1-{3-[1-(p-chlorobenzoyl-5-methoxy-2-methyl)-indolacetyl]}-imidazole | 78436-46-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-{3-[1-(p-chlorobenzoyl-5-methoxy-2-methyl)-indolacetyl]}-imidazole
• 英文别名: 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid imidazolide；1-(4-Chlorobenzoyl)-3-(2-(1H-imidazol-1-yl)-2-oxoethyl)-5-methoxy-2-methyl-1H-indole；2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-1-imidazol-1-ylethanone
• CAS: 78436-46-1
• 化学式: C₂₂H₁₈ClN₃O₃
• 分子量: 407.856
• InChiKey: FYEOZFNVLSIPGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  66.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-{3-[1-(p-chlorobenzoyl-5-methoxy-2-methyl)-indolacetyl]}-imidazole 在 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-N-[2-[2-(2-hydroxyethoxy)ethoxy]ethyl]acetamide
  参考文献：
  名称：

  Synthesis and stability of two indomethacin prodrugs

  摘要：

  The purpose of this study was to synthesize and study the in vitro enzymatic and non-enzymatic hydrolysis of indomethacin-TEG ester and amide prodrugs. It was found that the ester conjugate 10 was comparatively stable between pH 3 and 6 (half-life >90 h), with a half-life equal to 5.2 h in 80% buffered plasma. In contrast, the amide conjugate 12 appeared to be stable over the entire pH range studied with the only observed degradation being cleavage of the indolic N-4-chlorobenzoyl moiety. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.003
• 作为产物：
  描述：

  吲哚美辛 生成 1-{3-[1-(p-chlorobenzoyl-5-methoxy-2-methyl)-indolacetyl]}-imidazole
  参考文献：
  名称：

  FISNEROVA L.; RABEK V.; NEMECEK O., COLLECT. CZECH. CHEM. COMMUN., 1980, 45, NO 3, 901-905

  摘要：

  DOI：

文献信息

• Esters and amides containing the
  申请人：Dr. Karl Thomae GmbH

  公开号：US04362738A1

  公开（公告）日：1982-12-07

  Compounds of the formula ##STR1## wherein each X, which may be identical or different from the other X, is oxygen or imino; R.sub.1 is hydrogen, fluorine, chlorine or bromine; R.sub.2 and R.sub.3, which may be identical or different from each other, are each hydrogen; unsubstituted or mono-substituted alkyl of 1 to 6 carbon atoms, where the substituent is phenyl or dialkylamino with 1 to 3 carbon atoms in each alkyl moiety; pyridyl; or cycloalkyl of 5 to 7 carbon atoms; R.sub.2 and R.sub.3, together with each other and the nitrogen atoms to which they are attached, are pyrrolidino, piperidino, hexamethyleneimino, morpholino, N-aryl-piperazino or N-(alkyl of 1 to 3 carbon atoms)-piperazino; A is cycloalkylene of 5 to 7 carbon atoms; unsubstituted or substituted alkylene of 2 to 10 carbon atoms, where the substituents are one to two alkyls of 1 to 3 carbon atoms each, one to two carbalkoxys of 2 to 4 carbon atoms each, one to two phenyls, one to four hydroxyls, one halomethyl, one hydroxymethyl, one alkanoyloxy of 1 to 18 carbon atoms, one alkanoyloxymethyl of 1 to 18 carbon atoms in the alkanoyl moiety or one ##STR2## where R.sub.1, R.sub.2 and R.sub.3 have the meanings previously defined; or alkylene of 2 to 10 carbon atoms interrupted by oxygen, sulfur, sulfoxide, sulfonyl, phenyl, cyclohexyl, pyridyl, piperazino or unsubstituted or substituted imino, where the substituent on the imino group is alkyl of 1 to 6 carbon atoms, phenyl or phenylalkyl of 1 to 3 carbon atoms in the alkyl moiety; B is the acyl residue of an antiphlogistic carboxylic acid; and their non-toxic, pharmacologically acceptable acid addition salts. The compounds as well as their salts are useful as anti-inflammatories.

  公式##STR1##的化合物，其中每个X可以相同也可以不同于其他X，是氧或亚胺；R.sub.1是氢，氟，氯或溴；R.sub.2和R.sub.3，可以相同也可以相互不同，都是氢；未取代或单取代的1到6碳原子的烷基，其中取代基是苯基或1到3碳原子的二烷基氨基；吡啶基；或5到7碳原子的环烷基；R.sub.2和R.sub.3，与彼此以及它们所连接的氮原子一起，是吡咯烷基，哌啶基，己亚胺基，吗啉基，N-芳基哌嗪基或N-(1到3碳原子的烷基)哌嗪基；A是5到7碳原子的环烷基；未取代或取代的2到10碳原子的亚烷基，其中取代基是一到两个每个含有1到3碳原子的烷基，一到两个每个含有2到4碳原子的碳烷氧基，一到两个苯基，一到四个羟基，一个卤甲基，一个羟甲基，一个1到18碳原子的烷酰氧基，一个在烷酰基部分含有1到18碳原子的烷酰氧甲基或一个##STR2##其中R.sub.1，R.sub.2和R.sub.3具有先前定义的含义；或2到10碳原子的亚烷基，通过氧，硫，亚砜，磺酰基，苯基，环己基，吡啶基，哌嗪基或未取代或取代的亚胺基中断，其中亚胺基上的取代基是1到6碳原子的烷基，苯基或1到3碳原子的苯烷基；B是一种抗炎的羧酸的酰基残基；以及它们的非毒性，药理学上可接受的酸加成盐。这些化合物以及它们的盐可以用作抗炎药。
• Synthesis and Pharmacological Evaluation of Oligoethylene Ester Derivatives as Indomethacin Oral Prodrugs
  作者：Paolo De Caprariis、Francesco Palagiano、Franco Bonina、Lucia Montenegro、Michele D'Amico、Francesco Rossi

  DOI：10.1002/jps.2600831112

  日期：1994.11

  Five indomethacin oligoethylene ester derivatives (3-7) were synthesized and evaluated for their anti-inflammatory, analgesic, and ulcerogenic activity after oral administration. The molecular weight of the oligoethylene glycols used for synthesizing esters 3-7 ranged from 106 to 282. The chemical and enzymatic stabilities of esters 3-7 were evaluated in pH 7.4 and 2.0 buffers and in human plasma,

  合成了五种吲哚美辛低聚亚乙基酯衍生物（3-7），并在口服后评估了它们的抗炎，镇痛和促溃疡活性。用于合成酯3-7的低聚乙二醇的分子量范围为106至282。分别在pH 7.4和2.0缓冲液中以及在人血浆中评估了酯3-7的化学和酶稳定性。所有前药在pH 7.4磷酸盐缓冲液和pH 2.0缓冲液中均显示出良好的稳定性，并且易于被人血浆水解。酯3-7显示出抗炎活性，其确定为角叉菜胶诱导的水肿的抑制百分比，与消炎痛相似，尽管剂量更高。从扭曲的测试结果来看，我们观察到与消炎痛相比，所有前药均表现出更好或相似的镇痛活性。口服后，酯3-7对胃粘膜的刺激​​性明显比吲哚美辛低，而酯3-5虽然以比吲哚美辛更高的剂量给药，但未显示任何致溃疡活性。
• Fisnerova, Ludmila; Rabek, Vlastimil; Nemecek, Oldrich, Collection of Czechoslovak Chemical Communications, 1980, vol. 45, # 3, p. 901 - 905
  作者：Fisnerova, Ludmila、Rabek, Vlastimil、Nemecek, Oldrich

  DOI：——

  日期：——
• US4362738A
  申请人：——

  公开号：US4362738A

  公开（公告）日：1982-12-07
• Synthesis and stability of two indomethacin prodrugs
  作者：Shyamala Chandrasekaran、Abeer M. Al-Ghananeem、Robert M. Riggs、Peter A. Crooks

  DOI：10.1016/j.bmcl.2006.01.003

  日期：2006.4

  The purpose of this study was to synthesize and study the in vitro enzymatic and non-enzymatic hydrolysis of indomethacin-TEG ester and amide prodrugs. It was found that the ester conjugate 10 was comparatively stable between pH 3 and 6 (half-life >90 h), with a half-life equal to 5.2 h in 80% buffered plasma. In contrast, the amide conjugate 12 appeared to be stable over the entire pH range studied with the only observed degradation being cleavage of the indolic N-4-chlorobenzoyl moiety. (C) 2006 Elsevier Ltd. All rights reserved.