Arch. Pharm. Chem. Life Sci. 2012, 000, 1–7
Pyrazoline Derivatives as Selective hCOX-1 Inhibitors
5
Jcis ¼ 5.0 Hz, 1H, C4H-pyrazoline), 3.83–3.90 (dd, Jgem ¼ 17.4 Hz,
Jtrans ¼ 11.4 Hz, 1H, C4H-pyrazoline), 4.32–4.37 (q, J ¼ 7.1 Hz, 2H,
CH2), 6.08–6.12 (dd, Jcis ¼ 5.0 Hz, Jtrans ¼ 11.4 Hz, 1H, C5H-pyrazo-
line), 6.94–6.96 (m, 1H, C4H-thiophene), 7.13–7.22 (m, 4H,
C3H-thiophene, C5H-thiophene, and Ar), 7.58 (s, 1H, C4H-thiazole),
7.81–7.83 (m, 2H, Ar).
Ethyl 2-(5-(4-fluorophenyl)-3-p-tolyl-4,5-dihydropyrazol-
1-yl)thiazole-4-carboxylate (6)
Mp 169–1708C, 89% yield; 1H NMR (400 MHz, CDCl3) d 1.33–1.37
(t, J ¼ 7.1 Hz, 3H, CH3), 2.42 (s, 3H, CH3–Ar), 3.28–3.33
(dd, Jgem ¼ 17.4 Hz, Jcis ¼ 5.5 Hz, 1H, C4H-pyrazoline), 3.86–
3.93 (dd, Jgem ¼ 17.4 Hz, Jtrans ¼ 11.9 Hz, 1H, C4H-pyrazoline),
4.25–4.35 (q, J ¼ 7.1 Hz, 2H, CH2), 5.72–5.76 (dd, Jcis ¼ 5.5 Hz,
Jtrans ¼ 11.9 Hz, 1H, C5H-pyrazoline), 6.99–7.04 (m, 2H, Ar), 7.24–
7.26 (d, Jo ¼ 7.9 Hz, 2H, Ar), 7.33–7.37 (m, 2H, Ar), 7.51
(s, 1H, C4H-thiazole), 7.75–7.77 (d, Jo ¼ 7.9 Hz, 2H, Ar).
Ethyl 2-(3-(4-chlorophenyl)-5-p-tolyl-4,5-dihydropyrazol-
1-yl)thiazole-4-carboxylate (12)
Mp 116–1178C, 86% yield; 1H NMR (400 MHz, CDCl3) d 1.33–
1.37 (t, J ¼ 7.0 Hz, 3H, CH3), 2.32 (s, 3H, CH3–Ar), 3.27–3.32
(dd, Jgem ¼ 16.1 Hz, Jcis ¼ 4.6 Hz, 1H, C4H-pyrazoline), 3.83–
3.90 (dd, Jgem ¼ 16.1 Hz, Jtrans ¼ 12.2 Hz, 1H, C4H-pyrazoline),
4.28–4.32 (q, J ¼ 7.0 Hz, 2H, CH2), 5.75–5.77 (dd, Jcis ¼ 4.6 Hz,
Jtrans ¼ 12.2 Hz, 1H, C5H-pyrazoline), 7.13–7.15 (d, Jo ¼ 7.7 Hz,
2H, Ar), 7.24–7.26 (d, Jo ¼ 7.7 Hz, 2H, Ar), 7.40–7.42
(d, Jo ¼ 8.3 Hz, 2H, Ar), 7.51 (s, 1H, C4H-thiazole), 7.68–7.70
(d, Jo ¼ 8.3 Hz, 2H, Ar).
Ethyl 2-(5-(2,4-dichlorophenyl)-3-p-tolyl-4,5-
dihydropyrazol-1-yl)thiazole-4-carboxylate (7)
Mp 234–2358C, 80% yield; 1H NMR (400 MHz, CDCl3) d 1.35–
1.36 (t, J ¼ 7.1 Hz, 3H, CH3), 2.41 (s, 3H, CH3–Ar), 3.16–3.22
(dd, Jgem ¼ 17.6 Hz, Jcis ¼ 5.9 Hz, 1H, C4H-pyrazoline), 3.99–
4.04 (dd, Jgem ¼ 17.6 Hz, Jtrans ¼ 11.9 Hz, 1H, C4H-pyrazoline),
4.27–4.33 (q, J ¼ 7.1 Hz, 2H, CH2), 5.99–6.03 (dd, Jcis ¼ 5.9 Hz,
Jtrans ¼ 11.9 Hz, 1H, C5H-pyrazoline), 7.15–7.16 (m, 2H, Ar),
7.23–7.25 (d, Jo ¼ 7.8 Hz, 2H, Ar), 7.45 (m, 1H, Ar), 7.56
(s, 1H, C4H-thiazole), 7.71–7.73 (d, Jo ¼ 7.8 Hz, 2H, Ar).
Ethyl 2-(3-(4-chlorophenyl)-5-(4-fluorophenyl)-4,5-
dihydropyrazol-1-yl)thiazole-4-carboxylate (13)
Mp 231–2338C, 81% yield; 1H NMR (400 MHz, CDCl3) d 1.33–
1.37 (t, J ¼ 6.9 Hz, 3H, CH3), 3.32–3.33 (dd, Jgem ¼ 17.1 Hz,
Jcis ¼ 4.2 Hz, 1H, C4H-pyrazoline), 3.88–3.89 (dd, Jgem ¼ 17.1 Hz,
Jtrans ¼ 10.7 Hz, 1H, C4H-pyrazoline), 4.29–4.32 (q, J ¼ 6.9 Hz, 2H,
CH2), 5.81–5.82 (dd, Jcis ¼ 4.2 Hz, Jtrans ¼ 10.7 Hz, 1H, C5H-pyrazo-
line), 7.03–7.04 (m, 2H, Ar), 7.34–7.35 (m, 2H, Ar), 7.41–7.43 (m, 2H,
Ar), 7.53 (s, 1H, C4H-thiazole), 7.69–7.71 (m, 2H, Ar).
Ethyl 2-(5-(3,4-dichlorophenyl)-3-p-tolyl-4,5-
dihydropyrazol-1-yl)thiazole-4-carboxylate (8)
Mp 166–1678C, 90% yield; 1H NMR (400 MHz, CDCl3) d 1.34–
1.38 (t, J ¼ 7.0 Hz, 3H, CH3), 2.42 (s, 3H, CH3–Ar), 3.26–3.31
(dd, Jgem ¼ 17.4 Hz, Jcis ¼ 5.7 Hz, 1H, C4H-pyrazoline), 3.87–
3.95 (dd, Jgem ¼ 17.4 Hz, Jtrans ¼ 11.8 Hz, 1H, C4H-pyrazoline),
4.28–4.34 (q, J ¼ 7.0 Hz, 2H, CH2), 5.67–5.71 (dd, Jcis ¼ 5.7 Hz,
Jtrans ¼ 11.8 Hz, 1H, C5H-pyrazoline), 7.22–7.25 (m, 3H, Ar),
7.40–7.41 (d, Jo ¼ 7.9 Hz, 1H, Ar), 7.42 (s, 1H, Ar), 7.48 (s, 1H,
C4H-thiazole), 7.58–7.59 (d, Jo ¼ 7.9 Hz, 2H, Ar).
Ethyl 2-(3,5-bis(4-chlorophenyl)-4,5-dihydropyrazol-1-yl)-
thiazole-4-carboxylate (14)
Mp 159–1608C, 80% yield; 1H NMR (400 MHz, CDCl3) d 1.33–
1.37 (t, J ¼ 7.0 Hz, 3H, CH3), 3.25–3.30 (dd, Jgem ¼ 17.7 Hz,
Jcis ¼ 5.6 Hz, 1H, C4H-pyrazoline), 3.86–3.93 (dd, Jgem ¼ 17.7 Hz,
Jtrans ¼ 12.0 Hz, 1H, C4H-pyrazoline), 4.26–4.35 (q, J ¼ 7.0 Hz, 2H,
CH2), 5.74–5.78 (dd, Jcis ¼ 5.6 Hz, Jtrans ¼ 12.0 Hz, 1H, C5H-pyrazo-
line), 7.30–7.32 (m, 4H, Ar), 7.41–7.43 (d, Jo ¼ 8.4 Hz, 2H, Ar), 7.53
(s, 1H, C4H-thiazole), 7.68–7.70 (d, Jo ¼ 8.7 Hz, 2H, Ar).
Ethyl 2-(5-(thiophen-2-yl)-3-p-tolyl-4,5-dihydropyrazol-1-yl)-
thiazole-4-carboxylate (9)
Mp 126–1278C, 89% yield; 1H NMR (400 MHz, CDCl3) d 1.34–1.38
(t, J ¼ 7.0 Hz, 3H, CH3), 2.42 (s, 3H, CH3–Ar), 3.26–3.31
(dd, Jgem ¼ 17.4 Hz, Jcis ¼ 5.7 Hz, 1H, C4H-pyrazoline), 3.87–
3.95 (dd, Jgem ¼ 17.4 Hz, Jtrans ¼ 11.8 Hz, 1H, C4H-pyrazoline),
4.28–4.34 (q, J ¼ 7.0 Hz, 2H, CH2), 5.67–5.71 (dd, Jcis ¼ 5.7 Hz,
Jtrans ¼ 11.8 Hz, 1H, C5H-pyrazoline), 7.22–7.25 (m, 3H, Ar), 7.40–
7.41 (d, Jo ¼ 7.9 Hz, 1H, Ar), 7.42 (s, 1H, Ar), 7.48 (s, 1H,
C4H-thiazole), 7.58–7.59 (d, Jo ¼ 7.9 Hz, 2H, Ar).
Ethyl 2-(3-(furan-2-yl)-5-p-tolyl-4,5-dihydropyrazol-1-yl)-
thiazole-4-carboxylate (15)
Mp 104–1058C, 89% yield; 1H NMR (400 MHz, CDCl3) d 1.21–1.25
(t, J ¼ 7.1 Hz, 3H, CH3), 2.26 (s, 3H, CH3–Ar), 3.13–3.19
(dd, Jgem ¼ 17.6 Hz, Jcis ¼ 5.6 Hz, 1H, C4H-pyrazoline), 3.91–
3.98 (dd, Jgem ¼ 17.6 Hz, Jtrans ¼ 10.1 Hz, 1H, C4H-pyrazoline),
4.30–4.32 (q, J ¼ 7.1 Hz, 2H, CH2), 5.63–5.65 (dd, Jcis ¼ 5.6 Hz,
Jtrans ¼ 10.1 Hz, 1H, C5H-pyrazoline), 6.65–6.67 (m, 1H,
C4H-furan), 6.97–6.98 (m, 1H, C3H-furan), 7.21 (m, 1H, C5H-furan),
7.74 (s, 1H, C4H-thiazole), 7.88–7.89 (m, 2H, Ar), 7.90–7.91
(m, 2H, Ar).
Ethyl 2-(3-(4-fluorophenyl)-5-p-tolyl-4,5-dihydropyrazol-1-yl)-
thiazole-4-carboxylate (10)
Mp 162–1638C, 85% yield; 1H NMR (400 MHz, CDCl3) d 1.33–1.37
(t, J ¼ 7.2 Hz, 3H, CH3), 2.33 (s, 3H, CH3–Ar), 3.29–3.34
(dd, Jgem ¼ 16.2 Hz, Jcis ¼ 4.5 Hz, 1H, C4H-pyrazoline), 3.84–
3.89 (dd, Jgem ¼ 16.2 Hz, Jtrans ¼ 10.3 Hz, 1H, C4H-pyrazoline),
4.27–4.35 (q, J ¼ 7.2 Hz, 2H, CH2), 5.67–5.69 (dd, Jcis ¼ 4.5 Hz,
Jtrans ¼ 10.3 Hz, 1H, C5H-pyrazoline), 7.11–7.16 (m, 4H, Ar), 7.25
(s, 2H, Ar), 7.50 (s, 1H, C4H-thiazole), 7.74–7.78 (m, 2H, Ar).
Ethyl 2-(5-(4-fluorophenyl)-3-(furan-2-yl)-4,5-
dihydropyrazol-1-yl)thiazole-4-carboxylate (16)
Mp 167–1688C, 84% yield; 1H NMR (400 MHz, CDCl3) d 1.33–
1.36 (t, J ¼ 7.1 Hz, 3H, CH3), 3.24–3.29 (dd, Jgem ¼ 17.5 Hz,
Jcis ¼ 5.6 Hz, 1H, C4H-pyrazoline), 3.83–3.90 (dd, Jgem ¼ 17.5 Hz,
Jtrans ¼ 12.0 Hz, 1H, C4H-pyrazoline), 4.28–4.32 (q, J ¼ 7.1 Hz, 2H,
CH2), 5.72–5.76 (dd, Jcis ¼ 5.6 Hz, Jtrans ¼ 12.0 Hz, 1H, C5H-pyrazo-
line), 6.53–6.55 (m, 1H, C4H-furan), 6.77 (s, 1H, C3H-furan), 7.00–
Ethyl 2-(3-(4-fluorophenyl)-5-(thiophen-2-yl)-4,5-
dihydropyrazol-1-yl)thiazole-4-carboxylate (11)
Mp 162–1638C, 83% yield; 1H NMR (400 MHz, CDCl3) d 1.36–
1.40 (t, J ¼ 7.1 Hz, 3H, CH3), 3.47–3.53 (dd, Jgem ¼ 17.4 Hz,
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