188116-07-6Relevant articles and documents
Synthesis, pharmacology, and structure-activity relationships of novel imidazolones and pyrrolones as modulators of GABAA receptors
Grunwald, Christian,Rundfeldt, Chris,Lankau, Hans-Joachim,Arnold, Thomas,H?fgen, Norbert,Dost, Rita,Egerland, Ute,Hofmann, Hans-J?rg,Unverferth, Klaus
, p. 1855 - 1866 (2007/10/03)
New series of imidazolones and pyrrolones were synthesized. The compounds were tested regarding their anxiolytic properties due to modulation of the GABAA receptor response. Several derivatives exhibit considerable pharmacological activity while lacking the typical side effects of benzodiazepine receptor agonists. 1-(4-chlorophenyl)-4-morpholin-1-yl-1,5- dihydro-imidazol-2-one (2) and 1-(4-chlorophenyl)-4-piperidin-1-yl-1,5-dihydro- imidazol-2-one (3) were protective in the pentylenetetrazole test in rats with oral ED50 of 27.4 and 12.8 mg/kg and TD50 (rotarod) of >500 and 265 mg/kg, respectively. The minimum effective dose in the Vogel conflict test was 3 mg/kg for both compounds. Common structure-activity relationship and comparative molecular field analysis models of the various series of derivatives could be established which are in accordance with a GABAA mediated pharmacological action. The findings fit well into an established pharmacophore model. This model is refined by an additional steric restriction feature.
For a process for treatment of anxiety and tension
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, (2008/06/13)
A process for the treatment of anxiety and tension, which comprises administering to a patient in need therefor an anxiolytically effective amount of a compound of the formula STR1 wherein X is hydrogen, a C1-4 alkyl, C1-4 alkoxy, trifluoromethyl residue, or halogen; R1 and R2 are independently of each other a C1-4 alkyl, cycloalkyl, C2-4 hydroxyalkyl, or heteroalkyl residue, or R1 and R2 together form a C2-6 alkylene residue in which one --CH2 -- group can be replaced by oxygen, nitrogen or sulfur; n is 0 or 1, and m is 0 or a cardinal number from 1-5, or a pharmaceutically acceptable salt of the compound.