| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
In the course of our synthetic studies on a novel p21ras farnesyltransferase inhibitor, TAN-1813, a new method for construction of maleimide and a new coupling reaction of maleimide using phenylthio group as a leaving group were successfully developed. The reaction was applied to the coupling reaction of the maleimide segment with the decalin segment, which afforded the advanced key intermediate possessing whole carbon skeleton with all asymmetric carbon centers and functional groups present in the natural product.
A new synthetic route for the synthesis of FK228 analogues as novel HDAC inhibitors, was developed in a highly convergent and unified manner. Eight analogues were synthesized, and their biological evaluation disclosed novel aspects of structure-activity relationships. Further investigation of FK228 analogues identified FK-A11 as a promising candidates for novel anticancer agent. FK-A11 is currently conducting preclinical studies in Tohoku University Hospital.
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