Patent ID: 6512003
Filing Date: 2003-01-28
Classification: C07C,C07D,C07K

Abstract:
A method comprising:(a) contacting tubulin with a compound having the structure of formula I: â€ƒwherein: at least one of X1, X2, and X3 is O and the others are C; R1 and R2 are the same or different and are each independently H, provided both R1 and R2 are not H, or (C1-C8)alkyl, (C1-C8)cycloalkyl, (C1-C8)alkoxy, (C1-C8)aryloxy, (C1-C8)arylthio, (C1-C8)aryl, C(&boxH;)NRaRb or NRaRb, wherein Ra and Rb are each independently hydrogen, acyl, (C1-C8)alkyl, (C3-C7)cycloalkyl, (C6-C10)aryl, (C6-C10) heteroaryl, or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, morpholino, or thiomorpholino group, wherein one or more of R1, R2, Ra, and Rb can be substituted with at least one functional group selected from OH, SH, CO2H, halogen, CN, acyl, thioacyl, ester, thioester, (C1-C8)alkoxy, or (C1-C8)aryloxy; n and m are the same or different, and are each independently 0 to 7; S1 and S2 can be the same or different, and are each independently OH, SH, CO2H, halogen, CN, acyl, thioacyl, ester, thioester, (C1-C6)alkoxy, (C1-C6)aryloxy, (C1-C6)alkylthio, (C1-C6)arylthio, (C1-C6)alkyl, (C1-C6)alkenyl, (C1-C6)alkynyl, (C3-C7)cycloalkyl, (C6-C10)aryl, C(&boxH;O)NRaRb, NRaRb, or taken together, any two S1 and S2 can form a ring, and any two adjacent substituents can form a double bond between the two carbons to which they are attached, wherein S1 and S2 can be substituted with at least one functional group selected from OH, SH, CO2H, halogen, CN, acyl, thioacyl, ester, thioester, (C1-C8)alkoxy, or (C1-C8)aryloxy; and wherein said contacting inhibits polymerization of tubulin or induces depolymerization of tubulin.