Lactam derivatives and their use as hypotensive agents
AssigneeSankyo Company, Limited
InventorsHiroaki Yanagisawa, Sadao Ishihara, Akiko Ando, Takuro Kanazaki, Hiroyuki Koike, Yasuteru Iijima
Life of this patent
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Abstract
Compounds of formula (I): ##STR1## (wherein R.sup.1 and R.sup.3 are organic groups, A is a direct bond, --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CO--CH.sub.2, --O--CH.sub.2 -- or --S--CH.sub.2 --, B is lower alkylene and n is 1-3) are valuable hypotensive agents which may be prepared by a condensation reaction of the corresponding compound having an amino group at the 3-position.
Claims27
A compound of formula (I):
- ##STR9## in which:
- R.sup.1 represents a C.sub.1 -C.sub.10 alkyl group, a C.sub.3 -C.sub.8 cycloalkyl group, an aryl group or a heterocyclic group, or said alkyl group having at least one substituent selected from the group consisting of substituents (a) or said cycloalkyl, aryl or heterocyclic group having at least one substituent selected from the group consisting of substituents (a) and substituents (b);
- R.sup.3 represents a C.sub.1 -C.sub.10 alkyl group, a C.sub.3 -C.sub.8 cycloalkyl group, an aralkyl group wherein the alkyl part is C.sub.1 -C.sub.6 alkyl, an aryl group, a C.sub.1 -C.sub.6 alkyl group having a heterocyclic substituent or a heterocyclic group, where said heterocyclic group or said heterocyclic substituent is selected from the group consisting of tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, morpholinyl, furyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyridyl, quinolyl, isoquinolyl and indolyl, or said alkyl group having at least one substituent selected from the group consisting of substituents (a) or said cycloalkyl, aryl or heterocyclic group having at least one substituent selected from the group consisting of substituents (a) and (b);
- A represents a single bond, a methylene group, an ethylene group or a group of formula --CO--CH.sub.2 --, --O--CH.sub.2 -- or --S--CH.sub.2 --;
- B represents an alkylene group having from 1 to 4 carbon atoms;
- n is an integer from 1 to 3;
- substituents (a) are:
- hydroxy groups, C.sub.1 -C.sub.6 alkoxy groups, an aryl group having from 0 to 3 substituents selected from the group consisting of substituents (a) and substituents (b), aralkyloxy groups where the alkyl part is C.sub.1 -C.sub.6 alkyl and the aryl part has from 0 to 3 substituents selected from the group consisting of substituents (a) and (b), aryloxy groups, halogen atoms, nitro groups, cyano groups, carboxy groups, alkoxycarbonyl groups having a total of from 2 to 7 carbon atoms, amino groups, C.sub.1 -C.sub.6 alkylamino groups, dialkylamino groups wherein each alkyl part is C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 aliphatic or carbocyclic aryl acylamino groups carbamoyl groups, alkylcarbamoyl groups where the alkyl part is C.sub.1 -C.sub.6 alkyl, dialkylcarbamoyl groups where each alkyl part is C.sub.1 -C.sub.6 alkyl, mercapto groups, C.sub.1 -C.sub.6 alkylthio groups, arylthio groups, C.sub.1 -C.sub.6 alkylsulfonyl groups and arylsulfonyl groups wherein the aryl part has from 0 to 3 C.sub.1 -C.sub.6 alkyl substituents;
- substituents (b) are:
- C.sub.1 -C.sub.6 alkyl groups and aralkyl groups wherein the alkyl part is C.sub.1 -C.sub.6 alkyl and the aryl part has from 0 to 3 substituents selected from the group consisting of substituents (a) and substituents (b);
- and said aryl and said aryl part of said aralkyl, aralkyloxy, aryloxy, aryl acylamino, arylthio or arylsulfonyl is phenyl or naphthyl;
- and pharmaceutically acceptable salts and esters thereof.
t-butyl .alpha.-[3-(1-ethoxycarbonyl-3-phenylpropylamino)-2-oxo-6-phenylperhydroaz epin-1-yl]acetate.
.alpha.-[3-(1- ethoxycarbonyl-3-phenylpropylamino)-2-oxo-6-phenylperhydroazepin-1-yl]aceti c acid.
.al pha.-[3-(1-carboxy-3-phenylpropylamino)-2-oxo-6-phenylperhydroazepin-1-yl]a cetic acid.
t-butyl .alpha.-[3-(1-ethoxycarbonyl-3-phenylpropylamino)-6-(p-fluorophenyl)-2-oxo perhydroazepin-1-yl]acetate.
.alpha.-[3-(1-ethoxycarb onyl-3-phenylpropylamino)-6-(p-fluorophenyl)-2-oxoperhydroazepin-1-yl]aceti c acid.
.al pha.-[3-(1-carboxy-3-phenylpropylamino)-6-(p-fluorophenyl)-2-oxoperhydroaze pin-1-yl]acetic acid.
t-butyl .alpha.-[3-(1-butoxycarbonyl-3-phenylpropylamino)-6-(p-fluorophenyl)-2-oxo perhydroazepin-1-yl]acetate.
.alpha.-[3-(1-butoxycarb onyl-3-phenylpropylamino)-6-(p-fluorophenyl)-2-oxoperhydroazepin-1-yl]aceti c acid.
t-butyl .alpha.-[3-(1-butoxycarbonyl-3-phenylpropylamino)-2-oxo-6-phenylperhydroaz epin-1-yl]acetate.
.alpha.-[3-(1- butoxycarbonyl-3-phenylpropylamino)-2-oxo-6-phenylperhydroazepin-1-yl]aceti c acid.
.al pha.-{3(S)-[1(S)-ethoxycarbonyl-3-phenylpropylamino]-2-oxo-6(R)-phenylperhy droazepin-1-yl}acetic acid.
.alpha.-{3(S)-[1(S)-carb oxy-3-phenylpropylamino]-2-oxo-6(R)-phenylperhydroazepin-1-yl}acetic acid.
.alpha.-{3(S)-[1(S)-ethoxycarbonyl-3-phenylpropylamino]-6(R)-(p-fluorop henyl)-2-oxoperhydroazepin-1-yl}acetic acid.
.alpha.-{3(S)-[1(S)-carboxy-3-phenylprop ylamino]-6(R)-(p-fluorophenyl)-2-oxoperhydroazepin-1-yl}acetic acid.
.alpha.-{3(S)-[1(S)-butoxycarbonyl-3-phenylpropylamino]-6(R)-(p- fluorophenyl)-2-oxoperhydroazepin-1-yl}acetic acid.
.alpha.-{3(S)-[1(S)-butoxycarbonyl-3-phenylprop ylamino]-2-oxo-6(R)-phenylperhydroazepin-1-yl}acetic acid.
Dependencies are inferred from the claim text.