3430-18-0Relevant academic research and scientific papers
Preparation method of 2, 5-dibromo-3-methylpyridine
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Paragraph 0017; 0020; 0022; 0023; 0025; 0026; 0028, (2020/03/09)
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of 2, 5-dibromo-3-methylpyridine. The preparation method comprises the following steps: (1) adding 2-amino-3-methylpyridine and acetic anhydride into a four-neck flask, heating to reflux, and carrying out thin-layer chromatography tracking reaction; (2) when the temperature of a reaction liquid obtained in the step (1) is reduced to 20-25 DEG C, dropwise adding liquid bromine, reacting for 2-3 hours at 50-60 DEG C after dropwise adding of liquid bromine, adding water until all solids are dissolved, dropwise adding a sodium hydroxide solution, continuously reacting for 30 minutes after dropwise adding, and carrying out suction filtration, drying and recrystallization to obtain 2-amino-3-methyl-5-bromopyridine; and (3) adding the obtained 2-amino-3-methyl-5-bromopyridine into a hydrogen bromide solution, dropwise adding a saturated sodium nitrite solution under the catalysis of cuprous bromide, controlling the temperature to be -5 to 10 DEG C, and reacting for 2 to 4 hours to obtain 2, 5-dibromo-3-methylpyridine. The method provided by the invention has the beneficial effects ofmild reaction conditions, high yield, low cost and short process route, and is suitable for industrial production.
Synthesis method of (5-bromo-3-methyl-pyridine-2-yl)-methylamine
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Page/Page column 6-8, (2019/12/25)
The invention discloses a synthesis method of (5-bromo-3-methyl-pyridine-2-yl)-methylamine. The synthesis method includes: taking 2-amino-3-methylpyridine as the starting raw material, and carrying out bromination, diazotization, bromination and methylamination reactions to obtain (5-bromo-3-methyl-pyridine-2-yl)-methylamine. The method designs a brand-new synthetic route, has the characteristicsof mild reaction conditions, high product purity, and easily available starting raw material 2-amino-3-methylpyridine, and is easy for industrial production.
A 2, 5 - dibromo -3 - methyl pyridine preparation method (by machine translation)
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Paragraph 0017; 0020; 0022; 0023; 0025; 0026; 0028, (2019/05/28)
The invention belongs to the field of organic synthesis, in particular relates to a 2, 5 - dibromo - 3 - methyl pyridine preparation method, comprises the following steps: (1) the 2 - amino - 3 - methyl pyridine and acetic anhydride is added to the four flasks, heating to reflux, thin-layer chromatography the tracking reaction; (2) step (1) of reaction fluids in a temperature drop to 20 - 25 °C when, [...], paused, 50 - 60 °C reaction 2 - 3 h, to all solid-dissolving after adding water, sodium hydroxide solution, after adding continue to reaction 30 min, filtering, drying, recrystallize to get 2 - amino 3 - methyl - 5 - bromo pyridine; (3) the 2 - amino - 3 - methyl - 5 - bromo pyridine is added in a solution of hydrogen bromide, in the catalysis of cuprous bromide, [...] and sodium nitrite solution, temperature control in the - 5 - 10 °C, reaction 2 - 4 h, shall be 2, 5 - dibromo - 3 - methyl pyridine. The method of the invention is beneficial effect: mild reaction conditions, high yield, low cost, the process route is short, it is suitable for industrial production. (by machine translation)
Design, synthesis and biological evaluation of pyridone–aminal derivatives as MNK1/2 inhibitors
Yuan, Xinrui,Wu, Hanshu,Bu, Hong,Zheng, Peiyuan,Zhou, Jinpei,Zhang, Huibin
, p. 1211 - 1225 (2019/02/28)
Excessive phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) plays a major role in the dysregulation of mRNA translation and the activation of tumor cell signaling. eIF4E is exclusively phosphorylated by mitogen-activated protein kinase interacting kinases 1 and 2 (MNK1/2) on Ser209. So, MNK1/2 inhibitors could decrease the level of p-eIF4E and regulate tumor-associated signaling pathways. A series of pyridone–aminal derivatives were synthesized and evaluated as MNK1/2 inhibitors. Several compounds exhibited great inhibitory activity against MNK1/2 and selected compounds showed moderate to excellent anti-proliferative potency against hematologic cancer cell lines. In particular, compound 42i (MNK1 IC50 = 7.0 nM; MNK2 IC50 = 6.1 nM) proved to be the most potent compound against TMD-8 cell line with IC50 value of 0.91 μM. Furthermore, 42i could block the phosphorylation level of eIF4E in CT-26 cell line, and 42i inhibited the tumor growth of CT-26 allograft model significantly. These results indicated that compound 42i was a promising MNK1/2 inhibitor for the potent treatment of colon cancer.
Preparation method for 2,5-dibromo-3-methylpyridine
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Paragraph 0012; 0017, (2016/10/07)
The invention specifically relates to a preparation method for 2,5-dibromo-3-methylpyridine, which belongs to the field of organic synthesis. The preparation method comprises the following steps: (1) adding 2-amino-3-methylpyridine and acetic anhydride into a four-neck flask, carrying out heating to a reflux state and tracking a reaction via thin-layer chromatogram; (2) as the temperature of a reaction solution in the step (1) drops to 20 to 25 DEG C, adding liquid bromine drop by drop, then carrying out a reaction at 50 to 60 DEG C for 2 to 3 h after completion of the addition, adding water until all the solids are dissolved, then adding a sodium hydroxide solution drop by drop, continuing a reaction for 30 min after completion of the addition, and successively carrying out pumping filtration, drying and recrystallization so as to obtain 2-amino-3-methyl-5-bromopyridine; and (3) adding 2-amino-3-methyl-5-bromopyridine into a hydrogen bromide solution and under the catalysis of cuprous bromide, adding a saturated sodium nitrite solution drop by drop and carrying out a reaction at a temperature of -5 to 10 DEG C for 2 to 4 h so as to obtain 2,5-dibromo-3-methylpyridine. The method provided by the invention has the following beneficial effects: mild reaction conditions, high yield, low cost, short process route and suitability for industrial production.
AZAINDENOISOQUINOLINE TOPOISOMERASE I INHIBITORS
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Paragraph 0175, (2014/02/16)
The invention described herein pertains to substituted azaindenoisoquinoline compounds, in particular 7-, 8-, 9-, and 10-azaindenoisoquinoline compounds, which are inhibitors of topoisomerase I, processes and intermediates for their syntheses, pharmaceutical compositions of the compounds, and methods of using them in the treatment of cancer.
Azaindenoisoquinolines as topoisomerase i inhibitors and potential anticancer agents: A systematic study of structure-activity relationships
Kiselev, Evgeny,Agama, Keli,Pommier, Yves,Cushman, Mark
experimental part, p. 1682 - 1697 (2012/05/04)
A comprehensive study of a series of azaindenoisoquinoline topoisomerase I (Top1) inhibitors is reported. The synthetic pathways have been developed to prepare 7-, 8-, 9-, and 10-azaindenoisoquinolines. The present study shows that 7-azaindenoisoquinolines possess the greatest Top1 inhibitory activity and cytotoxicity. Additionally, the introduction of a methoxy group into the D-ring of 7-azaindenoisoquinolines improved their biological activities, leading to new lead molecules for further development. A series of QM calculations were performed on the model "sandwich" complexes of azaindenoisoquinolines with flanking DNA base pairs from the Drug-Top1-DNA ternary complex. The results of these calculations demonstrate how changes in two forces contributing to the π-π stacking (dispersion and charge-transfer interactions) affect the binding of the drug to the Top1-DNA cleavage complex and thus modulate the drug's Top1 inhibitory activity.
Acridone-based inhibitors of inosine 5′-monophosphate dehydrogenase: Discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1- yl)pyridin-3-yl)propan-2-yl)-2-fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419)
Watterson, Scott H.,Chen, Ping,Zhao, Yufen,Gu, Henry H.,Dhar, T. G. Murali,Xiao, Zili,Ballentine, Shelley K.,Shen, Zhongqi,Fleener, Catherine A.,Rouleau, Katherine A.,Obermeier, Mary,Yang, Zheng,McIntyre, Kim W.,Shuster, David J.,Witmer, Mark,Dambach, Donna,Chao, Sam,Mathur, Arvind,Chen, Bang-Chi,Barrish, Joel C.,Robl, Jeffrey A.,Townsend, Robert,Iwanowicz, Edwin J.
, p. 3730 - 3742 (2008/02/12)
Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5′- monophosphate to xanthosine-5′-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.
8-(BIARYL) QUINOLINE PDE4 INHIBITORS
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Page 71; 72, (2010/02/06)
8-(biaryl) quinolines wherein the bi-aryl group at the 8-position is in a meta relationship to the quinoline group, are PDE4 inhibitors useful in the treatment of asthma, chronic bronchitis, chronic obstructive pulmonary disease, eosinophilic granuloma, psoriasis and other benign or malignant proliferative skin diseases, endotoxic shock, laminitis in horses, colic in horses, septic shock, ulcerative colitis, Crohn's disease, reperfusion injury of the myocardium and brain, inflammatory arthritis, chronic glomerulonephritis, atopic dermatitis, urticaria, adult respiratory distress syndrome, chronic obstructive pulmonary disease in animals, diabetes insipidus, allergic rhinitis, allergic conjunctivitis, vernal conjunctivitis, arterial restenosis, ortherosclerosis, atherosclerosis, neurogenic inflammation, pain, cough, rheumatoid arthritis, ankylosing spondylitis, transplant rejection, graft versus host disease, hypersecretion of gastric acid, bacterial, fungal induced sepsis, viral induced sepsis, fungal induced septic shock, viral induced septic shock, inflammation-mediated chronic tissue degeneration, cytokine-mediated chronic tissue degeneration, osteoarthritis, cancer, cachexia, muscle wasting, depression, memory impairment, tumour growth, or cancerous invasion of normal tissues.In another aspect, the present invention is directed to a method of enhancing cognition in a healthy subject comprising administering a safe cognition enhancing amount of phosphodiesterase-4 inhibitor. In particular, this invention is directed to a method of enhancing memory, learning, retention, recall, awareness and judgement in health subjects comprising administering a safe and cognition enhancing amount of a phosphodiesterase-4 inhibitor.
Synthesis of the grass alkaloid perlolidine through a pyridyne cyclisation reaction
Kessar,Singh
, p. 1129 - 1131 (2007/10/03)
A synthesis of the grass alkaloid perlolidine is described in which the key step involves the pyridyne cyclisation of 2-benzyloxy-5-bromo-3-[(N-phenyl) aminomethyl] pyridine.
