4-chloro-5-iodo-2-(methoxymethyl)-6-methylpyrimidine | 215437-31-3

• 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-chloro-5-iodo-2-(methoxymethyl)-6-methylpyrimidine
• CAS: 215437-31-3
• 化学式: C₇H₈ClIN₂O
• 分子量: 298.511
• InChiKey: PKSCALKBWAANIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-chloro-5-iodo-2-(methoxymethyl)-6-methylpyrimidine 在 盐酸 、 potassium fluoride 、 copper(l) iodide 、 四(三苯基膦)钯 、 tris-(dibenzylideneacetone)dipalladium(0) 、 三溴化硼 、 sodium hydride 、 碳酸氢钠 、 lithium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 正丁醇 为溶剂， 反应 95.33h， 生成 8-[2'-(2-tert-Butyl-2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-5-hydroxy-2-hydroxymethyl-4-methyl-8H-pyrido[2,3-d]pyrimidin-7-one
  参考文献：
  名称：

  Metabolites of the Angiotensin II Antagonist Tasosartan:  The Importance of a Second Acidic Group

  摘要：

  Described in this paper is the synthesis and pharmacological activity of five metabolites of the angiotensin II antagonist tasosartan (1). Of particular interest is the effect of the additional acidic group of the enol metabolite (8) on activity. As suggested by the structural-activity relationship of other angiotensin II antagonist series, a second acidic group can improve receptor binding activity but decrease in vivo activity after oral dosing. The metabolic introduction of a second acidic group in tasosartan bypasses this problem and contributes to the excellent profile of the compound. A molecular modeling study provides a rationale for the role of the enol group of 8 in AT(1) receptor binding.

  DOI：

  10.1021/jm970690q
• 作为产物：
  描述：

  5-iodo-2-(methoxymethyl)-6-methylpyrimidin-4(3H)-one 在 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 1.5h， 以91%的产率得到4-chloro-5-iodo-2-(methoxymethyl)-6-methylpyrimidine
  参考文献：
  名称：

  Metabolites of the Angiotensin II Antagonist Tasosartan:  The Importance of a Second Acidic Group

  摘要：

  Described in this paper is the synthesis and pharmacological activity of five metabolites of the angiotensin II antagonist tasosartan (1). Of particular interest is the effect of the additional acidic group of the enol metabolite (8) on activity. As suggested by the structural-activity relationship of other angiotensin II antagonist series, a second acidic group can improve receptor binding activity but decrease in vivo activity after oral dosing. The metabolic introduction of a second acidic group in tasosartan bypasses this problem and contributes to the excellent profile of the compound. A molecular modeling study provides a rationale for the role of the enol group of 8 in AT(1) receptor binding.

  DOI：

  10.1021/jm970690q

文献信息

• Pyrimidine derivative
  申请人：Daiichi Sankyo Company, Limited

  公开号：US11034659B2

  公开（公告）日：2021-06-15

  Cystic fibrosis is developed through mutation of Cystic Fibrosis Transmembrane conductance Regulator (CFTR), which is one type of chloride channel. An object of the present invention is to provide compounds effective in the treatment of cystic fibrosis that open a chloride channel different from CFTR, which is the cause of the disease, and do not depend on CFTR. Compounds of the present invention are compounds or pharmaceutically acceptable salts thereof that open calcium dependent chloride channels (CaCCs) via G-protein coupled receptor 39 (GPR39) agonism to have strong chloride ion-secretory action, and are represented by the following general formula (I): General formula (I): wherein, X represents a carboxyl group or a tetrazolyl group; Q represents a C1-C3 alkylene group, an oxygen atom, a sulfur atom, etc.; G represents a phenyl group where the phenyl group may have 1 to 3 substituents independently selected from the group consisting of a halogen atom, a cyano group, a C1-C6 alkyl group, etc.; R1 represents a C1-C6 alkyl group, etc.; R2 represents a C1-C6 alkyl group that may have 1 to 3 substituents independently selected from the following group A, or a group selected from the following group B: Group A: a phenyl group and a pyridyl group, wherein the phenyl group and the pyridyl group may have 1 to 3 substituents independently selected from the following group D; Group B: —OH, —O-M, —SH, —S-M, —NH2, —NH-M, and —N-M2, wherein M is a C1-C6 alkyl group that may have 1 or 2 substituents independently selected from the following group C, or a C3-C6 cycloalkyl group that may have 1 or 2 substituents independently selected from the following group C; Group C: a halogen atom, a cyano group, a phenyl group, a pyridyl group, etc., wherein the phenyl group and the pyridyl group may have 1 to 3 substituents independently selected from the following group D; and Group D: a halogen atom, a cyano group, a C1-C6 alkyl group, etc.

  囊性纤维化是通过囊性纤维化跨膜传导调节器（CFTR）的突变而形成的，CFTR 是氯离子通道的一种。本发明的目的之一是提供对治疗囊性纤维化有效的化合物，这种化合物能打开不同于致病原因 CFTR 的氯离子通道，并且不依赖于 CFTR。 本发明的化合物是通过 G 蛋白偶联受体 39（GPR39）激动作用打开钙依赖性氯离子通道（CaCC），从而具有强氯离子分泌作用的化合物或其药学上可接受的盐，由以下通式（I）表示： 通式（I）： 其中 X 代表羧基或四唑基； Q 代表 C1-C3 烯基、氧原子、硫原子等； G 代表苯基，其中苯基可具有 1 至 3 个取代基，这些取代基独立地选自卤素原子、氰基、C1-C6 烷基等组成的组； R1 代表 C1-C6 烷基等； R2 代表 C1-C6 烷基，可具有 1 至 3 个独立选自以下 A 组的取代基，或一个选自以下 B 组的基团： A 组：苯基和吡啶基，其中苯基和吡啶基可具有 1 至 3 个独立选自以下 D 组的取代基； B组：-OH、-O-M、-SH、-S-M、-NH2、-NH-M和-N-M2，其中M是可具有1或2个独立选自以下基团C的取代基的C1-C6烷基，或可具有1或2个独立选自以下基团C的取代基的C3-C6环烷基； C 组：卤素原子、氰基、苯基、吡啶基等，其中苯基和吡啶基可具有 1 至 3 个独立选自以下 D 组的取代基；以及 基团 D：卤素原子、氰基、C1-C6 烷基等。
• PYRIMIDINE DERIVATIVE
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP3564216B1

  公开（公告）日：2021-10-27