Day: October 14, 2022

Kumar, Rahul; Turcaud, Serge; Micouin, Laurent published the artcile< The Reaction of Dimethylalkynylaluminum Reagents with Trimethylsilyldiazomethane: Original Reactivity Leading to New α-Silylated Alkynyl Hydrazones>, Electric Literature of 13808-65-6, the main research area is methylalkynylaluminum reaction silyldiazomethane preparation silylated alkynyl hydrazone.

Trimethylsilyldiazomethane does not react as a homologating reagent but as a C-electrophilic species with dimethylalkynylaluminum reagents. This unprecedented reactivity enables a simple access to unusual α-silylated alkynyl hydrazones.

Organic Letters published new progress about Alkynes Role: RCT (Reactant), RACT (Reactant or Reagent) (aluminated). 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Electric Literature of 13808-65-6.

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

Drew, Samuel L.; Thomas-Tran, Rhiannon; Beatty, Joel W.; Fournier, Jeremy; Lawson, Kenneth V.; Miles, Dillon H.; Mata, Guillaume; Sharif, Ehesan U.; Yan, Xuelei; Mailyan, Artur K.; Ginn, Elaine; Chen, Jie; Wong, Kent; Soni, Divyank; Dhanota, Puja; Chen, Pei-Yu; Shaqfeh, Stefan G.; Meleza, Cesar; Pham, Amber T.; Chen, Ada; Zhao, Xiaoning; Banuelos, Jesus; Jin, Lixia; Schindler, Ulrike; Walters, Matthew J.; Young, Stephen W.; Walker, Nigel P.; Leleti, Manmohan Reddy; Powers, Jay P.; Jeffrey, Jenna L. published the artcile< Discovery of Potent and Selective PI3Kγ Inhibitors>, Name: 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is PI3K gamma inhibitors ATP binding site SAR hydrogen bond.

The selective inhibition of the lipid signaling enzyme PI3Kγ constitutes an opportunity to mediate immunosuppression and inflammation within the tumor microenvironment but is difficult to achieve due to the high sequence homol. across the class I PI3K isoforms. Here, we describe the design of a novel series of potent PI3Kγ inhibitors that attain high isoform selectivity through the divergent projection of substituents into both the “”selectivity”” and “”alkyl-induced”” pockets within the ATP (ATP) binding site of PI3Kγ. These efforts have culminated in the discovery of 5-[2-amino-3-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl]-2-[(1S)-1-cyclopropylethyl]-7-(trifluoromethyl)-2,3-dihydro-1H-isoindol-1-one (4(I), IC50 = 0.064 μM, THP-1 cells), which displays >600-fold selectivity for PI3Kγ over the other class I isoforms and is a promising step toward the identification of a clin. development candidate. The structure-activity relationships identified throughout this campaign demonstrate that greater γ-selectivity can be achieved by inhibitors that occupy an “”alkyl-induced”” pocket and possess bicyclic hinge-binding motifs capable of forming more than one hydrogen bond to the hinge region of PI3Kγ.

Journal of Medicinal Chemistry published new progress about Crystal structure (compound 4 bound to hPI3Kγ). 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

Lyalin, Boris V.; Sigacheva, Vera L.; Kokorekin, Vladimir A.; Petrosyan, Vladimir A. published the artcile< A new synthesis of azopyrazoles by oxidation of C-aminopyrazoles on a NiO(OH) electrode>, Application of C7H11N3, the main research area is amino pyrazole electrochem oxidation; azopyrazole diastereoselective preparation.

Oxidation of C-amino-N-alkylpyrazoles on a NiO(OH) electrode in an aqueous alk. medium afforded the corresponding azopyrazoles. The success in implementation of these processes was due to the structure of C-aminopyrazoles.

Mendeleev Communications published new progress about Azo compounds Role: SPN (Synthetic Preparation), PREP (Preparation). 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Application of C7H11N3.

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

Adachi, Ikuo; Yamamori, Teruo; Hiramatsu, Yoshiharu; Sakai, Katsunori; Sato, Hatsuo; Kawakami, Masaru; Uno, Osamu; Ueda, Motohiko published the artcile< Studies on dihydropyridines. II. Synthesis of 4,7-dihydropyrazolo[3,4-b]pyridines with vasodilating and antihypertensive activities>, Formula: C7H11N3, the main research area is coronary vasodilator dihydropyrazolopyridine preparation; structure property relationship dihydropyrazolopyridine antihypertensive; pyrazolopyridine dihydro antihypertensive preparation; aminopyrazole unsaturated ketoester cyclocondensation; calcium channel blocker dihydropyrazolopyridine.

A series of 4-aryl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate derivatives I (R = Me, Ph, cyclopentyl; R1 = Me, Et, CHMe2, cyclohexyl, substituted phenethyl, etc.; R2 = 2-O2NC6H4, 3-O2NC6H4, 2-ClC6H4, 2.8-Cl2C6H4, pyridyl; R3 = H, Me, CHMe2, Ph, cycloalkyl, CO2Et, pyridyl, etc.) was prepared and the compounds were tested for Ca-blocking activity in isolated guinea pig portal vein, antihypertensive activity in spontaneously hypertensive rats, and coronary vasodilating effect in isolated guinea pig heart. A number of derivatives had potent antihypertensive and coronary vasodilating activities. The structure-activity relationships of the series indicated that a 3-cyclopentyl or 3-cyclohexyl substituent and a hydrophobic 5-ester moiety with moderate bulkiness were effective for increasing the pharmacol. potencies.

Chemical & Pharmaceutical Bulletin published new progress about Antihypertensives. 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Formula: C7H11N3.

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

Haydl, Alexander M.; Xu, Kun; Breit, Bernhard published the artcile< Regio- and Enantioselective Synthesis of N-Substituted Pyrazoles by Rhodium-Catalyzed Asymmetric Addition to Allenes>, Application In Synthesis of 13808-65-6, the main research area is pyrazole terminal alkene addition rhodium catalyst; allylated pyrazole asym preparation; allenes; allylic compounds; asymmetric catalysis; heterocycles; rhodium.

The rhodium-catalyzed asym. N-selective coupling of pyrazole derivatives with terminal allenes gives access to enantioenriched secondary and tertiary allylic pyrazoles, i.e. I, which can be employed for the synthesis of medicinally important targets. The reaction tolerates a large variety of functional groups and labeling experiments gave insights into the reaction mechanism. This new methodol. was further applied in a highly efficient synthesis of JAK 1/2 inhibitor (R)-ruxolitinib.

Angewandte Chemie, International Edition published new progress about Addition reaction catalysts, stereoselective. 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

Xun, Zhan; Feng, Xian; Wang, Jianjun; Shi, Daqing; Huang, Zhibin published the artcile< Multicomponent Strategy for the Preparation of Pyrrolo[1,2-a]pyrimidine Derivatives under Catalyst-Free and Microwave Irradiation Conditions>, Name: 3-Cyclopropyl-1-methyl-1H-pyrazol-5-amine, the main research area is pyrrolopyrimidine preparation microwave irradiation regioselective; aminopyrazole acetylenedicarboxylate malononitrile multicomponent reaction.

A simple and efficient one-pot procedure has been developed for the construction of pyrrolo[1,2-a]pyrimidines I (R = Me, Et; R1 = H, CH3, C6H5; R2 = Me, Ph, cyclopropyl) via the three-component domino reaction of 5-aminopyrazoles II, acetylenedicarboxylates RCO2CCCO2R and malononitrile under catalyst-free, microwave irradiation conditions. The key step in this transformation is the N-N bond cleavage reaction of the II substrate, which has been reported in this context for the first time in this study. The advantages of this protocol include readily available starting materials, short reaction times and good regioselectivity.

Chinese Journal of Chemistry published new progress about Microwave irradiation. 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Name: 3-Cyclopropyl-1-methyl-1H-pyrazol-5-amine.

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

He, Shuwen; Li, Peng; Dai, Xing; McComas, Casey C.; Du, Chunyan; Wang, Ping; Lai, Zhong; Liu, Hong; Yin, Jingjun; Bulger, Paul G.; Dang, Qun; Xiao, Dong; Zorn, Nicolas; Peng, Xuanjia; Nargund, Ravi P.; Palani, Anandan published the artcile< Facile functionalization at the C2 position of a highly substituted benzofuran>, Recommanded Product: 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is iodobenzofuran preparation Suzuki coupling; benzofuran preparation.

To expedite an SAR study on C(2) of a highly substituted benzofuran ring system, a method for the preparation of a key precursor, iodide I, was developed. From I, a diverse set of compounds with different substituents at C(2) were prepared efficiently by Suzuki reaction.

Tetrahedron Letters published new progress about Benzofurans Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Recommanded Product: 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

Saito, Tetsuji; Obitsu, Tetsuo; Minamoto, Chiaki; Sugiura, Tsuneyuki; Matsumura, Naoya; Ueno, Sonoko; Kishi, Akihiro; Katsumata, Seishi; Nakai, Hisao; Toda, Masa-Aki published the artcile< Pyrazolo[1,5-a]pyrimidines, triazolo[1,5-a]pyrimidines and their tricyclic derivatives as corticotropin-releasing factor 1 (CRF1) receptor antagonists>, Safety of 4-Chloro-2-(methylthio)pyrazolo[1,5-a][1,3,5]triazine, the main research area is pyrazolopyrimidine triazolopyrimidine preparation corticotropin releasing factor receptor antagonist; structure activity relationship CRF receptor antagonist pyrazolopyrimidine triazolopyrimidine.

To identify structurally novel CRF1 receptor antagonists, a series of bicyclic core antagonists, pyrazolo[1,5-a]pyrimidines, e.g. I (X = CH), triazolo[1,5-a]pyrimidines, e.g. I (X = N), imidazo[1,2-a]pyrimidines, e.g. II, and a pyrazolo[1,5-a][1,3,5]triazine, III, were designed, synthesized and evaluated as CRF1 receptor antagonists. Several compounds showed binding affinity (IC50 = 4.2-418 nM) and antagonist activity (EC50 = 4.0-889 nM). Compound I (X = CH) was found to show oral efficacy in an Elevated Plus Maze test in rats. Further chem. modification of them led us to discovery of the tricyclic core antagonists pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidines, e.g. IV. The discovery process of these compounds is presented, as is the study of the structure-activity relationship.

Bioorganic & Medicinal Chemistry published new progress about Aromatic amines Role: RCT (Reactant), RACT (Reactant or Reagent). 54346-19-9 belongs to class pyrazoles-derivatives, and the molecular formula is C6H5ClN4S, Safety of 4-Chloro-2-(methylthio)pyrazolo[1,5-a][1,3,5]triazine.

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

Pan, Jinpeng; Yin, Yan; Zhao, Lianhua; Feng, Yangbo published the artcile< Discovery of (S)-6-methoxy-chroman-3-carboxylic acid (4-pyridin-4-yl-phenyl)-amide as potent and isoform selective ROCK2 inhibitors>, Synthetic Route of 936250-20-3, the main research area is ROCK2 inhibitor selectivity methoxychromancarboxylatepyridin phenylamide; Chromans; Computational theoretical studies; Isoform selectivity; ROCK; ROCK inhibitors.

ROCK1 and ROCK2 are highly homologous isoforms. Accumulated studies indicate that they have distinct different functions, and the development of isoform selective ROCK inhibitors will pave new roads for the treatment of various diseases. In this work, a series of amide-chroman derivatives were synthesized and biol. evaluated in order to develop potent and isoform selective ROCK2 inhibitors. Remarkably, (S)-6-methoxy-chroman-3-carboxylic acid (4-pyridin-4-yl-phenyl)-amide ((S)-7c) possessed ROCK2 inhibitory activity with an IC50 value of 3 nM and 22.7-fold isoform selectivity (vs. ROCK1). Mol. docking indicated that hydrophobic interactions were the key element for the high potency and isoform selectivity of (S)-7c. The binding free energies predicted by MM/GBSA were in good agreement with the exptl. bioactivities, and the anal. of individual energy terms suggested that residue Lys105 in ROCK1 or Lys121 in ROCK2 was the key residue for the isoform selectivity of (S)-7c.

Bioorganic & Medicinal Chemistry published new progress about Free energy of binding. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Synthetic Route of 936250-20-3.

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

Huang, Qinhua; Johnson, Ted W.; Bailey, Simon; Brooun, Alexei; Bunker, Kevin D.; Burke, Benjamin J.; Collins, Michael R.; Cook, Andrew S.; Cui, J. Jean; Dack, Kevin N.; Deal, Judith G.; Deng, Ya-Li; Dinh, Dac; Engstrom, Lars D.; He, Mingying; Hoffman, Jacqui; Hoffman, Robert L.; Johnson, Patrick S.; Kania, Robert S.; Lam, Hieu; Lam, Justine L.; Le, Phuong T.; Li, Qiuhua; Lingardo, Laura; Liu, Wei; Lu, Melissa West; McTigue, Michele; Palmer, Cynthia L.; Richardson, Paul F.; Sach, Neal W.; Shen, Hong; Smeal, Tod; Smith, Graham L.; Stewart, Albert E.; Timofeevski, Sergei; Tsaparikos, Konstantinos; Wang, Hui; Zhu, Huichun; Zhu, Jinjiang; Zou, Helen Y.; Edwards, Martin P. published the artcile< Design of Potent and Selective Inhibitors to Overcome Clinical Anaplastic Lymphoma Kinase Mutations Resistant to Crizotinib>, COA of Formula: C11H19BN2O2, the main research area is crizotinib resistant lymphoma kinase mutation inhibitor preparation SAR.

Crizotinib, an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS pos. patients. Under pressure of crizotinib treatment, point mutations arise in the kinase domain of ALK, resulting in resistance and progressive disease. The successful application of both structure-based and lipophilic-efficiency-focused drug design resulted in aminopyridine (I), which was potent across a broad panel of engineered ALK mutant cell lines and showed suitable preclin. pharmacokinetics and robust tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M).

Journal of Medicinal Chemistry published new progress about Antitumor agents. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, COA of Formula: C11H19BN2O2.

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