Cobicistat, also known as GS9350, is an approved drug for use in the treatment of infection with the human immunodeficiency virus (HIV). Like ritonavir (Norvir), cobicistat is of interest not for its anti-HIV properties, but rather its ability to inhibit liver enzymes that metabolize other medications used to treat HIV, notably elvitegravir, an HIV integrase inhibitor currently under investigation itself. By combining cobicistat with elvitegravir, higher concentrations of elvitgravir are achieved in the body with lower dosing, theoretically enhancing elvitgravir's viral suppression while diminishing its adverse side-effects. In contrast with ritonavir, the only currently approved booster, cobicistat has no anti-HIV activity of its own. Cobicistat is a component of the four-drug, fixed-dose combination HIV treatment elvitegravir/cobicistat/emtricitabine/tenofovir (known as the "Quad Pill"). The Quad Pill was approved by the FDA in August 2012 for use in the United States and is owned by Gilead Sciences.
Xu L, Liu H, Hong A, Vivian R, Murray BP, Callebaut C, Choi YC, Lee MS, Chau J, Tsai LK, Stray KM, Strickley RG, Wang J, Tong L, Swaminathan S, Rhodes GR, Desai MC. Structure-activity relationships of diamine inhibitors of cytochrome P450 (CYP) 3A as novel pharmacoenhancers. Part II: P2/P3 region and discovery of cobicistat (GS-9350). Bioorg Med Chem Lett. 2014 Feb 1;24(3):995-9. doi: 10.1016/j.bmcl.2013.12.057. Epub 2013 Dec 21. PubMed PMID: 24412072.
Xu L, Liu H, Murray BP, Callebaut C, Lee MS, Hong A, Strickley RG, Tsai LK, Stray KM, Wang Y, Rhodes GR, Desai MC. Cobicistat (GS-9350): A Potent and Selective Inhibitor of Human CYP3A as a Novel Pharmacoenhancer. ACS Med Chem Lett. 2010 May 17;1(5):209-13. doi: 10.1021/ml1000257. eCollection 2010 Aug 12. PubMed PMID: 24900196; PubMed Central PMCID: PMC4007915.
Rama, Shankar; Vadali, Lakshmana Rao; Konda, Ramesh Babu; Jaldu, Ravikanth; Vemavarapu, Govardhana Phani Sharma; Palla, Vijay Kumar; Yerva, Eswara Reddy. Process for the preparation of cobicistat intermediates. WO 2014057498. (Assignee Mylan Laboratories Ltd., India)
Koziara, Joanna M.; Menning, Mark M.; Oliyai, Reza; Strickley, Robert G.; Yu, Richard; Kearney, Brian P.; Mathias, Anita A.. The use of solid carrier particles to improve the processability of pharmaceutical agent, cytochrome P450 inhibitor. WO 2009135179. (Assignee Gilead Sciences, Inc., USA)
Desai, Manoj C.; Hong, Allen Y.; Hui, Hon C.; Liu, Hongtao; Vivian, Radall W.; Xu, Lianhong. Preparation of peptidomimetics as modulators of pharmacokinetic properties of therapeutics by inhibiting cytochrome P450 monooxygenase. WO 2008103949. (Assignee Gilead Sciences, Inc., USA)
Chen, Benshun. Method for synthesizing cobicistat. CN 107513046. (Assignee Jiangsu Furui Biopharmaceutical Co., Ltd., Peop. Rep. China)
Chava, Satyanarayana; Gorantla, Seeta Rama Anjaneyulu; Indukuri, Venkata Sunil Kumar; Simhadri, Srinivas; Mohammed, Yaseen; Manda, Ananth Reddy. A process for preparation of cobicistat. IN 2015CH00619. (Assignee Laurus Labs Private Ltd., India)
Rajan, Srinivasan Thirumalai; Eswaraiah, Sajja; Madhusudhan, Gutta; Satyanarayana, Komati; Malleswara Reddy, Jakku. Process for the preparation of 1,3-thiazol-5-ylmethyl[(2R,5R)-5-{[(2S)-2- [(methyl{[2-(propan-2-yl)-1,3-thiazol-4-yl] methyl}carbamoyl)amino]-4-(morpholin-4-yl)butanoyl]amino}-1,6-diphenylhexan-2-yl]carbamate (cobicistat). WO 2016132378. (Assignee MSN Laboratories Private Limited, India)
Song, Xiaoye; Sheng, Xiaoxia; Sheng, Xiaohong; Jia, Qiang. Cobicistat pamoic acid salt and its preparation method, pharmaceutical composition and application. CN 105732538. (Assignee Hangzhou Pushai Pharmaceutical Technology Co., Ltd., Peop. Rep. China)
Rendell, Jacob; Mittelaman, Ariel; Gorohovsky, Sofia; Erlich, Motti. Preparation of cobicistat dihydrochloride. WO 2014105777. (Assignee Assia Chemical Industries Ltd., Israel; Teva Pharmaceuticals USA, Inc.)
