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

Anna Junker, Dirk Schepmann, Junichiro Yamaguchi, Kenichiro Itami, Andreas Faust, Klaus Kopka, Stefan Wagner, Bernhard Wünsch

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)177-186
Number of pages10
JournalOrganic and Biomolecular Chemistry
Volume12
Issue number1
DOIs
Publication statusPublished - 2014 Jan 7
Externally publishedYes

Fingerprint

Chemokine Receptors
cross coupling
Lead compounds
affinity
Cross Reactions
acquired immunodeficiency syndrome
lead compounds
Ammonium Compounds
Amides
bioavailability
human immunodeficiency virus
Biological Availability
Amines
HIV-1
Acquired Immunodeficiency Syndrome
amides
amines
selectivity
analogs
TAK 779

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

Cite this

Diverse modifications of the 4-methylphenyl moiety of TAK-779 by late-stage Suzuki-Miyaura cross-coupling. / Junker, Anna; Schepmann, Dirk; Yamaguchi, Junichiro; Itami, Kenichiro; Faust, Andreas; Kopka, Klaus; Wagner, Stefan; Wünsch, Bernhard.

In: Organic and Biomolecular Chemistry, Vol. 12, No. 1, 07.01.2014, p. 177-186.

Research output: Contribution to journalArticle

Junker, Anna ; Schepmann, Dirk ; Yamaguchi, Junichiro ; Itami, Kenichiro ; Faust, Andreas ; Kopka, Klaus ; Wagner, Stefan ; Wünsch, Bernhard. / Diverse modifications of the 4-methylphenyl moiety of TAK-779 by late-stage Suzuki-Miyaura cross-coupling. In: Organic and Biomolecular Chemistry. 2014 ; Vol. 12, No. 1. pp. 177-186.
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