Day: October 14, 2022

Zhao, Zean; Liu, Jin; Kuang, Peihua; Luo, Jian; Surineni, Goverdhan; Cen, Xiaolin; Wu, Ting; Cao, Ying; Zhou, Pingzheng; Pang, Jianxin; Zhang, Qun; Chen, Jianjun published the artcile< Discovery of novel verinurad analogs as dual inhibitors of URAT1 and GLUT9 with improved Druggability for the treatment of hyperuricemia>, Recommanded Product: 4-Chloro-3-hydroxypyridine, the main research area is hyperuricemia URAT1 GLUT9 verinurad druggability pharmacokinetics oral bioavailability; Dual inhibitors; GLUT9; URAT1; Verinurad; anti-hyperuricemic.

Verinurad (RDEA3170) is a selective URAT1 inhibitor under investigation for the treatment of gout and hyperuricemia. In an effort to further improve the pharmacodynamics/pharmacokinetics of verinurad and to increase the structural diversity, we designed novel verinurad analogs by introducing a linker (e.g. aminomethyl, amino or oxygen) between the naphthalene and the pyridine ring to increase the flexibility. These compounds were synthesized and tested for their in vitro URAT1-inhibitory activity. Most compounds exhibited potent inhibitory activities against URAT1 with IC50 values ranging from 0.24 μM to 16.35 μM. Among them, compound KPH2f exhibited the highest URAT1-inhibitory activity with IC50 of 0.24 μM, comparable to that of verinurad (IC50 = 0.17 μM). KPH2f also inhibited GLUT9 with an IC50 value of 9.37 ± 7.10 μM, indicating the dual URAT1/GLUT9 targeting capability. In addition, KPH2f showed little effects on OAT1 and ABCG2, and thus was unlikely to cause OAT1/ABCG2-mediated drug-drug interactions and/or to neutralize the uricosuric effects of URAT1/GLUT9 inhibitors. Importantly, KPH2f (10 mg/kg) was equally effective in reducing serum uric acid levels and exhibited higher uricosuric effects in a mice hyperuricemia model, as compared to verinurad (10 mg/kg). Furthermore, KPH2f demonstrated favorable pharmacokinetic properties with an oral bioavailability of 30.13%, clearly better than that of verinurad (21.47%). Moreover, KPH2f presented benign safety profiles without causing hERG toxicity, cytotoxicity in vitro (lower than verinurad), and renal damage in vivo. Collectively, these results suggest that KPH2f represents a novel, safe and effective dual URAT1/GLUT9 inhibitor with improved druggabilities and is worthy of further investigation as an anti-hyperuricemic drug candidate.

European Journal of Medicinal Chemistry published new progress about ATP-binding cassette transporter ABCG2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 96630-88-5 belongs to class pyridine-derivatives, and the molecular formula is C5H4ClNO, Recommanded Product: 4-Chloro-3-hydroxypyridine.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Spinner, E.; White, J. C. B. published the artcile< The spectra and structures of the cations and anions of substituted 2-hydroxypyridines (1,2-dihydro-2-oxopyridines)>, COA of Formula: C6H6ClNO, the main research area is .

The ir spectra of the hydrochlorides and hexachloroantimonates of 2-hydroxy- and 2-methoxypyridines containing substituents (3-, 4-, 5-, and 6-Me; 3- and 5-halo, and 3,5-dihalo; 6-OH) and the uv spectra of the cations have been determined The former cations are 2-hydroxypyridinium ions. H-bonding by the 2-OH proton seems to be responsible for the abnormally high ir intensity of the skeletal stretching band near 1640 cm.-1, which, in the past, caused it to be mistaken for a carbonyl stretching band. The ir, uv, and, where possible, Raman spectra of the Na salts of the above substituted 2-hydroxy-pyridines have also been determined The anions seem to have normal pyridoxide structures, with the neg. charge mainly on the O atom. 24 references

Journal of the Chemical Society [Section] B: Physical Organic published new progress about IR spectra. 13472-84-9 belongs to class pyridine-derivatives, and the molecular formula is C6H6ClNO, COA of Formula: C6H6ClNO.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Dabaghian, Farid; Khanavi, Mahnaz; Zarshenas, Mohammad M. published the artcile< Bioactive compounds with possible inhibitory activity of Angiotensin-Converting Enzyme-II; a gate to manage and prevent COVID-19>, Synthetic Route of 3731-53-1, the main research area is covid19 virus angiotensin converting enzyme II review.

A review. This letter to the editor looks at bioactive compounds with possible inhibitory activity of Angiotensin-Converting Enzyme-II.

Medical Hypotheses published new progress about COVID-19. 3731-53-1 belongs to class pyridine-derivatives, and the molecular formula is C6H8N2, Synthetic Route of 3731-53-1.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Song, Pinrao; Chen, Ming; Ma, Xiaodong; Xu, Lei; Liu, Tao; Zhou, Yubo; Hu, Yongzhou published the artcile< Identification of novel inhibitors of Aurora A with a 3-(pyrrolopyridin-2-yl)indazole scaffold>, Application In Synthesis of 22280-62-2, the main research area is inhibitor Aurora pyrrolopyridinylindazole scaffold; Antiproliferative agents; Aurora A inhibitors; Cell cycle profile; Pyrrolopyridin-indazoles; Selectivity.

A novel series of 3-(pyrrolopyridin-2-yl)indazole derivatives were synthesized and biol. evaluated for their anti-proliferative effects on five human cancer cell lines. As a result, all of them exhibited vigorous potency against HL60 cell line with IC50 values ranging from singe digital nanomolar to micromolar level. Besides, a majority of them displayed modest to good antiproliferative activities against the other four cell lines, including KB, SMMC-7721, HCT116, and A549. Particularly, compound 2y, as the most distinguished one in this series, demonstrated IC50 values of 8.3 nM and 1.3 nM against HL60 and HCT116 cell lines, resp. Afterwards, for exploring the mol. target, compounds2d, 2g and 2y were further selected to evaluate the inhibitory activities against a panel of kinases. Finally, they were identified to be targeting Aurora A kinase with significant selectivity over other kinases, such as CHK1, CDK2, MEK1, GSK3β, BRAF, IKKβ and PKC.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 22280-62-2 belongs to class pyridine-derivatives, and the molecular formula is C6H7N3O2, Application In Synthesis of 22280-62-2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Wang, Wenqi; Zhou, Zefeng; Sathe, Devavrat; Tang, Xuanting; Moran, Stephanie; Jin, Jing; Haeffner, Fredrik; Wang, Junpeng; Niu, Jia published the artcile< Degradable Vinyl Random Copolymers via Photocontrolled Radical Ring-Opening Cascade Copolymerization>, Formula: C33H21F3IrN3, the main research area is vinyl random copolymer photocontrolled radical ring opening cascade copolymerization; Cascade polymerization; Degradable polymer; Photocontrolled polymerization; Random copolymer; Reaction mechanism.

Degradable vinyl polymers by radical ring-opening polymerization are promising solutions to the challenges caused by non-degradable vinyl plastics. However, achieving even distributions of labile functional groups in the backbone of degradable vinyl polymers remains challenging. Herein, we report a photocatalytic approach to degradable vinyl random copolymers via radical ring-opening cascade copolymerization (rROCCP). The rROCCP of macrocyclic allylic sulfones and acrylates or acrylamides mediated by visible light at ambient temperature achieved near-unity comonomer reactivity ratios over the entire range of the feed compositions Exptl. and computational evidence revealed an unusual reversible inhibition of chain propagation by in situ generated sulfur dioxide (SO2), which was successfully overcome by reducing the solubility of SO2. This study provides a powerful approach to degradable vinyl random copolymers with comparable material properties to non-degradable vinyl polymers.

Angewandte Chemie, International Edition published new progress about Complex modulus, tan δ. 370878-69-6 belongs to class pyridine-derivatives, and the molecular formula is C33H21F3IrN3, Formula: C33H21F3IrN3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Degorce, Sebastien L.; Aagaard, Anna; Anjum, Rana; Cumming, Iain A.; Diene, Coura R.; Fallan, Charlene; Johnson, Tony; Leuchowius, Karl-Johan; Orton, Alexandra L.; Pearson, Stuart; Robb, Graeme R.; Rosen, Alan; Scarfe, Graeme B.; Scott, James S.; Smith, James M.; Steward, Oliver R.; Terstiege, Ina; Tucker, Michael J.; Turner, Paul; Wilkinson, Stephen D.; Wrigley, Gail L.; Xue, Yafeng published the artcile< Improving metabolic stability and removing aldehyde oxidase liability in a 5-azaquinazoline series of IRAK4 inhibitors>, Electric Literature of 329214-79-1, the main research area is preparation azaquinazoline derivative IRAK4 inhibitor pharmacokinetics; 5-Azaquinazoline; Aldehyde oxidase; DLBCL; IRAK4.

In this article, we report our efforts towards improving in vitro human clearance in a series of 5-azaquinazolines through a series of C4 truncations and C2 expansions. Extensive DMPK studies enabled us to tackle high Aldehyde Oxidase (AO) metabolism and unexpected discrepancies in human hepatocyte and liver microsomal intrinsic clearance. Our efforts culminated with the discovery of 5-azaquinazoline I, which also displayed exquisite selectivity for IRAK4, and showed synergistic in vitro activity against MyD88/CD79 double mutant ABC-DLBCL in combination with the covalent BTK inhibitor acalabrutinib.

Bioorganic & Medicinal Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 329214-79-1 belongs to class pyridine-derivatives, and the molecular formula is C11H16BNO2, Electric Literature of 329214-79-1.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Noori, Maryam; Shafaatian, Bita; Notash, Behrouz published the artcile< Synthesis of new platinum(IV) complexes through breaking disulfide bond; crystal structure determination, electrochemical, photoluminescence and DNA interaction investigation>, Recommanded Product: 1,2-Di(pyridin-2-yl)disulfane, the main research area is mercaptopyridinyl platinacycle preparation electrochem fluorescence DNA binding; crystal structure aryl mercaptopyridinyl platinacycle; mol structure aryl mercaptopyridinyl platinacycle.

New Pt(IV) complexes containing N2S2 donor atoms were synthesized by the reactions of [Pt(p-MeC6H4)2(SMe2)2] and [PtCl2(DMSO)2] with 2,2′-dithiopyridine (dtp) in 1:1 M ratio. In these reactions, 2-mercaptopyridine (mpy) ligands were formed through the cleavage of the disulfide bond in 2,2′-dithiopyridine. The mpy ligands were coordinated to the Pt center via the N and S atoms and the obtained Pt(IV) complexes exhibited octahedral geometry. The complexes were characterized by FTIR, 1H NMR, UV-visible, elemental analyses and conductometry. The crystal structure of the arylplatinum(IV) complex containing C2N2S2 donor atoms was determined by single crystal x-ray diffraction. The obtained molar conductance values revealed that the Pt(IV) complexes were nonelectrolytes. The interactions of the complexes with calf thymus DNA (CT-DNA) were studied by absorption and fluorescence spectroscopy, cyclic voltammetry and viscometry methods. The intrinsic binding constants (Kb) of the complexes with CT-DNA, obtained from UV-visible absorption data, were 9.60 × 104 M-1 and 11.56 × 104 M-1. Also, the enthalpy and entropy of the interaction between the Pt(IV) complexes and CT-DNA were calculated The obtained data revealed pos. enthalpy and entropy changes indicating a hydrophobic interaction between these complexes and CT-DNA.

Inorganica Chimica Acta published new progress about Bond cleavage (disulfide). 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

Li, Xiaotong; Ke, Weijun; Traore, Boubacar; Guo, Peijun; Hadar, Ido; Kepenekian, Mikael; Even, Jacky; Katan, Claudine; Stoumpos, Constantinos C.; Schaller, Richard D.; Kanatzidis, Mercouri G. published the artcile< Two-Dimensional Dion-Jacobson Hybrid Lead Iodide Perovskites with Aromatic Diammonium Cations>, Reference of 3731-53-1, the main research area is aminomethylpyridinium methylammonium lead iodide perovskite luminescence crystal structure.

Two-dimensional (2D) halide perovskites have extraordinary optoelectronic properties and structural tunability. Among them, the Dion-Jacobson phases with the inorganic layers stacking exactly on top of each other are less explored. Two-dimensional (2D) Dion-Jacobson halide perovskites are presented, which adopt the general formula of A’An-1PbnI3n+1 (A’ = 4-(aminomethyl)pyridinium (4AMPY), A = methylammonium (MA), n = 1-4). By modifying the position of the CH2NH3+ group from 4AMPY to 3AMPY (3AMPY = 3-(aminomethyl)pyridinium), the stacking of the inorganic layers changes from exactly eclipsed to slightly offset. The perovskite octahedra tilts are also different between the 2 series, with the 3AMPY series exhibiting smaller bandgaps than the 4AMPY series. Compared to the aliphatic cation of the same size (AMP = (aminomethyl)piperidinium), the aromatic spacers increase the rigidity of the cation, reduce the interlayer spacing, and decrease the dielec. mismatch between inorganic layer and the organic spacer, showing the indirect but powerful influence of the organic cations on the structure and consequently on the optical properties of the perovskite materials. All A’An-1PbnI3n+1 compounds exhibit strong luminescence (PL) at room temperature Preliminary solar cell devices based on the n = 4 perovskites as absorbers of both series exhibit promising performances, with a champion power conversion efficiency (PCE) of 9.20% for (3AMPY)(MA)3Pb4I13-based devices, which is higher than the (4AMPY)(MA)3Pb4I13 and the corresponding aliphatic analog (3AMP)(MA)3Pb4I13-based ones.

Journal of the American Chemical Society published new progress about Band gap. 3731-53-1 belongs to class pyridine-derivatives, and the molecular formula is C6H8N2, Reference of 3731-53-1.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Mikle, Gabor; Bede, Fanni; Kollar, Laszlo published the artcile< Synthesis of N-picolylcarboxamides in aminocarbonylation>, Quality Control of 3731-53-1, the main research area is picolylcarboxamide preparation; iodocamphene steroidal iodoalkene picolylamine aminocarbonylation palladium catalyst.

Palladium-catalyzed aminocarbonylation of iodocamphene and steroidal iodoalkenes was carried out in the presence of 2-, 3- and 4-picolylamine, as well as secondary amines possessing 1-picolyl substituent. In general, primary picolylamines require less than 2 h to achieve practically complete conversion. The secondary amines proved to be less reactive, requiring 6-24 h depending on the substrate structure. The corresponding carboxamides were isolated in moderate to excellent yields. The synthesis of α,β-unsaturated carboxamides is based on the synthesis of iodoalkene substrates from enolizable ketones.

Tetrahedron published new progress about Amides Role: SPN (Synthetic Preparation), PREP (Preparation). 3731-53-1 belongs to class pyridine-derivatives, and the molecular formula is C6H8N2, Quality Control of 3731-53-1.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ranjbar, Hoda; Soti, Monavareh; Janahmadi, Mahyar; Kohlmeier, Kristi A.; Sheibani, Vahid; Ahmadi-Zeidabadi, Meysam; Shabani, Mohammad published the artcile< Modulation of the CB1 cannabinoid receptor has potential therapeutic utility in the 3-acetylpyridine cerebellar ataxia rat model>, Formula: C7H7NO, the main research area is cannabinoid receptor acetylpyridine cerebellar ataxia therapeutic potential; CB1 receptor; Cannabinoid; Cerebellar ataxia; Purkinje cell.

Cerebellar ataxia is a neurodegenerative disorder leading to severe motor incoordination. Recently, it has been suggested that cannabinoids play a role in modulating ataxic symptoms. To understand the possible therapeutic effect of cannabinoids for the management of cerebellar ataxia, we used cannabinoid agonist/antagonists to target the cannabinoid type 1 receptor (CB1R) in the 3 acetyl pyridine (3AP) rat model of ataxia. The role of the CB1R was examined using three different doses of the CB1R agonist, WIN-55,212-2 (WIN; 0.1, 0.5, 1 mg/kg) administrated 30 min prior to 3AP (55 mg/kg, i.p.) which leads to motor impairment through destruction of the inferior olive. In some groups, the CB1R antagonist AM251 (1 mg/kg) was given in combination with WIN. Locomotor activity and motor coordination were impaired by 3AP, and the application of WIN did not ameliorate this effect. However, the abnormal gait, rearing and grooming caused by 3AP were prevented by co-administration of AM251 with WIN. While the addition of the CB1R antagonist improved some ataxic symptoms, there was no effect of AM251 on balance or locomotor activity when co-administrated with WIN. Behavioral testing indicated that not only did WIN fail to exert any protective effect on ataxic symptoms; it exacerbated ataxic symptoms, suggesting that CB1R agonists may not be the ideal therapeutic drug in this disorder. When taken together, the findings from the present study indicate that cannabinoid modulation of ataxia symptoms may not act solely through CB1Rs and other cannabinoid receptors should be considered in future studies.

Experimental Brain Research published new progress about Cannabinoid receptor 1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 350-03-8 belongs to class pyridine-derivatives, and the molecular formula is C7H7NO, Formula: C7H7NO.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem