Day: December 6, 2022

Federico, Leonardo Bruno published the artcileIdentification of known drugs as potential SARS-CoV-2 Mpro inhibitors using ligand- and structure-based virtual screening, COA of Formula: C18H19Cl2NO4, the main research area is SARSCoV2 mpro inhibitor ligand screening; COVID-19; SARS-CoV-2; drug repositioning; ligand-based drug discovery; main-protease (Mpro); structure-based drug discovery.

Background: The new coronavirus pandemic has had a significant impact worldwide, and therapeutic treatment for this viral infection is being strongly pursued. Efforts have been undertaken by medicinal chemists to discover mols. or known drugs that may be effective in COVID-19 treatment – in particular, targeting the main protease (Mpro) of the virus. Materials & methods: We have employed an innovative strategy – application of ligand- and structure-based virtual screening – using a special compilation of an approved and diverse set of SARS-CoV-2 crystallog. complexes that was recently published. Results and conclusion: We identified seven drugs with different original indications that might act as potential Mpro inhibitors and may be preferable to other drugs that have been repurposed. These drugs will be exptl. tested to confirm their potential Mpro inhibition and thus their effectiveness against COVID-19.

Future Medicinal Chemistry published new progress about Antiviral agents. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, COA of Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Beaulieu, Pierre L. published the artcileStructure-based design of novel HCV NS5B thumb pocket 2 allosteric inhibitors with submicromolar gt1 replicon potency: Discovery of a quinazolinone chemotype, HPLC of Formula: 81565-19-7, the main research area is crystal structure quinazolinone preparation hepatitis virus polymerase inhibitor antiviral.

The authors describe the structure-based design of a novel lead chemotype that binds to thumb pocket 2 of HCV NS5B polymerase and inhibits cell-based gt1 subgenomic reporter replicons at sub-micromolar concentrations (EC50 <200 nM). This new class of potent thumb pocket 2 inhibitors features a 1H-quinazolin-4-one scaffold derived from hybridization of a previously reported, low affinity thiazolone chemotype with the recently described anthranilic acid series. Guided by x-ray structural information, a key NS5B-ligand interaction involving the carboxylate group of anthranilic acid based inhibitors was replaced by a neutral two-point hydrogen bonding interaction between the quinazolinone scaffold and the protein backbone. The in vitro ADME and in vivo rat PK profile of representative analogs are also presented and provide areas for future optimization of this new class of HCV polymerase inhibitors. Bioorganic & Medicinal Chemistry Letters published new progress about Antiviral agents. 81565-19-7 belongs to class pyridine-derivatives, name is 3-Chloro-4-(trifluoromethyl)pyridine, and the molecular formula is C6H3ClF3N, HPLC of Formula: 81565-19-7.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Niu, Wanjie published the artcileInvestigating the interaction between nifedipine- and ritonavir-containing antiviral regimens: A physiologically based pharmacokinetic/pharmacodynamic analysis, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is nifedipine ritonavir antiviral; drug-drug interaction; nifedipine; pharmacodynamics; physiologically-based pharmacokinetic; ritonavir.

Aims : Hypertension is a common comorbidity of patients with COVID-19, SARS or HIV infection. Such patients are often concomitantly treated with antiviral and antihypertensive agents, including ritonavir and nifedipine. Since ritonavir is a strong inhibitor of CYP3A and nifedipine is mainly metabolized via CYP3A, the combination of ritonavir and nifedipine can potentially cause drug-drug interactions. This study provides guidance on nifedipine treatment during and after coadministration with ritonavir-containing regimens, using a physiol. based pharmacokinetic/pharmacodynamic (PBPK/PD) anal. Methods : The PBPK/PD models for 3 formations of nifedipine were developed based on the Simcyp nifedipine model and the models were verified using published data. The effects of ritonavir on nifedipine exposure and systolic blood pressure (SBP) were assessed for instant-release, sustained-release and controlled-release formulations in patients. Various nifedipine regimens were investigated when coadministered with or without ritonavir. Results : PBPK/PD models for 3 formulations of nifedipine were successfully established. The predicted maximum concentration (Cmax), area under plasma concentration-time curve (AUC), maximum reduction in SBP and area under effect-time curve were all within 0.5-2.0-fold of the observed data. Model simulations showed that the inhibitory effect of ritonavir on CYP3A4 increased the Cmax of nifedipine 17.92-48.85-fold and the AUC 63.30-84.01-fold at steady state and decreased the SBP by >40 mmHg. Thus, the combination of nifedipine and ritonavir could lead to severe hypotension. Conclusion : Ritonavir significantly affects the pharmacokinetics and antihypertensive effect of nifedipine. It is not recommended for patients to take nifedipine- and ritonavir-containing regimens simultaneously.

British Journal of Clinical Pharmacology published new progress about Antiviral agents. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Li, Hao published the artcileCalcium channel blockers reduce severe fever with thrombocytopenia syndrome virus (SFTSV) related fatality, Formula: C17H18N2O6, the main research area is benidipine hydrochloride antiviral agent severe fever thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne infectious disease caused by a novel phlebovirus (SFTS virus, SFTSV), was listed among the top 10 priority infectious diseases by the World Health Organization due to its high fatality of 12%-50% and possibility of pandemic transmission. Currently, effective anti-SFTSV intervention remains unavailable. Here, by screening a library of FDA-approved drugs, we found that benidipine hydrochloride, a calcium channel blocker (CCB), inhibited SFTSV replication in vitro. Benidipine hydrochloride was revealed to inhibit virus infection through impairing virus internalization and genome replication. Further experiments showed that a broad panel of CCBs, including nifedipine, inhibited SFTSV infection. The anti-SFTSV effect of these two CCBs was further analyzed in a humanized mouse model in which CCB treatment resulted in reduced viral load and decreased fatality rate. Importantly, by performing a retrospective clin. investigation on a large cohort of 2087 SFTS patients, we revealed that nifedipine administration enhanced virus clearance, improved clin. recovery, and remarkably reduced the case fatality rate by >5-fold. These findings are highly valuable for developing potential host-oriented therapeutics for SFTS and other lethal acute viral infections known to be inhibited by CCBs in vitro.

Cell Research published new progress about Antiviral agents. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Krishnaiah, Maddeboina published the artcileSynthesis and biological evaluation of 5-(fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles as inhibitors of transforming growth factor-β type I receptor kinase, Name: [1,2,4]Triazolo[1,5-a]pyridine-6-carbaldehyde, the main research area is triazolopyridinylimidazole pyridinyl preparation transforming growth factor kinase inhibitor; ALK5 inhibitor; Cancer; Fibrosis; Kinase assay; TGF-β.

To further optimize a clin. candidate (EW-7197), a series of 5-(3-, 4-, or 5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles have been synthesized and evaluated for their TGF-β type I receptor kinase (ALK5) and p38α MAP kinase inhibitory activity in an enzyme assay. The 5-(5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles displayed a level of potency similar to that of EW-7197 against both ALK5 (IC50 = 7.68-13.70 nM) and p38α MAP kinase (IC50 = 1240-3370 nM). Among them, I inhibited ALK5 with IC50 value of 7.68 nM in a kinase assay and displayed 82% inhibition at 100 nM in a luciferase reporter assay.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 614750-81-1 belongs to class pyridine-derivatives, name is [1,2,4]Triazolo[1,5-a]pyridine-6-carbaldehyde, and the molecular formula is C7H5N3O, Name: [1,2,4]Triazolo[1,5-a]pyridine-6-carbaldehyde.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Li, Lin published the artcileDiscovery of novel dual inhibitors of VEGFR and PI3K kinases containing 2-ureidothiazole scaffold, Product Details of C9H11N3O3, the main research area is phenylureidothiazolformamide preparation VEGFR PI3K kinase inhibitory anticancer SAR activity.

A series of compounds possessing 2-(3-phenyl)ureidothiazol-4-formamide derivatives with a 2-ureidothiazole scaffold were designed and synthesized. Some compounds demonstrated inhibition of cell proliferation against both MDA-MB-231 and HepG2 cell lines using Sorafenib as the pos. control. Compounds I showed a good to moderate inhibition on VEGFR-2 and PI3Kα which was proved by further mol. docking study. This study suggests that compound I is a potential dual inhibitor of VEGFR-2 and PI3Kα and is applicable for further investigation.

Chinese Chemical Letters published new progress about Antitumor agents. 26820-62-2 belongs to class pyridine-derivatives, name is 4-(5-Nitropyridin-2-yl)morpholine, and the molecular formula is C9H11N3O3, Product Details of C9H11N3O3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Qin, Mingze published the artcileDesign and synthesis of novel 2-(4-(2-(dimethylamino)ethyl)-4H-1,2,4-triazol-3-yl)pyridines as potential antitumor agents, SDS of cas: 24484-93-3, the main research area is triazolylpyridine dimethylaminoethyl preparation antitumor agent; 4-(2-(Dimethylamino)ethyl)-4H-1,2,4-triazole; Antitumor activity; Synthesis.

New 2-(4-(2-(dimethylamino)ethyl)-4H-1,2,4-triazol-3-yl)pyridine derivatives were synthesized and evaluated for their in vitro cytotoxicity against five cancer cell lines namely MKN-45, H460, HT-29, A549, and U87MG, as well as the normal cell line WI-38. Nearly all the compounds exhibited superior potency to sorafenib with a better selectivity towards the MKN-45, H460, and HT-29 cell lines. In addition, the enzymic screening result demonstrated that the optimized compounds possessed potent Raf kinase inhibition as well as favorable enzyme selectivity. The most promising compound, I, showed high levels of cytotoxicity against MKN-45, H460, and HT-29 cells with IC50 values of 51, 72, and 130 nM, resp., which are 45.5, 30.4, and 27.8 folds higher than the corresponding IC50 values for sorafenib against these cell lines. Structure-activity relationships revealed that the dimethylaminoethyl group was crucial for high activity.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 24484-93-3 belongs to class pyridine-derivatives, name is Methyl 4-chloropicolinate, and the molecular formula is C7H6ClNO2, SDS of cas: 24484-93-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

El-Damasy, Ashraf Kareem published the artcileDesign and synthesis of new potent anticancer benzothiazole amides and ureas featuring pyridylamide moiety and possessing dual B-RafV600E and C-Raf kinase inhibitory activities, Name: Methyl 4-chloropicolinate, the main research area is benzothiazole amide preparation Raf kinase inhibitory anticancer activity; urea benzothiazole preparation Raf kinase inhibitory anticancer activity; Amide; Anticancer activity; B-Raf(V600E); Benzothiazole; C-Raf; Pyridylamide; Urea.

A new series of benzothiazole amide and urea derivatives tethered with the privileged pyridylamide moiety by ether linkage at the 6-position of benzothiazole (22 final compounds) has been designed and synthesized as potent anticancer sorafenib analogs. A selected group of twelve derivatives was appraised for its antiproliferative activity over a panel of 60 human cancer cell lines at a single dose concentration of 10 μM at National Cancer Institute (NCI, USA). Some compounds exhibited promising growth inhibitions and thus were further tested in advanced 5-dose testing assay to determine their GI50 values. The cellular based assay results revealed that 3,5-bis-trifluoromethylphenyl urea derivative I is the best derivative with superior potency and efficacy compared to sorafenib as well as notable extended spectrum activity covering 57 human cancer cell lines. Kinase screening of compound I showed its kinase inhibitory effect against both B-RafV600E and C-Raf. Moreover, the most potent derivatives in cells were investigated for their RAF inhibitory activities, and the results were rationalized with the mol. docking study. Profiling of CYP450 and hERG channel inhibitory effects for the active compounds revealed their low possibilities to exhibit undesirable drug-drug interactions and cardiac side effects.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 24484-93-3 belongs to class pyridine-derivatives, name is Methyl 4-chloropicolinate, and the molecular formula is C7H6ClNO2, Name: Methyl 4-chloropicolinate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Schroeder, Gretchen M. published the artcileDiscovery of N-(4-(2-Amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a Selective and Orally Efficacious Inhibitor of the Met Kinase Superfamily, Application In Synthesis of 71255-09-9, the main research area is aminopyridinyloxy fluorophenyl dihydropyridine carboxamide preparation Met kinase inhibitor.

Substituted N-(4-(2-aminopyridin-4-yloxy)-3-fluoro-phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamides were identified as potent and selective Met kinase inhibitors. Substitution of the pyridine 3-position gave improved enzyme potency, while substitution of the pyridone 4-position led to improved aqueous solubility and kinase selectivity. Analog 10 demonstrated complete tumor stasis in a Met-dependent GTL-16 human gastric carcinoma xenograft model following oral administration. Because of its excellent in vivo efficacy and favorable pharmacokinetic and preclin. safety profiles, 10 has been advanced into phase I clin. trials.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 71255-09-9 belongs to class pyridine-derivatives, name is 2-Methoxynicotinaldehyde, and the molecular formula is C7H7NO2, Application In Synthesis of 71255-09-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zhong, Lili published the artcileSynthesis of deuterium-enriched sorafenib derivatives and evaluation of their biological activities, Application In Synthesis of 24484-93-3, the main research area is sorafenib deuterium anticancer agent cervical carcinoma; Antitumor activities; Deuterium substitution; Pharmacokinetics; Sorafenib.

Deuterium substitution has been widely known that can improve the pharmacokinetic profiles due to isotope effect. Herein, a series of deuterated sorafenib derivatives have been synthesized and characterized by 1H NMR, 13C NMR and MS. Their antitumor activities were evaluated in vitro against human hepatoma cell line HepG2 and human cervical carcinoma cell line HeLa. The LogP values were detected by high-performance liquid chromatog. Subsequently, the metabolic stability and pharmacokinetics study were assessed in vitro and in vivo.

Molecular Diversity published new progress about Antitumor agents. 24484-93-3 belongs to class pyridine-derivatives, name is Methyl 4-chloropicolinate, and the molecular formula is C7H6ClNO2, Application In Synthesis of 24484-93-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem