Tag: M.W=100-150

Steinig, Arno G. published the artcileNovel 6-aminofuro[3,2-c]pyridines as potent, orally efficacious inhibitors of cMET and RON kinases, Application In Synthesis of 197958-29-5, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(15), 4381-4387, database is CAplus and MEDLINE.

A series of novel 6-aminofuro[3,2-c]pyridines as kinase inhibitors is described, most notably, OSI-296. We discuss our exploration of structure-activity relationships and optimization leading to OSI-296 and disclose its pharmacol. activity against cMET and RON in cellular assays. OSI-296 is a potent and selective inhibitor of cMET and RON kinases that shows in vivo efficacy in tumor xenografts models upon oral dosing and is well tolerated.

Bioorganic & Medicinal Chemistry Letters 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 C10H9NO, Application In Synthesis of 197958-29-5.

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

Wu, Zi-Zhen published the artcileAminopyridines Potentiate Synaptic and Neuromuscular Transmission by Targeting the Voltage-activated Calcium Channel β Subunit, Application In Synthesis of 18437-58-6, the publication is Journal of Biological Chemistry (2009), 284(52), 36453-36461, database is CAplus and MEDLINE.

Aminopyridines such as 4-aminopyridine (4-AP) are widely used as voltage-activated K⁺ (Kv) channel blockers and can improve neuromuscular function in patients with spinal cord injury, myasthenia gravis, or multiple sclerosis. Here, we present novel evidence that 4-AP and several of its analogs directly stimulate high voltage-activated Ca²⁺ channels (HVACCs) in acutely dissociated neurons. 4-AP, 4-(aminomethyl)pyridine, 4-(methylamino)pyridine, and 4-di(methylamino)pyridine profoundly increased HVACC, but not T-type, currents in dissociated neurons from the rat dorsal root ganglion, superior cervical ganglion, and hippocampus. The widely used Kv channel blockers, including tetraethylammonium, α-dendrotoxin, phrixotoxin-2, and BDS-I, did not mimic or alter the effect of 4-AP on HVACCs. In HEK293 cells expressing various combinations of N-type (Cav2.2) channel subunits, 4-AP potentiated Ca²⁺ currents primarily through the intracellular β₃ subunit. In contrast, 4-AP had no effect on Cav3.2 channels expressed in HEK293 cells. Furthermore, blocking Kv channels did not mimic or change the potentiating effects of 4-AP on neurotransmitter release from sensory and motor nerve terminals. Thus, our findings challenge the conventional view that 4-AP facilitates synaptic and neuromuscular transmission by blocking Kv channels. Aminopyridines can directly target presynaptic HVACCs to potentiate neurotransmitter release independent of Kv channels.

Journal of Biological 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 C9H6N2O4, Application In Synthesis of 18437-58-6.

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

Yang, Xiaobao published the artcileStructure-Activity Relationship Studies for Enhancer of Zeste Homologue 2 (EZH2) and Enhancer of Zeste Homologue 1 (EZH1) Inhibitors, Formula: C5H6BNO2, the publication is Journal of Medicinal Chemistry (2016), 59(16), 7617-7633, database is CAplus and MEDLINE.

EZH2 or EZH1 (enhancer of zeste homolog 2 or 1) is the catalytic subunit of polycomb repressive complex 2 (PRC2) that catalyzes methylation of histone H3 lysine 27 (H3K27). PRC2 hyperactivity and/or hypertrimethylation of H3K27 are associated with numerous human cancers, therefore inhibition of PRC2 complex has emerged as a promising therapeutic approach. Recent studies have shown that EZH2 and EZH1 are not functionally redundant and inhibition of both EZH2 and EZH1 is necessary to block the progression of certain cancers such as MLL (mixed-lineage leukemia)-rearranged leukemias. Despite the significant advances in discovery of EZH2 inhibitors, there has not been a systematic structure-activity relation (SAR) study to investigate the selectivity between EZH2 and EZH1 inhibition. Here, the authors report the authors SAR studies that focus on modifications to various regions of the EZH2/1 inhibitor UNC1999 (5) to investigate the impact of the structural changes on EZH2 and EZH1 inhibition and selectivity.

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 C13H18BClO3, Formula: C5H6BNO2.

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

Zhang, Li published the artcileRegioselective synthesis of polysubstituted N2-alkyl/aryl-1,2,3-triazoles via 4-bromo-5-iodo-1,2,3-triazole, Category: pyridine-derivatives, the publication is Synlett (2012), 23(7), 1052-1056, database is CAplus.

The regioselective N(2)-substitution of 4-bromo-5-iodo-1,2,3-triazole with alkyl/aryl halides in the presence of K₂CO₃ in DMF produced the desired 2-substituted 4-bromo-5-iodo-1,2,3-triazoles as major products in good to excellent regioselectivity. Subsequent chemoselective Suzuki-Miyaura cross-coupling of N(2)-substituted 4-bromo-5-iodo-1,2,3-triazoles provided polysubstituted 1,2,3-triazoles efficiently.

Synlett 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 C13H10N2S, Category: pyridine-derivatives.

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

Cox, Paul A. published the artcileProtodeboronation of Heteroaromatic, Vinyl, and Cyclopropyl Boronic Acids: pH-Rate Profiles, Autocatalysis, and Disproportionation, Name: 2-Pyridinylboronic acid, the publication is Journal of the American Chemical Society (2016), 138(29), 9145-9157, database is CAplus and MEDLINE.

PH-rate profiles for aqueous-organic protodeboronation of 18 boronic acids, many widely viewed as unstable, have been studied by NMR and DFT. Rates were pH-dependent, and varied substantially between the boronic acids, with rate maxima that varied over 6 orders of magnitude. A mechanistic model containing five general pathways (k₁-k₅) has been developed, and together with input of [B]_tot, K_W, K_a, and K_aH, the protodeboronation kinetics can be correlated as a function of pH (1-13) for all 18 species. Cyclopropyl and vinyl boronic acids undergo very slow protodeboronation, as do 3- and 4-pyridyl boronic acids (t_0.5 > 1 wk, pH 12, 70 °C). In contrast, 2-pyridyl and 5-thiazolyl boronic acids undergo rapid protodeboronation (t_0.5 â‰?25-50 s, pH 7, 70 °C), via fragmentation of zwitterionic intermediates. Lewis acid additives (e.g., Cu, Zn salts) can attenuate (2-pyridyl) or accelerate (5-thiazolyl and 5-pyrazolyl) fragmentation. Two addnl. processes compete when the boronic acid and the boronate are present in sufficient proportions (pH = pK_a ± 1.6): (i) self-/autocatalysis and (ii) sequential disproportionations of boronic acid to borinic acid and borane.

Journal of the American Chemical Society 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, Name: 2-Pyridinylboronic acid.

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

Hoyt, Caroline B. published the artcileSelective C(sp³)-H Monoarylation Catalyzed by a Covalently Cross-Linked Reverse Micelle-Supported Palladium Catalyst, Name: 4-Amino-2-picoline, the publication is Advanced Synthesis & Catalysis (2017), 359(20), 3611-3617, database is CAplus.

In this work, we illustrate the performance of a solvated micelle-supported ligand as a platform for coordination with palladium for C-H arylation. The micelle-supported ligand is one of the first applications of a micelle-supported ligand for C-H arylation, and provides a tunable support for future elaboration. The use of a spatially constrained system promoted selectivity trends influenced by both the sterics and electronics of the system, differing from the homogeneous catalyst, with high yields and selectivities.

Advanced Synthesis & Catalysis 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, Name: 4-Amino-2-picoline.

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

Vekariya, Rakesh H. published the artcileSynthesis and Structure-Activity Relationships of 5′-Aryl-14-alkoxypyridomorphinans: Identification of a μ Opioid Receptor Agonist/δ Opioid Receptor Antagonist Ligand with Systemic Antinociceptive Activity and Diminished Opioid Side Effects, Product Details of C5H6BNO2, the publication is Journal of Medicinal Chemistry (2020), 63(14), 7663-7694, database is CAplus and MEDLINE.

We previously identified a pyridomorphinan (6, SRI-22138) possessing a 4-chlorophenyl substituent at the 5′-position on the pyridine and a 3-phenylpropoxy at the 14-position of the morphinan as a mixed μ opioid receptor (MOR) agonist and δ/κ opioid receptor (DOR/KOR) antagonist with potent antinociceptive activity and diminished tolerance and dependence in rodents. Structural variations at the 5′- and 14-positions of this mol. gave insights into the structure-activity relationships for binding and functional activity. Subtle structural changes exerted significant influence, particularly on the ability of the compounds to function as agonists at the MOR. In vivo evaluation identified compound 20(I) (SRI-39067) as a MOR agonist/DOR antagonist that produced systemically active potent antinociceptive activity in tail-flick assay in mice, with diminished tolerance, dependence/withdrawal, reward liability, and respiratory depression vs. morphine. These results support the hypothesis that mixed MOR agonist/DOR antagonist ligands may emerge as novel opioid analgesics with reduced side effects.

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 C9H5ClO4S, Product Details of C5H6BNO2.

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

Raboisson, Pierre published the artcileEvaluation of the anti-hepatitis C virus effect of novel potent, selective, and orally bioavailable JNK and VEGFR kinase inhibitors, Synthetic Route of 18437-58-6, the publication is Bioorganic & Medicinal Chemistry Letters (2007), 17(7), 1843-1849, database is CAplus and MEDLINE.

Screening of a focused library of TGF beta kinase inhibitors in the cellular HCV replicon model with luciferase read out yielded a number of low micromolar HCV inhibitors. Medicinal chem. driven optimization resulted in the discovery of 4-[2-(5-bromo-2-fluoro-phenyl)pteridin-4-ylamino]-N-[3-(2- oxopyrrolidin-1-yl)propyl]nicotinamide 36 with a replicon EC₅₀ of 64 nM, associated with a selective kinase inhibitory profile for human JNK kinases 2 and 3 as well as VEGFR-1, 2, and 3 kinases. Moreover, 36 showed an advantageous PK profile in mice. Experiments performed using different replicon constructs suggest that this series of kinase inhibitors might mediate their effect through the HCV non-structural protein 5A (NS5A).

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, Synthetic Route of 18437-58-6.

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

Oh, Sangmi published the artcileIdentification of Piperidine-3-carboxamide Derivatives Inducing Senescence-like Phenotype with Antimelanoma Activities, Category: pyridine-derivatives, the publication is ACS Medicinal Chemistry Letters (2021), 12(4), 563-571, database is CAplus and MEDLINE.

This study evaluated the potential use of senescence-inducing small mols. in the treatment of melanoma. We screened com. available small-mol. libraries with high-throughput screening and high-content screening image-based technol. Our findings showed an initial hit with the embedded N-arylpiperidine-3-carboxamide scaffold induced senescence-like phenotypic changes in human melanoma A375 cells without serious cytotoxicity against normal cells. A focused library containing diversely modified analogs were constructed and examined to evaluate the structure-activity relationship of N-arylpiperidine-3-carboxamide derivatives starting from hit 1. This work identified a novel compound with remarkable antiproliferative activity in vitro and demonstrated the key structural moieties within.

ACS Medicinal Chemistry Letters 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, Category: pyridine-derivatives.

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

Kim, Junwon published the artcileSerendipitous discovery of 2-((phenylsulfonyl)methyl)-thieno[3,2-d]pyrimidine derivatives as novel HIV-1 replication inhibitors, Safety of (6-Hydroxypyridin-3-yl)boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2014), 24(23), 5473-5477, database is CAplus and MEDLINE.

The authors identified a novel class of 2-[(phenylsulfonyl)methyl]thieno[3,2-d]pyrimidine compounds as potent HIV-1 replication inhibitors serendipitously during the process of evaluation of triazolothienopyrimidine (TTPM) compounds Herein, the authors report a synthesis and biol. evaluation of 2-[(phenylsulfonyl)methyl]thieno[3,2-d]pyrimidine compounds using a cell-based full replication assay to identify thienopyrimidine derivatives which could be further utilized as viable lead compounds The synthesis of the target compounds was achieved by a reaction of (chloro)[[(aryl)sulfonyl]methyl]thieno[3,2-d]pyrimidine with boronic acids, amines, phenol derivative

Bioorganic & Medicinal Chemistry Letters published new progress about 903899-13-8. 903899-13-8 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester,Alcohol,Boronic Acids,Boronic acid and ester, name is (6-Hydroxypyridin-3-yl)boronic acid, and the molecular formula is C5H6BNO3, Safety of (6-Hydroxypyridin-3-yl)boronic acid.

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