183004-94-6Relevant articles and documents
An improved and robust scale-up process aided with identification and control of critical process impurities in darunavir ethanolate
Girigani, Sathyanarayana,Singh, Harnam,Kola, Sankar Rao,Dayanand Yelmeli, Vijayalaxmi,Regula, Venu Gopal,Shah, Sakshi,Jain, Neelu,Kumar, Pramod
, p. 267 - 281 (2019/08/26)
A robust and safe industrial process, including five isolations and drying steps for widely prescribed anti-HIV (protease inhibitor) drug darunavir ethanolate 2, has been developed. A salient feature of this process is the development of procedures enabling the efficient synthesis of multi-kilogram quantity of darunavir ethanolate, and process demonstrations through plant scale preparation are offered where darunavir molecule has been prepared with overall > 70% chemical yield and > 99.8% purity without involving any purification procedure(s), with all possible process impurities below than the desired limit (not more than 0.08%) were isolated, synthesized and characterized. The developed process is entirely robust, very efficient and demonstrated up to kilograms scale.
PROCESS FOR THE PREPARATION OF SULFONAMIDES USEFUL AS RETROVIRAL PROTEASE INHIBITORS
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, (2013/03/26)
The present invention relates to a process for the preparation of sulfonamides useful as retroviral protease inhibitors.
Structure-based design of novel HIV-1 protease inhibitors to combat drug resistance
Ghosh, Arun K.,Sridhar, Perali Ramu,Leshchenko, Sofiya,Hussain, Azhar K.,Li, Jianfeng,Kovalevsky, Andrey Yu.,Walters, D. Eric,Wedekind, Joseph E.,Grum-Tokars, Valerie,Das, Debananda,Koh, Yasuhiro,Maeda, Kenji,Gatanaga, Hiroyuki,Weber, Irene T.,Mitsuya, Hiroaki
, p. 5252 - 5261 (2008/02/11)
Structure-based design and synthesis of novel HIV protease inhibitors are described. The inhibitors are designed specifically to interact with the backbone of HIV protease active site to combat drug resistance. Inhibitor 3 has exhibited exceedingly potent enzyme inhibitory and antiviral potency. Furthermore, this inhibitor maintains impressive potency against a wide spectrum of HIV including a variety of multi-PI-resistant clinical strains. The inhibitors incorporated a stereochemically defined 5-hexahydrocyclopenta[b] furanyl urethane as the P2-ligand into the (R)-(hydroxyethylamino)sulfonamide isostere. Optically active (3aS,5R,6aR)-5-hydroxy-hexahydrocyclopenta[e]furan was prepared by an enzymatic asymmetrization of meso-diacetate with acetyl cholinesterase, radical cyclization, and Lewis acid-catalyzed anomeric reduction as the key steps. A protein-ligand X-ray crystal structure of inhibitor 3-bound HIV-1 protease (1.35 ? resolution) revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone. This design strategy may lead to novel inhibitors that can combat drug resistance.
