Synthesis and anticholinergic activity of the four stereoisomers of 4-(dimethylamino)-2-phenyl-2-(2-pyridyl)pentanamide.
The four stereoisomers of 4-(dimethylamino)-2-phenyl-(2-pyridyl)pentanamide were synthesized, and the absolute configurations were determined by X-ray crystallography. Pharmacological testing for anticholinergic activity revealed great differences in potency among 10 (2R,4R,IC50 = 0.40 microM), 11 (2S,4S,31 microM), 12 (2R,4S,170 microM), and 13 (2S,4R,0.13 microM). A new drug application for the racemate 8 (FK176, vamicamide) has been filed in Japan for the treatment of overactive detrusor syndrome.
Oyasu
H
H
R & D Division, Fujisawa Pharmaceutical Company Ltd., Osaka, Japan.
Nagano
M
M
Akahane
A
A
Tomoi
M
M
Tada
T
T
Matsuo
M
M
D000818:Animals; D018360:Crystallography, X-Ray; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
D010276:Parasympatholytics; D011725:Pyridines; C083702:vamicamide