5-单丁基甲氨蝶呤 | 66147-31-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 5-单丁基甲氨蝶呤
• 英文名称: γ-n-butyl methotrexate
• 英文别名: 2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoyl}-glutamic acid 5-butyl ester；MTX-γ-monobutylester；5-Butoxy-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]-5-oxopentanoic acid
• CAS: 66147-31-7
• 化学式: C₂₄H₃₀N₈O₅
• 分子量: 510.553
• InChiKey: AJOXYVRHUDHOGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  37
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  200
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  5-单丁基甲氨蝶呤 、 3-氯甲基吡啶盐酸盐 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 以66%的产率得到(γ-n-butyl α-3-picolyl) methotrexate
  参考文献：
  名称：

  Methotrexate analogs. 19. Enhancement of the antitumor effect of methotrexate and 3',5'-dichloromethotrexate by the use of lipid-soluble diesters

  摘要：

  Lipophilic methotrexate (MTX) and 3',5'-dichloromethotrexate (DCM) diesters were prepared by HCl-catalyzed esterification or by neutral esterification using cesium carbonate and an alkyl or aralkyl halide in Me2SO. The products were tested for in vivo antitumor activity against L1210 leukemia in mice to test whether all MTX and DCM diesters are therapeutically equivalent in this species. Contrary to what has been found with simple primary dialkyl esters, ortho-substituted dibenzyl esters of MTX produce longer survival on a q3dX3 schedule than does MTX itself and show a dose-sparing effect comparable to that of MTX at shorter treatment intervals. Thus, MTX bis(6-chloropiperonyl) ester at an MTX-equivalent dose of 5.5 mg/kg gave a +88% increase in median life span (ILS), whereas for MTX a +88% ILS required 30 mg/kg. When the MTX-equivalent dose of MTX bis(6-chloropiperonyl) ester was increased to 40 mg/kg, a +167% ILS was observed, as compared with a +100% ILS with 60 mg/kg of the parent drug. High activity (greater than 100% ILS) was likewise shown by the bis(2,5-dimethylbenzyl), bis(2,6-dichlorobenzyl), and di-3-picolyl esters of MTX and by the bis(1-methylbutyl) ester of DCM. The results of this study indicate that MTX and DCM esters are not therapeutically equivalent in mice, despite the high serum esterase activity in this species, and that an up to 10-fold reduction in total administered dose on the q3dX3 schedule is feasible by this approach.

  DOI：

  10.1021/jm00364a017

文献信息

• ROSOWSKY, A.;YU, C. -S., J. MED. CHEM., 1983, 26, N 10, 1448-1452
  作者：ROSOWSKY, A.、YU, C. -S.

  DOI：——

  日期：——
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  公开号：US20080081831A1

  公开（公告）日：2008-04-03

  Peptidomimetics of cyclic peptides, and compositions comprising such peptidomimetics are provided. The peptidomimetics have a three-dimensional structure that is substantially similar to a three-dimensional structure of a cyclic peptide that comprises a cadherin cell adhesion recognition sequence HAV. Methods for using such peptidomimetics for modulating cadherin-mediated cell adhesion in a variety of contexts are also provided.
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  公开号：US20080260829A1

  公开（公告）日：2008-10-23

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  公开号：US7268115B2

  公开（公告）日：2007-09-11
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  申请人：——

  公开号：US7446120B2

  公开（公告）日：2008-11-04