Van Roey P, Bullion K A, Osawa Y, Browne L J, Bowman R M, Braun D G
Medical Foundation of Buffalo, NY 14203.
J Enzyme Inhib. 1991;5(2):119-32. doi: 10.3109/14756369109069065.
The crystal and molecular structures of 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile hydrochloride (CGS 16949A) and bis(p-cyanophenyl)imidazo-1-yl methane hemisuccinate (CGS 18320B) have been determined as part of structure-activity relationship studies of non-steroidal aromatase inhibitors. CGS 18320B crystallizes with two inhibitor molecules in the asymmetric unit that are similar in conformation. The cyanophenyl groups and the imidazole moieties in the CGS 18320B molecules display a propellor-like arrangement. The orientation of the imidazole ring in CGS 16949A, which is constrained by the piperidine ring, differs by about 80 degrees from the orientations in both CGS 18320B molecules. The conformations of both compounds are consistent with the proposed model (Banting et al. (1988) J. Enz. Inhibit., 2, 216) for inhibitor binding by positioning of the cyanophenyl group in the steroid A-ring binding site and interaction of the imidazole nitrogen with the iron of the haem.
作为非甾体芳香酶抑制剂构效关系研究的一部分，已确定了4-(5,6,7,8-四氢咪唑并[1,5-a]吡啶-5-基)苯甲腈盐酸盐（CGS 16949A）和双(对氰基苯基)咪唑-1-基甲烷半琥珀酸盐（CGS 18320B）的晶体结构和分子结构。CGS 18320B在不对称单元中与两个构象相似的抑制剂分子一起结晶。CGS 18320B分子中的氰基苯基和咪唑部分呈现出螺旋桨状排列。CGS 16949A中受哌啶环限制的咪唑环取向与两个CGS 18320B分子中的取向相差约80度。两种化合物的构象都与所提出的模型（Banting等人，(1988) J. Enz. Inhibit., 2, 216）一致，该模型通过氰基苯基在甾体A环结合位点的定位以及咪唑氮与血红素铁的相互作用来实现抑制剂结合。
