초록

Derivatives of Et-743 or Et-770 or Et-729 are provided. The derivatives are of the general formula (Ia) wherein the substituent groups take various permitted meanings.

대표청구항 ▼

The invention claimed is: 1. A compound of the general formula Ia: wherein R1, R2, and R5 are each independently selected from H, C(═O)R′, C(═O)OR′, P═O(OR′)2, substituted or unsubstituted C1-C18 alkyl, substituted or unsubstituted C2-C18 alkenyl, substi

The invention claimed is: 1. A compound of the general formula Ia: wherein R1, R2, and R5 are each independently selected from H, C(═O)R′, C(═O)OR′, P═O(OR′)2, substituted or unsubstituted C1-C18 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted C6-C18 carbocyclic aryl; wherein R6 and R7 are both ═O and the dotted lines indicate a quinone ring, or R6 is —OR3, where R3 is H, C(═O)R′, C(═O)OR′, substituted or unsubstituted C1-C18 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted C6-C18 carbocyclic aryl, R7 is H, and the dotted lines indicate a phenyl ring; wherein X2, X3, X4, X5, X6 are 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, unsubstituted C1-C24 alkyl, unsubstituted C2-C18 alkenyl, unsubstituted C2-C18 alkynyl, unsubstituted C6-C18 carbocyclic aryl, and unsubstituted heteroaromatic selected from coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, and benzothiazolyl; wherein X1 is independently selected from OR1, CN, (═O), or H; wherein when R1, R2, R3, R4, and R5 are substituted, the substituents are each independently selected from the group consisting of OH, OR′, SH, SR′, SOR′, SO2R′, C(═O)R′, C(═O)OR′, NO2, NH2, NHR′, N(R′)2, NHC(O)R′, CN, halogen, ═O, unsubstituted C1-C18 alkyl, unsubstituted C2-C18 alkenyl, unsubstituted C2-C18 alkynyl, unsubstituted C6-C18 carbocyclic aryl, and unsubstituted heterocyclic selected from coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholino and pyrrolindinyl; wherein each of the R′ groups is independently selected from the group consisting of H, OH, NO2, NH2, SH, CN, halogen, C(═O)H, C(═O)CH3; CO2H, PO(OR′)2, substituted or unsubstituted C1-C18 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, and substituted or unsubstituted C6-C18 carbocyclic aryl; wherein R4 is selected from C(═O)R′, C(═O)OR′, P═O(OR′)2, substituted or unsubstituted C2-C18 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, and substituted or unsubstituted C6-C18 carbocyclic aryl; wherein when R4 is C(═O)R′, C(═O)OR′, or P═O(OR′)2, then each of the R′ groups is independently selected from the group consisting of H, OH, NO2, NH2, SH, CN, halogen, C(═O)H, C(═O)CH3, CO2H, PO(OR′)2, substituted or unsubstituted C2-C18 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, and unsubstituted C6-C18 carbocyclic aryl; and wherein when R′ is substituted, the substituents are each independently selected from the group consisting of halogen, cyano, hydroxyl, nitro, azido, unsubstituted C1-C6 alkanoyl, carboxamido, unsubstituted C1-C12 alkyl, unsubstituted C2-C12 alkenyl, unsubstituted C2-C12 alkynyl, unsubstituted C1-C12 alkoxy, unsubstituted C6-C18 carbocyclic aryloxy, unsubstituted C1-C12 alkylthio, unsubstituted C1-C12 alkylsulfinyl, unsubstituted C1-C12 alkylsulfonyl, unsubstituted C1-C12 aminoalkyl, unsubstituted C6-C18 carbocyclic aryl, unsubstituted aralkyl and unsubstituted heterocyclic group which is selected from coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholino and pyrrolindinyl. 2. A compound according to claim 1, wherein: R6 is OR3; R1 and R3 are independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, C(═O)R′, or C(═O)OR′, where R′ is optionally substituted alkyl or optionally substituted alkenyl, the optional substituents being chosen from halo, amino, amino derived from amino acid, unsubstituted C6-C18 carbocyclic aryl or unsubstituted heterocyclic, which is selected from coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholino and pyrrolindinyl; R2 is hydrogen, alkyl or C(═O)OR′, where R′ is alkyl; R5 is hydrogen, alkyl or C(═O)OR′, where R′ is alkenyl; X1 is hydrogen, hydroxy, or cyano; X2, X4 and X5 are hydrogen; X3 is OR′, where R′ is alkyl; X6 is hydrogen or unsubstituted alkyl; R7 is hydrogen; and the dotted lines indicate a phenyl ring. 3. A compound according to claim 1, wherein R1 is: hydrogen; alkyl; C(═O)R′, where R′ is optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted heterocyclicalkyl, optionally substituted aminoalkyl, optionally substituted arylalkenyl, optionally substituted alkenyl, optionally substituted aralkyl; or C(═O)OR′, where R′ is alkyl or alkenyl. 4. A compound according to claim 1, wherein R2 is hydrogen, methyl, or alkoxycarbonyl. 5. A compound according to claim 1, wherein R3 is: hydrogen; alkyl; (C═O)R′, where R′ is optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclicalkyl, optionally substituted alkenyl, optionally substituted aralkyl; or (C═O)OR′, where R′ is alkyl, alkenyl, or aralkyl. 6. A compound according to claim 1,. wherein R4 is: C(═O)R′, where R′ is optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted aralkyl, optionally substituted arylalkenyl, optionally substituted aminoalkyl, optionally substituted heterocyclicalkyl; or (C═O)OR′, where R′ is alkyl, alkenyl, or aralkyl. 7. A compound according to claim 1, wherein R5 is: hydrogen; alkyl; (C═O)OR′, where R′ is alkenyl. 8. A compound according to claim 1, wherein X1 is hydrogen, hydroxy, or cyano. 9. A compound according to claim 1, wherein X2 is hydrogen. 10. A compound according to claim 1, wherein X3 is OR′, where R′ is alkyl. 11. A compound according to claim 1, wherein X4 is hydrogen. 12. A compound according to claim 1 ,wherein X5 is hydrogen. 13. A compound according to claim 1, wherein X6 is hydrogen or alkyl. 14. A compound according to claim 1, wherein R1 is C(═O)R′, where R′ is optionally substituted alkyl with at least 4 carbon atoms or optionally substituted alkenyl. 15. A compound according to claim 14, wherein the optional substituent of R1 is unsubstituted C6-C18 carbocyclic aryl or unsubstituted heterocyclic, which is selected from coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholino and pyrrolindinyl, or R′ is derived from an optionally protected amino acid. 16. A compound according to claim 1, wherein R3 is: hydrogen; C1-C6 alkyl; cinnamoyl; (C═O)R′ where R′ is C1-C18 alkyl, perfluoroC1-C4 alkyl, heterocyclicalkyl containing an alkyl of 1 to 6 carbon atoms with a unsubstituted ω-heterocyclic substituent which is selected from coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholino and pyrrolindinyl, allyl, or benzyl; or (C═O)OR′ where R′ is C1-C6 alkyl, vinyl, allyl, or benzyl. 17. A compound according to claim 1, wherein R4 is: unsubstituted cinnamoyl; or (C═)R′, where R′ is C12-C18 alkyl, ω-chloro- or perfluoro- C2-C4 alkyl, phenethyl, aminoacid, heterocyclicalkyl containing an alkyl of 2 to 6 carbon atoms with a unsubstituted ω-heterocyclic substituent which is selected from coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholino and pyrrolindinyl; or (C═O)OR′, where R′ is C2-C6 alkyl, vinyl, or allyl. 18. A pharmaceutical composition comprising a compound according to claim 1, and a pharmaceutical carrier. 19. A method of treating lung cancer, colon cancer, kidney cancer, prostate cancer, ovarian cancer, breast cancer, pancreas cancer, leukaemia or melanoma in a subject, which comprises administering to the subject a compound according to claim 1. 20. A compound according to claim 1 of formula: