Literature DB >> 24900750

Aminopyridyl/Pyrazinyl Spiro[indoline-3,4'-piperidine]-2-ones As Highly Selective and Efficacious c-Met/ALK Inhibitors.

Jingrong Li1, Nan Wu2, Yuanxin Tian1, Jiajie Zhang1, Shuguang Wu1.   

Abstract

A series of novel aminopyridyl/pyrazinyl-substituted spiro[indoline-3,4'-piperidine]-2-ones were designed, synthesized, and tested in various in vitro/in vivo pharmacological and antitumor assays. 6-[6-Amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-3-pyridyl]-1'-methylspiro[indoline-3,4'-piperidine]-2-one (compound 5b or SMU-B) was identified as a potent, highly selective, well-tolerated, and orally efficacious c-Met/ALK dual inhibitor, which showed pharmacodynamics effect by inhibiting c-Met phosphorylation in vivo and significant tumor growth inhibitions (>50%) in GTL-16 human gastric carcinoma xenograft models.

Entities:  

Keywords:  Hepatocyte growth factor receptor (HGFR or c-Met); aminopyrazine; aminopyridine; anaplastic lymphoma kinase (ALK); cancer; inhibitor; small molecule; spiro[indoline-3,4′-piperidine]-2-one

Year:  2013        PMID： 24900750      PMCID： PMC4027565          DOI： 10.1021/ml400203d

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


  23 in total

1.  Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine.

Authors:  Ajay N Jain
Journal:  J Med Chem       Date:  2003-02-13       Impact factor: 7.446

Review 2.  Targeting oncogenic ALK and MET: a promising therapeutic strategy for glioblastoma.

Authors:  Gerald C Wallace; Yaenette N Dixon-Mah; W Alex Vandergrift; Swapan K Ray; Catherine P Haar; Amber M Mittendorf; Sunil J Patel; Naren L Banik; Pierre Giglio; Arabinda Das
Journal:  Metab Brain Dis       Date:  2013-04-02       Impact factor: 3.584

3.  Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors.

Authors:  Christine M Lovly; Johannes M Heuckmann; Elisa de Stanchina; Heidi Chen; Roman K Thomas; Chris Liang; William Pao
Journal:  Cancer Res       Date:  2011-05-25       Impact factor: 12.701

4.  Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas.

Authors:  M F Di Renzo; M Olivero; T Martone; A Maffe; P Maggiora; A D Stefani; G Valente; S Giordano; G Cortesina; P M Comoglio
Journal:  Oncogene       Date:  2000-03-16       Impact factor: 9.867

5.  Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas.

Authors:  L Schmidt; F M Duh; F Chen; T Kishida; G Glenn; P Choyke; S W Scherer; Z Zhuang; I Lubensky; M Dean; R Allikmets; A Chidambaram; U R Bergerheim; J T Feltis; C Casadevall; A Zamarron; M Bernues; S Richard; C J Lips; M M Walther; L C Tsui; L Geil; M L Orcutt; T Stackhouse; J Lipan; L Slife; H Brauch; J Decker; G Niehans; M D Hughson; H Moch; S Storkel; M I Lerman; W M Linehan; B Zbar
Journal:  Nat Genet       Date:  1997-05       Impact factor: 38.330

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

Authors:  Alessandro Furlan; Francesco Colombo; Andrea Kover; Nathalie Issaly; Cristina Tintori; Lucilla Angeli; Vincent Leroux; Sébastien Letard; Mercedes Amat; Yasmine Asses; Bernard Maigret; Patrice Dubreuil; Maurizio Botta; Rosanna Dono; Joan Bosch; Oreste Piccolo; Daniele Passarella; Flavio Maina
Journal:  Eur J Med Chem       Date:  2011-11-04       Impact factor: 6.514

7.  A novel germ line juxtamembrane Met mutation in human gastric cancer.

Authors:  J H Lee; S U Han; H Cho; B Jennings; B Gerrard; M Dean; L Schmidt; B Zbar; G F Vande Woude
Journal:  Oncogene       Date:  2000-10-12       Impact factor: 9.867

Review 8.  ALK inhibitors: a new targeted therapy in the treatment of advanced NSCLC.

Authors:  Francesca Casaluce; Assunta Sgambato; Paolo Maione; Antonio Rossi; Carmine Ferrara; Alba Napolitano; Giovanni Palazzolo; Fortunato Ciardiello; Cesare Gridelli
Journal:  Target Oncol       Date:  2013-01-17       Impact factor: 4.493

9.  Amplification but not translocation of anaplastic lymphoma kinase is a frequent event in oesophageal cancer.

Authors:  Sebastian F Schoppmann; Berthold Streubel; Peter Birner
Journal:  Eur J Cancer       Date:  2013-03-13       Impact factor: 9.162

10.  Indazoles as potential c-Met inhibitors: design, synthesis and molecular docking studies.

Authors:  Lianbao Ye; Xiaomin Ou; Yuanxin Tian; Bangwei Yu; Yan Luo; Binghong Feng; Hansen Lin; Jiajie Zhang; Shuguang Wu
Journal:  Eur J Med Chem       Date:  2013-04-29       Impact factor: 6.514
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  3 in total

1.  Discovery and Biological Evaluation of Novel Dual EGFR/c-Met Inhibitors.

Authors:  Bálint Szokol; Pál Gyulavári; Ibolya Kurkó; Ferenc Baska; Csaba Szántai-Kis; Zoltán Greff; Zoltán Orfi; István Peták; Kinga Pénzes; Robert Torka; Axel Ullrich; László Orfi; Tibor Vántus; György Kéri
Journal:  ACS Med Chem Lett       Date:  2014-01-30       Impact factor: 4.345

2.  Data driven polypharmacological drug design for lung cancer: analyses for targeting ALK, MET, and EGFR.

Authors:  Dilip Narayanan; Osman A B S M Gani; Franz X E Gruber; Richard A Engh
Journal:  J Cheminform       Date:  2017-07-04       Impact factor: 5.514

3.  Three-Component Cascade Reaction of 1,1-Enediamines, N,N-Dimethylformamide Dimethyl Acetal, and 1,3-Dicarbonyl Compounds: Selective Synthesis of Diverse 2-Aminopyridine Derivatives.

Authors:  Quan-Xing Zi; Sheng-Jiao Yan; Chang-Long Yang; Kun Li; Jun Lin
Journal:  ACS Omega       Date:  2019-02-07
  3 in total

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