Benzothiazepine derivatives

1. A compound of formula (I):

wherein

M 1 is —CH 2 —;

M 2 is —NR 24 —;

one of R 1 and R 2 is selected from hydrogen or C 1-6 alkyl and the other is selected from C 1-6 alkyl;

v is 0;

R 4 and R 7 are hydrogen;

one of R 5 and R 6 is a group of formula (IA):

and the other of R 5 and R 6 is hydrogen or methylthio;

Z is —O—;

R 8 is hydrogen;

R 9 is hydrogen;

R 10 is selected from cyclohexyl, and phenyl optionally substituted by one or more substituents R 28 ;

R 11 is hydrogen;

R 13 is a group of formula (IB):

wherein:

R 14 is hydrogen;

R 15 is hydrogen;

R 16 is hydroxy;

R 17 is ethyl substituted on each carbon by one R 47 , wherein R 47 is hydroxyl, or R 17 is a group of formula (IC);

wherein:

R 18 is hydrogen;

R 19 is hydrogen;

R 20 is C 1-10 alkyl; wherein R 20 may be independently optionally substituted on carbon by one or more R 57 ; wherein R 57 is selected from halo or hydroxyl;

p is 1;

q is 0;

r is 3;

m is 0;

n is 1;

z is 0-3;

R 24 is hydrogen; and

each R 28 is selected from halo, hydroxy, and C 1-10 alkoxy;

or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof, wherein the hydrolysable ester is selected from the group consisting of: α-acyloxyalkyl ethers selected from acetoxymethoxy and 2,2-dimethylpropionyloxy-methoxy; and in vivo hydrolysable ester forming groups for hydroxy selected from alkanoyl, benzoyl, phenylacetyl, alkoxycarbonyl, dialkylcarbamoyl, N-(dialkylaminoethyl)-N-alkylcarbamoyl, dialkylaminoacetyl, and carboxyacetyl.

2. A compound according to claim 1 wherein one of R 1 and R 2 is C 1-4 -alkyl.

3. A compound having formula: (+/−)-trans-1,1-dioxo-3-ethyl-3-butyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N′-(2-(S)-3-(R)-4-(R)-5-(R)-2,3,4,5,6-pentahydroxyhexyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,4-benzothiazepine, or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof, wherein the hydrolysable ester is selected from the group consisting of: α-acyloxyalkyl ethers selected from acetoxymethoxy and 2,2-dimethylpropionyloxy-methoxy; and in vivo hydrolysable ester forming groups for hydroxy selected from alkanoyl, benzoyl, phenylacetyl, alkoxycarbonyl, dialkylcarbamoyl, N-(dialkylaminoethyl)-N-alkylcarbamoyl, dialkylaminoacetyl, and carboxyacetyl.

4. A process for preparing a compound of formula (I) or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof, as claimed in claim 1 , which process comprises of:

Process 1): for compounds of formula (I); reacting a compound of formula (IIa):

with a compound of formula (III):

wherein L is a displaceable group;

Process 2): reacting an acid of formula (IVa):

with an amine of formula (V):

Process 3): for compounds of formula (I) wherein R 13 is a group of formula (IB); reacting an acid of formula (VIa):

with an amine of formula (VI):

Process 4) for compounds of formula (I) wherein R 6 is methylthio ; reacting a compound of formula (Xb):

wherein L is a displaceable group; with a thiol of formula (XI):

R m —H  (XI)

wherein R m is methylthio;

and optionally:

i) converting a compound of the formula (I) into another compound of the formula (I);

ii) removing any protecting groups;

iii) forming a pharmaceutically acceptable salt or a prodrug.

5. A pharmaceutical composition which comprises a compound of formula (I), or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof, as in claim 1 , in association with a pharmaceutically-acceptable diluent or carrier, wherein the hydrolysable ester is selected from the group consisting of: α-acyloxyalkyl ethers selected from acetoxymethoxy and 2,2-dimethylpropionyloxy-methoxy; and in vivo hydrolysable ester forming groups for hydroxy selected from alkanoyl, benzoyl, phenylacetyl, alkoxycarbonyl, dialkylcarbamoyl, N-(dialkylaminoethyl)-N-alkylcarbamoyl, dialkylaminoacetyl, and carboxyacetyl.