Day: November 28, 2022

Graton, Jerome published the artcileHydrogen-Bond Accepting Properties of New Heteroaromatic Ring Chemical Motifs: A Theoretical Study, Recommanded Product: 1-Methylpyrazole, the publication is Journal of Chemical Information and Modeling (2016), 56(2), 322-334, database is CAplus and MEDLINE.

The prediction of hydrogen-bond (H-bond) acceptor ability is crucial in drug design. This important property is quantified in a large pK_BHX database of consistently measured values. We aim to expand the chem. diversity of the studied H-bond acceptors and to increase the range of H-bond strength considered. Two quantum chem. descriptors are contrasted, called ΔE(H) (the change in the energy of a topol. hydrogen atom upon complexation) and V_min (the local min. in the electrostatic potential on the H-bond accepting site). We performed a systematic anal. of the correlations between pK_BHX and V_min for an initial set of 106 compounds (including O- and N-containing subsets, as well as compounds including sulfur, chlorine, and π-bases). Correlations improve for family dependent subsets, and after outlier treatment, a set of 90 compounds was used to set up a linear equation to predict pK_BHX from V_min. This equation and a previously published equation, to predict pK_BHX from ΔE(H), were used to predict the pK_BHX values for 22 potentially biol. active heteroaromatic ring compounds, among which several structures still remain exptl. unavailable. H-Bond basicity of sp² nitrogen sites were consistently predicted with both descriptors. A worse agreement was found with carbonyl acceptor sites, with the stronger deviations observed for the lactam groups. It was shown that secondary interactions involving the neighboring NH group were influencing the results. Substitution of the NH group with an NMe group resulted in an improved consistency from both V_min and ΔE(H) predictions, the latter being more prominently affected by the Me substitution. Both approaches appear as efficient procedures for the H-bond ability prediction of novel heteroaromatic rings. Nevertheless, the ΔE(H) parameter presents slight chem. structure limitations and requires more detailed H-bond structure investigations.

Journal of Chemical Information and Modeling published new progress about 930-36-9. 930-36-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole, name is 1-Methylpyrazole, and the molecular formula is C4H6N2, Recommanded Product: 1-Methylpyrazole.

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

Robke, Lucas published the artcilePhenotypic Identification of a Novel Autophagy Inhibitor Chemotype Targeting Lipid Kinase VPS34, HPLC of Formula: 851435-28-4, the publication is Angewandte Chemie, International Edition (2017), 56(28), 8153-8157, database is CAplus and MEDLINE.

Autophagy is a critical regulator of cellular homeostasis and metabolism Interference with this process is considered a new approach for the treatment of disease, in particular cancer and neurol. disorders. Therefore, novel small-mol. autophagy modulators are in high demand. We describe the discovery of autophinib, a potent autophagy inhibitor with a novel chemotype. Autophinib was identified by means of a phenotypic assay monitoring the formation of autophagy-induced puncta, indicating accumulation of the lipidated cytosolic protein LC3 on the autophagosomal membrane. Target identification and validation revealed that autophinib inhibits autophagy induced by starvation or rapamycin by targeting the lipid kinase VPS34.

Angewandte Chemie, International Edition published new progress about 851435-28-4. 851435-28-4 belongs to pyrazoles-derivatives, auxiliary class Imidazole,Pyrimidine,Chloride,Amine, name is 2-Chloro-6-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine, and the molecular formula is C9H10ClN5, HPLC of Formula: 851435-28-4.

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

Gao, Yaojun published the artcileSynthesis of Pyrazolo[5,1-d][1,2,3,5]tetrazin-4(3H)-ones, Name: Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate, the publication is Journal of Combinatorial Chemistry (2010), 12(1), 69-74, database is CAplus and MEDLINE.

A solid-phase synthesis of 5-aminopyrazoles I (R¹ = H, CN, EtO₂C, Ph; R² = H, Me, Ph) has been developed and applied to the preparation of pyrazolo[5,1-d][1,2,3,5]tetrazin-4(3H)-ones II (R³ = n-hexyl, Ph, 4-ClC₆H₄, PhCH₂, PhCH₂CH₂). In this strategy, 5-aminopyrazoles I were converted into pyrazolo[5,1-d][1,2,3,5]tetrazines II in one-pot via diazotization followed cyclocondensation with isocyanates R³NCO.

Journal of Combinatorial Chemistry published new progress about 23286-70-6. 23286-70-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Ester, name is Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate, and the molecular formula is C7H11N3O2, Name: Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate.

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

Parmar, Narsidas J. published the artcileAn efficient domino Knoevenagel/hetero-Diels-Alder route to some novel thiochromenoquinoline-fused polyheterocycles, Computed Properties of 14580-22-4, the publication is Monatshefte fuer Chemie (2014), 145(7), 1179-1189, database is CAplus.

The 2-alkenylthiopyranoquinoline-3-carbaldehyde derived from 2-mercaptoquinoline-3-carbaldehyde and citral underwent smooth domino Knoevenagel/hetero-Diels-Alder reaction with heterocyclic mono- or diketones in tetrabutylammonium hydrogensulfate under solvent-free conditions and afforded a new class of thiochromenoquinoline-fused heterocycles in good yields. The reaction is highly diastereoselective and can be applied to analogs of carbocyclic diketones as well. The stereochem. of the products was confirmed by single-crystal X-ray diffraction and 2D NMR NOESY data.

Monatshefte fuer Chemie published new progress about 14580-22-4. 14580-22-4 belongs to pyrazoles-derivatives, auxiliary class Organic Pigment, name is 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone, and the molecular formula is C10H9ClN2O, Computed Properties of 14580-22-4.

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

Liang, Jun published the artcileFrom a novel HTS hit to potent, selective, and orally bioavailable KDM5 inhibitors, Related Products of pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(13), 2974-2981, database is CAplus and MEDLINE.

A high-throughput screening (HTS) of the Genentech/Roche library identified a novel, uncharged scaffold as a KDM5A inhibitor. Lacking insight into the binding mode, initial attempts to improve inhibitor potency failed to improve potency, and synthesis of analogs was further hampered by the presence of a C-C bond between the pyrrolidine and pyridine. Replacing this with a C-N bond significantly simplified synthesis, yielding pyrazole analog, [3-(4-bromo-1H-pyrazol-1-yl)-1-pyrrolidinyl][5-(1-methylethyl)-1H-pyrazol-3-yl]methanone (35), of which the authors obtained a co-crystal structure with KDM5A. Using structure-based design approach, the authors identified, N-[(3R)-1-[[5-(1-methylethyl)-1H-pyrazol-3-yl]carbonyl]-3-pyrrolidinyl]cyclopropanecarboxamide (50), with improved biochem., cell potency and reduced MW and lower lipophilicity (Log D) compared with the original hit. Furthermore, 50 showed lower clearance than [5-(1-methylethyl)-1H-pyrazol-3-yl][(3S)-3-[6-methyl-4-(1-methyl-1H-pyrazol-4-yl)-2-pyridinyl]-1-pyrrolidinyl]methanone (9) in mice. In combination with its remarkably low plasma protein binding (PPB) in mice (40%), oral dosing of 50 at 5 mg/kg resulted in unbound C_max ∼2-fold of its cell potency (PC9 H3K4Me3 0.96 μM), meeting the authors’ criteria for an in vivo tool compound from a new scaffold.

Bioorganic & Medicinal Chemistry Letters published new progress about 890590-91-7. 890590-91-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid, name is 3-Isopropyl-1H-pyrazole-5-carboxylic acid, and the molecular formula is C7H10N2O2, Related Products of pyrazoles-derivatives.

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

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

Kaur, Mahaldeep published the artcileThe Indigenous Volatile Inhibitor 2-Methyl-2-butene Impacts Biofilm Formation and Interspecies Interaction of the Pathogenic Mucorale Rhizopus arrhizus, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Microbial Ecology (2022), 83(2), 506-512, database is CAplus and MEDLINE.

2-Methyl-2-butene has recently been reported to be a quorum-based volatile self-inhibitor of spore germination and growth in pathogenic Mucorale Rhizopus arrhizus. The present study aimed to elucidate if this compound can influence R. arrhizus biofilm formation and interspecies interaction. The compound was found to significantly decrease R. arrhizus biofilm formation (p < 0.001), with nearly 25% and 50% lesser biomass in the biofilms cultured with exposure to 4 and 32μg/mL of 2-methyl-2-butene, resp. The growth of pre-formed biofilms was also impacted, albeit to a lesser extent. Addnl., 2-methyl-2-butene was found to self-limit R. arrhizus growth during interspecies interaction with Staphylococcus aureus and was detected at a substantially greater concentration in the headspace of co-cultures (2338.75μg/mL) compared with monocultures (69.52μg/mL). Some of the C5 derivatives of this compound (3-methyl-1-butanol, 2-methyl-2-butanol, and 3-methyl-1-butyne) were also observed to partially mimic its action, such as inhibition of spore germination, but did not impact R. arrhizus biofilm formation. Finally, the treated R. arrhizus displayed changes in fungal morphol. suggestive of cytoskeletal alterations, such as filopodia formation, blebs, increased longitudinal folds and/or corrugations, and finger-like and sheet-like surface protrusions, depending upon the concentration of the compound(s) and the planktonic or biofilm growth mode.

Microbial Ecology published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C22H21N3O3S, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide.

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

Siu, Tony published the artcileThe discovery of reverse tricyclic pyridone JAK2 inhibitors. Part 2: Lead optimization, Product Details of C3H5BN2O2, the publication is Bioorganic & Medicinal Chemistry Letters (2014), 24(6), 1466-1471, database is CAplus and MEDLINE.

This communication discusses the discovery of novel reverse tricyclic pyridones as inhibitors of Janus kinase 2 (JAK2). By using a kinase cross screening approach coupled with mol. modeling, a unique inhibitor-water interaction was discovered to impart excellent broad kinase selectivity. Improvements in intrinsic potency were achieved by utilizing a rapid library approach, while targeted structural changes to lower lipophilicity led to improved rat pharmacokinetics. This multi-pronged approach led to the identification of 31, which demonstrated encouraging rat pharmacokinetics, in vivo potency, and excellent off-target kinase selectivity.

Bioorganic & 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 C14H28O5S, Product Details of C3H5BN2O2.

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

Malysheva, Svetlana F. published the artcileCatalyst-free addition of secondary phosphine chalcogenides to pyrazolecarbaldehydes, Computed Properties of 930-36-9, the publication is Mendeleev Communications (2019), 29(6), 683-685, database is CAplus.

(Chalcogenophosphoryl)hydroxymethyl-substituted pyrazoles were obtained by catalyst-free reaction between 4- and 5-pyrazolecarbaldehydes and secondary phosphine chalcogenides R₂P(X)H [R = Ph, (CH₂)₂Ph, X = O, S, Se] at 23-50° in toluene.

Mendeleev Communications published new progress about 930-36-9. 930-36-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole, name is 1-Methylpyrazole, and the molecular formula is C4H6N2, Computed Properties of 930-36-9.

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