<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

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: <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
• 英文别名: 1-(4-chlorobenzyl)-2-(2,2-dimethyl-3-(1H-tetrazol-5-yl)propyl)-4-methyl-6-((5-phenylpyridin-2-yl)methoxy)-4,5-dihydro-1H-thiopyrano[2,3,4-cd]indole；2-[(4-chlorophenyl)methyl]-3-[2,2-dimethyl-3-(2H-tetrazol-5-yl)propyl]-6-methyl-9-[(5-phenylpyridin-2-yl)methoxy]-5-thia-2-azatricyclo[6.3.1.04,12]dodeca-1(12),3,8,10-tetraene
• 化学式: C₃₆H₃₅ClN₆OS
• 分子量: 635.233
• InChiKey: ZXTQNTHPGKKAHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-苯基-2-甲基吡啶N-氧化物 在 lithium aluminium tetrahydride 、 sodium hydride 、 三乙胺 、 三正丁基叠氮化锡 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 邻二氯苯 为溶剂， 反应 7.0h， 生成 <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
  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

文献信息

• Thiopyrano (2,3,4-c,d) indoles as inhibitors of leukotriene biosynthesis
  申请人：MERCK FROSST CANADA INC.

  公开号：EP0518426A1

  公开（公告）日：1992-12-16

  Compounds having the formula I: 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.

  具有式 I 的化合物： 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、脑痉挛、肾小球肾炎、肝炎、内毒素血症、银屑病、葡萄膜炎和异体移植排斥反应，以及预防动脉粥样硬化斑块的形成。
• Use of Ltb4 Inhibitors for the Treatment of B-Cell Leukemias and Lymphomas
  申请人：Claesson Hans-Erik

  公开号：US20080081835A1

  公开（公告）日：2008-04-03

  The invention relates to the use of an inhibitor of the biosynthesis and/or function of LTB 4 for the manufacture of a medicament for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), B-prolymphocytic leukemia (B-PLL) or B-cell lymphoma. Preferably, the inhibitor of the biosynthesis and/or function of LTB 4 is the inhibitor of 5-LO BWA4C or the inhibitor of FLAP MK-886.
• Method and composition for treating inflammatory disorders
  申请人：Pereswetoff-Morath Lena

  公开号：US20090220583A1

  公开（公告）日：2009-09-03

  There is provided homogeneous pharmaceutical compositions for the treatment of inflammatory disorders comprising an antiinflammatory and/or antihistaminic active ingredient, a polar lipid liposome and a pharmaceutically-acceptable aqueous carrier.
• Method and Composition for Treating Inflammatory Disorders
  申请人：Meda AB

  公开号：US20160166508A1

  公开（公告）日：2016-06-16

  There is provided homogeneous pharmaceutical compositions for the treatment of inflammatory disorders comprising an antiinflammatory and/or antihistaminic active ingredient, a polar lipid liposome and a pharmaceutically-acceptable aqueous carrier.
• US5202321A
  申请人：——

  公开号：US5202321A

  公开（公告）日：1993-04-13