Day: October 17, 2022

COA of Formula: C12H13N3O2On October 18, 2007 ,《Preparation and Optimization of a Series of 3-Carboxamido-5-phenacylaminopyrazole Bradykinin B1 Receptor Antagonists》 was published in Journal of Medicinal Chemistry. The article was written by Dressen, Darren; Garofalo, Albert W.; Hawkinson, Jon; Hom, Dennis; Jagodzinski, Jacek; Marugg, Jennifer L.; Neitzel, Martin L.; Pleiss, Michael A.; Szoke, Balazs; Tung, Jay S.; Wone, David W. G.; Wu, Jing; Zhang, Heather. The article contains the following contents:

The B1 receptor is an attractive target for the treatment of pain and inflammation. 3-Carboxamido-5-phenacylamino pyrazole B1 receptor antagonists are described that exhibit good potency against B1 and high selectivity over B2. Initially, N-unsubstituted pyrazoles were studied, but these compounds suffered from extensive glucuronidation in primates. This difficulty could be surmounted using N-substituted pyrazoles. Optimization efforts culminated in compound 41 {4-bromo-5-[(2-chlorobenzoyl)amino]-1-phenyl-N-[2-[1-(4-pyridinyl)-4-piperidinyl]ethyl]-1H-pyrazole-3-carboxamide}, which has high receptor potency and metabolic stability. In the experiment, the researchers used many compounds, for example, Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9COA of Formula: C12H13N3O2)

Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9) belongs to anime. Reduction of nitro compounds, RNO2, by hydrogen or other reducing agents produces primary amines cleanly (i.e., without a mixture of products), but the method is mostly used for aromatic amines because of the limited availability of aliphatic nitro compounds. Reduction of nitriles and oximes (R2C=NOH) also yields primary amines.COA of Formula: C12H13N3O2

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

Fuse, Shinichiro; Suzuki, Kensuke; Kuchimaru, Takahiro; Kadonosono, Tetsuya; Ueda, Hiroki; Sato, Shinichi; Kizaka-Kondoh, Shinae; Nakamura, Hiroyuki published an article in Bioorganic & Medicinal Chemistry. The title of the article was 《Design, synthesis, and evaluation of indeno[2,1-c]pyrazolones for use as inhibitors against hypoxia-inducible factor (HIF)-1 transcriptional activity》.Name: 1-Methylpyrazole The author mentioned the following in the article:

In this study, indeno[2,1-c]pyrazolones, compounds I [Y = C, N; R1 = H, Me; R2 = H, Me, Ph, etc] were designed as readily available synthetic inhibitors of HIF-1 transcriptional activity. Nine compounds were synthesized in 4-5 steps from com. available starting materials. In evaluations of the ability to inhibit the hypoxia-induced transcriptional activity of HIF-1, compound I [Y = C, R1 = H, R2 = 4-MeC6H4] showed a higher level compared with that of known inhibitor, YC-1. The compound I [Y = C, R1 = H, R2 = 4-MeC6H4] suppressed HIF-1α protein accumulation without affecting the levels of HIF-1α mRNA. The results came from multiple reactions, including the reaction of 1-Methylpyrazole(cas: 930-36-9Name: 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. Name: 1-Methylpyrazole

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

Harju, Kirsi; Kylaenlahti, Irene; Paananen, Timo; Polamo, Mika; Nielsen, John; Yli-Kauhaluoma, Jari published an article in Journal of Combinatorial Chemistry. The title of the article was 《Solid-Phase Synthesis of Pyrazolopyridines from Polymer-Bound Alkyne and Azomethine Imines》.Name: 2-Phenylpyrazolo[1,5-a]pyridine-3-carboxylic acid The author mentioned the following in the article:

Study was made of the 1,3-dipolar cycloaddition of polymer-bound alkynes [I; R = Me, Ph, CO2H; P = polymer residue of 4-(bromomethyl)phenoxymethyl polystyrene cross-linked with 1% divinylbenzene (bromo-Wang resin)] to azomethine imines generated in situ from N-aminopyridine iodides, i.e. 1-amino-2-methylpyridinium iodide, 2-aminoisoquinolinium iodide, 1-amino-4-methylquinolinium iodide, 1-amino-4-methoxycarbonylpyridinium iodide, 1-amino-3-methylpyridinium iodide, 1-amino-3-(hydroxymethyl)pyridinium iodide and 1-aminoquinolinium iodide. Aromatization of the cycloadducts gives polymer-bound pyrazolopyridines (II; R1 = Q-Q11; R2 = H, Me) that can be released from the resin as carboxylic acids (R1-CO2H) with trifluoroacetic acid or as Me esters (R1-CO2Me) with sodium methoxide. After reading the article, we found that the author used 2-Phenylpyrazolo[1,5-a]pyridine-3-carboxylic acid(cas: 80537-07-1Name: 2-Phenylpyrazolo[1,5-a]pyridine-3-carboxylic acid)

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, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Name: 2-Phenylpyrazolo[1,5-a]pyridine-3-carboxylic acid

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

In 2012,Kabir, M. Shahjahan; Namjoshi, Ojas A.; Verma, Ranjit; Lorenz, Michael; Phani Babu Tiruveedhula, V. V. N.; Monte, Aaron; Bertz, Steven H.; Schwabacher, Alan W.; Cook, James M. published 《Base-mediated stereospecific synthesis of aryloxy and amino substituted ethyl acrylates》.Journal of Organic Chemistry published the findings.Synthetic Route of C4H3F3N2 The information in the text is summarized as follows:

The stereospecific synthesis of aryloxy and amino substituted E- and Z-ethyl-3-acrylates is of interest because of their potential in the polymer industry and in medicinal chem. During work on a copper-catalyzed cross-coupling reaction of Et (E)- and (Z)-3-iodoacrylates with phenols and N-heterocycles, we discovered a very simple (nonmetallic) method for the stereospecific synthesis of aryloxy and amino substituted acrylates. To study this long-standing problem on the stereoselectivity of aryloxy and amino substituted acrylates, a series of O- and N-substituted nucleophiles was allowed to react with Et (E)- and (Z)-3-iodoacrylates. Screening of different bases indicated that DABCO (1,4-diazabicyclo[2.2.2]octane) afforded successful conversion of Et (E)- and (Z)-3-iodoacrylates into aryloxy and amino substituted Et acrylates in a stereospecific manner. Herein are the details of this DABCO-mediated stereospecific synthesis of aryloxy and amino substituted E- or Z-acrylates. The experimental part of the paper was very detailed, including the reaction process of 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,Testa, Christelle; Roger, Julien; Scheib, Stephanie; Fleurat-Lessard, Paul; Hierso, Jean-Cyrille published 《Palladium-Catalysed C-H Bond Electrophilic Fluorination of Highly Substituted Arylpyrazoles: Experimental and DFT Mechanistic Insights》.Advanced Synthesis & Catalysis published the findings.Related Products of 20154-03-4 The information in the text is summarized as follows:

A general protocol for palladium-catalyzed C-H mono- and di-fluorination of highly substituted arylpyrazoles is reported. Coupling pathways and substrate limitations are discussed in the light of complementary mechanistic exptl. and d. functional theory (DFT) studies. The mono- and di-ortho-fluorination of arylpyrazoles having substituted pyrazole groups and ortho-, meta-, or para-substituted arene moieties is achieved. Various pyrazole groups can efficiently promote the direct C-H activation/fluorination of substrates bearing valuable reactive ester, cyano, halide and nitro functions. The presence of methoxy, Me and trifluoromethyl is tolerated on the pyrazole directing groups. However, steric substituent effects have a marked influence which is evidenced by calculations DFT modeling suggested also a previously unseen outer-sphere oxidative addition of N-fluorobenzenesulfonimide (NFSI) to Pd(II) as an alternative mechanism to the commonly assumed Pd(II)/Pd(IV) process. This unprecedented proposal, which is supported by the mass spectrometry identification of a key Pd(II) monomer under the stoichiometric conditions deserves more attention. The influence of elaborate highly substituted directing groups on the course of Pd-catalyzed fluorination has generally received limited attention although this question has a crucial synthetic utility; herein, appropriate conditions for isolating pure products are reported. In addition to this study using 3-(Trifluoromethyl)-1H-pyrazole, there are many other studies that have used 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Related Products of 20154-03-4) was used in this study.

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.Related Products of 20154-03-4

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

In 2017,Bezencon, Olivier; Heidmann, Bibia; Siegrist, Romain; Stamm, Simon; Richard, Sylvia; Pozzi, Davide; Corminboeuf, Olivier; Roch, Catherine; Kessler, Melanie; Ertel, Eric A.; Reymond, Isabelle; Pfeifer, Thomas; de Kanter, Ruben; Toeroek-Schafroth, Michael; Moccia, Luca G.; Mawet, Jacques; Moon, Richard; Rey, Markus; Capeleto, Bruno; Fournier, Elvire published 《Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies》.Journal of Medicinal Chemistry published the findings.Quality Control of Methyl 1H-pyrazole-3-carboxylate The information in the text is summarized as follows:

The authors report the discovery and pharmacol. characterization of N-(1-benzyl-1H-pyrazol-3-yl)-2-phenylacetamide derivatives as potent, selective, brain-penetrating T-type calcium channel blockers. Optimization focused mainly on solubility, brain penetration, and the search for an aminopyrazole metabolite that would be neg. in an Ames test. This resulted in the preparation and complete characterization of compound 66b (ACT-709478 (N-(1-((5-cyanopyridin-2-yl)methyl)-1H-pyrazol-3-yl)-2-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)acetamide)), which has been selected as a clin. candidate. In the experiment, the researchers used many compounds, for example, Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4Quality Control 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.Quality Control of Methyl 1H-pyrazole-3-carboxylate

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

In 2018,Wang, Chenglin; Zhu, Mingfei; Lu, Xiuhong; Wang, Hong; Zhao, Weili; Zhang, Xiongwen; Dong, Xiaochun published 《Synthesis and evaluation of novel dimethylpyridazine derivatives as hedgehog signaling pathway inhibitors》.Bioorganic & Medicinal Chemistry published the findings.Application of 847818-74-0 The information in the text is summarized as follows:

The authors report herein the design and synthesis of a series of structural modified dimethylpyridazine compounds as novel hedgehog signaling pathway inhibitors. The bicyclic phthalazine core and 4-methylamino-piperidine moiety of Taladegib were replaced with dimethylpyridazine and different azacycle building blocks, resp. The in vitro Gli-luciferase assay results demonstrate that the new scaffold still retained potent inhibitory potency. Piperidin-4-amine moiety was found to be the best linker between pharmacophores dimethylpyridazine and fluorine substituted benzoyl group. Furthermore, the optimization of 1-methyl-1H-pyrazol and 4-fluoro-2-(trifluoromethyl)benzamide by different aliphatic or aromatic rings were also investigated and the SAR were described. Several new derivatives were found to show potent Hh signaling inhibitory activity with nanomolar IC50 values. Among these compounds, compound I showed the highest inhibitory potency with an IC50 value of 2.33 nM, which was comparable to the lead compound Taladegib. In vivo efficacy of I in a ptch+/-p53-/- mouse medulloblastoma allograft model also indicated encouraging results.1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Application of 847818-74-0) 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, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, antidiabetic and antibacterial activities. Application of 847818-74-0

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

Bagal, Sharan K.; Gregson, Clare; O Donovan, Daniel H.; Pike, Kurt G.; Bloecher, Andrew; Barton, Peter; Borodovsky, Alexandra; Code, Erin; Fillery, Shaun M.; Hsu, Jessie Hao-Ru; Kawatkar, Sameer P.; Li, Chengzhi; Longmire, David; Nai, Youfeng; Nash, Samuel C.; Pike, Andrew; Robinson, James; Read, Jon A.; Rawlins, Phillip B.; Shen, Minhui; Tang, Jia; Wang, Peng; Woods, Haley; Williamson, Beth published an article in 2021. The article was titled 《Diverse, Potent, and Efficacious Inhibitors That Target the EED Subunit of the Polycomb Repressive Complex 2 Methyltransferase》, and you may find the article in Journal of Medicinal Chemistry.Computed Properties of C10H17BN2O2 The information in the text is summarized as follows:

In this paper the discovery of potent and orally bioavailable EED ligands with good solubilities was disclosed. The solubility of the EED ligands was optimized through a variety of design tactics, with the resulting compounds exhibiting in vivo efficacy in EZH2-driven tumors. 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: 847818-74-0Computed Properties of 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, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Computed Properties of C10H17BN2O2

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

Hartmann, Markus; Huber, Jessica; Kramer, Jan S.; Heering, Jan; Pietsch, Larissa; Stark, Holger; Odadzic, Dalibor; Bischoff, Iris; Fuerst, Robert; Schroeder, Martin; Akutsu, Masato; Chaikuad, Apirat; Doetsch, Volker; Knapp, Stefan; Biondi, Ricardo M.; Rogov, Vladimir V.; Proschak, Ewgenij published an article in 2021. The article was titled 《Demonstrating Ligandability of the LC3A and LC3B Adapter Interface》, and you may find the article in Journal of Medicinal Chemistry.Formula: C10H17BN2O2 The information in the text is summarized as follows:

Autophagy is the common name for a number of lysosome-based degradation pathways of cytosolic cargos. The key components of autophagy are members of Atg8 family proteins involved in almost all steps of the process, from autophagosome formation to their selective fusion with lysosomes. In this study, we show that the homologous members of the human Atg8 family proteins, LC3A and LC3B, are druggable by a small mol. inhibitor novobiocin. Structure-activity relationship (SAR) studies of the 4-hydroxy coumarin core scaffold were performed, supported by a crystal structure of the LC3A complex with dihydronovobiocin I. The study reports the first nonpeptide inhibitors for these protein interaction targets and will lay the foundation for the development of more potent chem. probes for the Atg8 protein family which may also find applications for the development of autophagy-mediated degraders (AUTACs). 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: 847818-74-0Formula: 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

HPLC of Formula: 15366-34-4In 1995 ,《4-Methoxybenzyl, a versatile protecting group for the regiospecific lithiation and functionalization of pyrazoles》 appeared in Synthetic Communications. The author of the article were Subramanyam, Chakrapani. The article conveys some information:

The use of the 4-methoxybenzyl protecting group for the regiospecific metalation/functionalization of pyrazole was reported. The protection of 1H-pyrazole gave 1-[(4-methoxyphenyl)methyl]-1H-pyrazole which underwent regioselective lithiation to give 5-lithio-1-[(4-methoxyphenyl)methyl]-1H-pyrazole. Treatment of the latter with Et N-methoxy-N-methylcarbamate gave di-[1-[(4-methoxyphenyl)methyl]-1H-pyrazol-5-yl] methanone. Deprotection of the latter gave the desired di(1H-pyrazol-3-yl) methanone.Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4HPLC of Formula: 15366-34-4) 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.HPLC of Formula: 15366-34-4

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