Month: October 2022

Pierre, Fabrice; Chua, Peter C.; O’Brien, Sean E.; Siddiqui-Jain, Adam; Bourbon, Pauline; Haddach, Mustapha; Michaux, Jerome; Nagasawa, Johnny; Schwaebe, Michael K.; Stefan, Eric; Vialettes, Anne; Whitten, Jeffrey P.; Chen, Ta Kung; Darjania, Levan; Stansfield, Ryan; Anderes, Kenna; Bliesath, Josh; Drygin, Denis; Ho, Caroline; Omori, May; Proffitt, Chris; Streiner, Nicole; Trent, Katy; Rice, William G.; Ryckman, David M. published the artcile< Discovery and SAR of 5-(3-Chlorophenylamino)benzo[c][2,6]naphthyridine-8-carboxylic Acid (CX-4945), the first clinical stage inhibitor of protein kinase CK2 for the treatment of cancer>, Reference of 53636-56-9, the main research area is naphthyridinecarboxylic acid derivative CX4945 preparation antitumor structure activity; protein kinase CK2 target antitumor CX 4945 preparation.

Herein we chronicle the discovery of CX-4945 (I), a first-in-class, orally bioavailable ATP-competitive inhibitor of protein kinase CK2 in clin. trials for cancer. CK2 has long been considered a prime cancer drug target because of the roles of deregulated and overexpressed CK2 in cancer-promoting pro-survival and antiapoptotic pathways. These biol. properties as well as the suitability of CK2’s small ATP binding site for the design of selective inhibitors, led us to fashion novel therapeutic agents for cancer. The optimization leading to I (Ki = 0.38 nM) was guided by mol. modeling, suggesting a strong binding of I resulting from a combination of hydrophobic interactions, an ionic bridge with Lys68, and hydrogen bonding with the hinge region. I was highly selective, orally bioavailable across species (20-51%) and efficacious in xenograft models. The discovery of I will allow the therapeutic targeting of CK2 in humans for the first time.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 53636-56-9 belongs to class pyridine-derivatives, and the molecular formula is C7H6BrNO2, Reference of 53636-56-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Potapov, V. A.; Ishigeev, R. S.; Shkurchenko, I. V.; Amosova, S. V. published the artcile< Assembling of Thiazolo[3,2-a]pyridinium Salts via the Reaction of 2-Pyridinesulfenyl Halides with Vinyl Ethyl Ether>, Category: pyridine-derivatives, the main research area is pyridinesulfenyl halide vinyl ethyl ether regioselective heterocyclization; ethoxy thiazolopyridinum halide preparation.

The regio- and stereoselective synthesis of 3-ethoxy-2H,3H-[1,3]thiazolo[3,2-a]pyridin-4-ium halides via the reaction of 2-pyridinesulfenyl halides with vinyl Et ether was elaborated.

Russian Journal of General Chemistry published new progress about Ethers Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 2127-03-9 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2S2, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Liu, Ruiting; Tzounopoulos, Thanos; Wipf, Peter published the artcile< Synthesis and Optimization of Kv7 (KCNQ) Potassium Channel Agonists: The Role of Fluorines in Potency and Selectivity>, Formula: C7H7F3N2, the main research area is KCNQ potassium channel agonist preparation structure.

Based on the potent Kv7 agonist RL-81, we prepared new lead structures with greatly improved selectivity for Kv7.2/Kv7.3 over related potassium channels, i.e., Kv7.3/Kv7.5, Kv7.4, and Kv7.4/7.5. RL-36 and RL-12 maintain an agonist EC2x of ca. 1 μM on Kv7.2/Kv7.3 in a high-throughput assay on an automated electrophysiol. platform in HEK293 cells but lack activity on Kv7.3/Kv7.5, Kv7.4, and Kv7.4/7.5, resulting in a selectivity index SI > 10. RL-56 is remarkably potent, EC2x 0.11 ± 0.02 μM, and still shows an SI = 2.5. We also identified analogs with significant selectivity for Kv7.4/Kv7.5 over Kv7.2/Kv7.3. The extensive use of fluorine in iterative core structure modifications highlights the versatility of these substituents, including F, CF3, and SF5, to span orders of magnitude of potency and selectivity in medicinal chem. lead optimizations.

ACS Medicinal Chemistry Letters published new progress about Homo sapiens. 387350-39-2 belongs to class pyridine-derivatives, and the molecular formula is C7H7F3N2, Formula: C7H7F3N2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zhang, Keping; Ding, Chengqiang; Liu, Xiaolin; Gao, Jun; Wu, Datong; Qin, Yong; Kong, Yong published the artcile< A redox and pH dual-triggered drug delivery platform based on chitosan grafted tubular mesoporous silica>, Recommanded Product: 1,2-Di(pyridin-2-yl)disulfane, the main research area is chitosan tubular mesoporous silica hydrogen ion concentration drug delivery.

Tubular mesoporous silica (T-mSiO2) was facilely synthesized through a co-template method by using cetyltrimethylammonium bromide and α-Fe2O3 as the dual templates, and then disulfide (-SS-) bonds and carboxyl groups (-COOH) were introduced to the resultant T-mSiO2 via the reaction with 2-carboxyethyl 2-pyridyl disulfide. The obtained -SS- grafted T-mSiO2 (SS-T-mSiO2) was then grafted with chitosan (CS) via the amidation reaction between the -COOH groups on SS-T-mSiO2 and the -NH2 groups on CS. The CS grafted SS-T-mSiO2 (CS-SS-T-mSiO2) was fully characterized by various technologies such as transmission electron microscopy, energy dispersive X-ray spectroscopy and Fourier transform IR spectroscopy. Finally, the as-synthesized CS-SS-T-mSiO2 was used as the carrier for redox and pH dual-triggered delivery of 5-fluorouracil (5-FU), an anti-cancer drug, and the results indicate that the developed CS-SS-T-mSiO2 might be a potential responsive carrier for redox and pH dual-triggered drug delivery.

Ceramics International published new progress about Amidation. 2127-03-9 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2S2, Recommanded Product: 1,2-Di(pyridin-2-yl)disulfane.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Wan, Yupeng; Lyu, Heng; Du, Hengyi; Wang, Dunjia; Yin, Guodong published the artcile< Synthesis and photophysical properties of europium pentafluorinated β-diketonate complexes>, Product Details of C10H8N2, the main research area is preparation europium pentafluorinated beta diketonate dipyridine phenanthroline complex; photoluminescence europium pentafluorinated beta diketonate dipyridine phenanthroline complex; thermal decomposition europium pentafluorinated beta diketonate dipyridine phenanthroline complex.

Two pentafluorinated β-diketone ligands, 4,4,5,5,5-pentafluoro-1-(4-methoxyphenyl)pentane-1,3-dione (PFMP) and 4,4,5,5,5-pentafluoro-1-(4-dimethyl amino-phenyl)pentane-1,3-dione (PFAP), had been employed to synthesize six novel europium(III) complexes with ancillary ligands 2,2-dipyridine, 1,10-phenanthroline and 4,7-diphenyl-1,10-phenanthroline. The synthesized europium(III) complexes were characterized by FTIR, 1H NMR, UV-visible, luminescence spectroscopy, elemental anal. and TGA. The photoluminescence spectra of these complexes showed the typical europium(III) red emissions in solid state and chloroform solution, assigned to 5D0 → 7Fj (j = 0-4) transitions. The higher values of intensity parameter Ω2 indicated that the europium ion was in a highly polarizable ligand field in these complexes. Europium(III) complexes with the β-diketone PFMP exhibited much better photoluminescence properties than complexes with the β-diketone PFAP. Especially, the europium(III) complex of the β-diketone PFMP with the auxiliary ligand 2,2-dipyridine displayed the longest lifetime value, the highest quantum yield and good CIE color coordinates matching the pure red color (x = 0.67, y = 0.33) in these complexes. In addition, the proposed energy transfer mechanisms and the thermal stability of these complexes were also studied and analyzed.

Research on Chemical Intermediates published new progress about Emission spectra. 366-18-7 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2, Product Details of C10H8N2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Wu, Tong; Zhu, Jian; Strickland, Amy; Ko, Kwang Woo; Sasaki, Yo; Dingwall, Caitlin B.; Yamada, Yurie; Figley, Matthew D.; Mao, Xianrong; Neiner, Alicia; Bloom, A. Joseph; DiAntonio, Aaron; Milbrandt, Jeffrey published the artcile< Neurotoxins subvert the allosteric activation mechanism of SARM1 to induce neuronal loss>, Application In Synthesis of 350-03-8, the main research area is neurotoxin allosteric activation mechanism SARM neuronal loss; NAMPT; NMNAT; Vacor; base exchange reaction; mass spectrometry; metabolism; myelin; neurolytic block; sciatic nerve; tibial nerve.

SARM1 is an inducible TIR-domain NAD+ hydrolase that mediates pathol. axon degeneration. SARM1 is activated by an increased ratio of NMN to NAD+, which competes for binding to an allosteric activating site. When NMN binds, the TIR domain is released from autoinhibition, activating its NAD+ hydrolase activity. The discovery of this allosteric activating site led us to hypothesize that other NAD+-related metabolites might activate SARM1. Here, we show the nicotinamide analog 3-acetylpyridine (3-AP), first identified as a neurotoxin in the 1940s, is converted to 3-APMN, which activates SARM1 and induces SARM1-dependent NAD+ depletion, axon degeneration, and neuronal death. In mice, systemic treatment with 3-AP causes rapid SARM1-dependent death, while local application to the peripheral nerve induces SARM1-dependent axon degeneration. We identify 2-aminopyridine as another SARM1-dependent neurotoxin. These findings identify SARM1 as a candidate mediator of environmental neurotoxicity and suggest that SARM1 agonists could be developed into selective agents for neurolytic therapy.

Cell Reports published new progress about Allosterism. 350-03-8 belongs to class pyridine-derivatives, and the molecular formula is C7H7NO, Application In Synthesis of 350-03-8.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Puszko, Aniela published the artcile< UV spectra of 2-halo-4-aminopicolines>, Application In Synthesis of 79055-59-7, the main research area is UV spectra halo derivative aminopyridine.

The UV spectra of 2-halogen-4-aminopicolines were measured in various solvents and the influence of substituent and solvent on position band and intensity are discussed in details.

Prace Naukowe Akademii Ekonomicznej imienia Oskara Langego we Wroclawiu published new progress about Solvent effect. 79055-59-7 belongs to class pyridine-derivatives, and the molecular formula is C6H7BrN2, Application In Synthesis of 79055-59-7.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zhang, Chun; Santiago, Celine B.; Kou, Lei; Sigman, Matthew S. published the artcile< Alkenyl Carbonyl Derivatives in Enantioselective Redox Relay Heck Reactions: Accessing α,β-Unsaturated Systems>, Formula: C13H15F3N2O, the main research area is arylboronic acid unsaturated carbonyl enantioselective regioselective arylation Heck; aryl unsaturated carbonyl stereoselective preparation.

A highly enantioselective and site-selective Pd-catalyzed arylation of alkenes linked to carbonyl derivatives to yield α,β-unsaturated systems is reported. The high site selectivity is attributed to both a solvent effect and the polarized nature of the carbonyl group, both of which have been analyzed through multidimensional anal. tools. The reaction can be performed in an iterative fashion allowing for a diastereoselective installation of two aryl groups along an alkyl chain.

Journal of the American Chemical Society published new progress about Arylation, stereoselective (regioselective). 1416819-91-4 belongs to class pyridine-derivatives, and the molecular formula is C13H15F3N2O, Formula: C13H15F3N2O.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Amthor, Sebastian; Braun, Hanna; Groene, Julius; Nauroozi, Djawed; Jacob, Timo; Rau, Sven published the artcile< Tailored protective groups for surface immobilization of ruthenium dyes>, Application of C10H8N2, the main research area is phosphonatomethyl silylphosphonatomethyl bipyridine ruthenium complex preparation surface immobilization dye.

McKenna reaction conditions are applied to the [Ru(4,4′-(CH2PO3Et2)2)(bpy)](PF6)2 model chromophore in order to obtain [Ru(4,4′-(CH2PO3TMS2)2)(bpy)](Br2-x)(PF6)x (x = 0-2) (2) by replacing the alkyl moieties of the phosphonates with TMS groups (TMS = trimethylsilyl). The model complex is immobilized onto both NiO powder and NiO electrodes on FTO (fluorine doped tin oxide) using organic solvents. The stability of surface binding in aqueous media and the DSC performance of 2 are tested and compared to those of a conventional dye of structure [Ru(4,4′-(CH2PO3TBA2)2)(bpy)](PF6)2 (1) (TBA = tetra-Bu ammonium). This is the first example of a ruthenium based chromophore with a phosphonic acid silyl-ester being directly immobilized onto a NiO surface. In addition, complex 2 exhibits superior stability towards desorption in aqueous media and at the same time showing improved DSC performance and stability in acetonitrile and a slightly higher dye loading on the electrode surface compared to 1.

Dalton Transactions published new progress about Chromophores. 366-18-7 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2, Application of C10H8N2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Holladay, Mark W.; Bai, Hao; Li, Yihong; Lin, Nan-Horng; Daanen, Jerome F.; Ryther, Keith B.; Wasicak, James T.; Kincaid, John F.; He, Yun; Hettinger, Anne-Marie; Huang, Peggy; Anderson, David J.; Bannon, Anthony W.; Buckley, Michael J.; Campbell, Jeffrey E.; Donnelly-Roberts, Diana L.; Gunther, Karen L.; Kim, David J. B.; Kuntzweiler, Theresa A.; Sullivan, James P.; Decker, Michael W.; Arneric, Stephen P. published the artcile< Structure-activity studies related to ABT-594, a potent nonopioid analgesic agent: effect of pyridine and azetidine ring substitutions on nicotinic acetylcholine receptor binding affinity and analgesic activity in mice>, Application of C5H4ClNO, the main research area is ABT594 analog nonopioid analgesic structure; nicotinic receptor binding ABT594 analog structure.

Analogs of A-98593 (I) and its enantiomer ABT-594 (II) with diverse substituents on the pyridine ring were prepared and tested for affinity to nicotinic acetylcholine receptor binding sites in rat brain and for analgesic activity in the mouse hot plate assay. Numerous types of modifications were consistent with high affinity for [3H]cytisine binding sites. By contrast, only selected modifications resulted in retention of analgesic potency in the same range as I and II. Analogs of II with one or two Me substituents at the 3-position of the azetidine ring also were prepared and substantially less active in both assays.

Bioorganic & Medicinal Chemistry Letters published new progress about Analgesics. 96630-88-5 belongs to class pyridine-derivatives, and the molecular formula is C5H4ClNO, Application of C5H4ClNO.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem