Benzothiazepine derivatives for the treatment of hyperlipidemia

A compound of formula (I):

• wherein:
• One of R1 and R2 are selected from hydrogen, C1-6alkyl or C2-6alkenyl and the other is selected from C1-6alkyl or C2-6alkenyl;
• Ry is selected from hydrogen, hydroxy, C1-6alkyl, C1-4alkoxy and C1-6alkanoyloxy;
• Rz is selected from halo, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is 0 to 2, C1-6alkoxycarbonyl, N—(C1-6alkyl)sulphamoyl and N,N—(C1-6alkyl)2sulphamoyl;
• v is 0–5;
• one of R4 and R5 is a group of formula (IA):
• R3 and R6 and the other of R4 and R5 are independently selected from hydrogen, halo, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkanoyloxy, N—(C1-4alkyl)amino, N,N—(C1-4alkyl)2amino, C1-4alkanoylamino, N—(C1-4alkyl)carbamoyl, N,N—(C1-4alkyl)2carbamoyl, C1-4alkylS(O)a wherein a is 0 to 2, C1-4alkoxycarbonyl, N—(C1-4alkyl)sulphamoyl and N,N—(C1-4alkyl)2sulphamoyl;
• wherein R3 and R6 and the other of R4 and R5 may be optionally substituted on carbon by one or more R16;
• X is —O—, —N(Ra)—, —S(O)b— or —CH(Ra)—;
• wherein Ra is hydrogen or C1-6alkyl and b is 0–2;
• Ring A is aryl or heteroaryl;
• wherein Ring A is optionally substituted by one or more substituents selected from R17;
• R7 is hydrogen, C1-4alkyl, carbocyclyl or heterocyclyl;
• wherein R7 is optionally substituted by one or more substituents selected from R18;
• R8 is hydrogen or C1-4alkyl;
• R9 is hydrogen or C1-4alkyl;
• R10 is hydrogen, C1-4alkyl, carbocyclyl or heterocyclyl;
• wherein R10 is optionally substituted by one or more substituents selected from R19;
• R11 is carboxy, sulpho, sulphino, phosphono, —P(O)(ORc)(ORd), —P(O)(OH)(ORc), —P(O)(OH)(Rd) or —P(O)(ORc)(Rd) wherein Rc and Rd are independently selected from C1-6alkyl;
• or R11 is a group of formula (IB):
• wherein:
• Y is —N(Rx)—, —N(Rx)C(O)—, —O—, and —S(O)a-;
• wherein a is 0–2 and Rx is hydrogen or C1-4alkyl;
• R12 is hydrogen or C1-4alkyl;
• R13 and R14 are independently selected from hydrogen, C1-6alkyl, carbocyclyl or heterocyclyl;
• wherein R13 and R14 may be independently optionally substituted by one or more substituents selected from R20;
• R15 is carboxy, sulpho, sulphino, phosphono, —P(O)(ORe)(ORf), —P(O)(OH)(ORe), —P(O)(OH)(Re) or —P(O)(ORe)(Rf) wherein Re and Rf are independently selected from C1-6alkyl;
• or R15 is a group of formula (IC):
• wherein:
• R24 is selected from hydrogen or C1-4alkyl;
• R25 is selected from hydrogen, C1-4alkyl, carbocyclyl, heterocyclyl or R27;
• wherein said C1-4alkyl, carbocyclyl or heterocyclyl may be independently optionally substituted by one or more substituents selected from R28;
• R26 is selected from carboxy, sulpho, sulphino, phosphono, tetrazolyl, —P(O)(ORg)(ORh), —P(O)(OH)(ORg), —P(O)(OH)(Rg) or —P(O)(ORg)(Rh) wherein Rg and Rh are independently selected from C1-6alkyl;
• p is 1–3;
• wherein the values of R13 may be the same or different;
• q is 0–1;
• r is 0–3;
• wherein the values of R14 may be the same or different;
• m is 0–2;
• wherein the values of R10 may be the same or different;
• n is 1–3;
• wherein the values of R7 may be the same or different;
• z is 0–3;
• wherein the values of R25 may be the same or different;
• R16, R17 and R18 are independently selected from halo, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkanoyloxy, N—(C1-4alkyl)amino, N,N—(C1-4alkyl)2amino, C1-4alkanoylamino, N—(C1-4alkyl)carbamoyl, N,N—(C1-4alkyl)2carbamoyl, C1-4alkylS(O)a wherein a is 0 to 2, C1-4alkoxycarbonyl, N—(C1-4alkyl)sulphamoyl and N,N—(C1-4alkyl)2sulphamoyl;
• wherein R16, R17 and R18 may be independently optionally substituted on carbon by one or more R21;
• or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester formed on an available carboxy or hydroxy thereof, or an in vivo hydrolysable amide formed on an available carboxy thereof.