methyl 3-methoxy-4-<(6-nitroindol-1-yl)methyl>benzoate | 104437-17-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 3-methoxy-4-<(6-nitroindol-1-yl)methyl>benzoate
• 英文别名: methyl 3-methoxy-4-((6-nitro-1H-indol-1-yl)methyl)benzoate；methyl 3-methoxy-4-(6-nitroindol-1-ylmethyl)benzoate；methyl 3-methoxy-4-[(6-nitroindol-1-yl)methyl]benzoate
• CAS: 104437-17-4
• 化学式: C₁₈H₁₆N₂O₅
• 分子量: 340.335
• InChiKey: UAEBFPUJIXIFRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  86.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-methoxy-4-<(6-nitroindol-1-yl)methyl>benzoate 在 palladium on activated charcoal 氢气 、 溶剂黄146 、 乙酸乙酯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 48.25h， 生成 methyl 4-<<6-indol-1-yl>methyl>-3-methoxybenzoate
  参考文献：
  名称：

  Evolution of a series of peptidoleukotriene antagonists: synthesis and structure-activity relationships of 1,6-disubstituted indoles and indazoles

  摘要：

  A perception of structural similarities between two independent series of leukotriene antagonists (one emanating from FPL 55712 and one based upon the leukotrienes themselves) led to the discovery of a novel class of indole and indazole derived antagonists of peptidoleukotrienes. A systematic exploration of C-6 substituted 4-(indol-1-ylmethyl)-3-methoxybenzoic acids identified cyclopentylacetamide and cyclopentylurethane as preferred substituents. The corresponding indazoles were equipotent. These compounds are selective leukotriene antagonists with pKB values of 7.5-7.8 vs LTE4 on guinea pig trachea.

  DOI：

  10.1021/jm00168a036
• 作为产物：
  描述：

  3-甲氧基-4-甲基苯甲酸 在 溴 、 potassium carbonate 、 乙酰氯 作用下， 以 四氯化碳 、 丙酮 为溶剂， 反应 88.0h， 生成 methyl 3-methoxy-4-<(6-nitroindol-1-yl)methyl>benzoate
  参考文献：
  名称：

  Evolution of a series of peptidoleukotriene antagonists: synthesis and structure-activity relationships of 1,6-disubstituted indoles and indazoles

  摘要：

  A perception of structural similarities between two independent series of leukotriene antagonists (one emanating from FPL 55712 and one based upon the leukotrienes themselves) led to the discovery of a novel class of indole and indazole derived antagonists of peptidoleukotrienes. A systematic exploration of C-6 substituted 4-(indol-1-ylmethyl)-3-methoxybenzoic acids identified cyclopentylacetamide and cyclopentylurethane as preferred substituents. The corresponding indazoles were equipotent. These compounds are selective leukotriene antagonists with pKB values of 7.5-7.8 vs LTE4 on guinea pig trachea.

  DOI：

  10.1021/jm00168a036

文献信息

• Indazole compounds, pharmaceutical compositions and use
  申请人：ICI Americas Inc.

  公开号：US04997844A1

  公开（公告）日：1991-03-05

  The invention provides a series of novel heterocyclic amides of the formula I in which the group A CRa can be --CRb.dbd.CRa--, --CHRb--CHRa-- or --N.dbd.CRa--, the amidic group Re.L can be Re.X.CO.NH, Re.X.CS.NH or Re.NH.CO attached at position 4, 5 or 6 of the benzenoid moiety, Z is an acid group selected from the group consisting of carboxy, an acylsulphonamide residue of the formula CO.NH.SO.sub.n Rg and a tetrazolyl residue of the formula II, and the radicals Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, n, X, G.sup.1, Q and G.sup.2 have the meanings defined in the following specification. The compounds of formula I are leukotriene antagonists. The invention also provides pharmaceutically acceptable salts of the formula I compounds; pharmaceutical compositions containing the formula I compounds, or their salts, for use in the treatment of, for example, allergic or inflammatory diseases, or endotoxic or traumatic shock conditions; and processes for the manufacture of the formula I compounds, as well as intermediates for use in such manufacture.

  该发明提供了一系列新颖的杂环酰胺，其化学式为I，在该化学式中，基团A CRa可以是--CRb.dbd.CRa--，--CHRb--CHRa--或--N.dbd.CRa--，酰胺基团Re.L可以是连接在苯环部分的第4、5或6位的Re.X.CO.NH，Re.X.CS.NH或Re.NH.CO，Z是从羧基、公式CO.NH.SO.sub.n Rg的酰磺胺残基或公式II的四唑基残基中选择的酸基团，基团Ra、Rb、Rc、Rd、Re、Rf、Rg、Rh、n、X、G.sup.1、Q和G.sup.2的含义在以下说明中定义。化合物I的化学式是白三烯拮抗剂。该发明还提供了化合物I的药学上可接受的盐；含有化合物I或其盐的药物组合物，用于治疗过敏性或炎症性疾病、内毒素性休克或创伤性休克等疾病；以及用于制造化合物I的方法，以及用于该制造的中间体。
• Dual Farnesoid X Receptor/Soluble Epoxide Hydrolase Modulators Derived from Zafirlukast
  作者：Simone Schierle、Moritz Helmstädter、Jurema Schmidt、Markus Hartmann、Maximiliane Horz、Astrid Kaiser、Lilia Weizel、Pascal Heitel、Anna Proschak、Victor Hernandez‐Olmos、Ewgenij Proschak、Daniel Merk

  DOI：10.1002/cmdc.201900576

  日期：2020.1.7

  X receptor (FXR) and the enzyme soluble epoxide hydrolase (sEH) are validated molecular targets to treat metabolic disorders such as non-alcoholic steatohepatitis (NASH). Their simultaneous modulation in vivo has demonstrated a triad of anti-NASH effects and thus may generate synergistic efficacy. Here we report dual FXR activators/sEH inhibitors derived from the anti-asthma drug Zafirlukast. Systematic

  核法呢素X受体（FXR）和酶溶性环氧水解酶（sEH）是经过验证的分子靶标，可用于治疗代谢性疾病，例如非酒精性脂肪性肝炎（NASH）。它们在体内的同时调节已显示出三联体的抗NASH效应，因此可能产生协同功效。在这里，我们报告了来自抗哮喘药Zafirlukast的双重FXR激活剂/ sEH抑制剂。支架的系统结构优化对FXR和sEH产生了有利的双重功效，同时消除了先导药物的半胱氨酸白三烯受体拮抗作用。所得的多药理学活性谱在治疗肝脏相关的代谢性疾病方面有希望。
• Indole and indazole keto sulphones as leukotriene antagonists
  申请人：ICI Americas Inc.

  公开号：US04837235A1

  公开（公告）日：1989-06-06

  This invention provides a series of novel keto sulfones of formula I ##STR1## in which the group .dbd.A-- is selected from .dbd.C(Ra)-- and .dbd.N-- and the other radicals have the meanings defined in the following specification. The compounds of formula I are leukotriene antagonists. The invention also provides pharmaceutically acceptable salts of the formula I compounds; pharmaceutical compositions containing the formula I compound, or their salts, for use in the treatment of, for example, allergic or inflammatory diseases, or endotoxic or traumatic shock conditions; and processes for the manufacture of the formula I compounds, as well as intermediates for use in such manufacture.

  这项发明提供了一系列新颖的化合物，其化学式为I ##STR1## 其中，基团 .dbd.A-- 从 .dbd.C(Ra)-- 和 .dbd.N-- 中选择，其他基团的含义在下文规定。化合物I是白三烯拮抗剂。该发明还提供了化合物I的药学上可接受的盐；含有化合物I或其盐的药物组合物，用于治疗过敏性或炎症性疾病，或内毒素性或创伤性休克等疾病；以及用于制造化合物I的工艺，以及用于制造中间体的工艺。
• Heterocyclic amides and leucotriene antagonistic use thereof
  申请人：ICI Americas Inc.

  公开号：US05234942A1

  公开（公告）日：1993-08-10

  The invention provides a series of novel heterocyclic amides of the formula I in which the group A; CRa can be --CRb.dbd.CRa--, --CHRb--CHRa-- or --N.dbd.CRa--, the amidic group Re.L can be Rd.X.CO.NH, Re.X.CS.NH or Re.NH.CO attached to position 4, 5 or 6 of the benzenoid moiety, z is an acid group selected from the group consisting of carboxy, an acylsulphonamide residue of the formula CO.NH.SO.sub.n Rg and a tetrazolyl residue of the formula II and the radicals Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, n, X, G.sup.1,Q and G.sup.2 have the meanings defined in the following specification. The compounds of formula I are leukotriene antagonists. The invention also provides pharmaceutically acceptable salts of the formula I compounds; pharmaceutical compositions containing the formula I compounds, or their salts, for use in the treatment of, for example, allergic or inflammatory diseases, or endotoxic or traumatic shock conditions; and processes for the manufacture of the formula I compounds, as well as intermediates for use in such manufacture.

  本发明提供了一系列新型杂环酰胺，其化学式为I，其中A；CRa可以是--CRb.dbd.CRa--，--CHRb--CHRa--或--N.dbd.CRa--，酰胺基团Re.L可以是连接到苯环部分的4、5或6位置的Rd.X.CO.NH、Re.X.CS.NH或Re.NH.CO，z是从羧基、公式CO.NH.SO.sub.n Rg的酰基磺酰胺残基或公式II的四唑基残基中选择的酸基，而基团Ra、Rb、Rc、Rd、Re、Rf、Rg、Rh、n、X、G.sup.1、Q和G.sup.2的含义在下文规定。化合物I的是白三烯拮抗剂。本发明还提供了化合物I的药学上可接受的盐；含有化合物I或其盐的制药组合物，用于治疗过敏性或炎症性疾病、内毒素或创伤性休克等；以及化合物I的制备方法，以及用于制造这种化合物的中间体。
• BROWN, FREDERICK J.;YEE, YING K.;CRONK, LAURA A.;HEBBEL, KEVIN C.;KRELL, +, J. MED. CHEM., 33,(1990) N, C. 1771-1781
  作者：BROWN, FREDERICK J.、YEE, YING K.、CRONK, LAURA A.、HEBBEL, KEVIN C.、KRELL, +

  DOI：——

  日期：——