(E)-5,5-bis(3-chlorophenyl)-2,4-pentadienoic acid | 120553-26-6

• 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: (E)-5,5-bis(3-chlorophenyl)-2,4-pentadienoic acid
• 英文别名: (2E)-5,5-bis(3-chlorophenyl)penta-2,4-dienoic acid
• CAS: 120553-26-6
• 化学式: C₁₇H₁₂Cl₂O₂
• 分子量: 319.187
• InChiKey: UINMMWNRIXCJON-YCRREMRBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-5,5-bis(3-chlorophenyl)-2,4-pentadienoic acid 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (E)-5,5-bis(3-chlorophenyl)-N-[4-(3-pyridinyl)butyl]-2,4-pentadienamide
  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
• 作为产物：
  描述：

  3,3-二氯苯甲酮 在 sodium hydroxide 作用下， 反应 0.5h， 生成 (E)-5,5-bis(3-chlorophenyl)-2,4-pentadienoic 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

• Pentadieneamide compounds which have useful activity of treating a
  申请人：Hoffmann-La Roche Inc.

  公开号：US04975438A1

  公开（公告）日：1990-12-04

  Compounds of the formula ##STR1## Y is O or S, *A is paraphenylene or *--(CH.sub.2).sub.n --(X).sub.m --(CH.sub.2).sub.r --, X is O, S or --CH.dbd.CH--, n or r, independently, are integers from 0 to 3, s is an integer from 0 to 1, m is an integer from 0 to 1, provided that when m is 1, n+s must be at least 2, R.sub.1 and R.sub.2, independently, are hydrogen, lower alkyl, cycloalkyl, lower alkenyl, Het, Aryl, R.sub.3, R.sub.4 and R.sub.8, independently, are hydrogen, lower alkyl, aryl, R.sub.5 and R.sub.6, independently, are hydrogen or lower alkyl, R.sub.7 is hydrogen, lower alkyl, cycloalkyl, Het-lower alkyl or aryl, Het is a monocyclic 5- or 6-membered hetero aromatic or a bicyclic heteroaromatic radical containing one or two hetero atoms selected from nitrogen, oxygen and sulfur, which radical may be substituted by lower alkyl, halogen or aryl, and the asterisk denotes the point of attachment, and when R.sub.6 and R.sub.7 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, are described. The compounds of formula I 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, shock or transplant rejection.

  式为##STR1##的化合物，其中Y是O或S，*A是对苯基或*--(CH.sub.2).sub.n --(X).sub.m --(CH.sub.2).sub.r --，X是O，S或--CH.dbd.CH--，n或r分别是独立的0至3的整数，s是0至1的整数，m是0至1的整数，但当m为1时，n+s必须至少为2，R.sub.1和R.sub.2分别是氢，低烷基，环烷基，低烯基，Het，Aryl，R.sub.3、R.sub.4和R.sub.8分别是氢，低烷基，芳基，R.sub.5和R.sub.6分别是氢或低烷基，R.sub.7是氢，低烷基，环烷基，Het-低烷基或芳基，Het是一种单环5-或6-成员杂芳基或含有一或两个异原子（氮、氧和硫）的双环杂芳基基团，该基团可以被低烷基，卤素或芳基取代，星号表示连接点，当R.sub.6和R.sub.7不同时，它们的对映异构体和混合物，当R.sub.1和R.sub.2不同时，它们的几何异构体以及药学上可接受的酸盐也被描述。公式I的化合物表现为血小板活化因子（PAF）拮抗剂的活性，因此，它们对于具有过量血小板活化因子的疾病状态或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是有用的。
• Pentadieneamides
  申请人：Hoffmann-La Roche Inc.

  公开号：US04788206A1

  公开（公告）日：1988-11-29

  Compounds of the formula ##STR1## Y is O ir S, *A is paraphenylene or *----(CH.sub.2)n----(X).sub.m --(CH.sub.2).sub.r ----, X is O, S or --CH.dbd.CH--, n or r, independently, are integers from 0 to 3, s is an integer from 0 to 1, m is an integer from 0 to 1, provided that when m is 1, n+s must be at least 2, R.sub.1 and R.sub.2, independently, are hydrogen, lower alkyl, cycloalkyl, lower alkenyl, Het, aryl, R.sub.3, R.sub.4 and R.sub.8, independently, are hydrogen, lower alkyl, aryl, R.sub.5 and R.sub.6, independently, are hydrogen or lower alkyl, R.sub.7 is hydrogen, lower alkyl, cycloalkyl, Het-lower alkyl or aryl, Het is a monocyclic 5- or 6-membered hetero aromatic or a bicyclic heteroaromatic radical containing one or two hetero atoms selected from nitrogen, oxygen and sulfur, which radical may be substituted by lower alkyl, halogen or aryl, and the asterisk denotes the point of attachment, and when R.sub.6 and R.sub.7 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, are described. The compounds of formula I exhibit activity as platelet activating factor (PAF) antagonists and are, therefore, useful in disease states characerized by excess platelet activating factor or for the prevention and treatment of cardiovascular disease, pulmonary diseases, immunological disorders, inflammatory diseases, dermatological disorders, shock or transplant rejection.

  式##STR1##的化合物，其中Y为O或S，*A为对苯基或*----（CH.sub.2）n----（X）.sub.m--（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，s为0至1的整数，m为0至1的整数，但当m为1时，n+s必须至少为2，R.sub.1和R.sub.2独立地为氢、低碳基、环烷基、低烯基、Het、芳基，R.sub.3、R.sub.4和R.sub.8独立地为氢、低碳基、芳基，R.sub.5和R.sub.6独立地为氢或低碳基，R.sub.7为氢、低碳基、环烷基、Het-低碳基或芳基，Het为单环5-或6-成员杂芳基或含有从氮、氧和硫中选择的一个或两个杂原子的双环杂芳基基团，该基团可以被低碳基、卤素或芳基取代，星号表示附着点，当R.sub.6和R.sub.7不同时，它们的对映异构体和混合物，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加成盐。式I的化合物表现为血小板活化因子（PAF）拮抗剂的活性，因此在过量血小板活化因子或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、休克或移植排斥等疾病状态中有用。
• 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：——
• US4788206A
  申请人：——

  公开号：US4788206A

  公开（公告）日：1988-11-29
• US4975438A
  申请人：——

  公开号：US4975438A

  公开（公告）日：1990-12-04