Ligand-Receptor Interactions via Hydrogen-Bond Formation. Synthesis and Pharmacological Evaluation of Pyrrolo and Pyrido Analogues of the Cardiotonic Agent 7-Hydroxycyclindole

Article abstract of DOI:10.1021/jm00158a022

The syntheses of N,N-dimethyl-6,7,8,9-tetrahydro-3H,10H-pyrrolo<3,2-a>carbazol-7-amine (8), N,N-dimethyl-7,8,9,10-tetrahydro-11H-pyrido<3,2-a>carbazol-8-amine (9a), and the N,N,11-trimethyl analogue (9b) are described.The in vitro inotropic activity of these compounds, as well as the known cardiotonics amrinone and 7-hydroxycyclindole (7), was investigated.Compound 8, a pyrrolo analogue of 7, was devoid of inotropic activity, while the pyrido analogues 9 were equiactive to 7 and amrinone.These results suggest that the hydroxyl group of 7 functions as an H-bondacceptor, rather than a donor, and that on interaction of 7, and the pyrido analogues 9, with a common receptor, an orbital occupied by one of the oxygen lone pair electrons of 7 must assume the same orientation as the orbital occupied by the pyridine nitrogen lone pair.