Modification of a promiscuous inhibitor shifts the inhibition from γ-secretase to FLT-3

…, S Kolb, R Schubenel, K Baumann, B Schmidt

Index: Amombo, Ghislaine Marlyse Okala; Kramer, Thomas; Lo Monte, Fabio; Goering, Stefan; Fach, Matthias; Smith, Steven; Kolb, Stephanie; Schubenel, Robert; Baumann, Karlheinz; Schmidt, Boris Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 24 p. 7634 - 7640

Full Text: HTML

Citation Number: 3

Abstract

The inhibition of FLT-3 activity is an interesting target for the treatment of acute myeloid leukemia (AML). The serendipitous identification of FLT-3 inhibitors from a CK1/γ-secretase programme provided compounds with dual inhibitory activity. We analyzed the structure– activity relationship of these inhibitors and derivatized them to arrive at compounds with reduced impact on γ-secretase activity and enhanced FLT-3 inhibition.

Related Articles:

Inhibition of γ-secretase by the CK1 inhibitor IC261 does not depend on CK1δ

[Hoettecke, Nicole; Liebeck, Miriam; Baumann, Karlheinz; Schubenel, Robert; Winkler, Edith; Steiner, Harald; Schmidt, Boris Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 9 p. 2958 - 2963]

Synthesis of 2-phenylthiazolidine derivatives as cardiotonic agents. II. 2-(Phenylpiperazinoalkoxyphenyl) thiazolidine-3-thiocarboxamides and the corresponding …

[Nate; Matsuki; Tsunashima; Ohtsuka; Sekine; Oda; Honma; Ishida; Nakai; Wada Chemical and Pharmaceutical Bulletin, 1987 , vol. 35, # 6 p. 2394 - 2411]

New benzylidenethiazolidinediones as antibacterial agents

[Heerding, Dirk A.; Christmann, Lisa T.; Clark, Tammy J.; Holmes, David J.; Rittenhouse, Stephen F.; Takata, Dennis T.; Venslavsky, Joseph W. Bioorganic and Medicinal Chemistry Letters, 2003 , vol. 13, # 21 p. 3771 - 3773]

Relationship between chemical structure and anticonvulsive activity in 4, 4′-(α, ω-alkylenedioxy) diphenylsuccinimides

[Nesunts, N. S.; Avetisyan, S. A.; Dzhagatspanyan, I. A.; Akopyan, N. E.; Mndzhoyan, O. L. Pharmaceutical Chemistry Journal, 1983 , vol. 17, # 7 p. 480 - 484 Khimiko-Farmatsevticheskii Zhurnal, 1983 , vol. 17, # 7 p. 801 - 806]

More Articles...