52107-98-9Relevant articles and documents
An efficient synthesis of nilotinib (AMN107)
Huang, Wei-Sheng,Shakespeare, William C.
, p. 2121 - 2124 (2007)
A concise synthesis of AMN107, a compound currently undergoing several phase II/III clinical trials for chronic myelogenous leukemia is described. The new procedure reduces the number of synthetic steps from eight to four, with an overall yield of 65%. Georg Thieme Verlag Stuttgart.
Discovery of Potent Antiallergic Agents Based on ano-Aminopyridinyl Alkynyl Scaffold
Bai, Fang,Chen, Taiwen,Fan, Chen,Hu, Youhong,Li, Xin,Liu, Moting,Ma, Yanjie,Tang, Wei,Xiang, Caigui,Xie, Zhicheng
supporting information, p. 13588 - 13603 (2021/09/20)
Effective therapeutic agents are highly desired for immune-mediated allergic diseases. Herein, we report the design, synthesis, and structure-activity relationship of ano-aminopyridinyl alkyne series as novel orally bioavailable antiallergic agents, which
Accelerated Discovery of Novel Ponatinib Analogs with Improved Properties for the Treatment of Parkinson's Disease
Kaiser, Thomas M.,Dentmon, Zackery W.,Dalloul, Christopher E.,Sharma, Savita K.,Liotta, Dennis C.
supporting information, p. 491 - 496 (2020/04/30)
Parkinson's disease (PD) is a debilitating and common neurodegenerative disease. New insights implicating c-Abl activation as a driving force in PD have opened a new drug development avenue for PD treatment beyond the symptomatic relief by L-DOPA. BCR-Abl inhibitors, which include nilotinib and ponatinib, have been found to inhibit this process, and nilotinib has shown improvement in outcomes in a 12-patient, nonrandomized trial. However, nilotinib is a potent inhibitor of hERG, a cardiac K+ channel whose inhibition increases risk of sudden death. We used our machine learning approach to predict novel molecules that would inhibit c-Abl while also having minimal liability against hERG. Of our six novel compounds tested, we identified two that had c-Abl potencies comparable to nilotinib, but with significantly improved profiles regarding the hERG channel. Our best compound exhibited a hERG IC50 of 12.1 μM (compared to nilotinib with an IC50 of 0.45 μM and ponatinib with IC50 of 0.767 μM). This work is a step forward for a machine learning enabled, multiparameter optimization of a chemical space and represents a significant advance in the development of novel Parkinson's therapies.