(3Z)-3-(3,4-dihydro-2H-quinolin-1-ylimino)cyclohexan-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (3Z)-3-(3,4-dihydro-2H-quinolin-1-ylimino)cyclohexan-1-one
• 化学式: C₁₅H₁₈N₂O
• 分子量: 242.321
• InChiKey: MXQNTTFANZXYBY-SSZFMOIBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3Z)-3-(3,4-dihydro-2H-quinolin-1-ylimino)cyclohexan-1-one 以60的产率得到5,6,9,10-tetrahydro-4H-pyrido[3,2,1-jk]carbazol-11(8H)-one
  参考文献：
  名称：

  Process for the preparation of enantiomerically pure imidazolyl compounds

  摘要：

  本发明涉及一种制备对映纯的咪唑基化合物的方法，其通式为：其中：n为0或1；m为1或2；R1为氢、甲基或乙基；C*表示手性中心；以及其药学上可接受的酸加成盐。该方法包括：a)将光学活性形式的羧酸加入到上述化合物I的外消旋混合物的溶液中，然后从富含一种对映体的化合物I的晶体酸加成盐中分离出来，从富含另一种对映体的母液中分离出来；b)当富含不希望的对映体的晶体酸加成盐时，通过将母液中的对映体混合物与所述光学活性羧酸分离开来，然后将获得的化合物I的异构体混合物的溶液中加入所述羧酸的外消旋混合物，然后从富含所需对映体的化合物I的晶体酸加成盐中分离出来；c)可选地，将产物重结晶，直到获得所需的对映纯度；然后d)将所需对映体的酸加成盐转化为所需的对映纯咪唑基化合物I或其药学上可接受的酸加成盐，其特征在于使用丙氨酸作为所述羧酸。本发明还涉及一种消旋化和该式I化合物和D-丙氨酸的新酸加成盐的方法。

  公开号：

  EP0768309A1
• 作为产物：
  描述：

  1,2,3,4-四氢喹啉 在 lithium aluminium tetrahydride 、 硫酸 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (3Z)-3-(3,4-dihydro-2H-quinolin-1-ylimino)cyclohexan-1-one
  参考文献：
  名称：

  Development of high-affinity 5-HT3 receptor antagonists. Structure-affinity relationships of novel 1,7-annulated indole derivatives. 1

  摘要：

  On the basis of the structures of ondansetron and GR 65,630, its ring-opened C-linked methylimidazole analogue, novel 1,7-annelated indole derivatives were synthesized as potential 5-HT3 antagonists. Receptor binding studies show that all compounds display a high affinity for the 5-HT3 receptors. In both series annelation results in compounds being 7 and 4 times more potent than the references ondansetron and GR 65,630, respectively. Similar to ondansetron, the 1,7-annelated indoles show little stereoselectivity. The (-)-isomers are only slightly more potent than the (+)-isomers. The receptor binding profile of l-10-[(2-methyl-1H-imidazol-1-yl)methyl]-5,6,8,9,10,11-hexahydro-4H-pyrido[3,2,1-jk]carbazol-11-one hydrochloride (24b) (INN cilansetron) shows that the compound displays, besides a high affinity for 5-HT3 receptors (K(i) = 0. 19 nM), a weak affinity for sigma-receptors (K(i) = 340 nM), muscarine M1 receptors (K(i) = 910 nM), and 5-HT4 receptors (K(i_ = 960 nM) and no affinity (K(i) greater-than-or-equal-to 5000 nM) for all the other receptor types tested (n = 37). The new compounds fit the proposed necessary chemical template for binding: a heteroaromatic ring system, a coplanar carbonyl group, and a nitrogen center at well-defined distances. The enhanced potency of the annelated 1,7-indole derivatives indicates that the extra ring provides a favorable hydrophobic area for interaction with the 5-HT3 receptor site. In vivo cilansetron is more potent and induces less central side effects than ondansetron. At present cilansetron is in clinical trials.

  DOI：

  10.1021/jm00075a026

文献信息

• New anellated indole derivatives
  申请人：Duphar International Research B.V.

  公开号：US04939136A1

  公开（公告）日：1990-07-03

  The invention relates to new anellated indole derivatives of general formula 2, ##STR1## wherein p1 R.sub.0 is alkyl or alkoxy having 1-4 C-atoms, phenylalkoxy having 1-3 C-atoms in the alkoxy group, hydroxy, halogen, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, or a group R.sub.7 S(O).sub.p, wherein R.sub.7 is alkyl having 1-4 C-atoms and p has the value 0, 1 or 2, or R.sub.0 is a group R.sub.8 R.sub.9 N, R.sub.8 R.sub.9 N--CO--CH.sub.2 -- or R.sub.8 R.sub.9 --N--CO wherein R.sub.8 and R.sub.9 are hydrogen or alkyl having 1-4 C-atoms or R.sub.8 R.sub.9 N forms a saturated 5- or 6-membered ring and n has the value 0, 1 or 2, Z together with the carbon atom and nitrogen atom to which Z is bound and the intermediate carbon atom, forms a heterocyclic group consisting of 5-8 ring atoms, in which, in addition to the nitrogen atom already present, a --CO--group or a second hetero atom from the group N, O, S, S-O or SO.sub.2 may be present, which ring may be substituted with 1-3 alkyl groups having 1-4 C-atoms, a phenyl group or a spiroalkyl group (C.sub.2 -C.sub.5), or which ring may be anellated with a saturated or non-saturated carbocyclic or heterocyclic ring which consists of 5- or 6-ring atoms and which may be substituted with halogen, alkyl or alkoxy having 1-4 C-atoms, and m has the values 1-5, one of the groups R.sub.2, R.sub.3 and R.sub.4 is hydrogen, alkyl having 1-6 C-atoms, cycloalkyl having 3-7 C-atoms, alkenyl having 2-6 C-atoms or phenylalkyl having 1-3 C-atoms in the alkyl group, and the two other groups independently of each other are hydrogen or alkyl having 1-6 C-atoms, and the pharmaceutically acceptable acid addition salts thereof. These compounds are strong and selective antagonists of "neuronal" 5-hydroxytryptamine (5-HT) receptors, and have a considerably longer-lasting effect and lower toxicity in comparison with related known compounds.

  本发明涉及一种新的环化吲哚衍生物，其通式为2，其中p1R0是具有1-4个C原子的烷基或烷氧基，具有1-3个C原子的苯基烷氧基，羟基，卤素，三氟甲基，三氟甲氧基，三氟甲基硫基或R7S（O）p基团，其中R7是具有1-4个C原子的烷基，p的值为0、1或2，或R0是R8R9N基团，R8R9N-CO-CH2-基团或R8R9-N-CO基团，其中R8和R9是氢或具有1-4个C原子的烷基，或R8R9N形成饱和的5-或6-成员环且n的值为0、1或2，Z与其所结合的碳原子和氮原子以及中间的碳原子一起形成由5-8个环原子组成的杂环基团，其中除了已经存在的氮原子外，还可以存在一个-CO-基团或来自N、O、S、S-O或SO2的第二个杂原子，该环可以用具有1-4个C原子的1-3个烷基基团，苯基或螺环烷基（C2-C5）取代，或者该环可以与由5-或6个环原子组成的饱和或非饱和碳环或杂环环并联，该环可以用卤素、具有1-4个C原子的烷基或烷氧基取代，m的值为1-5，R2、R3和R4中的一个是氢，具有1-6个C原子的烷基，具有3-7个C原子的环烷基，具有2-6个C原子的烯基或具有1-3个C原子的苯基烷基，而另外两个基团独立地是氢或具有1-6个C原子的烷基，并且其药学上可接受的酸盐。这些化合物是“神经”5-羟色胺（5-HT）受体的强效和选择性拮抗剂，并且与相关已知化合物相比，具有更长的持续作用时间和更低的毒性。
• Drugs Fut. 1999, 24, 475
  作者：

  DOI：——

  日期：——
• J. Med. Chem. 1993, 36, 3693-3699
  作者：

  DOI：——

  日期：——