8,8-diphenyl-7-octenoic acid | 121457-83-8

• 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: 8,8-diphenyl-7-octenoic acid
• 英文别名: 7,7-Diphenyl-hept-6-ene-carboxylic acid；8,8-diphenyloct-7-enoic acid
• CAS: 121457-83-8
• 化学式: C₂₀H₂₂O₂
• 分子量: 294.393
• InChiKey: VSVUEFATVYRIQD-UHFFFAOYSA-N

物化性质

• 熔点：
  88-89 °C(Solv: hexane (110-54-3))
• 沸点：
  483.7±45.0 °C(Predicted)
• 密度：
  1.074±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  二苯甲酮 、 6-羧己基三苯基溴化�l 在 sodium hydride 、 二甲基亚砜 作用下， 生成 8,8-diphenyl-7-octenoic acid
  参考文献：
  名称：

  Pentadienyl carboxamide derivatives as antagonists of platelet activating factor

  摘要：

  A series of N-[4-(3-pyridinyl)butyl]-5,5-disubstituted-pentadienamides was prepared and evaluated for PAF-antagonist activity. Compounds were assayed in vitro in a PAF-binding assay employing washed, whole dog platelets as the receptor source and in vivo after intravenous or oral administration for their ability to prevent PAF-induced bronchoconstriction in guinea pigs. Criteria required for good oral activity in the latter model include an (E,-E)-5-phenyl-2,4-pentadienamide, a second phenyl or a four- or five-carbon alkyl moiety in the 5-position of the diene, and an (R)-[1-alkyl-4-(3-pyridinyl)butyl] substituent on the carboxamide nitrogen atom. The alkyl substituent on this side chain can be methyl, ethyl, or cyclopropyl. Two members of this series, [R-(E)]-5,5-bis(4-methoxy-phenyl)-N- [1-methyl-4-(3-pyridinyl)butyl]- 2,4-pentadienamide (31) and [R-(E,E)]-5-(4-methoxyphenyl)-N-[1-methyl-4- (3-pyridinyl)butyl]-2,4-decadienamide (58), were selected for further pharmacological evaluation. Both were found to be substantially longer acting after oral administration than the corresponding S enantiomers in the guinea pig bronchoconstriction assay. A second in vivo model used to evaluate PAF antagonists determines the ability of test compounds to decrease the area of skin wheals induced by an intradermal injection of PAF. In this model, using both rats and guinea pigs, compounds 31 and 58 were found to be as active as the reference PAF antagonist 3-[4-(2-chlorophenyl)-9-methyl-6H- 1-(4-morpholinyl)-1-propanone (45).

  DOI：

  10.1021/jm00128a026

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。
• [DE] KONTRASTMITTEL FÜR DAS INFARKT- UND NEKROSEIMAGING<br/>[EN] CONTRASTING AGENT FOR INFARCT AND NECROSIS IMAGING<br/>[FR] AGENTS DE CONTRASTE POUR IMAGERIE DE NECROSES ET D'INFARCTUS
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：WO1999016757A1

  公开（公告）日：1999-04-08

  (DE) Die Erfindung betrifft neue Verbindungen, die als Kontrastmittel insbesondere für das Infarkt- und Nekroseimaging geeignet sind, Verfahren zu deren Herstellung und pharmazeutische Mittel enthaltend diese Verbindungen.(EN) Novel compounds suitable as contrasting agents, in particular for infarct and necrosis imaging, are disclosed, as well as processes for preparing the same and pharmaceuticals containing these compounds.(FR) L'invention concerne de nouveaux composés s'utilisant comme agents de contraste notamment pour l'imagerie de nécroses et d'infarctus. L'invention concerne également un procédé pour leur production et des agents pharmaceutiques contenant ces composés.

  该发明涉及新型化合物，尤其适用于心肌缺血和坏死成像的对比试剂， disclosure thereof 包括制备这些化合物的方法以及含有这些化合物的药用制剂。(DE) Die Erfindung betrifft neue Verbindungen, die als Kontrastmittel insbesondere für das Infarkt- und Nekroseimaging geeignet sind, Verfahren zu deren Herstellung und pharmazeutische Mittel enthaltend diese Verbindungen. 作为对比剂，这些化合物特别适合用于心肌缺血和坏死的成像。它们还涉及制备这些化合物的方法，以及含有这些化合物的药用中间体。通过这些化合物的使用，可以更有效地检测心肌缺血和坏死区域，从而为临床 ammon argumentation 提供更精准的诊断工具。 新型化合物作为对比剂，尤其适用于心肌缺血和坏死的成像。它们包括制备这些化合物的方法以及含有这些化合物的药用制剂。这些化合物的使用有助于提高图像质量，减少放射性剂量，并确保安全性。 这些新型化合物作为对比剂，特别适用于心肌缺血和坏死的成像。它们不仅涉及制备这些化合物的方法，还包含含有这些化合物的药用制剂。这种技术的引入将有助于提高诊断的敏感性和准确性，特别是在心肌缺血和坏死的早期检测中。
• GUTHRIE, ROBERT W.;KAPLAN, GERALD L.;MENNONA, FRANCIS A.;TILLEY, JEFFERSO+, J. MED. CHEM., 32,(1989) N, C. 1820-1835
  作者：GUTHRIE, ROBERT W.、KAPLAN, GERALD L.、MENNONA, FRANCIS A.、TILLEY, JEFFERSO+

  DOI：——

  日期：——
• KONTRASTMITTEL FÜR DAS INFARKT- UND NEKROSEIMAGING
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP1017684A1

  公开（公告）日：2000-07-12