Nonpeptidal P2 ligands for HIV protease inhibitors: Structure-based design, synthesis, and biological evaluation

Journal of Medicinal Chemistry

Volumn 39, Issue 17, 1996, Pages 3278-3290

  Ghosh, Arun K ^a   Kincaid, John F ^a   Walters, D Eric ^c   Chen, Yan ^a   Chaudhuri, Narayan C ^a   Thompson, Wayne J ^b   Culberson, Chris ^b   Fitzgerald, Paula M D ^b   Lee, Hee Yoon ^b   McKee, Sean P ^b   Munson, Peter M ^b   Duong, Tien T ^b   Darke, Paul L ^b   Zugay, Joan A ^b   Schleif, William A ^b   Axel, Melinda G ^b   Lin, Juinn ^b   Huff, Joel R ^b  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

^c ROSALIND FRANKLIN UNIVERSITY OF MEDICINE AND SCIENCE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; PROTEINASE INHIBITOR; SAQUINAVIR; ASPARTIC ACID; FURAN DERIVATIVE; LIGAND; PROTEINASE; TETRAHYDROFURAN;

ARTICLE; BINDING SITE; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG POTENCY; DRUG SYNTHESIS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYDROGEN BOND; LIGAND BINDING; PROTEINASE INHIBITION; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; VIRUS INHIBITION; AMINO ACID SEQUENCE; CHEMICAL STRUCTURE; CHEMISTRY; COMPARATIVE STUDY; ENZYMOLOGY; HUMAN IMMUNODEFICIENCY VIRUS 1; METABOLISM; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; OPTICAL ROTATION; STEREOISOMERISM; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; ASPARTIC ACID; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; FURANS; HIV PROTEASE; HIV PROTEASE INHIBITORS; HIV-1; HYDROGEN BONDING; LIGANDS; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; MOLECULAR STRUCTURE; OPTICAL ROTATION; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 10144241705     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960128k     Document Type: Article

References (55)

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48. For details of the assay protocol, see ref 30.
49. 24 production was monitored as end point, and cell types other than MT4 were employed.
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53. (a) Delfraissy, J. F.; Sereni, D.; Brun-Vezinet, F.; Dussaix, E.; Krivine, A.; Dormont, J.; Bragman, K. A Phase I-II Dose Ranging Study of the Safety and Activity of Ro 31-8959 (HIV Proteinase Inhibitor) in Previously Zidovudine (ZDV) Treated HIV-Infected Individuals. Skinner, C.; Sedwick, A.; Bragman, K.; Pinching, A. J.; Weber, J. A Phase I-II Dose Ranging Study of the Safety and Activity of Ro 31-8959 (HIV Proteinase Inhibitor) in Asymptomatic or Mildly Symptomatic HIV-Infection. Abstracts at the 9th Int. Conf. on AIDS, Berlin, 1993.
54. (b) Teppler, H.; Pomerantz, R.; Bjornsson, T.; Pientka, J.; Osborne, B.; Woolfe, E.; Yen, K.; Duetsch, P.; Emini, E.; Squires, K.; Saag, M.; Waldman, S. 1st Natl. Conf. on Human Retroviruses and Related Infections, Washington, DC, Dec. 12-16, 1993; Session 77, L8.
55. Personal communication: Dr. Juinn Lin, Department of Animal Pharmacology, Merck Research Laboratories, West Point, PA. Details of these experiments will be published elsewhere.