1010702-53-0Relevant articles and documents
Synthesis of P1′-functionalized macrocyclic transition-state mimicking HIV-1 protease inhibitors encompassing a tertiary alcohol
De Rosa, Maria,Unge, Johan,Motwani, Hitesh V.,Rosenquist, ?sa,Vrang, Lotta,Wallberg, Hans,Larhed, Mats
, p. 6444 - 6457 (2014)
Seven novel tertiary alcohol containing linear HIV-1 protease inhibitors (PIs), decorated at the para position of the benzyl group in the P1′ side with (hetero)aromatic moieties, were synthesized and biologically evaluated. To study the inhibition and antiviral activity effect of P1-P3 macrocyclization, 14-and 15-membered macrocyclic PIs were prepared by ring-closing metathesis of the corresponding linear PIs. The macrocycles were more active than the linear precursors and compound 10f, with a 2-thiazolyl group in the P1′ position, was the most potent PI of this new series (Ki 2.2 nM, EC 50 0.2 μM). Co-crystallized complexes of both linear and macrocyclic PIs with the HIV-1 protease enzyme were prepared and analyzed.
Two-carbon-elongated HIV-1 protease inhibitors with a tertiary-alcohol- containing transition-state mimic
Wu, Xiongyu,?hrngren, Per,Ekegren, Jenny K.,Unge, Johan,Unge, Torsten,Wallberg, Hans,Samuelsson, Bertil,Hallberg, Anders,Larhed, Mats
, p. 1053 - 1057 (2008/09/20)
A new generation of HIV-1 protease inhibitors encompassing a tertiary-alcohol-based transition-state mimic has been developed. By elongation of the core structure of recently reported inhibitors with two carbon atoms and by varying the P1′ group of the co
