Patent ID: 6090785
Filing Date: 2000-07-18
Classification: A61K,C07K

Abstract:
A compound of formula I. ##STR22## or a pharmaceutically acceptable salt thereof wherein: R.sub.1 is substituted C.sub.1-6 alkyl, wherein the substituent is selected from the group consisting of:(a) hydrogen,(b) carboxy,(c) ##STR23## (d) aryl wherein the aryl group is selected from the group consisting of: (1) phenyl,(2) naphthyl,(3) pyridyl,(4) furyl,(5) pyrryl,(6) thienyl,(7) isothiazolyl,(8) imidazolyl,(9) benzimidazolyl,(10) tetrazolyl,(11) pyrazinyl,(12) pyrimidyl,(13) quinolyl,(14) isoquinolyl,(15) benzofuryl,(16) isobenzofuryl,(17) benzothienyl,(18) pyrazolyl,(19) indolyl,(20) isoindolyl,(21) purinyl,(22) carbazolyl,(23) isoxazolyl,(24) thiazolyl,(25) oxazolyl,(26) benzthiazolyl, and(27) benzoxazolyl,and mono and di-substituted aryl as defined above in items (1) to (27) wherein the substituents are independently selected from C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, halo, hydroxy, amino, C.sub.1-6 alkylamino, aminoC.sub.1-6 alkyl, carboxyl, carboxylC.sub.1-6 alkyl, and C.sub.1-6 alkylcarbonyl;(e) ##STR24## wherein R.sub.a and R.sub.b are each independently hydrogen; aryl and mono and di-substituted aryl as defined above (d); or substituted C.sub.1-6 alkyl wherein the substituent is selected from hydroxy, halo, and phenyl, or wherein R.sub.a and R.sub.b are joined such that together with the nitrogen and carbon atoms to which they are attached, there is formed a lactam or benzolactam ring wherein the lactam portion thereof is a ring of up to 8 atoms, said lactam or benzolactam have a single hetero atom;(f) ##STR25## wherein R.sub.a and R.sub.b are each independently hydrogen; C.sub.6-10 aryl and mono and di-substituted aryl as defined above (d); or substituted C.sub.1-6 alkyl wherein the substituent is selected from hydroxy, halo, and phenyl, or wherein R.sub.a and R.sub.b are joined such that together with the nitrogen and carbon atoms to which they are attached, there is formed a cyclic imide wherein the imide portion thereof is a ring of up to 8 atoms, said cyclic imide has a single hetero atom;(g) amino and substituted amino wherein the substituent is selected from C.sub.1-6 alkyl and aryl wherein aryl is defined in (d);R.sub.2 is substituted C.sub.7-12 alkyl wherein the substituent is hydrogen, amino, C.sub.1-3 alkylamino, C.sub.1-3 dialkylamino, or hydroxyl;R.sub.3 is(a) H,(b) C.sub.1-10 alkyl,(c) C aryl or C aryl C.sub.1-3 alkyl, wherein the aryl group is selected from the group consisting of(1) phenyl, and(2) substituted phenyl, wherein the substituent is carboxy, carboxyC.sub.1-3 alkyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl;AA is an amino acid of formula ##STR26## wherein R.sub.e and R.sub.f are individually selected from: (a) hydrogen,(b) C.sub.1-6 alkyl,(c) mercapto C.sub.1-6 alkyl,(d) hydroxy C.sub.1-6 alkyl,(e) carboxy C.sub.1-6 alkyl,(f) amino substituted C.sub.1-6 alkyl,(g) aminocarbonyl C.sub.1-6 alkyl,(h) mono- or di-C.sub.1-6 alkyl amino C.sub.1-6 alkyl,(i) guanidino C.sub.1-6 alkyl,(j) substituted phenyl C.sub.1-6 alkyl, wherein the substituent is hydrogen, hydroxy, carboxy, C.sub.1-4 alkyl, or C.sub.1-4 alkyloxy,(k) substituted indolyl C.sub.1-6 alkyl, wherein the substituent is hydrogen, hydroxy, carboxy, C.sub.1-4 alkyl, or C.sub.1-4 alkyloxy,(l) substituted imidazolyl C.sub.2-6 alkyl wherein the substituent is hydrogen, hydroxy, carboxy, C.sub.1-4 alkyl, or C.sub.1-4 alkyloxy,(m) substituted pyridyl C.sub..sub.1-6 alkyl wherein the substituent is hydrogen, hydroxy, carboxy, C.sub.1-4 alkyl, or C.sub.1-4 alkyloxy,(n) substituted pyridylamino C.sub.1-6 alkyl wherein the substituent is hydrogen, hydroxy, carboxy, C .sub.1-4 alkyl, or C.sub.1-4 alkyloxy,Z is ##STR27## wherein R.sub.5 and R.sub.6 are each individually selected from the group consisting of:(a) H,(b) C.sub.1-10 alkyl,(c) aryl or arylC.sub.1-6 alkyl, wherein the aryl group is selected from the group consisting of(1) phenyl,(2) naphthyl,(3) pyridyl,(4) pyrryl,(5) furyl,(6) thienyl,(7) isothiazolyl,(8) imidazolyl,(9) benzimidazolyl,(10) tetrazolyl,(11) pyrazinyl,(12) pyrimidyl,(13) quinolyl,(14) isoquinolyl,(15) benzofuryl,(16) isobenzofuryl,(17) benzothienyl,(18) pyrazolyl,(19) indolyl,(20) isoindolyl,(21) purinyl,(22) carbazolyl,(23) isoxazolyl,(24) benzthiazolyl,(25) benzoxazolyl,(26) thiazolyl, and(27) oxazolyl.