Claims for Patent: 7,763,615

Summary for Patent: 7,763,615

Title:	Ecteinascidin analogs for use as antitumour agents
Abstract:	Derivatives of ecteinascidin 736 of general formula (I) wherein the groups R1, R2, R3, R4 and R5 are each independently selected from the group consisting of H, OH, OR′, SH, SR′, SOR′, SO2R′, C(═O)R′, C(═O)OR′, NO2, NH2, NHR′, N(R′)2, NHC(O)R′, CN, halogen, ═O, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic; wherein X is independently selected of OR′, CN, (═O), or H; wherein each of the R′ groups is independently selected from the group consisting of H, OH, NO2, NH2, SH, CN, halogen, ═O, C(═O)H, C(═O)CH3, CO2H, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted aryl; wherein m is 0, 1 or 2; and wherein n is 0, 1, 2, 3, or 4, and their use as antitumoral agent.
Inventor(s):	Pilar Gallego, Carmen Cuevas, Simon Munt, Ignacio Manzanares, Valentin Martinez
Assignee:	Pharmamar SA
Application Number:	US10/485,536
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,763,615
Patent Claims:	1. A compound of the general formula I: wherein R1 is OH, OR′, SH, SR′, SOR′, SO2R′, NO2, NH2, NHR′, N(R′)2, NHC(═O)R′, CN, halogen, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted carbocyclic aryl selected from phenyl, naphthyl, biphenyl, phenanthryl and anthracyl, substituted or unsubstituted heterocyclic selected from coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholinyl and pyrrolidinyl; R2, R3, R4, and R5 are each independently selected from H, OH, OR′, SH, SR′, SOR′, SO2R′, C(═O)R′, C(═O)OR′, NO2, NH2, NHR′, N(R′)2, NHC(═O)R′, CN, halogen, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted carbocyclic aryl selected from phenyl, naphthyl, biphenyl, phenanthryl and anthracyl, and substituted or unsubstituted heterocyclic selected from coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholinyl and pyrrolidinyl; wherein X is independently selected from OR′, CN, (═O), and H; wherein each of the R′ groups is independently selected from the group consisting of H, OH, NO2, NH2, SH, CN, halogen, ═O, C(═O)H, C(═O)CH3, CO2H, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, and substituted or unsubstituted carbocyclic aryl selected from phenyl, naphthyl, biphenyl, phenanthryl and anthracyl; wherein m is 0, 1 or 2; and wherein n is 1, 2, 3 or 4. 2. A compound according to claim 1, wherein: R1 is hydroxy, halogen, alkyl, alkoxy or aralkyl; R2 and R3 are each independently selected from hydrogen, C(═O)R′, COOR′, and optionally substituted alkyl and optionally substituted alkenyl, wherein R′ is optionally substituted alkyl or optionally substituted alkenyl and wherein the optional substituents being chosen from halo, amino, amino derived from amino acid, carbocyclic aryl selected from phenyl, naphthyl, biphenyl, phenanthryl and anthracyl, or heterocyclic selected from coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholinyl and pyrrolindinyl; R4 is hydrogen, alkyl, alkenyl or C(═O)OR′, where R′ is alkenyl; R5 is hydrogen or alkyl; X is hydrogen, hydroxy, cyano or (═O); m is 0 or 1; and n is 1. 3. A compound according to claim 1, wherein R1 is hydroxy, fluorine, methyl, methoxy or benzyloxy, and n is 1. 4. A compound according to claim 1, wherein R2 is hydrogen, acetyl, trifluoromethylcarbonyl, heptafluorobutyryl, 3-chloropropionyl, cinnamoyl, t-butyl-O—CO—, allyl-O—CO— or vinyl-O—CO. 5. A compound according to claim 1 wherein R3 is hydrogen, allyl, CH3—(CH2)n—CO— where n is 1, 2, 4, 6, 12, 14 or 16; t-butyl-O—CO—, allyl-O—CO— or vinyl-O—CO. 6. A compound according to claim 1 wherein R4 is hydrogen, C1 to C3 alkyl, allyl, or vinyl-O—CO. 7. A compound according to claim 1 wherein R5 is hydrogen or methyl and m is 1. 8. A compound according to claim 1, wherein X is hydroxy. 9. A compound according to claim 1 wherein R2 is not acetyl. 10. A compound according to claim 1 wherein R3 is not hydrogen. 11. A compound according to claim 1 wherein R5 is not hydrogen. 12. A pharmaceutical composition which comprises a compound according to claim 1 together with a pharmaceutically acceptable diluent. 13. A method for the treatment of lung cancer, colon cancer, kidney cancer, prostate cancer, cervical cancer, ovarian cancer, breast cancer, pancreatic cancer, leukaemia or melanoma in a mammal, comprising administering to a mammal in need of such treatment an effective amount of a compound of general formula according to claim 1. 14. A compound according to claim 2, wherein R1 is hydroxy, fluorine, methyl, methoxy or benzyloxy, and n is 1. 15. A compound according to claim 2 wherein R2 is hydrogen, acetyl, trifluoromethylcarbonyl, heptafluorobutyryl, 3-chloropropionyl, cinnamoyl, t-butyl-O—CO—, allyl-O—CO— or vinyl-O—CO. 16. A compound according to claim 2 wherein R3 is hydrogen, allyl, CH3—(CH2)n—CO— where n is 1, 2, 4, 6, 12, 14 or 16, t-butyl-O—CO—, allyl-O—CO— or vinyl-O—CO—. 17. A compound according to claim 2 wherein R4 is hydrogen, C1 to C3 alkyl, allyl or vinyl-O—CO—. 18. A compound according to claim 2 wherein R5 is hydrogen or methyl and m is 1. 19. A compound according to claim 2 wherein X is hydroxy. 20. A compound according to claim 2 wherein X is cyano. 21. A compound according to claim 1 wherein X is cyano. 22. A compound according to claim 1 of formula: 23. A compound according to claim 1 of formula: 24. A compound according to claim 1 of formula: 25. A compound according to claim 1 of formula: 26. A compound according to claim 1 of formula: 27. A compound according to claim 1 of formula: 28. A compound according to claim 1 of formula: 29. A compound according to claim 1 of formula: 30. A compound according to claim 1 of formula: 31. A pharmaceutical composition which comprises a compound according to claim 2 together with a pharmaceutically acceptable diluent. 32. A method for the treatment of lung cancer, colon cancer, kidney cancer, prostate cancer, cervical cancer, ovarian cancer, breast cancer, pancreatic cancer, leukaemia or melanoma in a mammal, comprising administering to a mammal in need of such treatment an effective amount of a compound of general formula according to claim 2.