US 5,512,681 AGranted

Angiotensin II receptor blocking imidazolinone derivatives

AssigneeE. I. Du Pont de Nemours and Company

InventorsGeorge A. Boswell, Indawati DeLucca, Mimi L. Quan

Life of this patent

Estimating the term…

Abstract

Novel imidazolinone derivatives of formula (I), which are useful as angiotensin II antagonists, are disclosed: ##STR1##

Claims11

Dependent claims

A compound of formula (I) ##STR22## wherein:

R.sup.1 is other than in the ortho position and is:
##STR23## R.sup.2 is (a) H,
(b) halo (F, Cl, Br, I),
(c) C.sub.1 -C.sub.4 alkyl,
(d) C.sub.1 -C.sub.4 alkoxy,
(e) C.sub.1 -C.sub.4 acyloxy,
(f) C.sub.1 -C.sub.4 alkylthio,
(g) C.sub.1 -C.sub.4 alkylsulfinyl,
(h) C.sub.1 -C.sub.4 alkylsulfonyl,
(i) hydroxy (C.sub.1 -C.sub.4) alkyl,
(j) phenyl (C.sub.1 -C.sub.4) alkyl,
(k) --CO.sub.2 H,
(l) --CN,
(m) --CONHOR.sup.12,
(n) --SO.sub.2 NHR.sup.21,
(o) --NH.sub.2,
(p) C.sub.1 -C.sub.4 alkylamino,
(q) C.sub.1 -C.sub.4 dialkylamino,
(r) --NHSO.sub.2 R.sup.20,
(s) --NO.sub.2,
(t) furyl,
(u) aryl;
wherein aryl is phenyl optionally substituted with one or two substituents selected from the group consisting of halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, --NO.sub.2, CF.sub.3, C.sub.1 -C.sub.4 alkylthio, --OH, --NH.sub.2, C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 dialkylamino, --CN, --CO.sub.2 H, --CO.sub.2 CH.sub.3, --CO.sub.2 CH.sub.2 CH.sub.3, --CO.sub.2 -benzyl;
R.sup.3 is
(a) H,
(b) halo,
(c) C.sub.1 -C.sub.4 alkyl,
(d) C.sub.1 -C.sub.4 alkoxy,
(e) C.sub.1 -C.sub.4 alkoxyalkyl;
R.sup.4 is
(a) --CN,
(b) --NO.sub.2,
(c) --CO.sub.2 R.sup.11,
R.sup.5 is
(a) H,
(b) C.sub.1 -C.sub.6 alkyl,
(c) C.sub.3 -C.sub.6 cycloalkyl,
(d) C.sub.2 -C.sub.4 alkenyl,
(e) C.sub.2 -C.sub.4 alkynyl;
R.sup.6 is
(a) C.sub.1 -C.sub.10 alkyl,
(b) C.sub.3 -C.sub.8 alkenyl,
(c) C.sub.3 -C.sub.8 alkynyl,
(d) C.sub.3 -C.sub.8 cycloalkyl,
(e) C.sub.4 -C.sub.8 cycloalkenyl,
(f) C.sub.4 -C.sub.10 cycloalkylalkyl,
(g) C.sub.5 -C.sub.10 cycloalkylalkenyl,
(h) C.sub.5 -C.sub.10 cycloalkylalkynyl,
(i) --(CH.sub.2)SZ(CH.sub.2).sub.m R.sup.5,
(j) phenyl, optionally substituted with 1-2 substituents selected from the group of halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, --NO.sub.2, --NH.sub.2, --OH and benzyloxy,
(k) benzyl, optionally substituted on the phenyl ring with 1-2 substituents selected from the group of halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy and --NO.sub.2 ;
R.sup.7 and R.sup.8 taken together are --(CH.sub.2).sub.t --,
R.sup.9 and R.sup.10 taken together are O;
R.sup.11 is
(a) H,
(b) C.sub.1 -C.sub.4 alkyl,
(c) C.sub.1 -C.sub.4 cycloalkyl,
(d) phenyl,
(e) benzyl;
R.sup.12 is
(a) H,
(b) methyl,
(c) benzyl;
R.sup.13 is
(a) --CH.sub.2 CO.sub.2 H,
(b) --C(CF.sub.3).sub.2 OH,
(c) --CONHNHSO.sub.2 CF.sub.3,
(d) --CONHOR.sup.12,
(e) --CONHSO.sub.2 R.sup.20,
(f) --CONHSO.sub.2 NHR.sup.19,
(g) --C(OH)R.sup.19 PO.sub.3 H.sub.2,
(h) --NHCONHSO.sub.2 R.sup.20,
(i) --NHPO.sub.3 H.sub.2,
(j) --SO.sub.2 NHCOR.sup.20,
(k) --OPO.sub.3 H.sub.2,
(l) --OSO.sub.3 H,
(m) --PO(OH)R.sup.19,
(n) --PO.sub.3 H.sub.2,
(o) --SO.sub.3 H,
(p) --SO.sub.2 NHR.sup.19,
(q) --NHSO.sub.2 NHCOR.sup.20,
(r) --SO.sub.2 NHCONHR.sup.19, ##STR24## R.sup.19 is (a) H,
(b) C.sub.1 -C.sub.5 alkyl optionally substituted with a substituent selected from the group consisting of aryl, as defined above, --OH, --SH, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, --CF.sub.3, halo, --NO.sub.2, --CO.sub.2 H, --CO.sub.2 CH.sub.3, --CO.sub.2 -benzyl, --NH.sub.2, C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 dialkylamino, --PO.sub.3 H.sub.2,
(c) aryl, as defined above,
(d) benzyl
R.sup.20 is
(a) aryl, as defined above,
(b) C.sub.3 -C.sub.7 cycloalkyl,
(c) C.sub.1 -C.sub.4 perfluoroalkyl,
(d) C.sub.1 -C.sub.4 alkyl optionally substituted with a substituent selected from the group consisting of aryl, as defined above, --OH, --SH, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, --CF.sub.3, halo, --NO.sub.2, --CO.sub.2 H, --CO.sub.2 CH.sub.3, --CO.sub.2 -benzyl, --NH.sub.2, C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 dialkylamino, --PO.sub.3 H.sub.2,
(e) C.sub.1 -C.sub.4 alkoxy optionally substituted with a substituent selected from the group consisting of aryl as defined above, --OH, --SH, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, --CF.sub.3, halo, --NO.sub.2, --CO.sub.2 H, --CO.sub.2 CH.sub.3, --CO.sub.2 -benzyl, --NH.sub.2, C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 dialkylamino, --PO.sub.3 H.sub.2,
(f) furyl;
(g) thienyl;
R.sup.21 is
(a) H,
(b) C.sub.1 -C.sub.6 alkyl,
(c) phenyl,
(d) benzyl;
Z is
(a) --O--,
(b) --S--,
(c) --NR.sup.11 --;
m is 1 to 5;
n is 1 to 4;
t is 2 to 5;
or a pharmaceutically acceptable salt thereof.

103 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/128,784Filed 30 Sep 1993 · continuation in part
Priority: 19 Aug 1991
Granted: 30 Apr 1996
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 235/02
Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings: condensed with carbocyclic rings or…
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/12
Drugs for disorders of the cardiovascular system: antihypertensives
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00

Family

Serial747,023Parent of this continuation-in-part · filed 19 Aug 1991
Serial929,455Parent of this continuation-in-part · filed 14 Aug 1992
US 5,512,681 AThis patent

From the US filing history. Foreign family members aren’t listed.

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Citations

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A compound of formula (I) ##STR22## wherein:

R.sup.1 is other than in the ortho position and is:
##STR23## R.sup.2 is (a) H,
(b) halo (F, Cl, Br, I),
(c) C.sub.1 -C.sub.4 alkyl,
(d) C.sub.1 -C.sub.4 alkoxy,
(e) C.sub.1 -C.sub.4 acyloxy,
(f) C.sub.1 -C.sub.4 alkylthio,
(g) C.sub.1 -C.sub.4 alkylsulfinyl,
(h) C.sub.1 -C.sub.4 alkylsulfonyl,
(i) hydroxy (C.sub.1 -C.sub.4) alkyl,
(j) phenyl (C.sub.1 -C.sub.4) alkyl,
(k) --CO.sub.2 H,
(l) --CN,
(m) --CONHOR.sup.12,
(n) --SO.sub.2 NHR.sup.21,
(o) --NH.sub.2,
(p) C.sub.1 -C.sub.4 alkylamino,
(q) C.sub.1 -C.sub.4 dialkylamino,
(r) --NHSO.sub.2 R.sup.20,
(s) --NO.sub.2,
(t) furyl,
(u) aryl;
wherein aryl is phenyl optionally substituted with one or two substituents selected from the group consisting of halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, --NO.sub.2, CF.sub.3, C.sub.1 -C.sub.4 alkylthio, --OH, --NH.sub.2, C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 dialkylamino, --CN, --CO.sub.2 H, --CO.sub.2 CH.sub.3, --CO.sub.2 CH.sub.2 CH.sub.3, --CO.sub.2 -benzyl;
R.sup.3 is
(a) H,
(b) halo,
(c) C.sub.1 -C.sub.4 alkyl,
(d) C.sub.1 -C.sub.4 alkoxy,
(e) C.sub.1 -C.sub.4 alkoxyalkyl;
R.sup.4 is
(a) --CN,
(b) --NO.sub.2,
(c) --CO.sub.2 R.sup.11,
R.sup.5 is
(a) H,
(b) C.sub.1 -C.sub.6 alkyl,
(c) C.sub.3 -C.sub.6 cycloalkyl,
(d) C.sub.2 -C.sub.4 alkenyl,
(e) C.sub.2 -C.sub.4 alkynyl;
R.sup.6 is
(a) C.sub.1 -C.sub.10 alkyl,
(b) C.sub.3 -C.sub.8 alkenyl,
(c) C.sub.3 -C.sub.8 alkynyl,
(d) C.sub.3 -C.sub.8 cycloalkyl,
(e) C.sub.4 -C.sub.8 cycloalkenyl,
(f) C.sub.4 -C.sub.10 cycloalkylalkyl,
(g) C.sub.5 -C.sub.10 cycloalkylalkenyl,
(h) C.sub.5 -C.sub.10 cycloalkylalkynyl,
(i) --(CH.sub.2)SZ(CH.sub.2).sub.m R.sup.5,
(j) phenyl, optionally substituted with 1-2 substituents selected from the group of halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, --NO.sub.2, --NH.sub.2, --OH and benzyloxy,
(k) benzyl, optionally substituted on the phenyl ring with 1-2 substituents selected from the group of halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy and --NO.sub.2 ;
R.sup.7 and R.sup.8 taken together are --(CH.sub.2).sub.t --,
R.sup.9 and R.sup.10 taken together are O;
R.sup.11 is
(a) H,
(b) C.sub.1 -C.sub.4 alkyl,
(c) C.sub.1 -C.sub.4 cycloalkyl,
(d) phenyl,
(e) benzyl;
R.sup.12 is
(a) H,
(b) methyl,
(c) benzyl;
R.sup.13 is
(a) --CH.sub.2 CO.sub.2 H,
(b) --C(CF.sub.3).sub.2 OH,
(c) --CONHNHSO.sub.2 CF.sub.3,
(d) --CONHOR.sup.12,
(e) --CONHSO.sub.2 R.sup.20,
(f) --CONHSO.sub.2 NHR.sup.19,
(g) --C(OH)R.sup.19 PO.sub.3 H.sub.2,
(h) --NHCONHSO.sub.2 R.sup.20,
(i) --NHPO.sub.3 H.sub.2,
(j) --SO.sub.2 NHCOR.sup.20,
(k) --OPO.sub.3 H.sub.2,
(l) --OSO.sub.3 H,
(m) --PO(OH)R.sup.19,
(n) --PO.sub.3 H.sub.2,
(o) --SO.sub.3 H,
(p) --SO.sub.2 NHR.sup.19,
(q) --NHSO.sub.2 NHCOR.sup.20,
(r) --SO.sub.2 NHCONHR.sup.19, ##STR24## R.sup.19 is (a) H,
(b) C.sub.1 -C.sub.5 alkyl optionally substituted with a substituent selected from the group consisting of aryl, as defined above, --OH, --SH, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, --CF.sub.3, halo, --NO.sub.2, --CO.sub.2 H, --CO.sub.2 CH.sub.3, --CO.sub.2 -benzyl, --NH.sub.2, C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 dialkylamino, --PO.sub.3 H.sub.2,
(c) aryl, as defined above,
(d) benzyl
R.sup.20 is
(a) aryl, as defined above,
(b) C.sub.3 -C.sub.7 cycloalkyl,
(c) C.sub.1 -C.sub.4 perfluoroalkyl,
(d) C.sub.1 -C.sub.4 alkyl optionally substituted with a substituent selected from the group consisting of aryl, as defined above, --OH, --SH, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, --CF.sub.3, halo, --NO.sub.2, --CO.sub.2 H, --CO.sub.2 CH.sub.3, --CO.sub.2 -benzyl, --NH.sub.2, C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 dialkylamino, --PO.sub.3 H.sub.2,
(e) C.sub.1 -C.sub.4 alkoxy optionally substituted with a substituent selected from the group consisting of aryl as defined above, --OH, --SH, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, --CF.sub.3, halo, --NO.sub.2, --CO.sub.2 H, --CO.sub.2 CH.sub.3, --CO.sub.2 -benzyl, --NH.sub.2, C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 dialkylamino, --PO.sub.3 H.sub.2,
(f) furyl;
(g) thienyl;
R.sup.21 is
(a) H,
(b) C.sub.1 -C.sub.6 alkyl,
(c) phenyl,
(d) benzyl;
Z is
(a) --O--,
(b) --S--,
(c) --NR.sup.11 --;
m is 1 to 5;
n is 1 to 4;
t is 2 to 5;
or a pharmaceutically acceptable salt thereof.

103 more elements

Facts

Application

08/128,784Filed 30 Sep 1993 · continuation in part

Priority

19 Aug 1991

Granted

30 Apr 1996

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 235/02
Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings: condensed with carbocyclic rings or…
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/12
Drugs for disorders of the cardiovascular system: antihypertensives
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00