Month: November 2022

Yu, Zhifeng published the artcileDiscovery and characterization of bromodomain 2-specific inhibitors of BRDT, Quality Control of 5961-59-1, the main research area is carboximido indazole preparation bromodomain inhibitor SAR mol docking; BET bromodomains; DNA-encoded chemistry; male contraceptive; small-molecule inhibitors.

To assess the contribution of each BRDT bromodomain, collection of DNA-encoded chem. libraries I [R = Me, MeO; R1 = 2,4-dimethylphenyl, 4-amino-2-methyl-Ph, 1-methylindol-2-yl, etc.] II [R2 = Me, Et, i-Pr; R3 = acetamido, [4-(methylcarbamoyl)benzoyl]amino; R4 = 6-amino-3-pyridyl, 2-aminopyrimidin-5-yl, 6-amino-4-methyl-3-pyridyl, 6-amino-2-methyl-3-pyridyl] and III [R5 = R6 = R7 = H, Me; R8 = H, acetamido, methylcarbamoyl, benzamido; R9 = H, Me, MeO] for BRDT-BD1 and BRDT-BD2 binders was screened. High-enrichment hits was identified and resynthesized off-DNA and examined for their ability to compete with JQ1 in BRDT and BRD4 bromodomain AlphaScreen assays. These studies identified I [R = Me, R1 = 4-amino-2-methyl-phenyl] as a selective BRDT-BD2 inhibitor with low nanomolar potency and >1,000-fold selectivity over BRDT-BD1. Structure-activity relationship studies of I [R = Me, R1 = 4-amino-2-methyl-phenyl] produced a series of addnl. BRDT-BD2/BRD4-BD2 selective inhibitors, including III [R5 = Me, R6 = R7 = H, R8 = acetamido, R9 = Me], a truncated analog of I [R = Me, R1 = 4-amino-2-methyl-phenyl] with similar activity, and II [R2 = Me, R3 = [4-(methylcarbamoyl)benzoyl]amino, R4 = 6-amino-4-methyl-3-pyridyl] an analog with sixfold selectivity for BRDT-BD2 vs. BRD4-BD2. BROMOscan bromodomain profiling confirmed the great affinity and selectivity of I [R = Me, R1 = 4-amino-2-methyl-phenyl] and III [R5 = Me, R6 = R7 = H, R8 = acetamido, R9 = Me] on all BET BD2 vs. BD1 with the highest affinity for BRDT-BD2. Cocrystals of BRDT-BD2 with CDD-1102 and CDD-1302 were determined at 2.27 and 1.90 Å resolution, resp., and revealed BRDT-BD2 specific contacts that explain the high affinity and selectivity of these compounds These BD2-specific compounds and their binding to BRDT-BD2 are unique compared with recent reports and enabled further evaluation of their nonhormonal contraceptive potential in-vitro and in-vivo.

Proceedings of the National Academy of Sciences of the United States of America published new progress about Arylboronic acids Role: RCT (Reactant), RACT (Reactant or Reagent). 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Quality Control of 5961-59-1.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Marinova, Maya published the artcileSynthesis, Resolution, Configurational Stability, and Properties of Cationic Functionalized [5]Helicenes, Safety of 1,3-Dimethoxybenzene, the main research area is helicene dye preparation resolution configurational stability.

A straightforward approach to the synthesis of two different series of cationic [5]helicenes has been achieved including, in dioxa series, the possibility to introduce aromatic functional groups at the periphery of the helical structure. While photophys. study highlights that the introduction of aryl substituents at position 23 of the helical moieties has a negligible impact on the optical properties, styryl substituents allow a welcoming extension of the conjugation pathways. Finally, a red shift of the optical properties was evidenced upon introduction of nitrogen atoms in the helicene scaffold, leading to particularly good fluorescence efficiencies in the red domain for a helicenic dye. Detailed information on racemization kinetics was collected for the most stable species upon direct high-performance liquid chromatog. (HPLC) resolution or, when configurational lability was too high, through VT-HPLC anal. on the chiral stationary phase (ΔG‡ values ranging from 85.0 to 137.1 kJ·mol-1 and above).

Journal of Organic Chemistry published new progress about Activation enthalpy (for racemization). 151-10-0 belongs to class isoquinoline, name is 1,3-Dimethoxybenzene, and the molecular formula is C8H10O2, Safety of 1,3-Dimethoxybenzene.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Karmel, Caleb published the artcileMechanism of the Iridium-Catalyzed Silylation of Aromatic C-H Bonds, Category: isoquinoline, the main research area is arene silylation mechanism iridium catalysis.

Phenanthroline ligands and [Ir(cod)(OMe)]2 form complexes that catalyze the silylation of aromatic and aliphatic C-H bonds. However, no exptl. data on the identity of complexes related to the mechanism of this process or the mechanisms by which they react to functionalize C-H bonds have been reported. Herein, we describe our studies on the mechanism of the iridium-catalyzed silylation of aryl C-H bonds. The resting state of the catalyst is an iridium disilyl hydride complex (phenanthroline)Ir(SiMe(OTMS)2)2(H)(L), in which L varies with the arene and additives. An iridium disilyl hydride complex was isolated, characterized, and allowed to react with arenes to form aryl silanes. The kinetics of the reactions of electron-rich and electron-poor arenes showed that the rate-limiting step varies with the electronic properties of the arene. Computational studies on related iridium silyl complexes revealed that the high activity of iridium complexes with sterically encumbered phenanthroline ligands is due to a change in the number of silyl groups bound to iridium between the resting state of the catalyst containing the hindered phenanthroline and that containing less hindered phenanthroline.

Journal of the American Chemical Society published new progress about C-H bond activation. 151-10-0 belongs to class isoquinoline, name is 1,3-Dimethoxybenzene, and the molecular formula is C8H10O2, Category: isoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Li, Guangzhe published the artcileStructure-activity relationships study of neolamellarin A and its analogues as hypoxia inducible factor-1 (HIF-1) inhibitors, Computed Properties of 104-01-8, the main research area is neolamellarin A derivative preparation HIF1 inhibitory activity SAR; Anti-tumor; Hypoxia inducible factor (HIF)-1; Marine alkaloids; Neolamellarin A; Structure-activity relationship.

The novel marine pyrrole alkaloid neolamellarin A derived from sponge has been shown to inhibit hypoxia-induced HIF-1 activity. In this work, we designed and synthesized neolamellarin A (I) and its series of derivatives by a convergent synthetic strategy. The HIF-1 inhibitory activity and cytotoxicity of these compounds were evaluated in Hela cells by dual-luciferase reporter gene assay and MTT assay, resp. The results showed that neolamellarin A (IC50 = 10.8 ± 1.0 μM) and compound II (IC50 = 11.9 ± 3.6 μM) had the best HIF-1 inhibitory activity and low cytotoxicity. Our SAR research focused on the effects of key regions aliphatic carbon chain length, aromatic ring substituents and C-7 substituent on biol. activity, providing a basis for the subsequent research on the development of novel pyrrole alkaloids as HIF-1 inhibitors and design of small mol. probes for target protein identification.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Computed Properties of 104-01-8.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Daneshmand, Pargol published the artcileCyclic Ureate Tantalum Catalyst for Preferential Hydroaminoalkylation with Aliphatic Amines: Mechanistic Insights into Substrate Controlled Reactivity, Synthetic Route of 5961-59-1, the main research area is cyclic ureate tantalum catalyst preferential hydroaminoalkylation aliphatic amine.

The efficient and catalytic amination of unactivated alkenes with simple secondary alkyl amines is preferentially achieved. A sterically accessible, N,O-chelated cyclic ureate tantalum catalyst was prepared and characterized by X-ray crystallog. This optimized catalyst can be used for the hydroaminoalkylation of 1-octene with a variety of aryl and alkyl amines, but notably enhanced catalytic activity can be realized with challenging N-alkyl secondary amine substrates. This catalyst offers turnover frequencies of up to 60 h-1, affording full conversion at 5 mol% catalyst loading in approx. 20 min with these nucleophilic amines. Mechanistic investigations, including kinetic isotope effect (KIE) studies, reveal that catalytic turnover is limited by protonolysis of the intermediate 5-membered azametallacycle. A Hammett kinetic anal. shows that catalytic turnover is promoted by electron rich amine substrates that enable catalytic turnover. This more active catalyst is shown to be effective for late stage drug modification.

Journal of the American Chemical Society published new progress about Alkenes Role: PEP (Physical, Engineering or Chemical Process), PRP (Properties), RCT (Reactant), PROC (Process), RACT (Reactant or Reagent) (unactivated). 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Synthetic Route of 5961-59-1.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Vodnala, Nagaraju published the artcileLewis Acid-Promoted Typical Friedel-Crafts Reactions Using DMSO as a Carbon Source, Safety of 1,3-Dimethoxybenzene, the main research area is diarylmethane preparation; arene dimethyl sulfoxide Friedel Craft reaction Lewis acid catalyst.

A mild and efficient synthetic protocol for the synthesis of sym. and unsym. diarylmethanes (DAMs) R1CH2R2 (R1 = 4-methoxyphenyl, 2,4,6-trimethylphenyl, 1H-indol-3-yl, 4-hydroxy-2-oxo-2H-chromen-3-yl, etc.; R2 = 4-hydroxy-3,5-dimethylphenyl, 5-methylfuran-2-yl, 4-amino-3,5-bis(propan-2-yl)phenyl, etc.) was reported. Using DMSO as the C1 source and TMSOTf as the Lewis acid promoter, a series of functionalized sym. and unsym. DAMs was synthesized in high yields. Gratifyingly, DMSO plays a dual role as a solvent and a C1 source and can also be replaced with its deuterated counterpart, DMSO-d6, enabling the incorporation of the -CD2 moiety into the diarylmethane skeleton. The developed approach has been applied to a wide range of substrates having various functional groups, and this protocol has also been extended to the synthesis of an anti-breast cancer agent and an anticoagulant agent using common feedstock compounds In addition, the postulated mechanism has been explicitly demonstrated via control experiments

Journal of Organic Chemistry published new progress about Anticoagulants. 151-10-0 belongs to class isoquinoline, name is 1,3-Dimethoxybenzene, and the molecular formula is C8H10O2, Safety of 1,3-Dimethoxybenzene.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Porey, Arka published the artcileHydrogen-Bonding Assisted Catalytic Kinetic Resolution of Acyclic β-Hydroxy Amides, COA of Formula: C9H10O3, the main research area is acylaminoalkyl ester hydroxyamide kinetic resolution nonracemic preparation; indenooxazinotriazolylidene catalyst oxidative kinetic resolution hydroxyamide cinnamaldehyde; NHCs; enantioselectivity; hydrogen bonding; kinetic resolution; β-hydroxy amides.

Enantioenriched acyclic α-substituted β-hydroxy amides are valuable compounds in chem., material and medicinal sciences, but their enantioselective synthesis remains challenging. A catalytic kinetic resolution (KR) of such amides with selectivity factor(s) up to >200 is developed via enantioselective acylation of primary alc. with a cinnamaldehyde in the presence of an N-heterocyclic carbene. An enhanced selectivity for the catalytic KR process is realized using cyclic tertiary amine as base additive. Diastereomeric transition state models for the process are proposed to rationalize the origin of enantioselectivity.

Angewandte Chemie, International Edition published new progress about Enantioselective synthesis. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, COA of Formula: C9H10O3.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Yao, Yu published the artcileUPLC-MS/MS method for the determination of the herb composition of Tangshen formula and the in vivo pharmacokinetics of its metabolites in rat plasma, SDS of cas: 104-01-8, the main research area is Tangshen formula herb plasma metabolite pharmacokinetics UPLC MS; LC-MS/MS; Thermo Q Exactive™ Plus Orbitrap™ mass spectrometer; chemical constituents; pharmacokinetics; traditional Chinese medicines.

Tangshen formula (TSF) is a traditional Chinese medicine composed of seven medicinal herbs including Astragalus membranaceus, Rehmannia glutinosa Libosch, Citrus aurantium L., etc. which is used to treat diabetic nephropathy III, IV qi and yin deficiency and stasis syndrome. Most of the studies on TSF are pharmacol. and pharmacodynamic experiments There are few basic studies on its chem. substances, and the effective constituents are not clear. To analyze the main chem. components of TSF and the absorbed components in rat plasma following oral administration based on liquid chromatog. tandem mass spectrometry (LC-MS/MS). Moreover, providing a rapid and valid anal. strategy for simultaneous determination of six components in rat plasma and use it in pharmacokinetic studies. A total of 132 components were identified in TSF, and 44 components were identified in rat plasma after oral TSF, 35 of which were prototype components and nine were metabolic components. A sensitive and reliable LC-MS/MS method was developed for simultaneous determination of six components in rat plasma. The intra-day and inter-day precision relative standard deviation (RSD) was lower than 15%; the accuracy of low, medium and high concentrations ranged from 80% to 120%. The recovery met the requirements and the RSD of the recoveries was less than 15%. A total of 132 components were identified in TSF. The LC-MS/MS quant. method for the simultaneous determination of morroniside, loganin, notoginsenoside R1, ginsenoside Re, ginsenoside Rb1 and astragaloside IV in rat plasma was established for the first time. The pharmacokinetic parameters are clarified, which can guide the clin. medication of TSF.

Phytochemical Analysis published new progress about Arthrogryposis-renal dysfunction-cholestasis syndrome. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, SDS of cas: 104-01-8.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Jiang, Zheng-Meng published the artcileGreen and efficient extraction of different types of bioactive alkaloids using deep eutectic solvents, SDS of cas: 598-50-5, the main research area is Caulis Coptis Stephania Tetradium Sophora; bioactive alkaloid extraction deep eutectic solvent.

Deep eutectic solvents (DESs) have attracted increasing attention as eco-friendly and efficient alternatives to conventional organic solvents. In this study, five herbal medicines (HMs) including Caulis sinomenii, Coptis chinensis, Stephania tetrandra, Tetradium ruticarpum, and Sophora flavescens were selected for the first time to comprehensively evaluate the potential and effectiveness of DESs on the extraction of Morphinane, Protoberberine, Bisbenzylisoquinoline, Indole and Quinolizidine alkaloids, resp. A total of 75 types of binary or ternary DESs with different polarity, viscosity, pH, and solubilization abilities were tailored to screen a suitable DESs for extraction of morphinane alkaloids from Caulis sinomenii, and the extraction conditions were optimized using response surface methodol. (RSM) and artificial neural network hybridized with genetic algorithm (ANN-GA) for the first time. The results demonstrated that DESs were excellent solvents for extraction of alkaloids with superior efficiency to conventional extraction solvents. Moreover, both ANOVA and sensitivity anal. demonstrated that the most critical parameter for alkaloids extraction was water content in DESs. This study reveals the potential of eco-friendly DESs for applications involving the efficient extraction of bioactive alkaloids from natural sources.

Microchemical Journal published new progress about Coptis chinensis. 598-50-5 belongs to class isoquinoline, name is 1-Methylurea, and the molecular formula is C2H6N2O, SDS of cas: 598-50-5.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Kenia, Hasti published the artcileEthyl-4-(dimethylamino)-2-(4-methoxyphenyl) propanote as anxiolytic, anti-inflammatory and anti-bacterial agent, Synthetic Route of 104-01-8, the main research area is ethyl dimethylamino methoxyphenyl propanote preparation anxiolytic antipsychotic antidepressant antiinflammatory; antibacterial ethyl dimethylamino methoxyphenyl propanote preparation.

An improved process for the synthesis of ethyl-4-(dimethylamino)-2-(4-methoxyphenyl)propanote I was carried out by hydrolysis of 2-(4-methoxyphenyl)acetonitrile using sodium hydroxide to obtain 2-(4-methoxyphenyl)acetic acid which was then esterified with ethanol to obtain 2-(4-methoxyphenyl)acetate which on further Mannich reaction with paraformaldehyde and dimethylamine in presence of catalytic amount of tert-Bu ammonium bromide. Compound I was subjected to pharmacol. screening for anxiolytic activity by elevated plus maze test, open field test and motor co-ordination test by Rota rod. Compound I was also screened for in-vivo antipsychotic, in-vivo antidepressant, in-vitro anti-inflammatory activity by protein denaturation method and antibacterial activity by serial dilution method.

World Journal of Pharmacy and Pharmaceutical Sciences published new progress about Anti-inflammatory agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Synthetic Route of 104-01-8.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem