US 5,434,261 AGranted

Benzo-fused lactams promote release of growth hormone

AssigneeMerck & Co., Inc.

InventorsWilliam R. Schoen, Matthew J. Wyvratt, Jr.

Life of this patent

Estimating the term…

Abstract

There are disclosed certain novel compounds identified as benzo-fused lactams 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 benzo-fused lactams as the active ingredient thereof are also disclosed.

Claims6

Dependent claims

A compound having the formula:

##STR320## where L is ##STR321## ##STR322## 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.12a R.sup.12b N(CH.sub.2).sub.v --, R.sup.12a R.sup.12b NCO(CH.sub.2).sub.v --, R.sup.12a R.sup.12b NCOO(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 with the proviso that either R.sup.3a and R.sup.3b must be a substitutent other than hydrogen;
R.sup.9 is
R.sup.4a R.sup.12a NSO.sub.2 (CH.sub.2).sub.v --,
R.sup.4a R.sup.12a NN(R.sup.12b)SO.sub.2 (CH.sub.2).sub.v --,
R.sup.4a R.sup.12a NCSN(R.sup.12b)SO.sub.2 (CH.sub.2).sub.v --,
R.sup.4a R.sup.12a NCON(R.sup.12b)SO.sub.2 (CH.sub.2).sub.v --,
R.sup.4a R.sup.12a NN(R.sup.12b)CON(R.sup.12b)SO.sub.2 (CH.sub.2).sub.v --,
R.sup.4a R.sup.12a NN(R.sup.12b)CSN(R.sup.12b)SO.sub.2 (CH.sub.2).sub.v --,
or R.sup.13 OCON(R.sup.12b)SO.sub.2 (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.4a can be taken together to 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;
R.sup.4, R.sup.4a, 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, R.sup.1, R.sup.2 independently disubstituted phenyl C.sub.1 -C.sub.3 alkoxy, C.sub.1 -C.sub.20 -alkanoyloxy, C.sub.1 -C.sub.5 alkoxycarbonyl, carboxy, formyl or --NR.sup.10 R.sup.11 where R.sup.1, R.sup.2, R.sup.10 and R.sup.11 are as defined above;
or R.sup.4 and R.sup.5 can be taken together to 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, m is 0, 1 or 2 and R.sup.1 and R.sup.10 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 ##STR323## 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 substitutents 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, R.sup.1, R.sup.2 independently disubstituted phenyl C.sub.1 -C.sub.3 alkoxy, 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.1, R.sup.2, R.sup.7a, R.sup.10, R.sup.11 and m are as defined above;
or R.sup.8 and R.sup.8a can be taken together to form --(CH.sub.2).sub.t -- where t is 2 to 6;
and R.sup.8 and R.sup.8a can independently be joined to one or both of R.sup.4 and R.sup.5 to form alkylene bridges between the terminal nitrogen and the alkyl portion of the A group wherein the bridge contains from one to five carbon atoms;
and pharmaceutically acceptable salts thereof.

20 more elements

A compound which is selected from:

3-Amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 7-fluoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanami de;
3-Amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 7-methylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 7-methoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
2-Amino-2-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
2-Amino-2-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 7-fluoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
2-Amino-2-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanam ide;
2-Amino-2-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 7-methylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
2-Amino-2-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 7-methoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-bip henyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butana mide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-bip henyl]-4-yl]methyl]-7-fluoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)- yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-bip henyl]-4-yl]methyl]-7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1-benzaze pin-3(R)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-bip henyl]-4-yl]methyl]-7-methylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3 (R)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1'-bip henyl]-4-yl]methyl]-7-methoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R) -yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1' -biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]bu tanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1' -biphenyl]-4-yl]methyl]-7-fluoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3 (R)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1' -biphenyl]-4-yl]methyl]-7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo, 1H-1-benzazepin-3(R)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1' -biphenyl]-4-yl]methyl]-7-methylthio-2,3,4,5-tetrahydro-2oxo-1H-1-benzazepi n-3(R)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(benzamido)sulfonyl[1,1' -biphenyl]-4-yl]methyl]-7-methoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin- 3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -7-fluoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanam ide;
3-Amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -7-methylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -7-methoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
2-Amino-2-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
2-Amino-2-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -7-fluoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
2-Amino-2-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo -1H-1-benzazepin-3(R)-yl]propanamide;
2-Amino-2-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -7-methylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
2-Amino-2-methyl-N-[l-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -7-methoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-bi phenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butan amide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-bi phenyl]-4-yl]methyl]-7-fluoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R) -yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-bi phenyl]-4-yl]methyl]-7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1-benzaz epin-3(R)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-bi phenyl]-4-yl]methyl]-7-methylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin- 3(R)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1'-bi phenyl]-4-yl]methyl]-7-methoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R )-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1 '-biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]b utanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1 '-biphenyl]-4-yl]methyl]-7-fluoro-2,3,4,5-tetrahydro,2-oxo-1H-1-benzazepin- 3(R)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1 '-biphenyl]-4-yl]methyl]-7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1-be nzazepin-3(R)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1 '-biphenyl]-4-yl]methyl]-7-methylthio-2,3,4,5-tetrahydro-2oxo-1H-1-benzazep in-3(R)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(ethylamino)sulfonyl[1,1 '-biphenyl]-4-yl]methyl]-7-methoxy-2,3,4,5-tetrahydro-2oxo-1H-1-benzazepin- 3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-2,3, 4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-7-fl uoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-7-tr ifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-7-me thylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-7-me thoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
2-Amino-2-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-2,3, 4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
2-Amino-2-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-7-fl uoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
2-Amino-2-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-7-tr ifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
2-Amino-2-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-7-me thylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
2-Amino-2-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-7-me thoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-bipheny l]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-bipheny l]-4-yl]methyl]-7-fluoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]b utanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-bipheny l]-4-yl]methyl]-7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin- 3(R) -yl]butanamide;
-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-biphenyl ]-4-yl]methyl]-7-methylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-y l]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-bipheny l]-4-yl]methyl]-7-methoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl] butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-bip henyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butana mide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-bip henyl]-4-yl]methyl]-7-fluoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)- yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-bip henyl]-4-yl]methyl]-7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1-benzaze pin-3(R)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-bip henyl]-4-yl]methyl]-7-methylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3 (R)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(aminosulfonyl)[1,1'-bip henyl]-4-yl]methyl]-7-methoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R) -yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-7-fluoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
3-Amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butan amide;
3-Amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-7-methylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide ;
3-Amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-7-methoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide;
2-Amino-2-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
2-Amino-2-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-7-fluoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
2-Amino-2-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propa namide;
2-Amino-2-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-7-methylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamid e;
2-Amino-2-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-7-methoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'- biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]but anamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'- biphenyl]-4-yl]methyl]-7-fluoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3( R)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'- biphenyl]-4-yl]methyl]-7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1-benz azepin-3(R)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'- biphenyl]-4-yl]methyl]-7-methylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepi n-3(R)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1,1'- biphenyl]-4-yl]methyl]-7-methoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3 (R)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1 ,1'-biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl ]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1 ,1'-biphenyl]-4-yl]methyl]-7-fluoro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepi n-3(R)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1 ,1'-biphenyl]-4-yl]methyl]-7-trifluoromethyl-2,3,4,5-tetrahydro-2-oxo-1H-1- benzazepin-3(R)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1 ,1'-biphenyl]-4-yl]methyl]-7-methylthio-2,3,4,5-tetrahydro-2-oxo-1H-1-benza zepin-3(R)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[1-[[2'-(t-butylamino)sulfonyl[1 ,1'-biphenyl]-4-yl]methyl]-7-methoxy-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazep in-3(R)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butan amide;
3-Amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 8-methylthio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide ;
3-Amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 8-methoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide;
2-Amino-2-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
2-Amino-2-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
2-Amino-2-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propa namide;
2-Amino-2-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 8-methyl thio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
2-Amino-2-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1'-biphenyl]-4-yl]methyl]- 8-methoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1'-bip henyl]-4-yl]methyl]-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S) -yl]butanamide;
-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl-[1,1'-bip henyl]-4-yl]methyl]-8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3( S)-yl]butanamide;
-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl-[1,1'-bip henyl]-4-yl]methyl]-8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benzothi azepin-3(S)-yl]butanamide;
-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl-[1,1'-bip henyl]-4-yl]methyl]-8-methylthio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepi n-3(S)-yl]butanamide;
-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl-[1,1'-bip henyl]-4-yl]methyl]-8-methoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3 (S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1' -biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl ]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1' -biphenyl]-4-yl]methyl]-8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepi n-3(S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1' -biphenyl]-4-yl]methyl]-8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benz othiazepin-3(S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1' -biphenyl]-4-yl]methyl]-8-methylthio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothia zepin-3(S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(benzamido)sulfonyl[1,1' -biphenyl]-4-yl]methyl]-8-methoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazep in-3(S)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]buta namide;
3-Amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -8-methyl thio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -8-methoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide;
2-Amino-2-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
2-Amino-2-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
2-Amino-2-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]prop anamide;
2-Amino-2-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -8-methyl thio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
2-Amino-2-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-biphenyl]-4-yl]methyl] -8-methoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-bi phenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]bu tanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-bi phenyl]-4-yl]methyl]-8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3 (S)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-bi phenyl]-4-yl]methyl]-8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benzoth iazepin-3(S)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-bi phenyl]-4-yl]methyl]-8-methylthio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazep in-3(S)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1'-bi phenyl]-4-yl]methyl]-8-methoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin- 3(S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1 '-biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-y l]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1 '-biphenyl]-4-yl]methyl]-8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazep in-3(S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1 '-biphenyl]-4-yl]methyl]-8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-ben zothiazepin-3(S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1 '-biphenyl]-4-yl]methyl]-8-methylthio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothi azepin-3(S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(ethylamino)sulfonyl[1,1 '-biphenyl]-4-yl]methyl]-8-methoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiaze pin-3(S)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-2,3, 4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-8-fl uoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-8-tr ifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamid e;
3-Amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-8-me thylthio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-8-me thoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide;
2-Amino-2-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-2,3, 4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
2-Amino-2-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-8-fl uoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
2-Amino-2-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-8-tr ifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanami de;
2-Amino-2-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-8-me thylthio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
2-Amino-2-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-8-me thoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-bipheny l]-4-yl]methyl]-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanam ide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-bipheny l]-4-yl]methyl]-8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-y l]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-bipheny l]-4-yl]methyl]-8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazep in-3(S)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-bipheny l]-4-yl]methyl]-8-methylthio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3( S)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-bipheny l]-4-yl]methyl]-8-methoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)- yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-bip henyl]-4-yl]methyl]-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]but anamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-bip henyl]-4-yl]methyl]-8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3( S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-bip henyl]-4-yl]methyl]-8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benzothi azepin-3(S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-bip henyl]-4-yl]methyl]-8-methylthio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepi n-3(S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(aminosulfonyl)[1,1'-bip henyl]-4-yl]methyl]-8-methoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3 (S)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide;
3-Amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]bu tanamide;
3-Amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-8-methylthio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanam ide;
3-Amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-8-methoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]butanamide ;
2-Amino-2-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
2-Amino-2-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide ;
2-Amino-2-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]pr opanamide;
2-Amino-2-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-8-methylthio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propana mide;
2-Amino-2-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'-biphenyl]-4-yl]methy l]-8-methoxy -2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl]propanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'- biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S)-yl] butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'- biphenyl]-4-yl]methyl]-8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin -3(S)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'- biphenyl]-4-yl]methyl]-8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-benzo thiazepin-3(S)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'- biphenyl]-4-yl]methyl]-8-methylthio-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiaz epin-3(S)-yl]butanamide;
3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1,1'- biphenyl]-4-yl]methyl]-8-methoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepi n-3(S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1 ,1'-biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiazepin-3(S) -yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1 ,1'-biphenyl]-4-yl]methyl]-8-fluoro-2,3,4,5-tetrahydro-4-oxo-1,5-benzothiaz epin-3(S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1 ,1'-biphenyl]-4-yl]methyl]-8-trifluoromethyl-2,3,4,5-tetrahydro-4-oxo-1,5-b enzothiazepin-3(S)-yl]butanamide;
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1 ,1'-biphenyl]-4-yl]methyl]-8-methylthio-2,3,4,5-tetrahydro-4-oxo-1,5-benzot hiazepin-3(S)-yl]butanamide;
and
3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[5-[[2'-(t-butylamino)sulfonyl[1 ,1'-biphenyl]-4-yl]methyl]-8-methoxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothia zepin-3(S)-yl]butanamide.

158 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/097,149Filed 26 Jul 1993
Granted: 18 Jul 1995
Term ends: Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07D 215/38
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
C07D 223/16
Condensed with carbocyclic rings or ring systems: benzazepines; Hydrogenated benzazepines
C07D 225/06
Condensed with carbocyclic rings or ring systems: condensed with one six-membered ring
C07D 267/14
Condensed with carbocyclic rings or ring systems: condensed with one six-membered ring

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Abstract

A compound having the formula:

##STR320## where L is ##STR321## ##STR322## 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.12a R.sup.12b N(CH.sub.2).sub.v --, R.sup.12a R.sup.12b NCO(CH.sub.2).sub.v --, R.sup.12a R.sup.12b NCOO(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 with the proviso that either R.sup.3a and R.sup.3b must be a substitutent other than hydrogen;
R.sup.9 is
R.sup.4a R.sup.12a NSO.sub.2 (CH.sub.2).sub.v --,
R.sup.4a R.sup.12a NN(R.sup.12b)SO.sub.2 (CH.sub.2).sub.v --,
R.sup.4a R.sup.12a NCSN(R.sup.12b)SO.sub.2 (CH.sub.2).sub.v --,
R.sup.4a R.sup.12a NCON(R.sup.12b)SO.sub.2 (CH.sub.2).sub.v --,
R.sup.4a R.sup.12a NN(R.sup.12b)CON(R.sup.12b)SO.sub.2 (CH.sub.2).sub.v --,
R.sup.4a R.sup.12a NN(R.sup.12b)CSN(R.sup.12b)SO.sub.2 (CH.sub.2).sub.v --,
or R.sup.13 OCON(R.sup.12b)SO.sub.2 (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.4a can be taken together to 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;
R.sup.4, R.sup.4a, 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, R.sup.1, R.sup.2 independently disubstituted phenyl C.sub.1 -C.sub.3 alkoxy, C.sub.1 -C.sub.20 -alkanoyloxy, C.sub.1 -C.sub.5 alkoxycarbonyl, carboxy, formyl or --NR.sup.10 R.sup.11 where R.sup.1, R.sup.2, R.sup.10 and R.sup.11 are as defined above;
or R.sup.4 and R.sup.5 can be taken together to 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, m is 0, 1 or 2 and R.sup.1 and R.sup.10 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 ##STR323## 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 substitutents 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, R.sup.1, R.sup.2 independently disubstituted phenyl C.sub.1 -C.sub.3 alkoxy, 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.1, R.sup.2, R.sup.7a, R.sup.10, R.sup.11 and m are as defined above;
or R.sup.8 and R.sup.8a can be taken together to form --(CH.sub.2).sub.t -- where t is 2 to 6;
and R.sup.8 and R.sup.8a can independently be joined to one or both of R.sup.4 and R.sup.5 to form alkylene bridges between the terminal nitrogen and the alkyl portion of the A group wherein the bridge contains from one to five carbon atoms;
and pharmaceutically acceptable salts thereof.

20 more elements

Facts

Application

08/097,149Filed 26 Jul 1993

Granted

18 Jul 1995

Term ends

Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07D 215/38
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
C07D 223/16
Condensed with carbocyclic rings or ring systems: benzazepines; Hydrogenated benzazepines
C07D 225/06
Condensed with carbocyclic rings or ring systems: condensed with one six-membered ring
C07D 267/14
Condensed with carbocyclic rings or ring systems: condensed with one six-membered ring