Reuben R C, Khanna P L, Gazitt Y, Breslow R, Rifkind R A, Marks P A
J Biol Chem. 1978 Jun 25;253(12):4214-8.
Hexamethylenebisacetamide is a potent inducer of erythroid differentiation in murine erythroleukemia cells. A series of chemical compounds structurally related to hexamethylenebisacetamide were tested for inducing activity including polymethylene chains terminally substituted with various combinations of carboxylate, amino, amide, or sulfoxide groups. Effective "dimerization" of dimethyl sulfoxide through a linear polymethylene chain increases its inducing activity by a magnitude similar to that observed when N-methylacetamide is effectively dimerized in such a manner. It was found that all potent inducing agents possess both a hydrophilic and hydrophobic portion of the molecule, as well as a planar portion. All are Lewis bases, possessing a free electron pair available for hydrogen bonding. The polymethylene chain joining functional groups must be flexible and must be 5 to 6 carbon atoms in length to achieve maximal activity. Introduction of triple or double (cis or trans) bonds into the polymethylene chain does not alter activity.
六亚甲基双乙酰胺是鼠红细胞白血病细胞中红细胞分化的有效诱导剂。测试了一系列与六亚甲基双乙酰胺结构相关的化合物的诱导活性，这些化合物包括末端被羧酸盐、氨基、酰胺或亚砜基团的各种组合取代的聚亚甲基链。通过线性聚亚甲基链对二甲基亚砜进行有效的“二聚化”，可使其诱导活性提高到与以这种方式对N - 甲基乙酰胺进行有效二聚化时观察到的相似程度。研究发现，所有有效的诱导剂分子都具有亲水和疏水部分，以及一个平面部分。它们都是路易斯碱，拥有一个可用于氢键形成的孤对电子。连接官能团的聚亚甲基链必须具有柔性，且长度必须为5至6个碳原子才能实现最大活性。在聚亚甲基链中引入三键或双键（顺式或反式）不会改变活性。
