Day: December 1, 2022

Kharbanda, Anupreet published the artcileDiscovery of 4-aminoquinolines as highly selective TGFβR1 inhibitors with an attenuated MAP4K4 profile for potential applications in immuno-oncology, Formula: C3H5BN2O2, the publication is European Journal of Medicinal Chemistry (2021), 113763, database is CAplus and MEDLINE.

The tumor microenvironment contains high concentrations of TGFβ, a crucial immunosuppressive cytokine. TGFβ stimulates immune escape by promoting peripheral immune tolerance to avoid tumoricidal attack. Small-mol. inhibitors of TGFβR1 are a prospective method for next-generation immunotherapies. In the present study, we identified selective 4-aminoquinoline-based inhibitors of TGFβR1 through structural and rational-based design strategies. This led to the identification of [N-(2-(2,5-difluorophenyl)pyridin-4-yl)-7-(4-(methylsulfonyl)phenyl)quinolin-4-amine], which was found to be selective for TGFβR1 with the exception of MAP4K4 in the kinase profiling assay. The compound was then further optimized to remove MAP4K4 activity, since MAP4K4 is vital for proper T-cell function and its inhibition could exacerbate tumor immunosuppression. Optimization efforts led to [7-(4-(methylsulfonyl)phenyl)-N-(2-(m-tolyl)pyridin-4-yl)quinolin-4-amine] that inhibited TGFβR1 at an IC₅₀ of 0.79 ± 0.19 nM with 2000-fold selectivity against MAP4K4. 7-(4-(Methylsulfonyl)phenyl)-N-(2-(m-tolyl)pyridin-4-yl)quinolin-4-amine, represents a highly selective TGFβR1 inhibitor that has potential applications in immuno-oncol.

European 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, Formula: C3H5BN2O2.

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

Berger, Dan M. published the artcileNon-hinge-binding pyrazolo[1,5-a]pyrimidines as potent B-Raf kinase inhibitors, Safety of 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2009), 19(23), 6519-6523, database is CAplus and MEDLINE.

As part of our research effort to discover B-Raf kinase inhibitors, we prepared a series of C-3 substituted N-(3-(pyrazolo[1,5-a]pyrimidin-7-yl)phenyl)-3-(trifluoromethyl)benzamides. X-ray crystallog. studies revealed that one of the more potent inhibitors bound to B-Raf kinase without forming a hinge-binding hydrogen bond. With basic amine residues appended to C-3 aryl residues, cellular activity and solubility were enhanced over previously described compounds of this class.

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, Safety of 1H-Pyrazole-4-boronic acid.

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

Sun, Wen-Qing published the artcileProgrammable Self-Assembly of Heterometallic Palladium(II)-Copper(II) 1D Grid-Chain using Dinuclear Palladium(II) Corners with Pyrazole-Carboxylic Acid Ligands, Product Details of C8H7N3, the publication is Chemistry – An Asian Journal (2018), 13(9), 1108-1113, database is CAplus and MEDLINE.

A novel heterometallic diPd^II-diCu^II grid-chain, {[(bpy)₄Pd₄Cu₂L₄](NO₃)₄}_n (2; bpy = 2,2′-bipyridine), was synthesized through a programmable self-assembly approach from the mol. corners [(bpy)₂Pd₂(HL)(L)](NO₃) (1) as linkers with Cu^II nitrate by using the bifunctional H₂L ligand 4-(3,5-dimethyl-1H-pyrazol-4-yl)benzoic acid featuring primary (pyrazole) and secondary (HOBz) groups. Structural anal. revealed that 1-dimensional structure 2 consists of one [Cu₂(O₂CPh)₄]_n unit as a bridge and two [(bpy)₂Pd₂L₂]_n corners. Addnl., the catalytic effect of the heterometallic synergy on the Suzuki coupling reaction by using 2 was further explored.

Chemistry – An Asian Journal 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 C8H13NO3, Product Details of C8H7N3.

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

Simov, D. published the artcileAzo dye from 10-methyl-2-aminophenothiazine, Safety of 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone, the publication is Godishnik na Sofiiskiya Universitet Sv. Kliment Okhridski, Khimicheski Fakultet (1975), 543-54, database is CAplus.

Azo dyes (I, R = pyrazolone, hydroxynaphthalene, aniline, aminonaphthalene residues) were prepared by coupling diazotized 2-amino-10-methylphenothiazine [2031-24-5] with RH and dyed protein and synthetic fibers wetfast and, in some cases, lightfast shades. All dyes were characterized by elementary anal., m.p., visible, uv, and ir spectra, and Rf. In I where R is not a pyrazolone residue the equilibrium between the azo enol form and the quinone hydrazone form is fully shifted to the azo enol form.

Godishnik na Sofiiskiya Universitet Sv. Kliment Okhridski, Khimicheski Fakultet 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 C8H17Br, Safety of 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone.

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

Kajita, Harutake published the artcileA Oxidative Bromination of (Hetero)Arenes in the TMSBr/DMSO System: A Non-Aqueous Procedure Facilitates Synthetic Strategies, Formula: C4H6N2, the publication is ChemistrySelect (2017), 2(3), 1117-1121, database is CAplus.

An oxidative bromination protocol for aromatic compounds using trimethylsilyl bromide (TMSBr) and DMSO has been developed. This mild bromination system tolerates a wide variety of functionalities including amide, aldehyde, ester and acetal groups. Arylbromides and heteroarylbromides are produced in up to 95 % yield at 25°. Arenes bearing electron-donating groups are selectively brominated at the para position unless it is blocked. The highlight of this protocol consists in its non-aqueous conditions, which are fruitful particularly in the context of integrated synthetic systems. The utility of this method was demonstrated with three examples, in either of which the bromination was followed by another reaction: a “click” triazole formation, a Suzuki-Miyaura cross-coupling, or an aldehyde formation via lithium-bromine exchange, without the isolation of the bromide intermediate in any case. It is particularly remarkable for this non-aqueous protocol to allow lithiation reactions to sequentially follow the bromination.

ChemistrySelect 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, Formula: C4H6N2.

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

Jismy, Badr published the artcileEfficient access to 3,5-disubstituted 7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidines involving S_NAr and Suzuki cross-coupling reactions, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Molecules (2020), 25(9), 2062, database is CAplus and MEDLINE.

An efficient and original synthesis of various 3,5-disubstituted 7-(trifluoromethyl)pyrazolo [1,5-a]pyrimidines was reported. A library of compounds diversely substituted in C-3 and C-5 positions was easily prepared from a common starting material, 3-bromo-7-(trifluoromethyl)pyrazolo[1,5-a] pyrimidin-5-one. In C-5 position, a S_NAr type reaction was achieved by first activating the C-O bond of the lactam function with PyBroP (Bromotripyrrolidinophosphonium hexafluorophosphate), followed by the addition of amine or thiol giving monosubstituted derivatives, whereas in C-3 position, arylation was performed via Suzuki-Miyaura cross-coupling using the com. available aromatic and heteroaromatic boronic acids. Moreover, trifluoromethylated analogs of potent Pim1 kinase inhibitors were designed following this concise synthetic methodol.

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 C3H5BN2O2, Recommanded Product: 1H-Pyrazole-4-boronic acid.

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

Aravindakshan, Aghil Soorya published the artcileAnalysis of bio-active compounds present in the leaves and stem of Trichosanthes roxb. using GC-MS technique with respect to its anti-inflammatory action, Recommanded Product: 1-Methylpyrazole, the publication is International Journal of Pharmacy and Pharmaceutical Sciences (2021), 13(2), 7-13, database is CAplus.

Structural elucidation studies on Trichosanthes lobata Et acetate and methanol extracts of leaf and stem parts through Gas Chromatog.-Mass Spectrometry (GC-MS) technique with respect to anti-inflammatory potential. Extracts obtained with shade dried and powd. samples in successive solvent extraction using Et acetate and methanol by Soxhlet apparatus and subjected to GC-MS anal. and interpreted for its anti-inflammatory compounds The study revealed that the extraction solvent used was able to recover compound of classes such as organic acid esters and conjugated alkaloids in larger quantities than other classes of compounds and they varied with leaf and stem and also with the polarity of solvents used. In total compounds identified, GC-MS profile of the Et Acetate leaf extract of T. lobata contained 41 compounds, stem extract contained 45 compounds which have reported bioassays in PubChem. Whereas GC-MS profile of methanol leaf extract of T. lobata contained 66 compounds and stem extract contained 46 compounds having bioassay reports in PubChem. A large number of phytochem. peaks with good area percentage were found in methanolic extract We were also able to find out potent anti-inflammatory compounds including Octanoic acid, Dodecanoic acid, Octadecane, Enoic acid, Hexanoic acid, Quinazolin-8-one, Ilicic acid, Pentadecanoic acid, Oxaspiro, Benzeneacetic acid, etc. from the extracts T. lobata contains phytocompounds against inflammation which may serve as a new drug lead of natural products origin in future and make it employable in modern pharmacol. practices.

International Journal of Pharmacy and Pharmaceutical Sciences 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

Gowri, M. published the artcileNovel Heterocyclic Schiff Base, (Z)-4-((2-((2-Aminophenyl)disulfanyl)phenylimino) (Phenyl)Methyl)-3-Methyl-1-Phenyl-1H-Pyrazol-5-ol Crystals for Enzymatic Studies, Name: 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, the publication is Molecular Crystals and Liquid Crystals (2015), 606(1), 199-207, database is CAplus.

A new dithio Schiff base was synthesized and characterized by spectroscopic (FTIR, UV-visible, H¹-NMR, and C¹³-NMR) and x-ray diffraction studies. Mol. interactions (inter and intra) between the neutral entities are discussed. Schiff base ligand, (Z)-4-((2-((2-aminophenyl)disulfanyl)phenylimino)(phenyl)methyl)-3-methyl-1-phenyl-1H-pyrazol-5-ol (), was synthesized by the reaction between 2-phenyl-4-benzoyl-5-methyl-pyrazolin-3-one and 2-amino thio phenol (1:2 molar ratio). The structural elucidation was done by spectroscopic (FTIR, UV-visible, H¹-NMR, C¹³-NMR) and x-ray diffraction studies. Single crystal x-ray diffraction studies revealed that has monoclinic system with space group P21/c with a 15.654(4) Å, b 12.848(4) Å, c 14.219(4) Å; α 90., β 113.65(6), γ 90.°, and Z = 4. The possible intramol. (C-H···N) and intermol. (C-H···O, C-H···S, N-H···O) interactions of were also been discussed.

Molecular Crystals and Liquid Crystals 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, Name: 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one.

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

Lee, Liang Wei published the artcileModulation of the volatile and non-volatile profiles of coffee fermented with Yarrowia lipolytica: II. Roasted coffee, Recommanded Product: 1-Methylpyrazole, the publication is LWT–Food Science and Technology (2017), 32-42, database is CAplus.

The fermentation of green coffee beans by Yarrowia lipolytica led to significant changes in the volatile and non-volatile profiles of green coffees (Part I). Therefore, the objective of this continuation study was to evaluate the effects of fermentation after roasting by characterizing the volatile profiles of coffees at three different roast levels and non-volatile profiles of coffee where the effects of fermentation on volatiles were most prominent (light roast). Y. lipolytica fermentation led to significant changes in the volatile profiles of roasted coffees which arose from both the modification of aroma precursors and the retention of volatile profile changes observed in green fermented coffees. The levels of 4-vinylguaiacol and 4-vinylphenol were 1.2-fold and 1.6-fold higher in light roasted fermented coffees resp. and could be explained by the higher levels detected in green fermented coffees before roasting. The levels of γ-butyrolactone were 5 times higher in light roasted fermented coffees than unfermented coffees. The increase in sulfur compounds levels and decrease in ketones levels were attributed to changes in the concentrations of aroma precursors like sugars and amino acids. Thus, this study highlighted the potential of utilizing yeast fermentation of green coffee beans for coffee aroma modulation.

LWT–Food Science and Technology 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

Lim, Jongwon published the artcileDiscovery of 1-Amino-5H-pyrido[4,3-b]indol-4-carboxamide Inhibitors of Janus Kinase 2 (JAK2) for the Treatment of Myeloproliferative Disorders, Synthetic Route of 724710-02-5, the publication is Journal of Medicinal Chemistry (2011), 54(20), 7334-7349, database is CAplus and MEDLINE.

The JAK-STAT pathway mediates signaling by cytokines, which control survival, proliferation, and differentiation of a variety of cells. In recent years, a single point mutation (V617F) in the tyrosine kinase JAK2 was found to be present with a high incidence in myeloproliferative disorders (MPDs). This mutation led to hyperactivation of JAK2, cytokine-independent signaling, and subsequent activation of downstream signaling networks. The genetic, biol., and physiol. evidence suggests that JAK2 inhibitors could be effective in treating MPDs. De novo design efforts of new scaffolds identified 1-amino-5H-pyrido[4,3-b]indol-4-carboxamides as a new viable lead series. Subsequent optimization of cell potency, metabolic stability, and off-target activities of the leads led to the discovery of 7-(2-aminopyrimidin-5-yl)-1-{[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-5H-pyrido[4,3-b]indole-4-carboxamide (65). Compound 65 is a potent, orally active inhibitor of JAK2 with excellent selectivity, PK profile, and in vivo efficacy in animal models.

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, Synthetic Route of 724710-02-5.

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