Novel Antitumor Acetamide, Pyrrole, Pyrrolopyrimidine, Thiocyanate, Hydrazone, Pyrazole, Isothiocyanate and Thiophene Derivatives Containing a Biologically Active Pyrazole Moiety

Abstract

4-Amino-N-(1-phenyl-1H-pyrazol-5-yl)-benzenesulfonamide (sulfaphenazole) 1 was selected as strategic starting material for the synthesis of some novel acetamide 2, pyrrole 4, pyrrolo[2,3-d]pyrimidine 5, thiocyanate 6, hydrazone 7a,b pyrazole 8, isothiocyanate 9 and thiophene 12 derivatives to evaluate the antitumor activity. Compound 4 was more effective than the reference drug, doxorubicin (CAS 23214-92-8) as positive control.

Key words

Acetamide, hydrazone, pyrazole derivatives, pyrrole, pyrrolopyrimidine, thiocyanate - Antitumor activity

• References

• 1 Elguero J. Comprehensive Hetero-cyclic Chemistry. Vol. 5 Katrizky AR, Rees CW, Scriven EFV. editors Oxford: Perga-mon Press; 1996
• 2 Ghorab MM. Synthesis and radiation stability of some new biologically active pyrazolo[3,4-d]pyrimidines. Acta Pharm. 2000; 50: 93-110
• 3 Ghorab MM, Zeinab HI, Soad MA, Anhar AA. Antimicrobial activity of some amino acid, imidazole and sulfonamide derivatives of pyrazolo[3,4-d]Apyrimidine. Heteroatom Chem. 2004; 15 (1) 57-62
• 4 Penning TD, Talley JJ, Bertenshaw SR, Carter JS, Collins PW, Docter S et al. Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-58635, celecoxib). J Med Chem. 1997; 40: 1347-65
• 5 Abou El Ella DA, Ghorab MM, Noaman E Heiba HI, Khalil Al. Molecular modeling study and synthesis of novel pyrrolo[2,3-d]pyrimidines and pyrrolotriazolopyrimidines of expected antitumor and radioprotective activities. Bioorg Med Chem. 2008; 16 (5) 2391-402
• 6 Ghorab MM, Abou El Ella DA, Noaman E, Heiba HI, Khalil Al. Computer-based ligand design and synthesis of some new sulfonamides bearing pyrrole or pyrrolopyrimidine moieties having potential antitumor and radioprotective activities. Phosphorus Sulfur Silicon. 2008; 183 (1) 90-104
• 7 Ghorab MM, Noaman E, Ismail MMF, Heiba HI, Ammar YA. Sayed, MY. Novel antitumor and radioprotective sulfonamides containing pyrrolo[2,3-d]pyrimidines. Arzneimittelforschung. 2006; 56 (6) 405-13
• 8 Ismail MMF, Ghorab MM, Noaman E, Ammar YA, Heiba HI, Sayed MY. Novel synthesis of pyrrolo[2,3-d]pyrimidines bearing sulfonamide moieties as potential antitumor and radioprotective agents. Arzneimittelforschung. 2006; 56 (4) 301-308
• 9 El-Gaby MSA, Abdel-Hamide SG, Ghorab MM, El-Sayed SM. Synthesis and in-vitro anticancer activity of some new pyrimidines. Acta Pharm. 1999; 49: 149-58
• 10 Tsutomu T, Toshiaki K, Hitoshi S, Yoshinori T, Katsutashi I. Ethyl-3-methyl-1-(2,4-dinitrophenyl)-1H-pyrazole-4-carboxylate. Jpn Kokoi Tokyo Koho JP 01 106 866. Chem Abstr. 1989; 111: 194759h
• 11 Ismail MMF, Ghorab MM, Mohamed EMA, Ali HM, El-Gaby MSA. Antitumor activity of some novel 1,2,5-thiadiazole derivatives. Phosphorus Sulfur Silicon. 2008; 183 (1) 1-14
• 12 Ghorab MM, Ragab FA, Noaman E, Heiba HI, El-Hossary EM. Synthesis of some novel quinolines and pyrimido[4,5-b]quinolines, bearing sulfonamide moiety as potential anticancer and radioprotective agents. Arzneimittelforschung. 2007; 57 (12) 795-803
• 13 Abdel-Hamid AO, Ismail ZH, El-Gendy MS, Ghorab MM. Reactions with hydrazonoyl halides 53: Synthesis and antimicrobial activity of triazolino[3,4-a]pyrimidines and 5-arylazo-thiazoles. Phosphorus Sulfur Silicon. 2004; 182: 2409-18
• 14 Ghorab MM, Barakat SE, Saker HM, Abd Rabo MM. Synthesis and antitumor activity of some novel quinazoline derivatives. Arzneimittelforschung. 2006; 56 (9) 665-70
• 15 Ghorab MM, Ragab FA, Noaman E, Heiba HI, Galal M. Synthesis of certain new thieno[2,3-d]pyrimidines as potential antitumor and radioprotective agents. Arzneimittelforschung. 2006; 56 (7) 553-60
• 16 El-Merzabani MM, El-Aaser AA, El-Dueini AK, El Masry AM. A bioassay of antimitotic alkaloids of Catharanthus roseus. Planta Med. 1979; 36: 87-90
• 17 Raffa D, Daidone G, Maggio B, Cascioferro S, Plescia S, Schillaci D. Synthesis and antileukemic activity of new 3-(1-phenyl)-3-methylpyrazol-5-yl)-2-styrylquinazolin-4(3H)-ones. Farmaco. 2004; 59: 215-21
• 18 Takemoto DJ, Dunford C, McMurray MM. The cytotoxic and cytostatic effects of the bitter melon (Momardica charantia) on human lymphocytes. Toxicon. 1982; 20: 593-599
• 19 El-Merzabani MM, El-Aaser AA, Attia MA, El-Duweini AK, Ghazal AM. Screening system for Egyptian plants with potential anti-tumor activity. Planta Med. 1979; 36: 150-5
• 20 Mizuno Y, Ikehara MJ, Watanabe KA, Suzaki S, Itoh TJ. Synthetic studies of potential antimetabolites. IX. The anomeric configuration of Tubercidin. Org Chem. 1963; 28: 3329-3331