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Spirodiketopiperazine-based CCR5 antagonist: discovery of an antiretroviral drug candidate.

Authors :
Nishizawa R
Nishiyama T
Hisaichi K
Minamoto C
Matsunaga N
Takaoka Y
Nakai H
Jenkinson S
Kazmierski WM
Tada H
Sagawa K
Shibayama S
Fukushima D
Maeda K
Mitsuya H
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 Feb 15; Vol. 21 (4), pp. 1141-5. Date of Electronic Publication: 2010 Dec 28.
Publication Year :
2011

Abstract

Following the discovery that hydroxylated derivative 3 (Fig. 1) was one of the oxidative metabolites of the original lead 1, it was found that hydroxylated compound 4 possesses higher in vitro anti-HIV potency than the corresponding non-hydroxylated compound 2. Structural hybridation of 4 with the orally available analog 5 resulted in another orally-available spirodiketopiperazine CCR5 antagonist 6a that possesses more favorable pharmaceutical profile for use as a drug candidate.<br /> (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
21
Issue :
4
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
21256008
Full Text :
https://doi.org/10.1016/j.bmcl.2010.12.109