Alpha(2) adrenoceptor agonists as potential analgesic agents. 1. (Imidazolylmethyl)oxazoles and -thiazoles.
A series of (imidazolylmethyl)oxazoles and -thiazoles were prepared and evaluated as alpha(2) adrenoceptor agonists. These compounds were also tested in in vivo paradigms that are predictive of analgesic activity. Variations in both the imidazole and thiazole portions of the molecule were investigated. Some of the more potent compounds such as 22, 26, 45, and 53 displayed alpha(2) receptor binding in the 10-20 nM range and also had significant antinociceptive activity in the mouse abdominal irritant test (MAIT).
Boyd
R E
RE
Drug Discovery Division, The R. W. Johnson Pharmaceutical Research Institute, Welsh and McKean Roads, Spring House, Pennsylvania 19477, USA.
Press
J B
JB
Rasmussen
C R
CR
Raffa
R B
RB
Codd
E E
EE
Connelly
C D
CD
Bennett
D J
DJ
Kirifides
A L
AL
Gardocki
J F
JF
Reynolds
B
B
Hortenstein
J T
JT
Reitz
A B
AB
D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000700:Analgesics / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D010080:Oxazoles; D018341:Receptors, Adrenergic, alpha-2; D013844:Thiazoles