2qu5 › Citations

Design, synthesis, and evaluation of orally active benzimidazoles and benzoxazoles as vascular endothelial growth factor-2 receptor tyrosine kinase inhibitors.

Potashman MH, Bready J, Coxon A, DeMelfi TM, DiPietro L, Doerr N, Elbaum D, Estrada J, Gallant P, Germain J, Gu Y, Harmange JC, Kaufman SA, Kendall R, Kim JL, Kumar GN, Long AM, Neervannan S, Patel VF, Polverino A, Rose P, Plas Sv, Whittington D, Zanon R, Zhao H
J Med Chem 50 4351-73 (2007)
Cited: 58 times
EuropePMC logo PMID: 17696416

Abstract

Inhibition of the VEGF signaling pathway has become a valuable approach in the treatment of cancers. Guided by X-ray crystallography and molecular modeling, a series of 2-aminobenzimidazoles and 2-aminobenzoxazoles were identified as potent inhibitors of VEGFR-2 (KDR) in both enzymatic and HUVEC cellular proliferation assays. In this report we describe the synthesis and structure-activity relationship of a series of 2-aminobenzimidazoles and benzoxazoles, culminating in the identification of benzoxazole 22 as a potent and selective VEGFR-2 inhibitor displaying a good pharmacokinetic profile. Compound 22 demonstrated efficacy in both the murine matrigel model for vascular permeability (79% inhibition observed at 100 mg/kg) and the rat corneal angiogenesis model (ED(50) = 16.3 mg/kg).

Reviews - 2qu5 mentioned but not cited (3)

  1. Recent advances in the pharmacological diversification of quinazoline/quinazolinone hybrids. Auti PS, George G, Paul AT. RSC Adv 10 41353-41392 (2020)
  2. Research Progress of Small Molecule VEGFR/c-Met Inhibitors as Anticancer Agents (2016-Present). Zhang Q, Zheng P, Zhu W. Molecules 25 E2666 (2020)
  3. Target-Based Small Molecule Drug Discovery for Colorectal Cancer: A Review of Molecular Pathways and In Silico Studies. Moshawih S, Lim AF, Ardianto C, Goh KW, Kifli N, Goh HP, Jarrar Q, Ming LC. Biomolecules 12 878 (2022)

Articles - 2qu5 mentioned but not cited (11)

  1. Transformer neural network for protein-specific de novo drug generation as a machine translation problem. Grechishnikova D. Sci Rep 11 321 (2021)
  2. Identification of Druggable Kinase Target Conformations Using Markov Model Metastable States Analysis of apo-Abl. Paul F, Meng Y, Roux B. J Chem Theory Comput 16 1896-1912 (2020)
  3. Design, Synthesis and Biological Activity Evaluation of S-Substituted 1H-5-Mercapto-1,2,4-Triazole Derivatives as Antiproliferative Agents in Colorectal Cancer. Mioc M, Avram S, Bercean V, Kurunczi L, Ghiulai RM, Oprean C, Coricovac DE, Dehelean C, Mioc A, Balan-Porcarasu M, Tatu C, Soica C. Front Chem 6 373 (2018)
  4. Disruption of Angiogenesis by Anthocyanin-Rich Extracts of Hibiscus sabdariffa. Joshua M, Okere C, Sylvester O, Yahaya M, Precious O, Dluya T, Um JY, Neksumi M, Boyd J, Vincent-Tyndall J, Choo DW, Gutsaeva DR, Jahng WJ. Int J Sci Eng Res 8 299-307 (2017)
  5. Alchemical Grid Dock (AlGDock) calculations in the D3R Grand Challenge 3 : Binding free energies between flexible ligands and rigid receptors. Xie B, Minh DDL. J Comput Aided Mol Des 33 61-69 (2019)
  6. Apoptosis Inducing 1,3,4-Oxadiazole Conjugates of Capsaicin: Their In Vitro Antiproliferative and In Silico Studies. Naaz F, Ahmad F, Lone BA, Khan A, Sharma K, IntzarAli, ShaharYar M, Pokharel YR, Shafi S. ACS Med Chem Lett 12 1694-1702 (2021)
  7. Cytotoxicity of Amphotericin B and AmBisome: In Silico and In Vivo Evaluation Employing the Chick Embryo Model. Khosravi A, Sharifi I, Tavakkoli H, Molaakbari E, Bahraminegad S, Salarkia E, Seyedi F, Keyhani A, Salari Z, Sharifi F, Bamorovat M, Afgar A, Dabiri S. Front Pharmacol 13 860598 (2022)
  8. In Vitro Cytotoxic Activity and Phytochemical Characterization (UPLC/T-TOF-MS/MS) of the Watermelon (Citrullus lanatus) Rind Extract. El Gizawy HA, El-Haddad AE, Attia YM, Fahim SA, Zafer MM, Saadeldeen AM. Molecules 27 2480 (2022)
  9. Molecular docking of 1H-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors. Chandra, Javaregowda VG, Doreswamy BH, Ningaiah S, Bhadraiah UK, Kemparaju K, Madegowda M. Bioinformation 10 413-418 (2014)
  10. The Automatic Solution of Macromolecular Crystal Structures via Molecular Replacement Techniques: REMO22 and Its Pipeline. Carrozzini B, Cascarano GL, Giacovazzo C. Int J Mol Sci 24 6070 (2023)
  11. The inhibitory effect of 6-gingerol and cisplatin on ovarian cancer and antitumor activity: In silico, in vitro, and in vivo. Salari Z, Khosravi A, Pourkhandani E, Molaakbari E, Salarkia E, Keyhani A, Sharifi I, Tavakkoli H, Sohbati S, Dabiri S, Ren G, Shafie'ei M. Front Oncol 13 1098429 (2023)


Reviews citing this publication (2)

  1. Protein kinase inhibitors: contributions from structure to clinical compounds. Johnson LN. Q Rev Biophys 42 1-40 (2009)
  2. Development of anti-angiogenic tyrosine kinases inhibitors: molecular structures and binding modes. Zhang J, Zhang L, Wang Y, Zhao G. Cancer Chemother Pharmacol 77 905-926 (2016)

Articles citing this publication (42)

  1. Small-molecule inhibitors binding to protein kinase. Part II: the novel pharmacophore approach of type II and type III inhibition. Backes A, Zech B, Felber B, Klebl B, Müller G. Expert Opin Drug Discov 3 1427-1449 (2008)
  2. The R1275Q neuroblastoma mutant and certain ATP-competitive inhibitors stabilize alternative activation loop conformations of anaplastic lymphoma kinase. Epstein LF, Chen H, Emkey R, Whittington DA. J Biol Chem 287 37447-37457 (2012)
  3. Discovery of quinazolin-4-amines bearing benzimidazole fragments as dual inhibitors of c-Met and VEGFR-2. Shi L, Wu TT, Wang Z, Xue JY, Xu YG. Bioorg Med Chem 22 4735-4744 (2014)
  4. Fragment-Based Discovery of Potent and Selective DDR1/2 Inhibitors. Murray CW, Berdini V, Buck IM, Carr ME, Cleasby A, Coyle JE, Curry JE, Day JE, Day PJ, Hearn K, Iqbal A, Lee LY, Martins V, Mortenson PN, Munck JM, Page LW, Patel S, Roomans S, Smith K, Tamanini E, Saxty G. ACS Med Chem Lett 6 798-803 (2015)
  5. Cobalt-catalyzed intramolecular C-N and C-O cross-coupling reactions: synthesis of benzimidazoles and benzoxazoles. Saha P, Ali MA, Ghosh P, Punniyamurthy T. Org Biomol Chem 8 5692-5699 (2010)
  6. Exploration for novel inhibitors showing back-to-front approach against VEGFR-2 kinase domain (4AG8) employing molecular docking mechanism and molecular dynamics simulations. Rampogu S, Baek A, Zeb A, Lee KW. BMC Cancer 18 264 (2018)
  7. Lacosamide isothiocyanate-based agents: novel agents to target and identify lacosamide receptors. Park KD, Morieux P, Salomé C, Cotten SW, Reamtong O, Eyers C, Gaskell SJ, Stables JP, Liu R, Kohn H. J Med Chem 52 6897-6911 (2009)
  8. Design, synthesis and biological activities of thiourea containing sorafenib analogs as antitumor agents. Yao J, Chen J, He Z, Sun W, Xu W. Bioorg Med Chem 20 2923-2929 (2012)
  9. Inhibition of cell proliferation, vascular endothelial growth factor and tumor growth by albendazole. Pourgholami MH, Cai ZY, Wang L, Badar S, Links M, Morris DL. Cancer Invest 27 171-177 (2009)
  10. Design, synthesis, in-vitro antiproliferative activity and kinase profile of new picolinamide based 2-amido and ureido quinoline derivatives. El-Damasy AK, Seo SH, Cho NC, Kang SB, Pae AN, Kim KS, Keum G. Eur J Med Chem 101 754-768 (2015)
  11. Receptor-guided 3D-QSAR approach for the discovery of c-kit tyrosine kinase inhibitors. Almerico AM, Tutone M, Lauria A. J Mol Model 18 2885-2895 (2012)
  12. Identification of Quinoline-Based RIP2 Kinase Inhibitors with an Improved Therapeutic Index to the hERG Ion Channel. Haile PA, Casillas LN, Bury MJ, Mehlmann JF, Singhaus R, Charnley AK, Hughes TV, DeMartino MP, Wang GZ, Romano JJ, Dong X, Plotnikov NV, Lakdawala AS, Convery MA, Votta BJ, Lipshutz DB, Desai BM, Swift B, Capriotti CA, Berger SB, Mahajan MK, Reilly MA, Rivera EJ, Sun HH, Nagilla R, LePage C, Ouellette MT, Totoritis RD, Donovan BT, Brown BS, Chaudhary KW, Gough PJ, Bertin J, Marquis RW. ACS Med Chem Lett 9 1039-1044 (2018)
  13. Direct transition-metal-free intramolecular C-O bond formation: synthesis of benzoxazole derivatives. Peng J, Zong C, Ye M, Chen T, Gao D, Wang Y, Chen C. Org Biomol Chem 9 1225-1230 (2011)
  14. Flavonoids as a scaffold for development of novel anti-angiogenic agents: An experimental and computational enquiry. Gacche RN, Meshram RJ, Shegokar HD, Gond DS, Kamble SS, Dhabadge VN, Utage BG, Patil KK, More RA. Arch Biochem Biophys 577-578 35-48 (2015)
  15. Design, synthesis and evaluation of novel rhodanine-containing sorafenib analogs as potential antitumor agents. Li W, Zhai X, Zhong Z, Li G, Pu Y, Gong P. Arch Pharm (Weinheim) 344 349-357 (2011)
  16. Discovery of VEGFR2 inhibitors by integrating naïve Bayesian classification, molecular docking and drug screening approaches. Kang, Pang X, Lian W, Xu L, Wang J, Jia H, Zhang B, Liu AL, Du GH. RSC Adv 8 5286-5297 (2018)
  17. Benzimidazole inhibitors of the protein kinase CHK2: clarification of the binding mode by flexible side chain docking and protein-ligand crystallography. Matijssen C, Silva-Santisteban MC, Westwood IM, Siddique S, Choi V, Sheldrake P, van Montfort RL, Blagg J. Bioorg Med Chem 20 6630-6639 (2012)
  18. Binding to an Unusual Inactive Kinase Conformation by Highly Selective Inhibitors of Inositol-Requiring Enzyme 1α Kinase-Endoribonuclease. Colombano G, Caldwell JJ, Matthews TP, Bhatia C, Joshi A, McHardy T, Mok NY, Newbatt Y, Pickard L, Strover J, Hedayat S, Walton MI, Myers SM, Jones AM, Saville H, McAndrew C, Burke R, Eccles SA, Davies FE, Bayliss R, Collins I. J Med Chem 62 2447-2465 (2019)
  19. 3D-QSAR study of Chk1 kinase inhibitors based on docking. Zhao L, Liu Y, Hu S, Zhang H. J Mol Model 18 3669-3694 (2012)
  20. Design and synthesis of 5,6-fused heterocyclic amides as Raf kinase inhibitors. Ramurthy S, Aikawa M, Amiri P, Costales A, Hashash A, Jansen JM, Lin S, Ma S, Renhowe PA, Shafer CM, Subramanian S, Sung L, Verhagen J. Bioorg Med Chem Lett 21 3286-3289 (2011)
  21. Discovery and SAR study of c-Met kinase inhibitors bearing an 3-amino-benzo[d]isoxazole or 3-aminoindazole scaffold. Jiang X, Liu H, Song Z, Peng X, Ji Y, Yao Q, Geng M, Ai J, Zhang A. Bioorg Med Chem 23 564-578 (2015)
  22. Discovery of potent vascular endothelial growth factor receptor-2 inhibitors. Papakyriakou A, Katsarou ME, Belimezi M, Karpusas M, Vourloumis D. ChemMedChem 5 118-129 (2010)
  23. Molecular modeling studies of vascular endothelial growth factor receptor tyrosine kinase inhibitors using QSAR and docking. Du J, Lei B, Qin J, Liu H, Yao X. J Mol Graph Model 27 642-654 (2009)
  24. A novel approach towards design, synthesis and evaluation of some Schiff base analogues of 2-aminopyridine and 2-aminobezothiazole against hepatocellular carcinoma. Chacko S, Samanta S. Biomed Pharmacother 89 162-176 (2017)
  25. Application of shape-based and pharmacophore-based in silico screens for identification of Type II protein kinase inhibitors. Mucs D, Bryce RA, Bonnet P. J Comput Aided Mol Des 25 569-581 (2011)
  26. Discovery of novel vascular endothelial growth factor receptor 2 inhibitors: a virtual screening approach. Zhang L, Wang X, Feng J, Jia Y, Xu F, Xu W. Chem Biol Drug Des 80 893-901 (2012)
  27. Oxazoles revisited: On the nature of binding of benzoxazole and 2-methylbenzoxazole with the zinc and palladium halides. Jones RC, Chojnacka MW, Quail JW, Gardiner MG, Decken A, Yates BF, Gossage RA. Dalton Trans 40 1594-1600 (2011)
  28. Design, synthesis and biological activities of sorafenib derivatives as antitumor agents. Yao J, He Z, Chen J, Sun W, Fang H, Xu W. Bioorg Med Chem Lett 22 6549-6553 (2012)
  29. Synthesis of Various 2-Aminobenzoxazoles: The Study of Cyclization and Smiles Rearrangement. Šlachtová V, Chasák J, Brulíková L. ACS Omega 4 19314-19323 (2019)
  30. Benzamide capped peptidomimetics as non-ATP competitive inhibitors of CDK2 using the REPLACE strategy. Premnath PN, Craig SN, Liu S, McInnes C. Bioorg Med Chem Lett 26 3754-3760 (2016)
  31. Design and synthesis of 2-iminothiazolidin-4-one moiety-containing compounds as potent antiproliferative agents. Zhai X, Li W, Chen D, Lai R, Liu J, Gong P. Arch Pharm (Weinheim) 345 360-367 (2012)
  32. Design, synthesis and molecular modeling study for some new 2-substituted benzimidazoles as dual inhibitors for VEGFR-2 and c-Met. Ibrahim HA, Awadallah FM, Refaat HM, Amin KM. Future Med Chem 10 493-509 (2018)
  33. Novel Nanomolar Allosteric Modulators of AMPA Receptor of Bis(pyrimidine) Series: Synthesis, Biotesting and SAR Analysis. Sedenkova KN, Zverev DV, Nazarova AA, Lavrov MI, Radchenko EV, Grishin YK, Gabrel'yan AV, Zamoyski VL, Grigoriev VV, Averina EB, Palyulin VA. Molecules 27 8252 (2022)
  34. Copper-catalyzed synthesis of 2-aminophenyl benzothiazoles: a novel approach. Boddapati SNM, Kurmarayuni CM, Mutchu BR, Tamminana R, Bollikolla HB. Org Biomol Chem 16 8267-8272 (2018)
  35. Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates via a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers. Eissa IH, El-Haggar R, Dahab MA, Ahmed MF, Mahdy HA, Alsantali RI, Elwan A, Masurier N, Fatahala SS. J Enzyme Inhib Med Chem 37 1587-1599 (2022)
  36. Synthesis and cytotoxic evaluation of novel N-methyl-4-phenoxypicolinamide derivatives. Li W, Zhai X, Ding L, Sun L, Chen X, Gong P, Sun T. Molecules 16 5130-5141 (2011)
  37. Synthesis, Molecular Docking, and Biological Evaluation of a New Series of Benzothiazinones and Their Benzothiazinyl Acetate Derivatives as Anticancer Agents against MCF-7 Human Breast Cancer Cells and as Anti-Inflammatory Agents. Ramzan F, Nabi SA, Lone MS, Imtiyaz K, Urooj L, Vishakha V, Sharma K, Rizvi MMA, Shafi S, Samim M, Bano S, Javed K. ACS Omega 8 6650-6662 (2023)
  38. Automatic α-helix identification in Patterson maps. Caliandro R, Dibenedetto D, Cascarano GL, Mazzone A, Nico G. Acta Crystallogr D Biol Crystallogr 68 1-12 (2012)
  39. Design and synthesis of novel N-[3-(benzimidazol-2-ylamino)phenyl]amine and N-[3-(benzoxazol-2-ylamino)phenyl]amine derivatives as potential anticancer agents. Kumar HY, Murumkar PR, Srinivasan BP, Pawar V, Yadav MR. Mol Divers 26 2269-2293 (2022)
  40. Synthesis and Biological Evaluation of Novel 4-(4-Formamidophenylamino)-N-methylpicolinamide Derivatives as Potential Antitumor Agents. Meng N, Zhou S, Hu M, Xu Y, Xia Y, Zeng X, Yu L. Molecules 26 1150 (2021)
  41. Synthesis and biological evaluation of novel 4-(2-fluorophenoxy)-2-(1H-tetrazol-1-yl)pyridines bearing semicarbazone moieties as potent antitumor agents. Qin M, Liao W, Xu C, Fu B, Ren J, Gu Y, Gong P. Arch Pharm (Weinheim) 346 840-850 (2013)
  42. Synthesis, structure and Hirshfeld surface analysis of a coordination compound of cadmium acetate with 2-amino-benzoxazole. Razzoqova S, Ibragimov A, Torambetov B, Kadirova S, Holczbauer T, Ashurov J, Ibragimov B. Acta Crystallogr E Crystallogr Commun 79 862-866 (2023)


Quick links