(bis(benzyloxy)phosphoryloxy)methyl-3-amino-4-methylbenzoyl(cyclopropyl)-carbamate | 948842-78-2

• 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: (bis(benzyloxy)phosphoryloxy)methyl-3-amino-4-methylbenzoyl(cyclopropyl)-carbamate
• 英文别名: bis(phenylmethoxy)phosphoryloxymethyl N-(3-amino-4-methylbenzoyl)-N-cyclopropylcarbamate
• CAS: 948842-78-2
• 化学式: C₂₇H₂₉N₂O₇P
• 分子量: 524.51
• InChiKey: NPHGDPDRHXSWNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-chloro-5-methyl-N-propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide 、 (bis(benzyloxy)phosphoryloxy)methyl-3-amino-4-methylbenzoyl(cyclopropyl)-carbamate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 phosphonooxymethylcyclopropyl(4-methyl-3-(5-methyl-6-(propylcarbamoyl)-pyrrolo-[1,2-f][1,2,4]triazin-4-ylamino)benzoyl)carbamate
  参考文献：
  名称：

  Synthesis and evaluation of carbamoylmethylene linked prodrugs of BMS-582949, a clinical p38α inhibitor

  摘要：

  A series of carbamoylmethylene linked prodrugs of 1 (BMS-582949), a clinical p38 alpha inhibitor, were synthesized and evaluated. Though the phosphoryloxymethylene carbamates (3, 4, and 5) and alpha-aminoacyloxymethylene carbamates (22, 23, and 26) were found unstable at neutral pH values, fumaric acid derived acyloxymethylene carbamates (2, 28, and 31) were highly stable under both acidic and neutral conditions. Prodrugs 2 and 31 were also highly soluble at both acidic and neutral pH values. At a solution dose of 14.2 mpk (equivalent to 10 mpk of 1), 2 gave essentially the same exposure of 1 compared to dosing 10 mpk of 1 itself. At a suspension dose of 142 mpk (equivalent to 100 mpk of 1), 2 demonstrated that it could overcome the solubility issue associated with 1 and provide a much higher exposure of I. To our knowledge, the unique type of prodrugs like 2, 28, and 31 was not reported in the past and could represent a novel prodrug approach for secondary amides, a class of molecules frequently identified as drug candidates. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.022
• 作为产物：
  描述：

  3-硝基-N-环丙基-4-甲基-苯甲酰胺 在 氯化铵 、 sodium iodide 、 lithium hexamethyldisilazane 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 、 甲苯 为溶剂， 生成 (bis(benzyloxy)phosphoryloxy)methyl-3-amino-4-methylbenzoyl(cyclopropyl)-carbamate
  参考文献：
  名称：

  Synthesis and evaluation of carbamoylmethylene linked prodrugs of BMS-582949, a clinical p38α inhibitor

  摘要：

  A series of carbamoylmethylene linked prodrugs of 1 (BMS-582949), a clinical p38 alpha inhibitor, were synthesized and evaluated. Though the phosphoryloxymethylene carbamates (3, 4, and 5) and alpha-aminoacyloxymethylene carbamates (22, 23, and 26) were found unstable at neutral pH values, fumaric acid derived acyloxymethylene carbamates (2, 28, and 31) were highly stable under both acidic and neutral conditions. Prodrugs 2 and 31 were also highly soluble at both acidic and neutral pH values. At a solution dose of 14.2 mpk (equivalent to 10 mpk of 1), 2 gave essentially the same exposure of 1 compared to dosing 10 mpk of 1 itself. At a suspension dose of 142 mpk (equivalent to 100 mpk of 1), 2 demonstrated that it could overcome the solubility issue associated with 1 and provide a much higher exposure of I. To our knowledge, the unique type of prodrugs like 2, 28, and 31 was not reported in the past and could represent a novel prodrug approach for secondary amides, a class of molecules frequently identified as drug candidates. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.022

文献信息

• PYRROLOTRIAZINE ANILINE PRODRUG COMPOUNDS USEFUL AS KINASE INHIBITORS
  申请人：Liu Chunjian

  公开号：US20070213300A1

  公开（公告）日：2007-09-13

  Compounds having the Formula (I), including pharmaceutically acceptable salts thereof, wherein at least one of X 1 , X 2 or X 3 is and any remaining X 1 , X 2 or X 3 is hydrogen, which are useful as kinase inhibitors, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , A 1 , A 2 and m are as described herein.

  具有化学式（I）的化合物，包括其药学上可接受的盐，其中X1、X2或X3中至少有一个是氢，其余的X1、X2或X3是氢，这些化合物可用作激酶抑制剂，其中R1、R2、R3、R4、R5、R6、A1、A2和m如本文所述。
• Pyrrolotriazine aniline prodrug compounds useful as kinase inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：US07572795B2

  公开（公告）日：2009-08-11

  Compounds having the Formula (I), including pharmaceutically acceptable salts thereof, wherein at least one of X1, X2 or X3 is and any remaining X1, X2 or X3 is hydrogen, which are useful as kinase inhibitors, wherein R1, R2, R3, R4, R5, R6, A1, A2 and m are as described herein.

  具有公式(I)的化合物，包括其药学上可接受的盐，其中X1、X2或X3中至少一个是氮，其余的X1、X2或X3为氢，这些化合物可用作激酶抑制剂，其中R1、R2、R3、R4、R5、R6、A1、A2和m如此描述。
• US7572795B2
  申请人：——

  公开号：US7572795B2

  公开（公告）日：2009-08-11