- Discovery of ortho-carborane-conjugated triazines as selective topoisomerase I/II inhibitors
-
The cell growth inhibition profile of 2,4-(2-methyl-ortho-carboranyl)-4- (dimethylamino)-1,3,5-triazine (TAZ-6) was found to be similar to that of ICRF-193, a topoisomerase II inhibitor, as revealed by COMPARE analysis (correlation coefficient (r)≤0.724). Various mono-and di-ortho-carborane- substituted 1,3,5-triazines were synthesized based on the structure of TAZ-6 and tested for their ability to inhibit cell growth and the activities of topoisomerases I and II. Among the compounds synthesized, 3c, 4c, and 4f completely inhibited topoisomerase I activity without affecting topoisomerase II activity, whereas 3a and 3d completely inhibited topoisomerase II activity without affecting topoisomerase I activity, at 100μM.
- Nakamura, Hiroyuki,Shoji, Atsushi,Takeuchi, Ayano,Ban, Hyun Seung,Lee, Jong-Dae,Yamori, Takao,Kang, Sang Ook
-
scheme or table
p. 1430 - 1437
(2012/02/06)
-
- Treatment of prostate cancer, melanoma or hepatic cancer
-
The present application describes a method of treating prostate cancer, melanoma or hepatic cancer in a subject in need thereof, the method comprising administering to said subject a therapeutically effective amount of the heterocyclic compound represented by Formula I or its pharmaceutically acceptable salt:
- -
-
Page/Page column 4
(2008/06/13)
-
- 2-CYANO-1,3,5-TRIAZINE-4,6-DIAMINE DERIVATIVES
-
The invention relates to the use of a 2-cyano-1,3,5-triazine -4,6-diamine derivative having general formula (I), wherein R1 is (C1-6)alkyl, (C3-8)cycloalkyl, aryl, aryl(C1-4)alkyl, aryloxy(C1-4)alkyl, heteroaryl or heteroaryloxy(C1-4)alkyl; R2 is H or (C1-4)alkyl; or R1 and R2 together with the nitrogen to which they are bound form a 4-8 membered heterocyclic ring, optionally further comprising 1 or more heteroatoms selected from O, S or NR5, which ring may be substituted with (C1-4)alkyl, (C3-8)cycloalkyl, aryl, aryl(C1-4)alkyl or NR6R7,and which ring may be fused to a benzene ring; R3 is (C1-6)alkyl, (C3-8) cycloalkyl (optionally comprising 1 or more heteroatoms selected from O, S or NR8), aryl, aryl(C1-4)alkyl or heteroaryl; R4 is H or (C1-4)alkyl; or R3 and R4 together with the nitrogen to which they are bound form a 4-8 membered heterocyclic ring, optionally further comprising 1 or more heteroatoms selected from O, S or NR9; R5, R8 and R9 are independently H, (C1-4)alkyl, (C3-8) cycloalkyl, aryl or aryl(C1-4)alkyl; R6 and R7 are independently H or (C1-4)alkyl; or R6 and R7 form together with the nitrogen to which they are bound a 4-8 membered heterocyclic ring; or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment of osteoporosis and atherosclerosis.
- -
-
Page/Page column 14
(2010/02/10)
-
- AZOLE METHYLIDENE CYANIDE DERIVATIVES AND THEIR USE AS PROTEIN KINASE MODULATORS
-
The present invention is related to azole derivatives notably for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such azole derivatives. Said azole derivatives are modulators of the protein kinase signalling pathways, particularly the one involving c-Jun N-terminal kinase and/or Glycogen Kinase Synthase 3. The present invention is furthermore related to novel azole derivatives as well as to methods of their preparation. X is O, S or NR0, with R0 being H or an unsubstituted or substituted C1 -C6 alkyl; A is 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl or triazinyl group.
- -
-
-