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Novel biguanide-based derivatives scouted as TAAR1 agonists : Synthesis, biological evaluation, ADME prediction and molecular docking studies. / Tonelli, Michele; Espinoza, Stefano; Gainetdinov, Raul R.; Cichero, Elena.

In: European Journal of Medicinal Chemistry, Vol. 127, 01.01.2017, p. 781-792.

Research output: Contribution to journal › Article › peer-review

Harvard

Tonelli, M, Espinoza, S, Gainetdinov, RR & Cichero, E 2017, 'Novel biguanide-based derivatives scouted as TAAR1 agonists: Synthesis, biological evaluation, ADME prediction and molecular docking studies', European Journal of Medicinal Chemistry, vol. 127, pp. 781-792. https://doi.org/10.1016/j.ejmech.2016.10.058

APA

Tonelli, M., Espinoza, S., Gainetdinov, R. R., & Cichero, E. (2017). Novel biguanide-based derivatives scouted as TAAR1 agonists: Synthesis, biological evaluation, ADME prediction and molecular docking studies. European Journal of Medicinal Chemistry, 127, 781-792. https://doi.org/10.1016/j.ejmech.2016.10.058

Vancouver

Tonelli M, Espinoza S, Gainetdinov RR, Cichero E. Novel biguanide-based derivatives scouted as TAAR1 agonists: Synthesis, biological evaluation, ADME prediction and molecular docking studies. European Journal of Medicinal Chemistry. 2017 Jan 1;127:781-792. https://doi.org/10.1016/j.ejmech.2016.10.058

Author

Tonelli, Michele ; Espinoza, Stefano ; Gainetdinov, Raul R. ; Cichero, Elena. / Novel biguanide-based derivatives scouted as TAAR1 agonists : Synthesis, biological evaluation, ADME prediction and molecular docking studies. In: European Journal of Medicinal Chemistry. 2017 ; Vol. 127. pp. 781-792.

BibTeX

@article{16bd731dd63c4fb5b95ed9c01c2ec7ae,
title = "Novel biguanide-based derivatives scouted as TAAR1 agonists: Synthesis, biological evaluation, ADME prediction and molecular docking studies",
abstract = "Trace amines (TAs) are endogenous neuromodulators that play a functional role in the synaptic transmission within central nervous system (CNS), targeting trace amine-associated receptors (TAARs). Starting from our previous computational studies on TAAR1 and TAAR5 interactions with the unselective ligand 3-iodothyronamine (T1AM), we investigated the functional activity at murine and human TAAR1 and murine TAAR5 receptors of twenty-seven biguanide-based derivatives, including six newly synthesized compounds. Phenyl (BIG2, BIG4, BIG8 and BIG22) or benzyl (BIG10-BIG16) biguanides were found to be selective murine and human TAAR1 agonists with potencies in nanomolar or low micromolar range, respectively. In particular, compounds BIG2 and BIG12-BIG14 were the most promising and they could be considered valuable lead compounds worthy of further investigations. In addition to the interest for developing more effective human TAAR1 ligands, the disclosed here potent murine TAAR1 agonists could offer suitable tools for studying the pharmacology of TAAR1 receptor.",
keywords = "Benzyl biguanide derivatives, Murine and human TAAR1 agonists, Phenyl biguanide derivatives, Trace amine-associated receptors (TAARs)",
author = "Michele Tonelli and Stefano Espinoza and Gainetdinov, {Raul R.} and Elena Cichero",
year = "2017",
month = jan,
day = "1",
doi = "10.1016/j.ejmech.2016.10.058",
language = "English",
volume = "127",
pages = "781--792",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Novel biguanide-based derivatives scouted as TAAR1 agonists

T2 - Synthesis, biological evaluation, ADME prediction and molecular docking studies

AU - Tonelli, Michele

AU - Espinoza, Stefano

AU - Gainetdinov, Raul R.

AU - Cichero, Elena

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Trace amines (TAs) are endogenous neuromodulators that play a functional role in the synaptic transmission within central nervous system (CNS), targeting trace amine-associated receptors (TAARs). Starting from our previous computational studies on TAAR1 and TAAR5 interactions with the unselective ligand 3-iodothyronamine (T1AM), we investigated the functional activity at murine and human TAAR1 and murine TAAR5 receptors of twenty-seven biguanide-based derivatives, including six newly synthesized compounds. Phenyl (BIG2, BIG4, BIG8 and BIG22) or benzyl (BIG10-BIG16) biguanides were found to be selective murine and human TAAR1 agonists with potencies in nanomolar or low micromolar range, respectively. In particular, compounds BIG2 and BIG12-BIG14 were the most promising and they could be considered valuable lead compounds worthy of further investigations. In addition to the interest for developing more effective human TAAR1 ligands, the disclosed here potent murine TAAR1 agonists could offer suitable tools for studying the pharmacology of TAAR1 receptor.

AB - Trace amines (TAs) are endogenous neuromodulators that play a functional role in the synaptic transmission within central nervous system (CNS), targeting trace amine-associated receptors (TAARs). Starting from our previous computational studies on TAAR1 and TAAR5 interactions with the unselective ligand 3-iodothyronamine (T1AM), we investigated the functional activity at murine and human TAAR1 and murine TAAR5 receptors of twenty-seven biguanide-based derivatives, including six newly synthesized compounds. Phenyl (BIG2, BIG4, BIG8 and BIG22) or benzyl (BIG10-BIG16) biguanides were found to be selective murine and human TAAR1 agonists with potencies in nanomolar or low micromolar range, respectively. In particular, compounds BIG2 and BIG12-BIG14 were the most promising and they could be considered valuable lead compounds worthy of further investigations. In addition to the interest for developing more effective human TAAR1 ligands, the disclosed here potent murine TAAR1 agonists could offer suitable tools for studying the pharmacology of TAAR1 receptor.

KW - Benzyl biguanide derivatives

KW - Murine and human TAAR1 agonists

KW - Phenyl biguanide derivatives

KW - Trace amine-associated receptors (TAARs)

UR - http://www.scopus.com/inward/record.url?scp=85006136302&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2016.10.058

DO - 10.1016/j.ejmech.2016.10.058

M3 - Article

C2 - 27823885

AN - SCOPUS:85006136302

VL - 127

SP - 781

EP - 792

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

ER -

ID: 36298553