N-[3,5-bis(trifluoromethyl)benzyl]-2-chloro-N-(3-hydroxypropyl)-4-iodo-3-pyridinecarboxamide | 544671-79-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[3,5-bis(trifluoromethyl)benzyl]-2-chloro-N-(3-hydroxypropyl)-4-iodo-3-pyridinecarboxamide
• 英文别名: N-[3,5-bis(trifluoromethyl)benzyl]-2-chloro-N-(3-hydroxypropyl)-4-iodonicotinamide；N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-chloro-N-(3-hydroxypropyl)-4-iodopyridine-3-carboxamide
• CAS: 544671-79-6
• 化学式: C₁₈H₁₄ClF₆IN₂O₂
• 分子量: 566.669
• InChiKey: PPYGEQBWQKZAIQ-UHFFFAOYSA-N

物化性质

• 熔点：
  99-102 °C
• 沸点：
  550.9±50.0 °C(Predicted)
• 密度：
  1.716±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  53.4
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-[3,5-bis(trifluoromethyl)benzyl]-2-chloro-N-(3-hydroxypropyl)-4-iodo-3-pyridinecarboxamide 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 甲苯 为溶剂， 反应 13.0h， 生成 5-[[3,5-bis(trifluoromethyl)phenyl]methyl]-7-(2-chlorophenyl)-3,4-dihydro-2H-pyrido[4,3-b][1,5]oxazocin-6-one
  参考文献：
  名称：

  Convenient synthesis of 7-aryl-3,4,5,6-tetrahydro-2H-pyrido[4,5-b]- and [2,3-b]-1,5-oxazocine-6-ones

  摘要：

  A convenient and diversity-oriented method for synthesis of the novel 7-aryl-3,4,5,6-tetrahydro-2H-pyrido[4,5-b]-1,5-oxazocine-6-one skeleton 1 and the very rarely described 7-aryl-3,4,5,6-tetrahydro-2H-pyrido[2,3-b]-1,5-oxazocine-6-one skeleton 2, featuring cyclization using nucleophilic aromatic substitution (SNAr) and Suzuki coupling, is described. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2004.09.104
• 作为产物：
  描述：

  2-氯-4-碘烟酸 在 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 N-[3,5-bis(trifluoromethyl)benzyl]-2-chloro-N-(3-hydroxypropyl)-4-iodo-3-pyridinecarboxamide
  参考文献：
  名称：

  设计，合成和评估新型2-取代-4-芳基-6,7,8,9-四氢-5H-嘧啶[4,5-b] [1,5]恶唑啉-5-酮类药物作为NK1拮抗剂。

  摘要：

  制备了一系列新颖的双环嘧啶衍生物，作为寻找旨在治疗尿失禁的NK1拮抗剂的一部分。其中3g，带有4-乙酰基哌嗪基和2-甲基苯基的嘧啶并[4,5-b] [1,5]恶唑啉衍生物，显示出有效的NK1拮抗剂活性，其K（B）值​​为为0.105 nM，显着增加了豚鼠的有效膀胱容量（0.3 mg / kg iv时为59.4％，id 3 mg / kg时为62.8％）。此外，使用尿烷麻醉的豚鼠模型，通过扩张诱导的节律性膀胱收缩试验确定了3g对膀胱功能的影响似乎与另一种经典的抗尿蛋白尿症托特罗定不同。化合物3g有望成为治疗尿失禁的有前途的药物。

  DOI：

  10.1016/j.bmc.2005.06.015

文献信息

• Fused bicyclic pyridine derivative as tachykinin receptor antagonist
  申请人：Seto Shigeki

  公开号：US20050101591A1

  公开（公告）日：2005-05-12

  A fused bicyclic pyridine derivative represented by the following general formula (1), or a salt thereof: wherein the rings A and B are each a benzene ring, which may have 1 to 3 substituents (any adjacent two of which may be bound to one another to form a ring) that are each independently selected from the group consisting of a halogen atom, a substituted or unsubstituted C 1 to C 6 alkyl group, and a substituted or unsubstituted C 1 to C 6 alkoxyl group; R is a C 1 to C 6 alkylsulfonyl group, a C 1 to C 6 alkylcarbonyl group, a C 1 to C 6 alkoxycarbonyl group, or a formyl group; m is 1 or 2; n is 2 or 3; and q is 1 or 2.

  以下是一种由以下通式（1）表示的融合双环吡啶衍生物，或其盐： 其中，环A和环B均为苯环，可以具有1至3个取代基（任意相邻两个取代基可以相互结合形成环），每个取代基独立地选自由卤素原子，取代或未取代的C1至C6烷基基团，以及取代或未取代的C1至C6烷氧基基团；R为C1至C6烷基磺酰基、C1至C6烷基羰基基团、C1至C6烷氧基羰基基团或甲酰基；m为1或2；n为2或3；q为1或2。
• Fused bicyclic pyridine derivatives as tachykinin receptor antagonists
  申请人：Seto Shigeki

  公开号：US20050107375A1

  公开（公告）日：2005-05-19

  A novel fused bicyclic pyridine derivative or a salt thereof that acts as a tachykinin receptor antagonist, in particular as an NK1 receptor antagonist, is represented by the following general formula (1): wherein the rings A and B are each a benzene ring which may have 1 to 3 substituents (any adjacent two of which may be bound to one another to form a ring); the ring C is a nitrogen-containing ring having a hydrogen atom substituted with a nitrogen atom; R 1 and R 2 are each independently a hydrogen atom, a C 1 to C 6 alkyl group, a C 1 to C 6 alkylsulfonyl group, a C 1 to C 6 alkylcarbonyl group, or a C 1 to C 6 alkoxycarbonyl group, or R 1 and R 2 are bound to one another to form the ring D; m is 1 or 2; n is 2 or 3; and q is an integer from 1 to 4.

  下列一种新型的融合双环吡啶衍生物或其盐，作为一种速激肽受体拮抗剂，特别是NK1受体拮抗剂，其通式如下（1）：其中，环A和环B分别为苯环，可以有1-3个取代基（任意相邻两个可以结合形成环）；环C为含氮环，氢原子被氮原子取代；R1和R2分别为氢原子、C1-C6烷基、C1-C6烷基磺酰基、C1-C6烷基羰基或C1-C6烷氧羰基，或R1和R2结合形成环D；m为1或2；n为2或3；q为1-4的整数。
• FUSED BICYCLIC PYRIDINE DERIVATIVES AS TACHYKININ RECEPTOR ANTAGONISTS
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：EP1457493A1

  公开（公告）日：2004-09-15

  A novel fused bicyclic pyridine derivative or a salt thereof that acts as a tachykinin receptor antagonist, in particular as an NK1 receptor antagonist, is represented by the following general formula (1):    wherein the rings A and B are each a benzene'ring which may have 1 to 3 substituents (any adjacent two of which may be bound to one another to form a ring);    the ring C is a nitrogen-containing ring having a hydrogen atom substituted with a nitrogen atom;    R1 and R2 are each independently a hydrogen atom, a C1 to C6 alkyl group, a C1 to C6 alkylsulfonyl group, a C1 to C6 alkylcarbonyl group, or a C1 to C6 alkoxycarbonyl group, or R1 and R2 are bound to one another to form the ring D; m is 1 or 2; n is 2 or 3; and q is an integer from 1 to 4.

  一种可作为速激肽受体拮抗剂，特别是 NK1 受体拮抗剂的新型融合双环吡啶衍生物或其盐由下式（1）表示： 其中环 A 和环 B 各为苯环，可有 1 至 3 个取代基（其中任意相邻的两个可相互结合形成环）； 环 C 是含氮环，其中有一个被氮原子取代的氢原子； R1和R2各自独立地为氢原子、C1至C6烷基、C1至C6烷磺酰基、C1至C6烷羰基或C1至C6烷氧羰基，或R1和R2彼此结合形成环D；m为1或2；n为2或3；q为1至4的整数。
• FUSED BICYCLIC PYRIDINE DERIVATIVE AS TACHYKININ RECEPTOR ANTAGONIST
  申请人：KYORIN PHARMACEUTICAL CO., LTD.

  公开号：EP1489083B1

  公开（公告）日：2007-06-06
• EP1457493
  申请人：——

  公开号：——

  公开（公告）日：——