Title:
DNA-PK阻害薬
Document Type and Number:
Japanese Patent JP4332032
Kind Code:
B2
Abstract:
The invention relates to the use of compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, in the preparation of a medicament for inhibiting the activity of DNA-PK, wherein R1 and R2 are independently hydrogen, an optionally substituted C1-7 alkyl group, C3-20 heterocyclyl group, or C5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; X and Y are selected from CR4 and O, O and CR′4 and NR″4 and N, where the unsaturation is in the appropriate place in the ring, and where one of R3 and R4 or R′4 is an optionally substituted C3-20 heteroaryl or C5-20 aryl group, and the other of R3 and R4 or R′4 is H, or R3 and R4 or R″4 together are —A—B—, which collectively represent a fused optionally substituted aromatic ring. The compounds also selectively inhibit the activity of DNA-PK compared to PI 3-kinase and/or ATM.
Inventors:
Griffin, Roger, John
Golding, Bernard, Thomas
Newell, David, Richard
Calvert, Hillary, Alan
Curtin, Nikola, Jane
Hardcastle, ian, robert
Martin, Niort, Morrison, Bur
Smith, Graeme, Cameron, Murray
Rigoro, Laurent, Jean, Martin
Cockcroft, xiao-lin, fan
Rho, Vincent, Juniors, Min-Ray
Workman, paul
Renault, Florence, Elaine
Natrey, bernard, paul
Golding, Bernard, Thomas
Newell, David, Richard
Calvert, Hillary, Alan
Curtin, Nikola, Jane
Hardcastle, ian, robert
Martin, Niort, Morrison, Bur
Smith, Graeme, Cameron, Murray
Rigoro, Laurent, Jean, Martin
Cockcroft, xiao-lin, fan
Rho, Vincent, Juniors, Min-Ray
Workman, paul
Renault, Florence, Elaine
Natrey, bernard, paul
Application Number:
JP2003528797A
Publication Date:
September 16, 2009
Filing Date:
August 14, 2002
Export Citation:
Assignee:
CANCER RESEARCH TECHNOLOGY LIMITED
International Classes:
C07D265/30; A61K31/352; C07D311/22; A61K31/4025; A61K31/427; A61K31/453; A61K31/496; A61K31/519; A61K31/5375; A61K31/5377; A61K31/538; A61K31/541; A61K31/55; A61P9/00; A61P31/14; A61P35/00; A61P43/00; C07D309/38; C07D311/92; C07D405/04; C07D405/10; C07D405/12; C07D407/04; C07D407/12; C07D409/04; C07D409/12; C07D411/04; C07D413/04; C07D417/04; C07D453/02; C07D471/04
Domestic Patent References:
| JP5501886A | ||||
| JP4502322A | ||||
| JP5509302A |
Foreign References:
| WO2001053266A1 | ||||
| WO1999039720A1 |
Other References:
VLAHOS, C. J., et al.,A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-benzopyran-4-one(LY294002),Journal of Biological Chemistry,1994年,269(7),p. 5241-5248
ROMA, G., et al.,Pyran derivatives XX. 2-Aminochromone benzo-fused derivatives with antiproliferative properties ,Farmaco,1998年,53(7),p. 494-503
ROMA, G., et al.,Synthesis, antiplatelet activity and comparative molecular field analysis of substituted 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones, their congeners and isosteric analogues,Bioorganic & Medicinal Chemistry,2000年,8(4),p. 751-768
ERMILI, A., et al.,Chemical and pharmacological research on pyran derivatives. Note VI. 2-(Dialkylamino)-4-oxo-4H-naphthol[1,2-b]pyrans and derivatives,Farmaco Edizione Scientifica,1976年,31(9),p. 627-648
IZZARD, R. A., et al.,Competitive and Noncompetitive Inhibitor of the DNA-dependent Protein Kinase,CANCER RESEARCH,1999年,59,p. 2581-2586
ROSENZWEIG, K. E., et al.,Radiosensitization of Human Tumor Cells by the Phosphatidylinositol 3-Kinase Inhibitors Wortmannin and LY294002 Correlates with Inhibition of DNA-dependent Protein Kinase and Prolonged G2-M Delay,Clinical Cancer Research,1997年,3,p. 1149-1156
FUKUCHI, K., et al.,Phosphatidylinositol 3-kinase inhibitors, Wortmannin or LY294002, inhibited accumulation of p21 protein after γ-irradiation by stabilization of the protein,Biochimica et Biophysica Acta,2000年,1496,p. 207-220
ROMA, G., et al.,Pyran derivatives XX. 2-Aminochromone benzo-fused derivatives with antiproliferative properties ,Farmaco,1998年,53(7),p. 494-503
ROMA, G., et al.,Synthesis, antiplatelet activity and comparative molecular field analysis of substituted 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones, their congeners and isosteric analogues,Bioorganic & Medicinal Chemistry,2000年,8(4),p. 751-768
ERMILI, A., et al.,Chemical and pharmacological research on pyran derivatives. Note VI. 2-(Dialkylamino)-4-oxo-4H-naphthol[1,2-b]pyrans and derivatives,Farmaco Edizione Scientifica,1976年,31(9),p. 627-648
IZZARD, R. A., et al.,Competitive and Noncompetitive Inhibitor of the DNA-dependent Protein Kinase,CANCER RESEARCH,1999年,59,p. 2581-2586
ROSENZWEIG, K. E., et al.,Radiosensitization of Human Tumor Cells by the Phosphatidylinositol 3-Kinase Inhibitors Wortmannin and LY294002 Correlates with Inhibition of DNA-dependent Protein Kinase and Prolonged G2-M Delay,Clinical Cancer Research,1997年,3,p. 1149-1156
FUKUCHI, K., et al.,Phosphatidylinositol 3-kinase inhibitors, Wortmannin or LY294002, inhibited accumulation of p21 protein after γ-irradiation by stabilization of the protein,Biochimica et Biophysica Acta,2000年,1496,p. 207-220
Attorney, Agent or Firm:
Yusuke Hiraki
Ishii Teiji
Satoshi Fujita
Eiichi Arai
Ishii Teiji
Satoshi Fujita
Eiichi Arai