1181573-36-3Relevant articles and documents
Compound with nitrogen-containing bridge ring, spiro or fused ring structure and application thereof
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Paragraph 0150-0152, (2020/08/12)
The invention discloses a compound with a nitrogen-containing bridge ring, spiro or fused ring structure and application of the compound. The compound has an obvious inhibition effect on the activityof protein kinase, can be used as a BTK inhibitor for preparing drugs for treating BTK-mediated diseases including, but not limited to, autoimmune diseases, malignant tumors and the like, and has a wide application prospect.
Preparation method of high-purity Ledipasvir intermediate
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, (2017/02/24)
The invention discloses a preparation method of a high-purity Ledipasvir intermediate (1R, 3S and 4S)-N-t-butylcarbonyl-2-azabicyalo[2.2.1] heptane-3-carboxylic acid. According to the method, (1R, 3S and 4S)-N-t-butylcarbonyl-2-azabicyalo[2.2.1] heptane-3-carboxylate serves as an initial raw material, and the Ledipasvir intermediate is obtained through enzymatic hydrolysis. A test proves that the high-purity Ledipasvir intermediate is obtained and a feasible path is provided for reducing production cost and improving drug use safety. Meanwhile, the method has the advantages that operation is easy, environment friendliness is achieved, the yield is high, selectivity is high and cost is low; large-scale production can be achieved, and industrial application and popularization are facilitated.
Discovery of ledipasvir (GS-5885): A potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection
Link, John O.,Taylor, James G.,Xu, Lianhong,Mitchell, Michael,Guo, Hongyan,Liu, Hongtao,Kato, Darryl,Kirschberg, Thorsten,Sun, Jianyu,Squires, Neil,Parrish, Jay,Keller, Terry,Yang, Zheng-Yu,Yang, Chris,Matles, Mike,Wang, Yujin,Wang, Kelly,Cheng, Guofeng,Tian, Yang,Mogalian, Erik,Mondou, Elsa,Cornpropst, Melanie,Perry, Jason,Desai, Manoj C.
supporting information, p. 2033 - 2046 (2014/04/03)
A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal [2.2.1]azabicyclic ring system was discovered. Optimization of antiviral potency and pharmacokinetics led to the identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31 pM) has an extended plasma half-life of 37-45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.