X-ray structures of new substituted 2-(pyrazol-1-yl)-2′-nitroacetanilides with pharmacological activity
Tóm tắt
The X-ray structures of four pharmacologically active lidocaine analogs, containing substituted pyrazole moieties as the basic residue and an o-nitrophenyl moiety as the hydrophobic residue, have been determined. They are 2-(pyrazol-1-yl)-2′-nitroacetanilide (1), 2-(3,5-dimethyl-pyrazol-1-yl)-2′-nitroacetanilide (2), 2-(3,5-dimethyl-4-iodo-pyrazol-1-yl)-2′-nitroacetanilide (3), and 2-(3,5-dimethyl-4-nitro-pyrazol-1-yl)-2′-nitroacetanilide (4). Crystal data are 1: space group Pn with a = 4.6944(1), b = 22.3890(3), c = 15.7481(2) Å, β = 96.810(1)°, Z = 6; 2: P
$$\overline {\text{1}} $$
with a = 4.7277(2), b = 11.6878(5), c = 12.0355(6) Å, α = 87.689(2), β = 85.048(2), γ = 85.975(2)°, Z = 2; 3: I2/a with a = 24.108(5), b = 4.7321(9), c = 25.337(5) Å, β = 96.09(3)°, Z = 8; 4: P21 with a = 5.7788(2), b = 8.9844(3), c = 14.0304(5) Å, β = 101.611(1)°, Z = 2. Molecules of compound 1 adopt a unique, folded conformation stabilized by intramolecular hydrogen bonds and the crystal structure lacks significant intermolecular interactions. In contrast, molecules of 2–4 adopt common, extended conformations and their crystal structures are based on linear arrays of hydrogen bonded (N—H...O=C) molecules. Compound 3 displayed the highest local anesthetic activity while 2 was the most active in tests for anti-arrhythmic effects.
Tài liệu tham khảo
Iovu, M.; Zalaru, C.; Dumitrascu, F.; Loloiu, T. Anal. Univ. Buc., 1999, 8, 97.
Cambridge Structural Database and Cambridge Structural Database System, Version 5.23; Cambridge Crystallographic Data Centre, University Chemical Laboratory: Cambridge, England, April 2002.
Smith, E.R.; Duce, B.R. J. Pharmacol. Exp. Ther. 1971, 179, 580.
Bianchi, C. Br. J. Pharmacol. 1956, 11, 104.
Hackenberger, F. Die Pharmazie, 1979, 34(8), 491.
Caliendo, G.; Greco, G.; Grieco, P.; Mattace Raso, G.; Meli, R.; Novellino, E.; Perissutti, E.; Santagada, V. Eur. J. Med. Chem. 1996, 31, 99.
Simionovici, M.; Carstea, A.; Vladescu, C. Pharmacological Research and Drug Prospecting; Medical Publishing House: Bucharest, Romania, 1983, p 415.
COLLECT. Nonius 2000; Delft, The Netherlands: Nonius BV, 2000.
Otwinowski, Z.; Minor, W. In Methods in Enzymology; Carter, C.W.; Sweet, R.M., Eds.; Academic Press: New York, 1996, p 307.
Sheldrick, G.M. Acta Crystallogr. 1990, A46, 467.
Sheldrick, G.M. SHELX-97, Program for the Refinement of Crystal Structures; University of Göttingen: Germany, 1997.
Spek, A.L. Acta Crystallogr. 1990, A46, C34.
Farrugia, L.J. ORTEP-3 for Windows, Version 1.05; University of Glasgow: Glasgow, UK, 1999. J. Appl. Crystallogr. 1997, 30, 565.
Zalaru, C.; Caira, M.R.; Iovu, M.; Cristea, E. Activitatea farmacologica si structura cu raze-x a noilor 2-(pirazol-1-il)-2′-nitroacetanilide Poster presented at the XIIth National Congress of Pharmacy with international participation, Oct. 17–19, 2002, Bucharest, Romania.