methyl 1-methyl-1H-indole-3-carboxamidate hydrochloride | 125818-09-9

• 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: methyl 1-methyl-1H-indole-3-carboxamidate hydrochloride
• 英文别名: Methyl (1-Methylindol-3-yl)imidate Hydrochloride；Methyl 1-methylindole-3-carboximidate;hydrochloride
• CAS: 125818-09-9
• 化学式: C₁₁H₁₂N₂O*ClH
• 分子量: 224.69
• InChiKey: BNOUKBRJVPLBQS-UHFFFAOYSA-N

物化性质

• 熔点：
  156-158 °C(Solv: methanol (67-56-1); ethyl ether (60-29-7))

计算性质

• 辛醇/水分配系数(LogP)：
  2.57
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  38
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl 1-methyl-1H-indole-3-carboxamidate hydrochloride 在 劳森试剂 、 氨 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 24.67h， 生成 3-<2-(1-methyl-1H-indol-3-yl)-1,3-thiazol-4-yl>pyridine hydrobromide
  参考文献：
  名称：

  Novel 5-HT3 antagonists. Indole oxadiazoles

  摘要：

  The synthesis and biochemical evaluation of a series of indole oxadiazole 5-HT3 antagonists are described. The key pharmacophoric elements have been defined as a basic nitrogen, a linking group capable of H-bonding interactions, and an aromatic moiety. The steric limitations of the aromatic binding site have been determined by substitution about the indole ring. Variation of the heterocyclic linking group has shown that while two hydrogen-bonding interactions are possible, only one is essential for high affinity. The environment of the basic nitrogen has been investigated and shown to be optimal when constrained within an azabicyclic system. These results have been incorporated into a proposed binding model for the 5-HT3 antagonist binding site, in which the optimum distance between the aromatic binding site and the basic amine is 8.4-8.9 angstrom and the steric limitations are defined by van der Waals difference mapping.

  DOI：

  10.1021/jm00105a021
• 作为产物：
  描述：

  1-甲基吲哚-3-甲醛 在 盐酸 、 磷酸二氢铵 、 溶剂黄146 作用下， 以 various solvent(s) 为溶剂， 反应 36.0h， 生成 methyl 1-methyl-1H-indole-3-carboxamidate hydrochloride
  参考文献：
  名称：

  Novel 5-HT3 antagonists: indol-3-ylspiro(azabicycloalkane-3,5'(4'H)oxazoles)

  摘要：

  The synthesis and biochemical evaluation of a series of spirofused indole oxazoline 5-HT3 antagonists is described in which the oxazoline ring acts as a bioisosteric replacement for esters and amides. The effect of substitution about the indole ring has shown the steric limitations of the aromatic binding site. Incorporation of a variety of azabicyclic systems within the rigid spirofused framework has allowed the definition of a binding model which incorporates a number of known antagonists and agonists. In this model steric constraints limit substitution around the indole ring although there is some bulk tolerance at the 1- and 2-positions. The importance of constraining the basic nitrogen within an azabicyclic system is underlined by comparison with the monocyclic piperidine. The highest affinity was observed for those compounds in which the basic nitrogen occupies a bridgehead position, the most potent analogue in this group being the azabicyclic [3.3.1] system (pIC50 = 8.95), suggesting lipophilic interactions may play a role in increasing affinity. A suggested model for agonist binding is included in which the basic nitrogens are superimposed and the 5-hydroxyl group of 5-HT is superimposed on the H-bond-accepting atom of the heterocyclic linking group.

  DOI：

  10.1021/jm00084a007

文献信息

• Synthesis of indole oxazolines, potent 5-HT3 antagonists
  作者：Christopher J Swain、Clare Kueen、Raymond Baker

  DOI：10.1016/s0040-4039(00)97385-4

  日期：1990.1
• Swain, Christopher J.; Kneen, Clare; Herbert, Richard, Journal of the Chemical Society. Perkin transactions I, 1990, # 11, p. 3183 - 3186
  作者：Swain, Christopher J.、Kneen, Clare、Herbert, Richard、Baker, Raymond

  DOI：——

  日期：——
• KARAKHANOV, R. A.;KELAREV, V. I.;KOKOSOVA, A. S.;NASYROV, I. M.;KUSHETZOV+, PROC. 5TH CONF. APPL. CHEM. UNIT. OPER. AND PROCESS., BALATONFURED, 3-7 S+
  作者：KARAKHANOV, R. A.、KELAREV, V. I.、KOKOSOVA, A. S.、NASYROV, I. M.、KUSHETZOV+

  DOI：——

  日期：——
• BAKER, RAYMOND;SAUNDERA, JOHN;SWAIN, CHRISTOPHER
  作者：BAKER, RAYMOND、SAUNDERA, JOHN、SWAIN, CHRISTOPHER

  DOI：——

  日期：——
• SWAIN, CHRISTOPHER J.;KNEEN, CLARE;BAKER, RAYMOND, TETRAHEDRON LETT., 31,(1990) N7, C. 2445-2448
  作者：SWAIN, CHRISTOPHER J.、KNEEN, CLARE、BAKER, RAYMOND

  DOI：——

  日期：——