The synthesis and SAR of a novel 3-benzazepine series of 5-HT2C agonists is described. Compound 7d (lorcaserin, APD356) was identified as one of the more potent and selective compounds in vitro (pEC50 values in functional assays measuring [(3)H]phosphoinositol turnover: 5-HT2C = 8.1; 5-HT2A = 6.8; 5-HT2B = 6.1) and was potent in an acute in vivo rat food intake model upon oral administration (ED50 at 6 h = 18 mg/kg). Lorcaserin was further characterized in a single-dose pharmacokinetic study in rat (t1/2 = 3.7 h; F = 86%) and a 28-day model of weight gain in growing Sprague-Dawley rat (8.5% decrease in weight gain observed at 36 mg/kg b.i.d.). Lorcaserin was selected for further evaluation in clinical trials for the treatment of obesity.

Lysine is a precursor for the synthesis of an aminobutyl C-functionalised tetra-azacyclododecane tetra-acid which has been linked to 872.3 antibody and may be labelled with 9OY to form a kinetically stable complex of potential use in radio i m mu not h e ra py .

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C-Functionalised triazacyclododecane and triazacyclononane triacid macrocycles have been covalently attached to a monoclonal antibody and may be labelled with l l l l n to form kinetically inert radiolabelled complexes.