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US 5,283,241 AGranted
Benzo-fused lactams promote release of growth hormone
AssigneeMerck & Co., Inc.
InventorsRichard J. Bochis, Matthew J. Wyvratt, William R. Schoen
Life of this patent
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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. The compounds are prepared by substitution of an amino-lactam with a substituted amide function. Growth promoting compositions containing such benzo-fused lactams as the active ingredient thereof are also disclosed. ##STR1## Where L is ##STR2##
Claims8
A compound having the formula:
- ##STR276## where L is ##STR277## n is 0 or 1;
- p is 0 to 3;
- q is 0 to 4;
- w is 0 or 1;
- X is C.dbd.O or ##STR278## m is 0 to 2;
- 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 with the proviso that either R.sup.3a or R.sup.3b must be a substituent other than hydrogen;
- R.sup.9 is:
- 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 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;
- and v is as defined above;
- R.sup.4, 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 substituted or R.sup.1, R.sup.2 independently disubstituted phenyl C.sub.1 -C.sub.3 alkoxy, R.sup.1 substituted or 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 where R.sup.10 and R.sup.11 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, 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;
- 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, 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 ##STR279## 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 substituted or R.sup.1, R.sup.2 independently disubstituted phenyl C.sub.1 -C.sub.3 alkoxy, R.sup.1 substituted or 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 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 1 to 5 carbon atoms;
- and pharmaceutically acceptable salts thereof.
27 more elements
Dependencies are inferred from the claim text.