(E)-3-(6-methoxy-3-pentyl-1H-inden-2-yl)-2-propenoic acid methyl ester | 121458-50-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚和异茚
• 英文名称: (E)-3-(6-methoxy-3-pentyl-1H-inden-2-yl)-2-propenoic acid methyl ester
• 英文别名: methyl (E)-3-(6-methoxy-3-pentyl-1H-inden-2-yl)prop-2-enoate
• CAS: 121458-50-2
• 化学式: C₁₉H₂₄O₃
• 分子量: 300.398
• InChiKey: QXZZUEAVJHVRRZ-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-3-(6-methoxy-3-pentyl-1H-inden-2-yl)-2-propenoic acid methyl ester 在 sodium hydroxide 、 草酰氯 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 1.33h， 生成 (E)-3-(6-methoxy-3-pentyl-1H-inden-2-yl)-2-propenoic acid chloride
  参考文献：
  名称：

  Propenyl carboxamide derivatives as antagonists of platelet-activating factor

  摘要：

  A series of N-[4-(3-pyridinyl)butyl] 3-substituted propenyl carboxamide derivatives bearing an unsaturated bicyclic moiety in the 3-position was prepared and evaluated for PAF (platelet activating factor) antagonist activity. These compounds represent conformationally constrained direct analogues of the corresponding potent 5-aryl-pentadienecarboxamides (5). Most of the new compounds were active in a PAF-binding assay employing whole, washed dog platelets as the receptor source and inhibited PAF-induced bronchoconstriction in guinea pigs after intravenous administration. However, oral activity in the PAF-induced bronchoconstriction model was highly sensitive to the nature and substitution of the bicyclic ring system. The most interesting compounds included [R-(E)]-(1-butyl-6-methoxy-2-naphthyl)-N-[1-methyl-4-(3- pyridinyl)butyl]-2-propenamide (4b), [R-(E)]-(3-butyl-6-methoxy-2- benzo[b]thiophene-yl)-N-[1-methyl-4-(3-pyridinyl)butyl]-2-propenamide (4k), and [R-(E)]-(3-butyl-6-methoxy-1-methyl-2-indoly)-N-[1-ethyl-4- (3-pyridinyl)butyl]-2-propenamide (4l) which inhibited PAF-induced broncho-constriction in guinea pigs with IC50s of 3.0-5.4 mg/kg, when the animals were challenged 2 h after drug treatment. They were also highly effective 6 h after a 50 mg/kg oral dose. This study supports the notion that the key remote aromatic ring present in the 5-arylpentadienecarboxamides (5) is preferentially coplanar with the diene system for good PAF antagonist activity.

  DOI：

  10.1021/jm00172a029
• 作为产物：
  描述：

  正戊基溴化镁 在 盐酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.17h， 生成 (E)-3-(6-methoxy-3-pentyl-1H-inden-2-yl)-2-propenoic acid methyl ester
  参考文献：
  名称：

  Propenyl carboxamide derivatives as antagonists of platelet-activating factor

  摘要：

  A series of N-[4-(3-pyridinyl)butyl] 3-substituted propenyl carboxamide derivatives bearing an unsaturated bicyclic moiety in the 3-position was prepared and evaluated for PAF (platelet activating factor) antagonist activity. These compounds represent conformationally constrained direct analogues of the corresponding potent 5-aryl-pentadienecarboxamides (5). Most of the new compounds were active in a PAF-binding assay employing whole, washed dog platelets as the receptor source and inhibited PAF-induced bronchoconstriction in guinea pigs after intravenous administration. However, oral activity in the PAF-induced bronchoconstriction model was highly sensitive to the nature and substitution of the bicyclic ring system. The most interesting compounds included [R-(E)]-(1-butyl-6-methoxy-2-naphthyl)-N-[1-methyl-4-(3- pyridinyl)butyl]-2-propenamide (4b), [R-(E)]-(3-butyl-6-methoxy-2- benzo[b]thiophene-yl)-N-[1-methyl-4-(3-pyridinyl)butyl]-2-propenamide (4k), and [R-(E)]-(3-butyl-6-methoxy-1-methyl-2-indoly)-N-[1-ethyl-4- (3-pyridinyl)butyl]-2-propenamide (4l) which inhibited PAF-induced broncho-constriction in guinea pigs with IC50s of 3.0-5.4 mg/kg, when the animals were challenged 2 h after drug treatment. They were also highly effective 6 h after a 50 mg/kg oral dose. This study supports the notion that the key remote aromatic ring present in the 5-arylpentadienecarboxamides (5) is preferentially coplanar with the diene system for good PAF antagonist activity.

  DOI：

  10.1021/jm00172a029

文献信息

• Pyridine compounds which are useful in treating a disease state
  申请人：Hoffman-La Roche Inc.

  公开号：US04927838A1

  公开（公告）日：1990-05-22

  The invention relates to compounds of the formula ##STR1## wherein Y and Y' are hydrogen or taken together are O or S, *A is paraphenylene or *----(CH.sub.2).sub.n --(X).sub.s --(CH.sub.2).sub.r ----, X is O, S or --CH.dbd.CH--, n or r, independently, are integers from 0 to 3, m is an integer from 0 to 1, s is an integer from 0 to 1, provided that when s is 1, n+m must be at least 2, t is an integer from 0 to 10, R.sub.1 and R.sub.2, independently, are lower alkyl, lower alkenyl or aryl, or one of R.sub.1 or R.sub.2 is hydrogen and the other is ##STR2## wherein W is ##STR3## --CH.sub.2 --CH.sub.2 --, --CH.sub.2 --, O, S, or ##STR4## and X.sub.1 is lower alkyl, phenyl unsubstituted or mono-, di- or trisubstituted by lower alkoxy, lower alkyl or halogen, and X.sub.2, X.sub.3 and X.sub.4, independently, are hydrogen, lower alkyl, lower alkoxy or halogen, R.sub.3 is hydrogen, lower alkyl or aryl, R.sub.4 is hydrogen, lower alkyl, aryl, aryl-lower alkyl or acyl, R.sub.5 is hydrogen or lower alkyl, R.sub.6 is hydrogen, lower alkyl, cycloalkyl, Het-lower alkyl or aryl, Het is a monocyclic 6-membered heteroaromatic radical containing one or two nitrogen atoms, which radical may be substituted by lower alkyl, halogen or aryl, and the asterisk denotes the point of attachment, and when R.sub.5 and R.sub.6 are different, their enantiomers and racemic mixtures thereof, when R.sub.1 and R.sub.2 are different, their geometric isomers, and pharmaceutically acceptable acid addition salts thereof.

  本发明涉及公式##STR1##的化合物，其中Y和Y'为氢或一起取O或S，*A为对苯二甲基或*----（CH.sub.2).sub.n --(X).sub.s --(CH.sub.2).sub.r ----，X为O、S或--CH.dbd.CH--，n或r独立地为0至3的整数，m为0至1的整数，s为0至1的整数，但当s为1时，n+m必须至少为2，t为0至10的整数，R.sub.1和R.sub.2独立地为较低的烷基、较低的烯基或芳基，或R.sub.1或R.sub.2之一为氢，另一个为##STR2##其中W为##STR3## --CH.sub.2 --CH.sub.2 --，--CH.sub.2 --，O，S或##STR4##，X.sub.1为较低的烷基、未取代的苯基或被较低的烷氧基、较低的烷基或卤素单、二或三取代的苯基，X.sub.2、X.sub.3和X.sub.4独立地为氢、较低的烷基、较低的烷氧基或卤素，R.sub.3为氢、较低的烷基或芳基，R.sub.4为氢、较低的烷基、芳基、芳基-较低的烷基或酰基，R.sub.5为氢或较低的烷基，R.sub.6为氢、较低的烷基、环烷基、Het-较低的烷基或芳基，Het是一种含有一个或两个氮原子的单环6成员杂环芳基，该基团可以被较低的烷基、卤素或芳基取代，星号表示附着点，当R.sub.5和R.sub.6不同时，它们的对映异构体和外消旋混合物，当R.sub.1和R.sub.2不同时，它们的几何异构体，以及其药学上可接受的酸添加盐。
• Substituted alkene carboxylic acid amides and derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0298466A2

  公开（公告）日：1989-01-11

  There are described compounds of the general formula wherein Y and Y′ are hydrogen or taken together are O or S, *A is paraphenylene or *-(CH₂)n-(X)s-(CH₂)r-, X is O, S or -CH=CH-, n and r, independently are integers from 0 to 3, m is the integer 0 or 1, s is the integer 0 or 1, provided that when s is 1, n+m is at least 2, t is an integer from 0 to 10, R₁ and R₂, independently, are lower alkyl, lower alkenyl or aryl, or one of R₁ and R₂ is hydrogen and the other is W is -CX₃=CX₄-, -CH₂-CH₂-, -CH₂-, O, S or -NX₅-, X₁ is lower alkyl, phenyl or phenyl with up to 3 substituents selected from lower alkoxy, lower alkyl and halogen, X₂, X₃ and X₄, independently, are hydrogen, lower alkyl, lower alkoxy or halogen, X₅ is lower alkyl, R₃ is hydrogen, lower alkyl or aryl, R₄ is hydrogen, lower alkyl, aryl, aryl-lower alkyl or acyl, R₅ is hydrogen or lower alkyl, R₆ is hydrogen,     lower alkyl, lower cycloalkyl, Het-lower alkyl or aryl, Het is a monocyclic 6-membered heteroaromatic radical containing one or two nitrogen atoms, which radical may be substituted by lower alkyl, halogen or aryl, and the asterisk denotes the point of attachment, when R₅ and R₆ are different, enantiomers and racemic mixtures thereof, when R₁ and R₂ are different, geometric isomers thereof, and pharmaceutically acceptable acid addition salts thereof. These compounds exhibit activity as platelet activating factor (PAF) antagonists and are, therefore, useful in disease states characterized by excess platelet activating factor or for the prevention and treatment of cardiovascular diseases, pulmonary diseases, immunological disorders, inflammatory diseases, dermatological disorders, shocks or transplant rejections.

  所述化合物通式如下 其中 Y 和 Y′为氢或合起来为 O 或 S，*A 为对苯二甲酸或 *-(CH₂)n-(X)s-(CH₂)r-，X 为 O、S 或-CH=CH-，n 和 r 独立地为 0 至 3 的整数，m 为 0 或 1 的整数、s 是 0 或 1 的整数，条件是当 s 为 1 时，n+m 至少为 2，t 是 0 至 10 的整数，R₁ 和 R₂ 独立地是低级烷基、低级烯基或芳基，或者 R₁ 和 R₂ 中的一个是氢，另一个是 W 是-CX₃=CX₄-、-CH₂-CH₂-、-CH₂-、O、S 或-NX₅-，X₁ 是低级烷基、苯基或带有最多 3 个选自低级烷氧基、低级烷基和卤素的取代基的苯基，X₂、X₃ 和 X₄ 独立地、是氢、低级烷基、低级烷氧基或卤素，X₅ 是低级烷基，R₃ 是氢、低级烷基或芳基，R₄ 是氢、低级烷基、芳基、芳基-低级烷基或酰基，R₅ 是氢或低级烷基，R₆ 是氢、 R₅是氢或低级烷基，R₆是氢、低级烷基、低级环烷基、Het-低级烷基或芳基，Het 是含有一个或两个氮原子的单环六元杂芳基，该基可被低级烷基、卤素或芳基取代，星号表示连接点、 当 R₅ 和 R₆ 不同时，其对映体和外消旋混合物；当 R₁ 和 R₂ 不同时，其几何异构体；以及其药学上可接受的酸加成盐。 这些化合物具有血小板活化因子（PAF）拮抗剂的活性，因此可用于以血小板活化因子过量为特征的疾病状态，或用于预防和治疗心血管疾病、肺部疾病、免疫性疾病、炎症性疾病、皮肤病、休克或移植排斥反应。
• GUTHRIE, ROBERT W.;KAPLAN, GERALD L.;MENNONA, FRANCIS A.;TILLEY, JEFFERSO+, J. MED. CHEM., 33,(1990) N0, C. 2856-2864
  作者：GUTHRIE, ROBERT W.、KAPLAN, GERALD L.、MENNONA, FRANCIS A.、TILLEY, JEFFERSO+

  DOI：——

  日期：——
• US4927838A
  申请人：——

  公开号：US4927838A

  公开（公告）日：1990-05-22
• Propenyl carboxamide derivatives as antagonists of platelet-activating factor
  作者：Robert W. Guthrie、Gerald L. Kaplan、Francis A. Mennona、Jefferson W. Tilley、Richard W. Kierstead、Margaret O'Donnell、Herman Crowley、Bohdan Yaremko、Ann F. Welton

  DOI：10.1021/jm00172a029

  日期：1990.10

  A series of N-[4-(3-pyridinyl)butyl] 3-substituted propenyl carboxamide derivatives bearing an unsaturated bicyclic moiety in the 3-position was prepared and evaluated for PAF (platelet activating factor) antagonist activity. These compounds represent conformationally constrained direct analogues of the corresponding potent 5-aryl-pentadienecarboxamides (5). Most of the new compounds were active in a PAF-binding assay employing whole, washed dog platelets as the receptor source and inhibited PAF-induced bronchoconstriction in guinea pigs after intravenous administration. However, oral activity in the PAF-induced bronchoconstriction model was highly sensitive to the nature and substitution of the bicyclic ring system. The most interesting compounds included [R-(E)]-(1-butyl-6-methoxy-2-naphthyl)-N-[1-methyl-4-(3- pyridinyl)butyl]-2-propenamide (4b), [R-(E)]-(3-butyl-6-methoxy-2- benzo[b]thiophene-yl)-N-[1-methyl-4-(3-pyridinyl)butyl]-2-propenamide (4k), and [R-(E)]-(3-butyl-6-methoxy-1-methyl-2-indoly)-N-[1-ethyl-4- (3-pyridinyl)butyl]-2-propenamide (4l) which inhibited PAF-induced broncho-constriction in guinea pigs with IC50s of 3.0-5.4 mg/kg, when the animals were challenged 2 h after drug treatment. They were also highly effective 6 h after a 50 mg/kg oral dose. This study supports the notion that the key remote aromatic ring present in the 5-arylpentadienecarboxamides (5) is preferentially coplanar with the diene system for good PAF antagonist activity.