Month: October 2022

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

Application of 844501-71-9In 2011 ,《SAR studies of 4-pyridyl heterocyclic anilines that selectively induce autophagic cell death in von Hippel-Lindau-deficient renal cell carcinoma cells》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Bonnet, Muriel; Flanagan, Jack U.; Chan, Denise A.; Lai, Edwin W.; Nguyen, Phuong; Giaccia, Amato J.; Hay, Michael P.. The article conveys some information:

We recently identified a class of pyridyl aniline thiazoles (PAT) that displayed selective cytotoxicity for von Hippel-Lindau (VHL) deficient renal cell carcinoma (RCC) cells in vitro and in vivo. Structure-activity relationship (SAR) studies were used to develop a comparative mol. field anal. (CoMFA) model that related VHL-selective potency to the three-dimensional arrangement of chem. features of the chemotype. We now report the further mol. alignment-guided exploration of the chemotype to discover potent and selective PAT analogs. The contribution of the central thiazole ring was explored using a series of five- and six-membered ring heterocyclic replacements to vary the electronic and steric interactions in the central unit. We also explored a pos. steric CoMFA contour adjacent to the pyridyl ring using Pd-catalyzed cross-coupling Suzuki-Miyaura, Sonogashira and nucleophilic displacement reactions to prepare of a series of aryl-, alkynyl-, alkoxy- and alkylamino-substituted pyridines, resp. In vitro potency and selectivity were determined using paired RCC cell lines: the VHL-null cell line RCC4 and the VHL-pos. cell line RCC4-VHL. Active analogs selectively induced autophagy in RCC4 cells. We have used the new SAR data to further develop the CoMFA model, and compared this to a 2D-QSAR method. Our progress towards realizing the therapeutic potential of this chemotype as a targeted cytotoxic therapy for the treatment of RCC by exploiting the absence of the VHL tumor suppressor gene is reported. 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: 844501-71-9Application of 844501-71-9)

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, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Application of 844501-71-9

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

Application In Synthesis of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleIn 2020 ,《Damage Incorporated: Discovery of the Potent, Highly Selective, Orally Available ATR Inhibitor BAY 1895344 with Favorable Pharmacokinetic Properties and Promising Efficacy in Monotherapy and in Combination Treatments in Preclinical Tumor Models》 was published in Journal of Medicinal Chemistry. The article was written by Luecking, Ulrich; Wortmann, Lars; Wengner, Antje M.; Lefranc, Julien; Lienau, Philip; Briem, Hans; Siemeister, Gerhard; Boemer, Ulf; Denner, Karsten; Schaefer, Martina; Koppitz, Marcus; Eis, Knut; Bartels, Florian; Bader, Benjamin; Bone, Wilhelm; Moosmayer, Dieter; Holton, Simon J.; Eberspaecher, Uwe; Grudzinska-Goebel, Joanna; Schatz, Christoph; Deeg, Gesa; Mumberg, Dominik; von Nussbaum, Franz. The article contains the following contents:

The ATR kinase plays a key role in the DNA damage response by activating essential signaling pathways of DNA damage repair, especially in response to replication stress. Because DNA damage and replication stress are major sources of genomic instability, selective ATR inhibition has been recognized as a promising new approach in cancer therapy. We now report the identification and preclin. evaluation of the novel, clin. ATR inhibitor BAY 1895344(I). Starting from quinoline 2 with weak ATR inhibitory activity, lead optimization efforts focusing on potency, selectivity, and oral bioavailability led to the discovery of the potent, highly selective, orally available ATR inhibitor BAY 1895344, which exhibited strong monotherapy efficacy in cancer xenograft models that carry certain DNA damage repair deficiencies. Moreover, combination treatment of BAY 1895344 with certain DNA damage inducing chemotherapy resulted in synergistic antitumor activity. BAY 1895344 is currently under clin. investigation in patients with advanced solid tumors and lymphomas (NCT03188965). In the experiment, the researchers used 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Application In Synthesis of 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, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Application In Synthesis of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

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

Synthetic Route of C4H3F3N2In 2021 ,《Berotralstat (BCX7353): Structure-Guided Design of a Potent, Selective, and Oral Plasma Kallikrein Inhibitor to Prevent Attacks of Hereditary Angioedema (HAE)》 was published in Journal of Medicinal Chemistry. The article was written by Kotian, Pravin L.; Wu, Minwan; Vadlakonda, Satish; Chintareddy, Venkat; Lu, Pengcheng; Juarez, Luis; Kellogg-Yelder, Debra; Chen, Xilin; Muppa, Saritha; Chambers-Wilson, Ramanda; Davis Parker, Cynthia; Williams, Jason; Polach, Kevin J.; Zhang, Weihe; Raman, Krishnan; Babu, Yarlagadda S.. The article contains the following contents:

Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that affects an estimated 1 in 50 000 individuals worldwide. Until recently, prophylactic HAE treatment options were limited to injectables, a burdensome administration route that has driven the need for an oral treatment. A substantial body of evidence has shown that potent and selective plasma kallikrein inhibitors that block the generation of bradykinin represent a promising approach for the treatment of HAE. Berotralstat (BCX7353, discovered by BioCryst Pharmaceuticals using a structure-guided drug design strategy) is a synthetic plasma kallikrein inhibitor that is potent and highly selective over other structurally related serine proteases. This once-daily, small-mol. drug is the first orally bioavailable prophylactic treatment for HAE attacks, having successfully completed a Phase III clin. trial (meeting its primary end point) and recently receiving the U.S. Food and Drug Administration’s approval for the prophylactic treatment of HAE attacks in patients 12 years and older. In the experiment, the researchers used 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Synthetic Route of C4H3F3N2)

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.Synthetic Route of C4H3F3N2

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

Recommanded Product: 474432-62-7On March 24, 2016, Getlik, Matthaus; Smil, David; Zepeda-Velazquez, Carlos; Bolshan, Yuri; Poda, Gennady; Wu, Hong; Dong, Aiping; Kuznetsova, Ekaterina; Marcellus, Richard; Senisterra, Guillermo; Dombrovski, Ludmila; Hajian, Taraneh; Kiyota, Taira; Schapira, Matthieu; Arrowsmith, Cheryl H.; Brown, Peter J.; Vedadi, Masoud; Al-awar, Rima published an article in Journal of Medicinal Chemistry. The article was 《Structure-Based Optimization of a Small Molecule Antagonist of the Interaction Between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1)》. The article mentions the following:

WD repeat-containing protein 5 (WDR5) is an important component of the multiprotein complex essential for activating mixed-lineage leukemia 1 (MLL1). Rearrangement of the MLL1 gene is associated with onset and progression of acute myeloid and lymphoblastic leukemias, and targeting the WDR5-MLL1 interaction may result in new cancer therapeutics. Our previous work showed that binding of small mol. ligands to WDR5 can modulate its interaction with MLL1, suppressing MLL1 methyltransferase activity. Initial structure-activity relationship studies identified N-(2-(4-methylpiperazin-1-yl)-5-substituted-phenyl) benzamides as potent and selective antagonists of this protein-protein interaction. Guided by crystal structure data and supported by in silico library design, we optimized the scaffold by varying the C-1 benzamide and C-5 substituents. This allowed us to develop the first highly potent (Kdisp < 100 nM) small mol. antagonists of the WDR5-MLL1 interaction and demonstrate that N-(4-(4-methylpiperazin-1-yl)-3'-(morpholinomethyl)-[1,1'-biphenyl]-3-yl)-6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide 16d (OICR-9429) is a potent and selective chem. probe suitable to help dissect the biol. role of WDR5. In the experiment, the researchers used Pyrazolo[1,5-a]pyridine-7-carboxylic acid(cas: 474432-62-7Recommanded Product: 474432-62-7)

Pyrazolo[1,5-a]pyridine-7-carboxylic acid(cas: 474432-62-7) 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. Recommanded Product: 474432-62-7

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

HPLC of Formula: 930-36-9On September 24, 2020 ,《Discovery of DS-1971a, a Potent, Selective NaV1.7 Inhibitor》 was published in Journal of Medicinal Chemistry. The article was written by Shinozuka, Tsuyoshi; Kobayashi, Hiroyuki; Suzuki, Sayaka; Tanaka, Kyosuke; Karanjule, Narayan; Hayashi, Noriyuki; Tsuda, Toshifumi; Tokumaru, Eri; Inoue, Masahiro; Ueda, Kiyono; Kimoto, Hiroko; Domon, Yuki; Takahashi, Sakiko; Kubota, Kazufumi; Yokoyama, Tomihisa; Shimizugawa, Akiko; Koishi, Ryuta; Fujiwara, Chie; Asano, Daigo; Sakakura, Tomoko; Takasuna, Kiyoshi; Abe, Yasuyuki; Watanabe, Toshiyuki; Kitano, Yutaka. The article contains the following contents:

A highly potent, selective NaV1.7 inhibitor, DS-1971a(I), has been discovered. Exploration of the left-hand Ph ring of sulfonamide derivatives (I and II) led to the discovery of novel series of cycloalkane derivatives with high NaV1.7 inhibitory potency in vitro. As the right-hand heteroaromatic ring affected the mechanism-based inhibition liability of CYP3A4, replacement of this moiety resulted in the generation of 4-pyrimidyl derivatives Addnl., GSH adducts formation, which can cause idiosyncratic drug toxicity, was successfully avoided by this modification. An addnl. optimization led to the discovery of DS-1971a. In preclin. studies, DS-1971a demonstrated highly potent selective in vitro profile with robust efficacy in vivo. DS-1971a exhibited a favorable toxicol. profile, which enabled multiple-dose studies of up to 600 mg bid or 400 mg tid (1200 mg/day) administered for 14 days to healthy human males. DS-1971a is expected to exert potent efficacy in patients with peripheral neuropathic pain, with a favorable safety profile. The experimental part of the paper was very detailed, including the reaction process of 1-Methylpyrazole(cas: 930-36-9HPLC of Formula: 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. HPLC of Formula: 930-36-9

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