4--α-methylcinnamoyl>-N-<1,1-bis(ethoxycarbonyl)methyl>amino>butyric acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 缩酚酸和缩酚酸环醚类
• 英文名称: 4--α-methylcinnamoyl>-N-<1,1-bis(ethoxycarbonyl)methyl>amino>butyric acid
• 英文别名: 4-[[(E)-3-[4-(4-carbamimidoylphenoxy)carbonylphenyl]-2-methylprop-2-enoyl]-(1,3-diethoxy-1,3-dioxopropan-2-yl)amino]butanoic acid
• 化学式: C₂₉H₃₃N₃O₉
• 分子量: 567.596
• InChiKey: YIDFKKISZUBLCG-ISLYRVAYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  41
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  186
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  酮基丙二酸二乙酯 在 palladium on activated charcoal 氢气 、 三氟乙酸 作用下， 以 吡啶 、 苯 为溶剂， 反应 21.0h， 生成 4--α-methylcinnamoyl>-N-<1,1-bis(ethoxycarbonyl)methyl>amino>butyric acid
  参考文献：
  名称：

  新型口服活性丝氨酸蛋白酶抑制剂：其良好口服活性的结构要求。

  摘要：

  描述了对4-羟基苯甲m丝氨酸蛋白酶抑制剂的一系列对位取代的苯甲酸酯的良好口服活性的合成和结构要求。发现良好的口服活性所需的结构为通式II，其相应的酯必须在通过粘膜吸收之前在肠中或在吸收之后在血浆中水解。利用血浆抗胰蛋白酶活性对口服吸收进行生物学评估可用于快速评估。通过在口服给药后测量其实际血浆浓度，确认化合物14和16b在血浆浓度-时间曲线（AUC）下显示出良好的面积。他们的血浆浓度对应于他们的血浆抗胰蛋白酶活性。讨论了结构-口活动关系。

  DOI：

  10.1021/jm00022a017

文献信息

• Amidinophenol derivatives
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP0588655A1

  公开（公告）日：1994-03-23

  Amidinophenol derivatives of the formula (I): wherein R¹ and R² are (i) H, (ii) C1-4 alkyl, (iii) C1-4 alkoxy, (iv) C2-5 acyl, (v) halogen, (vi) NO₂, (vii) benzoyl, (viii) COOR⁴(in which R⁴ is C1-3 alkyl); A is bond, C1-4 alkylene, -C(R⁵)=C(R⁶)- (in which R⁵ and R⁶ are H or C1-4 alkyl); R³ is (i) CON(R⁷)(R⁸), (ii) CON(R⁹)-CH(R⁷)(R⁸) or (iii) (in which R⁷ and R⁸ are (1) H, (2) phenyl, (3) C7-10 phenylalkyl, (4) pheny or C7-10 phenylalkyl substituted by 1or 2 C1-4 alkyl, halogen or R¹¹-COOR¹² (in which R¹¹ is bond, C1-8 alkylene, C2-8 alkenylene, C2-8 alkynylene; R¹² is H, C1-4 alkyl, C7-10 phenylalkyl, phenyl, allyl, propargyl), (5) C1-10 alkyl, (6) C2-10 alkenyl having 1 to 3 double bonds, (7) C2-10 alkynyl having 1 or 2 triple bonds, (8) R11a-COXR¹²(in which R11a is (a) bond, (b) C1-8 alkylene, (c) C2-8 alkylene in which 1 or 2 carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene, (d) C2-8 alkenylene, (e) C4-8 alkenylene in which 1 or 2 carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene, (f) C2-8 alkynylene, (g)C4-8 alkynylene in which 1 or 2 carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene; X is -O- or -NH-), (9) C1-4 alkyl substituted by a 7-14 membered, bi- or tri-cyclic hetero ring containing one N atom, (10) C3-7 cycloalkyl); R⁹ is (1) H, (2) C1-8 alkyl, (3) C7-10 phenylalkyl, (4) C2-10 alkenyl having 1 to 3 double bonds, (5) C2-10 alkynyl having 1 or 2 triple bonds, (6) R¹¹-COOR¹², (7) C3-7 cycloalkyl; is 4-7 membered, mono-cyclic hetero ring containing 1 or 2 N atom; R¹⁰ is H, C7-10 phenylalkyl or COOR¹³(in which R¹³ is H, C1-4 alkyl or C7-10 phenylalkyl)); with the proviso that (i) both R⁷ and R⁸ do not represent hydrogen at the same time, and (ii) when at least one group in R⁷, R⁸ and R⁹ represents the group containing t-butyl ester, the other groups do not represent the group containing carboxy; or an acid addition salt thereof, have inhibitory activities on PLA₂ and on various proteases such as trypsin, plasmin, thrombin, kallikrein, especially trypsin, and are useful for the prevention and/or the treatment of various inflammatory diseases, allergic diseases, disseminated intravascular coagulation, pancreatitis, severity in pancreatitis and multiple organ failure.

  式 (I) 的脒基苯酚衍生物： 其中 R¹ 和 R² 是：(i) H，(ii) C1-4 烷基，(iii) C1-4 烷氧基，(iv) C2-5酰基，(v) 卤素，(vi) NO₂，(vii) 苯甲酰基，(viii) COOR⁴（其中 R⁴ 是 C1-3 烷基）；A 是键、C1-4 亚烷基、-C(R⁵)=C(R⁶)-（其中 R⁵ 和 R⁶ 是 H 或 C1-4 烷基）；R³ 是 (i) CON(R⁷)(R⁸)、(ii) CON(R𠞙)-CH(R⁷)(R⁸) 或 (iii) (其中 R⁷ 和 R⁸ 是 (1) H，(2) 苯基，(3) C7-10 苯基烷基，(4) 被 1 或 2 个 C1-4 烷基、卤素或 R¹-COOR¹² 取代的苯基或 C7-10 苯基烷基（其中 R¹ 是键、C1-8 亚烷基、C2-8 亚烯基、C2-8 亚炔基）；R¹²为H、C1-4烷基、C7-10苯基烷基、苯基、烯丙基、丙炔基），(5) C1-10烷基，(6) 具有 1 至 3 个双键的 C2-10 烯基，(7) 具有 1 或 2 个三键的 C2-10 烷基，(8) R11a-COXR¹²（其中 R11a 为 (a) 键，(b) C1-8 亚烷基，(c) 主链中 1 或 2 个碳原子被硫取代的 C2-8 亚烷基、(d) C2-8 烯，(e) C4-8 烯，其中主链中 1 或 2 个碳原子被硫取代，或硫和苯， (f) C2-8 烯，(g) C4-8 烯，其中主链中 1 或 2 个碳原子被硫取代，或硫和苯；X是-O-或-NH-)，(9)被含有一个N原子的7-14个成员的双环或三环杂环取代的C1-4烷基，(10)C3-7环烷基；）R𠞙 是 (1) H，(2) C1-8 烷基，(3) C7-10 苯基，(4) 具有 1 至 3 个双键的 C2-10 烯基，(5) 具有 1 或 2 个三键的 C2-10 烷基，(6) R¹¹-COOR¹²，(7) C3-7 环烷基；R¹⁰是 H、C7-10 苯基烷基或 COOR¹³（其中 R¹³ 是 H、C1-4 烷基或 C7-10 苯基烷基）；但 (i) R⁷ 和 R⁸ 不能同时代表氢，以及 (ii) 当 R⁷、R⁸ 和 R⁹ 中至少有一个基团代表含叔丁酯的基团时，其他基团不能代表含羧基的基团；或其酸加成盐，对聚乳酸₂和各种蛋白酶如胰蛋白酶、凝血酶、凝血酶、胰凝乳蛋白酶，尤其是胰蛋白酶具有抑制活性，可用于预防和/或治疗各种炎症性疾病、过敏性疾病、弥散性血管内凝血、胰腺炎、胰腺炎严重程度和多器官功能衰竭。
• THERAPEUTIC AGENT FOR DIABETES COMPRISING PROTEASE-INHIBITING COMPOUND
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1815865A1

  公开（公告）日：2007-08-08

  The problem of the present invention is to provide a preventive and/or therapeutic agent for diabetes and/or complications of diabetes based on the novel mode of action. The protease-inhibiting compound according to the present invention is a compound represented by the general formula (I) [wherein all the symbols have the same meanings as described in the specification], its salt or solvate, or a prodrug thereof, is useful as a preventive and/or therapeutic agent for diabetes and/or complications of diabetes.

  本发明的问题是提供一种基于新作用模式的糖尿病和/或糖尿病并发症的预防和/或治疗剂。 根据本发明的蛋白酶抑制化合物是由通式（I）代表的化合物 [其中所有符号的含义与说明书所述相同]的化合物、其盐或溶液或其原药，可用作糖尿病和/或糖尿病并发症的预防和/或治疗剂。
• Therapeutic Agent for Diabetes Comprising Protease-Inhibiting Compound
  申请人：Sakai Yoshiki

  公开号：US20080009537A1

  公开（公告）日：2008-01-10

  The problem of the present invention is to provide a preventive and/or therapeutic agent for diabetes and/or complications of diabetes based on the novel mode of action. The protease-inhibiting compound according to the present invention is a compound represented by the general formula (I) [wherein all the symbols have the same meanings as described in the specification], its salt or solvate, or a prodrug thereof, is useful as a preventive and/or therapeutic agent for diabetes and/or complications of diabetes.
• US5432178A
  申请人：——

  公开号：US5432178A

  公开（公告）日：1995-07-11
• US5614555A
  申请人：——

  公开号：US5614555A

  公开（公告）日：1997-03-25