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    • 7. 发明申请
    • Method of inhibiting neurotrophin-receptor binding
    • 抑制神经营养因子受体结合的方法
    • US20060063793A1
    • 2006-03-23
    • US11267129
    • 2005-11-07
    • Gregory RossIgor ShamovskySandra MaroneDonald WeaverRichard Riopelle
    • Gregory RossIgor ShamovskySandra MaroneDonald WeaverRichard Riopelle
    • A61K31/4745
    • C07D221/14A61K31/00A61K31/473A61K31/4745
    • The present invention relates to compositions which inhibit the binding of nerve growth factor to the p75NTR common neurotrophin receptor and methods of use thereof. In one embodiment, the compound which inhibits binding of nerve growth factor to p75NTR comprises, particularly when bound to nerve growth factor, at least two of the following: (1) a first electronegative atom or functional group positioned to interact with Lys34 of nerve growth factor; (2) a second electronegative atom or functional group positioned to interact with Lys95 of nerve growth factor; (3) a third electronegative atom or functional group positioned to interact with Lys88 of nerve growth factor; (4) a fourth electronegative atom or functional group positioned to interact with Lys32 of nerve growth factor; and (5) a hydrophobic moiety which interacts with the hydrophobic region formed by Ile31, Phe101 and Phe86 of nerve growth factor.
    • 本发明涉及抑制神经生长因子与普通神经营养因子受体的结合的组合物及其使用方法。 在一个实施方案中,抑制神经生长因子与p75NTR的结合的化合物特别包括当与神经生长因子结合时,至少两个以下:(1)第一电负性原子或官能团 定位成与神经生长因子的Lys 34相互作用; (2)定位为与神经生长因子的Lys 95相互作用的第二电负性原子或官能团; (3)定位为与神经生长因子的Lys 80相互作用的第三电负性原子或官能团; (4)定位为与神经生长因子的Lys 32相互作用的第四电负性原子或官能团; 和(5)与神经生长因子的Ile 31,Phe 101和Phe 86形成的疏水区相互作用的疏水部分。