title: Cyclopenta[g]quinazoline-based antifolates: the effect of the chirality at the 6-position on the inhibition of thymidylate synthase (TS).
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.
authors.affiliation: 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
authors.forename: V
authors.initials: V
authors.lastname: Bavetsias
authors.forename: J H
authors.initials: JH
authors.lastname: Marriott
authors.forename: D S
authors.initials: DS
authors.lastname: Theti
authors.forename: J C
authors.initials: JC
authors.lastname: Melin
authors.forename: S C
authors.initials: SC
authors.lastname: Wilson
authors.forename: A L
authors.initials: AL
authors.lastname: Jackman
mesh_terms: D001671:Biochemistry / Q000379:methods; D003517:Cyclopentanes / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005493:Folic Acid Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
chemical_list: C448339:6-1c quinazoline; D003517:Cyclopentanes; D005493:Folic Acid Antagonists; D011799:Quinazolines; D013940:Thymidylate Synthase