614-61-9Relevant articles and documents
Discovery, synthesis and biological characterization of a series of: N -(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1 H -pyrazol-5-yl)acetamide ethers as novel GIRK1/2 potassium channel activators
Alnouti, Yazen,Aretz, Christopher D.,Chhonker, Yashpal S.,Dhuria, Nikilesh V.,Du, Yu,Gautam, Nagsen,Hopkins, Corey R.,Kumar, Sushil,Lesiak, Lauren,Sharma, Swagat,Weaver, C. David
supporting information, p. 1366 - 1373 (2021/09/28)
The present study describes the discovery and characterization of a series of N-(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1H-pyrazol-5-yl)acetamide ethers as G protein-gated inwardly-rectifying potassium (GIRK) channel activators. From our previous lead optimization efforts, we have identified a new ether-based scaffold and paired this with a novel sulfone-based head group to identify a potent and selective GIRK1/2 activator. In addition, we evaluated the compounds in tier 1 DMPK assays and have identified compounds that display nanomolar potency as GIRK1/2 activators with improved metabolic stability over the prototypical urea-based compounds. This journal is
Dechlorination of 2,4-dichlorophenoxyacetic acid using biochar-supported nano-palladium/iron: Preparation, characterization, and influencing factors
Zhou, Hongyi,Huang, Ning,Zhao, Yongkang,Baig, Shams Ali,Xiang, Junchao
, (2020/09/23)
In the present study, peanut shell, a green waste raw material, was used to prepare biochar (BC) and to obtain BC-supported nano-palladium/iron (BC-nPd/Fe) composites for removing 2,4-dichlorophenoxyacetic acid (2,4-D) from water. Characterization analysis demonstrated that nPd/Fe particles were well dispersed on the BC surface with weakened magnetic properties. The average particle diameter and specific surface area of nPd/Fe were 101.3 nm and 6.7 m2 g?1, whereas the corresponding values of the BC-nPd/Fe materials were 88.8 nm and 14.8 m2 g?1, respectively. Several factors were found to influence the dechlorination of 2,4-D, including the weight ratio of BC to Fe, Pd loading ratio, initial solution pH, 2,4-D concentration, and reaction temperature. Dechlorination results indicated that the 2,4-D removal and phenoxyacetic acid (PA) generation rates were 44.1% and 20.1%, respectively, in the nPd/Fe system, and 100.0% and 92.1%, respectively, in the BC-nPd/Fe system. The dechlorination of 2,4-D was well described by the pseudo-first-order kinetic model (R2 > 0.97), and the observed rate constants kobs were 0.0042 min (nPd/Fe) and 0.0578 min (BC-nPd/Fe), respectively. The reaction mechanism indicated that the dechlorination hydrogenation was the main process to remove 2,4-D from water in the BC-nPd/Fe system. In addition, BC inhibited the formation of a passivation layer on the particle surface during the reaction, thus maintaining the high reactivity of BC-nPd/Fe. The easy preparation technique, high 2,4-D dechlorination capacity, and mild reaction conditions suggest that BC-nPd/Fe may be a promising alternative composite to remove 2,4-D from water.
Optimizing TRPM4 inhibitors in the MHFP6 chemical space
Delalande, Clémence,Awale, Mahendra,Rubin, Matthias,Probst, Daniel,Ozhathil, Lijo C.,Gertsch, Jürg,Abriel, Hugues,Reymond, Jean-Louis
, p. 167 - 177 (2019/02/01)
We recently reported 4-chloro-2-(2-chlorophenoxy)acetamido)benzoic acid (CBA) as the first potent inhibitor of TRPM4, a cation channel implicated in cardiac diseases and prostate cancer. Herein we report a structure-activity relationship (SAR) study of CBA resulting in two new potent analogs. To design and interpret our SAR we used interactive color-coded 3D-maps representing similarities between compounds calculated with MHFP6 (MinHash fingerprint up to six bonds), a new molecular fingerprint outperforming other fingerprints in benchmarking virtual screening studies. We further illustrate the general applicability of our method by visualizing the structural diversity of active compounds from benchmarking sets in relation to decoy molecules and to drugs. MHFP6 chemical space 3D-maps might be generally helpful in designing, interpreting and communicating the results of SAR studies. The modified WebMolCS is accessible at http://gdb.unibe.ch and the code is available at https://github.com/reymond-group/webMolCS for off-line use.
