120452-49-5Relevant articles and documents
NOVEL COMPOUNDS
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Page/Page column 45; 47, (2009/03/07)
The invention provides compounds of general formula (I) or a pharmaceutically acceptable salt, polymorph or solvate thereof, including all tautomers and stereoisomers thereof, wherein K, W, X; Y and Z are described throughout the description and claims. T
Solid-phase synthesis of C-terminal peptide aldehydes from amino acetals anchored to a backbone amide linker (BAL) handle
Guillaumie,Kappel,Kelly,Barany,Jensen
, p. 6131 - 6135 (2007/10/03)
Peptide aldehydes were synthesized, starting from amino acetals, by a Solid-phase backbone amide linker (BAL) strategy. (C) 2000 Elsevier Science Ltd.
Design, synthesis, and evaluation of tetrahydropyrimidinones as an example of a general approach to nonpeptide HIV protease inhibitors
De Lucca, George V.,Liang, Jing,Aldrich, Paul E.,Calabrese, Joe,Cordova, Beverly,Klabe, Ronald M.,Rayner, Marlene M.,Chang, Chong-Hwan
, p. 1707 - 1719 (2007/10/03)
Re-examination of the design of the cyclic urea class of HIV protease (HIVPR) inhibitors suggests a general approach to designing novel nonpeptide cyclic HIVPR inhibitors. This process involves the inversion of the stereochemical centers of the core transition-state isostere of the linear HIVPR inhibitors and cyclization of the resulting core using an appropriate cyclizing reagent. As an example, this process is applied to the diamino alcohol class of HIVPR inhibitors to give tetrahydropyrimidinones. Conformational analysis of the tetrahydropyrimidinones and modeling of its interaction with the active site of HIVPR suggested modifications which led to very potent inhibitors of HIVPR (24 with a K(i) = 0.018 nM). The X-ray crystallographic structure of the complex of 24 with HIVPR confirms the analysis and modeling predictions. The example reported in this study and other examples that are cited indicate that this process may be generally applicable to other linear inhibitors.
Preparation and structure-activity relationship of novel P1/P1'- substituted cyclic urea-based human immunodeficiency virus type-1 protease inhibitors
Nugiel,Jacobs,Worley,Patel,Kaltenbach III,Meyer,Jadhav,De Lucca,Smyser,Klabe,Bacheler,Rayner,Seitz
, p. 2156 - 2169 (2007/10/03)
A series of novel P1/P1'-substituted cyclic urea-based HIV-1 protease inhibitors was prepared. Three different synthetic schemes were used to assemble these compounds. The first approach uses amino acid-based starting materials and was originally used to prepare DMP 323. The other two approaches use L-tartaric acid or L-mannitol as the starting material. The required four contiguous R,S,S,R centers of the cyclic urea scaffold are introduced using substrate control methodology. Each approach has specific advantages based on the desired P1/P1' substituent. Designing analogs based on the enzyme's natural substrates provided compounds with reduced activity. Attempts at exploiting hydrogen bond sites in the S1/S1' pocket, suggested by molecular modeling studies, were not fruitful. Several analogs had better binding affinity compared to our initial leads. Modulating the compound's physical properties led to a 10-fold improvement in translation resulting in better overall antiviral activity.
An efficient and enantioselective synthesis of a chiral primary amine
Son, Youngchan,Park, Chihyo,Koh, Jong Sung,Choy, Nakyen,Lee, Chang S.,Choi, Ho-Il,Kim, Sung Chun,Yoon, Heungsik
, p. 3745 - 3746 (2007/10/02)
An efficient and enantioselective method for the preparation of a chiral primary amine has been developed. Starting from N-protected L or D-amino acid the sequence involves coupling with N-methoxy-N-methylamine, acylation, olefination with potassium bis(trimethylsilyl)amide, and hydrogenation.
