ethyl (E)-7-(3-pyridyl)-7-phenylhept-6-enoate | 93944-00-4

• 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: ethyl (E)-7-(3-pyridyl)-7-phenylhept-6-enoate
• 英文别名: ethyl (E)-7phenyl-7-(3-pyridyl)-6-heptenoate；ethyl (E)-7-phenyl-7-(pyridin-3-yl)-6-heptenoate；(E)-7-phenyl-7-(3-pyridyl)-6-heptenoate ethyl ester；Ethyl (E)-7-phenyl-7-(3-pyridyl)-6-heptenoate；ethyl (E)-7-phenyl-7-pyridin-3-ylhept-6-enoate
• CAS: 93944-00-4
• 化学式: C₂₀H₂₃NO₂
• 分子量: 309.408
• InChiKey: JEQHQLCBOOCOCY-CPNJWEJPSA-N

物化性质

• 沸点：
  452.0±44.0 °C(Predicted)
• 密度：
  1.057±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (E)-7-(3-pyridyl)-7-phenylhept-6-enoate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 伊波格雷
  参考文献：
  名称：

  Thromboxane synthetase inhibitors (TXSI). Design, synthesis, and evaluation of a novel series of .omega.-pyridylalkenoic acids

  摘要：

  A novel series of omega-pyridylalkenoic acids has been prepared by applying the Wittig reaction. Modifications were made in the omega-aryl moiety, the alkylene chain length, the alpha-methylene group adjacent to the carbonyl group, and the carboxyl group of the molecule. The compounds were tested as inhibitors of thromboxane synthetase in an in vitro assay and in ex vivo experiments with the rat. Most members of this new class of thromboxane synthetase inhibitors (TXSI) showed good activity in both assay systems. (E)-7-Phenyl-7-(3-pyridyl)-6-heptenoic acid (9c; CV-4151) was one of the most potent compounds in in vitro enzyme inhibition (IC50 = 2.6 X 10(-8) M) and, when orally administered, the most potent and long acting in the inhibition of blood thromboxane A2 production in the rat. New conceptual models I-III for the enzyme-substrate (prostaglandin H2, PGH2) and the enzyme-TXSI interactions are proposed for understanding the molecular design and structure-activity relations.

  DOI：

  10.1021/jm00381a005
• 作为产物：
  描述：

  (E,Z)-7-phenyl-7-(pyridin-3-yl)-6-heptenoic acid 在 硫酸 作用下， 以 乙醇 为溶剂， 生成 (Z)-7-phenyl-7-(3-pyridyl)-6-heptenoate ethyl ester 、 ethyl (E)-7-(3-pyridyl)-7-phenylhept-6-enoate
  参考文献：
  名称：

  EP807626

  摘要：

  公开号：

文献信息

• Thromboxane synthetase inhibiting 3-(1-alkenyl) pyridines
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04563446A1

  公开（公告）日：1986-01-07

  Novel compounds of the formula: ##STR1## wherein R.sup.2 is an aromatic or heterocyclic group, which may optionally be substituted, R.sup.2 is a methyl group, a hydroxymethyl group, a nitroxymethyl group, a formyl group, a nitrogen-containing five-membered ring-methyl group, an acetal-methyl group, a trialkylsilyloxymethyl group, an alkyl- or aryl-sulfonyloxymethyl group, an alkyl- or aryl-sulfonylaminocarbonyloxymethyl group, an acyloxymethyl group, an alkoxycarbonyloxymethyl group, a halogenomethyl group, an alkoxymethyl group, an aryloxymethyl group, a cyano group, a carbamoyl group which may optionally be substituted, a carbamoyloxymethyl group which may optionally be substituted, a thiocarbamoyloxymethyl group which may optionally be substituted, and an alkoxycarbonyl group, n is an integer of 1 to 20, and ##STR2## provided that n is an integer of 9 to 20 when ##STR3## and, at the same time, R.sup.2 is a carboxyl group or an alkoxycarbonyl group, or a pharmacologically acceptable salt thereof, have a selective inhibitory action on biosynthesis of thromboxane A.sub.2 (TXA.sub.2) and an effect of enhancing the production of prostaglandin I.sub.2 (PGI.sub.2), and can be used for mammals to prevent and treat arterial thrombosis caused by platelet aggregation or ischemic diseases caused by vasospasms in cardiac, cerebral and peripheral circulatory system (e.g. cardiac infarction, stroke, occlusion of blood vessels in kidney, lung and other organs, pectic ulcer, etc.).

  式（I）的新化合物：##STR1## 其中R2是芳香族或杂环基团，可任选被取代，R2是甲基、羟甲基、硝羟甲基、甲酰基、含氮五元环甲基、缩醛甲基、三烷基硅氧甲基、烷基或芳基磺酰氧甲基、烷基或芳基磺酰氨基羰氧甲基、酰氧甲基、烷氧羰氧甲基、卤甲基、烷氧甲基、芳氧甲基、氰基、可任选被取代的氨基甲酰基、可任选被取代的氨基甲酰氧甲基、可任选被取代的硫代氨基甲酰氧甲基和烷氧羰基，n是1至20的整数，且##STR2## 条件是当##STR3## 时，n是9至20的整数，同时，R2是羧基或烷氧羰基，或其药理学上可接受的盐，具有选择性抑制血栓素A2（TXA2）生物合成和增强前列环素I2（PGI2）产生的作用，可用于预防和治疗由血小板聚集或血管痉挛引起的动脉血栓形成或心肌、脑和外周循环系统的缺血性疾病（例如心肌梗死、中风、肾、肺和其他器官的血管闭塞、消化性溃疡等）。
• N-HYDROXYUREA DERIVATIVES
  申请人：Nikken Chemicals Company, Limited

  公开号：EP0807626A1

  公开（公告）日：1997-11-19

  An N-hydroxyurea derivative or a pharmacologically acceptable salt thereof having the formula (I): wherein, A represents CH, CH-CH2, CH-O, or C=CH, X represents O or S, B represents a C1 to C8 alkylene, C2 to C6 alkenylene, m-phenylene, or p-phenylene, R represents a hydrogen atom, halogen atom, C1 to C4 alkyl which may be substituted with a halogen atom, C1 to C4 alkoxy which may be substituted with a halogen atom, or nitro, R1 represents a hydrogen atom, C1 to C4 lower alkyl, or phenyl, and R2 represents a hydrogen atom, C1 to C4 alkyl, cycloalkyl, phenyl which may be substituted with a substituent, or methanesulfonyl.

  一种具有式(I)的 N-羟基脲衍生物或其药理学上可接受的盐： 其中，A 代表 CH、CH-CH2、CH-O 或 C=CH，X 代表 O 或 S，B 代表 C1 至 C8 亚烷基、C2 至 C6 烯基、间苯二酚或对苯二酚，R 代表氢原子、卤素原子、可被卤素原子取代的 C1 至 C4 烷基、可被卤素原子取代的 C1 至 C4 烷氧基或硝基，R1 代表氢原子、卤素原子、可被卤素原子取代的 C1 至 C4 烷氧基或硝基、R1 代表氢原子、C1-C4 低级烷基或苯基，R2 代表氢原子、C1-C4 烷基、环烷基、可被取代基取代的苯基或甲磺酰基。
• A Novel Approach to Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors Based on the Link of 1,3-Dioxane-Thromboxane Receptor Antagonists and -Thromboxane Synthase Inhibitors
  作者：Norman Ackerley、Andrew G. Brewster、George R. Brown、David S. Clarke、Alan J. Foubister、Stephen J. Griffin、Julian A. Hudson、Michael J. Smithers、Paul R. O. Whittamore

  DOI：10.1021/jm00010a005

  日期：1995.5

  A new class of dual-acting racemic thromboxane receptor antagonist/thromboxane synthase inhibitors is reported, based on the novel approach of linking the known thromboxane synthase inhibitors (TXSI) dazoxiben (2) or isbogrel(11) (separately) to thromboxane receptor antagonists (TXRA) from the 1,3-dioxane series, such as ICI 192605 (10). Dual activity was observed in vitro with inhibition of human microsomal thromboxane synthase in the range IC50 = 0.01-1.0 mu M and receptor antagonist activity by inhibition of U46619-induced human platelet aggregation in the range pA(2) = 5.5-7.0. The in vitro results also showed that very large groups could be tolerated at the selected substitution positions of the TXRA and TXSI components. Oral activity was observed in ex vivo tests in both rats and dogs at a dose of 10 mg/kg. Thus, (E)-7-[4-[[4-[(2SR,4SR,5RS)-5-[(Z)-5-carboxypent-2-enyl]-4-(2-hydroxyphenyl)-1,3-dioxan-2-yl]benzyl]oxy]phenyl]-7-(3-pyridyl)hept-6-enoic acid (110) was both an antagonist (pA(2) = 6.7) and a synthase inhibitor (IC50 = 0.02 mu M). On oral dosing (10 mg/kg) to rats and dogs, 110 showed significant TXRA activity [concentration ratio >64 (rat, 3 h) and >59 +/- 11.3 (dog, 2 h) vs ex vivo U46619-induced platelet aggregation]. Inhibition of thromboxane synthase at the respective time points in these experiments was 81 +/- 4.4% (rat) and 69 +/- 4.8% (dog).
• KATO, KANEYOSHI;OHKAWA, SHIGENORI;TERAO, SHINJI;TERASHITA, ZEN-ICHI;NISHI+, J. MED. CHEM., 1985, 28, N 3, 287-294
  作者：KATO, KANEYOSHI、OHKAWA, SHIGENORI、TERAO, SHINJI、TERASHITA, ZEN-ICHI、NISHI+

  DOI：——

  日期：——