Chemistry: molecular biology and microbiology – Process of utilizing an enzyme or micro-organism to destroy... – Resolution of optical isomers or purification of organic...
Patent
1994-05-19
1998-03-10
Marx, Irene
Chemistry: molecular biology and microbiology
Process of utilizing an enzyme or micro-organism to destroy...
Resolution of optical isomers or purification of organic...
435117, 435118, 435119, 435911, C12P 1700
Patent
active
057260559
DESCRIPTION:
BRIEF SUMMARY
This application was filed under 35 USC 371 as the national phase of PCT/GB92/02140.
This invention relates to a novel process for preparing certain substituted thiazolidinedione derivatives, to certain novel compounds, to pharmaceutical compositions comprising such compounds and to the use of such compounds in medicine.
European Patent Application, Publication Nnmber 0 306228 discloses inter alia certain thiazolidinedione derivatives of formula (A): ##STR1## or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof, and/or a pharmaceutically acceptable solvate thereof, wherein: A.sup.a represents a substituted or unsubstituted aromatic heterocyclyl group;
R.sup.a represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group;
R.sup.b and R.sup.c each represent hydrogen or R.sup.b and R.sup.c together represent a bond;
A.sup.b represents a benzene ring having in total up to five substituents; and
n' represents an integer in the range of from 2 to 6.
EP 0306228 also discloses a process for converting compounds of formula (A), in particular a process for reducing the benzylidene double bond of compounds of formula (A) wherein R.sup.b and R.sup.c together represent a bond to provide compounds of formula (A) wherein R.sup.b and R.sup.c each represent hydrogen.
Particular reduction methods disclosed in EP 0306228 are catalytic reduction methods and metal/solvent reducing methods.
It has now been discovered that the reduction of the benzylidene double bond of the compound of formula (A) may be effected by a reductase enzyme from a microorganism, in particular from a yeast microorganism, and surprisingly that the said reduction proceeds in a structure specific manner. The reduction is also capable of proceeding in an enantioselective manner.
Certain of the compounds obtained in the process are novel and are indicated to show good blood-glucose lowering activity and are therefore of potential use in the treatment and/or prophylaxis of hyperglycaemia and are of particular use in the treatment of Type II diabetes.
These compounds are also indicated to be of potential use for the treatment and/or prophylaxis of other diseases including hyperlipidaemia, hypertension, cardiovascular disease and certain eating disorders.
Accordingly, the present invention provides a process for preparing a compound of formula (I): ##STR2## or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof and/or a pharmaceutically acceptable solvate thereof, wherein: T represents a substituted or unsubstituted aryl group and T.sup.1 is O or S; which process comprises, treating a compound of formula (II): ##STR3## or a tautomeric form thereof and/or a salt thereof and/or a solvate thereof, wherein T and T.sup.1 are as defined in relation to formula (I), with a microbial reductase obtained from an appropriate red yeast; and thereafter, as required, preparing a pharmaceutically acceptable salt and/or a pharmaceutically acceptable solvate of the compound of formula (I) or a tautomeric form thereof.
Suitably T represents a moiety selected from the list consisting of (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Il), (Im), (In), (Io) and (Ip): ##STR4## wherein A.sup.1, A.sup.2, R.sup.1 and n are as defined in relation to formula (I) of EP 0306228; ##STR5## wherein R.sup.2, L.sup.1, L.sup.2 and L.sup.3 are as defined in relation to formula (I) of EP 0008203; ##STR6## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, W and n are as defined in relation to formula (I) of EP 0139421; ##STR7## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined in relation to formula (I) of EP 0032128; ##STR8## wherein A, R, R.sup.1 and X are as defined in relation to formula (I) of EP 0428312; ##STR9## when A, B, R and R.sup.1 are as defined in relation to formula (II) of EP 0428312; ##STR10## wherein R.sup.1 is as defined in relation to formula (I) of EP 0489663; ##STR11## wherein R.sup.1, R.sup
REFERENCES:
patent: 4410734 (1983-10-01), Martin
patent: 5002953 (1991-03-01), Hindley
patent: 5232925 (1993-08-01), Hindley
Chemical and Pharmaceutical bulletin, vol. 32, No. 9, 1984, Tokyo JP, pp. 4460-4465, Takashi Sohda et al.
Kieslida, K, "Microbial trans formations" 1976, Wiley and Sons, pp. 674-680.
ATCC Catalogue of Yeasts, 1990, pp. 50-53.
Hindley Richard Mark
Woroniecki Stefan Roland
Kinzig Charles M.
Lentz Edward T.
Marx Irene
SmithKline Beecham Plc
Venetianer Stephen
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