Category: 89003-95-2

Zhou, Jie; Bie, Jianbo; Wang, Xiaoyu; Liu, Quan; Li, Rongcui; Chen, Hualong; Hu, Jinping; Cao, Hui; Ji, Wenming; Li, Yan; Liu, Shuainan; Shen, Zhufang; Xu, Bailing published the artcile< Discovery of N-Arylsulfonyl-Indole-2-Carboxamide Derivatives as Potent, Selective, and Orally Bioavailable Fructose-1,6-Bisphosphatase Inhibitors-Design, Synthesis, In Vivo Glucose Lowering Effects, and X-ray Crystal Complex Analysis>, Related Products of 89003-95-2, the main research area is T2MD liver FBPase inhibitors glucose lowering crystal structure binding.

Liver fructose-1,6-bisphosphatase (FBPase) is a key enzyme in the gluconeogenesis pathway. Inhibiting FBPase activity represents a potential treatment for type 2 diabetes mellitus. A series of novel N-arylsulfonyl-4-arylamino-indole-2-carboxamide derivatives have been disclosed as FBPase inhibitors. Through extensive structure-activity relationship investigations, a promising candidate mol. Cpd118 [sodium (7-chloro-4-((3-methoxyphenyl)amino)-1-methyl-1H-indole-2-carbonyl] [(4-methoxyphenyl)sulfonyl)amide](I) has been identified with high inhibitory activity against human liver FBPase (IC50, 0.029 ± 0.006 μM) and high selectivity relative to the other six AMP-binding enzymes. Importantly, Cpd118 produced significant glucose-lowering effects on both type 2 diabetic KKAy mice and ZDF rats as demonstrated by substantial reductions in the fasting and postprandial blood glucose levels, as well as the HbA1c level. Furthermore, Cpd118 elicited a favorable pharmacokinetic profile with an oral bioavailability of 99.1%. Moreover, the X-ray crystal structure of the Cpd118-FBPase complex was resolved, which revealed a unique binding mode and provided a structural basis for its high potency and selectivity.

Journal of Medicinal Chemistry published new progress about Bioavailability. 89003-95-2 belongs to class bromides-buliding-blocks, and the molecular formula is C8H4BrNO, Related Products of 89003-95-2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Chen, Lu; Tian, Jun; Zhan, Yizhou; Ren, Jun; Wang, Zhong-Wen published the artcile< Lewis Acid-Catalyzed Intramolecular [3+2] Cross-Cycloaddition of Donor-Acceptor Epoxides with Alkenes for Construction of Oxa-[n.2.1] Skeletons>, COA of Formula: C8H4BrNO, the main research area is oxa skeleton preparation; epoxide alkene cycloaddition.

The first LA-catalyzed [3+2] intramol. cross-cycloaddition of GDA-epoxides with carbon-carbon double bonds was developed for construction of bridged oxa-[n.2.1] skeletons I [R1 = H, 7-F, 7-Me, etc.; R2 = R3 = Me, OMe].

Chinese Journal of Chemistry published new progress about Alkenes Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 89003-95-2 belongs to class bromides-buliding-blocks, and the molecular formula is C8H4BrNO, COA of Formula: C8H4BrNO.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Tan, Mei-Ling; Tong, Shuo; Hou, Sheng-Kai; You, Jingsong; Wang, Mei-Xiang published the artcile< Copper-Catalyzed N,N-Diarylation of Amides for the Construction of 9,10-Dihydroacridine Structure and Applications in the Synthesis of Diverse Nitrogen-Embedded Polyacenes>, Synthetic Route of 89003-95-2, the main research area is amide haloarylmethane diarylation copper; acyldihydroacridine preparation deacylation oxidative aromatization; tetracene pentacene preparation; polyacene preparation; copper arylation catalyst.

A CuI/DMEDA catalyzed N,N-diarylation reaction of amides with various di(o-bromoaryl)methanes to produce diverse 9,10-dihydroacridine derivatives, is reported. The resulting 9,10-dihydroacridine derivatives were oxidized selectively under mild conditions to afford acridine, acridinone, and acridinium derivatives The copper-catalyzed N,N-diarylation reaction coupled with oxidative aromatization reaction enabled the facile construction of nitrogen atom-embedded tetracenes and pentacenes of different ortho-fused patterns. The luminescence properties, especially the effect of fusion pattern on fluorescence emission of acquired N-polyacenes, were also demonstrated.

Organic Letters published new progress about Absorption. 89003-95-2 belongs to class bromides-buliding-blocks, and the molecular formula is C8H4BrNO, Synthetic Route of 89003-95-2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Zhu, Bin-Bin; Ye, Wen-Bo; He, Zhi-Tao; Zhang, Shu-Sheng; Feng, Chen-Guo; Lin, Guo-Qiang published the artcile< Regioselective Tandem C-H Alkylation/Coupling Reaction of ortho-Iodophenylethylenes via C,C-Pallada(II)cycles>, Quality Control of 89003-95-2, the main research area is styrene iodo regioselective diastereoselective alkylation nucleophilic substitution palladacycle pyridone.

Five-membered C,C-pallada(II)cycles are a unique class of diorganopalladium species with favorable stability and an electron-rich nature, leading to efficient sequential reactions with diverse electrophiles and nucleophiles. Specifically, the development of aryl-alkenyl-palladacycle-based transformations could provide an attractive approach with regio- and stereocontrol for the construction of multifunctionalized arylethylenes. However, currently, the C,C-pallada(II)cycle formation relies on a rigid skeleton or steric congestion in the backbone to promote cyclopalladation, and the formation of aryl-alkenyl-palladacycle without an α-substituent has not been achieved. Furthermore, reactions that could discriminate between the two sp2 carbon centers of such C(sp2),C(sp2)-palladacycle remain elusive. Herein, a regioselective three-component tandem alkylation/coupling reaction applicable for a variety of non-, α-, or β-substituted and α,β-disubstituted ortho-iodophenylethylenes is reported. Electron-rich 2-pyridone ligands are employed to enable the cyclopalladation process leading to aryl-alkenyl-palladacycle intermediates, of which the two C-Pd bonds are discriminated toward alkylation by their inherent steric and electronic differences. Good linear free-energy relationships between regio-/chemoselectivities and Hammett σ values are observed

ACS Catalysis published new progress about Alkylation catalysts, regioselective. 89003-95-2 belongs to class bromides-buliding-blocks, and the molecular formula is C8H4BrNO, Quality Control of 89003-95-2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Parhi, Biswajit; Gurjar, Jitendra; Pramanik, Suman; Midya, Abhisek; Ghorai, Prasanta published the artcile< Organocatalytic Enantioselective Intramolecular Oxa-Michael Reaction of Enols: Synthesis of Chiral Isochromenes>, Computed Properties of 89003-95-2, the main research area is isochromene enantioselective synthesis; oxa Michael reaction enol squaramide catalyst.

An unprecedented enantioselective intramol. oxa-Michael reaction of enols has been described. A squaramide-containing tertiary amine based bifunctional organocatalyst efficiently activates the o-homoformyl chalcones to provide the chiral isochromenes in moderate yields and good to excellent enantioselectivities. Further, late-stage functionalizations of the vinyl ether moiety of the chiral isochromene products have also been exemplified.

Journal of Organic Chemistry published new progress about Benzopyrans Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 89003-95-2 belongs to class bromides-buliding-blocks, and the molecular formula is C8H4BrNO, Computed Properties of 89003-95-2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Mu, Xingye; Yu, Hanxiao; Peng, Henian; Xiong, Wenrui; Wu, Ting; Tang, Wenjun published the artcile< Construction of Various Bridged Polycyclic Skeletons by Palladium-Catalyzed Dearomatization>, Recommanded Product: 4-Bromo-3-formylbenzonitrile, the main research area is tetracyclic arene chemoselective enantioselective preparation; aspernomine strychnochromine core ring system preparation; dracaenone analog preparation; palladium benzoxaphospholane catalyst dearomatization cyclization bromoaryl bicycle; enantioselective desymmetrization bromophenyl bromobenzyl bicycle palladium benzoxaphospholane catalyst; bridged tetracyclic systems; dearomative cyclization; homogeneous catalysis; monophosphorus ligands; palladium.

In the presence of [Pd(cinnamyl)Cl]2, an arylbenzoxaphospholane ligand, and K2CO3 in toluene, bromoaryl-substituted bicyclic phenols such as I underwent dearomative cyclization reactions to yield tetracyclic arenes such as II; a variety of ring systems with differing bridging patterns and carbocyclic and heterocyclic linkers were prepared using the method. The method was used to prepare partial ring systems for the alkaloids aspernomine and strychnochromine and to prepare dracaenone analogs. Bis(bromophenyl)- and bis(bromobenzyl)-substituted bicycles underwent enantioselective desymmetrization by dearomative cyclization using [Pd(cinnamyl)Cl]2 and nonracemic arylbenzoxaphospholane ligands to give bromoaryl- and bromobenzyl-substituted tetracycles in 33-99% ee (absolute configuration undetermined).

Angewandte Chemie, International Edition published new progress about Aryl bromides Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 89003-95-2 belongs to class bromides-buliding-blocks, and the molecular formula is C8H4BrNO, Recommanded Product: 4-Bromo-3-formylbenzonitrile.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Murugesan, Natesan; Gu, Zhengxiang; Fadnis, Leena; Tellew, John E.; Baska, Rose Ann F.; Yang, Yifan; Beyer, Sophie M.; Monshizadegan, Hossain; Dickinson, Kenneth E.; Valentine, Maria T.; Humphreys, W. Griffith; Lan, Shih-Jung; Ewing, William R.; Carlson, Kenneth E.; Kowala, Mark C.; Zahler, Robert; Macor, John E. published the artcile< Dual Angiotensin II and Endothelin A Receptor Antagonists: Synthesis of 2'-Substituted N-3-Isoxazolyl Biphenylsulfonamides with Improved Potency and Pharmacokinetics>, Synthetic Route of 89003-95-2, the main research area is angiotensin endothelin antagonist isoxazolyl biphenylsulfonamide preparation pharmacokinetics; antihypertensive synergism angiotensin endothelin antagonist isoxazolyl biphenylsulfonamide preparation pharmacokinetics.

In a previous report its was demonstrated that merging together key structural elements present in an AT1 receptor antagonist (irbesartan) with key structural elements in a biphenylsulfonamide ETA receptor antagonist followed by addnl. optimization provided a product which is a dual-action receptor antagonist (DARA), which potently blocked both AT1 and ETA receptors. Described herein are our efforts directed toward improving both the pharmacokinetic profile as well as the AT1 and ETA receptor potency of 4′-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′-biphenyl]-2-sulfonamide (I). Efforts centered on modifying the 2′-side chain of I and examining the (isoxazolyl)sulfonamide moiety in I. This effort resulted in the discovery of 4′-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′-(ethoxymethyl)[1,1′-biphenyl]-2-sulfonamide (II) as a highly potent second-generation DARA. This compound also showed substantially improved pharmacokinetic properties compared to I. In rats, DARA II reduced blood pressure elevations caused by i.v. infusion of Ang II or big ET-1 to a greater extent and with longer duration than DARA I or AT1 or ETA receptor antagonists alone. II clearly demonstrated superiority over irbesartan (an AT1 receptor antagonist) in the normal SHR model of hypertension in a dose-dependent manner, demonstrating the synergy of AT1 and ETA receptor blockade in a single mol. The crystal and mol. structures of II were reported.

Journal of Medicinal Chemistry published new progress about Angiotensin II receptor antagonists. 89003-95-2 belongs to class bromides-buliding-blocks, and the molecular formula is C8H4BrNO, Synthetic Route of 89003-95-2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Zhang, Xiaoyun; Yang, Yuan; Liang, Yun published the artcile< Palladium-catalyzed double N-arylation to synthesize multisubstituted dibenzoazepine derivatives>, Application of C8H4BrNO, the main research area is double arylation primary amine bisbromophenylethene palladium catalyst; dibenzoazepine preparation.

Palladium-catalyzed double N-arylation of primary amines with (Z)-1,2-bis(2-bromophenyl)ethenes was investigated. E.g., in presence of Pd2(dba)3 and DPEphos, double N-arylation of 4-FC6H4NH2 with (Z)-1,2-bis(2-bromophenyl)ethene gave 81% dibenzoazepine derivative (I). A variety of dibenzoazepine derivatives were synthesized in good to excellent yields.

Tetrahedron Letters published new progress about Arylation. 89003-95-2 belongs to class bromides-buliding-blocks, and the molecular formula is C8H4BrNO, Application of C8H4BrNO.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Cui, Guonan; Lai, Fangfang; Wang, Xiaoyu; Chen, Xiaoguang; Xu, Bailing published the artcile< Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as IDO1/TDO dual inhibitors>, Recommanded Product: 4-Bromo-3-formylbenzonitrile, the main research area is indole carboxylic acid preparation SAR mol docking; indoleamine tryptophan dioxygenase dual inhibitor; Dual inhibitors; Indole-2-carboxylic acid; Indoleamine 2,3-dioxygenase 1; Tryptophan 2,3-dioxygenase.

Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are involved in the key steps of tryptophan metabolism and are potential new targets for tumor immunotherapy. In this work, a variety of indole-2-carboxylic acid derivatives I (R1 = H, 7-F, NHAc, etc.; X = NH, NMe, S; Y = NH, S, -NHCH2-, etc.; Ar = 4-F-3-Cl-C6H3, 4-F-3-OMe-C6H3, 3-Cl-3-OMe-C6H3, etc.) were synthesized, and their inhibitory activities against both enzymes along with structure-activity relationships were investigated. As a result, a number of 6-acetamido-indole-2-carboxylic acid derivatives were found to be potent dual inhibitors with IC50 values at low micromolar levels. Among them, compound I (R1 = 6-NHAc, X = N, Y = NH, Ar = 3,4-di-F-C6H3) was the most potent inhibitor with an IC50 value of 1.17μM for IDO1, and 1.55μM for TDO, resp. In addition, a para-benzoquinone derivative II, resulted from the oxidation of compound I (R1 = 6-NHEt, X = NH, Y = NH, Ar = 4-F-3-Cl-C6H3), was also identified and it showed strong inhibition against the two enzymes with IC50 values at the double digit nanomolar level. Using mol. docking and mol. dynamic simulations, authors predicted the binding modes of this class of compounds within IDO1 and TDO binding pocket. The results provide insights for further structural optimization of this series of IDO1/TDO dual inhibitors.

European Journal of Medicinal Chemistry published new progress about Aromatic carboxylic acids Role: PAC (Pharmacological Activity), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), PREP (Preparation), USES (Uses). 89003-95-2 belongs to class bromides-buliding-blocks, and the molecular formula is C8H4BrNO, Recommanded Product: 4-Bromo-3-formylbenzonitrile.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Ravindra, Barnala; Das, Braja Gopal; Ghorai, Prasanta published the artcile< Organocatalytic, Enantioselective, Intramolecular Oxa-Michael Reaction of Alkoxyboronate: A New Strategy for Enantioenriched 1-Substituted 1,3-Dihydroisobenzofurans>, Computed Properties of 89003-95-2, the main research area is chalcone formyl pinacolborane squaramide organocatalyst reduction intramol oxa Michael; dihydroisobenzofuran stereoselective preparation.

An unprecedented strategy for the synthesis of enantioenriched 1-substituted 1,3-dihydroisobenzofurans via an enantioselective oxa-Michael reaction of o-alkoxyboronate containing chalcone has been accomplished employing cinchona alkaloid based squaramide bifunctional organocatalyst in the presence of proton source. The corresponding alkoxyboronate intermediates have been readily prepared in situ from o-formyl chalcones using neutral borane as hydride source and a tertiary amine moiety which is a counterpart of the catalyst.

Organic Letters published new progress about Aryl aldehydes Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 89003-95-2 belongs to class bromides-buliding-blocks, and the molecular formula is C8H4BrNO, Computed Properties of 89003-95-2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary