Alvarez M, Granados R, Mauleón D, Rosell G, Salas M, Sallés J, Valls N
J Med Chem. 1987 Jul;30(7):1186-93. doi: 10.1021/jm00390a011.
The synthesis and irreversible alpha-blocking activity in the rat vas deferens of a series of tetra- and diamine disulfides 2-38, structural analogues of benextramine (BHC), are described. All compounds containing a central cystamine moiety displayed an irreversible alpha-adrenergic blockade at concentrations ranging from 10(-4) to 6 X 10(-6)M. Potency was increased in cystamines N,N'-disubstituted with 6-aminohexyl groups, especially when the outer nitrogen atoms bear arylalkyl substituents or are enclosed in a ring. However, N,N,N',N'-tetrasubstituted cystamines were poor blockers. Structural specificity in the outer portion of the tetramine disulfide is low, since many types of substituents gave rise to potent alpha-blockers. Even replacement of the outer amines with nonbasic ethers or amides was observed to maintain irreversible alpha-blockade.
本文描述了一系列四胺和二胺二硫化物2-38（苯苄胺（BHC）的结构类似物）在大鼠输精管中的合成及其不可逆的α-阻断活性。所有含有中心胱胺部分的化合物在10^(-4)至6×10^(-6)M的浓度范围内均表现出不可逆的α-肾上腺素能阻断作用。当胱胺的N，N'-位被6-氨基己基二取代时，其效力增强，特别是当外部氮原子带有芳基烷基取代基或被封闭在环中时。然而，N，N，N'，N'-四取代的胱胺是较差的阻断剂。四胺二硫化物外部部分的结构特异性较低，因为许多类型的取代基都能产生强效的α-阻断剂。甚至观察到用非碱性醚或酰胺取代外部胺也能维持不可逆的α-阻断作用。
