CAS: 1508250-71-2; (R,E)-N-(7-Chloro-1-(1-(4-(Dimethylamino)But-2-Enoyl)Azepan-3-yl)-1H-Benzo[d]Imidazol-2-yl)-2-Methylisonicotinamide

📜3-氯-2-氟硝基苯置于盐酸,1-羟基苯并三唑,溶剂黄146,盐酸-N-乙基-N'-(3-二甲氨基丙基)碳二亚胺,N,N-二异丙基乙胺,N-[(Dimethylamino)-3-Oxo-1H-1,2,3-Triazolo[4,5-B]Pyridin-1-Yl-Methylene]-N-Methylmethanaminium Hexafluorophosphate,锌体系中,用 1,4-二氧六环,甲醇,水,N,N-二甲基甲酰胺,乙腈 用作溶剂,化学反应 54.0H,反应生成N-[7-氯-1-[(3R)-1-[(2E)-4-(二甲基氨基)-1-氧代-2-丁烯-1-基]六氢-1H-氮杂革-3-基]-1H-苯并咪唑-2-基]-2-甲基-4-吡啶羧酰胺
参考文献:(r,E)-N-(7-氯-1-(1-[4-(二甲基氨基)丁-2-烯酰基]氮杂潘-3-基)-1 H-苯并[ D ]咪唑-2-的发现yl)-2-Methylisonicotinamide(egf816),一种新颖,有效且具有wt致癌性(l858R,Ex19Del)和抗性(t790M)egfr突变体的共价抑制剂,用于治疗egfr突变型非小细胞肺癌
标题:(r,E)-N-(7-氯-1-(1-[4-(二甲基氨基)丁-2-烯酰基]氮杂潘-3-基)-1 H-苯并[ D ]咪唑-2-的发现yl)-2-Methylisonicotinamide(egf816),一种新颖,有效且具有wt致癌性(l858R,Ex19Del)和抗性(t790M)egfr突变体的共价抑制剂,用于治疗egfr突变型非小细胞肺癌
摘要:在过去的十年中,第一代和第二代egfr抑制剂对具有egfr激活突变的肺癌患者的治疗效果有显着改善.但是,通过关守残基的继发性t790M突变产生的抗药性以及来自野生型(wt)egfr抑制的剂量限制毒性最终都限制了这些疗法控制突变egfr驱动的肿瘤的全部潜力,因此迫切需要新的疗法.在这里,我们描述了我们发现47(egf816,Nazartinib)的方法,这是一种新颖的共价突变选择性egfr抑制剂,对致癌和t790M耐药的egfr突变均具有同等活性.通过分子对接研究,我们转化了突变体选择性高通量筛选命中分子(7)转化为具有靶向活性的多种共价egfr抑制剂,这些抑制剂对egfr突变体具有同等活性,并且具有非常好的wt-Egfr选择性.我们使用了简短的体内功效研究,对具有非常好耐受性和功效的化合物进行优先排序,最终导致选择47种作为临床候选药物.
Doi:10.1021/acs.Jmedchem.5B01985

专利信息

专利号:US-2004058888-A1
优先权日:2000-01-13
标题:Methods for synthesis of alpha-d-gal (1~>3) gal-containing oligosaccharides
发明人：BORNAGHI LAURENT; DEKANY GYULA; DRINNAN NICHOLAS BARRY; PAPAGEORGIOU JOHN; WEST MICHAEL LEO
摘要:This invention relates to reagents and methods for synthesis of biologically active di- and tri-saccharides comprising α-D-Gal(1→3)-D-Gal. In particular the invention provides novel reagents, intermediates and processes for the solution or solid phase synthesis of α-D-galactopyranosyl-(1→3)-D-galactose, and derivatives thereof. In one preferred embodiments the invention provides a protected monosaccharide building block of general formula (II): in which R 3 is methoxy or methyl; R 1 is H, benzoyl, pivaloyl, 4-chlorobenzoyl, acetyl, chloroacetyl, levulinoyl, 4-methylbenzoyl, benzyl, 3,4-methylenedioxybenzyl, 4-methoxybenzyl, 4-chlorobenzyl, 4-acetamidobenzyl, or 4-azidobenzyl; and R 2 is H, Fmoc, benzoyl, pivaloyl, 4-chlorobenzoyl, acetyl, chloroacetyl, levulinoyl, 4-methylbenzoyl, benzyl, 3,4-methylenedioxybenzyl, 4-methoxybenzyl, 4 -chlorobenzyl, 4-acetamidobenzyl, or 4-azidobenzyl.

专利号:US-2018297925-A1
优先权日:2015-10-12
标题 :Methods for total synthesis of resolvin e1
发明人：JAGTAP PRAKASH
权利人:SALZMAN LOVELACE INVEST LTD
摘要:Methods for total chemical synthesis of Resolvin E1 (RvE1) include Wittig reaction of two compounds having hydroxyl protecting group in the presence of a strong base, removal of the hydroxyl-protecting groups with a deprotecting reagent to produce a compound having an ester group, and hydrolysis of the ester group to obtain RvE1

专利号:US-6133409-A
优先权日:1996-12-19
标 题:Process for the solid phase synthesis of aldehyde, ketone, oxime, amine, hydroxamic acid and αβ-unsaturated carboxylic acid and aldehyde compounds
发明人：SALVINO JOSEPH M; MORTON GEORGE C; MASON HELEN J; LABAUDINIERE RICHARD F
权利人:AVENTIS PHARM PROD INC
摘要:This invention is directed to a process for the solid phase synthesis of aldehyde, ketone, oxime, amine, hydroxamic acid and alpha , beta -unsaturated carboxylic acid and aldehyde compounds and to polymeric hydroxylamine resin compounds useful therefor.

专利号:US-4818816-A
优先权日:1981-04-28
标 题:Process for the organic synthesis of oligosaccharides and derivatives thereof
发明人：PETITOU MAURICE; JACQUINET JEAN-CLAUDE; SINAY PIERRE; CHOAY JEAN; LORMEAU JEAN-CLAUDE; NASSR MAHMOUD
权利人:CHOAY SA
摘要:The invention relates to a process for the organic synthesis of oligosaccharides constituting or comprising fragments of acid mucopolysaccharides comprising the reaction of two compounds constituted or terminated by units of glucosamine structure and of uronic acid structure respectively, said units being specifically substituted. This process particularly enables valuable anticoagulant drugs to be obtained.

专利号:US-2010159540-A1
优先权日:2007-03-26
标题:Synthesis of resolvins and intermediates, compounds prepared thereby, and uses thereof
发明人：RODRIGUEZ ANA; SPUR BERND
权利人:RODRIGUEZ ANA; SPUR BERND
摘要:Methods are disclosed for the preparation of a new class of lipid mediators known as resolvins, with Resolvin D6 (4,17-dihydroxy-5E,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid) being exemplary. Also disclosed are methods for the efficient synthesis of key intermediates in the preparation of such resolvins, such as isotopically labeled ω-3 fatty acid metabolites, and derivatives and analogs thereof. The invention likewise extends to the intermediates so prepared, and to the resolvins prepared with their use.

专利号:US-5446158-A
优先权日:1989-01-11
标题:Process for synthesis of FK-506 and tricarbonyl intermediates
发明人：JONES TODD K; MILLS SANDER G; ASKIN DAVID; REAMER ROBERT A; DESMOND RICHARD; TSCHAEN DAVID M; VOLANTE RALPH P; SHINKAI ICHIRO
权利人:MERCK & CO INC
摘要:A process is described for the total synthesis of the macrolide immunosuppressant, FK-506, and important tricarbonyl process intermediates thereof. The tricarbonyl intermediates can be produced by the mild oxidation of 2,3-dihydroxy carboxylate compounds containing olefin moieties.