Tag: M.W=100-150

Oh, Sangmi published the artcileIdentification of Piperidine-3-carboxamide Derivatives Inducing Senescence-like Phenotype with Antimelanoma Activities, Recommanded Product: (1H-Pyrazol-5-yl)boronic acid, the publication is ACS Medicinal Chemistry Letters (2021), 12(4), 563-571, database is CAplus and MEDLINE.

This study evaluated the potential use of senescence-inducing small mols. in the treatment of melanoma. We screened com. available small-mol. libraries with high-throughput screening and high-content screening image-based technol. Our findings showed an initial hit with the embedded N-arylpiperidine-3-carboxamide scaffold induced senescence-like phenotypic changes in human melanoma A375 cells without serious cytotoxicity against normal cells. A focused library containing diversely modified analogs were constructed and examined to evaluate the structure-activity relationship of N-arylpiperidine-3-carboxamide derivatives starting from hit 1. This work identified a novel compound with remarkable antiproliferative activity in vitro and demonstrated the key structural moieties within.

ACS Medicinal Chemistry Letters 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, Recommanded Product: (1H-Pyrazol-5-yl)boronic acid.

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

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

Cox, Paul A. published the artcileProtodeboronation of Heteroaromatic, Vinyl, and Cyclopropyl Boronic Acids: pH-Rate Profiles, Autocatalysis, and Disproportionation, HPLC of Formula: 724710-02-5, the publication is Journal of the American Chemical Society (2016), 138(29), 9145-9157, database is CAplus and MEDLINE.

PH-rate profiles for aqueous-organic protodeboronation of 18 boronic acids, many widely viewed as unstable, have been studied by NMR and DFT. Rates were pH-dependent, and varied substantially between the boronic acids, with rate maxima that varied over 6 orders of magnitude. A mechanistic model containing five general pathways (k₁-k₅) has been developed, and together with input of [B]_tot, K_W, K_a, and K_aH, the protodeboronation kinetics can be correlated as a function of pH (1-13) for all 18 species. Cyclopropyl and vinyl boronic acids undergo very slow protodeboronation, as do 3- and 4-pyridyl boronic acids (t_0.5 > 1 wk, pH 12, 70 °C). In contrast, 2-pyridyl and 5-thiazolyl boronic acids undergo rapid protodeboronation (t_0.5 ≈ 25-50 s, pH 7, 70 °C), via fragmentation of zwitterionic intermediates. Lewis acid additives (e.g., Cu, Zn salts) can attenuate (2-pyridyl) or accelerate (5-thiazolyl and 5-pyrazolyl) fragmentation. Two addnl. processes compete when the boronic acid and the boronate are present in sufficient proportions (pH = pK_a ± 1.6): (i) self-/autocatalysis and (ii) sequential disproportionations of boronic acid to borinic acid and borane.

Journal of the American Chemical Society 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, HPLC of Formula: 724710-02-5.

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

Cox, Paul A. published the artcileProtodeboronation of Heteroaromatic, Vinyl, and Cyclopropyl Boronic Acids: pH-Rate Profiles, Autocatalysis, and Disproportionation, Quality Control of 763120-58-7, the publication is Journal of the American Chemical Society (2016), 138(29), 9145-9157, database is CAplus and MEDLINE.

PH-rate profiles for aqueous-organic protodeboronation of 18 boronic acids, many widely viewed as unstable, have been studied by NMR and DFT. Rates were pH-dependent, and varied substantially between the boronic acids, with rate maxima that varied over 6 orders of magnitude. A mechanistic model containing five general pathways (k₁-k₅) has been developed, and together with input of [B]_tot, K_W, K_a, and K_aH, the protodeboronation kinetics can be correlated as a function of pH (1-13) for all 18 species. Cyclopropyl and vinyl boronic acids undergo very slow protodeboronation, as do 3- and 4-pyridyl boronic acids (t_0.5 > 1 wk, pH 12, 70 °C). In contrast, 2-pyridyl and 5-thiazolyl boronic acids undergo rapid protodeboronation (t_0.5 ≈ 25-50 s, pH 7, 70 °C), via fragmentation of zwitterionic intermediates. Lewis acid additives (e.g., Cu, Zn salts) can attenuate (2-pyridyl) or accelerate (5-thiazolyl and 5-pyrazolyl) fragmentation. Two addnl. processes compete when the boronic acid and the boronate are present in sufficient proportions (pH = pK_a ± 1.6): (i) self-/autocatalysis and (ii) sequential disproportionations of boronic acid to borinic acid and borane.

Journal of the American Chemical Society 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, 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

Mulyana, Yanyan published the artcileNew cobalt(II) and zinc(II) coordination frameworks incorporating a pyridyl-pyrazole ditopic ligand, Category: pyrazoles-derivatives, the publication is Dalton Transactions (2005), 1598-1601, database is CAplus and MEDLINE.

The metal-directed assembly of new mol. frameworks incorporating 4-(4-pyridyl)pyrazole (HL), containing non-linear coordination vectors, is presented. Three metallo-arrays of types [Co(LH₂)₂(NO₃)₄], [Co(LH₂)₂(H₂O)₄][NO₃]₄·H₂O and [Zn₂(L)₂Cl₂]·2EtOH. The cobalt(II) in [Co(LH₂)₂(NO₃)₄] displays distorted octahedral geometry with the two protonated pyridylpyrazole ligands coordinated through their pyrazole nitrogen atoms in a trans-orientation and the remaining four coordination sites occupied by nitrate anions. Two internal hydrogen bonds occur between each pyrazole NH and the oxygens of adjacent coordinated nitrato ligands. Short intermol. hydrogen bonds also occur between the two pyridinium hydrogens and bound nitrate ligands on different mols. to yield a two-dimensional hydrogen-bonded array. Two of these arrays interpenetrate to form an extended two dimensional layer. The two-dimensional layers stack throughout the crystal structure. A second product of type [Co(LH₂)₂(H₂O)₄][NO₃]₄·H₂O exists as two crystallog. independent forms that are chem. similar. In each form, the two protonated pyridylpyrazole ligands occupy trans positions about the cobalt with the remaining four coordination sites being filled by water mols. to yield a distorted octahedral coordination geometry. Intramol. hydrogen-bonding is observed between the two non-coordinated pyrazoyl nitrogen atoms and bound water oxygen atoms. The third complex, [Zn₂(L)₂Cl₂]·2EtOH, contains dimer units consisting of two zinc(II) ions bridged by two pyrazoylate groups in which the coordination geometry of each zinc approximates a tetrahedron. Each zinc is bound to two deprotonated pyridylpyrazolato ligands, one pyridyl group (from a different dimeric unit) and one chloro ligand. Each pyridyl nitrogen thus connects each of these zinc dimers to an adjacent dimer unit, forming a three-dimensional network containing small voids. The latter are occupied by ethanol mols. which form hydrogen bonds to the chloro ligands.

Dalton Transactions published new progress about 19959-71-8. 19959-71-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Pyridine, name is 4-(1H-Pyrazol-4-yl)pyridine, and the molecular formula is C8H7N3, Category: pyrazoles-derivatives.

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

Peterson, L. K. published the artcileMechanism of the transition metal-catalyzed reaction of 1,1′-carbonyldipyrazoles with aldehydes and ketones, Recommanded Product: 1H-Pyrazole-1-carbonyl chloride, the publication is Canadian Journal of Chemistry (1974), 52(13), 2367-74, database is CAplus.

The metal-catalyzed reaction of 1,1′-carbonyldipyrazoles with aldehydes or ketones to give 1,1′-alkylidenedipyrazoles and CO2, the latter being derived from the amide carbonyl group as shown by labeling experiments, is sensitive to electronic and steric substituent effects. Under comparable reaction conditions, 1,1′-carbonyldiimidazole, N-acetylpyrazole, and 1-pyrazole-N,N-diethylcarbonamide do not react with acetone while pyrazole-1-carbo(N’-phenylhydrazide) yields an anilino isocyanate dimer. These results are interpreted in terms of a mechanism that involves coordination of the metal ion at the 2,2′-N atoms of the pyrazole rings and heterolytic cleavage of an amide bond, followed by formation of a carbamate intermediate, decarboxylation, and metal ion exchange. Unsym. substituted 1,1′-carbonyldipyrazoles equilibrate thermally with their resp. sym. analogs by an intermol. exchange mechanism.

Canadian Journal of Chemistry published new progress about 53355-55-8. 53355-55-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Chloride,acyl chloride,Amide, name is 1H-Pyrazole-1-carbonyl chloride, and the molecular formula is C4H3ClN2O, Recommanded Product: 1H-Pyrazole-1-carbonyl chloride.

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

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

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