2-(2-chloroethyl)-2H-naphth<1,8-cd>isothiazole 1,1-dioxide | 127625-84-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(2-chloroethyl)-2H-naphth<1,8-cd>isothiazole 1,1-dioxide
• 英文别名: 2-(2-chloroethyl)naphtho[1,8-cd]isothiazole 1,1-dioxide；2-(2-chloroethyl)-2H-naphth(1,8-cd)isothiazole 1,1-dioxide；3-(2-chloroethyl)-2λ6-thia-3-azatricyclo[6.3.1.04,12]dodeca-1(11),4,6,8(12),9-pentaene 2,2-dioxide
• CAS: 127625-84-7
• 化学式: C₁₂H₁₀ClNO₂S
• 分子量: 267.736
• InChiKey: CFKZJBWBVXVDOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(1-indenylmethyl)piperidine 、 2-(2-chloroethyl)-2H-naphth<1,8-cd>isothiazole 1,1-dioxide 在 碳酸氢钠 、 草酸 作用下， 以 四氢呋喃 、 N-甲基乙酰胺 、 丙酮 为溶剂， 生成 2-{2-[4-(1-Indenylmethyl)piperidino]ethyl}naphtho[1,8-cd]isothiazole 1,1-dioxide
  参考文献：
  名称：

  Heterocyclic derivatives, their preparation and medicinal products

  摘要：

  揭示了具有以下结构的化合物：R.sub.1--(CH.sub.2).sub.n--Het，其中R.sub.1代表以下结构的残基##STR1##X代表氢原子或烷基基团，Y代表氢原子或烷基或烷氧基团，Z代表烷基基团，n等于2或3，Het代表取代的哌啶基（在4位取代有1-茚基亚甲基、1-茚基或1-茚基基团或具有链--(CH.sub.2).sub.m--R.sub.2或.dbd.CH--R.sub.2)，取代的1,2,3,6-四氢-1-吡啶基（在4位取代有链--(CH.sub.2).sub.m--R.sub.2），m等于1或2，R.sub.2代表可选取代的2-或3-吲哚基团，1-或2-茚基、1-或2-茚基、可选取代的1,2,3,4-四氢-5H-吡啶并[4,3-b]吲哚-2-基团、1,2,3,4-四氢-3-喹啉基团、可选取代的1,2,3,4-四氢-2-萘基团或1-吲哚基团，它们的制备以及含有它们的药物产品。

  公开号：

  US05114949A1
• 作为产物：
  描述：

  1,8-萘内酰亚胺 、 1-溴-2-氯乙烷 以 N-甲基乙酰胺 、 环己烷 、 乙酸乙酯 、 paraffin 为溶剂， 生成 2-(2-chloroethyl)-2H-naphth<1,8-cd>isothiazole 1,1-dioxide
  参考文献：
  名称：

  Heterocyclic derivatives, their preparation and medicinal products

  摘要：

  揭示了具有以下结构的化合物：R.sub.1--(CH.sub.2).sub.n--Het，其中R.sub.1代表以下结构的残基##STR1##X代表氢原子或烷基基团，Y代表氢原子或烷基或烷氧基团，Z代表烷基基团，n等于2或3，Het代表取代的哌啶基（在4位取代有1-茚基亚甲基、1-茚基或1-茚基基团或具有链--(CH.sub.2).sub.m--R.sub.2或.dbd.CH--R.sub.2)，取代的1,2,3,6-四氢-1-吡啶基（在4位取代有链--(CH.sub.2).sub.m--R.sub.2），m等于1或2，R.sub.2代表可选取代的2-或3-吲哚基团，1-或2-茚基、1-或2-茚基、可选取代的1,2,3,4-四氢-5H-吡啶并[4,3-b]吲哚-2-基团、1,2,3,4-四氢-3-喹啉基团、可选取代的1,2,3,4-四氢-2-萘基团或1-吲哚基团，它们的制备以及含有它们的药物产品。

  公开号：

  US05114949A1

文献信息

• New indole derivatives as potent and selective serotonin uptake inhibitors
  作者：Jean Luc Malleron、Claude Gueremy、Serge Mignani、Jean Francois Peyronel、Alain Truchon、Jean Charles Blanchard、Adam Doble、Pierre Laduron、Odile Piot

  DOI：10.1021/jm00061a010

  日期：1993.4

  series of new indole derivatives (2-28) has been prepared in the search for novel 5-HT uptake inhibitors. These compounds were obtained by the condensation of N-(chloroalkyl) naphthalenesultam derivatives with the appropriate amine in presence of a base, at reflux of DMF or THF. The yields were moderate (12-56%), except for the piperazine derivative 20 (85%). The affinity of the compounds for uptake site

  为了寻找新的5-HT摄取抑制剂，已经制备了一系列新的吲哚衍生物（2-28）。在DMF或THF的回流下，在碱的存在下，通过将N-（氯烷基）萘磺酰胺衍生物与适当的胺缩合获得这些化合物。除了哌嗪衍生物20（85％）以外，产率中等（12-56％）。测量了化合物对摄取位点和5-HT 2，α1和D 2受体的亲和力。通过5-HTP诱导症状的增强作用在体内研究了某些化合物。最有效和选择性最大的化合物（摄取的5-HT2与α1，D2位点相比）含有3-[（（4-哌啶基）甲基]吲哚部分。5-氟-3-[（4-哌啶基）甲基]吲哚本身（化合物1）对摄取位点显示出高亲和力，但缺乏体内活性。该化合物的N-甲基化消除了亲和力。相比之下，通过连接至萘磺胺或相关杂环的双碳链进行的N取代导致化合物对摄取位点表现出高亲和力。其中之一是1- [2- [4-（（5-氟-1H-吲哚-3-基）甲基-1-哌啶基]乙基] -5,6-二氢-1H，4H-1
• Derivatives of (AZA)naphthalenesultam, their preparation and
  申请人：Rhone-Poulenc Sante

  公开号：US05021420A1

  公开（公告）日：1991-06-04

  This invention relates to a compound ##STR1## in which R.sub.1 represents a 1,2,3,6-tetrahydro-1-pyridyl radical substituted in the 4-position by (a) a phenyl radical, (b) a phenyl radical substituted by a halogen atom or an alkyl, hydroxy or alkoxy radical, (c) a 3-indolyl radical, (d) a 3-indolyl radical substituted on the nitrogen atom by an alkyl or alkylcarbonyl radical and/or in the 5-position by a halogen atom or (e) a 3-(5-hydroxyindolyl) radical. a 1-piperazinyl radical substituted in the 4-position by (a) a phenyl radical, (b) a phenyl radical substituted by an alkoxy, alkyl, hydroxy, nitro or amino radical or a halogen atom, (c) a 1,2-benzisothiazol-3-yl radical, (d) a 1,2-benzisoxazol-3-yl radical or (e) a 2-pyridyl radical. a piperidino radical substituted in the 4-position by (a) a phenyl radical, (b) a phenyl radical substituted by a halogen atom or a hydroxy, alkyl or alkoxy radical, (c) two phenyl radicals, (d) a bis(4-fluorophenyl)methylene radical, (e) a 4-fluorobenzoyl radical, (f) a 2-oxo-1-benzimidazolinyl radical, (g) a 2-oxo-1-benzimidazolinyl radical substituted in the 3-position by an alkylcarbonyl or benzoyl radical, (b) a hydroxy radical and a phenyl radical optionally substituted with an alkyl, alkoxy or hydroxy radical or a halogen atom, (i) a 3-indolyl radical, (j) a 3-indolyl radical substituted on the nitrogen atom by an alkyl or alkylcarbonyl radical and/or in the 5-position by a halogen atom or (k) a 3-(5-hydroxyindolyl) radical. either: R.sub.2 and R.sub.3, which are identical, represent a hydrogen or halogen atom and R.sub.4 represents a hydrogen atom or R.sub.2 and R.sub.4 represent a hydrogen atom and R.sub.3 represents a halogen atom or an acetylamino radical or R.sub.2 and R.sub.3 represent a hydrogen atom and R.sub.4 represents a halogen atom and R.sub.5 represents a --CH.dbd. group. or R.sub.2, R.sub.3 and R.sub.4 represent a hydrogen atom and R.sub.5 represents a nitrogen atom. R.sub.6 represents an alkylene chain containing 2 to 4 carbon atoms or a propylene chain substituted in the 1- or 3-position by an alkyl radical or in the 2-position by an alkyl, alkoxy, hydroxy, dialkylamino, piperidino, morpholino or thiomorpholino radical, with the reservation that when R.sub.6 represents a propylene radical substituted in the 2-position by a dialkylamino, piperidino, morpholino or thiomorpholino radical, R.sub.1 cannot be a radical containing a hydroxy radical, and their salts, are useful in therapy for their ability to block serotonin receptors.

  本发明涉及化合物##STR1## 其中R.sub.1代表1,2,3,6-四氢-1-吡啶基取代在4位上的基团，所述基团可以是(a)苯基基团，(b)被卤素原子或烷基、羟基或烷氧基取代的苯基基团，(c)3-吲哚基基团，(d)在氮原子上取代烷基或烷基羰基基团和/或在5位上取代卤素原子的3-吲哚基基团，或(e)3-(5-羟基吲哚基)基团；1-哌嗪基取代在4位上的基团，所述基团可以是(a)苯基基团，(b)被烷氧基、烷基、羟基、硝基或氨基基团或卤素原子取代的苯基基团，(c)1,2-苯并异噻唑-3-基基团，(d)1,2-苯并异恶唑-3-基基团或(e)2-吡啶基基团；取代在4位的哌啶基基团，所述基团可以是(a)苯基基团，(b)被卤素原子或羟基、烷基或烷氧基取代的苯基基团，(c)两个苯基基团，(d)双(4-氟苯基)亚甲基基团，(e)4-氟苯甲酰基基团，(f)2-氧代-1-苯并咪唑啉基团，(g)在3位上取代烷基羰基或苯甲酰基基团的2-氧代-1-苯并咪唑啉基团，(h)羟基基团和一个苯基基团，所述苯基基团可以选择取代烷基、烷氧基或羟基基团或卤素原子，(i)3-吲哚基基团，(j)在氮原子上取代烷基或烷基羰基基团和/或在5位上取代卤素原子的3-吲哚基基团，或(k)3-(5-羟基吲哚基)基团。R.sub.2和R.sub.3相同，分别代表氢原子或卤素原子，R.sub.4代表氢原子，或者R.sub.2和R.sub.4代表氢原子，R.sub.3代表卤素原子或乙酰氨基基团，或者R.sub.2和R.sub.3代表氢原子，R.sub.4代表卤素原子，R.sub.5代表--CH.dbd.基团，或者R.sub.2、R.sub.3和R.sub.4代表氢原子，R.sub.5代表氮原子。R.sub.6代表含有2到4个碳原子的烷基链或在1位或3位上取代烷基基团或在2位上取代烷基、烷氧基、羟基、二烷基氨基、哌啶基、吗啉基或硫代吗啉基的丙烯基链，但当R.sub.6代表在2位上取代二烷基氨基、哌啶基、吗啉基或硫代吗啉基的丙烯基链时，R.sub.1不能是含有羟基基团的基团。这些化合物及其盐在治疗中具有阻断血清素受体的能力。
• Derivatives of (AZA) naphthalensultam, their preparation and
  申请人：Rhone-Poulenc Sante

  公开号：US05036075A1

  公开（公告）日：1991-07-30

  This invention relates to a compound of the formula: ##STR1## in which R.sub.1 represents a 1,2,3,6-tetrahydro-1-pyridyl radical substituted in the 4-position. a 1-piperazinyl radical substituted in the 4-position. a piperidino radical substituted in the 4-position either: R.sub.2 and R.sub.3, which are identical, represent a hydrogen or halogen atom and R.sub.4 represents a hydrogen atom or R.sub.2 and R.sub.4 represent a hydrogen atom and R.sub.3 represents a halogen atom or an acetylamino radical or R.sub.2 and R.sub.3 represent a hydrogen atom and R.sub.4 represents a halogen atom and R.sub.5 represents a --CH.dbd. group. or R.sub.2, R.sub.3 and R.sub.4 represent a hydrogen atom and R.sub.5 represents a nitrogen atom. R.sub.6 represents an alkylene chain containing 2 to 4 carbon atoms or a propylene chain substituted in the 1- or 3-position by an alkyl radical or in the 2-position by an alkyl, alkoxy, hydroxy, dialkylamino, piperidino, morpholino or thiomorpholino radical, and their salts, are useful in therapy for their ability to block serotonin receptors.

  本发明涉及一种式为：##STR1##其中R.sub.1代表在4位取代的1,2,3,6-四氢-1-吡啶基基团，4位取代的1-哌嗪基基团或4位取代的哌啶基基团，其中：R.sub.2和R.sub.3相同，代表氢或卤素原子，R.sub.4代表氢原子，或R.sub.2和R.sub.4代表氢原子，R.sub.3代表卤素原子或乙酰氨基基团，或R.sub.2和R.sub.3代表氢原子，R.sub.4代表卤素原子，R.sub.5代表--CH.dbd.基团，或R.sub.2、R.sub.3和R.sub.4代表氢原子，R.sub.5代表氮原子。R.sub.6代表含有2至4个碳原子的烷基链或在1-或3-位被烷基基团取代的丙烯基链，或在2-位被烷基、烷氧基、羟基、二烷基氨基基团、哌啶基、吗啉基或硫代吗啉基取代的丙烯基链，以及它们的盐，用于治疗因其阻断5-羟色胺受体的能力而具有的功效。
• Naphthosultam derivatives: a new class of potent and selective 5-HT2 antagonists
  作者：Jean Luc Malleron、Marie Therese Comte、Claude Gueremy、Jean Francis Peyronel、Alain Truchon、Jean Charles Blanchard、Adam Doble、Odile Piot、Jean Luc Zundel

  DOI：10.1021/jm00112a025

  日期：1991.8

  A series of 2-(aminoalkyl)naphth[1,8-cd]isothiazole 1,1-dioxides was synthesized and examined in various receptor binding tests. Most compounds demonstrated high affinity for the 5-HT2 receptor with moderate to high selectivity. A member of this series, compound 24 (RP 62203), displays high 5-HT2 receptor affinity (K(i) = 0.26 nM), which is respectively more than 100 and 1000 times higher than its affinity for alpha-1 (K(i) = 38 nM) and D2 (K(i) > 1000 nM) receptors. This compound is a potent orally effective and long lasting 5-HT2 antagonist in the mescaline-induced head-twitches test in mice and rats.
• COMTE, MARIE-THERESE;MALLERON, JEAN-LUC;PEYRONEL, JEAN-FRANCOIS;TRUCHON, +
  作者：COMTE, MARIE-THERESE、MALLERON, JEAN-LUC、PEYRONEL, JEAN-FRANCOIS、TRUCHON, +

  DOI：——

  日期：——