Synthesis and configurational assignment of 1,2-dihydroimidazo[5,1-b] quinazoline-3,9-diones: Novel NMDA receptor antagonists

A. Váradi, P. Horváth, T. Kurtán, Attila Mándi, Gerg Tóth, A. Gergely, J. Kökösi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

NMDA receptors form a major subdivision of the ionotropic glutamate receptor family that mediates excitatory synaptic transmission in the brain. Series of 1-substituted 1,2-dihydroimidazo[5,1-b]quinazolinediones were synthesized and found to have potent nanomolar activity at the glycine site of the NMDA receptor. Imidazoquinazolinediones were prepared by cyclocondensation of 4-oxo-quinazoline-2-carboxamide with aldehydes and orthoesters with good yields. The formed enantiomers were separated by chiral HPLC. The absolute configuration of pure enantiomers is elucidated by combined CD/Quantumchemical time-dependent DFT calculation method (TDDFT).

Original languageEnglish
Pages (from-to)10365-10371
Number of pages7
JournalTetrahedron
Volume68
Issue number50
DOIs
Publication statusPublished - Dec 16 2012

Fingerprint

Quinazolines
Enantiomers
N-Methyl-D-Aspartate Receptors
Quinazolinones
Ionotropic Glutamate Receptors
Aldehydes
Discrete Fourier transforms
Synaptic Transmission
Glycine
Brain
High Pressure Liquid Chromatography

Keywords

  • Absolute configuration
  • HPLC-ECD
  • NMDA antagonist
  • Quinazoline
  • TDDFT ECD calculation

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

@article{cee7f1d946cc48ee964637ac4de8fd65,
title = "Synthesis and configurational assignment of 1,2-dihydroimidazo[5,1-b] quinazoline-3,9-diones: Novel NMDA receptor antagonists",
abstract = "NMDA receptors form a major subdivision of the ionotropic glutamate receptor family that mediates excitatory synaptic transmission in the brain. Series of 1-substituted 1,2-dihydroimidazo[5,1-b]quinazolinediones were synthesized and found to have potent nanomolar activity at the glycine site of the NMDA receptor. Imidazoquinazolinediones were prepared by cyclocondensation of 4-oxo-quinazoline-2-carboxamide with aldehydes and orthoesters with good yields. The formed enantiomers were separated by chiral HPLC. The absolute configuration of pure enantiomers is elucidated by combined CD/Quantumchemical time-dependent DFT calculation method (TDDFT).",
keywords = "Absolute configuration, HPLC-ECD, NMDA antagonist, Quinazoline, TDDFT ECD calculation",
author = "A. V{\'a}radi and P. Horv{\'a}th and T. Kurt{\'a}n and Attila M{\'a}ndi and Gerg T{\'o}th and A. Gergely and J. K{\"o}k{\"o}si",
year = "2012",
month = "12",
day = "16",
doi = "10.1016/j.tet.2012.09.086",
language = "English",
volume = "68",
pages = "10365--10371",
journal = "Tetrahedron",
issn = "0040-4020",
publisher = "Elsevier Limited",
number = "50",

}

TY - JOUR

T1 - Synthesis and configurational assignment of 1,2-dihydroimidazo[5,1-b] quinazoline-3,9-diones

T2 - Novel NMDA receptor antagonists

AU - Váradi, A.

AU - Horváth, P.

AU - Kurtán, T.

AU - Mándi, Attila

AU - Tóth, Gerg

AU - Gergely, A.

AU - Kökösi, J.

PY - 2012/12/16

Y1 - 2012/12/16

N2 - NMDA receptors form a major subdivision of the ionotropic glutamate receptor family that mediates excitatory synaptic transmission in the brain. Series of 1-substituted 1,2-dihydroimidazo[5,1-b]quinazolinediones were synthesized and found to have potent nanomolar activity at the glycine site of the NMDA receptor. Imidazoquinazolinediones were prepared by cyclocondensation of 4-oxo-quinazoline-2-carboxamide with aldehydes and orthoesters with good yields. The formed enantiomers were separated by chiral HPLC. The absolute configuration of pure enantiomers is elucidated by combined CD/Quantumchemical time-dependent DFT calculation method (TDDFT).

AB - NMDA receptors form a major subdivision of the ionotropic glutamate receptor family that mediates excitatory synaptic transmission in the brain. Series of 1-substituted 1,2-dihydroimidazo[5,1-b]quinazolinediones were synthesized and found to have potent nanomolar activity at the glycine site of the NMDA receptor. Imidazoquinazolinediones were prepared by cyclocondensation of 4-oxo-quinazoline-2-carboxamide with aldehydes and orthoesters with good yields. The formed enantiomers were separated by chiral HPLC. The absolute configuration of pure enantiomers is elucidated by combined CD/Quantumchemical time-dependent DFT calculation method (TDDFT).

KW - Absolute configuration

KW - HPLC-ECD

KW - NMDA antagonist

KW - Quinazoline

KW - TDDFT ECD calculation

UR - http://www.scopus.com/inward/record.url?scp=84869088753&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84869088753&partnerID=8YFLogxK

U2 - 10.1016/j.tet.2012.09.086

DO - 10.1016/j.tet.2012.09.086

M3 - Article

AN - SCOPUS:84869088753

VL - 68

SP - 10365

EP - 10371

JO - Tetrahedron

JF - Tetrahedron

SN - 0040-4020

IS - 50

ER -