Synthesis and HIV-integrase strand transfer inhibition activity of 7-hydroxy[1,3]thiazolo[5,4-b]pyridin-5(4H)-ones.
An efficient synthesis of methyl 7-hydroxy[1,3]thiazolo[5,4-b]pyridin-5(4H)-one-6-carboxylates (8-10 and 16) and 6-carboxamides (17-20) is described. Sub-micromolar enzyme inhibition of HIV integrase was achieved with several carboxamide analogs which were superior to their carboxylic ester congeners.
Boros
Eric E
EE
GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709, USA. eric.e.boros@gsk.com
Johns
Brian A
BA
Garvey
Edward P
EP
Koble
Cecilia S
CS
Miller
Wayne H
WH
D006678:HIV / Q000201:enzymology*; D019427:HIV Integrase; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
D019428:HIV Integrase Inhibitors; D007659:Ketones; D011725:Pyridines; D013844:Thiazoles; D019427:HIV Integrase