788824-56-6Relevant articles and documents
A new efficient synthetic method for 3-iodothyronamine and its potent hypothermic efficacy
Kim, Joong-Gon,Song, Young-Kyu,Jeon, Su-Yeon,Lim, Ye-Ji,Ju, Hyunwoo,Choi, Inho,Chung, Chan-Moon
, p. 2205 - 2208 (2011)
We developed a new efficient synthetic method for a 3-iodothyronamine (T1AM) that has advantages of less synthetic steps and much higher overall yield compared to those in the conventional method. Our animal study showed that T1AM synthesized by the method exerted a potent hypothermic effect in non-hibernator mice.
Regioselective deiodination of iodothyronamines, endogenous thyroid hormone derivatives, by deiodinase mimics
Mondal, Santanu,Mugesh, Govindasamy
, p. 11120 - 11128,9 (2014/11/27)
Iodothyronine deiodinases (IDs) are mammalian selenoenzymes that play an important role in the activation and inactivation￡ of thyroid hormones. It is known that iodothyronamines (TnAMs), produced by the decarboxylation of thyroid hormones, act as substrates for deiodinases. To understand whether decarboxylation alters the rate and/or regioselectivity of deiodination by using synthetic deiodinase mimics, we studied the deiodination of different iodothyronamines. The triiodo derivative 3,3,5-triiodothyronamine (T3 AM) is deiodinated at the inner ring by naphthyl-based deiodinase mimics, which is similar to the deiodination of 3,3,5-triiodothyronine (T3). However, T3 AM undergoes much slower deiodination than T3. Detailed experimental and theoretical investigations suggest that T3 AM forms a weaker halogen bond with selenium donors than T3. Kinetic studies and single-crystal X-ray structures of T3 and T3 AM reveal that intermolecular I...I interactions may play an important role in deiodination. The formation of hydrogen- and halogen-bonding assemblies, which leads to the formation of a dimeric species of T3 in solution, facilitates the interactions between the selenium and iodine atoms. In contrast, T3 AM, which does not have I...I interactions, undergoes much slower deiodination.
Trace amine-associated receptor agonists: Synthesis and evaluation of thyronamines and related analogues
Hart, Matthew E.,Suchland, Katherine L.,Miyakawa, Motonori,Bunzow, James R.,Grandy, David K.,Scanlan, Thomas S.
, p. 1101 - 1112 (2007/10/03)
We have previously shown that several thyronamines, decarboxylated and deiodinated metabolites of the thyroid hormone, potently activate an orphan G protein-coupled receptor in vitro (TAAR1) and induced hypothermia in vivo on a rapid time scale [Scanlan, T. S.; Suchland, K. L.; Hart, M. E.; Chiellini, G.; Huang, Y.; Kruzich, P. J.; Frascarelli, S.; Crossley, D. A.; Bunzow, J. R.; Ronca-Testoni, S.; Lin, E. T.; Hatton, D.; Zucchi, R.; Grandy, D. K. 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat. Med. 2004, 10 (6), 638-642]. Herein, we report the synthesis of these thyronamines. Additionally, a large number of thyroamine derivatives were synthesized in an effort to understand the molecular basis of TAAR1 activation and hypothermia induction. Several derivatives were found to potently activate both rTAAR1 and mTAAR1 in vitro (compounds 77, 85, 91, and 92). When administered to mice at a 50 mg/kg dose, these derivatives all induced significant hypothermia within 60 min and exhibited a hypothermic induction profile analogous to 3-iodothyronamine (1, T1AM) except 91, which proved to be more efficacious. On the basis of this result, a dose-dependent profile for 91 was generated and an ED50 of 30 μmol/kg was calculated. Compound 91 proved to be more potent than T1AM for TAAR1 activation and exhibits increased potency and efficacy for hypothermia induction. These data further strengthen the pharmacological correlation linking TAAR1 activation by thyronamines and hypothermia induction in mice.
