137431-06-2Relevant articles and documents
Synthesis and biological evaluation of novel substitutedy-[1-benzyl-3-(3- tert-butylcarbamoyl-octahydroisoquinolin-2yl)-2-hydroxy-propyl] -2-[(2-oxo-2h-chromene-3-carbonyl) amino] succinamide analogs as anti-viral and anti-HIV agents
Reddy, Y. Thirupathi,Reddy, P. Narsimha,Crooks, Peter A.,Clercq, Erik De,Rao, G. V. Panakala,Rajitha
scheme or table, p. 419 - 426 (2010/03/24)
A series of novel substituted N1 [1-benzy1-3-(3-tert- butylcarbamoyloctahydroisoquinolin-2y1)-2-hydroxypropyl]-2-[(2-oxo-2H-chromene- 3-carbonyl) amino] succinamide analogs has been synthesized and evaluated for their anti-viral activity agains
The synthesis of labelled forms of saquinavir
Wiltshire,Prior,Dhesi,Trach,Schlageter,Schoenenberger
, p. 1103 - 1126 (2007/10/03)
The development of the HIV-protease inhibitor, saquinavir (Ro 31-8959), required a range of analytical methods for the measurement of the parent drug and drug-related material in biological fluids. This paper describes the synthesis of 14-carbon and tritium labelled compounds used for in vivo and in vitro investigations of the absorption and disposition of saquinavir in animals and man. It also discusses the preparation of saquinavir labelled with deuterium and stable isotopes of carbon and nitrogen. These forms of the drug were needed for bioequivalence studies in which HPLC/MS/MS was employed for the measurement of plasma concentrations. Finally, the synthesis of a 125-iodine labelled tracer used in a radioimmunoassay for saquinavir is described.
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.
Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959
Parkes, Kevin E. B.,Bushnell, David J.,Crackett, Peter H.,Dunsdon, Stephen J.,Freeman, Andrew C.,et al.
, p. 3656 - 3664 (2007/10/02)
Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials.Six approaches for the large-scale synthesis of this compound have been studied.All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5.They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation.The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1.Kilogram quantities of Ro 31-8959 have been prepared using this route.
