Cyclopenta[g]quinazoline-based antifolates: the effect of the chirality at the 6-position on the inhibition of thymidylate synthase (TS)

V Bavetsias; J H Marriott; D S Theti; J C Melin; S C Wilson; A L Jackman

doi:10.1016/s0960-894x(01)00612-6

Cyclopenta[g]quinazoline-based antifolates: the effect of the chirality at the 6-position on the inhibition of thymidylate synthase (TS)

Bioorg Med Chem Lett. 2001 Dec 3;11(23):3015-7. doi: 10.1016/s0960-894x(01)00612-6.

Authors

V Bavetsias¹, J H Marriott, D S Theti, J C Melin, S C Wilson, A L Jackman

Affiliation

¹ CRC Centre for Cancer Therapeutics at The Institute of Cancer Research, Chemistry Department, CRC Laboratory, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK. vassilio@icr.ac.uk

PMID: 11714600
DOI: 10.1016/s0960-894x(01)00612-6

Abstract

Cyclopenta[g]quinazoline-based inhibitors of thymidylate synthase (TS) possess a chiral centre at the 6-position of the molecule. The effect of this chirality on the inhibition of TS was investigated by synthesising compounds 6S-1a-c, 6R-1a-c. It was shown, in particular with the diastereoisomers 6S-1c, 6R-1c, that the inhibitory activity against TS is mainly due to the 6S diastereoisomer rather than the 6R diastereoisomer, which is virtually inactive.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biochemistry / methods
Cyclopentanes / chemistry
Cyclopentanes / pharmacology
Drug Evaluation, Preclinical
Folic Acid Antagonists / chemistry*
Folic Acid Antagonists / pharmacology*
Quinazolines / chemistry
Quinazolines / pharmacology
Structure-Activity Relationship
Thymidylate Synthase / antagonists & inhibitors*

Substances

6-1c quinazoline
Cyclopentanes
Folic Acid Antagonists
Quinazolines
Thymidylate Synthase