Day: October 17, 2022

Zhao, Yujun; Zhou, Bing; Bai, Longchuan; Liu, Liu; Yang, Chao-Yie; Meagher, Jennifer L.; Stuckey, Jeanne A.; McEachern, Donna; Przybranowski, Sally; Wang, Mi; Ran, Xu; Aguilar, Angelo; Hu, Yang; Kampf, Jeff W.; Li, Xiaoqin; Zhao, Ting; Li, Siwei; Wen, Bo; Sun, Duxin; Wang, Shaomeng published the artcile< Structure-Based Discovery of CF53 as a Potent and Orally Bioavailable Bromodomain and Extra-Terminal (BET) Bromodomain Inhibitor>, Synthetic Route of 118430-74-3, the main research area is pyrazole pyrimido indole preparation bromodomain inhibitor cancer.

We report the structure-based discovery of CF53 (28) as a highly potent and orally active inhibitor of bromodomain and extra-terminal (BET) proteins. By the incorporation of a NH-pyrazole group into the 9H-pyrimido[4,5-b]indole core, we identified a series of compounds that bind to BRD4 BD1 protein with Ki values of <1 nM and achieve low nanomolar potencies in the cell growth inhibition of leukemia and breast cancer cells. The most-promising compound, CF53, possesses excellent oral pharmacokinetic properties and achieves significant antitumor activity in both triple-neg. breast cancer and acute leukemia xenograft models in mice. Determination of the co-crystal structure of CF53 with the BRD4 BD1 protein provides a structural basis for its high binding affinity to BET proteins. CF53 is very selective over non-BET bromodomain-containing proteins. These data establish CF53 as a potent, selective, and orally active BET inhibitor, which warrants further evaluation for advanced preclin. development. Journal of Medicinal Chemistry published new progress about Antitumor agents. 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Synthetic Route of 118430-74-3.

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

Auwers, K. v.; Breyhan, Th. published the artcile< Further observations on alkylation and acylation of pyrazoles>, COA of Formula: C6H8N2O2, the main research area is .

3(5)- Methyl-5(3)-chloropyrazole with MeBr (8 hrs. at 100) gives 100% of the 1,3-di-Me derivative; CH2N2 gives largely the 1,3-di-Me derivative with some of the 1,5-isomer; the Na salt with Mel gives 100% of the 1,5-isomer. 3(5)- Phenylpyrazole (I) with MeBr (1 day at 100°) gives principally 1-methyl-3-phenylpyrazole, with some of the 5-Ph isomer; the Na salt with MeI yields 100% of the 5-Ph isomer. Excess ClCO2Me gives 1-carbomethoxy-3-phenylpyrazole (II), m. 76°. The Na derivative of BzCH:CHOH and MeO2CNHNH2 in dilute Et4OH give a nearly quant. yield of the carbomethoxyhydrazone of benzoylacetaldehyde, m. 152°; POCl3 in CHCl3 yields the 5-Ph isomer of II, m. 63-4°, with some II. I and SO2Cl2 give 4-chloro-5(3)- phenylpyrazole (III), b11 193°, m. 102°. 1-Methyl-4- chloro-3-phenylpyrazole (IV), pale brown, b9 163-5°; 5-Ph isomer (V), b12 153-6°. III and MeI with Na give about equal quantities of IV and V; Me2SO, in NaOH also give a mixture of the 2 isomers; MeBr gives essentially IV; CH2N2 reacts only slightly with III. II and SO2Cl2 give the 4-Cl derivative (VI), m. 89-90°; the 5-Ph isomer, m. 113-15°. III and ClCO2Me give VI. 3(5)-Methyl-5(3)-phenylpyrazole and MeBr (8 hrs. at 100°) give principally 1,5- dimethyl-3-phenylpyrazole, with some of the isomer; the Na salt with MeI gives the same products. 1-Carbomethoxy-3-phenyl-5-methylpyrazole, m. 74-5°; it is unchanged after heating with MeBr at 100° for 1 day; 4-Cl derivative, m. 107°. The carbomethoxyhydrazone of benzoylacetone, pale yellow, m. 121-2°; POCl3 gives 1-carbomethoxy-3-methyl-5-phenylpyrazole, m. 58-9°; 4-Cl derivative, m. 97°. Me pyrazole-3(5)-carboxylate, m. 139-40°; both MeBr and CH2N2 give principally Me 1-methylpyrazole-5-carboxylate, b9 73°, with a little of the 1,3-isomer, bg 120°. Me 5(3)-methylpyrazole-3(5)-carboxylate and CH2N2 give principally the 1,3-di-Me derivative, with some 1,5-isomer; the Et ester behaved similarly; there was no reaction with MeBr; MeI gives the almost pure 1,5-di- Me derivative; the Na salt with MeI gives principally the 1,3- isomer; EtI gives the 1-ethyl-5-methyl derivative; the salt with AcCl in C6H6 yields the 1-Ac derivative, m. 68.5-9.5°, and with ClCO2Me in Et2O the 1-MeO2C derivative Me 3(5)-phenylpyrazole-5(3)-carboxylate does not react with MeBr; with Mel it yields Me 1-methyl-3-phenylpyrazole 5-carboxylate; the Na salt and Mel in C6H6 give the same compound; the free ester or the Na salt and ClCO2Me yield a N-carbomethoxy derivative, m. 95°; the Et ester also does not react with EtBr; the Na salt and EtI give Et 1-ethyl-3- phenylpyrazole-5-carboxylate; the Na salt does not react with AcCl. 3(5)-Phenylpyrazole-5(3)-carboxylic acid (VII) and ClCO22Me give a N-carbomethoxy derivative, m. 126- 6.5°; with Cl the CO2Me group is split off. The 4-Cl derivative of VII m. 258-61°; it does not yield a CO2Me derivative

Journal fuer Praktische Chemie (Leipzig) published new progress about Acylation. 17827-61-1 belongs to class pyrazoles-derivatives, and the molecular formula is C6H8N2O2, COA of Formula: C6H8N2O2.

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

Broom, N. J. P.; Elder, J. S.; Hannan, P. C. T.; Pons, J. E.; O’Hanlon, P. J.; Walker, G.; Wilson, J.; Woodall, P. published the artcile< The chemistry of pseudomonic acid. Part 14. Synthesis and in vivo biological activity of heterocycle-substituted oxazole derivatives>, Electric Literature of 17827-61-1, the main research area is pseudomonic acid heterocycle oxazole derivative preparation; bactericide heterocycle oxazole derivative preparation.

Semisynthetic analogs of pseudomonic acid A were prepd containing a heterocycle-substituted oxazole. Derivatives in which the heterocycle was thiophene, furan, pyridine, or isoxazole showed good antibacterial potency and were further evaluated in vivo. Both pharmacokinetic parameters and oral activity against an exptl. i.p. sepsis were superior to results obtained from previously described pseudomonic acid A derivatives

Journal of Antibiotics published new progress about 17827-61-1. 17827-61-1 belongs to class pyrazoles-derivatives, and the molecular formula is C6H8N2O2, Electric Literature of 17827-61-1.

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

Dong, Xinrui; Jiang, Wenhua; Hua, Dexiang; Wang, Xiaohui; Xu, Liang; Wu, Xiaoxing published the artcile< Radical-mediated vicinal addition of alkoxysulfonyl/fluorosulfonyl and trifluoromethyl groups to aryl alkyl alkynes>, Safety of 1-(4-Bromophenyl)-1H-pyrazole, the main research area is trifluoromethylalkenylsulfonate ester sulfonyl fluoride preparation diastereoselective; aryl alkyl alkyne alkoxy fluorosulfonyl trifluoromethylation radical mediator.

The addition of sulfonyl radicals to alkenes and alkynes is a valuable method for constructing useful highly functionalized sulfonyl compounds The underexplored alkoxy- and fluorosulfonyl radicals are easily accessed by CF3 radical addition to readily available allylsulfonic acid derivatives and then β-fragmentation. These substituted sulfonyl radicals add to aryl alkyl alkynes to give vinyl radicals that are trapped by trifluoromethyl transfer to provide tetra-substituted alkenes bearing the privileged alkoxy- or fluorosulfonyl group on one carbon and a trifluoromethyl group on the other. This process exhibits broad functional group compatibility and allows for the late-stage functionalization of drug mols., demonstrating its potential in drug discovery and chem. biol. And alkyl allylsulfonates/allylsulfonyl fluoride.

Chemical Science published new progress about Alkynes, aryl Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation) (alkyl). 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

Perrocheau, Jacques; Carrie, Robert; Fleury, Jean-Pierre published the artcile< Thermal and photochemical evolution of triazolines obtained by addition of diazo compounds to methyl esters of oximino-malonodinitriles, oximino-cyanoacetates and oximino-malonates>, HPLC of Formula: 17827-61-1, the main research area is thermolysis triazoline; photolysis triazoline; triazoline thermolysis photolysis; aziridine.

Thermolysis of 1,2,3-triazolines I [R = Ts, COC6H4Z-4, Ac; R1 = H, Me, Ph, (MeO)2CH] leads to the corresponding aziridines only when X = Y = CO2Me, and then with a very low yield. However, photolysis or evolution in the presence of trifluoroacetic acid gives good results when carried out at sufficiently low temperature The thermolysis study of I shows a new route to 1,2,3-triazoline decomposition that has not yet been mentioned in the literature. The easy elimination of the p-toluenesulfonate or benzoate group explains this particular behavior.

Canadian Journal of Chemistry published new progress about Photolysis. 17827-61-1 belongs to class pyrazoles-derivatives, and the molecular formula is C6H8N2O2, HPLC of Formula: 17827-61-1.

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

Hilpert, Lukas J.; Sieger, Simon V.; Haydl, Alexander M.; Breit, Bernhard published the artcile< Palladium- and Rhodium-Catalyzed Dynamic Kinetic Resolution of Racemic Internal Allenes Towards Chiral Pyrazoles>, Synthetic Route of 13808-65-6, the main research area is pyrazole allene palladium rhodium catalyst chemoselective regioselective enantioselective hydroamination; alkenylpyrazole preparation; asymmetric catalysis; dynamic kinetic resolution; internal allenes; palladium; rhodium.

A complementing Pd- and Rh-catalyzed dynamic kinetic resolution (DKR) of racemic allenes leading to N-allylated pyrazoles was described. Such compounds are of enormous interest in medicinal chem. as certified drugs and potential drug candidates. The new methods feature high chemo-, regio- and enantioselectivities aside from displaying a broad substrate scope and functional group compatibility. A mechanistic rational accounting for allene racemization and trans-alkene selectivity was discussed.

Angewandte Chemie, International Edition published new progress about Aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Synthetic Route of 13808-65-6.

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

Saal, Christoph; Becker, Axel; Krier, Mireille; Fuchss, Thomas published the artcile< Atropisomerism - A Neglected Way to Escape Out of Solubility Flatlands>, Name: 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is atropisomer aqueous solubility enantiomers; ATM; ATM-inhibitor; Ataxia-telangiectasia mutated kinase; Atropisomerism; Chirality; Crystal structure; Dissolution; Kinase inhibitor; M4076; Solubility.

Low solubility of drugs represents a major challenge during research and development. Ways to overcome this are either focused on formulation development or optimization of the mol. structure of the drug. The latter is not only governed by the constitution of the mol. but also by its stereochem. Development of enantiomers in contrast to racemic mixtures has become the state of the art over the last decades as this leads to higher potency and selectivity. Thus, enantiopure drugs require lower doses compared to their racemates. Addnl., selecting one enantiomer also leads to improved solubility of the drug compared to its racemic compound While this effect is well known for enantiomers and racemic compounds where chirality is introduced via a chiral central atom, here we describe the first case where improved solubility is realized by selecting an axially chiral atropisomer.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about Atropisomers. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Name: 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

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

Song, Bao; Cao, Ningtao; Zhang, Jie; Xie, Jianwei published the artcile< Copper pyrithione (CuPT)-catalyzed/mediated amination and thioarylation of (hetero)aryl halides: A competition>, Electric Literature of 13788-92-6, the main research area is arylhalide pyrazole copper pyrithione catalyst amination coupling reaction; arylpyrazole preparation; copper pyrithione aryl halide thioarylation coupling reaction; aryl thiopyridineoxide preparation.

A facile method for the synthesis of N-arylheterocycles and di(hetero)aryl sulfides under mild condition was described. In these transformations, copper pyrithione (CuPT) was used as the copper catalyst for CN coupling, while served as catalyst and coupled partner for CS coupling with high yields and broad substrate tolerance. The S-arylation process was also utilized for the construction of valuable bioactive 2-sulfonylpyridine 1-oxide derivatives

Molecular Catalysis published new progress about Amination. 13788-92-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Electric Literature of 13788-92-6.

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

de Paz, Jose Luis G.; Elguero, Jose; Foces-Foces, Concepcion; Llamas-Saiz, Antonio L.; Aguilar-Parrilla, Francisco; Klein, Olivier; Limbach, Hans-Heinrich published the artcile< Theoretical study of the structure and tautomerism of N1-unsubstituted pyrazoles in the solid state>, Application In Synthesis of 13808-65-6, the main research area is pyrazole oligomer structure tautomerism MO.

Ab initio theor. calculations were performed on the pyrazole cyclic dimer, trimer and tetramers as well as on linear oligomers, assuming that there is no relaxation of the geometry during the proton transfer. The ground state and a wide variety of transition states, corresponding to different pathways for intermol. proton transfer, were explored, and the results compared with exptl. data from crystallog. and solid-state NMR spectroscopy. For the simplest case of the dimer, the reaction path corresponding to a double proton transfer was explored as well as the effect of relaxing the geometry.

Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry published new progress about Hartree-Fock method. 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Application In Synthesis of 13808-65-6.

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

Zhang, Jin; Peng, Ju-Fang; Wang, Tao; Kang, Yang; Jing, Sisi; Zhang, Zun-Ting published the artcile< Synthesis and biological evaluation of arylpyrazoles as fungicides against phytopathogenic fungi>, Related Products of 13808-65-6, the main research area is arylpyrazole synthesis fungicide phytopathogenic fungus; Antifungal; Arylpyrazoles; Phytopathogens fungi; Structure-activity relationship.

Abstract: 3-phenol-1H-pyrazoles (2), 4-halogeno-3-phenol-1H-pyrazoles (3) and 2-(1-phenol-1H-pyrazol-5-yl)phenols (4) were prepared by the condensation of (E)-3-(dimethylamino)-1-phenylprop-2-en-1-ones and hydrazine hydrate or phenylhydrazine in good yields. They were evaluated against five phytopathogens fungi, namely Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani and Fusarium solani in vitro. Most of the above-mentioned compounds exhibited activities. For example, 4-chloro-2-(1H-pyrazol-3-yl)phenol (3k) and 4-bromo-3-phenol-1H-pyrazole (3b) showed good and broad-spectrum antifungal properties against Cytospora sp., C. gloeosporioides, Botrytis cinerea, Alternaria solani and F. Solani with IC50 values ranging from 4.66 to 12.47 μg/mL. The results showed that pyrazoles with one aryl group at 3-position (2 and 3) exhibited better antibacterial activity than those with two aryl substituents (4). In addition, the existence of an electron-withdrawing group, a substituent on the ortho-position of phenol ring or a halogen atom at the 4-position of the pyrazole enhanced the antifungal activity of pyrazoles 2 and 3. Graphical Abstract: A series of arylpyrazole derivatives was facilely prepared and was evaluated against five phytopathogens fungi including Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani in vitro. Most of those compounds exhibited remarkable antifungal activities and were superior to the pos. control hymexazol. [Figure not available: see fulltext.].

Molecular Diversity published new progress about Alternaria solani. 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Related Products of 13808-65-6.

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