6-(1-methyl-1H-pyrazol-5-yl)pyridin-3-amine

• 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: 6-(1-methyl-1H-pyrazol-5-yl)pyridin-3-amine
• 英文别名: 6-(1-Methyl-1H-pyrazol-5-yl)pyridin-3-amine；6-(2-methylpyrazol-3-yl)pyridin-3-amine
• 化学式: C₉H₁₀N₄
• 分子量: 174.205
• InChiKey: MSFAAVFCFNEXGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  56.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(1-methyl-1H-pyrazol-5-yl)pyridin-3-amine 在 sodium acetate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙腈 为溶剂， 反应 50.0h， 生成 2-(6-(1-methyl-1H-pyrazol-5-yl)pyridin-3-ylamino)propanoic acid
  参考文献：
  名称：

  Discovery and Optimization of a Porcupine Inhibitor

  摘要：

  Wnt proteins regulate various cellular functions and serve distinct roles in normal development throughout life. Wnt signaling is dysregulated in various diseases including cancers. Porcupine (PORCN) is a membrane-bound O-acyltransferase that palmitoleates the Wnts and hence is essential for their secretion and function. The inhibition of PORCN could serve as a therapeutic approach for the treatment of a number of Wnt-dependent cancers. Herein, we describe the identification of a Wnt secretion inhibitor from cellular high throughput screening. Classical SAR based cellular optimization provided us with a PORCN inhibitor with nanomolar activity and excellent bioavallability that demonstrated efficacy in a Wnt-driven murine tumor model. Finally, we also discovered that enantiomeric PORCN inhibitors show very different activity in our reporter assay, suggesting that such compounds may be useful for mode of action studies on the PORCN O-acyltransferase.

  DOI：

  10.1021/acs.jmedchem.5b00507
• 作为产物：
  描述：

  2-溴-5-硝基吡啶 在 potassium phosphate 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 作用下， 以 1,4-二氧六环 、 水 、 乙酸乙酯 为溶剂， 反应 28.0h， 生成 6-(1-methyl-1H-pyrazol-5-yl)pyridin-3-amine
  参考文献：
  名称：

  Discovery and Optimization of a Porcupine Inhibitor

  摘要：

  Wnt proteins regulate various cellular functions and serve distinct roles in normal development throughout life. Wnt signaling is dysregulated in various diseases including cancers. Porcupine (PORCN) is a membrane-bound O-acyltransferase that palmitoleates the Wnts and hence is essential for their secretion and function. The inhibition of PORCN could serve as a therapeutic approach for the treatment of a number of Wnt-dependent cancers. Herein, we describe the identification of a Wnt secretion inhibitor from cellular high throughput screening. Classical SAR based cellular optimization provided us with a PORCN inhibitor with nanomolar activity and excellent bioavallability that demonstrated efficacy in a Wnt-driven murine tumor model. Finally, we also discovered that enantiomeric PORCN inhibitors show very different activity in our reporter assay, suggesting that such compounds may be useful for mode of action studies on the PORCN O-acyltransferase.

  DOI：

  10.1021/acs.jmedchem.5b00507

文献信息

• [EN] WNT PATHWAY MODULATORS<br/>[FR] MODULATEURS DE LA VOIE WNT
  申请人：AGENCY SCIENCE TECH & RES

  公开号：WO2014175832A1

  公开（公告）日：2014-10-30

  The invention provides a compound of structure Ar1-Ar2-X-C(R1R2)-C(=O)-N(R3)-Ar3-Ar4 for modulating WNT activity. In this structure, Ar1, Ar2, Ar3 and Ar4 are, independently, optionally substituted aryl or heteroaryl groups; R1 and R3 are, independently, H or optionally substituted alkyl groups; R2 is H or an optionally substituted alkyl group or an alkylene group which, together with the carbon atom to which it is attached and X, forms a non-aromatic ring or an alkylene group which, together with the carbon atom to which it is attached and X and two adjacent atoms of Ar2, forms a non-aromatic ring; X is O, CR4R5, N or NR4, wherein if X is N, it is bonded to R2; R4 is H, optionally substituted alkyl or an alkylene chain, optionally containing a heteroatom and/or a carbonyl group, which, together with the C or N to which it is attached and two adjacent atoms of Ar2, forms a non-aromatic ring; R5 is H, NH2 or an optionally substituted alkyl group.

  该发明提供了一种结构为Ar1-Ar2-X-C(R1R2)-C(=O)-N(R3)-Ar3-Ar4的化合物，用于调节WNT活性。在这种结构中，Ar1、Ar2、Ar3和Ar4分别是可选择取代的芳基或杂环芳基；R1和R3分别是H或可选择取代的烷基；R2是H或可选择取代的烷基或与其连接的碳原子和X形成非芳香环的烷基，或者与其连接的碳原子、X和Ar2的两个相邻原子形成非芳香环的烷基；X是O、CR4R5、N或NR4，如果X是N，则与R2相结合；R4是H、可选择取代的烷基或含有杂原子和/或羰基的烷基链，与其连接的C或N以及Ar2的两个相邻原子形成非芳香环；R5是H、NH2或可选择取代的烷基。
• Discovery and Optimization of a Porcupine Inhibitor
  作者：Athisayamani Jeyaraj Duraiswamy、May Ann Lee、Babita Madan、Shi Hua Ang、Eldwin Sum Wai Tan、Wei Wen Vivien Cheong、Zhiyuan Ke、Vishal Pendharkar、Li Jun Ding、Yun Shan Chew、Vithya Manoharan、Kanda Sangthongpitag、Jenefer Alam、Anders Poulsen、Soo Yei Ho、David M. Virshup、Thomas H. Keller

  DOI：10.1021/acs.jmedchem.5b00507

  日期：2015.8.13

  Wnt proteins regulate various cellular functions and serve distinct roles in normal development throughout life. Wnt signaling is dysregulated in various diseases including cancers. Porcupine (PORCN) is a membrane-bound O-acyltransferase that palmitoleates the Wnts and hence is essential for their secretion and function. The inhibition of PORCN could serve as a therapeutic approach for the treatment of a number of Wnt-dependent cancers. Herein, we describe the identification of a Wnt secretion inhibitor from cellular high throughput screening. Classical SAR based cellular optimization provided us with a PORCN inhibitor with nanomolar activity and excellent bioavallability that demonstrated efficacy in a Wnt-driven murine tumor model. Finally, we also discovered that enantiomeric PORCN inhibitors show very different activity in our reporter assay, suggesting that such compounds may be useful for mode of action studies on the PORCN O-acyltransferase.