Proof of concept study for designed multiple ligands targeting the dopamine D2, serotonin 5-HT2A, and muscarinic M1 acetylcholine receptors

Monika Szabo, Herman Dirnawan Lim, Carmen Klein Herenbrink, Arthur Christopoulos, Jonathan Robert David Lane, Benvenuto Capuano

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Herein we describe the hybridization of a benzoxazinone M1 scaffold with D2 privileged structures derived from putative and clinically relevant antipsychotics to develop designed multiple ligands. The M1 mAChR is an attractive target for the cognitive deficits in key CNS disorders. Moreover, activity at D2 and 5-HT2A receptors has proven useful for antipsychotic efficacy. We identified 9 which retained functional activity at the target M1 mAChR and D2R and demonstrated high affinity for the 5-HT2AR.
Original languageEnglish
Pages (from-to)1550 - 1555
Number of pages6
JournalJournal of Medicinal Chemistry
Volume58
Issue number3
DOIs
Publication statusPublished - 2015

Cite this

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title = "Proof of concept study for designed multiple ligands targeting the dopamine D2, serotonin 5-HT2A, and muscarinic M1 acetylcholine receptors",
abstract = "Herein we describe the hybridization of a benzoxazinone M1 scaffold with D2 privileged structures derived from putative and clinically relevant antipsychotics to develop designed multiple ligands. The M1 mAChR is an attractive target for the cognitive deficits in key CNS disorders. Moreover, activity at D2 and 5-HT2A receptors has proven useful for antipsychotic efficacy. We identified 9 which retained functional activity at the target M1 mAChR and D2R and demonstrated high affinity for the 5-HT2AR.",
author = "Monika Szabo and Lim, {Herman Dirnawan} and {Klein Herenbrink}, Carmen and Arthur Christopoulos and Lane, {Jonathan Robert David} and Benvenuto Capuano",
year = "2015",
doi = "10.1021/jm5013243",
language = "English",
volume = "58",
pages = "1550 -- 1555",
journal = "Journal of Medicinal Chemistry",
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publisher = "AMER CHEMICAL SOC",
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Proof of concept study for designed multiple ligands targeting the dopamine D2, serotonin 5-HT2A, and muscarinic M1 acetylcholine receptors. / Szabo, Monika; Lim, Herman Dirnawan; Klein Herenbrink, Carmen; Christopoulos, Arthur; Lane, Jonathan Robert David; Capuano, Benvenuto.

In: Journal of Medicinal Chemistry, Vol. 58, No. 3, 2015, p. 1550 - 1555.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Proof of concept study for designed multiple ligands targeting the dopamine D2, serotonin 5-HT2A, and muscarinic M1 acetylcholine receptors

AU - Szabo, Monika

AU - Lim, Herman Dirnawan

AU - Klein Herenbrink, Carmen

AU - Christopoulos, Arthur

AU - Lane, Jonathan Robert David

AU - Capuano, Benvenuto

PY - 2015

Y1 - 2015

N2 - Herein we describe the hybridization of a benzoxazinone M1 scaffold with D2 privileged structures derived from putative and clinically relevant antipsychotics to develop designed multiple ligands. The M1 mAChR is an attractive target for the cognitive deficits in key CNS disorders. Moreover, activity at D2 and 5-HT2A receptors has proven useful for antipsychotic efficacy. We identified 9 which retained functional activity at the target M1 mAChR and D2R and demonstrated high affinity for the 5-HT2AR.

AB - Herein we describe the hybridization of a benzoxazinone M1 scaffold with D2 privileged structures derived from putative and clinically relevant antipsychotics to develop designed multiple ligands. The M1 mAChR is an attractive target for the cognitive deficits in key CNS disorders. Moreover, activity at D2 and 5-HT2A receptors has proven useful for antipsychotic efficacy. We identified 9 which retained functional activity at the target M1 mAChR and D2R and demonstrated high affinity for the 5-HT2AR.

UR - http://pubs.acs.org/doi/pdf/10.1021/jm5013243

U2 - 10.1021/jm5013243

DO - 10.1021/jm5013243

M3 - Article

VL - 58

SP - 1550

EP - 1555

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

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ER -