Category: 763120-58-7

Woods, Keith W. published the artcileAminopyrimidinone Cdc7 Kinase Inhibitors, Synthetic Route of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(5), 1940-1943, database is CAplus and MEDLINE.

We have investigated the SAR of a series of pyrimidinone-containing Cdc7 kinase inhibitors. A wide range of amine substitutions give potent compounds with activities (K_i) less than 1 nM. Kinase selectivity is reasonable and cytotoxicity corresponds to inhibition of MCM2 phosphorylation.

Bioorganic & Medicinal Chemistry Letters published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C11H10N4, Synthetic Route of 763120-58-7.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Lee, Je-Heon published the artcileDiscovery of substituted indole derivatives as allosteric inhibitors of m⁶A-RNA methyltransferase, METTL3 -14 complex, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Drug Development Research (2022), 83(3), 783-799, database is CAplus and MEDLINE.

In this study, the discovery of the first allosteric inhibitor of the METTL3-14 complex I = [R¹ = H, CH₃; R² = (4-methoxycarbonylphenoxy), (4-carbamoylphenoxy), (4-carboxyphenoxy), etc.] and II [R³ = 4-Cl-Ph, 4-F-phenyl; R⁴ = Ph, benzyl, [4-(3,5-dichlorophenyl)phenyl], etc] was described based on structure-activity relationship (SAR) and optimization studies of the hit compound, 4-[2-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]-ethoxy]benzoic acid. Compound II [R³ = 4-F-phenyl; R⁴ = [4-(3,5-dichlorophenyl)phenyl]] was optimized throughout the modifications of 4 different regions of the structure, and it displayed potent enzyme inhibitory activity of the METTL3-14 complex (IC₅₀ = 2.81μM) and an antiproliferative effect in the AML cell lines by suppressing the m6A level of mRNA. The inhibition mechanism and binding mode of II [R³ = 4-F-phenyl; R⁴ = [4-(3,5-dichlorophenyl)phenyl]], were based on the interaction of the reversible and noncompetitive inhibitory profile at the allosteric site along with selectivity for the METTL3-14 complex relative to each subunit enzyme or truncated complex enzyme.

Drug Development Research published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Recommanded Product: 1H-Pyrazole-4-boronic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Takeuchi, Craig S. published the artcileDiscovery of a Novel Class of Highly Potent, Selective, ATP-Competitive, and Orally Bioavailable Inhibitors of the Mammalian Target of Rapamycin (mTOR), Quality Control of 763120-58-7, the publication is Journal of Medicinal Chemistry (2013), 56(6), 2218-2234, database is CAplus and MEDLINE.

A series of novel, highly potent, selective, and ATP-competitive mammalian target of rapamycin (mTOR) inhibitors based on a benzoxazepine scaffold have been identified. Lead optimization resulted in the discovery of inhibitors with low nanomolar activity and greater than 1000-fold selectivity over the closely related PI3K kinases. Compound I (XL388) inhibited cellular phosphorylation of mTOR complex 1 (p-p70S6K, pS6, and p-4E-BP1) and mTOR complex 2 (pAKT (S473)) substrates. Furthermore, this compound displayed good pharmacokinetics and oral exposure in multiple species with moderate bioavailability. Oral administration of compound I to athymic nude mice implanted with human tumor xenografts afforded significant and dose-dependent antitumor activity.

Journal of Medicinal Chemistry published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C17H20ClN3, Quality Control of 763120-58-7.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Keyari, Charles M. published the artcileSynthesis of New Quinolinequinone Derivatives and Preliminary Exploration of their Cytotoxic Properties, Application of 1H-Pyrazole-4-boronic acid, the publication is Journal of Medicinal Chemistry (2013), 56(10), 3806-3819, database is CAplus and MEDLINE.

A series of 7-amino- and 7-acetamidoquinoline-5,8-diones with aryl substituents at the 2-position were synthesized, characterized, and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. The synthesis of lavendamycin analogs is illustrated. Metabolism studies demonstrated that 7-amino analogs were generally better substrates for NQO1 than 7-amido analogs, as were compounds with smaller heteroaromatic substituents at the C-2 position. Surprisingly, only two compounds, 7-acetamido-2-(8′-quinolinyl)quinoline-5,8-dione and 7-amino-2-(2-pyridinyl)quinoline-5,8-dione, showed selective cytotoxicity toward the NQO1-expressing MDA468-NQ16 breast cancer cells vs. the NQO1-null MDA468-WT cells. For all other compounds, NQO1 protected against quinoline-5,8-dione cytotoxicity. Compound I showed potent activity against human breast cancer cells expressing or not expressing NQO1, with resp. IC₅₀ values of 190 nM and 140 nM and a low NQO1-mediated reduction rate, which suggests that the mode of action of I differs from that of lavendamycin and involves an unidentified target(s).

Journal of Medicinal Chemistry published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Application of 1H-Pyrazole-4-boronic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Antonow, Dyeison published the artcileStructure-Activity Relationships of Monomeric C2-Aryl Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) Antitumor Agents, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Journal of Medicinal Chemistry (2010), 53(7), 2927-2941, database is CAplus and MEDLINE.

A comprehensive SAR investigation of the C2-position of pyrrolo[2,1-c][1,4]benzodiazepine (PBD) monomer antitumor agents is reported, establishing the mol. requirements for optimal in vitro cytotoxicity and DNA-binding affinity. Both carbocyclic and heterocyclic C2-aryl substituents have been studied ranging from single aryl rings to fused ring systems, and also styryl substituents, establishing across a library of 80 analogs that C2-aryl and styryl substituents significantly enhance both DNA-binding affinity and in vitro cytotoxicity, with a correlation between the two. The optimal C2-grouping for both DNA-binding affinity and cytotoxicity was found to be the C2-quinolinyl moiety which, according to mol. modeling, is due to the overall fit of the mol. in the DNA minor groove, and potential specific contacts with functional groups in the floor and walls of the groove. This analog (I) was shown to delay tumor growth in a HCT-116 (bowel) human tumor xenograft model.

Journal of Medicinal Chemistry published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Recommanded Product: 1H-Pyrazole-4-boronic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Zhang, Lingzhi published the artcileDiscovery of novel dual extracellular regulated protein kinases (ERK) and phosphoinositide 3-kinase (PI3K) inhibitors as a promising strategy for cancer therapy, Related Products of pyrazoles-derivatives, the publication is Molecules (2020), 25(23), 5693, database is CAplus and MEDLINE.

The scaffold-hopping generation of a series of 1H-pyrazolo[3,4-d]pyrimidines I (R¹ = 2-methylpyridin-4-yl, 1-methyl-1H-pyrazol-4-yl; R² = Bn, cyclopentyl) dual ERK/PI3K inhibitors was reported. 1-(7-(1H-Pyrazol-4-yl)pyrido[3,2-d]pyrimidin-2-yl)-3-cyclopentylurea was the most promising candidate, with potent inhibitory activities against both ERK2 and PI3Kα which displays superior anti-proliferative profiles against HCT116 and HEC1B cancer cells. Meanwhile, 1-(7-(1H-pyrazol-4-yl)pyrido[3,2-d]pyrimidin-2-yl)-3-cyclopentylurea possessed acceptable pharmacokinetic profiles and showed more efficacious anti-tumor activity than GDDC-0980 and the corresponding drug combination (BVD-523 + GDDC-0980) in HCT-116 xenograft model, with a tumor growth inhibitory rate of 51% without causing observable toxic effects. All the results indicated that 1-(7-(1H-pyrazol-4-yl)pyrido[3,2-d]pyrimidin-2-yl)-3-cyclopentylurea was a highly effective anticancer compound and provided a promising basis for further optimization towards dual ERK/PI3K inhibitors.

Molecules published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C10H2F12NiO4, Related Products of pyrazoles-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Schmitt, Christian published the artcileDesign and synthesis of a library of lead-like 2,4-bisheterocyclic substituted thiophenes as selective Dyrk/Clk inhibitors, Category: pyrazoles-derivatives, the publication is PLoS One (2014), 9(3), e87851/1-e87851/20, 20 pp., database is CAplus and MEDLINE.

The Dyrk family of protein kinases is implicated in the pathogenesis of several diseases, including cancer and neurodegeneration. Pharmacol. inhibitors were mainly described for Dyrk1A so far, but in fewer cases for Dyrk1B, Dyrk2 or other isoforms. Herein, we report the development and optimization of 2,4-bisheterocyclic substituted thiophenes as a novel class of Dyrk inhibitors. The optimized hit compounds displayed favorable pharmacokinetic properties and high ligand efficiencies, and inhibited Dyrk1B in intact cells. In a larger selectivity screen, only Clk1 and Clk4 were identified as addnl. targets of compound 48, but no other kinases frequently reported as off-targets. Interestingly, Dyrk1A is implicated in the regulation of alternative splicing, a function shared with Clk1/Clk4; thus, some of the dual inhibitors might be useful as efficient splicing modulators. A further compound (29) inhibited Dyrk1A and 1B with an IC50 of 130 nM, showing a moderate selectivity over Dyrk2. Since penetration of the central nervous system (CNS) seems possible based on the physicochem. properties, this compound might serve as a lead for the development of potential therapeutic agents against glioblastoma. Furthermore, an inhibitor selective for Dyrk2 (24) was also identified, which might be are suitable as a pharmacol. tool to dissect Dyrk2 isoform-mediated functions.

PLoS One published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Category: pyrazoles-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

He, Yuanjun published the artcileSynthesis and SAR of novel quinazolines as potent and brain-penetrant c-jun N-terminal kinase (JNK) inhibitors, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2011), 21(6), 1719-1723, database is CAplus and MEDLINE.

Quinazoline I (R = H) was discovered as a novel c-jun N-terminal kinase (JNK) inhibitor with good brain penetration and pharmacokinetic (PK) properties. A number of analogs which were potent both in the biochem. and cellular assays were discovered. Quinazoline I (R = Cl)(II) was found to be a potent JNK3 inhibitor (IC₅₀ = 40 nM), with >500-fold selectivity over p38, and had good PK and brain penetration properties. With these properties, II is considered a potential candidate for in vivo evaluation.

Bioorganic & Medicinal Chemistry Letters published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Recommanded Product: 1H-Pyrazole-4-boronic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Wang, Guofang published the artcileDenitrogenative Pd/Cu-catalyzed Suzuki-type Cross-coupling of Aryltrifluoroborates with Arylhydrazine Hydrochlorides in Water under Room Temperature, Related Products of pyrazoles-derivatives, the publication is Applied Organometallic Chemistry (2018), 32(3), n/a, database is CAplus.

In the presence of Pd(NH₃)₂Cl₂ and CuCl₂ using K₂CO₃, potassium aryltrifluoroborates (and a styryltrifluoroborate) underwent green and aerobic denitrogenative coupling reactions with arylhydrazine monohydrochlorides in water to yield biaryls and trans-stilbene in 62-95% yields.

Applied Organometallic Chemistry published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C10H18O, Related Products of pyrazoles-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Cui, J. Jean published the artcileDiscovery of a Novel Class of Exquisitely Selective Mesenchymal-Epithelial Transition Factor (c-MET) Protein Kinase Inhibitors and Identification of the Clinical Candidate 2-(4-(1-(Quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol (PF-04217903) for the Treatment of Cancer, HPLC of Formula: 763120-58-7, the publication is Journal of Medicinal Chemistry (2012), 55(18), 8091-8109, database is CAplus and MEDLINE.

The c-MET receptor tyrosine kinase is an attractive oncol. target because of its critical role in human oncogenesis and tumor progression. An oxindole hydrazide hit 6 (VI) was identified during a c-MET HTS campaign and subsequently demonstrated to have an unusual degree of selectivity against a broad array of other kinases. The cocrystal structure of the related oxindole hydrazide c-MET inhibitor 10 (X) with a nonphosphorylated c-MET kinase domain revealed a unique binding mode associated with the exquisite selectivity profile. The chem. labile oxindole hydrazide scaffold was replaced with a chem. and metabolically stable triazolopyrazine scaffold using structure based drug design. Medicinal chem. lead optimization produced 2-(4-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol (2, II, PF-04217903), an extremely potent and exquisitely selective c-MET inhibitor. 2 Demonstrated effective tumor growth inhibition in c-MET dependent tumor models with good oral PK properties and an acceptable safety profile in preclin. studies. 2 Progressed to clin. evaluation in a Phase I oncol. setting.

Journal of Medicinal Chemistry published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, HPLC of Formula: 763120-58-7.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics