An extended compound library of spiro[cycloalkane-pyridazinones] with a high Fsp3 character is targeted. There are two possibilities to improve the physicochemical parameters of a drug candidate molecules or building blocks, either to replace the aromatic systems with bioisoster heteroaromatic moieties, e.g. with one or two nitrogen containing ring systems (pyridines, pyridazines, pyrimidines, etc.), or to increase the Fsp3 character of the compounds. Using a new synthetic approach, the Grignard reaction of 2-oxaspiro[4.5]decane-1,3-dione and 2-oxaspiro[4.4]nonane-1,3-dione with p-halophenyl- or p-alkylphenyl-magnesium bromide resulted in the formation of the corresponding 2-oxoethyl-cycloalkanecarboxylic acids, which served as starting materials for the pyridazinones by reaction with hydrazine or phenylhydrazine. The pyridazinones obtained were alkylated with methyliodide or benzylbromide. 16 Novel 4-tolyl- or 4-halophenyl-2,3-diazaspiro[5.5]undec-3-en-1-one and 4-tolyl- or 4-halopyhenyl-7,8-diazaspiro[4.5]dec-8-en-6-one, and their N-methyl, N-benzyl, and N-phenyl derivatives were synthetized. The physicochemical parameters and the Fsp3 character of the novel compounds obtained were studied. A few of them showed excellent logP and clogP values, but the introduction of a further phenyl group seemed to be disadvantageous.

具有高Fsp3特征的螺环[环烷-吡啶并酮]的扩展化合物库为目标。有两种可能性可以改善候选药物分子或结构单元的物理化学参数，可以用生物等排杂芳族部分取代芳香族系统，例如用一个或两个含氮环系统（吡啶，哒嗪，嘧啶等）代替，或以增加化合物的Fsp3特性。使用一种新的合成方法，导致了2-氧杂螺[4.5]癸烷-1,3-二酮和2-氧杂螺[4.4]壬烷-1,3-二酮与对卤代苯基-或对烷基苯基-溴化镁的格利雅反应在形成相应的2-氧代乙基-环链烷羧酸时，通过与肼或苯肼反应，将其用作吡啶并酮的起始原料。用甲基碘或苄基溴将所得的哒嗪酮烷基化。16新颖的4-甲苯基或4-卤代苯基-2,3-二氮杂螺[5.5]十一烷基-3-烯-1-酮和4-甲苯基或4-卤代苯甲基-7,8-二氮杂螺[4.5] dec-8-合成了烯-6-及其N-甲基，N-苄基和N-苯基衍生物。研究了获得的新型化合物的理化参数和Fsp3特性。它们中的一些显示出优异的logP和clogP值，但是引入另外的苯基似乎是不利的。研究了获得的新型化合物的理化参数和Fsp3特性。它们中的一些显示出优异的logP和clogP值，但是引入另外的苯基似乎是不利的。研究了获得的新型化合物的理化参数和Fsp3特性。它们中的一些显示出优异的logP和clogP值，但是引入另外的苯基似乎是不利的。