Tag: 200-300

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

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

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

Name: Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylateOn March 27, 2008, Silvestri, Romano; Cascio, Maria Grazia; La Regina, Giuseppe; Piscitelli, Francesco; Lavecchia, Antonio; Brizzi, Antonella; Pasquini, Serena; Botta, Maurizio; Novellino, Ettore; Di Marzo, Vincenzo; Corelli, Federico published an article in Journal of Medicinal Chemistry. The article was 《Synthesis, cannabinoid receptor affinity, and molecular modeling studies of substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides》. The article mentions the following:

The new 1-phenyl-5-(1H-pyrrol-1-yl)pyrazole-3-carboxamides were compared with the reference compounds AM251 and SR144528 for cannabinoid hCB1 and hCB2 receptor affinity. Compounds bearing 2,4-dichlorophenyl or 2,4-difluorophenyl groups at position 1 and 2,5-dimethylpyrrole moiety at position 5 of the pyrazole nucleus were generally more selective for hCB1. On the other hand, the N-cyclohexyl group at the 3-carboxamide was the determinant for the hCB2 selectivity, in particular when a 3,4-dichlorophenyl group was also present at position 1. Compound I was the most selective ligand for the hCB1 receptor (Ki (CB2)/Ki (CB1) = 140.7). Derivative II, the most potent hCB1 ligand (Ki = 5.6 nM), was equipotent to AM251 and behaved as an inverse agonist in the cAMP assay (EC50 ∼1 nM). The carbonyl oxygen of both I and II formed a H-bond with K3.28(192), while the substituents at the nitrogen fitted in a pocket formed by lipophilic residues. This H-bonding interaction was proposed to account for the high affinity for receptors’ inactive state and the inverse agonist activity. The experimental part of the paper was very detailed, including the reaction process of Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9Name: Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate)

Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9) belongs to anime. To avoid the problem of multiple alkylation, methods have been devised for “blocking” substitution so that only one alkyl group is introduced. The Gabriel synthesis is one such method; it utilizes phthalimide, C6H4(CO)2NH, whose one acidic hydrogen atom has been removed upon the addition of a base such as KOH to form a salt.Name: Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate

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

HPLC of Formula: 847818-72-8On May 12, 2016 ,《Discovery of a Highly Potent and Selective Indenoindolone Type 1 Pan-FLT3 Inhibitor》 appeared in ACS Medicinal Chemistry Letters. The author of the article were Hatcher, John M.; Weisberg, Ellen; Sim, Taebo; Stone, Richard M.; Liu, Suiyang; Griffin, James D.; Gray, Nathanael S.. The article conveys some information:

For a subpopulation of acute myeloid leukemia (AML) patients, the mutationally activated tyrosine kinase FLT3, has emerged as a promising target for therapy. The development of drug resistance due to mutation is a growing concern for mutant FLT3 inhibitors, such as PKC412, Quizartinib, PLX3397, and Crenolanib. Thus, there is a need to develop novel FLT3 inhibitors that overcome these mutations. Here the authors report the development of a novel type I ATP competitive inhibitor, I, that is extremely potent and selective for FLT3. I also has the highest affinity for three constitutively active isoforms of FLT3 (FLT3-ITD, FLT3-N841I, and FLT3-D835V) compared to a panel 456 other kinases. The unique and specific kinase inhibition profile suggests that this chemotype may represent an attractive starting point for the development of further improved FLT3 inhibitors with therapeutic potential in tumors harboring deregulated FLT3 activity. In the experimental materials used by the author, we found N,N-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanamine(cas: 847818-72-8HPLC of Formula: 847818-72-8)

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, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, antidiabetic and antibacterial activities. HPLC of Formula: 847818-72-8

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

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

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

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

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