Synthesis And Activity Screening Of β₃ Adrenergic Agonists

The functional presence ofβ3 adrenergic receptor(β3AR) agonists have be well associated with the controls of obesity,noninsulin dependent diabetes,grastrointestinal dysfunction,disease of prostate,dyslipoproteinemia,urinary frequency and urinary incontinence. In the past two decades, a large number ofβ3 AR agonists were developed, including the derivatives of arylethanolamine and aryloxypropanolamine. To get higher activity and selectivity profile, people are still searching for novel structure compunds ofβ3AR agonists, which include the derivatives of phenylpropanolamine. In this research, nine analogous compounds were designed and synthesized on the base of the principle of structure-activity relationship ofβ3AR agonists, L-23, L-4 and L-8 belonging to derivatives of phenylethanolamine, L-27, L-2701, L-2702, L-14, L-1401 and L-1402 belonging to the novel derivatives of phenylpropanolamine. All compounds were identified by IR, 1H-NMR and MS. All compounds had a good agonistic activity onβ3-CHO cell in vitro except for L-23. L-1401 was discovered had the highest agonistic activity.By comparison, this paper found that the phenylpropanolamine derivatives might have lower agonistic activity onβ3-CHO cell in vitro than the phenylethanolamine derivatives, which need future authenticates. Meanwhile we also found that the (1R, 2S) configuration of phenylpropanolamine derivatives was optimization asβ3AR agonists.