferably, D is H. More preferably, each E is C. More preferably, X' is CH2, O, or NH. More preferably, Y is C or N. More preferably, Ri IV is CH2CO2R', SR', or O, forming a ketone. More preferably, R2 IV is selected from the group consisting of CN, NO2, CI, and H. In Formula (Id), more preferably still, X' is CH2 or O. More preferably still, R ιv is CH 2 C0 2 R' or SR'. More preferably still, R 2 ' v is H, CN, or N0 2 . In Formula (Id), most preferably, X' is CH2. Most preferably, Y is C. Most preferably, R 2 ' v is CN or N0 2 . As used herein, "alkyl" refers to an optionally substituted hydrocarbon group joined by single carbon-carbon bonds. The alkyl hydrocarbon group may be linear, branched or cyclic, saturated or unsaturated cyclic, saturated or unsaturated. The substituents are selected from aryl, F, CI, Br, I, N(R)2, SR and OR, wherein R represents C _4 alkyl or C3-6 cycloalkyl, unless otherwise indicated. Preferably, no more than three substituents are present. Preferably, the alkyl group is unsubstituted. Preferably, the alkyl group is linear. Preferably, the alkyl group is saturated. Preferably, the alkyl group is unsubstituted. As used herein "cycloalkyl" refers to optionally substituted 3-7 membered carbocyclic rings wherein any substituents are selected from the group consisting of, F, CI, Br, I, N(R)2, SR and OR, wherein R represents C 1.4 alkyl or C3_g cycloalkyl, unless otherwise indicated. As used herein "heterocycloalkyl" refers to optionally substituted 4, 5, 6 or 7 membered heterocyclic rings containing 1 to 2 heteroatoms selected from N, O, and S. As used herein, "aryl" refers to an optionally substituted aromatic group with at least one ring having a conjugated pi-electron system, containing up to two conjugated or fused ring systems. Aryl includes carbocyclic aryl, and biaryl groups, all of which may be optionally substituted. Preferred aryl include phenyl and naphthyl. More preferred aryl include phenyl. Preferred substituents are selected from the group consisting of halo, C \.A alkyl, OCF3 CF3 OMe, CN, OSO2 R and N02, wherein R represents C\.A alkyl or C3.6 cycloalkyl. As used herein, "acyl" refers to C 1.4 alkylcarbonyl. As used herein, "alkenyl" refers to an optionally substituted hydrocarbon group containing at least one carbon-carbon double bond and containing up to 5 carbon atoms joined together. The alkenyl hydrocarbon chain may be straight, branched or cyclic. Any substituents are selected from the group consisting of halo, C1.4 alkyl, OCF3, CF3, OMe, CN, OSO2 R and NOj wherein R represents C1.4 alkyl or C3.6 cycloalkyl. Preferably, the alkenyl group is unsubstituted. As used herein, "alkynyl" refers to an optionally substituted hydrocarbon group containing at least one carbon-carbon triple bond between the carbon atoms and containing up to 5 carbon atoms joined together. The alkynyl hydrocarbon group may be straight-chained, branched or cyclic. Any substituents are selected from the group consisting of halo, C\.A alkyl, OCF3, CF3, OMe, CN, OSO2 R and NO2, wherein R represents C1-.4 alkyl or C3.6 cycloalkyl. Preferably, the alkynyl group is unsubstituted. The compounds of the present invention may contain one or more asymmetric carbon atoms and may exist in racemic and optically active forms. All of these compounds and diastereomers are contemplated to be within the scope of the present invention. Preferred compounds of the present invention include the following compounds: (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (4-methoxypheny l)ethy lamino] -propan-2-ol ; (R)- 3-[2-cyano-4-[N-[4-methylphenylsulfonyl]amino]phenoxy]-l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (4-methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[ N-methylsulfonylamino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[ N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (2-naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (benzyloxy)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-3- phenylpropylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-4- phenylbutylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-ethylcarbonyl]phenoxy]-l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N'-morpholino]ureido]phenoxy]-l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N'-morpholino]ureido]phenoxy]-l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N'-morpholino]ureido]phenoxy]- l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-t2-cyano-4-[N-methyl-N'-morpholino]ureido]phenoxy]- 1-[ 1 , 1 -dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- propylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- piperidinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- morpholiny lcarbony l)phenoxy ] -propan-2-ol ; (R)- 1 -[ 1 , l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2,3-dichloro-4-(N- mo holinylcarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[2,3-dichloro-4-(N- morpholinylcarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2,3-dichloro-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(2-naphthyl)ethy lamino]-3- [2,3-dichloro-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxypheny l)ethylamino]-3- [2-cyano, 3-chloro-4-(N- morpholinylcarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano, 3-chloro-4-(N- morpholinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano, 3-chloro-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano, 3-chloro-4-(N,N- dipropy laminocarbonyl)phenoxy ]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- pyrrolidinylcarbonyl)phenoxy]-propan-2-ol ; (R)-l -[ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- piperazinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthyl)ethy lamino]-3- [2-cyano-4-(N-piperidinylcarbony l)phenoxy ]- propan-2-ol; (R)- 1-[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N- morpholinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N-piperazinylcarbony l)phenoxy]- propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthy l)ethylamino]-3-[2-cyano-4-(N- pyrrolidinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-3-(phenyl)propylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethyl-4-(phenyl)butylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-3-(phenoxy)propylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; and (R)-l-[l,l-dimethyl-2-(oxybenzyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol. N-[3-(3-chloro-2-cyano-4-dipropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1-dimethylethylamine; N-[3-(2,3-dichloro-4-dipropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(2,3-dichlorophenyl)- 1 , 1 -dimethylethylamine; N-[3'-(3-chloro-2-cyano-4-dimethylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-morpholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)- 1 , 1-dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-thiomoφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2- naphthy 1)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-thiomoφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)-l,l-dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(2'-cyanoeth-l-yl)-cyclopropylsulfamoyl]phenoxy-2(R)- hydroxypropy l]-2-(4- methoxyphen l)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(2'-cyanoeth-l-yl)-cyclopropylsulfamoyl]phenoxy-2(R)- hydroxypropyl]-2-(2-napthyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(benzyl-cyclopropyl)sulfamoyl]phenoxy-2(R)-hydroxypropyl]-2-(2- napthyl)- 1 , 1 -dimethylethylamine ; N-[3-[3-chloro-2-cyano-4-(benzyl-cyclopropyl)sulfamoyl]phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(4'-N-t-butoxycarbonylpiperazino)sulfamyl]phenoxy-2(R)- hydroxypropy l]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(4'-N-t-butoxycarbonylpiperazino)sulfamyl]phenoxy)-2(R)- hydroxypropyl]-2-(2-naphthyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-dipropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)-l,l- dimethy lethy lamine ; N-[3-(2,3-dichloro-4-pyrrolidinolsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-pyperidinolsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-cyclopropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-dipropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1,1 -dimethylethylamine; N-[3-(2,3-dichloro-4-propylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)-l,l- dimethy lethy lamine ; N-[3-(2,3-dichloro-4-sulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)-l,l- dimethylethylamine; N- [3-(2,3-dichloro-4-methylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1,1- dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- fluorophenyl)- 1 , 1-dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(benzyloxy)- 1,1 -dimethylethylamine; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy- 2(R)-hydroxypropyl]-3-pheny 1-1,1 - dimethylpropylamine; and N- [3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy- 2(R)-hydroxypropyl]-4-phenyl- 1,1- dimethylbuty lamine; (R)- 1 - [ 1 , 1 -dimethyl-2-(4-methoxypheny l)ethylamino]-3- [ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[ 10, 1 l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(S)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(2-naphthyl)ethylamino]-3-[ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-2-(2-naphthy l)ethy lamino]-3- [10,11 -dihydro-2-cy ano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(S)-acetic acid]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[10-ethylthio-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[10-ethylthio-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[ 10, 11 -dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid ]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[ 10, 11 -dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(S)-acetic acid ]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(2-naphthy l)ethylamino]-3-[ 10, 11 -dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid ]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthy l)ethylamino]-3-[ 10, 11 -dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(S)-acetic acid ]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxypheny l)ethylamino]-3-[ 10-ethylthio-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1-[ 1 , l-dimethyl-2-(2-naphthyl)ethylamino]-3-[ 10-ethylthio-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[10-ethylthio-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1 -[ 1 , l-dimethyl-2-(2-naphthyl)ethylamino]-3-[ 10-ethylthio-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy- 10-oxo-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[3-oxy-10-oxo-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)-l -[ 1 , 1 -dimethyl-3-phenyl-propylamino]-3-[ 10, 1 l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethy l-4-phenyl-butylamino]-3-[ 10, 1 l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy 1-2-phenoxy-ethy lamino]-3-[ 10,11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-oxybenzyl-ethylamino]-3-[ 10,11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthalenyl)ethylamino]-3-[3-oxy-dibenz[b,f|[l,4]oxazepin- 1 l(10H)-one]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxypheny l]-3-[3-oxy-dibenz[b,f] [ 1 ,4]oxazepin- 11 ( 10H)-one]- propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethyl-2-( 1 , 1 -dimethy l-4-phenyl)-buty lamino]-3- [3-oxy-dibenz[b,f] [ 1 ,4]oxazepin- 1 l(10H)-one]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethyl-2-( 1 , 1 -dimethyl-2-oxybenzy l)-ethylamino]-3-[3-oxy- dibenz[b,f] [ 1 ,4]oxazepin- 11(10H)-one]-propan-2-ol monohydrochloride; (R)-l-[l,l-dimethyl-2-[(2-naphthalenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [b,f][l,4]oxazepin]-2-propanol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin]-2-propanol monohydrochloride ; (R)- 1-[ 1 , l-dimethyl-2-( 1 , 1 -dimethyl-4-phenyl)-butylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f][l,4]oxazepin]-2-propanol monohydrochloride; (R)- 1-[ 1 , 1 -dimethy l-2-( 1 , 1 -dimethyl-2-oxybenzyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin]-2-propanol monohydrochloride; (R)-l-[l,l-dimethyl-2-(2-naphthalenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [b,f] [ 1 ,4]oxazepin- 11(10H)-carboxymethyl]-propan-2-ol monohydrochloride; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [b,f] [ 1 ,4]oxazepin- 11(10H)-carboxymethyl]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethy l-2-( 1 , 1 -dimethyl-4-phenyl)-butylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin- 11(10H)-carboxy methyl]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethy l-2-( 1 , 1 -dimethy l-2-oxybenzyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz f b,f] [ 1 ,4]oxazepin- 11(10H)-carboxymethyl]-propan-2-ol monohydrochloride; and pharmaceutically acceptable salts thereof. Trifluoroacetate and hydrochloride salts are preferred. Hydrochloride salts are more preferred. More preferred compounds of the present invention include: (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (4-methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-[4-methylphenylsulfonyl]amino]phenoxy]-l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol ; (R)- 3-[2-cyano-4-[N-methyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (4-methoxyphenyI)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[ N-methylsulfonylamino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[ N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; and (R)- 3-[2-cyano-4- [N-benzy 1-N- [4-methy Ipheny lsulf ony 1] amino]phenoxy ] - 1 - [ 1 , 1 -dimethy 1-2- (2-naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N'-moφholino]ureido]phenoxy]-l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N'-moφholino]ureido]phenoxy]- 1-[ 1 , 1 -dimethy l-2-(4- methoxyphenyl)ethylamino]-propan-2-ol ; (R)- 3-[2-cyano-4-[N-methyl-N'-moφholino]ureido]phenoxy]- 1 -[1,1 -dimethy l-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N'-moφholino]ureido]phenoxy]-l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- piperidinylcarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano, 3-chloro-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano, 3-chloro-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-2-(4-methoxy phenyl)ethy lamino] -3- [2-cy ano-4-(N- pyrrolidinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-2-(2-naphthyl)ethylamino]-3- [2-cy ano-4-(N-piperidiny lcarbony l)phenoxy ] - propan-2-ol; and (R)- 1 - [ 1 , 1 -dimethyl-2-(2-naphthy l)ethy lamino]-3- [2-cy ano-4-(N- pyrrolidinylcarbonyl)phenoxy]-propan-2-ol. N-[3-(3-chloro-2-cyano-4- dimethylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1,1- di ethy lethy lamine ; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxypheny 1)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-thiomoφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2- naphthyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-thiomoφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(benzyl-cyclopropyl)sulfamoyl]phenoxy-2(R)-hydroxypropyl]-2-(2- napthyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(benzyl-cyclopropyl)sulfamoyl]phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-dipropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)- 1,1- dimethylethylamine; N-[3-(2,3-dichloro-4-pyrrolidinolsulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-piperidinolsulfamyl)phenoxy-2(R)-hydroxypropyl][2-(4-methoxyphenyl)- 1,1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(2'-cyanoeth-l-yl)-cyclopropylsulfamoyl]phenoxy-2(R)- hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(2'-cyanoeth-l-yl)-cyclopropylsulfamoyl]phenoxy-2(R)- hydroxypropyl]-2-(2-napthyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(benzyloxy)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-dipropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(benzyloxy)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy- 2(R)-hydroxypropyl]-3-phenyl- 1,1- dimethy lpropylamine; and N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy- 2(R)-hydroxypropyl]-4-phenyl-l,l- dimethylbutylamine; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxypheny l)ethylamino]-3-[ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(S)-acetic acid]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[10,l l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[10,l l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(S)-acetic acid]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-310-ethylthio-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-310-ethylthio-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[10,l l-dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[ 10, 1 l-dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(S)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(2-naphthy l)ethylamino]-3-[ 10, 11 -dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(2-naphthyl)ethylamino]-3-[ 10, 11 -dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(S)-acetic acid]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[ 10-ethylthio-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[10-ethylthio-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy 1-3-pheny 1-propy lamino] -3- [ 10, 11 -dihy dro-2-cy ano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)-l-[l,l-dimethyl-4-phenyl-butylamino]-3-[10,l l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy 1-2-phenoxy-ethy lamino] -3- [ 10, 11 -dihy dro-2-cy ano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; and (R)- 1 - [ 1 , 1 -dimethyl-2-oxybenzyl-ethylamino]-3-[ 10,1 l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethy l-2-(2-naphthalenyl)ethylamino]-3-[3-oxy-dibenz[b,f] [1 ,4]oxazepin- 1 l(10H)-one]-propan-2-ol monohydrochloride; (R)- 1 - [ 1 , 1 -dimethy l-2-(4-methoxyphenyl]-3-[3-oxy-dibenz[b,f] [ 1 ,4]oxazepin- 11 ( 10H)-one]- propan-2-ol monohydrochloride; (R)- 1-[ 1, 1 -dimethy l-2-(l, l-dimethyl-4-phenyl)-butylamino]-3-[3-oxy-dibenz[b,f][ 1 ,4]oxazepin- 1 l(10H)-one]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethyl-2-( 1 , 1 -dimethyl-2-oxybenzyl)-ethylamino]-3-[3-oxy- dibenz[b,f][l,4]oxazepin-l l(10H)-one]-propan-2-ol monohydrochloride; (R)-l-[l,l-dimethyl-2-[(2-naphthalenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [b,f][ 1 ,4]oxazepin]-2-propanol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin]-2-propanol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethyl-2-( 1 , 1 -dimethyl-4-pheny l)-butylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin]-2-propanol monohydrochloride; (R)- 1-[ 1 , 1 -dimethy l-2-( 1, 1 -dimethy 1-2-oxybenzy l)ethylamino]-3- [3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin]-2-propanol monohydrochloride; (R)-l-[l,l-dimethyl-2-(2-naphthalenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [b,f][ 1 ,4]oxazepin- 11 ( 10H)-carboxymethyl]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f][l,4]oxazepin-l l(10H)-carboxymethyl]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , l-dimethyl-2-( 1 , 1 -dimethyl-4-phenyl)-butylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f][l,4]oxazepin-l l(10H)-carboxymethyl]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethy l-2-( 1 , 1 -dimethy l-2-oxybenzyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f][ 1 ,4]oxazepin- 11 (10H)-carboxymethyl]-propan-2-ol monohydrochloride; and pharmaceutically acceptable salts thereof. The most preferred compounds of the present invention include: (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (4-methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-[4-methylphenylsulfonyl]amino]phenoxy]- 1 -[ 1 , 1 -dimethyl-2-(4- methoxypheny l)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4- [N-methyl-N- [4-methy lphenylsulfonyl]amino]phenoxy ]- 1 -[ 1 , 1 -dimethyl-2- (4-methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxypheny l)ethylamino] -propan-2-ol ; (R)- 3-[2-cyano-4-[N-benzyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-olt; (R)- 3-[2-cyano-4-[N-benzyl-N-[methylsulfonyl]amino]phenoxy]- 1 -[ 1 , 1 -dimethy l-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3- [2-cy ano-4- [N-benzy l-N'-moφholino]ureido]phenoxy] - 1 - [ 1 , 1 -dimethy l-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N'-moφholino]ureido]phenoxy]-l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N'-moφholino]ureido]phenoxy]- l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol ; (R)- 3-[2-cyano-4-[N-methyl-N'-moφholino]ureido]phenoxy]-l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol and (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (2-naphthyl)ethylamino]-propan-2-ol ; (R)- 1 -[ 1 , l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- piperidinylcarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dime yl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- pyrrolidinylcarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N-piperidinylcarbonyl)phenoxy]- propan-2-ol; and (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N- pyrrolidinylcarbonyl)phenoxy]-propan-2-ol. N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1,1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-thiomoφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2- naphthy 1)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-thiomoφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 ,1-dimethylethylamine; N-[3-(2,3-dichloro-4-pyrrolidinolsulfamyI)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-piperidinolsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(benzyloxy)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(2'-cyanoeth-l-yl)-cyclopropylsulfamoyl]phenoxy-2(R)- hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1-dimethylethylamine; N- [3-[3-chloro-2-cyano-4-(2'-cyanoeth- 1 -y l)-cyclopropylsulfamoyl]phenoxy-2(R)- hydroxypropyl]-2-(2-napthyl)-l,l-dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(benzyloxy)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy- 2(R)-hydroxypropyl]-4-phenyl-l,l- dimethylbutylamine; N-[3-(2,3-dichloro-4-moφholinosύlfamyl)phenoxy- 2(R)-hydroxypropyl]-3-phenyl-l,l- dimethylpropylamine; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy- 2(R)-hydroxypropyl]-4-phenyl-l,l- dimethylbutylamine; (R)- 1 - [ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethy lamino]-3-[ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-2-(4-methoxypheny l)ethylamino]-3- [ 10,11 -dihydro-2-cy ano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(S)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(2-naphthyl)ethylamino]-3-[ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(2-naphthyl)ethylamino]-3-[ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(S)-acetic acid]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[10-ethylthio-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; and (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthyl)ethy lamino]-3-[ 10-ethylthio-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthalenyl)ethy lamino]-3-[3-oxy-dibenz[b,f] [ 1 ,4]oxazepin- 1 l(10H)-one]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxyphenyl]-3-[3-oxy-dibenz[b,f] [ 1 ,4]oxazepin- 11(10H)-one]- propan-2-ol monohydrochloride; (R)- 1-[ 1 , l-dimethyl-2-[(2-naphthalenyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f][ 1 ,4]oxazepin]-2-propanol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f][ 1 ,4]oxazepin]-2-propanol monohydrochloride; (R)-l-[l,l-dimethyl-2-(2-naphthalenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [b,f][l,4]oxazepin-l l(10H)-carboxymethyl]-propan-2-ol monohydrochloride; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [b,f][ 1 ,4]oxazepin- 11(10H)-carboxymethyl]-propan-2-ol monohydrochloride; and pharmaceutically acceptable salts thereof. The present compounds can be formulated as pharmaceutically acceptable salts and complexes thereof. Pharmaceutically acceptable salts are non-toxic salts in the amounts and concentrations at which they are administered. -" Pharmaceutically acceptable salts include acid addition salts such as those containing sulfate, hydrochloride, fumarate, maleate, phosphate, sulfamate, acetate, citrate, lactate, tartrate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, cyclohexylsulfamate and quinate. Pharmaceutically acceptable salts can be obtained from acids such as hydrochloric acid, maleic acid, sulfuric acid, phosphoric acid, sulfamic acid, acetic acid, citric acid, lactic acid, tartaric acid, malonic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, cyclohexylsulfamic acid, fumaric acid, and quinic acid. Pharmaceutically acceptable salts also include basic addition salts such as those containing benzathine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine, procaine, aluminum, calcium, lithium, magnesium, potassium, sodium, ammonium, alkylamine, and zinc, when acidic functional groups, such as carboxylic acid or phenol are present. The present invention provides compounds of Formula (I) above which can be prepared using standard techniques. An overall strategy for preparing preferred compounds described herein can be carried out as described in this section. Using the protocols described herein as a model, one of ordinary skill in the art can readily produce other compounds of the present invention. Scheme 1 Scheme 2. Scheme 3 (Ph 3 P) 4 Pd CO, R-,R 2 NH DMF heat Scheme 4 cheme 5 Hydroxylamine hydrochloride Et 3 N. EtOH, Reflux, 18 hrs Scheme 6 Scheme 7 Scheme 8. Scheme 9 A general procedure used to synthesize many of the compounds can be carried out as described in Scheme 1, above: A solution of aryl alcohol (X-OH) in acetone was treated with an appropriate base such as K2CO3, heated for 15 min. R-glycidyl nosy late was added and the reaction continued overnight to give the corresponding glycidyl ether (Scheme 1). In the case of an alkyl alcohol, a stronger base, e.g. NaH in DMF was used. This method can also be used for aryl alcohols. A solution of the substituted glycidyl ether and excess amine (typically 1,1- dimethyl-2-(4-methyloxyphenyl)ethylamine) in absolute ethanol, acetonitrile, THF or any other similar solvent in the presence of a suitable catalyst such as I -CIO4 is stirred overnight at reflux. The product is purified by normal phase chromatography. Hydrochloride salts are prepared by treatment of the corresponding free base with HCl either in gas phase or 4M dioxane solution, or any other standard method. The synthesis of the corresponding o-substituted aryl ethers is described in Scheme 2-9. For example, treatment of a 2-cyano-4-nitrophenol (Scheme 2) with K-2CO3 followed by methyl iodide, yields the corresponding aryl methyl ether, treatment with Fe powder or any other reducing agent capable of reducing the aryl nitro group in the presence on the nitrile, gives the corresponding aniline. Reaction of the thus obtained aniline with an appropriate sulfonyl or carbonyl chloride such as tosyl, or mesyl chloride or 4- moφholinecarbonyl chloride, in the presence or triethyl amine produces the corresponding sulfonamide or urea. Alkylation of the sulfonamide nitrogen can be carried out via deprotonation with an appropriate base such as NaH in an appropriate anhydrous solvent such as DMF, followed by treatment with the desired alkyl halide such as benzyl bromide. The methyl ether was then removed with Me3PhSi and I2 or with Lil in collidine, or any other standard deprotection method known to a chemist skilled in the art. The 2,3-disubstituted methyl ether (Scheme 3).is treated with bromine in the presence of Fe resulting in regiospecific bromination. The resulting bromide can then be treated under carbonylamidation conditions, (Ph3)4Pd, CO, R R2NH, DMF, heat to give the resulting amide which is deprotected with Lil in collidine to give the corresponding aryl alcohol. Treatment of an ortho-substituted aryl ether Scheme 4 with SOCI2 followed by a primary or secondary amine gives the p-sulfonamide. The methyl ether is then removed with Me3PhSi and I2 or with Lil in an appropriate solvent such as collidine, or any other deprotection method known to a chemist skilled in the art (Scheme 2), to yield the desired arylalcohol. The methyl aryl ether (Scheme 5) is converted to the corresponding aryl alcohol with AlC^/EtSH. The cyano group is introduced selectively adjacent to the aryl alcohol by treating the aryl alcohol with paraformaldehyde and SnCl4 to give the formyl derivative. Conversion of the formyl group to the corresponding oxime and dehydration with AC2O gives the cyano-aryl ester. Final hydrolysis of the aryl ester gives the desired aryl alcohol. Deprotection of the methyl aryl ether of the ketone(Scheme 6). gives the aryl alcohol as well as the thio enolether. Nucleophilic displacement of the aryl fluoride (Scheme 7) with the potassium salt of the phenol gives a biaryl ether which is reduced and then cyclized to give a cyclic amide which is converted to the corresponding aryl alcohol via deprotection with AlC^/EtSH. The amide from Scheme 7 is reduced to the tricyclic anilide (Scheme 8) which is converted to the corresponding aryl alcohol via deprotection with AlC^/EtSH. The tricyclic anilide from Scheme 8 is alkylated with the appropriate electrophile to give the corresponding N-alkylated material (Scheme 9). With appropriate manipulation and protection of any chemical functionality, synthesis of the remaining compounds of Formula (I) is accomplished by methods analogous to Schemes 1-9. In order to use a compound of Formula (I) or a pharmaceutically acceptable salt thereof for the treatment of humans and other mammals, it is normally formulated in accordance with standard pharmaceutical practice as a pharmaceutical composition. The calcilytic compounds can be administered by different routes including intravenous, intraperitoneal, subcutaneous, intramuscular, oral, topical (transdermal), or transmucosal administration. For systemic administration, oral administration is preferred. For oral administration, for example, the compounds can be formulated into conventional oral dosage forms such as capsules, tablets, and liquid preparations such as syrups, elixirs, and concentrated drops. Alternatively, injection (parenteral administration) may be used, e.g., intramuscular, intravenous, intraperitoneal, and subcutaneous. For injection, the compounds of the invention are formulated in liquid solutions, preferably, in physiologically compatible buffers or solutions, such as saline solution, Hank's solution, or Ringer's solution. In addition, the compounds may be formulated in solid form and redissolved or suspended immediately prior to use. Lyophilized forms can also be produced. Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, bile salts and fusidic acid derivatives. In addition, detergents may be used to facilitate permeation. Transmucosal administration, for example, may be through nasal sprays, rectal suppositories, or vaginal suppositories. For topical administration, the compounds of the invention can be formulated into ointments, salves, gels, or creams, as is generally known in the art. The amounts of various calcilytic compounds to be administered can be determined by standard procedures taking into account factors such as the compound IC50, EC50, the biological half-life of the compound, the age, size and weight of the patient, and the disease or disorder associated with the patient. The importance of these and other factors to be considered are known to those of ordinary skill in the art. Amounts administered also depend on the routes of administration and the degree of oral bioavailability. For example, for compounds with low oral bioavailability, relatively higher doses will have to be administered or the number of doses will have to be increased. Preferably the composition is in unit dosage form. For oral application, for example, a tablet, or capsule may be administered, for nasal application, a metered aerosol dose may be administered, for transdermal application, a topical formulation or patch may be administered and for transmucosal delivery, a buccal patch may be administered. In each case, dosing is such that the patient may administer a single dose. Each dosage unit for oral administration contains suitably from 0.01 to 500 mg/Kg, and preferably from 0.1 to 50 mg/Kg, of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, calculated as the free base. The daily dosage for parenteral, nasal, oral inhalation, transmucosal or transdermal routes contains suitably from 0.01 mg to 100 mg/Kg, of a compound of Formula(I). A topical formulation contains suitably 0.01 to 5.0% of a compound of Formula (I). The active ingredient may be administered from 1 to 6 times per day, preferably once, sufficient to exhibit the desired activity, as is readily apparent to one skilled in the art. As used herein, "modulator" means antagonist. As used herein, "treatment" of a disease includes, but is not limited to prevention, retardation and prophylaxis of the disease. The compounds of the present invention preferably exhibit a ratio of β-receptor binding to calcium receptor binding (in Kj values) of 3 or greater, more preferably of 10 or greater, most preferably of 30 or greater. Diseases and disorders which might be treated or prevented, based upon the affected cells, include bone and mineral-related diseases or disorders; hypoparathyroidism; those of the central nervous system such as seizures, stroke, head trauma, spinal cord injury, hypoxia- induced nerve cell damage, such as occurs in cardiac arrest or neonatal distress, epilepsy, neurodegenerative diseases such as Alzheimer's disease, Huntington's disease and Parkinson's disease, dementia, muscle tension, depression, anxiety, panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, schizophrenia, neuroleptic malignant syndrome, and Tourette's syndrome; diseases involving excess water reabsoφtion by the kidney, such as syndrome of inappropriate ADH secretion (SIADH), diseases involving abnormally low serum parathyroid levels, cirrhosis, congestive heart failure, and nephrosis; hypertension; preventing and or decreasing renal toxicity from cationic antibiotics { .g., aminoglycoside antibiotics); gut motility disorders such as diarrhea and spastic colon; GI ulcer diseases; GI diseases with excessive calcium absoφtion such as sarcoidosis; autoimmune diseases and organ transplant rejection; squamous cell carcinoma, and pancreatitis. In a preferred embodiment of the present invention, the present compounds are used to increase serum parathyroid ("PTH") levels in a pulsatile manner. Increasing serum PTH levels can be helpful in treating diseases such as hypoparathyroidism, osteosarcoma,, periodontal disease, fracture, osteoarthritis, rheumatoid arthritis, Paget's disease, humoral hypercalcemia malignancy and osteoporosis. Increasing serum PTH levels can be used to treat various diseases including bone and mineral related diseases. Various embodiments of the present invention include administering the compound to a patient to cause an increase in serum PTH having a duration up to one hour, one hour to twenty- four hours, one hour to twelve hours, one hour to six hours, one hour to five hours, one hour to four hours, two to five hours, two hours to four hours, or three hours to about six hours. Various additional embodiments include administering the compound to a patient to cause an increase in serum PTH up to 0.5 fold, 0.5 to 5 fold, 5 fold to 10 fold, and at least 10 fold, greater than the peak serum PTH in the patient. The peak serum level is measured with respect to the patient not undergoing treatment. Compositions of Formula (I) and their pharmaceutically acceptable salts which are active when given orally can be formulated as syrups, tablets, capsules and lozenges. A syrup formulation will generally consist of a suspension or solution of the compound or salt in a liquid carrier for example, ethanol, peanut oil. olive oil, glycerine or water with a flavoring or coloring agent. Where the composition is in the form of a tablet, any pharmaceutical carrier routinely used for preparing solid formulations may be used. Examples of such carriers include magnesium stearate, terra alba, talc, gelatin, acacia, stearic acid, starch, lactose and sucrose. Where the composition is in the form of a capsule, any routine encapsulation is suitable, for example using the aforementioned carriers in a hard gelatin capsule shell. Where the composition is in the form of a soft gelatin shell capsule any pharmaceutical carrier routinely used for preparing dispersions or suspensions may be considered, for example aqueous gums, celluloses, silicates or oils, and are incoφorated in a soft gelatin capsule shell. Typical parenteral compositions consist of a solution or suspension of a compound or salt in a sterile aqueous or non-aqueous carrier optionally containing a parenterally acceptable oil, for example polyethylene glycol, polyvinylpyrrolidone, lecithin, arachis oil or sesame oil. Typical compositions for inhalation are in the form of a solution, suspension or emulsion that may be administered as a dry powder or in the form of an aerosol using a conventional propellant such as dichlorodifluoromethane or trichlorofluoromethane. A typical suppository formulation comprises a compound of Formula (I) or a pharmaceutically acceptable salt thereof which is active when administered in this way, with a binding and/or lubricating agent, for example polymeric glycols, gelatins, cocoa-butter or other low melting vegetable waxes or fats or their synthetic analogs. Typical dermal and transdermal formulations comprise a conventional aqueous or non- aqueous vehicle, for example a cream, ointment, lotion or paste or are in the form of a medicated plaster, patch or membrane. Preferably the composition is in unit dosage form, for example a tablet, capsule or metered aerosol dose, so that the patient may administer a single dose. No unacceptable toxological effects are expected when compounds of the present invention are administered in accordance with the present invention. The biological activity of the compounds of Formula (I) are demonstrated by the following tests: (I) Calcium Receptor Inhibitor Assay Calcilytic activity was measured by determining the IC5 Q of the test compound for blocking increases of intracellular Ca^+ elicited by extracellular Ca^ + in HEK 293 4.0-7 cells stably expressing the human calcium receptor. HEK 293 4.0-7 cells were constructed as described by Rogers et al., J. Bone Miner. Res. 10 Suppl. 1 :S483, 1995 (hereby incoφorated by reference herein). Intracellular Ca^+ increases were elicited by increasing extracellular Ca^ + from 1 to 1J5 mM. Intracellular Ca2+ was measured using fluo-3, a fluorescent calcium indicator. The procedure was as follows: Cells were maintained in T-150 flasks in selection media (DMEM supplemented with 10% fetal bovine semm and 200 ug/mL hygromycin B), under 5% CO2:95% air at 37 °C and were grown up to 90% confluency. The medium was decanted and the cell monolayer was washed twice with phosphate-buffered saline (PBS) kept at 37 °C. After the second wash, 6 mL of 0.02% EDTA in PBS was added and incubated for 4 minutes at 37 °C. Following the incubation, cells were dispersed by gentle agitation. Cells from 2 or 3 flasks were pooled and pelleted (100 x g). The cellular pellet was resuspended in 10-15 mL of SPF-PCB+ and pelleted again by centrifugation. This washing was done twice. Sulfate- and phosphate-free parathyroid cell buffer (SPF-PCB) contains 20 mM Na-Hepes, pH 7.4, 126 mM NaCl, 5 mM KC1, and 1 mM MgCl 2 . SPF-PCB was made up and stored at 4 °C. On the day of use, SPF-PCB was supplemented with 1 mg/mL of D-glucose and 1 mM CaCl2 and then split into two fractions. To one fraction, bovine serum albumin (BSA; fraction V, ICN) was added at 5 mg/mL (SPF-PCB+). This buffer was used for washing, loading and maintaining the cells. The BSA-free fraction was used for diluting the cells in the cuvette for measurements of fluorescence. The pellet was resuspended in 10 mL of SPF-PCB+ containing 2.2 uM fluo-3 (Molecular Probes) and incubated at room temperature for 35 minutes. Following the incubation period, the cells were pelleted by centrifugation. The resulting pellet was washed with SPF-PCB+. After this washing, cells were resuspended in SPF-PCB+ at a density of 1-2 x 10" cells/mL. For recording fluorescent signals, 300 uL of cell suspension were diluted in 1.2 mL of SPF buffer containing 1 mM CaCl2 and 1 mg/mL of D-glucose. Measurements of fluorescence were performed at 37 °C with constant stirring using a spectrofluorimeter. Excitation and emission wavelengths were measured at 485 and 535 nm, respectively. To calibrate fluorescence signals, digitonin (5 mg/mL in ethanol) was added to obtain F max , and the apparent F m } n was determined by adding Tris-EGTA (2.5 M Tris-Base, 0.3 M EGTA). The concentration of intracellular calcium was calculated using the following equation: Intracellular calcium = (F-F m j n /F max ) x Kd; where Kd = 400 nM. To determine the potential calcilytic activity of test compounds, cells were incubated with test compound (or vehicle as a control) for 90 seconds before increasing the concentration of extracellular Ca^ + from 1 to 2mM. Calcilytic compounds were detected by their ability to block, in a concentration-dependent manner, increases in the concentration of intracellular Ca^ + elicited by extracellular Ca^ + . In general, those compounds having lower IC50 values in the Calcium Receptor Inhibitor Assay are more preferred compounds. Compounds having an IC50 greater than 50 uM were considered to be inactive. Preferred compounds are those having an IC50 °f 10uM or lower, more preferred compounds have an IC50 of luM, and most preferred compounds have an IC50 of 0. luM or lower. (II) Calcium Receptor Binding Assay HEK 293 4.0-7 cells stably transfected with the Human Parathyroid Calcium Receptor("HuPCaR") were scaled up in T180 tissue culture flasks. Plasma membrane is obtained by polytron homogenization or glass douncing in buffer (50mM Tris-HCl pH 7.4, ImM EDTA, 3mM MgCl2) in the presence of a protease inhibitor cocktail containing luM Leupeptin, 0.04 uM Pepstatin, and 1 mM PMSF. Aliquoted membrane was snap frozen and stored at - 80°C. ^H labeled compound was radiolabeled to a radiospecific activity of 81Ci/mmole and was aliquoted and stored in liquid nitrogen for radiochemical stability. A typical reaction mixture contains 2 nM ^H compound ((R,R)-N-4'-methoxy-t-3-3'- methyl- 1 '-ethy Ipheny 1- 1 -( 1 -naphthy l)ethy lamine), 4- 10 ug membrane in homogenization buffer containing 0.1% gelatin and 10% EtOH in a reaction volume of 0.5 mL. Incubation is performed in 12 x 75 polyethylene tubes in an ice water bath. To each tube 25 uL of test sample in 100% EtOH is added, followed by 400 uL of cold incubation buffer, and 25 uL of 20 nM 3 H- compound in 100% EtOH. The binding reaction is initiated by the addition of 50 uL of 80-200 ug/mL HEK 293 4.0-7 membrane diluted in incubation buffer, and allowed to incubate at 4°C for 30 min. Wash buffer is 50 mM Tris-HCl containing 0.1 % PEL Nonspecific binding is determined by the addition of 100-fold excess of unlabeled homologous ligand, and is generally 30% of total binding. The binding reaction is terminated by rapid filtration onto 1% PEI pretreated GF/C filters using a Brandel Harvestor. Filters are placed in scintillation fluid and radioactivity assessed by liquid scintillation counting. Ill B-adrenergic Receptor Binding Assay The β-Adrenergic Receptor Binding Assay is carried out as follows. Incubations are performed in polypropylene reaction tubes in a 37 °C water bath. To each tube 50 uL of test sample is added, followed by 300 uL of assay buffer (50 mM Tris-HCl, pH 7.5), and 50 uL of 20 nM [ 3 H]-dihydroalprenolol. The binding reaction is initiated by the addition of 100 uL of 3.75 mg/mL well-washed rat cortex membranes in assay buffer, and allowed to incubate at 37 °C for 30 minutes. Non-specific binding is determined in the presence of 10 μM alprenolol. The final concentration of reactants is: 2 nM H]-dihydroalprenolol, and 75 mg/mL rat cortex membrane in a reaction volume of 0.5 mL. The binding reaction is terminated by rapid filtration with ice-cold assay buffer onto GF/C filters (Brandel, Gaithersburg, MD) which have been soaked for 15 minutes in assay buffer. The reaction is first diluted with 3 mL of cold assay buffer (4 °C), then aspirated onto the filter followed by 3 x 3 mL washes. Filter disks are placed in 7-mL polypropylene scintillation vials with 5 mL of ScintiSafe 50% (Fisher Scientific, Pittsburgh, PA), and counted overnight. β-adrenergic activity can be reduced using appropriate functional groups and structural modifications, β-adrenergic receptor activity and binding to the β-adrenergic receptor can be measured using standard techniques. For example, see Riva et al, Mol. Pharmacol. -?6:201-210, 1989. In one embodiment of the present invention the calcilytic compounds have a K j > 0.1 uM, at the β-adrenergic receptor as measured using the β-Adrenergic Receptor Binding Assay described above. In other embodiments, using the β-Adrenergic Receptor Assay calcilytic compounds have a K j > 1.0 uM, and Kj > 10.0 uM. The following examples are illustrative, but not limiting of the embodiments of the present invention. EXAMPLES Example 1 Preparation of (R)- 3-r2-cvano-4-rN-benzyl-N-r4-methylphenylsulfonvI1aminophenoxy1- 1- n,l-dimethyl-2-(4-methoxyphenyl)ethylamino1-propan-2-ol hydrochloride salt a) 5-Nitro-2-methoxybenzonitrile A mixture of 2-cyano-4-nitrophenol (3.5 g, 21 mmol), K2CO3 (5.9 g, 42 mmol), and Mel (9.08 g, 64 mmol) in acetone (50 mL) was heated at reflux overnight. The mixture was cooled and concentrated, taken up in H2O, stirred, filtered the yellow solid, dried by air (3.0 g, 79%). 1H NMR (400 MHz, CDCI3): d 4.08 (s, 3H), 7.12 (d, J = 9.2 Hz, IH), 8.5 (m, 2H). b) 5-Amino-2-methoxylbenzonitrile The compound of Example l(a ) (8.5 g, 47.7 mmol) from above, Fe powder (13.3 g, 238.6 mmol), and NH4CI (1.3 g, 23.9 mmol) in EtOH/H 2 O (100 mL, 9:1) was heated at reflux in 2h. The mixture was filtered hot. The filtrate was concentrated, taken up in H2O, stirred, filtered and the tan solid thus obtained air dried to obtain 5.0 g (71 %) of the of the above named compound. 1H NMR (400 MHz, CDCI3): d 4.08 (s, 3H), 5.50 (s, 2H), 7.12 (d, J = 9.2 Hz, IH), 8.50 (m, 2H). c) 2-Methoxy-5-[[N-4-methylphenyl]sulfonyl]aminobenzonitrile To a stirred mixture of the compound of Example 1(b) (2.0 g, 13.6 mmol), and Et3N (1.44 g, 14J moles) in CH2CI2 (20 mL) was added p-toluenesulfonyl chloride. (2.72 g, 14.7 mmol). After stirring at RT overnight, the mixmre was concentrated, taken up in H2O, extracted with EtOAc, washed with brine, dried over MgSθ4, filtered, concentrated, triturated with Et2θ to give 2.50 g (60%) of the above named compound as an off-white solid. H NMR (400 MHz, CDCI3): d 2.48 (s, 3H), 3.95 (s, 3H), 6.80 (d, J = 9.1 Hz, 2H), 7.03 ( d, j = 9.2 Hz, IH), 7.40 ( m, 2H), 7.52 (d, J = 9.1 Hz, 2H), 9.55 (s, IH). d) 2-Methoxy-5-[[N-4-methylphenyl]sulfonyl-N-benzyl]aminobenzonitrile To a stirred suspension of NaH (pre- washed with hexane, 60% oil, 0.15 g, 3.6 mmol) in DMF (20 mL) was added the compound of Example 1 (c) (1.0 g, 3.3 mmol) in portions. After stirring at RT for lh, benzyl bromide (0.6 g, 3.4 mmol) was added, and continued to stir at RT ovemight. The mixture was quenched with H2O, extracted with EtOAc. The organic extracts were washed with brine, dried over MgS04, concentrated to give 0J g (58%) of the above named compound as a brown solid. 1H NMR (400 MHz, CDCI3): d 2.49 (s, 3H), 3.87 (s, 3H), 4.68 (s, 2H), 6.80 (d, J = 9.1 Hz, 2H), 7.01 (d, 2.7 Hz, IH), 7.25 (m, 7H), 7.50 (d, j = 9.1 Hz, 2H). e) 2-Hydroxyl-5-[[N-4-methylphenyI]sulfonyl-N-benzyl]aminobenzonitrile A mixture of the compound of Example 1(d) (0J0 g, 1J mmol), PhSiMβ3 (0.41 g, 2.6 mmol), and iodine (0.67 g, 2.6751 mmol) was heated at 130 C in 3h. The mixture was cooled and added saturated aqueous NaHS03, extracted with EtOAc. The organic extracts were washed with H2O, brine, dried over MgSθ4, filtered, concentrated, and purified by flash column chromatography (40% EtOAc/Hexane) to afford the title compound as a light brown solid (0.20 g, 30%).1H NMR (400 MHz, CDCI3): d 2.49 (s, 3H), 4.68 (s, 2H), 6.80 (d, J = 9.1 Hz, 2H), 7.01 ( d, 2.7 Hz, IH), 7.25 (m, 7H), 7.50 (d, J = 9.1 Hz, 2H). f) 2-Cyano-4- [N-benzyl-N-[4-methylphenylsulfonyl]amino]phenyl giycidol A mixture of the compound of Example 1(e) (0.20 g, 0.5 mmol), K2CO3, and 2R-(-)- glycidyl-3-nitrobenzenesulfonate (0.16 g, 0.6 mmol) in acetone (5 mL) was refluxed in 24h. The mixture was cooled, concentrated, taken up in H2O, extracted with EtOAc(3x). The organic extracts were washed with saturated NaHCθ3, brine, dried over MgSθ4, filtered, concentrated, and purified by flash column chromatography (35% EtOAc/Hexane) to afford the title compound (0.148 g, 65%) as an off white foam. H NMR (400 MHz, CDCI3): d 2.29 (s, 3H), 2.85 {t, J = 4.5 Hz, IH), 2.95 (t, J = 4.5 Hz, IH), 3.40 (m, IH), 4.10 (dd, J = 5.4, 11.4 Hz, IH), 4.43 (dd, J = 2.6, 11.4 Hz, IH), 4.68 (s, 2H), 6.80 (d, J = 9.1 Hz, 2H), 7.01 ( d, 2.7 Hz, IH), 7.25 (m, 7H), 7.50 (d, J = 9.1 Hz, 2H). g) N-[2R-Hydroxy-3-[[2-cyano-4-[N-benzyl-N-[4-methylphenyl sulfonyl]amino] phenoxy]propyl-l,l-dimethyl-2-[4-methoxyphenyl]ethylamine hydrochloride A mixture of the compound of Example 1(f) (0.145 g, 0.3 mmol), LiC104 (0.10 g, 0.6 mmol), and 4-methoxypheny 1-1,1 -dimethyl (0.07 g, 0.4 mmol) in dried acetonitrile (5 mL) was heated at reflux in 24h. The mixture was cooled and concentrated, taken up in H2O, extracted with EtOAc (3x). The combined organic extracts were washed with brine, dried over MgSO4, filtered, concentrated, and purified by flash column chromatography (3% MeOH/CH2θ2) to afford a colorless oil which was stirred in methanol and added 4M HCl, concentrated, and triturated in ether to give the title compound (0.120 g, 60%) as an off white solid. ^H NMR (400 MHz, DMSO-d 6 ): d 1.09 (s, 3H), 1.11( s, 3H),2.42 (s, 3H), 2.64 (s, 2H), 3.10 (dd, J = 7.2, 14.4 Hz, IH), 3.25 (dd, J = 7.2, 14.4 Hz, IH), 3.34 (s, 3H), 3.71 (s, 3H),4.21 (m, 2H), 4.30 (m, 1H),4.63 (s, 2H), 6.90 (d, J = 7.2 Hz, 2H), 7.12 (d, J = 7.2 Hz, 2H), 7.22 (d, J = 7.3 Hz, IH), 7.33, (m, 5H), 7.63 (d, J = 7.3 Hz, 2H), 8.06 (s, IH), MS (M+l, m z): 614.4. Anal. Calculated, for C35H39N3O4SHCI 1.25H 2 0: C, 62.48; H, 6.21; N, 6.24; Found: C, 62.44; H, 6.30; N, 6.25. Example 2 Preparation of (R - 3-r2-cvano-4-N-r4-methylphenylsulfonvπaminophenoxyl- 1-fl.l- dimethyl-2-(4-methoxyphenyl ethylamino1-propan-2-ol hydrochloride salt a) 2-Hydroxyl-5-[[N-4-methylphenyl]suIfonyl]aminobenzonitrile A mixture of the compound of Example 1(d) (0.50 g, 1.6542 mmol), PhSiMe3 (0.40 g, 2.5 mmol), and iodine (0.63 g, 2.5 mmol) was heated at 130 C in 3h. The mixture was cooled and added saturated aqueous NaHSθ3, extracted with EtOAc. The organic extracts were washed with H2O, brine, dried over MgSθ4, filtered, concentrated, and purified by flash column chromatography (40% EtOAc/Hexane) to afford the titie compound (0.25 g, 51%) as a light yellow solid. 1H NMR (400 MHz, CDCI3): d 2.49 (s, 3H), 4.68 (s, 2H), 6.80 (d, J = 9.1 Hz, 2H), 7.01 ( d, 2.7 Hz, IH), 7.25 (m, 7H), 7.50 (d, J = 9.1 Hz, 2H), 9.55 (s, IH). b) 2-Cyano-4-N-[4-methylphenyl]sulfonyl]amino]phenyI glycidol A mixture of the compound of Example 2(a) (0.25 g, 0.8 mmol), K2CO3 (0.12 g, 0.9 mmol), and 2R-(-)-glycidyl-3-nitrobenzenesuIfonate (0.2 g, 0.9 mmol) in acetone (5 mL) was refluxed in 24h. The mixmre was cooled, concentrated, taken up in H2O, extracted with EtOAc(3x). The organic extracts were washed with saturated NaHCθ3, brine, dried over MgSθ4, filtered, concentrated, and purified by flash column chromatography (60% EtOAc/Hexane) to afford the title compound (0.15 g, 65%) as an off white foam. *H NMR (400 MHz, CDCI3): d 2.29 (s, 3H), 2.85 (t, J = 4.5 Hz, IH), 2.95 (t, J = 4.5 Hz, IH), 3.40 (m, IH), 4.10 (dd, J = 5.4, 11.4 Hz, IH), 4.43 (dd, J = 2.6, 11.4 Hz, IH), 4.68 (s, 2H), 6.80 (d, J = 9.1 Hz, 2H), 7.01 ( d, J = 9.3 Hz, IH), 7.25 (m, 2H), 7.50 (d, J = 9.1 Hz, 2H), 9.55 (s, IH). c) N-[2R-Hydroxy-3-[[2-cyano-4-[N-benzyl-N-[4-methylphenyI]sulfonyl]amino] phenoxy]propyl-l,l-dimethyl-2-[4-methoxyphenyl]ethylamine hydrochloride A mixture of the compound of Example 2(b) (0.22 g, 0.8 mmol), LiC ->4 (0.21 g, 0.1.5 mmol), and 4-methoxypheny 1-1,1 -dimethyl ethylamine(0.16 g, 0.9 mmol) in dried acetonitrile (5 mL) was heated at reflux in 24h. The mixture was cooled and concentrated, taken up in H2O, extracted with EtOAc (3x). The combined organic extracts were washed with brine, dried over MgS04, filtered, concentrated, and purified by flash column chromatography (3% MeOH CH2Cl2) to afford as a colorless oil which was stirred in methanol and added 4M HCl, concentrated, and triturated in ether to give the title compound (64 mg, 16%) as a yellow foam. 1H NMR (400 MHz, DMSO-D 6 ): d 1.09 (s, 3H), 1.11( s, 3H), 2.64 (s, 2H), 3.10 (dd, J = 7.2, 14.4 Hz, IH), 3.25 (dd, J = 7.2, 14.4 Hz, IH), 3.34 (s, 3H), 3.71 (s, 3H),4.21 (m, 2H), 4.30 (m, 1H),5.90 (d, J = 7.6 Hz, IH), 6.90 (d, J = 7.2 Hz, 2H), 7.12 (d, J = 7.2 Hz, 2H), 7.22 (d, J = 7.3 Hz, IH), 7.33, (m, 5H), 7.63 (d, J = 7.3 Hz, 2H), 8.06 (s, IH), 10.47 (s, IH). MS (M+l, m/z): 524.4. Anal. Calcd. for C 2 H33N3θ 5 SHCl: C, 60.05; H, 6.11; N, 7.50; Found: C, 60.40; H, 6.30; N, 7.25. Example 3 Preparation of (R)- 3-r2-cyano-4-rN-methyl-N-r4-methylphenylsulfonyllaminol phenoxyl-l-ri.l-dimethyl-2-(4-methoxyphenyl)ethylaminol-propan-2-ol hydrochloride salt a) 2-Methoxy-5-[[N-4-methylphenyl]sulfonyl-N-benzyl]aminobenzonitrile To a stirred suspension of NaH (pre-washed with hexane, 60% oil, 0.080 g, 1.9 mmol) ) in THF (15 mL) was added compound from Example 1(c) (0.50 g, 1.6 mmol) in portions. After stirring at RT for lh, methyl iodide (0.28 g, 1.9 mmol) was added, and refluxed in 4h. The mixture was cooled, taken up in H2O, extracted with EtOAc. The organic extracts were washed with brine, dried over MgS04 and concentrated to give the title compound (0.45 g, 86%) as a yellow solid. *H NMR (400 MHz, CDCI3): d 2.49 (s, 3H), 3.10 (s, 3H), 3.87 (s, 3H), 6.92 (d, J = 9.1 Hz, IH), 7.11 ( d, 2.7 Hz, IH), 7.25 (d, J = 8.1 Hz, 2H), 7.45 (m, 3H). b) 2-Hydroxyl-5-[N-methyl-N-[4-methylphenylsulfonyl]amino]benzonitrile A mixture of the compound of Example 3(a) (0.45 g, 1.4 mmol), PhSiMe3 ( 0.42 g, 2.8 mmol), and iodine ( 0.72 g, 2.8 mmol) was heated at 130 C in 3h. The mixture was cooled and added saturated aqueous NaHS03, extracted with EtOAc. The organic extracts were washed with H2O, brine, dried over MgSU4, filtered, concentrated, and purified by flash column chromatography (40% EtOAc/Hexane) to afford the title compound (0.214 g, 50%) as a light yellow oil. 1H NMR (400 MHz, CDCI3): d 2.49 (s, 3H), 3.10 (s, 3H), 6.92 (d, J = 9.1 Hz, IH), 7.11 ( d, 2.7 Hz, IH), 7.25 (d, J = 8.1 Hz, 2H), 7.45 (m, 3H). c) 2-Cyano-4-[N-benzyl-N-[4-methylphenylsulfonyI]amino]phenyl glycidol A mixture of the compound of Example 3(b) (0.2 g, 0.7 mmol), K2CO3 (0.20 g, 1.4 mmol), and 2R-(-)-glycidyl-3-nitrobenzenesulfonate (0.2 g, 0.7 mmol) in acetone (5 mL) was refluxed in 24h. The mixture was cooled, concentrated, taken up in H2O, extracted with EtOAc (3x). The organic extracts were washed with saturated NaHC03, brine, dried over MgSθ4, filtered, concentrated to afford the title compound as a tan solid (0.24 g, 95%).^H-NMR (400 MHz, CDCI3): d 2.44 (s, 3H), 2.85 (t, J = 4.5 Hz, IH), 2.97 (t, J = 4.5 Hz, IH), 3.15 (s, 3H), 3.42 (m, IH), 4.12 (dd, J = 5.4, 11.4 Hz, IH), 4.42 (dd, J = 2.6, 11.4 Hz, IH), 6.97 (d, J = 9.1 Hz, IH), 7.13 (d, J = 2.7 Hz, IH), 7.27 (d, J = 8.1 Hz, 2H), 7.41 (m, 3H). d) (R)- 3-[2-cyano-4-[N-methyl-N-[4-methyIphenylsulfonyl]amino]phenoxy]- 1-[1,1- dimethyl-2-(4-methoxyphenyl)ethylamino]-propan-2-ol hydrochloride salt A mixture of the compound of Example 3(c) (0.24 g, 0.7 mmol), LiC104 (0.092 g, 0.7 mmol), and 4-methoxypheny 1-1,1 -dimethyl ethy lamine (0.12 g, 0.7 mmol) in dried acetonitrile (5 mL) was heated at reflux in 24h. The mixture was cooled and concentrated, taken up in H2O, extracted with EtOAc (3x). The combined organic extracts were washed with brine, dried over MgSO filtered, concentrated, and purified by flash column chromatography (5% MeOH/CH2θ2) to afford an off white foam which was stirred in methanol and added 4M HCl, concentrated, and triturated in ether to give the title compound as an off white solid (0.20 g, 55%). NMR (400 MHz, DMSO-d 6 ): d 1.09 (s, 3H), 1.11( s, 3H), 2.41 (s, 3H), 2.64 (s, 2H), 3.10 (dd, J = 7.2, 14.4 Hz, IH), 3.25 (dd, J = 7.2, 14.4 Hz, 1H),3.08 (s, 3H), 3.78 (s, 3H),3.98 (m, IH), 4.20 (t, J = 7.2 Hz, 2H),4.60 (s, IH), 6.80 (d, J = 10.8 Hz, 2H), 6.95 (d, J = 10.8 Hz, IH), 7.06 (d, J = 10.8 Hz, IH), 7.11 (d, J = 3.6 Hz, IH), 7.27 (d, J = 10.8 Hz, 2H), 7.36 (d, J 10.8 Hz, IH), 7.41 (d, J = 10.8 Hz, 2H). MS (M+l, m/z): 524.4. Anal. Calcd. for C 29 H 35 N 3°5 S HC1:C > 60 - 67 ; H - 6 - 32 ; N ' 7 - 32 ÷ Found: c > 60 - 4 °; H > 6 - 3 °; N/7.50. Example 4 Preparation of (R)- 3-r2-cvano-4-rN-benzyl-N-rmethylsuIfonyl1amino1phenoxy1- 1-fl.l- dimethyl-2-(4-methoxyphenyl)ethylamino1-propan-2-ol hydrochloride salt a) 5-Amino-2- fluorobenzonitrile A mixture of 5-nitro-2-fluorobenzonitrile (10 g, 60.2 mmol), Fe powder (17 g, 0.3 mol), and NH C1 (1.7 g, 30 mmol) in EtOH/H 2 O (100 mL, 9:1) was heated at reflux in 2h. The mixture was filtered at hot. The filtrate was concentrated, taken up in H2O, stirred, filtered air- dried to obtain the title solid as a tan solid, (5.0 g, 71%). 1 H NMR (400 MHz, DMSO-dg): d 5.54 (s, 2H), 6.85 (m, 2H), 7.16 (t, J = 8.1 Hz, IH). b) 2-Fluoro-5-[N-methylsulfonyl]aminobenzonitrile To a stirred, cooled (0 C) mixture of the compound of Example 4(a) (5.0 g, 36.7 mmol), and Et3N (3.9 g, 38.5 mol) in CH2CI2 (20 mL) was added methanesulfonyl chloride (4.42 g, 38.5 mmol). After stirring at RT overnight, the mixture was quenched with H2O, extracted with ether. The combined organic extracts were washed with brine, dried over MgS04, filtered, concentrated to afford the title compound as a brown solid (6.8 g, 87%). ^H NMR (400 MHz, DMSO-d 6 ): d 3.10 (s, 3H), 7.50 (m, 2H), 7.76 (t, J = 8.1 Hz, IH), 10.4 (s, IH). c) 2-Fluoro-5-[[-N-methyI]sulfonyl-N-benzyl]aminobenzonitrile To a stirred suspension of NaH (pre-washed with hexane, 60% oil, 0.20 g, 4.7 mmol) in DMF (15 mL) was added the compound from Example 4(b) (1.0 g, 4.7 mmol) in fluorobenzonitrile portions. After stirring at RT for lh, benzyl bromide (0.80 g, 4.7 mmol) was added, and stirred ovemight, quenched with H2O, extracted with ether, washed with brine, dried over MgSU4, concentrated, and purified by flash column chromatography (50% EtOAc/Hexane) to afford the title compound as an orange oil (1.03 g, 73%).1H NMR (400 MHz, CDCI3): d 3.05 (s, 3H), 4.80 (s, 2H), 7.20 (m, 6H), 7.50 (m, 2H). d) 2-Hydroxy-5- [N-benzyl-N-methylsuIfonyl]aminobenzonitrile A mixture of the compound from Example 4(c) (2 g, 6.7 mmol), KOAc (1 g, 10.1 mmol), and 18-crown-6 ether (2.7 g 10.17 mmol) in MeCN (30 mL) was heated at reflux for 24h. The mixture was cooled and 20 mL of IN NaOH were added, stirred at RT for 48 h, concentrated, extracted with ether (discarded). The aqueous layer was acidified, and extracted with EtOAc, dried over MgS04, and concentrated to give the title compound as an orange foam (1.2 g, 51%). l K NMR (400 MHz, CDCI3): d 3.05 (s, 3H), 4.75 (s, 2H), 6.90 (d, J = 9.1 Hz, IH), 7.31 (m, 7H). e) 2-Cyano-4-[[N-benzyl-N-methylsulfonyl]amino]phenyl glycidol A mixture of the compound of Example 4(d) (1.1 g, 3.8 mmol), K2CO3 ( 1.06 g, 7.6 mmol), and 2R-(-)-glycidyl-3-nitrobenzenesulfonate (1.0 g, 3.8 mmol) in acetone (20 mL) was heated at reflux in 24h. The mixture was cooled, concentrated, taken up in H2O, extracted with EtOAc(3x). The organic extracts were washed with saturated NaHC03, brine, dried over MgSθ4, filtered, and concentrated to afford the title compound as a yellow solid (1.4 g, 99%). *H NMR (400 MHz, CDCI3): d 2.85 (t, J = 4.5 Hz, IH), 2.97 (t, J = 4.5 Hz, IH), 3.00 (s, 3H), 3.40 (m, IH), 4.05 (dd, J = 5.4, 11.4 Hz, IH), 4.42 (dd, J = 2.6, 11.4 Hz, IH), 4.79 (s, 2H), 6.97 (d, J = 9.1 Hz, IH), 7.24 (m, 5H), 7.37(dd, J = 2.6, 9.1 Hz, IH), 7.41 (d, J = 2.6, IH). f) (R)- 3-[2-cyano-4-[N-benzyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol hydrochloride salt A mixture of the compound from Example 4(e) (0.50 g, 1.4 mmol), LiC104 (0.19 g, 1.4 mmol), and 4-methoxypheny 1-1,1 -dimethyl ethylamine(0.25 g, 1.4 mmol) in dried acetonitrile (5 mL) was heated at reflux in 24h. The mixture was cooled and concentrated, taken up in H2O, extracted with EtOAc (3x). The combined organic extracts were washed with brine, dried over MgS04, filtered, concentrated, and purified by flash column chromatography (4% MeOH/CH2Cl2) to afford a yellow foam which was stirred in methanol and added 4M HCl, concentrated, and triturated in ether to give the title compound as a yellow foam (0.70 g, 87%). 1 H NMR (400 MHz, DMSO-d 6 ): d 1.09 (s, 3H), 1.11( s, 3H), 2.41 (s, 3H), 2.64 (s, 2H), 3.10 (dd, J = 7.2, 14.4 Hz, IH), 3.25 (dd, J = 7.2, 14.4 Hz, 1H),3.08 (s, 3H), 3.78 (s, 3H),3.98 (m, IH), 4.20 (t, J = 7.2 Hz, 2H),4.60 (s, IH), 6.80 (d, J = 10.8 Hz, 2H), 6.95 (d, J = 10.8 Hz, IH), 7.06 (d, J = 10.8 Hz, IH), 7.11 (d, J = 3.6 Hz, IH), 7.27 (d, J = 10.8 Hz, 2H), 7.36 (d, J 10.8 Hz, IH), 7.41 (d, J = 10.8 Hz, 2H). MS (M+l, m z): 524.4. Anal. Calcd. for C29H35N3O5S HCl: C, 60.67; H, 6.32; N, 7.32; Found: C, 60.40; H, 6.30; N.7.50. Example 5 Preparation of (R)- 3-r2-cvano-4-rN-methyl-N-rmethylsulfonyIlamino1phenoxy1- 1-H-.1- dimethyl-2-(4-methoxyphenyl)ethylamino1-propan-2-ol hydrochloride salt a) 2-Methoxy-5-[[N-methyl]sulfonyl]aminobenzonitrile Following the procedure in Example 4(b), the title compound was prepared as a tan solid (2.50 g, 82%). 1H NMR (400 MHz, CDCI3): d 3.02 (s, 3H), 3.95 (s, 3H), 7.25 (d, J = 9.1 Hz, IH), 7.72 (d, J = 9.1 Hz, IH), 7.85 (s, IH), 9.60 (s, IH). b) 2-Methoxy-5-[N-methyl-N-methylsulfonyl]aminobenzonitrile Following the procedure in Example 3(a), the title compound was prepared as a yellow solid (0.44 g, 83%). 1H NMR (400 MHz, DMSO-d 6 ): d 3.02 (s, 3H), 3.25(s, 3H), 3.95 (s, 3H), 7.25 (d, J = 9.1 Hz, IH), 7.72 (d, J = 9.1 Hz, IH), 7.85 (s, IH). c) 2-Hydroxy-5-[N-methyl-N-methylsulfonyl]aminobenzonitrile Following the Example 3(b) the title compound was prepared as a tan solid (0.068 g, 16%). l U NMR (400 MHz, DMSO-d 6 ): d 3.02 (s, 3H), 3.25(s, 3H), 7.25 (d, J = 9.1 Hz, IH), 7.72 (d, J = 9.1 Hz, IH), 7.85 (s, IH). d) 2-Cyano-4-[[N-methyl-N-methylsulfonyl]amino]phenyl glycidol Following the procedure in Example 3(c), the title compound was prepared as a brown oil (0.083, 99%). *H NMR (400 MHz, CDC1 3 ): d 2.45 (s, 3H),2.85 (t, J = 4.5 Hz, IH), 2.97 (t, J = 4.5 Hz, IH), 3.00 (s, 3H), 3.40 (m, IH), 4.05 (dd, J = 5.4, 11.4 Hz, IH), 4.42 (dd, J = 2.6, 11.4 Hz, IH), 6.97 (d, J = 9.1 Hz, IH), 7.45 (m, 2H). e) (R)- 3-[2-cyano-4-[N-methyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol hydrochloride salt Following the procedure in Example 3(d), the title compound was prepared as a tan solid (0.07 g, 48%). MS (M+l, m/z): 462.2 Anal. Calcd. for C23H31N3O5SHCI H 2 0: C, 53.52; H, 6.64; N, 8.13; Found: C, 53.39; H, 6.38; N.7.94. Example 6 Preparation of (R)- 3-l " 2-cvano-4-r N-methylsuIfonylaminolphenoxyl- 1-f l,l-dimethyl-2-(4- methoxyphenyl)ethylaminol-propan-2-ol hydrochloride salt A solution of the compound of Example 4(f) (0.30 , 0.5 mmol) in MeOH (5 mL) was hydrogenated in 10% Pd/C (0.07 g) at RT in ovemight. The catalyst was filtered, and the filtrate was concentrated, and purified by flash column chromatography (7% MeOH/CH2θ2) to afford a yellow oil which was dissolved in MeOH and added 4M HCl in p-dioxane, concentrated, triturated in ether to afford the title compound as a yellow foam (0.08 g, 32%). *H NMR (400 MHz, CDCI3): d 1.04 (s, 3H), 1.06 (s, 3H), 2.62 (s, 2H), 2.82 (dd, J = 7.2, 14.4 Hz, IH), 2.92 (dd, J = 7.2, 14.4 Hz, IH), 2..97 (s, 3H), 3.77 (s, 3H), 3.95 (m, IH), 4.09 (d, J = 7.2 Hz, 2H), 6.80 (d, J = 10.8 HZ, 2H), 7.05 (d, J = 10.8 Hz, IH), 7.08 (d, J = 10.8 Hz, 2H), 7.42 (m, 2H).. MS (M+l, m/z): 448.3. Anal. Calcd. for C22H29N3O5SHCI2H2O: C, 51.10; H, 6.62; N, 8.12; Found: C, 50.86; H, 6.42; NJ.90. Example 7 Preparation of (R)- 3-r2-cvano-4-rN-benzvI-N-fmethylsulfonvnamino1phenoxy1- 1-11.1- dimethyl-2-(2-naphthyl)ethylamino1-propan-2-ol hydrochloride salt A mixture of Experiment 4e (0.36 g, 1 mmol), LiClθ4 (0.14 g, 1 mmol), and 1,1- dimethyl-2-[2-naphthyl]ethylamine (0.2 g, 1 mmol) in dried acetonitrile (8 mL) was heated at reflux in 24 h. The mixture was cooled and concentrated, taken up in H2O, extracted with EtOAc (3x). The combined organic extracts were washed with brine, dried over MgSO4, filtered, concentrated, and purified by flash column chromatography (3% MeOH/CH2Cl2) to afford the title compound as a yellow foam (0.40 g, 71%). l U NMR (400 MHz, CDCI3): d 1.09 (s, 3H), 1.11( s, 3H), 2.81 (dd, J = 7.2, 14.4 Hz, IH), 2.85 (d, J = 3.6 Hz, 2H), 2.90 (s, 3H), 2.96 (dd, J = 7.2, 14.4 Hz, 1H),3.91 (m, IH), 4.04 (d, J = 7.2 Hz, 2H), 4.76 (s, 2H), 6.95 (d, J = 7.2 Hz, IH), 7.27 (m, 1 IH), 7.55 (s, IH), 7.80 (m,2H). MS (M+l, m z): 468.2. Anal. Calcd. for C32H35N3O4SH2O: C, 66.75; H, 6.47; N, 7.29; Found: C, 66.84; H, 6.20; N.7.50. Example 8 Preparation of (R)- 3-l " 2-cvano-4-r N-rmethylsulfonyllaminolphenoxyl- l-H.l-dimethyl-2- (2-naphthyl)ethylaminol-propan-2-ol hydrochloride salt A solution of the compound from Example 7(a) (0.20 , 0.3 mmol) in MeOH (5 mL) was hydrogenated in 10% Pd/C (0.06 g) at RT in ovemight. The catalyst was filtered, and the filtrate was concentrated, and purified by flash column chromatography (5% MeOH/CH2θ2) to afford a yellow oil which was dissolved in MeOH and added 4M HCl in p-dioxane, concentrated, triturated in ether to afford the title compound as a yellow solid (0.08 g, 44%). ^H NMR (400 MHz, CDCI3): d 1.09 (s, 3H), 1.1 l(s, 3H), 2.81 (dd, J = 7.2, 14.4 Hz, IH), 2.85 (d, J = 3.6 Hz, 2H), 2.90 (s, 3H), 2.96 (dd, J = 7.2, 14.4 Hz, 1H),3.91 (m, IH), 4.04 (d, J = 7.2 Hz, 2H), 6.95 (d, J = 7.2 Hz, IH), 7.27 (m, 6H), 7.55 (s, IH), 7.80 (m, 2H). MS (M+l, m/z): 468.2. Anal. Calcd. for C25H29N3O4S HC10.25H 2 O: C, 55.60; H, 6.34; N, 7.70; Found: C, 55.60; H, 6.20; N.7.50. Example 9 Preparation of N-r(R)-2-Hvdroxy-3-(2-cvano-3-chlorophenoxy propyl-l.l-dimethyl-2- benzyloxyethylamine To a 0 °C mixmre of NaH (0.8g, 33.7 mmole) in DMF (15 mL) was added slowly 3- amino-3-methylpropanol. After stirring at 0 °C for 3h, the reaction was allowed to warm to room temperature and benzyl bromide (5J6g, 33 J mmole) was added slowly then stirred at room temperature an additional 18h. H2O (150 mL) was added to quench the reaction then the amine was extracted into diethyl ether (3x100 mL). The organic layers were combined, washed with saturated NaCl(aq) (100 mL), dried over sodium sulfate, and concentrated in vacuo. The residue was purified by short path distillation to afford 2. Ig of the title compound. GC/EI-MS m/z (rel. int.) 179 (M+, .0), 92 (6), 91 (75), 88 (8), 77 (11), 65 (26), 62 (6), 58 (100), 57 (6), 51 (7), 43 (5), 42 (17), 41 (10). Example 10 Preparation of (R)-l-n.l-dimethvI-2-(4-methoxyphenyl)ethylamino1-3-r2-cvano-4-(N.N- dipropylaminocarbonyl)phenoxy1-propan-2-ol hydrochloride salt a) Preparation of 2-cyano-4 (N,N-dipropyl aminocarbonyl)methoxy phenol. Methyl-3-cyano-4-methoxy benzoate (5g, 26 mmol Lancaster) was dissolved in 100 mL of methanol and treated with IM NaOH aqueous (52 mL, 52 mmol) for 5 h. at room temperature. The reaction was evaporated to half volume, acidified with aqueous 3N HCl, extracted with CHC13, dried over anhydrous MgS04, filtered and evaporated to give 3.5g of the corresponding acid which was carried on with out further purification. The material from above (3g, 16.9 mmol) was dissolved in 40 mL of benzene and 1 mL of DMF and treated with oxalyl chloride (1.52 mL, 17.4 mmol). The resulting reaction mixture was stirred at room temperature for 1.5 h. The reaction was cooled to 0 °C and treated with DIEA (4.55 mL, 26.1 mmol) and then split into four equal portions. One portion (6.33 mmol) was treated with dipropylamine (880 uL, 6.33 mmol) and then stirred at room temperature for 16 h. The reaction was diluted with EtOAc, washed with brine, dried over anhydrous MgS04, filtered and evaporated. The residue was purified by flash chromatography (silica gel 5% MeOH in CHC13) to give 820 mg of the above named compound. 1H NMR (CDC13, 250 MHz) d 7.6-7.3 (2H, m), 7.02 (IH, d), 3.97 (3H, s), 3.4-3.2 (4H, m), 1.6 (4H, br s), 0.9-0.8 (6H, m). b) Preparation of 2-cyano-4-(N,N-dipropylaminocarbonyI)phenol The compound of Example 10(a) (820 mg, 3.1 mmol) from above was dissolved in 40 mL of collidine and treated with Lil (845 mg, 6.31 mmol) and stirred at reflux for 16 h. The reaction was taken into 3N HCl, extracted with EtOAc, dried over anhydrous MgS04, filter and evaporated to give 630 mg (2.04 mmol) of the above named compound contaminated with approximately 20% of unreacted methyl ether. 1H NMR (CDCI3, 250 MHz) d 7.6-7.3 (2H, m), 7.02 (IH, d), 3.4-3.2 (4H, m), 1.6 (4H, br s), 0.9-0.8 (6H, m). c) Preparation of [2-cyano-4-(N,N-dipropylaminocarbonyl)]phenyl R-glycidyl ether The compound of example 10(b) (470 mg, 2.04 mmol), K2CO3 (563 mg, 4.08 mmol), and (2R)-(-)-glycidyl-3-nitrobenzenesulfonate (528 mg, 2.04 mmol) were heated in acetone (30 mL) at reflux for 18 h. The solvent was concentrated in vacuo to half of the volume, poured into H2O and extracted with EtOAc. The combined organic extracts were dried (MgSθ4), evaporated and the residue purified by column chromatography (silica gel, 80% EtOAc/hexanes) to give the titie compound as a clear oil. 1H NMR (CDCI3, 250 MHz) d 7.6-7.3 (2H, m), 7.02 (IH, d), 4.47-4.41 (IH, d of d), 4.13-4.08 (IH, m) 3.4-3.2 (5H, m), 2.86-2.83 (2H, m) 1.6 (4H, br s), 0.9-0.8 (6H, m). d) Preparation of (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol A solution of the compound of Example 10 (c) (380 mg, 2.1 mmol) and lidiium perchlorate (426 mg, 4.02 mmol) in ethanol (25 mL) was heated at reflux for 12 h. The reaction was evaporated and purified by flash chromatography (silica gel 5% MeOH in chloroform) to give the free base of the above name compound. This material was dissolved in dichloromethane and treated with 1 molar equivalent of IN HCl/methanol. Upon addition of ether, crystals formed and were subsequently collected and dried in a vacuum oven to give 150 mg of the title. ESMS [M+Hf = 482; 1H NMR (CDCI3, 360 MHz @ 300 K) d 7J-7J6 (2H, m), 7.2-7.1 (3H, m), 6.9-6.8 (2H, m), 4.3-4.2 (4H, m), 3J6 (3H, s), 3.5-3.1 (6H, m), 2.95 (2H, s), 1.7-1.5 (4H, m), 1.3 (6H, d), 0.9-0J (6H, m). Example 11 Preparation of (R)-l-π > l-dimethyl-2-(4-methoxyphenyl)ethylamino1-3-r2-cvano-4-(N- p prrooppyyllaammiinnoo))pphheennooxxyv1l--pprrooppaann--22--ooll a) Preparation of (R)-l-[l,l-dimethyI-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- propylamino)phenoxy]-propan-2-ol hydrochloride salt Following the procedure outlined in Example 10 but substituting propyl amine for dipropylamine in Example 10(a) 7 mg of the title compound was prepared. ESMS [M+H] * = 440; *H NMR (CDC1 3 , 360 MHz) @ 300 K d 7.7-7.76 (2H, m), 7.2-7.1 (3H, m), 6.9-6.8 (2H, m), 4.3-4.2 (4H, m), 3.76 (3H, s), 3.5-3.1 (4H, m), 2.95 (2H, s), 1.7-1.5 (2H, m), 1.3 (6H, d), 0.9-0.7 (3H, m). Example 12 Preparation of (R)-l-n.l-dimethyl-2-(4-methoxyphenyl)ethylamino1-3-r2-cvano-4-( N- piperidinvIcarbonyl)phenoxyl-propan-2-ol hydrochloride salt a) Preparation of (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- piperidinylcarbonyl)phenoxy]-propan-2-ol Following the procedure outlined in Example 10 but substituting piperidine for dipropylamine in Example 10(a.) 150 mg of the title compound was prepared. ESMS [M+H] + = 467, *H NMR (CDCI3, 360 MHz, @ 300 K) d 7.6-7.75 (2H, m), 7.1-7.0 (3H, m), 6.8-6.7 (2H, m), 4.13-3.91 (3H, m), 3.76 (3H, s), 2.95-2.8 (2H, m), 2.62 (2H, m), 1.6-1.5 (6H, m), 1.03 (6H, d). Example 13 Preparation of (R)-l-[l.l-dimethyl-2-(4-methoxyphenyl)ethylaminol-3-r2. 3-dichloro-4-(N- morpholvnylcarbonyl)phenoxy1-propan-2-ol hydrochloride salt (a) 2,3-Dichloro-4-bromoanisole. Bromination of 2,3-dichloroanisole (Aldrich, l.Og, 5.65 mmol) using the method of Wyrick, S.D.; Smith, F.T.; Kemp, W.E.; Grippo, A.A. Journal of Medicinal Chemistry, 1987, Vol. 30, No.10 P. gave 729 mg (50%) of the title compound as a white solid. 1H NMR (250 MHz, CDCI3) d 7.51 (d, J=8.5 Hz, IH), 6.77 (d, J=8.5 Hz, IH), 3.92 (s, 3H). (b) 2,3-Dichloro-4-(morpholinocarbonyl)anisole The compound of Example 13(a) (150 mg, 0.59 mmol) was dissolved in DMF (8 mL) and moφholine was added (0.52 mL, 5.9 mmol). Argon was bubbled through the solution for 5 min followed by CO for 5 min. Tetrakis(triphenylphosphine)palladium(0) was added (75 mg, 0.065 mmol), CO was bubbled for an additional 5 min, and the mixmre was stirred at 110 °C for 4h under CO (balloon). DMF was evaporated at reduced pressure and then azeotroped with xylenes. The residue was purified by flash chromatography (silica gel, .2.5 x 20.5 cm, 50% EtOAc/hexanes) to give 90 mg (53%) of the title compound . *H NMR(400 MHZ, CDCI3) d 7.19 (d, J=9.5 Hz, IH), 6.92 (d, J=9.5 Hz, IH), 3.94 (s, 3H), 3.93-3.83 (m, IH), 3.81-3.74 (m, 3H), 3.74-3.56 (m, 2H), 3.34-3.18 (m, 2H). (c) 2,3-Dichloro-4-(morpholinocarbonyl)phenol The compound of Example 13(b) (76 mg, 0.26 mmol) was demethylated following the method of T. Harrison J.C.S. Chem. Comm., 1969, p. 616 to give the title compound as a crude brown oil which was used in the next step without further purification. *H NMR(400 MHz, CDCI3) d 7.07 (d, J=10.5 Hz, IH), 7.03 (d, J=10.5 Hz, IH), 3.92-3.82 (m, IH), 3.82-3.72 (m, 3H), 3.72-3.55 (m, 2H), 3.36-3.19 (m, 2H). (d) 2,3-Dichloro-4-(N-morpholinocarbonyl)phenyl glycidyl ether. The compound of Example 13(c) (72 mg), (2R)-(-)-glycidyl 3-nitrobenzenesulfonate (85 mg, 0.33 mmol), and K2CO3 (50 mg, 0.36 mmol) were stirred at reflux in acetone for 14h. The reaction mixture was cooled, filtered, evaporated, and the residue was purified by flash chromatography (silica gel, 2.5 x 17.5 cm, 50%-70%-100% EtOAc/hexanes) to give 42 mg (49%) of the title compound. 1H NMR(250 MHz, CDCI3) d 7.17 (d, J=8.5 Hz, IH), 6.95 (dd, J=7.9, 7.2 Hz, IH), 4.46-4.31 (m, IH), 4.08-3.98 (m, IH), 3.95-3.85 (m, IH), 3.85-3.72 (m, 3H), 3.72-3.53 (m, 2H), 3.46-3.36 (m, IH), 3.36-3.15 (m, 2H), 3.00-2.78 (m, 2H). (e) (R)-l-[l,l-diethyl-2-(4-methoxyphenyl)ethylamino]-3-[2,3-dichloro-4-(N- morpholinocarbonyl)phenoxy]-propan-2-ol hydrochloride salt The compound of 13(d) (42 mg, 0.127 mmol) and 1,1 -dimethy 1-2- (4-methoxyphenyl)ethylamine (28 mg, 0.156 mmol) were dissolved in CH3CN (10 mL), LiClθ4 (21 mg, 0.197 mmol) was added, and the mixture was stirred at reflux for 18h. The mixture was concentrated in vacuo and purified by flash chromatography (silica gel, 2.5 x 17.5 cm, 200 mL 5% MeOH/CHCl 3 , 100 mL 10% MeOH/CHCl 3 ) to give 55 mg (85%) of the title compound as its free base. This material was converted to the corresponding HCl salt by dissolving the free base in CH2CI2, treating the resulting solution with 105 uL of HCl in MeOH and then first evaporating the CH2CI2 followed by evaporating from hexanes. MS (ES) m/e 511.2 [M+H] + ; J H NMR(360 MHz, DMSO/TFA) d 8.58 (m, 2H), 7.39 (d, J=8.6, IH), 7.29 (d, J=8.6, IH), 7.16 (d, J=8.6, 2H), 6.92 (d, J=8.6, 2H), 4.30-4.11 (m, 3H), 3.76 (s, 3H), 3.73-3.61 (m, 4H), 3.58-3.51 (m, 2H), 3.40-3.28 (m, IH), 3.21-3.07 (m, 3H), 2.92 (s, 2H), 1.23 (s, 6H). Example 14 Preparation of (RV 3-r2-cvano-4-rN-methyl-N'-morpholino1ureidolphenoxyl-l-[l.l- dimethyl-2-(2-naphthyl)ethylaminol-propan-2-ol; a) 2-Methoxyl-5-N-[[4-morphoIino]carbonyl]amino benzonitrile To a stirred mixture of 2-methoxyl-5-aminobenzonitrile (2 g, 12.34 mmol), and pyridine (1.28 g, 16.2 mmol) in dried CH2CI2 (20 mL) was added 4-moφholinecarbonyl chloride (2.42 g, 16.2 mmol). After stirring at RT for 24 h, the mixture was diluted with CH2CI2 and washed with H2O, brine, dried over MgS04, concentrated to give an orange solid (3.04g, 86%) 1H NMR: (400MHz, DMSO-d 6 ): d 3.23 (t, J = 4.9Hz, 4H), 3.47 (t, J = 4.9 Hz, 4H), 3.9 (s, 3H), 6.89 (d, J = 9 Hz, IH), 7.3 (d, J = 9Hz, IH), 8.01 (s, IH). b) 2-Methoxyl-5-[N-methyl-N-[[4-morphoIino]carbonyl]amino] benzonitrile. To a stirred suspension of NaH (60%, pre-washed with hexane, 0.2 g, 4.98 mmol) in dry DMF (10 mL) was added example 14a (1 g, 3.8 mmol) . After stirring at RT in 1 h, methyl iodide (1.62 g, 11.5 mmol) was added and stirred ovemight, taken up in H2O, extracted with EtOAc. The organic extracts were washed with brine, dried over MgSθ4, concentrated to give a brown oil (1.0 g, 98%). *H NMR: (400MHz, DMSO-d 6 ): d 2.95 (s, 3H), 3.23 (t, J = 4.9Hz, 4H), 3.47 (t, J = 4.9Hz, 4H), 3.9 (s, 3H), 6.89 (d, J = 9 Hz, IH), 7.3 (d, J=9Hz, IH), 8.01 (s, IH). c) 2-Hydroxy-5-[N-methyl-N-[[4-morpholino]carbonyl]amino]benzonitrile. Following the example le, the title compound was prepared as a yellow oil (0.33g, 40%). 1H NMR: (400MHz, DMSO-d 6 ): d 2.95 (s, 3H), 3.23 (t, J = 4.9Hz, 4H), 3.47 (t, J = 4.9Hz, 4H), 6.89 (d, J = 9Hz, IH), 7.3 (d, J = 9Hz, IH), 8.01 (s, IH). d) 2-Cyano-5-[N-methyl-N-[[4-morpholino]carbonyl]amino]phenyl glycidol. Following the example lf, the title compound was prepared as a brown oil (0.23g, 60%). !H NMR (400MHz, DMSO-d 6 ): d 2.85 (t, J = 4.5Hz, IH), 2.95 (s, 3H), 2.97 (t, J = 4.5Hz, IH), 3.23 (t, J = 4.9Hz, 4H), 3.42 (m,lH), 3.47 (t, J = 4.9Hz, 4H), 4.12 (dd, J = 5.4, 11.4Hz, IH), 4.42 (dd, J = 5.4, 11.4Hz, IH), 6.89 (d, I = 9 Hz, IH), 7.3 (d, J = 9Hz, IH), 8.01 (s, IH). e) Synthesis of (R)- 3-[2-cyano-4-[N-methyl-N'-morpholino]ureido]phenoxy]-l-[l,l- dimethyI-2-(2-naphthyI)ethylamino]-propan-2-ol. Following the procedure in example 7, the title compound was prepared as an off white foam (0.6g, 56%) *H NMR (400 MHz, DMSO-d 6 ): d 1.09 (s, 3H), 1.11 (s, 3H), 2.85 (t, J=4.5Hz, IH), 2.95 (s, 3H), 2.97 (t, J = 4.5Hz, IH), 3.23 (t, J = 4.9Hz, 4H), 3.42 (m,lH), 3.47 (t, J = 4.9Hz, 4H), 4.12 (dd, J = 5.4, 11.4Hz, IH), 4.42 (dd, J = 5.4, 11.4Hz, IH), 7.12 (d, J = 7.2 Hz, IH), 7.27 (m, 5H), 7.35 d, J = 7.2Hz, IH), 7.55 (s, IH), 7.67 (s, IH), 7.76 (d, J = 7.2Hz, IH). MS (m+l, m/z): 417.6. Anal. Calcd. for C3 0 H3 6 N 4 O 4 1.5H 2 O: C, 66.28; H, 7.23; N, 10.3; Found: C, 66.61; H, 6.96; N, 9.92. Example 15 N-r3-(2.3-dichloro-4-dipropylsulfamoyl)phenoxy-2(R)-hvdroxypropyll-2-(4- methoxyphenylVl.l-dimethylethylamine hydrochloride a) (2,3-dichloro-4-methoxy)phenylsufonylchloride 2,3-dichloroanisole (Aldrich, 9.0g, 50.8mmole) was utilized in the method of H. Harada et al Chem Pharm Bull (1987) 35(8) 3195-3214 to give the title compound as a white solid (13.3, 95%). b) N,N-dipropyl-(2,3-dichloro-4-methoxy)phenylsuIfonamide The compound of 15(a) (8.0g, 29.0 mmol) was dissolved in CH2CI2 (200 mL) and dipropylamine (11.9 mL, 87.1 mmol) in EtOH (40 ml) was added at -20 °C. The ice bath was removed and the mixture stirred 1.5 h. The mixture was poured into H2O and extracted with CH2CI2. The combined organic extracts were washed with H2O, brine concentrated in vacuo and azeotroped with toluene to yield the title compound as a light brown-tinted oil (9.8g, 100%). H NMR (400MHz, CDCI3) d 8.05 (d, J=10Hz, IH), 6.92 (d, J=10Hz, IH), 4.00 (s, 3H), 3.23 (t, J=8, 17Hz, 4H), 1.52 (m, 4H), 0.83 (t, J=8,13Hz, 6H). c) N,N-dipropyl-2,3-dichloro-4-hydroxyphenylsulfonamide The compound from Example 15(b) (10.0 g, 29.4 mmol), I2 (14.9 g, 58.8 mmol) and trimethylphenylsilane (15.1 mL, 88.2 mmol) were stirred together and heated to 110 C for 18 h. The mixture was poured into aqueous Na2S2θ3, extracted with EtOAc, dried (MgSO4), concentrated to dryness in vacuo and purified by column chromatography (silica gel, 40%EtOAc/Hexanes) to give a clear oil (9.2g, 86%). *H NMR (400MHz, CDCI3) d 7.98 (d, J=10 Hz, IH), 7.05 (d, J=10Hz, IH), 6.29 (bs, IH), 3.24(t, J=9, 18Hz, 4H), 1.56 (m, 4H), 0.84 (t, J=8,14 Hz, 6H). d) [2,3-dichloro-4-(N,N-dipropylsulfamoyl)]phenyl glycidyl ether The compound of Example 15(c) (5.0 g, 15.3 mmol), K2CO3 (6.4 g, 46.0 mmol), and (2R)-(-)-glycidyl 3-nitrobenzenesulfonate (5.6 g, 15.3 mmol) were heated in acetone (250 mL) to reflux 18 h. The solvent was concentrated in vacuo to half volume, poured into H2O, extracted with EtO c, the combined organic extracts were dried over MgSO4, evaporated and purified by column chromatography (silica gel, 40% EtOAc/Hexanes) to give the title compound as a clear oil (4.9g, 84%). l U NMR (400MHz, CDCI3) d 8.04 (d, J=8Hz, IH), 6.94 (d, J=8Hz, IH), 4.45 (dd, J=l,9Hz, IH), 4.11 (dd, J=7,l lHz, IH), 3.44 (m, IH), 3.24 (t, J=9,18Hz, 4H), 2.97 (m,lH), 2.87(m, IH), 1.52 (m, 4H), 0.84 (t, J=6,14Hz, 6H). e) N-[3-(2,3-dichloro-4-dipropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-N-[2-(4- methoxyphenyl)-l,l-dimethyl]ethyIamine hydrochloride salt The compound from Example 15(d) (1.6 g, 4.2 mmol), 1,1 -dimethy l-2-(4- methoxyphenyl)ethylamine (0J5 g, 4.2 mmol) and LiClθ4 (0.89 g, 8.4 mmol) were dissolved in CH3CN (150 mL) and refluxed 18h. The mixture was concentrated in vacuo and purified by column chromatography (silica gel, 8%MeOH/CH2Cl2) to yield the title compound as a white solid (l.Og, 44%). This was converted to the HCl salt by adding 1J mL of IM HCl in MeOH, stirring 5 min, concentrating in vacuo, azeotroping with toluene then CH2CI2. MS (ES) m/e 561.1[M+H]VH NMR (400MHz, CDCI3) d 9.94 (bs, IH), 8.02 (d, J=8Hz, IH), 7.14 (d, J=8Hz, 2H), 6.96 (d, J=8Hz, IH), 6.86 (d, J=7Hz, IH), 4J8 (m, IH), 4.30 (m, IH), 4.20 (m, IH), 3.80 (s, 3H), 3.68 (m, 2H), 3.43 (bs, IH), 3.23 (t, J=7,14Hz, 4H), 3.12 (m, 2H), 1.50 (q, J=5,13Hz, 4H), 1.43 (s, 3H), 1.38 (s, 3H), 0.83 (t, J=8,13, 6H). Example 16 N-r3-(2.3-dichloro-4-dipropylsulfamoyl)phenoxy-2(R)-hvdroxypropyll-2-(2.3- dichlorophenyl)-l.l-dimethylethylamine hydrochloride Following the procedure of Example 15, except substituting 1,1 -dimethy l-2-(2,3- dichlorophenyl)ethylamine for l,l-dimethyl-2-(4-methoxyphenyl)ethylamine, the title compound was prepared (33 mg). MS (ES) m/e 599.1 [M+H] + ; 1H NMR (400MHz, CDCl 3 )d 8.01(d, J=10Hz, IH), 7.36(m, 2H), 7.06(d, J=9Hz, IH), 6.94(d, J=10Hz, IH), 4.60(bm, IH), 4.18(m, 2H), 3.34(d, J=l lHz, IH), 3.23(t, J=7Hz, 4H), 3.18(d, J=12Hz, IH), 3.08(s, 2H), 1.53(q, J=6,13Hz, 4H), 1.34(2 x s, 6H), 0.84(t, J=10Hz, 6H). Example 17 N-r3-(3-chloro-2-cvano-4-dimethylsulfamoyl)phenoxy-2(R)-hvdroxypropyll-2-(4- methoxyphenyl " )-Ll-dimethylethylamine hydrochloride a) 2-Chloro-6-methoxybenzonitrile 2-Chloro-6-fluorobenzonitrile (Aldrich, 5.0 g, 32.1 mmol) was dissolved in MeOH (100 mL), NaOMe (7.4 mL of 25%wt. solution, 32.1 mmol) and refluxed 18h. The mixture was concentrated poured into EtOAc/H2θ and extracted with EtOAc to give the title compound (5.3g, 59%). b) (2-chloro-3-cyano-4-methoxy)phenylsulfonylchloride Following the procedure from example 15(a) except substituting compound example 17(a) for 2,3-dichloroanisole, the title compound was prepared. c) N-[2(R)-hydroxy-3-(3-chloro-2-cyanophenoxy-4-dimethylsulfonamidyl)propyI]-N-[2-(4- methoxyphenyl)-l,l-dimethylethyl]amine hydrochloride Following the procedure of Example 15(b)-15(e), except substituting dimethylamine for dipropylamine, and substituting compound of example 17 (b) for Example 15(a) the title compound was prepared (21 mg) MS (ES) m/e 496.2[M+H] + ; 1 H NMR (400MHz, CDC1 ) d 8.22(d, J=10Hz, IH), 7.1 l(m, 3H), 6.82(d, 2H), 4.28(m, 2H), 4.20(m, IH), 3.80(s, 3H), 3.12(dd, J=2,12Hz, IH), 2.98(dd, J=10, 12Hz, IH), 2.88(s,6H), 2J8(s, 2H), 1.18(s, 6H). Example 18 N-r3-(2.3-dichloro-4-morpholinosulfamoyl)phenoxy-2(R)-hvdroxypropyll-2-(4- methoxyphenvD-l.l-dimethylethylamine Following the procedure of Example 15, except substituting moφholine for dipropylamine, the title compound was prepared (5mg). 1H NMR (400MHz, CDCI3) d 8.04(d, J=8Hz, IH), 7.14(d, J=9Hz, 2H), 7.00(d, J=9Hz, IH), 6.87(d, J=8Hz, 2H), 4J6(m, IH), 4.28(m, 2H), 3.82(s, 3H), 3Jl(m, 5H), 3.49(m, IH), 3.24(m, 4H), 3.1 l(m, 2H), 1.52(s, 3H), 1.43(s, 3H). Example 19 N-r3-(3-chloro-2-cvano-4-morpholinosulfamoyl)phenoxy-2(R)-hvdroxypropyn-2-(4- methoxyphenvD-l.l-dimethylethylamine hydrochloride The title compound (70 mg) was prepared by the method of Example 17(c) substituting the method of I. T. Harrison Chem. Comm. 1969 p. 616 for procedure from example 1(c) and substituting moφholine for dimethylamine. MS (ES) m/e 538.2ΪM+H] * ; 1 !! NMR (400MHz, CDC1 3 ) d 8.20(d, J=9Hz, IH), 7.120m, 3H), 6.81(d, J=9Hz, IH), 4.20-4.31(m, 3H), 3.80(s, 3H), 3.72(m, 4H), 3.28(m, 4H), 3.13(d, J=10Hz, IH), 3.00(m, IH), 2.80(s, 2H), 1.18(s, 6H). Example 20 N-r3-(3-chloro-2-cvano-4-pyrrolidinosulfamoyl)phenoxy-2(R)-hvdroxypropyn-2-(4- methoxyphenyl)-l,l-dimethylethylamine hydrochloride; The title compound (105 mg) was prepared by the method of Example 19 substituting pyrrolidine for moφholine. MS (ES) m/e 522.1^+^;^ NMR (400MHz, CDCI3) d 8.23(d, J=9Hz, IH), 7.1 l(d, J=9Hz, 2H), 7.07(d, J=9Hz, IH), 6.83(d, J=9Hz, 2H), 4.27(d, J=4Hz, 2H), 4.18(m, IH), 3.80(s, 3H), 3.40(m, 4H), 3.10(dd, J=2.10Hz, IH), 2.94(dd, J=8,12Hz, IH), 2J5(s, 2H), 1.95(m, 4H), 1.16(s, 6H). Example 21 N-r3-(3-chloro-2-cvano-4-pyrrolidinosulfamoyl)phenoxy-2(R)-hvdroxypropyIl-2-(4- fluorophenyl)-l.l-dimethylethylamine hydrochloride: The title compound (35 mg) was prepared by the method of Example 20 substituting, l,l-dimethyl-2-(4-fluorophenyI)ethylamine for ), 1,1 -dimethy l-2-(4- methoxyphenyl)ethylamine. MS (ES) m/e SlO.lfM+Hf; 1 !! NMR (400MHz, CDCI3) d 8.20(d, J=l lHz, IH), 1.10-7.30(m, 3H), 6.99(m, 2H), 4.89(m, IH), 4.03(dd, J=2,10Hz, IH), 3.95(dd, J=4,12Hz, IH), 3.39(m, 5H), 3.24(dd, J=3,10Hz, IH), 1.96(m, 4H), 1.23(s, 6H). Example 22 N-r3-(3-chloro-2-cvano-4- p yrrolidinosulfamoyl) p henoxy-2(R)-hvdrox yp ro p yH-2- ( 2- napthvD-l.l-dimethylethylamine hydrochloride The title compound (130 mg) was prepared by the method of Example 20 substituting , l,l-dimethyl-2-(2-napthylethy lamine for ), l,l-dimethyl-2-(4-methoxyphenyl)ethylamine. MS (ES) m e 542.2[M+H] + ;1H NMR (400 MHz, CDCI3) d 8.23(d, J=10Hz, IH), 7.80(m, 3H), 7.67(s, IH), 7.45(m, 2H), 7.35(d, IH), 3.38(m, 4H), 3.19(d, J=12Hz, IH), 3.06(m, IH), 3.04(s, 2H), 1.95(m, 4H), 1.37(s, 6H). Example 23 N-r3-(3-chloro-2-cvano-4-morphoIinosulfamoyl phenoxy-2(R)-hvdroxypropyll-2-(4- fluorophenyl)-l.l-dimethylethylamine hydrochloride The title compound (130 mg) was prepared by the method of Example 19 substituting 1,1 -dimethy l-2-(4-fluorophenyl)ethy lamine) for l,l-dimethyl-2-(4-methoxyphenyl)ethylamine. MS (ES) m/e 526.2^+^^ NMR (400MHz, CDCI3) d 8.20(d, J=9Hz, IH), 7.22(m, 2H), 7.13(d, J=9HZ, IH), 7.01(d, J=9Hz), 4.82(d, J=7Hz, IH), 4.68(m, IH), 4.39(m, 2H), 3J3(m, 4H), 3.55-3.36(m, 2H), 3.27(m, 4H), 3.12(dd, J=12,22Hz, 2H), 1.45(2xs, 6H). Example 24 N-r3-(3-chloro-2-cvano-4-morpholinosulfamoyl " )phenoxy-2(R)-hvdroxypropyll-2-(2- naphthvD-l.l-dimethylethylamine hydrochloride The title compound (100 mg) was prepared by the method of Example 19 substituting , l,l-dimethyl-2-(2-napthylethylamine) for 1,1 -dimethy l-2-(4-methoxyphenyl)ethy lamine. MS (ES) m/e 558.2^+^;^ NMR (400MHz, CDCI3) d 8.17(d, J=9Hz, IH), 7J8(m, 3H), 7.65(s, IH), 7.45(m, 2H), 7.33(d, J=10Hz, IH), 7.03(d, J=9Hz, IH), 4.26(d, J=3Hz, 2H), 4.20(m, IH), 3J5(m, 4H), 3.26(m, 4H), 3.17(dd, J=2,12Hz, IH), 3.01(m, 3H), 1.23(s, 6H). Example 25 N-r3-(3-chloro-2-cvano-4-thiomorpholinosulfamoyl)phenoxy-2(R)-hvdroxypropyll-2-(2- naphthvD-l.l-dimethylethylamine hydrochloride The title compound (30 mg) was prepared by the method of Example 24 substituting thiomoφholine for moφholine. MS (ES) m/e 574.2[M+H] + ; 1H NMR (400MHz, CDCI3) d 8.17(d, J=9Hz, IH), 7J7(m, 3H), 7.66(s, IH), 7.43(m, 2H), 7.32(d, J=9Hz, IH), 7.02(d, J=9Hz, IH), 4.23(m, 3H), 3.54(m, 4H), 3.13(d, J=12Hz, IH), 3.02(m, 3H), 2.68(m, 4H), 1.26(s, 6H). Example 26 N-r3-(3-chloro-2-cvano-4-thiomorpholinosulfamoyl)phenoxy-2(R)-hvdroxypropyl1-2-(4- methoxyphenvD-l.l-dimethylethylamine hydrochloride The title compound (30 mg) was prepared by the method of Example 19 substituting thiomoφholine for moφholine. MS (ES) m/e 554.3[M+H] + ; 1 H NMR (400MHz, CDC1 3 ) d 8.13(d, J=10Hz, IH), 7.02(d, J=9Hz, 2H), 6.98(d, J=10Hz, IH), 6J6(d, J=9Hz, 2H), 4.17(d, I=4Hz, 2H), 4.02(m, IH), 3J3(s, 3H), 3.52(m, 2H), 2.97(dd, I=2,10Hz, IH), 2.82(dd, J=8,l lHz, IH), 2.64(m, 6H), 1.06(s, 6H). Example 27 N-r3-r3-chloro-2-cvano-4-(2'-cvanoeth-l-yl)-cvclopropylsulfamovHphenoxy-2(R)- hvdroxypropyIl-2-(4-methoxyphenyl)-l.l-dimethylethylamine hydrochloride The title compound (70 mg) was prepared by the method of Example 19 substituting 3- (cyclopropylamino)propionitrile (Transworld Chemicals) for moφholine. MS (ES) m/e 561.3CM+H3MH NMR (400MHz, CDCI3) d 8.20(d, J=Hz, IH), 7.01(d, J=8Hz, 3H), 6J4(d, J=9Hz, IH), 4.18(m, 2H), 3.96(m, IH), 3.69(m, 5H), 2.94(dd, J=3,l lHz, IH,) 2J8(d, IH), 2J3(t, J=7,12Hz, 2H), 2.49(m, IH), 1.04(s, 6H), 0.62(m, 2H), 0.53(m, 2H). Example 28 N-r3-r3-chloro-2-cvano-4-(2'-cvanoeth-l-yl)-cvclopropyIsuIfamoyllphenoxy-2(R)- hvdroxypropyl1-2-(2-napthyl -l.l-dimethvIethylanιine hydrochloride The title compound (85 mg) was prepared by the method of Example 27 substituting l,l-dimethyl-2-(2-napthylethy lamine) for 1,1 -dimethy l-2-(4-methoxyphenyl)ethy lamine. MS (ES) m/e 581.3[M+H] + ; 1 H NMR (400MHz, CDCI3) d 8.17(d, J=10Hz, IH), 7Jl(m, IH), 7.67(d, J=9Hz, 2H), 7.53(s, IH), 7.38(m, 2H), 7.26(d, J=8Hz, IH), 6.94(d, J=9Hz, IH), 4.15(m, 2H), 3.96(m, IH), 3.69(t, J=8,14Hz, 2H), 2.98(dd, I=2,12Hz, IH), 2.82(m, 3H), 2J4(t, J=2,12Hz, 2H), 2.49(m, IH), 1.08(s, 6H), 0.59(m, 2H), 0.40(m, 2H). Example 29 N-r3-r3-chloro-2-cvano-4-(benzvI-cvclopropyl)sulfamoyllphenoxy-2(R)-hvdroxypropyl1-2- (2- napthyl)-l.l-dimethylethylamine hydrochloride: a) N-cyclopropyl(2-chloro-3-cyano-4-methoxyphenyl)sulfonamide The title compound was prepared utilizing the compound of Example 17(b) by the method of Example 15(b) substituting cyclopropy lamine (Aldrich) for dipropylamine. b) N-cyclopropyl-N-benzyl(2-chloro-3-cyano-4-methoxyphenyl)sulfonamide The compound of Example 29(a) (1.3 g, 5.0 mmol), K2CO3(0.69 g, 5.0 mmol) and benzyl bromide (0.60 mL, 5.0 mmol) in acetone (40 mL) were refluxed 18 h. The solution was concentrated and poured into EtOAc/H2θ and extracted with EtOAc, dried and concentrated to dryness in vacuo to yield the title compound (1.8g, 96%). *H NMR (400 MHz, CDCI3) d 8.25(d, J=10Hz, IH), 7.39-7.20(m, 5H), 6.92(d, J=10Hz, IH), 4.58(s, 2H), 3.96(s, 3H), 2.26(m, IH), 0.46(m, 2H), 0.36(m, 2H) c) N-2(R)-hydroxy-3-[3-chloro-2-cyano-4-[(N-propionitrile-N- cyclopropyl)sulfamidyl]phenoxypropyl]-N-[2-(2-napthylphenyl)-l,l-dimethylethyl]amine hydrochloride The title compound (25 mg) was prepared by the method of Example 24 substituting the compound of Example 29(b) for. N-moφholino(2-chloro-3-cyano-4- methoxyphenyl)sulfonamide. MS (ES) m/e 618.3[M+Hf ^H NMR (400MHz, CDCI3) d 8.16(d, J=10Hz, IH), 7J0(m, 3H), 7.57(s, IH), 7.36(m, 4H), 7.25(m, 4H), 6.88(d, J=9Hz, IH), 4.54(s, 2H), 4.14(d, J=3Hz, 2H), 4.01(m, IH), 3.02(dd, J=2,l lHz, IH), 2.87(m, 3H), 2.22(m, IH), 2.1 l(m, 6H), 0.46(m, 2H), 0.33(m, 2H). Example 30 N-r3-r3-chloro-2-cvano-4-(benzyl-cyclopropyl)sulfamoyllphenoxy- ' 2(R)-hvdroxypropyll-2- (4-methoxγphenyl)-l.l-dimethylethylamine hydrochloride: The title compound (105 mg) was prepared by the method of Example 29 substituting 1,1 -dimethy l-2-(4-methoxyphenyl)ethylamine for l,l-dimethyl-2-(2-napthylethylamine). MS (ES) m/e 598.3^+^^ NMR (400MHz, CDCI3) d 8.18(d, J=9Hz, IH), 7.36-7.13(m, 5H), 7.01(d, J=9Hz, 2H), 6.95(d, J=10Hz, IH), 6J2(d, J=9Hz, 2H), 4.56(s, 2H), 4.15(m, 2H), 4.01(m, IH), 3J0(s, 3H), 2.98 (m, IH), 2.84(d, J=9,12Hz, IH), 2.62(s, 2H), 2.22(m, IH) 1.04(s, 6H), 0.44(m, 2H), 0.35(m, 2H). Example 31 N-r3-r3-chloro-2-cvano-4-(4'-N-t-butoxycarbonylpiperazino)sulfamovπphenoxy)-2(R)- hvdroxypropyll-2-(4-methoxyphenyl)-l.l-dimethylethylamine hydrochloride The title compound (20 mg) was prepared by the method of Example 19 substituting t- butyl-1-piperazinecarboxylate (Aldrich) for moφholine. MS (ES) m/e 637.4[M+H] >^H NMR (400MHz, CDC1 3 ) d 8.15(d, J=9Hz, IH), 7.05(m, 4H), 6J7(m, 3H), 4.21(m, 3H), 3J3(s, 3H), 3.46(m, 4H), 3.27(m, 4H), 3.07(m, IH), 2.92(m, IH), 2J2(s, 2H), 1.41(s, 9H), 1.12(s, 6H). Example 32 N-r3-(2.3-dichIoro-4-dipropylsulfamoyl)phenoxy-2(R)-hvdroxypropyn-2-(2-naphthyl)-l.l- dimethylethylamine hydrochloride Following the procedure of Example 15, substituting 1,1 -dimethy l-2-(2- naphthyl)ethylamine for 1,1 -dimethyl- 2-(4-methoxyphenyl)ethylamine in 15(e), the title compound was prepared (157 mg). MS (ES) m/e 581.2 [M+H] + ;1H NMR (400MHz, CDCI3) dlO.OO (m, IH), 8.24 (m, IH), 7.98 (d, J=10.5Hz, IH), 7.81 (m, 3H), 7J3 (s, IH), 7.48 (m, 2H), 7.34 (d, J=8Hz, IH), 6.87 (d, J=10.5Hz, IH), 4.80 (m, IH), 4.28-4.12 (m, 2H), 3.55-3.30 (m, 2H), 3.37 (s, 2H), 3.23 (t, J=8Hz, 4H), 1.53 (m, 10H), 0.83 (t, J=8Hz, 6H). Example 33 N-r3-(2.3-dichloro-4-propylsulfamoyl)phenoxy-2(R)-hvdroxypropyll-2-(4-methoxyphenyl)- 1.1-dimethylethylamine hydrochloride Following the procedure of Example 15, substituting propylamine for dipropylamine in 1(b), the title compound was prepared (211 mg). MS (ES) m/e 519.1 [M+Hp^H NMR (400MHz, DMSO) d 9.00 ( , IH), 8.69 (m, IH), 7.95 (d, J=9Hz, IH), 7.92 (m, IH), 7.37 (d, J=9Hz, IH), 7.15 (d, J=9Hz, 2H), 6.91 (d, J=9Hz, 2H), 6.04 (m, IH), 4.38-4.23 (m, 3H), 3J4 (s, 3H), 3.39-3.28 (m, IH), 3.19-3.06 (m, IH), 2.95 (s, 2H), 1.42-1.31 (m, 2H), 1.22 (s, 6H). Example 34 N-[3-(2.3-dichloro-4-sulfamovI)phenoxy-2(R)-hvdroxypropyn-2-(4-methoxyphenyl)-l.l- dimethylethylamine hydrochloride Following the procedure of Example 15, substituting ammonia (2M in methanol) for dipropylamine in 15(b), the title compound was prepared (14 mg). Purification by preparative HPLC [PRP-1, 21.5x250 mm, 30% CH 3 CN/H 2 0 containing 0.1% TFA]. MS (ES) m/e 477.0 [M+H] + ; Η NMR (360 MHz, CDC1 3 ) d7.98 (d, J=9.5Hz, IH), 7.10 (d, J=12Hz, 2H), 6.93 (d, J=l lHz, IH), 6.85 (d, J=9.5Hz, 2H), 4.55 (m, IH), 4.29-4.21 (m, IH), 4.15-4.08 (m, IH), 3.78 (s, 3H), 3.43-3.33 (m, IH), 3.19-3.09 (m, IH), 2.98 (dd, J=13, 39 Hz, 2H), 1.44 (s, 3H), 1.35 (s, 3H). Example 35 N-r3-(2.3-dichloro-4-methylsulfamoyl)phenoxy-2(R)-hvdroxypropyll-2-(4-methoxyphenyl)- 1.1-dimethylethylamine hydrochloride Following the procedure of Example 15, substituting methy lamine (2M in methanol) for dipropylamine in 15(b), the title compound was prepared (123 mg). MS (ES) m/e 491.1 [M+H]VH NMR (400MHz, DMSO) d 7.94 (d, J=9Hz, IH), 7.75 (m, IH), 7.39 (d, J=9Hz, IH), 7.14 (d, J=9Hz, 2H), 6.89 (d, J=9Hz, 2H), 4.36-4.19 (m, 3H), 3.74 (s, 3H), 3.33-3.23 (m, IH), 3.15-3.03 (m, IH), 2.92 (s, 2H), 2.45 (d, J=6 Hz, 3H), 1.20 (s, 6H). Example 36 N-r3-(2.3-dichloro-4-pyrrolidinosulfamoyl)phenoxy-2(R)-hvdroxypropyn-2-(4- methoxyphenvD-l.l-dimethylethylamine hydrochloride Following the procedure of Example 15, substituting pyrrolidine for dipropylamine in 15(b), the title compound was prepared (255 mg). MS (ES) m/e 531.2 [M+HJ^H NMR (400MHz, DMSO) d 9.05 (m, IH), 8.72 (m, IH), 7.97 (d, J=10.5Hz, IH), 7.39 (d, J=10.5Hz, IH), 7.15 (d, J=9Hz, 2H), 6.90 (d, J=9Hz, 2H), 6.08-6.00 (m, IH), 4.39-4.23 (m, 3H), 3.73 (s, 3H), 3.32-3.21 (m, 5H), 3.19-3.06 (m, IH), 2.95 (s, 2H), 1.85 (m, 4H), 1.22 (s, 6H). Example 37 N-r3-(2.3-dichloro-4-piperidinosulfamoyl)phenoxy-2(R)-hvdroxypropyll-2-(4- methoxyphenyl)-l.l-dimethylethylaπune hydrochloride Following the procedure of Example 15, substituting piperidine for dipropylamine in 15(b), the title compound was prepared (800 mg). MS (ES) m/e 545.3 [M+H]VH NMR (400MHz, DMSO) d 9.05 (m, IH), 8.74 (m, IH), 7.97 (d, J=9Hz, IH), 7.40 (d, J=9Hz, IH), 7.16 (d, J=9Hz, 2H), 6.91 (d, J=9Hz, 2H), 6.09-6.00 (m, IH), 4.40-4.22 (m, 3H), 3.75 (s, 3H), 3.40- 3.27 (m, IH), 3.22-3.06 (m, 5H), 2.96 (s, 2H), 1.59-1.42 (m, 6H), 1.23 (s, 6H). Example 38 N-r3-(2.3-dichloro-4-cvclopropylsulfamovI)phenoxy-2(R)-hvdroxypropyIl-2-(4- methoxyphenvD-l.l-dimethylethylamine hydrochloride Following the procedure of Example 15, substituting cyclopropy lamine for dipropylamine in 15(b) and following the deprotection procedure referenced in Example 5 in place of the procedure of 15(c), the titie compound was prepared (138 mg). MS (ES) m/e 517.1 [M+H]VH NMR (400MHz, DMSO) d 9.11-8.90 (bs, IH), 8.82-8.59 (bs, IH), 8.29 (m, IH), 8.01 (d, J=9Hz, IH), 7.41 (d, J=9Hz, IH), 7.16 (d, J=9Hz, 2H), 6.90 (d, J=9Hz, 2H), 6.11-5.94 (bs, IH), 4.39-4.22 (m, 3H), 3.74 (s, 3H), 3.37-3.24 (m, IH), 3.16-3.04 (m, IH), 2.93 (s, 2H), 2.18 (m, IH), 1.21 (s, 6H), 0.50-0.36 (m, 4H). Example 39 N-r3-r3-chloro-2-cvano-4-(4'-N-t-butoxycarbonylpiperazino)sulfamovnphenoxy)-2(R)- hvdroxypropyll-2-C2-naphthvI)-l.l-dimethylethylamine hydrochloride: The title compound (10 mg) was prepared by the method of example 31 substituting l,l-dimethyl-2-(2-napthyl)ethylamine for l,l-dimethyl-2-(4-methoxyphenyl)ethylamine. MS (ES) m/e 657.4[M+H] + ; 1 H NMR (400MHz, CDC1 3 ) d 8.09(d, J=9Hz, IH), 7.77(m, IH), 7.74(m, 2H), 7.59(s, IH), 7.39(m, 2H), 7.25(d, J=8Hz, IH), 6.92(d, J=9Hz, IH), 4.16(d, J=4Hz, 2H), 4.00(m, IH), 3.42(m, 4H), 3.18(m, 4H), 3.09(dd, J=2,10Hz, IH), 2.87(s, 2H), 2.87(m, IH), 1.40(s, 9H), 1.10(2s, 6H). Example 40 Preparation of (R)- 3-r2-cvano-4-rN-benzyl-N'-morphoIino1ureido1phenoxy1-l-ri.l- dimethyl-2-(2-naphthyl)ethylaminol-propan-2-ol. a) 2-Methoxyl-5-N-[[4-morpholino]carbonyl]amino benzonitrile To a stirred mixture of 2-methoxyl-5-aminobenzonitrile (2 g, 12.34 mmol), and pyridine (1.28 g, 16.2 mmol) in dried CH2CI2 (20 mL) was added 4-moφholinecarbonyl chloride (2.42 g, 16.2 mmol). After stirring at RT for 24 h, the mixture was diluted with CH2CI2 and washed with H2O, brine, dried over MgSθ4, concentrated to give an orange solid (3.04g, 86%) 1H NMR: (400MHz, DMSO-d 6 ): d 3.23 (t, J = 4.9Hz, 4H), 3.47 (t, J = 4.9 Hz, 4H), 3.9 (s, 3H), 6.89 (d, J = 9 Hz, IH), 7.3 (d, J = 9Hz, IH), 8.01 (s, IH). b) 2-Methoxyl-5-[N-methyl-N-[[4-morpholino]carbonyl]amino] benzonitrile. To a stirred suspension of NaH (60%, pre- washed with hexane, 0.2 g, 4.98 mmol) in dry DMF (10 mL) was added example 14a (1 g, 3.8 mmol) . After stirring at RT in 1 h, methyl iodide (1.62 g, 11.5 mmol) was added and stirred ovemight, taken up in H2O, extracted with EtOAc. The organic extracts were washed with brine, dried over MgSU4, concentrated to give a brown oil (1.0 g, 98%). 1H NMR: (400MHz, DMSO-d 6 ): d 2.95 (s, 3H), 3.23 (t, J = 4.9Hz, 4H), 3.47 (t, J = 4.9Hz, 4H), 3.9 (s, 3H), 6.89 (d, J = 9 Hz, IH), 7.3 (d, J=9Hz, IH), 8.01 (s, IH). c) 2-Hydroxy-5-[N-methyl-N-[[4-morphoIino]carbonyI]amino]benzonitrile. Following the example le, the title compound was prepared as a yellow oil (0.33g, 40%). 1H NMR: (400MHz, DMSO-d 6 ): d 2.95 (s, 3H), 3.23 (t, J = 4.9Hz, 4H), 3.47 (t, J = 4.9Hz, 4H), 6.89 (d, J = 9Hz, IH), 7.3 (d, J = 9Hz, IH), 8.01 (s, IH). d) 2-Cyano-5-[N-methyl-N-[[4-morpholino]carbonyl]amino]phenyl lycidol. Following the example lf, the title compound was prepared as a brown oil (0.23g, 60%). 1H NMR (400MHz, DMSO-d 6 ): d 2.85 (t, J = 4.5Hz, IH), 2.95 (s, 3H), 2.97 (t, J = 4.5Hz, IH), 3.23 (t, J = 4.9Hz, 4H), 3.42 (m,lH), 3.47 (t, J = 4.9Hz, 4H), 4.12 (dd, J = 5.4, 11.4Hz, IH), 4.42 (dd, J = 5.4, 11.4Hz, IH), 6.89 (d, J = 9 Hz, IH), 7.3 (d, J = 9Hz, IH), 8.01 (s, IH). e) Synthesis of (R)- 3-[2-cyano-4-[N-benzyl-N'-morphoIino]ureido]phenoxy]-l-[l,l- dimethyl-2-(2-naphthyl)ethylamino]-propan-2-ol. Following the procedure in example 7, the title compound was prepared as an off white foam (0.6g, 56%) *H NMR (400 MHz, DMSO-d 6 ): d 1.09 (s, 3H), 1.11 (s, 3H), 2.85 (t, J=4.5Hz, IH), 2.95 (s, 3H), 2.97 (t, J = 4.5Hz, IH), 3.23 (t, J = 4.9Hz, 4H), 3.42 (m,lH), 3.47 (t, J = 4.9Hz, 4H), 4.12 (dd, J = 5.4, 11.4Hz, IH), 4.42 (dd, J = 5.4, 11.4Hz, IH), 7.12 (d, J = 7.2 Hz, IH), 7.27 ( , 5H), 7.35 d, J = 7.2Hz, IH), 7.55 (s, IH), 7.67 (s, IH), 7.76 (d, J = 7.2Hz, IH). MS (m+l, m/z): 417.6. Anal. Calcd. for C 3 oH3 6 N 4 O4 1.5H 2 O: C, 66.28; H, 7.23; N, 10.3; Found: C, 66.61; H, 6.96; N, 9.92. Example 40 Preparation of N-r2R-Hvdroxy-3-r2-cyano-4-[N-benzyl-N-f C4- moφholino)carbonyllamino1phenoxylpropylll.1-dimethyl-2-r2-napthyllethylamine a) 2-Methoxyl-5-[N-benzyI-N-[[4-morpholino]carbonyl]amino] benzonitrile Following the procedure in example 14b, the title compound was prepared as a tan solid (1.2g, 81%): 1H NMR: (400MHz, DMSO-d 6 ): d 3.23 (t, J = 4.9Hz, 4H), 3.47 (t, J = 4.9Hz, 4H), 3.9 (s, 3H), 4.8 (s, 2H), 6.89 (d, J = 9 Hz, IH), 7.28 (m, 5H), 7.43 (d, J = 9Hz, IH), 8.01 (s, IH). b) 2-Hydroxy-5-[N-benzyl-N-[[4-morpholino]carbonyl]amino]benzonitrile Following the example in example 14c, the title compound was prepared as a light yellow foam (0.64g, 74%).1H NMR: (400MHz, DMSO-d 6 ): d 3.23 (t, J = 4.9Hz, 4H), 3.47 (t, J = 4.9Hz, 4H), 4.8 (s, 2H), 6.89 (d, J = 9 Hz, IH), 7.28 (m, 5H), 7.43 (d, J = 9Hz, IH), 8.01 (s, IH). c) 2-Cyano-5-[N-benzyI-N-[[4-morpholino]carbonyl]amino]phenyl glycidol Following the procedure in example lf, the titie compound was prepared as an off white foam 0.7 lg, 95%). *H NMR: (400MHz, DMSO-d 6 ): d 2.75 (t, J = 4.5Hz, IH), 2.85 (t, J = 4.5Hz, IH), 3.23 (t, J = 4.9Hz, 4H), 3.47 (t, J = 4.9Hz, 4H), 4.71 (s, 2H), 6.89 (d, J = 9 Hz, IH), 7.28 (m, 5H), 7.43 (d, J = 9Hz, IH), 8.01 (s, IH). d) Synthesis of (R)- 3-[2-cyano-4-[N-benzyI-N'-morpholino]ureido]phenoxy]-l-[l,l- dimethyl-2-(2-naphthyl)ethylamino]-propan-2-ol. Following the procedure in example 7, the title compound was prepared as yellow solid (0.6g, 56%). H NMR (400 MHz, DMSO-d 6 ): d 1.09 (s, 3H), 1.11 (s, 3H), 2.80 (m, 4H), 3.15 (t, J = 4.9Hz, 4H), 3.47 (t, J = 4.9Hz, 4H), 3.85 (m, IH), 4.12 (m, 2H), 4.71 (s, 2H), 5.1 (m, IH), 7.12 (d, J = 7.2 Hz, IH), 7.27 (m, 6H), 7.35 (d, J = 7.2Hz, IH), 7.47 ( , 2H), 7.55 (s, IH), 7.67 (s, IH), 7.76 (d, J = 7.2Hz, IH), 7.79 (m, 2H). MS (m+l, m/z): 593.7. Anal. Calcd. for C36H40N4O4 H 2 0: C, 70.68; H, 7.08; N, 9.15; Found: C, 70.9; H, 6.94; N, 8.84. Example 41 Preparation of (R)-l-ri.l-dimethyl-2-(4-methoxyphenyl)ethylamino1-3-ri0.11-dihvdro-2- cyano-3-oxy-5H-dibenzora.d1cvcloheptene-10-(R)-acetic acid1-propan-2-ol hydrochloride salt a) Ethyl 10,ll-dihydro-3-hydroxyl-5H-dibenzo[a,d]cycloheptene-10-(R)-acetate. AICI3 (2.2g, 17 mmol) was added to a cold solution of methyl-(10R)-(10,l l-dihydro-3- methyloxy-5H-dibenzo[a,d]cycloheptene-10-acetate (l.Og, 3.4 mmol) and ethylmercaptan (1.2 mL, 17 mmol) in CH2CI2 (15 mL). After 2 h at 0 °C, the solution was concentrated and residue treated with ice/water (50 mL) and CH2CI2 (50 mL). The organic layer was separated and washed with water (2X) and concentrated to give 0.95g (95%) of the title compound. H NMR (400 MHz, DMSO-d 6 ) δ 1.1-1.3 (m, 3H), 2.4-2.8 (m, 3H), 3.0-3.8 (m, 4H), 4.0-4.2 (m, 3H), 6.5- 7.2 (m, 7H), 9.1-9.2 (s, IH). b) Ethyl 10,ll-dihydro-3-hydroxyl-2-formyI-5H-dibenzo[a,d]cycloheptene-10-(R)-acetate. A solution of ethyl 10,l l-dihydro-3-hydroxyl-5H-dibenzo[a,d]cycloheptene-10-(R)- acetate (2.9g, 9.8 mmol), SnCl4 (0.15 mL, 1.3 mmol) and tributylamine (1.2 mL, 5.2 mmol) in toluene (60 mL) was stirred at RT for 20 min under an argon atmosphere. Paraformaldehyde (0.86 g) was added and the solution was heated at reflux for 18 h. The solution was cooled to RT and poured into water and acidified with aqueous HCl (3M) to pH 2 (litmus paper). Ethyl ether was added and the layers separated. The organic layer was washed with water and concentrated. Flash chromatography (silica gel, 50% EtOAc/Hexane) yielded 2.5g (70%) of the title compound. l H NMR (400 MHz, DMSO-d 6 ) 6 1.1 - 1.3 (m, 3H), 2.5-3.2 (m, 4H), 3.6-4.2 (m, 5H), 6.5-7.4 (m, 6H), 10.1-10.2 (s, IH), 10.5-10.6 (s, IH). c) Ethyl 10,ll-dihydro-3-hydroxyI-2-iminohydroxyI-5H-dibenzo[a,d] cycloheptene- 10-(R)-acetate. A solution of ethyl 10,ll-dihydro-3-hydroxyl-2-formyl-5H-dibenzo[a,d]cycloheptene- 10-(R)-acetate (1.2g, 3.8 mmol), hydroxylamine hydrochloride (0.68g, 9.8 mmol) and triethy lamine (1.4 mL, 10 mmol) in EtOH (20 mL) was heated at reflux under an argon atmosphere. After 18 h the solution was concentrated to give 2.5g of the crude title compound which was used in the next step without further purification. d) Ethyl 10,1 l-dihydro-2-cyano-3-oxyacetyl-5H-dibenzo[a,d]cycloheptene- 10-(R)-acetate. A solution of ethyl 10,l l-dihydro-3-hydroxyl-2-iminohydroxyl-5H- dibenzo[a,d]cycloheptene-10-(R)-acetate (2.5g, 3.8 mmol) in acetic anhydride (30 mL) was heated at reflux for 30 min. The solution was then concentrated. Flash chromatography (silica gel, 30% EtOAc/Hexane) yielded 0.8g (58%) of the title compound. l VL NMR (400 MHz, DMSO-d 6 ) δ 1.1-1.3 (m, 3H), 2.2-3.1 (m, 6H), 3.2-4.4 (m, 6H), 7.0-7.2 (m, 4H), 7.3-7.4 (s, IH), 7.6-7.7 (m, IH). e) Ethyl 10,ll-dihydro-2-cyano-3-hydroxyI-5H-dibenzo[a,d]cycloheptene-10-(R)-acetate. A solution of ethyl 10,l l-dihydro-2-cyano-3-oxyacetyl-5H-dibenzo[a,d]cycloheptene- 10-(R)-acetate (0.8g, 2.2 mmol) in EtOH/water (1:1, 10 mL) was treated with K2CO3 (0J6g, 5.5 mmol). After 3 h the solution was concentrated. The residue was partitioned between EtOAc/water and aqueous HCl (IM) was added to adjust the solution to pH 2 (litmus paper). The EtOAc layer was separated and washed with water (2X) and concentrated to give 0.65g (92%) of the title compound. l H NMR (400 MHz, DMSO-d 6 ) δ 1.1-1.2 (m, 3H), 2.6-3.2 (m, 4H), 3.6-4.2 (m, 5H), 6.8-6.9 (s, IH), 7.0-7.2 (m, 4H), 7.3-7.4 (s, IH), 10.8-10.9 (s, IH). f) (2R)-Glycidyl-[ethyl 10,ll-dihydro-2-cyano-3-oxy-5H-dibenzo[a,d] cycloheptene- 10-(R)- acetate]. A solution of ethyl 10,l l-dihydro-2-cyano-3-hydroxyl-5H-dibenzo[a,d]cycloheptene- 10-(R)-acetate (0.67g, 2.1 mmol), (2R)-gycidyl 3-nitrobenzenesulfonate (Aldrich Chemicals, 0.54g, 2.1 mmol) and K2CO3 (0.864g, 6.3 mmol) in acetone (20 mL) was heated at reflux for 18 hr. The solution was filtered and the filtrate was concentrated to give 0.8g of the titie compound which was used in the next step without further purification. g) (R)-l-[l,l-dimethyI-2-(4-methoxyphenyl)ethylamino]-3-[ethyl-10,ll-dihydro-2-cyano-3- oxy-5H-dibenzo[a,d]cycloheptene-10-(R)-acetate]-propan-2-ol hydrochloride salt A solution of (2R)-glycidyl-(ethyl-10,l l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetate) (0.8g, 2.1 mmol), 1,1 -dimethy l-2-(4- methoxyphenyl)ethyl amine (0.375g, 2.1 mmol) and LiC104 (0.445g, 4.2 mmol) in CH3CN (10 mL) was heated at reflux for 18 hr. After this time the solution was concentrated. Flash chromatography (silica gel, 5% CH3OH/CH2G2) and treatment with HCl in MeOH yielded 0.7g (60%) of the title compound. MS (ES) m/e 557.3 (M+H) + ; 1H NMR (DMSO-d 6 ) δ 1.0-1.3 (m, 9H), 2.5-3.2 (m, 8H), 3.4-4.3 (m, 11H), 5.9-6.0 (s, IH), 6.8-7.2 (m, 8H), 7.2-7.3 (s, IH), 7.4- 7.5 (s, IH), 8.4-8.5 (broad s, 2H). h) (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[10,ll-dihydro-2-cyano-3-oxy- 5H-dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol hydrochloride salt. A solution of (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[ethyl-10,l 1- dihydro-2-cyano-3-oxy-5H-dibenzo[a,d]cycloheptene-10-(R)-acetate]-propan-2-ol (0.6g, 1.1 mmol) in EtOH/water (1:1, 4 mL) was treated with aqueous NaOH (IM, 2 mL, 2 mmol). After 18 h the solution was concentrated and water (10 mL) was added. Solution was cooled and acidified with aqueous HCl (IM) (pH 6, litmus paper). The solution was filtered and the solid precipitate was triturated with EtOAc. Filtration and drying in vacuo gave 0.25g (45%) of the title compound. MS (ES) m/e 529.4 (M+H) + ; *H NMR (400 MHz, DMSO-d 6 ) δ 1.1-1.2 (s, 6H), 2.5-3.2 (m, 5H), 3.3-3.4 (s, 3H), 4.0-4.3 (m, 4H), 6.8-7.2 ( , 8H), 7.2-7.3 (s, IH), 7.4-7.5 (s, IH). Example 42 Preparation of (R)-l-fl.l-dimethyl-2-(4-methoxyphenv0ethylaminol-3-rethyl-10.11- dihvdro-2-cvano-3-oxy-5H-dibenzofa.dlcvcloheptene-10-(R/S)-acetatel-propan-2-ol a) (2R)-Glycidyl-(ethyl-10,ll-dihydro-3-oxy-5H-dibenzo[a,d]cycloheptene-10-(R/S)- acetate) Following the procedure of Example 41 (f) except substituting ethyl-(R/S)-10,l 1- dihydro-3-hydroxyl-5H-dibenzo[a,d]cycloheptene-10-acetate for compound of Example 41(e), OJg of the title compound was prepared and used without further purification in the next step. b) (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethyIamino]-3-[ethyl-10,ll-dihydro-2-cyano-3- oxy-5H-dibenzo[a,d]cycloheptene-10-(R/S)-acetate]-propan-2-ol hydrochloride salt Following the procedure of Example 41(g) except substituting (2R)-glycidyl-(ethyl- 10,l l-dihydro-3-oxy-5H-dibenzo[a,d]cycloheptene-10-(R/S)-acetate)(0Jg, 2.1 mmol) for compound of Example 41(f), 0.44g (45%) of the title compound was prepared. MS (ES) m/e 532.4 (M+H) + ; 1H NMR (400 MHz, DMSO-d6) δ 1.1-1.2 (s, 9H), 2.5-3.2 (m, 9H), 3.5-4.2 (m, 11H), 6.7-7.2 (m, 11H). Example 43 Preparation of (R)-l-fl,l-dimethyl-2-(4-methoxyphenyl)ethylamino1-3-ri0.11-dihydro-2- cvano-3-oxy-5H-dibenzora.dlcvcloheptene-10-(R/S)-acetic acidl-propan-2-ol hydrochloride salt a) (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[10,ll-dihydro-2-cyano-3-oxy- 5H-dibenzo[a,d]cycloheptene-10-(R/S)-acetic acid]-propan-2-ol hydrochloride salt. Following the procedure of Example 41 (h) except substituting (R)-l-[l,l-dimethyl-2- (4-methoxyphenyl)ethylamino]-3- [ethyl- 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R S)-acetate]-propan-2-ol hydrochloride salt for compound of Example 41 (g), 0.118g (55%) of the title compound was prepared. MS (ES) m/e 504.2 (M+H) + ; *H NMR (400 MHz, DMSO-d 6 ) δ 1.1-1.2 (m, 6H), 2.4-4.3 (m, 20H), 6.7-7.2 (m, 1 IH). Example 44 Preparation of (R)-l-π.l-dimethyl-2-(4-methoxyphenyl)ethylamino1-3-rethyl-10.11- dihvdro-2-cvano-3-oxy-5H-dibenzora.dlcvcloheptene-10-(R)-acetate1-propan-2-ol hydrochloride salt. a) (2R)-Glycidyl ethyl-10,ll-dihydro-2-cyano-3-oxy-5H-dibenzo[a,d]cycloheptene-10-(R)- acetate Following the procedure of Example 41 (f) except substituting ethyl- 10, 11 -dihy dro-2- cyano-3-oxyl-5H-dibenzo[a,d]cycloheptene-10-(R)-acetate.(0.337g, 1.1 mmol) for the compound of Example 41 (e), 0.37g of the title compound was prepared and used as without further purification in the next step. b) (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[ethyl-10,ll-dihydro-2-cyano-3- oxy-5H-dibenzo[a,d]cycloheptene-10-(R)-acetate]-propan-2-ol hydrochloride salt. Following the procedure of Example 41 (g) except substituting (2R)-glycidyl ethyl- 10,l l-dihydro-2-cyano-3-oxy-5H-dibenzo[a,d]cycloheptene-10-(R)-acetate (0.37g, 1.1 mmol) for the compound of Example 41 (f), 0.125g (22%) of the title compound was prepared. MS (ES) m/e 532.3 (M+H) + ; 1H NMR (400 MHz, DMSO-d 6 ) δ 1.1-1.3 (m, 9H), 2.5-4.3 (m, 20H), 5.7-5.9 (s, IH), 6.7-7.2 (m, 11H), 8.2-8.4 (broad s, 2H). Example 45 Preparation of (R)-l-ri.l-dimethyl-2-(4-methoxyphenyl)ethylaminol-3-f 10.1 l-dihvdro-2- cvano-3-oxy-5H-dibenzo[a.d1cvcloheptene-10-(R)-acetic acidl-propan-2-ol hydrochloride salt a) (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[10,ll-dihydro-2-cyano-3-oxy- 5H-dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol hydrochloride salt. Following the procedure of Example 41 (h) except substituting (R)-l-[l,l-dimethyl-2- (4-methoxyphenyl)ethylamino]-3-[ethyl-10,l l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetate]-propan-2-ol hydrochloride salt (0.07g, 0.13 mmol) for the compound of Example 1 (g), 0.03 g (50%) of the title compound was prepared. MS (ES) m/e 504.4 (M+H) + ; l H NMR (400 MHz, DMSO-d 6 ) δ 1.1-1.2 (s, 6H), 2.5-3.3 (m, 7H), 3.5-4.3 (m, 12H), 6.8-7.2 (m, 8H), 7.2-7.3 (s, IH), 7.4-7.5 (s, IH). Example 46 Preparation of (R)-l-ri.l-dimethyl-2-(4-methoxyphenyl)ethylaminol-3-rethyl-10.11- dihvdro-2-cvano-3-oxy-5H-dibenzora.dlcvcloheptene-10-(S)-acetate1-propan-2-ol hydrochloride salt. a) (R)-l-[l,l-dimethyl-2-(4-methoxyphenyI)ethylamino]-3-[ethyl-10,ll-dihydro-2-cyano-3- oxy-5H-dibenzo[a,d]cycloheptene-10-(S)-acetate]-propan-2-ol hydrochloride salt. The 10-R,S-diastereoisomers from Example 42 (b) were resolved as their free base using a Chiralpak AD column (21.2 x 250 mm, 10 mL/min, 75% hexane/ethanol, 0.1% die y lamine). The pure diastereoisomers were converted to the corresponding HCl salts by treatment with HCl in MeOH to yield (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3- [ethy 1- 10, 11 -dihydro-2-cyano-3-oxy-5H-dibenzo[a,d]cycloheptene- 10-(S)-acetate]-propan-2-ol hydrochloride salt (20 mg)and (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[ethyl- 10, 11 -dihydro-2-cyano-3-oxy-5H-dibenzo[a,d]cycloheptene- 10-(R)-acetate]-propan-2-ol hydrochloride salt (20 mg) which was identical to material synthesized in Example 44 (b). Example 47 Preparation of (R)-l-n.l-dimethvI-2-(2-naphthyl)ethylamino1-3-rethyl-10.11-dihvdro-2- cvano-3-oxy-5H-dibenzora.d1cycloheptene-10-(S)-acetatel-propan-2-ol hydrochloride salt. a) Ethyl-10,ll-dihydro-2-formyl-3-hydroxyl-5H-dibenzo[a,d]cycloheptene-10-(S)-acetate. Following the procedure of Example 41 (b) except substituting ethyl-10,l l-dihydro-3- hydroxyl-5H-dibenzo[a,d]cycloheptene-10-(S)-acetate (l.Og, 3.4 mmol) for the compound of Example 41 (a) 0.9 g (41%) of the title compound was prepared. J H NMR (400 MHz, DMSO- d 6 ) δ 1.1-1.2 (m, 3H), 2- -4.2 ( m > 9H), 6.8-6.9 (s, IH), 7.0-7.3 (m, 4H), 7.3-7.4 (s, IH), 10.1- 10.2 (s, IH), 10.5-10.6 (s, IH). b) Ethyl-10,ll-dihydro-2-iminohydroxyI-3-hydroxyl-5H-dibenzo[a,d]cycIoheptene-10-(S)- acetate. Following the procedure of Example 41 (c) except substituting ethyl- 10,1 l-dihydro-2- formyl-3-hydroxyl-5H-dibenzo[a,d]cycloheptene-10-(S)-acetate(0.9 g, 2.8 mmol) for the compound of Example 41 (b) 0.9 g of the title compound was prepared and used without purification in the next step. c) Ethyl-10,ll-dihydro-2- cyano-3-hydroxyacetyl -5H-dibenzo[a,d]cycloheptene-10-(S)- acetate. Following the procedure of Example 41 (d) except substituting ethy 1-10,11 -dihy dro-2- iminohydroxyl-3-hydroxyl-5H-dibenzo[a,d]cycloheptene-10-(S)-acetate(0.9 g, 2.6 mmol) for the compound of Example 41 (c) 0.3 g (32%) of the titie compound was prepared. H NMR (400 MHz, DMSO-d 6 ) δ 1.1-1.2 (m, 3H), 2.3-2.4 (s, 3H), 2.5-4.3 (m, 9H), 7.0-7.3 (m, 4H), 7.3- 7.4 (s, IH), 7.6-7.7 (s, IH). d) Ethyl-10,ll-dihydro-2-cyano-3-hydroxyl-5H-dibenzo[a,d]cycloheptene-10-(S)-acetate. Following the procedure of Example 41 (e) except substituting ethyl- 10, 11 -dihy dro-2- cyano-3-hydroxyacetyl-5H-dibenzo[a,d]cycloheptene-10-(S)-acetate (0.3 g, 2.6 mmol) for the compound of Example 41 (d) 0.3 g (75%) of the title compound was prepared. H NMR (400 MHz, DMSO-d 6 ) δ 1.1-1.2 (m, 3H), 2.5-4.2 (m, 9H), 6.8-6.9 (s, IH), 7.0-7.3 (m, 4H), 7.3-7.4 (s, IH). e) (2R)-Glycidyl-(ethyl-10,ll-dihydro-2-cyano-3-oxyl-5H-dibenzo[a,d]cycloheptene-10-(S)- acetate). Following the procedure of Example 41 (f) except substituting ethyl- 10,1 l-dihydro-2- cyano-3-hydroxyl-5H-dibenzo[a,d]cycloheptene-10-(S)-acetate(0.2 g, 0.6 mmol) for the compound of Example 41 (e) 0.2 g (87%)of the title compound was prepared and used without further purification in the next step. f) (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[ethyl-10,ll-dihydro-2-cyano-3-oxy- 5H-dibenzo[a,d]cycloheptene-10-(S)-acetate]-propan-2-ol hydrochloride salt. Following the procedure of Example 41 (g) except substituting (2R)-glycidyl-(ethyl- 10,ll-dihydro-2-cyano-3-oxyl-5H-dibenzo[a,d]cycloheptene-10-(S)-acetate).(0.23 g, 0.62 mmol) for the compound of Example 41 (f) 0.3 g (86%) of the titie compound was prepared. MS (ES) m/e 577.3 (M+H) + ; H NMR (400 MHz, DMSO-d 6 ) δ 1.1-1.3 (m, 9H), 2.5-4.3 (m, 16H), 7.1-8.0 (m, 13H). Example 48 Preparation of (R)-l-ri.l-dimethyl-2-(2-naphthyl)ethylamino1-3-ri0.11-dihvdro-2-cvano-3- oxy-5H-dibenzora.d1cvcloheptene-10-(S)-acetic acidl-propan-2-ol hydrochloride salt. a) (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[10,ll-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(S)-acetic acid]-propan-2-ol hydrochloride salt. Following the procedure of Example 41 (h) except substituting (R)-l-[l,l-dimethyl-2- (2-naphthyl)ethylamino]-3-[ethyl-10,l l-dihydro-2-cyano-3-oxy-5H-dibenzo[a,d]cycloheptene- 10-(S)-acetate]-propan-2-ol hydrochloride salt (0.14 g, 0.24 mmol) for the compound of Example 41 (g) 0.066 g (50%) of the title compound was prepared. MS (ES) m/e 549.4 (M+H) + ; 1H NMR (400 MHz, DMSO-d 6 ) δ 1.1-1.3 (m, 6H), 2.5-4.3 (m, 14H), 7.0-7.9 (m, 13H). Example 49 Preparation of (R)-l-ri.l-dimethvI-2-(4-methoxyphenyl)ethylaminol-3-r3-oxy-10-ethylthio- 5H-dibenzo[a.dlcvcloheptenel-propan-2-ol hydrochloride salt a) 3-Hydroxyl-10-ethylthio-5H-dibenzo[a,d]cycloheptene. A cold solution of 3-hydroxyl-10-oxy-5H-dibenzo[a,d]cycloheptene (3.0 g, 12.6 mmol) and ethylmercaptan (6.5 mL, 86 mmol) in CH2CI2 (50 mL) was treated with AICI3 (8.4g, 60 mmol). After 3 h the solution was concentrated. Flash chromatography (silica gel, 30% EtOAc/Hexane) gave 2.4 g (70%) of the title compound. 1H NMR (400 MHz, DMSO-dg) δ 1.1- 1.3 (m, 3H), 2.6-2J (m, 2H), 3.3-3.4 (s, 2H), 6.5-7.8 (m, 8H), 9.5-9.6 (s, IH). b) (2R)-Glycidyl-(3-oxyI-10-ethylthio-5H-dibenzo[a,d]cycloheptene). Following the procedure of Example 41 (f) except 3-hydroxyl-10-ethylthio-5H- dibenzo[a,d]cycloheptene (1.2 g, 4.5 mmol) for the compound of Example 41 (e) 1.3 g of the title compound was prepared and used without further purification in the next step. c) (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-10-ethylthio-5H- dibenzo[a,d]cycloheptene]-propan-2-oI hydrochloride salt. Following the procedure of Example 41 (g) except substituting (2R)-glycidyl-(3-oxyl- 10-ethylthio-5H-dibenzo[a,d]cycloheptene) (0.65 g, 2.0 mmol) for the compound of Example 41 (f) 0.5 g (50%) of the title compound was prepared. MS (ES) m/e 504.3 (M+H) + ; l B NMR (400 MHz, DMSO-d 6 ) δ 1.1-1.3 (m, 9H), 2.7-4.2 (m, 14H), 6.8-7.8 (m, 12H). Example 50 Preparation of (R)-l-n.l-dimethyl-2-(2-naphthyl)ethylamino1-3-r3-oxy-10-ethylthio-5H- dibenzora.dlcvcloheptenel-propan-2-ol hydrochloride salt. a) (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[3-oxy-10-ethylthio-5H- dibenzo[a,d]cycloheptene]-propan-2-ol hydrochloride salt. Following the procedure of Example 41 (g) except substituting (2R)-glycidyl-(3-oxy-10- ethylthio-5H-dibenzo[a,d]cycloheptene) (0.65 g, 2.0 mmol) for the compound of Example 41 (f) 0.2 g (20%) of the title compound was prepared. MS (ES) m/e 524.3 (M+H) + ; l H NMR (400 MHz, DMSO-d 6 ) δ 1.1-1.3 (m, 9H), 2.7-4.2 (m, 11H), 6.8-7.8 (m, 14H). Example 51 Preparation of (R)-l-ri.l-dimethyl-2-(4-methoxyphenvI)ethylamino1-3-r3-oxy-10-oxy-5H- dibenzora.dlcvcloheptenel-propan-2-ol hydrochloride salt. a) (2R)-Glycidyl(3-oxy-10-oxy-5H-dibenzo[a,d]cycloheptene). Following the procedure of Example 41 (f) except substituting 3-hydroxyl-10-oxy-5H- dibenzo[a,d]cycloheptene (0.9 g, 4.0 mmol) for the compound of Example 41(e) 1.1 g of the title compound was prepared and used without further purification in the next step. b) (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-10-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-o! hydrochloride salt Following the procedure of Example 41 (g) except (2R)-glycidyl-(3-oxy-10-oxy-5H- dibenzo[a,d]cycloheptene) (0.6 g, 2.1 mmol) for the compound of Example 41 (f) 0.2g (20%) of the title compound was prepared. MS (ES) m/e 460.3 (M+H) + ; *H NMR (400 MHz, DMSO-dg) δ 1.0-1.3 (m, 6H), 2.9-4.3 (m, 14H), 6.8-8.0 (m, 11H). Example 52 Preparation of (R)-l-ri.l-dimethyl-2-(4-methoxyphenyl)ethylamino1-3-rethyl-10.11- dihvdro-2-cvano-3-oxy-5H-dibenzofa.d1cvcloheptene-10-(R)-acetatel-propan-2-ol hydrochloride salt. a) (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[ethyl-10,ll-dihydro-2-cyano-3- oxy-5H-dibenzo[a,d]cycloheptene-10-(R)-acetate]-propan-2-ol hydrochloride salt. A solution of (2R)-glycidyl-( ethyl-10,l l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetate) (0.8 g, 2.1 mmol), l,l-dimethyl-2-(4- methoxyphenyl)ethyl amine (0.375 g, 2.1 mmol) and LiC104 (0.445 g, 4.2 mmol) in CH3CN (10 mL) was heated at reflux for 18 hr. The solution was then concentrated. Flash chromatography (silica gel, 5% CH3OH CH2CI2) and treatment with HCl in MeOH yielded 0.7g (60%) of the titie compound. MS (ES) m/e 557.3 (M+H) + ; 1H NMR (DMSO-d 6 ) δ 1.0-1.3 (m, 9H), 2.5-3.2 (m, 8H), 3.4-4.3 (m, 11H), 5.9-6.0 (s, IH), 6.8-7.2 (m, 8H), 7.2-7.3 (s, IH), 7.4- 7.5 (s, IH), 8.4-8.5 (broad s, 2H). Example 53 Preparation of (-R>-l-π.l-dimethyl-2-(2-naphthalenyl)ethylamino1-3-f3-oxy- dibenzrø.fin.41oxazepin-ll(10H)-one1-propan-2-ol monohydrochloride. a) 2-Carboxymethyl-5-methoxy-phenyl-oxy-(3-nitrobenzene) A solution of 2-carboxymethyl-5-methoxyphenol (34.1 g, 0.187 mol), 2- nitrofluorobenzene (19.7 mL, 0.187 mol), and K 2 C0 3 (65 g, 0.467 mol) in DMF (200 mL) was heated to 110 °C for 18 h. The solution was diluted with water (200 mL) and extracted with ethyl acetate. The ethyl acetate layer was concentrated to give the crude title compound which was used as is for the next step (57 g). b) 2-Carboxymethyl-5-methoxy-phenyl-oxy-(3-aminobenzene) A solution of 2-carboxymethyl-5-methoxy-phenyl-oxy-(3-nitrobenzene) (57 g, 0.187 mol) and 10% Pd/C (11 g) was hydrogenated in MeOH (1000 mL) at 50 psi for 2 h. The solution was filtered through Celite® and the filtrate was concentrated. Flash chromatography (silica gel, 20% EtOAc Hexane) yielded the title compound (49.3 g, 96%): MS (ES) m e 274.1 (M + H)+. c) 3-Methoxy-dibenz[fe A ][l,4]oxazepin-ll(10H). A solution of 2-carboxymethyl-5-methoxy-phenyl-oxy-(3-aminobenzene) (9.2 g, 37 mmol) in toluene (400 mL) was treated with AlMe3 (2M in toluene, 16 mL, 32 mmol). The solution was heated at reflux for 3 h and allowed to run at RT for 18 h. The reaction solution was poured into a 5% NaHCθ3 solution and ethyl acetate was added. The ethyl acetate layer was separated and washed with water (2X) and brine (IX). The ethyl acetate layer was concentrated to give the title compound (7.4 g, 91%): 1H NMR (400 MHz, DMSO- d 6 ) δ 3.8-3.9 (s, 3H), 6.8-7.9 (m, 7H). d) 3-Hydroxy-dibenz[fc/|[l,4]oxazepin-ll(10H). To a cold solution of 9-methoxy-dibenz[£>,/][l,4]oxazepin-l l(10H) (1 g, 4.1 mmol) and ethylmercaptan (1.5 mL, 20 mmol) in CH2CI2 (15 mL) was added AICI3 (2.8g, 20 mmol). After 2 h at 0 C, the solution was concentrated and residue was treated with ice/water (50 mL) and CH2CI2 (50 mL). The organic layer was separated and washed with water (2X). The organic layer was concentrated to give the cmde title compound which was used as is for the next step (0.95g). H NMR (400 MHz, DMSO-d 6 ) δ 6.4-7.9 (m, 7H), 10.1-10.2 (s, IH), 10.4- 10.5 (s, IH). e) 2-R-Glycidyl-(9-oxy-dibenzfø/|[l,4]oxazepin-ll(10H) A solution of 9-hydroxy-dibenz[feJ] [ 1 ,4]oxazepin- 11 ( 1 OH) (0.51 g 2.2 mmol), 2-R- gycidyl 3-nitrobenzenesulfonate (0.582g, 2.2 mmol) and K2CO3 (0.93g, 6.6 mmol) in acetone (20 mL) was heated to reflux for 18 hr. Solution was filtered and the filtrate was concentrated to give the title compound which was used as is for the next step (0.64g). f) (-R)-l-ri.l-Dimethyl-2-(2-naphthalenyl)ethylaminol-3-r3-oxy-dibenzr6.fin.41oxazepin- 11 (10H)-one1-propan-2-ol monohydrochloride. A solution of 2R-glycicyl-(9-oxy-dibenz[fc,/][l,4]oxazepin-l l(10H)( 0.10 g, 0.4 mmol) and 1,1 -dimethy l-2-(2-naphthyl)ethyl amine (0.07 g, 0.4 mmol) in EtOH (5 mL) was heated to reflux for 18 hr. The solution was concentrated, and purified by flash chromatography (silica gel, 5% CH3OH/CH2CI2). Treatment of the isolated product with HCl in MeOH yielded the title compound (O.lg, 60%). MS (ES) m/e 483.1 (M + H) + ; !-HNMR (DMSO-d 6 ) δ 1.2-1.4 (m, 6H), 2.5-4.5 (m, 8H), 6.0-6.1 (s, IH), 6.8-7.9 (m, 8H), 8J-9.2 (m, 2H), 10.3-10.4 (s, IH). Example 54 Preparation of (R)-l-ri.l-dimethvI-2-(2-naphthalenyl)ethylaminol-3-r3-oxy-9.10- dihvdrodibenz r >. iπ.41oxazepin1-2-propanol monohydrochloride. a) 3-Methoxy-(9,10-dihydrodibenzfø/I[l,4]azepin). A solution of 3-methoxy-dibenz[7>, l[l,4]oxazepin-l l(10H) (7.4 g, 30J mmol) in THF (200 mL) was treated dropwise with LiAlH4 (30 mL, IM in THF). Solution was cooled to 0 C and treated carefully with water (2 mL). After 20 min., NaF (5 g, 120 mmol) in water (10 mL) was added to the solution. The solution was stirred at RT for 1 h. The solution was filtered and filtrate was concentrated to give the cmde title compound which is used as is for the next step (7.6 g). MS (ES) m/e 228.0 (M + H) + . b) 3-Hydroxy-(9,10-dihydrodibenz[i Λ ][l,4]azepin). Following the procedure of Example 53 (d) except substituting 3-methoxy-(9,10- dihydrodibenz[&,/|[l,4]azepin) (1 g, 4.4 mmol) for the compound of Example 53 (c), the cmde title compound was prepared and used as is for the next step (0.89 g). c) 2R-Glycidyl-(3-oxy-dibenz[ft A ][l,4] azepin-ll(lOH) Following the procedure of Example 53 (e) except substituting 3-hydroxy-(9,10- dihydrodibenz[&,/][l,4]azepin) (0.89 g, 4.4 mmol) for the compound of Example 53 (d) the cmde title compound was prepared and used as is for the next step (1.0 g). d) (R)-l-[l,l-dimethyl-2-(2-naphthalenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [6χ ][l,4]oxazepin]-2-propanol monohydrochloride. Following the procedure of Example 53 (f) except substituting 2-R-glycicyl-(3-oxy- dibenz[fcJ][l,4] azepin-11(10H) (0.4 g, 1.5 mmol) for the compound of Example 53 (g) the titie compound was prepared (0.3 g, 43%). MS (ES) m/e 469.2 (M + H)+. 1 HNMR (400 MHz, DMSO-d 6 ) δ 1.2-1.3 (s, 6H), 2.4-4.3 (m, 7H), 6.7-8.0 (m, 14H), 8.7-9.3 (m, 2H). Example 55 Preparation of (R)-l-ri.l-dimethvI-2-(2-naphthalenyl)ethylaminol-3-r3-oxy-9.10- dihvdrodibenz r&.fl-1.4Ioxazepin-ll(10H)- ethylcarboxymethyll-propan-2-ol monohydrochloride a) EthyI-3-methoxy-dibenz[ft Λ ][l,4]azepine-ll(10H)-acetate A solution of 3-methoxy-(9,10-dihydrodibenz[&, |[l,4]azepin (1.0 g, 4.4 mmol), triethylamine (0.6 mL, 4.4 mmol) and methylbromoacetate (0.49 mL, 4.4 mmol) in acetonitrile (10 mL) was heated at reflux for 18 h. The solution was concentrated to give the cmde title compound and used as is for the next step (1.2 g). b) Ethyl-3-hydroxy-dibenz[7» x ][l,4]azepine-ll(10H)-acetate Following the procedure of Example 53 (d) except substituting ethyl-3-methoxy- dibenz[£,/|[l,4]azepine-l l(10H)-acetate (1.2 g, 4.4 mmol) for the compound of Example 53 (c) the cmde title compound was prepared and used as is for the next step (1.1 g). c) Ethyl 2R-Glycidyl-(3-oxy-dibenz[6 A ][l,4] azepin-ll( 10H) acetate Following the procedure of Example 53 (e) except substituting ethyl-3-hydroxy- dibenz[fo,/][l,4]azepine-l l(10H)-acetate (1.6 g, 4.4 mmol) for the compound of Example 53 (d) the cmde title compound was prepared and used as is for the next step (1.7 g) d) (R)-l-[l,l-dimethyl-2-(2-naphthalenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [^ A ][lj4]oxazepin-ll(10H)-ethylcarboxymethyl]-propan-2-ol monohydrochloride Following the procedure of Example 53 (f) except substituting ethyl 2R-glycidyl-(3- oxy-dibenz[&J][l,4] azepin-1 l(10H)acetate (0.09g, 0.25 mmol) for the compound of Example 53 (g) the titie compound was prepared (0.07 g, 50%). MS (ES) m/e 555.2 (M + H)+; 1H NMR (400 MHz, DMSO-d 6 ) δ 1.0-1.3 (s, 9H), 2.4-4.6 (m, 9H), 6J-8.0 (m, 14H), 8.7-9.3 (m, 2H). The above nuclear magnetic resonance spectra are recorded at either 250 or 400 MHz using, respectively, a Bruker AM 250 or Bmker AC 400 spectrometer. CDCI3 is deuteriochloroform, DMSO-d6 is hexadeuteriodimethylsulfoxide, and CD3OD is tetradeuteriomethanol. Chemical shifts are reported in parts per million δ downfield from the internal standard tetramethylsilane. Abbreviations for NMR data are as follows: s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet, dd=doublet of doublets, dt=doublet of triplets, app=apparent, br=broad. J indicates the NMR coupling constant measured in Hertz (Hz). Continuous wave infrared (IR) spectra are recorded on a Perkin-Elmer 683 infrared spectrometer, and Fourier transform infrared (FΗR) spectra are recorded on a Nicolet Impact 400 D infrared spectrometer. IR and FTIR spectra are recorded in transmission mode, and band positions are reported in inverse wavenumbers (cm-1). Mass spectra are taken on either VG 70 FE, PE Syx API III, or VG ZAB HF instruments, using fast atom bombardment (FAB) or electrospray (ES) ionization techniques. Elemental analyses are obtained using a Perkin-Elmer 240C elemental analyzer. Melting points are taken on a Thomas-Hoover melting point apparatus and are uncorrected. All temperatures are reported in degrees Celsius. Analtech Silica Gel GF and E. Merck Silica Gel 60 F-254 thin layer plates are used for thin layer chromatography. Both flash and gravity chromatography are carried out on E. Merck Kieselgel 60 (230-400 mesh) silica gel. Analytical and preparative HPLC are carried out on Rainin or Beckman chromatographs. ODS refers to an octadecylsilyl derivatized silica gel chromatographic support. 5 uApex-ODS indicates an octadecylsilyl derivatized silica gel chromatographic support having a nominal particle size of 5 u, made by Jones Chromatography, Littleton, Colorado. YMC ODS-AQ® is an ODS chromatographic support and is a registered trademark of YMC Co. Ltd., Kyoto, Japan. PRP-1® is a polymeric (styrene-divinylbenzene) chromatographic support, and is a registered trademark of Hamilton Co., Reno, Nevada) Celite® is a filter aid composed of acid-washed diatomaceous silica, and is a registered trademark of Manville Coφ., Denver, Colorado. Formulations for pharmaceutical use incoφorating compounds of the present invention can be prepared in various forms and with numerous excipients. Examples of such formulations are given below. Example 56 Inhalant Formulation A compound of Formula (I), (1 mg to 100 mg) is aerosolized from a metered dose inhaler to deliver the desired amount of drug per use. Example 57 Tablet Formulation Tablets/Ingredients Per Tablet 1. Active ingredient 40 mg (Cpd of Form. (I) 2. Com Starch 20 mg 3. Alginic acid 20 mg 4. Sodium Alginate 20 mg 5. Mg stearate 1.3 mg Procedure for tablet formulation: Ingredients 1, 2, 3 and 4 are blended in a suitable mixer/blender. Sufficient water is added portion- wise to the blend with careful mixing after each addition until the mass is of a consistency to permit its conversion to wet granules. The wet mass is converted to granules by passing it through an oscillating granulator using a No. 8 mesh (2.38 mm) screen. The wet granules are then dried in an oven at 140°F (60°C) until dry. The dry granules are lubricated with ingredient No. 5, and the lubricated granules are compressed on a suitable tablet press. Example 58 Parenteral Formulation A pharmaceutical composition for parenteral administration is prepared by dissolving an appropriate amount of a compound of formula I in polyethylene glycol with heating. This solution is then diluted with water for injections (to 100 mL). The solution is then rendered sterile by filtration through a 0.22 micron membrane filter and sealed in sterile containers. All publications, including but not limited to patents and patent applications cited in this specification are herein incoφorated by reference as if each individual publication were specifically and individually indicated to be incoφorated by reference as though fully set forth.

Claims: What is claimed is: 1. A compound according toFormula (I): Formula (I) wherein: Y is a covalent bond, alkylene or alkenylene of up to 4 carbon atoms, unsubstituted or substituted by C .4 alkyl; Y2 is methylene, unsubstituted or substituted by C\.A alkyl or CF3. Z is selected from the group consisting of a covalent bond, O, S, NH, N-C1-.4 alkyl, 0(CH2) n , (CH 2 ) n O, NR"' C=0 and C=ONR"', where R'" is C .4 alkyl and n is an integer from 1 to 3, R3 and R4 are, independently, methyl or ethyl, or, together, form cyclopropyl; R5 is phenyl or naphthyl, unsubstituted or substituted with one or more substituents selected from the group consisting of OH, Ci^alkyl CH(CH3)2, halo, halo C1-.4 alkyl, C1.4 alkoxy, C3. 6 cycloalkyl, OSO 2 R , , CN, N0 2 , OCF3, CF3, and CH 2 CF 3 , wherein R ,v represents Cι_ 4 alkyl or C3.6 cycloalkyl; G is a covalent bond or C-Rg wherein Rg is H, OH or O (forming a carbonyl moiety); R 7 is H, OH, or O-C .4 alkyl; Rg is H or C1-.4 alkyl; or R7 and Rg together form a carbonyl moiety; the -A-B- moiety is represented by CH2CH2, a covalent bond, -CH=CH- or -C=C-; and X is selected from the group consisting of sub-formulae (Ia), (lb), (Ic) (Id) and (Ie) hereinbelow: (la) (Ic) (Id) (le) wherein : in sub-formula (Ia): W is selected from the group consisting of R , SO2R1, C(O)R , SO2 R R ', C(0)NR R ', C(0)OR Sθ3Rι', wherein Ri and Rj' are independently selected from the group consisting of hydrogen, C . alkyl, C3-.6 cycloalkyl, C2.5 alkenyl, C2.5 alkynyl, heterocycloalkyl aryl and aryl C .4 alkyl; or Ri and R\ together form a 3 to 7 membered optionally substituted heterocyclic ring; wherein any substituents are selected from the group consisting of CN, aryl, CO2R, CO2NHR, OH, OR, NH2, halo, CF3, OCF3 and NO2; wherein R represents C1--4 alkyl, or C3.6 cycloalkyl; X is selected from the group consisting of CN, NO2, CI, F, Br, I, H, R', OR', CF3, OCF3 and OSO2R', wherein R' represents C\.A alkyl, or C3.6 cycloalkyl; X2 , X3 and X4 are, independently, selected from the group consisting of CN, NO2, CI, F, Br, I, H, R", OR", CF3, OCF3 and OS0 2 R", wherein R" is Cι_ 4 alkyl or haloalkyl; or Xi and X 2 together form an aryl or heteroaryl ring, substituted or unsubstituted; wherein the heteroatom is selected from N, S and O; and any substituents are selected from the group consisting of halo, C1-.4 alkyl, OCF3, CF3, OMe, CN, OSO2R' and NO2; or X3 and X4 independently represent C(0)Rι; provided that when there are multiple halo substitutions in the haloalkyl, halo represents F; also provided that either X or X3 is hydrogen; and R2 is selected from the group consisting of hydrogen, C1.4 alkyl, C3.5 cycloalkyl, C2-.5 alkenyl, C2-.5 alkynyl, heterocycloalkyl aryl and aryl-Cι- alkyl; in sub-formula (lb): Xl" is selected from the group consisting of CN, NO2, CI, F, Br, I, H, R, OR, CF3, OCF3 and OSO2R, wherein R represents C1.4 alkyl, or C3.6 cycloalkyl; X2", X3" and X4" are, independently, selected from the group consisting of CN, NO2, CI, F, Br, I, H, R', OR', CF3, OCF3 and OS0 2 R', wherein R' is C 1.4 alkyl or haloalkyl; provided that when there are multiple halo substitutions in the haloalkyl, halo represents F, or X j " and X2" together form an aryl or heteroaryl ring, substituted or unsubstituted; wherein the heteroatom is selected from N, S and O and any substituents are selected from the group consisting of halo, C1.4 alkyl, OCF3, CF3, OMe, CN, OSO 2 -Cι_ alkyl, OS0 2 -C 3 . 6 cycloalkyl and N0 2 ; or X3" and X4" independently represent C(0)R ; provided that either X " or X3" is hydrogen; and Rl" and R2" are, independently, selected from the group consisting of hydrogen, C \.A alkyl, C3-6 cycloalkyl, C2.5 alkenyl, C2.5 alkynyl, heterocycloalkyl and aryl; or R " and R2" together form a 3 to 7 membered optionally substituted heterocyclic ring, optionally containing an additional heteroatom selected from O, S and N; wherein any substituents are selected from the group consisting of CN, aryl, CO 2 R", C0 2 NHR", OH, OR", NH 2 , halo, CF3, OCF3 and NO2; wherein R" represents C1-.4 alkyl, or C^. cycloalkyl; in sub-formula (Ic): Xl'" is selected from the group consisting of CN, NO 2 , CI, F, Br, I, H, R, OR, CF3, OCF3 and OSO2R, wherein R represents C .A alkyl, or C3.6 cycloalkyl; X2'", X3'", and X4'" are, independently, selected from the group consisting of CN, NO2, CI, F, Br, I, H, R', OR', CF3, OCF3 and OSO2R', wherein R' is Cι_ 4 alkyl or haloalkyl; provided that when there are multiple halo substitutions in the haloalkyl, halo represents F; or X '" and X2'" together form an aryl or heteroaryl ring, substituted or unsubstituted; wherein the heteroatom is selected from N, S and O and the substituents are selected from the group consisting of halo, C\_ A alkyl, OCF3, CF3, OMe, CN, OSO 2 -Cι_ 4 alkyl, OSO 2 -C3_ 6 cycloalkyl and N0 2 ; or X3'" and X4 '" independently represent C(0)Rι; provided that either Xi'" or X3'" represents hydrogen; and Rl'" and R2'" are, independently, selected from the group consisting of hydrogen, C1--4 alkyl, C3.6 cycloalkyl, C2-.5 alkenyl, C2-.5 alkynyl, heterocycloalkyl and aryl; or Ri'and R2'" together form a 3 to 7 membered optionally substituted heterocyclic ring optionally containing an additional heteroatom selected from O, S and N; wherein the substituents are selected from the group consisting of CN, aryl, CO 2 R", C0 2 NHR", OH, OR", NH 2 , halo, CF3, OCF3 and N0 2 ; wherein R" represents C\_A alkyl, or C3--6 cycloalkyl; in sub-formula (Id): D is selected from the group consisting of CN, N0 2 , CI, F, Br, I, R, OR, SR, CF3, OCF3 and OSO2R, wherein R represents C1-.4 alkyl, C3-.6 cycloalkyl, or CJ.JO aryl or heteroaryl wherein the heteroatom is selected from N, S and O and substituents are selected from the group consisting of halo, Cι_ alkyl, OCF3, CF3, OMe, CN, OSO2-C1.4 alkyl, OS0 2 -C 3 . 6 cycloalkyl and N0 2 ; n is the integer 1 or 2; each E is independently C or N, provided that no more than two E moieties are N; further provided that when n is 2, each E is C; a and b are optionally present bonds; Ri ,v is selected from the group consisting of (CH2) n Cθ2R', (CH2) n CO2H, (CH2) n CONR'2, (CH2) n CH 2 OR', OR', SR', CN, N0 2 , CI, F, Br, I, CF 3 , OCF 3 , OSO 2 R\ R' and H; wherein R' is Cι_4 alkyl, or C3.6 cycloalkyl; or R IV is O, forming a ketone such that Y R ,v represents -C=O; R2 IV is selected from the group consisting of hydrogen, CN, NO2 CI, F, Br, I, H, R", OR", CF3, OCF3, and OSO2R"; wherein R" represents C \ .A alkyl, or C3.6 cycloalkyl. Y is selected from the group consisting of C, CH, O, N and S; provided that when Y is S, Ri IV is O; further provided that when Y is O, Ri IV is not present; X' is selected from the group consisting of CH2, NH, O and S; and attachment is at the carbon atom marked 3; in sub-formula (Ie): Xl"" is selected from the group consisting of CN, NO2, CI, F, Br, I, H, R', OR', CF3, OCF3 and OSO2R', wherein R' represents C\.A alkyl, or C3.6 cycloalkyl; X2"", X3"" and X4"" are, independently, selected from the group consisting of CN, NO2, CI, F, Br, I, H, R", OR", CF3, OCF3 and OS0 2 R", wherein R" is Cι_ 4 alkyl or haloalkyl; or X!"" and X2"" together form an aryl or heteroaryl ring, substituted or unsubstituted; wherein the heteroatom is selected from N, S and O; and any substituents are selected from the group consisting of halo, Cι_ alkyl, OCF3, CF 3 , OMe, CN, OS0 2 R' and NO 2 ; or X "" and X "" independently represent C(0)R ; provided that when there are multiple halo substitutions in the haloalkyl, halo represents F; also provided that either Xi"" or X3"" is hydrogen; and R9 is selected from the group consisting of 0-CH2-alkyl, 0-CH2-aryl and O-aryl. 2. A compound according to claim 1 selected from Formula (II) hereinbelow: Formula (II) wherein: R9 is selected from the group consisting of H, OH, OCH3, CI, F, CH3, CH2CH3 and CH(CH 3 ) 2 ; RlO is selected from the group consisting of H, CI, F, CF3 and CH3; or R9 and RIQ form an optionally substituted fused phenyl ring; and Rl 1 is selected from methyl, H or F. 3. A compound according to claim 2 wherein: in sub-formula (Ia): Xi is selected from the group consisting of CN, NO2, CI, F, Br, I and H; X2, X3 and X4 are, independently, selected from the group consisting of CI, F, Br, I and H; and Rl, Ri'and R2 are, independently, selected from the group consisting of C _4 alkyl, C3.5 cycloalkyl, heterocycloalkyl, aryl or arylC^alkyl;. in sub-formula (lb): Xi " is selected from the group consisting of CN, NO2, CI, F, Br, I and H; X2", X3" and X4" are, independently, selected from the group consisting of CI, F, Br, I and H; and Rl" and R2" are, independently, selected from the group consisting of C 1.4 alkyl, C3. cycloalkyl, heterocycloalkyl or aryl; or R " and R2" together form an optionally substimted 3-7 membered ring; in sub-formula (Ic): Xl"' is selected from the group consisting of CN, NO2, CI, F, Br, I and H; X2'", X3'" and X4'" are, independently, selected from the group consisting of CI, F, Br, I and H; and Rl'" and R2'"are, independently, selected from the group consisting of C j _4 alkyl, C3-.6 cycloalkyl, heterocycloalkyl or aryl; or Ri'" and R2'" together form an optionally substimted 3-7 membered ring; in sub-formula (Id): D is selected from the group consisting of CI, F, Br, I, R, OR, SR, and H; Rj ιv is selected from the group consisting of (CH2) n Cθ2R\ (CH2) n Cθ2H, (CH2) n CONR'2, (CH 2 )nCH 2 OR', OR', SR', R' and H; wherein R' is Cι_ 4 alkyl or C 3 . 6 cycloalkyl; or Ri I is O, forming a ketone such that Y Ri lv represents -C=O; and R2 IV is selected from the group consisting of hydrogen, CN, NO2 CI, Br, F and I. 4. A compound according to claim 1 selected from the group consisting of: (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (4-methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3- [2-cyano-4- [N- [4-methy Ipheny lsulf ony l]amino]phenoxy ]- 1 -[1,1 -dimethy l-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4- [N-methyl-N-[4-methylphenylsulfonyl]amino]phenoxy ]- 1 -[ 1 , 1 -dimethyl-2- (4-methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[ N-methylsulfonylamino]phenoxy]- 1 -[1,1 -dimethy l-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[ N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (2-naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (benzyloxy)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[ 1,1 -dimethy 1-3- phenylpropylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-4- phenylbutylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-ethylcarbonyl]phenoxy]-l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N'-moφholino]ureido]phenoxy]-l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N'-moφholino]ureido]phenoxy]-l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N'-moφholino]ureido]phenoxy]- l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N'-moφholino]ureido]phenoxy]-l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- propylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- piperidinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimemyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- moφholinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[2,3-dichloro-4-(N- moφholinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethy l-2-(2-naphthyl)ethylamino]-3-[2,3-dichloro-4-(N- moφholinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[2,3-dichloro-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3-[2,3-dichloro-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano, 3-chloro-4-(N- moφholinylcarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano, 3-chloro-4-(N- moφholinylcarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano, 3-chloro-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-oI; (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthy l)ethylamino]-3-[2-cyano, 3-chloro-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- pyrrolidinylcarbonyl)phenoxy]-propan-2-ol ; (R)- 1 -[ 1 , l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- piperazinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N-piperidinylcarbonyl)phenoxy]- propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N- moφholinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3- [2-cyano-4-(N-piperaziny lcarbonyl)phenoxy ]- propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N- pyrrolidinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , l-dimethyl-3-(phenyl)propylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-4-(phenyl)butylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-3-(phenoxy)propylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethyl-2-(oxybenzyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol. N-[3-(3-chloro-2-cyano-4-dipropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxypheny 1)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-dipropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(2,3-dichlorophenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-dimethylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-thiomoφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2- naphthy 1)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-thiomoφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(2'-cyanoeth-l-yl)-cyclopropylsulfamoyl]phenoxy-2(R)- hydroxypropyl]-2-(4-methoxypheny 1)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(2'-cyanoeth-l-yl)-cyclopropylsulfamoyl]phenoxy-2(R)- hydroxypropyl]-2-(2-napthyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(benzyl-cyclopropyl)sulfamoyl]phenoxy-2(R)-hydroxypropyl]-2-(2- napthyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(benzyl-cyclopropyl)sulfamoyl]phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(4'-N-t-butoxycarbonylpiperazino)sulfamyl]phenoxy-2(R)- hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(4'-N-t-butoxycarbonylpiperazino)sulfamyl]phenoxy)-2(R)- hydroxypropyl]-2-(2-naphthyl)- 1 , 1 -dimethylethylamine; N- [3-(2,3-dichloro-4-dipropy lsulfamoy l)phenoxy-2(R)-hydroxypropy l]-2-(2-naphthyl)- 1,1- dimethylethylamine; N-[3-(2,3-dichloro-4-pyrrolidinolsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-pyperidinolsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-cyclopropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-dipropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N- [3-(2,3-dichloro-4-propylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1,1- dimethylethylamine; N-[3-(2,3-dichloro-4-sulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1,1- dimethylethylamine; N-[3-(2,3-dichloro-4-methylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)-l,l- dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- fluorophenyl)-l,l-dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(benzyloxy)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy- 2(R)-hydroxypropyl]-3-phenyl-l,l- dimethylpropylamine; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy- 2(R)-hydroxypropyl]-4-pheny 1-1,1 - dimethylbutylamine; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[10,l l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[10,l l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(S)-acetic acid]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[10,l l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)- 1- [ 1 , 1 -dimethy l-2-(2-naphthyl)ethylamino]-3- [ 10, 1 l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(S)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethylamino]-3- [ 10-ethylthio-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3-[ 10-ethylthio-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[ 10, 1 l-dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid ]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[ 10, 11 -dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(S)-acetic acid ]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[10,l l-dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid ]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(2-naphthy l)ethylamino]-3-[ 10, 11 -dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(S)-acetic acid ]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[ 10-ethylthio-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-2-(2-naphthyl)ethylamino]-3- [ 10-ethylthio-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[10-ethylthio-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[10-ethylthio-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-10-oxo-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3-[3-oxy- 10-oxo-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethyl-3-phenyl-propylamino]-3-[ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)- 1-[ 1 , l-dimethyl-4-phenyl-butylamino]-3-[ 10, 1 l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-phenoxy-ethylamino]-3-[ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy 1-2-oxybenzy 1-ethy lamino] -3- [ 10, 11 -dihydro-2-cy ano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)- 1-[ 1 , l-dimethyl-2-(2-naphthalenyl)ethylamino]-3-[3-oxy-dibenz[6,/] [ 1 ,4]oxazepin- 11 ( 10H)- one]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxyphenyl]-3-[3-oxy-dibenz[b,f] [ 1 ,4]oxazepin- 11(10H)-one]- propan-2-ol monohydrochloride; (R)- 1 - [ 1 , 1 -dimethy l-2-( 1 , 1 -dimethy l-4-phenyl)-butylamino]-3-[3-oxy-dibenz[b,f] [ 1 ,4]oxazepin- 1 l(10H)-one]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethy l-2-( 1 , 1 -dimethy 1-2-oxybenzy l)-ethylamino]-3-[3-oxy- dibenz[£>J] [ 1 ,4]oxazepin- 11(10H)-one]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethyl-2-[(2-naphthalenyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin] -2-propanol monohydrochloride; (R)- 1 - [ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3- [3-oxy-9, 10-dihydrodibenz [b,f][l,4]oxazepin]-2-propanol monohydrochloride; (R)- 1 - [ 1 , l-dimethyl-2-( 1 , 1 -dimethyl-4-phenyl)-butylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin]-2-propanol monohydrochloride; (R)- 1-[ 1 , 1 -dimethy l-2-( 1 , 1 -dimethyl-2-oxybenzyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f][l,4]oxazepin]-2-propanol monohydrochloride; (R)- 1 -[ 1 , l-dimethyl-2-(2-naphthalenyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f][ 1 ,4]oxazepin- 11(10H)-carboxy methyl]-propan-2-ol monohydrochloride; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [b,f][ 1 ,4]oxazepin- 11(10H)-carboxymethyl]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethyl-2-( 1 , 1 -dimethy 1-4-pheny l)-butylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin- 11(10H)-carboxymethyl]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethy l-2-( 1 , 1 -dimethy l-2-oxybenzyl)ethy lamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f][l,4]oxazepin-l l(10H)-carboxymethyl]-propan-2-ol monohydrochloride; and pharmaceutically acceptable salts thereof. 5. A compound according to claim 4 selected from the group consisting of: (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (4-methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-[4-methylphenylsulfonyl]amino]phenoxy]-l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol ; (R)- 3-[2-cyano-4-[N-methyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[ 1,1 -dimethy 1-2- (4-methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N-[methylsulfonyl]amino]phenoxy]- l-[ 1,1 -dimethy l-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[ N-methylsulfonylamino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[ N-[methylsulfonyl]amino]phenoxy]- l-[ 1,1 -dimethy l-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (2-naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N'-moφholino]ureido]phenoxy]-l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N'-moφholino]ureido]phenoxy]-l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol ; (R)- 3-[2-cyano-4-[N-methyl-N'-moφholino]ureido]phenoxy]- l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N'-moφholino]ureido]phenoxy]-l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- piperidinylcarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano, 3-chloro-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)-l -[ 1 , 1 -dimethy l-2-(2-naphthyl)ethylamino]-3-[2-cyano, 3-chloro-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)- 1-[ 1 , l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- pyrrolidinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-2-(2-naphthyl)ethylamino]-3- [2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N-piperidinylcarbonyl)phenoxy]- propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N- pyrrolidinylcarbonyl)phenoxy]-propan-2-ol. N-[3-(3-chloro-2-cyano-4- dimethylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1,1- dimethylethylamine; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)- 1,1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-thiomoφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2- naphthy 1)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-thiomoφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(benzyl-cyclopropyl)sulfamoyl]phenoxy-2(R)-hydroxypropyl]-2-(2- napthyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(benzyl-cyclopropyl)sulfamoyl]phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)-l , 1-dimethylethylamine; N-[3-(2,3-dichloro-4-dipropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)-l,l- dimethylethylamine; N-[3-(2,3-dichloro-4-pyrrolidinolsulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1-dimethylethylamine; N-[3-(2,3-dichloro-4-piperidinolsulfamyl)phenoxy-2(R)-hydroxypropyl][2-(4-methoxyphenyl)- 1 , 1 -dimethyljethy lamine; N-[3-[3-chloro-2-cyano-4-(2'-cyanoeth-l-yl)-cyclopropylsulfamoyl]phenoxy-2(R)- hydroxypropyl]-2-(4-methoxyphenyl)-l,l-dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(2'-cyanoeth-l-yl)-cyclopropylsulfamoyl]phenoxy-2(R)- hydroxypropyl]-2-(2-napthyl)- 1,1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(benzyloxy)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-dipropylsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(benzyloxy)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy- 2(R)-hydroxypropyl]-3-phenyl-l,l- dimethylpropy lamine; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy- 2(R)-hydroxypropyl]-4-phenyl-l,l- dimethylbutylamine; (R)- 1 - [ 1 , 1 -dimethy l-2-(4-methoxypheny l)ethylamino]-3- [ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3- [ 10, 11 -dihydro-2-cy ano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(S)-acetic acid]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[10,l l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(2-naphthy l)ethy lamino]-3- [ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(S)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-310-ethylthio-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-2-(4-methoxypheny l)ethy lamino]-310-ethy lthio-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[ 10, 11 -dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[ 10, 11 -dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(S)-acetic acid]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-2-(2-naphthyl)ethylamino]-3-[ 10, 11 -dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[10,l l-dihydro-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(S)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[ 10-ethylthio-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)-l-[l , 1 -dimethyI-2-(2-naphthyl)ethylamino]-3-[ 10-ethylthio-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-3-phenyl-propylamino]-3-[ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-4-pheny l-butylamino]-3-[ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-phenoxy-ethylamino]-3-[ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-oxybenzyl-ethy lamino]-3-[ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthalenyl)ethylamino]-3-[3-oxy-dibenz[b,f][l,4]oxazepin- 11(10H)-one]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethyl-2-(4-methoxypheny l]-3-[3-oxy-dibenz[b,f] [ 1 ,4]oxazepin- 11 (10H)-one]- propan-2-ol monohydrochloride; (R)- 1-[ 1 , 1 -dimethy l-2-( 1 , 1 -dimethyl-4-phenyl)-butylamino]-3-[3-oxy-dibenz[b,f][ 1 ,4]oxazepin- 1 l(10H)-one]-propan-2-ol monohydrochloride; (R)-l-[l,l-dimethyl-2-(l,l-dimethyl-2-oxybenzyl)-ethylamino]-3-[3-oxy- dibenz[b,f] [ 1 ,4]oxazepin- 11(10H)-one]-propan-2-ol monohydrochloride; (R)-l-[l,l-dimethyl-2-[(2-naphthalenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [b,f] [ 1 ,4]oxazepin]-2-propanol monohydrochloride; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [b,f][l,4]oxazepin]-2-propanol monohydrochloride; (R)- 1 - [ 1 , 1 -dimethy l-2-( 1 , 1 -dimethyl-4-phenyl)-butylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin]-2-propanol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethy l-2-( 1 , l-dimethyl-2-oxybenzyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f][l,4]oxazepin]-2-propanol monohydrochloride; (R)- 1-[ 1 , l-dimethyl-2-(2-naphthalenyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin- 11 ( 10H)-carboxymethyl]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin- 11(10H)-carboxy methyl]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimeti yl-2-( 1 , 1 -dimethyl-4-phenyl)-butylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin- 11(10H)-carboxymethyl]-propan-2-ol monohydrochloride; (R)- 1 -[ 1 , 1 -dimethy l-2-( 1 , 1 -dimethyl-2-oxybenzyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin- 11(10H)-carboxy methyl]-propan-2-ol monohydrochloride; and pharmaceutically acceptable salts thereof. 6. A compound according to claim 5 selected from the group consisting of: (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (4-methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-[4-methylphenylsulfonyl]amino]phenoxy]-l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- 1 -[ 1 , 1 -dimethy 1-2- (4-methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N-[methylsulfonyl]amino]phenoxy]- 1 -[ 1 , 1 -dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N-[methylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3- [2-cyano-4-[N-benzyl-N'-moφholino]ureido]phenoxy]- 1 -[ 1 , 1 -dimethy l-2-(2- naphthyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-benzyl-N'-moφholino]ureido]phenoxy]-l-[l,l-dimethyl-2-(4- methoxyphenyl)ethylamino]-propan-2-ol; (R)- 3-[2-cyano-4-[N-methyl-N'-moφholino]ureido]phenoxy]- l-[l,l-dimethyl-2-(2- naphthyl)ethylamino]-propan-2-ol ; (R)- 3-[2-cyano-4-[N-methyl-N'-moφholino]ureido]phenoxy ]- 1 - [ 1 , 1 -dimethy l-2-(4- methoxyphenyl)ethylamino]-propan-2-ol (R)- 3-[2-cyano-4-[N-benzyl-N-[4-methylphenylsulfonyl]amino]phenoxy]- l-[l,l-dimethyl-2- (2-naphthyl)ethylamino]-propan-2-ol ; (R)- 1 -[ 1 , l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- piperidinylcarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[2-cyano-4-(N- pyrrolidinylcarbonyl)phenoxy]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N,N- dipropylaminocarbonyl)phenoxy]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N-piperidinylcarbonyl)phenoxy]- propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[2-cyano-4-(N- pyrrolidinylcarbonyl)phenoxy]-propan-2-ol; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-pyrrolidinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2-naphthyl)- 1,1-dimethylethylamine; N-[3-(3-chloro-2-cyano-4-thiomoφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(2- naphthyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-thiomoφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-pyrrolidinolsulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-piperidinolsulfamoyl)phenoxy-2(R)-hydroxypropyl]-2-(4- methoxyphenyl)- 1 , 1-dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(benzyloxy)- 1,1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(2'-cyanoeth-l-yl)-cyclopropylsulfamoyl]phenoxy-2(R)- hydroxypropyl]-2-(4-methoxyphenyl)- 1 , 1 -dimethylethylamine; N-[3-[3-chloro-2-cyano-4-(2'-cyanoeth-l-yl)-cyclopropylsulfamoyl]phenoxy-2(R)- hydroxypropyl]-2-(2-napthyl)- 1 , 1 -dimethylethylamine; N-[3-(3-chloro-2-cyano-4-moφholinosulfamyl)phenoxy-2(R)-hydroxypropyl]-2-(benzyloxy)- 1 , 1 -dimethylethylamine; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy- 2(R)-hydroxypropyl]-4-phenyl-l,l- dimethylbutylamine; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy- 2(R)-hydroxypropyl]-3-phenyl-l,l- dimethylpropylamine; N-[3-(2,3-dichloro-4-moφholinosulfamyl)phenoxy- 2(R)-hydroxypropyl]-4-pheny 1-1,1 - dimethylbutylamine; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[10,l l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(R)-acetic acid]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[10,l l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(S)-acetic acid]-propan-2-ol; (R)- 1-[ 1 , 1 -dimethy l-2-(2-naphthyl)ethylamino]-3-[ 10, 1 l-dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene- 10-(R)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , 1 -dimethy l-2-(2-naphthyl)ethylamino]-3-[ 10, 11 -dihydro-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene-10-(S)-acetic acid]-propan-2-ol; (R)- 1 -[ 1 , l-dimethyl-2-(2-naphthyl)ethylamino]-3-[ 10-ethylthio-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)-l-[l,l-dimethyl-2-(2-naphthyl)ethylamino]-3-[10-ethylthio-2-cyano-3-oxy-5H- dibenzo[a,d]cycloheptene]-propan-2-ol; (R)- 1 - [ 1 , 1 -dimethy l-2-(2-naphthalenyl)ethy lamino] -3- [3-oxy-dibenz[b,f] [ 1 ,4] oxazepin- l l(10H)-one]-propan-2-ol monohydrochloride; (R)- 1 - [ 1 , 1 -dimethyl-2-(4-methoxypheny l]-3- [3-oxy-dibenz[b,f] [ 1 ,4] oxazepin- 11(10H)-one] - propan-2-ol monohydrochloride; (R)- 1 -[ 1 , l-dimethyl-2-[(2-naphthalenyl)ethylamino]-3-[3-oxy-9, 10-dihydrodibenz [b,f] [ 1 ,4]oxazepin]-2-propanol monohydrochloride; (R)- 1-[ 1 , 1 -dimethy l-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [b,f] [ 1 ,4]oxazepin]-2-propanol monohydrochloride; (R)-l-[l,l-dimethyl-2-(2-naphthalenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [b,f][l,4]oxazepin-l l(10H)-carboxymethyl]-propan-2-ol monohydrochloride; (R)-l-[l,l-dimethyl-2-(4-methoxyphenyl)ethylamino]-3-[3-oxy-9,10-dihydrodibenz [b,f][l,4]oxazepin-l l(10H)-carboxymethyl]-propan-2-ol monohydrochloride; and pharmaceutically acceptable salts thereof. 7. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. 8. A method of antagonizing a calcium receptor which comprises administering to a subject in need thereof, an effective amount of a compound of claim 1. 9. A method of treating a disease or disorder characterized by an abnormal bone or mineral homeostasis, which comprises administering to a subject in need of treatment thereof an effective amount of a compound of claim 1. 10. A method according to claim 9 wherein the bone or mineral disease or disorder is selected from the group consisting of: osteosarcoma, periodontal disease, fracture healing, osteoarthritis, rheumatoid arthritis, Paget's disease, humoral hypercalcemia malignancy, and osteoporosis. 11. A method according to claim 10 wherein the bone or mineral disease or disorder is osteoporosis. 12. A method of increasing semm parathyroid levels which comprises administering to a subject in need of treatment an effective amount of a compound according to claim 1.

Inventors: BARMORE ROBERT M, BHATNAGAR PRADIP KUMAR, BRYAN WILLIAM M, BURGESS JOELLE LORRAINE, CALLAHAN JAMES FRANCIS, CALVO RAUL ROLANDO, DEL MAR ERIC G, LAGO MARIA AMPARO, NGUYEN THOMAS THE, SHEEHAN DEREK, SMITH ROBERT LAWRENCE, SOUTHALL LINDA SUE, VAN WAGENEN BRADFORD C, BARMORE, ROBERT, M., BHATNAGAR, PRADIP, KUMAR, BRYAN, WILLIAM, M., BURGESS, JOELLE, LORRAINE, CALLAHAN, JAMES, FRANCIS, CALVO, RAUL, ROLANDO, DEL MAR, ERIC, G., LAGO, MARIA AMPARO, NGUYEN, THOMAS, THE, SHEEHAN, DEREK, SMITH, ROBERT, LAWRENCE, SOUTHALL, LINDA, SUE, VAN WAGENEN, BRADFORD, C.
Applicants: BARMORE ROBERT M, BHATNAGAR PRADIP KUMAR, BRYAN WILLIAM M, BURGESS JOELLE LORRAINE, CALLAHAN JAMES FRANCIS, CALVO RAUL ROLANDO, DEL MAR ERIC G, LAGO MARIA AMPARO, NGUYEN THOMAS THE, NPS PHARMA INC, SHEEHAN DEREK, SMITH ROBERT LAWRENCE, SMITHKLINE BEECHAM CORP, SOUTHALL LINDA SUE, WAGENEN BRADFORD C VAN, BARMORE, ROBERT, M., BHATNAGAR, PRADIP, KUMAR, BRYAN, WILLIAM, M., BURGESS, JOELLE, LORRAINE, CALLAHAN, JAMES, FRANCIS, CALVO, RAUL, ROLANDO, DEL MAR, ERIC, G., LAGO, MARIA AMPARO, NGUYEN, THOMAS, THE, NPS PHARMACEUTICALS, INC., SHEEHAN, DEREK, SMITH, ROBERT, LAWRENCE, SMITHKLINE BEECHAM CORPORATION, SOUTHALL, LINDA, SUE, VAN WAGENEN, BRADFORD, C.
Application year: 1998
Main classification: C07C255
IPC codes: A61K31, A61P1, A61P3, A61P5, A61P19, A61P35, C07C255, C07C311, C07C323, C07D267, C07D295