Synthesis and evaluation of [2-(4-quinolyloxy)phenyl]methanone derivatives: Novel selective inhibitors of transforming growth factor-β kinase

Journal of Medicinal Chemistry

Volumn 51, Issue 11, 2008, Pages 3326-3329

  Shimizu, Toshiyuki ^a   Kimura, Kaname ^a   Sakai, Teruyuki ^a   Kawakami, Kazuki ^a   Miyazaki, Tetsuko ^a   Nakouji, Masayoshi ^a   Ogawa, Akira ^a   Ohuchi, Hitomi ^a   Shimizu, Kiyoshi ^a  

^a KYOWA HAKKO KOGYO CO LTD   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

[2 (4 QUINOLYLOXY)PHENYL]METHANONE DERIVATIVE; QUINOLINE DERIVATIVE; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 1;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; PROTEIN DOMAIN; PROTON NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ACTIVIN RECEPTORS, TYPE I; CELL LINE, TUMOR; GENES, REPORTER; HUMANS; LUCIFERASES; PHOSPHORYLATION; QUINOLINES; SMAD2 PROTEIN; SMAD3 PROTEIN; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSFORMING GROWTH FACTOR BETA;

EID: 45249089195     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm701626z     Document Type: Article

References (13)

1. Heldin, C. H.; Miyazono, K.; ten Dijke, P. TGF-β Signaling from Cell Membrane to Nucleus through SMAD Proteins. Nature 1997, 390, 465-471.
2. Shi, Y.; Massague, J. Mechanism of TGF-β Signaling from Cell Membrane to the Nucleus. Cell 2003, 113, 685-700.
3. Leask, A.; Abraham, D. J. TGF-beta Signaling and the Fibrotic Response. FASEB J. 2004, 17, 816-827.
4. Agrotis, A.; Kalinina, N.; Bobik, A. Transforming Growth Factor-beta and Smad Signaling and Cardiovascular Disorders. Curr. Vasc. Pharmacol. 2005, 3, 55-61.
5. Elliott, R. L.; Blobe, G. C. Role of Transforming Growth Factor Beta in Human Cancer. J. Clin. Oncol. 2005, 23, 2078-2093.
6. Bello-DeOcampo, D.; Tindall, D. J. TGF-beta1/Smad Signaling in Prostate Cancer. Curr. Drug Targets 2003, 4, 197-207.
7. Gold, L. I. The Role for Transforming Growth Factor-beta (TGF-beta) in Human Cancer. Crit. Rev. Oncog. 1999, 10, 303-360.
8. For review: Yingling, J. M.; Blanchard, K. L.; Sawyer, J. S. Development of TGF-β Signaling Inhibitors for Cancer Therapy. Nat. Rev. Drug Discovery 2004, 3, 1011-1022.
9. Furuta, T.; Sakai, T.; Senga, T.; Osawa, T.; Kubo, K.; Shimizu, T.; Suzuki, R.; Yoshino, T.; Endo, M.; Miwa, A. Identification of Potent and Selective Inhibitors of PDGF Receptor Autophosphorylation. J. Med. Chem. 2006, 49, 2186-2192.
10. Shimizu, T.; Fujiwara, Y.; Osawa, T.; Sakai, T.; Kubo, K.; Kubo, K.; Nishitoba, T.; Murooka, H.; Iwai, A.; Fukushima, K.; Yoshino, T.; Miwa, A. Orally Active Anti-Proliferation Agents: Novel Diphenylamine Derivatives as FGF-R2 Autophosphorylation Inhibitors. Bioorg. Med. Chem. Lett. 2004, 14, 2935-2940.
11. Kubo, K.; Shimizu, T.; Ohyama, S.; Murooka, H.; Iwai, A.; Nakamura, K.; Hasegawa, K.; Kobayashi, Y.; Takahashi, N.; Takahashi, K.; Kato, S.; Izawa, T.; Isoe, T. Novel Potent Orally Active Selective VEGFR-2 Tyrosine Kinase Inhibitors: Synthesis, Structure-Activity Relationship, and Antitumor Activities of N-Phenyl-N′-{4-(4-quinolyloxy)phenyl}-ureas. J. Med. Chem. 2005, 48, 1359-1366.
12. i of 0.15 μM.
13. Jonk, L. J.; Itoh, S.; Heldin, C. H.; ten Dijke, P.; Kruijer, W. Identification and Functional Characterization of a Smad Binding Element (SBE) in the JunB Promoter That Acts as a Transforming Growth Factor-beta, Activin, and Bone Morphogenese Protein-Inducible Enhancer. J. Biol. Chem. 1998, 273, 21145-21152.