- COMPOUNDS AND COMPOSITIONS AS SYK KINASE INHIBITORS
-
Provided herein area novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated Syk kinase activity.
- -
-
Page/Page column 92
(2011/02/24)
-
- Synthesis and pharmacological properties of N-[4-[4-(1H-indol-3- yl)piperidinoalkyl]-2-thiazolyl]alkanesulfonamides as novel antiallergic agents
-
A number of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2- thiazolyl]alkanesulfonamides (8-21) were synthesized and evaluated for their preventive effects on systemic anaphylaxis in guinea pigs. Structure-activity analysis revealed that methane- and ethanesulfonamide derivatives having a one to three methylene tether between the piperidine and thiazole rings exhibited potent activity but the introduction of a substituent on the indole part reduced the activity. Administration (100 mg/kg p.o.) of the four compounds 8, 9, 12, 13, together with ketotifen, oxatomide, terfenadine and azelastine as reference compounds, to mice revealed that only compound 8 caused no significant increase of the sleeping time induced by hexobarbital. In addition, compound 8 (10 mg/kg i.v.) did not change the electroencephalogram in conscious rabbits. These results led to the selection of N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2-thiazolyl]methanesulfonamide (8, FK613) for further development as a novel antiallergic agent. Clinical evaluation of FK613 is now in progress.
- Shigenaga,Manabe,Matsuda,Fujii,Hiroi,Matsuo
-
p. 1589 - 1595
(2007/10/02)
-