Tag: M.W=100-150

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

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

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

Rizwan, Komal published the artcilePalladium catalyzed cross-coupling of 3-methylthiophene-2-carbonyl chloride with aryl/het-aryl boronic acids: a convenient method for synthesis of thienyl ketones, Synthetic Route of 724710-02-5, the publication is Journal of Sulfur Chemistry (2022), 43(5), 494-506, database is CAplus.

A protocol for the synthesis of thienyl ketones was developed via Pd(0) catalyzed cross-coupling reaction. The desired thienyl ketones were synthesized by cross coupling of 3-methylthiophene-2-carbonyl chloride with variety of aryl/heteroarylboronic acids in good to excellent yields (46-91%) under mild conditions (1.5 equiv Cs₂CO₃ at 50°C). Different functional groups were well tolerated under the developed reaction conditions.

Journal of Sulfur Chemistry published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C3H5BN2O2, Synthetic Route of 724710-02-5.

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

Lin, Cai published the artcileExploration of 6-methyl-7-(Hetero)Aryl-7-Deazapurine ribonucleosides as antileishmanial agents, Category: pyrazoles-derivatives, the publication is European Journal of Medicinal Chemistry (2022), 114367, database is CAplus and MEDLINE.

Leishmaniasis causes high mortality and morbidity in tropical and subtropical regions of Africa, Asia, the Americas and southern Europe, and is characterized by diverse clin. manifestations. The Leishmania parasite is deficient in de novo purine synthesis, and therefore acquires purines from the host and processes these using a purine salvage pathway. In vitro screening of an inhouse purine nucleoside library and analog synthesis afforded the 6-methyl-7-(2-pyridyl)-7-deazapurine ribonucleoside analog, e.g. I, as a promising hit. Encouraged by the favorable in vitro metabolic stability, an in vivo study was performed using an early curative L. infantum hamster model. When orally administrated at 50 mg/kg once daily (s.i.d) for 10 days, I was devoid of side effects, however, it only poorly reduced amastigote burdens in the major target organs.

European Journal of Medicinal Chemistry published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C3H5BN2O2, Category: 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

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

Nemec, Vaclav published the artcileHighly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core, Name: (1H-Pyrazol-5-yl)boronic acid, the publication is European Journal of Medicinal Chemistry (2021), 113299, database is CAplus and MEDLINE.

The furo [3,2-b]pyridine motif represents a relatively underexplored central pharmacophore in the area of kinase inhibitors. Herein, author’s report flexible synthesis of 3,5-disubstituted furo[3,2-b]pyridines that relies on chemoselective couplings of newly prepared 5-chloro-3-iodofuro[3,2-b]pyridine. This methodol. allowed efficient second-generation synthesis of the state-of-the-art chem. biol. probe for CLK1/2/4 I, and identification of the highly selective inhibitors of HIPKs II and III which are presented and characterized in this study, including the X-ray crystal structure of II in HIPK2.chem. biol. probe.

European Journal of Medicinal Chemistry published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C3H5BN2O2, Name: (1H-Pyrazol-5-yl)boronic acid.

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

Szanto, Gabor published the artcileNew P2X3 receptor antagonists. Part 2: Identification and SAR of quinazolinones, Name: 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2016), 26(16), 3905-3912, database is CAplus and MEDLINE.

Numerous potent P2X3 antagonists have been discovered and the therapeutic potential of P2X3 antagonism already comprises proof-of-concept data obtained in clin. trials with the most advanced compound The authors have lately reported the discovery and optimization of thia-triaza-tricycle compounds with potent P2X3 antagonistic properties. This Letter describes the SAR of a back-up series containing a 4-oxo-quinazoline central ring. The discovery of the highly potent compounds I is presented.

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 C23H43NP2, Name: 1H-Pyrazole-4-boronic acid.

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

Wang, Gary T. published the artcileLead optimization of methionine aminopeptidase-2 (MetAP2) inhibitors containing sulfonamides of 5,6-disubstituted anthranilic acids, COA of Formula: C3H5BN2O2, the publication is Bioorganic & Medicinal Chemistry Letters (2007), 17(10), 2817-2822, database is CAplus and MEDLINE.

A series of aryl sulfonamides of 5,6-disubstituted anthranilic acids were identified as potent inhibitors of methionine aminopeptidase-2 (MetAP2). Small alkyl groups and 3-furyl were tolerated at the 5-position of anthranilic acid, while -OCH₃, CH₃, and Cl were found optimal for the 6-position. Placement of 2-aminoethoxy group at the 6-position enabled interaction with the second Mn²⁺ but did not result in enhancement in potency. Introduction of a tertiary amino moiety at the ortho-position of the sulfonyl Ph ring gave reduced protein binding and improved cellular activity, but led to lower oral bioavailability.

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 C6H20Cl2N4, COA of Formula: C3H5BN2O2.

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