Day: October 19, 2022

Formula: C10H17BN2O2In 2017 ,《A novel and efficient route for synthesis of Taladegib》 was published in Journal of Chemical Research. The article was written by Guo, Mingliang; Hong, Kwon Ho; Lv, Yongfeng; Ding, Yu; Li, Congcong; Xu, Hua; Qi, Wenxiu; Chen, Junqing; Ji, Min; Cai, Jin. The article contains the following contents:

Taladegib (LY-2940680), a small mol. Hedgehog signaling pathway inhibitor, was obtained from N-benzyl-4-piperidone via Borch reductive amination, acylation with 4-fluoro-2-(trifluoromethyl)benzoyl chloride, debenzylation, substitution with 1,4-dichlorophthalazine and Suzuki cross-coupling reaction with 1-methyl-1H-pyrazole-5-boronic acid. The advantages of this synthesis route were the elimination of Boc protection and deprotection and the inexpensive starting materials. Furthermore, the debenzylation reaction was achieved with simplified operational procedure using ammonium formate as hydrogen source that provided high reaction yield. This synthetic procedure was suitable for large-scale production of the compound for biol. evaluation and further study. The results came from multiple reactions, including the reaction of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Formula: C10H17BN2O2)

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, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, monoamine oxidase inhibitory, anti-inflammatory, antidiabetic and antibacterial activities. Formula: C10H17BN2O2

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

《1,2,3-Triazines. IV. Synthesis of 1,2,3-triazinecarboxylates》 was written by Neunhoeffer, Hans; Bopp, Ralf; Diehl, Werner. Safety of Methyl 1H-pyrazole-3-carboxylateThis research focused ontriazine preparation; triazinecarboxylate preparation; rearrangement cyclopropenyl azide; pyrazolotriazinone preparation; ring expansion pyrazolamine alkoxycarbonyl; aminopyrazole alkoxycarbonyl ring enlargement. The article conveys some information:

Some 1,2,3-triazinecarboxylates I ((R = Me, ethyl; R1 = aryl; R2 = aryl, trimethylsilyl) were prepared by rearrangement of intermediate (alkoxycarbonyl)cyclopropenyl azides II (same R, R1, R2) as well as by oxidation of 1-aminopyrazoles. Reaction of 1-aminopyrazole-5-carboxylates with tri-Et orthoformate and ammonia gave pyrazolo[3,2-f][1,2,4]triazin-4-ones. The results came from multiple reactions, including the reaction of Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4Safety of Methyl 1H-pyrazole-3-carboxylate)

Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4) 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.Safety of Methyl 1H-pyrazole-3-carboxylate

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

《Novel Quinazolinone Inhibitors of ALK2 Flip between Alternate Binding Modes: Structure-Activity Relationship, Structural Characterization, Kinase Profiling, and Cellular Proof of Concept》 was written by Hudson, Liam; Mui, James; Vazquez, Santiago; Carvalho, Diana M.; Williams, Eleanor; Jones, Chris; Bullock, Alex N.; Hoelder, Swen. Quality Control of 4-Bromo-5-cyclopropyl-1H-pyrazole And the article was included in Journal of Medicinal Chemistry on August 23 ,2018. The article conveys some information:

Structure-activity relationship and crystallog. data revealed that quinazolinone-containing fragments flip between two distinct modes of binding to activin receptor-like kinase-2 (ALK2). We explored both binding modes to discover potent inhibitors and characterized the chem. modifications that triggered the flip in binding mode. We report kinase selectivity and demonstrate that compounds of this series modulate ALK2 in cancer cells. These inhibitors are attractive starting points for the discovery of more advanced ALK2 inhibitors. In the part of experimental materials, we found many familiar compounds, such as 4-Bromo-5-cyclopropyl-1H-pyrazole(cas: 957345-28-7Quality Control of 4-Bromo-5-cyclopropyl-1H-pyrazole)

4-Bromo-5-cyclopropyl-1H-pyrazole(cas: 957345-28-7) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, monoamine oxidase inhibitory, anti-inflammatory, antidiabetic and antibacterial activities. Quality Control of 4-Bromo-5-cyclopropyl-1H-pyrazole

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

《Synthesis and properties of N-vinyl-3-and N-vinyl-5-pyrazolecarboxylic esters》 was written by Attaryan, H. S.; Grigoryan, A. J.; Panossyan, G. A.; Matsoyan, S. G.. Recommanded Product: Methyl 1H-pyrazole-3-carboxylateThis research focused onvinyl pyrazolecarboxylic ester synthesis radical polymerization copolymerization. The article conveys some information:

Esterification of pyrazolecarboxylic acid by aliphatic alcs. ROH (R=CH3, C2H5,iso-C3H7, C4H9) leads to the formation of corresponding esters; vinylation of the esters in the presence of mercury sulfate leads to the formation of N-vinyl-3- and N-vinyl-5-pyrazolecarboxylic acids. Polymerization and homopolymerization of the obtained monomers in the presence of a radical initiator was studied. In both cases, N-vinyl-5-pyrazolecarboxylic acid is more active. The reactivity ratios in polymerization for Me esters were calculate r1=0.71 and r2=2.7.Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4Recommanded Product: Methyl 1H-pyrazole-3-carboxylate) was used in this study.

Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4) 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: Methyl 1H-pyrazole-3-carboxylate

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

Hayashi, Hiroki; Takano, Hideaki; Katsuyama, Hitomi; Harabuchi, Yu; Maeda, Satoshi; Mita, Tsuyoshi published an article in Chemistry – A European Journal. The title of the article was 《Synthesis of difluoroglycine derivatives from amines, difluorocarbene, and CO2: computational design, scope, and applications》.Application In Synthesis of 1-Methylpyrazole The author mentioned the following in the article:

A three-component reaction (3CR) for the synthesis of difluoroglycine derivatives has been achieved by using amines, difluorocarbene (generated in situ), and the abundant, inexpensive, and nontoxic C1 source CO2. Various tert-amines and pyridine, (iso)quinoline, imidazole, thiazole, and pyrazole derivatives were incorporated, and the corresponding products were isolated in solid form without purification by column chromatog. on silica gel. Detailed reaction profiles of the 3CR were obtained from computational anal. using DFT calculations, and the results critically suggest that simple ammonia is not applicable to this reaction. In addition, as strongly supported by computational predictions, a new reagent that can generate difluorocarbene at 0°C without any additives was discovered. Finally, radical substitution reactions of the obtained difluoroglycine derivatives under photoredox conditions, as well as a synthetic application as an N-heterocyclic carbene ligand are shown. After reading the article, we found that the author used 1-Methylpyrazole(cas: 930-36-9Application In Synthesis of 1-Methylpyrazole)

1-Methylpyrazole(cas: 930-36-9) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Application In Synthesis of 1-Methylpyrazole

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

In 2016,Advanced Synthesis & Catalysis included an article by Alam, Khyarul; Kim, Seong Min; Kim, Do Joong; Park, Jin Kyoon. Application of 80537-07-1. The article was titled 《Development of Structurally Diverse N-Heterocyclic Carbene Ligands via Palladium-Copper-Catalyzed Decarboxylative Arylation of Pyrazolo[1,5-a]pyridine-3-carboxylic Acid》. The information in the text is summarized as follows:

A series of fused non-classical normal N-heterocyclic carbenes, Pyrpy-NHC precursors derived from pyrazolo[1,5-a]pyridines, has been prepared using palladium-copper-catalyzed decarboxylative arylation of pyrazolo[1,5-a]pyridine-3-carboxylic acid. Air-stable palladium and rhodium complexes of these ligands have been synthesized via mild transmetalation of Ag-Pyrpy-NHC. The structural properties of Rh(Pyrpy-NHC)(COD)Cl complexes were determined via X-ray anal. The measurement of the CO stretching frequencies of dicarbonyl Rh-Pyrpy-NHC complexes revealed that the electron donating strength of Pyrpy-NHC could be tuned by varying the substituents of the aryl group. A catalytic study of the Pd-Pyrpy-NHC complexes revealed promising activity in the Suzuki-Miyaura reaction under ambient atm. conditions. The experimental part of the paper was very detailed, including the reaction process of 2-Phenylpyrazolo[1,5-a]pyridine-3-carboxylic acid(cas: 80537-07-1Application of 80537-07-1)

2-Phenylpyrazolo[1,5-a]pyridine-3-carboxylic acid(cas: 80537-07-1) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, monoamine oxidase inhibitory, anti-inflammatory, antidiabetic and antibacterial activities. Application of 80537-07-1

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

Kudashev, Anton; Baudoin, Olivier published their research in Chemistry – A European Journal on December 15 ,2021. The article was titled 《Site-Selective Pd-Catalyzed C(sp3)-H Arylation of Heteroaromatic Ketones》.Related Products of 930-36-9 The article contains the following contents:

A ligand-controlled site-selective C(sp3)-H arylation of heteroaromatic ketones had been developed using Pd catalysis to gave ArC(O)CHR1CH2R2 [Ar = thiazol-2-yl, 2-pyridyl, 2-quinolyl, etc.; R1 = Ph, 4-MeC6H4, 2-naphthyl, etc.; R2 = H, Me, ph, etc.]. The reaction occurred selectively at the α- or β-position of the ketone side-chain. The switch from α- or β-arylation was realized by addition of a pyridone ligand. The α-arylation process showed broad scope and high site- and chemoselectivity, whereas the β-arylation was more limited. Mechanistic investigations suggested that α-arylation occurs through C-H activation/oxidative addition/reductive elimination whereas β-arylation involves desaturation and aryl insertion. After reading the article, we found that the author used 1-Methylpyrazole(cas: 930-36-9Related Products of 930-36-9)

1-Methylpyrazole(cas: 930-36-9) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Related Products of 930-36-9

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

Kumar, Sanjeev; Waldo, Jesse P.; Jaipuri, Firoz A.; Marcinowicz, Agnieszka; Van Allen, Clarissa; Adams, James; Kesharwani, Tanay; Zhang, Xiaoxia; Metz, Richard; Oh, Angela J.; Harris, Seth F.; Mautino, Mario R. published an article in Journal of Medicinal Chemistry. The title of the article was 《Discovery of Clinical Candidate (1R,4r)-4-((R)-2-((S)-6-Fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a Potent and Selective Inhibitor of Indoleamine 2,3-Dioxygenase 1》.Recommanded Product: Methyl 1-methyl-1H-pyrazole-4-carboxylate The author mentioned the following in the article:

A novel class of 5-substituted 5H-imidazo[5,1-a]isoindoles are described as potent inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1). A structure-based drug design approach was used to elaborate the 5H-imidazo[5,1-a]isoindole core and to improve potency and pharmacol. properties. Suitably placed hydrophobic and polar functional groups in the lead mol. allowed improvement of IDO1 inhibitory activity while minimizing off-target liabilities. Structure-activity relationship studies focused on optimizing IDO1 inhibition potency and a pharmacokinetic profile amenable to oral dosing while controlling CYP450 and hERG inhibitory properties. In the experiment, the researchers used many compounds, for example, Methyl 1-methyl-1H-pyrazole-4-carboxylate(cas: 5952-93-2Recommanded Product: Methyl 1-methyl-1H-pyrazole-4-carboxylate)

Methyl 1-methyl-1H-pyrazole-4-carboxylate(cas: 5952-93-2) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Recommanded Product: Methyl 1-methyl-1H-pyrazole-4-carboxylate

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

Ul′yanovskii, Nikolay V.; Kosyakov, Dmitry S.; Popov, Mark S.; Shavrina, Irina S.; Ivakhnov, Artem D.; Kenessov, Bulat; Lebedev, Albert T. published their research in Microchemical Journal on December 31 ,2021. The article was titled 《Rapid quantification and screening of nitrogen-containing rocket fuel transformation products by vortex assisted liquid-liquid microextraction and gas chromatography – high-resolution Orbitrap mass spectrometry》.Safety of 1-Methylpyrazole The article contains the following contents:

Existing and newly developed technologies for clean-up of wastewaters and soils contaminated with rocket fuel unsym. dimethylhydrazine (UDMH) are based on the oxidative treatment, as well as gasification in supercritical water. Being easily transformed by a radical mechanism, UDMH is capable of producing an extremely wide range of potentially hazardous nitrogen-containing products. Their identification and simultaneous quantification at low concentrations in water samples by gas chromatog. is a challenging task requiring a matrix change. We proposed a combination of dispersive vortex-assisted liquid-liquid microextraction (VALLME) of analytes followed by gas chromatog. – Orbitrap mass spectrometry allowing simultaneous target anal. and non-targeted screening. Dichloromethane and chloroform provided rapid (10 min) and effective extraction of most of UDMH transformation products. The maximum recoveries were achieved by alkalizing and saturating the aqueous samples with ammonium sulfate. The use of pyridine-d5 as an internal standard allowed developing an approach to the simultaneous determination of 24 compounds of various classes with detection limits for the most analytes in the range 0.02-1.1 μg L-1 and accuracy of 81-117% with low-cost, simple, and rapid sample preparation procedure. Extraction with a 100 μL of chloroform allowed further increasing sensitivity up to one order of magnitude and attaining LOD values for 20 compounds in the range of 0.002-0.1 μg L-1 comparable with that obtained by vacuum-assisted headspace solid-phase microextraction The developed method was validated and tested for the analyses of real samples – degraded aqueous solution of rocket fuel, products of UDMH treatment in supercritical water and aqueous extract of soil from the place of carrier rocket accidental crash. Twenty-nine compounds that were not previously described as UDMH transformation products were tentatively identified.1-Methylpyrazole(cas: 930-36-9Safety of 1-Methylpyrazole) was used in this study.

1-Methylpyrazole(cas: 930-36-9) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Safety of 1-Methylpyrazole

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

Zhang, Lingtian; Moccia, Marialuisa; Briggs, David C.; Bharate, Jaideep B.; Lakkaniga, Naga Rajiv; Knowles, Phillip; Yan, Wei; Tran, Phuc; Kharbanda, Anupreet; Wang, Xiuqi; Leung, Yuet-Kin; Frett, Brendan; Santoro, Massimo; McDonald, Neil Q.; Carlomagno, Francesca; Li, Hong-yu published an article on January 27 ,2022. The article was titled 《Discovery of N-Trisubstituted Pyrimidine Derivatives as Type I RET and RET Gatekeeper Mutant Inhibitors with a Novel Kinase Binding Pose》, and you may find the article in Journal of Medicinal Chemistry.Application of 930-36-9 The information in the text is summarized as follows:

Mutations of the rearranged during transfection (RET) kinase are frequently reported in cancer, which make it as an attractive therapeutic target. Herein, we discovered a series of N-trisubstituted pyrimidine derivatives as potent inhibitors for both wild-type (weight) RET and RETV804M, which is a resistant mutant for several FDA-approved inhibitors. The X-ray structure of a representative inhibitor with RET revealed that the compound binds in a unique pose that bifurcates beneath the P-loop and confirmed the compound as a type I inhibitor. Through the structure-activity relationship (SAR) study, compound 20 (I) was identified as a lead compound, showing potent inhibition of both RET and RETV804M. Addnl., compound 20 displayed potent antiproliferative activity of CCDC6-RET-driven LC-2/ad cells. Anal. of RET phosphorylation indicated that biol. activity was mediated by RET inhibition. Collectively, N-trisubstituted pyrimidine derivatives could serve as scaffolds for the discovery and development of potent inhibitors of type I RET and its gatekeeper mutant for the treatment of RET-driven cancers. The results came from multiple reactions, including the reaction of 1-Methylpyrazole(cas: 930-36-9Application of 930-36-9)

1-Methylpyrazole(cas: 930-36-9) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Application of 930-36-9

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