1-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid 4-methoxy-benzylamide | 449210-09-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 1-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid 4-methoxy-benzylamide
• 英文别名: N-[(4-methoxyphenyl)methyl]-1-methyl-2,4-dioxopyrido[2,3-d]pyrimidine-6-carboxamide
• CAS: 449210-09-7
• 化学式: C₁₇H₁₆N₄O₄
• 分子量: 340.338
• InChiKey: VRHHJBVFRMFFNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

文献信息

• Quinazolines as MMP-13 inhibitors
  申请人：——

  公开号：US20020193377A1

  公开（公告）日：2002-12-19

  A compound selected from those of formula (I): 1 in which: R 1 represents a group selected from hydrogen, amino, alkyl, alkenyl, aminoalkyl, aryl, arylalkyl, heterocycle, and cycloalkylalkyl, optionally substituted, W represents oxygen, sulfhur, or ═N—R′, in which R′ is as defined in the description, X 1 , X 2 and X 3 represent nitrogen or —C—R 6 in which R 6 is as defined in the description, Y represents oxygen, sulfhur, —NH, or —N(C 1 -C 6 )alkyl, Z represents oxygen, sulfhur, —NR 7 in which R 7 is as defined in the description, and 59 optionally carbon atom, n is an integer from 1 to 8 inclusive, Z 1 represents —CR 8 R 9 wherein R 8 and R 9 are as defined in the description, A represents aromatic or non-aromatic, heterocyclic or non-heterocyclic ring system, m is an integer from 0 to 7 inclusive, the group(s) R 2 is (are) is as defined in the description, R 3 represents hydrogen, alkyl, alkenyl, alkynyl, ot a group of formula: 2 in which Z 2 , B, R 5 , P and q are as defined in the description, optionally, the racemic forms thereof, isomers thereof, N-oxydes thereof, and the pharmaceutically acceptable salts thereof, and medicinal products containing the same are useful as specific inhibitors of type-13 matrix metalloprotease.

  从以下化学式（I）中选择的一种化合物： 其中： R1代表从氢、氨基、烷基、烯基、氨基烷基、芳基、芳基烷基、杂环和环烷基烷基中选择的基团，可选择取代； W代表氧、硫或═N—R′，其中R′如描述中定义； X1、X2和X3代表氮或—C—R6，其中R6如描述中定义； Y代表氧、硫、—NH或—N（C1-C6）烷基； Z代表氧、硫、—NR7，其中R7如描述中定义，且可选地是碳原子； n为1到8之间的整数； Z1代表—CR8R9，其中R8和R9如描述中定义； A代表芳香或非芳香、杂环或非杂环环系统； m为0到7之间的整数； R2代表如描述中定义的基团； R3代表氢、烷基、烯基、炔基或化学式2中的基团： 其中Z2、B、R5、P和q如描述中定义； 可选地，它们的外消旋体、异构体、N-氧化物和药学上可接受的盐，以及含有它们的药物制剂，可用作特异性抑制剂13型基质金属蛋白酶。
• 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。