2-Amino-6-chloro-3,4-dihydroquinazoline: A novel 5-HT3 receptor antagonist with antidepressant character

Małgorzata Dukat; Katie Alix; Jessica Worsham; Shailesh Khatri; Marvin K. Schulte

doi:10.1016/j.bmcl.2013.08.072

2-Amino-6-chloro-3,4-dihydroquinazoline: A novel 5-HT₃ receptor antagonist with antidepressant character

Małgorzata Dukat, Katie Alix, Jessica Worsham, Shailesh Khatri, Marvin K. Schulte

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

36 Scopus citations

Abstract

2-Amino-6-chloro-3,4-dihydroquinazoline HCl (A6CDQ, 4) binds at 5-HT ₃ serotonin receptors and displays antidepressant-like action in the mouse tail suspension test (TST). Empirically, 4 was demonstrated to be a 5-HT₃ receptor antagonist (two-electrode voltage clamp recordings using frog oocytes; IC₅₀ = 0.26 μM), and one that should readily penetrate the blood-brain barrier (log P = 1.86). 5-HT₃ receptor antagonists represent a potential approach to the development of new antidepressants, and 4 is an example of a structurally novel 5-HT₃ receptor antagonist that is active in a preclinical antidepressant model (i.e., the mouse TST).

Original language	English
Pages (from-to)	5945-5948
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2013.08.072
State	Published - 1 Nov 2013
Externally published	Yes

Keywords

5-HT receptors
Antagonists
Antidepressants
TST (tail suspension test)

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10.1016/j.bmcl.2013.08.072

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title = "2-Amino-6-chloro-3,4-dihydroquinazoline: A novel 5-HT3 receptor antagonist with antidepressant character",

abstract = "2-Amino-6-chloro-3,4-dihydroquinazoline HCl (A6CDQ, 4) binds at 5-HT 3 serotonin receptors and displays antidepressant-like action in the mouse tail suspension test (TST). Empirically, 4 was demonstrated to be a 5-HT3 receptor antagonist (two-electrode voltage clamp recordings using frog oocytes; IC50 = 0.26 μM), and one that should readily penetrate the blood-brain barrier (log P = 1.86). 5-HT3 receptor antagonists represent a potential approach to the development of new antidepressants, and 4 is an example of a structurally novel 5-HT3 receptor antagonist that is active in a preclinical antidepressant model (i.e., the mouse TST).",

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T2 - A novel 5-HT3 receptor antagonist with antidepressant character

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AU - Worsham, Jessica

AU - Khatri, Shailesh

AU - Schulte, Marvin K.

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AB - 2-Amino-6-chloro-3,4-dihydroquinazoline HCl (A6CDQ, 4) binds at 5-HT 3 serotonin receptors and displays antidepressant-like action in the mouse tail suspension test (TST). Empirically, 4 was demonstrated to be a 5-HT3 receptor antagonist (two-electrode voltage clamp recordings using frog oocytes; IC50 = 0.26 μM), and one that should readily penetrate the blood-brain barrier (log P = 1.86). 5-HT3 receptor antagonists represent a potential approach to the development of new antidepressants, and 4 is an example of a structurally novel 5-HT3 receptor antagonist that is active in a preclinical antidepressant model (i.e., the mouse TST).

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KW - Antagonists

KW - Antidepressants

KW - TST (tail suspension test)

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DO - 10.1016/j.bmcl.2013.08.072

M3 - Article

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ER -

2-Amino-6-chloro-3,4-dihydroquinazoline: A novel 5-HT₃ receptor antagonist with antidepressant character

Abstract

Keywords

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