Category: 1256345-74-0

Zhang, Chun-Hui published the artcilePotent noncovalent inhibitors of the main protease of SARS-CoV-2 from molecular sculpting of the drug perampanel guided by free energy perturbation calculations, Safety of (3-Chloro-5-propoxyphenyl)boronic acid, the publication is ACS Central Science (2021), 7(3), 467-475, database is CAplus and MEDLINE.

Starting from our previous finding of 14 known drugs as inhibitors of the main protease (M^pro) of SARS-CoV-2, the virus responsible for COVID-19, we have redesigned the weak hit perampanel to yield multiple noncovalent, nonpeptidic inhibitors with ca. 20 nM IC₅₀ values in a kinetic assay. Free-energy perturbation (FEP) calculations for M^pro-ligand complexes provided valuable guidance on beneficial modifications that rapidly delivered the potent analogs. The design efforts were confirmed and augmented by determination of high-resolution X-ray crystal structures for five analogs bound to M^pro. Results of cell-based antiviral assays further demonstrated the potential of the compounds for treatment of COVID-19. In addition to the possible therapeutic significance, the work clearly demonstrates the power of computational chem. for drug discovery, especially FEP-guided lead optimization.

ACS Central Science published new progress about 1256345-74-0. 1256345-74-0 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Boronic acid and ester,Benzene,Ether,Boronic Acids,Boronic acid and ester, name is (3-Chloro-5-propoxyphenyl)boronic acid, and the molecular formula is C8H5F3O2S, Safety of (3-Chloro-5-propoxyphenyl)boronic acid.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Zhang, Chun-Hui published the artcileOptimization of triarylpyridinone inhibitors of the main protease of SARS-CoV-2 to low-nanomolar antiviral potency, SDS of cas: 1256345-74-0, the publication is ACS Medicinal Chemistry Letters (2021), 12(8), 1325-1332, database is CAplus and MEDLINE.

Non-covalent inhibitors of the main protease (M^pro) of SARS-CoV-2 having a pyridinone core were previously reported with IC₅₀ values as low as 0.018μM for inhibition of enzymic activity and EC₅₀ values as low as 0.8μM for inhibition of viral replication in Vero E6 cells. The series has now been further advanced by consideration of placement of substituted five-membered-ring heterocycles in the S4 pocket of M^pro and N-methylation of a uracil ring. Free energy perturbation calculations provided guidance on the choice of the heterocycles, and protein crystallog. confirmed the desired S4 placement. Here we report inhibitors with EC₅₀ values as low as 0.080μM, while remdesivir yields values of 0.5-2μM in side-by-side testing with infectious SARS-CoV-2. A key factor in the improvement is enhanced cell permeability, as reflected in PAMPA measurements. Compounds 19 (I) and 21 (II) are particularly promising as potential therapies for COVID-19, featuring IC₅₀ values of 0.044-0.061μM, EC₅₀ values of ca. 0.1μM, good aqueous solubility, and no cytotoxicity.

ACS Medicinal Chemistry Letters published new progress about 1256345-74-0. 1256345-74-0 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Boronic acid and ester,Benzene,Ether,Boronic Acids,Boronic acid and ester, name is (3-Chloro-5-propoxyphenyl)boronic acid, and the molecular formula is C18H34N4O5S, SDS of cas: 1256345-74-0.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Xiong, Yusheng published the artcileDiscovery of a novel glucagon receptor antagonist N-[(4-{(1S)-1-[3-(3, 5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-β-alanine (MK-0893) for the treatment of type II diabetes, COA of Formula: C9H12BClO3, the publication is Journal of Medicinal Chemistry (2012), 55(13), 6137-6148, database is CAplus and MEDLINE.

A potent, selective glucagon receptor antagonist I was discovered by optimization of a previously identified lead. Compound I is a reversible and competitive antagonist with high binding affinity (IC₅₀ of 6.6 nM) and functional cAMP activity (IC₅₀ of 15.7 nM). It is selective for glucagon receptor relative to other family B GPCRs, showing IC₅₀ values of 1020 nM for GIPR, 9200 nM for PAC1, and >10000 nM for GLP-1R, VPAC1, and VPAC2. Compound I blunted glucagon-induced glucose elevation in hGCGR mice and rhesus monkeys. It also lowered ambient glucose levels in both acute and chronic mouse models: in hGCGR ob/ob mice it reduced glucose (AUC 0-6 h) by 32% and 39% at 3 and 10 mpk single doses, resp. In hGCGR mice on a high fat diet, compound I at 3, and 10 mpk po in feed lowered blood glucose levels by 89% and 94% at day 10, resp., relative to the difference between the vehicle control and lean hGCGR mice. On the basis of its favorable biol. and DMPK properties, compound I (MK-0893) was selected for further preclin. and clin. evaluations.

Journal of Medicinal Chemistry published new progress about 1256345-74-0. 1256345-74-0 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Boronic acid and ester,Benzene,Ether,Boronic Acids,Boronic acid and ester, name is (3-Chloro-5-propoxyphenyl)boronic acid, and the molecular formula is C10H15ClO3S, COA of Formula: C9H12BClO3.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics