1-methyl-7-methoxy-2-indolinethione | 131071-42-6

• 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-methyl-7-methoxy-2-indolinethione
• 英文别名: 7-methoxy-1-methyl-2-indolinethione；7-methoxy-1-methyl-3H-indole-2-thione
• CAS: 131071-42-6
• 化学式: C₁₀H₁₁NOS
• 分子量: 193.269
• InChiKey: LZUQPCCOZLXTBF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  44.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-methyl-7-methoxy-2-indolinethione 在 air 、 sodium hydride 作用下， 以 甲醇 为溶剂， 生成 2-[[3-(C-hydroxy-N-phenylcarbonimidoyl)-7-methoxy-1-methylindol-2-yl]disulfanyl]-7-methoxy-1-methyl-N-phenylindole-3-carboximidic acid
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 3. Structure-Activity Relationships for Inhibition of Protein Tyrosine Kinases by Nuclear-Substituted Derivatives of 2,2'-Dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamide)

  摘要：

  A series of indole-substituted 2,2'-dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamides) were prepared and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase. The compounds were synthesized by conversion of appropriate 1-methyloxindoles to 1-methyl-2-indolinethiones with P2S5 followed by subsequent reaction with NaH and phenyl isocyanate and oxidative dimerization of the resulting 2,3-dihydro-N-phenyl-2-thioxo-1H-indole-3-carboxamides. The parent compound and many of the substituted analogues were moderately potent inhibitors of both kinase enzymes, but no clear relationships were seen between substitution on the indole ring and inhibitory activity, While 4-substituted compounds were generally inactive, 5-substituted derivatives with electron-withdrawing groups showed inhibitory activity. However, none of the substituted compounds showed significantly better activity than the unsubstituted parent compound. There was generally a good correlation between activity against the EGFR and pp60(v-src) kinases, but several compounds did show some specificity (>20-fold) of inhibition; 5-Cl and 5-Br derivatives preferentially inhibited pp60(v-src), while the 5-CF3 compound preferentially inhibited EGFR. Selected compounds from the series were found to inhibit the growth of Swiss 3T3 fibroblasts with IC(50)s in the range 2-25 mu M, the most active being 4-substituted derivatives. The compounds inhibited bFGF-mediated protein tyrosine phosphorylation in intact cells more effectively than EGFR- or PDGF-mediated phosphorylation.

  DOI：

  10.1021/jm00039a016
• 作为产物：
  描述：

  7-Methoxy-N-methyl-oxindol 以78%的产率得到1-methyl-7-methoxy-2-indolinethione
  参考文献：
  名称：

  Novel tricyclic indole compound

  摘要：

  本发明涉及一般式为：##STR1## 的化合物，其中A、B、G、D可以相同或不同，分别表示氢原子或卤素原子、低级烷氧基或者选择性地带有一个或多个卤素原子的低级烷基；X表示氢原子、线性或支链低级烷基或者SO.sub.2 E基团，其中E表示线性或支链低级烷基或者选择性地带有一个线性或支链低级烷基取代的芳基基团；T表示氢原子或低级烷基；R.sub.3表示氢原子或线性或支链低级烷基或者选择性地带有一个或多个线性或支链低级烷基取代的芳基基团；n和m可以相同或不同，分别表示0或1；R.sub.1和R.sub.2可以相同或不同，分别表示氢原子或线性或支链低级烷基，或者选择性地，R.sup.1和R.sup.2与它们连接的氮原子一起形成饱和或不饱和的、单环或双环的含氮杂环系统，每个环都是5或6元环，可以选择性地包含来自氮、氧或硫的其他杂原子，并且可以选择性地带有一个或多个线性或支链低级烷基或烷氧基取代的芳基基团，或者带有一个或多个本身可以选择性地带有一个或多个低级烷基、低级烷氧基或三氟甲基基团或者选择性地带有一个或多个卤素原子的芳基基团，或者选择性地，R.sup.1表示一个基团##STR2## 其中R.sub.4、R.sub.5和R.sub.6可以相同或不同，分别表示氢原子或线性或支链低级烷基，或者选择性地，R.sub.4和R.sub.5一起形成(CH.sub.2).sub.p的桥，p在2到4之间，或选择性地，R.sub.1表示一个二苯并[a,d]环庚-5-基团，R.sub.2表示氢原子，必要时，它们的异构体以及它们与药学上可接受的酸形成的加合物。药物制品。

  公开号：

  US05030646A1

文献信息

• Novel tricyclic indole compound
  申请人：Adir et Compagnie

  公开号：US05030646A1

  公开（公告）日：1991-07-09

  The invention relates to compounds of general formula: ##STR1## in which A, B, G, D which may be identical or different, each denote a hydrogen atom or a halogen atom, a lower alkoxy group or alternatively a lower alkyl group optionally substituted with one or more halogen atoms, X denotes a hydrogen atom, a linear or branched lower alkyl group or a group SO.sub.2 E in which E denotes a linear or branched lower alkyl group or an aryl group optionally substituted with a linear or branched lower alkyl group, T denotes a hydrogen atom or a lower alkyl group, R.sub.3 denotes a hydrogen atom or a linear or branched lower alkyl group or an aryl group optionally substituted with one or more linear or branched lower alkyl groups, n and m, which may be identical or different, each denote 0 or 1, R.sub.1 and R.sub.2, which may be identical or different, each denote a hydrogen atom or a linear or branched lower alkyl group, or alternatively, R.sup.1 and R.sup.2 form, together with the nitrogen atom to which they are linked, a saturated or unsaturated, mono- or bicyclic nitrogenous heterocyclic system, each ring being 5- or 6-membered and optionally comprising one or two other hetero atoms selected from nitrogen, oxygen or sulfur, and optionally substituted with one or more linear or branched lower alkyl or alkoxy groups or with an aryl group which is itself optionally substituted with one or more lower alkyl, lower alkoxy or trifluoromethyl groups or alternatively one or more halogen atoms, or alternatively, R.sup.1 denotes a group ##STR2## in which R.sub.4, R.sub.5 and R.sub.6, which may be identical or different, each denote a hydrogen atom or a linear or branched lower alkyl group, or alternatively R.sub.4 forms with R.sub.5 a bridge (CH.sub.2).sub.p, p being between 2 and 4, or alternatively R.sub.1 denotes a dibenzo[a,d]cyclohept-5-yl group and R.sub.2 denotes a hydrogen atom, where appropriate, their isomers and also their addition salts with a pharmaceutically acceptable acid. Medicinal products.

  本发明涉及一般式为：##STR1## 的化合物，其中A、B、G、D可以相同或不同，分别表示氢原子或卤素原子、低级烷氧基或者选择性地带有一个或多个卤素原子的低级烷基；X表示氢原子、线性或支链低级烷基或者SO.sub.2 E基团，其中E表示线性或支链低级烷基或者选择性地带有一个线性或支链低级烷基取代的芳基基团；T表示氢原子或低级烷基；R.sub.3表示氢原子或线性或支链低级烷基或者选择性地带有一个或多个线性或支链低级烷基取代的芳基基团；n和m可以相同或不同，分别表示0或1；R.sub.1和R.sub.2可以相同或不同，分别表示氢原子或线性或支链低级烷基，或者选择性地，R.sup.1和R.sup.2与它们连接的氮原子一起形成饱和或不饱和的、单环或双环的含氮杂环系统，每个环都是5或6元环，可以选择性地包含来自氮、氧或硫的其他杂原子，并且可以选择性地带有一个或多个线性或支链低级烷基或烷氧基取代的芳基基团，或者带有一个或多个本身可以选择性地带有一个或多个低级烷基、低级烷氧基或三氟甲基基团或者选择性地带有一个或多个卤素原子的芳基基团，或者选择性地，R.sup.1表示一个基团##STR2## 其中R.sub.4、R.sub.5和R.sub.6可以相同或不同，分别表示氢原子或线性或支链低级烷基，或者选择性地，R.sub.4和R.sub.5一起形成(CH.sub.2).sub.p的桥，p在2到4之间，或选择性地，R.sub.1表示一个二苯并[a,d]环庚-5-基团，R.sub.2表示氢原子，必要时，它们的异构体以及它们与药学上可接受的酸形成的加合物。药物制品。
• Rewcastle Gordon W., Palmer Brian D., Dobrusin Ellen M., Fry David W., Kr+, J. Med. Chem, 37 (1994) N 13, S 2033-2042
  作者：Rewcastle Gordon W., Palmer Brian D., Dobrusin Ellen M., Fry David W., Kr+

  DOI：——

  日期：——
• 2-THIOINDOLES (SELENOINDOLES) AND RELATED DISULFIDES (SELENIDES) WHICH INHIBIT PROTEIN TYROSINE KINASES AND WHICH HAVE ANTITUMOR PROPERTIES
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0654024A1

  公开（公告）日：1995-05-24
• US5030646A
  申请人：——

  公开号：US5030646A

  公开（公告）日：1991-07-09
• US5464861A
  申请人：——

  公开号：US5464861A

  公开（公告）日：1995-11-07