M.W=150-200 | Page 19 of 112 | pyrazoles-derivatives

Jiang, Xiaolong team published research on European Journal of Medicinal Chemistry in 2015 | 269410-08-4

HPLC of Formula: 269410-08-4, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, also known as 4-Pyrazoleboronic acid pinacol ester , is a useful research compound. Its molecular formula is C9H15BN2O2 and its molecular weight is 194.04 g/mol. The purity is usually 95%.

4-Pyrazoleboronic acid pinacol ester is a useful reagent for Suzuki-Miyaura cross-couplings as well as Ruthenium-catalyzed asymmetric hydrogenation. 4-Pyrazoleboronic acid pinacol ester is also a useful reagent for preparing VEGF, Aurora, RHO (ROCK), Janus Kinase 2, c-MET, ALK, S-nitrsoflutathione reductase, CDC7, Acetyl-CoA carboxylase inhibitors.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

4-Pyrazoleboronic acid pinacol ester is an organic compound that is the product of a bifunctional coupling reaction between 4-pyrazolecarboxylic acid and pinacol. It has been shown to inhibit protein S6 kinase, which is involved in the regulation of cell growth and proliferation. This compound has also been shown to be effective against cancer cells, including those that are resistant to conventional chemotherapeutic drugs. 4-Pyrazoleboronic acid pinacol ester may also be used as a precursor for other compounds with pharmaceutical activity., 269410-08-4.

Pyrazoles can be selectively lithiated at different carbons and subsequently react with electrophiles depending on the substitution patterns. 269410-08-4, formula is C9H15BN2O2, Name is 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1-Methyl-5-(trifluoromethyl)pyrazole underwent deprotonation and subsequent carboxylation mainly or exclusively at either the 4-position of the heterocycle or at the nitrogen-attached methyl group. HPLC of Formula: 269410-08-4.

Jiang, Xiaolong;Zhou, Ji;Ai, Jing;Song, Zilan;Peng, Xia;Xing, Li;Xi, Yong;Guo, Junfeng;Yao, Qizheng;Ding, Jian;Geng, Meiyu;Zhang, Ao research published 《 Novel tetracyclic benzo[b]carbazolones as highly potent and orally bioavailable ALK inhibitors: Design, synthesis, and structure-activity relationship study》, the research content is summarized as follows. Four series of tetracyclic benzo[b]carbazolone compounds possessing more rotatable bonds and higher mol. flexibility were designed by either inserting a linker within the C8-side chain or by opening the middle ketone ring on the basis of Alectinib (CH5424802). Compound I was identified showing nearly identical high potency against both wild-type and the gatekeeper mutant ALK kinase (3.4 vs. 3.9 nM). This compound has favorable PK profile with an oral bioavailability of 67.1% in rats. Moreover, compound I showed significant growth inhibition against ALK driven cancer cells and KARPAS-299 xenograft model.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

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

Han, Sang Hoon team published research on Journal of Medicinal Chemistry in 2022 | 269410-08-4

SDS of cas: 269410-08-4, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, also known as 4-Pyrazoleboronic acid pinacol ester , is a useful research compound. Its molecular formula is C9H15BN2O2 and its molecular weight is 194.04 g/mol. The purity is usually 95%.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

Han, Sang Hoon;Goins, Christopher M.;Arya, Tarun;Shin, Woo-Jin;Maw, Joshua;Hooper, Alice;Sonawane, Dhiraj P.;Porter, Matthew R.;Bannister, Breyanne E.;Crouch, Rachel D.;Lindsey, A. Abigail;Lakatos, Gabriella;Martinez, Steven R.;Alvarado, Joseph;Akers, Wendell S.;Wang, Nancy S.;Jung, Jae U.;Macdonald, Jonathan D.;Stauffer, Shaun R. research published 《 Structure-based optimization of ML300-derived, noncovalent inhibitors targeting the severe acute respiratory syndrome coronavirus 3CL protease (SARS-CoV-2 3CL^pro)》, the research content is summarized as follows. Starting from the MLPCN probe compound ML300, a structure-based optimization campaign was initiated against the recent severe acute respiratory syndrome coronavirus (SARS-CoV-2) main protease (3CL^pro). X-ray structures of SARS-CoV-1 and SARS-CoV-2 3CL^pro enzymes in complex with multiple ML300-based inhibitors, including the original probe ML300, were obtained and proved instrumental in guiding chem. toward probe compound 41 (I)(CCF0058981). The disclosed inhibitors utilize a noncovalent mode of action and complex in a noncanonical binding mode not observed by peptidic 3CL^pro inhibitors. In vitro DMPK profiling highlights key areas where further optimization in the series is required to obtain useful in vivo probes. Antiviral activity was established using a SARS-CoV-2-infected Vero E6 cell viability assay and a plaque formation assay. I demonstrates nanomolar activity in these resp. assays, comparable in potency to remdesivir. These findings have implications for antiviral development to combat current and future SARS-like zoonotic coronavirus outbreaks.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

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

Hanan, Emily J. team published research on Bioorganic & Medicinal Chemistry Letters in 2016 | 269410-08-4

269410-08-4, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, also known as 4-Pyrazoleboronic acid pinacol ester , is a useful research compound. Its molecular formula is C9H15BN2O2 and its molecular weight is 194.04 g/mol. The purity is usually 95%.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. 269410-08-4, formula is C9H15BN2O2, Name is 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. Pyrazole is a weak base, with pKb 11.5 (pKa of the conjugated acid 2.49 at 25 °C).Pyrazole used as a ligand to prepare organometallic compounds. Recommanded Product: 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

Hanan, Emily J.;Baumgardner, Matt;Bryan, Marian C.;Chen, Yuan;Eigenbrot, Charles;Fan, Peter;Gu, Xiao-Hui;La, Hank;Malek, Shiva;Purkey, Hans E.;Schaefer, Gabriele;Schmidt, Stephen;Sideris, Steve;Yen, Ivana;Yu, Christine;Heffron, Timothy P. research published 《 4-Aminoindazolyl-dihydrofuro[3,4-d]pyrimidines as non-covalent inhibitors of mutant epidermal growth factor receptor tyrosine kinase》, the research content is summarized as follows. The treatment of epidermal growth factor receptor (EGFR)-driven non-small cell lung cancers with the T790M resistance mutation remains a significant unmet medical need. The authors report the identification of 4-aminoindazolyl-dihydrofuro[3,4-d]pyrimidines as non-covalent inhibitors of EGFR, with excellent activity against the T790M resistance double mutants and initial single activating mutants. Using an optimization strategy focused on structure-based design and improving PK properties through metabolite identification, the authors obtained advanced leads with high oral exposure.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

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

Hao, Junliang team published research on Journal of Medicinal Chemistry in 2022 | 269410-08-4

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

Pyrazoles and pyrimidines have diverse biological and pharmacological activities. 269410-08-4, formula is C9H15BN2O2, Name is 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. There are a number of antimicrobial compounds containing pyrazole moiety as the core unit. Application of C9H15BN2O2.

Hao, Junliang;Beck, James;Zhou, Xin;Lackner, Gregory L.;Johnston, Richard;Reinhard, Matt;Goldsmith, Paul;Hollinshead, Sean;Dehlinger, Veronique;Filla, Sandra A.;Wang, Xu-shan;Richardson, Jeffery;Posada, Maria;Mohutsky, Mike;Schober, Doug;Katner, Jason S.;Chen, Qi;Hu, Bingjie;Remick, David M.;Coates, David A.;Mathes, Brian M.;Hawk, Mai K.;Svensson, Kjell A.;Hembre, Erik research published 《 Synthesis and Preclinical Characterization of LY3154885, a Human Dopamine D1 Receptor Positive Allosteric Modulator with an Improved Nonclinical Drug-Drug Interaction Risk Profile》, the research content is summarized as follows. Results from recently completed clin. studies suggest the dopamine D1 receptor pos. allosteric modulator (PAM) mevidalen (1) could offer unique value for lewy body dementia (LBD) patients. In nonclin. assessments, 1 was mainly eliminated by CYP3A4-mediated metabolism, therefore at the risk of being a victim of drug-drug interactions (DDI) with CYP3A4 inhibitors and inducers. An effort was initiated to identify a new D1 PAM with an improved DDI risk profile. While attempts to introduce addnl. metabolic pathways mediated by other CYP isoforms failed to provide mols. with an acceptable profile, we discovered that the relative contribution of CYP-mediated oxidation and UGT-mediated conjugation could be tuned to reduce the CYP3A4-mediated victim DDI risk. We have identified LY3154885 (5)(I), a D1 PAM that possesses similar in vitro and in vivo pharmacol. properties as 1, but is metabolized mainly by UGT, predicting it could potentially offer lower victim DDI risk in clinic.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

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

Hatcher, John M. team published research on Journal of Medicinal Chemistry in 2015 | 269410-08-4

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

Hatcher, John M.;Bahcall, Magda;Choi, Hwan Geun;Gao, Yang;Sim, Taebo;George, Rani;Janne, Pasi A.;Gray, Nathanael S. research published 《 Discovery of Inhibitors That Overcome the G1202R Anaplastic Lymphoma Kinase Resistance Mutation》, the research content is summarized as follows. 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.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

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

He, Yonghe team published research on Crystal Growth & Design in 2018 | 269410-08-4

COA of Formula: C9H15BN2O2, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, also known as 4-Pyrazoleboronic acid pinacol ester , is a useful research compound. Its molecular formula is C9H15BN2O2 and its molecular weight is 194.04 g/mol. The purity is usually 95%.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

He, Yonghe;Hu, Jie-Ying;Wong, Yan-Lung;Diao, Yingxue;Xian, Wan-Ru;He, Jun;Zeller, Matthias;Xu, Zhengtao research published 《 Beadwork and Network: Strings of Silver Ions Stitch Large-π Pyrazolate Patches into a Two-dimensional Sheet》, the research content is summarized as follows. Breaking the cycle of Ag pyrazolates: instead of the common loops (e.g., the Ag₃N₆ ring), the authors report an infinite array in which the equispaced Ag(I) ions form a zigzag chain, with the associated anthracene bis(pyrazolate) linkers cofacially aligned one to another. In addition to the strong Ag(I)-N bonds and the distinct argentophilic interactions, the Ag(I) ions also form interlayer, metal-π contacts with the anthracene cores. The resultant two-dimensional network exhibits significant electronic interaction between the Ag(I) centers and the large aromatic linker mol., as revealed by the red shift of photoemission spectra and the significant reduction of the electronic band edge as determined by diffuse reflectance spectroscopy. The solid sample is stable in air and H₂O.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

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

Hillig, Roman C. team published research on Proceedings of the National Academy of Sciences of the United States of America in 2019 | 269410-08-4

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

Hillig, Roman C.;Sautier, Brice;Schroeder, Jens;Moosmayer, Dieter;Hilpmann, AndrA;Stegmann, Christian M.;Werbeck, Nicolas D.;Briem, Hans;Boemer, Ulf;Weiske, Joerg;Badock, Volker;Mastouri, Julia;Petersen, Kirstin;Siemeister, Gerhard;Kahmann, Jan D.;Wegener, Dennis;Boehnke, Niels;Eis, Knut;Graham, Keith;Wortmann, Lars;von Nussbaum, Franz;Bader, Benjamin research published 《 Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction》, the research content is summarized as follows. Since the late 1980s, mutations in the RAS genes have been recognized as major oncogenes with a high occurrence rate in human cancers. Such mutations reduce the ability of the small GTPase RAS to hydrolyze GTP, keeping this mol. switch in a constitutively active GTP-bound form that drives, unchecked, oncogenic downstream signaling. One strategy to reduce the levels of active RAS is to target guanine nucleotide exchange factors, which allow RAS to cycle from the inactive GDP-bound state to the active GTP-bound form. Here, we describe the identification of potent and cell-active small-mol. inhibitors which efficiently disrupt the interaction between KRAS and its exchange factor SOS1, a mode of action confirmed by a series of biophys. techniques. The binding sites, mode of action, and selectivity were elucidated using crystal structures of KRAS^G12C-SOS1, SOS1, and SOS2. By preventing formation of the KRAS-SOS1 complex, these inhibitors block reloading of KRAS with GTP, leading to antiproliferative activity. The final compound 23(I, BAY-293) selectively inhibits the KRAS-SOS1 interaction with an IC₅₀ of 21 nM and is a valuable chem. probe for future investigations.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

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

Hilpert, Lukas J. team published research on Angewandte Chemie, International Edition in 2019 | 269410-08-4

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

Pyrazoles are synthesized by the reaction of α,β-unsaturated aldehydes with hydrazine and subsequent dehydrogenation. 269410-08-4, formula is C9H15BN2O2, Name is 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. Substituted pyrazoles are prepared by condensation of 1,3-diketones with hydrazine (Knorr-type reactions). For example, acetylacetone and hydrazine gives 3,5-dimethylpyrazole. HPLC of Formula: 269410-08-4.

Hilpert, Lukas J.;Sieger, Simon V.;Haydl, Alexander M.;Breit, Bernhard research published 《 Palladium- and Rhodium-Catalyzed Dynamic Kinetic Resolution of Racemic Internal Allenes Towards Chiral Pyrazoles》, the research content is summarized as follows. A complementing Pd- and Rh-catalyzed dynamic kinetic resolution (DKR) of racemic allenes leading to N-allylated pyrazoles was described. Such compounds are of enormous interest in medicinal chem. as certified drugs and potential drug candidates. The new methods feature high chemo-, regio- and enantioselectivities aside from displaying a broad substrate scope and functional group compatibility. A mechanistic rational accounting for allene racemization and trans-alkene selectivity was discussed.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

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

Hou, Shaohua team published research on European Journal of Medicinal Chemistry in 2021 | 269410-08-4

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

Hou, Shaohua;Yang, Xiping;Tong, Yu;Yang, Yuejing;Chen, Quanwei;Wan, Boheng;Wei, Ran;Wang, Yuchen;Zhang, Yanmin;Kong, Bo;Huang, Jianhang;Chen, Yadong;Lu, Tao;Hu, Qinghua;Du, Ding research published 《 Structure-based discovery of 1H-indole-2-carboxamide derivatives as potent ASK1 inhibitors for potential treatment of ulcerative colitis》, the research content is summarized as follows. Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase (MAPK) family, is implicated in many human diseases. Here, we describe the structural optimization of a hit compound and conduct further structure-activity relationship (SAR) studies that result in the development of the indole-2-carboxamide I. I displays potent anti-ASK1 kinase activity and stronger inhibitory effect on ASK1 in AP1-HEK293 cells than previously described ASK1 inhibitor GS-4997. Besides improved in vitro activity, I also exhibits an appropriate in vivo PK profile. In a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC), I shows significant anti-UC efficacy and markedly attenuates DSS-induced body weight loss, colonic shortening, elevation in disease activity index (DAI) and inflammatory cell infiltration in colon tissues. Mechanistically, I represses the phosphorylation of ASK1-p38/JNK signaling pathways and suppresses the overexpression of inflammatory cytokines. Together, these findings suggest that ASK1 inhibitors can potentially be used as a therapeutic strategy for UC.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

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

Gilles, Philippe team published research on European Journal of Medicinal Chemistry in 2020 | 269410-08-4

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

Gilles, Philippe;Kashyap, Rudra S.;Freitas, Maria Joao;Ceusters, Sam;Van Asch, Koen;Janssens, Anke;De Jonghe, Steven;Persoons, Leentje;Cobbaut, Mathias;Daelemans, Dirk;Van Lint, Johan;Voet, Arnout R. D.;De Borggraeve, Wim M. research published 《 Design, synthesis and biological evaluation of pyrazolo[3,4-d]pyrimidine-based protein kinase D inhibitors》, the research content is summarized as follows. Novel pyrazolo[3,4-d]pyrimidine based pan-PKD inhibitors I [R¹ = tBu, 3,3-dimethylbutyl, Bn, etc.; R² = pyrrol-3-yl, indol-3-yl, naphthalen-1-yl, etc.] with structural variety at position 1 were synthesized and evaluated for biol. activity. Compounds I were evaluated for PKD inhibition against full length PKD using Promega’s ADP-Glo^TM kinase activity assay and syntide-2 as a substrate. Starting from compound I [R¹ = tBu; R² = indol-3-yl] a known PKD inhibitor with IC₅₀ values in the range of 94-108 nM, compound I [R¹ = (piperidin-4-yl)methyl; R² = indol-3-yl] was identified with an improved biochem. inhibitory activity against PKD (IC₅₀ = 17-35 nM). Subsequent cellular assays demonstrated that compounds I [R¹ = tBu, (piperidin-4-yl)methyl; R² = indol-3-yl] inhibited PKD-dependent cortactin phosphorylation. Furthermore, the biochem. inhibitory activity of I [R¹ = tBu; R² = indol-3-yl] and 1-NM-PP1 against CAMKIIα and PKCδ was investigated and no notable inhibition was observed at compound concentrations of 1 and 10μM. Some of the synthesized PKD inhibitor compounds I [R¹ = tBu, (piperidin-4-yl)methyl, 2,2-dimethyl-propan-1-ol, (1-Me-piperidin-4-yl)methyl; R² = indol-3-yl, 1-Me-indol-3-yl, 2-ethoxyquinolin-6-yl] and some known PKD inhibitors (CRT0066101, 1-NM-PP1) were evaluated for their antitumor activity in a panel of eight different cancer cell lines. A screening against different cancer cell lines demonstrated that compound I [R¹ = tBu; R² = indol-3-yl] was potent and versatile antitumoral agent.

4-Pyrazoleboronic acid pinacol ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds.

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