title: Design, synthesis, and X-ray crystallographic analysis of a novel class of HIV-1 protease inhibitors.
abstract: In the present paper, design, synthesis, X-ray crystallographic analysis, and HIV-1 protease inhibitory activities of a novel class of compounds are disclosed. Compounds 28-30, 32, 35, and 40 were synthesized and found to be inhibitors of the HIV-1 protease. The crucial step in their synthesis involved an unusual endo radical cyclization process. Absolute stereochemistry of the three asymmetric centers in the above compounds have been established to be (4S,2'R,3'S) for optimal potency. X-ray crystallographic analysis has been used to determine the binding mode of the inhibitors to the HIV-1 protease.
authors.affiliation: Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States. akganguly1@aol.com
authors.forename: Ashit K
authors.initials: AK
authors.lastname: Ganguly
authors.forename: Sesha S
authors.initials: SS
authors.lastname: Alluri
authors.forename: Danielle
authors.initials: D
authors.lastname: Caroccia
authors.forename: Dipshikha
authors.initials: D
authors.lastname: Biswas
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Wang
authors.forename: Eunhee
authors.initials: E
authors.lastname: Kang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Andrew T
authors.initials: AT
authors.lastname: McPhail
authors.forename: Steven S
authors.initials: SS
authors.lastname: Carroll
authors.forename: Christine
authors.initials: C
authors.lastname: Burlein
authors.forename: Vandna
authors.initials: V
authors.lastname: Munshi
authors.forename: Peter
authors.initials: P
authors.lastname: Orth
authors.forename: Corey
authors.initials: C
authors.lastname: Strickland
mesh_terms: D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D015195:Drug Design; D016333:HIV Protease / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013841:Thiazepines / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D002219:Carbamates; D017320:HIV Protease Inhibitors; D013841:Thiazepines; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1