4-(2-fluoroethyl)piperidine hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(2-fluoroethyl)piperidine hydrochloride
• 英文别名: 4-(2-fluoroethyl)piperidine;hydrochloride
• 化学式: C₇H₁₄FN*ClH
• 分子量: 167.654
• InChiKey: XSIYTVGVMNMDHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.77
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  12
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(2-fluoroethyl)piperidine hydrochloride 在 盐酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  The Discovery of orally available thrombin inhibitors : Studies towards the optimisation of CGH1668

  摘要：

  The chemical optimisation of CGH1668 1 is described employing an in vivo model of absorption to determine the influence on bioavailability of single Feint modifications to five key molecular templates. The discovery of an orally bioavailable and selective thrombin inhibitor, 24, highlights the utility of this approach. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00640-4
• 作为产物：
  描述：

  N-Boc-4-哌啶乙醇 在 盐酸 、 一氟三氯甲烷 、 溶剂黄146 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 反应 2.0h， 生成 4-(2-fluoroethyl)piperidine hydrochloride
  参考文献：
  名称：

  Design and Synthesis of Thrombin Inhibitors:  Analogues of MD-805 with Reduced Stereogenicity and Improved Potency

  摘要：

  Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibit;ors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.g. 45g) of increased potency. An enantioselective route was developed to 3(R)-methyl-1,2,3,4-tetrahydroquinolinesulfonyl chloride. Inhibitors containing this enantiomerically pure P3 (42d) had similar potency to the racemic material and provided support, with modeling studies, for the preparation of the gem 3,3-disubstituted compounds. A series of inhibitors containing the novel 3,3-dimethyl-1,2,3,4-tetrahydroquinolinesulfonyl (DMTHQS) P3 (Table 5) were synthesized and showed a similar activity profile as the monomethyl series. The combination of P3-DMTHQS, PB-FEP, and P1-arginine (45g) had a K-i of 6 nM (MD-805 K-i = 85 nM). In animal models of both venous and arterial thrombosis, one inhibitor (42e) was shown to produce a dose-dependent inhibition of thrombus formation that in some situations was superior to that of MD-805.

  DOI：

  10.1021/jm9811209

文献信息

• [EN] SELECTIVE LIGANDS FOR TAU AGGREGATES<br/>[FR] LIGANDS SÉLECTIFS POUR AGRÉGATS TAU
  申请人：KARIN & STEN MORTSTEDT CBD SOLUTIONS AB

  公开号：WO2019197502A1

  公开（公告）日：2019-10-17

  The invention provides a compound of formula (I): or a pharmaceutically acceptable salt, ester, amide or carbamate thereof, or a salt of such an ester, amide or carbamate.The invention further provides uses of the compounds of formula (I) and compositions comprising compounds of formula (I), including the use of such compounds for the detection of tau deposits, and the use of such compounds and compositions as diagnostic agents in the diagnosis or monitoring of the progression of a disease or disorder such as Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy,or for the prevention or treatment of a disease or disorder such as Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy.

  该发明提供了化合物的结构式(I)：或其药学上可接受的盐、酯、酰胺或碳酸酯，或此类酯、酰胺或碳酸酯的盐。该发明还提供了化合物的结构式(I)的用途和包括化合物的结构式(I)的组合物，包括利用这些化合物检测tau沉积物的用途，以及将这些化合物和组合物用作诊断剂在诊断或监测疾病或障碍的进展，如阿尔茨海默病、皮质基底节变性和进行性上核性麻痹症，或用于预防或治疗疾病或障碍，如阿尔茨海默病、皮质基底节变性和进行性上核性麻痹症。
• [EN] 2-PHENYL OR 2-HETARYL IMIDAZOL[1,2-a]PYRIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE 2-PHÉNYL- OU 2-HÉTARYL-IMIDAZOL[1,2-A]PYRIDINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014177458A1

  公开（公告）日：2014-11-06

  The invention relates to compounds of formulas I and II, formula I or formula II wherein R1 is hydrogen, lower alkyl, lower alkoxy, halogen, S-lower alkyl, lower alkoxy substituted by halogen, di-lower alkyl amino, C(O)O-lower alkyl, lower alkyl substituted by hydroxy or hydroxy; R2 is hydrogen, lower alkyl, halogen, lower alkoxy, S-lower alkyl, lower alkoxy substituted by halogen, O(CH2)2-lower alkoxy substituted by halogen, di-lower alkyl amino, alkyl amino, NH-lower alkyl substituted by halogen, N(lower alkyl)-benzyl, lower alkyl substituted by hydroxy, heterocycloalkyl optionally substituted by halogen, CH2-lower alkoxy, CH2-lower alkoxy substituted by halogen or hydroxy; or R1 and R2 form together with the carbon atoms to which they are attached a ring containing -OCH2CH2O-, OCH2O-, OCH2CH2CH2O- or -NHC(O)CH2O-; R3 is hydrogen or lower alkoxy; R4 is hydrogen or lower alkyl; R5 is lower alkyl, cycloalkyl, lower alkyl substituted by hydroxy or lower alkyl substituted by halogen; or R4 and R5 form together with the nitrogen atom to which they are attached a ring containing -CH2CH2CHRCH2CH2-, -CH2CHRCH2CH2-, -CH2CH2OCH2CH2-, -CH2CH2NR'CH2CH2-, CH2CHR- or -CH2CH2CH2-; wherein R is hydrogen, halogen, lower alkyl, lower alkoxy or lower alkyl substituted by halogen; R' is lower alkyl substituted by halogen; Ra is hydrogen or H; Rb is hydrogen, hydroxy or 3H; R6 is hydrogen, halogen or lower alkyl; HetAr is selected from the group consisting of thiophenyl, furanyl, thiozolyl, benzofuranyl, pyrazolyl, benzoimidazolyl or pyridinyl; n is 1 or 2; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof. The present compounds are suitable as imaging tool, which will improve diagnosis by identifying potential patients with excess of tau aggregates in the brain, which may be likely to develop Alzheimer's disease.

  本发明涉及式I和式II的化合物，式I或式II中，R1为氢、低级烷基、低级烷氧基、卤素、S-低级烷基、卤素取代的低级烷氧基、二-低级烷基氨基、C(O)O-低级烷基、羟基取代的低级烷基或羟基；R2为氢、低级烷基、卤素、低级烷氧基、S-低级烷基、卤素取代的低级烷氧基、O(CH2)2-卤素取代的低级烷氧基、二-低级烷基氨基、烷基氨基、NH-卤素取代的低级烷基、N(低级烷基)-苄基、羟基取代的低级烷基、任选卤素取代的杂环烷基、CH2-低级烷氧基、CH2-卤素或羟基取代的低级烷氧基；或者R1和R2与其所连接的碳原子一起形成含有-OCH2CH2O-、OCH2O-、OCH2CH2CH2O-或-NHC(O)CH2O-的环；R3为氢或低级烷氧基；R4为氢或低级烷基；R5为低级烷基、环烷基、羟基取代的低级烷基或卤素取代的低级烷基；或者R4和R5与其所连接的氮原子一起形成含有-CH2CH2CHRCH2CH2-、-CH2CHRCH2CH2-、-CH2CH2OCH2CH2-、-CH2CH2NR'CH2CH2-、CH2CHR-或-CH2CH2CH2-的环；其中R为氢、卤素、低级烷基、低级烷氧基或卤素取代的低级烷基；R'为卤素取代的低级烷基；Ra为氢或H；Rb为氢、羟基或3H；R6为氢、卤素或低级烷基；HetAr选自噻吩基、呋喃基、噻唑基、苯并呋喃基、吡唑基、苯并咪唑基或吡啶基；n为1或2；或为药学上可接受的酸加成盐、外消旋混合物或其相应的对映体和/或光学异构体。本发明的化合物适合作为成像工具，通过识别大脑中tau聚集体过量的潜在患者，将有助于改善诊断，这些患者可能发展为阿尔茨海默病。
• [EN] 2-PHENYLIMIDAZO[1,2-A]PYRIMIDINES AS IMAGING AGENTS<br/>[FR] 2-PHÉNYLIMIDAZO[1,2-A]PYRIMIDINES EN TANT QU'AGENTS D'IMAGERIE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014187762A1

  公开（公告）日：2014-11-27

  The present invention relates to compounds of general formula (I) wherein R1 is phenyl, optionally substituted by one or two substituents, selected from 3H, halogen, lower alkyl, di-methyl-amino, NHC(O)-lower alkyl, C(O)O-lower alkyl, lower alkoxy, OC(3H)3, O11CH3, OCH2CH218F, lower alkoxy substituted by halogen, hydroxy, lower alkyl substituted by hydroxy, S-lower alkyl, or by a heterocyclyl group; or is benzo[d][l,3]dioxol-5-yl, 2,3-dihydrobenzo[b][l,4]dioxin-6-yl, indolin-2-one, or is heteroaryl, selected from the group consisting of thiophenyl, benzofuranyl, benzothiophenyl, pyrazinyl, or benzothiazolyl; R2 is hydrogen, lower alkyl or lower alkyl substituted by halogen; R3 is lower alkyl, C(3H)3, 11CH3, lower alkyl substituted by halogen, -(CH2)2-O-lower alkyl substituted by halogen or cycloalkyl; or R2 and R3 form together with the N-atom to which they are attach a ring containing -CH2CH2CHRCH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2-NR-CH2CH2-, -CH2CH2-O-CH2CH2-, -CH2CH2CHRCH2-, -CH2CHRCH2- or (A); R is hydrogen, halogen, lower alkyl substituted by halogen or lower alkoxy; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof. The compounds are suitable as imaging tool, which will improve diagnosis by identifying potential patients with excess of tau aggregates in the brain, which may be likely to develop Alzheimer' s disease.

  本发明涉及通式(I)的化合物，其中R1为苯基，可选择性地被一个或两个取代基取代，这些取代基选自3H、卤素、低级烷基、二甲基氨基、NHC(O)-低级烷基、C(O)O-低级烷基、低级烷氧基、OC(3H)3、O11CH3、OCH2CH218F、被卤素取代的低级烷氧基、羟基、被羟基取代的低级烷基、S-低级烷基，或被杂环基团取代；或者R1为苯并[d][1,3]二氧环戊烯-5-基、2,3-二氢苯并[b][1,4]二氧杂环己烯-6-基、茚满酮-2-基，或者为杂芳基，选自噻吩基、苯并呋喃基、苯并噻吩基、吡嗪基或苯并噻唑基；R2为氢、低级烷基或被卤素取代的低级烷基；R3为低级烷基、C(3H)3、11CH3、被卤素取代的低级烷基、-(CH2)2-O-被卤素取代的低级烷基或环烷基；或者R2和R3与其所连接的N原子一起形成含有-CH2CH2CHRCH2CH2-、-CH2CH2CH2CH2-、-CH2CH2CH2CH2-、-CH2CH2-NR-CH2CH2-、-CH2CH2-O-CH2CH2-、-CH2CH2CHRCH2-、-CH2CHRCH2-或(A)的环；R为氢、卤素、被卤素取代的低级烷基或低级烷氧基；或者为药学上可接受的酸加成盐，为外消旋混合物或其相应的对映异构体和/或光学异构体。这些化合物适合作为成像工具，通过识别大脑中tau聚集体过剩的潜在患者，从而改善诊断，这些患者可能发展为阿尔茨海默病。
• Identification of Three Novel Radiotracers for Imaging Aggregated Tau in Alzheimer’s Disease with Positron Emission Tomography
  作者：Luca C. Gobbi、Henner Knust、Matthias Körner、Michael Honer、Christian Czech、Sara Belli、Dieter Muri、Martin R. Edelmann、Thomas Hartung、Isabella Erbsmehl、Sandra Grall-Ulsemer、Andreas Koblet、Marianne Rueher、Sandra Steiner、Hayden T. Ravert、William B. Mathews、Daniel P. Holt、Hiroto Kuwabara、Heather Valentine、Robert F. Dannals、Dean F. Wong、Edilio Borroni

  DOI：10.1021/acs.jmedchem.7b00632

  日期：2017.9.14

  disease and are prominent targets for novel therapeutics as well as for biomarkers for diagnostic in vivo imaging. In recent years much attention has been devoted to the discovery and development of new PET tracers to image tau aggregates in the living human brain. Access to a selective PET tracer to image and quantify tau aggregates represents a unique tool to support the development of any novel therapeutic

  tau和β淀粉样蛋白（Aβ）斑块的聚集体构成了阿尔茨海默氏病的组织病理学标志，是新型疗法以及用于体内诊断的生物标志物的重要靶标。近年来，人们对新型PET示踪剂的发现和开发投入了大量精力，以描绘人脑中tau聚集体的图像。获得选择性PET示踪剂以成像和定量tau聚集体的方法代表了一种独特的工具，可支持针对tau病理形式的任何新型治疗剂的开发。本文所述研究的目的是鉴定这种新颖的放射性示踪剂。这项工作的结果是，我们发现了三种新颖的PET示踪剂（2-（4- [ 11 [ C]甲氧基苯基]咪唑并[1,2- a ]吡啶7-胺7]（[ 11 C] RO6924963），N- [ 11 C]甲基-2-（3-甲基苯基）咪唑并[1,2- a ]嘧啶-7-胺8（[ 11 C] RO6931643）和[ 18 F]对tau神经原纤维缠结具有高亲和力的2-（6-氟吡啶-3--3-基）吡咯并[2,3- b：4,5- c
• [EN] THROMBIN INHIBITORS<br/>[FR] INHIBITEURS DE LA THROMBINE
  申请人：NOVARTIS AG

  公开号：WO1997046553A1

  公开（公告）日：1997-12-11

  (EN) The present invention provides a compound of general formula (I) in which Y is a primary or secondary amino group; R2 is the residue of a natural or synthetic amino acid; R3 is hydrogen or a C1-C8 alkyl chain which may be substituted by hydroxy or halogen; and X is (CH2)n where n is 1, 2, or 3, or is CH2N or represents a fused phenyl ring which is optionally substituted by one or two methoxy groups or a salt thereof.(FR) L'invention concerne un composé de formule générale (I), ou son sel, formule dans laquelle Y est un groupe amino primaire ou secondaire; R2 est le résidu d'un acide aminé naturel ou synthétique; R3 est hydrogène ou une chaîne alkyle C1-C8 qu'on peut substituer par hydroxy ou halogène; et X est (CH2)n où n est égal à 1, 2 ou 3, ou bien est CH2N ou représente un noyau phénylique condensé éventuellement substitué par un ou deux groupes méthoxy.

  本发明提供了通式（I）的化合物，其中Y是一级或二级氨基团；R2是天然或合成氨基酸的残基；R3是氢或C1-C8烷基链，可以被羟基或卤素取代；X是（CH2）n，其中n为1、2或3，或者是CH2N或代表一个融合的苯环，该环可以选择地被一个或两个甲氧基取代，或其盐。