( )-cis-4,5,7a,8,9,10,11,11a-Octahydro-7H-10-methylmdolo[1,7-bc][2,6]- naphthyridine: A 5-HT2C/2B Receptor Antagonist with Low 5-HT2a Receptor Affinity

Abstract

The indolonaphthyridine 8 is described as a selective 5-HT2c/2b vs 5-HT2A receptor antagonist. The compound was synthesized in seven steps starting from indoline and isonicotinic acid chloride. The key step is a photocyclization of the indolinyl tetrahydropyridinocarbamic acid ethyl ester 4 to the cis-octahydroindolo[l,7-bc][2,6]naphthyridinecarbamic acid ethyl ester 5. The synthesis was accomplished by reduction with aluminum hydride and racemic resolution. The indolonaphthyridine 8 exerted the binding profile of a selective 5-HT2C receptor ligand (p-KD 7.8) and behaved as an antagonist on the 5-HT-induced accumulation of inositol phosphates in pig choroid plexus cells (p-KB 7.13). Compound..