6505-08-4Relevant academic research and scientific papers
Antiarrhythmic Hit to Lead Refinement in a Dish Using Patient-Derived iPSC Cardiomyocytes
Cashman, John R.,Ryan, Daniel,McKeithan, Wesley L.,Okolotowicz, Karl,Gomez-Galeno, Jorge,Johnson, Mark,Sampson, Kevin J.,Kass, Robert S.,Pezhouman, Arash,Karagueuzian, Hrayr S.,Mercola, Mark
, p. 5384 - 5403 (2021/05/29)
Ventricular cardiac arrhythmia (VA) arises in acquired or congenital heart disease. Long QT syndrome type-3 (LQT3) is a congenital form of VA caused by cardiac sodium channel (INaL) SCN5A mutations that prolongs cardiac action potential (AP) and enhances INaL current. Mexiletine inhibits INaL and shortens the QT interval in LQT3 patients. Above therapeutic doses, mexiletine prolongs the cardiac AP. We explored structure-activity relationships (SAR) for AP shortening and prolongation using dynamic medicinal chemistry and AP kinetics in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Using patient-derived LQT3 and healthy hiPSC-CMs, we resolved distinct SAR for AP shortening and prolongation effects in mexiletine analogues and synthesized new analogues with enhanced potency and selectivity for INaL. This resulted in compounds with decreased AP prolongation effects, increased metabolic stability, increased INaL selectivity, and decreased avidity for the potassium channel. This study highlights using hiPSC-CMs to guide medicinal chemistry and "drug development in a dish".
COMPOUNDS AS INHIBITORS OF SODIUM CHANNELS
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Paragraph 0302; 0309; 0310, (2018/01/17)
Methods and small molecule compounds for inhibition of sodium channels are provided. One example of a class of compounds that may be used is represented by the compound of Formula (I) or a pharmaceutically acceptable salt, N-oxide or solvate thereof, wherein A, B, D, R, R1, R'1, R2, R3, R4, R5, R6, R7, R8 are as described herein.
A (different) bright ammonia amide carbamate derivative and application thereof (by machine translation)
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Paragraph 0071; 0072; 0073; 0090; 0091, (2017/07/14)
The invention belongs to the field of plant, relates to a general formula (I) is shown in a (different) bright ammonia amide carbamate derivatives and their pharmaceutically acceptable salt, wherein substituent R has the definition given in the specification, the invention also relates to the general formula (I) preparation of compounds of the, specifically for the preparation of the intermediate of its development and application of plant disease control. (by machine translation)
Design, synthesis and effect of the introduction of a propargyloxy group on the fungicidal activities of 1-substituted phenoxypropan-2-amino valinamide carbamate derivatives
Li, Jian-Qiang,Wang, Zhi-Peng,Gao, Yang,Zhao, Wei-Guang
, p. 82131 - 82137 (2016/09/09)
The cell walls of oomycetes are composed of cellulose, making cellulose synthase enzymes good targets for carboxylic acid amide fungicides. Valinamide carbamates are amino acid fungicides that represent excellent alternatives to conventional synthetic pesticides in terms of their ability to reduce the negative impacts of these compounds on human health and the environment. In a continuation of our research towards the development of new cellulose synthase inhibitors, we have developed a series of "stretched" analogues of iprovalicarb by the introduction of an additional OCH2 linker. The bioassay results indicated that compounds containing a small group at the para-position of phenyl gave excellent fungicidal activities with EC50 values ranging from 0.59 to 2.06 μmol L-1. Most notably, the introduction of a propargyloxy group led to a pronounced increase in the fungicidal activity. Furthermore, compound 7o bearing a propargyloxy group was identified as the most promising candidate because of its excellent fungicidal potency against oomycete diseases and good fungicidal activity against non-oomycete diseases.
CARBAZOLYL-(4)-OXYPROPANOLAMINE COMPOUNDS AND THERAPEUTIC COMPOSITIONS
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, (2008/06/13)
Carbazolyl-(4)-oxypropanolamine compounds of the formula where in R1 is hydrogen, lower alkanoyl or aroyl; R2 is hydrogen, lower alkyl or arylalkyl; R3 is hydrogen or lower alkyl; R4is hydrogen or lower alkyl, or when X is oxygen, R4 together with R5 can
