用于硼中子俘获疗法的（氨基烷基胺）-N-氨基烷基氮杂壬硼烷（11）衍生物的合成

Synthesis of (aminoalkylamine)-N-aminoalkyl)azanonaborane(11) derivatives for boron neutron capture therapy.

作者信息

El-Zaria Mohamed E, Dörfler Udo, Gabel Detlef

机构信息

Department of Chemistry, University of Bremen, P.O. Box 330440, D-28334 Bremen, Germany.

出版信息

J Med Chem. 2002 Dec 19;45(26):5817-9. doi: 10.1021/jm020971k.

DOI:10.1021/jm020971k

PMID:12477367

Abstract

New boron-containing polyamine have been synthesized: (aminoalkylamine)-N-(aminoalkyl)azanonaborane(11) derivatives [H(2)N(CH(2))(n)H(2)NB(8)H(11)NH(CH(2))(n)NH(2)], where n = 4-6 and 12, and [H(2)N(CH(2))(3)H(2)NB(8)H(11)NH(CH(2))(4)NH(2)]. (4-Aminobutylamine)-N-(4-aminobutyl)azanonaborane and (3-aminopropylamine)-N-(4-aminobutyl)azanonaborane were less toxic in vitro (LD(50) of approximately 700 and approximately 1100 microM, respectively) than spermine, while (4-aminobutylamine)-N-isopropylazanonaborane with its hydrophobic isopropyl group and those with n = 5, 6, and 12 were already toxic under similar conditions (LD(50) << 500 microM). These compounds may be useful as delivery agents for boron neutron capture therapy.

摘要

已合成了新型含硼多胺

（氨基烷基胺）-N-（氨基烷基）氮杂壬硼烷（11）衍生物[H₂N(CH₂)ₙH₂NB₈H₁₁NH(CH₂)ₙNH₂]，其中n = 4 - 6和12，以及[H₂N(CH₂)₃H₂NB₈H₁₁NH(CH₂)₄NH₂]。（4-氨基丁胺）-N-（4-氨基丁基）氮杂壬硼烷和（3-氨基丙胺）-N-（4-氨基丁基）氮杂壬硼烷在体外的毒性（半数致死量分别约为700和约1100微摩尔）比精胺小，而具有疏水性异丙基的（4-氨基丁胺）-N-异丙基氮杂壬硼烷以及n = 5、6和12的那些化合物在类似条件下已具有毒性（半数致死量 << 500微摩尔）。这些化合物可用作硼中子俘获疗法的递送剂。