3-哌嗪-1-基-1,2-苯并噻唑1,1-二氧化物 | 131540-88-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: 3-哌嗪-1-基-1,2-苯并噻唑1,1-二氧化物
• 英文名称: 3-piperazin-1-yl-benzo[d]isothiazole 1,1-dioxide
• 英文别名: Benzisothiazole-piperazine sulfone；4-(1,1-dioxo-1,2-benzisothiazol-3-yl)-1-piperazine；3-(1-piperazinyl)-1,2-benzisothiazole 1,1-dioxide；1-(1,1-dioxo-1,2-benzisothiazol-3-yl)piperazine；3-Piperazin-1-yl-benzo[]isothiazole 1,1-dioxide；1,2-Benzisothiazole, 3-(1-piperazinyl)-, 1,1-dioxide；3-piperazin-1-yl-1,2-benzothiazole 1,1-dioxide
• CAS: 131540-88-0
• 化学式: C₁₁H₁₃N₃O₂S
• mdl: MFCD01442091
• 分子量: 251.309
• InChiKey: JPBXIPJNXUMSSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  70.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-哌嗪-1-基-1,2-苯并噻唑1,1-二氧化物 、 8-(4-bromobutyl)-2-hydroxy-8-azaspiro<4.5>decane-7,9-dione 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 8-<4-<4-(1,2-benzisothiazol-3-yl)-1-piperazinyl>butyl>-2-hydroxy-8-azaspiro<4.5>decane-7,9-dione S,S-dioxide
  参考文献：
  名称：

  Synthesis and biological activity of the putative metabolites of the atypical antipsychotic agent tiospirone

  摘要：

  Putative oxidative metabolites of the lead antipsychotic agent tiospirone (1) were synthesized to assist in the identification of the authentic metabolic products found in human urine samples. Thus far, six authentic metabolites have been correlated to the synthetic species. 4a The putative metabolites were further examined in vitro to assess their central nervous system therapeutic potential. SAR analysis of these derivatives indicates that hydroxyl substitution, particularly in the azaspirodecanedione region of the molecule, diminishes the dopamine D-2 affinity of the species without significantly altering the serotonin type-1A and type-2 interactions. In addition, an increase in alpha-1-adrenergic affinity appears to be linked to the attenuation of effects at the dopamine receptors. The biological profile of the 6-hydroxytiospirone metabolite 42 was exemplary in these respects and the in vivo actions of this compound suggest potent antipsychotic potential with a minimal liability for extrapyramidal side effects (EPS). While compound 42 has been unambiguously characterized as an actual human metabolite of tiospirone, the role of 42 in the observed antipsychotic activity of the parent drug, if any, has not yet been determined.

  DOI：

  10.1021/jm00115a024
• 作为产物：
  描述：

  3-(1-哌嗪基)-1,2-苯并异噻唑 在 盐酸 、 sodium periodate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 54.0h， 生成 3-哌嗪-1-基-1,2-苯并噻唑1,1-二氧化物
  参考文献：
  名称：

  Synthesis and biological activity of the putative metabolites of the atypical antipsychotic agent tiospirone

  摘要：

  Putative oxidative metabolites of the lead antipsychotic agent tiospirone (1) were synthesized to assist in the identification of the authentic metabolic products found in human urine samples. Thus far, six authentic metabolites have been correlated to the synthetic species. 4a The putative metabolites were further examined in vitro to assess their central nervous system therapeutic potential. SAR analysis of these derivatives indicates that hydroxyl substitution, particularly in the azaspirodecanedione region of the molecule, diminishes the dopamine D-2 affinity of the species without significantly altering the serotonin type-1A and type-2 interactions. In addition, an increase in alpha-1-adrenergic affinity appears to be linked to the attenuation of effects at the dopamine receptors. The biological profile of the 6-hydroxytiospirone metabolite 42 was exemplary in these respects and the in vivo actions of this compound suggest potent antipsychotic potential with a minimal liability for extrapyramidal side effects (EPS). While compound 42 has been unambiguously characterized as an actual human metabolite of tiospirone, the role of 42 in the observed antipsychotic activity of the parent drug, if any, has not yet been determined.

  DOI：

  10.1021/jm00115a024

文献信息

• 3-[4-(1-substituted-4-piperazinyl)butyl]-4-thiazolidinone and related
  申请人：Hoechst-Roussel Pharmaceuticals Incorporated

  公开号：US05229388A1

  公开（公告）日：1993-07-20

  There are disclosed compounds of the formula, ##STR1## where n is 0, 1 or 2; A is ##STR2## where X in each occurrence is independently hydrogen, halogen, loweralkyl, hydroxy, nitro, loweralkoxy, amino, cyano, trifluoromethyl or methylthio; Y in each occurrence is independently hydrogen, halogen, loweralkyl, hydroxy, nitro, loweralkoxy, amino, cyano, trifluoromethyl or methylthio; m is 1 or 2; k is 1 or 2; R.sub.1 and R.sub.2 are independently hydrogen, loweralkyl, ##STR3## or aryl except that when R.sub.1 is ##STR4## or aryl, R.sub.2 is hydrogen, or alternatively R.sub.1 +R.sub.2 taken together with the carbon atom to which they are attached form a cyclopentane, cyclohexane, cycloheptane, pyran, thiopyran, indan or piperidine ring; R.sub.3 and R.sub.4 are independently hydrogen or loweralkyl, or alternatively R.sub.3 +R.sub.4 taken together with the carbon atom to which they are attached form a cyclopentane, cyclohexane, cycloheptane, pyran, thiopyran, pyrrolidine or piperidine ring, the term aryl signifying an unsubstituted phenyl group or a phenyl group substituted with 1, 2 or 3 substituents each of which being independently loweralkyl, loweralkoxy, hydroxy, halogen, loweralkylthio, cyano, amino or trifluoromethyl, which are useful as antipsychotic, analgesic, anticonvulsant and anxiolytic agents.

  公式中披露了化合物，其中n为0、1或2；A为其中X在每次出现时独立地为氢、卤素、较低烷基、羟基、硝基、较低烷氧基、氨基、氰基、三氟甲基或甲硫基；Y在每次出现时独立地为氢、卤素、较低烷基、羟基、硝基、较低烷氧基、氨基、氰基、三氟甲基或甲硫基；m为1或2；k为1或2；R.sub.1和R.sub.2独立地为氢、较低烷基、或芳基，但当R.sub.1为或芳基时，R.sub.2为氢，或者R.sub.1 +R.sub.2与它们附着的碳原子一起形成环戊烷、环己烷、环庚烷、吡喃、硫代吡喃、茚或哌啶环；R.sub.3和R.sub.4独立地为氢或较低烷基，或者R.sub.3 +R.sub.4与它们附着的碳原子一起形成环戊烷、环己烷、环庚烷、吡喃、硫代吡喃、吡咯烷或哌啶环，术语芳基表示未取代的苯基或一个苯基，其上取代基为1、2或3个，每个取代基独立地为较低烷基、较低烷氧基、羟基、卤素、较低烷硫基、氰基、氨基或三氟甲基，这些化合物可用作抗精神病、镇痛、抗癫痫和抗焦虑药物。
• 3-[4-(1-Substituted-4-piperazinyl)butyl]-4-thiazolidinone compounds
  申请人：Hoechst-Roussel Pharmaceuticals Inc.

  公开号：US04933453A1

  公开（公告）日：1990-06-12

  3-[4-1-substituted-4-piperazinyl)butyl]-4-thiazolidinone compounds which are useful as antipsychotic, analgesic, anticonvulsant and anxiolytic agents.

  3-[4-（1-取代-4-哌嗪基）丁基]-4-噻唑烷酮化合物可用作抗精神病药、镇痛药、抗抽搐药和抗焦虑药。
• Structure−Activity Relationships of a Series of Novel (Piperazinylbutyl)thiazolidinone Antipsychotic Agents Related to 3-[4-[4-(6-Fluorobenzo[<i>b</i>]thien-3-yl)-1-piperazinyl]butyl]-2,5,5-trimethyl-4- thiazolidinone Maleate
  作者：Nicholas J. Hrib、John G. Jurcak、Deborah E. Bregna、Kendra L. Burgher、Harold B. Hartman、Sharon Kafka、Lisa L. Kerman、Sam Kongsamut、Joachim E. Roehr、Mark R. Szewczak、Ann T. Woods-Kettelberger、Roy Corbett

  DOI：10.1021/jm960268u

  日期：1996.1.1

  butyl thiazolidinones structurally related to this compound were prepared and evaluated in vitro for dopamine D2 and serotonin 5HT2 and 5HT1A receptor affinity. The compounds were examined in vivo in animal models of potential antipsychotic activity and screened in models predictive of extrapyramidal side effect (EPS) liability. The synthesis of these compounds, details of their structure-activity relationships

  HP-236（3- [4- [4-（6-氟苯并[b]噻吩-3-基）-1-哌嗪基]丁基] -2,5,5-三甲基-4-噻唑烷酮马来酸酯； P-9236） （54）显示了潜在的非典型抗精神病药活性的药理学特征。制备了与该化合物结构相关的一系列哌嗪基丁基丁基噻唑烷酮，并在体外评估了多巴胺D2和5-羟色胺5HT2和5HT1A受体的亲和力。在具有潜在抗精神病活性的动物模型中对化合物进行了体内检查，并在预测锥体束外副作用（EPS）责任的模型中进行了筛选。描述了这些化合物的合成，其结构-活性关系的详细信息以及新的先导化合物50的发现，以及化合物50和54的分布图的进一步发展。
• Method for treating allergies using substituted pyrazoles
  申请人：——

  公开号：US20030069240A1

  公开（公告）日：2003-04-10

  A method for treating an allergic condition, including an atopic allergic condition, using substituted pyrazoles.

  使用取代吡唑烷类化合物治疗过敏症状的方法，包括特应性过敏症状。
• Substituted pyrazoles
  申请人：——

  公开号：US20020040020A1

  公开（公告）日：2002-04-04

  Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases mediated by cathepsin S are described.

  本文描述了替代吡唑的制造方法，包含它们的组合物，以及使用它们治疗例如由cathepsin S介导的自身免疫疾病的方法。