Synthesis of novel diarylpyrimidine analogues and their antiviral activity against human immunodeficiency virus type 1

Jerome Guillemont; Elisabeth Pasquier; Patrice Palandjian; Daniel Vernier; Sandrine Gaurrand; Paul J Lewi; Jan Heeres; Marc R de Jonge; Lucien M H Koymans; Frits F D Daeyaert; Maarten H Vinkers; Eddy Arnold; Kalyan Das; Rudi Pauwels; Koen Andries; Marie-Pierre de Béthune; Eva Bettens; Kurt Hertogs; Piet Wigerinck; Philip Timmerman; Paul A J Janssen

doi:10.1021/jm040838n

Synthesis of novel diarylpyrimidine analogues and their antiviral activity against human immunodeficiency virus type 1

J Med Chem. 2005 Mar 24;48(6):2072-9. doi: 10.1021/jm040838n.

Affiliation

¹ Medicinal Chemistry Department, Johnson & Johnson Pharmaceutical Research and Development, Campus de Maigremont BP615, Val de Reuil, France. jguillem@prdfr.jnj.com

PMID: 15771449
DOI: 10.1021/jm040838n

Abstract

This paper reports the synthesis and the antiviral properties of new diarylpyrimidine (DAPY) compounds as nonnucleoside reverse transcriptase inhibitors (NNRTIs). The synthesis program around this new DAPY series was further optimized to produce compounds displaying improved activity against a panel of eight clinically relevant single and double mutant strains of human immunodeficiency virus type 1 (HIV-1).

MeSH terms

Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / pharmacology
Anti-HIV Agents / toxicity
Cell Line
Drug Resistance, Viral
HIV Reverse Transcriptase / genetics
HIV Reverse Transcriptase / metabolism*
HIV-1 / drug effects*
HIV-1 / genetics
Humans
Mutation
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology
Pyrimidines / toxicity
Reverse Transcriptase Inhibitors / chemical synthesis*
Reverse Transcriptase Inhibitors / pharmacology
Reverse Transcriptase Inhibitors / toxicity
Stereoisomerism
Structure-Activity Relationship

Substances

Anti-HIV Agents
Pyrimidines
Reverse Transcriptase Inhibitors
HIV Reverse Transcriptase