Patent number: 4689414
Abstract: Cardiovascular activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof, wherein R.sub.1 is alkyl, cycloalkyl, aryl, heterocyclo, --(CH.sub.2).sub.n --Y.sub.2, --(CH.sub.2).sub.p --Y.sub.3 or halo substituted alkyl;R.sub.2 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, --(CH.sub.2).sub.n --Y.sub.1, or halo substituted alkyl;R.sub.3 is hydrogen, alkyl, cycloalkyl, aryl, heterocyclo, --(CH.sub.2).sub.n --Y.sub.2, --(CH.sub.2).sub.p --Y.sub.3, or halo substituted alkyl;R.sub.4 is aryl or heterocyclo;R.sub.5 is hydrogen, alkyl, aryl, arylalkyl, cyano, nitro, ##STR2## Y.sub.1 is cycloalkyl, aryl, heterocyclo, hydroxyl, alkoxy, aryl-(CH.sub.2).sub.m --O--, mercapto, alkylthio, aryl-(CH.sub.2).sub.m --S--, amino, substituted amino, carbamoyl, ##STR3## Y.sub.2 is cycloalkyl, aryl, heterocyclo, carbamoyl, ##STR4## amino, or substituted amino; m is 0 or an integer of 1 to 6;n is an integer of 1 to 6; andp is an integer of 2 to 6.
Type:
Grant
Filed:
February 24, 1986
Date of Patent:
August 25, 1987
Assignee:
E. R. Squibb & Sons, Inc.
Inventor:
Karnail Atwal
Patent number: 4684655
Abstract: Cardiovascular activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof wherein X is oxygen or sulfur;R.sub.1 is alkyl, cycloalkyl, alkenyl, alkynyl, aryl --(CH.sub.2).sub.n --Y.sub.2, --(CH.sub.2).sub.p --Y.sub.3 or halo substituted alkyl;R.sub.2 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, --(CH.sub.2).sub.n --Y.sub.1, or halo substituted alkyl;R.sub.3 is hydrogen, alkyl, cycloalkyl, aryl, heterocyclo, --(CH.sub.2).sub.n --Y.sub.2, --(CH.sub.2).sub.p --Y.sub.3, or halo substituted alkyl;R.sub.4 is aryl or heterocyclo;Y.sub.1 is cycloalkyl, aryl, heterocyclo, hydroxyl, alkoxy, aryl--(CH.sub.2).sub.m --O--, mercapto, alkylthio, aryl--(CH.sub.2).sub.m --S--, amino, substituted amino, carbamoyl ##STR2## Y.sub.2 is cycloalkyl, aryl, heterocyclo, carbamoyl, ##STR3## Y.sub.3 is hydroxyl, alkoxy, aryl--(CH.sub.2).sub.m --O--, mercapto, alkylthio, aryl--(CH.sub.2).sub.
Type:
Grant
Filed:
March 14, 1986
Date of Patent:
August 4, 1987
Assignee:
E. R. Squibb & Sons, Inc.
Inventor:
Karnail Atwal
Patent number: 4684656
Abstract: Cardiovascular activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof wherein X is oxygen or sulfur;R.sub.1 is alkyl, cycloalkyl, aryl, heterocyclo, --(CH.sub.2).sub.n --Y.sub.1, or halo substituted alkyl;R.sub.2 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, --(CH.sub.2).sub.n --Y.sub.1, or halo substituted alkyl;R.sub.3 is hydrogen, alkyl, cycloalkyl, aryl, heterocyclo, --(CH.sub.2).sub.n --Y.sub.2, --(CH.sub.2).sub.p --Y.sub.3, or halo substituted alkyl;R.sub.4 is aryl or heterocyclo;Y.sub.1 is cycloalkyl, aryl, heterocyclo, hydroxyl, alkoxy, aryl--(CH.sub.2).sub.m --O--, mercapto, alkylthio, aryl--(CH.sub.2).sub.m --S--, amino, substituted amino, carbamoyl, ##STR2## Y.sub.2 is cycloalkyl, aryl, heterocyclo, carbamoyl, ##STR3## Y.sub.3 is hydroxyl, alkoxy, aryl--(CH.sub.2).sub.m --O--, mercapto, alkylthio, aryl--(CH.sub.2).sub.
Type:
Grant
Filed:
March 14, 1986
Date of Patent:
August 4, 1987
Assignee:
E. R. Squibb & Sons, Inc.
Inventor:
Karnail Atwal
Patent number: 4680409
Abstract: Compounds having the formula ##STR1## wherein R.sub.1 and R.sub.2 are each independently hydrogen or alkyl of 1 to 4 carbon atoms, or R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a cycloalkyl ring;R.sub.3 is hydrogen or alkyl;R.sub.4 is hydrogen or alkyl, and R.sub.5 is hydrogen, alkyl, phenyl, substituted phenyl, a 4,5,6 or 7-membered heterocycle, phenylalkyl, (substituted phenyl)alkyl, (4,5,6 or 7-membered heterocycle)alkyl, ##STR2## or together R.sub.4 and R.sub.5 are .dbd.CH--Y.sub.7 ; wherein Y.sub.1 is hydrogen, alkyl, phenyl, substituted phenyl, methylcarbonyl, trifluoromethylcarbonyl, phenylcarbonyl, (substituted phenyl)carbonyl, carboxymethyl, methylsulfonyl, phenylsulfonyl, (substituted phenyl)sulfonyl, aminocarbonyl, aminocarbonylamino, aminoethyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, phenylcarbonylamino, (substituted phenyl)carbonylamino, 1-pyrrolidinyl or 1-piperidinyl; Y.sub.
Type:
Grant
Filed:
December 23, 1985
Date of Patent:
July 14, 1987
Assignee:
E. R. Squibb & Sons, Inc.
Inventor:
Uwe D. Treuner
Patent number: 4670541
Abstract: An enkephalin-degrading aminopeptidase enzyme is inhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salt thereof, wherein R.sub.1 and R.sub.2 are each independently hydrogen, alkyl, carboxyalkyl, halo substituted alkyl, hydroxyalkyl, aminoalkyl, mercaptoalkyl, alkylthioalkyl, (cycloalkyl)alkyl, (heteroaryl)alkyl, arylalkyl, carbamoylalkyl, guanidinylalkyl, or heteroaryl;R.sub.3 is hydroxy, alkoxy, (substituted alkyl)oxy, arylalkoxy, (heteroaryl)alkoxy or --NY.sub.1 Y.sub.2, wherein Y.sub.1 and Y.sub.2 are each independently hydrogen, alkyl, aryl, or arylalkyl or Y.sub.1 is hydrogen and Y.sub.2 is substituted alkyl or (heteroaryl)alkyl;A.sub.1 is glycyl, alanyl, leucyl, phenylalanyl, arginyl, sarcosyl, seryl, asparagyl, lysyl, glutamyl, histidyl, tryptophyl, cysteinyl, methionyl, threonyl, tyrosyl, leucyl, valyl, aspartyl, prolyl, norleucyl, norvalyl, or ##STR2## wherein n.sub.6 is an integer of 2 to 15;A.sub.2, A.sub.3, A.sub.4 and A.sub.
Type:
Grant
Filed:
May 10, 1985
Date of Patent:
June 2, 1987
Assignee:
E. R. Squibb & Sons, Inc.
Inventors:
Norma G. Delaney, Eric M. Gordon
Patent number: 4670554
Abstract: Antibacterial activity is exhibited by .beta.-lactams having a 3-acylamino substituent and in the 1-position a substituent having the formula ##STR1## wherein R.sub.5 and R.sub.6 are the same or different and each is hydrogen, alkyl, alkenyl, alkynyl, phenyl, substituted phenyl, cycloalkyl or a 4,5,6 or 7-membered heterocycle, or R.sub.5 and R.sub.6 together with the carbon atom to which they are attached are cycloalkyl or a 4,5,6 or 7-membered heterocycle, or one of R.sub.5 and R.sub.6 is hydrogen and the other is azido, halomethyl, dihalomethyl, trihalomethyl, alkoxycarbonyl, alkenyl, alkynyl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, --CH.sub.2 X.sub.1, --S--X.sub.2, --O--X.sub.2, or ##STR2## R.sub.7 is hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, 1-(ethoxycarbonyloxy)ethyl, 1,3-dihydro-3-oxo-1-isobenzofuranyl, ##STR3## wherein R' is hydrogen or alkyl, R" is alkyl or phenyl, R"' is hydrogen, methyl or phenyl, and R.sup.iv is hydrogen or together with R"' is --(CH.sub.2).sub.
Type:
Grant
Filed:
May 31, 1983
Date of Patent:
June 2, 1987
Assignee:
E. R. Squibb & Sons, Inc.
Inventors:
William H. Koster, Hermann Breuer
Patent number: 4670553
Abstract: Antibacterial activity is exhibited by compounds having the formula ##STR1## and salts thereof, wherein R.sub.1 is acyl;R.sub.2 is hydrogen or methoxy;R.sub.3 and R.sub.4 are the same or different and each is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl or a 5,6 or 7-membered heterocycle or one of R.sub.3 and R.sub.4 is hydrogen and the other is azido, halomethyl, dihalomethyl, trihalomethyl, alkoxycarbonyl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, ##STR2## X.sub.1 is azido, amino, hydroxy, alkanoylamino, alkylsulfonyloxy, arylsulfonyloxy, aryl, cyano, --S--X.sub.2 or --O--X.sub.2 ;X.sub.2 is alkyl, substituted alkyl, aryl, arylalkyl, alkanoyl, substituted alkanoyl, arylcarbonyl or heteroarylcarbonyl;one of X.sub.3 and X.sub.4 is hydrogen and the other is hydrogen or alkyl, or X.sub.3 and X.sub.4 when taken together with the carbon atom to which they are attached from a cycloalkyl group;X.sub.
Type:
Grant
Filed:
November 26, 1982
Date of Patent:
June 2, 1987
Assignee:
E. R. Squibb & Sons, Inc.
Inventors:
Hermann Breuer, Theodor Denzel