Category: 29027-20-1

Yu, Xiao-Long; Kuang, Liping; Chen, Su; Zhu, Xiao-Long; Li, Zhong-Liang; Tan, Bin; Liu, Xin-Yuan published the artcile< Counteranion-Controlled Unprecedented Diastereo- and Enantioselective Tandem Formal Povarov Reaction for Construction of Bioactive Octahydro-Dipyrroloquinolines>, SDS of cas: 29027-20-1, the main research area is metal phosphate catalyst counteranion stereoselective tandem formal Povarov reaction; octahydro dipyrroloquinoline stereoselective preparation antiproliferative activity.

The asym. inverse-electron-demand hetero-Diels-Alder (IEHDA) reactions of imines and dienophiles have emerged as an attractive tool for derivatizing optically active complex azaheterocycles. In comparison, such reactions involving iminium ions remain great challenges because of low association of iminium ions with neutral catalytic centers. To overcome this, we report a metal-phosphate-catalyzed asym. tandem hydroamination/formal Povarov reaction of secondary aminoalkynes via a chiral counteranion-controlled iminium ion intermediate strategy. Critical to the success of this challenging strategy was chiral phosphate as an ion pair to achieve counteranion-controlled asym. reaction of in situ-generated iminium ions. This method enables a convenient, powerful, and atom-economical access to tetracyclic octahydro-dipyrroloquinoline frameworks bearing multiple contiguous stereogenic centers in good yields with diastereo- and enantioselectivities, from acyclic starting materials, and the catalyst loadings could be as low as 1 mol %. The asym. cross-coupling reaction of different aminoalkynes has further been demonstrated with good results. Furthermore, this methodol. was applied to enantioselective synthesis of incargranine B aglycon epimer in only two steps. The reaction is demonstrated to proceed through a stepwise process for formal Povarov reaction.

ACS Catalysis published new progress about Alkynyl compounds, alkynyl amines Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 29027-20-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H8ClN, SDS of cas: 29027-20-1.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Khadse, Saurabh C.; Talele, Gokul S.; Agrawal, Surendra S. published the artcile< Aminocarbonyl Arylvinylbenzamides as Gastric Sparing Anti-inflammatory Agents>, HPLC of Formula: 29027-20-1, the main research area is aminocarbonyl arylvinylbenzamide preparation antiinflammatory gastrotoxicity gastrointestinal ulcer hypermotility.

Some (E/Z)-aminocarbonyl arylvinylbenzamides (B1-B15) were synthesized, evaluated for anti-inflammatory activity and ulcerogenic tendency, and their effect on gastro-intestinal motility in the rats was studied. These benzamides comprising of aliphatic unsaturated region situated between two amide linkages were synthesized by nucleophilic ring opening of appropriate az-lactones (AZ1-AZ4) by suitable amines. The characterization of newly synthesized benzamides was performed by IR, 1H- and 13C-NMR, mass and elemental anal. Amongst the tested compounds, benzamide B1, B2, B4, B5, and B13 were able to produce comparable or superior anti-inflammatory activity at 10 and 20 mg/kg p.o. dose with respect to standard diclofenac in carrageenan induced rat paw edema model with lessened propensity to cause gastro-intestinal hypermotility and were found to have nil tendencies to generate gastric ulcers.

Archiv der Pharmazie (Weinheim, Germany) published new progress about Anti-inflammatory agents. 29027-20-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H8ClN, HPLC of Formula: 29027-20-1.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Grella, Melissa Phelps; Danso-Danquah, Richmond; Safo, Martin K.; Joshi, Gajanan S.; Kister, Jean; Marden, Michael; Hoffman, Stephen J.; Abraham, Donald J. published the artcile< Synthesis and Structure-Activity Relationships of Chiral Allosteric Modifiers of Hemoglobin>, Electric Literature of 29027-20-1, the main research area is chiral allosteric modifier Hb preparation; structure activity aryloxyalkanoicacid preparation Hb.

A series of allosteric effectors of Hb, 2-(aryloxy)-2-alkanoicacids, was prepared to investigate the effect of the stereocenter on allosteric activity. The chiral analogs were based on the lead compound, RSR13, with different alkyl/alkanoic and cycloalkyl/cycloalkanoic groups positioned at the acidic chiral center. Of the 23 racemic mols. synthesized, 5 were selected for resolution based on structure-activity relationships. One chiral analog, (-)-(1R,2R)-1-[4-[[(3,5-dimethylanilino)carbonyl]methyl]phenoxy]-2-methylcyclopentanecarboxylic acid (I), exhibited greater in vitro activity in Hb solutions than its antipode, racemate, and RSR13. Compound I was equipotent with RSR13 in whole blood, is a candidate for in vivo animal studies, and if efficacious and safe has a potential for use in humans. In general, it was found that chirality affects allosteric effector activity with measurable differences observed between enantiomers and the racemates.

Journal of Medicinal Chemistry published new progress about Chirality. 29027-20-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H8ClN, Electric Literature of 29027-20-1.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Li, Liang; Yang, Dongfeng; Zhao, Zhongrui; Song, Yongkang; Zhao, Lei; Liu, Rui; Liu, Guohua published the artcile< Boron tetrafluoride anion bonding dual active species within a large-pore mesoporous silica for two-step successive organic transformaion to prepare optically pure amino alcohols>, Category: chlorides-buliding-blocks, the main research area is boron tetrafluoride mesoporous silica amino alc organic transformaion preparation; anion bonding; asymmetric catalysis; heterogeneous catalyst; silica; tandem reaction.

Development of a simple and easy handing process for preparation of multifunctional heterogenous catalysts and exploration of their applications in sequential organic transformation are of great significance in heterogeneous asym. catalysis. Herein, through the utilization of a BF4- anion-bonding strategy, we anchor conveniently both organic bases and chiral ruthenium complex into the nanopores of Me-FDU-12, fabricating a Lewis base/Ru bifunctional heterogeneous catalyst. As we envisaged, cyclic amine as a Lewis base promotes an intermol. aza-Michael addition between enones and arylamines, affording γ-secondary amino ketones featuring with aryl motif, whereas ruthenium/diamine species as catalytic promoter boosts an asym. transfer hydrogenation of γ-secondary amino ketones to γ-secondary amino alcs. As expected, both enhance synergistically the aza-Michael addition/asym. transfer hydrogenation one-pot enantioselective organic transformation, producing chiral γ-secondary amino alcs. with up to 98% enantioselectivity. Unique features, such as operationally simple one-step synthesis of heterogeneous catalyst, homo-like catalytic environment as well as green sustainable process make this heterogeneous catalyst an attracting in a practical preparation of optically pure pharmaceutical intermediates of antidepressants.

Frontiers in Chemistry (Lausanne, Switzerland) published new progress about Aza-Michael reaction catalysts. 29027-20-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H8ClN, Category: chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Zhuang, Xiaohui; Shi, Xiayue; Zhu, Rui; Sun, Bin; Su, WeiKe; Jin, Can published the artcile< Photocatalytic intramolecular radical cyclization involved synergistic SET and HAT: synthesis of 3,3-difluoro-γ-lactams>, Synthetic Route of 29027-20-1, the main research area is difluoro lactam preparation regioselective; allyl propargyl bromo difluoro arylacetamide photocatalytic intramol radical cyclization.

A mild and metal-free protocol for visible-light induced intramol. radical cyclization of N-allyl(propargyl)-2-bromo-2,2-difluoro-N-arylacetamide was developed. This strategy showed excellent regioselectivity and simple operation to synthesize 4-substituted 3,3-difluoro-γ-lactams I [R1 = Ph, 4-FC6H4, 3,5-di-MeC6H3, etc.; R2 = H, Me; R3 = H, Me, CO2Me, etc.; R4 = H, 4-MeOC6H4; X = (CHR4)n; n = 1, 2] and II [R4 = H, Me, Et] with a broad substrate scope. Moreover, mechanistic studies revealed that this transformation proceeded through a cascade radical-type cyclization and hydrogen atom transfer process with PMDETA as a hydrogen-atom donor.

Organic Chemistry Frontiers published new progress about Amides Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation) (allyl). 29027-20-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H8ClN, Synthetic Route of 29027-20-1.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Roy, Sudeshna; Sileikyte, Justina; Schiavone, Marco; Neuenswander, Benjamin; Argenton, Francesco; Aube, Jeffrey; Hedrick, Michael P.; Chung, Thomas D. Y.; Forte, Michael A.; Bernardi, Paolo; Schoenen, Frank J. published the artcile< Discovery, Synthesis, and Optimization of Diarylisoxazole-3-carboxamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore>, Application In Synthesis of 29027-20-1, the main research area is diarylisoxazole carboxamide preparation mitochondrial permeability transition pore inhibitor human; structure activity relationship; calcium retention capacity; mitochondria; muscular dystrophy; permeability transition; zebrafish.

The mitochondrial permeability transition pore (mtPTP) is a Ca2+-requiring mega-channel which, under pathol. conditions, leads to the deregulated release of Ca2+ and mitochondrial dysfunction, ultimately resulting in cell death. Although the mtPTP is a potential therapeutic target for many human pathologies, its potential as a drug target is currently unrealized. Herein, an optimization effort initiated around hit, 5-(3-hydroxyphenyl)-N-(3,4,5-trimethoxyphenyl)isoxazole-3-carboxamide, which was found to possess promising inhibitory activity against mitochondrial swelling (EC50<0.39 M) and showed no interference on the inner mitochondrial membrane potential (rhodamine 123 uptake EC50>100 M) is described. This enabled the construction of a series of picomolar mtPTP inhibitors that also potently increase the calcium retention capacity of the mitochondria. Finally, the therapeutic potential and in vivo efficacy of one of the most potent analogs, N-(3-chloro-2-methylphenyl)-5-(4-fluoro-3-hydroxyphenyl)isoxazole-3-carboxamide, was validated in a biol. relevant zebrafish model of collagen VI congenital muscular dystrophies.

ChemMedChem published new progress about Aromatic amines Role: RCT (Reactant), RACT (Reactant or Reagent). 29027-20-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H8ClN, Application In Synthesis of 29027-20-1.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Sisco, Edward; Barnes, Korry L. published the artcile< Design, Synthesis, and Biological Evaluation of Novel 1,3-Oxazole Sulfonamides as Tubulin Polymerization Inhibitors>, Application In Synthesis of 29027-20-1, the main research area is oxazolyl sulfonamide preparation antitumor SAR tubulin polymerization inhibitor; cyclopropyl oxazolyl benzenesulfonyl chloride amine coupling reaction.

A series of novel 1,3-oxazole sulfonamides I (R = 4-FC6H4NH2, -CH2CH2SO2Me, 1-Naph, etc; R’ = H, Me)were constructed and screened for their potential to inhibit cancer cell growth. These compounds were evaluated against the full NCI-60 human tumor cell lines, with the majority exhibiting promising overall growth inhibitory properties. They displayed high specificity within the panel of leukemia cell lines vs. all other lines tested. When examined in the dose-response assay, GI50 values fell within the low micromolar to nanomolar ranges. 1,3-Oxazole sulfonamide I (R = 4-Cl-3-CF3C6H3NH2, R’ = H) displayed the best average growth inhibition, whereas the 2-chloro-5-methylphenyl and 1-naphthyl substituents on the sulfonamide nitrogen proved to be the most potent leukemia inhibitors with mean GI50 values of 48.8 and 44.7 nM, resp. In vitro tubulin polymerization experiments revealed that this class of compounds effectively binds to tubulin and induces the depolymerization of microtubules within cells.

ACS Medicinal Chemistry Letters published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 29027-20-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H8ClN, Application In Synthesis of 29027-20-1.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Tilekar, Kalpana; Hess, Jessica D.; Upadhyay, Neha; Schweipert, Markus; Flath, Felix; Gutierrez, Denisse A.; Loiodice, Fulvio; Lavecchia, Antonio; Meyer-Almes, Franz-Josef; Aguilera, Renato J.; Ramaa, C. S. published the artcile< HDAC4 Inhibitors with Cyclic Linker and Non-hydroxamate Zinc Binding Group: Design, Synthesis, HDAC Screening and in vitro Cytotoxicity evaluation.>, Application of C7H8ClN, the main research area is HDAC inhibitor screening cytotoxicity cyclic linker nonhydroxamate zinc binding.

Recent evidences highlight the usefulness of small mol. (Histone deacetylase 4) HDAC4 inhibitors in the several preclin. paradigms. Major toxicity and mutagenicity issues associated with hydroxamate HDAC inhibitors, stimulated us to develop potent non-hydroxamate inhibitors. In the present work a novel series of thiazolidinedione (TZD) derivatives with pyridine as cyclic linker and TZD ring as zinc binding group was designed and screened in a panel of isoenzymes of HDACs, wherein the most potent compounds exhibiting HDAC4 IC50-values<5 μM were 5 v, 5 w, 5 y and 5 z (IC50=4.2±1 μM, 0.75±0.03 μM, 4.9±0.5 and 2.3±0.5 μM, resp.). The docking studies displayed the unique binding mode of this series of compound at active site of HDAC4, wherein TZD ring was indicated as zinc binding group. Further, 5 w and 5 y were found as the most potent antiproliferative agent in lymphoblastic leukemia (CCRF-CEM) and breast cancer MDA-MB-231 cells. Compound 5 y was found to induce the apoptosis and DNA fragmentation of CEM cells. The western blotting anal. of 5 y also showed the presence of cleaved caspases supporting their apoptotic nature. Further, Class IIa (HDAC4) selectivity of 5 y was also supported by western blotting observations, wherein 5 y caused the accumulation of acetylated H3 but not of acetylated Tubulin. Thus, our findings endorse the further investigation of this series of compounds for their potential as targeted cancer therapeutic agents. ChemistrySelect published new progress about Acetylated histone H3 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 29027-20-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H8ClN, Application of C7H8ClN.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Du, Guangyan; Rao, Suman; Gurbani, Deepak; Henning, Nathaniel J.; Jiang, Jie; Che, Jianwei; Yang, Annan; Ficarro, Scott B.; Marto, Jarrod A.; Aguirre, Andrew J.; Sorger, Peter K.; Westover, Kenneth D.; Zhang, Tinghu; Gray, Nathanael S. published the artcile< Structure-Based Design of a Potent and Selective Covalent Inhibitor for SRC Kinase That Targets a P-Loop Cysteine>, Application of C7H8ClN, the main research area is drug target design SRC kinase inhibitor antitumor.

SRC is a major regulator of many signaling pathways and contributes to cancer development. However, development of a selective SRC inhibitor has been challenging, and FDA-approved SRC inhibitors, dasatinib and bosutinib, are multi-targeted kinase inhibitors. Here, we describe our efforts to develop a selective SRC covalent inhibitor by targeting cysteine 277 on the P-loop of SRC. Using a promiscuous covalent kinase inhibitor (CKI) SM1-71 as a starting point, we developed covalent inhibitor 15a, which discriminates SRC from other covalent targets of SM1-71 including TAK1 and FGFR1. As an irreversible covalent inhibitor, compound 15a exhibited sustained inhibition of SRC signaling both in vitro and in vivo. Moreover, 15a exhibited potent antiproliferative effects in nonsmall cell lung cancer cell lines harboring SRC activation, thus providing evidence that this approach may be promising for further drug development efforts.

Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 29027-20-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H8ClN, Application of C7H8ClN.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Gao, Mingshan; Duan, Lei; Luo, Jinfeng; Zhang, Lianwen; Lu, Xiaoyun; Zhang, Yan; Zhang, Zhang; Tu, Zhengchao; Xu, Yong; Ren, Xiaomei; Ding, Ke published the artcile< Discovery and Optimization of 3-(2-(Pyrazolo[1,5-a]pyrimidin-6-yl)ethynyl)benzamides as Novel Selective and Orally Bioavailable Discoidin Domain Receptor 1 (DDR1) Inhibitors>, Safety of 3-Chloro-5-methylaniline, the main research area is pyrazolopyrimidinylethynylbenzamide preparation discoidin domain receptor 1 inhibitor; antitumor activity pharmacokinetics pyrazolopyrimidine substituted ethynylbenzamide.

Discoidin domain receptor 1 (DDR1) is an emerging potential mol. target for new anticancer drug discovery. The authors have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (I and II) inhibited the enzymic activity of DDR1, with IC50 values of 6.8 and 7.0 nM, resp., but were significantly less potent in suppressing the kinase activities of DDR2, Bcr-Abl, and c-Kit. Further study revealed that I bound with DDR1 with a Kd value of 0.6 nM, while it was significantly less potent to the other 455 kinases tested. The S(35) and S(10) selectivity scores of I were 0.035 and 0.008, resp. The compounds also potently inhibited the proliferation of cancer cells expressing high levels of DDR1 and strongly suppressed cancer cell invasion, adhesion, and tumorigenicity. Preliminary pharmacokinetic studies suggested that they possessed good PK profiles, with oral bioavailabilities of 67.4% and 56.2%, resp.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 29027-20-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H8ClN, Safety of 3-Chloro-5-methylaniline.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics