Synthesis and Evaluation of Efavirenz (Sustiva TM) Analogues as HIV-1 Reverse Transcriptase Inhibitors: Replacement of the Cyclopropylacetylene Side Chain

• Published in: Bioorganic & medicinal chemistry letters Vol. 11; no. 9; pp. 1177 - 1179
• Main Authors: Cocuzza, Anthony J., Chidester, Dennis R., Cordova, Beverly C., Jeffrey, Susan, Parsons, Rodney L., Bacheler, Lee T., Erickson-Viitanen, Susan, Trainor, George L., Ko, Soo S.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 07-05-2001; Elsevier
• Subjects: Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Benzoxazines; Biological and medical sciences; HIV Reverse Transcriptase - antagonists & inhibitors; HIV Reverse Transcriptase - genetics; Medical sciences; Mutation; Oxazines - chemical synthesis; Oxazines - pharmacology; Pharmacology. Drug treatments; Reverse Transcriptase Inhibitors - chemical synthesis; Reverse Transcriptase Inhibitors - pharmacology; Structure-Activity Relationship; RNA-directed DNA polymerase; Acetylenic compound; HIV-1 virus; Thiazole derivatives; Furan derivatives; Organic carbamate; Efavirenz; Pyridine derivatives; Thiophene derivatives; Structure activity relation; Chlorine Organic compounds; Vinylic compound; Bicyclic compound; Antiviral; Aromatic compound; Chemical synthesis; Oxygen nitrogen heterocycle; Enzyme; Transferases; Retroviridae; Enzyme inhibitor; Lentivirus; In vitro; Virus; Nucleotidyltransferases; Fluorine Organic compounds; Human immunodeficiency virus
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(01)00192-5

Two series of efavirenz analogues have been developed: one in which the cyclopropane ring has been replaced by small heterocycles and another in which the entire acetylenic side chain has been replaced by alkyloxy groups. Several members of both series show equivalent potency to efavirenz against both wild-type virus and the key K103N mutant.
Two potent series of efavirenz analogues have been developed: one in which the cyclopropane ring has been replaced by small heterocycles and another in which the entire acetylenic side chain has been replaced by alkyloxy groups.