Doller D, Chackalamannil S, Czarniecki M, McQuade R, Ruperto V
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Bioorg Med Chem Lett. 1999 Mar 22;9(6):901-6. doi: 10.1016/s0960-894x(99)00101-8.
A parallel synthesis of racemic himbacine analogs was carried out by N-alkylation of various commercially available cyclic amine derivatives with the alkylating agent 4 which bears the tricyclic unit of himbacine. Several of these analogs have potency comparable to that of himbacine, albeit lacking the desired selectivity. Structure-activity relationship studies support the existence of a hydrophobic pocket in the receptor where the piperidine ring of dihydrohimbacine binds.
通过将各种市售的环状胺衍生物与带有海巴辛三环单元的烷基化剂4进行N-烷基化反应，对外消旋海巴辛类似物进行了平行合成。这些类似物中有几种具有与海巴辛相当的效力，尽管缺乏所需的选择性。构效关系研究支持受体中存在一个疏水口袋，二氢海巴辛的哌啶环与之结合。
