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. 2000 Jul 17;10(14):1527-30.
doi: 10.1016/s0960-894x(00)00276-6.

Combinatorial diversification of indinavir: in vivo mixture dosing of an HIV protease inhibitor library

T A Rano  1 , Y Cheng, T T Huening, F Zhang, W A Schleif, L Gabryelski, D B Olsen, L C Kuo, J H Lin, X Xu, T V Olah, D A McLoughlin, R King, K T Chapman, J R Tata
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Combinatorial diversification of indinavir: in vivo mixture dosing of an HIV protease inhibitor library

T A Rano et al. Bioorg Med Chem Lett. .

Abstract

An efficient combination solution-phase/solid-phase route enabling the diversification of the P1', P2', and P3 subsites of indinavir has been established. The synthetic sequence can facilitate the rapid generation of HIV protease inhibitors possessing more favorable pharmacokinetic properties as well as enhanced potencies. Multiple compound dosing in vivo may also accelerate the identification of potential drug candidates.

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