Day: November 23, 2022

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

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

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

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

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