jm8014052_si_001医.pdfVIP

Supporting Information A Series of 2,4-Disubstituted Quinolines as a New Class of Allosteric Enhancers of the Adenosine A Receptor 3 Laura H. Heitman, Anikó Göblyös, Annelien J. M. Zweemer, Renée Bakker, Thea Mulder-Krieger, Jacobus P. D. van Veldhoven, Henk de Vries, Johannes Brussee, Adriaan P. IJzerman* Table of Contents: S1: Title page S2-S7: Synthetic procedures and spectral data of compounds 2-33 S8: Elemental analysis of compounds 16-33 Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands *To whom correspondence should be addressed. Phone: +31- (0)71 527 4651. Fax: +31- (0)71 527 4565. E-mail address: ijzerman@lacdr.leidenuniv.nl (A.P. IJzerman) S1 Synthetic procedures and spectral data Quinoline-1-oxide (2). To a solution of quinoline (25.83 g, 0.2 mol) in acetic acid (70 mL) was added H O (35% in water, 1.5 eq, 29 mL) and the reaction mixture was 2 2 stirred at 70 ºC for 21 hours. pH was adjusted to 8 with 2M NaOH and the reaction mixture was extracted with DCM (4 x 80 mL). The organic layer was dried over MgSO and evaporated. The product was purified by column chromatography, with 4 ethyl acetate as the eluent. The product was crystallized from ethyl acetate. Yield: 21.72 g, 72% of yellow solid. 1H NMR (CDCl ) δ 7.30 (t, 1H, J = 7.66, 6.96 Hz, Ar), 3 7.61-7.90 (m, 4H, Ar), 8.54 (d, 1H, J = 5.84 Hz, Ar), 8.75 (d, 1H, J = 8.78 Hz, Ar). 4-Nitroquinoline-1-oxide (3). Compound 2 (19.10 g, 0.13 mol) was dissol