Abstract
A structure for the self-condensation product of 2-(1H-indol-2-yl) ethyl tosylate 2a, previously proposed as 6,7,14,15-tetrahydro-15aH-azocino[1,2- a: 6,5-b] diindole 3a, was revised based on the C-13-2D-INADEQUATE experiment, and proved to be 7,7a, 13,14-tetrahydro-6H-cyclobuta[ b] pyrimido[1,2- a: 3,4-a'] diindole 4a. A mechanism for the unexpected formation of this novel hexacyclic heterocycle was proposed and its NMR solution structure was elucidated. Five derivatives of the title ring skeleton 12 - 16 designed as melatonin receptor ligands were synthesized and their affinities for the human MT1 and MT2 receptors were determined. Both butyramides 13 and 15, as well as the non-methoxy acetamide 12 exhibited micromolar binding affinities for both receptors being slightly MT2 selective. The methoxy acetamide 14 showed the best pharmacological profile exhibiting a five times higher affinity for MT1 (K-i = 49 nM) than for MT2 ( Ki = 246 nM) receptor.