4-[bis(4-fluorophenyl)methylene]-1-(2-hydroxyethyl)piperidine | 131742-16-0

• 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: 4-[bis(4-fluorophenyl)methylene]-1-(2-hydroxyethyl)piperidine
• 英文别名: 2-[4-[Bis(4-fluorophenyl)methylidene]piperidin-1-yl]ethanol
• CAS: 131742-16-0
• 化学式: C₂₀H₂₁F₂NO
• 分子量: 329.39
• InChiKey: REJRLANXOOYSBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[bis(4-fluorophenyl)methylene]-1-(2-hydroxyethyl)piperidine 在 氯化亚砜 作用下， 以 氯仿 为溶剂， 反应 16.0h， 生成 4-[Bis(4-fluorophenyl)methylene]-1-(chloroethyl)piperidine
  参考文献：
  名称：

  3- [2- [4-(4-Fluorobenzoyl)piperidin- 1-yl]ethyl] -5,6,7,8-tetrahydro-4(3H)-quinazolinones: serotonin 5-HT2A receptor antagonists endowed with potent central action

  摘要：

  A series of 5,6,7,8-tetrahydro-4(3H)-quinazolinones substituted at the 3-position with 4-benzoyl-1-ethylpiperidine, 4-(4-fluorobenzoyl)-1-ethylpiperidine, 4-[bis-(4-fluorophenyl)methylene]-1-ethylpiperidine, or 4-(4-fluorophenyl)-1-propylpiperazine have been prepared and evaluated in binding assays to determine their affinity at serotonin 5-HT2A receptors as well as in a functional test, ie, wet dog shakes (WDS) induced by L-5-hydroxytryptophan (L-5-HTP), a behavioural response which is mediated by stimulation of 5-HT receptors. Among the compounds prepared. 3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-5,6,7,8-tetrahydro-4(3H)-quinazolinone (10b) and 2-methyl-3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-5,6,7,8-tetrahydro-4(3H)-quinazolinone (10b) proved to be the most potent 5-HT,, receptor antagonists. In binding assays, the two compounds displayed similar affinity for 5-HT, receptors in the nanomolar range to ketanserin and ritanserin. In the WDS test, they were even more potent than ketanserin and ritanserin. Compound 10b, which was found to possess the highest potency and duration of action in the WDS test, was chosen for a preliminary evaluation of its ability to inhibit ethanol intake in rats, a response linked to blockade of the central 5-HT2A, receptors. This compound significantly reduced ethanol intake in rats from the first day of treatment. The results of the present study indicate that 10b is a potent centrally acting antagonist at 5-HT2A receptors.

  DOI：

  10.1016/s0223-5234(97)83291-6
• 作为产物：
  描述：

  2-碘乙醇 、 4-(双(4-氟苯基)亚甲基)哌啶 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 16.0h， 生成 4-[bis(4-fluorophenyl)methylene]-1-(2-hydroxyethyl)piperidine
  参考文献：
  名称：

  3- [2- [4-(4-Fluorobenzoyl)piperidin- 1-yl]ethyl] -5,6,7,8-tetrahydro-4(3H)-quinazolinones: serotonin 5-HT2A receptor antagonists endowed with potent central action

  摘要：

  A series of 5,6,7,8-tetrahydro-4(3H)-quinazolinones substituted at the 3-position with 4-benzoyl-1-ethylpiperidine, 4-(4-fluorobenzoyl)-1-ethylpiperidine, 4-[bis-(4-fluorophenyl)methylene]-1-ethylpiperidine, or 4-(4-fluorophenyl)-1-propylpiperazine have been prepared and evaluated in binding assays to determine their affinity at serotonin 5-HT2A receptors as well as in a functional test, ie, wet dog shakes (WDS) induced by L-5-hydroxytryptophan (L-5-HTP), a behavioural response which is mediated by stimulation of 5-HT receptors. Among the compounds prepared. 3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-5,6,7,8-tetrahydro-4(3H)-quinazolinone (10b) and 2-methyl-3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-5,6,7,8-tetrahydro-4(3H)-quinazolinone (10b) proved to be the most potent 5-HT,, receptor antagonists. In binding assays, the two compounds displayed similar affinity for 5-HT, receptors in the nanomolar range to ketanserin and ritanserin. In the WDS test, they were even more potent than ketanserin and ritanserin. Compound 10b, which was found to possess the highest potency and duration of action in the WDS test, was chosen for a preliminary evaluation of its ability to inhibit ethanol intake in rats, a response linked to blockade of the central 5-HT2A, receptors. This compound significantly reduced ethanol intake in rats from the first day of treatment. The results of the present study indicate that 10b is a potent centrally acting antagonist at 5-HT2A receptors.

  DOI：

  10.1016/s0223-5234(97)83291-6

文献信息

• Heterocyclic compound having serotonine 2-receptor antagonistic activity
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：US05232924A1

  公开（公告）日：1993-08-03

  A heterocyclic compound represented by formula (I): ##STR1## wherein R.sup.1 represents a hydrogen atom, an alkyl group, an aryl group which may be substituted with one or more substituents selected from the group consisting of a halogen atom, an alkoxy group, an alkyl group and a trihalogenomethyl group; .lambda. represents 0 or 1; ring A represents a 6 membered heterocyclic ring containing the nitrogen atom shared with the triazine ring and which may contain one or more double bonds; Y represents a substituted or unsubstituted alkylene group having 1 to 15 carbon atoms; and Q represents a group represented by formula (II): ##STR2## wherein R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are represented by substituents disclosed herein; or salt thereof, and intermediates therefor are described. The compound of formula (I) or salt thereof exhibit selective serotonin 2-receptor antagonistic activity and are useful for the prevention or treatment of circulatory diseases, e.g., ischemic heart diseases, cerebral vessel disturbances, and peripheral circulation disturbances.

  一种由式(I)表示的杂环化合物：##STR1##其中R1表示氢原子、烷基组、可能被一个或多个选自卤素原子、烷氧基组、烷基组和三卤甲基组的取代基取代的芳基组；λ表示0或1；环A表示含有与三嗪环共用氮原子的6元杂环环，该环可能含有一个或多个双键；Y表示具有1至15个碳原子的取代或未取代的亚烷基组；Q表示由式(II)表示的组：##STR2##其中R2、R3、R4和R5由本文披露的取代基表示；或其盐，以及其中间体。式(I)的化合物或其盐表现出对血清素2受体的选择性拮抗活性，并可用于预防或治疗循环系统疾病，例如缺血性心脏病、脑血管障碍和外周循环障碍。
• Syntheses of 5-HT2 antagonist activity of bicyclic 1,2,4-triazol-3(2H)-one and 1,3,5-triazine-2,4(3H)-dione derivatives
  作者：Yoshifumi Watanabe、Hiroyuki Usui、Shozo Kobayashi、Hirotaka Yoshiwara、Toshiro Shibano、Tsuyoshi Tanaka、Yoshiyuki Morishima、Megumi Yasuoka、Munefumi Kanao

  DOI：10.1021/jm00079a026

  日期：1992.1

  2,4-triazol-3(2H)-one and 1,3,5-triazine-2,4(3H)-dione derivatives with a 4-[bis(4-fluoro-phenyl)methylene]piperidine or 4-(4-fluorobenzoyl)piperidine group has been prepared and tested for 5-HT2 and alpha 1 receptor antagonist activity. Among the compounds prepared, 2-[2-[4-[bis(4-fluorophenyl)methylene]-piperidin-1-yl]ethyl]- 5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one (7b) had the most

  一系列带有4- [双（4-氟-苯基）亚甲基的双环1,2,4-三唑-3（2H）-one和1,3,5-三嗪-2,4（3H）-二酮衍生物已制备]哌啶或4-（4-氟苯甲酰基）哌啶基团并测试了5-HT 2和α1受体拮抗剂的活性。在制备的化合物中，2- [2- [2- [4- [双（4-氟苯基）亚甲基]-哌啶-1-基]乙基] -5,6,7,8-四氢-1,2,4-三唑[ 4,3-a] pyridin-3（2H）-one（7b）具有最有效的5-HT2拮抗剂活性，高于利坦色林（2），而7b在体内未显示出α1拮抗剂活性。当测试阻断5-羟色氨酸诱导的头部抽搐的能力时，中央5-HT 2受体拮抗作用约为2的1/30。化合物21b，3- [2- [4-（4-氟苯甲酰基）哌啶-1-基]乙基] -6,7,8,9-四氢-2H-吡啶基[1,2-a] -1,3， 5-三嗪-2，4（3H）-二酮也显示出有效的5-HT2拮抗剂活性
• Heterocyclic triazin or triazolo compounds having serotonin 2-receptor antagonistic activity
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0401707B1

  公开（公告）日：1994-09-21
• US5232924A
  申请人：——

  公开号：US5232924A

  公开（公告）日：1993-08-03
• Simplified analogues of ritanserin and their affinity at 5-HT2A, 5-HT2B and 5-HT2C serotonin receptors
  作者：Francesco Claudi、Loredana Scoccia、Gianfabio Giorgioni、Gabriella Marucci、Antonio Di Stefano、Stefania Gessi、Anna Siniscalchi、Pier Andrea Borea

  DOI：10.1016/s0223-5234(98)80029-9

  日期：1998.9

  The 5-HT2 serotonin antagonist ritanserin (6-2-[4-[bis(4-fluorophenyl)methylene]-1-piperidinyl]ethyl}-7-methyl-5H-thiazole[3,2-a]pyrimidin-5-one, 2) binds with high affinity to 5-HT2A, 5-HT2B and 5-HT2C serotonin receptors. With the aim of exploring how simplification of the thiazolepyrimidinone nucleus of 2 affects the affinity and selectivity for 5-HT2A, 5-HT2B and 5-HT2C subtypes, some derivatives of 4-[bis(4-fluorophenyl)methylene]piperidine were synthesized, and their 5-HT2A and 5-HT2C receptor binding affinities and 5-HT2B antagonistic affinity evaluated. The new compounds bind the three 5-HT2 subtypes with lower affinity than did 2. Simplification of the thiazolepyrimidinone nucleus of ritanserin has only slight influence on the selectivity for 5-HT2 subtypes. The results suggest that the thiazolepyrimidinone moiety participates in key binding interactions and is determinant for high affinity at 5-HT2 receptor subtypes. Some derivatives showed antagonistic activity at 5-HT2A receptor. (C) Elsevier, Paris.