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Spirodiketopiperazine-based CCR5 antagonist: discovery of an antiretroviral drug candidate.
- 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.)
- Subjects :
- Administration, Oral
Animals
Anti-HIV Agents chemical synthesis
Anti-HIV Agents pharmacokinetics
Cell Line, Tumor
Diketopiperazines chemical synthesis
Diketopiperazines pharmacokinetics
Diketopiperazines pharmacology
Drug Evaluation, Preclinical
HIV Core Protein p24 metabolism
HIV-1 metabolism
Humans
Microsomes, Liver metabolism
Rats
Receptors, CCR5 metabolism
Spiro Compounds chemical synthesis
Spiro Compounds pharmacology
Stereoisomerism
Anti-HIV Agents chemistry
CCR5 Receptor Antagonists
Diketopiperazines chemistry
Spiro Compounds chemistry
Subjects
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