4-<<6-(2-cyclopentylacetamido)-2,3-dihydrobenz-1,4-oxazin-4-yl>methyl>-3-methoxybenzoic acid | 107786-70-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-<<6-(2-cyclopentylacetamido)-2,3-dihydrobenz-1,4-oxazin-4-yl>methyl>-3-methoxybenzoic acid
• 英文别名: 4-[6-(2-Cyclopentylacetamido)-2,3-dihydrobenz-1,4-oxazin-4-ylmethyl]-3-methoxybenzoic acid；4-[[6-[(2-Cyclopentylacetyl)amino]-2,3-dihydro-1,4-benzoxazin-4-yl]methyl]-3-methoxybenzoic acid
• CAS: 107786-70-9
• 化学式: C₂₄H₂₈N₂O₅
• 分子量: 424.497
• InChiKey: FIABUTJDKBDPKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  邻氯苯磺酰胺 、 4-<<6-(2-cyclopentylacetamido)-2,3-dihydrobenz-1,4-oxazin-4-yl>methyl>-3-methoxybenzoic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以45%的产率得到N-{4-[4-(2-Chloro-benzenesulfonylaminocarbonyl)-2-methoxy-benzyl]-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl}-2-cyclopentyl-acetamide
  参考文献：
  名称：

  Synthesis and in vitro LTD4 antagonist activity of bicyclic and monocyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides

  摘要：

  The dissociation constants (KB) at the LTD4 receptor on guinea pig trachea of a series of monocyclic and bicyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides have been measured. The KB was found to be remarkably tolerant of changes in the electronic constitution and lipophilicity of the bicyclic ring system (template). Thus, N-[4[[6-[[(cyclopentyloxy)carbonyl]amino]benzimidazol-1- yl]methyl]-3-methoxybenzoyl]benzenesulfonamide (11a) and N-[4-[[5-[[(cyclopentyloxy)carbonyl]amino]benzo[b]thien-3- yl]methyl]-3-methoxybenzoyl]benzene-sulfonamide (25a) had closely similar affinities (pKB, 9.20 and 9.31, respectively; LTE4 as agonist). It has been shown that the hetero-ring of the template need not be aromatic in order to achieve high affinity, since indoline 31 and 2,3-dihydrobenz-1,4-oxazines 37a-c had pKBs greater than 9. Further, it has been shown that an o-aminophenone (see 42 and Figure 3) can function as a template; the template in 42 [see iii] is bicyclic by virtue of the presence of an intramolecular hydrogen bond. In contrast, when the template is a phenyl ring (48), receptor affinity is markedly reduced. These findings support the notion that central bicyclic ring system in this family of peptidoleukotriene antagonists is a molecular feature which helps to preorganize the acylamino and acidic chains and thereby facilitate the molecular recognition event.

  DOI：

  10.1021/jm00171a043
• 作为产物：
  描述：

  4-溴甲基-3-甲氧基苯甲酸甲酯 在 palladium on activated charcoal 4-二甲氨基吡啶 、 lithium hydroxide 、 氢气 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium iodide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 丙酮 为溶剂， 反应 104.0h， 生成 4-<<6-(2-cyclopentylacetamido)-2,3-dihydrobenz-1,4-oxazin-4-yl>methyl>-3-methoxybenzoic acid
  参考文献：
  名称：

  Synthesis and in vitro LTD4 antagonist activity of bicyclic and monocyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides

  摘要：

  The dissociation constants (KB) at the LTD4 receptor on guinea pig trachea of a series of monocyclic and bicyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides have been measured. The KB was found to be remarkably tolerant of changes in the electronic constitution and lipophilicity of the bicyclic ring system (template). Thus, N-[4[[6-[[(cyclopentyloxy)carbonyl]amino]benzimidazol-1- yl]methyl]-3-methoxybenzoyl]benzenesulfonamide (11a) and N-[4-[[5-[[(cyclopentyloxy)carbonyl]amino]benzo[b]thien-3- yl]methyl]-3-methoxybenzoyl]benzene-sulfonamide (25a) had closely similar affinities (pKB, 9.20 and 9.31, respectively; LTE4 as agonist). It has been shown that the hetero-ring of the template need not be aromatic in order to achieve high affinity, since indoline 31 and 2,3-dihydrobenz-1,4-oxazines 37a-c had pKBs greater than 9. Further, it has been shown that an o-aminophenone (see 42 and Figure 3) can function as a template; the template in 42 [see iii] is bicyclic by virtue of the presence of an intramolecular hydrogen bond. In contrast, when the template is a phenyl ring (48), receptor affinity is markedly reduced. These findings support the notion that central bicyclic ring system in this family of peptidoleukotriene antagonists is a molecular feature which helps to preorganize the acylamino and acidic chains and thereby facilitate the molecular recognition event.

  DOI：

  10.1021/jm00171a043

文献信息

• Heterocyclic amide derivatives
  申请人：ICI AMERICAS INC.

  公开号：EP0199543B1

  公开（公告）日：1991-12-04
• MATASSA, VICTOR G.;BROWN, FREDERICK J.;BERNSTEIN, PETER R.;SHAPIRO, HOWAR+, J. MED. CHEM., 33,(1990) N, C. 2621-2629
  作者：MATASSA, VICTOR G.、BROWN, FREDERICK J.、BERNSTEIN, PETER R.、SHAPIRO, HOWAR+

  DOI：——

  日期：——
• US4859692A
  申请人：——

  公开号：US4859692A

  公开（公告）日：1989-08-22
• US5030643A
  申请人：——

  公开号：US5030643A

  公开（公告）日：1991-07-09
• US5179112A
  申请人：——

  公开号：US5179112A

  公开（公告）日：1993-01-12