2-(6-chloro-5-methylpyridin-3-yl)acetic acid | 1000546-06-4

• 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: 2-(6-chloro-5-methylpyridin-3-yl)acetic acid
• CAS: 1000546-06-4
• 化学式: C₈H₈ClNO₂
• mdl: MFCD09925187
• 分子量: 185.61
• InChiKey: BLMQSKNWZLCAEW-UHFFFAOYSA-N

物化性质

• 沸点：
  349.5±37.0 °C(Predicted)
• 密度：
  1.341±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P362,P403+P233,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-(6-chloro-5-methylpyridin-3-yl)acetic acid 在 四(三苯基膦)钯 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 2-(2',3-dimethyl[2,4'-bipyridin]-5-yl)-N-(9-oxo-9H-fluoren-2-yl)acetamide
  参考文献：
  名称：

  Design, synthesis, and evaluation of potent Wnt signaling inhibitors featuring a fused 3-ring system

  摘要：

  The Wnt signaling pathway is a critical developmental pathway which operates through control of cellular functions such as proliferation and differentiation. Aberrant Wnt signaling has been linked to the formation and metastasis of tumors. Porcupine, a member of the membrane -bound O-acyltransferase family of proteins, is an important component of the Wnt pathway. Porcupine catalyzes the palmitoylation of Wnt proteins, a process needed for their secretion and activity. Here we report a novel series of compounds obtained by a scaffold hybridization strategy from a known porcupine inhibitor class. The leading compound 59 demonstrated subnanomolar inhibition of Wnt signaling in a paracrine cellular assay. Compound 59 also showed excellent chemical, plasma and liver microsomal stabilities. Furthermore, compound 59 exhibited good pharmacokinetic profiles with 30% oral bioavailability in rat. Collectively, these results strongly support further optimization of this novel scaffold to develop better Wnt pathway inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.026
• 作为产物：
  描述：

  2-甲基-2-丁烯腈 在 sodium tetrahydroborate 、 氯化亚砜 、 硫酸 、 水 、 potassium carbonate 、 potassium iodide 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 27.0h， 生成 2-(6-chloro-5-methylpyridin-3-yl)acetic acid
  参考文献：
  名称：

  Design, synthesis, and evaluation of potent Wnt signaling inhibitors featuring a fused 3-ring system

  摘要：

  The Wnt signaling pathway is a critical developmental pathway which operates through control of cellular functions such as proliferation and differentiation. Aberrant Wnt signaling has been linked to the formation and metastasis of tumors. Porcupine, a member of the membrane -bound O-acyltransferase family of proteins, is an important component of the Wnt pathway. Porcupine catalyzes the palmitoylation of Wnt proteins, a process needed for their secretion and activity. Here we report a novel series of compounds obtained by a scaffold hybridization strategy from a known porcupine inhibitor class. The leading compound 59 demonstrated subnanomolar inhibition of Wnt signaling in a paracrine cellular assay. Compound 59 also showed excellent chemical, plasma and liver microsomal stabilities. Furthermore, compound 59 exhibited good pharmacokinetic profiles with 30% oral bioavailability in rat. Collectively, these results strongly support further optimization of this novel scaffold to develop better Wnt pathway inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.026

文献信息

• [EN] PERFLUORINATED CYCLOPROPYL FUSED 1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE<br/>[FR] COMPOSÉS À BASE DE 1,3-OXAZIN-2-AMINE FUSIONNÉE AVEC DU CYCLOPROPYLE PERFLUORÉ UTILISABLES EN TANT QU'INHIBITEURS DE LA BÊTA-SÉCRÉTASE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2014138484A1

  公开（公告）日：2014-09-12

  PERFLUORINATED CYCLOPROPYL FUSED 1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE ABSTRACT OF THE DISCLOSURE The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: INSERT STRUCTURE HERE} I wherein variables A4, A5, A6, A8, each of Ra, Rb, R1, R2, R3 and R7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas II and III, and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.

  本发明提供了一类新的化合物，用于调节β-分泌酶（BACE）活性。这些化合物具有一般的化学式I：在此插入结构} I，其中变量A4、A5、A6、A8，以及化学式I中的每个Ra、Rb、R1、R2、R3和R7，在本文中分别定义。该发明还提供了包含这些化合物的药物组合物，以及用于治疗与A-beta斑块形成和沉积相关的疾病和/或症状的化合物和组合物的用途，这些疾病和症状是由BACE的生物活性引起的。这种由BACE介导的疾病包括阿尔茨海默病、认知缺陷、认知障碍、精神分裂症和其他中枢神经系统疾病。该发明还提供了化学式II和III的化合物，以及其亚式化合物、中间体和制备本发明化合物的方法。
• PERFLUORINATED 5,6-DIHYDRO-4H-1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE
  申请人：AMGEN INC.

  公开号：US20140249104A1

  公开（公告）日：2014-09-04

  The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A 4 , A 5 , A 6 , A 8 , each of R 1 and R 2 , R 3 and R 7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas II and III, and sub-formula embodiments thereof, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III.

  本发明提供了一类新的化合物，用于调节β-分泌酶（BACE）活性。这些化合物的通用公式为I： 其中变量A4，A5，A6，A8，公式I中的R1和R2，R3和R7各自独立定义如下。本发明还提供了包含这些化合物的药物组合物，以及使用这些化合物和组合物治疗与A-β斑块形成和沉积相关的疾病和/或状况，这些疾病和/或状况是由BACE的生物活性引起的。这样的BACE介导的疾病包括，例如，阿尔茨海默病，认知缺陷，认知障碍，精神分裂症和其他中枢神经系统疾病。本发明进一步提供了公式II和III的化合物，以及其子公式的实施例，中间体和用于制备公式I-III化合物的过程和方法。
• [EN] N- (HETERO)ARYL, 2- (HETERO)ARYL-SUBSTITUTED ACETAMIDES FOR USE AS WNT SIGNALING MODULATORS<br/>[FR] ACÉTAMIDES À SUBSTITUTION N-(HÉTÉRO)ARYL, 2-(HÉTÉRO)ARYLE POUR UNE UTILISATION EN TANT QUE MODULATEURS DE LA VOIE DE SIGNALISATION WNT
  申请人：IRM LLC

  公开号：WO2010101849A1

  公开（公告）日：2010-09-10

  The present invention relates to compounds of formulae 1 and 2 and methods for modulating the Wnt signaling pathway using these compounds, wherein A1, A2, B, Y and Z all represent rings.

  本发明涉及公式1和2的化合物，以及使用这些化合物调节Wnt信号通路的方法，其中A1、A2、B、Y和Z都代表环。
• Discovery of Pyridinyl Acetamide Derivatives as Potent, Selective, and Orally Bioavailable Porcupine Inhibitors
  作者：Dai Cheng、Jun Liu、Dong Han、Guobao Zhang、Wenqi Gao、Mindy H. Hsieh、Nicholas Ng、Shailaja Kasibhatla、Celin Tompkins、Jie Li、Auzon Steffy、Fangxian Sun、Chun Li、H. Martin Seidel、Jennifer L. Harris、Shifeng Pan

  DOI：10.1021/acsmedchemlett.6b00038

  日期：2016.7.14

  high-throughput screen for inhibitors of Wnt secretion and pathway activation. A lead structure (GNF-1331) was identified from the screen. Further studies identified the molecular target of GNF-1331 as Porcupine, a membrane bound O-acyl transferase. Structure-activity relationship studies led to the discovery of a novel series of potent and selective Porcupine inhibitors. Compound 19, GNF-6231, demonstrated

  异常Wnt信号传导的阻断是多种癌症中的一种有吸引力的治疗方法。我们开发并执行了针对Wnt分泌和途径激活抑制剂的细胞高通量筛选。从屏幕上识别出引线结构（GNF-1331）。进一步的研究确定了GNF-1331的分子靶标为豪猪（一种膜结合的O-酰基转移酶）。结构-活性关系研究导致发现了一系列新型的有效和选择性豪猪抑制剂。在小鼠MMTV-WNT1异种移植肿瘤模型中，化合物19 GNF-6231表现出出色的途径抑制作用，并诱导了强大的抗肿瘤功效。
• N-(hetero)aryl, 2-(hetero)aryl—substituted acetamides for use as Wnt signaling modulators
  申请人：Cheng Dai

  公开号：US08546396B2

  公开（公告）日：2013-10-01

  The present invention relates to compounds of formulae 1 and 2 and methods for modulating the Wnt signaling pathway using these compounds, wherein A1, A2, B, Y and Z all represent rings.

  本发明涉及式1和式2的化合物以及利用这些化合物调节Wnt信号通路的方法，其中A1、A2、B、Y和Z均表示环。