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Kevin Maupin ACF Abstract FY10

The Synthesis of Novel Indane Derivatives as Regulators of TAAR Activity: An Updated Approach

Conference Name: Spring 2010/239th National Meeting of the American Chemical Society

3-iodothyronamine (T1AM) is a metabolically active derivative of thyroid hormone. Research has shown that T1AM and other similar thyronamine analogs are potent activators of the trace amine associated receptor (TAAR1) in vitro. This research has also shown that the binding of TAAR1 by these thyronamines rapidly induces physiological responses in opposition to those seen by T1AM’s origin thyroid hormones, thyroxine (T4 ) and 3, 5, 3’ triiodothyronine (T3 ). (Scanlan et al, 2004; Hart et al, 2006) To date, several potent agonists have been identified, however, reported antagonists have been modest at best. Previous research in our lab, involving the enantomeric pair of Apomorphine, has shown an interesting regulatory pattern at TAAR1. For example R(-)Apomorphine has been shown to effectively activate TAAR1, while S(+)Apomorphine showed dose dependent inhibition of TAAR1 activation in these same cells. Previously we presented the attempted synthesis of a novel amino-indane compound. The final step of the original synthetic route yielded an hydroxy-indane by an unknown mechanism. Alternative methods were proposed to achieve our target molecule. Here we present the use of aziridination chemistry for addition of an amine functional group to 4 related indenes. By testing analogs of T1AM, more potent agonists and antagonists could be uncovered. Developing these compounds could not only lead to a better understanding of TAAR1 receptor’s role in biology, but advancements in the treatment of patients with thyroid hormone related diseases.

Kevin A. Maupin and Matthew E. Hart

1 Campus Drive, Grand Valley State University Allendale, MI 49401-9403