1-[(4-氯苯基)甲基]-3-[(1,1-二甲基乙基)硫基]-5-甲氧基-ALPHA,ALPHA-二甲基-1H-吲哚-2-丙酸乙酯 | 154325-76-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 1-[(4-氯苯基)甲基]-3-[(1,1-二甲基乙基)硫基]-5-甲氧基-ALPHA,ALPHA-二甲基-1H-吲哚-2-丙酸乙酯
• 英文名称: 3-[1-(4-chloro-benzyl)-3-tert-butylsulfanyl-5-methoxy-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester
• 英文别名: ethyl 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-methoxy-1H-indol-2-yl)-2,2-dimethylpropanoate；ethyl 3-[1-(4-chlorobenzyl)-3-(1,1-dimethylethylthio)-5-methoxyindol-2-yl]-2,2-dimethylpropionate；ethyl 3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-methoxyindol-2-yl]-2,2-dimethylpropionate；ethyl 3-[3-tert-butylsulfanyl-1-[(4-chlorophenyl)methyl]-5-methoxyindol-2-yl]-2,2-dimethylpropanoate
• CAS: 154325-76-5
• 化学式: C₂₇H₃₄ClNO₃S
• 分子量: 488.091
• InChiKey: JPXNJCVPJOZELR-UHFFFAOYSA-N

物化性质

• 沸点：
  601.5±55.0 °C(Predicted)
• 密度：
  1.13

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  65.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  1-[(4-氯苯基)甲基]-3-[(1,1-二甲基乙基)硫基]-5-甲氧基-ALPHA,ALPHA-二甲基-1H-吲哚-2-丙酸乙酯 在 aluminum (III) chloride 、 叔丁基硫醇 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 1-[(4-氯苯基)甲基]-3-[(1,1-二甲基乙基)硫基]-5-羟基-alpha,alpha-二甲基-1H-吲哚-2-丙酸乙酯
  参考文献：
  名称：

  WO2008/67566

  摘要：

  公开号：
• 作为产物：
  描述：

  4-甲氧基苯肼盐酸盐 在 四丁基溴化铵 、 溶剂黄146 、 二异丙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 144.0h， 生成 1-[(4-氯苯基)甲基]-3-[(1,1-二甲基乙基)硫基]-5-甲氧基-ALPHA,ALPHA-二甲基-1H-吲哚-2-丙酸乙酯
  参考文献：
  名称：

  Synthesis of indolylalkoxyiminoalkylcarboxylates as leukotriene biosynthesis inhibitors

  摘要：

  A series of substituted indolylalkoxyiminoalkylcarboxylates were found to be potent leuko triene biosynthesis inhibitors. The structure-activity relationships were investigated. Representative potent inhibitors identified were the quinolyl 3a (A-86885) and pyridyl 3b (A-86886) congeners with in vitro IC(50)s of 21 and 9 nM and in vivo leukotriene inhibition in the rat with oral ED(50)s of 0.9 and 1.7 mg/kg, respectively. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(96)00265-9

文献信息

• 5-LIPOXYGENASE-ACTIVATING PROTEIN (FLAP) INHIBITORS
  申请人：Hutchinson H. John

  公开号：US20070105866A1

  公开（公告）日：2007-05-10

  Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.

  本发明描述了调节5-脂氧合酶激活蛋白(FLAP)活性的化合物和含有该化合物的药物组合物。本发明还描述了单独使用和与其他化合物联合使用FLAP调节剂，用于治疗呼吸系统、心血管系统和其他白三烯依赖性或白三烯介导的状况或疾病。
• [EN] REDUCTION OF PRO-INFLAMMATORY HDL USING A LEUKOTRIENE INHIBITOR<br/>[FR] RÉDUCTION DE HDL PRO-INFLAMMATOIRE À L'AIDE D'UN INHIBITEUR DE LEUCOTRIÈNE
  申请人：AUTOIMMUNE PHARMA LLC

  公开号：WO2018152405A1

  公开（公告）日：2018-08-23

  A method involving the administration of a therapeutically effective amount of a leukotriene inhibitor, a pharmaceutically acceptable salt, a pharmaceutically acceptable N-oxide, a pharmaceutically active metabolite, a pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof to a human for reducing a level of pro-inflammatory HDL in the human. Various examples of leukotriene inhibitors, including 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxy-pyridin- 3-yl)-benzyl]-5-(5-methyl-pyridin-2-ylmethoxy)-1H-indol-2-yl]-2, 2-dimethyl-propionic acid, are disclosed for administration for the reduction of pro-inflammatory HDL in a human. Reduction of pro-inflammatory HDL by the leukotriene inhibitor may include conversion of at least a portion of pro-inflammatory HDL to anti-inflammatory HDL.

  一种方法，涉及给人类施用治疗有效量的白细胞三烯抑制剂、药物可接受的盐、药物可接受的N-氧化物、药物活性代谢物、药物可接受的的前药或其药物可接受的溶剂化物，以降低人类中的前炎症高密度脂蛋白(HDL)水平。公开了各种白细胞三烯抑制剂，包括3-[3-叔丁基硫基-1-[4-(6-乙氧基-吡啶-3-基)-苄基]-5-(5-甲基-吡啶-2-基甲氧基)-1H-吲哚-2-基]-2,2-二甲基丙酸，用于施用以降低人类中的前炎症HDL。通过白细胞三烯抑制剂降低前炎症HDL可能包括将至少部分前炎症HDL转化为抗炎症HDL。
• Thiopyrano(2,3,4-c,d) indolyloxime ether alkylcarboxylates
  申请人：Abbott Laboratories

  公开号：US05420282A1

  公开（公告）日：1995-05-30

  Compounds of the structure ##STR1## wherein R.sup.1 is selected from the group consisting of ##STR2## are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

  结构为##STR1##的化合物，其中R.sup.1从##STR2##组成的群体中选择，是脂氧合酶酶的有效抑制剂，从而抑制白三烯的生物合成。这些化合物在治疗或缓解过敏和炎症性疾病状态中很有用。
• Indole iminooxy derivatives which inhibit leukotriene biosynthesis
  申请人：Abbott Laboratories

  公开号：US05399699A1

  公开（公告）日：1995-03-21

  Compounds of the structure ##STR1## where A.sub.1 is alkylene or cycloalkylene; A.sub.2 is a valence bond, alkylene, or cycloalkylene; R.sub.1 is selected from hydrogen, alkylthio, optionally substituted phenylthio, optionally substituted phenylalkylthio, optionally substituted 2-, 3- and 4-pyridylthio, optionally substituted 2- and 3-thienylthio, and optionally substituted 2-thiazolylthio; R.sup.2 is selected from optionally substituted phenylalkyl and optionally substituted heteroarylakyl; R.sup.3 is selected from alkyl, alkoxy, optionally substituted phenyl, optionally substituted phenoxy, optionally substituted phenylalkyl, optionally substituted phenylalkoxy, optionally substituted naphthyl,optionally substituted naphthyloxy, optionally substituted naphthylalkyl, optionally substituted naphthylalkoxy, optionally substituted heteroaryl, optionally substituted heteroaryloxy, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy; R.sup.4 is selected from hydrogen and optionally substituted alkyl; and Z is selected from --COOB, --C(OB)R.sup.6 R.sup.6, --COOalkyl, --COOalkylaryl, --CONR.sup.5 R.sup.6, and --COR.sup.6 are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment of amelioration of allergic and inflammatory disease states.

  结构式为##STR1##的化合物，其中A.sub.1是烷基或环烷基；A.sub.2是一个价键，烷基或环烷基；R.sub.1从氢、烷硫基、可选取代苯硫基、可选取代苯基烷基硫基、可选取代2-、3-和4-吡啶基硫基、可选取代2-和3-噻吩基硫基和可选取代2-噻唑基硫基中选择；R.sup.2从可选取代苯基烷基和可选取代杂环烷基烷基中选择；R.sup.3从烷基、烷氧基、可选取代苯基、可选取代苯氧基、可选取代苯基烷基、可选取代苯基烷氧基、可选取代萘基、可选取代萘氧基、可选取代萘基烷基、可选取代萘基烷氧基、可选取代杂环基、可选取代杂环氧基、可选取代杂环基烷基和可选取代杂环基烷氧基中选择；R.sup.4从氢和可选取代烷基中选择；Z从--COOB、--C(OB)R.sup.6 R.sup.6、--COOalkyl、--COOalkylaryl、--CONR.sup.5 R.sup.6和--COR.sup.6中选择，这些化合物是脂氧合酶酶的有效抑制剂，因此抑制了白三烯的生物合成。这些化合物在治疗过敏和炎症疾病状态方面是有用的。
• Indole carboxylate derivatives which inhibit leukotriene biosynthesis
  申请人：Abbott Laboratories

  公开号：US05288743A1

  公开（公告）日：1994-02-22

  Compounds of the structure ##STR1## where A is straight or branched divalent alkylene or divalent cycloalkylene, R.sub.1 is selected from hydrogen; alkylthio; optionally substituted phenylthio; optionally substituted phenylalkylthio; optionally substituted 2-, 3-, and 4-pyridyl; optionally substituted 2-, and 3-thienylthio; and optionally substituted 2-thiazolythio, R.sub.2 is selected from --COOB; --COOalkyl; --COOalkyl(carbocyclic aryl); --CONR.sub.5 R.sub.6 ; --COR.sub.6 ; and --OH, R.sub.3 is selected from phenylalkyl and heteroarylalkyl, and R.sub.4 is selected from optionally substituted alkoxy(carbocyclic aryl); optionally substituted carbocyclic aryloxy; optionally substituted heteroarylalkoxy; and optionally substituted heteroaryloxy are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

  结构式为##STR1##的化合物，其中A是直链或分支的二价烷基或二价环烷基，R.sub.1选自氢；烷基硫；可选取取代的苯基硫；可选取取代的苯基烷基硫；可选取取代的2-，3-和4-吡啶基；可选取取代的2-和3-噻吩硫；以及可选取取代的2-噻唑硫，R.sub.2选自--COOB；--COO烷基；--COO烷基(环烷基芳基)；--CONR.sub.5 R.sub.6；--COR.sub.6；和--OH，R.sub.3选自苯基烷基和杂环烷基烷基，R.sub.4选自可选取取代的烷氧基(环烷基芳基)；可选取取代的环烷基氧基；可选取取代的杂环烷基烷氧基；以及可选取取代的杂环氧基，是脂氧合酶酶的有效抑制剂，从而抑制白三烯的生物合成。这些化合物在治疗或缓解过敏和炎症性疾病状态方面是有用的。