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Sci. Pharm. 2013, 81(2), 393-422; doi:10.3797/scipharm.1211-21

Synthesis, Anti-Inflammatory, and Ulcerogenicity Studies of Novel Substituted and Fused Pyrazolo[3,4-d]pyrimidin-4-ones

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt
Received: 25 November 2013 / Accepted: 7 January 2013 / Published: 7 January 2013
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Abstract

In the present investigation, some new pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives (7–12) as well as fused pyrazolo[3',4':4,5]pyrimido[1,2-b]pyridazin-4(1H)-one (14–16) and 7,8,9,10-tetrahydropyrazolo[3',4':4,5]pyrimido[1,2-b]-cinnolin-4(1H)-one (17) ring systems were synthesized using the starting compound 5-amino-6-methyl-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (5). The structures of the newly synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis. The theoretical calculation of their lipophilicity as C log P was performed. The anti-inflammatory activity of all newly synthesized compounds was evaluated using the carrageenan-induced paw edema test in rats using indomethacin as the reference drug. Ulcer indices for the most active compounds were calculated. Seven compounds (10b, 11a–f) showed consistently good anti-inflammatory activity. In particular, 5-{[4-(4-bromophenyl)-3-(4-chlorophenyl)-1,3-thiazol-2(3H)-ylidene]amino}-6-methyl-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimi-din-4-one (11e) and its 3,4-bis(4-chlorophenyl) analog (11f) were found to be the most effective among the other derivatives, showing activity comparable to that of indomethacin with minimal ulcerogenic effects. Correlation of the biological data of the active compounds with their theoretically calculated C log P values revealed that lipophilicity influences the biological response.
Keywords: Pyrazolo[3,4-d]pyrimidin-4-ones; Pyrazolo[3',4':4,5]pyrimido[1,2-b]pyridazin-4-ones; 7,8,9,10-Tetrahydropyrazolo[3',4':4,5]pyrimido[1,2-b]cinnolin-4-one; C log P; Synthesis; Anti-inflammatory activity; Ulcerogenicity Pyrazolo[3,4-d]pyrimidin-4-ones; Pyrazolo[3',4':4,5]pyrimido[1,2-b]pyridazin-4-ones; 7,8,9,10-Tetrahydropyrazolo[3',4':4,5]pyrimido[1,2-b]cinnolin-4-one; C log P; Synthesis; Anti-inflammatory activity; Ulcerogenicity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

EL-TOMBARY, A.A. Synthesis, Anti-Inflammatory, and Ulcerogenicity Studies of Novel Substituted and Fused Pyrazolo[3,4-d]pyrimidin-4-ones. Sci. Pharm. 2013, 81, 393-422.

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