4-Chloro-2-(chloromethyl)-1H-1lambda~6~,2-benzothiazole-1,1,3(2H)-trione | 133741-72-7

• 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: 4-Chloro-2-(chloromethyl)-1H-1lambda~6~,2-benzothiazole-1,1,3(2H)-trione
• 英文别名: 4-chloro-2-(chloromethyl)-1,1-dioxo-1,2-benzothiazol-3-one
• CAS: 133741-72-7
• 化学式: C₈H₅Cl₂NO₃S
• 分子量: 266.1
• InChiKey: WCFNFNINPFMFAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 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：
  62.8
• 氢给体数：
  0
• 氢受体数：
  3

文献信息

• 2-Saccharinylmethyl aryl carboxylates useful as proteolytic enzyme inhibitors and compositions and method of use
  申请人：STERLING WINTHROP INC.

  公开号：EP0483928A1

  公开（公告）日：1992-05-06

  4-R⁴-R⁵-2-Saccharinylmethyl aryl carboxylates, useful in the treatment of degenerative diseases, are prepared by reacting a 4-R⁴-R⁵-2-halomethylsaccharin with an arylcarboxylic acid in the presence of an acid-acceptor.

  4-R⁴-R⁵-2-糖精甲基芳基羧酸盐可用于治疗退行性疾病，其制备方法是将 4-R⁴-R⁵-2-halomethylsaccharin 与芳基羧酸在酸受体存在的情况下进行反应。
• Novel 2-saccharinylmethyl and 4,5,6,7-tetrahydro-2-saccharinylmethyl phosphates, phosphonates and phosphinates useful as proteolytic enzyme inhibitors and compositions and method of use thereof
  申请人：STERLING WINTHROP INC.

  公开号：EP0549073A1

  公开（公告）日：1993-06-30

  Novel 4-R₁-R₂-R₃-2-saccharinylmethyl, 4-R₄-4-R₅-6-R₆-4,5,6,7-tetrahydro-2-saccharinylmethyl and 4,7-C-4,5,6,7-tetrahydro-2-saccharinylmethyl phosphates, phosphonates and phosphinates of formulas I, II and IIA respectively are useful in the treatment of degenerative diseases, and compositions containing them, methods for using them to treat degenerative diseases, and processes for their preparation by reaction of the corresponding 2-halomethylsaccharins with a phosphate, phosphonate or phosphinic acidderivative.

  分别为式 I、II 和 IIA 的新型 4-R₁-R₂-R₃-2-糖精基甲基、4-R₄-4-R₅-6-R₆-4,5,6,7-四氢-2-糖精基甲基和 4,7-C-4,5,6,7-四氢-2-糖精基甲基膦酸盐、膦酸盐和膦酸盐 可用于治疗退行性疾病，以及含有这些物质的组合物、使用这些物质治疗退行性疾病的方法，以及通过相应的 2-半甲基糖与磷酸盐、膦酸盐或膦酸衍生物反应制备这些物质的工艺。
• 2-Substituted saccharin derivative proteolytic enzyme inhibitors
  申请人：STERLING WINTHROP INC.

  公开号：EP0542372A1

  公开（公告）日：1993-05-19

  Novel 2-substituted saccharins which inhibit the enzymatic activity of proteolytic enzymes are useful in the treatment of degenerative diseases and have the formula    wherein:    L is -O-, -S-, -SO- or -SO₂-;    m and n are each independently 0 or 1;    R₁ is substituted phenyl, heterocyclyl or substitued heterocyclyl or,    when L is -O- and n is 1, R₁ is cycloheptatrienon-2-yl or,    when L is -S- and n is 1, R₁ is cyano or lower-alkoxythiocarbonyl or,    when L is -SO₂- and n is 1, R₁ is lower-alkyl or trifluoromethyl;    R₂ is hydrogen, lower-alkoxycarbonyl, phenyl or phenylthio; and    R₃ and R₄ are each hydrogen or various substituents,    and processes for preparation and pharmaceutical compositions and method of use thereof are disclosed.

  新型 2-取代糖精能抑制蛋白水解酶的酶活性，可用于治疗退行性疾病，其分子式为 其中 L是-O-、-S-、-SO-或-SO₂-； m 和 n 各自独立地为 0 或 1； R₁ 是取代的苯基、杂环基或取代的杂环基；或 当 L 为-O-且 n 为 1 时，R₁ 为环庚三壬-2-基，或 当 L 为-S-且 n 为 1 时，R₁ 为氰基或低级烷氧基硫代羰基；或 当 L 为-SO₂- 且 n 为 1 时，R₁ 为低级烷基或三氟甲基； R₂ 是氢、低级烷氧基羰基、苯基或苯硫基；以及 R₃ 和 R₄ 各为氢或各种取代基、 本发明公开了制备工艺、药物组合物及其使用方法。
• 2-Saccharinylmethyl heterocyclic carboxylates useful as proteolytic enzyme inhibitors and pharmaceutical compositions containing them
  申请人：STERLING WINTHROP INC.

  公开号：EP0550111A1

  公开（公告）日：1993-07-07

  4-R⁴-R⁵-2-Saccharinylmethyl heterocyclic carboxylates, having the formula: wherein:    Het is a 5- or 6-membered monocyclic heterocycle or a 9- or 10-membered bicyclic heterocycle containing from 1 to 2 heteroatoms selected from oxygen, nitrogen and sulfur or said heterocycles substituted by from one to three, the same or different, members of the group consisting of lower-alkyl, perfluorolower-alkyl, lower-alkoxy, oxo, phenyl, halogen, and -O-(C₂-C₁₀ alkylene)-N=B where N=B is dilower-alkylamino, 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 1-piperazinyl, or 4-lower-alkyl-1-piperazinyl;    R⁴ is hydrogen, halogen , lower-alkyl, perfluorolower-alkyl, perchlorolower-alkyl, lower-alkenyl, lower-alkynyl, cyano, carboxamido, amino, lower-alkylamino, dilower-alkylamino, lower-alkoxy, benzyloxy, lower-alkoxycarbonyl, hydroxy or phenyl; and    R⁵ is hydrogen or from one to two substituents in any of the 5-, 6- or 7-positions. The compounds of the present invention inhibit the activity of serine proteases, specifically human leukocyte elastase and the chymotrypsin-like enzymes, and are thus useful in the treatment of degenerative disease conditions such as emohysema, rheumatoid arthritis, pancreatitis, cystic fibrosis, chronic bronchitis, adult respiratory distress syndrome, inflammatory bowel disease, psoriasis, bullous pemphigoid and alpha-1-antitrypsin deficiency.

  4-R⁴-R⁵-2-糖精甲基杂环羧酸盐，其化学式为 其中 Het 是 5 或 6 元单环杂环或 9 或 10 元双环杂环，其中含有 1 至 2 个选自氧、氮和硫的杂原子，或所述杂环被 1 至 3 个相同或不同的杂原子取代、由低级烷基、全氟低级烷基、低级烷氧基、氧代、苯基、卤素和-O-(C₂-C₁₀亚烷基)-N=B 组成的组中的成员，其中 N=B 是稀低级烷基氨基、1-吡咯烷基、1-哌啶基、4-吗啉基、1-哌嗪基或 4-低级烷基-1-哌嗪基； R⁴ 是氢、卤素、低级烷基、全氟低级烷基、全氯低级烷基、低级烯基、低级炔基、氰基、羧酰胺基、氨基、低级烷基氨基、稀释低级烷基氨基、低级烷氧基、苄氧基、低级烷氧基羰基、羟基或苯基；以及 R⁵ 是氢或 5、6 或 7 位上的一至两个取代基。 本发明的化合物可抑制丝氨酸蛋白酶的活性，特别是人白细胞弹性蛋白酶和糜蛋白酶样酶，因此可用于治疗退行性疾病，如肺气肿、类风湿性关节炎、胰腺炎、囊性纤维化、慢性支气管炎、成人呼吸窘迫综合征、炎症性肠病、银屑病、大疱性类天疱疮和α-1-抗胰蛋白酶缺乏症。
• 2-Saccharinylmethyl aryl and aryloxy acetates useful as proteolytic enzyme inhibitors and pharmaceutical compositions contaning them
  申请人：STERLING WINTHROP INC.

  公开号：EP0550112A1

  公开（公告）日：1993-07-07

  4-R⁴-R⁵-2-Saccharinylmethyl aryl and aryloxy acetates, having the formula: wherein: mis zero or one, n is zero or one, and the sum of m + n is zero or one; R1is hydrogen or lower-alkyl; R2is hydrogen or lower-alkyl; R3is phenyl or phenyl substituted by from one to three, the same or different, members of the group consisting of lower-alkyl perfluorolower-alkyl, lower-alkoxy and halogen; R4is hydrogen, halogen, lower-alkyl, perfluorolower-alkyl, perchlorolower-alkyl, lower-alkenyl, lower-alkynyl, cyano, carboxamido, amino, lower-alkylamino, dilower-alkylamino, lower-alkoxy, benzyloxy, lower-alkoxycarbonyl, hydroxy or phenyl; and R5is hydrogen or from one to two substituents in any of the 5-, 6- or 7-positions. The compounds of the present invention inhibit the activity of serine proteases, specifically human leukocyte elastase and the chymotrypsin-like enzymes, and are thus useful in the treatment of degenerative disease conditions such as emphysema, rheumatoid arthritis, pancreatitis, cysticfibrosis, chronic bronchitis, adult respiratory distress syndrome, inflammatory bowel disease, psoriasis, bullous pemphigoid and alpha-1-antitrypsin deficiency.

  4-R⁴-R⁵-2-糖精甲基芳基和芳氧基乙酸酯，其式为 其中 mis为零或一，n为零或一，m+n之和为零或一； R1 是氢或低级烷基； R2 是氢或低级烷基 R3 是苯基或被 1 至 3 个相同或不同的低级烷基全氟低级烷基、低级烷氧基和卤素组成的组中的成员取代的苯基； R4 是氢、卤素、低级烷基、全氟低级烷基、全氯低级烷基、低级烯基、低级炔 基、氰基、羧酰胺基、氨基、低级烷基氨基、稀释低级烷基氨基、低级烷氧基、 苄氧基、低级烷氧基羰基、羟基或苯基；以及 R5 为氢或 5、6 或 7 位上的一至两个取代基。 本发明的化合物可抑制丝氨酸蛋白酶的活性，特别是人白细胞弹性蛋白酶和糜蛋白酶样酶，因此可用于治疗退行性疾病，如肺气肿、类风湿性关节炎、胰腺炎、囊性纤维化、慢性支气管炎、成人呼吸窘迫综合征、炎症性肠病、银屑病、大疱性类天疱疮和α-1-抗胰蛋白酶缺乏症。