Category: pyrazoles-derivatives

Li, Chaomin published the artcileSulfone Displacement Approach for Large-Scale Synthesis of 4-Chloro-N-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-amine, Quality Control of 1462286-01-6, the publication is Organic Process Research & Development (2022), 26(1), 137-143, database is CAplus.

Route evaluation, process development, and large-scale manufacturing of title compound I were described. The improved route consists of two linear chem. steps: oxidation of 4-chloro-2-(methylthio)pyrimidine to 4-chloro-2-(methylsulfonyl)pyrimidine and displacement of the sulfonyl with N-(1-methyl-1H-pyrazol-4-yl)formamide under basic conditions followed by in situ hydrolysis of the N-formyl intermediate to deliver compound I. N-(1-Methyl-1H-pyrazol-4-yl)formamide was readily prepared from 1-methyl-1H-pyrazol-4-amine via reaction with formic acid.

Organic Process Research & Development published new progress about 1462286-01-6. 1462286-01-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazoles, name is 4-Chloro-N-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-amine, and the molecular formula is C8H8ClN5, Quality Control of 1462286-01-6.

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

Qian, Yimin published the artcileDiscovery of Highly Selective and Orally Active Lysophosphatidic Acid Receptor-1 Antagonists with Potent Activity on Human Lung Fibroblasts, Related Products of pyrazoles-derivatives, the publication is Journal of Medicinal Chemistry (2012), 55(17), 7920-7939, database is CAplus and MEDLINE.

Lysophosphatidic acid is a class of bioactive phospholipid that mediates most of its biol. effects through LPA receptors, of which six isoforms have been identified. The recent results from LPA1 knockout mice suggested that blocking LPA1 signaling could provide a potential novel approach for the treatment of idiopathic pulmonary fibrosis. Here, we report the design and synthesis of pyrazole- and triazole-derived carbamates as LPA1-selective and LPA1/3 dual antagonists. In particular, compound I, the most selective LPA1 antagonist reported, inhibited proliferation and contraction of normal human lung fibroblasts (NHLF) following LPA stimulation. Oral dosing of compound I to mice resulted in a dose-dependent reduction of plasma histamine levels in a murine LPA challenge model. Furthermore, we applied our novel antagonists as chem. probes and investigated the contribution of LPA1/2/3 in mediating the pro-fibrotic responses. Our results suggest LPA1 as the major receptor subtype mediating LPA-induced proliferation and contraction of NHLF.

Journal of Medicinal Chemistry published new progress about 105675-85-2. 105675-85-2 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Bromide,Amine, name is 4-Bromo-1-methyl-1H-pyrazol-5-amine, and the molecular formula is C4H6BrN3, Related Products of pyrazoles-derivatives.

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

Bodnarchuk, N. D. published the artcileSubstituted 1,1-diaminoethylenes, Name: Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate, the publication is Zhurnal Organicheskoi Khimii (1973), 9(1), 36-8, database is CAplus.

Six RO2CCX:C(NH2)CY3 (I; R = Me, Et, Me2CH, Me3C; X = MeO2C, EtO2C, Me3CO2C, CN; Y = Cl, F) reacted with R1NH2 [R1 = Pr, Bu, C6H13, HOCH2CH2, Me2CHCH2, NH2, Et2NCH2CH(OH)CH2] to give 18 corresponding RO2CCX:C(NH2)NHR1 in 71-95% yield; I (Y = F) required higher reaction temperatures than I (Y = Cl). EtO2CC(COMe):C(NH2)CF3 and N2H4.H2O in DMF yielded 95% pyrazole II (R2 = Me); EtO2CC(CN):C(NH2)NHNH2 was cyclized to 98 % II (R2 = NH2) in refluxing PhOEt.

Zhurnal Organicheskoi Khimii 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

Wu, Xia published the artcileIodine-Catalyzed Oxidative Coupling To Construct C-O Bonds for the Synthesis of 2,3-Dihydrooxepines, Synthetic Route of 14580-22-4, the publication is Organic Letters (2017), 19(17), 4584-4587, database is CAplus and MEDLINE.

The iodine-catalyzed catalytic formal [3 + 3 + 1] cycloaddition for the preparation of a seven-membered O-heterocyclic ring is presented, which is an achievement of Me and carbonyl group reactivity of 3-methyl-5-pyrazolones to forge the C_sp3-O bond. This novel protocol provides a straightforward and efficient access to structurally diverse fused O-heterocycles through an iodine-catalyzed iodination/Kornblum oxidation/oxidative coupling/C-O bond formation cascade reaction. This approach demonstrates the unprecedented concurrent realization of the unique reactivity among the Me, methylene, and carbonyl groups in 3-methyl-5-pyrazolones for the construction of 2,3-dihydrooxepine rings. Moreover, a broad substrate scope displays a graceful diversity-oriented synthetic approach.

Organic Letters 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 C5H5NO3S, Synthetic Route of 14580-22-4.

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

Brindani, Nicoletta published the artcileIdentification, Structure-Activity Relationship, and Biological Characterization of 2,3,4,5-Tetrahydro-1H-pyrido[4,3-b]indoles as a Novel Class of CFTR Potentiators, Synthetic Route of 890590-91-7, the publication is Journal of Medicinal Chemistry (2020), 63(19), 11169-11194, database is CAplus and MEDLINE.

Cystic fibrosis (CF) is a life-threatening autosomal recessive disease, caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel. CFTR modulators have been reported to address the basic defects associated with CF-causing mutations, partially restoring the CFTR function in terms of protein processing and/or channel gating. Small-mol. compounds, called potentiators, are known to ameliorate the gating defect. In this study, we describe the identification of the 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole core as a novel chemotype of potentiators. In-depth structure-activity relationship studies led to the discovery of enantiomerically pure I endowed with a good efficacy in rescuing the gating defect of F508del- and G551D-CFTR and a promising in vitro druglike profile. The in vivo characterization of γ-carboline I showed considerable exposure levels and good oral bioavailability, with detectable distribution to the lungs after oral administration to rats. Overall, these findings may represent an encouraging starting point to further expand this chem. class, adding a new chemotype to the existing classes of CFTR potentiators.

Journal of Medicinal Chemistry 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, Synthetic Route of 890590-91-7.

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

Ege, Guenter published the artcileReactions with diazoazoles, VII. 3H-Azolo-1,2,4-triazoles by 1,8- or 1,12-electrocyclizations of 3H-pyrazol-3-one- or 3H-indazol-3-one-(diorganylmethylene)hydrazones, Application In Synthesis of 23286-70-6, the publication is Chemische Berichte (1984), 117(5), 1726-47, database is CAplus.

Pyrazolotriazoles I [R¹ = Ph, Me, PhCH₂, H; R² = Ph, H, CO₂Et; R¹R² = (CH:CH)₂; R³ = Ph, Me; R⁴ = Ph, 4-MeOC₆H₄, 4-O₂NC₆H₄; R³R⁴ = 2-C₆H₄XC₆H₄-2, (CPh:CPh)₂; X = bond, CH₂CH₂, O, CO, SO₂] were prepared by cyclizing diazopyrazoles II with R³C(:N₂)R⁴ and with fluorene ylides III (R⁵ = PPh₃, piperidino, SMe₂, SO₂), or by cyclodehydrogenation of hydrazones IV. In both methods, the annulation of the triazole system results from 1,8- or 1,12-electrocyclization of intermediate azines, as, e.g., V.

Chemische Berichte 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, Application In Synthesis of 23286-70-6.

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

Kozlyuk, Natalia published the artcileA fragment-based approach to discovery of Receptor for Advanced Glycation End products inhibitors, Synthetic Route of 724710-02-5, the publication is Proteins: Structure, Function, and Bioinformatics (2021), 89(11), 1399-1412, database is CAplus and MEDLINE.

The Receptor for Advanced Glycation End products (RAGE) is a pattern recognition receptor that signals for inflammation via the NF-κB pathway. RAGE has been pursued as a potential target to suppress symptoms of diabetes and is of interest in a number of other diseases associated with chronic inflammation, such as inflammatory bowel disease and bronchopulmonary dysplasia. Screening and optimization have previously produced small mols. that inhibit the activity of RAGE in cell-based assays, but efforts to develop a therapeutically viable direct-binding RAGE inhibitor have yet to be successful. Here, we show that a fragment-based approach can be applied to discover fundamentally new types of RAGE inhibitors that specifically target the ligand-binding surface. A series of systematic assays of structural stability, solubility, and crystallization were performed to select constructs of the RAGE ligand-binding domain and optimize conditions for NMR-based screening and co-crystallization of RAGE with hit fragments. An NMR-based screen of a highly curated ∼14 000-member fragment library produced 21 fragment leads. Of these, three were selected for elaboration based on structure-activity relationships generated through cycles of structural anal. by X-ray crystallog., structure-guided design principles, and synthetic chem. These results, combined with crystal structures of the first linked fragment compounds, demonstrate the applicability of the fragment-based approach to the discovery of RAGE inhibitors.

Proteins: Structure, Function, and Bioinformatics 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

Kozlyuk, Natalia published the artcileA fragment-based approach to discovery of Receptor for Advanced Glycation End products inhibitors, Synthetic Route of 763120-58-7, the publication is Proteins: Structure, Function, and Bioinformatics (2021), 89(11), 1399-1412, database is CAplus and MEDLINE.

The Receptor for Advanced Glycation End products (RAGE) is a pattern recognition receptor that signals for inflammation via the NF-κB pathway. RAGE has been pursued as a potential target to suppress symptoms of diabetes and is of interest in a number of other diseases associated with chronic inflammation, such as inflammatory bowel disease and bronchopulmonary dysplasia. Screening and optimization have previously produced small mols. that inhibit the activity of RAGE in cell-based assays, but efforts to develop a therapeutically viable direct-binding RAGE inhibitor have yet to be successful. Here, we show that a fragment-based approach can be applied to discover fundamentally new types of RAGE inhibitors that specifically target the ligand-binding surface. A series of systematic assays of structural stability, solubility, and crystallization were performed to select constructs of the RAGE ligand-binding domain and optimize conditions for NMR-based screening and co-crystallization of RAGE with hit fragments. An NMR-based screen of a highly curated ∼14 000-member fragment library produced 21 fragment leads. Of these, three were selected for elaboration based on structure-activity relationships generated through cycles of structural anal. by X-ray crystallog., structure-guided design principles, and synthetic chem. These results, combined with crystal structures of the first linked fragment compounds, demonstrate the applicability of the fragment-based approach to the discovery of RAGE inhibitors.

Proteins: Structure, Function, and Bioinformatics 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, Synthetic Route of 763120-58-7.

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

Bauer, Udo published the artcileDiscovery of 4-hydroxy-1,6-naphthyridine-3-carbonitrile derivatives as novel PDE10A inhibitors, Application In Synthesis of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(5), 1944-1948, database is CAplus and MEDLINE.

A series of 1,6-naphthyridine-based compounds, e.g., I (R¹ = OEt, Cl, CH₂OH, morpholinomethyl, etc.), was synthesized as potent phosphodiesterase 10A (PDE10A) inhibitors. For example, (bromophenyl)naphthyridinecarbonitrile II reacted with [2-(trifluoromethoxy)phenyl]boronic acid in the presence of PPh₃/Pd(OAc)₂/Na₂CO₃ in THF/H₂O and heated for 30 min to 150°C in a microwave oven to give the biphenyl naphthyridine III. Structure-based chem. modifications of the discovered chemotype served to further improve potency and selectivity over DHODH, laying the foundation for future optimization efforts.

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, Application In Synthesis of 763120-58-7.

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

Toure, B. Barry published the artcileToward the Validation of Maternal Embryonic Leucine Zipper Kinase: Discovery, Optimization of Highly Potent and Selective Inhibitors, and Preliminary Biology Insight, HPLC of Formula: 19959-71-8, the publication is Journal of Medicinal Chemistry (2016), 59(10), 4711-4723, database is CAplus and MEDLINE.

MELK kinase has been implicated in playing an important role in tumorigenesis. Our previous studies suggested that MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. Herein we describe the discovery and optimization of novel MELK inhibitors 8a and 8b that recapitulate the cellular effects observed by short hairpin RNA (shRNA)-mediated MELK knockdown in cellular models. We also discovered a novel fluorine-induced hydrophobic collapse that locked the ligand in its bioactive conformation and led to a 20-fold gain in potency. These novel pharmacol. inhibitors achieved high exposure in vivo and were well tolerated, which may allow further in vivo evaluation.

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 C12H10O4S, HPLC of Formula: 19959-71-8.

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