Triazolopyridazine derivatives: Synthesis, cytotoxic evaluation, c-Met kinase activity and molecular docking

被引：7

作者：

Ahmed, Eman M. ^{[1
]}

Khalil, Nadia A. ^{[1
]}

Taher, Azza T. ^{[1
,2
]}

Refaey, Rana H. ^{[3
]}

Nissan, Yassin M. ^{[3
,4
]}

机构：

[1] Cairo Univ, Fac Pharm, Pharmaceut Organ Chem Dept, Cairo, Egypt

[2] October 6 Univ, Pharmaceut Organ Chem Dept, Fac Pharm, Giza, Egypt

[3] October Univ Modern Sci & Arts MSA, Pharmaceut Chem Dept, Fac Pharm, Giza, Egypt

[4] Cairo Univ, Pharmaceut Chem Dept, Fac Pharm, Kasr Elini St, Cairo 11562, Egypt

来源：

BIOORGANIC CHEMISTRY | 2019年 / 92卷

关键词：

Triazolopyridazines; Pyridazines; Cytotoxic activity; c-Met kinase; NATIONAL-CANCER-INSTITUTE; HEPATOCYTE GROWTH-FACTOR; DRUG DISCOVERY; INHIBITORS; DESIGN; OPTIMIZATION;

D O I：

10.1016/j.bioorg.2019.103272

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Novel series of some triazolo [4,3-b]pyridazine derivatives were designed and synthesized. All the newly synthesized compounds were evaluated for their cytotoxic activity at 10(-5) M concentration towards 60 cancer cell lines according to USA NCI protocol. Most of the synthesized compounds showed good activity against SR (leukemia) cell panel. The most active compounds, 2f and 4a were subjected for further evaluation at a five dose level screening and their efficacy for c-Met kinase inhibition was determined in vitro. Binding mode of these derivatives was explored via molecular docking.

引用

页数：9

共 34 条

[1] Design, synthesis, and evaluation of anti-inflammatory and ulcerogenicity of novel pyridazinone derivatives [J].

Abouzid, K. A. M. ;

Khalil, N. A. ;

Ahmed, E. M. ;

Esmat, A. ;

Al-Abd, A. M. .

MEDICINAL CHEMISTRY RESEARCH, 2012, 21 (11) :3581-3590

[2] 3-[(6-Arylamino)pyridazinylamino]benzoic acids: design, synthesis and in vitro evaluation of anticancer activity [J].

Abouzid, Khaled A. M. ;

Khalil, Nadia A. ;

Ahmed, Eman M. ;

Mohamed, Khaled Omar .

ARCHIVES OF PHARMACAL RESEARCH, 2013, 36 (01) :41-50

[3] Discovery and optimization of triazolopyridazines as potent and selective inhibitors of the c-Met kinase [J].

Albrecht, Brian K. ;

Harmange, Jean-Christophe ;

Bauer, David ;

Berry, Loren ;

Bode, Christiane ;

Boezio, Alessandro A. ;

Chen, April ;

Choquette, Deborah ;

Dussault, Isabelle ;

Fridrich, Cary ;

Hirai, Satoko ;

Hoffman, Doug ;

Larrow, Jay F. ;

Kaplan-Lefko, Paula ;

Lin, Jasmine ;

Lohman, Julia ;

Long, Alexander M. ;

Moriguchi, Jodi ;

O'Connor, Anne ;

Potashman, Michele H. ;

Reese, Monica ;

Rex, Karen ;

Siegmund, Aaron ;

Shah, Kavita ;

Shimanovich, Roman ;

Springer, Stephanie K. ;

Teffera, Yohannes ;

Yang, Yajing ;

Zhang, Yihong ;

Bellon, Steven F. .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (10) :2879-2882

[4] The Protein Data Bank [J].

Berman, HM ;

Westbrook, J ;

Feng, Z ;

Gilliland, G ;

Bhat, TN ;

Weissig, H ;

Shindyalov, IN ;

Bourne, PE .

NUCLEIC ACIDS RESEARCH, 2000, 28 (01) :235-242

[5] Met, metastasis, motility and more [J].

Birchmeier, C ;

Birchmeier, W ;

Gherardi, E ;

Vande Woude, GF .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2003, 4 (12) :915-925

[6] Discovery and optimization of potent and selective triazolopyridazine series of c-Met inhibitors [J].

Boezio, Alessandro A. ;

Berry, Loren ;

Albrecht, Brian K. ;

Bauer, David ;

Bellon, Steven F. ;

Bode, Christiane ;

Chen, April ;

Choquette, Deborah ;

Dussault, Isabelle ;

Hirai, Satoko ;

Kaplan-Lefko, Paula ;

Larrow, Jay F. ;

Lin, Min-Hwa Jasmine ;

Lohman, Julia ;

Potashman, Michele H. ;

Rex, Karen ;

Santostefano, Michael ;

Shah, Kavita ;

Shimanovich, Roman ;

Springer, Stephanie K. ;

Teffera, Yohannes ;

Yang, Yajing ;

Zhang, Yihong ;

Harmange, Jean-Christophe .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (22) :6307-6312

[7] SOME PRACTICAL CONSIDERATIONS AND APPLICATIONS OF THE NATIONAL-CANCER-INSTITUTE IN-VITRO ANTICANCER DRUG DISCOVERY SCREEN [J].

BOYD, MR ;

PAULI, KD .

DRUG DEVELOPMENT RESEARCH, 1995, 34 (02) :91-109

[8] SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo [J].

Buchanan, Sean G. ;

Hendle, Jorg ;

Lee, Patrick S. ;

Smith, Christopher R. ;

Bounaud, Pierre-Yves ;

Jessen, Katti A. ;

Tang, Crystal M. ;

Huser, Nanni H. ;

Felce, Jeremy D. ;

Froning, Karen J. ;

Peterman, Marshall C. ;

Aubol, Brandon E. ;

Gessert, Steve F. ;

Sauder, Michael ;

Schwinn, Kenneth D. ;

Russell, Marijane ;

Rooney, Isabelle A. ;

Adams, Jason ;

Leon, Barbara C. ;

Do, Tuan H. ;

Blaney, Jeff M. ;

Sprengeler, Paul A. ;

Thompson, Devon A. ;

Smyth, Lydia ;

Pelletier, Laura A. ;

Atwell, Shane ;

Holme, Kevin ;

Wasserman, Stephen R. ;

Emtage, Spencer ;

Burley, Stephen K. ;

Reich, Siegfried H. .

MOLECULAR CANCER THERAPEUTICS, 2009, 8 (12) :3181-3190

[9] Drug development of MET inhibitors: targeting oncogene addiction and expedience [J].

Comoglio, Paolo M. ;

Giordano, Silvia ;

Trusolino, Livio .

NATURE REVIEWS DRUG DISCOVERY, 2008, 7 (06) :504-516

[10] Identification of new aminoacid amides containing the imidazo[2,1-b]benzothiazol-2-ylphenyl moiety as inhibitors of tumorigenesis by oncogenic Met signaling [J].

Furlan, Alessandro ;

Colombo, Francesco ;

Kover, Andrea ;

Issaly, Nathalie ;

Tintori, Cristina ;

Angeli, Lucilla ;

Leroux, Vincent ;

Letard, Sebastien ;

Amat, Mercedes ;

Asses, Yasmine ;

Maigret, Bernard ;

Dubreuil, Patrice ;

Botta, Maurizio ;

Dono, Rosanna ;

Bosch, Joan ;

Piccolo, Oreste ;

Passarella, Daniele ;

Maina, Flavio .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 47 :239-254

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