Design, synthesis and anxiolytic-like activity of 1-arylpyrrolo[1,2-a]pyrazine-3-carboxamides.
A series of 1-arylpyrrolo[1,2-a]pyrazine-3-carboxamides were designed and synthesized as 18kDa translocator protein (TSPO) ligands. Anxiolytic-like activity of compounds was evaluated in the open field test and elevated plus maze test. Compounds 1a and 1b demonstrated high anxiolytic-like effect in the dose range of 0.1-1.0mg/kg comparable with that of diazepam. The involvement of TSPO receptor in the mechanism of anxiolytic-like activity of new compounds was proved by antagonism of the most active compound 1a with TSPO selective inhibitor PK11195. In vitro binding studies demonstrated high TSPO affinities for compounds 1a and 1b.
Federal State Budgetary Institution 'Research Zakusov Institute of Pharmacology', Baltiyskaya Str., 8, Moscow 125315, Russia. Electronic address: g.mokrov@gmail.com.
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GV
Mokrov
Federal State Budgetary Institution 'Research Zakusov Institute of Pharmacology', Baltiyskaya Str., 8, Moscow 125315, Russia.
O A
OA
Deeva
Federal State Budgetary Institution 'Research Zakusov Institute of Pharmacology', Baltiyskaya Str., 8, Moscow 125315, Russia.
T A
TA
Gudasheva
Federal State Budgetary Institution 'Research Zakusov Institute of Pharmacology', Baltiyskaya Str., 8, Moscow 125315, Russia.
S A
SA
Yarkov
Federal State Budgetary Institution 'Research Zakusov Institute of Pharmacology', Baltiyskaya Str., 8, Moscow 125315, Russia.
M A
MA
Yarkova
Federal State Budgetary Institution 'Research Zakusov Institute of Pharmacology', Baltiyskaya Str., 8, Moscow 125315, Russia.
S B
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Seredenin
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001665:Binding Sites; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D015870:Gene Expression; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects; D011485:Protein Binding; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D018079:Receptors, GABA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
D000577:Amides; D014151:Anti-Anxiety Agents; C463819:Bzrp protein, mouse; D007546:Isoquinolines; D008024:Ligands; D011719:Pyrazines; D018079:Receptors, GABA; D003975:Diazepam; C037850:PK 11195
Anxiolytic activity; Elevated plus maze test; Open field test; PK11195; Pyrrolo[1,2-a]pyrazines; TSPO; Vinyl azides