Rybczynski P J, Combs D W, Jacobs K, Shank R P, Dubinsky B
The R. W. Johnson Pharmaceutical Research Institute, Route 202, P.O. Box 300, Raritan, New Jersey 08876, USA.
J Med Chem. 1999 Jul 1;42(13):2403-8. doi: 10.1021/jm9805889.
A series of 3-aryl-1-(arylsulfonyl)-1,4,5,6-tetrahydropyridazine allosteric modulators of the GABAA receptor was synthesized, and biological activity was examined in vitro and in vivo. Beginning with 1a, stepwise modification of the substituents and conservation of the scaffold yielded a chemical series in which the modulatory activity was enhanced by the presence of GABA. The SAR suggests, but does not establish, that the compounds bind to the steroid binding site on the GABAA receptor. The GABA shift for each compound indicates that all compounds in this series are either agonists or partial agonists.
合成了一系列GABAA受体的3-芳基-1-(芳基磺酰基)-1,4,5,6-四氢哒嗪变构调节剂，并在体外和体内检测了其生物活性。从1a开始，对取代基进行逐步修饰并保留骨架，得到了一个化学系列，其中GABA的存在增强了调节活性。构效关系表明（但未确定）这些化合物与GABAA受体上的类固醇结合位点结合。每种化合物的GABA位移表明该系列中的所有化合物均为激动剂或部分激动剂。
