methyl 4-(6-iodo-1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl)-benzoate | 451471-63-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: methyl 4-(6-iodo-1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl)-benzoate
• 英文别名: 4-(6-Iodo-1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl)-benzoic acid methyl ester；methyl 4-[(6-iodo-1-methyl-2,4-dioxoquinazolin-3-yl)methyl]benzoate
• CAS: 451471-63-9
• 化学式: C₁₈H₁₅IN₂O₄
• 分子量: 450.233
• InChiKey: RUUYAUBXFBGLDE-UHFFFAOYSA-N

物化性质

• 沸点：
  564.7±60.0 °C(Predicted)
• 密度：
  1.669±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-(6-iodo-1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl)-benzoate 在 copper(l) iodide 、 四(三苯基膦)钯 、 sodium acetate 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-[1-methyl-2,4-dioxo-6-(3-phenylprop-1-yn-1-yl)-1,4-dihydro-2H-quinazolin-3-ylmethyl]benzoic acid
  参考文献：
  名称：

  An efficient synthesis of isotope-labeled PD0331179 and its labeled metabolite

  摘要：

  4-[1-甲基-2,4-二氧-6-(3-苯基-丙-1-炔基)-1,4-二氢-2H-喹唑啉-3-基甲基]-苯甲酸，PD0331179，正在作为基质金属蛋白酶-13的抑制剂进行研究。14C标记和2H标记的PD0331179及其2H标记代谢物（PD0335699）是支持其临床前和临床研究所需的。以[14C]苯甲酸为起始材料高效制备了[14C] 3-苯基-1-三甲基/三苯基硅基炔，并将其作为合成[14C] PD0331179的关键标记试剂。开发了一种芳基碘化物与三烷基硅基炔的一锅耦合反应，以提高合成效率。这些合成的具体细节已报告。版权 © 2012 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.2963
• 作为产物：
  描述：

  N-甲基蒽 在 N-甲基吗啉 、 碘 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 4-(6-iodo-1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl)-benzoate
  参考文献：
  名称：

  An efficient synthesis of isotope-labeled PD0331179 and its labeled metabolite

  摘要：

  4-[1-甲基-2,4-二氧-6-(3-苯基-丙-1-炔基)-1,4-二氢-2H-喹唑啉-3-基甲基]-苯甲酸，PD0331179，正在作为基质金属蛋白酶-13的抑制剂进行研究。14C标记和2H标记的PD0331179及其2H标记代谢物（PD0335699）是支持其临床前和临床研究所需的。以[14C]苯甲酸为起始材料高效制备了[14C] 3-苯基-1-三甲基/三苯基硅基炔，并将其作为合成[14C] PD0331179的关键标记试剂。开发了一种芳基碘化物与三烷基硅基炔的一锅耦合反应，以提高合成效率。这些合成的具体细节已报告。版权 © 2012 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.2963

文献信息

• Matrix metalloproteinase inhibitors
  申请人：——

  公开号：US20030078276A1

  公开（公告）日：2003-04-24

  Compounds are provided that bind allosterically to the catalytic domain of MMP-13 and comprise a hydrophobic group, first and second hydrogen bond acceptors and at least one, and preferably both, of a third hydrogen bond acceptor and a second hydrophobic group. Cartesian coordinates for centroids of the above features are defined in the specification. When the ligand binds to MMP-13, the first, second and third (when present) hydrogen bond acceptors bond respectively with Thr245, Thr 247 and Met 253, the first hydrophobic group locates within the S1′ channel of MMP-13 and the second hydrophobic group (when present) is relatively open to solvent. The compounds specifically inhibit the matrix metalloproteinase-13 enzyme and thus are useful for treating diseases resulting from tissue breakdown, such as heart disease, multiple sclerosis, arthritis, atherosclerosis, and osteoporosis.

  提供了一些与MMP-13的催化结构域发生变构结合的化合物，包括一个疏水基团，第一和第二氢键受体，以及至少一个，最好是两个，第三氢键受体和第二疏水基团。上述特征的质心的笛卡尔坐标在说明书中定义。当配体与MMP-13结合时，第一、第二和第三（存在时）氢键受体分别与Thr245、Thr247和Met253结合，第一个疏水基团位于MMP-13的S1'通道内，第二疏水基团（存在时）相对于溶剂是开放的。这些化合物特异性地抑制基质金属蛋白酶-13酶，因此可用于治疗由组织分解引起的疾病，如心脏病、多发性硬化症、关节炎、动脉粥样硬化和骨质疏松症。
• Alkynylated fused ring pyrimidine compounds
  申请人：——

  公开号：US20030130278A1

  公开（公告）日：2003-07-10

  A compound selected from those of formula (I): 1 wherein W 1 represents O, S, or —NR 3 in which R 3 represents hydrogen, alkyl, OH or CN; W 2 represents a group selected from hydrogen, CF 3 , NH 2 , monoalkylamino, dialkylamino, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkylalkyl, heterocycle, these groups being optionally substituted, or W 1 and W 2 form together a group of formula —N═X 4 —W 3 — as defined in the description, X 1 , X 2 and X 3 represent N or C optionally substituted, n is 0 to 8, Z represents —CR 12 R 13 , wherein R 12 and R 13 are as defined in the description, A represents a ring system, the groups R 2 represent hydrogen or various chemical groups as defined in the description, q is 0 to 7; R 1 represents hydrogen, alkyl, alkenyl, alkynyl, or a ring system, and optionally, its optical isomers, N-oxide, and addition salts thereof with a pharmaceutically-acceptable acid or base, and medicinal products containing the same are useful as specific inhibitors of type-13 matrix metalloprotease.

  从公式（I）中选择的一种化合物：其中W1代表O、S或—NR3，其中R3代表氢、烷基、OH或CN；W2代表从氢、CF3、NH2、单烷基氨基、二烷基氨基、烷基、烯基、炔基、芳基、芳基烷基、环烷基烷基、杂环烷基中选择的一个基团，这些基团可以选择性地被取代，或者W1和W2一起形成一个公式为—N═X4—W3—的基团，如描述中定义的，X1、X2和X3代表N或C，可以选择性地被取代，n为0到8，Z代表—CR12R13，其中R12和R13如描述中定义，A代表一个环系统，基团R2代表氢或描述中定义的各种化学基团，q为0到7；R1代表氢、烷基、烯基、炔基或一个环系统，以及其光学异构体、N-氧化物和与药学上可接受的酸或碱形成的加合物，以及含有它们的药用产品作为特异性抑制剂对13型基质金属蛋白酶具有用处。
• Method of determining potential allosterically-binding matrix metalloproteinase inhibitors
  申请人：Andrianjara Charles

  公开号：US20050004126A1

  公开（公告）日：2005-01-06

  Compounds are provided that bind allosterically to the catalytic domain of MMP-13 and comprise a hydrophobic group, first and second hydrogen bond acceptors and at least one, and preferably both, of a third hydrogen bond acceptor and a second hydrophobic group. Cartesian coordinates for centroids of the above features are defined in the specification. When the ligand binds to MMP-13, the first, second and third (when present) hydrogen bond acceptors bond respectively with Thr245, Thr 247 and Met 253, the first hydrophobic group locates within the S1′ channel of MMP-13 and the second hydrophobic group (when present) is relatively open to solvent. The compounds specifically inhibit the matrix metalloproteinase-13 enzyme and thus are useful for treating diseases resulting from tissue breakdown, such as heart disease, multiple sclerosis, arthritis, atherosclerosis, and osteoporosis.

  提供了一种与MMP-13催化域发生变构作用的化合物，其中包括一个疏水基团、第一和第二氢键受体以及至少一个第三氢键受体和第二个疏水基团，最好是两者都有。上述特征的笛卡尔坐标在说明书中有定义。当配体与MMP-13结合时，第一、第二和第三（存在时）氢键受体分别与Thr245、Thr 247和Met 253结合，第一疏水基团位于MMP-13的S1'通道内，第二疏水基团（存在时）相对于溶剂较为开放。这些化合物特异性地抑制了基质金属蛋白酶-13酶，因此可用于治疗由组织分解引起的疾病，如心脏病、多发性硬化症、关节炎、动脉粥样硬化和骨质疏松症。
• Matrix metalloproteinase inhibitors and methods for identification of lead compounds
  申请人：——

  公开号：US20040171543A1

  公开（公告）日：2004-09-02

  The invention relates to compounds that are selective inhibitors of matrix metalloproteinases, to pharmaceutical compositions containing them and to their use in the prevention and/or treatment of MMP-associated diseases. The invention also relates to methods for identification of lead compounds that are selective inhibitors of matrix metalloproteinases. The compounds have the properties that they: (a) bind allosterically to a matrix metalloproteinase or small group of metallic metalloproteinases; (b) bind into at least the S1′ pocket, at least the S1″ pocket (as defined) or at least the S1′ pocket and the S1″ pocket of said matrix metalloproteinase; and (c) exhibit selectivity for a matrix metalloproteinase or group of matrix metalloproteinases other than MMP-13.

  本发明涉及选择性抑制基质金属蛋白酶的化合物，包括含有它们的药物组成物，以及它们在预防和/或治疗与MMP相关的疾病中的应用。本发明还涉及识别选择性抑制基质金属蛋白酶的先导化合物的方法。这些化合物具有以下特性：(a)与基质金属蛋白酶或少量金属金属蛋白酶发生异构作用；(b)至少结合于所述基质金属蛋白酶的S1'口袋、至少结合于S1"口袋（如定义所述）或至少结合于所述基质金属蛋白酶的S1'口袋和S1"口袋；以及(c)表现出选择性，对MMP-13以外的基质金属蛋白酶或基质金属蛋白酶组具有选择性。
• Alkynylated quinazoline compounds
  申请人：Gaudilliere Bernard

  公开号：US06962922B2

  公开（公告）日：2005-11-08

  A compound selected from those of formula (I): wherein W 1 represents O, S, or —NR 3 in which R 3 represents hydrogen, alkyl, OH or CN; W 2 represents a group selected from hydrogen, CF 3 , NH 2 , monoalkylamino, dialkylamino, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkylalkyl, heterocycle, these groups being optionally substituted, or W 1 and W 2 form together a group of formula —N═X 4 —W 3 — as defined in the description, X 1 , X 2 and X 3 represent N or C optionally substituted, n is 0 to 8, Z represents —CR 12 R 13 , wherein R 12 and R 13 are as defined in the description, A represents a ring system, the groups R 2 represent hydrogen or various chemical groups as defined in the description, q is 0 to 7; R 1 represents hydrogen, alkyl, alkenyl, alkynyl, or a ring system, and optionally, its optical isomers, N-oxide, and addition salts thereof with a pharmaceutically-acceptable acid or base, and medicinal products containing the same are useful as specific inhibitors of type-13 matrix metalloprotease.

  从式（I）中选择的化合物： 其中，W1表示O、S或—NR3，其中R3表示氢、烷基、羟基或氰基；W2表示从氢、CF3、NH2、单烷基氨基、二烷基氨基、烷基、烯基、炔基、芳基、芳基烷基、环烷基烷基、杂环等选择的基团，这些基团可以选择性地被取代，或者W1和W2组成一个式为—N═X4—W3—的基团，其中X1、X2和X3表示N或C，可以选择性地被取代，n为0至8，Z表示—CR12R13，其中R12和R13如说明中所定义，A表示一个环系，基团R2表示氢或如说明中所定义的各种化学基团，q为0至7；R1表示氢、烷基、烯基、炔基或一个环系，以及其光学异构体、N-氧化物和与药学上可接受的酸或碱形成的加合盐，以及含有它们的药物制剂，用作特异性抑制剂13型基质金属蛋白酶。