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US 5,856,484 AGranted
Sulfonylaminopyrimidine carboxylic acid derivatives having endothelin inhibiting activity
AssigneeHoffmann-La Roche Inc.
InventorsVolker Breu, Kaspar Burri, Jean-Marie Cassal, Martine Clozel, Georges Hirth, Bernd-Michael Loffler, Marcel Muller, Werner Neidhart, Henri Ramuz
Life of this patent
Estimating the term…
Abstract
Compounds of formula I: ##STR1## are disclosed. The compounds inhibit the binding of endothelin to its receptors.
Claims94
A compound of the formula:
- ##STR4## wherein R.sup.1 is phenyl;
- a substituted phenyl substituted by a chemical group selected from the group consisting of lower alkyl, lower alkoxy, methylenedioxy, ethylenedioxy, lower-alkanoyl, hydroxy, amino, mono-lower-alkylamino, di-lower-alkylamino or halogen;
- or heterocyclyl selected from the group consisting of 2-furyl, 3-furyl, pyrimidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-tetrazolyl-4-pyridyl, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, thiazolyl, imidazolyl, pyrrolyl and tetrazolyl;
- R.sup.2 is phenyl or a substituted phenyl substituted by a chemical group selected from the group consisting of lower alkyl, lower alkoxy, methylenedioxy, ethylenedioxy, lower-alkanoyl, hydroxy, amino, mono-lower-alkylamino, di-lower-alkylamino and halogen;
- R.sup.3 is hydroxy, lower alkoxy or --NR.sup.4 R.sup.5 ;
- R.sup.4 is hydrogen or --R.sup.6 and
- R.sup.5 is hydrogen or --(CH.sub.2)mR.sup.6 or
- R.sup.4 and R.sup.5 together are an N-heterocyclylic chosen from the group consisting of morpholino, piperidino, piperazino and N.sup.4 -lower -alkylpiperazino;
- R.sup.6 is phenyl;
- cycloalkyl;
- lower-alkyl;
- hydroxy lower alkyl;
- amino-lower-alkyl;
- carboxy-lower-alkyl;
- lower-alkoxycarbonyl- lower-alkyl;
- a substituted phenyl substituted by a chemical group selected from the group consisting of lower alkyl, lower alkoxy, methylenedioxy, ethylenedioxy, lower-alkanoyl, hydroxy, amino, mono-lower-alkylamino, di-lower-alkylamino or halogen;
- or heterocyclyl chosen from the group consisting of 2-furyl, 3-furyl, pyrimidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-tetrazolyl-4-pyridyl, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, thiazolyl, imidazolyl, pyrrolyl and tetrazolyl;
- R.sup.a is hydrogen, lower-alkyl or hydroxy;
- R.sup.b is hydrogen or lower alkyl;
- X is oxygen or sulfur;
- Y is oxygen or sulfur;
- Z is hydrogen;
- lower-alkyl;
- aryl;
- aryl-lower-alkyl;
- heterocyclyl selected from the group consisting of 2-furyl, 3-furyl, pyrimidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-tetrazolyl-4-pyridyl, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, thiazolyl, imidazolyl, pyrrolyl and tetrazolyl;
- or heterocyclyl selected from the group consisting of 2-furyl, 3-furyl, pyrimidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-tetrazolyl-4-pyridyl, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl. 3-thienyl, isoxazolyl, oxazolyl, thiazolyl, imidazolyl, pyrrolyl and tetrazolyl, wherein the heterocyclyl is substituted with lower-alkyl;
- m is 0, 1, or 2;
- and,
- n is 0, 1, or 2;
- and pharmaceutically acceptable salts thereof.
28 more elements
A compound of the formula:
- ##STR5## wherein A is formyl or furan-2-yl;
- R.sup.1 is phenyl;
- a substituted phenyl substituted by a chemical group selected from the group consisting of lower alkyl, lower alkoxy, methylenedioxy, ethylenedioxy, lower-alkanoyl, hydroxy, amino, mono-lower-alkylamino, di-lower-alkylamino and halogen;
- or heterocyclyl selected from the group consisting of 2-furyl, 3-furyl, pyrimidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-tetrazolyl-4-pyridyl, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, thiazolyl, imidazolyl, pyrrolyl and tetrazolyl;
- R.sup.2 is phenyl or a substituted phenyl substituted by a chemical group selected from the group consisting of lower alkyl, lower alkoxy, methylenedioxy, ethylenedioxy, lower-alkanoyl, hydroxy, amino, mono-lower-alkylamino, di-lower-alkylamino and halogen;
- R.sup.a' is a protected hydroxy, hydrogen, lower-alkyl or hydroxy;
- R.sup.b is hydrogen or lower alkyl;
- X is oxygen or sulfur;
- Y is oxygen or sulfur;
- n is 0, 1, or 2;
- Z' is a hydroxy protecting group;
- hydrogen;
- lower-alkyl;
- aryl;
- aryl-lower-alkyl;
- heterocyclyl selected from the group consisting of 2-furyl, 3-furyl, pyrimidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-tetrazolyl-4-pyridyl, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, thiazolyl, imidazolyl, pyrrolyl and tetrazolyl;
- or heterocyclyl selected from the group consisting of 2-furyl, 3-furyl, pyrimidinyl, 2-pyridyl, 3-pridyl, 4-pyridyl, 2-tetrazolyl-4-pyridyl, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, thiazolyl, imidazolyl, pyrrolyl and tetrazolyl, wherein the heterocyclyl is substituted with lower-alkyl.
14 more elements
Dependencies are inferred from the claim text.