4-amino-6-(2,6-dichlorophenyl)-8-methyl-2-(4-(2-morpholinoethoxy)-phenylamino)pyrido[2,3-d]pyrimidin-7(8H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-amino-6-(2,6-dichlorophenyl)-8-methyl-2-(4-(2-morpholinoethoxy)-phenylamino)pyrido[2,3-d]pyrimidin-7(8H)-one
• 英文别名: 4-amino-6-(2,6-dichloro phenyl)-8-methyl-2-(4-(2-morpholinoethoxy)-phenylamino)-pyrido[2,3-d]pyrimidin-7(8H)-one；4-amino-6-(2,6-dichlorophenyl)-8-methyl-2-[4-(2-morpholin-4-ylethoxy)anilino]pyrido[2,3-d]pyrimidin-7-one
• 化学式: C₂₆H₂₆Cl₂N₆O₃
• 分子量: 541.437
• InChiKey: MDUBLSIVMWTAMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  methyl 2-(2,6-dichlorophenyl)acrylate 在 copper(l) iodide 、 溴 、 sodium methylate 、 sodium hydride 、 caesium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 二甲基亚砜 、 mineral oil 为溶剂， 反应 25.0h， 生成 4-amino-6-(2,6-dichlorophenyl)-8-methyl-2-(4-(2-morpholinoethoxy)-phenylamino)pyrido[2,3-d]pyrimidin-7(8H)-one
  参考文献：
  名称：

  4-Amino-2-arylamino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7-(8H)-ones as BCR kinase inhibitors for B lymphoid malignancies

  摘要：

  A new family of 4-aminopyrido[2,3-d]pyrimidines active against non-Hodgkin's lymphomas (NHLs) is described. Among these compounds, 19 inhibits the most upstream tyrosine kinases in the B cell receptor (BCR) signaling pathway which are involved in the mature B cell neoplasms. Thus, 19 showed anti-proliferative activity at 24 h and 48 h against a panel of 20 NHLs cell lines with GI(50) ranging from 1.3 to 6.91 mu M at 24 h, and 1.4-7.2 mu M at 48 h, being this effect related to a significant (20-90%) inhibition of the phosphorylation of the BCR-related kinases Btk, Syk, and Lyn. Most importantly, 19 was able to induce a 63% reduction in Rec-1 cell proliferation, which was significantly greater than the 31% and 3% blockade of proliferation observed after cell treatment with R406, a Syk inhibitor, and ibrutinib, a Btk inhibitor, respectively. The computational blind docking and ligand binding within the pockets of Btk, Syk and Lyn kinases showed that compound 19 presents the same kind of interactions of described cocrystallized inhibitors. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.018

文献信息

• 4-Amino-6-(2,6-dichlorophenyl)-2-(phenylamino)-pyrido[2,3-d]pyrimidin-7(8H)-one derivatives, synthesis and uses thereof
  申请人：Institut Quimic De Sarriá Cets, Fundació Privada

  公开号：EP2813504A1

  公开（公告）日：2014-12-17

  The present invention is related to 4-amino-6-(2,6-dichlorophenyl)-2-(phenylamino)-pyrido[2,3-d]pyrimidin-7(8H)-one derivatives, to the preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in the treatment and/or prevention of a non-Hodgkin's lymphoma.

  本发明涉及4-氨基-6-(2,6-二氯苯基)-2-(苯胺基)-吡啶并[2,3-d]嘧啶-7(8H)-酮衍生物，以及制备这类化合物、包含它们的药物组合物，以及它们在治疗和/或预防非霍奇金淋巴瘤中的应用。
• [EN] 4-AMINO-6-(2,6-DICHLOROPHENYL)-2-(PHENYLAMINO)-PYRIDO[2,3-d]PYRIMIDIN-7(8H)-ONE DERIVATIVES, SYNTHESIS AND USES THEREOF<br/>[FR] DÉRIVÉS 4-AMINO-6-(2,6-DICHLOROPHÉNYL)-2-(PHÉNYLAMINO)-PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE, SYNTHÈSE ET UTILISATIONS DE CES DERNIERS
  申请人：INST QUÍMIC DE SARRIÁ CETS FUNDACIÓ PRIVADA

  公开号：WO2014198960A1

  公开（公告）日：2014-12-18

  The present invention is related to 4-amino-6-(2,6-dichlorophenyl)-2- (phenylamino)-pyrido[2,3-d]pyrimidin-7(8H)-one derivatives, to the preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in the treatment and/or prevention of a non-Hodgkin's lymphoma.

  本发明涉及4-氨基-6-(2,6-二氯苯基)-2-(苯胺基)-吡啶并[2,3-d]嘧啶-7(8H)-酮衍生物，以及制备这类化合物、包含它们的药物组合物，以及它们在治疗和/或预防非霍奇金淋巴瘤中的应用。
• 4-AMINO-6-(2,6-DICHLOROPHENYL)-2-(PHENYLAMINO)-PYRIDO[2,3-d]PYRIMIDIN-7(8H)-ONE DERIVATIVES, SYNTHESIS AND USES THEREOF
  申请人：Institut Químic De Sarriá, Cets Fundació Privada

  公开号：US20160176866A1

  公开（公告）日：2016-06-23

  The present invention is related to 4-amino-6-(2,6-dichlorophenyl)-2-(phenylamino)-pyrido[2,3-d]pyrimidin-7(8H)-one derivatives, to the preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in the treatment and/or prevention of a non-Hodgkin's lymphoma.

  本发明涉及4-氨基-6-(2,6-二氯苯基)-2-(苯基氨基)-吡啶[2,3-d]嘧啶-7(8H)-酮衍生物，其制备方法，包含它们的制药组合物，以及它们在非何杰金淋巴瘤的治疗和/或预防中的应用。
• 4-AMINO-6-(2,6-DICHLOROPHENYL)-2-(PHENYLAMINO)-PYRIDO(2,3-D)PYRIMIDIN-7(8H)-ONE DERIVATIVES, SYNTHESIS AND USES THEREOF
  申请人：Institut Químic de Sarriá CETS Fundació Privada

  公开号：EP3008063B1

  公开（公告）日：2017-04-19
• US9630962B2
  申请人：——

  公开号：US9630962B2

  公开（公告）日：2017-04-25