Category: pyrazoles-derivatives

Hong, Fang-Tsao published the artcileSmall Molecule Disruptors of the Glucokinase-Glucokinase Regulatory Protein Interaction: 4. Exploration of a Novel Binding Pocket, HPLC of Formula: 724710-02-5, the publication is Journal of Medicinal Chemistry (2014), 57(14), 5949-5964, database is CAplus and MEDLINE.

Structure-activity relationship investigations conducted at the 5-position of the N-pyridine ring of a series of N-arylsulfonyl-N’-2-pyridinyl-piperazines led to the identification of a novel bis-pyridinyl piperazine sulfonamide I that was a potent disruptor of the glucokinase-glucokinase regulatory protein (GK-GKRP) interaction. Anal. of the x-ray cocrystal of compound I bound to hGKRP revealed that the 3-pyridine ring moiety occupied a previously unexplored binding pocket within the protein. Key features of this new binding mode included forming favorable contacts with the top face of the Ala27-Val28-Pro29 (“shelf region”) as well as an edge-to-face interaction with the Tyr24 side chain. Compound I was potent in both biochem. and cellular assays (IC₅₀ = 0.005 μM and EC₅₀ = 0.205 μM, resp.) and exhibited acceptable pharmacokinetic properties for in vivo evaluation. When administered to db/db mice (100 mg/kg, po), compound I demonstrated a robust pharmacodynamic effect and significantly reduced blood glucose levels up to 6 h postdose.

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, HPLC of Formula: 724710-02-5.

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

Kublicki, Marcin published the artcile1,4-Phenylenebis((1-methyl-1H-pyrazol-5-yl)borinic 8-oxyquinolinate) as a photoredox catalyst in the atom transfer radical addition of iodoperfluoroalkanes to alkenyl groups bearing organoboron compounds, Category: pyrazoles-derivatives, the publication is Tetrahedron Letters (2019), 60(29), 1918-1923, database is CAplus.

The key photocatalytic properties of a transition-metal-free heteroleptic complex I (1) derived from 1,4-phenyldiboronic acid were evaluated. This compound was utilized in the atom transfer radical addition of iodoperfluoroalkanes C_nF_2n+1I (n = 1-4) to a series of allylic arylboronate compounds CH₂:CHCH₂XAr[B] [X = bond, O, CH₂; Ar = phenylene, thiophenediyl; [B] = B(OH)₂, BF₃K] to give C-I activation products, [B]ArXCH₂CHICH₂C_nF_2n+1 (2–14). The products of these reactions retained the B-C bond, and Suzuki-Miyaura coupling of one product gave biphenyl derivatives The X-ray anal. of one of the obtained perfluoroalkylated boronic acids revealed the presence of open star-shaped channels.

Tetrahedron Letters 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, Category: pyrazoles-derivatives.

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

Kurasawa, Osamu published the artcileIdentification of a new class of potent Cdc7 inhibitors designed by putative pharmacophore model: Synthesis and biological evaluation of 2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-ones, Quality Control of 1009071-34-4, the publication is Bioorganic & Medicinal Chemistry (2017), 25(7), 2133-2147, database is CAplus and MEDLINE.

Cell division cycle 7 (Cdc7) is a serine/threonine kinase that plays important roles in the regulation of DNA replication process. A genetic study indicates that Cdc7 inhibition can induce selective tumor-cell death in a p53-dependent manner, suggesting that Cdc7 is an attractive target for the treatment of cancers. In order to identify a new class of potent Cdc7 inhibitors, we generated a putative pharmacophore model based on in silico docking anal. of a known inhibitor with Cdc7 homol. model. The pharmacophore model provided a min. structural motif of Cdc7 inhibitor, by which preliminary medicinal chem. efforts identified a dihydrothieno[3,2-d]-pyrimidin-4(1H)-one scaffold having a heteroaromatic hinge-binding moiety. The structure-activity relationship (SAR) studies resulted in the discovery of new, potent, and selective Cdc7 inhibitors 14a, c, e. Furthermore, the high selectivity of 14c, e for Cdc7 over Rho-associated protein kinase 1 (ROCK1) is discussed by utilizing a docking study with Cdc7 and ROCK2 crystal structures.

Bioorganic & Medicinal Chemistry published new progress about 1009071-34-4. 1009071-34-4 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester, name is tert-Butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate, and the molecular formula is C15H25BN2O4, Quality Control of 1009071-34-4.

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

Asegbeloyin, J. N. published the artcileSynthesis, characterization and antimicrobial screening of some 4-acylpyrazoloimines and some 3d transition metal(II) complexes, Quality Control of 4551-69-3, the publication is Asian Journal of Chemistry (2014), 26(9), 2753-2758, database is CAplus.

Some acylhydroxypyrazole acylhydrazones, e.g., I (R = pentyl, Pr), and their 3d transition metal(II) complexes were synthesized. The ligands and their 3d transition metal complexes were characterized by elemental anal., molar conductance, magnetic susceptibility measurements and spectroscopic methods. The ligands behaved as mono-anion ONO or ONS donor mols. Microanal., electronic spectral and magnetic measurements showed the metal complexes as ML₂ type. All the synthesized compounds were screened for their in vitro antimicrobial activity against some gram pos. and gram neg. clin. bacterial strains. Antimicrobial activity test results showed that the metallic derivatives are more active against the bacterial strains than the imines.

Asian Journal of Chemistry published new progress about 4551-69-3. 4551-69-3 belongs to pyrazoles-derivatives, auxiliary class Benzenes, name is 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, and the molecular formula is C17H14N2O2, Quality Control of 4551-69-3.

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

Deng, Xianming published the artcileExpanding the Diversity of Allosteric Bcr-Abl Inhibitors, Category: pyrazoles-derivatives, the publication is Journal of Medicinal Chemistry (2010), 53(19), 6934-6946, database is CAplus and MEDLINE.

Inhibition of Bcr-Abl kinase activity by imatinib for the treatment of chronic myeloid leukemia (CML) currently serves as the paradigm for targeting dominant oncogenes with small mols. The discovery of GNF-2 (I, R = H) and GNF-5 (I, R = CH₂CH₂OH) was recently reported as selective non-ATP competitive inhibitors of cellular Bcr-Abl kinase activity that target the myristate binding site. Herein is used cell-based structure-activity relationships to guide the optimization and diversification of ligands that are capable of binding to the myristate binding site and rationalize the findings based upon an Abl-compound I (R = H) cocrystal. The structure-activity relationships required to obtain potent antiproliferative activity against Bcr-Abl transformed cells is elucidated, and the discovery of new compounds II (R¹ = 4-(NH₂SO₂)C₆H₄, 4-(MeSO₂NH)C₆H₄, 4-pyrazolyl), III, and IV that display improved potency or pharmacol. properties is reported. This work demonstrates that a variety of structures can effectively target the Bcr-Abl myristate binding site and provides new leads for developing drugs that can target this binding site.

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, Category: pyrazoles-derivatives.

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

Davoren, Jennifer E. published the artcileDesign and optimization of selective azaindole amide M₁ positive allosteric modulators, Application In Synthesis of 19959-71-8, the publication is Bioorganic & Medicinal Chemistry Letters (2016), 26(2), 650-655, database is CAplus and MEDLINE.

Selective activation of the M₁ receptor via a pos. allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimer’s disease. A novel series of azaindole amides and their key pharmacophore elements are described. The nitrogen of the azaindole core is a key design element as it forms an intramol. hydrogen bond with the amide N-H thus reinforcing the bioactive conformation predicted by published SAR and the authors’ homol. model. Representative compound 25 is a potent and selective M₁ PAM that has well aligned physicochem. properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies.

Bioorganic & Medicinal Chemistry Letters 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, Application In Synthesis of 19959-71-8.

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

Katane, Masumi published the artcileIdentification of Novel d-Amino Acid Oxidase Inhibitors by in Silico Screening and Their Functional Characterization in Vitro, Category: pyrazoles-derivatives, the publication is Journal of Medicinal Chemistry (2013), 56(5), 1894-1907, database is CAplus and MEDLINE.

D-Amino acid oxidase (DAO) is a degradative enzyme that is stereospecific for d-amino acids, including d-serine and d-alanine, which are potential coagonists of the N-methyl-d-aspartate (NMDA) receptor. Dysfunction of NMDA receptor-mediated neurotransmission has been implicated in the onset of various mental disorders such as schizophrenia. Hence, a DAO inhibitor that augments the brain levels of d-serine and/or d-alanine and thereby activates NMDA receptor function is expected to be an antipsychotic drug, for instance, in the treatment of schizophrenia. In the search for potent DAO inhibitor(s), a large number of compounds were screened in silico, and several compounds were estimated as candidates. These compounds were then characterized and evaluated as novel DAO inhibitors in vitro. The results reported in this study indicate that some of these compounds are possible lead compounds for the development of a clin. useful DAO inhibitor and have the potential to serve as active site probes to elucidate the structure-function relationships of DAO.

Journal of Medicinal Chemistry 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

Suzuki, Yumiko published the artcileDiscovery of a Potent Anticancer Agent PVHD303 with in Vivo Activity, Computed Properties of 724710-02-5, the publication is ACS Medicinal Chemistry Letters (2020), 11(6), 1287-1291, database is CAplus and MEDLINE.

As a part of our continuous structure-activity relationship (SAR) studies on 1-(quinazolin-4-yl)-1-(4-methoxyphenyl)ethan-1-ols, the synthesis of derivatives and their cytotoxicity against the human lung cancer cell line A549 were explored. This led to the discovery of 1-(2-(furan-3-yl)quinazolin-4-yl)-1-(4-methoxyphenyl)ethan-1-ol (PVHD303) with potent antiproliferative activity. PVHD303 disturbed microtubule formation at the centrosomes and inhibited the growth of tumors dose-dependently in the HCT116 human colon cancer xenograft model in vivo.

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 C9H10O4, Computed Properties of 724710-02-5.

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

Machrouhi, Fouzia published the artcileThe rational design of a novel potent analogue of the 5′-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity, SDS of cas: 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(22), 6394-6399, database is CAplus and MEDLINE.

We have designed and synthesized analogs of compound C, [4-(2-piperidinyl-1-ylethoxy)phenyl]-3-(4-pyridinyl)pyrazolo[1,5-a]pyrimidine, a non-specific inhibitor of 5′-AMP-activated protein kinase (AMPK), using a computational fragment-based drug design (FBDD) approach. Synthesizing only twenty-seven analogs yielded a compound that was equipotent to compound C in the inhibition of the human AMPK (hAMPK) α2 subunit in the heterotrimeric complex in vitro, exhibited significantly improved selectivity against a subset of relevant kinases, and demonstrated enhanced cellular inhibition of AMPK.

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, SDS of cas: 763120-58-7.

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

Keskin, Fatma Ela published the artcileThe Role of Different Molecular Markers in Papillary Thyroid Cancer Patients with Acromegaly, Application of 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Experimental and Clinical Endocrinology & Diabetes (2019), 127(7), 437-444, database is CAplus and MEDLINE.

Prevalence of papillary thyroid cancer (PTC) is increased in patients with acromegaly. We aimed to determine the protein expression of BRAF, RAS, RET, insulin like growth factor 1(IGF1), Galectine 3, CD56 in patients with PTC related acromegaly and to compare the extensity of these expressions with normal PTC patients and benign thyroid nodules. We studied 313 patients with acromegaly followed in Cerrahpasa Medical Faculty, Endocrinol. and Metabolism Clinic between 1998 and 2015. On the basis of availability of pathol. specimen of thyroid tissues, thyroid samples of 13 patients from 19 with acromegaly related PTC (APTC), 20 normal PTC and 20 patients with multinodulary goiter (MNG) were histopathol. evaluated. Protein expressions were determined via immunohistochem. staining in ex-vivo tumor samples and benign nodules. The incidence of PTC in acromegaly patients were 6% (n = 19). Among patients with PTC, APTC and MNG, all the immunohistochem. protein expressions we have studied were higher in papillary thyroid cancer groups (p<0.01, for all). Between PTC group without acromegaly and APTC, galectin 3 and IGF1 expression was significantly higher in acromegalic patients (p<0.01 for all) while RAS was predominantly higher in PTC patients without acromegaly (p<0.01). BRAF expression was not higher in PTC with acromegaly patients compared to PTC patients without acromegaly. Galectine 3 and IGF1 were expressed more intensively in APTC. These pos. protein expressions may have more influence on determining malign nodules among acromegaly patients.

Experimental and Clinical Endocrinology & Diabetes 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, Application of 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