Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists

A compound of the following formula I, or an enantiomer, diastereomer, salt or metabolite thereof:

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• R2 is hydrogen, halogen, —CHO, alkyl, haloalkyl, (cycloalkyl)alkyl, alkenyl, alkynyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, aryloxy alkoxyalkoxy, cyano, hydroxy, hydroxyalkyl, nitro, —CH(OR13)(OR14), —(CH2)wY;
• with the proviso that when R1 is B, R2 is not hydrogen, halogen, alkyl, haloalkyl, alkoxy, hydroxyalkyl, nitro, —(CH2)wNR19R20 or —NHSO2R22;
• R3 is heteroaryl;
• R4 and R5 are each independently alkyl, hydroxyalkyl, cycloalkyl, hydroxy substituted cycloalkyl, alkoxyalkyl, or hydroxy substituted alkoxyalkyl, or R4 and R5 together form a cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl or tetrahydropyranyl ring which may be optionally substituted with one or more hydroxy groups;
• R6 is alkyl, hydroxyalkyl, haloalkyl, hydroxy substituted haloalkyl, cycloalkyl, hydroxy substituted cycloalkyl, (cycloalkyl)alkyl, hydroxy substituted (cycloalkyl)alkyl, aralkyl, alkoxy, hydroxy substituted alkoxy, alkoxyalkyl, hydroxy substituted alkoxyalkyl, or —NR16R17;
• R7 is —(CH2)w—CO2R15, —(CH2)w—(C═O)NR16R17, —(CH2)w—NR15(C═O)NR16R17, —(CH2)w—(C═O)R15, tetrazolyl, oxadiazolyl or triazolyl wherein said tetrazolyl, oxadiazolyl or triazolyl may optionally be substituted with hydrogen, alkyl, hydroxy or halogen;
• R8, R9, R9a, R10 and R12 are each independently hydrogen, halogen, alkyl, hydroxyalkyl, cycloalkyl, (cycloalkyl)alkyl, aryl, heteroaryl, arylalkyl, alkylthioalkyl, alkoxy or alkoxyalkyl, or R9 and R9a together with the carbon atom to which they are bonded form a cycloalkyl ring;
• R11 and R11a are each independently hydrogen, alkoxy, or together form a carbonyl;
• R13 and R14 are alkyl or together form a five to six-membered ring;
• R15, R16 and R17 are independently hydrogen, alkyl, hydroxyalkyl, cycloalkyl, (cycloalkyl)alkyl, alkoxyalkyl, aralkyl, heterocycloalkyl, aryl, heteroaryl or —(CH2)wQ, or R16 and R17 may together form a four to six-membered heterocyclic ring;
• n is 1 or 2;
• w is 0, 1, or 2;
• Y is heteroaryl, —COOH, —COOR18, —CONR19R20, —NR19R20, —NR19—OR20, —NR21(C═O)R22, —NR2,(C═O)NR19R20, —N(R19)-(alk)-NR21(C═O)R22, —NR21(C═O)OR18, —NR21SO2R22, —SO2R22, Q, R or S;
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• R18, R19, R20, R21 and R22 are each independently hydrogen, alkyl, haloalkyl, alkoxyalkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, or R19 and R20 may together form a four to seven-membered heterocyclic ring;
• R23 and R24 are each independently hydrogen, alkyl or cycloalkyl, or may together form a three to seven membered cycloalkyl ring;
• Z is oxygen, or
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• x is 2, 3 or 4;
• R25, R26 and R27, are each independently hydrogen, alkyl or cycloalkyl, or R26 and R27 may together form a three to seven-membered cycloalkyl ring;
• R101, R102, R103, and R104 are each independently hydrogen, halogen, —CHO, alkyl, haloalkyl, (cycloalkyl)alkyl, alkenyl, alkynyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, alkoxyalkoxy, cyano, hydroxy, hydroxyalkyl, nitro, —CH(OR13)(OR14), or —(CH2)wY;
• wherein said rings;
• aryl alone or as part of another group;
• or heteroaryl alone or as part of another group may each optionally be substituted by one or more hydrogen, halogen, cyano, alkyl, hydroxyalkyl, alkoxy, nitro or trifluoromethyl groups;
• provided that when R1 is A said compound is other than
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