Novel bicyclic pyrazoles as potent ALK2 (R206H) inhibitors for the treatment of fibrodysplasia ossificans progressiva
Mutant activin receptor-like kinase-2 (ALK2) is associated with the pathogenesis of fibrodysplasia ossificans progressiva, making it an attractive target for therapeutic intervention. We synthesized a new series of bicyclic pyrazoles and evaluated their mutant ALK2 enzyme inhibitory activities, leading to the identification of 8 as the most potent inhibitor. This compound showed moderate microsomal metabolic stability and human ether-a-go-go related gene (hERG) safety. In C2C12 cells carrying mutant ALK2 (R206H), 8 efficiently inhibited the bone morphogenetic protein (BMP)-induced alkaline phosphatase activity.
14B(R) isomers of novel tetracyclic compounds having anti-allergic and anti-asthmatic activities, and their use
An optically active compound of formula (I): STR1 in which R3 represents groups of formula --A--COOR4, wherein A represents alkylene groups having 3 or 5 carbon atoms and R4 represents hydrogen or an alkyl group having 1 to 4 carbon atoms; or a pharmaceutically acceptable salt thereof.
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(2008/06/13)
Tetracyclic compounds having anti-allergic and anti-asthmatic activities and their use
Compounds of formula (I): STR1 in which: Q is nitrogen or =CH--; R1 and R2 are hydrogen, alkyl, alkoxy, hydroxy, trifluoromethyl or halogen; and R3 is a substituted alkyl groups or a pharmaceutically acceptable salt thereof have valuable anti-allergic and anti-asthmatic activities. The compounds are prepared by reacting a corresponding compound where R3 is replaced by a hydrogen atom with a compound to introduce the group R3.
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(2008/06/13)
Antibacterial agents, and 4-thio azetidinone intermediates
This invention relates to 2-substituted and 2,6-disubstituted penem compounds of the formula STR1 wherein Y is hydrogen, halo or certain organic substituents and X represents certain organic substituents. Also included in the invention are pharmaceutically acceptable salts of the above compounds and derivatives of the above compounds in which the carboxyl group at the 3-position is protected as by an easily removable ester protecting group. The compounds of the present invention are potent antibacterial agents or are of use as intermediates in the preparation of such agents.
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(2008/06/13)
2,6-Disubstituted penem compounds
This invention relates to 2-substituted and 2,6-disubstituted penem compounds of the formula STR1 wherein Y is hydrogen, halo or certain organic radicals and X represents certain hetero-interrupted substituted alkyl radicals. Also included in the invention are pharmaceutically acceptable salts of the above compounds and derivatives of the above compounds in which the carboxyl group at the 3-position is protected as by an easily removable ester protecting group. The compounds of the present invention are potent antibacterial agents or are of use as intermediates in the preparation of such agents.