Synthesis and D2-like binding affinity of 4,5-dihydro-1H-benzo[g]indole-3-carboxamide derivatives as conformationally restricted 5-phenyl-pyrrole-3-carboxamide analogs.
A series of 4,5-dihydro-1H-benzo[g]-indole-3-carboxamide derivatives 2a-g were synthesized as conformationally restricted analogs of the dopamine D2-like 5-phenylpyrrole-3-carboxamide ligands and evaluated for their affinity for the dopamine D2-like receptors. In this series, N3-[(1-ethyltetrahydro-1H-2-pyrrolyl)methyl]-4,5-dihydro-1H-benzo[ g]indole- 3-carboxamide (2a) showed the highest affinity for D2-like receptors (IC50 = 160 nM). Replacement of the N-(1-ethyl-2-pyrrolidinyl)methyl side chain with a 2-(N,N-diethylamino)ethyl or a 1-benzyl-4-piperidinyl group (2b, 2d) decreased affinity for the D2-like receptor. The other compounds tested were found to be devoid of D2-like binding affinity.
Pinna
G A
GA
Dipartimento Farmaco-Chimico-Tossicologico, Università di Sassari, Italy.
Curzu
M M
MM
Sechi
M
M
Chelucci
G
G
Vianello
P
P
Maciocco
E
E
D000818:Animals; D001549:Benzamides / Q000378:metabolism; D001667:Binding, Competitive; D018492:Dopamine Antagonists / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008968:Molecular Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013329:Structure-Activity Relationship
D001549:Benzamides; D018492:Dopamine Antagonists; D007211:Indoles; D017448:Receptors, Dopamine D2; C030265:nemonapride