Month: October 2022

Bagal, Sharan K.; Omoto, Kiyoyuki; Blakemore, David C.; Bungay, Peter J.; Bilsland, James G.; Clarke, Philip J.; Corbett, Matthew S.; Cronin, Ciaran N.; Cui, J. Jean; Dias, Rebecca; Flanagan, Neil J.; Greasley, Samantha E.; Grimley, Rachel; Johnson, Eric; Fengas, David; Kitching, Linda; Kraus, Michelle L.; McAlpine, Indrawan; Nagata, Asako; Waldron, Gareth J.; Warmus, Joseph S. published an article on January 10 ,2019. The article was titled 《Discovery of Allosteric, Potent, Subtype Selective, and Peripherally Restricted TrkA Kinase Inhibitors》, and you may find the article in Journal of Medicinal Chemistry.SDS of cas: 866837-96-9 The information in the text is summarized as follows:

Tropomyosin receptor kinases (TrkA, TrkB, TrkC) are activated by hormones of the neurotrophin family: nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4). Moreover, the NGF antibody tanezumab has provided clin. proof of concept for inhibition of the TrkA kinase pathway in pain leading to significant interest in the development of small mol. inhibitors of TrkA. However, achieving TrkA subtype selectivity over TrkB and TrkC via a Type I and Type II inhibitor binding mode has proven challenging and Type III or Type IV allosteric inhibitors may present a more promising selectivity design approach. Furthermore, TrkA inhibitors with minimal brain availability are required to deliver an appropriate safety profile. Herein, we describe the discovery of a highly potent, subtype selective, peripherally restricted, efficacious, and well-tolerated series of allosteric TrkA inhibitors that culminated in the delivery of candidate quality compound 23. In the experiment, the researchers used many compounds, for example, Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9SDS of cas: 866837-96-9)

Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9) belongs to anime. Left-handed and right-handed forms (mirror-image configurations, known as optical isomers or enantiomers) are possible when all the substituents on the central nitrogen atom are different (i.e., the nitrogen is chiral). With amines, there is extremely rapid inversion in which the two configurations are interconverted.SDS of cas: 866837-96-9

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

Hatcher, John M.; Bahcall, Magda; Choi, Hwan Geun; Gao, Yang; Sim, Taebo; George, Rani; Janne, Pasi A.; Gray, Nathanael S. published their research in Journal of Medicinal Chemistry on December 10 ,2015. The article was titled 《Discovery of Inhibitors That Overcome the G1202R Anaplastic Lymphoma Kinase Resistance Mutation》.COA of Formula: C14H26BN3O2 The article contains the following contents:

The treatment of patients with advanced nonsmall-cell lung cancer harboring chromosomal rearrangements of anaplastic lymphoma kinase (ALK) has been revolutionized by the development of crizotinib, a small-mol. inhibitor of ALK, ROS1, and MET. However, resistance to crizotinib inevitably develops through a variety of mechanisms, leading to relapse both systemically and in the central nervous system (CNS). This has motivated the development of “”second-generation”” ALK inhibitors, including alectinib and ceritinib, that overcome some of the mutations leading to resistance. However, most of the reported ALK inhibitors do not show inhibition of the G1202R mutant, which is one of the most common mutations. Herein, the authors report the development of a structural analog of alectinib I that is potent against the G1202R mutant as well as a variety of other frequently observed mutants. In addition, I is capable of penetrating the CNS of mice following oral dosing. In the experiment, the researchers used N,N-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanamine(cas: 847818-72-8COA of Formula: C14H26BN3O2)

N,N-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanamine(cas: 847818-72-8) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. COA of Formula: C14H26BN3O2

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

In 2012,Bhanuchandra, M.; Kuram, Malleswara Rao; Sahoo, Akhila K. published 《A convenient approach to β-heteroarylated (C-N bond) ketones from Cs2CO3 promoted reaction between propargyl alcohols and nitrogen-heterocycles》.Organic & Biomolecular Chemistry published the findings.Synthetic Route of C4H3F3N2 The information in the text is summarized as follows:

An efficient and direct approach to β-heteroarylated (C-N bond) ketones is demonstrated. Base promoted redox isomerization of propargyl alc. to α,β-unsaturated ketone followed by conjugate addition to NH-heteroarenes affords a wide range of β-heteroarylated ketones in good to excellent yields. Aryl, heteroaryl, alkyl C(sp), and terminal alkynes containing unactivated propargyl alcs. effectively undergo redox-isomerization conjugate addition (RICA) with NH-heteroarenes. Reaction of 3-substituted pyrazoles or indazole with propargyl alcs. enables highly regioselective products. A diverse range of NH-bearing nucleophiles such as: pyrazoles, imidazole, triazoles, pyrrole, indoles, and aniline participate in this reaction and deliver the corresponding β-heteroarylated ketones. In the experiment, the researchers used many compounds, for example, 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Synthetic Route of C4H3F3N2)

3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4) belongs to pyrazoles. The application of pyrazole derivatives in the development of anticancer agents has been thoroughly investigated and verified. Moreover, the medicinal features of a number of natural products incorporating pyrazole moiety such as pyrazofurin, pyrazofurin B, pyrazole-3(5)-carboxylic acid and 4-methylpyrazole-3(5)-carboxylic acid have been reported.Synthetic Route of C4H3F3N2

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

In 2015,Jiang, Xiaolong; Liu, Hongyan; Song, Zilan; Peng, Xia; Ji, Yinchun; Yao, Qizheng; Geng, Meiyu; Ai, Jing; Zhang, Ao published 《Discovery and SAR study of c-Met kinase inhibitors bearing an 3-amino-benzo[d]isoxazole or 3-aminoindazole scaffold》.Bioorganic & Medicinal Chemistry published the findings.Category: pyrazoles-derivatives The information in the text is summarized as follows:

A series of 3-amino-benzo[d]isoxazole-/3-aminoindazole-based compounds were designed, synthesized and pharmacol. evaluated as tyrosine kinase c-Met inhibitors. The SAR study was conducted leading to identification of nine compounds with IC50s less than 10 nM against c-Met. Compound I stood out as the most potent c-Met inhibitor displaying potent inhibitory effects both at enzymic (IC50 = 1.8 nM) and cellular (IC50 = 0.18 μM on EBC-1 cells) levels. In addition, I had a relatively good selectivity compared to a panel of the inhouse 14 RTKs. In the experiment, the researchers used many compounds, for example, 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Category: pyrazoles-derivatives)

1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, antidiabetic and antibacterial activities. Category: pyrazoles-derivatives

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

In 2016,Petrella, Stephanie; Aubry, Alexandra; Janvier, Genevieve; Coutant, Eloi P.; Cartier, Alex; Dao, Thuy-Ha; Bonhomme, Frederic J.; Motreff, Laurence; Pissis, Cedric; Bizet, Chantal; Clermont, Dominique; Begaud, Evelyne; Retailleau, Pascal; Munier-Lehmann, Helene; Capton, Estelle; Mayer, Claudine; Janin, Yves L. published 《Synthesis and evaluation of original bioisosteres of bacterial type IIA topoisomerases inhibitors》.Canadian Journal of Chemistry published the findings.SDS of cas: 20154-03-4 The information in the text is summarized as follows:

A recently discovered series of inhibitors of the ATPase function of bacterial type IIA topoisomerases featuring a carboxypyrrole component led the authors to attempt to replace this group with a potentially bioisosteric carboxypyrazole. Accordingly, synthetic pathways to 2-(4-(1H-pyrazole-5-carboxamido)piperidin-1-yl)thiazole-5-carboxylic acids or 2-(4-(N-methyl-1H-pyrazole-5-carboxamido)piperidin-1-yl)thiazole-5-carboxylic acids featuring an array of substituents on the pyrazole ring were explored. Unfortunately, none of the analogs made were effective on the ATPase function of Mycobacterium tuberculosis gyrase as well on the DNA supercoiling activity of the whole gyrase of M. tuberculosis and Escherichia coli. However, this work is still providing original insights in chem. as well as in the structure-activity relationships of this series of inhibitors. In addition to this study using 3-(Trifluoromethyl)-1H-pyrazole, there are many other studies that have used 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4SDS of cas: 20154-03-4) was used in this study.

3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4) belongs to pyrazoles. The application of pyrazole derivatives in the development of anticancer agents has been thoroughly investigated and verified. Moreover, the medicinal features of a number of natural products incorporating pyrazole moiety such as pyrazofurin, pyrazofurin B, pyrazole-3(5)-carboxylic acid and 4-methylpyrazole-3(5)-carboxylic acid have been reported.SDS of cas: 20154-03-4

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

《Design and synthesis of Imidazo[1,2-b]pyridazine IRAK4 inhibitors for the treatment of mutant MYD88 L265P diffuse large B-cell lymphoma》 was written by Chen, Yun; Bai, Gang; Ning, Yi; Cai, Shi; Zhang, Tao; Song, Peiran; Zhou, Jinpei; Duan, Wenhu; Ding, Jian; Xie, Hua; Zhang, Huibin. Quality Control of 3-(Trifluoromethyl)-1H-pyrazole And the article was included in European Journal of Medicinal Chemistry in 2020. The article conveys some information:

The design, synthesis and structure-activity relationships of imidazo[1,2-b]pyridazines I [R = 2-aminoethyl, 3-amino-piperidin-1-yl, piperazin-1-yl, etc.; R1 = CF2, CF3, CN, etc.; R2 =Me, Et, iPr, etc.; R3 = H, Me] as potent IRAK4 inhibitors was reported. The representative compound I [R = amino-piperidin-3-yl; R1 = CF2; R2 = Me; R3 = H] exhibited excellent IRAK4 potency (IRAK4 IC50 = 1.3 nM) and favorable kinase selectivity profile. It demonstrated cellular selectivity for activated B cell-like (ABC) subtype DLBCL with MYD88 L265P mutation in cytotoxicity assay. The kinase inhibitory efficiency of compound I [R = amino-piperidin-3-yl; R1 = CF2; R2 = Me; R3 = H] was further validated by western blot anal. of phosphorylation of IRAK4 and downstream signaling in OCI-LY10 and TMD8 cells. Besides, combination of compound I [R = amino-piperidin-3-yl; R1 = CF2; R2 = Me; R3 = H] and BTK inhibitor ibrutinib synergistically reduced the viability of TMD8 cells. These results indicated that compound I [R = amino-piperidin-3-yl; R1 = CF2; R2 = Me; R3 = H] could be a promising IRAK4 inhibitor for the treatment of mutant MYD88 DLBCL. After reading the article, we found that the author used 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Quality Control of 3-(Trifluoromethyl)-1H-pyrazole)

3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4) belongs to pyrazoles. The application of pyrazole derivatives in the development of anticancer agents has been thoroughly investigated and verified. Moreover, the medicinal features of a number of natural products incorporating pyrazole moiety such as pyrazofurin, pyrazofurin B, pyrazole-3(5)-carboxylic acid and 4-methylpyrazole-3(5)-carboxylic acid have been reported.Quality Control of 3-(Trifluoromethyl)-1H-pyrazole

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

Nale, Sagar D.; Thombal, Raju S.; Lee, Yong Rok published their research in Asian Journal of Organic Chemistry in 2021. The article was titled 《Ruthenium(II)-Catalyzed Direct Ortho Functionalization of 1-Arylpyrazoles with Maleimides: A Condition Controlled Installation of Succinimides and Maleimides on Arenes》.Electric Literature of C4H3F3N2 The article contains the following contents:

Ruthenium(II)-catalyzed switchable ortho functionalization of 1-arylpyrazoles I (R1 = 2-Me, 4-OMe, 4-Cl, etc.; R2 = H, Me, CF3) and 1-(1-naphthalenyl)-1H-pyrazole with maleimides II (R3 = C2H5, C6H5, 4-BrC6H4, etc.) is developed in this study. This divergent reaction proceeds via five-membered ruthenacycle formation and selectively installs diverse succinimides III (R4 = 3-Me, 5-OMe, 5-Cl, etc.) and maleimides IV substituents on the aromatic ring of 1-arylpyrazoles I through alkylation and alkenylation under acidic and basic conditions. This methodol. features broad substrate scope, high functional group tolerance, selective functionalization, and superior reactivity. The experimental part of the paper was very detailed, including the reaction process of 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Electric Literature of C4H3F3N2)

3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4) belongs to pyrazoles. The application of pyrazole derivatives in the development of anticancer agents has been thoroughly investigated and verified. Moreover, the medicinal features of a number of natural products incorporating pyrazole moiety such as pyrazofurin, pyrazofurin B, pyrazole-3(5)-carboxylic acid and 4-methylpyrazole-3(5)-carboxylic acid have been reported.Electric Literature of C4H3F3N2

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

Polina, Saibabu; Putta, V. P. Rama Kishore; Gujjarappa, Raghuram; Pujar, Prasad Pralhad; Malakar, Chandi C. published their research in Journal of Heterocyclic Chemistry in 2021. The article was titled 《Aza-Michael addition of 1,2-diazoles to structurally diverse enones: Efficient methods toward β-amino ketones》.COA of Formula: C5H6N2O2 The article contains the following contents:

An efficient and mild protocol was realized using 1,2-diazoles and related heterocycles with cyclic and acyclic enones in presence of T3P (2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide) toward the regioselective formation of N-cycloalkyl heterocycles at room temperature The developed reaction conditions showcased good selectivity over a wide range of 1,2-diazoles and enones by delivering N-cycloalkyl heterocycles in excellent yields. In the experiment, the researchers used many compounds, for example, Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4COA of Formula: C5H6N2O2)

Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4) belongs to pyrazoles. The application of pyrazole derivatives in the development of anticancer agents has been thoroughly investigated and verified. Moreover, the medicinal features of a number of natural products incorporating pyrazole moiety such as pyrazofurin, pyrazofurin B, pyrazole-3(5)-carboxylic acid and 4-methylpyrazole-3(5)-carboxylic acid have been reported.COA of Formula: C5H6N2O2

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

Name: 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleIn 2022 ,《Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306》 appeared in Journal of Medicinal Chemistry. The author of the article were Szychowski, Janek; Papp, Robert; Dietrich, Evelyne; Liu, Bingcan; Vallee, Frederic; Leclaire, Marie-Eve; Fourtounis, Jimmy; Martino, Giovanni; Perryman, Alexander L.; Pau, Victor; Yin, Shou Yun; Mader, Pavel; Roulston, Anne; Truchon, Jean-Francois; Marshall, C. Gary; Diallo, Mohamed; Duffy, Nicole M.; Stocco, Rino; Godbout, Claude; Bonneau-Fortin, Alexanne; Kryczka, Rosie; Bhaskaran, Vivek; Mao, Daniel; Orlicky, Stephen; Beaulieu, Patrick; Turcotte, Pascal; Kurinov, Igor; Sicheri, Frank; Mamane, Yael; Gallant, Michel; Black, W. Cameron. The article conveys some information:

PKMYT1 is a regulator of CDK1 phosphorylation and is a compelling therapeutic target for the treatment of certain types of DNA damage response cancers due to its established synthetic lethal relationship with CCNE1 amplification. To date, no selective inhibitors have been reported for this kinase that would allow for investigation of the pharmacol. role of PKMYT1. To address this need compound 1 was identified as a weak PKMYT1 inhibitor. Introduction of a dimethylphenol increased potency on PKMYT1. These dimethylphenol analogs were found to exist as atropisomers that could be separated and profiled as single enantiomers. Structure-based drug design enabled optimization of cell-based potency. Parallel optimization of ADME properties led to the identification of potent and selective inhibitors of PKMYT1. RP-6306 inhibits CCNE1-amplified tumor cell growth in several preclin. xenograft models. The first-in-class clin. candidate RP-6306 is currently being evaluated in Phase 1 clin. trials for treatment of various solid tumors. In the part of experimental materials, we found many familiar compounds, such as 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Name: 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole)

1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Name: 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

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

Recommanded Product: 3-(Trifluoromethyl)-1H-pyrazoleIn 2019 ,《Chemo- and regioselective reactions of 5-bromo enones/enaminones with pyrazoles》 was published in Organic & Biomolecular Chemistry. The article was written by Moraes, Paulo A.; Lobo, Marcio M.; Marangoni, Mario A.; Meyer, Alexandre R.; Frizzo, Clarissa P.; Bonacorso, Helio G.; Martins, Marcos A. P.; Zanatta, Nilo. The article contains the following contents:

Reaction of 5-bromo enones with pyrazoles provided a series of unexpected N,O-aminal derivatives, I [Y = Me, CF3; R1 = H, Me; R2 = H, Me, n-Pr, etc.; R3 = Me, Et, n-Pr, n-Bu; R1R2 = (CH2)3, (CH2)4] through a 1,4-conjugated addition at the β-carbon of the 5-bromo enones instead of the expected nucleophilic substitution of the bromine. This reaction also furnished the 1,3-regioisomer of the pyrazole. A similar reaction of pyrazoles using 5-bromo enaminones furnished only N-alkylated pyrazoles II [R4 = Me, i-Bu, (CH2)4, etc.] with high regioselectivity and at good yields through nucleophilic substitution of the bromine. In the part of experimental materials, we found many familiar compounds, such as 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Recommanded Product: 3-(Trifluoromethyl)-1H-pyrazole)

3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4) belongs to pyrazoles. Pyrazole derivatives have been reported to exhibit a wide range of applications in medicinal chemistry and pharmacology. A large number of drugs incorporating pyrazole structure have been utilized as partial agonists for nicotinic acid receptors, antidepressants, antimicrobial agents, antiviral agents, and antifungal agents solely or along with the combination of other structural motifs.Recommanded Product: 3-(Trifluoromethyl)-1H-pyrazole

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