Synthesis and structural, biochemical, and pharmacological study of 3 beta-acyloxy-3 alpha-methoxycarbonyltropane derivatives.
A series of 3 beta-acyloxy-3 alpha-methoxycarbonyltropanes were synthesized and studied by 1H and 13C NMR spectroscopy, and the crystal structure of 3 alpha-methoxycarbonyl-3 beta-pyridincarbonyloxytropane (5d) was determined by X-ray diffraction. In CDCl3 solution, compounds 5a-f display the same preferred conformation. The pyrrolidine and piperidine rings adopt an envelope conformation flattened at N-8 and a distorted chair conformation puckered at N-8 and flattened at C3, respectively, with the N-substituent in the equatorial position with respect to the piperidine ring. The pharmacological profile of one of these compounds makes it an adequate candidate for the design of novel GABAB antagonist agents.
Departamento de Quimica Orgánica, Campus Universitario de Alcalá, Spain.
E
E
Gálvez
M L
ML
Izquierdo
C
C
Burgos
M S
MS
Arias
J
J
Sanz-Aparicio
I
I
Fonseca
F
F
Gago
G
G
Baldominos
P
P
López
J C
JC
Prieto
D000818:Animals; D003461:Crystallography; D018756:GABA Antagonists; D006168:Guinea Pigs; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009130:Muscle, Smooth / Q000187:drug effects; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D018756:GABA Antagonists; D014326:Tropanes