3-chloro-4-methoxy-1,2-benzoisothiazole | 103486-06-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 3-chloro-4-methoxy-1,2-benzoisothiazole
• 英文别名: 3-chloro-4-methoxy-1,2-benzisothiazole；3-chloro-4-methoxybenzisothiazole；3-chloro-4-methoxybenzo[d]isothiazole；3-chloro-4-methoxy-1,2-benzothiazole
• CAS: 103486-06-2
• 化学式: C₈H₆ClNOS
• 分子量: 199.661
• InChiKey: IGTDKILBEHZLJM-UHFFFAOYSA-N

物化性质

• 沸点：
  225.8±22.0 °C(Predicted)
• 密度：
  1.404±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  50.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-chloro-4-methoxy-1,2-benzoisothiazole 在 盐酸 、 正丁基锂 作用下， 反应 0.25h， 生成 4-Methoxy-1,2-benzisothiazol-3-yl Piperazine Hydrochloride
  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：

  邻甲氧基苯甲酸 在 sodium hydroxide 、 正丁基锂 、 氯化亚砜 、 五氯化磷 、 N,N-二甲基甲酰胺 、 间氯过氧苯甲酸 、 氯甲酸三氯甲酯 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 21.5h， 生成 3-chloro-4-methoxy-1,2-benzoisothiazole
  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

• An Aryne-Based Route to Substituted Benzoisothiazoles
  作者：Yiding Chen、Michael C. Willis

  DOI：10.1021/acs.orglett.5b02347

  日期：2015.10.2

  The combination of arynes, generated using fluoride from the corresponding 2-(trimethylsilyl)aryl triflates, and 3-hydroxy-4-aminothiadiazoles leads to the selective formation of 3-amino-substituted benzo[d]isothiazoles. Variation of the substitution pattern of the aryne precursor, and of the thiadiazole, is possible, with the target heterocycles being obtained in good to excellent yields. In all cases

  使用由相应的2-（三甲基甲硅烷基）芳基三氟甲磺酸酯氟化物生成的芳烃与3-羟基-4-氨基噻二唑的组合导致选择性地形成3-氨基取代的苯并[ d ]异噻唑。可以改变芳烃前体和噻二唑的取代方式，并以高至优异的产率获得目标杂环。在所有情况下，使用3-羟基-4-氨基噻二唑都会在产物杂环中引入氨基取代基。
• Analgesic 1,2-benzisothiazol-3-ylpiperazine derivatives
  申请人：Bristol-Myers Company

  公开号：US04590196A1

  公开（公告）日：1986-05-20

  A series of non-opiate analgesics of Formula I ##STR1## wherein R.sup.1 is hydrogen, alkyl, aralkyl, or aryloxyalkyl; R.sup.2 is alkyl or hydrogen; and R.sup.3 and R.sup.4 are independently selected from hydrogen, alkyl, acyloxy, alkoxy, alkylthio, halogen, hydroxyl, or trifluoromethyl; or a pharmaceutically acceptable acid addition salt.

  一系列化学式为I的非阿片类镇痛剂，其中R1为氢、烷基、芳基烷基或芳基氧烷基；R2为烷基或氢；R3和R4独立地选择氢、烷基、酰氧基、烷氧基、烷基硫基、卤素、羟基或三氟甲基；或其药学上可接受的酸盐。
• Acyclic Ikur inhibitors
  申请人：Johnson A. James

  公开号：US20070082909A1

  公开（公告）日：2007-04-12

  A compound of formula I wherein R 1 , R 2 , R 3 , R 4 and R 5 are described herein.

  一种化合物，其化学式为I，其中R1，R2，R3，R4和R5的描述如下。
• ACYCLIC IKUR INHIBITORS
  申请人：Johnson James A.

  公开号：US20120094983A1

  公开（公告）日：2012-04-19

  A compound of formula I wherein R 1 , R 2 , R 3 , R 4 and R 5 are described herein.

  化合物I的公式如下，其中R1、R2、R3、R4和R5的描述如下。
• WO2007/30582
  申请人：——

  公开号：——

  公开（公告）日：——