Arch. Pharm. Chem. Life Sci. 2005, 338, 329−334
Bio-active Pyridine and Pyrido[3,2-c]pyridazine Derivatives
333
fluxed for 2 h in each case, left to cool to room temperature, poured
on crushed ice, and neutralized with HCl. The precipitated solid
products that appeared were filtered off, washed, dried, and recrys-
tallized from dioxan to afford the title compounds:
(s, 3H, CH3), 6.3 (s, 2H), 7.1Ϫ8.0 (m, 12H, ar. H and NH2), 9.4
(s, 1H).
9d Crimson red solid (yield 3.7 g, 8.58 mmol) mp 237°C;
C22H17N5O5; νmax (KBr) 3385Ϫ3185 (br. NH2 and OH), 1653,
1660, and 1685 (3 CO); δH (300 MHz, DMSO-d6) 3.85 (s, 3H, CH3),
6.45 (s, 2H), 7.28Ϫ8.05 (m, 11H, ar. H and NH2), 9.55 (s, 1H).
8a Dark red powder (yield 3.3 g, 8.64 mmol) mp 245°C;
C21H14N6O2 (m/e ϭ 382); νmax (KBr) 3450Ϫ3200 (br. NH2, NH,
OH), 2210 (CN), 1655 (CO); δH (300 MHz, DMSO-d6) 7.1Ϫ8.0 (m,
12H, ar. H and NH2), 8.25 (s, 1H, NH), 9.5 (s, 1H, OH).
12 Brick red powder (yield 3.7 g, 8.69 mmol) mp >340°C;
C22H14N6O4 (m/e ϭ 426); νmax (KBr) 3390Ϫ3210 (br. NH2 and
OH), 1655, 1669, and 1684 (3 CO); δH (300 MHz, DMSO-d6) 6.42
(s, 2H), 7.1Ϫ8.1 (m, 11H, ar. H and NH2), 9.45 (s, 1H).
8b Reddish green powder (yield 3.4 g, 8.19 mmol) mp 263°C;
C
21H13ClN6O2 (m/e ϭ 415, 417); νmax (KBr) 3430Ϫ3150 (br. NH2,
NH, OH), 2215 (CN), 1653 (CO); δH (300 MHz, DMSO-d6)
7.15Ϫ8.0 (m, 11H, ar. H and NH2), 8.27 (s, 1H, NH), 9.45 (s,1H,
OH).
Biology
Molluscicidal activity tests
8c Dark red powder (yield 3.1 g, 7.8 mmol) mp >350°C;
C22H16N6O2 (m/e ϭ 396); νmax (KBr) 3390Ϫ3100 (br. NH2, NH,
OH), 2208 (CN), 1655 (CO); δH (300 MHz, DMSO-d6) 2.45
(s,3H,CH3), 7.1Ϫ7.9 (m, 11H, ar. H and NH2), 8.20 (s, 1H, NH),
9.4 (s, 1H, OH).
The molluscicidal activity tests were carried out by determination
of the full lethal dose LC100 of each compound under investigation.
Biomphalaria alexandrina snails were collected from the field (water
canals) and maintained under laboratory conditions for a period of
30 days before use and fed daily by lettuce leaves. The snails were
then examined to ensure that they were free of parasitic infection.
A series of concentrations (seven) ranging from 2 ppm to 15 ppm
of each compound under investigation was prepared. The required
weight of the compound under investigation was mixed thoroughly
with a few drops of Tween 20 and 2 mL of DMSO to render the
compounds completely soluble, followed by addition of the appro-
priate volume of nontreated raw water (taken directly from the
River Nile or its branches/canals) to get a homogeneous suspension
(turbid) with the requisite concentration and placed in glass jar ves-
sels 15 ϫ 25 ϫ 20 cm dimensions fitted with air bubblers. Ten snails
having the same size and diameter (ca. 7 mm) were used in each
experiment and maintained in the test solution under laboratory
conditions at ambient temperature for 24 h. Each experiment was
repeated three times and the mean number of killed snails was taken
for each concentration as shown in Table 1. A control group was
taken by placing 10 snails in water containing few drops of Tween
20 and 2 mL of DMSO. These bioassays are in accordance with the
W.H.O. guidelines [27] .
8d Crimson red crystalline solid (yield 3.3 g, 8.0 mmol) mp 216°C;
C22H16N6O3 (m/e ϭ 412); νmax (KBr) 3420Ϫ3140 (br. NH2, NH,
OH), 2215 (CN), 1660 (CO); δH (300 MHz, DMSO-d6) 3.75 (s, 3H,
CH3), 7.2Ϫ8.05 (m, 11H, ar. H and NH2), 8.32 (s, 1H, NH), 9.55
(s, 1H, OH).
10 Dark brown solid (yield 3.5 g, 8.6 mmol) mp 210°C;
C22H13N7O2 (m/e ϭ 407); νmax (KBr) 3370Ϫ3205 (br. NH2, NH,
OH), 2215 (CN), 1655 (CO); δH (300 MHz, DMSO-d6) 7.25Ϫ7.90
(m, 11H, ar. H and NH2), 8.35 (s, 1H, NH), 9.4 (s, 1H, OH).
11 Dark reddish brown solid (yield 3.5 g, 8.58 mmol) mp 280°C;
C22H12N6O3 (m/e ϭ 408); νmax (KBr) 3450Ϫ3200 (br. NH2 and
OH), 2218 (CN), 1680 and 1655 (2 CO); δH (300 MHz, DMSO-d6)
6.70Ϫ7.85 (m, 11H, ar. H and NH2), 9.45(s, 1H, OH). 13C NMR δ
94 (s), 104.3 (s), 114.3 (s), 115.7 (d), 119.0 (d), 123.5 (s), 129.2 (d),
129.8 (d), 130.5 (d), 134.6 (d), 135.0 (d), 137.1 (s), 148.0 (s), 155.8
(s), 160.2 (s), 161.0 (s), 162.5 (s), 187.1 (s), 189.0 (s).
8-Amino-2-aryl-7-benzoyl-4-carboxamido-6-hydroxypyrido[3,2-c]-
pyridazin-3-ones 9aϪd, and 4-amino-3-benzoyl-12-carboxamido-2-
hydroxy[3,2-c]pyridazino[2Ј,3Ј-a]quinazolin-10-one 12; General pro-
cedure
References
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(Weinheim) 1992, 325, 301Ϫ305.
To a solution of each of 8aϪd, 10 or 11 (10 mmol) in 25 mL acetic
acid 2 mL of conc. H2SO4 and 2 mL of water were added and the
mixture was refluxed for 1 h. After being cooled to room tempera-
ture, it was poured on crushed ice, and neutralized cautiously with
ammonia solution. The solid precipitates were collected by fil-
tration, washed with water, and recrystallized from acetic acid to
afford the title compounds:
[3] F. M. Abdelrazek, A. M. Salah El-Din, A. E. Mekky, Tetra-
hedron 2001, 57, 6787Ϫ6791; and references therein.
[4] F. M. Abdelrazek, N. H. Metwally, Afinidad 2004, 61,
134Ϫ138.
[5] M. Rizk, I. M. Faddah, A. El-Ansary; Egypt. J. Pharm. Sci.,
1994, 35, 477Ϫ478.
9a Red crystalline solid (yield 3.2 g, 7.98 mmol) mp 285°C;
C21H15N5O4 (m/e ϭ 401); νmax (KBr) 3395Ϫ3200 (br., NH2 and
[6] N. I. El-Mamlouk, A. El-Ansary, S. A. Ahmed, H. Zaki,
Egypt. J. Bilh., 1996, 17, 62Ϫ65.
[7] A. Z. Abdelhamid, J. Biol. Med. Sci. Ther. 1991, 7, 136Ϫ139.
OH), 1650, 1665, and1680 (3CO); δH (300 MHz, DMSO-d6) 6.4 (s,
2H), 7.1Ϫ8.0 (m, 12H, ar. H and NH2), 9.5 (s, 1H). 13C NMR δ
109 (s), 121.5 (d), 124.3 (d), 128.7 (d), 129.1 (d), 129.8 (d), 130.1 (s),
134.3 (d), 136.9 (s), 138.5 (s), 155.5 (s), 156.5 (s), 161.0 (s), 164.5
(s), 166 (s), 168.7 (s), 187.5 (s).
[8] F. M. Abdelrazek, G. A. M. Nawwar, Egypt. J. Chem. 1991,
34, 559Ϫ564.
[9] G. A. M. Nawwar, F. M. Abdelrazek, R. H. Swellam, Arch.
Pharm. (Weinheim) 1991, 324, 875Ϫ877.
9b Reddish powder (yield 3.6 g, 8.27 mmol) mp 276°C;
C21H14ClN5O4; νmax (KBr) 3400Ϫ3200 (br. NH2 and OH), 1655,
1663, and 1670 (3 CO); δH (300 MHz, DMSO-d6) 6.42 (s, 2H),
7.15Ϫ7.85 (m, 11H, ar. H and NH2), 9.35 (s, 1H).
[10] F. M. Abdelrazek, P. Metz, E. K. Farrag, Arch. Pharm. Pharm.
Med. Chem. 2004, 337, 482Ϫ485.
[11] E. Mizuta, K. Nishikawa, K. Omura, Y. Oka, Chem. Pharm.
Bull. 1976, 24, 2078Ϫ85.
9c Reddish brown powder (yield 3.4 g, 8.19 mmol) mp 291°C;
C22H17N5O4 (m/e ϭ 415); νmax (KBr) 3425Ϫ3210 (br. NH2 and
OH), 1655, 1660, and 1675 (3 CO); δH (300 MHz, DMSO-d6) 2.55
[12] L. Kuczynski, M. Leonard, A. Aleksander, W. Banaszkiewicz,
S. Responds, Pol. J. Pharmacol. Pharm. 1983, 34, 223Ϫ228.
© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim