Skip to main content

Advertisement

SpringerLink
Log in

Design and synthesis of some thieno[2,3-c]pyridazine derivatives of expected anticancer activity

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

Design and synthesis of some new thienopyridazine derivatives as anticancer agents were the goal of this work. Accordingly, a series of novel compounds were synthesized via reacting thienopyridazine carboxylic acid hydrazide with different organic reagents. Twelve novel compounds were selected by National Cancer Institute for a full anticancer screening assay where seven of the investigated compounds showed non-selective broad spectrum and promising activity almost against all cancer cell lines. One of the most active compounds was chosen to be evaluated against 60-cell line panel at five concentration levels and revealed a remarkable growth inhibition activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Scheme 2
Scheme 3

Similar content being viewed by others

References

  • Abadi AH, Eissa AA, Hassan GS (2003) Synthesis of novel 1,3,4-trisubstituted pyrazole derivatives and their evaluation as antitumor and antiangiogenic agents. Chem Pharm Bull 51:838–844

    Article  PubMed  CAS  Google Scholar 

  • Abbate F, Casini A, Owa T, Scozzafava A, Supura CT (2004) Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX. J Bioorg Med Chem Lett 14:217–223

    Article  CAS  Google Scholar 

  • Abdel-Hamid MK, Abdel-Hafez AA, El-Koussi NA, Mahfouz NA, Innocenti A, Supuran CT (2007) Design, synthesis, and docking studies of new 1,3,4-thiadiazole-2-thione derivatives with carbonic anhydrase inhibitory activity. Bioorg Med Chem 15:6975–6984

    Article  PubMed  CAS  Google Scholar 

  • Aboraia AS, Abdel-Rahman HM, Mahfouz NM, EL-Gendy MA (2006) Novel 5-(2-hydroxyphenyl)-3-substituted-2,3-dihydro-1,3,4-oxadiazole-2-thione derivatives: promising anticancer agents. Bioorg Med Chem 14:1236–1246

    Article  PubMed  CAS  Google Scholar 

  • Akbas E, Beber I (2005) Antibacterial and antifungal activities of new pyrazolo[3,4-d]pyridazine derivatives. Eur J Med Chem 40:401–405

    Article  PubMed  CAS  Google Scholar 

  • Bakhite EA, Mohamed OS, Radwan SM (2002) Synthesis and some reactions of new thieno[2,3-c]pyridazine derivatives. Bull Korean Chem Soc 23:1715–1718

    Article  CAS  Google Scholar 

  • Billman HJ, Schmidgall RL (1970) Preparation and antitumor activity of some Schiff bases of 2-amino-4,5-dichlorobenzenesulfonanilid and 2-amino-p-toluenesulfonanilide. J Pharm Sci 59:1191–1194

    Article  PubMed  CAS  Google Scholar 

  • Brana MF, Cacho M, Garcia LM, Mayoral EP, Lopez B, Pascual BDP, Ramos A, Acero N, Llinares F, Munoz D, Lozach O, Meije l (2005) Pyrazolo[3,4-c]pyridazines as novel and selective inhibitors of cyclin-dependent kinases. J Med Chem 48:6843–6854

    Article  PubMed  CAS  Google Scholar 

  • Byth KF, Cooper N, Culshaw JD, Heaton DW, Oakes SEJ, Minshull CA, Norman RA, Pauptil RA, Tucker JA, Breed J, Pannifer A, Rowsell S, Stanway JJ, Valentino APTh (2004) Imidazo[1,2-b]pyridazines: a potent and selective class of cyclin-dependent kinase inhibitors. Bioorg Med Chem Lett 14:2249–2252

    Article  PubMed  CAS  Google Scholar 

  • Combs DW, Rampulla MS, Demers JP, Falotico R, Moore BJ (1992) Heteroatom analogs of bemoradan: chemistry and cardiotonic activity of 1,4-benzothiazinylpyridazinones. J Med Chem 35:172–176

    Article  PubMed  CAS  Google Scholar 

  • Curran WV, Ross A (1974) 6-Phenyl-4,5-dihydro-3(2H)-pyridazinones. Series of hypotensive agents. J Med Chem 17:273–281

    Article  PubMed  CAS  Google Scholar 

  • Deeb A, El-Mariah F, Hosny M (2004) Pyridazine derivatives and related compounds. Part 13: synthesis and antimicrobial activity of some pyridazino[3′,4′:3,4]pyrazolo[5,1-c]-1,2,4-triazine. Bioorg Med Chem Lett 14:5013–5017

    Article  PubMed  CAS  Google Scholar 

  • Dilovic I, Rubcic M, Vrdoljak V, Pavelic SK, Kralj M, Piantanida MC (2008) Novel thiosemicarbazone derivatives as potential antitumor agents: synthesis, physicochemical and structural properties, DNA interactions and antiproliferative activity. Bioorg Med Chem 16:5189–5198

    Article  PubMed  CAS  Google Scholar 

  • Elzbieta W, Prukaia D (1998) New isomeric N-substituted hydrazones of 2-, 3-, and 4-pyridinecarboxyaldehydes. J Heterocycl Chem 35:381–387

    Article  Google Scholar 

  • Esteves-Souza A, Pissinate K, Nascimento MDG, Greenberg NF, Echevarria A (1998) Synthesis, cytotoxicity, and DNA-topoisomerase inhibitory activity of new asymmetric ureas and thioureas. Bioorg Med Chem 14:492–499

    Article  Google Scholar 

  • French FA, Blanz EJ, Doamaral JR, French DA (1970) Carcinostatic activity of thiosemicarbazones of formyl heteroaromatic compounds.VI. 1-Formylisoquinoline derivatives bearing additional ring substituent, with notes on mechanism of action. J Med Chem 13:1117–1124

    Article  PubMed  CAS  Google Scholar 

  • Gerard P, Giovanni P, Paolo D (1986) Conformational behavior and E/Z isomerization of N-acyl and N-aroylhydrazones. Tetrahedron 42:3649–3654

    Article  Google Scholar 

  • Hassall CH, Johnson WH, Theobald CJ (1979) Amino acids and peptides. Part 21. Synthesis of a congener of the cyclohexadepsipeptide antibiotic, monamycin. J Chem Soc Perkin 1:1451–1454

    Article  Google Scholar 

  • Kamal El-Dean AM, Radwan SM, Abdel Moneam MI (1996) Synthesis and reactivity of some pyridazine derivatives. Afinidid 53:387–391

    CAS  Google Scholar 

  • Kandile NG, Mohamed MI, Zaky H, Mohamed HM (2009) Novel pyridazine derivatives: synthesis and antimicrobial activity evaluation. Eur J Med Chem 44:1989–1996

    Article  PubMed  CAS  Google Scholar 

  • Khalil AA, Abdel Hamide SG, Al-Obaid AM, El-Subbagh HI (2003) Substituted quinazolines, part 2. Synthesis and in vitro anticancer evaluation of new 2-substituted mercapto-3H-quinazoline analogs. Arch Pharm Med Chem 2:95–103

    Article  Google Scholar 

  • Lewis RT, Blackaby WB, Blackburn T, Jennings ASR, Pike A, Wilson RA, Hallett DJ, Cook SM, Ferris P, Marshall GR, Reynolds DS, Sheppard WFA, Smith AJ, Stanley BSJ, Tye SJ, Wafford KA, Atack JR (2006) A pyridazine series of alpha2/alpha3 subtype selective GABAA agonists for the treatment of anxiety. J Med Chem 49:2600–2610

    Article  PubMed  CAS  Google Scholar 

  • Loetchutinat C, Chau F, Mankhetkorn S (2003) Synthesis and evaluation of 5-aryl-3-(4-hydroxyphenyl)-1,3,4-oxadiazole-2-(3H)-thiones as p-glycoprotein inhibitors. Chem Pharm Bull 51:728–730

    Article  PubMed  CAS  Google Scholar 

  • Malinka W, Redzicka OA (2004) New derivatives of pyrrolo[3,4-d]pyridazinone and their anticancer effects. IL Farmaco 59:457–462

    Article  PubMed  CAS  Google Scholar 

  • McClusky A, Bowyer MC, Collins E, Sim ATR, Sakoff JA, Baldwin ML (2000) Anhydride modified cantharidin analogues: synthesis, inhibition of protein phosphatases 1 and 2A and anticancer activity. Bioorg Med Chem Lett 10:1687–1690

    Article  Google Scholar 

  • McEvoy FG, Allen GR (1974) 6-(Substituted phenyl)-5-substituted-4,5-dihydro-3(2H)-pyridazinones antihypertensive agents. J Med Chem 17:281–286

    Article  PubMed  CAS  Google Scholar 

  • Mertens A, Friebe GW, Beckmann BM, Kampe W, Kling L, Saal WVD (1990) Nonsteroidal cardiotonics. 3. New 4,5-dihydro-6-(1H-indol-5-yl)pyridazin-3(2H)-ones and related compounds with positive inotropic activities. J Med Chem 33:2870–2875

    Article  PubMed  CAS  Google Scholar 

  • Modi JDS, Sabins S, Deliwala CV (1970) Schiff bases from benzaldehyde nitrogen mustards and aminophenyl-thiazoles. J Med Chem 13:935–941

    Article  PubMed  CAS  Google Scholar 

  • Monk A, Scudiero DA, Skehan P, Shoemaker RH, Paull KD et al (1991) DTP, DCTD tumor repository a catalog of in vitro cell lines, transplantable animal and human tumors and micro assays. J Natl Cancer Inst 83:757–766

    Article  Google Scholar 

  • Moreau S, Coudert P, Rubat C, Gardette D, Vallee-Goyet D, Couquelet J, Bastide P, Tronche P (1994) Synthesis and anticonvulsant properties of new benzylpyridazine derivatives. J Med Chem 37:2153–2160

    Article  PubMed  CAS  Google Scholar 

  • Mylari BL, Armento SJ, Beebe DA, Conn EL, Coutcher J, Dina BMS, Gorman TTO, Linhares MC, Martin WH, Oates PJ, Tess DA, Withbro GJ, Zembrowski WJ (2005) A novel series of non-carboxylic acid, non-hydantoin inhibitors of aldose reductase with potent oral activity in diabetic rat models 6-(5-chloro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one and congeners. J Med Chem 48:6326–6339

    Article  PubMed  CAS  Google Scholar 

  • Nagawade RR, Khanna VV, Bhagwat SS, Shinde DV (2005) Synthesis of new series of 1-aryl-1,4-dihydro-4-oxo-6-methyl pyridazine-3-carboxylic acid as potential antibacterial agents. Eur J Med Chem 40:1325–1330

    Article  PubMed  CAS  Google Scholar 

  • Owa T, Yoshino H, Okauchi T, Yoshimatsu K, Ozawa Y, HataSugi N, Nagasu T, Koyanagi N, Kitoh K (1999) Discovery of novel antitumor sulfonamides targeting G1 phase of the cell cycle. J Med Chem 42:3789–3799

    Article  PubMed  CAS  Google Scholar 

  • Piaz VD, Giovannoni MP, Castellana C (1997) Novel heterocyclic-fused pyridazinones as potent and selective phosphodiesterase IV inhibitors. J Med Chem 40:1417–1421

    Article  Google Scholar 

  • Pieretti S, Dominici L, Giannuario AD, Cesari N, Piaz VD (2006) Local anti-inflammatory effect and behavioral studies on new PDE4 inhibitors. Life Sci 79:791–800

    Article  PubMed  CAS  Google Scholar 

  • Pifferi G, Parravicini F, Carpi C, Dorigotti L (1975) Synthesis and antihypertensive properties of new 3-hydrazinopyridazine derivatives. J Med Chem 18:741–746

    Article  PubMed  CAS  Google Scholar 

  • Popp FD (1961) Synthesis of potential anticancer agents. II. Some Schiff bases. J Org Chem 26:1566–1568

    Article  CAS  Google Scholar 

  • Popp FD, Kirsch W (1961) Synthesis of potential anticancer agents. V. Schiff bases and related compounds. J Org Chem 26:3858–3860

    Article  CAS  Google Scholar 

  • Quiroga AG, Perez JM, Lopez-Solera IJM, Masagur JR, Luque A, Roman P, Edwards A, Alonso C, Navarro-Ranninger C (1998) Novel tetranuclear orthometalated complexes of Pd(II) and Pt(II) derived from p-isopropyl benzaldehyde thiosemicarbazone with cytotoxic activity in cis-DDP resistant tumor cell lines. Interaction of these complexes with DNA. J Med Chem 41:1399–1408

    Article  PubMed  CAS  Google Scholar 

  • Radwan SM, Bakhite EA (1999) Synthesis of novel thieno[2,3-c]pyridazines and related heterocycles. Monatsh Chem 130:1117–1128

    CAS  Google Scholar 

  • Rathish IG, Javed K, Bano S, Ahmad S, Alam MS, Pillai KK (2009) Synthesis and blood glucose lowering effect of novel pyridazinone substituted benzene sulfonylurea derivatives. Eur J Med Chem 44:2673–2678

    Article  PubMed  CAS  Google Scholar 

  • Rohet F, Rubat C, Coudert P, Couquelet J (1997) Synthesis and analgesic effects of 3-substituted-4,6-diarylpyridazine derivatives of the arylpiperazine class. Bioorg Med Chem 5:655–659

    Article  PubMed  CAS  Google Scholar 

  • Rostom SAF, Shalaby MA, El-Demellawy MA (2003) Polysubstituted pyrazoles, part 5. Synthesis of new 1-(4-chlorophenyl)-4-hydroxy-1H-pyrazole-3-carboxylic acid hydrazide analogs and some derived ring systems. A novel class of potential antitumor and anti-HCV agents. Eur J Med Chem 38:959–974

    Article  PubMed  CAS  Google Scholar 

  • Salgin-Goksen U, Gokhan-Kelekci N, Goktas O, Koysal Y, Kilic E, Isak S, Aktay G, Ozalp M (2007) 1-Acylthiosemicarbazides, 1,2,4-triazole-5(4H)-thiones, 1,3,4-thiadiazoles and hydrazones containing 5-methyl- 2-benzoxazolinones: synthesis, analgesic, anti-inflammatory and antimicrobial activities. Bioorg Med Chem 15:5738–5751

    Article  PubMed  Google Scholar 

  • Schmidt P, Druey J (1954) Heilmittel chemische Studien in der heterocyclischen Reihe. 5. Mitteilung. Pyridazine II. Eine neue Pyridazinsynthese. Helv Chim Acta 37:134–140

    Article  CAS  Google Scholar 

  • Shenvei SL, Brian SE, Xavier TF (F. Hoffman-La Roche). PCT Int Appl Wo2005 105,808-(Cl. c07d495/04). 10 Nov, 2005, US Appl. 2004/PV568, 372, 4 May 2004, Chem. Abst. (2005) 143: 440248x

  • Takaya M, Sato M, Terashima K, Tanizaw H, Maki Y (1979) A new non-steroidal analgesic-anti inflammatory agent. Synthesis and activity of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone and related compounds. J Med Chem 22:53–58

    Article  PubMed  CAS  Google Scholar 

  • Tewari KT, Mishra AJ (2001) Synthesis and anti-inflammatory activities of N4, N5-disubstituted-3-methyl-1H-pyrazolo[3,4-c]pyridazines. Bioorg Med Chem 9:715–718

    Article  PubMed  CAS  Google Scholar 

  • Tomil MC, Estevez I, Ravina E, Orallo F (1998) Study of the vasorelaxant action of 6-aryl-5-piperidino-3-hydrazinopyridazines in isolated rat thoracic aorta: comparison with hydralazine. Gen Pharmacol 30:201–207

    Article  Google Scholar 

  • Urban M, Sarek J, Klinot J, Korinkova G, Hajduch M (2004) Synthesis of A-seco derivatives of betulinic acid with cytotoxic activity. J Nat Prod 67:1100–1105

    Article  PubMed  CAS  Google Scholar 

  • Wermuth CG, Schlewer G, Bourguignon JJ, Maghioros G, Bouchet MJ, Moire C, Kan JP, Worms P, Biziere K (1989) 3-Aminopyridazine derivatives with atypical antidepressant, serotonergic and dopaminergic activities. J Med Chem 32:528–537

    Article  PubMed  CAS  Google Scholar 

  • Wu J, Song B, Chen H, Bhadury P, Hu D (2009) Synthesis and antifungal activity of 5-chloro-6-phenyl-pyridazin-3(2H)-one derivatives. Molecules 14:3676–3687

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi M, Maruyama N, Koga T, Kamel K, Akima M, Kuroki T, Hamana M, Ohi N (1995) Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. V. Thienopyridazinone derivatives. Chem Pharm Bull 43:236–240

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Thanks are due to the NCI, Bethesda, MD, for performing the antitumour testing of the synthesized compounds.

Author information

Authors and Affiliations

  1. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11561, Egypt

    Afaf K. El-Ansary, Aliaa M. Kamal & Mokhtar AbdHafiz Al-Ghorafi

Authors
  1. Afaf K. El-Ansary
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aliaa M. Kamal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mokhtar AbdHafiz Al-Ghorafi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aliaa M. Kamal.

Rights and permissions

Reprints and permissions

About this article

Cite this article

El-Ansary, A.K., Kamal, A.M. & Al-Ghorafi, M.A. Design and synthesis of some thieno[2,3-c]pyridazine derivatives of expected anticancer activity. Med Chem Res 22, 2589–2601 (2013). https://doi.org/10.1007/s00044-012-0258-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-012-0258-9

Keywords

Search

Navigation