Pharmaceutical compositions

Details Pharmaceutical compositions Pharmaceutical compositions

C - Chemistry, Metallurgy

07

K

C07K 5/078 (2006.01) A61K 38/05 (2006.01) A61K 47/48 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2710693

Synthesis natural tubulisine derivatives of formula (A) having a high cytotoxicity (see formula A) wherein: B is selected from CH2, CH2-CH2 or CH2-CH2-CH2, D is an aromatic linker, X1 is alkyl or alkenyl, X2 is selected from the X2a, substituted or non substituted, selected from: aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, or heteroaryl--alkyl, X2b: alkylene-O-alkyl, wherein alkylene is C2-C10, X2,: CH2-O-alkyl, X3 is selected from H, or together with X4 forms the group =O, X4 is selected from H, halogen, OH, SH, alkyl, alkenyl, (OR5)n-OR6, OC (O) R7, NR6R7, or together with X4 forms the group =O, R5 is an alkylene, n is zero or an integer from 1 to 10, R6 and R7, equal to or different from each other, have the following meanings: z1: H, alkyl, z2 substituted or non substituted: aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkyl- alkyl, X5 is z2, or has the meaning of z3=alkyl, alkenyl, X6 is selected from NR8R9, OR8, NH-NR8R9, SR8, R10, wherein R8 and R9, equal to or different from each other, have the same meanings of R6, R10 has the same meanings as R6 but excluding H, X7 is z3 or H, X8 is selected from z3, H, halogen, OH, SH, OCH3.

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