4-fluoro-2-(4-methylthiophenylthio)-benzoic acid | 58913-04-5

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-fluoro-2-(4-methylthiophenylthio)-benzoic acid
• 英文别名: 2-(p-Methylthiophenylthio)-4-fluoro-benzoic acid；4-fluoro-2-(4-methylsulfanylphenyl)sulfanylbenzoic acid
• CAS: 58913-04-5
• 化学式: C₁₄H₁₁FO₂S₂
• 分子量: 294.371
• InChiKey: YKQMRAULXKEKNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  87.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-fluoro-2-(4-methylthiophenylthio)-benzoic acid 在 氢氧化钾 、 氯化亚砜 、 红铝 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 生成 [4-Fluoro-2-(4-methylsulfanyl-phenylsulfanyl)-phenyl]-acetic acid
  参考文献：
  名称：

  Kopicova,Z. et al., Collection of Czechoslovak Chemical Communications, 1975, vol. 40, p. 3519 - 3529

  摘要：

  DOI：
• 作为产物：
  描述：

  4-甲硫基苯硫醇 、 2-溴-4-氟苯甲酸 在 铜 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-fluoro-2-(4-methylthiophenylthio)-benzoic acid
  参考文献：
  名称：

  Kopicova,Z. et al., Collection of Czechoslovak Chemical Communications, 1975, vol. 40, p. 3519 - 3529

  摘要：

  DOI：

文献信息

• 2-Methylthio-6-fluoro-9-(1-methyl-4-piperidylidene)-thioxanthene and
  申请人：Kefalas A/S

  公开号：US04235916A1

  公开（公告）日：1980-11-25

  The present invention relates to the novel compound 2-methylthio-6-fluoro-9-(1-methyl-4-piperidylidene)-thioxanthene of the formula ##STR1## and its non-toxic acid addition salts, which compounds have strong and longlasting neuroleptic properties and, at the same time, a low degree of undesired side effects such as extrapyrimidal side effects. The invention moreover relates to a method for the preparation of said novel compounds, pharmaceutical compositions containing same, which may be administered to animals, including human beings, orally or parentally. Further the invention relates to a method for producing an antipsychotic effect in warmblooded animals by administering to said animals an antipsychotically effective amount of one of said novel compounds.

  本发明涉及新型化合物2-甲硫基-6-氟-9-(1-甲基-4-哌啶基亚)硫代黄酮，其化学式如下所示：并且其无毒酸盐，这些化合物具有强大且持久的神经阻滞特性，同时具有低程度的不良副作用，如锥体外系副作用。此外，本发明还涉及一种制备上述新型化合物的方法，含有相同化合物的药物组合物，可口服或注射给动物，包括人类。此外，本发明还涉及通过向暖血动物投与其中一种新型化合物的抗精神病作用有效量来产生抗精神病效应的方法。
• Xanthene and thioxanthene derivatives, compositions thereof and
  申请人：Kefalas A/S

  公开号：US04285956A1

  公开（公告）日：1981-08-25

  The present invention relates to novel thioxanthene and xanthene derivatives which have useful pharmacodynamic activity, such as neuroleptic activity and antiemetic activity, methods for the preparation of said derivatives, pharmaceutical compositions containing same, and a method for the treatment of psychic disorders by administering a therapeutically active amount of one of said derivatives to a living animal body, including human beings. The new compounds of the present invention correspond to the Formula I: ##STR1## wherein X is a halogen atom, an alkyl group with from one to four carbon atoms inclusive, an alkyloxy group with from one to four carbon atoms inclusive, a methylthio group, a methylsulphonyl group, a dimethylsulfamoyl group, a trifluoromethyl group or an acetyl group; Y is hydrogen, fluorine or a methyl group; Z is oxygen or sulphur; n is an integer from zero to three inclusive, and R is a cycloalkyl group with from four to six carbon atoms inclusive in the ring substituted with from one to four substituents selected from optionally esterified hydroxy- or hydroxymethyl groups, methyl groups, amino groups, acetamido groups, mesylamino groups or oxo groups, a five- or six-: membered saturated heterocyclic ring having one or two heteroatoms selected from oxygen and nitrogen atoms and being optionally substituted with an optionally esterified hydroxy group or oxo group, any esterified hydroxy group present being an ester of an aliphatic carboxylic acid having from ten to twentytwo carbon atoms inclusive, as well as their non-toxic pharmaceutically acceptable acid addition salts with the proviso that methyl is present only when one of the other named substituents is also present.

  本发明涉及新型噻吩和苯氧基衍生物，其具有有用的药理活性，如神经元抑制活性和抗恶心活性，以及制备这些衍生物的方法，含有这些衍生物的制药组合物，以及通过向活体动物体内给予其中一种衍生物的治疗有效剂量来治疗心理障碍的方法，包括人类。本发明的新化合物对应于公式I：##STR1## 其中X是卤素原子，具有1至4个碳原子的烷基，具有1至4个碳原子的烷氧基，甲基硫基，甲基磺酰基，二甲基磺酰胺基，三氟甲基或乙酰基; Y是氢，氟或甲基; Z是氧或硫; n是0至3的整数，R是环中具有4至6个碳原子的环烷基，其被选择自可选的酯化羟基或羟甲基基团，甲基基团，氨基团，乙酰胺基团，甲磺酰氨基团或氧代基团的1至4个取代基所取代，具有1个或2个氧和氮原子的5或6元饱和杂环环，可选地取代具有可选的酯化羟基或氧代基团，存在的任何酯化羟基均为具有10至22个碳原子的脂肪族羧酸的酯，以及它们的无毒药学上可接受的酸加盐，前提是当存在其他命名的取代基之一时，甲基仅存在。
• Xanthene and thioxanthene derivatives, compositions thereof, and
  申请人：Kefalas A/S

  公开号：US04309429A1

  公开（公告）日：1982-01-05

  The present invention relates to novel thioxanthene and xanthene derivatives which have useful pharmacodynamic activity, such as neuroleptic activity and antiemetic activity, methods for the preparation of said derivatives, pharmaceutical compositions containing same, and a method for the treatment of psychic disorders by administering a therapeutically active amount of one of said derivatives to a living animal body, including human beings. The new compounds of the present invention correspond to the Formula I: ##STR1## wherein X is a halogen atom, an alkyl group with from one to four carbon atoms inclusive, an alkyloxy group with from one to four carbon atoms inclusive, a methylthio group, a methylsulphonyl group, a dimethylsulfamoyl group, a trifluoromethyl group or an acetyl group; Y is hydrogen, fluorine or a methyl group; Z is oxygen or sulphur; n is an integer from zero to three inclusive, and R is a cycloalkyl group with from four to six carbon atoms inclusive in the ring substituted with from one to four substituents selected from optionally esterified hydroxy- or hydroxymethyl groups, methyl groups, amino groups, acetamido groups, mesylamino groups or oxo groups, a five- or six-membered saturated heterocyclic ring having one or two heteroatoms selected from oxygen and nitrogen atoms and being optionally substituted with an optionally esterified hydroxy group or oxo group, any esterified hydroxy group present being an ester of an aliphatic carboxylic acid having from ten to twenty-two carbon atoms inclusive, as well as their non-toxic pharmaceutically acceptable acid addition salts.

  本发明涉及新型噻吩并二氢苯并呋喃衍生物，其具有有用的药理活性，如神经精神药物活性和抗恶心活性，以及制备该衍生物的方法，含有该衍生物的制药组合物，以及通过向生物体内给予其中一种衍生物的治疗有效量来治疗精神障碍的方法，包括人类。本发明的新化合物对应于公式I：##STR1## 其中X是卤素原子、含有1至4个碳原子的烷基、含有1至4个碳原子的烷氧基、甲硫基、甲基磺酰基、二甲基磺酰胺基、三氟甲基基或乙酰基；Y是氢、氟或甲基；Z是氧或硫；n是从零到三的整数，R是环中含有从一到四个取自可选择酯化羟基或羟甲基基团、甲基基团、氨基基团、乙酰胺基团、甲磺酰胺基团或氧基团的取代基的含有四至六个碳原子的环烷基，或含有一个或两个取自氧和氮原子的杂原子的五元或六元饱和杂环，可选择用含有10至22个碳原子的脂肪族羧酸酯的羟基酸酯酸化，任何存在的酯化羟基基团都是非毒性的药用可接受酸盐。
• Methylthiofluorothioxanthene derivative, its preparation and compositions containing it
  申请人：KEFALAS A/S

  公开号：EP0002902A1

  公开（公告）日：1979-07-11

  The compound 2-methylthio-6-fluoro-9-(1-methyl-4-piperidylidene)-thioxanthene of the formula: and its non-toxic acid addition salts have been shown in animal experiment to possess very strong and longlasting neuroleptic properties and, at the same time, a low degree of undesired side effects such as extrapyrimidal side effects. They also have a low acute toxicity which makes the therapeutic index favourable. Moreover, they have strong anticholinergic effects. The compound may conveniently be prepared by dehydrating 2-methylthio-6-fluoro-9-(1-methyl-4-piperidylidene)-thioxanthen-ol-9 of the formula: by conventional means. The compound of formula I and its acid addition salts may be administered in the form of tablets, capsules, powders, syrups, suppositories or solutions for injection.

  式中的 2-甲硫基-6-氟-9-(1-甲基-4-哌啶亚基)-噻吨化合物及其无毒酸加成盐在动物实验中已被证明具有非常强和持久的神经安定特性，同时副作用小，如嘧啶外作用： 动物实验表明，2-甲硫基-6-氟-9-(1-甲基-4-哌啶亚基)-硫杂蒽及其无毒酸加成盐具有非常强而持久的神经安定特性，同时，其不良副作用（如嘧啶外副作用）也很低。它们的急性毒性也很低，因此治疗指数很高。 此外，它们还具有很强的抗胆碱能作用。 该化合物可通过常规方法脱水制备式 2-甲硫基-6-氟-9-(1-甲基-4-哌啶亚基)-硫杂蒽醇-9： 通过常规方法制备。 式 I 的化合物及其酸加成盐可以片剂、胶囊、粉末、糖浆、栓剂或注射液的形式给药。
• Xanthone and thioxanthone derivatives, their preparation and pharmaceutical compositions containing them
  申请人：KEFALAS A/S

  公开号：EP0005607A1

  公开（公告）日：1979-11-28

  Xanthone- and thioxanthone derivatives of the formula: wherein X is a halogen atom, an alkyl group, an alkyloxy group, said alkyl and alkyloxy groups having from one to four carbon atoms inclusive, a methylthio group, a methyl- suphonyl group, a dimethylsulphamoyl group, a trifluoromethyl group, or an acetyl group; Y is hydrogen, fluorine or a methyl group; Z is oxygen or sulphur; n is an integer from zero to three inclusive, and R is a cycloalkyl group with from four to six carbon atoms inclusive in the ring, substituted with from one to four substituents selected from optionally esterified hydroxy- or hydroxymethyl groups, methyl groups, amono groups, acetamino groups, mesylamino groups or oxo groups, a five-or six-membered saturated heterocyclic ring having one or two hetero atoms selected from oxygen and nitrogen atoms and being optionally substituted with an optionally esterified hydroxy group, any esterified hydroxy group present being an ester of an aliphatic carboxylic acid having from ten to twentytwo carbon atoms inclusive, or an oxo group, as well as their non-toxic pharmaceutically acceptable acid addition salts. Methods for the preparation of compounds of Formula I and novel intermediates used in said methods. The novel compounds of Formula I having strong, and sometimes very long-lasting neuroleptic effects, at the same time showing relatively low extrapyrimidal side effects, a low acute toxicity and moderately strong anticholinergic effects and comparatively low undesired sedative effects.

  式中的氧雜蔥酮和硫雜蔥酮衍生物： 其中 X 是卤素原子、烷基、烷氧基（烷基和烷氧基的碳原子数从 1 个到 4 个不等）、甲硫基、甲上酰基、二甲基氨基磺酰基、三氟甲基或乙酰基； Y 是氢、氟或甲基 Z 是氧或硫； n 是 0 至 3（包括 3）的整数，且 R 是环烷基，在环中有 4 至 6 个碳原子，被 1 至 4 个取代基取代，这些取代基可选 自经酯化的羟基或羟甲基、甲基、氨基、乙酰氨基、间氨基或氧代基、五元或六元饱和杂环，具有一个或两个选自氧原子和氮原子的杂原子，并被任选的酯化羟基取代，其中任何酯化羟基均为具有 10 至 22 个碳原子（含）的脂肪族羧酸的酯或氧代基团，以及它们的无毒药学上可接受的酸加成盐。 式 I 化合物的制备方法以及用于上述方法的新型中间体。 式 I 的新型化合物具有较强的，有时是非常持久的神经安定作用，同时显示出相对较低的嘧啶外副作用、较低的急性毒性和中等强度的抗胆碱能作用，以及相对较低的不期望的镇静作用。