5,6,9,10-tetrahydro-4H-pyrido[3,2,1-jk]carbazol-11(8H)-one | 120635-49-6

• 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: 5,6,9,10-tetrahydro-4H-pyrido[3,2,1-jk]carbazol-11(8H)-one
• 英文别名: 1-azatetracyclo[7.6.1.05,16.010,15]hexadeca-5(16),6,8,10(15)-tetraen-11-one
• CAS: 120635-49-6
• 化学式: C₁₅H₁₅NO
• 分子量: 225.29
• InChiKey: PTPNWPSSNHDCFX-UHFFFAOYSA-N

物化性质

• 沸点：
  449.3±14.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5,6,9,10-tetrahydro-4H-pyrido[3,2,1-jk]carbazol-11(8H)-one 在 盐酸羟胺 、 sodium acetate 作用下， 以 乙醇 、 水 为溶剂， 以95%的产率得到5,6,9,10-tetrahydro-4H-pyrido[3,2,1-jk]carbazol-11(8H)-one oxime
  参考文献：
  名称：

  Substituted heterocycle fused gamma-carbolines

  摘要：

  本发明涉及通过给予由结构式（I）1所代表的化合物或其药学上可接受的盐形式来治疗成瘾行为和睡眠障碍的方法，其中R1、R5、R6a、R6b、R7、R8、R9、X、b、k、m和n以及虚线在此处描述。本发明治疗方法中使用的化合物是5-羟色胺激动剂和拮抗剂，对于控制或预防包括成瘾行为和睡眠障碍在内的中枢神经系统紊乱是有用的。

  公开号：

  US20040209864A1
• 作为产物：
  描述：

  1,2-环己二酮 在 甲酸 、 bis[dichloro(pentamethylcyclopentadienyl)iridium(III)] 、 三氟乙酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 对二甲苯 、 水 为溶剂， 反应 18.0h， 生成 5,6,9,10-tetrahydro-4H-pyrido[3,2,1-jk]carbazol-11(8H)-one
  参考文献：
  名称：

  Iridium/Acid Cocatalyzed Direct Access to Fused Indoles via Transfer Hydrogenative Annulation of Quinolines and 1,2-Diketones

  摘要：

  Herein, we present an unprecedented iridium/acid cocatalyzed construction of fused indoles via transfer hydrogenative annulation of nonactivated quinolines and 1,2-diketones. The products are assembled via initial reduction followed by selective coupling of 1,2-diketones with the N and C8 sites of the quinolyl skeleton. The developed synthetic method features operational simplicity, readily available feedstocks, applicability for streamline synthesis of functional molecules, high step and atom efficiency, and generation of water as the byproduct.

  DOI：

  10.1021/acs.orglett.0c00500

文献信息

• New annelated indole derivatives
  申请人：DUPHAR INTERNATIONAL RESEARCH B.V

  公开号：EP0375045A1

  公开（公告）日：1990-06-27

  The invention relates to a group of new annelated indole derivatives of the formula having an antagonistic activity on 5-HT receptors. The compounds can be used for the treatment of symptoms which are caused by excessive stimulation of said receptors in the gastrointestinal system, the central nervous system, the cardiovascular system, the respiratory system, and for alleviating or preventing withdrawal symptoms which are induced by abuse of drugs.

  本发明涉及一类新的稠合吲哚衍生物，具有对5-HT受体的拮抗活性。这些化合物可用于治疗由胃肠道系统、中枢神经系统、心血管系统、呼吸系统中所述受体过度刺激引起的症状，以及减轻或预防滥用药物引起的戒断症状。
• [EN] NOVEL PROCESS FOR THE PREPARATION OF IMIDAZOLYL COMPOUNDS<br/>[FR] PROCEDE DE PREPARATION DE COMPOSES IMIDAZOLYLE
  申请人：SOLVAY PHARM BV

  公开号：WO2004046116A1

  公开（公告）日：2004-06-03

  The present invention relates to a method for the preparation of an imidazolyl compound of the general formula (I), wherein: Ra and Rb each separately are (C1-C6)alkyl, (C1-C6)alkoxyalkyl, optionally substituted aryl or heteroaryl; or wherein Ra and Rb together form a further homocyclic or heterocyclic system comprising one or more rings; Ra’ and Rb’ each are hydrogen or together form a carbon-carbon double bond, said carbon-carbon double bond optionally being part of an aromatic system; Rc is hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C1,-C6)alkoxyalkyl or halogen; Rd is hydrogen or (C1-C4)aIkyl; Re is hydrogen or (C1-C4)aIkyl; m is 1 or 2; and R1, is hydrogen or (C1-C4)aIkyl; as well as its acid addition salt;characterized in that a compound of the general formula (II) is reacted with a compound of the formula (III), wherein: R is a hydrogen, a (C1-C4)alkyl group optionally substituted with a hydroxygroup or an optionally substituted aryl group, R', R', R'' and R'' each individually are a hydrogen or a (C1-C4)aIkyl group; followed by a reaction with a compound of the formula (IV), wherein R1, Rd and Re have the meanings defined above; and optionally followed by a reaction with a suitable acid. De method according to the present invention is especially useful for the preparation of ondansetron and cilansetron.

  本发明涉及一种制备通式（I）的咪唑基化合物的方法，其中：Ra和Rb各自分别为（C1-C6）烷基，（C1-C6）烷氧基烷基，可选择取代的芳基或杂环芳基；或者Ra和Rb一起形成进一步的同环或异环系统，包括一个或多个环；Ra'和Rb'各自为氢或一起形成碳-碳双键，所述碳-碳双键可选择地是芳香系统的一部分；Rc为氢，（C1-C6）烷基，（C1-C6）烷氧基，（C1-C6）烷氧基烷基或卤素；Rd为氢或（C1-C4）烷基；Re为氢或（C1-C4）烷基；m为1或2；R1为氢或（C1-C4）烷基；以及其酸盐；其特征在于通式（II）的化合物与通式（III）的化合物发生反应，其中：R为氢，（C1-C4）烷基，可选择地取代羟基或可选择取代的芳基的基团，R'、R''、R'''和R''''各自为氢或（C1-C4）烷基；随后与通式（IV）的化合物发生反应，其中R1、Rd和Re具有上述定义的含义；并可随后与适当的酸发生反应。根据本发明的方法特别适用于制备昂丹司特龙和西兰司特龙。
• 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。
• Process for the preparation of enantiomerically pure imidazolyl compounds
  申请人：DUPHAR INTERNATIONAL RESEARCH B.V

  公开号：EP0768309A1

  公开（公告）日：1997-04-16

  The invention relates to a method for the preparation of an enantiomerically pure imidazolyl compound of the general formula wherein: n is 0 or 1; m is 1 or 2; R1 is hydrogen, methyl or ethyl; and C* denotes a chiral centre; as well as its pharmaceutically acceptable acid addition salt; by a) adding a carboxylic acid in an optically active form to a solution of a racemic mixture of the above compound I, followed by separation of the crystallized acid addition salt of said mixture of enantiomers of compound I enriched in one enantiomer, from the mother liquor enriched in the other enantiomer b) when the crystallized acid addition salt is enriched in the undesired enantiomer, by then separating the mixture of enantiomers in the mother liquor from said optically active carboxylic acid, followed by addition of a racemic mixture of said carboxylic acid to a solution of the obtained mixture of isomers of I, and by separation of the crystallized acid addition salt of said mixture, enriched in the desired enantiomer, from the mother liquor, and (c) optionally recrystallizing the product until the desired enantiomeric purity is obtained, and by then (d) converting this acid-addition salt of the desired enantiomer to the desired enantiomerically pure imidazolyl compound of the general formula I or to its pharmaceutically acceptable acid addition salt,    characterized in that pyroglutamic acid is used as said carboxylic acid. The invention further relates to a method of racemisation and to a new acid addition salt of this formula I compound and D-pyroglutamic acid.

  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。
• [(Imidazol-4(and 5)-yl)methyl] tetracyclic ketones having 5-HT.sub.3
  申请人：Glaxo Group Limited

  公开号：US05045545A1

  公开（公告）日：1991-09-03

  The invention relates to tetracyclic ketones of the general formula (I) ##STR1## wherein n represents 1, 2 or 3; Im represents an imidazolyl group of the formula: ##STR2## wherein one of the groups represented by R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3 -7cycloalkyl, C.sub.3-6 alkenyl, phenyl or phenylC.sub.1-3 alkyl group, and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group; Y represents a group --(CH.sub.2)m--, where m represents 2, 3 or 4, or a group --X(CH.sub.2).sub.p --, where p represents 2 or 3, X represents an oxygen or a sulphur atom or a group NR.sup.4, where R.sup.4 is a C.sub.1-6 alkyl group, and X is attached to the benzene ring moiety of the molecule; and physiologically acceptable salts and solvates thereof. The compounds are potent and selective antagonists of the effect of 5-HT at 5-HT.sub.3 receptors and are useful, for example, in the treatment of psychotic disorders, anxiety, and nausea and vomiting.

  本发明涉及通式（I）的四环酮类化合物：##STR1## 其中，n代表1、2或3；Im代表式：##STR2## 其中，R1、R2和R3中的一个是氢原子或C1-6烷基、C3-7环烷基、C3-6烯基、苯基或苯基C1-3烷基；另外两个可以相同也可以不同，分别表示氢原子或C1-6烷基。Y代表基团--(CH2)m--，其中m代表2、3或4或者代表基团--X(CH2)p--，其中p代表2或3，X代表氧原子、硫原子或基团NR4，其中R4是C1-6烷基，且X连接到分子的苯环部分；以及其生理上可接受的盐和溶剂合物。这些化合物是5-HT3受体5-HT效应的有效和选择性拮抗剂，在精神疾病、焦虑、恶心和呕吐等治疗中有用。