Format

Send to:

Choose Destination
See comment in PubMed Commons below
Org Biomol Chem. 2014 Jan 7;12(1):177-86. doi: 10.1039/c3ob41873a. Epub 2013 Nov 12.

Diverse modifications of the 4-methylphenyl moiety of TAK-779 by late-stage Suzuki-Miyaura cross-coupling.

Author information

  • 1Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstr. 48, D-48149 Münster, Germany. wuensch@uni-muenster.de.

Abstract

Chemokine receptor 5 (CCR5) antagonists provide a new therapeutic approach in the treatment of HIV-1 (AIDS). TAK-779 displays high affinity and selectivity for the CCR5 receptor and serves as a lead compound for the development of further antagonists. In order to increase the oral bioavailability replacement of the quaternary ammonium structure by a tertiary amine and modification of the 4-methylphenyl moiety were envisaged. Herein, a new synthetic strategy for the development of TAK-779 analogs by late stage diversification is reported. The Suzuki-Miyaura cross-coupling reactions allowed various modifications of the central amide building block 3 at the end of the synthesis leading to compounds 2f and 2h with a promising CCR5 binding affinity.

PMID:
24217712
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Royal Society of Chemistry
    Loading ...
    Write to the Help Desk