Hit-to-lead optimization of mouse Trace Amine Associated Receptor 1 (mTAAR1) agonists with a diphenylmethane-scaffold: Design, Synthesis, and biological study. / Chiellini, G; Nesi, G; Sestito, S; Chiarugi, S; Runfola, M; Espinoza, S; Sabatini, M; Bellusci, L; Laurino, A; Cichero, E; Gainetdinov, RR; Fossa, P; Raimondi, L; Zucchi, R; Rapposelli, S.
In: Journal of Medicinal Chemistry, 2016.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Hit-to-lead optimization of mouse Trace Amine Associated Receptor 1 (mTAAR1) agonists with a diphenylmethane-scaffold: Design, Synthesis, and biological study.
AU - Chiellini, G
AU - Nesi, G
AU - Sestito, S
AU - Chiarugi, S
AU - Runfola, M
AU - Espinoza, S
AU - Sabatini, M
AU - Bellusci, L
AU - Laurino, A
AU - Cichero, E
AU - Gainetdinov, RR
AU - Fossa, P
AU - Raimondi, L
AU - Zucchi, R
AU - Rapposelli, S.
PY - 2016
Y1 - 2016
N2 - The trace amine-associated receptor 1 (TAAR1) is a G-protein-coupled receptors (GPCR) potently activated by a variety of molecules besides trace amines (TAs), including thyroid hormone-derivatives like 3-iodothyronamine (T1AM), catechol-O-methyltransferase products like 3-methoxytyramine, and amphetamine-related compounds. Accordingly, TAAR1 is considered a promising target for medicinal development. To gain more insights into TAAR1 physiological functions and validation of its therapeutic potential we recently developed a new class of thyronamine-like derivatives. Among them compound SG2 showed high affinity and potent agonist activity at mouse TAAR1. In the present work we describe design, the synthesis and SAR study of a new series of compounds (1-16) obtained by introducing specific structural changes at key points of our lead-compound SG2 skeleton. Five of the newly synthesized compounds displayed mTAAR1 agonist activity higher than both SG2 and T1AM. Selected diphenylmethane analogs, namely 1 and 2, sho
AB - The trace amine-associated receptor 1 (TAAR1) is a G-protein-coupled receptors (GPCR) potently activated by a variety of molecules besides trace amines (TAs), including thyroid hormone-derivatives like 3-iodothyronamine (T1AM), catechol-O-methyltransferase products like 3-methoxytyramine, and amphetamine-related compounds. Accordingly, TAAR1 is considered a promising target for medicinal development. To gain more insights into TAAR1 physiological functions and validation of its therapeutic potential we recently developed a new class of thyronamine-like derivatives. Among them compound SG2 showed high affinity and potent agonist activity at mouse TAAR1. In the present work we describe design, the synthesis and SAR study of a new series of compounds (1-16) obtained by introducing specific structural changes at key points of our lead-compound SG2 skeleton. Five of the newly synthesized compounds displayed mTAAR1 agonist activity higher than both SG2 and T1AM. Selected diphenylmethane analogs, namely 1 and 2, sho
M3 - статья
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
ER -
ID: 7598887