Category: 18437-58-6

Cui, Jiaxin published the artcileDiscovery of bis-aryl urea derivatives as potent and selective Limk inhibitors: Exploring Limk1 activity and Limk1/ROCK2 selectivity through a combined computational study, HPLC of Formula: 18437-58-6, the publication is Bioorganic & Medicinal Chemistry (2015), 23(23), 7464-7477, database is CAplus and MEDLINE.

Lim kinase (Limk), a proline/serine-rich sequence, can regulate the polymerization of the actin filaments by phosphorylating, and it is found to be highly involved in various human diseases. In this paper, 47 reported Limk1 inhibitors with bis-aryl urea scaffold were used to design potent and selective Limk inhibitors by computational approaches. Firstly, the structure-Limk1 activity relationship models (3D-QSAR) and structure-Limk1/ROCK2 selectivity relationship models (3D-QSSR) were developed and both 3D-QSAR and 3D-QSSR models showed good correlative and predictive abilities. Then, the mol. docking and mol. dynamics (MD) simulations were employed to validate the optimal docking conformation and explore the binding affinities. Finally, five new compounds were designed and all of them exhibited good Limk1 inhibition and Limk1/ROCK2 selectivity after synthesis and biol. evaluation, which demonstrated that the obtained information from computational studies were valuable to guide Limk inhibitors’ design.

Bioorganic & 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, HPLC of Formula: 18437-58-6.

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

Dunn, A. D. published the artcileBromination of Pyridines. II. Bromination of aminopicolines, Computed Properties of 18437-58-6, the publication is Journal fuer Praktische Chemie (Leipzig) (1989), 331(3), 369-74, database is CAplus.

The bromination of all 10 possible aminopicolines was investigated. In general, the major brominated product was that corresponding to electrophilic attack at the site para or ortho to the amino group.

Journal fuer Praktische Chemie (Leipzig) 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, Computed Properties of 18437-58-6.

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

Yule, Ian A. published the artcilePyridine-3-carboxamide-6-yl-ureas as novel inhibitors of bacterial DNA gyrase: Structure based design, synthesis, SAR and antimicrobial activity, Recommanded Product: 4-Amino-2-picoline, the publication is European Journal of Medicinal Chemistry (2014), 31-38, database is CAplus and MEDLINE.

The development of antibacterial drugs based on novel chemotypes is essential to the future management of serious drug resistant infections. We herein report the design, synthesis and SAR of a novel series of N-ethylurea inhibitors based on a pyridine-3-carboxamide scaffold targeting the ATPase sub-unit of DNA gyrase. Consideration of structural aspects of the GyrB ATPase site has aided the development of this series resulting in derivatives that demonstrate excellent enzyme inhibitory activity coupled to potent Gram pos. antibacterial efficacy.

European 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 C6H12N2O, Recommanded Product: 4-Amino-2-picoline.

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

Rombouts, Frederik J. R. published the artcileDiscovery of N-(4-[¹⁸F]Fluoro-5-methylpyridin-2-yl)isoquinolin-6-amine (JNJ-64326067), a New Promising Tau Positron Emission Tomography Imaging Tracer, Synthetic Route of 18437-58-6, the publication is Journal of Medicinal Chemistry (2019), 62(6), 2974-2987, database is CAplus and MEDLINE.

In Alzheimer’s disease, the d. and spread of aggregated tau protein track well with neurodegeneration and cognitive decline, making the imaging of aggregated tau a compelling biomarker. A structure-activity relationship exploration around an isoquinoline hit, followed by an exploration of tolerated fluorination positions, allowed us to identify 9 (JNJ-64326067), a potent and selective binder to aggregated tau with a favorable pharmacokinetic profile and no apparent off-target binding. This was confirmed in rat and monkey positron emission tomog. studies using [¹⁸F]9.

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, Synthetic Route of 18437-58-6.

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

Schroeder, Tenna Juul published the artcileThe identification of AF38469: An orally bioavailable inhibitor of the VPS10P family sorting receptor Sortilin, Recommanded Product: 4-Amino-2-picoline, the publication is Bioorganic & Medicinal Chemistry Letters (2014), 24(1), 177-180, database is CAplus and MEDLINE.

The identification of the novel, selective, orally bioavailable sortilin inhibitor AF38469 [5-(trifluoromethyl)-2- [(6-methylpyridin-2-ylamino)carbonyl]]benzoic acid is described. Structure-activity relationships and syntheses are reported, along with an X-ray crystal structure of the sortilin-AF38469 protein-inhibitor complex.

Bioorganic & Medicinal Chemistry Letters 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

Blake, James F. published the artcileDiscovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development, HPLC of Formula: 18437-58-6, the publication is Journal of Medicinal Chemistry (2016), 59(12), 5650-5660, database is CAplus and MEDLINE.

The extracellular signal-regulated kinases ERK1/2 represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutations in BRAF or RAS or by upstream oncogenic signaling. While targeting upstream nodes with RAF and MEK inhibitors has proven effective clin., resistance frequently develops through reactivation of the pathway. Simultaneous targeting of multiple nodes in the pathway, such as MEK and ERK, offers the prospect of enhanced efficacy as well as reduced potential for acquired resistance. Described herein is the discovery and characterization of GDC-0994 (22), an orally bioavailable small mol. inhibitor selective for ERK kinase activity.

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, HPLC of Formula: 18437-58-6.

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

van Veldhoven, Jacobus P. D. published the artcileTargeting the K_v11.1 (hERG) channel with allosteric modulators. Synthesis and biological evaluation of three novel series of LUF7346 derivatives, Computed Properties of 18437-58-6, the publication is European Journal of Medicinal Chemistry (2021), 113033, database is CAplus and MEDLINE.

Three novel series of substituted benzophenones for their allosteric modulation of the human Kv11.1 (hERG) channel were synthesized and evaluated. Effects of this is compared with reference compound LUF7346 previously shown to shorten the action potential of cardiomyocytes derived from human stem cells. Most compounds behaved as neg. allosteric modulators (NAMs) of [3H]dofetilide binding to the channel. Compound III [R = 2-Cl; R¹ = CH₂cPr; X= Y = C] was the most potent amongst all ligands, remarkably reducing the affinity of dofetilide in competitive displacement assays. One of the other II [R = H; X = N] tested in a second radioligand binding set-up, displayed unusual displacement characteristics with a pseudo-Hill coefficient significantly distinct from unity, further indicative of its allosteric effects on the channel. Some compounds were evaluated in a more physiol. relevant context in beating cardiomyocytes derived from human induced pluripotent stem cells. Surprisingly, the compounds tested showed effects quite different from the reference NAM LUF7346. For instance, compound I [R = 3-Me] prolonged, rather than shortened, the field potential duration, while it did not influence this parameter when the field potential was already prolonged by dofetilide. In subsequent patch clamp studies on HEK293 cells expressing the hERG channel the compounds behaved as channel blockers. In conclusion, new allosteric modulators of the hERG channel were successfully synthesized and identified . Unexpectedly, their effects differed from the reference compound in functional assays on hERG-HEK293 cells and human cardiomyocytes, to the extent that the compounds behaved as stand-alone channel blockers.

European 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 C7H8BClO2, Computed Properties of 18437-58-6.

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

Berg, Ulf published the artcileTransition State Structural Variations in the Menshutkin Reaction. A Computational Study of Steric and Electronic Substituent Effects, COA of Formula: C6H8N2, the publication is Journal of Organic Chemistry (1995), 60(7), 1975-80, database is CAplus.

Transition structures for the gas phase S_N2 reactions of substituted pyridines with Me chloride, bromide, and iodide, resp., have been localized by the AMPAC program using the AM1 Hamiltonian. The reactions are strongly endothermic (ΔE ≈ 40-60 kcal/mol) and have activation barriers of ca. 70 kcal/mol, and the calculated order of leaving group (X) abilities is I < Br < Cl. The carbon-nitrogen bond is longer for the more reactive leaving group. The structural parameters are relatively insensitive to substitutions in the pyridine ring. Increasing the steric strain in the ortho position (Me to tert-Bu or 2,6-dimethyl) leads to looser and earlier transition states, whereas substitution with electron-withdrawing groups in the para position has very little effect on the transition structure. Solvent effects were briefly mimicked by means of a dipole placed on the N· · ·C· · ·X axis with the pos. charge pointing toward X. This results in a decrease of the activation barrier, a less endothermic reaction, earlier transition state, and a larger neg. charge on X. The consequences of steric effects in this reaction are discussed.

Journal of Organic 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, COA of Formula: C6H8N2.

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

Shimeno, Hiroshi published the artcileInhibition of rat liver tryptophan pyrrolase activity and elevation of brain tryptophan concentration by administration of DL-α-amino-β-pyridinepropanoic acid (pyridylalanine) analogs, Computed Properties of 18437-58-6, the publication is Journal of Enzyme Inhibition (1987), 2(1), 57-66, database is CAplus and MEDLINE.

Single doses of DL-α-amino-β-(2-pyridine)propanoic acid (2-PA, 100 mg/kg) decreased the holoenzyme and apoenzyme activities of rat liver tryptophan pyrrolase (TP) and increased brain tryptophan, serotonin (5-HT) and 5-hydroxyindole-3-ylacetic acid concentrations 2-PA had no inhibitory effect on either of the enzyme activities in vitro, but its expected metabolites were effective. Single doses of DL-α-amino-β-(3-pyridine)propanoic acid (3-PA, 100 mg/kg) decreased only the holoenzyme activity and elevated brain tryptophan and its metabolites levels in rats. 3-PA and its metabolite, 3-pyridylpyruvate, inhibited only the holoenzyme activity in vitro. DL-α-Amino-β-(4-pyridine)propanoic acid (4-PA) caused changes in liver TP (holo- and apoenzyme forms) activity and brain tryptophan concentration only after repeated administration (100 mg/kg/day). 4-PA was a weak inhibitor of the holoenzyme, but its metabolites apparently inhibited the holo- and apoenzyme activities in vitro. These findings suggest that PA analogs (and(or) their metabolites) increased brain tryptophan (and hence 5-HT synthesis) by directly inhibiting liver TP activity.

Journal of Enzyme Inhibition 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 C8H11NO, Computed Properties of 18437-58-6.

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

Hertog, Adriaan Den published the artcileThe action of some new aminopyridines on mammalian nonmyelinated nerve fibers, Application In Synthesis of 18437-58-6, the publication is European Journal of Pharmacology (1987), 142(1), 115-20, database is CAplus.

The effects of a recently synthesized series of aminopyridines (APs) 2-methyl-4-AP, 2-chloro-4-AP, and 2-(N,N-methylbenzyl)amino-4-AP (2A-7) on voltage-operated Na⁺ and K⁺ channels and on the Na⁺ pump activity of nonmyelinated fibers of the guinea-pig vagus nerve were studied with the sucrose-gap method. The compound action potential evoked by elec. stimulation and the propagation velocity along the nerve were not affected by 2-methyl-4-AP or 2-chloro-4-AP up to a concentration of 10^-3 M. The post-tetanic potential (PTH) evoked by repetitive stimulation of the nerve and reflecting Na⁺ pumping was also not affected by these agents. The amplitude and duration of the compound action potential were enhanced to some extent by 2-methyl-4-AP at the highest concentration used (3 × 10^-3 M); this action was also observed and was more pronounced with 4-aminopyridine (4-AP). The other aminopyridine 2A-7 (3 × 10^-5-3 × 10^-4 M) caused suppression of the compound action potential, a diminished propagation velocity and a reduction of the PTH, an action also observed with lidocaine. These results show that 2-methyl-4-AP and 3-chloro-4-AP did not affect the voltage-operated Na⁺ or K⁺ channels in nonmyelinated fibers of the vagus nerve. Only 2-methyl-4-AP had a small 4-AP-like action at high concentrations The aminopyridine 2A-7 possesses a local anesthetic action as reflected by the inhibition of voltage-operated Na⁺ channels.

European Journal of Pharmacology 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, Application In Synthesis of 18437-58-6.

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