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Fluorinated conformationally restricted gamma-aminobutyric acid aminotransferase inhibitors.

Abstract：

:On the basis of the structures of several potent inhibitor molecules for gamma-aminobutryric acid aminotransferase (GABA-AT) that were previously reported, six modified fluorine-containing conformationally restricted analogues were designed, synthesized, and tested as GABA-AT inhibitors. The syntheses of all six molecules followed from a readily synthesized ketone intermediate. Three of the molecules were found to be irreversible inhibitors of GABA-AT with comparable or larger k(inact)/K(I) values than that of vigabatrin, a clinically used antiepilepsy drug, and the other three were reversible inhibitors. A possible mechanism for inactivation by one of the inactivators is proposed.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Lu H,Silverman RB

doi

10.1021/jm0608715

subject

Has Abstract

pub_date

2006-12-14 00:00:00

pages

7404-12

issue

25

eissn

0022-2623

issn

1520-4804

journal_volume

49

pub_type

杂志文章

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