3-(2-chlorobenzyloxy)pyridin-2-amine | 107229-61-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-(2-chlorobenzyloxy)pyridin-2-amine
• 英文别名: 2-Amino-3-(2-chlorobenzyloxy)pyridine；3-[(2-chlorophenyl)methoxy]pyridin-2-amine
• CAS: 107229-61-8
• 化学式: C₁₂H₁₁ClN₂O
• mdl: MFCD11195107
• 分子量: 234.685
• InChiKey: DUZCURUMGFQSTD-UHFFFAOYSA-N

物化性质

• 熔点：
  100-101 °C(Solv: dichloromethane (75-09-2))
• 沸点：
  390.4±32.0 °C(Predicted)
• 密度：
  1.292±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.083
• 拓扑面积：
  48.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  氯乙基异氰酸酯 、 3-(2-chlorobenzyloxy)pyridin-2-amine 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以61%的产率得到1-(3-(2-chlorobenzyloxy)pyridin-2-yl)-3-(2-chloroethyl)urea
  参考文献：
  名称：

  Discovery of 1-(3-(benzyloxy)pyridin-2-yl)-3-(2-(piperazin-1-yl)ethyl)urea: A new modulator for amyloid beta-induced mitochondrial dysfunction

  摘要：

  Herein, we report a new series of aliphatic substituted pyridyl-urea small molecules synthesized as potential modulators for amyloid beta (A beta) induced mitochondrial dysfunction. Their blocking activities against A beta-induced mitochondrial permeability transition pore (mPTP) opening were evaluated by JC-1 assay which measures the change of mitochondrial membrane potential (Delta Psi m). The inhibitory activity of sixteen compounds against A beta-induced mPTP opening was superior or almost similar to that of the standard Cyclosporin A (CsA). Among them, 1-(3-(benzyloxy) pyridin-2-yl)-3-(2-(piperazin-1-yl)ethyl)urea (5x) effectively maintained mitochondrial function and cell viabilities on ATP assay, MTT assay, and ROS assay. Using CDocker algorithm, a molecular docking model presented a plausible binding mode for 5x with cyclophilin D (CypD) receptor as a major component of mPTP. Moreover, hERG and BBB-PAMPA assays presented safe cardiotoxicity and high CNS bioavailability profiles for 5x. Taken as a whole, this report presents compound 5x as a new nonpeptidyl mPTP blocker may hold a promise for further development of Alzheimer's disease (AD) therapeutics. (C) 2016 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2016.12.057
• 作为产物：
  描述：

  2-氨基-3-羟基吡啶 、 2-氯苄溴 在 四丁基溴化铵 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 18.25h， 生成 3-(2-chlorobenzyloxy)pyridin-2-amine
  参考文献：
  名称：

  新型吡啶基/吡嗪基硫脲衍生物的合成和评价：针对淀粉样β诱导的毒性的神经保护

  摘要：

  在本文中，我们报告了使用JC-1测定法合成新的26个小分子，这些小分子针对β淀粉样蛋白（Aβ）诱导的线粒体通透性转换孔（mPTP）的打开，该方法可测量线粒体膜电位（ΔΨm）的变化。17种化合物对Aβ诱导的mPTP开放的神经保护作用优于标准环孢菌素A（CsA）。评价了十五种引发绿色至红色荧光百分比增加小于40.0％的衍生物对ATP产生，细胞活力和针对Aβ诱导的神经元细胞死亡的神经保护作用的影响。在评估的化合物中，衍生物9w，9r和9k关于ATP的产生和细胞活力具有安全性。此外，它们表现出显着的神经保护作用（分别为69.3％，51.8和48.2％）。使用CDocker算法进行的分子建模研究预测了可能的结合模式，从而解释了所引起的mPTP阻断活性。因此，这项研究表明化合物9w，9r和9k作为进一步开发针对阿尔茨海默氏病的新疗法的先导。

  DOI：

  10.1016/j.ejmech.2017.09.043

文献信息

• [EN] 3-`(HETERO) ARYLMETHOXY ! PYRIDINES AND THEIR ANALOGUES AS P38 MAP KINASE INHIBITORS<br/>[FR] 3-(HETERO) ARYLMETHOXY PYRIDINES ET LEURS ANALOGUES EN TANT QU'INHIBITEURS DE LA P38 MAP KINASE
  申请人：ASTEX TECHNOLOGY LTD

  公开号：WO2004004720A1

  公开（公告）日：2004-01-15

  Compounds of the formula (I), wherein: -X=Y- is selected from -CR2=CR3- and -CR2=N-; R1 is selected from H, halo, NRR', NHC(=O)R, NHC(=O)NRR', NH2SO2R, and C(=O)NRR'; R2 and R3 (where present) are independently selected from H, optionally substituted C1-7 alkyl, optionally substituted C5-20 aryl, optionally substituted C3-20 heterocyclyl, halo, amino, amido, hydroxy, ether, thio, thioether, acylamido, ureido and sulfonamino; R4 is an optionally substituted C5-20 aryl or C5-20 heteroaryl group; and R5 is selected from R5’, halo, NHR5’, C(=O)NHR5’, OR5’, SR5’, NHC(=O)R5’, NHC(=O)NHR5’, NHS(=O)R5’, wherein R5’ is H or C1-3 alkyl (optionally substituted by halo, NH2, OH, SH) are disclosed for use in therapy and for treating diseases ameliorated by inhibiting p38 MAP kinase.

  化合物的结构式（I），其中：-X=Y-选自-CR2=CR3-和-CR2=N-；R1选自H、卤素、NRR'、NHC（=O）R、NHC（=O）NRR'、NH2SO2R和C（=O）NRR'；R2和R3（如存在）独立选自H、可选择取代的C1-7烷基、可选择取代的C5-20芳基、可选择取代的C3-20杂环烷基、卤素、氨基、酰胺基、羟基、醚基、硫醚基、酰胺基、脲基和磺胺基；R4是可选择取代的C5-20芳基或C5-20杂芳基；R5选自R5'、卤素、NHR5'、C（=O）NHR5'、OR5'、SR5'、NHC（=O）R5'、NHC（=O）NHR5'、NHS（=O）R5'，其中R5'为H或C1-3烷基（可选择由卤素、NH2、OH、SH取代）用于治疗和治疗通过抑制p38 MAP激酶改善的疾病。
• [(alkoxy)pyridinyl]amine compounds which are useful in the treatment of
  申请人：SmithKline Beecham Intercredit B.V.

  公开号：US05409943A1

  公开（公告）日：1995-04-25

  The present invention relates to N-pyridylamidine and N-pyridylguanidine derivatives of general formula (I) in which: Ar.sup.1 is an optionally substituted phenyl ring; Ar.sup.2 is an optionally substituted phenyl ring; R.sup.1 is hydrogen or C.sub.1-4 alkyl; R.sup.2 is hydrogen or C.sub.1-4 alkyl; R.sup.3 is hydrogen or C.sub.1-4 alkyl; R.sup.4 is hydrogen, halogen, C.sub.1-6 alkyl or C.sub.1-6 alkoxy; X is CH.sub.2 or NR.sup.5, and R.sup.5 is hydrogen or C.sub.1-4 alkyl, and the salts thereof, and their use in therapy as gastric acid secretion inhibitors.

  本发明涉及一般式(I)的N-吡啶基脒和N-吡啶基胍衍生物，其中：Ar.sup.1是可选择取代的苯环；Ar.sup.2是可选择取代的苯环；R.sup.1是氢或C.sub.1-4烷基；R.sup.2是氢或C.sub.1-4烷基；R.sup.3是氢或C.sub.1-4烷基；R.sup.4是氢，卤素，C.sub.1-6烷基或C.sub.1-6烷氧基；X是CH.sub.2或NR.sup.5，R.sup.5是氢或C.sub.1-4烷基，以及它们的盐，以及它们在治疗中作为胃酸分泌抑制剂的用途。
• Synthesis and evaluation of 2-(3-arylureido)pyridines and 2-(3-arylureido)pyrazines as potential modulators of Aβ-induced mitochondrial dysfunction in Alzheimer's disease
  作者：Ahmed Elkamhawy、Jung-eun Park、Ahmed H.E. Hassan、Ae Nim Pae、Jiyoun Lee、Beoung-Geon Park、Eun Joo Roh

  DOI：10.1016/j.ejmech.2017.12.045

  日期：2018.1

  A series of 2-(3-arylureido)pyridines and 2-(3-benzylureido)pyridines were synthesized and evaluated as potential modulators for amyloid beta (Aβ)-induced mitochondrial dysfunction in Alzheimer's disease (AD). The blocking activities of forty one small molecules against Aβ-induced mitochondrial permeability transition pore (mPTP) opening were evaluated by JC-1 assay which measures the change of mitochondrial

  合成了一系列的2-（3-芳基脲基）吡啶和2-（3-苄基脲基）吡啶，并将其评估为淀粉样β（Aβ）诱导的阿尔茨海默氏病（AD）中的线粒体功能障碍的潜在调节剂。通过测量线粒体膜电位（ΔΨm）变化的JC-1分析评估了41个小分子对Aβ诱导的线粒体通透性转变孔（mPTP）开口的阻断活性。25种化合物对Aβ诱导的mPTP开放的抑制活性优于标准环孢菌素A（CsA）。就线粒体和细胞安全性而言，已鉴定出六种命中化合物可能是安全的，并对其对Aβ诱导的ATP产生的恶化和细胞毒性的保护作用进行了评估。其中，化合物7fb已被鉴定为保护神经元细胞免受67％的神经细胞毒性和43％的5μM浓度的Aβ诱导的线粒体ATP抑制抑制的先导化合物。使用CDocker算法，分子对接模型以亲环蛋白D（CypD）受体作为mPTP的主要成分，为这些化合物提供了一种可能的结合模式。因此，本报告提出化合物7fb作为一种新的非肽基mPTP阻断剂
• [EN] RAF KINASE INHIBITORS<br/>[FR] INHIBITEURS DE RAF KINASE
  申请人：ASTEX TECHNOLOGY LTD

  公开号：WO2005002673A1

  公开（公告）日：2005-01-13

  The use of a compound of the formula I or a pharmaceutically acceptable salt or solvate thereof, for the manufacture of a medicament for use in the treatment of a condition ameliorated by the inhibition of raf kinase, wherein: -X=Y- is selected from -CR2=CR3- and -CR2=N-; R1 is selected from H, halo, NRR', NHC (=O)R, NHC (=O)NRR', NH2SO2R, and C (=O)NRR', where R and R' are independently selected from H and C1-4 alkyl, and are optionally substituted by OH, NH2, SO2-NH2, C5-20 carboaryl, C5-20 heteroaryl and C3-20 heterocyclyl, or may together form, with the nitrogen atom to which they are attached, an optionally substituted nitrogen containing C5-7 heterocyclyl group; R2 and R3 (where present) are independently selected from H, optionally substituted C1-7 alkyl, optionally substituted C5-20 aryl, optionally substituted C3-20 heterocyclyl, halo, amino, amido, hydroxy, ether, thio, thioether, acylamido, ureido and sulfonamino; R4 an optionally substituted C5-20 carboaryl or C5-20 heteroaryl group; and R5 is selected from R5', halo, NHR5', C(=O)NHR5', OR5', SR5', NHC (=O)R5', NHC (=O)NHR5', NHS (=O) 2R5', wherein R5' is H or C1-3 alkyl (optionally substituted by halo, NH2, OH, SH).

  使用公式I的化合物或其药学上可接受的盐或溶剂制造药物，用于治疗通过抑制Raf激酶改善的疾病，其中：-X=Y-选择自-CR2=CR3-和-CR2=N-；R1选择自H、卤素、NRR'、NHC(=O)R、NHC(=O)NRR'、NH2SO2R和C(=O)NRR'，其中R和R'独立选择自H和C1-4烷基，可选择性地被OH、NH2、SO2-NH2、C5-20碳基芳基、C5-20杂环芳基和C3-20杂环基取代，或者与它们附着的氮原子一起形成一个可选择性地被取代的含氮C5-7杂环基；R2和R3（存在时）独立选择自H、可选择性地被取代的C1-7烷基、可选择性地被取代的C5-20芳基、可选择性地被取代的C3-20杂环基、卤素、氨基、酰胺、羟基、醚、硫、硫醚、酰胺基、脲基和磺酰氨基；R4为可选择性地被取代的C5-20碳基芳基或C5-20杂环芳基；R5选择自R5'、卤素、NHR5'、C(=O)NHR5'、OR5'、SR5'、NHC(=O)R5'、NHC(=O)NHR5'和NHS(=O)2R5'，其中R5'为H或C1-3烷基（可选择性地被卤素、NH2、OH、SH取代）。
• Aminoheteroaryl compounds as protein kinase inhibitors
  申请人：Cui Jean Jingrong

  公开号：US20050009840A1

  公开（公告）日：2005-01-13

  Aminopyridine and aminopyrazine compounds of formula (1), compositions including these compounds, and methods of their use are provided. Preferred compounds of formula 1 have activity as protein kinase inhibitors, including as inhibitors of c-MET.

  提供了公式（1）的氨基吡啶和氨基吡嗪化合物、包括这些化合物的组合物以及它们的使用方法。公式1的优选化合物具有作为蛋白激酶抑制剂的活性，包括作为c-MET的抑制剂。