The syntheses for two cis-decahydroquinoline-5-carboxylic acid epimers (1 and 2) which contain the =N(C)3CO2H (gamma-aminobutyric acid; GABA) moiety are described. Both intra-and intermolecular [4 + 2] cycloaddition reactions were employed for the construction of key intermediates. 1H NMR studies provided evidence for the preferred solution conformations of the two diastereomers. Pharmacological studies revealed that these isomers have little affinity for GABA receptors in vitro relative to GABA agonists. However, expected but weak stereoselective activity was observed when these analogues were assessed for their ability to inhibit high-affinity [3H]GABA uptake into rat brain synaptosomes. These data are discussed in light of structure-activity studies of other neurotransmitter analogues, and a preliminary hypothesis based upon conformational analysis is presented to explain the results.
A series of 12-aminotetrahydroisoquinocarbazoles and related compounds were synthesized using an intramolecular Diels-Alder reaction and screened for antiarrhythmic activity in chloroform-induced ventricular arrhythmias in mice. Several compounds showed more potent activity than disopyramide. There was some correlation between substituents on aromatic ring and angular position, and antiarrhythmic activity. An amino group or some functional groups containing an amino group on C-12 seemed to be essential to exhibit the activity. Ring size also influenced the activity. The compound (+)-10 (RS-2135) had the most favorable combination of antiarrhythmic activity and toxicity and was selected for further evaluation.
N‐Chlorsuccinimid (I) liefert die Sulfoniumsalze (II), die mit den Indolen (III) zu den Salzen (IV) umgesetzt und dann durch Erwärmen auf Raumtemperatur zu (V) in hohen Gesamtausbeuten gespalten werden.
A series of methyl 9H-pyridazino[3,4-b]indole-3-carboxylates and related compounds were synthesized using a Diels-Alder reaction of methyl 3-(1H-indol-3-yl)-2-propenoates and dibenzyl azodicarboxylate. Several compounds were found to have high affinity for the benzodiazepine receptor. Their structure-activity relationships are discussed.
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