Synthesis and analgesic activity of some side-chain modified anpirtoline derivatives.
New derivatives of anpirtoline and deazaanpirtoline modified in the side chain have been synthesized. The series includes compounds 3 with side-chains containing piperidine or pyrrolidine rings, compounds 4 containing 8-azabicyclo[3.2.1]octane moiety, and compounds 5 having piperazine ring in their side-chains. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. Optimized structures (PM3-MOPAC, Alchemy 2000, Tripos Inc.) of the synthesized compounds 3-5 were compared with that of anpirtoline.
Rádl
S
S
Research Institute of Pharmacy and Biochemistry, Prague, Czech Republic.
Hezky
P
P
Proska
J
J
Hejnová
L
L
Krejcí
I
I
D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008958:Models, Molecular; D015394:Molecular Structure; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism
D000700:Analgesics; D010880:Piperidines; D011725:Pyridines; D011759:Pyrrolidines; D011985:Receptors, Serotonin; C075631:anpirtoline