초록 ▼

Provided herein are compounds for detection, diagnosis and treatment of target tissues or target compositions, including hyperproliferative tissues such as tumors, using photodynamic methods. In particular, photosensitizer compounds that collect in hyperproliferative tissue are provided. In another

Provided herein are compounds for detection, diagnosis and treatment of target tissues or target compositions, including hyperproliferative tissues such as tumors, using photodynamic methods. In particular, photosensitizer compounds that collect in hyperproliferative tissue are provided. In another embodiment, compounds that absorb light at a wavelength of from about 700 to about 850 nm are provided. In a further embodiment, compounds that are detectable by magnetic resonance imaging are provided.

대표청구항 ▼

1. A compound of the formula: or a pharmaceutically acceptable derivative thereof, wherein: R1 and R2 are each independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, —C(O)Ra or —COORa, or —CH(CH3)(ORa) or —CH(CH3)(O(CH2)nXRa) where Ra is hydrogen, substituted or uns

1. A compound of the formula: or a pharmaceutically acceptable derivative thereof, wherein: R1 and R2 are each independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, —C(O)Ra or —COORa, or —CH(CH3)(ORa) or —CH(CH3)(O(CH2)nXRa) where Ra is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted cycloalkyl; where R2 may be —CH═CH2, —CH(OR20) CH3, —C(O)Me, —(═NR21)CH3 or —CH(NHR21)CH3 where X is an aryl or heteroaryl group;n is an integer of 0 to 6;where R20 is methyl, butyl, heptyl, docecyl or 3,5-bis(trifluoromethyl)-benzyl; andR21 is 3,5,-bis(trifluoromethyl)benzyl;R1a and R2a are each independently hydrogen or substituted or unsubstituted alkyl, or together form a covalent bond;R3 and R4 are each independently hydrogen or substituted or unsubstituted alkyl;R3a and R4a are each independently hydrogen or substituted or unsubstituted alkyl, or together form a covalent bond;R5 is hydrogen or substituted or unsubstituted alkyl;R6 and R6a are each independently hydrogen or substituted or unsubstituted alkyl, or together form ═O;R7 is a covalent bond, alkylene, azaalkyl, or azaaraalkyl or ═NR20 where R20 is 3,5-bis(tri-fluoromethyl)benzyl or —CH2X—R1 or YR1 where Y is an aryl or heteroaryl group;R8 and R8aare each independently hydrogen or substituted or unsubstituted alkyl or together form ═O;R9 and R10 are each independently hydrogen, or substituted or unsubstituted alkyl and R9 may be —CH2CH2COOR2 where R2 is an alkyl group that may optionally substituted with one or more fluorine atoms;each of R1-R10, when substituted, is substituted with one or more substituents each independently selected from Q, where Q is alkyl, haloalkyl, halo, pseudohalo, —COORb where Rb is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl aryl, heteroaryl, araalkyl, or ORc where Rc is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl, or CONRdRe where Rd and Re are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl, or NRfRg where Rf and Rg are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl, or ═NRh where Rh is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or is an amino acid residue;each Q is independently unsubstituted or is substituted with one or more substituents each independently selected from Q1, where Q1 is alkyl, haloalkyl, halo, pseudohalo, or —COORb where Rb is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl aryl, heteroaryl, araalkyl, or ORc where Rc is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl, or CONRd Re where Rd and Re are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl, or NRfRg where Rf and Rg are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl, or ═NRh where Rh is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl, or is an amino acid residue;with the proviso that the compound contains at least one fluorine atom in at least one 3,5,-bis(trifluoromethyl)benzyl group or in at least one R, R1, or R2 group. 2. The compound of claim 1, wherein: R1 is methyl;R1a and R2a together form a covalent bond;R3 is methyl;R4 is ethyl;R3a and R4a are each independently hydrogen, or together form a covalent bond;R5 is methyl;R9 is CH2CH2COOH or CH2CH2COOMe;R10 is methyl. 3. The compound of claim 1, wherein: R2 is CH═CH2, CH(OR20)CH3, C(O)Me, C(═NR21)CH3 or CH(NHR21)CH3;where R20 is methyl, butyl, heptyl, dodecyl or 3,5-bis(trifluoromethyl)benzyl; andR21 is 3,5-bis(trifluoromethyl)benzyl. 4. The compound of claim 1 having the formula: or a pharmaceutically acceptable derivative thereof. 5. The compound of claim 1 having the formula: or a pharmaceutically acceptable derivative thereof, wherein: R is methyl, butyl, heptyl or dodecyl. 6. The compound of claim 1 having the formula: or a pharmaceutically acceptable derivative thereof, wherein: R is methyl, butyl, heptyl or dodecyl. 7. The compound of claim 1 having the formula: or a pharmaceutically acceptable derivative thereof. 8. The compound of claim 1 having the formula: or a pharmaceutically acceptable derivative thereof, wherein: R is methyl, butyl, heptyl or dodecyl. 9. The compound of claim 1 having the formula: or a pharmaceutically acceptable derivative thereof. 10. The compound of claim 1 having the formula: or a pharmaceutically acceptable derivative thereof. 11. The compound of claim 1 having the formula or a pharmaceutically acceptable derivative thereof, wherein: X is an aryl or heteroaryl group;R and R1 are each independently alkyl, aryl, or heteroaryl groups having 1-20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; andR2is an alkyl group, optionally substituted with one or more fluorine atoms. 12. The compound of claim 1 having the formula: or a pharmaceutically acceptable derivative thereof, wherein: X is an aryl or heteroaryl group;n is an integer from 0 to 6;R and R1 are each independently alkyl, aryl, or heteroaryl groups having 1-20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; andR2 is an alkyl group, optionally substituted with one or more fluorine atoms. 13. The compound of claim 1 having the formula or a pharmaceutically acceptable derivative thereof, wherein: X is an aryl or heteroaryl group;R and R1 are each independently alkyl, aryl, or heteroaryl groups having 1-20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; andR2 is an alkyl group, optionally substituted with one or more fluorine atoms. 14. The compound of claim 1 having the formula: or a pharmaceutically acceptable derivative thereof, wherein: X is an aryl or heteroaryl group;n is an integer from 0 to 6;R and R1 are each independently alkyl, aryl, or heteroaryl groups having 1-20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; andR2 is an alkyl group, optionally substituted with one or more fluorine atoms. 15. The compound of claim 1 having the formula or a pharmaceutically acceptable derivative thereof, wherein: X and Y are each independently an aryl or heteroaryl group;n is an integer from 0 to 6;R and R1 are each independently alkyl, aryl, or heteroaryl groups having 1-20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; andR2 is an alkyl group, optionally substituted with one or more fluorine atoms. 16. A pharmaceutical composition, comprising a compound of claim 1 or a pharmaceutically acceptable derivative thereof in a pharmaceutically acceptable carrier. 17. The compound of claim 10 or a pharmaceutically acceptable derivative thereof when used for the detection or treatment or both of hyperproliferative tissue. 18. The compound of claim 11 or a pharmaceutically acceptable derivative thereof when used for the detection or treatment or both of hyperproliferative tissue. 19. The compound of claim 12 or a pharmaceutically acceptable derivative thereof when used for the detection or treatment or both of hyperproliferative tissue. 20. A compound of the formula: wherein: said compound is pharmaceutically acceptable;R1 and R2 are each independently alkyl, alkenyl, —C(O)Ra or —COORa or —CH(CH3)(ORa) or —CH(CH3)(O(CH2)nXRa) where Ra is hydrogen, alkyl, alkenyl, alkenyl, or cycloalkyl; where R2 may also be, —C(═NR21)CH3, or —CH(NHR21)CH3;where X is an aryl or heteroaryl group;n is an integer of 0 to 6;R21 is 3,5-bis(trifluoromethyl)benzyl;R1a and R2a are each independently hydrogen or substituted or unsubstituted alkyl, or together form a covalent bond;R3 and R4 are each independently hydrogen or substituted or unsubstituted alkyl;R3a and R4a are each independently hydrogen or substituted or unsubstituted alkyl, or together form a covalent bond;R5 is hydrogen or substituted or unsubstituted alkyl;R6 and R6a are each independently hydrogen or substituted or unsubstituted alkyl, or together form ═O;R7 is a covalent bond, alkylene, azaalkyl, or azaaraalkyl or  where R20 is 3,5-bis(trifluoromethyl)benzyl;R8 and R8a are each independently hydrogen or substituted or unsubstituted alkyl or together form ═O;R9 and R10 are each independently hydrogen, or substituted or unsubstituted alkyl and R9 may be —CH2CH2COOR2 where R2 is an alkyl group that may be optionally substituted with one or more fluorine atoms;each of each of R3-R6, R8-R10, R1a-R4a, R6a, and R8a, when substituted, is substituted with one or more substituents each independently selected from Q, where Q is alkyl, haloalkyl, halo or —COORb where Rb is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, araalkyl, or ORc where Rc is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl or CONRdRe where Rd and Re are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl, or NRfRg where Rf and Rg are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl;each Q is independently unsubstituted or is substituted with one or more substituents each independently selected from Q1, where Q1 is alkyl, haloalkyl, halo, pseudohalo, or —COORb where Rb is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, araalkyl, or ORc where Rc is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl or CONRdRe where Rd and Re are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl, or NRfRg where Rf and Rg are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl;with the proviso that the compound contains at least one 3,5-bis(trifluoromethyl)benzyl group. 21. The compound of claim 20 wherein: R1 is methyl;R1a and R2a together form a covalent bond;R3 is methyl;R4 is ethyl;R3a and R4a are each independently hydrogen, or together form a covalent bond;R5 is methyl;R9 is CH2CH2COOMe;R10 is methyl. 22. The compound of claim 20, wherein: R2 is CH═CH2, C(O)Me, C(═NR21)CH3, CH(NHR21)CH3, and R21 is 3,5-bis(trifluoromethyl)benzyl. 23. A compound having the formula: 24. A compound having the formula: wherein R is methyl, butyl, heptyl or dodecyl. 25. A compound having the formula: wherein R is methyl, butyl, heptyl or dodecyl. 26. A compound having the formula: 27. A compound having the formula: wherein R is methyl, butyl, heptyl or dodecyl. 28. A compound having the formula: 29. A compound having the formula: 30. A compound having the formula: wherein: X is an aryl or heteroaryl group;R and R1 are each independently alkyl groups having 1-20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; andR2 is an alkyl group, optionally substituted with one or more fluorine atoms. 31. A compound having the formula: wherein: X is an aryl or heteroaryl group;n is an integer from 0 to 6;R and R1 are each independently alkyl groups having 1-20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; andR2 is an alkyl group, optionally substituted with one or more fluorine atoms. 32. A compound having the formula: wherein: X is an aryl or heteroaryl group;R and R1 are each independently alkyl groups having 1-20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; andR2 is an alkyl group, optionally substituted with one or more fluorine atoms. 33. A compound having the formula: wherein: X and Y are each independently an aryl or heteroaryl group;n is an integer from 0 to 6;R and R1 are each independently alkyl groups having 1-20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; andR2 is an alkyl group, optionally substituted with one or more fluorine atoms. 34. A pharmaceutical composition, comprising a compound of claim 20 in a pharmaceutically acceptable carrier.