A series of nine novel 3-acetamide-azepino[4,5-b]indol-4-ones and nine novel 3-tetrazolylmethyl-azepino[4,5-b]indol-4-ones were synthesized by Ugi-type / free radical mediated cyclization in moderate to good yields (52-90%) and (40-83%) respectively. Several stepwise methodologies toward compounds having the azepino[4,5-b]indol-4-one core have been reported in which the last step was the construction of the azepine ring e.g. via: (i) S_EAr, (ii) Pd-catalyzed alkyne arylations, (iii) lactamizations, (iv) photocyclizations, and (v) free radical mediated. Azepino[4,5-b]indol-4-one is the core of various natural bioactive products such as the malassezindoles.  The main hypothesis in this work was that the 3-tetrazolylmethyl-azepino[4,5-b]indol-4-ones and the 3-acetamide-azepino[4,5-b]indol-4-ones may show binding affinity on the 5-Ht₆R and hence may be candidates to further assays in vitro as 5-Ht₆R antagonists. Interestingly, a lead binding value was exhibited by one of our 3-acetamide-azepino[4,5-b]indol-4-ones (Ki = 211 nM).