2-<methyl>-7-phenoxy-1,4-benzodioxan

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-<methyl>-7-phenoxy-1,4-benzodioxan
• 英文别名: 2-(N-aminocarbonyl-N-hydroxy)aminomethyl-7-phenoxy-1,4-benzodioxane；2-{[N-(aminocarbonyl)-N-hydroxyamino]methyl}-7-phenoxy-1,4-benzodioxan；2-[[N-(aminocarbonyl)-N-hydroxyamino]methyl]-7-phenoxy-1,4-benzodioxan；1-hydroxy-1-[(6-phenoxy-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]urea
• 化学式: C₁₆H₁₆N₂O₅
• 分子量: 316.313
• InChiKey: XOLKNHSFXBOXGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  94.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  三甲基硅基异氰酸酯 、 2-<(N-hydroxyamino)methyl>-7-phenoxy-1,4-benzodioxan 以 1,4-二氧六环 为溶剂， 生成 2-<methyl>-7-phenoxy-1,4-benzodioxan
  参考文献：
  名称：

  Certain benzodioxole, benzodioxane and benzodioxepin derivatives useful

  摘要：

  该发明涉及式为##STR1##的化合物，其中每个R独立地表示氢，较低的烷基，卤素，三氟甲基，较低的烷氧基，环烷基或杂环芳基，环烷氧基或杂环芳氧基，环烷基或杂环芳基-较低烷氧基，环烷基或杂环芳基-较低烷基，C.sub.3-C.sub.7-环烷基-较低烷氧基或C.sub.3-C.sub.7-环烷氧基; n表示1，2，3或4; m表示0，1或2; A表示直接键或较低的烷基; X表示氧或硫; R.sub.1表示氢，酰基，较低的烷氧羰基，氨基羰基，单-或双-较低烷基氨基羰基，较低烯基氨基羰基，较低炔基氨基羰基，环烷基或杂环芳基-较低烷基氨基羰基，环烷基或杂环芳基氨基羰基，C.sub.3-C.sub.7-环烷基氨基羰基或C.sub.3-C.sub.7-环烷基-较低烷基氨基羰基; R.sub.2表示较低的烷基，较低的烷氧羰基-较低的烷基，C.sub.3-C.sub.7-环烷基，环烷基或杂环芳基-较低烷基，C.sub.3-C.sub.7-环烷基-较低烷基，氨基，单-或双-较低烷基氨基，较低烯基氨基，较低炔基氨基，环烷基或杂环芳基-较低烷基氨基，环烷基或杂环芳基氨基，C.sub.3-C.sub.7-环烷基氨基，C.sub.3-C.sub.7-环烷基-较低烷基氨基，较低烷氧羰基-较低烷基氨基或较低烷氧基; R.sub.3和R.sub.4独立地表示氢或较低的烷基;以及其药学上可接受的盐; 该化合物可用作5-脂氧酶抑制剂。

  公开号：

  US05120758A1

文献信息

• Certain benzodioxole, benzodioxane and benzodioxepin derivatives useful
  申请人：Ciba-Geigy Corporation

  公开号：US05120758A1

  公开（公告）日：1992-06-09

  The invention relates to the compounds of the formula ##STR1## wherein each R independently represents hydrogen, lower alkyl, halogen, trifluoromethyl, lower alkoxy, carbocyclic or heterocyclic aryl, carbocyclic or heterocyclic aryloxy, carbocyclic or heterocyclic aryl-lower alkyloxy, carbocyclic or heterocyclic aryl-lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl-lower alkyloxy, or C.sub.3 -C.sub.7 -cycloalkyloxy; n represents 1, 2, 3 or 4; m represents 0, 1 or 2; A represents a direct bond or lower alkylene; X represents oxygen or sulfur; R.sub.1 represents hydrogen, acyl, lower alkoxycarbonyl, aminocarbonyl, mono- or di-lower alkylaminocarbonyl, lower alkenylaminocarbonyl, lower alkynylaminocarbonyl, carbocyclic or heterocyclic aryl-lower alkylaminocarbonyl, carbocyclic or heterocyclic arylaminocarbonyl, C.sub.3 -C.sub.7 -cycloalkylaminocarbonyl or C.sub.3 -C.sub.7 -cycloalkyl-lower alkylaminocarbonyl; R.sub.2 represents lower alkyl, lower alkoxycarbonyl-lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, carbocyclic or heterocyclic aryl, carbocyclic or heterocyclic aryl-lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl-lower alkyl, amino, mono- or di-lower alkylamino, lower alkenylamino, lower alkynylamino, carbocyclic or heterocyclic aryl-lower alkylamino, carbocyclic or heterocyclic arylamino, C.sub.3 -C.sub.7 -cycloalkylamino, C.sub.3 -C.sub.7 -cycloalkyl-lower alkylamino, lower alkoxycarbonyl-lower alkylamino or lower alkoxy; R.sub.3 and R.sub.4 independently represent hydrogen or lower alkyl; and pharmaceutically acceptable salts thereof; which are useful as 5-lipoxygenase inhibitors.

  该发明涉及式为##STR1##的化合物，其中每个R独立地表示氢，较低的烷基，卤素，三氟甲基，较低的烷氧基，环烷基或杂环芳基，环烷氧基或杂环芳氧基，环烷基或杂环芳基-较低烷氧基，环烷基或杂环芳基-较低烷基，C.sub.3-C.sub.7-环烷基-较低烷氧基或C.sub.3-C.sub.7-环烷氧基; n表示1，2，3或4; m表示0，1或2; A表示直接键或较低的烷基; X表示氧或硫; R.sub.1表示氢，酰基，较低的烷氧羰基，氨基羰基，单-或双-较低烷基氨基羰基，较低烯基氨基羰基，较低炔基氨基羰基，环烷基或杂环芳基-较低烷基氨基羰基，环烷基或杂环芳基氨基羰基，C.sub.3-C.sub.7-环烷基氨基羰基或C.sub.3-C.sub.7-环烷基-较低烷基氨基羰基; R.sub.2表示较低的烷基，较低的烷氧羰基-较低的烷基，C.sub.3-C.sub.7-环烷基，环烷基或杂环芳基-较低烷基，C.sub.3-C.sub.7-环烷基-较低烷基，氨基，单-或双-较低烷基氨基，较低烯基氨基，较低炔基氨基，环烷基或杂环芳基-较低烷基氨基，环烷基或杂环芳基氨基，C.sub.3-C.sub.7-环烷基氨基，C.sub.3-C.sub.7-环烷基-较低烷基氨基，较低烷氧羰基-较低烷基氨基或较低烷氧基; R.sub.3和R.sub.4独立地表示氢或较低的烷基;以及其药学上可接受的盐; 该化合物可用作5-脂氧酶抑制剂。
• Certain benzodioxole, benzodioxane and benzodioxepin derivatives
  申请人：CIBA-GEIGY AG

  公开号：EP0498770A1

  公开（公告）日：1992-08-12

  The invention relates to the compounds of the formula I wherein each R independently represents hydrogen, lower alkyl, halogen, trifluoromethyl, lower alkoxy, carbocyclic or heterocyclic aryl, carbocyclic or heterocyclic aryloxy, carbocyclic or heterocyclic aryl-lower alkyloxy, carbocyclic or heterocyclic aryl-lower alkyl, C₃-C₇-cycloalkyl-lower alkyloxy, or C₃-C₇-cycloalkyloxy; n represents 1, 2, 3 or 4; m represents 0, 1 or 2; A represents a direct bond or lower alkylene; X represents oxygen or sulfur, R₁ represents hydrogen, acyl, lower alkoxycarbonyl, aminocarbonyl, mono- or di-lower alkylaminocarbonyl, lower alkenylaminocarbonyl, lower alkynylaminocarbonyl, carbocyclic or heterocyclic aryl-lower alkylaminocarbonyl, carbocyclic or heterocyclic arylaminocarbonyl, C₃-C₇-cycloalkylaminocarbonyl or C₃-C₇-cycloalkyl-lower alkylaminocarbonyl; R₂ represents lower alkyl, lower alkoxycarbonyl-lower alkyl, C₃-C₇-cycloalkyl, carbocyclic or heterocyclic aryl, carbocyclic or heterocyclic aryl-lower alkyl, C₃-C₇-cycloalkyl-lower alkyl, amino, mono- or di-lower alkylamino, lower alkenylamino, lower alkynylamino, carbocyclic or heterocyclic aryl-lower alkylamino, carbocyclic or heterocyclic arylamino, C₃-C₇-cycloalkylamino, C₃-C₇-cycloalkyl-lower alkylamino, lower alkoxycarbonyl-lower alkylamino or lower alkoxy; R₃ and R₄ independently represent hydrogen or lower alkyl; and pharmaceutically acceptable salts thereof; which are useful as 5-lipoxygenase inhibitors.

  本发明涉及式 I 的化合物 其中每个 R 独立地代表氢、低级烷基、卤素、三氟甲基、低级烷氧基、碳环或杂环芳基、碳环或杂环芳氧基、碳环或杂环芳基-低级烷氧基、碳环或杂环芳基-低级烷基、C₃-C₇-环烷基-低级烷氧基或 C₃-C₇-环烷氧基；n 代表 1、2、3 或 4； m 代表 0、1 或 2；A 代表直接键或低级亚烷基；X 代表氧或硫，R₁ 代表氢、酰基、低级烷氧基羰基、氨基羰基、单或双低级烷基氨基羰基、低级烯基氨基羰基、低级炔基氨基羰基、碳环或杂环芳基-低级烷基氨基羰基、碳环或杂环芳基氨基羰基、C₃-C₇-环烷基氨基羰基或 C₃-C₇-环烷基-低级烷基氨基羰基；R₂ 代表低级烷基、低级烷氧基羰基-低级烷基、C₃-C₇-环烷基、碳环或杂环芳基、碳环或杂环芳基-低级烷基、C₃-C₇-环烷基-低级烷基、氨基、单-或双-低级烷基氨基、低级烯基氨基、低级炔基氨基、碳环或杂环芳基-低级烷基氨基、碳环或杂环芳基氨基、C₃-C₇-环烷基氨基、C₃-C₇-环烷基-低级烷基氨基、低级烷氧基羰基-低级烷基氨基或低级烷氧基；R₃ 和 R₄ 独立地代表氢或低级烷基；以及它们的药学上可接受的盐；可用作 5-脂氧合酶抑制剂。
• JPH04338386A
  申请人：——

  公开号：JPH04338386A

  公开（公告）日：1992-11-25
• US5120758A
  申请人：——

  公开号：US5120758A

  公开（公告）日：1992-06-09
• Derivatives of 2-[[N-(Aminocarbonyl)-N-hydroxyamino]methyl]-1,4-benzodioxan as Orally Active 5-Lipoxygenase Inhibitors
  作者：Yoshitaka Satoh、Colleen Powers、Leticia M. Toledo、Timothy J. Kowalski、Paul A. Peters、Earl F. Kimble

  DOI：10.1021/jm00001a012

  日期：1995.1

  N-Hydroxyureas based on the 1,4-benzodioxan template were prepared from appropriately substituted 1,4-benzodioxan-2-methanols as the key intermediates and evaluated in the in vitro guinea pig polymorphonuclear leukocyte 5-lipoxygenase (5-LO) assay for their 5-LO inhibitory activity. Placement of a 7-phenoxy or 7-p-fluorophenoxy substituent resulted in a dramatic increase in in vitro potency. Selected compounds were subsequently assayed in an ex vivo dog model of LTB(4) synthesis at a dose of 1.0 mg/kg. The 7-phenoxy derivatives 16 and 17 showed modest duration of action (DA) in this dog model. The g-regioisomers 21 and 22 were less potent. Replacement of the 7-phenoxy group of 16 with the p-fluorophenoxy moiety enhanced the DA dramatically. Compound 18 (CGS 25667), which had an IC50 value of 100 nM in the in vitro guinea pig 5-LO assay, had a DA of 8.5 h (zileuton, DA = 8.5 h) at the oral dose of 1.0 mg/kg. Optical antipodes (24, 26) of 18 were independently synthesized in high (>95%) enantiomeric purity from commercially available optically active glycidyl tosylates and evaluated. In the in vitro assay, the 2S-(-)-enantiomer (24, CGS 25997, IC50 = 85 nM) was found to be twice as active as the 2R-(+)-counterpart (26, CGS 25998, IC50 - 180 nM). In the ex vivo experiment, 24, which dose dependently inhibited plasma 5-LO activity, was shown to be significantly longer acting than 26, with a DA of 8.4 h when dosed orally at 1.0 mg/kg.