13764-20-0Relevant academic research and scientific papers
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.
Novel methyllycaconitine analogues selective for the α4β2 over α7 nicotinic acetylcholine receptors
Gallagher, Ryan,Qudah, Taima,Balle, Thomas,Chebib, Mary,McLeod, Malcolm D.
, (2021/11/27)
Analogues of methyllycaconitine (MLA) based on a (3-ethyl-9-methylidene-3-azabicyclo[3.3.1]nonan-1-yl)methanol template have been designed and synthesised that incorporate the modified ester sidechains distinct from that present in the natural product. Electrophysiology experiments using Xenopus oocytes expressing nicotinic acetylcholine receptors (nAChRs) revealed selected analogues served as non-competitive inhibitors that showed selectivity for the α4β2α7 nAChR subtypes, and selectivity for the (α4)3(β2)2(α4)2(β2)3 stoichiometry. This study more clearly defines the biological effects of MLA analogues and identifies strategies for the development of MLA analogues as selective ligands for the α4β2 nAChR subtype.
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.
Metal-Free Aerobic Oxidative Selective C-C Bond Cleavage in Heteroaryl-Containing Primary and Secondary Alcohols
Xia, Anjie,Qi, Xueyu,Mao, Xin,Wu, Xiaoai,Yang, Xin,Zhang, Rong,Xiang, Zhiyu,Lian, Zhong,Chen, Yingchun,Yang, Shengyong
supporting information, (2019/05/07)
A transition-metal-free aerobic oxidative selective C-C bond-cleavage reaction in primary and secondary heteroaryl alcohols is reported. This reaction was highly efficient and tolerated various heteroaryl alcohols, generating a carboxylic acid derivative and a neutral heteroaromatic compound. Experimental studies combined with density functional theory calculations revealed the mechanism underlying the selective C-C bond cleavage. This strategy also provides an alternative simple approach to carboxylation reaction.
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
Rhodium catalyzed cyanation of chelation assisted C-H bonds
Chaitanya, Manthena,Yadagiri, Dongari,Anbarasan, Pazhamalai
, p. 4960 - 4963 (2013/10/22)
A rhodium-catalyzed cyanation of chelation assisted C-H bonds is described employing N-cyano-N-phenyl-p-methylbenzenesulfonamide as an efficient cyanating reagent. The present method allowed the synthesis of various benzonitirle derivatives in good to excellent yield. A number of chelating groups are also effective in the present cyanation of C-H bonds. In addition, the developed methodology was applied in the formal synthesis of the isoquinoline alkaloid, menisporphine.
Rhodium(I)-catalyzed direct carboxylation of arenes with CO2 via chelation-assisted C-H bond activation
Mizuno, Hajime,Takaya, Jun,Iwasawa, Nobuharu
supporting information; experimental part, p. 1251 - 1253 (2011/04/16)
Rh-catalyzed direct carboxylation of unactivated aryl C-H bond under atmospheric pressure of carbon dioxide was realized via chelation-assisted C-H activation for the first time. Variously substituted and functionalized 2-arylpyridines and 1-arylpyrazoles underwent the carboxylation in the presence of the rhodium catalyst and a stoichiometric methylating reagent, AlMe 2(OMe), to give carboxylated products in good yields. The catalysis is proposed to consist of methylrhodium(I) species as the key intermediate, which undergoes C-H activation to afford rhodium(III), followed by reductive elimination of methane to give nucleophilic arylrhodium(I). This approach demonstrates promising application of C-H bond activation strategy in the field of carbon dioxide fixation.
Design and synthesis of 6-fluoro-2-naphthyl derivatives as novel CCR3 antagonists with reduced CYP2D6 inhibition
Sato, Ippei,Morihira, Koichiro,Inami, Hiroshi,Kubota, Hirokazu,Morokata, Tatsuaki,Suzuki, Keiko,Iura, Yosuke,Nitta, Aiko,Imaoka, Takayuki,Takahashi, Toshiya,Takeuchi, Makoto,Ohta, Mitsuaki,Tsukamoto, Shin-ichi
, p. 8607 - 8618 (2008/12/23)
In our previous study on discovering novel types of CCR3 antagonists, we found a fluoronaphthalene derivative (1) that exhibited potent CCR3 inhibitory activity with an IC50 value of 20 nM. However, compound 1 also inhibited human cytochrome P450 2D6 (CYP2D6) with an IC50 value of 400 nM. In order to reduce its CYP2D6 inhibitory activity, we performed further systematic structural modifications on 1. In particular, we focused on reducing the number of lipophilic moieties in the biphenyl part of 1, using C log D7.4 values as the reference index of lipophilicity. This research led to the identification of N-{(3-exo)-8-[(6-fluoro-2-naphthyl)methyl]-8-azabicyclo[3.2.1]oct-3-yl}-3-(piperidin-1-ylcarbonyl)isonicotinamide 1-oxide (30) which showed comparable CCR3 inhibitory activity (IC50 = 23 nM) with much reduced CYP2D6 inhibitory activity (IC50 = 29,000 nM) compared with 1.
