Synthesis and potential biological activity of some novel 3-[(N ...

A. H. Mandour et al.: Synthesis and potential biological activity of some novel 3-[(N-substituted indol-3-yl)methyleneamino]-6-amino-4aryl-pyrano(2,3-c)pyrazole-5-carbonitriles
and 3,6-diamino-4-(N-substituted indol-3-yl)pyrano(2,3-c)pyrazole-5-carbonitriles, Acta Pharm.
62 (2012) 15–30.
3,6-Diamino-4-(N-substituted-indol-3-yl)pyrano(2,3-c)pyrazole-5-carbonitriles (7a-g). Method
A. – A mixture of 3-amino-5-pyrazolone (0.99 g, 0.01 mol) and the appropriate N-substituted-3-indolylidene
malononitrile 5a-g (0.01 mol) in absolute ethanol (20 mL) containing
triethylamine (0.5 mL) was refluxed for 1–4 h. The formed precipitate was filtered off
after cooling, air dried and recrystallized from dioxane. Method B. – To a solution of malononitrile
(0.66 g, 0.01 mol) in absolute ethanol (10 mL) and triethylamine (0.5 mL), the
appropriate compound 6a-g (0.01 mol) was added. The reaction mixture was refluxed
for 3–4 h, and the solid that formed after cooling was filtered off, air dried and recrystallized
from dioxane.
Biological assays
Animals. – Adult male albino rats (Harlan Sprague-Dawley), weighing 150–180 g,
were used for the evaluation of anti-inflammatory activity. Animals were fasted for 12
hours before the assay. Adult Swiss Webster mice of both sexes (Harlan Sprague-Dawley),
weighing 20–25 g, were fasted for 12–24 hours and used for the assessment of analgesic
and anticonvulsant activities. All animals were obtained from the animal house
colony of the National Research Centre, Cairo, Egypt. Animals were allowed free access
to water and were fed a standard diet. Research was conducted in accordance with the
ethical rules on animal experimentation, approved by the Ethics Committee of the National
Research Centre, Cairo, Egypt.
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7a 3243 (NH2 ), 3164 (NH),
2211 (CN), 1640 (C=N), 1617
(C=C), 1044 (C-O-C)
7b 3321, 3184 (NH2 ), 2205 (CN),
1664 (C=N), 1602 (C=C),
1197(C-O-C)
7c 3429, 3317 (NH2 ), 2206 (CN),
1735 (C=O), 1629 (C=N),
1582 (C=C), 1106 (C-O-C)
7d 3426, 3316 (NH2 ), 2203 (CN),
1626 (C=O), 1585 (C=N),
1508 (C=C), 1106 (C-O-C),
755 (Cl)
7e 3429, 3316 (NH2 ), 2204 (CN),
1628 (C=O), 1683 (C=N),
1552 (C=C), 1106 (C-O-C),
755 (Cl)
7f 3324 (NH2, br), 2212 (CN),
1620 (C=N), 1573 (C=C),
1368, 1130 (SO2 ), 1106
(C-O-C)
7g 3324 (NH2, br), 2212 (CN),
1618 (C=N), 1522 (C= C),
1376, 1176 (SO2 ), 1128
(C-O-C), 748 (Br)
9.0 (s, 1H, NH indole), 8.1 (s, 1H,
H-2 indole), 7.5–7.9 (m, 4H, Ar-H),
6.9 (s, 2H, NH 2 ), 3.8 (s, 2H, NH 2 )
11.88 (s, 2H, NH 2 ), 8.34 (s, 1H,
H-2 indole), 7.84 (s, 2H, NH 2 ),
7.1–7.5 (m, 9H, Ar-H)
11.9, 5.9 (2s, 4H, 2NH 2 ), 8.25
(s, 1H, H-2 indole), 7.1– 8.1
(m, 9H, Ar-H)
9.9, 5.7 (2s, 4H, 2NH 2 ), 8.3
(s, 1H, H-2 indole), 7.2–7.9
(m, 8H, Ar-H)
290 (M + , 2), 159
(10), 143 (50), 142
(100), 117 (76)
318 (M + , 7), 159
(100), 157 (20), 117
(14), 91 (32)
428 (M + , 100), 430
(M + +2, 30) 193
(40), 117 (50), 91
(40)
508 (M + , 37), 510
(M + +2, 36) 348
(100), 219 (53),
155 (47), 77 (77)