/image/Raltegravir.jpg "Raltegravir (Potassium) - Synthetic Route")
Raltegravir, also known as MK-0518, is an antiretroviral drug used to treat HIV infection. Raltegravir is a human immunodeficiency virus (HIV) integrase strand transfer inhibitor (HIV-1 INSTI) with HIV-1 antiviral activity. Raltegravir binds to and inhibits integrase, an HIV enzyme that inserts viral genetic material into the genetic material of the infected human cell. Inhibition of integrase prevents insertion of HIV DNA into the human DNA genome, thus blocking HIV replication. It received approval by the U.S. Food and Drug Administration (FDA) in October 2007, the first of a new class of HIV drugs, the integrase inhibitors, to receive such approval.
Patil, Gulabrao D.; Kshirsagar, Siddheshwar W.; Shinde, Shivnath B.; Patil, Pankaj S.; Deshpande, Mangesh S.; Chaudhari, Ashok T.; Sonawane, Swapnil P.; Maikap, Golak C.; Gurjar, Mukund K. Identification, Synthesis, and Strategy For Minimization of Potential Impurities Observed In Raltegravir Potassium Drug Substance. Organic Process Research & Development. Volume 16. Issue 8. Pages 1422-1429. 2012.
Belyk, Kevin, M.; Morrison, Henry, G.; Jones, Philip; Summa, Vincenzo. Preparation of N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(1-methyl-1-{[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino}ethyl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide potassium salts as HIV integrase inhibitors. Assignee Merck & Co. Inc., USA; Eletti S.P.A. Istituto Di Ricerche Di Biologia Molecolare P. Ang. WO 2006060712. (2006).
Summa, Vincenzo; Petrocchi, Alessia; Bonelli, Fabio; Crescenzi, Benedetta; Donghi, Monica; Ferrara, Marco; Fiore, Fabrizio; Gardelli, Cristina; Gonzalez Paz, Odalys; Hazuda, Daria J.; Jones, Philip; Kinzel, Olaf; Laufer, Ralph; Monteagudo, Edith; Muraglia, Ester; Nizi, Emanuela; Orvieto, Federica; Pace, Paola; Pescatore, Giovanna; Scarpelli, Rita; Stillmock, Kara; Witmer, Marc V.; Rowley, Michael. Discovery of Raltegravir, a Potent, Selective Orally Bioavailable HIV-Integrase Inhibitor for the Treatment of HIV-AIDS Infection. Journal of Medicinal Chemistry. Volume 51. Issue 18. Pages 5843-5855. 2008.
Crescenzi, Benedetta; Gardelli, Cristina; Muraglia, Ester; Nizi, Emanuela; Orvieto, Federica; Pace, Paola; Pescatore, Giovanna; Petrocchi, Alessia; Poma, Marco; Rowley, Michael; Scarpelli, Rita; Summa, Vincenzo. Preparation of N-substituted hydroxypyrimidinone carboxamide inhibitors of HIV integrase. Assignee Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa, Italy. WO 2003035077. (2003).
Humphrey, Guy R.; Pye, Philip J.; Zhong, Yong-Li; Angelaud, Remy; Askin, David; Belyk, Kevin M.; Maligres, Peter E.; Mancheno, Danny E.; Miller, Ross A.; Reamer, Robert A.; Weissman, Steven A. Development of a Second-Generation, Highly Efficient Manufacturing Route for the HIV Integrase Inhibitor Raltegravir Potassium. Organic Process Research & Development. Volume 15. Issue 1. Pages 73-83. 2011.
Wang, Ziwen; Wang, Mingxiao; Yao, Xue; Li, Yue; Qiao, Wentao; Geng, Yunqi; Liu, Yuxiu; Wang, Qingmin. Hydroxyl may not be indispensable for raltegravir: Design, synthesis and SAR Studies of raltegravir derivatives as HIV-1 inhibitors. European Journal of Medicinal Chemistry. Volume 50. Pages 361-369. 2012.
Stathakis, Christos I.; Gkizis, Petros L.; Alexandraki, Elli S.; Trakossas, Sakellarios; Terzidis, Michael; Neokosmidis, Efstratios; Zacharis, Constantinos K.; Vasiliadou, Christina; Vastardi, Elli; Andreou, Thanos; Zitrou, Asteria; Varvogli, Anastasia-Aikaterini; Koftis, Theocharis V. (Chloromethyl)dimethylchlorosilane-KF: A Two-Step Solution to the Selectivity Problem in the Methylation of a Pyrimidone Intermediate en Route to Raltegravir. Organic Process Research & Development. Volume 21. Issue 9. Pages 1413-1418. 2017.
Guo, Diliang; Liu, Guannan; Li, Jian; Zhou, Yu; Xu, Jinyi; Jiang, Hualing; Liu, Hong. Improved synthesis of raltegravir. Zhongguo Yaoke Daxue Xuebao. Volume 40. Issue 4. Pages 297-301. 2009.
Rege, Bhagwant; Kaighn, Kimberly; Ghosh, Soumojeet; Alani, Laman. Taste-masked tablets and granules. Assignee Merck & Co., Inc., USA. WO 2007087188. (2007).
Reddy, Buddidet Shankar; Reddy, Sanapureddy Jagan Mohan; Reddy, Danda Subba; Shankar, Gangadhara Bhima; Somannavar, Yallappa Somappa; Kishore, Karumanchi; Sivakumaran, Meenakshisunderam. An improved process for the preparation of raltegravir. Assignee Aurobindo Pharma Ltd., India. IN 2014CH05652. (2016).
