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Updated: Jul 11, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Design, synthesis, and preliminary pharmacological evaluation of new quinoline derivatives as nicotinic ligands
Luca Guandalini1, Monica Norcini, Katia Varani
1Laboratory of Design, Synthesis and Study of Biologically Active Heterocycles (HeteroBioLab), Department of Pharmaceutical Sciences, University of Florence, via Ugo Schiff 6, I-50019 Sesto Fiorentino, Italy.
Abstract:
A series of nicotinic ligands, carrying a quinoline nucleus, and characterized by a pharmacophoric distance between the quinoline nitrogen (H-bond acceptor) and the cationic nitrogen atoms higher than that proposed in the classical pharmacophoric models, have been synthesized and tested for their affinity for the central nicotinic receptor. The enantiomers of the nicotine analogue 1-methyl-2-pyrrolidinyl-6-quinoline and of its methiodide display enantioselectivity in binding studies, but not when tested in vivo; on alpha7* nicotinic receptor enantioselectivity is inverted with respect to the alpha4beta2* subtype. N,N,N-Trimethyl-4-(quinolin-6-yl)but-3-yn-1-ammonium iodide (3c) and trans-N,N,N-trimethyl-4-(quinolin-6-yl)but-3-en-1-ammonium iodide (4c), showing pharmacophoric distances in the range 8.5-10.4 A, interact with the alpha4beta2* nicotinic receptor with Ki in the microM range; compound 3c shows preference for the alpha7* subtype.
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