Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists

A compound of the following formula I, enantiomers, diastereomers, salts and solvates thereof:

• wherein:
• 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;
• 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;
• R13 and R14 are alkyl or together form a five to six-membered ring;
• 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;
• w is 0, 1, or 2;
• Y is heteroaryl, —COOH, —COOR18, —CONR19R20, —NR19R20, —NR19—OR20, —NR21(C═O)R22, —NR21(C═O)NR19R20, —N(R19)-(alk)—NR21(C═O)R22, —NR21(C═O)OR18, —NR21SO2R22, —SO2R22, Q, R or S;
• 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,
• 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 said compound is other than