Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin
First Claim
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1. A compound that has formula I:
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or a pharmaceutically acceptable salt or ester thereof, wherein;
Ar1 is a bicyclic or tricyclic carbon or heterocyclic ring;
Ar2 has formula (I);
wherein;
Ar2 is substituted with one or more than one substituent, each of which is selected independently from the selections set forth for R26 and R13, in which R26 and R13 are each independently selected from H, OH, OHNH, NH2, NO2, halide, pseudohalide, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heterolaryl, alkoxy, alkylamino, dialkylamino, alkylthio, haloalkoxy, haloalkyl, alkylsulfinyl, alkylsulfonyl, aryloxy, arylamino, arylthio, arylsulfinyl, arylsulfonyl, haloalkyl, haloaryl, alkoxycarbonyl, carbonyl, alkylcarbonyl, aminocarbonyl, arylcarbonyl, formyl, substituted or unsubstituted amido, substituted or unsubstituted ureido, in which the alkyl, alkenyl and alkynyl portions contain from 1 up to about 14 carbon atoms, and are either straight or branched chains or cyclic, and the aryl portions contain from about 4 to about 16 carbons, with the proviso that if there is only one R13, it is not hydrogen.
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Abstract
Biphenylsulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, bicyclic or tricyclic carbon or heterocyclic ring biphenylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.
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Citations
14 Claims
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1. A compound that has formula I:
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or a pharmaceutically acceptable salt or ester thereof, wherein; Ar1 is a bicyclic or tricyclic carbon or heterocyclic ring;
Ar2 has formula (I);
wherein; Ar2 is substituted with one or more than one substituent, each of which is selected independently from the selections set forth for R26 and R13, in which R26 and R13 are each independently selected from H, OH, OHNH, NH2, NO2, halide, pseudohalide, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heterolaryl, alkoxy, alkylamino, dialkylamino, alkylthio, haloalkoxy, haloalkyl, alkylsulfinyl, alkylsulfonyl, aryloxy, arylamino, arylthio, arylsulfinyl, arylsulfonyl, haloalkyl, haloaryl, alkoxycarbonyl, carbonyl, alkylcarbonyl, aminocarbonyl, arylcarbonyl, formyl, substituted or unsubstituted amido, substituted or unsubstituted ureido, in which the alkyl, alkenyl and alkynyl portions contain from 1 up to about 14 carbon atoms, and are either straight or branched chains or cyclic, and the aryl portions contain from about 4 to about 16 carbons, with the proviso that if there is only one R13, it is not hydrogen. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
the contacting is effected prior to, simultaneously with or subsequent to contacting the receptors with the endothelin peptide.
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10. A method for altering endothelin receptor-mediated activity, comprising contacting endothelin receptors with one or more compounds of claim 1.
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11. A pharmaceutical composition formulated for single dosage administration, comprising an effective amount of one or more compounds of claim 1, wherein the amount is effective for ameliorating the symptoms of an endothelin-mediated disease.
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12. An article of manufacture, comprising packaging material and one or more compounds of claim 1 contained within the packaging material, wherein the compound is effective for antagonizing the effects of endothelin, ameliorating the symptoms of an endothelin-mediated disorder, or inhibiting the binding of an endothelin peptide to an ET receptor with an IC50 of less than about 10 μ
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13. The compounds of claim 1 in which the alkyl, alkenyl and alkynyl portions contain from 1 up to about 6 carbon atoms.
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14. The compounds of claim 1 in which the aryl portions contain from about 4 to about 10 carbons.
Specification