920274-04-0Relevant articles and documents
Stereocomplementary Synthesis of Pharmaceutically Relevant Chiral 2-Aryl-Substituted Pyrrolidines Using Imine Reductases
Chen, Fei-Fei,Chen, Qi,Li, Bo-Bo,Xu, Jian-He,Zhang, Yu-Hui,Zheng, Gao-Wei,Zhou, Xin-Yi
supporting information, p. 3367 - 3372 (2020/04/21)
Exploring a collection of naturally occurring imine reductases (IREDs) identified two stereocomplementary IREDs with reducing activity toward sterically hindered 2-aryl-substituted pyrrolines. Using (R)-selective ScIR and (S)-selective SvIR, various chiral 2-aryl-substituted pyrrolidines with excellent enantioselectivity (>99% ee) were stereocomplementarily synthesized in good yield (60-80%), demonstrating the feasibility of IREDs for generating pharmaceutically relevant chiral 2-aryl-substituted pyrrolidine intermediates.
Enantioselective Synthesis of 2-Substituted Pyrrolidines via Intramolecular Reductive Amination
Chang, Mingxin,Guo, Haodong,Huang, Haizhou,Zhang, Tao,Zhao, Wenlei,Zhou, Huan
, p. 2713 - 2719 (2019/06/19)
Catalyzed by the complex generated in situ from iridium and the chiral ferrocene ligand, tert -butyl (4-oxo-4-arylbutyl)carbamate substrates were deprotected and then reductively cyclised to form 2-substituted arylpyrrolidines in a one-pot manner, in which the intramolecular reductive amination was the key step. A range of chiral 2-substituted arylpyrrolidines were synthesised in up to 98percent yield and 92percent ee.
Enantioselective Direct Synthesis of Free Cyclic Amines via Intramolecular Reductive Amination
Zhang, Ying,Yan, Qiaozhi,Zi, Guofu,Hou, Guohua
supporting information, p. 4215 - 4218 (2017/08/23)
Chiral cyclic amines can be prepared via intramolecular reductive amination of N-Boc-protected amino ketones in a one-pot process. With the complex of iridium and f-spiroPhos as the catalyst, a range of N-Boc-protected amino ketones are smoothly transformed into chiral cyclic free amines in high yields and excellent enantioselectivities (up to 97% ee). Moreover, this method can also be successfully applied to the synthesis of a κ-opioid receptor selective antagonist, (S)-1.
A Kinome-Wide Selective Radiolabeled TrkB/C Inhibitor for in Vitro and in Vivo Neuroimaging: Synthesis, Preclinical Evaluation, and First-in-Human
Bernard-Gauthier, Vadim,Bailey, Justin J.,Mossine, Andrew V.,Lindner, Simon,Vomacka, Lena,Aliaga, Arturo,Shao, Xia,Quesada, Carole A.,Sherman, Phillip,Mahringer, Anne,Kostikov, Alexey,Grand'Maison, Marilyn,Rosa-Neto, Pedro,Soucy, Jean-Paul,Thiel, Alexander,Kaplan, David R.,Fricker, Gert,W?ngler, Bj?rn,Bartenstein, Peter,Schirrmacher, Ralf,Scott, Peter J. H.
, p. 6897 - 6910 (2017/09/07)
The proto-oncogenes NTRK1/2/3 encode the tropomyosin receptor kinases TrkA/B/C which play pivotal roles in neurobiology and cancer. We describe herein the discovery of [11C]-(R)-3 ([11C]-(R)-IPMICF16), a first-in-class positron emission tomography (PET) TrkB/C-targeting radiolabeled kinase inhibitor lead. Relying on extensive human kinome vetting, we show that (R)-3 is the most potent and most selective TrkB/C inhibitor characterized to date. It is demonstrated that [11C]-(R)-3 readily crosses the blood-brain barrier (BBB) in rodents and selectively binds to TrkB/C receptors in vivo, as evidenced by entrectinib blocking studies. Substantial TrkB/C-specific binding in human brain tissue is observed in vitro, with specific reduction in the hippocampus of Alzheimer's disease (AD) versus healthy brains. We additionally provide preliminary translational data regarding the brain disposition of [11C]-(R)-3 in primates including first-in-human assessment. These results illustrate for the first time the use of a kinome-wide selective radioactive chemical probe for endogenous kinase PET neuroimaging in human.
