Benzothiazepine and benzothiazepine derivatives with ileal bile acid transport (IBAT) inhibotory activity for the treatment hyperlipidaemia

A compound of formula (I):

• wherein:
• Rv is selected from hydrogen or C1-6alkyl;
• 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;
• Rx and Ry are independently selected from hydrogen, hydroxy, amino, mercapto, C1-6alkyl, C1-6alkoxy, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, C1-6alkylS(O)a wherein a is 0 to 2;
• M is selected from —N— or —CH—;
• 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 C1-6allkyl;
• or R11 is a group of formula (IB) or (IC):
• R19, R20, R24 and R26 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, N,N-(C1-4alkyl)2sulphamoyl, carbocyclyl, heterocyclyl, benzyloxycarbonylamino, (C1-4alkyl)3silyl, sulpho, sulphino, amidino, phosphono, —P(O)(ORa)(ORb), —P(O)(OH)(ORa), —P(O)(OH)(Ra) or —P(O)(ORa)(Rb), wherein Ra and Rb are independently selected from C1-6alkyl;
• wherein R19, R20, R24 and R26 may be independently optionally substituted on carbon by one or more R22;
• R21 and R22 are independently selected from halo, hydroxy, cyano, carbamoyl, ureido, amino, nitro, carboxy, carbamoyl, mercapto, sulphamoyl, trifluoromethyl, tifluoromethoxy, methyl, ethyl, methoxy, ethoxy, vinyl, allyl, ethynyl, methoxycarbonyl, formyl, acetyl, formamido, acetylamino, acetoxy, methylamino, dimethylamino, N-methylcarbamoyl, N,N-dimethylcarbamoyl, methylthio, methylsulphinyl, mesyl, N-methylsulphamoyl and N,N-dimethylsulphamoyl;
• R23 is carboxy, sulpho, sulphino, phosphono, —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;
• R25 is selected from C1-6alkyl, C1-6alkanoyl, C1-6alkylsulphonyl, C1-6alkoxycarbonyl, carbamoyl, N-(C1-6alkyl)carbamoyl, N,N-(C1-6alkyl)carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulphonyl;
• wherein “heteroaryl” is a totally unsaturated, mono or bicyclic ring containing 3–12 atoms of which at least one atom is chosen from nitrogen, sulphur or oxygen, which may, unless otherwise specified, be carbon or nitrogen linked;
• wherein a “heterocyclyl” is a saturated, partially saturated or unsaturated, mono or bicyclic ring containing 3–12 atoms of which at least one atom is chosen from nitrogen, sulphur or oxygen, which may, unless otherwise specified, be carbon or nitrogen linked, wherein a CH2 group can optionally be replaced by a C(O) or a ring sulphur atom may be optionally oxidised to form the S oxides;
• and
• wherein a “carbocyclyl” is a saturated, partially saturated or unsaturated, mono or bicyclic carbon ring that contains 3–12 atoms;
• wherein a CH2 group can optionally be replaced by a C(O);
• or a pharmaceutically acceptable salt thereof.