Day: December 5, 2022

Guccione, Salvatore published the artcileSynthesis of 3-methyl-substituted pyrazolotriazolopyrimidin-4-one and pyrazolothiazolopyrimidin-4-one derivatives, SDS of cas: 23286-70-6, the publication is Journal of Heterocyclic Chemistry (1996), 33(2), 459-463, database is CAplus.

As a part of a research on anti-inflammatory analgesic compounds 3-Me substituted pyrazolotriazolopyrimidin-4-one derivatives (R = Ph, 4-chlorophenyl) and pyrazolothiazolopyrimidin-4-one derivatives II (R¹ = H, Br) were prepared by previously reported procedures. None of the compounds showed improved activity when compared with the previously reported unsubstituted analogs.

Journal of Heterocyclic 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, SDS of cas: 23286-70-6.

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

Garai, Sumanta published the artcileDesign, synthesis, and pharmacological profiling of cannabinoid 1 receptor allosteric modulators: Preclinical efficacy of C2-group GAT211 congeners for reducing intraocular pressure, Synthetic Route of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry (2021), 116421, database is CAplus and MEDLINE.

Allosteric modulators of cannabinoid 1 receptor (CB1R) show translational promise over orthosteric ligands due to their potential to elicit therapeutic benefit without cannabimimetic side effects. The prototypic 2-phenylindole CB1R allosteric modulator, GAT211 (1), demonstrates preclin. efficacy in various disease models. The limited systematic structure-activity relationship (SAR) data at the C2 position of the indole ring within GAT211 invites the opportunity for further modifications to improve GAT211′s pharmacol. profile while serving to amplify and variegate this library of therapeutically attractive agents. These considerations prompted this focused SAR study in which we substituted the GAT211 C2-Ph ring with heteroaromatic substituents. The synthesized GAT211 analogs were then evaluated in vitro as CB1R allosteric modulators in cAMP and β-arrestin2 assays with CP55,940 as the orthosteric ligand. Furan and thiophene rings (15c-f and 15m) were the best-tolerated substituents at the C2 position of GAT211 for engagement with human CB1R (hCB1R). The SAR around the novel ligands reported allowed direct exptl. characterization of the interaction profile of that pharmacophore with its binding domain in functional, human CB1R, thus offering guidance for accessing subsequent-generation hCB1R allosteric modulators as potential therapeutics. The most potent analog, 15d, markedly promoted orthosteric ligand binding to hCB1R. Pharmacol. profiling in the GTPγS and mouse vas deferens assays demonstrated that 15d behaves as a CB1R agonist-pos. allosteric modulator (ago-PAM), as confirmed electrophysiol. in autoptic neurons. In vivo, 15d was efficacious as a topical agent that significantly reduced intraocular pressure (IOP) in the ocular normotensive murine model of glaucoma. Since elevated IOP is a decisive risk factor for glaucoma and attendant vision loss, our data support the proposition that the 2-phenylindole class of CB1R ago-PAMs has therapeutic potential for glaucoma and other diseases where potentiation of CB1R signaling may be therapeutic.

Bioorganic & 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, Synthetic Route of 763120-58-7.

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

Garai, Sumanta published the artcileDesign, synthesis, and pharmacological profiling of cannabinoid 1 receptor allosteric modulators: Preclinical efficacy of C2-group GAT211 congeners for reducing intraocular pressure, Formula: C3H5BN2O2, the publication is Bioorganic & Medicinal Chemistry (2021), 116421, database is CAplus and MEDLINE.

Allosteric modulators of cannabinoid 1 receptor (CB1R) show translational promise over orthosteric ligands due to their potential to elicit therapeutic benefit without cannabimimetic side effects. The prototypic 2-phenylindole CB1R allosteric modulator, GAT211 (1), demonstrates preclin. efficacy in various disease models. The limited systematic structure-activity relationship (SAR) data at the C2 position of the indole ring within GAT211 invites the opportunity for further modifications to improve GAT211′s pharmacol. profile while serving to amplify and variegate this library of therapeutically attractive agents. These considerations prompted this focused SAR study in which we substituted the GAT211 C2-Ph ring with heteroaromatic substituents. The synthesized GAT211 analogs were then evaluated in vitro as CB1R allosteric modulators in cAMP and β-arrestin2 assays with CP55,940 as the orthosteric ligand. Furan and thiophene rings (15c-f and 15m) were the best-tolerated substituents at the C2 position of GAT211 for engagement with human CB1R (hCB1R). The SAR around the novel ligands reported allowed direct exptl. characterization of the interaction profile of that pharmacophore with its binding domain in functional, human CB1R, thus offering guidance for accessing subsequent-generation hCB1R allosteric modulators as potential therapeutics. The most potent analog, 15d, markedly promoted orthosteric ligand binding to hCB1R. Pharmacol. profiling in the GTPγS and mouse vas deferens assays demonstrated that 15d behaves as a CB1R agonist-pos. allosteric modulator (ago-PAM), as confirmed electrophysiol. in autoptic neurons. In vivo, 15d was efficacious as a topical agent that significantly reduced intraocular pressure (IOP) in the ocular normotensive murine model of glaucoma. Since elevated IOP is a decisive risk factor for glaucoma and attendant vision loss, our data support the proposition that the 2-phenylindole class of CB1R ago-PAMs has therapeutic potential for glaucoma and other diseases where potentiation of CB1R signaling may be therapeutic.

Bioorganic & 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

Vannam, Raghu published the artcileTargeted degradation of the enhancer lysine acetyltransferases CBP and p300, Application of tert-Butyl 3-bromo-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate, the publication is Cell Chemical Biology (2021), 28(4), 503-514.e12, database is CAplus and MEDLINE.

The enhancer factors CREB-binding protein (CBP) and p300 (also known as KAT3A and KAT3B) maintain gene expression programs through lysine acetylation of chromatin and transcriptional regulators and by scaffolding functions mediated by several protein-protein interaction domains. Small mol. inhibitors that target some of these domains have been developed; however, they cannot completely ablate p300/CBP function in cells. Here we describe a chem. degrader of p300/CBP, dCBP-1. Leveraging structures of ligand-bound p300/CBP domains, we use in silico modeling of ternary complex formation with the E3 ubiquitin ligase cereblon to enable degrader design. dCBP-1 is exceptionally potent at killing multiple myeloma cells and can abolish the enhancer that drives MYC oncogene expression. As an efficient degrader of this unique class of acetyltransferases, dCBP-1 is a useful tool alongside domain inhibitors for dissecting the mechanism by which these factors coordinate enhancer activity in normal and diseased cells.

Cell Chemical Biology published new progress about 1936429-06-9. 1936429-06-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazoles, name is tert-Butyl 3-bromo-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate, and the molecular formula is C14H10O4, Application of tert-Butyl 3-bromo-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate.

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

Mikami, Satoshi published the artcileDiscovery of an Orally Bioavailable, Brain-Penetrating, in Vivo Active Phosphodiesterase 2A Inhibitor Lead Series for the Treatment of Cognitive Disorders, Application In Synthesis of 23286-70-6, the publication is Journal of Medicinal Chemistry (2017), 60(18), 7658-7676, database is CAplus and MEDLINE.

Herein, the authors describe the discovery of a potent, selective, brain-penetrating, in vivo active phosphodiesterase (PDE) 2A inhibitor lead series. To identify high-quality leads suitable for optimization and enable validation of the physiol. function of PDE2A in vivo, structural modifications of the high-throughput screening hit were performed. The lead generation efforts revealed three key potency-enhancing functionalities with minimal increases in mol. weight (MW) and no change in topol. polar surface area (TPSA). Combining these structural elements led to the identification of 6-methyl-N-((1R)-1-(4-(trifluoromethoxy)phenyl)propyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (38a), a mol. with the desired balance of preclin. properties. Further characterization by cocrystal structure anal. of (38a) bound to PDE2A uncovered a unique binding mode and provided insights into its observed potency and PDE selectivity. Compound (38a) significantly elevated 3′,5′-cGMP levels in mouse brain following oral administration, thus validating this compound as a useful pharmacol. tool and an attractive lead for future optimization.

Journal of Medicinal 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, Application In Synthesis of 23286-70-6.

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

Maurya, Mannar R. published the artcileVanadium(IV and V) complexes of pyrazolone based ligands: Synthesis, structural characterization and catalytic applications, Related Products of pyrazoles-derivatives, the publication is Dalton Transactions (2016), 45(43), 17343-17364, database is CAplus and MEDLINE.

The ONO donor ligands obtained from the condensation of 4-benzoyl-3-methyl-1-phenyl-2-pyrazoline-5-one (Hbp) with benzoylhydrazide (H₂bp-bhz I), furoylhydrazide (H₂bp-fah II), nicotinoylhydrazide (H₂bp-nah III) and isonicotinoylhydrazide (H₂bp-inh IV), upon treatment with [V^IVO(acac)₂], give [V^IVO(bp-bhz)(H₂O)] 1, [V^IVO(bp-fah)(H₂O)] 2, [V^IVO(bp-nah)(H₂O)] 3 and [V^IVO(bp-inh)(H₂O)] 4, resp. At neutral pH the in situ generated aqueous K[H₂V^VO₄] reacts with ligands I and II, forming potassium salts, K(H₂O)₂[V^VO₂(bp-bhz)] 5 and K(H₂O)₂[V^VO₂(bp-fah)] 6, while ligands III and IV give neutral complexes, [V^VO₂(Hbp-nah)] 9 and [V^VO₂(Hbp-inh)] 10, resp. Acidification of aqueous solutions of 5 and 6 with HCl also gives neutral complexes [V^VO₂(Hbp-bhz)] 7 and [V^VO₂(Hbp-fah)] 8, resp. Complexes 1–4, upon slow aerial oxidation in methanol, convert into monooxidovanadium(V) complexes, [V^VO(bp-bhz)(OMe)] 11, [V^VO(bp-fah)(OMe)] 12, [V^VO(bp-nah)(OMe)] 13 and [V^VO(bp-inh)(OMe)] 14, resp. All complexes were characterized by various spectroscopic techniques like FTIR, UV-visible, EPR (for complexes 1–4) and NMR (¹H, ¹³C and ⁵¹V), elemental anal., TG and single crystal x-ray diffraction (for complexes 5–10 and 12). In the solid state, all complexes characterized by x-ray diffraction show the metal ion 5-coordinated in a distorted square pyramidal geometry. Complexes 11–14 were tested as catalysts for the one-pot three-component (ethylacetoacetate, benzaldehyde and ammonium acetate) dynamic covalent assembly, via Hantzsch reaction, using hydrogen peroxide as oxidant in solution and under solvent-free conditions. The complexes are also active catalysts for the oxidation of tetralin to tetralone with H₂O₂ as oxidant. The influence of the amounts of catalyst and oxidant, and solvent, temperature and time on the catalyzed reactions was investigated.

Dalton Transactions 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, Related Products of pyrazoles-derivatives.

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

Dong, Kaiwu published the artcileEfficient Palladium-Catalyzed Alkoxycarbonylation of Bulk Industrial Olefins Using Ferrocenyl Phosphine Ligands, Category: pyrazoles-derivatives, the publication is Angewandte Chemie, International Edition (2017), 56(19), 5267-5271, database is CAplus and MEDLINE.

The development of ligands plays a key role and provides important innovations in homogeneous catalysis. In this context, authors report a novel class of ferrocenyl phosphines for the alkoxycarbonylation of industrially important alkenes. A basic feature of ligands is the combination of sterically hindered and amphoteric moieties on the P atoms, which leads to improved activity and productivity for alkoxycarbonylation reactions compared to the current industrial state-of-the-art ligand 1,2-bis((di-tert-butylphosphino)methyl)benzene. Advantageously, palladium catalysts with these novel ligands also enable such transformations without addnl. acid under milder reaction conditions. The practicability of the optimized ligand was demonstrated by preparation on >10 g scale and its use in palladium-catalyzed carbonylations on kilogram scale.

Angewandte Chemie, International Edition 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

Semenov, Valentin A. published the artcileCalculation of ¹⁵N NMR Chemical Shifts in a Diversity of Nitrogen-Containing Compounds Using Composite Method Approximation at the DFT, MP2, and CCSD Levels, Application In Synthesis of 930-36-9, the publication is Journal of Physical Chemistry A (2019), 123(39), 8417-8426, database is CAplus and MEDLINE.

Computations of 15N NMR chem. shifts in 93 diverse nitrogen-containing compounds representing almost all known classes are performed at the d. functional theory (DFT), second-order Moller-Plesset perturbation theory (MP2), and coupled cluster singles and doubles (CCSD) levels using the composite method approximation (CMA) in comparison with exptl. results. It is shown that the CMA-DFT and CMA-CCSD methods provided the best performance characterized by a normalized mean absolute error of 1.1-1.3% as compared to 2.3% for the CMA-MP2 results. Taking into account solvent effects within the conductor-like polarizable continuum model decreased the normalized mean absolute error by 0.4% for the CMA-DFT and by 0.2% for the CMA-CCSD calculations

Journal of Physical Chemistry A 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 C10H9IO4, Application In Synthesis of 930-36-9.

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

Sathiyaraj, Subbaiyan published the artcileSynthesis, Spectral Characterization, DNA Binding, DNA Cleavage, and Antioxidant Studies of Ruthenium(III) Heterocyclic Thiosemicarbazone Complexes, Application In Synthesis of 4551-69-3, the publication is Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry (2014), 44(9), 1261-1271, database is CAplus.

The reactions of benzothiazolyl thiosemicarbazone with [RuX₃(PPh₃)₃] (X = Cl/Br) in a 1:1 molar ratio gave stable solid complexes corresponding to [RuX(PPh₃)₂(L)]. Structural features were determined by anal. and spectral techniques. DNA binding properties of the ligands and its Ru(III) complexes were studied by electronic absorption spectroscopy. The complexes show good binding affinity to calf-thymus DNA. Gel electrophoresis of pBR322 DNA with complexes demonstrated that the complexes exhibit excellent cleavage activity via oxidative pathway. The antioxidant activity of the free ligands and its complexes was determined by DPPH and hydroxyl radicals. The complexes possess potent antioxidant activity.

Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal 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, Application In Synthesis of 4551-69-3.

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