C-[5-chloro-4-(2,3,4,5-tetrahydro-pyran-2-yloxymethyl)-pyridin-3-yl]-methylamine | 1174132-87-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: C-[5-chloro-4-(2,3,4,5-tetrahydro-pyran-2-yloxymethyl)-pyridin-3-yl]-methylamine
• 英文别名: C-[5-Chloro-4-(tetrahydro-pyran-2-yloxymethyl)-pyridin-3-yl]-methylamine；[5-chloro-4-(oxan-2-yloxymethyl)pyridin-3-yl]methanamine
• CAS: 1174132-87-6
• 化学式: C₁₂H₁₇ClN₂O₂
• 分子量: 256.732
• InChiKey: LBHRVAVDJXCGEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  57.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  C-[5-chloro-4-(2,3,4,5-tetrahydro-pyran-2-yloxymethyl)-pyridin-3-yl]-methylamine 、 异丁酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-[5-chloro-4-(2,3,4,5-tetrahydro-pyran-2-yloxymethyl)-pyridin-3-ylmethyl]-isobutyramide
  参考文献：
  名称：

  Novel Small Molecule Bradykinin B₂ Receptor Antagonists

  摘要：

  Blockade of the bradykinin B, receptor provides therapeutic benefit in hereditary angioedema (HAE) and potentially in many other diseases. Herein, we describe the development of highly potent B, receptor antagonists with a molecular weight of approximately 500 g/mol. First, known quinoline-based B-2 receptor antagonists were stripped down to their shared core motif 53, which turned out to be the minimum pharmacophore. Targeted modifications of 53 resulted in the highly water-soluble lead compound 8a. Extensive exploration of its structure-activity relationship resulted in a series of highly potent B-2 receptor antagonists, featuring a hydrogen bond accepting functionality, which presumably interacts with the side chain of Asn-107 of the B-2 receptor, Optimization of the microsomal stability and cytochrome P450 inhibition eventually led to the discovery of the highly potent and orally available B-2 receptor antagonist 52e (JSM 10292), which showed the best overall properties.

  DOI：

  10.1021/jm9002445
• 作为产物：
  描述：

  3-azidomethyl-5-chloro-4-(tetrahydro-pyran-2-yloxymethyl)-pyridine 在 水 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 C-[5-chloro-4-(2,3,4,5-tetrahydro-pyran-2-yloxymethyl)-pyridin-3-yl]-methylamine
  参考文献：
  名称：

  Novel Small Molecule Bradykinin B₂ Receptor Antagonists

  摘要：

  Blockade of the bradykinin B, receptor provides therapeutic benefit in hereditary angioedema (HAE) and potentially in many other diseases. Herein, we describe the development of highly potent B, receptor antagonists with a molecular weight of approximately 500 g/mol. First, known quinoline-based B-2 receptor antagonists were stripped down to their shared core motif 53, which turned out to be the minimum pharmacophore. Targeted modifications of 53 resulted in the highly water-soluble lead compound 8a. Extensive exploration of its structure-activity relationship resulted in a series of highly potent B-2 receptor antagonists, featuring a hydrogen bond accepting functionality, which presumably interacts with the side chain of Asn-107 of the B-2 receptor, Optimization of the microsomal stability and cytochrome P450 inhibition eventually led to the discovery of the highly potent and orally available B-2 receptor antagonist 52e (JSM 10292), which showed the best overall properties.

  DOI：

  10.1021/jm9002445

文献信息

• 8-OXY-QUINOLINE DERIVATIVES AS BRADYKININ B2 RECEPTOR MODULATORS
  申请人：Gibson Christoph

  公开号：US20100234344A1

  公开（公告）日：2010-09-16

  The present invention is related to compound of the formula (I): or a pharmacologically acceptable salt, solvate, or hydrate thereof, wherein A is a 6-membered heteroaryl having from 1 to 3 heteroatoms, each independently selected from N or O and the other substituents are defined as in the claims.

  本发明涉及公式(I)的化合物或其药理学上可接受的盐、溶剂合物或水合物，其中A是一种具有1至3个杂原子的6元杂环芳基，每个杂原子独立地选自N或O，其它取代基如权利要求所定义。
• 8-oxy-quinoline derivatives as bradykinin B2 receptor modulators
  申请人：Gibson Christoph

  公开号：US08410134B2

  公开（公告）日：2013-04-02

  The present invention is related to compound of the formula (I): or a pharmacologically acceptable salt, solvate, or hydrate thereof, wherein A is a 6-membered heteroaryl having from 1 to 3 heteroatoms, each independently selected from N or O and the other substituents are defined as in the claims.

  本发明涉及公式（I）的化合物或其药学上可接受的盐、溶剂或水合物，其中A是具有1至3个杂原子的6元杂环芳基，每个杂原子独立选择自N或O，其他取代基如权利要求所定义。
• US8410134B2
  申请人：——

  公开号：US8410134B2

  公开（公告）日：2013-04-02
• [EN] 8-OXY-QUINOLINE DERIVATIVES AS BRADYKININ B2 RECEPTOR MODULATORS<br/>[FR] DÉRIVÉS DE 8-OXY-QUINOLÉINE COMME MODULATEURS DU RÉCEPTEUR B2 DE LA BRADYKININE
  申请人：JERINI AG

  公开号：WO2008116620A1

  公开（公告）日：2008-10-02

  [EN] The present invention is related to compound of the formula (I): or a pharmacologically acceptable salt, solvate, or hydrate thereof, wherein A is a 6-membered heteroaryl having from 1 to 3 heteroatoms, each independently selected from N or O and the other substituents are defined as in the claims.
  [FR] La présente invention porte sur un composé de la formule (I) : ou sur un sel, un solvate ou hydrate pharmacologiquement acceptable de celui-ci, où A est un hétéroaryle à 6 chaînons ayant de 1 à 3 hétéroatome, chacun choisi indépendamment parmi N ou O ; et les autres substituants sont tels que définis dans les revendications.
• Novel Small Molecule Bradykinin B₂ Receptor Antagonists
  作者：Christoph Gibson、Karsten Schnatbaum、Jochen R. Pfeifer、Elsa Locardi、Matthias Paschke、Ulf Reimer、Uwe Richter、Dirk Scharn、Alexander Faussner、Thomas Tradler

  DOI：10.1021/jm9002445

  日期：2009.7.23

  Blockade of the bradykinin B, receptor provides therapeutic benefit in hereditary angioedema (HAE) and potentially in many other diseases. Herein, we describe the development of highly potent B, receptor antagonists with a molecular weight of approximately 500 g/mol. First, known quinoline-based B-2 receptor antagonists were stripped down to their shared core motif 53, which turned out to be the minimum pharmacophore. Targeted modifications of 53 resulted in the highly water-soluble lead compound 8a. Extensive exploration of its structure-activity relationship resulted in a series of highly potent B-2 receptor antagonists, featuring a hydrogen bond accepting functionality, which presumably interacts with the side chain of Asn-107 of the B-2 receptor, Optimization of the microsomal stability and cytochrome P450 inhibition eventually led to the discovery of the highly potent and orally available B-2 receptor antagonist 52e (JSM 10292), which showed the best overall properties.