Download MendeleyEpsilon substituted lysinol derivatives as HIV-1 protease inhibitors.
Jones, K.L., Holloway, M.K., Su, H.P., Carroll, S.S., Burlein, C., Touch, S., DiStefano, D.J., Sanchez, R.I., Williams, T.M., Vacca, J.P., Coburn, C.A.(2010) Bioorg Med Chem Lett 20: 4065-4068
- PubMed: 20547452
- DOI: https://doi.org/10.1016/j.bmcl.2010.05.082
- Primary Citation of Related Structures:
3M9F - PubMed Abstract:
A series of HIV-1 protease inhibitors containing an epsilon substituted lysinol backbone was synthesized. Two novel synthetic routes using N-boc-L-glutamic acid alpha-benzyl ester and 2,6-diaminopimelic acid were developed. Incorporation of this epsilon substituent enabled access to the S2 pocket of the enzyme, affording high potency inhibitors. Modeling studies and synthetic efforts suggest the potency increase is due to both conformational bias and van der Waals interactions with the S2 pocket.
Organizational Affiliation:
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. kristen_jones@merck.com
