Kovac T, Kajfez F, Sunjić V, Blazević N, Kolbah D
J Med Chem. 1979 Sep;22(9):1093-6. doi: 10.1021/jm00195a016.
Starting from 3-hydroxy-1,4-benzodiazepin-2-ones 1--3, via 3-chloro derivatives 4--6, 13 new C(3)-substituted 1,4-benzodiazepin-2-ones were synthesized. Reaction of 4--6 with ethylene glycol yielded 3-(beta-hydroxyethyl) derivatives 7--9. Similar reaction with the isopropylidene derivative of glycerol afforded 10--12, which on hydrolysis of the isopropylidene group hielded glycerol derivatives 13--15. Reaction of trichloroacetyl chloride with oxazepam and temazepam yielded the corresponding trichloroacetyl esters 16 and 17. The beta-hydroxyethyl derivative 7 was conjugated with an acetylated glucopyranose derivative to give isomeric 18 and 19. Partition coefficients (log Poct) and central nervous system activities (in six stranded tests) were determined for 7--15 as well as several standard compounds. Most of the compounds exhibiting beneficial central nervous system activity had Poct values between 1.71 and 2.48. No correlation between lipophilicity and central nervous system activity could be discerned for these compounds.
从3-羟基-1,4-苯并二氮杂卓-2-酮1 - 3出发，经3-氯衍生物4 - 6，合成了13种新的C(3)-取代的1,4-苯并二氮杂卓-2-酮。4 - 6与乙二醇反应生成3-(β-羟乙基)衍生物7 - 9。与甘油的亚异丙基衍生物发生类似反应得到10 - 12，其亚异丙基水解后得到甘油衍生物13 - 15。三氯乙酰氯与奥沙西泮和替马西泮反应生成相应的三氯乙酰酯16和17。β-羟乙基衍生物7与乙酰化吡喃葡萄糖衍生物共轭得到异构体18和19。测定了7 - 15以及几种标准化合物的分配系数(log Poct)和中枢神经系统活性(在六股试验中)。大多数表现出有益中枢神经系统活性的化合物的Poct值在1.71至2.48之间。对于这些化合物，未发现亲脂性与中枢神经系统活性之间存在相关性。
