Month: October 2022

Chen, Deheng; Lu, Tian; Yan, Ziqin; Lu, Wenchao; Zhou, Feilong; Lyu, Xilin; Xu, Biling; Jiang, Hualiang; Chen, Kaixian; Luo, Cheng; Zhao, Yujun published the artcile< Discovery, structural insight, and bioactivities of BY27 as a selective inhibitor of the second bromodomains of BET proteins>, SDS of cas: 118430-74-3, the main research area is benzodiazepine BET bromodomain BD2 protein inhibitor preparation cancer; BD2; BET protein; Bromodomain; Crystal structure; Selective.

Recently, selective inhibition of BET BD2 is emerging as a promising strategy for drug discovery. Despite significant progress in this area, systematic studies of selective BET BD2 inhibitors are still few. In this study, we report the discovery of a potent and selective BET BD2 inhibitor BY27 (47). Our high resolution co-crystal structures of 47/BRD2 BD1 and BD2 showed that the triazole group of 47, water mols., H433 and N429 in BRD2 BD2 established a water-bridged H-bonding network, which is responsible for the observed selectivities. DNA microarray anal. of HepG2 cells treated with 47 or OTX015 demonstrated the transcriptome impact differences between a BET BD2 selective inhibitor and a pan BET inhibitor. In a MV4-11 mouse xenograft model, 47 caused 67% of tumor growth inhibition and was less toxic than a pan BET inhibitor 1 at high doses. We conclude that the improved safety profile of selective BET BD2 inhibitors warrant future studies in BET associated diseases.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, SDS of cas: 118430-74-3.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Huang, He; Strater, Zack M.; Rauch, Michael; Shee, James; Sisto, Thomas J.; Nuckolls, Colin; Lambert, Tristan H. published the artcile< Electrophotocatalysis with a trisaminocyclopropenium radical dication>, Computed Properties of 13788-92-6, the main research area is radical dication trisaminocyclopropenium photoelectrochem catalyst; C−H functionalization; Electrophotocatalysis; oxidation; radical dication; trisaminocyclopropenium ion.

Visible-light photocatalysis and electrocatalysis are two powerful strategies for the promotion of chem. reactions. Here, these two modalities are combined in an electrophotocatalytic oxidation platform. This chem. employs a trisaminocyclopropenium (TAC) ion catalyst, which is electrochem. oxidized to form a cyclopropenium radical dication intermediate. The radical dication undergoes photoexcitation with visible light to produce an excited-state species with oxidizing power (3.33 V vs. SCE) sufficient to oxidize benzene and halogenated benzenes via single-electron transfer (SET), resulting in C-H/N-H coupling with azoles. A rationale for the strongly oxidizing behavior of the photoexcited species is provided, while the stability of the catalyst is rationalized by a particular conformation of the cis-2,6-dimethylpiperidine moieties.

Angewandte Chemie, International Edition published new progress about C-H bond activation. 13788-92-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Computed Properties of 13788-92-6.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Tan, Yun-Xuan; Liu, Xing-Yu; Zhang, Shuo-Qing; Xie, Pei-Pei; Wang, Xin; Feng, Kai-Rui; Yang, Shao-Qian; He, Zhi-Tao; Hong, Xin; Tian, Ping; Lin, Guo-Qiang published the artcile< An unconventional trans-exo-selective cyclization of alkyne-tethered cyclohexadienones initiated by rhodium(III)-catalyzed C-H activation via insertion relay>, Computed Properties of 13788-92-6, the main research area is rhodium carbon hydrogen activation catalysis alkyne cyclohexadienone cyclization.

Different from the established trans-endo-selective cyclization of alkyne-tethered electrophiles that involve an E/Z isomerization process, herein, the authors present a novel strategy to allow trans-exo-selective arylative cyclization of 1,6-enynes. Through initiation of rhodium(III)-catalyzed C-H activation, a diverse range of N-heterocyclic directing groups, including pyridine, pyrazole, imidazo[1,2-a] pyridine, benzoxazole, benzothiazole, and purine, was feasible for the cascade transformation, exhibiting high efficiency (up to 92% yield), broad substrate scope, and excellent functional group compatibility. Moreover, the modification of natural products and pharmaceutical compounds was also demonstrated to showcase its synthetic utility. Based on d. functional theory (DFT) calculations, a key three-membered ring intermediate through the insertion relay, rather than the direct E/Z isomerization of alkenyl rhodium species, controlled the stereochem. outcome for this trans-exo-selective cyclization. The subsequent ring-opening protonation of the more favored rotamer led to exclusive trans-exo-selectivity.

CCS Chemistry published new progress about C-H bond activation. 13788-92-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Computed Properties of 13788-92-6.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Poslusney, Michael S.; Melancon, Bruce J.; Gentry, Patrick R.; Sheffler, Douglas J.; Bridges, Thomas M.; Utley, Thomas J.; Daniels, J. Scott; Niswender, Colleen M.; Conn, P. Jeffrey; Lindsley, Craig W.; Wood, Michael R. published the artcile< Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: The continued optimization of an MLPCN probe molecule>, Related Products of 1046832-21-6, the main research area is spirocycle preparation SAR human rat muscarinic M1 receptor selectivity; pos allosteric modulator SAR spirocycle MLPCN probe mol.

This Letter describes the further optimization of an MLPCN probe mol. (ML137) through the introduction of 5- and 6-membered spirocycles in place of the isatin ketone. Interestingly divergent structure-activity relationships, when compared to earlier M1 PAMs, are presented. These novel spirocycles, e.g. I, possess improved efficacy relative to ML137, while also maintaining high selectivity for the human and rat muscarinic M1 receptor subtype.

Bioorganic & Medicinal Chemistry Letters published new progress about Homo sapiens. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Related Products of 1046832-21-6.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Liu, Haidong; Ge, Liang; Wang, Ding-Xing; Chen, Nan; Feng, Chao published the artcile< Photoredox-Coupled F-Nucleophilic Addition: Allylation of gem-Difluoroalkenes>, Safety of 1-(4-Bromophenyl)-1H-pyrazole, the main research area is homoallylic trifluoromethane preparation; gem difluoroalkene photoredox coupled fluoroallylation; allylic compounds; fluorine; photochemistry; radicals; reaction mechanisms.

A novel strategy for the expedient construction of CF3-embeded tertiary/quaternary carbon centers was developed by taking advantage of photoredox catalysis. Thanks to a key step of single-electron oxidation, electron-rich gem-difluoroalkenes, which otherwise are essentially reluctant towards F-nucleophilic addition, now readily participate in this fluoroallylation reaction. Furthermore, this strategy provides an elegant example for the generation, as well as functionalization, of α-CF3-substituted benzylic radical intermediates using cheap and readily available starting materials.

Angewandte Chemie, International Edition published new progress about Allylation (fluoro). 13788-92-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Safety of 1-(4-Bromophenyl)-1H-pyrazole.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Olsen, Kathryn L.; Jensen, Matthew R.; MacKay, James A. published the artcile< A mild halogenation of pyrazoles using sodium halide salts and Oxone>, Name: 4-Bromo-3-phenyl-1H-pyrazole, the main research area is pyrazole halogenation sodium halide oxone green chem.

A mild, inexpensive, and operationally simple pyrazole halogenation method utilizing Oxone and sodium halide salts is reported. This work documents 17 examples of alkyl, aryl, allyl, and benzyl substituted 4-chloro and 4-bromopyrazoles, obtained in up to 93% yield. Reactions are performed in water under ambient conditions and generation of organic byproducts is avoided.

Tetrahedron Letters published new progress about Alkali metal halides, sodium halides Role: RGT (Reagent), RACT (Reactant or Reagent). 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Name: 4-Bromo-3-phenyl-1H-pyrazole.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Osawa, Akio; Kaiho, Terumitsu; Ito, Takashi; Okada, Mamiko; Kawabata, Chikako; Yamaguchi, Kentaro; Igeta, Hiroshi published the artcile< Reactions of N-aminopyrazoles with halogenating reagents and synthesis of 1,2,3-triazines>, Product Details of C9H7BrN2, the main research area is triazine; pyrazolamine reaction halogenating agent; ring expansion aminopyrazole.

Reactions of N-aminopyrazoles with halogenating reagents (Cl2, Br2, I2, BrCl, ICl, IBr, N-chlorosuccinimide, and N-bromosuccinimide) were examined Some of these reagents preferentially leas to oxidation of the amino group to give the corresponding 1,2,3-triazines as major products, while others mainly gave either or both of 1-amino-4-halopyrazoles and 5-halo-1,2,3-triazines as the result of halogenation of the 4-position of the pyrazole ring prior to the oxidation of the amino group. In some cases, the oxidation of the amino group and the halogenation of the pyrazole ring proceeded concurrently to form not only the unhalogenated triazines but also the 1-amino-4-halopyrazines and the 5-halotriazines. Various reagents and reaction conditions were explored to utilize the reaction for the synthesis of halogenated and unhalogenated 1,2,3-triazines.

Chemical & Pharmaceutical Bulletin published new progress about Halogenation. 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Product Details of C9H7BrN2.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Schulte, James P. II; Tweedie, Scott R. published the artcile< Palladium-catalyzed couplings of heteroaryl amines with aryl halides using sodium phenolate as the stoichiometric base>, Category: pyrazoles-derivatives, the main research area is microwave mediated palladium catalyzed coupling heteroaryl amine aryl halide; pyrazole pyridine pyrazine isoxazole arylamino preparation.

Heteroaryl amines are efficiently coupled (in two hours) to aryl halides with catalytic Pd2(dba)3 and Xantphos to provide the corresponding biaryl amines under microwave and standard thermal conditions. E.g., 3-tert-butyl-1-methyl-1H-pyrazol-5-amine reacts with p-bromobenzonitrile in the presence of 1.25 mol% Pd2(dba)3, 3 mo% Xantphos ligand and 1,5 equivalent NaOPh/dioxane under microwave conditions to give 91% yield of biarylamine I. The use of organic-soluble Na phenolate (NaOPh) as the stoichiometric base promotes facile coupling of a variety of substrates in excellent yields.

Synlett published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent) (heteroaryl). 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Category: pyrazoles-derivatives.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Foces-Foces, Concepcion; Alkorta, Ibon; Elguero, Jose published the artcile< Supramolecular structure of 1H-pyrazoles in the solid state: a crystallographic and ab initio study>, Formula: C9H7BrN2, the main research area is pyrazole derivative supramol structure solid state ab initio.

The secondary structure of 1H-unsubstituted pyrazole derivatives bearing only one hydrogen-donor group and one or more acceptor groups has been analyzed in terms of some descriptors representing the substituents at C3 and C5. The substituent at C4 appears to affect mainly the tertiary or quaternary structure of these compounds The proposed semi-quant. model, which explains most hydrogen-bonded motifs as a combination of the effects of substituents at C3 and C5, has also been examined as a function of the steric and polarizability effects of these substituents represented by molar refractivity. The model also applies to other five-membered rings (1,2,4-triazoles, 1,2,4-diazaphospholes and 1,2,4-diazaarsoles). Furthermore, ab initio calculations at RHF/6-31G* have been performed to discover the relative stability of three of the four hydrogen-bond patterns displayed by several sym. pyrazoles (dimers, trimers, tetramers). The fourth motif, catemers, has only been discussed geometrically.

Acta Crystallographica, Section B: Structural Science published new progress about Density functional theory. 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Formula: C9H7BrN2.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Gopalsamy, Ariamala; Aulabaugh, Ann E.; Barakat, Amey; Beaumont, Kevin C.; Cabral, Shawn; Canterbury, Daniel P.; Casimiro-Garcia, Agustin; Chang, Jeanne S.; Chen, Ming Z.; Choi, Chulho; Dow, Robert L.; Fadeyi, Olugbeminiyi O.; Feng, Xidong; France, Scott P.; Howard, Roger M.; Janz, Jay M.; Jasti, Jayasankar; Jasuja, Reema; Jones, Lyn H.; King-Ahmad, Amanda; Knee, Kelly M.; Kohrt, Jeffrey T.; Limberakis, Chris; Liras, Spiros; Martinez, Carlos A.; McClure, Kim F.; Narayanan, Arjun; Narula, Jatin; Novak, Jonathan J.; O’Connell, Thomas N.; Parikh, Mihir D.; Piotrowski, David W.; Plotnikova, Olga; Robinson, Ralph P.; Sahasrabudhe, Parag V.; Sharma, Raman; Thuma, Benjamin A.; Vasa, Dipy; Wei, Liuqing; Wenzel, A. Zane; Withka, Jane M.; Xiao, Jun; Yayla, Hatice G. published the artcile< PF-07059013: A Noncovalent Modulator of Hemoglobin for Treatment of Sickle Cell Disease>, Reference of 936250-20-3, the main research area is pf07059013 noncovalent Hb modulator sickle cell disease.

Sickle cell disease (SCD) is a genetic disorder caused by a single point mutation (β6 Glu → Val) on the β-chain of adult Hb (HbA) that results in sickled Hb (HbS). In the deoxygenated state, polymerization of HbS leads to sickling of red blood cells (RBC). Several downstream consequences of polymerization and RBC sickling include vaso-occlusion, hemolytic anemia, and stroke. We report the design of a noncovalent modulator of HbS, clin. candidate PF-07059013 (23). The seminal hit mol. was discovered by virtual screening and confirmed through a series of biochem. and biophys. studies. After a significant optimization effort, we arrived at 23, a compound that specifically binds to Hb with nanomolar affinity and displays strong partitioning into RBCs. In a 2-wk multiple dose study using Townes SCD mice, 23 showed a 37.8% (±9.0%) reduction in sickling compared to vehicle treated mice. 23 (PF-07059013) has advanced to phase 1 clin. trials.

Journal of Medicinal Chemistry published new progress about Crystal structure. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Reference of 936250-20-3.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics