tert-butyl ((1R)-1-{5-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)carbamate | 1048963-82-1

• 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: tert-butyl ((1R)-1-{5-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)carbamate
• 英文别名: Tert-butyl((1r)-1-{5-[5-chloro-3-fluoro-2-(2-methyl-2h-tetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)carbamate；tert-butyl N-[(1R)-1-[5-[5-chloro-3-fluoro-2-(2-methyltetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl]ethyl]carbamate
• CAS: 1048963-82-1
• 化学式: C₂₀H₂₁ClF₂N₆O₂
• 分子量: 450.876
• InChiKey: NURGBHVCXLVSMM-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  94.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl ((1R)-1-{5-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)carbamate 在 盐酸 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.55h， 生成 N-((1R)-1-{5-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)-1,3-dihydroxycyclopentanecarboxamide
  参考文献：
  名称：

  WO2006/132837

  摘要：

  公开号：
• 作为产物：
  描述：

  5-(2-bromo-4-chloro-6-fluorophenyl)-2-methyl-2H-tetrazole 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride potassium acetate 、 联硼酸频那醇酯 、 potassium carbonate 作用下， 以 二甲基亚砜 、 水 为溶剂， 反应 21.0h， 生成 tert-butyl ((1R)-1-{5-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)carbamate
  参考文献：
  名称：

  WO2006/132837

  摘要：

  公开号：

文献信息

• 1-Hydroxycycloalkanecarboxamide derivatives
  申请人：Kuduk Scott D.

  公开号：US20090062349A1

  公开（公告）日：2009-03-05

  α-Hydroxycycloalkanecarboxamide derivatives of formula (I) or a pharmaceutically acceptable salt thereof, wherein formula (a) is a single or double bond; R 1 , R 2 and R 3 are each independently selected from H, halogen and OH; or R 1 and R 2 attached to the same carbon atom together represent oxo; R 4 is H or methyl; R 5 is Cl or I 2 ; R 6 is selected from —CO 2 —C 3-4 alkyl, —O—C 1-4 alkyl, —O—C 1-4 haloalkyl, 2-methyltetrazol-5-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 5-halomethyl-1,2,4-oxadiazol-3-yl, 3-halomethyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, 5-halomethyl-1,2,3-triazolyl, and 5-methyl-1,2,3-triazolyl; R 7 and R 8 are each independently Cl or I 2 ; and n is 0 or 1, are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.

  式(I)中，α-羟基环烷基羧酰胺衍生物或其药学上可接受的盐，其中式(a)为单键或双键；R1、R2和R3各自独立地选自H、卤素和OH；或者R1和R2结合到同一碳原子上表示氧代基；R4为H或甲基；R5选自Cl或I2；R6选自—CO2—C3-4烷基、—O—C1-4烷基、—O—C1-4卤代烷基、2-甲基四唑-5-基、5-甲基-1,2,4-噁二唑-3-基、3-甲基-1,2,4-噁二唑-5-基、5-卤代甲基-1,2,4-噁二唑-3-基、3-卤代甲基-1,2,4-噁二唑-5-基、四唑-5-基、5-卤代甲基-1,2,3-三唑基和5-甲基-1,2,3-三唑基；R7和R8各自独立地选自Cl或I2；n为0或1。这些化合物是Bradykinin B1拮抗剂或反向激动剂，可用于治疗或预防与Bradykinin B1通路相关的疼痛和炎症症状。
• 1-hydroxycycloalkanecarboxamide derivatives
  申请人：Merck Sharp & Dohme Corp.

  公开号：US07816380B2

  公开（公告）日：2010-10-19

  α-Hydroxycycloalkanecarboxamide derivatives of formula (I) or a pharmaceutically acceptable salt thereof, wherein formula (a) is a single or double bond; R1, R2 and R3 are each independently selected from H, halogen and OH; or R1 and R2 attached to the same carbon atom together represent oxo; R4 is H or methyl; R5 is Cl or I2; R6 is selected from —CO2—C1-4alkyl, —O—C1-4alkyl, —O—C1-4haloalkyl, 2-methyltetrazol-5-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 5-halomethyl-1,2,4-oxadiazol-3-yl, 3-halomethyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, 5-halomethyl-1,2,3-triazolyl, and 5-methyl-1,2,3-triazolyl; R7 and R8 are each independently Cl or I2; and n is 0 or 1, are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.

  式(I)或其药学上可接受的盐，其中式(a)表示单键或双键；R1、R2和R3各自独立地选择自H、卤素和OH；或者R1和R2结合到同一碳原子上表示氧代；R4为H或甲基；R5为Cl或I2；R6选择自—CO2—C1-4烷基、—O—C1-4烷基、—O—C1-4卤代烷基、2-甲基四唑-5-基、5-甲基-1,2,4-噁二唑-3-基、3-甲基-1,2,4-噁二唑-5-基、5-卤代甲基-1,2,4-噁二唑-3-基、3-卤代甲基-1,2,4-噁二唑-5-基、四唑-5-基、5-卤代甲基-1,2,3-三唑基和5-甲基-1,2,3-三唑基；R7和R8各自独立地为Cl或I2；n为0或1。这些化合物是Bradykinin B1拮抗剂或反向激动剂，用于治疗或预防与Bradykinin B1通路相关的疼痛和炎症等症状。
• Bradykinin B1 receptor antagonists: An α-hydroxy amide with an improved metabolism profile
  作者：Scott D. Kuduk、Ronald K. Chang、Robert M. DiPardo、Christina N. Di Marco、Kathy L. Murphy、Richard W. Ransom、Duane R. Reiss、Cuyue Tang、Thomayant Prueksaritanont、Douglas J. Pettibone、Mark G. Bock

  DOI：10.1016/j.bmcl.2008.07.126

  日期：2008.9

  A series of carbo-and heterocyclic alpha-hydroxy amide-derived bradykinin B(1) antagonists were prepared and evaluated. A 4,4-difluorocyclohexyl alpha-hydroxy amide was incorporated along with a 2-methyl tetrazole in lieu of an oxadiazole to afford a suitable compound with good pharmacokinetic properties, CNS penetration, and clearance by multiple metabolic pathways. (C) 2008 Elsevier Ltd. All rights reserved.
• Novel small molecule bradykinin B1 receptor antagonists. Part 1: Benzamides and semicarbazides
  作者：Marco Schaudt、Elsa Locardi、Gunther Zischinsky、Roland Stragies、Jochen R. Pfeifer、Christoph Gibson、Dirk Scharn、Uwe Richter、Holger Kalkhof、Klaus Dinkel、Karsten Schnatbaum

  DOI：10.1016/j.bmcl.2009.11.119

  日期：2010.2

  The synthesis and SAR of two series of bradykinin B-1 receptor antagonists is described. The benzamide moiety proved to be a suitable replacement for the aryl ester functionality of biaryl based antagonists. In addition, it was found that semicarbazides can effectively replace cyclopropyl amino acids. The compounds with the best overall pro. le were biaryl semicarbazides which display high antagonistic activity, low Caco-2 efflux and high oral bioavailability in the rat. (C) 2009 Elsevier Ltd. All rights reserved.