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US 5,492,917 AGranted
Endothelin antagonists incorporating a cyclobutane
AssigneeMerck & Co., Inc.
InventorsRalph A. Rivero, Peter D. Williams, Daniel F. Veber
Life of this patent
Estimating the term…
Abstract
Novel compounds of the general structural formula I: ##STR1## have endothelin antagonist activity and are therefore useful in treating cardiovascular disorders, such as hypertension, pulmonary hypertension, postischemic renal failure, vasospasm, cerebral and cardiac ischemia, myocardial infarction, endotoxic shock, inflammatory diseases including Raynaud's disease and asthma.
Claims15
A compound of structural Formula I:
- ##STR19## or a pharmaceutically acceptable salt thereof, wherein:
- R.sup.1a and R.sup.1b groups are independently:
- (a) H, except that one and only of R.sup.1a and R.sup.1b can be hydrogen, when X is O, and R.sup.4a and R.sup.4b are both CO.sub.2 H,
- (b) halo(F, Cl, Br, I),
- (c) (C.sub.1 -C.sub.4) alkoxy,
- (d) (C.sub.1 -C.sub.5) alkyl,
- (e) (C.sub.1 -C.sub.5) alkylamino,
- (f) (C.sub.1 -C.sub.5) alkylthio,
- (g) (C.sub.1 -C.sub.5) perfluoroalkyl,
- (h) SCF.sub.3,
- (i) NH.sub.2,
- (j) NHCOR.sup.2,
- (k) NR.sup.3 COR.sup.2,
- (l) COR.sup.2,
- (m) NO.sub.2,
- (n) aryl, wherein aryl is defined as phenyl or naphthyl which is unsubstituted or substituted with substituents selected from the group consisting of:
- halo(F, Cl, Br, I), (C.sub.1 -C.sub.4) alkoxy, (C.sub.1 -C.sub.4) alkyl, (C.sub.1 -C.sub.4) alkylamino, (C.sub.1 -C.sub.4) alkylthio, or (C.sub.1 -C.sub.4) perfluoroalkyl, or CO-aryl, or
- (o) CH.sub.2 -aryl, wherein aryl is as defined above in R.sup.1 (n);
- R.sup.2 is:
- (a) halo(F, CI, Br, I),
- (b) (C.sub.1 -C.sub.4) alkoxy,
- (c) (C.sub.1 -C.sub.5) alkyl,
- (d) (C.sub.1 -C.sub.5) alkylamino,
- (e) aryl, wherein aryl is defined as phenyl or naphthyl, which is unsubstituted or substituted with one or two substituents selected from the group consisting of:
- halo(F, Cl, Br), (C.sub.1 -C.sub.4) alkoxy, (C.sub.1 -C.sub.4) alkyl, (C.sub.1 -C.sub.4) alkylamino, (C.sub.1 -C.sub.4) alkylthio, or (C.sub.1 -C.sub.4) perfluoroalkyl, or
- (f) CH.sub.2 -aryl, wherein aryl is as defined above in R.sup.2 (e);
- R.sup.3 is:
- (a) (C.sub.1 -C.sub.5) alkyl,
- (b) aryl, wherein aryl is defined as phenyl or naphthyl, which is unsubstituted or substituted with one or two substituents selected from the group consisting of:
- halo(F, Cl, Br), (C.sub.1 -C.sub.4) alkoxy, (C.sub.1 -C.sub.4) alkyl, (C.sub.1 -C.sub.4) alkylthio, or (C.sub.1 -C.sub.4) perfluoroalkyl, or
- (c) CH.sub.2 -aryl, wherein aryl is as defined above in R.sup.3 (b);
- R.sup.4a and R.sup.4b groups are independently:
- (a) CH.sub.2 OH,
- (b) CO.sub.2 H,
- (c) CO.sub.2 CH.sub.3,
- (d) CONH.sub.2,
- (e) CONHR.sup.3,
- (f) CON(R.sup.3).sub.2, ##STR20## X is:
- (a) O,
- (b) H, H,
- (c) OH, H,
- (d) OR.sup.3, H, or
- (e) .dbd.CHR.sup.3.
40 more elements
Dependencies are inferred from the claim text.