Synthesis and biological evaluation of novel allophenylnorstatine-based HIV-1 protease inhibitors incorporating high affinity P2-ligands.
A series of stereochemically defined cyclic ethers as P2-ligands were incorporated in an allophenylnorstatine-based isostere to provide a new series of HIV-1 protease inhibitors. Inhibitors 3b and 3c, containing conformationally constrained cyclic ethers, displayed impressive enzymatic and antiviral properties and represent promising lead compounds for further optimization.
Ghosh
Arun K
AK
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, United States. akghosh@purdue.edu
Gemma
Sandra
S
Simoni
Elena
E
Baldridge
Abigail
A
Walters
D Eric
DE
Ide
Kazuhiko
K
Tojo
Yasushi
Y
Koh
Yasuhiro
Y
Amano
Masayuki
M
Mitsuya
Hiroaki
H
D000818:Animals; D006224:Cricetinae; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005663:Furans / Q000737:chemistry* / Q000378:metabolism; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D010654:Phenylbutyrates / Q000138:chemical synthesis* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D013237:Stereoisomerism
D005663:Furans; D017320:HIV Protease Inhibitors; D008024:Ligands; D010654:Phenylbutyrates; C018674:tetrahydrofuran; C034940:3-amino-2-hydroxy-4-phenylbutanoic acid; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1