4-[(4-fluorophenyl)phenylmethylene]piperidine | 58113-21-6

• 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: 4-[(4-fluorophenyl)phenylmethylene]piperidine
• 英文别名: 4-[α-(p-fluorophenyl)-α-phenylmethylene]piperidine；4-[(4-Fluorophenyl)(phenyl)methylidene]piperidine；4-[(4-fluorophenyl)-phenylmethylidene]piperidine
• CAS: 58113-21-6
• 化学式: C₁₈H₁₈FN
• 分子量: 267.346
• InChiKey: FKMLLIPWGOCZPG-UHFFFAOYSA-N

物化性质

• 沸点：
  405.4±40.0 °C(Predicted)
• 密度：
  1.109±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-[(4-fluorophenyl)phenylmethylene]piperidine 在 盐酸 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 4-(4-((4-fluorophenyl)(phenyl)methylene)piperidin-1-yl)-butanal
  参考文献：
  名称：

  Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography

  摘要：

  Increased activity of efflux transporters, e.g., P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), at the blood brain barrier is a pathological hallmark of many neurological diseases, and the resulting multiple drug resistance represents a major clinical challenge. Noninvasive imaging of transporter activity can help to clarify the underlying mechanisms of drug resistance and facilitate diagnosis, patient stratification, and treatment monitoring. We have developed a metabolically activated radiotracer for functional imaging of P-gp/BCRP activity with positron emission tomography (PET). In preclinical studies, the tracer showed excellent initial brain uptake and clean conversion to the desired metabolite, although at a sluggish rate. Blocking with P-gp/BCRP modulators led to increased levels of brain radioactivity; however, dynamic PET did not show differential clearance rates between treatment and control groups. Our results provide proof-of-concept for development of prodrug tracers for imaging of P- /BCRP function in vivo but also highlight some challenges associated with this strategy.

  DOI：

  10.1021/acs.jmedchem.5b00652
• 作为产物：
  描述：

  4-((4-氟苯基)(羟基)甲基)哌啶-1-甲酸叔丁酯 在 戴斯-马丁氧化剂 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 4-[(4-fluorophenyl)phenylmethylene]piperidine
  参考文献：
  名称：

  Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography

  摘要：

  Increased activity of efflux transporters, e.g., P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), at the blood brain barrier is a pathological hallmark of many neurological diseases, and the resulting multiple drug resistance represents a major clinical challenge. Noninvasive imaging of transporter activity can help to clarify the underlying mechanisms of drug resistance and facilitate diagnosis, patient stratification, and treatment monitoring. We have developed a metabolically activated radiotracer for functional imaging of P-gp/BCRP activity with positron emission tomography (PET). In preclinical studies, the tracer showed excellent initial brain uptake and clean conversion to the desired metabolite, although at a sluggish rate. Blocking with P-gp/BCRP modulators led to increased levels of brain radioactivity; however, dynamic PET did not show differential clearance rates between treatment and control groups. Our results provide proof-of-concept for development of prodrug tracers for imaging of P- /BCRP function in vivo but also highlight some challenges associated with this strategy.

  DOI：

  10.1021/acs.jmedchem.5b00652

文献信息

• Arylalkylheterocyclic amines,N-substituted by aryloxyalkyl group in a
  申请人：A. H. Robins Company, Incorporated

  公开号：US04950674A1

  公开（公告）日：1990-08-21

  A method of inhibiting Type 1 allergic responses in a living animal body with substituted heterocyclic amines is disclosed wherein the active agents are expressed generally by the formula which includes certain known and certain known compounds: ##STR1## wherein P is zero, one or two; m is one to six inclusive; A is selected from hydrogen, hydroxy or cyano; d is zero or one; Q is --CH--, CH.sub.2 -- or ##STR2## n is zero or one and when Q is --CH-- and n is one, a double bond is formed with one of the adjacent carbons but not both at the same time, and when n and d are zero at the same time, a double bond is formed between the .alpha. carbon and a carbon of the central heterocyclic amine ring; Ar, D and R are selected from phenyl, substituted phenyl, pyridinyl, thienyl, furanyl or naphthyl and in addition, R may have the values benzyl, substituted benzyl, cycloalkyl or loweralkyl and D may additionally have the values: 2H-1-benzopyran-2-one,4-oxo-4H-1-benzopyran-2-carboxylic acid loweralkyl ester, 2,3-dihydro-4H-1-benzopyran-4-one, 1,4-benzodioxanloweralkyl-2-yl or 1,1'-biphenyl-4-yl and the pharmaceutically acceptable salts thereof.

  揭示了一种利用取代杂环胺抑制活体动物体内的1型过敏反应的方法，其中活性剂通常由以下公式表示：其中P为零、一或二；m为一到六（包括六）；A选自氢、羟基或氰基；d为零或一；Q为--CH--、CH.sub.2--或n为零或一，当Q为--CH--且n为一时，与相邻碳之一形成双键，但不同时与两个相邻碳形成双键；当n和d同时为零时，在中心杂环胺环的α碳和一个碳之间形成双键；Ar、D和R选自苯基、取代苯基、吡啶基、噻吩基、呋喃基或萘基，此外，R可能具有苄基、取代苄基、环烷基或较低烷基的值，D还可能具有以下值：2H-1-苯并吡喃-2-酮、4-氧代-4H-1-苯并吡喃-2-羧酸较低烷基酯、2,3-二氢-4H-1-苯并吡喃-4-酮、1,4-苯并二氧杂环较低烷基-2-基或1,1'-联苯基-4-基，以及其药学上可接受的盐。
• [EN] NEW HETEROCYCLIC COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS HÉTÉROCYCLIQUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2019105915A1

  公开（公告）日：2019-06-06

  The invention provides new heterocyclic compounds having the general formula (IA) wherein A, L, X, Y, m, n, R1 and R2 are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.

  这项发明提供了具有通式（IA）的新杂环化合物，其中A、L、X、Y、m、n、R1和R2如本文所述，包括这些化合物的组合物，制造这些化合物的方法以及使用这些化合物的方法。
• 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

  该发明涉及公式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的总和不得小于3也不得大于5，q=0或1，R是1,2,3,4-四氢-3-喹唑啉基团，可选择性取代的，1,3,4,6,11,11a-六氢-1,3-二氧-2H-吡嘧啶[1,2,-b]异喹啉-2-基团，1,2-二氢-1-氧-2-邻菲啰啉基团，可选择性取代的，公式W的2,6-二氧-1-哌嗪基团：##STR2##（R.sub.3是2-吡啶基团或可选择性取代的苯基团），公式Z的基团：##STR3##（R.sub.4是氨甲酰基团，氰基团，羟基羰基基团或具有1到6个碳原子的烷氧羰基基团），或公式Y的基团：##STR4##（R.sub.5是2-嘧啶基团，1-异喹啉基团，2-喹啉基团，2-吡啶基团，苄基团，可选择性取代的，2-噻唑基团，可选择性取代的，或2-苯并噻唑基团），且R.sub.1和R.sub.2，相同或不同，各为取代的苯基团，或R.sub.1是苯基团，R.sub.2是2-吡啶基团（这两个基团可能各自被取代），或R.sub.1和R.sub.2，连同它们连接的碳原子，形成芴基团。药用产品
• 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
• 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。