136522-17-3Relevant articles and documents
Reduction of peptide character of HIV protease inhibitors that exhibit nanomolar potency against multidrug resistant HIV-1 strains
Tamamura, Hirokazu,Koh, Yasuhiro,Ueda, Satoshi,Sasaki, Yoshikazu,Yamasaki, Tomonori,Aoki, Manabu,Maeda, Kenji,Watai, Yoriko,Arikuni, Hisashi,Otaka, Akira,Mitsuya, Hiroaki,Fujii, Nobutaka
, p. 1764 - 1768 (2007/10/03)
Novel HIV protease inhibitors containing a hydroxyethylamine dipeptide isostere as a transition state-mimic king structure were synthesized by combining substructures of known HIV protease inhibitors. Among them, TYA5 and TYB5 were proven to be not only p
Synthesis of the HIV-proteinase inhibitor Saquinavir: A challenge for process research
Goehring, Wolfgang,Gokhale, Surendra,Hilpert, Hans,Roessler, Felix,Schlageter, Markus,Vogt, Peter
, p. 532 - 537 (2007/10/03)
The task of process research, namely developing efficient, economically and technically as well as ecologically feasible syntheses in time, is demonstrated on the HIV-proteinase inhibitor Saquinavir (1), a complex molecule comprising six stereo-centres. Based on the first 26-step research synthesis furnishing a 10% overall yield, process research established a new, short 11-step synthesis affording a 50% overall yield.
The Development of Cyclic Sulfolanes as Novel and High-Affinity P2 Ligands for HIV-1 Protease Inhibitors
Ghosh, Arun K.,Lee, Hee Yoon,Thompson, Wayne J.,Culberson, Chris,Holloway, M. Katharine,et al.
, p. 1177 - 1188 (2007/10/02)
Design and synthesis of a novel series of protease inhibitors incorporating conformationally constrained cyclic ligands for the S2-substrate binding site of HIV-1 protease is described. We recently reported urethanes of 3-tetrahydrofuranyl as P2 ligands for HIV-1 protease inhibitors. Subsequently, we have found that the urethane of 3(S)-hydroxysulfolane further increased the in vitro potency of these inhibitors. Furthermore, introduction of a small 2-alkyl group cis to the 3-hydroxyl group of either heterocyclic system further enhanced enzyme affinity. The cis-2-isopropyl group thus far offered optimum enhancement of the inhibitory properties. This led to the discovery of inhibitor 43 (IC50 3.5 nM, CIC95 50+/-14 nM) of comparable in vitro antiviral potency to the current clinical candidate 1 (Ro 31-8959) but of reduced molecular weight due to the exclusion of the P3 quinoline ligand. Also, it has been demonstrated that the octahydropyrindene derivative 34 is an effective replacement of the P1' decahydroisoquinoline derivative.