Phenol, 2,3-diamino-6-methoxy- | 67394-74-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: Phenol, 2,3-diamino-6-methoxy-
• 英文别名: 2,3-diamino-6-methoxyphenol
• CAS: 67394-74-5
• 化学式: C₇H₁₀N₂O₂
• 分子量: 154.169
• InChiKey: BVNDBUHVNQWXFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  81.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Phenol, 2,3-diamino-6-methoxy- 在 吡啶 、 盐酸 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 116.0h， 生成 4-{[tert-butyl(dimethyl)silyl]oxy}-1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-5-methoxy-1H-benzimidazole
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Analogues of the Pan Class I Phosphatidylinositol 3-Kinase (PI3K) Inhibitor 2-(Difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474)

  摘要：

  A structure activity relationship (SAR) study of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474) identified substitution at the 4 and 6 positions of the benzimidazole ring as having significant effects on the potency of substituted derivatives. The 6-amino-4-methoxy analogue displayed a greater than 1000-fold potency enhancement over the corresponding 6-aza-4-methoxy analogue against all three class Ia PI 3-kinase enzymes (p110 alpha, p110 beta, and p110 delta) and also displayed significant potency against two mutant forms of the p110 alpha isoform (H1047R and E545K). This compound was also evaluated in vivo against a U87MG human glioblastoma tumor xenograft model in Ragl(-/-) mice, and at a dose of 50 mg/kg given by ip injection at a qd x 10 dosing schedule it dramatically reduced cancer growth by 81% compared to untreated controls.

  DOI：

  10.1021/jm200688y
• 作为产物：
  描述：

  3-methoxy-6-nitro-2-[(phenylsulfonyl)oxy]benzoic acid 在 氯化亚砜 、 sodium azide 、 palladium on activated charcoal 、 氢气 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.5h， 生成 Phenol, 2,3-diamino-6-methoxy-
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Analogues of the Pan Class I Phosphatidylinositol 3-Kinase (PI3K) Inhibitor 2-(Difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474)

  摘要：

  A structure activity relationship (SAR) study of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474) identified substitution at the 4 and 6 positions of the benzimidazole ring as having significant effects on the potency of substituted derivatives. The 6-amino-4-methoxy analogue displayed a greater than 1000-fold potency enhancement over the corresponding 6-aza-4-methoxy analogue against all three class Ia PI 3-kinase enzymes (p110 alpha, p110 beta, and p110 delta) and also displayed significant potency against two mutant forms of the p110 alpha isoform (H1047R and E545K). This compound was also evaluated in vivo against a U87MG human glioblastoma tumor xenograft model in Ragl(-/-) mice, and at a dose of 50 mg/kg given by ip injection at a qd x 10 dosing schedule it dramatically reduced cancer growth by 81% compared to untreated controls.

  DOI：

  10.1021/jm200688y

文献信息

• BARTON J. W.; GOODLAND M. C.; GOOLD K. J.; HADLEY J.; MCOMIE J. F. W., TETRAHEDRON, 1978, 34, NO 4, 495-498
  作者：BARTON J. W.、 GOODLAND M. C.、 GOOLD K. J.、 HADLEY J.、 MCOMIE J. F. W.

  DOI：——

  日期：——
• Synthesis and Biological Evaluation of Novel Analogues of the Pan Class I Phosphatidylinositol 3-Kinase (PI3K) Inhibitor 2-(Difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1<i>H</i>-benzimidazole (ZSTK474)
  作者：Gordon W. Rewcastle、Swarna A. Gamage、Jack U. Flanagan、Raphael Frederick、William A. Denny、Bruce C. Baguley、Philip Kestell、Ripudaman Singh、Jackie D. Kendall、Elaine S. Marshall、Claire L. Lill、Woo-Jeong Lee、Sharada Kolekar、Christina M. Buchanan、Stephen M. F. Jamieson、Peter R. Shepherd

  DOI：10.1021/jm200688y

  日期：2011.10.27

  A structure activity relationship (SAR) study of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474) identified substitution at the 4 and 6 positions of the benzimidazole ring as having significant effects on the potency of substituted derivatives. The 6-amino-4-methoxy analogue displayed a greater than 1000-fold potency enhancement over the corresponding 6-aza-4-methoxy analogue against all three class Ia PI 3-kinase enzymes (p110 alpha, p110 beta, and p110 delta) and also displayed significant potency against two mutant forms of the p110 alpha isoform (H1047R and E545K). This compound was also evaluated in vivo against a U87MG human glioblastoma tumor xenograft model in Ragl(-/-) mice, and at a dose of 50 mg/kg given by ip injection at a qd x 10 dosing schedule it dramatically reduced cancer growth by 81% compared to untreated controls.