2CEN

P1' Extended HIV-1 Protease Inhibitors Encompassing a Tertiary Alcohol in the Transition-State Mimicking Scaffold

Summary for 2CEN

• Entry DOI: 10.2210/pdb2cen/pdb
• Related: 1WBK 1WBM 2CEJ 2CEM
• Descriptor: POL PROTEIN, {(1S)-1-[N'-[(2S)-2-HYDROXY-2-((1S,2R)-2-HYDROXY-INDAN-1-YLCARBAMOYL)-3-PHENYL-PROPYL]-N'-[4-(PYRIDINE-2-YL)-BENZYL]-HYDRAZINOCARBONYL]-2,2-DIMETHYL-PROPYL}-CARBAMIC ACID METHYL ESTER (3 entities in total)
• Functional Keywords: hiv-1, protease, inhibitor, aspartyl protease, hydrolase
• Biological source: HUMAN IMMUNODEFICIENCY VIRUS 1
• Total number of polymer chains: 2
• Total formula weight: 22287.32

Authors

Ginman, N.,Ekegren, J.K.,Johansson, A.,Wallberg, H.,Larhed, M.,Samuelsson, B.,Hallberg, A.,Unge, T. (deposition date: 2006-02-08, release date: 2007-02-13, Last modification date: 2023-12-13)

Primary citation

Ekegren, J.K.,Ginman, N.,Johansson, A.,Wallberg, H.,Larhed, M.,Samuelsson, B.,Unge, T.,Hallberg, A.
Microwave-Accelerated Synthesis of P1'-Extended HIV-1 Protease Inhibitors Encompassing a Tertiary Alcohol in the Transition-State Mimicking Scaffold.
J.Med.Chem., 49:1828-, 2006

PubMed Abstract: Two series of P1'-extended HIV-1 protease inhibitors comprising a tertiary alcohol in the transition-state mimic exhibiting Ki values ranging from 2.1 to 93 nM have been synthesized. Microwave-accelerated palladium-catalyzed cross-couplings were utilized to rapidly optimize the P1' side chain. High cellular antiviral potencies were encountered when the P1' benzyl group was elongated with a 3- or 4-pyridyl substituent (EC50 = 0.18-0.22 microM). X-ray crystallographic data were obtained for three inhibitors cocrystallized with the enzyme.

PubMed: 16509598
DOI: 10.1021/JM051239Z

Experimental method

X-RAY DIFFRACTION (1.7 Å)