[2-Amino-6-(2,6-dichlorophenyl)-7-oxo-7H-pyrido[2,3-d]-pyrimidin-8-yl]-acetic acid methyl ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [2-Amino-6-(2,6-dichlorophenyl)-7-oxo-7H-pyrido[2,3-d]-pyrimidin-8-yl]-acetic acid methyl ester
• 英文别名: [2-amino-6-(2,6-dichlorophenyl)-7-oxo-7H-pyrido[2,3-d]pyrimidin-8-yl]-acetic acid methyl ester；Pyrido[2,3-d]pyrimidin-7-one deriv. 9；methyl 2-[2-amino-6-(2,6-dichlorophenyl)-7-oxopyrido[2,3-d]pyrimidin-8-yl]acetate
• 化学式: C₁₆H₁₂Cl₂N₄O₃
• 分子量: 379.202
• InChiKey: KNIFQDAVGJMBRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  98.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  氯乙酸甲酯 、 2-amino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]-pyrimidin-7(8H)-one 在 NaH 作用下， 以 N-甲基乙酰胺 、 (2S)-N-methyl-1-phenylpropan-2-amine hydrate 、 正己烷 、 mineral oil 为溶剂， 以152 mg (61%)的产率得到[2-Amino-6-(2,6-dichlorophenyl)-7-oxo-7H-pyrido[2,3-d]-pyrimidin-8-yl]-acetic acid methyl ester
  参考文献：
  名称：

  Pyrido\x9b2, 3-d!pyrimidines for inhibiting protein tyrosine kinase

  摘要：

  6-芳基吡啶[2,3-d]嘧啶7-亚胺，7-酮和7-硫醚是蛋白酪氨酸激酶的抑制剂，因此在治疗由此介导的细胞增殖方面非常有用。这些化合物在治疗癌症、动脉粥样硬化、再狭窄和牛皮癣方面特别有用。

  公开号：

  US05733914A1

文献信息

• Synthesis and Tyrosine Kinase Inhibitory Activity of a Series of 2-Amino-8<i>H</i>-pyrido[2,3-<i>d</i>]pyrimidines:  Identification of Potent, Selective Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitors
  作者：Diane H. Boschelli、Zhipei Wu、Sylvester R. Klutchko、H. D. Hollis Showalter、James M. Hamby、Gina H. Lu、Terry C. Major、Tawny K. Dahring、Brian Batley、Robert L. Panek、Joan Keiser、Brian G. Hartl、Alan J. Kraker、Wayne D. Klohs、Bill J. Roberts、Sandra Patmore、William L. Elliott、Randy Steinkampf、Laura A. Bradford、Hussein Hallak、Annette M. Doherty

  DOI：10.1021/jm980398y

  日期：1998.10.1

  N-8 of the pyrido[2,3-d]pyrimidine core provided several analogues that retained potency, including derivatives that were biased toward inhibition of the TK activity of PDGFr. Analogues of 2a with a 3-thiophene or an unsubstituted phenyl group at C-6 were the most potent inhibitors. Compound 54, which had IC50 values of 31, 88, and 31 nM against PDGFr, FGFr, and c-src TK activity, respectively, was

  化合物库的筛选导致鉴定出2-氨基-6-（2,6-二氯苯基）-8-甲基吡啶并[2,3-d]嘧啶（1）作为血小板衍生的生长因子受体的抑制剂（ PDGFr），成纤维细胞生长因子受体（FGFr）和c-src酪氨酸激酶（TKs）。用4-（N，N-二乙基氨基乙氧基）苯基氨基取代C-2为1的伯氨基得到2a，其对所有三个TK的活性均大大提高。在目前的工作中，吡啶并[2,3-d]嘧啶核的C-6处的芳族基团和N-8处的烷基基团的变化提供了几种保留效力的类似物，包括偏向于抑制甲壳素的衍生物。 PDGFr的TK活性。2a在C-6处带有3-噻吩或未取代的苯基的类似物是最有效的抑制剂。化合物54的IC50值为31，
• [EN] PYRIDO[2,3-d]PYRIMIDINES FOR INHIBITING PROTEIN TYROSINE KINASE MEDIATED CELLULAR PROLIFERATION<br/>[FR] PYRIDO[2,3-d]PYRIMIDINES DESTINEES A INHIBER LA PROLIFERATION CELLULAIRE INDUITE PAR LES TYROSINES KINASES
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1996034867A1

  公开（公告）日：1996-11-07

  (EN) 6-Aryl pyrido[2,3-d]pyrimidine 7-imines, 7-ones, and 7-thiones o f formula (I) are inhibitors of protein tyrosine kinases, and are thus useful in treating cellular proliferation mediated thereby. The compounds are especially useful in treating cancer, atherosclerosis, restenosis, and psoriasis.(FR) On décrit des 6-aryl pyrido[2,3-d]pyrimidine 7-imines, 7-ones, et 7-thiones, formule (I) qui sont des inhibiteurs des tyrosines kinases et sont, par conséquent, utiles dans le traitement de la prolifération cellulaires induite par ces protéines. Ces composés sont notamment utiles dans le traitement du cancer, de l'athérosclérose, de la sténose récidivante et du psoriasis.

  带有苯基的6-位的pyrido[2,3-d]pyrimidine 7-imines、7-ones和7-thiones（通用式为I）是抑制蛋白酪氨酸激酶的化合物，因此对通过这些蛋白质引发的细胞分裂具有治疗作用。这些化合物尤其适用于治疗癌症、动脉硬化、再狭窄和银屑病。
• PYRIDO[2,3-d]PYRIMIDINES FOR INHIBITING PROTEIN TYROSINE KINASE MEDIATED CELLULAR PROLIFERATION
  申请人：Warner-Lambert Company LLC

  公开号：EP0823908B1

  公开（公告）日：2006-11-02
• PYRIDO 2,3-d]PYRIMIDINES FOR INHIBITING PROTEIN TYROSINE KINASE MEDIATED CELLULAR PROLIFERATION
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0823908A1

  公开（公告）日：1998-02-18
• [EN] PYRIDOPYRIMIDINE DERIVATIVES<br/>[FR] DERIVES DE PYRIDOPYRIMIDINE
  申请人：GPC BIOTECH AG

  公开号：WO2005105097A2

  公开（公告）日：2005-11-10

  The present invention relates to the use of pyridopyrimidine derivatives having the general formula (I) wherein X represents =NH, =N-Acyl, =O, or =S; R1 represents -NR3R4, -SR3, -SO-R3, -SO2-R3, -OR3; R2, R3, and R4 are independently of each other hydrogen, -(CH2)nPh*, heteroaryl, C3-C7-cycloalkyl, C1-C6-alkyl, C1-C6-alkanoyl, C2-C6-alkenyl, C2-C6-alkynyl; wherein the cycloalkyl, alkyl, alkanoyl, alkenyl, alkynyl residues can optionally substituted by one or more of the following groups: -NR5R6, phenyl, substituted phenyl, thioalkyl, alkyloxy, hydroxy, carboxy, halogen, cycloalkyl; R5 and R6 are independently of each other hydrogen, (CH2)nPh*, heteroaryl, C3-C7-cycloalkyl, C1-C6-alkyl, C1-C6-alkanoyl, C2-C6-alkenyl, C2-C6-alkynyl; R5 and R6 can be taken together with the nitrogen to which they are attached to complete a ring having 3 to 7 carbon atoms, optionally containing 1, 2, or 3 heteroatoms selected from nitrogen, oxygen, and sulfur; Ph* represents phenyl or substituted phenyl; n is 0, 1, 2, or 3; R4 can optionally be -CO-R3, -CO-OR3, -SO2-R3, -SO2-NR5R6, -CO-NR5R6, -CS-NR5R6, -C(=NH)-R3, -C(=NH)-NR5R6; R3 and R4 can be taken together with the nitrogen to which they are attached to complete a ring having 3 to 7 carbon atoms, optionally containing 1, 2, or 3 heteroatoms selected from nitrogen, oxygen, and sulfur; Ar represents phenyl, substituted phenyl, or heteroaryl; and pharmaceutically acceptable salts thereof for prophylaxis and/or treatment of inflammatory diseases, neurodegenerative disorders, immunological diseases, neuroimmunological diseases, autoimmune diseases, diabetes, transplant rejection, infective diseases, prion diseases, cardiovascular diseases and disorders.