Tag: M.W=100-150

Johnson, James A. published the artcileDiscovery of a Hydroxypyridinone APJ Receptor Agonist as a Clinical Candidate, Quality Control of 151-10-0, the main research area is APJ receptor agonist pharmacokinetic oral bioavailability pharmacodynamic.

Apelin-13 is an endogenous peptidic agonist of the apelin receptor (APJ) receptor with the potential for improving cardiac function in heart failure patients. However, the low plasma stability of apelin-13 necessitates continuous i.v. infusion for therapeutic use. There are several approaches to increase the stability of apelin-13 including attachment of pharmacokinetic enhancing groups, stabilized peptides, and Fc-fusion approaches. We sought a small-mol. APJ receptor agonist approach to target a compound with a pharmacokinetic profile amenable for chronic oral administration. This manuscript describes sequential optimization of the pyrimidinone series, leading to pyridinone 14(I), with in vitro potency equivalent to the endogenous ligand apelin-13 and with an excellent oral bioavailability and PK profile in multiple preclin. species. Compound 14 exhibited robust pharmacodynamic effects similar to apelin-13 in an acute rat pressure-volume loop model and was advanced as a clin. candidate.

Journal of Medicinal Chemistry published new progress about Apelin receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 151-10-0 belongs to class isoquinoline, name is 1,3-Dimethoxybenzene, and the molecular formula is C8H10O2, Quality Control of 151-10-0.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Ji, Wangqin published the artcileCopper-catalyzed cyclization reaction: synthesis of trifluoromethylated indolinyl ketones, Quality Control of 5961-59-1, the main research area is aryl fluorobutenone alkylaniline copper catalyst diastereoselective cyclization; aroyl fluoroalkyl alkylindole preparation.

A novel, simple, effective and rapid synthetic method to construct the C-2 trifluoromethylated indolinyl ketones via a copper-catalyzed cyclization reaction between N-alkylanilines and β-(trifluoromethyl)-α,β-unsaturated enones was developed. The results of the control experiments showed that the reaction may involve a radical mechanism by a single-electron transfer process. Moreover, a broad substrate scope and good functional groups, high diastereoselectivities (dr, up to >20 : 1) as well as gram-scale synthesis make this approach highly attractive.

Chemical Communications (Cambridge, United Kingdom) published new progress about Aryl ketones Role: PRP (Properties), SPN (Synthetic Preparation), PREP (Preparation). 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

Ruijten, Dieter published the artcileHydrogen Borrowing: towards Aliphatic Tertiary Amines from Lignin Model Compounds Using a Supported Copper Catalyst, Product Details of C8H11NO, the main research area is amine aliphatic tertiary preparation; benzenepropanol amination secondary amine copper zirconium oxide lignin model; Amination; Heterogeneous catalysis; Hydrogen transfer; Lignin; tertiary amines.

Upcoming biorefineries, such as lignin-first, provide renewable aromatics containing unique aliphatic alcs. In this context, a Cu-ZrO2 catalyzed hydrogen borrowing approach was established to yield tertiary amine from the lignin model monomer 3-(3,4-dimethoxyphenyl)-1-propanol and the actual lignin-derived monomers, 3-(4-hydroxyphenyl)-1-propanol and dihydroconiferyl alc., with dimethylamine. Various industrial metal catalysts were evaluated, resulting in nearly quant. mass balances for most catalysts. Identified intermediates, side and reaction products were placed into a corresponding reaction network, supported by kinetic evolution experiments Cu-ZrO2 was selected as the most suitable catalyst combining high alc. conversion with respectable aliphatic tertiary amine selectivity. Low pressure H2 was key for high catalyst activity and tertiary amine selectivity, mainly by hindering undesired reactant dimethylamine disproportionation and alc. amidation. Besides dimethylamine model, diverse secondary amine reactants were tested with moderate to high tertiary amine yields. As most active catalytic site, highly dispersed Cu species in strong contact with ZrO2 is suggested. ToF-SIMS, N2O chemisorption, TGA and XPS of spent Cu-ZrO2 revealed that imperfect amine product desorption and declining surface Cu lowered the catalytic activity upon catalyst reuse, while thermal reduction readily restored the initial activity and selectivity demonstrating catalyst reuse.

ChemSusChem published new progress about Aliphatic amines, secondary amines 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, Product Details of C8H11NO.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Oh, Hyeonji published the artcileSynthesis of Bicyclic N-Heterocycles via Photoredox Cycloaddition of Imino-Alkynes and Imino-Alkenes, HPLC of Formula: 151-10-0, the main research area is pyrrolizidinone preparation diastereoselective density functional theory; imino alkyne photoredox cycloaddition photocatalyst; dihydro oxazine preparation diastereoselective density functional theory; alkene imino photoredox cycloaddition photocatalyst.

This redox-neutral reaction involves formal imine-alkyne metathesis followed by redox-mediated annulation with concomitant rearrangement. The synthesis of pyrrolizidinones I [n = 1,2; R1 = H, Me; R2 = H, Me, Ph, C(O)OMe; R3 = H, Me, C(O)OMe; R2R3 = -(CH2)5-; R4 = 4-chlorophenyl, pyrimidin-5-yl, isoquinolin-4-yl, etc.; R5 = i-Pr, Et, Bn, t-Bu; R6 = i-Pr, Et, Bn, t-Bu] based on intramol. imine-alkynes II [2+2] cycloaddition under visible light photocatalysis have been reported. In contrast, the use of imino-alkenes III [X = CH2, O, S(O)2, TsN; R7 = H, Me; R8 = H, Me, Ph, etc.; R7R8 = -(CH2)5-; R9 = H, Me] provides dihydro-1,4-oxazines IV via an alternative [4+2] cycloaddition pathway. The proposed reaction mechanisms were supported by control experiments and DFT calculations

ACS Catalysis published new progress about Alkenes Role: PRP (Properties), RCT (Reactant), RACT (Reactant or Reagent) (imino-). 151-10-0 belongs to class isoquinoline, name is 1,3-Dimethoxybenzene, and the molecular formula is C8H10O2, HPLC of Formula: 151-10-0.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Gasnot, Julien published the artcileTaming the Reactivity of Phosphiranium Salts: Site-Selective C-Centered Ring Opening for Direct Synthesis of Phosphinoethylamines, Computed Properties of 5961-59-1, the main research area is phosphiranium salt preparation nucleophilic ring opening aniline nitrogen nucleophile; phosphinoethylamine preparation; nucleophilic ring opening; phosphinoethyl amines; phosphiranium ions; selectivity; steric protection.

Advances in the field of P chem. are documented, by revealing the synthetic utility of previously underused quaternary phosphiranium salts (QPrS) as three-chain-atom electrophilic building blocks. Notably, control of their challenging C-centered electrophilicity is disclosed with an expedient synthesis of tertiary β-anilino phosphines as a proof-of-concept.

Angewandte Chemie, International Edition published new progress about Amines Role: SPN (Synthetic Preparation), PREP (Preparation) (phosphinoethylamines). 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Computed Properties of 5961-59-1.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Zhao, Lanxiao published the artcileCalcium-Catalyzed Dehydrogenative Silylation of Aromatic Ethers with Hydrosilane, Name: 1,3-Dimethoxybenzene, the main research area is calcium benzyl complex catalyzed dehydrogenative silylation aromatic ether hydrosilane; scorpionate supported calcium benzyl ether complex preparation crystal structure; mol structure scorpionate supported calcium benzyl ether complex; silyl substituted aromatic ether derivative preparation.

The catalytic regioselective C-H silylation of a wide range of alkoxy-substituted benzene derivatives with primary hydrosilane was achieved using scorpionate-supported Ca benzyl complex [(TpAd,iPr)Ca(p-CH2C6H4Me)(THP)] (1) (TpAd,iPr = hydrotris(3-adamantyl-5-isopropylpyrazolyl)borate, THP = tetrahydropyran) as the precatalyst. This protocol offers an atom-efficient and straightforward method for the synthesis of a variety of silyl-substituted aromatic ether derivatives without a H acceptor and free of transition metal. Ca anisyl complexes [(TpAd,iPr)Ca(o-MeO-m-Br-C6H3)] (5) and [(TpAd,iPr)Ca(o-Me-OCH2C6H4)] (6), proposed as the catalytic reaction intermediates, were isolated and structurally characterized.

ACS Catalysis published new progress about Benzenoid aromatic compounds Role: RCT (Reactant), RACT (Reactant or Reagent). 151-10-0 belongs to class isoquinoline, name is 1,3-Dimethoxybenzene, and the molecular formula is C8H10O2, Name: 1,3-Dimethoxybenzene.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Moritz, Amy E. published the artcileDiscovery, Optimization, and Characterization of ML417: A Novel and Highly Selective D3 Dopamine Receptor Agonist, Category: isoquinoline, the main research area is D3R agonists ML417 beta arrestin G protein neurodegeneration pharmacokinetics.

To identify novel D3 dopamine receptor (D3R) agonists, we conducted a high-throughput screen using a β-arrestin recruitment assay. Counterscreening of the hit compounds provided an assessment of their selectivity, efficacy, and potency. The most promising scaffold was optimized through medicinal chem. resulting in enhanced potency and selectivity. The optimized compound, ML417 (20)(I), potently promotes D3R-mediated β-arrestin translocation, G protein activation, and ERK1/2 phosphorylation (pERK) while lacking activity at other dopamine receptors. Screening of ML417 against multiple G protein-coupled receptors revealed exceptional global selectivity. Mol. modeling suggests that ML417 interacts with the D3R in a unique manner, possibly explaining its remarkable selectivity. ML417 was also found to protect against neurodegeneration of dopaminergic neurons derived from iPSCs. Together with promising pharmacokinetics and toxicol. profiles, these results suggest that ML417 is a novel and uniquely selective D3R agonist that may serve as both a research tool and a therapeutic lead for the treatment of neuropsychiatric disorders.

Journal of Medicinal Chemistry published new progress about Dopaminergic neuron. 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Category: isoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Solomonov, Boris N. published the artcileAn approach for the calculation of vaporization enthalpies of aromatic and heteroaromatic compounds at 298.15 K applicable to supercooled liquids, Recommanded Product: 1,3-Dimethoxybenzene, the main research area is aromatic heteroaromatic compound supercooled liquid vaporization enthalpy calculation.

An approach for the calculation of the vaporization enthalpies of aromatic and heteroaromatic compounds at T = 298.15 K with accuracy competitive with experiment was proposed. The vaporization enthalpies may be calculated from the solution enthalpies of liquid and solvation enthalpies in benzene. The solution enthalpies of liquids were shown to be constant within a given type of aromatic compounds For a set of 67 liquid and 41 solid aromatic and heteroaromatic compounds not capable of intermol. hydrogen bonding, it was exptl. demonstrated that the solution enthalpies of liquids or supercooled liquids in benzene were equal to 1 ± 1 kJ·mol-1. The way to consider intermol. hydrogen bonding, e.g., in phenol, aniline, pyrrole derivatives, was also proposed. The methods for solvation enthalpy calculation were proposed previously. The calculated and literature vaporization enthalpies values of 415 aromatic and heteroaromatic compounds were compared. Average absolute deviation amounted to 1.3 kJ·mol-1. The proposed approach is especially valuable for calculation of the vaporization enthalpies of low-volatile compounds, including those solid at T = 298.15 K.

Journal of Molecular Liquids published new progress about Calculators. 151-10-0 belongs to class isoquinoline, name is 1,3-Dimethoxybenzene, and the molecular formula is C8H10O2, Recommanded Product: 1,3-Dimethoxybenzene.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Manning-Geist, Beryl L. published the artcilePhase II study of enzalutamide in androgen receptor positive, recurrent, high- and low-grade serous ovarian cancer, Application In Synthesis of 151-10-0, the main research area is enzalutamide anticancer agent androgen receptor ovarian cancer; Androgen receptor expression; Enzalutamide; Ovarian cancer; Recurrent ovarian cancer; Serous ovarian cancer.

We sought to determine the safety and efficacy of the oral androgen receptor antagonist enzalutamide in patients with previously treated, recurrent, AR-pos. (AR+) ovarian cancer. This was a single-institution phase II study of patients with AR+ ovarian cancer with measurable disease with 1-3 prior lines of chemotherapy; patients were screened for enrollment from 11/2013-7/2018. Following consent, archival tissue was evaluated for AR+. Enrolled patients received daily enzalutamide 160 mg until progression of disease or treatment discontinuation. Adverse events were graded by CTCAE v4.0. Co-primary endpoints were 6-mo progression-free survival (PFS6) and overall response rate (ORR) by RECIST 1.1 criteria. During the study period, 160 patients were screened and 59 (45 high-grade serous [HGS] and 14 low-grade serous [LGS]) consented to treatment on study. There was 1 confirmed and 1 unconfirmed partial response. The ORR was 1.7% (90% CI: 0.2-100%). The overall PFS6 rate (as binary) was 22% (90% CI: 15.1-100%). The 6-mo PFS rate (as time to event) was 19.8% for HGS patients (90% CI: 12.7-100%) and 38.5% (90% CI: 21.7%-100%) for LGS patients. Grade 3 toxicities occurred in 6 patients (one toxicity (Grade 3 rash) was considered a dose-limiting toxicity). One patient died of cardiac arrest after 42 days on treatment of a cardiac arrest not attributed to study drug. The study met its primary endpoint, with a PFS6 rate of 22% (n = 13); however, the overall response rate was low. Enzalutamide was well tolerated and may be a potential treatment option in select patients.

Gynecologic Oncology published new progress about Androgen receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 151-10-0 belongs to class isoquinoline, name is 1,3-Dimethoxybenzene, and the molecular formula is C8H10O2, Application In Synthesis of 151-10-0.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Cui, Xin-Feng published the artcileRhodium-catalyzed tandem acylmethylation/annulation of N-nitrosoanilines with sulfoxonium ylides for the synthesis of substituted indazole N-oxides, Quality Control of 5961-59-1, the main research area is indazole nitrogen oxide preparation; nitrosoaniline sulfoxonium ylide acylmethylation cyclization rhodium catalyst.

An atom-economical protocol for synthesizing indazole N-oxides e.g., I from readily available N-nitrosoanilines e.g., C6H5N(CH3)N(=O) and sulfoxonium ylides RC(O)CH=S(O)(CH3)2 (R = Ph, cyclohexyl, furan-2-yl, t-Bu, etc.) through the rhodium(III)-catalyzed C-H activation and cyclization reaction is described here. This protocol employs nitroso as a traceless directing group. The transformation features powerful reactivity, tolerates various functional groups, and proceeds with moderate to good yields under an ambient atm., providing a straightforward approach to access structurally diverse and valuable indazole N-oxide derivatives e.g., I. Importantly, this new annulation process represents a hitherto unobserved reactivity pattern for the N-nitroso group.

Organic & Biomolecular Chemistry published new progress about C-H bond activation. 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