153181-22-7Relevant articles and documents
Carbonylation of functionalized diamine diols to cyclic ureas: Application to derivatives of DMP 450
Darko, Ampofo K.,Curran, F. Chris,Copin, Chloé,McElwee-White, Lisa
, p. 3976 - 3983 (2011/06/25)
Synthesis of the cyclic urea core structure of the HIV protease inhibitor DMP 450 has been achieved via W(CO)6/I2-catalyzed carbonylation of diamine intermediates. Carbonylations of related functionalized diamines to derivatives of the DMP 450 core structure were also examined. Selected diamine diol substrates could be converted to the cyclic urea core structure by catalytic carbonylation without protection of the diol functionality.
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.
