CaSR Antagonist

Abstract

A compound represented by the following formula (1), a pharmaceutically acceptable salt thereof or an optically active form thereof: wherein each symbol is as defined in the specification. A compound having a calcium-sensing receptor antagonistic action, a pharmaceutical composition comprising the compound, particularly a calcium receptor antagonist and a therapeutic drug for osteoporosis are provided.

1 . A compound represented by the following formula (1): 
       
         
           
           
               
               
           
         
         wherein 
         n is 0 or 1, 
         p is an integer of 1 to 3, 
         R 1  is a hydroxyl group, a C 1-6  alkoxy group or R A ,
 wherein R A  is R C —OC(═O)O—C 1-4  alkylene-O— or OH—NH—,
 wherein R C  is a C 1-6  alkyl group or a C 3-6  cycloalkyl group, 
 
 
         R 2  and R 3  are the same or different and each is a hydrogen atom, a hydroxyl group, a halogen atom, an amino group, a C 1-7  acylamino group, a halo C 1-6  alkyl group, a carboxyl group, a C 1-6  alkoxy-carbonyl group, a C 1-6  alkoxy group, a halo C 1-6  alkoxy group, a C 1-6  alkyl group, a hydroxy-C 1-6  alkyl group, a C 1-7  acylamino-C 1-6  alkyl group, a C 2-6  alkenyl group, an aralkyl group, a phenyl group, a C 1-6  alkylamino group, a di(C 1-6  alkyl)amino group, a C 1-6  alkoxy-C 1-6  alkyl group, a mercapto group, a cyano group, a nitro group, a morpholino group, a piperidino group or a pyrrolidino group, or R 2  and R 3  are joined to form an ethyleneoxy group, 
         X 1  is —C═C—, —C═N—, an oxygen atom or a sulfur atom, 
         Z is —S—, —SO—, —SO 2 —, —(CH 2 ) m1 —O—, —O—(CH 2 ) m1 —, —(CH 2 ) m2 —NH—, —NH—(CH 2 ) m2 —, —(CH 2 ) m3 —N(CH 2 )—, —N(CH 3 )—(CH 2 ) m3 —, a C 1-4  alkylene group, —SO 2 —N(CH 3 )—, —N(CH 3 )—SO 2 —, —NHCO—, —CONH— or a C 2-4  alkenylene group,
 wherein m1, m2 and m3 are each an integer of 0 to 2, 
 
         X 2  is —C═C—, an oxygen atom or a sulfur atom, 
         R 4  is a C 1-6  alkyl group or a C 3-6  cycloalkyl group, 
         R 5  is a hydrogen atom or R B ,
 wherein R B  is a C 1-7  acyl group optionally substituted by a carboxyl group, 
 
         Y is a carbon atom or a nitrogen atom, and 
         R 6 , R 7  and R 8  are the same or different and each is a hydrogen atom, a halogen atom, a C 1-6  alkyl group, a C 1-6  alkoxy group, a halo C 1-6  alkyl group, a halo C 1-6  alkoxy group, a carboxyl group, a hydroxyl group, a cyano group, a nitro group, a phenyl group, a C 3-6  cycloalkyl group, a di(C 1-6  alkyl)aminocarbonyl group or a hydroxy-C 1-6  alkyl group, or adjacent R 6  and R 7  are joined to form —CH═CH—CH═CH—, —C(OH)═CH—CH═CH—, —CH═C(OH)—CH═CH—, —O—(CH 2 ) k1 —O—, —O—(CH 2 ) k2 — or —(CH 2 ) k3 —,
 wherein k1 is an integer of 1 to 4, k2 is an integer of 2 to 5, k3 is an integer of 3 to 6, 
 
         provided that when R 2  and R 3  are both hydrogen atoms and n is 1, then Z should be a group other than —SO 2 —N(CH 3 )— wherein sulfur atom is bonded to ring V and a nitrogen atom is bonded to ring W, a pharmaceutically acceptable salt thereof or an optically active form thereof. 
       
     
     
         2 . The compound of  claim 1 , which has a configuration represented by the following formula (1′) 
       
         
           
           
               
               
           
         
         wherein each symbol is as defined in  claim 1 , or a pharmaceutically acceptable salt thereof. 
       
     
     
         3 . The compound of  claim 1  or  2 , wherein n is 1, or a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         4 . The compound of  claim 3 , wherein
 n is 1,   p is 1,   R 1  is a hydroxyl group or a C 1-6  alkoxy group,   R 2  and R 3  are the same or different and each is a hydrogen atom, a hydroxyl group, a halogen atom, an amino group, a C 1-7  acylamino group, a trifluoromethyl group, a C 1-6  alkoxy-carbonyl group, a C 1-6  alkoxy group, a C 1-6  alkyl group, a hydroxy-C 1-6  alkyl group, a C 2-6  alkenyl group, a phenyl group, a benzyl group, a di(C 1-6 alkyl)amino group or a nitro group, or R 2  and R 3  are joined to form an ethyleneoxy group,   X 1  is —C═C— or —C═N—,   X 2  is —C═C—,   Z is —S—, —SO—, —SO 2 —, —(CH 2 ) m1 —O—, —O—(CH 2 ) m1 —, —(CH 2 ) m2 —NH—, —NH—(CH 2 ) m2 —, —(CH 2 ) m3 —N(CH 3 )—, —N(CH 3 )—(CH 2 ) m3 —, a C 1-4  alkylene group or a C 2-4  alkenylene group,
 wherein m1, m2 and m3 are each an integer of 0 to 2, 
   R 4  is a C 1-6  alkyl group or a C 3-6  cycloalkyl group,   R 5  is a hydrogen atom,   Y is a carbon atom or a nitrogen atom, and   R 6 , R 7  and R 8  are the same or different and each is a hydrogen atom, a halogen atom, a C 1-6  alkyl group or a C 1-6  alkoxy group, or adjacent R 6  and R 7  are joined to form —CH═CH—CH═CH—,   a pharmaceutically acceptable salt thereof or an optically active form thereof.   
     
     
         5 . The compound of  claim 4 , wherein
 n is 1,   p is 1,   R 1  is a hydroxyl group or a C 1-6  alkoxy group,   R 2  and R 3  are the same or different and each is a hydrogen atom, a halogen atom, a C 1-6  alkoxy group or a C 1-6  alkyl group,   X 1  is —C═C—,   Z is —S—, —SO—, —SO 2 —, —(CH 2 ) m1 —O—, —O—(CH 2 ) m1 —, —CH 2 —NH—, —NH—CH 2 —, —N(CH 3 )—, methylene or vinylene,
 wherein m1 is 0 or 1, 
   X 2  is —C═C—,   R 4  is a methyl group or a cyclopropyl group,   R 5  is a hydrogen atom,   Y is a carbon atom or a nitrogen atom, and   R 6 , R 7  and R 8  are the same or different and each is a hydrogen atom, a halogen atom or a C 1-6  alkyl group, or adjacent R 6  and   R 7  are joined to form —CH═CH—CH═CH—,   a pharmaceutically acceptable salt thereof or an optically active form thereof.   
     
     
         6 . The compound of  claim 3 , which is selected from the group consisting of
 4-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]benzoic acid,   4-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]-3-methoxybenzoic acid,   methyl 4-[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]benzoate,   4-[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]benzoic acid,   4-[2-[1-[(2R)-3-[[1-(quinolin-3-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]benzoic acid,   4-[2-[1-[(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]benzoic acid,   4-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]benzoic acid,   3-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]benzoic acid,   4-[2-[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenyl]vinyl]benzoic acid,   3-[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenylthio]benzoic acid,   4-[2-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenyl]vinyl]benzoic acid,   4-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-1-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]-3,5-dimethylbenzoic acid,   4-[2-[1-[(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]-3,5-dimethylbenzoic acid,   4-[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]benzyl]benzoic acid,   3-[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]benzyl]benzoic acid,   4-[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenylthio]benzoic acid,   4-[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenylsulfinyl]benzoic acid,   4-[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenylsulfonyl]benzoic acid,   4-[[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenylamino]methyl]benzoic acid,   2-[[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]methyl]benzoic acid,   3-[[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]methyl]benzoic acid,   4-[[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]methyl]benzoic acid,   3-[[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]methyl]benzoic acid,   4-[[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]methyl]benzoic acid,   3-fluoro-4-[[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]methyl]benzoic acid,   4-[[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]methyl]-3-methylbenzoic acid,   4-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]-3,5-dimethoxybenzoic acid,   4-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]-3-nitrobenzoic acid,   4-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]-2-nitrobenzoic acid,   4-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]-3-chlorobenzoic acid,   4-[2-[1-[((2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]-2-chlorobenzoic acid,   4-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]-2-trifluoromethylbenzoic acid,   4-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]-3-trifluoromethylbenzoic acid,   4-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]-3-fluorobenzoic acid,   4-[2-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]benzoic acid, and   4-[2-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenoxy]-5-methylbenzoic acid,   a pharmaceutically acceptable salt thereof or an optically active form thereof.   
     
     
         7 . The compound of  claim 1  or  2 , wherein n is 0, a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         8 . The compound of  claim 7 , wherein
 n is 0,   p is 1,   R 1  is a hydroxyl group or a C 1-6  alkoxy group,   R 2  and R 3  are the same or different and each is a hydrogen atom, a hydroxyl group, a halogen atom, an amino group, a C 1-7  acylamino group, a trifluoromethyl group, a C 1-6  alkoxy-carbonyl group, a C 1-6  alkoxy group, a C 1-6  alkyl group, a hydroxy-C 1-6  alkyl group, a C 2-6  alkenyl group, a phenyl group, a benzyl group, a di(C 1-6 alkyl)amino group or a nitro group, or   R 2  and R 3  are joined to form an ethyleneoxy group,   X 1  is —C═C— or —C═N—,   X 2  is —C═C—,   R 4  is a C 1-6  alkyl group or a C 3-6  cycloalkyl group,   R 5  is a hydrogen atom,   Y is a carbon atom or a nitrogen atom, and,   R 6 , R 7  and R 8  are the same or different and each is a hydrogen atom, a halogen atom, a C 1-6  alkyl group or a C 1-6  alkoxy group, or adjacent R 6  and R 7  are joined to form —CH═CH—CH═CH—,   a pharmaceutically acceptable salt thereof or an optically active form thereof.   
     
     
         9 . The compound of  claim 8 , wherein
 n is 0,   p is 1,   R 1  is a hydroxyl group or a C 1-6  alkoxy group,   R 2  and R 3  are the same or different and each is a hydrogen atom, a hydroxyl group, a halogen atom, an amino group, a C 1-7  acylamino group, a trifluoromethyl group, a C 1-6  alkoxy-carbonyl group, a C 1-6  alkoxy group, a C 1-6  alkyl group, a hydroxy-C 1-6  alkyl group, a C 2-6  alkenyl group, a phenyl group, a benzyl group, a di(C 1-6  alkyl)amino group or a nitro group, or   R 2  and R 3  are joined to form an ethyleneoxy group,   X 1  is —C═C— or —C═N—,   X 2  is —C═C—,   R 4  is a methyl group or a cyclopropyl group,   R 5  is a hydrogen atom,   Y is a carbon atom, and   R 6 , R 7  and R 8  are the same or different and each is a hydrogen atom, a halogen atom, a C 1-6  alkyl group or a C 1-6  alkoxy group, or adjacent R 6  and R 7  are joined to faun —CH═CH—CH═CH—, a pharmaceutically acceptable salt thereof or an optically active form thereof.   
     
     
         10 . The compound of  claim 7 , which is selected from the group consisting of 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid,
 2′-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-chloro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(2,3-difluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(2-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-ethyl-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 3-methyl-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-5-carboxylic acid, 
 methyl 2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-3,5-dicarboxylate, 
 2′-[(cyclopropyl)[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]methyl]-3 methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[(cyclopropyl)[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]methyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-5-carboxylic acid, 
 2′-[(cyclopropyl) [(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]methyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[(cyclopropyl) [(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]methyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methoxyphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 3-methyl-2′-[1-[(2R)-3-[[1-(3,4-dimethylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-methoxyphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-ethylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-2,5-difluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methoxybiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-2-methoxybiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-(trifluoromethyl)biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(2-fluoro-4-methoxyphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-(trifluoromethyl)biphenyl-4-carboxylic acid, 
 3-ethyl-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3,4-dichlorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-(trifluoromethyl)biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-isopropylbiphenyl-4-carboxylic acid, 
 3-ethyl-2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-isopropylbiphenyl-4-carboxylic acid, 
 2-chloro-6-[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenyl]pyridine-3-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-propylbiphenyl-4-carboxylic acid, 
 2,3-dimethyl-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-propylbiphenyl-4-carboxylic acid, 
 2-chloro-6-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenyl]pyridine-3-carboxylic acid, 
 3,5-dimethyl-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-m-terphenyl-4′-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-2,3-dimethylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3,5-dimethylbiphenyl-4-carboxylic acid, 
 4-(hydroxymethyl)-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-3-carboxylic acid, 
 3-isobutyl-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-isobutylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-4-(hydroxymethyl)biphenyl-3-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-(2-methyl-1-propenyl)biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-hydroxybiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-hydroxybiphenyl-4-carboxylic acid, 
 3-ethyl-2′-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-isopropylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-(1-methylpropyl)biphenyl-4-carboxylic acid, 
 2-methyl-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 3-methyl-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 4-fluoro-2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-3-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3,4-dichlorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-2-methylbiphenyl-4-carboxylic acid, 
 6-fluoro-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-3-carboxylic acid, 
 3-fluoro-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-chlorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3,4-dichlorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2-fluoro-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[(cyclopropyl) [(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]methyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[(cyclopropyl) [(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]methyl]-3-fluorobiphenyl-4-carboxylic acid, 
 2′-[(cyclopropyl) [(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]methyl]-2-fluorobiphenyl-4-carboxylic acid, 
 2′-[(cyclopropyl) [(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]methyl]-2-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3,4-dichlorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-2-fluorobiphenyl-4-carboxylic acid, 
 3-chloro-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-nitrobiphenyl-4-carboxylic acid, 
 3-amino-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 3-(acetylamino)-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 3-chloro-2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(2-methoxy-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2,3-dihydro-5-[2-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenyl]benzofuran-7-carboxylic acid, 
 2,6-dimethyl-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-2,6-dimethylbiphenyl-4-carboxylic acid, 
 3-(dimethylamino)-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2,3-dihydro-5-[2-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenyl]benzofuran-7-carboxylic acid, 
 3-benzyl-2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methoxybiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methoxybiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methoxybiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-2-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-2-methylbiphenyl-4-carboxylic acid, 
 4-methyl-2′-[1-[(2R)-3-[[1-(naphthalen-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-3-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-4-methylbiphenyl-3-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3,5-dichlorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(2,5-difluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(5-chloro-2-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-trifluoromethylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(5-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3,5-ditrifluoromethylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-methyl-3,5-dimethoxyphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3,5-dimethoxyphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-trifluoromethylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-t-butylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-t-butylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-t-butylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methoxybiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-morpholinobiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-(trifluoromethoxy)biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-trifluoromethyl-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-(hydroxymethyl)biphenyl-4-carboxylic acid, and 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-carboxylbiphenyl-4-carboxylic acid, 
 a pharmaceutically acceptable salt thereof or an optically active form thereof. 
 
     
     
         11 . A compound represented by the following formula (1″), a pharmaceutically acceptable salt thereof or an optically active form thereof: 
       
         
           
           
               
               
           
         
         wherein 
         R 1 ′ is a hydroxyl group or a C 1-6  alkoxy group, 
         R 2 ′ is a hydroxyl group, a halogen atom, an amino group, a C 1-7  acylamino group, a halo C 1-6  alkyl group, a C 1-6  alkoxy-carbonyl group, a C 1-6  alkoxy group, a halo C 1-6  alkoxy group, a C 1-6  alkyl group, a hydroxy-C 1-6  alkyl group, a di(C 1-6  alkyl)amino group or a nitro group, 
         R 4 ′ is a C 1-6  alkyl group or a C 3-6  cycloalkyl group, 
         R 6 ′ is a halogen atom, a C 1-6  alkyl group, a C 1-6  alkoxy group or a halo C 1-6  alkyl group, or when R 7 ′ is adjacent, R 6 ′ and R 7 ′ are linked to form —CH═CH—CH═CH—, and 
         R 7 ′ is a hydrogen atom, a halogen atom, a C 1-6  alkyl group, a C 1-6  alkoxy group or a halo C 1-6  alkyl group. 
       
     
     
         12 . A compound represented by the following formula (1′″), a pharmaceutically acceptable salt thereof or an optically active form thereof: 
       
         
           
           
               
               
           
         
         wherein 
         R 2 ″ is a C 1-6  alkyl group, 
         R 4 ″ is a methyl group or a cyclopropyl group, 
         R 6 ″ is a halogen atom or a C 1-6  alkyl group, and 
         R 7 ″ is a hydrogen atom, a halogen atom, a C 1-6  alkyl group, a C 1-6  alkoxy group or a halo C 1-6  alkyl group. 
       
     
     
         13 . The compound of  claim 11  or  12 , which is selected from the group consisting of
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-chloro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(2-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-ethyl-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-5-carboxylic acid, 
 2′-[(cyclopropyl) [(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]methyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[(cyclopropyl) [(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]methyl]-3-methylbiphenyl-4-carboxylic acid, 
 3-methyl-2′-[1-[(2R)-3-[[1-(3,4-dimethylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-methoxyphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-ethylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 3-ethyl-2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-isopropylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-propylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-isobutylbiphenyl-4-carboxylic acid, 
 3-ethyl-2′-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-isopropylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-(1-methylpropyl)biphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-chlorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3,4-dichlorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-methoxy-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3,5-dichlorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-trifluoromethylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-t-butylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-t-butylbiphenyl-4-carboxylic acid, 
 2′-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-t-butylbiphenyl-4-carboxylic acid and 
 2′-[1-[(2R)-3-[[1-(3-trifluoromethyl-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid 
 a pharmaceutically acceptable salt thereof or an optically active form thereof. 
 
     
     
         14 . The compound of  claim 13 , which is selected from the group consisting of
 2′-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid,   2′-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid,   2′-[1-[(2R)-3-[[1-(3-chloro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid and   2′-[1-[(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid,   a pharmaceutically acceptable salt thereof or an optically active form thereof.   
     
     
         15 . 2′-[1-[(2R)-3-[[1-(3-Fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         16 . 2′-[1-[(2R)-3-[[1-(4-Chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         17 . 2′-[1-[(2R)-3-[[1-(3-Chloro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         18 . 2′-[1-[(2R)-3-[[1-(4-Chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         19 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier, and a compound of any of  claims 1  to  18 , a pharmaceutically acceptable salt thereof or an optically active form thereof as an active ingredient. 
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein the active ingredient is a compound of any of  claims 3  to  6 , a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         21 . The pharmaceutical composition of  claim 19 , wherein the active ingredient is a compound of any of  claims 7  to  10 , a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         22 . The pharmaceutical composition of  claim 19 , wherein the active ingredient is a compound of any of  claims 11  to  18 , a pharmaceutically acceptable salt thereof or an optically is active form thereof. 
     
     
         23 . A therapeutic drug for osteoporosis, which comprises a pharmaceutically acceptable carrier, and a compound of any of  claims 1  to  18 , a pharmaceutically acceptable salt thereof or an optically active form thereof, as an active ingredient. 
     
     
         24 . The therapeutic drug for osteoporosis of  claim 23 , wherein the active ingredient is a compound of any of  claims 3  to  6 , a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         25 . The therapeutic drug for osteoporosis of  claim 23 , wherein the active ingredient is a compound of any of  claims 7  to  10 , a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         26 . The therapeutic drug for osteoporosis of  claim 23 , wherein the active ingredient is a compound of any of  claims 11  to  18 , a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         27 . The therapeutic drug for osteoporosis of any of  claims 23  to  26 , which is used for concomitant use with a different therapeutic drug for osteoporosis. 
     
     
         28 . The therapeutic drug for osteoporosis of  claim 27 , wherein the different therapeutic drug for osteoporosis is selected from the group consisting of a calcium agent, a vitamin D preparation, a vitamin K preparation, a female hormone preparation, an estrogen antagonist preparation, an anabolic steroid preparation, a parathyroid hormone preparation, a calcitonin preparation, a bisphosphonate preparation and an ipriflavone preparation. 
     
     
         29 . A method for treating osteoporosis, which comprises administering an effective amount of a compound of any of  claims 1  to  18 , a pharmaceutically acceptable salt thereof or an optically active form thereof to a patient with osteoporosis. 
     
     
         30 . A calcium receptor antagonist comprising a pharmaceutically acceptable carrier, and a compound of any of  claims 1  to  18 , a pharmaceutically acceptable salt thereof or an optically active form thereof as an active ingredient. 
     
     
         31 . A calcium receptor antagonist of  claim 30 , wherein the active ingredient is a compound of any of  claims 3  to  6 , a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         32 . The calcium receptor antagonist of  claim 30 , wherein the active ingredient is a compound of any of  claims 7  to  10 , a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         33 . The calcium receptor antagonist of  claim 30 , wherein the active ingredient is a compound of any of  claims 11  to  18 , a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         34 . A calcium receptor antagonist having an IC 50  value of a calcium receptor antagonistic action which is not less than 10 times the IC 50  value of an inhibitory action of metabolic enzyme P450. 
     
     
         35 . The calcium receptor antagonist of  claim 34 , wherein the IC 50  value of the calcium receptor antagonistic action is not less than 100 times the IC 50  value of an inhibitory action of metabolic enzyme P450. 
     
     
         36 . The calcium receptor antagonist of  claim 34 , wherein the metabolic enzyme P450 is CYP2D6. 
     
     
         37 . The calcium receptor antagonist of  claim 35 , wherein the metabolic enzyme P450 is CYP2D6. 
     
     
         38 . A calcium receptor antagonist having an IC 50  value of a calcium receptor antagonistic action is not more than 0.1 μM, and an IC 50  value of an inhibitory action of the metabolic enzyme CYP2D6 is not less than 1 μM. 
     
     
         39 . The calcium receptor antagonist of  claim 38 , wherein the IC 50  value of the calcium receptor antagonistic action is not more than 0.1 μM, and the IC 50  value of the inhibitory action of the metabolic enzyme CYP2D6 is not less than 10 μM. 
     
     
         40 . The calcium receptor antagonist of any of  claims 30  to  33 , wherein the calcium receptor antagonist is described in any of  claims 34  to  37 . 
     
     
         41 . A PTH secretagogue comprising a pharmaceutical acceptable carrier and a compound of any of  claims 1  to  18 , a pharmaceutically acceptable salt thereof or an optically active form thereof as an active ingredient. 
     
     
         42 . The PTH secretagogue of  claim 41 , wherein the active ingredient is a compound of any of  claims 3  to  6 , a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         43 . The PTH secretagogue of  claim 41 , wherein the active ingredient is a compound of any of  claims 7  to  10 , a pharmaceutically acceptable salt thereof or an optically active form thereof. 
     
     
         44 . The PTH secretagogue of  claim 41 , wherein the active ingredient is a compound of any of  claims 11  to  18 , a pharmaceutically acceptable salt thereof or an optically active form thereof.