Patent CA-2158863-A1 (CA)
Title: Taxanes having a pyridyl substituted side-chain
Inventor: HOLTON ROBERT A
IPC: A61P35/02
Filed: 1994-03-21
Abstract: Taxane derivatives having a pyridyl substituted C13 side-chain. The derivatives are of the formula:    wherein X1 is -OX6, -SX7, or -NX8X9;      X2 is hydrogen, C1-15 alkyl, C1-15 alkenyl, C1-15 alkynyl, C6-15 aryl, or C6-15 heteroaryl;      X3 is hydrogen;      X4 is pyridyl;      X5 is -COX10, or -SO2X11;      X6 is hydrogen, C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, C6-is aryl, C6-15 heteroaryl, or a hydroxy protecting group;      X7 is C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, C6-15 aryl, C6-15 heteroaryl, or sulfhydryl protecting group;      X8 is hydrogen, C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, C6-15 aryl, C6-15 heteroaryl, or heterosubstituted C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, C6-15 aryl or C6-15 heteroaryl;      X9 is an amino protecting group;      X10 is C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, C6-15 aryl, C6-15 heteroaryl, t-butoxy, or heterosubstituted C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, C6-15 aryl or C6-15 heteroaryl;      X11 is C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, C6-15 aryl, C6-15 heteroaryl, -OX10 or -NX8X14:      X14 is hydrogen, C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, C6-is aryl, or C6-15 heteroaryl;      R1 is hydrogen, hydroxy, protected hydroxy or together with R14 forms a carbonate;      R2 is hydrogen, hydroxy, -OCOR31 or together with R2a forms an oxo;      R2a is hydrogen or taken together with R2 forms an oxo or;      R4 is hydrogen, together with R4a forms an oxo, oxirane or methylene, or together with R5a and the carbon atoms to which they are attached form an oxetane ring;      R4a is hydrogen, C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, C6-15 aryl, C6-15 heteroaryl, cyano, hydroxy, -OCOR30, or together with R4 forms an oxo, oxirane or methylene;      R5 is hydrogen or together with R5a forms an oxo;      R5a is hydrogen, hydroxy, protected hydroxy, acyloxy, together with R5 forms an oxo, or together with R4 and the carbon atoms to which they are attached form an oxetane ring;      R6 is hydrogen, C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, C6-15 aryl, or C6-15 heteroaryl, hydroxy, protected hydroxy or together with R6a forms an oxo;      R6a is hydrogen, C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, C6-is aryl, or C6-is heteroaryl, hydroxy, protected hydroxy or together with R6 forms an oxo;      R7 is hydrogen or together with R7a forms an oxo;      R7a is halogen, hydroxy, or together with R7 forms an oxo;      R9 together with R9a forms an oxo;      R10 is hydrogen:      R10a is -OCOR29, hydroxy, or protected hydroxy;      R14 is hydrogen, C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, C6-is aryl, Cg-15 heteroaryl, hydroxy, protected hydroxy or together with R1 forms a carbonate:      R14a is hydrogen, C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, C6-15 aryl, or C6-15 heteroaryl;      R29 and R30, are independently hydrogen, C1-15 alkyl, C1-15 alkenyl, C1-15 alkynyl, monocyclic C6-15 aryl or monocyclic C6-is heteroaryl; and R31 is hydrogen, C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl, phenyl or monocyclic C6-15 heteroaryl.      The derivates are useful as antitumor and antileukemia agents.