methyl 5-(tert-butylthio)-2,2-dimethyl-4-oxopentanoate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: methyl 5-(tert-butylthio)-2,2-dimethyl-4-oxopentanoate
• 英文别名: methyl 5-(t-butylthio)-2,2-dimethyl-4-oxopentanoate；Methyl 5-t-butylthio-2,2-dimethyl-4-oxopentanoate；methyl 5-tert-butylsulfanyl-2,2-dimethyl-4-oxopentanoate
• 化学式: C₁₂H₂₂O₃S
• 分子量: 246.371
• InChiKey: CJWFVFIKOBWANB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  68.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 5-(tert-butylthio)-2,2-dimethyl-4-oxopentanoate 在 盐酸 、 氯化亚砜 、 吡啶盐酸盐 、 sodium 、 sodium hydride 、 对甲苯磺酸 、 三苯基膦 作用下， 以 甲醇 、 叔丁醇 为溶剂， 反应 143.92h， 生成 methyl 3-(6-mercapto-4-methyl-4,5-dihydro-1H-thiopyrano<2,3,4-c,d>indol-2-yl)-2,2-dimethylpropanoate
  参考文献：
  名称：

  Substituted thiopyrano[2,3,4-c,d]indoles as potent, selective, and orally active inhibitors of 5-lipoxygenase. Synthesis and biological evaluation of L-691,816

  摘要：

  Thiopyrano[2,3,4-c,d]indoles are a new class of 5-lipoxygenase (5-LO) inhibitors. SAR studies have demonstrated that the thiopyran ring, the 5-phenylpyridine substituent, and an acidic functional group on a four-carbon C-2 side chain are all required for optimal inhibitor potency. In contrast, the indolic nitrogen may be substituted with a variety of lipophilic groups. As a result of the SAR investigation, 44 (L-691,816; 5-[3-[1-(4-chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methoxy]-4,5-dihydro-1H-thiopyrano[2,3,4-c,d]indol-2-yl]-2,2-dimethylpropyl]-1H-tetrazole) has been identified as a potent inhibitor of the 5-LO reaction both in vitro and in a range of in vivo models. Compound 44 inhibits 5-HPETE production by both rat and human 5-LO and LTB4 synthesis in human PMN leukocytes (IC50s 16,75, and 10 nM, respectively). The mechanism of inhibition of 5-LO activity by compound 44 appears to involve the formation of a reversible deadend complex with the enzyme and does not involve reduction of the nonheme iron of 5-LO. Compound 44 is highly selective for 5-LO when compared to the inhibition of human FLAP, porcine 12-LO, and also ram seminal vesicle cyclooxygenase. In addition, 44 is orally active in a rat pleurisy model (inhibition of LTB4, ED50 = 1.9 mg/kg; 8 h pretreatment) as well as in the hyperreactive rat model of antigen-induced dyspnea (ED50 = 0.1 mg/kg;2-h pretreatment). Excellent functional activity was also observed in both the conscious allergic monkey and sheep models of asthma. In the latter case, the functional activity observed correlated with the inhibition of urinary LTE4 excretion.

  DOI：

  10.1021/jm00071a008
• 作为产物：
  描述：

  methyl 5-bromo-2,2-dimethyl-4-oxopentanoate 、 叔丁基硫醇 在 叔丁基硫醇 作用下， 生成 methyl 5-(tert-butylthio)-2,2-dimethyl-4-oxopentanoate
  参考文献：
  名称：

  3-hetero-substituted-n-benzyl-indoles and prevention of leucotriene

  摘要：

  具有以下式子的化合物：##STR1##是白三烯生物合成的抑制剂。这些化合物可用作抗哮喘、抗过敏、抗炎和细胞保护剂。它们还可用于治疗腹泻、高血压、心绞痛、血小板聚集、脑痉挛、早产、自然流产、痛经和偏头痛。

  公开号：

  US05081138A1

文献信息

• (Quinolin-2-ylmethoxy)indoles as inhibitors of the biosynthesis of
  申请人：Merck Frosst Canada, Inc.

  公开号：US05204344A1

  公开（公告）日：1993-04-20

  Compounds having the formula I: ##STR1## are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

  具有以下化学式的化合物I：##STR1## 是白三烯生物合成抑制剂。这些化合物可用作抗哮喘、抗过敏、抗炎和细胞保护剂。它们还可用于治疗腹泻、高血压、心绞痛、血小板聚集、脑痉挛、早产、自然流产、月经痛和偏头痛。
• Thiopyrano[2,3,4-c,d]indoles as inhibitors of leukotriene biosynthesis
  申请人：Merck Frosst Canada, Inc.

  公开号：US05202321A1

  公开（公告）日：1993-04-13

  Compounds having the formula I: ##STR1## are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, psoriasis, uveitis and allograft rejection and in preventing the formation of atherosclerotic plaques.

  具有公式I的化合物：##STR1## 是白三烯生物合成的抑制剂。这些化合物可用作抗哮喘、抗过敏、抗炎和细胞保护剂。它们还可用于治疗心绞痛、脑血管痉挛、肾小球肾炎、肝炎、内毒素血症、牛皮癣、葡萄膜炎和移植排斥，并预防动脉粥样硬化斑块的形成。
• 3-hetero-substituted-n-benzyl-indoles and prevention of leucotriene
  申请人：Merck Frosst Canada, Inc.

  公开号：US05081138A1

  公开（公告）日：1992-01-14

  Compounds having the formula: ##STR1## are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

  具有以下化学式的化合物：##STR1## 是白三烯生物合成的抑制剂。这些化合物可用作抗哮喘、抗过敏、抗炎和细胞保护剂。它们还可用于治疗腹泻、高血压、心绞痛、血小板聚集、脑痉挛、早产、自然流产、经期疼痛和偏头痛。
• (Quinolin-2-ylmethoxy)indole/cyclodextrin complex
  申请人：Merck Frosst Canada, Inc.

  公开号：US05254541A1

  公开（公告）日：1993-10-19

  A complex of cyclodextrin and 3-[N-(p-chlorobenzyl)-3-(t-buthylthio)-5-(quinolin-2-ylmethoxy)indol-2-yl] -2,2-dimethylpropanoic acid, sodium salt is more soluble in water than the sodium salt alone. The complex is useful as an anti-asthmatic, anti-allergic, anti-inflammatory, or cytoprotective agent. It is also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

  环糊精和3-[N-(对氯苯甲基)-3-(叔丁基硫基)-5-(喹诺啉-2-基甲氧基)吲哚-2-基]-2,2-二甲基丙酸钠盐的复合物在水中比单独的钠盐更溶解。该复合物可用作抗哮喘、抗过敏、抗炎症或细胞保护剂。它还可用于治疗腹泻、高血压、心绞痛、血小板聚集、脑痉挛、早产、自然流产、经期疼痛和偏头痛。
• Amorphous (quinolin-2-ylmethoxy)indole compounds which have useful
  申请人：Merck Frosst Canada, Inc.

  公开号：US05254567A1

  公开（公告）日：1993-10-19

  A form of 3-[N-(p-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-ylmethoxy)indol-2-yl]- 2,2-dimethylpropanoic acid sodium salt, obtained by freeze or spray drying, is more soluble in water than the crystalline form thereof. The compound is useful as an anti-asthmatic, anti-allergic, anti-inflammatory, or cytoprotective agent. It is also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

  一种3-[N-(对氯苄基)-3-(叔丁基硫基)-5-(喹啉-2-基甲氧基)吲哚-2-基]-2,2-二甲基丙酸钠盐的形式，通过冷冻或喷雾干燥得到，比其结晶形式更容易溶解于水中。该化合物可用作抗哮喘、抗过敏、抗炎或细胞保护剂。它还可用于治疗腹泻、高血压、心绞痛、血小板聚集、脑痉挛、早产、自然流产、痛经和偏头痛。