Category: pyridine-derivatives

Maafi, Mounir published the artcilePhotokinetics of Dacarbazine and Nifedipine under polychromatic light irradiation and their application as new reliable actinometers for the ultraviolet range, Related Products of pyridine-derivatives, the publication is Scientific Reports (2022), 12(1), 7622, database is CAplus and MEDLINE.

The photokinetic behavior of drugs driven by polychromatic light is an area of pharmaceutics that has not received a lot of attention. Most often, such photokinetic data is treated by thermal kinetic models (i.e., the classical 0th-, 1st- or 2nd-order equations). Such models were not anal. derived from the rate-laws of the photodegradation reactions. Polychromatic light kinetic modeling is hence of importance, as a means to providing adequate toolkits and metrics. This paper aims at proposing two reliable drug-actinometers useful for polychromatic UVA range. The general actinometric methodol. offered here is also useful for any drugs/materials obeying a primary photoprocess where both reactant and photoproduct absorb the incident light, of the AB(1φ)εB≠0 type. The present method has been consolidated by the η-order kinetics. This framework further demonstrated the lamp-specificity of actinometers. Overall, Dacarbazine and Nifedipine photodegradations obeyed η-order kinetics, and stand as effective actinometers that can be recommended for the ICH Q1b photostability testing.

Scientific Reports published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Related Products of pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Ontoria, Jesus M. published the artcileIdentification of Novel, Selective, and Stable Inhibitors of Class II Histone Deacetylases: Validation Studies of the Inhibition of the Enzymatic Activity of HDAC4 by Small Molecules as a Novel Approach for Cancer Therapy, Synthetic Route of 197958-29-5, the publication is Journal of Medicinal Chemistry (2009), 52(21), 6782-6789, database is CAplus and MEDLINE.

5-Aryl-2-(trifluoroacetyl)thiophenes were identified as a new series of class II HDAC inhibitors (HDACi). Further development of this new series led to compounds such as 6h(I), a potent inhibitor of HDAC4 and HDAC6 (HDAC4 WT IC₅₀ = 310 nM, HDAC6 IC₅₀ = 70 nM) that displays 40-fold selectivity over HDAC1 and improved stability in HCT116 cancer cells (t₁/₂ = 11 h). Compounds 6h and 2(II) show inhibition of α-tubulin deacetylation in HCT116 cells at 1 μM concentration and antiproliferation effects only at concentrations where inhibition of histone H3 deacetylation is observed

Journal of Medicinal Chemistry published new progress about 197958-29-5. 197958-29-5 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester, name is 2-Pyridinylboronic acid, and the molecular formula is C5H6BNO2, Synthetic Route of 197958-29-5.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

DiMauro, Erin F. published the artcileApplication of a Parallel Synthetic Strategy in the Discovery of Biaryl Acyl Sulfonamides as Efficient and Selective Na_V1.7 Inhibitors, Product Details of C15H23BClNO3, the publication is Journal of Medicinal Chemistry (2016), 59(17), 7818-7839, database is CAplus and MEDLINE.

The majority of potent and selective hNa_V1.7 inhibitors possess common pharmacophoric features that include a heteroaryl sulfonamide headgroup and a lipophilic aromatic tail group. Recently, reports of similar aromatic tail groups in combination with an acyl sulfonamide headgroup have emerged, with the acyl sulfonamide bestowing levels of selectivity over hNa_V1.5 comparable to the heteroaryl sulfonamide. Beginning with com. available carboxylic acids that met selected pharmacophoric requirements in the lipophilic tail, a parallel synthetic approach was applied to rapidly generate the derived acyl sulfonamides. A biaryl acyl sulfonamide hit from this library was elaborated, optimizing for potency and selectivity with attention to physicochem. properties. The resulting novel leads are potent, ligand and lipophilic efficient, and selective over hNa_V1.5. Representative lead I demonstrates selectivity over other human Na_V isoforms and good pharmacokinetics in rodents. The biaryl acyl sulfonamides reported herein may also offer ADME advantages over known heteroaryl sulfonamide inhibitors.

Journal of Medicinal Chemistry published new progress about 1387634-81-2. 1387634-81-2 belongs to pyridine-derivatives, auxiliary class Boronate Esters,Boronate Esters,Boronic acid and ester,Boronic acid and ester, name is 3-Chloro-2-isobutoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, and the molecular formula is C15H23BClNO3, Product Details of C15H23BClNO3.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Down, Kenneth published the artcileDiscovery of GSK251: A Highly Potent, Highly Selective, Orally Bioavailable Inhibitor of PI3Kδ with a Novel Binding Mode, Recommanded Product: 4-Amino-2-picoline, the publication is Journal of Medicinal Chemistry (2021), 64(18), 13780-13792, database is CAplus and MEDLINE.

Optimization of a previously reported lead series of PI3Kδ inhibitors with a novel binding mode led to the identification of a clin. candidate compound 31 (GSK251)(I). Removal of an embedded Ames-pos. heteroaromatic amine by reversing a sulfonamide followed by locating an interaction with Trp760 led to a highly selective compound 9 (II). Further optimization to avoid glutathione trapping, to enhance potency and selectivity, and to optimize an oral pharmacokinetic profile led to the discovery of compound 31 (GSK251) that had a low predicted daily dose (45 mg, b.i.d) and a rat toxicity profile suitable for further development.

Journal of Medicinal Chemistry published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, Recommanded Product: 4-Amino-2-picoline.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Moustani, Chrysavgi published the artcileNovel aqueous-phase hydrogenation reaction of the key biorefinery platform chemical levulinic acid into γ-valerolactone employing highly active, selective and stable water-soluble ruthenium catalysts modified with nitrogen-containing ligands, Related Products of pyridine-derivatives, the publication is Applied Catalysis, B: Environmental (2018), 82-92, database is CAplus.

High catalytic activities (TO = 000 ^-1) have been achieved by novel water-soluble ruthenium catalysts modified with nitrogen-containing ligands such as the bathophenanthrolinedisulfonic acid disodium salt (BPhDS) in the hydrogenation reaction of the renewable polar platform chem. levulinic acid (LA) which possesses a central relevance in the development of biorefineries of the future in a sustainable way to produce with essentially quant. selectivity of 99.9 mol% γ-valerolactone (GVL) in aqueous media. The apparent activation energy of the Ru/BPhDS catalyst was calculated and amounts a relative low value of 53.3 J/mol when one considers that in the LA hydrogenation reaction this catalyst reduces a less reactive keto group into alc. functionality. A recycling experiment of the Ru/BPhDS catalyst by extraction after addition of di-Et ether has shown that the catalyst is stable without loss of activity and selectivity in a consecutive run.

Applied Catalysis, B: Environmental published new progress about 636-73-7. 636-73-7 belongs to pyridine-derivatives, auxiliary class Pyridine,Sulfonic acid, name is Pyridine-3-sulfonic acid, and the molecular formula is C5H5NO3S, Related Products of pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Johnson, Ted W. published the artcileDiscovery of (10R)-7-Amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a Macrocyclic Inhibitor of Anaplastic Lymphoma Kinase (ALK) and c-ros Oncogene 1 (ROS1) with Preclinical Brain Exposure and Broad-Spectrum Potency against ALK-Resistant Mutations, Related Products of pyridine-derivatives, the publication is Journal of Medicinal Chemistry (2014), 57(11), 4720-4744, database is CAplus and MEDLINE.

Although crizotinib demonstrates robust efficacy in anaplastic lymphoma kinase (ALK)-pos. non-small-cell lung carcinoma patients, progression during treatment eventually develops. Resistant patient samples revealed a variety of point mutations in the kinase domain of ALK, including the L1196M gatekeeper mutation. In addition, some patients progress due to cancer metastasis in the brain. Using structure-based drug design, lipophilic efficiency, and phys.-property-based optimization, highly potent macrocyclic ALK inhibitors were prepared with good absorption, distribution, metabolism, and excretion (ADME), low propensity for p-glycoprotein 1-mediated efflux, and good passive permeability. These structurally unusual macrocyclic inhibitors were potent against wild-type ALK and clin. reported ALK kinase domain mutations. Significant synthetic challenges were overcome, utilizing novel transformations to enable the use of these macrocycles in drug discovery paradigms. This work led to the discovery of 8k (PF-06463922), combining broad-spectrum potency, central nervous system ADME, and a high degree of kinase selectivity.

Journal of Medicinal Chemistry published new progress about 1454848-00-0. 1454848-00-0 belongs to pyridine-derivatives, auxiliary class Aromatic Fluorinated Building Blocks, name is (R)-Methyl 2-(1-((2-amino-5-bromopyridin-3-yl)oxy)ethyl)-4-fluorobenzoate, and the molecular formula is C15H14BrFN2O3, Related Products of pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Lee, Hon Cheung published the artcileStructural determinants of nicotinic acid adenine dinucleotide phosphate important for its calcium-mobilizing activity, Name: Pyridine-3-sulfonic acid, the publication is Journal of Biological Chemistry (1997), 272(33), 20378-20383, database is CAplus and MEDLINE.

Nicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes Ca²⁺ through a mechanism totally independent of cyclic ADP-ribose or inositol trisphosphate. The structural determinants important for its Ca²⁺ release activity were investigated using a series of analogs. It is shown that changing the 3-carboxyl group of the nicotinic acid (NA) moiety in NAADP to either an uncharged carbinol or from the 3-position to the 4-position of the pyridine ring totally eliminates the Ca²⁺ release activity. Conversion of the 3-carboxyl to other neg. charged groups, either 3-sulfonate, 3-acetate, or 3-quinoline carboxylate, retains the Ca²⁺ release activity, although their half-maximal effective concentrations (EC₅₀) are 100-200-fold higher. Changing the 6-amino group of the adenine to a hydroxyl group results in more than a 1000-fold decrease in the Ca²⁺ release activity. Conversion of the 2′-phosphate to 2′,3′-cyclic phosphate or 3′-phosphate likewise increases the EC₅₀ by about 5- and 20-fold, resp. Similar to NAADP, all of the active analogs can also desensitize the Ca²⁺ release mechanism at subthreshold concentrations, suggesting that this novel property is intrinsic to the release mechanism. The series of analogs used was produced by using ADP-ribosyl cyclase to catalyze the exchange of the nicotinamide group of various analogs of NADP with various analogs of NA. An important determinant in NA that is crucial to the base exchange reaction was shown to be the 2-position of the pyridine ring. Neither pyridine-2-carboxylate nor 2-methyl-NA support the exchange reaction. The neg. charge and the position of the 3-carboxyl group ware nonessential since both pyridine-3-carbinol and pyridine-4-carboxylate support the base exchange reaction. In addition to the information on the structure-activity relationships of NAADP and NA, this study also demonstrates the utility of the base exchange reaction as a general approach for synthesizing NAADP analogs.

Journal of Biological Chemistry published new progress about 636-73-7. 636-73-7 belongs to pyridine-derivatives, auxiliary class Pyridine,Sulfonic acid, name is Pyridine-3-sulfonic acid, and the molecular formula is C5H5NO3S, Name: Pyridine-3-sulfonic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Hashemi, Marzieh published the artcileEnhancing the Anticonvulsant Effects of Nifedipine in Rats Through Encapsulation with Water-Soluble β-Cyclodextrin Polymer, Related Products of pyridine-derivatives, the publication is Pharmaceutical Chemistry Journal (2022), 55(10), 1023-1027, database is CAplus.

Encapsulation is one of the efficient methods recently developed for improving drug delivery. The present study was designed to encapsulate nifedipine (NIF) by water-soluble β-cyclodextrin polymer (β-CDP) and to evaluate the effects of this carrier on NIF-induced anticonvulsant effects. Adult male Wistar rats weighting 200 – 250 g (n = 7) received NIF or encapsulated NIF (β-CDP/NIF) (5, 10 and 20 mg/kg, i.p.), diazepam (2 mg/kg, i.p. as pos. control), and vehicle. Then, pentylenetetrazol (PTZ, 80 mg/kg, i.p.) was injected about 30 min after the drug injection. Changes in the onset time of seizures and duration of their different stages (tonic and tonic-clonic) and total convulsions duration, percentage mortality and percentage of seizure protection were assessed in all test groups. Latency of the seizure onset and duration of tonic and tonic-clonic seizures were significantly decreased in β-CDP/NIF group in comparison with NIF-treated rats (p < 0.05). On the other hand, percentage mortality was significantly decreased and percentage protection was increased by β-CDP/NIF in comparison to NIF (p < 0.05). Therefore, it was concluded that the encapsulation of NIF by β-CDP led to enhancement of the anticonvulsant effects of NIF in rats.

Pharmaceutical Chemistry Journal published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Related Products of pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem