3c1x Citations

Identification of pyrrolo[2,1-f][1,2,4]triazine-based inhibitors of Met kinase.

Abstract

An amide library derived from the pyrrolo[2,1-f][1,2,4]triazine scaffold led to the identification of modest inhibitors of Met kinase activity. Introduction of polar side chains at C-6 of the pyrrolotriazine core provided significant improvements in in vitro potency. The amide moiety could be replaced with acylurea and malonamide substituents to give compounds with improved potency in the Met-driven GTL-16 human gastric carcinoma cell line. Acylurea pyrrolotriazines with substitution at C-5 demonstrated single digit nanomolar kinase activity. X-ray crystallography revealed that the C-5 substituted pyrrolotriazines bind to the Met kinase domain in an ATP-competitive manner.

Articles - 3c1x mentioned but not cited (4)

  1. Data driven polypharmacological drug design for lung cancer: analyses for targeting ALK, MET, and EGFR. Narayanan D, Gani OABSM, Gruber FXE, Engh RA. J Cheminform 9 43 (2017)
  2. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)
  3. Large-Scale Virtual Screening Against the MET Kinase Domain Identifies a New Putative Inhibitor Type. Bresso E, Furlan A, Noel P, Leroux V, Maina F, Dono R, Maigret B. Molecules 25 E938 (2020)
  4. Prediction of kinase-inhibitor binding affinity using energetic parameters. Usha S, Selvaraj S. Bioinformation 12 172-181 (2016)


Reviews citing this publication (3)

  1. Small molecule c-Met kinase inhibitors: a review of recent patents. Porter J. Expert Opin Ther Pat 20 159-177 (2010)
  2. Structural biology contributions to tyrosine kinase drug discovery. Cowan-Jacob SW, Möbitz H, Fabbro D. Curr Opin Cell Biol 21 280-287 (2009)
  3. Pyrrolo[2,1-f][1,2,4]triazine: a promising fused heterocycle to target kinases in cancer therapy. Singh S, Utreja D, Kumar V. Med Chem Res 1-25 (2021)

Articles citing this publication (20)

  1. Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors. Cai ZW, Wei D, Schroeder GM, Cornelius LA, Kim K, Chen XT, Schmidt RJ, Williams DK, Tokarski JS, An Y, Sack JS, Manne V, Kamath A, Zhang Y, Marathe P, Hunt JT, Lombardo LJ, Fargnoli J, Borzilleri RM. Bioorg Med Chem Lett 18 3224-3229 (2008)
  2. N-(4-(6,7-Disubstituted-quinolin-4-yloxy)-3-fluorophenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: a novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors. Mannion M, Raeppel S, Claridge S, Zhou N, Saavedra O, Isakovic L, Zhan L, Gaudette F, Raeppel F, Déziel R, Beaulieu N, Nguyen H, Chute I, Beaulieu C, Dupont I, Robert MF, Lefebvre S, Dubay M, Rahil J, Wang J, Ste-Croix H, Robert Macleod A, Besterman JM, Vaisburg A. Bioorg Med Chem Lett 19 6552-6556 (2009)
  3. Docking and quantitative structure-activity relationship studies for 3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)aniline, 3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline, and 4-(4-amino-2-fluorophenoxy)-2-pyridinylamine derivatives as c-Met kinase inhibitors. Caballero J, Quiliano M, Alzate-Morales JH, Zimic M, Deharo E. J Comput Aided Mol Des 25 349-369 (2011)
  4. Identification and synthesis of N'-(2-oxoindolin-3-ylidene)hydrazide derivatives against c-Met kinase. Liang Z, Zhang D, Ai J, Chen L, Wang H, Kong X, Zheng M, Liu H, Luo C, Geng M, Jiang H, Chen K. Bioorg Med Chem Lett 21 3749-3754 (2011)
  5. N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: a novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors. Raeppel S, Claridge S, Saavedra O, Gaudette F, Zhan L, Mannion M, Zhou N, Raeppel F, Granger MC, Isakovic L, Déziel R, Nguyen H, Beaulieu N, Beaulieu C, Dupont I, Robert MF, Lefebvre S, Dubay M, Rahil J, Wang J, Ste-Croix H, Robert Macleod A, Besterman J, Vaisburg A. Bioorg Med Chem Lett 19 1323-1328 (2009)
  6. N3-arylmalonamides: a new series of thieno[3,2-b]pyridine based inhibitors of c-Met and VEGFR2 tyrosine kinases. Saavedra O, Claridge S, Zhan L, Raeppel F, Granger MC, Raeppel S, Mannion M, Gaudette F, Zhou N, Isakovic L, Bernstein N, Déziel R, Nguyen H, Beaulieu N, Beaulieu C, Dupont I, Wang J, Macleod AR, Besterman JM, Vaisburg A. Bioorg Med Chem Lett 19 6836-6839 (2009)
  7. Novel acylureidoindolin-2-one derivatives as dual Aurora B/FLT3 inhibitors for the treatment of acute myeloid leukemia. Jagtap AD, Chang PT, Liu JR, Wang HC, Kondekar NB, Shen LJ, Tseng HW, Chen GS, Chern JW. Eur J Med Chem 85 268-288 (2014)
  8. Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors. Williams DK, Chen XT, Tarby C, Kaltenbach R, Cai ZW, Tokarski JS, An Y, Sack JS, Wautlet B, Gullo-Brown J, Henley BJ, Jeyaseelan R, Kellar K, Manne V, Trainor GL, Lombardo LJ, Fargnoli J, Borzilleri RM. Bioorg Med Chem Lett 20 2998-3002 (2010)
  9. Structure-Based Design of Type II Inhibitors Applied to Maternal Embryonic Leucine Zipper Kinase. Johnson CN, Adelinet C, Berdini V, Beke L, Bonnet P, Brehmer D, Calo F, Coyle JE, Day PJ, Frederickson M, Freyne EJ, Gilissen RA, Hamlett CC, Howard S, Meerpoel L, Mevellec L, McMenamin R, Pasquier E, Patel S, Rees DC, Linders JT. ACS Med Chem Lett 6 31-36 (2015)
  10. Discovering potent inhibitors against c-Met kinase: molecular design, organic synthesis and bioassay. Liang Z, Ding X, Ai J, Kong X, Chen L, Chen L, Luo C, Geng M, Liu H, Chen K, Jiang H. Org Biomol Chem 10 421-430 (2012)
  11. Pyridazinone derivatives displaying highly potent and selective inhibitory activities against c-Met tyrosine kinase. Liu Y, Jin S, Peng X, Lu D, Zeng L, Sun Y, Ai J, Geng M, Hu Y. Eur J Med Chem 108 322-333 (2016)
  12. Synthesis and biological evaluation of 2-amino-5-aryl-3-benzylthiopyridine scaffold based potent c-Met inhibitors. Zhang D, Zhang X, Ai J, Zhai Y, Liang Z, Wang Y, Chen Y, Li C, Zhao F, Jiang H, Geng M, Luo C, Liu H. Bioorg Med Chem 21 6804-6820 (2013)
  13. Investigation on the 1,6-naphthyridine motif: discovery and SAR study of 1H-imidazo[4,5-h][1,6]naphthyridin-2(3H)-one-based c-Met kinase inhibitors. Wang Y, Xu ZL, Ai J, Peng X, Lin JP, Ji YC, Geng MY, Long YQ. Org Biomol Chem 11 1545-1562 (2013)
  14. Target identification, lead optimization and antitumor evaluation of some new 1,2,4-triazines as c-Met kinase inhibitors. El-Wakil MH, Ashour HM, Saudi MN, Hassan AM, Labouta IM. Bioorg Chem 73 154-169 (2017)
  15. Development of efficient docking strategies and structure-activity relationship study of the c-Met type II inhibitors. Li MJ, Wu GZ, Kaas Q, Jiang T, Yu RL. J Mol Graph Model 75 241-249 (2017)
  16. Discovery of 3H-imidazo[4,5-b]pyridines as potent c-Met kinase inhibitors: design, synthesis, and biological evaluation. Chen D, Wang Y, Ma Y, Xiong B, Ai J, Chen Y, Geng M, Shen J. ChemMedChem 7 1057-1070 (2012)
  17. Discovery of novel c-Met inhibitors bearing a 3-carboxyl piperidin-2-one scaffold. Zhang W, Ai J, Shi D, Peng X, Ji Y, Liu J, Geng M, Li Y. Molecules 19 2655-2673 (2014)
  18. Novel 3-phenylquinazolin-2,4(1H,3H)-diones as dual VEGFR-2/c-Met-TK inhibitors: design, synthesis, and biological evaluation. Hassan A, Mosallam AM, Ibrahim AOA, Badr M, Abdelmonsef AH. Sci Rep 13 18567 (2023)
  19. Phenanthrotriazine Derivatives Containing Arylidine Hydrazone Moieties as Novel Potential c-Met Inhibitors with Anticancer Effect. Edraki N, Jamei MH, Haghighijoo Z, Kayani Z, Raufi E, Eskandari M, Firouzi M, Sadeghpour H, Miri R, Khoshneviszadeh M, Firuzi O. Iran J Pharm Res 20 516-531 (2021)
  20. Regio- and Diastereoselective 1,3-Dipolar Cycloadditions of 1,2,4-Triazin-1-ium Ylides: a Straightforward Synthetic Route to Polysubstituted Pyrrolo[2,1-f][1,2,4]triazines. Galeta J, Šlachtová V, Dračínský M, Vrabel M. ACS Omega 7 21233-21238 (2022)