4-morpholino-6-(2-tetrahydropyranyl)oxymethyl-2-pyridinecarboxylic acid | 196499-65-7

• 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: 4-morpholino-6-(2-tetrahydropyranyl)oxymethyl-2-pyridinecarboxylic acid
• 英文别名: 4-Morpholin-4-yl-6-(oxan-2-yloxymethyl)pyridine-2-carboxylic acid
• CAS: 196499-65-7
• 化学式: C₁₆H₂₂N₂O₅
• 分子量: 322.361
• InChiKey: UOCTZJQLPDMQPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  81.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-morpholino-6-(2-tetrahydropyranyl)oxymethyl-2-pyridinecarboxylic acid 在 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成
  参考文献：
  名称：

  Optimization of a series of 2,4-diaminopyridines as neuropeptide Y Y1 receptor antagonists with reduced hERG activity

  摘要：

  The synthesis and evaluation of a series of 2,4-diaminopyridine-based neuropeptide Y Y1 ( NPY Y1) receptor antagonists are described. Compound 1 was previously reported by our laboratory to be a potent and selective Y1 antagonist; however, 1 was also found to have potent hERG inhibitory activity. The main focus of this communication is structure-activity relationship development aimed at eliminating the hERG activity of 1. This resulted in the identification of compound 3d as a potent and selective NPY Y1 antagonist with reduced hERG liability. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.05.069
• 作为产物：
  描述：

  在 甲醇 、 水 、 sodium hydroxide 作用下， 生成 4-morpholino-6-(2-tetrahydropyranyl)oxymethyl-2-pyridinecarboxylic acid
  参考文献：
  名称：

  Optimization of a series of 2,4-diaminopyridines as neuropeptide Y Y1 receptor antagonists with reduced hERG activity

  摘要：

  The synthesis and evaluation of a series of 2,4-diaminopyridine-based neuropeptide Y Y1 ( NPY Y1) receptor antagonists are described. Compound 1 was previously reported by our laboratory to be a potent and selective Y1 antagonist; however, 1 was also found to have potent hERG inhibitory activity. The main focus of this communication is structure-activity relationship development aimed at eliminating the hERG activity of 1. This resulted in the identification of compound 3d as a potent and selective NPY Y1 antagonist with reduced hERG liability. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.05.069

文献信息

• Aminopyridine derivatives
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US06011039A1

  公开（公告）日：2000-01-04

  A compound represented by the formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition for hyperphagia, obesity or diabetes, which comprises such a compound or salt as an active ingredient: ##STR1## wherein Ar.sup.1, Ar.sup.2, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and W are as defined.

  化合物(I)及其药学上可接受的盐，以及包含该化合物或盐作为活性成分的用于治疗过度进食、肥胖或糖尿病的制药组合物：##STR1## 其中，Ar.sup.1，Ar.sup.2，R.sup.1，R.sup.2，R.sup.3，R.sup.4和W的定义如上。
• AMINOPYRIDINE DERIVATIVES
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP0889034A1

  公开（公告）日：1999-01-07

  The present invention relates to a compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof, and a treating agent for hyperphagia, obesity or diabetes, which comprises such a compound or salt as an active ingredient: [wherein Ar1 is an aryl group or an aromatic heterocyclic group, which may be substituted by a group selected from the group consisting of a lower alkyl group, a lower hydroxyalkyl group, a lower alkylene group and a group represented by -NRaRb; R1 is a hydrogen atom or a lower alkyl group; each of R2 and R3 which are the same or different, is a lower alkyl group, or both of R2 and R3 are bonded to each other to form an alkylene group which may have an oxygen atom or a sulfur atom interposed, said alkylene group being a group which may be substituted by one or two lower alkyl groups; R4 is a hydrogen atom, or a lower alkyl group which may be substituted by a group selected from the group consisting of a hydroxyl group, an amino group, a carbamoyl group and a lower alkoxycarbonyl group; Ar2 is an aryl group or an aromatic heterocyclic group, which may be substituted by a group selected from the group consisting of a halogen atom, a hydroxyl group, a lower alkyl group, a lower haloalkyl group, a lower alkoxy group, a lower alkylthio group, a lower hydroxyalkyl group, a lower alkoxy-lower alkyl group, a group represented by -NRcRd and a group represented by -NRe-CO-NRfRg; W is an oxygen atom, a sulfur atom, or a group represented by -CHRj- or -NRk-].

  本发明涉及一种通式(I)代表的化合物或其药学上可接受的盐，以及一种治疗食欲亢进、肥胖或糖尿病的药物，其有效成分包括这样的化合物或盐： [其中 Ar1 是芳基或芳香杂环基，可被选自由低级烷基、低级羟烷基、低级亚烷基和 -NRaRb 所代表的基团组成的基团取代；R1 是氢原子或低级烷基；相同或不同的 R2 和 R3 中的每一个都是低级烷基，或 R2 和 R3 两者相互键合形成一个亚烷基，该亚烷基中可能有一个氧原子或一个硫原子，所述亚烷基是一个可被一个或两个低级烷基取代的基团；R4 是氢原子，或可被选自羟基、氨基、氨基甲酰基和低级烷氧基羰基的基团取代的低级烷基；Ar2 是芳基或芳香杂环基，可被选自由卤素原子、羟基、低级烷基、低级卤代 烷基、低级烷氧基、低级烷硫基、低级羟烷基、低级烷氧基-低级烷基、由 -NRcRd 表示的基团和由 -NRe-CO-NRfRg 表示的基团组成的组取代；W 是氧原子、硫原子或由 -CHRj- 或 -NRk- 代表的基团]。
• US6011039A
  申请人：——

  公开号：US6011039A

  公开（公告）日：2000-01-04
• Optimization of a series of 2,4-diaminopyridines as neuropeptide Y Y1 receptor antagonists with reduced hERG activity
  作者：Minoru Kameda、Kensuke Kobayashi、Hirokatsu Ito、Hiroshi Miyazoe、Toshiaki Tsujino、Chisato Nakama、Hiroshi Kawamoto、Makoto Ando、Sayaka Ito、Tomoki Suzuki、Tetsuya Kanno、Takeshi Tanaka、Yoshio Tahara、Takeshi Tani、Sachiko Tanaka、Shigeru Tokita、Nagaaki Sato

  DOI：10.1016/j.bmcl.2009.05.069

  日期：2009.8

  The synthesis and evaluation of a series of 2,4-diaminopyridine-based neuropeptide Y Y1 ( NPY Y1) receptor antagonists are described. Compound 1 was previously reported by our laboratory to be a potent and selective Y1 antagonist; however, 1 was also found to have potent hERG inhibitory activity. The main focus of this communication is structure-activity relationship development aimed at eliminating the hERG activity of 1. This resulted in the identification of compound 3d as a potent and selective NPY Y1 antagonist with reduced hERG liability. (C) 2009 Elsevier Ltd. All rights reserved.