Synthesis and Structure‐Activity Relationship Studies of Pyrazole‐based Heterocycles as Antitumor Agents |
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| Authors: | Ahmad M Farag Abdelrahman S Mayhoub Taha M A Eldebss Abdel‐Galil E Amr Korany A K Ali Naglaa A Abdel‐Hafez Mohamed M Abdulla |
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| Institution: | 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al‐Azhar University, Cairo, Egypt;2. Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt. Fax: +20 235 727‐556;3. Department of Applied Chemistry, National Research Center, Dokki, Giza, Egypt;4. Research Units, Hi‐Care Pharmaceutical Co., Cairo, Egypt |
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| Abstract: | Several 4‐cyano‐1,5‐diphenylpyrazoles attached to different heterocyclic ring systems at position 3 were synthesized starting from ethyl 4‐cyano‐1,5‐diphenyl‐1H‐pyrazole‐3‐carboxylate 1 . The newly synthesized compounds were tested in vivo for their anti‐estrogenic effects and evaluated in vitro for their cytotoxic properties against estrogen‐dependent tumors. 3‐(5‐Mercapto‐1,3,4‐oxadiazole‐2‐yl)‐1,5‐diphenyl‐1H‐pyrazole‐4‐carbonitrile 13 revealed the highest cytotoxic activity with a GI50 value equal to 40 nM against the IGROVI ovarian tumor cell line. It also showed an anti‐estrogen activity 1.6 more effective than the reference drug, in addition to a high tolerable dose. 3‐(5‐(Methylthio)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1,5‐diphenyl‐1H‐pyrazole‐4‐carbonitrile 7 was found to have the highest anti‐estrogenic activity, while 1,5‐diphenyl‐3‐5‐(phenylamino)‐1,3,4‐thiadiazol‐2‐yl]‐1H‐pyrazole‐4‐carbonitrile 11 showed the lowest activity. The oral LD50 values revealed that most of the tested compounds are relatively nontoxic. |
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| Keywords: | Anti‐estrogenic activity 1 5‐Diphenylpyrazoles 1 3 4‐Oxadiazoles 1 3 4‐Thiadiazole 1 2 4‐Triazoles |
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