4-[Bis(4-fluorophenyl)methylene]-1-(chloroethyl)piperidine | 131741-82-7

• 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-(chloroethyl)piperidine
• 英文别名: 4-[bis(4-fluorophenyl)methylidene]-1-(2-chloroethyl)piperidine
• CAS: 131741-82-7
• 化学式: C₂₀H₂₀ClF₂N
• 分子量: 347.835
• InChiKey: DLKRXUGTSNHYPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 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：
  3.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-苄基乙酰胺 、 4-[Bis(4-fluorophenyl)methylene]-1-(chloroethyl)piperidine 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以48%的产率得到N-benzyl-2-[4-[bis(4-fluorophenyl)methylidene]piperidin-1-yl]ethanamine
  参考文献：
  名称：

  Simplified analogues of ritanserin and their affinity at 5-HT2A, 5-HT2B and 5-HT2C serotonin receptors

  摘要：

  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.

  DOI：

  10.1016/s0223-5234(98)80029-9
• 作为产物：
  描述：

  4-(双(4-氟苯基)亚甲基)哌啶 在 氯化亚砜 、 potassium carbonate 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 32.0h， 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

文献信息

• Bis(aryl)alkene compounds
  申请人：Adir et Compagnie

  公开号：US05028607A1

  公开（公告）日：1991-07-02

  The invention relates to compounds of formula I: ##STR1## in which m=2-4, n and p, which may be identical or different, are an integer equal to 1, 2 or 3, with the proviso that the sum of n and p is not less than 3 and not more than 5, q=0 or 1, R is a 1,2,3,4-tetrahydro-3-quinazolinyl radical, optionally substituted, a 1,3,4,6,11,11a-hexahydro-1,3-dioxo-2H-pyrazino[1,2,-b]isoquinol-2-yl radical, a 1,2-dihydro-1-oxo-2-phthalazinyl radical, optionally substituted, a 2,6-dioxo-1-piperazinyl radical of formula W: ##STR2## (R.sub.3 is a 2-pyridyl radical or an optionally substituted phenyl radical), a radical of formula Z: ##STR3## (R.sub.4 is a carbamoyl radical, a cyano radical, a hydroxycarbonyl radical or an alkoxycarbonyl radical having 1 to 6 carbon atms), or a radical of formula Y: ##STR4## (R.sub.5 is a 2-pyrimidinyl radical, a 1-isoquinolyl radical, a 2-quinolyl radical, a 2-pyridyl radical, a benzyl radical, optionally substituted, a 2-thiazolyl radical, optionally substituted, or a 2-benzothiazolyl radical) and either R.sub.1 and R.sub.2, identical or different, each are a substituted phenyl radical, or R.sub.1 is a phenyl radical and R.sub.2 a 2-pyridyl radical (it being possible for each of these two radicals to be substituted), or R.sub.1 and R.sub.2, together with the carbon atom to which they are attached, form a fluorene radical. Medicinal products

  本发明涉及式I的化合物：##STR1## 其中m=2-4，n和p可以相同或不同，是等于1、2或3的整数，但n和p的和不小于3且不大于5，q=0或1，R是1,2,3,4-四氢-3-喹唑啉基基团，可选地取代，1,3,4,6,11,11a-六氢-1,3-二氧杂-2H-吡嗪[1,2,-b]异喹啉-2-基基团，1,2-二氢-1-氧-2-菲啰啉基基团，可选地取代，式W的2,6-二氧-1-哌嗪基基团：##STR2## （R.sub.3是2-吡啶基基团或可选地取代的苯基基团），式Z的基团：##STR3## （R.sub.4是氨基甲酰基基团，氰基，羟基甲酰基基团或有1到6个碳原子的烷氧基甲酰基基团），或式Y的基团：##STR4## （R.sub.5是2-嘧啶基基团，1-异喹啉基基团，2-喹啉基基团，2-吡啶基基团，苄基基团，可选地取代，2-噻唑基基团，可选地取代，或2-苯并噻唑基基团），且R.sub.1和R.sub.2要么相同或不同，每个都是取代的苯基基团，要么R.sub.1是苯基基团，R.sub.2是2-吡啶基基团（这两个基团可能被取代），要么R.sub.1和R.sub.2与它们连接的碳原子一起形成芴基基团。药物制品
• Bis(aryl)alkene pyrrolidine compounds
  申请人：Adir et Compagnie

  公开号：US05079249A1

  公开（公告）日：1992-01-07

  The invention relates to compounds of formula I: ##STR1## in which m=2-4, n and p, which may be identical or different, are an integer equal to 1, 2 or 3, with the proviso that the sum of n and p q=0 or 1, R is a 1,2,3,4-tetrahydro-2,4-dioxo-3-quinazolinyl radical, optionally substituted, a 1,3,4,6,11,11a-hexahydro-1,3-dioxo-2H-pyrazino[1,2-b]isoquinol-2-yl radical, a 1,2-dihydro-1-oxo-2-phthalazinyl radical, optionally substituted, a 2,6-dioxo-1-piperazinyl radical of formula W: ##STR2## (R.sub.3 is a 2-pyridyl radical or an optionally substituted phenyl radical), a radical of formula Z: ##STR3## (R.sub.4 is a carbamoyl radical, a cyano radical, a hydroxycarbonyl radical or an alkoxycarbonyl radical having 1 to 6 carbon atoms), or a radical of formula Y: ##STR4## (R.sub.5 is a 2-pyrimidinyl radical, a 1-isoquinolyl radical, a 2-quinolyl radical, a 2-pyridyl radical, a benzyl radical, optionally substituted, a 2-thiazolyl radical, optionally substituted, or a 2-benzothiazolyl radical) and either R.sub.1 and R.sub.2, identical or different, each are a substituted phenyl radical, or R.sub.1 is a phenyl radical and R.sub.2 a 2-pyridyl radical (it being possible for each of these two radicals to be substituted), or R.sub.1 and R.sub.2, together with the carbon atom to which they are attached, form a fluorene radical. These compounds are useful as Serotonin Antagonists.

  本发明涉及以下式子的化合物：##STR1## 其中m=2-4，n和p，可以相同也可以不同，为1、2或3的整数，但n和p的和q=0或1，R是1,2,3,4-四氢-2,4-二氧-3-喹唑啉基基团，可选取代，1,3,4,6,11,11a-六氢-1,3-二氧-2H-吡嗪并[1,2-b]异喹啉-2-基基团，1,2-二氢-1-氧-2-菲啰啉基基团，可选取代，式子W的2,6-二氧-1-哌嗪基基团：##STR2##（其中R.sub.3是2-吡啶基基团或可选取代的苯基基团），式子Z的基团：##STR3##（其中R.sub.4是氨基甲酰基基团，氰基，羟基甲酰基基团或1-6碳原子的烷氧基甲酰基基团），或式子Y的基团：##STR4##（其中R.sub.5是2-嘧啶基基团，1-异喹啉基基团，2-喹啉基基团，2-吡啶基基团，苄基基团，可选取代，2-噻唑基基团，可选取代，或2-苯并噻唑基基团），且R.sub.1和R.sub.2要么相同且各为取代的苯基基团，要么R.sub.1是苯基基团且R.sub.2是2-吡啶基基团（这两个基团都可以取代），要么R.sub.1和R.sub.2与它们连接的碳原子一起形成芴基基团。这些化合物可用作5-羟色胺拮抗剂。
• Bis (aryl) alkene compounds of homopiperidines useful as
  申请人：Adir et Compagnie

  公开号：US05071847A1

  公开（公告）日：1991-12-10

  The invention relates to compounds of formula I: ##STR1## in which m=2-4, n and p, which may be identical or different, are an integer equal to 1, 2 or 3, with the proviso that the sum of n and p is 5, q=0 or 1, R is a 1,2,3,4-tetrahydro-3-quinazolinyl radical, optionally substituted, a 1,3,4,6,11,11a-hexahydro-1,3-dioxo-2H-pyrazino[1,2-b]isoquinol-2-yl radical, a 1,2-dihydro-1-oxo-2-phthalazinyl radical, optionally substituted, a 2,6-dioxo-1-piperazinyl radical of formula W: ##STR2## (R.sub.3 is a 2-pyridyl radical or an optionally substituted phenyl radical), a radical of formula Z: ##STR3## (R.sub.4 is a carbamoyl radical, a cyano radical, a hydroxycarbonyl radical or an alkoxycarbonyl radical having 1 to 6 carbon atoms), or a radical of formula Y: ##STR4## (R.sub.5 is a 2-pyrimidinyl radical, a 1-isoquinolyl radical, a 2-quinolyl radical, a 2-pyridyl radical, a benzyl radical, optionally substituted, a 2-thiazolyl radical, optionally substituted, or a 2-benzothiazolyl radical) and either R.sub.1 and R.sub.2, identical or different, each are a substituted phenyl radical, or R.sub.1 is a phenyl radical and R.sub.2 a 2-pyridyl radical (it being possible for each of these two radicals to be substituted), or R.sub.1 and R.sub.2, together with the carbon atom to which they are attached, form a fluorene radical. The compound have serotonin-antagonistic properties.

  本发明涉及公式I的化合物：##STR1## 其中m = 2-4，n和p可以相同也可以不同，是等于1，2或3的整数，但n和p的和为5，q = 0或1，R是1,2,3,4-四氢-3-喹唑啉基基团，可选择性取代，1,3,4,6,11,11a-六氢-1,3-二氧杂-2H-吡嗪[1,2-b]异喹啉-2-基基团，1,2-二氢-1-氧杂-2-萘啉基基团，可选择性取代，公式W的2,6-二氧-1-哌嗪基基团：##STR2## （其中R.sub.3是2-吡啶基基团或可选择性取代的苯基基团），公式Z的基团：##STR3## （其中R.sub.4是氨基甲酰基基团，氰基，羟基甲酰基基团或具有1到6个碳原子的烷氧基甲酰基基团），或公式Y的基团：##STR4## （其中R.sub.5是2-嘧啶基基团，1-异喹啉基基团，2-喹啉基基团，2-吡啶基基团，苄基基团，可选择性取代，2-噻唑基基团，可选择性取代，或2-苯并噻唑基基团），且R.sub.1和R.sub.2，相同或不同，均为取代苯基基团，或R.sub.1是苯基基团，R.sub.2是2-吡啶基基团（这两个基团均可能被取代），或R.sub.1和R.sub.2与它们连接的碳原子一起形成芴基基团。该化合物具有5-羟色胺拮抗作用。
• 5-HT1A and 5-HT2A ligands with anxiolytic and antipanic-like properties
  作者：O. Diouf、P. Carato、P. Depreux、J.P. Bonte、D.H. Caignard、B. Guardiola-Lemaître、M.C. Rettori、C. Belzung、Daniel Lesieur

  DOI：10.1016/s0960-894x(97)10023-3

  日期：1997.10

  A series of new benzothiazolin-2-one, benzoxazolin-2-one and benzoxazin-3-one derivatives were synthesized and their binding profile at 5-HT1A, 5-HT2A, 5-HT2C as well as D-2 and alpha(1) receptors was determined. All studied compounds displayed high to moderate affinity for both 5-HT1A and 5-HT2A receptor subtypes. Among these, one compound (29) emerged since it exhibited potent antagonist activities at 5-HT1A, 5-HT2A, D-2 and alpha(1) central receptors and showed anxiolytic and antipanic-like effects in mice. 29 is currently undergoing preclinical evaluation. (C) 1997 Elsevier Science Ltd.
• US5028607A
  申请人：——

  公开号：US5028607A

  公开（公告）日：1991-07-02