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Fused bicycles as arylketone bioisosteres leading to potent, orally active thiadiazole H3 antagonists.

Authors :
Xiao D
Palani A
Sofolarides M
Aslanian R
West RE Jr
Williams SM
Wu RL
Hwa J
Sondey C
Lachowicz J
Korfmacher WA
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2012 May 01; Vol. 22 (9), pp. 3354-7. Date of Electronic Publication: 2012 Mar 08.
Publication Year :
2012

Abstract

A structure-activity relationship study was undertaken to address the lack of oral exposure of the H3 antagonist 1, which incorporated an arylketone. Among a number of sub-series, the 4H-pyrido[1,2-a]pyrimidin-4-one analog 21 showed an improved PK profile in rat and mouse and was active in an obesity model. The pyrimidin-4-one proved to be a novel and useful ketone bioisostere.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
22
Issue :
9
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
22464130
Full Text :
https://doi.org/10.1016/j.bmcl.2012.02.076