pyrazoles-derivatives

In 1960,Gundermann, Karl Dietrich; Thomas, Rainer published 《Mercaptoacrylic acid derivatives. VII. The effect of thioether groups on the stabilization of 1-pyrazoline-3-carboxylic acid derivatives》.Chemische Berichte published the findings.Product Details of 15366-34-4 The information in the text is summarized as follows:

cf. CA 54, 289b. 3-Alkylthio-1-pyrazoline-3-carboxylic acid esters, readily obtained from α-alkylthioacrylic acid esters and CH2N2, split off mercaptans at room temperature to yield pyrazole-3-carboxylic acid esters, but N at 50° to give mixtures of 1-alkylthiocyclopropane-1-carboxylic acid esters and α-alkylthiocrotonic acid esters. Pyrazoline derivs, from α-alkylthioacrylonitriles and CH2N2 underwent only a stabilization reaction with the elimination of N. CH2:C(SMe)CO2Me (21.4 g.) in 200 cc. Et2O treated with CH2N2 from 25 g. H2NCON(NO)Me (I) in 200 cc. Et2O, kept overnight, filtered, evaporated in vacuo at 30°, the resulting light yellow, oily pyrazoline derivative added dropwise to a flask preheated to 90-100°, heated about 0.5 hr. on the steam bath, and fractionated gave 19.8 g. 3:1 mixture of the Me ester (II) of 1-methylthiocyclopropane-1-carboxylic acid (III) and Me α-(methylthio)crotonate (IV), b15 70-82°, n20D 1.4835. (III-IV mixture (15 g.) and 50 cc. 20% HCl refluxed about 6 hrs., evaporated in vacuo, and the residue (7.7 g.) recrystallized from 20% HCl gave III, m. 65-6°, b0.2 84-6°, Rf 0.90 (4:1:5 BuOH-glacial AcOH-H2O), colorless prisms; III with CH2N2 gave 100% pure II, b14 74°, n20D 1.4823. II treated room temperature with concentrated NH4OH and evaporated yielded the amide of III, prisms, m. 89° (petr. ether). Crude pyrazoline derivative from CH2:C(SMe)CO2Me and CH2N2 kept 1 week at room temperature and filtered gave the Me ester of pyrazole-3-carboxylic acid (V), m. 140° (aqueous MeOH), which was saponified to V, m. 212°. II-III mixture (3 g.) treated about 24 hrs. at room temperature with liquid NH3 gave 0.6 g. MeCH(NH2)-CH(SMe)CO2H, Rf 0.64; saponification of the nonbasic portion of the product gave 1.7 g. III. Me3CSH (45 g.) added dropwise with stirring to 60 g. CH2:CClCO2Me and 2.3 g. NaOMe at 45-50°, kept overnight, diluted with Et2O, washed, dried, and fractionated gave 68.7 g. Me3CSCH2CHClCO2Me (VI), b0.4 85-6°, b0.2 77-8°, n20D 1.4790. VI (42 g.), 26.2 g. powd. KBr, 22.2 g. Et3N, and 170 cc. HCONMe2 gave in the usual manner 22.8 g. Me2CSC(:CH2)CO2Me (VII), b12 92-3°. n20D 1.4795. VII (8.6 g.) in 70 cc. Et2O treated with CH2N2 from 10 g. I in 100 cc. Et2O, the product decomposed at 85-90°, and fractionated gave 7.0 g. oil, b12 83-5°, n20D 1.4803; the oil refluxed 1 hr. on the steam bath with 2 volumes 20% aqueous NaOH and 1 volume MeOH, filtered, acidified, and the product isolated with Et2O gave 3.8 g. 1-tert-butylthiocyclopropane-1-carboxylic acid, b0.2 93-4°, n22D 1.4955. The crude product from VII and CH2N2 kept 8 days at room temperature yielded 90% Me ester of V. CH2:C(SMe)CN (8 g.) in 80 cc. Et2O treated with CH2N2 from 12 g. I, the crude product dropped at 80-90° into a flask, and the residue fractionated yielded 6.85 g. 4:1 mixture of the nitrile of III and MeCH:C(SMe)CN, b11 67-9°, n20D 1.4900; the mixture heated 4 hrs. with a 5-fold amount 1:1 glacial AcOH-HCl, evaporated, the residue extracted with Me2CO, and the extract worked up gave 60% III. CH2:C(SCH2Ph)CN (11.5 g.) and CH2N2 from 11 g. I yielded similarly 10.53 g. 4:1 mixture of 1-benzylthio-1-cyanocyclopropane and MeCH:C(SCH2Ph)CN, b0.15 104-6°, n20D 1.5676; a 10-g. portion in 100 g. AcOH-HCl heated 7 hrs. on the steam bath and evaporated, the residue treated with Et2O and aqueous NaHCO3, and the aqueous phase acidified gave 5.55 g. 1-benzylthiocyclopropane-1-carboxylic acid, prisms, m. 132-3° (C6H6-petr. ether). MeCH:C(SMe)CO2Me (10 g.) in 100 cc. Et2O treated with CH2N2 from 10 g. I in 100 cc. Et2O, 1 g. of the resulting crude pyrazoline ester kept at room temperature, and filtered gave 0.51 g. Me 4-methylpyrazole-3-carboxylate (VIII), m. 172° (aqueous MeOH). Crude pyrazoline ester (12 g.) added dropwise to a flask at 110-13° gave 5.5 g. VIII, m. 172°; the residue from the petr. ether washings gave 2.65 g. unidentified oil, b15 88-91°, n20D 1.4902, which by acid hydrolysis gave MeSH. In the experiment, the researchers used many compounds, for example, Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4Product Details of 15366-34-4)

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.Product Details of 15366-34-4

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

In 2011,Cui, J. Jean; Tran-Dube, Michelle; Shen, Hong; Nambu, Mitchell; Kung, Pei-Pei; Pairish, Mason; Jia, Lei; Meng, Jerry; Funk, Lee; Botrous, Iriny; McTigue, Michele; Grodsky, Neil; Ryan, Kevin; Padrique, Ellen; Alton, Gordon; Timofeevski, Sergei; Yamazaki, Shinji; Li, Qiuhua; Zou, Helen; Christensen, James; Mroczkowski, Barbara; Bender, Steve; Kania, Robert S.; Edwards, Martin P. published 《Structure Based Drug Design of Crizotinib (PF-02341066), a Potent and Selective Dual Inhibitor of Mesenchymal-Epithelial Transition Factor (c-MET) Kinase and Anaplastic Lymphoma Kinase (ALK)》.Journal of Medicinal Chemistry published the findings.Synthetic Route of C9H15BN2O2 The information in the text is summarized as follows:

Because of the critical roles of aberrant signaling in cancer, both c-MET and ALK receptor tyrosine kinases are attractive oncol. targets for therapeutic intervention. The cocrystal structure of 3 (PHA-665752), bound to c-MET kinase domain, revealed a novel ATP site environment, which served as the target to guide parallel, multiattribute drug design. A novel 2-amino-5-aryl-3-benzyloxypyridine series was created to more effectively make the key interactions achieved with 3. In the novel series, the 2-aminopyridine core allowed a 3-benzyloxy group to reach into the same pocket as the 2,6-dichlorophenyl group of 3 via a more direct vector and thus with a better ligand efficiency (LE). Further optimization of the lead series generated the clin. candidate crizotinib (PF-02341066), which demonstrated potent in vitro and in vivo c-MET kinase and ALK inhibition, effective tumor growth inhibition, and good pharmaceutical properties. The experimental part of the paper was very detailed, including the reaction process of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9Synthetic Route of C9H15BN2O2)

3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9) 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. Synthetic Route of C9H15BN2O2

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

In 2012,Chandrasekhar, Vadapalli; Nagarajan, Loganathan; Hossain, Sakiat; Gopal, Kandasamy; Ghosh, Surajit; Verma, Sandeep published 《Multicomponent Assembly of Anionic and Neutral Decanuclear Copper(II) Phosphonate Cages》.Inorganic Chemistry published the findings.HPLC of Formula: 20154-03-4 The information in the text is summarized as follows:

A multicomponent synthetic strategy involving Cu(II) ions, tert-butylphosphonic acid (t-BuPO3H2) and 3-substituted pyrazole ligands was adopted for the synthesis of soluble mol. Cu(II) phosphonates. The use of six different 3-substituted pyrazoles, 3-R-PzH [R = H, Me, CF3, Ph, 2-pyridyl (2-Py), and 2-methoxyphenyl (2-MeO-C6H4)] as ancillary ligands afforded nine different decanuclear cages, [Cu5(μ3-OH)2(O3P-t-Bu)3(3-R-Pz)2(X)2]2·(Y) where R = H, X = t-BuPO3H, and Y = (Et3NH+)4(solvent) (1); R = Me, X = 3-MePzH, and Y = solvent (2); R = Me, X = t-BuPO3H, and Y = (Et3NH+)4(solvent) (3); R = CF3, X = t-BuPO3H, and Y = (Et3NH+)4(solvent) (4); R = Ph, X = 3-PhPzH, and Y = solvent (5); R = 2-Py, X = 0.5 MeOH, and Y = solvent (6); R = 2-Py, X = none, and Y = solvent (7); R = 2-Py, X = H2O, and Y = (Et3NH+·PF6-)2(solvent) (8); R = 2-MeO-C6H4, X = MeOH or 0.5:0.5 MeOH/H2O, and Y = solvent (9). Compounds 1-6, 8, and 9 were isolated using a direct synthetic method which involves the reaction of Cu(II) salts and the ligands, while 7 was obtained from an indirect route involving the reaction of preformed Cu-pyridylpyrazolate precursor complexes and t-BuPO3H2. The decametallic compounds 1-9 possess a butterfly-shaped core. The core of the cages 1, 3, and 4 are tetraanionic and contain more phosphonates than pyrazole ligands, while the other cages are neutral and contain more pyrazoles than phosphonate ligands. Compounds 1-6 were studied by electrospray ionization-high-resolution mass spectrometry (ESI-HRMS). The decanuclear cage 6 is a good plasmid modifier. The experimental part of the paper was very detailed, including the reaction process of 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4HPLC of Formula: 20154-03-4)

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.HPLC of Formula: 20154-03-4

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

In 2018,Liang, Yufan; Zhang, Xiaheng; MacMillan, David W. C. published 《Decarboxylative sp3 C-N coupling via dual copper and photoredox catalysis》.Nature (London, United Kingdom) published the findings.Recommanded Product: 3-(Trifluoromethyl)-1H-pyrazole The information in the text is summarized as follows:

Over the past three decades, considerable progress has been made in the development of methods to construct sp2 carbon-nitrogen (C-N) bonds using palladium, copper or nickel catalysis. However, the incorporation of alkyl substrates to form sp3 C-N bonds remains one of the major challenges in the field of cross-coupling chem. Here we demonstrate that the synergistic combination of copper catalysis and photoredox catalysis can provide a general platform from which to address this challenge. This cross-coupling system uses naturally abundant alkyl carboxylic acids and com. available nitrogen nucleophiles as coupling partners. It is applicable to a wide variety of primary, secondary and tertiary alkyl carboxylic acids (through iodonium activation), as well as a vast array of nitrogen nucleophiles: nitrogen heterocycles, amides, sulfonamides and anilines can undergo C-N coupling to provide N-alkyl products in good to excellent efficiency, at room temperature and on short timescales (five minutes to one hour). We demonstrate that this C-N coupling protocol proceeds with high regioselectivity using substrates that contain several amine groups, and can also be applied to complex drug mols., enabling the rapid construction of mol. complexity and the late-stage functionalization of bioactive pharmaceuticals. In the experimental materials used by the author, we found 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Recommanded Product: 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.Recommanded Product: 3-(Trifluoromethyl)-1H-pyrazole

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

The author of 《Phenotypic Screening-Based Identification of 3,4-Disubstituted Piperidine Derivatives as Macrophage M2 Polarization Modulators: An Opportunity for Treating Multiple Sclerosis》 were Weng, Qinjie; Che, Jinxin; Zhang, Zhikang; Zheng, Jiahuan; Zhan, Wenhu; Lin, Sendong; Tian, Tian; Wang, Jincheng; Gai, Renhua; Hu, Yongzhou; Yang, Bo; He, Qiaojun; Dong, Xiaowu. And the article was published in Journal of Medicinal Chemistry in 2019. Name: 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole The author mentioned the following in the article:

Multiple sclerosis (MS) is a disease of the autoimmune-mediated disorder in the central nervous system, for which no effective therapeutic agent is currently available. The regulation of macrophage polarization toward M2 is a general benefit for treating MS. The gene biomarker-based phenotypic screening approach was developed, and 3,4-disubstituted piperidine derivative S-28 was identified as a lead compound modulating macrophage M2 polarization. Further SAR studies resulted in the discovery of the most potent modulator D11 that showed good oral bioavailability and significant in vivo therapeutic effects. Mechanistic studies demonstrated that the M2 polarization macrophages modulated by D11 mainly functioned through inhibiting the proliferation of T-cells and activating the phosphorylation of Stat3 and Akt. Therefore, the gene biomarker-based phenotypic screening was demonstrated as a promising tool for the discovery of novel macrophage M2 polarization modulators. Compound D11 may serve as a promising starting point for the development of therapeutics to treat MS. In the experimental materials used by the author, we found 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, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, 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

The author of 《Discovery of 3,4,6-Trisubstituted Piperidine Derivatives as Orally Active, Low hERG Blocking Akt Inhibitors via Conformational Restriction and Structure-Based Design》 were Dong, Xiaowu; Zhan, Wenhu; Zhao, Mengting; Che, Jinxin; Dai, Xiaoyang; Wu, Yizhe; Xu, Lei; Zhou, Yubo; Zhao, Yanmei; Tian, Tian; Cheng, Gang; Jin, Zegao; Li, Jia; Shao, Yanfei; He, Qiaojun; Yang, Bo; Weng, Qinjie; Hu, Yongzhou. And the article was published in Journal of Medicinal Chemistry in 2019. COA of Formula: C10H17BN2O2 The author mentioned the following in the article:

A series of 3,4-disubstituted piperidine derivatives were obtained based on a conformational restriction strategy and a lead compound, A12, that exhibited potent in vitro and in vivo antitumor efficacies; however, obvious safety issues limited its further development. Thus, systematic exploration of the structure-activity relationship of compound A12, involving the Ph group, hinge-linkage, and piperidine moiety, led to the discovery of the superior 3,4,6-trisubstituted piperidine derivative E22. E22 showed increased potency in Akt1 and cancer cell inhibition, remarkably reduced human ether-a-go-go-related gene blockage, and significantly improved safety profiles. Compound E22 also exhibited good kinase selectivity, had a good pharmacokinetic profile, and displayed very potent in vivo antitumor efficacy, with over 90% tumor growth inhibition in the SKOV3 xenograft model. Further mechanistic studies were conducted to demonstrate that compound E22 could significantly inhibit the phosphorylation of proteins downstream of Akt kinase in cells and tumor tissue from the xenograft model. In addition to this study using 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, there are many other studies that have used 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0COA of Formula: C10H17BN2O2) was used in this study.

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. COA of Formula: C10H17BN2O2

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

《Cation-Anion and Anion-CO2 Interactions in Triethyl(octyl)phosphonium Ionic Liquids with Aprotic Heterocyclic Anions (AHAs)》 was published in Journal of Physical Chemistry B in 2020. These research results belong to Oh, Seungmin; Morales-Collazo, Oscar; Keller, Austin N.; Brennecke, Joan F.. Quality Control of 3-(Trifluoromethyl)-1H-pyrazole The article mentions the following:

Ionic liquids with aprotic heterocyclic anions (AHAs) have been developed for postcombustion CO2 capture applications. The anions of AHA ILs play a significant role in tuning anion-CO2 complexation. In addition, AHAs are able to trigger the abstraction of acidic protons located at the α position of phosphonium cations by forming hydrogen bonds between cations and anions, eventually leading to cation-driven CO2 complexation. Here we investigate the role of the anion in cation-anion hydrogen bonding and ylide formation. Using CO2 uptake measurements, 31P NMR, attenuated total reflection-Fourier transform IR (ATR-FTIR), deuterium exchange equilibrium and rates, two-dimensional nuclear Overhauser effect spectroscopy (2D NOESY), and d. functional theory calculations, we show that the key is the proximity of the neg. charged nitrogen atoms on the anion to the α protons, which is governed not just by anion basicity but by sterics. Thus, we show that triethyl(octyl)phosphonium 3-methyl-5-trifluoromethylpyrazolide is much more effective in hydrogen-bonding with and deprotonating the cation than the equivalent [P2228] ILs with more basic 2-cyanopyrrolide and 3-trifluoromethylpyrazolide anions. In the part of experimental materials, we found many familiar compounds, such as 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

SDS of cas: 15366-34-4In 2008 ,《Effects of Introduction of Hydrophobic Group on Ribavirin Base on Mutation Induction and Anti-RNA Viral Activity》 was published in Journal of Medicinal Chemistry. The article was written by Moriyama, Kei; Suzuki, Tetsuya; Negishi, Kazuo; Graci, Jason D.; Thompson, Corinne N.; Cameron, Craig E.; Watanabe, Masahiko. The article contains the following contents:

One of the possible mechanisms of antiviral action of ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, 1) is the accumulation of mutations in viral genomic RNA. The ambiguous incorporation of 5′-triphosphate of ribavirin (RTP, 8) by a viral RNA-dependent RNA polymerase (RdRp) is a key step of the mutation induction. The authors synthesized three ribavirin analogs that possess hydrophobic groups, 4-iodo-1-β-D-ribofuranosylpyrazole-3-carboxamide (I), 4-propynyl-1-β-D-ribofuranosylpyrazole-3-carboxamide (II), and 4-phenylethynyl-1-β-D-ribofuranosylpyrazole-3-carboxamide (III), and the corresponding triphosphates (IV, V, and VI, resp.). Steady-state kinetics anal. of the incorporation of these triphosphate analogs by a poliovirus RdRp, 3Dpol, revealed that while the incorporation efficiency of IV was comparable to RTP, V and VI showed lower efficiency than RTP. Antipolioviral activity of I and II was much more moderate than ribavirin, and III showed no antipolioviral activity. Effects of substituting groups on the incorporation efficiency by 3Dpol and a strategy for a rational design of more active ribavirin analogs are discussed. In the experimental materials used by the author, we found Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4SDS of cas: 15366-34-4)

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.SDS of cas: 15366-34-4

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