Thiolated paclitaxels for reaction with gold nanoparticles as drug delivery agents
View Patent ↗Thioloated taxane derivatives are linked to colloidal metal particles such as gold nanoparticles for use as antitumor agents. The antitumor agents may be targeted to tumors.
1. A compound of formula 1
wherein
R 1 is phenyl, tert-butoxy, or C 1-6 alkyloxy;
R 2 is phenyl, 4-fluorophenyl, 4-methylphenyl, 2-furanyl, 2-thienyl, isopropyl, isobutenyl, cyclopropyl, 3-furanyl, 3-thienyl, or 2-propenyl;
R 3 is benzoyl, m-methoxybenzoyl, m -azidobenzoyl, or m -chlorobenzoyl;
R 4 is C(O)R x where R x is: H; C 1-6 alkyl, optionally substituted with one to six halogen atoms, which may be the same or different; C 3-6 cycloalkyl; or C 2-6 alkenyl or hydroxyl;
R 5 is H; or methyl; or C(O)R x , where R x is: H, C 1-6 alkyl, optionally substituted with one to six halogen atoms, which may be the same or different; C 3-6 cycloalkyl; C 2-6 alkenyl or hydroxyl; and
M1 is sulfur bearing substituent linked to a colloidal metal particle, wherein the compound has a structure selected from the group consisting of structures 2-4, 6-11, 16-18, 27 and 33
where n is an integer between 0 and 100, and X is said colloidal metal nanoparticle.
2. The compound as set forth in claim 1 , wherein said colloidal metal nanoparticle contains gold.
3. A compound of formula 1
wherein
R 1 is phenyl, tert-butoxy, or C 1-6 alkyloxy;
R 2 is phenyl, 4-fluorophenyl, 4-methylphenyl, 2-furanyl, 2-thienyl, isopropyl, isobutenyl, cyclopropyl, 3-furanyl, 3-thienyl, or 2-propenyl;
R 3 is benzoyl, m-methoxybenzoyl, m -azidobenzoyl, or m -chlorobenzoyl;
R 4 is C(O)R x where R x is: H; C 1-6 alkyl, optionally substituted with one to six halogen atoms, which may be the same or different; C 3-6 cycloalkyl; or C 2-6 alkenyl or hydroxyl;
R 5 is H; or methyl; or C(O)R x , where R x is: H, C 1-6 alkyl, optionally substituted with one to six halogen atoms, which may be the same or different; C 3-6 cycloalkyl; C 2-6 alkenyl or hydroxyl; and
M1 is a thiopyridyl or lipoic acid sulphur-bearing substituent.
4. The compound of claim 3 , wherein the compound has a structure selected from the group consisting of structures 12-16, 20, 60, 64 and 70
where * is a chiral center.
5. The compound of claim 3 , wherein the compound has a structure selected from the group consisting of structures 19, 36, 6, 13, 5.1B, 28, 47, 74, 54 and 56