(S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands: Further Exploration of Bioisosteric Replacements, Structural and Biological Investigation.

Simone Brogi; Marghertia Brindisi; Stefania Butini; Giridhar Kshirsagar; Samuele Maramai; Giulia Chemi; Sandra Gemma; Giuseppe Campiani; Ettore Novellino; Paolo Fiorenzani; Jessica Pinassi; Anna Maria Aloisi; Mikko Gynther; Raminta Venskutonyte; Liwei Han; Karla Andrea Frydenvang; Jette Sandholm Jensen Kastrup; Darryl S Pickering

doi:10.1021/acs.jmedchem.8b00099

(S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands: Further Exploration of Bioisosteric Replacements, Structural and Biological Investigation.

Simone Brogi, Marghertia Brindisi, Stefania Butini, Giridhar Kshirsagar, Samuele Maramai, Giulia Chemi, Sandra Gemma, Giuseppe Campiani, Ettore Novellino, Paolo Fiorenzani, Jessica Pinassi, Anna Maria Aloisi, Mikko Gynther, Raminta Venskutonyte, Liwei Han, Karla Andrea Frydenvang, Jette Sandholm Jensen Kastrup, Darryl S Pickering

6 Citations (Scopus)

Abstract

Starting from 1-4 and 7 structural templates, analogues based on bioisosteric replacements (5a-c vs 1, 2 and 6 vs 7) were synthesized for completing the SAR analysis. Interesting binding properties at GluA2, GluK1, and GluK3 receptors were discovered. The requirements for GluK3 interaction were elucidated by determining the X-ray structures of the GluK3-LBD with 2 and 5c and by computational studies. Antinociceptive potential was demonstrated for GluK1 partial agonist 3 and antagonist 7 (2 mg/kg ip).

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	61
Issue number	5
Pages (from-to)	2124-2130
Number of pages	7
ISSN	0022-2623
DOIs	https://doi.org/10.1021/acs.jmedchem.8b00099
Publication status	Published - 8 Mar 2018

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Brogi, S., Brindisi, M., Butini, S., Kshirsagar, G., Maramai, S., Chemi, G., Gemma, S., Campiani, G., Novellino, E., Fiorenzani, P., Pinassi, J., Aloisi, A. M., Gynther, M., Venskutonyte, R., Han, L., Frydenvang, K. A., Kastrup, J. S. J., & Pickering, D. S. (2018). (S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands: Further Exploration of Bioisosteric Replacements, Structural and Biological Investigation. Journal of Medicinal Chemistry, 61(5), 2124-2130. https://doi.org/10.1021/acs.jmedchem.8b00099

(S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands: Further Exploration of Bioisosteric Replacements, Structural and Biological Investigation. / Brogi, Simone; Brindisi, Marghertia; Butini, Stefania et al.

In: Journal of Medicinal Chemistry, Vol. 61, No. 5, 08.03.2018, p. 2124-2130.

Research output: Contribution to journal › Journal article › Research › peer-review

Brogi, S, Brindisi, M, Butini, S, Kshirsagar, G, Maramai, S, Chemi, G, Gemma, S, Campiani, G, Novellino, E, Fiorenzani, P, Pinassi, J, Aloisi, AM, Gynther, M, Venskutonyte, R, Han, L, Frydenvang, KA , Kastrup, JSJ & Pickering, DS 2018, '(S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands: Further Exploration of Bioisosteric Replacements, Structural and Biological Investigation.', Journal of Medicinal Chemistry, vol. 61, no. 5, pp. 2124-2130. https://doi.org/10.1021/acs.jmedchem.8b00099

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title = "(S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands: Further Exploration of Bioisosteric Replacements, Structural and Biological Investigation.",

abstract = "Starting from 1-4 and 7 structural templates, analogues based on bioisosteric replacements (5a-c vs 1, 2 and 6 vs 7) were synthesized for completing the SAR analysis. Interesting binding properties at GluA2, GluK1, and GluK3 receptors were discovered. The requirements for GluK3 interaction were elucidated by determining the X-ray structures of the GluK3-LBD with 2 and 5c and by computational studies. Antinociceptive potential was demonstrated for GluK1 partial agonist 3 and antagonist 7 (2 mg/kg ip).",

author = "Simone Brogi and Marghertia Brindisi and Stefania Butini and Giridhar Kshirsagar and Samuele Maramai and Giulia Chemi and Sandra Gemma and Giuseppe Campiani and Ettore Novellino and Paolo Fiorenzani and Jessica Pinassi and Aloisi, {Anna Maria} and Mikko Gynther and Raminta Venskutonyte and Liwei Han and Frydenvang, {Karla Andrea} and Kastrup, {Jette Sandholm Jensen} and Pickering, {Darryl S}",

year = "2018",

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doi = "10.1021/acs.jmedchem.8b00099",

language = "English",

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T1 - (S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands: Further Exploration of Bioisosteric Replacements, Structural and Biological Investigation.

AU - Brogi, Simone

AU - Brindisi, Marghertia

AU - Butini, Stefania

AU - Kshirsagar, Giridhar

AU - Maramai, Samuele

AU - Chemi, Giulia

AU - Gemma, Sandra

AU - Campiani, Giuseppe

AU - Novellino, Ettore

AU - Fiorenzani, Paolo

AU - Pinassi, Jessica

AU - Aloisi, Anna Maria

AU - Gynther, Mikko

AU - Venskutonyte, Raminta

AU - Han, Liwei

AU - Frydenvang, Karla Andrea

AU - Kastrup, Jette Sandholm Jensen

AU - Pickering, Darryl S

PY - 2018/3/8

Y1 - 2018/3/8

N2 - Starting from 1-4 and 7 structural templates, analogues based on bioisosteric replacements (5a-c vs 1, 2 and 6 vs 7) were synthesized for completing the SAR analysis. Interesting binding properties at GluA2, GluK1, and GluK3 receptors were discovered. The requirements for GluK3 interaction were elucidated by determining the X-ray structures of the GluK3-LBD with 2 and 5c and by computational studies. Antinociceptive potential was demonstrated for GluK1 partial agonist 3 and antagonist 7 (2 mg/kg ip).

AB - Starting from 1-4 and 7 structural templates, analogues based on bioisosteric replacements (5a-c vs 1, 2 and 6 vs 7) were synthesized for completing the SAR analysis. Interesting binding properties at GluA2, GluK1, and GluK3 receptors were discovered. The requirements for GluK3 interaction were elucidated by determining the X-ray structures of the GluK3-LBD with 2 and 5c and by computational studies. Antinociceptive potential was demonstrated for GluK1 partial agonist 3 and antagonist 7 (2 mg/kg ip).

U2 - 10.1021/acs.jmedchem.8b00099

DO - 10.1021/acs.jmedchem.8b00099

M3 - Journal article

C2 - 29451794

SN - 0022-2623

VL - 61

SP - 2124

EP - 2130

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 5

ER -

(S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands: Further Exploration of Bioisosteric Replacements, Structural and Biological Investigation.

Abstract

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