Claims for Patent: 5,317,017

Summary for Patent: 5,317,017

Title:	N-biphenyl-3-amido substituted benzolactams stimulate growth hormone release
Abstract:	There are disclosed certain compounds identified as N-biphenyl-3-amido substituted benzolactams which promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to increase the stature of those afflicted with a lack of a normal secretion of natural growth hormone. Growth promoting compositions containing such benzolactams as the active ingredient thereof are also disclosed.
Inventor(s):	Ok; Hyun O. (Edison, NJ), Schoen; William R. (Edison, NJ), Wyvratt; Matthew (Mountainside, NJ)
Assignee:	Merck & Co., Inc. (Rahway, NJ)
Application Number:	07/954,220
Patent Claims:	1. A compound having the formula: ##STR51## where L is ##STR52## q is 0 to 4; w is 0 or 1; R.sup.1, R.sup.2, R.sup.1a, R.sup.2a, R.sup.1b, and R.sup.2b are independently hydrogen, halogen, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.3 perfluoroalkyl, C.sub.1 -C.sub.3 perfluoroalkoxy, --S(O).sub.m R.sup.7a, cyano, nitro, R.sup.7b O(CH.sub.2).sub.v --, R.sup.7b COO(CH.sub.2).sub.v --, R.sup.7b OCO(CH.sub.2).sub.v --, R.sup.4 R.sup.5 N(CH.sub.2).sub.v --, R.sup.7b CON(R.sup.4)(CH.sub.2).sub.v --, R.sup.4 R.sup.5 NCO(CH.sub.2).sub.v --, phenyl or substituted phenyl where the substituents are from 1 to 3 of halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, or hydroxy; R.sup.7a and R.sup.7b are independently hydrogen, C.sub.1 -C.sub.3 perfluoroalkyl, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, where the substituents are phenyl or substituted phenyl; phenyl or substituted phenyl where the phenyl substituents are from 1 to 3 of halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, or hydroxy and v is 0 to 3; R.sup.3a and R.sup.3b are independently hydrogen, R.sup.9, C.sub.1 -C.sub.6 alkyl substituted with R.sup.9, phenyl substituted with R.sup.9, or phenoxy substituted with R.sup.9 ; m is 0 to 2; R.sup.9 is ##STR53## R.sup.7b O(CH.sub.2).sub.v --, R.sup.7b COO(CH.sub.2).sub.v --, R.sup.7b OCO(CH.sub.2).sub.v --, R.sup.7b CO(CH.sub.2).sub.v --, R.sup.7b (CH.sub.2).sub.v CO--, R.sup.4 R.sup.5 N(CH.sub.2).sub.v --, R.sup.7b CON(R.sup.4)(CH.sub.2).sub.v --, R.sup.4 R.sup.5 NCO(CH.sub.2).sub.v --, R.sup.4 R.sup.5 NCS(CH.sub.2).sub.v --, R.sup.4 R.sup.5 NN(R.sup.5)CO(CH.sub.2).sub.v --, R.sup.4 R.sup.5 NN(R.sup.5)CS(CH.sub.2).sub.v --, R.sup.7b CON(R.sup.4)N(R.sup.5)CO(CH.sub.2).sub.v --, R.sup.7b CON(R.sup.4)N(R.sup.5)CS(CH.sub.2).sub.v --, R.sup.4 N(OR.sup.7b)CO(CH.sub.2).sub.v --, R.sup.7a CON(OR.sup.7b)CO(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NCON(R.sup.12b)(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NCSN(R.sup.12b)(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NN(R.sup.12b)CSN(R.sup.12c)(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NN(R.sup.12b)CON(R.sup.12c)(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NN(R.sup.12b)COO(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NCOO(CH.sub.2).sub.v -- or R.sup.13 OCON(R.sup.12b)(CH.sub.2).sub.v --, where v is 0 to 3; R.sup.12a, R.sup.12b and R.sup.12c are independently R.sup.5a, OR.sup.5a, or COR.sup.5a ; R.sup.12a and R.sup.12b, or R.sup.12b and R.sup.12c, or R.sup.13 and R.sup.12b, or R.sup.12a and R.sup.4b when taken together form --(CH.sub.2).sub.r --B--(CH.sub.2).sub.s -- where B is CHR.sup.1, O, S(O).sub.m or NR.sup.10, m is 0, 1 or 2, r and s are independently 0 to 3 and R.sup.1 and R.sup.10 are as defined; R.sup.13 is C.sub.1 -C.sub.3 perfluoroalkyl, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, where the substitutents are hydroxy, --NR.sup.10 R.sup.11, carboxy, phenyl or substituted phenyl; phenyl or substituted phenyl where the substituents on the phenyl are from 1 to 3 of halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or hydroxy; where R.sup.10 and R.sup.11 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, phenyl, phenyl C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.5 -alkoxycarbonyl, or C.sub.1 -C.sub.5 -alkanoyl-C.sub.1 -C.sub.6 alkyl; X is --CH.sub.2 CH(R.sup.20)--, --CH(R.sup.21)CH.sub.2 --, --CH(R.sup.21)CH(R.sup.20)--, --CH.dbd.C(R.sup.20)--, --C(R.sup.21).dbd.CH--, --C(R.sup.21).dbd.C(R.sup.20)--, --S(O).sub.m CH(R.sup.20)-- or --OCH(R.sup.20)--; R.sup.20 and R.sup.21 are independently hydrogen, R.sup.1, R.sup.2 independently disubstituted phenyl, R.sup.1, R.sup.2 independently disubstituted thiophenyl, C.sub.1 -C.sub.10 alkyl, substituted C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, substituted C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl, substituted C.sub.2 -C.sub.10 alkynyl where the substituents on the alkyl, alkenyl, alkynyl are from 1 to 3 of hydroxy, C.sub.1 -C.sub.6 alkoxy, fluoro, R.sup.1 substituted phenyl, --NR.sup.10 R.sup.11, carboxy, C.sub.1 -C.sub.5 alkoxycarbonyl, formyl or R.sup.20 and R.sup.21 when taken together form --(CH.sub.2).sub.r B(CH.sub.2).sub.s -- where B, r, s, R.sup.1, R.sup.2, R.sup.10 and R.sup.11 are as defined above, with the proviso that R.sup.20 and R.sup.21 cannot both be hydrogen; R.sup.4, R.sup.4a, R.sup.4b, R.sup.5 and R.sup.5a are independently hydrogen, phenyl, substituted phenyl, C.sub.1 -C.sub.10 alkyl, substituted C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.10 alkenyl, substituted C.sub.3 -C.sub.10 alkenyl, C.sub.3 -C.sub.10 alkynyl, or substituted C.sub.3 -C.sub.10 alkynyl where the substituents on the phenyl, alkyl, alkenyl or alkynyl are from 1 to 5 of hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.3 -C.sub.7 cycloalkyl, fluoro, R.sup.1, R.sup.2 independently disubstituted phenyl C.sub.1 -C.sub.3 alkoxy, R.sup.1, R.sup.2 independently disubstituted phenyl, C.sub.1 -C.sub.20 -alkanoyloxy, C.sub.1 -C.sub.5 alkoxycarbonyl, carboxy, formyl, or --NR.sup.10 R.sup.11 ; or R.sup.4 and R.sup.5 when taken to form --(CH.sub.2).sub.r B(CH.sub.2).sub.s -- where B, r, s, R.sup.1, R.sup.2, R.sup.10 and R.sup.11 are as defined above; R.sup.6 is hydrogen, C.sub.1 -C.sub.10 alkyl, phenyl or phenyl C.sub.1 -C.sub.10 alkyl; A is ##STR54## where x and y are independently 0-3; R.sup.8 and R.sup.8a are independently hydrogen, C.sub.1 -C.sub.10 alkyl, trifluoromethyl, phenyl, substituted C.sub.1 -C.sub.10 alkyl where the substituents are from 1 to 3 of imidazolyl, indolyl, hydroxy, fluoro, S(O).sub.m R.sup.7a, C.sub.1 -C.sub.6 alkoxy, C.sub.3 -C.sub.7 cycloalkyl, R.sup.1, R.sup.2 independently disubstituted phenyl C.sub.1 -C.sub.3 alkoxy, R.sup.1, R.sup.2 independently disubstituted phenyl, C.sub.1 -C.sub.5 -alkanoyloxy, C.sub.1 -C.sub.5 alkoxycarbonyl, carboxy, formyl, or --NR.sup.10 R.sup.11 where R.sup.10 and R.sup.11 are as defined above; or R.sup.8 and R.sup.8a when taken together form --(CH.sub.2).sub.t -- where t is 2 to 6; and R.sup.8 and R.sup.8a when independently joined to one or both of R.sup.4 and R.sup.5 form alkylene bridges between the terminal nitrogen and the alkyl portion of the A group wherein the bridge contains from 1 to 5 carbon atoms; or pharmaceutically acceptable salts thereof. 2. A compound of claim 1 wherein: q is 0 to 2; w is 0 or 1; R.sup.1, R.sup.2, R.sup.1a, R.sup.2a, R.sup.1b, and R.sup.2b are independently hydrogen, halogen, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.3 perfluoroalkyl, --S(O).sub.m R.sup.7a, R.sup.7b O(CH.sub.2).sub.v --, R.sup.7b COO(CH.sub.2).sub.v --, R.sup.7b OCO(CH.sub.2).sub.v --, phenyl or substituted phenyl where the substituents are from 1 to 3 of halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, or hydroxy; m is 0 to 2; R.sup.7a and R.sup.7b are independently hydrogen, C.sub.1 -C.sub.3 perfluoroalkyl, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, where the substituents are phenyl; phenyl and v is 0 to 2; R.sup.3a and R.sup.3b are independently hydrogen, R.sup.9, C.sub.1 -C.sub.6 alkyl substituted with R.sup.9, phenyl substituted with R.sup.9, or phenoxy substituted with R.sup.9 ; R.sup.9 is ##STR55## R.sup.7b O(CH.sub.2).sub.v --, R.sup.7b COO(CH.sub.2).sub.v --, R.sup.7b OCO(CH.sub.2).sub.v --, R.sup.7b CO(CH.sub.2).sub.v --, R.sup.4 R.sup.5 N(CH.sub.2).sub.v --, R.sup.7b CON(R.sup.4)(CH.sub.2).sub.v --, R.sup.4 R.sup.5 NCO(CH.sub.2).sub.v --, R.sup.4 R.sup.5 NCS(CH.sub.2).sub.v --, R.sup.4 R.sup.5 NN(R.sup.5)CO(CH.sub.2).sub.v --, R.sup.7b CON(R.sup.4)N(R.sup.5)CO(CH.sub.2).sub.v --, R.sup.4 N(OR.sup.7b)CO(CH.sub.2).sub.v --, R.sup.7a CON(OR.sup.7b)CO(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NCON(R.sup.12b)(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NCSN(R.sup.12b)(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NN(R.sup.12b)CON(R.sup.12c)(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NN(R.sup.12b)COO(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NCOO(CH.sub.2).sub.v -- or R.sup.13 OCON(R.sup.12b)(CH.sub.2).sub.v --, where v is 0 to 3; R.sup.12a, R.sup.12b and R.sup.12c are independently R.sup.5a, OR.sup.5a, or COR.sup.5a ; R.sup.12a and R.sup.12b, or R.sup.12b and R.sup.12c, or R.sup.13 and R.sup.12b, or R.sup.12a and R.sup.4b when taken together form --(CH.sub.2).sub.r --B--(CH.sub.2).sub.s -- where B is CHR.sup.1, O, S(O).sub.m or NR.sup.10, m is 0, 1 or 2, r and s are independently 0 to 3, R.sup.1 is as defined above and R.sup.10 is hydrogen, C.sub.1 -C.sub.6 alkyl, phenyl C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.5 alkanoyl-C.sub.1 -C.sub.6 alkyl. R.sup.13 is C.sub.1 -C.sub.3 perfluoroalkyl, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, where the substitutents are hydroxy, --NR.sup.10 R.sup.11, carboxy, phenyl or substituted phenyl; phenyl or substituted phenyl where the substituents on the phenyl are from 1 to 3 of halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or hydroxy; where X is as defined in claim 1; R.sup.4, R.sup.4a, R.sup.4b, R.sup.5 and R.sup.5a are independently hydrogen, phenyl, substituted phenyl, C.sub.1 -C.sub.10 alkyl, substituted C.sub.1 -C.sub.10 alkyl, where the substituents on the alkyl or phenyl are from 1 to 5 of hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.3 -C.sub.7 cycloalkyl, fluoro, R.sup.1, R.sup.2 independently disubstituted phenyl C.sub.1 -C.sub.3 alkoxy, R.sup.1, R.sup.2 independently disubstituted phenyl, C.sub.1 -C.sub.20 -alkanoyloxy, C.sub.1 -C.sub.5 alkoxycarbonyl, carboxy, formyl; R.sup.4 and R.sup.5 when taken together form --(CH.sub.2).sub.r B(CH.sub.2).sub.s -- where B is CHR.sup.1, O, S(O).sub.m or N--R.sup.10, r and s are independently 1 to 3 and R.sup.1 and R.sup.10 are as defined above; R.sup.6 is hydrogen, C.sub.1 -C.sub.10 alkyl or phenyl C.sub.1 -C.sub.10 alkyl; A is ##STR56## where x and y are independently 0-2; R.sup.8 and R.sup.8a are independently hydrogen, C.sub.1 -C.sub.10 alkyl, substituted C.sub.1 -C.sub.10 alkyl where the substituents are from 1 to 3 of imidazolyl, indolyl, hydroxy, fluoro, S(O).sub.m R.sup.7a, C.sub.1 -C.sub.6 alkoxy, R.sup.1, R.sup.2 independently disubstituted phenyl, C.sub.1 -C.sub.5 -alkanoyloxy, C.sub.1 -C.sub.5 alkoxycarbonyl, carboxy, formyl, or --NR.sup.10 R.sup.11 where R.sup.10 and R.sup.11 are independently hydrogen, C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.5 alkanyol-C.sub.1 -C.sub.6 alkyl; or R.sup.8 and R.sup.8a when taken together form --(CH.sub.2).sub.t -- where t is 2 to 4; and R.sup.8 and R.sup.8a when independently joined to one or both of R.sup.4 and R.sup.5 form alkylene bridges between the terminal nitrogen and the alkyl portion of the A group wherein the bridge contains from 1 to 5 carbon atoms; or pharmaceutically acceptable salts thereof. 3. A compound of claim 2 wherein: q is 0 to 2; w is 0 or 1; R.sup.1, R.sup.2, R.sup.1a, R.sup.2a, R.sup.1b, and R.sup.2b are independently hydrogen, halogen, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.3 perfluoroalkyl, --S(O).sub.m R.sup.7a, R.sup.7b O(CH.sub.2).sub.v --, R.sup.7b COO(CH.sub.2).sub.v --, R.sup.7b OCO(CH.sub.2).sub.v --, phenyl or substituted phenyl where the substituents are from 1 to 3 of halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, or hydroxy; m is 0 to 1; R.sup.7a and R.sup.7b are independently hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, where the substituents are phenyl; phenyl and v is 0 to 2; R.sup.3a and R.sup.3b are independently hydrogen, R.sup.9, C.sub.1 -C.sub.6 alkyl substituted with R.sup.9, phenyl substituted with R.sup.9 or phenoxy substituted with R.sup.9 ; R.sup.9 is ##STR57## R.sup.7b O(CH.sub.2).sub.v --, R.sup.7b COO(CH.sub.2).sub.v --, R.sup.7b OCO(CH.sub.2).sub.v --, R.sup.7b CO(CH.sub.2).sub.v --, R.sup.4 R.sup.5 N(CH.sub.2).sub.v --, R.sup.7b CON(R.sup.4)(CH.sub.2).sub.v --, R.sup.4 R.sup.5 NCO(CH.sub.2).sub.v --, R.sup.4 R.sup.5 NCS(CH.sub.2).sub.v --, R.sup.4 N(OR.sup.7b)CO(CH.sub.2).sub.v --, R.sup.7a CON(OR.sup.7b)CO(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NCON(R.sup.12b)(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NCSN(R.sup.12b)(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NN(R.sup.12b)CON(R.sup.12c)(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NN(R.sup.12b)COO(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NCOO(CH.sub.2).sub.v -- or R.sup.13 OCON(R.sup.12b)(CH.sub.2).sub.v --, where v is 0 to 2; R.sup.12a, R.sup.12b and R.sup.12c are independently R.sup.5a or OR.sup.5a R.sup.12a and R.sup.12b, or R.sup.12b and R.sup.12c, or R.sup.13 and R.sup.12b, or R.sup.12a and R.sup.4b when taken together form --(CH.sub.2).sub.r --B--(CH.sub.2).sub.s -- where B is CHR.sup.1, O, S(O).sub.m or NR.sup.10, m is 0, 1 or 2, r and s are independently 0 to 2, R.sup.1 is as defined above and R.sup.10 is hydrogen, C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.5 alkanoyl-C.sub.1 -C.sub.6 alkyl. R.sup.13 is C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, where the substitutents are phenyl or substituted phenyl; phenyl or substituted phenyl where the substituents on the phenyl are from 1 to 3 of halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or hydroxy; R.sup.4, R.sup.4a, R.sup.4b, R.sup.5 and R.sup.5a are independently hydrogen, C.sub.1 -C.sub.10 alkyl, substituted C.sub.1 -C.sub.10 alkyl, where the substituents on the alkyl are from 1 to 5 of hydroxy, C.sub.1 -C.sub.6 alkoxy, fluoro, R.sup.1, R.sup.2 independently disubstituted phenyl C.sub.1 -C.sub.20 -alkanoyloxy, C.sub.1 -C.sub.5 alkoxycarbonyl or carboxy; R.sup.6 is hydrogen or C.sub.1 -C.sub.10 alkyl; A is ##STR58## where x and y are independently 0-2; R.sup.8 and R.sup.8a are independently hydrogen, C.sub.1 -C.sub.10 alkyl, substituted C.sub.1 -C.sub.10 alkyl where the substituents are from 1 to 3 of imidazolyl, indolyl, hydroxy, fluoro, S(O).sub.m R.sup.7a, C.sub.1 -C.sub.6 alkoxy, R.sup.1, R.sup.2 independently disubstituted phenyl, C.sub.1 -C.sub.5 -alkanoyloxy, C.sub.1 -C.sub.5 alkoxycarbonyl, carboxy; or R.sup.8 and R.sup.8a when taken together form --(CH.sub.2).sub.t -- where t is 2; or R.sup.8 and R.sup.8a when independently joined to one or both of R.sup.4 and R.sup.5 form alkylene bridges between the terminal nitrogen and the alkyl portion of the A group wherein the bridge contains from 1 to 5 carbon atoms; or pharmaceutically acceptable salts thereof. 4. A compound of claim 3 wherein: q is 1 w is 1; R.sup.1, R.sup.2, R.sup.1a, R.sup.2a, R.sup.1b, and R.sup.2b are independently hydrogen, halogen, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.3 perfluoroalkyl, --S(O).sub.m R.sup.7a, R.sup.7b O(CH.sub.2).sub.v --, R.sup.7b COO(CH.sub.2).sub.v --, R.sup.7b OCO(CH.sub.2).sub.v --, phenyl or substituted phenyl where the substituents are from 1 to 3 of halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, or hydroxy; m is 0 to 1; R.sup.7a and R.sup.7b are independently hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, where the substituents are phenyl; phenyl and v is 0 to 1; R.sup.3a and R.sup.3b are independently hydrogen, R.sup.9, C.sub.1 -C.sub.6 alkyl substituted with R.sup.9 ; R.sup.9 is ##STR59## R.sup.7b O(CH.sub.2).sub.v --, R.sup.7b COO(CH.sub.2).sub.v --, R.sup.7b OCO(CH.sub.2).sub.v --, R.sup.7b CO(CH.sub.2).sub.v --, R.sup.7b CON(R.sup.4)(CH.sub.2).sub.v --, R.sup.4 R.sup.5 NCO(CH.sub.2).sub.v --, R.sup.4 R.sup.5 NCS(CH.sub.2).sub.v --, R.sup.4 N(OR.sup.7b)CO(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NCON(R.sup.12b)(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NN(R.sup.12b)CON(R.sup.12c)(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NN(R.sup.12b)COO(CH.sub.2).sub.v --, R.sup.4b R.sup.12a NCOO(CH.sub.2).sub.v -- or R.sup.13 OCON(R.sup.12b)(CH.sub.2).sub.v --, where v is 0 to 1; R.sup.12a, R.sup.12b and R.sup.12c are independently R.sup.5a. R.sup.12a and R.sup.12b, or R.sup.12b and R.sup.12c, or R.sup.13 and R.sup.12b or R.sup.12a and R.sup.4b when taken together form --(CH.sub.2).sub.r --B--(CH.sub.2).sub.s -- where B is CHR.sup.1, O, S(O).sub.m or NR.sup.10, m is 0, 1 or 2, r and s are independently 0 to 2, R.sup.1 is as defined above and R.sup.10 is hydrogen, C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.5 alkanoyl-C.sub.1 -C.sub.6 alkyl; R.sup.13 is C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, where the substitutents are phenyl or substituted phenyl; phenyl or substituted phenyl where the substituents on the phenyl are from 1 to 3 of halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or hydroxy; R.sup.4, R.sup.4a, R.sup.4b, R.sup.5 and R.sup.5a are independently hydrogen, C.sub.1 -C.sub.10 alkyl, substituted C.sub.1 -C.sub.10 alkyl, where the substituents on the alkyl are from 1 to 3 of hydroxy, C.sub.1 -C.sub.3 alkoxy, fluoro, R.sup.1, R.sup.2 independently disubstituted phenyl C.sub.1 -C.sub.20 alkanoyloxy, C.sub.1 -C.sub.5 alkoxycarbonyl or carboxy; R.sup.6 is hydrogen; A is ##STR60## where x and y are independently 0-1; R.sup.8 and R.sup.8a are independently hydrogen, C.sub.1 -C.sub.10 alkyl, substituted C.sub.1 -C.sub.10 alkyl where the substituents are from 1 to 3 of imidazolyl, indolyl, hydroxy, fluoro, S(O).sub.m R.sup.7a, C.sub.1 -C.sub.6 alkoxy, R.sup.1, R.sup.2 independently disubstituted phenyl, C.sub.1 -C.sub.5 -alkanoyloxy, C.sub.1 -C.sub.5 alkoxycarbonyl, carboxy; or R.sup.8 and R.sup.8a when taken together form --(CH.sub.2).sub.t -- where t is 2; and R.sup.8 and R.sup.8a when independently joined to one or both of R.sup.4 and R.sup.5 form alkylene bridges between the terminal nitrogen and the alkyl portion of the A group wherein the bridge contains from 1 to 5 carbon atoms; or pharmaceutically acceptable salts thereof. 5. A stereospecific compound of claim 1 having the following structural formula: ##STR61## where R.sup.1, R.sup.2, X, q, L, w, R.sup.1a, R.sup.2a, R.sup.3a, R.sup.4, R.sup.5, R.sup.6, and A are as defined in claim 1 6. A compound of claim 1 which is: 3-Amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-(4-methoxyphenyl)-1-[[2'-(1H -tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-1-benzazepin-3-yl]-butanamid e; 3-Amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-phenyl-1-[[2'-(1H-tetrazol-5 -yl)[1,1'-biphenyl]-4-yl]methyl]-1H-1-benzazepin-3-yl]-butanamide; 3-Amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-(4-methoxyphenyl)-1-[[2'-(1H -tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-1-benzazepin-3-yl]-butanamid e; 3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-(4-metho xyphenyl)-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-1-benzaz epin-3-yl]-butanamide; 3-Amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-5-methyl-1-[[2'-(1H-tetrazol-5 -yl)[1,1'-biphenyl]-4-yl]methyl]-1H-1-benzazepin-3-yl]-butanamide; 3-Amino-3-methyl-N-[7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-5-methyl-1-[ [2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-1-benzazepin-3-yl]-bu tanamide; 3-Amino-3-methyl-N-[7-fluoro-2,3,4,5-tetrahydro-2-oxo-5-methyl-1-[[2'-(1H-t etrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-1-benzazepin-3-yl]-butanamide; 3-Amino-3-methyl-N-[7-methylthio-2,3,4,5-tetrahydro-2-oxo-5-methyl-1-[[2'-( 1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-1-benzazepin-3-yl]-butanam ide; 3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-phenylth io-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-y l]-butanamide; 3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-5-phenylth io-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-y l]-butanamide; 3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-5-methyl-1 -[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-b utanamide; 3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-phen ylthio-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin -3-yl]-butanamide; 3-Amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-methyl-1-[[2'-(1H-tetrazol-5 -yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-butanamide; 3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-methyl-1 -[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-b utanamide; 3-Amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4,5-dimethyl-1-[[2'-(1H-tetraz ol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-butanamide; 3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-phenylth io-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-y l]-butanamide; 3-[2(S)-Dihydroxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-methyl -1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl] -butanamide; 2-Amino-2-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-(4-methoxyphenyl)-1-[[2'-(1H -tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-propanamid e; 2-Amino-2-methyl-N-[7-methylthio-2,3,4,5-tetrahydro-2-oxo-4-(4-methoxypheny l)-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-y l]-propanamide; 2-Amino-2-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-phenyl-1-[[2'-(1H-tetrazol-5 -yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-propanamide; 2-Amino-2-methyl-N-[2,3,4,5-tetrahydro-2-oxo-5-methyl-1-[[2'-(1H-tetrazol-5 -yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-propanamide; 2-Amino-2-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-methyl-1-[[2'-(1H-tetrazol-5 -yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-propanamide; 2-Amino-2-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4,5-dimethyl-1-[[2'-(1H-tetraz ol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-propanamide; 2-Amino-2-methyl-N-[7-fluoro-2,3,4,5-tetrahydro-2-oxo-5-methyl-1-[[2'-(1H-t etrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-propanamide; 2-Amino-2-methyl-N-[7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-4-methyl-1-[ [2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-pro panamide; N-Ethyl-4'-[[3-[(3-amino-3-methyl-1-oxobutyl)-amino]-2,3,4,5-tetrahydro-2-o xo-4-methyl-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carboxamide; 4'-[[3-[(3-Amino-3-methyl-1-oxobutyl)-amino]-2,3,4,5-tetrahydro-2-oxo-5-met hyl-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carboxamide; N-Ethyl-4'-[[3-[(3-amino-3-methyl-1-oxobutyl)-amino]-2,3,4,5-tetrahydro-2-o xo-4,5-dimethyl-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carboxamide; N-Ethyl-4'-[[3-[(3-amino-3-methyl-1-oxobutyl)-amino]-2,3,4,5-tetrahydro-2-o xo-4-(4-methoxyphenyl)-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carbox amide; ' -[[3-[(3-Amino-3-methyl-1-oxobutyl)-amino]-2,3,4,5-tetrahydro-2-oxo-5-phe nylthio-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carboxamide; N-Ethyl-4'-[[3-[(3-amino-3-methyl-1-oxopropyl)-amino]-2,3,4,5-tetrahydro-2- oxo-4-(4-methyl)-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carboxamide; N-Ethyl-4'-[[3-[(3-amino-3-methyl-1-oxopropyl)-amino]-2,3,4,5-tetrahydro-2- oxo-5-methyl-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carboxamide; N-Ethyl-4'-[[3-[(3-amino-3-methyl-1-oxopropyl)-amino]-7-fluoro-2,3,4,5-tetr ahydro-2-oxo-5-methyl-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carboxa mide; N-Ethyl-4'-[[3-[(3-amino-3-methyl-1-oxopropyl)-amino]-2,3,4,5-tetrahydro-2- oxo-4,5-dimethyl-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carboxamide; N-Ethyl-4'-[[3-[(3-amino-3-methyl-1-oxopropyl)-amino]-2,3,4,5-tetrahydro-2- oxo-4-(4-methoxyphenyl)-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carbo xamide; N-Ethyl-4'-[[3-[[3-[2(R)-hydroxypropylamino]-3-methyl-1-oxobutyl]amino]-2,3 ,4,5-tetrahydro-2-oxo-4-methyl-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]- 2-carboxamide; N-4'-[[3-[[3-[2(R)-Hydroxypropylamino]-3-methyl-1-oxobutyl]amino]-2,3,4,5-t etrahydro-2-oxo-5-phenyl-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carb oxamide; N-4'-[[3-[[3-[2(R)-Hydroxypropylamino]-3-methyl-1-oxobutyl]amino]-7-fluoro- 2,3,4,5-tetrahydro-2-oxo-5-methyl-1H-1-benzazepin-1-yl]methyl][1,1'-bipheny l]-2-carboxamide; N-Ethyl-4'-[[3-[[3-[2(R)-hydroxypropylamino]-3-methyl-1-oxobutyl]amino]-2,3 ,4,5-tetrahydro-2-oxo-4,5-dimethyl-1H-1-benzazepin-1-yl]methyl]1,1'-bipheny l]-2-carboxamide; N-Ethyl-4'-[[3-[(3-[(3-[2(R)-hydroxypropylamino]-3-methyl-1-oxobutyl)amino] -2,3,4,5-tetrahydro-2-oxo-4-(4-methoxyphenyl)-1H-1-benzazepin-1-yl]-methyl] -[1,1'-biphenyl]-2-carboxamide; ' -[[3-[(3-[(3-[2(R)-Hydroxypropylamino]-3-methyl-1-oxobutyl)amino]-2,3,4,5 -tetrahydro-2-oxo-5-phenylthio-1H-1-benzazepin-1-yl]-methyl]-[1,1'-biphenyl ]-2-carboxamide; N-Ethyl-4'-[[3-[(3-[2(S),3-dihydroxypropylamino]-3-methyl-1-oxobutyl)amino] -2,3,4,5-tetrahydro-2-oxo-4-methyl-1H-1-benzazepin-1-yl]-methyl]-[1,1'-biph enyl]-2-carboxamide; ' -[[3-[(3-[2(S),3-Dihydroxypropylamino]-3-methyl-1-oxobutyl)amino]-2,3,4,5 -tetrahydro-2-oxo-5-methyl-1H-1-benzazepin-1-yl]-methyl]-[1,1'-biphenyl]-2- carboxamide; N-Ethyl-4'-[[3-[(3-[2(S),3-dihydroxypropylamino]-3-methyl-1-oxobutyl)amino] -2,3,4,5-tetrahydro-2-oxo-4-(4-methoxyphenyl)-1H-1-benzazepin-1-yl]-methyl] -[1,1'-biphenyl]-2-carboxamide; N-[1-[[2'-[Methylaminocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-t etrahydro-2-oxo-4-methyl-1H-1-benzazepin-3-yl]-3-amino-3-methylbutanamide; N-[1-[[2'-[Methylaminocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-t etrahydro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-3-amino-3-methylbutanamide; N-[1-[[2'-[Morpholinocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-te trahydro-2-oxo-4-methyl-1H-1-benzazepin-3-yl]-3-amino-3-methylbutanamide; N-[1-[[2'-[[(2-Hydroxyethylamino)carbonyl]amino]-[1,1'-biphenyl]-4-yl]methy l]-2,3,4,5-tetrahydro-2-oxo-4-methyl-1H-1-benzazepin-3-yl]-3-amino-3-methyl butanamide; N-[1-[[2'-[[(2-Hydroxyethylamino)carbonyl]amino]-[1,1'-biphenyl]-4-yl]methy l]-2,3,4,5-tetrahydro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-3-amino-3-methyl butanamide; N-[1-[[2'-[[(2-Hydroxyethylamino)carbonyl]amino]-[1,1'-biphenyl]-4-yl]methy l]-2,3,4,5-tetrahydro-2-oxo-4-(4-methoxyphenyl)-1H-1-benzazepin-3-yl]-3-ami no-3-methylbutanamide; N-[1-[[2'-[[(2-Hydroxyethylamino)carbonyl]amino]-[1,1'-biphenyl]-4-yl]methy l]-2,3,4,5-tetrahydro-2-oxo-5-phenyl-1H-1-benzazepin-3-yl]-3-amino-3-methyl butanamide; N-[1-[[2'-[[(2-Hydroxyethylamino)carbonyl]amino]-[1,1'-biphenyl]-4-yl]methy l]-2,3,4,5-tetrahydro-2-oxo-4,5-dimethyl-1H-1-benzazepin-3-yl]-3-amino-3-me thylbutanamide; N-[1-[[2'-[(Methylaminocarbonyl)oxy][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-te trahydro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-3-amino-3-methylbutanamide; N-[1-[[2'-[2-[(Methylaminocarbonyl)amino]phenoxy]-1,1'-biphenyl]-4-yl]methy l]-2,3,4,5-tetrahydro-2-oxo-4-methyl-1H-1-benzazepin-3-yl]-3-amino-3-methyl butanamide; N-[1-[[2'-[(Methylaminocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5- tetrahydro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-3-(2(R)-hydroxypropyl)amino -3-methylbutanamide; N-[1-[[2'-[(Methylaminocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5- tetrahydro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-3-[2(S),3-dihydroxypropyl]- amino-3-methylbutanamide; N-[1-[[2'-[(Morpholinocarbonyl)amino][1,1'-phenyl]-4-yl]methyl]-2,3,4,5-tet rahydro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-3-(2(R)-hydroxypropyl)amino-3- methylbutanamide; N-[1-[[2'-[(Morpholinocarbonyl)amino][1,1'-phenyl]-4-yl]methyl]-2,3,4,5-tet rahydro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-3-[2(S),3-dihydroxypropyl]-ami no-3-methylbutanamide; N-[1-[[2'-[[(2-Hydroxyethylamino)carbonyl]amino]-[1,1'-biphenyl]-4-yl]methy l]-2,3,4,5-tetrahydro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-3-(2(R)-hydroxyp ropyl)amino-3-methylbutanamide; N-[1-[[2'-[[(2-Hydroxyethylamino)carbonyl]amino]-[1,1'-biphenyl]-4-yl]methy l]-2,3,4,5-tetrahydro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-3-[2(S),3-dihydr oxypropyl]-amino-3-methylbutanamide; N-[1-[[2'-[(Methylaminocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5- tetrahydro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-2-amino-2-methylpropanamide ; N-[1-[[2'-[(Methylaminocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-7-fluoro -2,3,4,5-tetrahydro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-2-amino-2-methylpr opanamide; N-[1-[[2'-[(Methylaminocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-7-2,3,4, 5-tetrahydro-2-oxo-5-phenyl-1H-1-benzazepin-3-yl]-2-amino-2-methylpropanami de; N-[1-[[2'-[(Methylaminocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-7-2,3,4, 5-tetrahydro-2-oxo-4-methyl-1H-1-benzazepin-3-yl]-2-amino-2-methylpropanami de; N-[1-[[2'-[(Morpholinocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-t etrahydro-2-oxo-4-(4-methoxyphenyl)-1H-1-benzazepin-3-yl]-2-amino-2-methylp ropanamide; N-[1-[[2'-[[(2-Hydroxyethylamino)carbonyl]amino]-[1,1'-biphenyl]-4-yl]methy l]-2,3,4,5-tetrahydro-2-oxo-4-(4-methoxyphenyl)-1H-1-benzazepin-3-yl]-2-ami no-2-methylpropanamide; N-[1-[[2'-[(Methylaminocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-7-fluoro -2,3,4,5-tetrahydro-2-oxo-4-methyl-1H-1-benzazepin-3-yl]-3-(2(R)-hydroxypro pyl)amino-3-methylbutanamide; N-[1-[[2'-[(Methylaminocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-7-fluoro -2,3,4,5-tetrahydro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-3-(2(R)-hydroxypro pyl)amino-3-methylbutanamide; N-[1-[[2'-[(Methylaminocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-7-fluoro -2,3,4,5-tetrahydro-2-oxo-4-phenyl-1H-1-benzazepin-3-yl]-3-[2(S)-dihydroxyp ropyl]amino-3-methylbutanamide; N-[1-[[2'-[[(2-Hydroxyethylamino)carbonyl]amino]-[1,1'-biphenyl]-4-yl]methy l]-7-fluoro-2,3,4,5-tetrahydro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-3-(2(R) -hydroxypropyl)amino-3-methylbutanamide; 3-Amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-(4-methoxyphenyl)-1-[[2'-hyd roxymethyl[1,1'-biphenyl]-4-yl]methyl]-1H-1-benzazepin-3-yl]-butanamide; 3-Amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-5-methyl-1-[[2'-hydroxymethyl[ 1,1'-biphenyl]-4-yl]-methyl]-1H-1-benzazepin-3-yl]-butanamide; 3-Amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-4-methyl-1-[[2'-hydroxymethyl[ 1,1'-biphenyl]-4-yl]-methyl]-1H-1-benzazepin-3-yl]-butanamide; 3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-5-methyl-1 -[[2'-hydroxymethyl[1,1'-biphenyl]-4-yl]-methyl]-1H-1-benzazepin-3-yl]-buta namide; 2-Amino-2-methyl-N-[2,3,4,5-tetrahydro-2-oxo-5-methyl-1-[[2'-hydroxymethyl[ 1,1'-biphenyl]-4-yl]-methyl]-1H-1-benzazepin-3-yl]-butanamide; 3-Amino-3-methyl-N-[2,3-dihydro-2-oxo-5-methyl-1-[[2'-(1H-tetrazol-5-yl)[1, 1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-butanamide; 3-Amino-3-methyl-N-[2,3-dihydro-2-oxo-4-(4-methoxyphenyl)-1-[[2'-(1H-tetraz ol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-butanamide; 3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[2,3-dihydro-2-oxo-5-methyl-1-[[2'-( 1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]-methyl]-1H-1-benzazepin-3-yl]-butan amide; 2-Amino-2-methyl-N-[2,3-dihydro-2-oxo-5-methyl-1-[[2'-(1H-tetrazol-5-yl)[1, 1'-biphenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-propanamide; N-Ethyl-4'-[[3-[(3-amino-3-methyl-1-oxobutyl)-amino]-2,3-dihydro-2-oxo-5-me thyl-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carboxamide; N-[1-[[2'-[Methylaminocarbonyl)amino][1,1'-biphenyl]-4-yl]methyl]-2,3-dihyd ro-2-oxo-5-methyl-1H-1-benzazepin-3-yl]-3-amino-3-methylbutanamide; N-[1-[[2'-[Methylaminocarbonyl)oxy][1,1'-biphenyl]-4-yl]methyl]-2,3-dihydro -2-oxo-5-methyl-1H-1-benzazepin-3-yl]-3-amino-3-methylbutanamide; 3-Amino-3-methyl-N-[2,3-dihydro-2-oxo-5-methyl-1-[[2'-hydroxymethyl[1,1'-bi phenyl]-4-yl]methyl-1H-1-benzazepin-3-yl]-butanamide; 3-Amino-3-methyl-N-[2,3,4,5-tetrahydro-4-oxo-2-(4-methoxyphenyl)-5-[[2'-(1H -tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl-5H-1,5-benzothiazepin-3-yl]-buta namide; 3-Amino-3-methyl-N-[2,3,4,5-tetrahydro-4-oxo-2-methyl-5-[[2'-(1H-tetrazol-5 -yl)[1,1'-biphenyl]-4-yl]methyl-5H-1,5-benzothiazepin-3-yl]-butanamide; 2-Amino-3-methyl-N-[2,3,4,5-tetrahydro-4-oxo-2-methyl-5-[[2'-(1H-tetrazol-5 -yl)[1,1'-biphenyl]-4-yl]methyl-5H-1,5-benzothiazepin-3-yl]-propanamide; 3-Amino-3-methyl-N-[2,3,4,5-tetrahydro-4-oxo-2-methyl-5-[[2'-hydroxymethyl[ 1,1'-biphenyl]-4-yl]-methyl-5H-1,5-benzothiazepin-3-yl]-butanamide; N-Ethyl-4'-[[3-[(3-amino-3-methyl-1-oxobutyl)-amino]-2,3,4,5-tetrahydro-4-o xo-2-methyl-5H-5-benzothiazepin-5-yl]methyl][1,1'-biphenyl]-2-carboxamide; 4'-[[3-[(3-[2(S),3-Dihydroxypropylamino]-3-methyl-1-oxobutyl)amino]-2,3,4,5 -tetrahydro-4-oxo-2-methyl-5H-5-benzothiazepin-5-yl]methyl][1,1'-biphenyl]- 2-carboxamide; N-[5-[[2'-[(Methylamino)carbonyl]amino][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5 -tetrahydro-2-methyl-4-oxo-5H-1,5-benzothiazepin-3-yl]-3-amino-3-methylbuta namide; N-[5-[[2'-[(Hydroxyethylamino)carbonyl]amino][1,1'-biphenyl]-4-yl]methyl]-2 ,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3-yl]-3-amino-3-methylbutanamide ; N-[5-[[2'-[(Methylamino)carbonyl]amino][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5 -tetrahydro-4-oxo-1,5-benzothiazepin-3-yl]-3-(2(R)-hydroxypropyl)amino-3-me thylbutanamide; N-[5-[[2'-[(Morpholino)carbonyl]amino][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5- tetrahydro-4-oxo-1,5-benzothiazepin-3-yl]-3-(2(R)-hydroxypropyl)amino-3-met hylbutanamide; N-[5-[[2'-[(Hydroxyethylamino)carbonyl]amino][1,1'-biphenyl]-4-yl]methyl]-2 ,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3-yl]-3-(2(R)-hydroxypropyl)amin o-3-methylbutanamide; N-[5-[[2'-[(Methylamino)carbonyl]amino][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5 -tetrahydro-4-oxo-1,5-benzothiazepin-3-yl]-3-(2(S),3-dihydroxypropyl]-amino -3-methylbutanamide; 7. A method for increasing levels of endogenous growth hormone in a human or an animal which comprises administering to such human or animal an effective amount of a compound of claim 1. 8. A composition useful for increasing the endogenous production or release of growth hormone in a human or an animal which comprises an inert carrier and an effective amount of a compound of claim 1. 9. A composition useful for increasing the endogenous production/release of growth hormone in a human or an animal which comprises an inert carrier and an effective amount of a compound of claim 1 used in combination with other growth hormone secretagogues including GHRP-6 or GHRP-1, growth hormone releasing factor (GRF) or one of its analogs, IGF-1 or IGF-2, or B-HT920. 10. A method for the treatment of obesity which comprises administering to an obese patient a compound of claim 1 in combination with an .alpha..sub.2 adrenergic agonist. 11. A composition for the treatment of obesity which comprises an inert carrier and a compound of claim 1 in combination with an .alpha..sub.2 adrenergic agonist. 12. A method for the treatment of osteoporosis which comprises administering to a patient with osteoporosis a compound of claim 1 in combination with parathyroid hormone. 13. A composition for the treatment of osteoporosis which comprises an inert carrier and a compound of claim 1 in combination with parathyroid hormone.

Details for Patent 5,317,017

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2039-02-26