THIENO-PYRIDINE SULFONAMIDES DERIVATIVES THEREOF AND RELATED COMPOUNDS THAT MODULATE THE ACTIVITY OF ENDOTHELIN
First Claim
1. A sulfonamide compound of formula (I) wherein:
- Ar1, which contains from 1 to 30 carbon atoms, is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl and fused bicyclic or tricyclic rings, wherein the alkyl, alkenyl and alkynyl groups may be straight or branched chains, or straight or branched chains that include cyclic portions; and
Ar2 is a group of formula;
Y is N or O+;
X is S, O, or NR11 in which R11, which is hydrogen or contains up to about 30 carbon atoms, is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, C(O)R15 and S(O)nR15 in which n is 0-2; and
R15, which is selected independently from R11, is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl and cycloalkynyl;
R3, R4 and R5 are selected from (i), (ii), (iii) or (iv);
(i) R3, R4 and R5 are each selected independently from among H, NHOH, NH2, NO2, N3, halide, pseudohalide, alkyl, alkenyl, alkynyl, alkylaryl, aryloxy, aryl, heteroaryl, alkoxy, alkylamino, alkylthio, alkoxyalkyl, alkylsulfinyl, alkylsulfonyl, aryloxy, arylamino, arylthio, arylsulfinyl, arylsulfonyl, haloalkyl, haloaryl, alkoxycarbonyl, alkylcarbonyl, arylcarbonyl, formyl and amido, where the alkyl, alkenyl and alkynyl portions are straight or branched chains of from about 1 up to about 10 carbons, and the aryl portions contain from 3 up to about 10 carbons;
or (ii) two of R3, R4 and R5 form 1,3-butadienyl, 4-dimethylamino-1,3-butadienyl, 1-chloro-1,3-butadienyl, 1-aza-1,3-butadienyl or 2-aza-1,3-butadienyl groups or form alkylenedioxy; and
the other of R3, R4 and R5 is as defined in (i);
or (iii) two of R3, R4 and R5 are independently selected from alkyl, alkoxy, halide, aminoalkyl and dialkylaminoalkyl, in which the alkyl and alkoxy groups contain from 1 to 10 carbons, and are straight or branched chains and the other is H;
or (iv) any two of R3, R4 and R5, which are each selected as in (i), form fused carbocyclic or heterocyclic rings and the other is selected as in (i); and
R7 is hydrogen or contains up to about 50 carbon atoms and is selected from hydrogen, halide, pseudohalide, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryloxy, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, OH, CN, C(O)R18, CO2R8, (CH2)rCOR18, (CH2)rCO(CH2)sR18, SH, S(O)n, (CH2)rR18, S(O)nR18 in which n is 0-2, and r is 0 to 6, HNOH, NR18R19, NO2, N3, OR18, R19NCOR18 and CONR19R18, in which R19 is selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, alkoxy, aryloxy, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, C(O)R20 and S(O)nR20 in which n is 0-2; and
R18 and R20 are independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, alkoxy, aryloxy, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl and cycloalkynyl; and
any of the groups set forth for R7 is unsubstituted or substituted with any substituents set forth for Z, which is hydrogen, halide, pseudohalide, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryloxy, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, OH, CN, C(O)R21, CO2R21, SH, S(O)nR21 in which n is 0-2, NHOH, NR22R21, NO2, N3, OR21, R22NCOR21 or CONR22R21;
R22 is selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, alkoxy, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, C(O)R23 and S(O)nR23 in which n is 0-2; and
R21 and R23 are independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl and cycloalkynyl.
2 Assignments
0 Petitions
Accused Products
Abstract
Methods, compositions, and compounds for modulating the activity of an endothelin peptide are provided. The methods use compositions that contain compounds that include those of the formula:
where X is selected from groups that include O, S, and NH; Y is selected from O+ and N, and R1 and R2 are each selected independently from among alkyl, lower alkenyl, lower alkynyl, lower haloalkyl, halide, pseudohalide or H, except that R2 is not halide. R3, R4 and R5 are selected from among groups that include hydrogen, halide, alkoxy, alkyl, haloalkyl; and R7 is selected from groups that include (CH2)rR18, in which r is 0 to 6 and R18 is selected from groups that include aryl, particularly pyrimidinyl and phenyl. The methods are effected by contacting endothelin receptors with one or more of the compounds or with compositions containing one or more of the compounds prior to, simultaneously with, or subsequent to contacting the receptors with an endothelin peptide.
1 Citation
14 Claims
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1. A sulfonamide compound of formula (I)
wherein: -
Ar1, which contains from 1 to 30 carbon atoms, is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl and fused bicyclic or tricyclic rings, wherein the alkyl, alkenyl and alkynyl groups may be straight or branched chains, or straight or branched chains that include cyclic portions; and
Ar2 is a group of formula;
Y is N or O+;
X is S, O, or NR11 in which R11, which is hydrogen or contains up to about 30 carbon atoms, is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, C(O)R15 and S(O)nR15 in which n is 0-2; and
R15, which is selected independently from R11, is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl and cycloalkynyl;
R3, R4 and R5 are selected from (i), (ii), (iii) or (iv);
(i) R3, R4 and R5 are each selected independently from among H, NHOH, NH2, NO2, N3, halide, pseudohalide, alkyl, alkenyl, alkynyl, alkylaryl, aryloxy, aryl, heteroaryl, alkoxy, alkylamino, alkylthio, alkoxyalkyl, alkylsulfinyl, alkylsulfonyl, aryloxy, arylamino, arylthio, arylsulfinyl, arylsulfonyl, haloalkyl, haloaryl, alkoxycarbonyl, alkylcarbonyl, arylcarbonyl, formyl and amido, where the alkyl, alkenyl and alkynyl portions are straight or branched chains of from about 1 up to about 10 carbons, and the aryl portions contain from 3 up to about 10 carbons;
or(ii) two of R3, R4 and R5 form 1,3-butadienyl, 4-dimethylamino-1,3-butadienyl, 1-chloro-1,3-butadienyl, 1-aza-1,3-butadienyl or 2-aza-1,3-butadienyl groups or form alkylenedioxy; and
the other of R3, R4 and R5 is as defined in (i);
or(iii) two of R3, R4 and R5 are independently selected from alkyl, alkoxy, halide, aminoalkyl and dialkylaminoalkyl, in which the alkyl and alkoxy groups contain from 1 to 10 carbons, and are straight or branched chains and the other is H;
or(iv) any two of R3, R4 and R5, which are each selected as in (i), form fused carbocyclic or heterocyclic rings and the other is selected as in (i); and
R7 is hydrogen or contains up to about 50 carbon atoms and is selected from hydrogen, halide, pseudohalide, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryloxy, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, OH, CN, C(O)R18, CO2R8, (CH2)rCOR18, (CH2)rCO(CH2)sR18, SH, S(O)n, (CH2)rR18, S(O)nR18 in which n is 0-2, and r is 0 to 6, HNOH, NR18R19, NO2, N3, OR18, R19NCOR18 and CONR19R18, in which R19 is selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, alkoxy, aryloxy, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, C(O)R20 and S(O)nR20 in which n is 0-2; and
R18 and R20 are independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, alkoxy, aryloxy, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl and cycloalkynyl; and
any of the groups set forth for R7 is unsubstituted or substituted with any substituents set forth for Z, which is hydrogen, halide, pseudohalide, alkyl, alkoxy, alkenyl, alkynyl, aryl, aryloxy, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, OH, CN, C(O)R21, CO2R21, SH, S(O)nR21 in which n is 0-2, NHOH, NR22R21, NO2, N3, OR21, R22NCOR21 or CONR22R21;
R22 is selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, alkoxy, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, C(O)R23 and S(O)nR23 in which n is 0-2; and
R21 and R23 are independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl and cycloalkynyl. - View Dependent Claims (2, 3, 4, 13)
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- 5. A method of altering nitric oxide levels, comprising administering an effective amount of an endothelin antagonist, whereby nitric oxide levels are altered.
Specification