RESUMO
The absolute configuration was established as (S,S,S) by the R-factor test and by careful measurement of 197 enantiomorph-sensitive Friedel pairs of reflections. The determination also confirms the absolute stereochemistry of (-)-3-aminoquinuclidine, a compound used in the preparation of the title material. The cyclohexane/tetrahydrofuran ring fusion is cis. The quinuclidine moiety has almost perfect threefold symmetry; the front and rear halves are twisted about this axis by 15 degrees. Quinuclidine-N--H ... Cl- and amide-N--H ... Cl- hydrogen bonds link screw-dyad-related molecules along the b axis.
Assuntos
Amidas/química , Compostos Bicíclicos Heterocíclicos com Pontes , Compostos Bicíclicos com Pontes/química , Antagonistas da Serotonina/química , Conformação Molecular , EstereoisomerismoRESUMO
A number of aryl substituted amidinoureas have been prepared and examined for their gastrointestinal spasmolytic, antimotility, antidiarrheal and antisecretory effects. In general, antisecretory and antimotility effects have been found to be associated with each other in these compounds. The structure-activity relationships found show that substitution of the aromatic ring in positions other than 2 and 6 correlates poorly with potency, and potency of such compounds is low. In contrast to this, 2,6-disubstitution confers high potency. The potency of 2,6-disubstituted compounds declines sharply with increasing weight of substitution of the amidinourea chain, with the important exception of the N-alkoxyamidinoureas. Increasing the molecular weight of an N-alkoxy substituent has a much less profound effect than the corresponding increase has in an N-alkyl substituent. High potency in an amidinourea may well be related to low basicity (or a high pKa value for its conjugate salt) but there is insufficient data to support this hypothesis fully. The actual tautomeric structure of an amidinourea probably affects its potency and this is discussed briefly.
