Tosco Paolo, Bertinaria Massimo, Di Stilo Antonella, Cena Clara, Fruttero Roberta, Gasco Alberto
Dipartimento di Scienza e Tecnologia del Farmaco, Via P. Giuria 9, I-10125 Torino, Italy.
Farmaco. 2005 Jun-Jul;60(6-7):507-12. doi: 10.1016/j.farmac.2005.04.007.
Recently a series of H3-antagonists related to Imoproxifan was realised (I); in these products the oxime substructure of the lead was constrained in NO-donor furoxan systems and in the corresponding furazan derivatives. In this paper, a new series of compounds derived from I by substituting the imidazole ring with the ethoxycarbonylpiperazino moiety present in the non-imidazole H3-ligand A-923 is described. For all the products synthesis and preliminary pharmacological characterisation, as well as their hydrophilic-lipophilic balance, are reported. The imidazole ring replacement generally results in a decreased H3-antagonist activity with respect to the analogues of series I and, in some cases, induces relaxing effects on the electrically contracted guinea-pig ileum, probably due to increased affinity for other receptor systems.
最近，一系列与咪普罗昔芬相关的H3拮抗剂被研发出来（I）；在这些产物中，先导化合物的肟亚结构被限制在一氧化氮供体呋咱体系及相应的呋嗪衍生物中。本文描述了通过用非咪唑H3配体A-923中存在的乙氧羰基哌嗪基部分取代咪唑环而从I衍生得到的一系列新化合物。报道了所有产物的合成、初步药理学表征及其亲水亲脂平衡。与I系列类似物相比，咪唑环的取代通常导致H3拮抗剂活性降低，并且在某些情况下，对电刺激收缩的豚鼠回肠产生松弛作用，这可能是由于对其他受体系统的亲和力增加所致。
