2-苯基咪唑并[1,2-a]吡啶-7-基氨基甲酸叔丁酯 | 1278407-53-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-苯基咪唑并[1,2-a]吡啶-7-基氨基甲酸叔丁酯
• 英文名称: tert-butyl 2-phenylimidazo[1,2-a]pyridin-7-ylcarbamate
• 英文别名: (2-Phenyl-imidazo[1,2-a]pyridin-7-yl)-carbamic acid tert-butyl ester；tert-butyl N-(2-phenylimidazo[1,2-a]pyridin-7-yl)carbamate
• CAS: 1278407-53-6
• 化学式: C₁₈H₁₉N₃O₂
• 分子量: 309.368
• InChiKey: HSGRCURIWMTTIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-苯基咪唑并[1,2-a]吡啶-7-基氨基甲酸叔丁酯 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以73%的产率得到2-phenylimidazo[1,2-a]pyridin-7-ylamine
  参考文献：
  名称：

  [EN] IMIDAZOPYRIDINE OR IMIDAZOPYRIMIDINE DERIVATIVES AS PHOSPHODIESTERASE 10A INHIBITORS
  [FR] DÉRIVÉS D'IMIDAZOPYRIDINE OU D'IMIDAZOPYRIMIDINE EN TANT QU'INHIBITEURS DE PHOSPHODIESTÉRASE 10A

  摘要：

  这项发明涉及式（I）的新型咪唑吡啶衍生物，其中R1、R2、R3、R4、R5和A如描述和权利要求中定义，并且其生理上可接受的盐和酯。这些化合物抑制PDE10A并可用作药物。

  公开号：

  WO2011036127A1
• 作为产物：
  描述：

  2-氨基异烟酸甲酯 在 叠氮磷酸二苯酯 、 水 、 碳酸氢钠 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 5.0h， 生成 2-苯基咪唑并[1,2-a]吡啶-7-基氨基甲酸叔丁酯
  参考文献：
  名称：

  NOVEL IMIDAZOPYRIDINES

  摘要：

  这项发明涉及公式(I)的新型咪唑吡啶衍生物，其中R1、R2、R3、R4、R5和A的定义如描述和权利要求中所述，以及其生理上可接受的盐和酯。这些化合物抑制PDE10A，可用于治疗各种疾病，包括中枢神经系统疾病，如阿尔茨海默病、帕金森病和精神分裂症。

  公开号：

  US20110071128A1

文献信息

• [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。
• 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] IMIDAZOPYRIDINE OR IMIDAZOPYRIMIDINE DERIVATIVES AS PHOSPHODIESTERASE 10A INHIBITORS<br/>[FR] DÉRIVÉS D'IMIDAZOPYRIDINE OU D'IMIDAZOPYRIMIDINE EN TANT QU'INHIBITEURS DE PHOSPHODIESTÉRASE 10A
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011036127A1

  公开（公告）日：2011-03-31

  The invention is concerned with novel imidazopyridine derivatives of formula (I) wherein R1, R2, R3, R4, R5 and A are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds inhibit PDE10A and can be used as medicaments.

  这项发明涉及式（I）的新型咪唑吡啶衍生物，其中R1、R2、R3、R4、R5和A如描述和权利要求中定义，并且其生理上可接受的盐和酯。这些化合物抑制PDE10A并可用作药物。
• Imidazopyridines
  申请人：Hoffmann-La Roche Inc.

  公开号：US08017604B2

  公开（公告）日：2011-09-13

  The invention is concerned with novel imidazopyridine derivatives of formula (I) wherein R1, R2, R3, R4, R5 and A are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds inhibit PDE10A and can be used for the treatment of various diseases, including central nervous system disorders such as Alzheimer's disease, Parkinson's disease, and schizophrenia.

  该发明涉及式（I）的新型咪唑吡啶衍生物，其中R1、R2、R3、R4、R5和A如说明书和权利要求中所定义，以及其生理学上可接受的盐和酯。这些化合物抑制PDE10A，并可用于治疗各种疾病，包括中枢神经系统疾病，如阿尔茨海默病、帕金森病和精神分裂症。
• 2-PHENYL OR 2-HETARYL IMIDAZOL[1,2-a]PYRIDINE DERIVATIVES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20160244441A1

  公开（公告）日：2016-08-25

  The invention relates to compounds of formulas I and II wherein R 1 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; R 2 is hydrogen, lower alkyl, halogen, lower alkoxy, S-lower alkyl, lower alkoxy substituted by halogen, O(CH 2 ) 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, CH 2 -lower alkoxy, CH 2 -lower alkoxy substituted by halogen or hydroxy; or R 1 and R 2 form together with the carbon atoms to which they are attached a ring containing —OCH 2 CH 2 O—, OCH 2 O—, OCH 2 CH 2 CH 2 O— or —NHC(O)CH 2 O—; R 3 is hydrogen or lower alkoxy; R 4 is hydrogen or lower alkyl; R 5 is lower alkyl, cycloalkyl, lower alkyl substituted by hydroxy or lower alkyl substituted by halogen; or R 4 and R 5 form together with the nitrogen atom to which they are attached a ring containing —CH 2 CH 2 CHRCH 2 CH 2 —, —CH 2 CHRCH 2 CH 2 —, —CH 2 CH 2 OCH 2 CH 2 —CH 2 CH 2 NR′CH 2 CH 2 —, CH 2 CHR— or —CH 2 CH 2 CH 2 —; wherein R is hydrogen, halogen, lower alkyl, lower alkoxy or lower alkyl substituted by halogen; R′ is lower alkyl substituted by halogen; R a is hydrogen or 3 H; R b is hydrogen, hydroxy or 3 H; R 6 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.

  该发明涉及公式I和II的化合物，其中：R1为氢，低烷基，低烷氧基，卤素，S-低烷基，低烷氧基取代的卤素，二烷基氨基，C（O）O-低烷基，低烷基取代的羟基或羟基；R2为氢，低烷基，卤素，低烷氧基，S-低烷基，低烷氧基取代的卤素，O（CH2）2-低烷氧基取代的卤素，二烷基氨基，烷基氨基，NH-低烷基取代的卤素，N（低烷基）-苄基，低烷基取代的羟基，杂环烷基可选地取代卤素，CH2-低烷氧基，CH2-低烷氧基取代的卤素或羟基；或R1和R2与它们所连接的碳原子一起形成一个环，其中包含-OCH2CH2O-、OCH2O-、OCH2CH2CH2O-或-NHC（O）CH2O-；R3为氢或低烷氧基；R4为氢或低烷基；R5为低烷基，环烷基，低烷基取代的羟基或低烷基取代的卤素；或R4和R5与它们所连接的氮原子一起形成一个环，其中包含-CH2CH2CHRCH2CH2-、-CH2CHRCH2CH2-、-CH2CH2OCH2CH2-CH2CH2NR′CH2CH2-、CH2CHR-或-CH2CH2CH2-；其中R为氢，卤素，低烷基，低烷氧基或低烷基取代的卤素；R′为低烷基取代的卤素；Ra为氢或3H；Rb为氢，羟基或3H；R6为氢，卤素或低烷基；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；或其药学上可接受的酸加成盐，其外消旋混合物或其对应的对映异构体和/或光学异构体。这些化合物适用于成像工具，通过识别大脑中tau聚集过多的潜在患者，有助于改善诊断，这可能会导致阿尔茨海默病的发展。