Download MendeleyMicrowave-Accelerated Synthesis of P1'-Extended HIV-1 Protease Inhibitors Encompassing a Tertiary Alcohol in the Transition-State Mimicking Scaffold
Ekegren, J.K., Ginman, N., Johansson, A., Wallberg, H., Larhed, M., Samuelsson, B., Unge, T., Hallberg, A.(2006) J Med Chem 49: 1828
- PubMed: 16509598
- DOI: https://doi.org/10.1021/jm051239z
- Primary Citation of Related Structures:
2CEJ, 2CEM, 2CEN - 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.
Organizational Affiliation:
Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, BMC, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.
