13764-20-0Relevant articles and documents
Isolation and structure elucidation of the major photodegradation products of pirmenol hydrochloride
Sakano,Ishii,Ichikawa,Harasawa,Minohara,Yamamura,Nishiyama
, p. 1363 - 1366 (1994)
Column chromatography, thin-layer chromatography, high-performance liquid chromatography, nuclear magnetic resonance spectrometry, and high-resolution mass spectrometry were employed to separate and identify the photodegradation products of pirmenol hydrochloride [(±)-cis-α-[3-(2,6-dimethyl-1- piperidinyl)propyl]-α-phenyl-2-pyridinemethanol monohydrochloride monohydrate], a new antiarrhythmic drug. A methanol solution of pirmenol was irradiated using a low-pressure mercury lamp. The solution afforded four major degradation products, three of which were identified as 3-(cis-2,6- dimethylpiperidinyl)propyl 2-(2-pyridyl)phenyl ketone, 2-(2-pyridyl)benzoic acid, and methyl 2-(2-pyridyl)-benzoate. The degradation followed apparent- first-order reaction kinetics. In addition, the possible photodegradation pathways are discussed with reference to reaction mechanisms.
Design, synthesis, and biological evaluation of tetrahydroquinolin derivatives as potent inhibitors of CBP bromodomain
Bi, Xiaoyang,Chen, Kaixian,Chen, Yu,Ding, Hong,Jiang, Hao,Jiang, Hualiang,Lu, Tian,Lu, Wenchao,Luo, Cheng,Sun, Zhongya,Xu, Pan,Zhang, Fengcai,Zhang, Naixia,Zhou, Bing
supporting information, (2020/06/21)
CREB-binding protein (CBP) is a large multi-domain protein containing a HAT domain catalyzing transacetylation and a bromodomain responsible for acetylated lysine recognition. CBPs could act as transcription co-activators to regulate gene expression and have been shown to play a significant role in the development and progression of many cancers. Herein, through in silico screening two hit compounds with tetrahydroquinolin methyl carbamate scaffold were discovered, among which DC-CPin7 showed an in vitro inhibitory activity with the TR-FRET IC50 value of 2.5 ± 0.3 μM. We obtained a high-resolution co-crystal structure of the CBP bromodomain in complex with DC-CPin7 to guide following structure-based rational drug design, which yielded over ten DC-CPin7 derivatives with much higher potency, among which DC-CPin711 showed approximately 40-fold potency compared with hit compound DC-CPin7 with an in vitro TR-FRET IC50 value of 63.3 ± 4.0 nM. Notably, DC-CPin711 showed over 150-fold selectivity against BRD4 bromodomains. Moreover, DC-CPin711 showed micromolar level of anti-leukemia proliferation through G1 phase cell cycle arrest and cell apoptosis. In summary, through a combination of computational and crystal-based structure optimization, DC-CPin711 showed potent in vitro inhibitory activities to CBP bromodomain with a decent selectivity towards BRD4 bromodomains and good cellular activity to leukemia cells, which could further be applied to related biological and translational studies as well as serve as a lead compound for future development of potent and selective CBP bromodomain inhibitors.
Cobalt-catalyzed C-H cyanation of arenes and heteroarenes
Li, Jie,Ackermann, Lutz
, p. 3635 - 3638 (2015/03/18)
Carboxylate assistance proved to be the key for the success of efficient cobalt(III)-catalyzed C-H cyanations. Thus, an in situ generated cationic cobalt complex was identified as a versatile catalyst for the site-selective synthesis of various aromatic a
