Literature DB >> 27096042

Evolution of a New Class of VEGFR-2 Inhibitors from Scaffold Morphing and Redesign.

Nello Mainolfi1, Rajeshri Karki1, Fang Liu2, Karen Anderson2.   

Abstract

Anti-VEGF therapy is a clinically validated treatment for age-related macular degeneration (AMD). We have recently reported the discovery of oral VEGFR-2 inhibitors that are selectively distributed to the ocular tissues. Herein we report a further development of those compounds and in particular the validation of the hypothesis that aminoheterocycles such as aminoisoxazoles and aminopyrazoles could also function as effective "hinge" binding moieties leading to a new class of KDR (kinase insert domain containing receptor) inhibitors.

Entities:  

Keywords:  KDR; VEGF; Vascular endothelial growth factor receptor 2; amino heterocycles; hinge binding; scaffold morphing

Year:  2016        PMID： 27096042      PMCID： PMC4834667          DOI： 10.1021/acsmedchemlett.5b00486

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  16 in total

1.  Vascular endothelial growth factor increases microvascular permeability via a Ca(2+)-dependent pathway.

Authors:  D O Bates; F E Curry
Journal:  Am J Physiol       Date:  1997-08

2.  Discovery of Oral VEGFR-2 Inhibitors with Prolonged Ocular Retention That Are Efficacious in Models of Wet Age-Related Macular Degeneration.

Authors:  Erik L Meredith; Nello Mainolfi; Stephen Poor; Yubin Qiu; Karl Miranda; James Powers; Donglei Liu; Fupeng Ma; Catherine Solovay; Chang Rao; Leland Johnson; Nan Ji; Gerald Artman; Leo Hardegger; Shawn Hanks; Siyuan Shen; Amber Woolfenden; Elizabeth Fassbender; Jeremy M Sivak; Yiqin Zhang; Debby Long; Rosemarie Cepeda; Fang Liu; Vinayak P Hosagrahara; Wendy Lee; Peter Tarsa; Karen Anderson; Jason Elliott; Bruce Jaffee
Journal:  J Med Chem       Date:  2015-11-30       Impact factor: 7.446

3.  Discovery of novel benzimidazoles as potent inhibitors of TIE-2 and VEGFR-2 tyrosine kinase receptors.

Authors:  Masaichi Hasegawa; Naohiko Nishigaki; Yoshiaki Washio; Kazuya Kano; Philip A Harris; Hideyuki Sato; Ichiro Mori; Rob I West; Megumi Shibahara; Hiroko Toyoda; Liping Wang; Robert T Nolte; James M Veal; Mui Cheung
Journal:  J Med Chem       Date:  2007-08-04       Impact factor: 7.446

Review 4.  The biology of vascular endothelial growth factor.

Authors:  N Ferrara; T Davis-Smyth
Journal:  Endocr Rev       Date:  1997-02       Impact factor: 19.871

5.  Ranibizumab versus verteporfin for neovascular age-related macular degeneration.

Authors:  David M Brown; Peter K Kaiser; Mark Michels; Gisele Soubrane; Jeffrey S Heier; Robert Y Kim; Judy P Sy; Susan Schneider
Journal:  N Engl J Med       Date:  2006-10-05       Impact factor: 91.245

Review 6.  VEGF receptor signal transduction.

Authors:  T Matsumoto; L Claesson-Welsh
Journal:  Sci STKE       Date:  2001-12-11

7.  Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.

Authors:  Francesca Musumeci; Marco Radi; Chiara Brullo; Silvia Schenone
Journal:  J Med Chem       Date:  2012-11-06       Impact factor: 7.446

Review 8.  Antiangiogenic agents: an update on small molecule VEGFR inhibitors.

Authors:  S Schenone; F Bondavalli; M Botta
Journal:  Curr Med Chem       Date:  2007       Impact factor: 4.530

9.  The discovery of N-(1,3-thiazol-2-yl)pyridin-2-amines as potent inhibitors of KDR kinase.

Authors:  Mark T Bilodeau; Leonard D Rodman; Georgia B McGaughey; Kathleen E Coll; Timothy J Koester; William F Hoffman; Randall W Hungate; Richard L Kendall; Rosemary C McFall; Keith W Rickert; Ruth Z Rutledge; Kenneth A Thomas
Journal:  Bioorg Med Chem Lett       Date:  2004-06-07       Impact factor: 2.823

10.  Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes.

Authors:  P F Lopez; B D Sippy; H M Lambert; A B Thach; D R Hinton
Journal:  Invest Ophthalmol Vis Sci       Date:  1996-04       Impact factor: 4.799
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  3 in total

Review 1.  Kinase inhibitors: the road ahead.

Authors:  Fleur M Ferguson; Nathanael S Gray
Journal:  Nat Rev Drug Discov       Date:  2018-03-16       Impact factor: 84.694

2.  Multi-target weapons: diaryl-pyrazoline thiazolidinediones simultaneously targeting VEGFR-2 and HDAC cancer hallmarks.

Authors:  Neha Upadhyay; Kalpana Tilekar; Sabreena Safuan; Alan P Kumar; Markus Schweipert; Franz-Josef Meyer-Almes; Ramaa C S
Journal:  RSC Med Chem       Date:  2021-07-27

3.  Novel piperazine-chalcone hybrids and related pyrazoline analogues targeting VEGFR-2 kinase; design, synthesis, molecular docking studies, and anticancer evaluation.

Authors:  Marwa F Ahmed; Eman Y Santali; Radwan El-Haggar
Journal:  J Enzyme Inhib Med Chem       Date:  2021-12       Impact factor: 5.051
  3 in total

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