MGS-0039

MGS-0039
IUPAC ime
	(1R,2R,3R,5R,6R)-2-amino-3-(3,4-dihlorobenziloksi)-6-fluorobiciklo[3.1.0]heksan-2,6-dikarbokskilna kiselina
Pravni status
Pravni status	Nije regulisan;
Identifikatori
CAS broj	569686-87-9
ATC kod	None
PubChem	CID 9886034
ChemSpider	8061707
Hemijski podaci
Formula	C15H14Cl2NO5
Molarna masa	378,179 g/mol
	SMILES F[C@@]2(C(=O)O)[C@H]3[C@@](C(=O)O)(N)[C@H](OCc1ccc(Cl)c(Cl)c1)C[C@@H]23; ;
	InChI InChI=1S/C15H14Cl2FNO5/c16-8-2-1-6(3-9(8)17)5-24-10-4-7-11(14(7,18)12(20)21)15(10,19)13(22)23/h1-3,7,10-11H,4-5,19H2,(H,20,21)(H,22,23)/t7-,10-,11+,14-,15+/m1/s1 ; Key:LFAGGDAZZKUVKO-JAGWWQSPSA-N ;

MGS-0039 je lek koji se koristi u naučnim istraživanjima. On deluje kao potentan i selektivan antagonist grupe II metabotropnih glutamatnih receptora (mGluR_2/3).^[1]^[2] On proizvodi antidepresivne i anksiolitičke efekte u životinjskim studijama,^[3]^[4]^[5]^[6] i pokazano je da pojačava otpuštanje dopamina i serotonina u specifičnim oblastima mozga.^[7]^[8] Istraživanja pokazuju da do toga može doći sličnim mehanizmom kao i kod srodnog glutaminergičnog leka ketamina.^[9]^[10]

Reference

^ Chaki, S.; Yoshikawa, R.; Hirota, S.; Shimazaki, T.; Maeda, M.; Kawashima, N.; Yoshimizu, T.; Yasuhara, A.; Sakagami, K.; Okuyama, S.; Nakanishi, S.; Nakazato, A. (март 2004). „MGS0039: A potent and selective group II metabotropic glutamate receptor antagonist with antidepressant-like activity”. Neuropharmacology. 46 (4): 457—67. PMID 14975669. doi:10.1016/j.neuropharm.2003.10.009.
^ Nakazato, A.; Sakagami, K.; Yasuhara, A.; Ohta, H.; Yoshikawa, R.; Itoh, M.; Nakamura, M.; Chaki, S. (август 2004). „Synthesis, in vitro pharmacology, structure-activity relationships, and pharmacokinetics of 3-alkoxy-2-amino-6-fluorobicyclo3.1.0hexane-2,6-dicarboxylic acid derivatives as potent and selective group II metabotropic glutamate receptor antagonists”. Journal of Medicinal Chemistry. 47 (18): 4570—87. PMID 15317467. doi:10.1021/jm0400294.
^ Shimazaki, T.; Iijima, M.; Chaki, S. (октобар 2004). „Anxiolytic-like activity of MGS0039, a potent group II metabotropic glutamate receptor antagonist, in a marble-burying behavior test”. European Journal of Pharmacology. 501 (1–3): 121—5. PMID 15464070. doi:10.1016/j.ejphar.2004.08.016.
^ Yasuhara, A.; Nakamura, M.; Sakagami, K.; Shimazaki, T.; Yoshikawa, R.; Chaki, S.; Ohta, H.; Nakazato, A. (јун 2006). „Prodrugs of 3-(3,4-dichlorobenzyloxy)-2-amino-6-fluorobicyclo3.1.0hexane-2,6-dicarboxylic acid (MGS0039): A potent and orally active group II mGluR antagonist with antidepressant-like potential”. Bioorganic & Medicinal Chemistry. 14 (12): 4193—207. PMID 16487713. doi:10.1016/j.bmc.2006.01.060.
^ Yoshimizu, T.; Shimazaki, T.; Ito, A.; Chaki, S. (јул 2006). „An mGluR2/3 antagonist, MGS0039, exerts antidepressant and anxiolytic effects in behavioral models in rats”. Psychopharmacology. 186 (4): 587—93. PMID 16612616. doi:10.1007/s00213-006-0390-7.
^ Stachowicz, K.; Wierońska, J.; Domin, H.; Chaki, S.; Pilc, A. (2011). „Anxiolytic-like activity of MGS0039, a selective group II mGlu receptor antagonist, is serotonin- and GABA-dependent”. Pharmacological Reports. 63 (4): 880—7. PMID 22001975. doi:10.1016/s1734-1140(11)70603-x.
^ Kawashima, N.; Karasawa, J.; Shimazaki, T.; Chaki, S.; Okuyama, S.; Yasuhara, A.; Nakazato, A. (април 2005). „Neuropharmacological profiles of antagonists of group II metabotropic glutamate receptors”. Neuroscience Letters. 378 (3): 131—4. PMID 15781145. doi:10.1016/j.neulet.2004.12.021.
^ Karasawa, J.; Yoshimizu, T.; Chaki, S. (јануар 2006). „A metabotropic glutamate 2/3 receptor antagonist, MGS0039, increases extracellular dopamine levels in the nucleus accumbens shell”. Neuroscience Letters. 393 (2–3): 127—30. PMID 16233956. doi:10.1016/j.neulet.2005.09.058.
^ Pałucha-Poniewiera, A.; Wierońska, J. M.; Brański, P.; Stachowicz, K.; Chaki, S.; Pilc, A. (децембар 2010). „On the mechanism of the antidepressant-like action of group II mGlu receptor antagonist, MGS0039”. Psychopharmacology. 212 (4): 523—35. PMC 2981731 . PMID 20703449. doi:10.1007/s00213-010-1978-5.
^ Koike, H.; Iijima, M.; Chaki, S. (децембар 2011). „Involvement of the mammalian target of rapamycin signaling in the antidepressant-like effect of group II metabotropic glutamate receptor antagonists”. Neuropharmacology. 61 (8): 1419—23. PMID 21903115. doi:10.1016/j.neuropharm.2011.08.034.

Spoljašnje veze

[1] Chaki, S.; Yoshikawa, R.; Hirota, S.; Shimazaki, T.; Maeda, M.; Kawashima, N.; Yoshimizu, T.; Yasuhara, A.; Sakagami, K.; Okuyama, S.; Nakanishi, S.; Nakazato, A. (март 2004). „MGS0039: A potent and selective group II metabotropic glutamate receptor antagonist with antidepressant-like activity”. Neuropharmacology. 46 (4): 457—67. PMID 14975669. doi:10.1016/j.neuropharm.2003.10.009.

[2] Nakazato, A.; Sakagami, K.; Yasuhara, A.; Ohta, H.; Yoshikawa, R.; Itoh, M.; Nakamura, M.; Chaki, S. (август 2004). „Synthesis, in vitro pharmacology, structure-activity relationships, and pharmacokinetics of 3-alkoxy-2-amino-6-fluorobicyclo3.1.0hexane-2,6-dicarboxylic acid derivatives as potent and selective group II metabotropic glutamate receptor antagonists”. Journal of Medicinal Chemistry. 47 (18): 4570—87. PMID 15317467. doi:10.1021/jm0400294.

[3] Shimazaki, T.; Iijima, M.; Chaki, S. (октобар 2004). „Anxiolytic-like activity of MGS0039, a potent group II metabotropic glutamate receptor antagonist, in a marble-burying behavior test”. European Journal of Pharmacology. 501 (1–3): 121—5. PMID 15464070. doi:10.1016/j.ejphar.2004.08.016.

[4] Yasuhara, A.; Nakamura, M.; Sakagami, K.; Shimazaki, T.; Yoshikawa, R.; Chaki, S.; Ohta, H.; Nakazato, A. (јун 2006). „Prodrugs of 3-(3,4-dichlorobenzyloxy)-2-amino-6-fluorobicyclo3.1.0hexane-2,6-dicarboxylic acid (MGS0039): A potent and orally active group II mGluR antagonist with antidepressant-like potential”. Bioorganic & Medicinal Chemistry. 14 (12): 4193—207. PMID 16487713. doi:10.1016/j.bmc.2006.01.060.

[5] Yoshimizu, T.; Shimazaki, T.; Ito, A.; Chaki, S. (јул 2006). „An mGluR2/3 antagonist, MGS0039, exerts antidepressant and anxiolytic effects in behavioral models in rats”. Psychopharmacology. 186 (4): 587—93. PMID 16612616. doi:10.1007/s00213-006-0390-7.

[6] Stachowicz, K.; Wierońska, J.; Domin, H.; Chaki, S.; Pilc, A. (2011). „Anxiolytic-like activity of MGS0039, a selective group II mGlu receptor antagonist, is serotonin- and GABA-dependent”. Pharmacological Reports. 63 (4): 880—7. PMID 22001975. doi:10.1016/s1734-1140(11)70603-x.

[7] Kawashima, N.; Karasawa, J.; Shimazaki, T.; Chaki, S.; Okuyama, S.; Yasuhara, A.; Nakazato, A. (април 2005). „Neuropharmacological profiles of antagonists of group II metabotropic glutamate receptors”. Neuroscience Letters. 378 (3): 131—4. PMID 15781145. doi:10.1016/j.neulet.2004.12.021.

[8] Karasawa, J.; Yoshimizu, T.; Chaki, S. (јануар 2006). „A metabotropic glutamate 2/3 receptor antagonist, MGS0039, increases extracellular dopamine levels in the nucleus accumbens shell”. Neuroscience Letters. 393 (2–3): 127—30. PMID 16233956. doi:10.1016/j.neulet.2005.09.058.

[9] Pałucha-Poniewiera, A.; Wierońska, J. M.; Brański, P.; Stachowicz, K.; Chaki, S.; Pilc, A. (децембар 2010). „On the mechanism of the antidepressant-like action of group II mGlu receptor antagonist, MGS0039”. Psychopharmacology. 212 (4): 523—35. PMC 2981731 . PMID 20703449. doi:10.1007/s00213-010-1978-5.

[10] Koike, H.; Iijima, M.; Chaki, S. (децембар 2011). „Involvement of the mammalian target of rapamycin signaling in the antidepressant-like effect of group II metabotropic glutamate receptor antagonists”. Neuropharmacology. 61 (8): 1419—23. PMID 21903115. doi:10.1016/j.neuropharm.2011.08.034.

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