Claims
- 1. A compound of the formula ##STR8## and salts and/or metallated and/or labeled and/or conjugated forms thereof wherein R.sup.1 is alkyl (1-6C);
- Y is --OH or --NR.sup.2.sub.2 or --NHNR.sup.2.sub.2 wherein each R.sup.2 is independently H or a substituted or unsubstituted hydrocarbon radical of 1-10C, or wherein both R.sup.2 taken together provide a cyclic or multicyclic amine of 1-20C; or is --OR.sup.3 wherein R.sup.3 is alkyl (1-10C) substituted with at least one heteroatom-containing substituent;
- n is an integer of 0-6
- each X is independently --OH; or --OR.sup.4, wherein R.sup.4 is an unsubstituted hydrocarbon radical of 1-10C; or is --NR.sup.2.sub.2 or --NHNR.sup.2.sub.2 wherein R.sup.2 is defined as above; or is --OR.sup.3 wherein R.sup.3 is as defined above; and
- R.sup.5 is vinyl or a derivative thereof.
- 2. The compound of claim 1 wherein n is 2.
- 3. The compound of claim 1 wherein R.sup.5 is vinyl, --CHOR', --CHO, --COOR', --CH(OR')CH.sub.3, --CH(OR')CH.sub.2 OR', --CH(SR')CH.sub.3, --CH(NR').sub.2 CH.sub.3, --CH(CN)CH.sub.3, --CH(COOR')CH.sub.3, --CH(OOCR')CH.sub.3, --CH(NR'COR')CH.sub.3, --CH(CONR'.sub.2)CH.sub.3, --CH(halo)CH.sub.3, or --CH(halo)CH.sub.2 (halo) wherein R' is H, or a hydrocarbon radical (1-6C) optionally substituted with a heteroatom-containing substituent or wherein R.sup.5 is an organic group of less than 12C resulting from direct or indirect derivatization of the vinyl group, or wherein R.sup.5 comprises a group containing 1-3 tetrapyrrole-type nuclei.
- 4. The compound of claim 2 wherein R.sup.5 is vinyl, --CHOR', --CHO, --COOR', --CH(OR')CH.sub.3, --CH(OR')CH.sub.2 OR.varies., --CH(SR')CH.sub.3, --CH(NR').sub.2 CH.sub.3, --CH(CN)CH.sub.3, --CH(COOR')CH.sub.3, --CH(OOCR')CH.sub.3, --CH(NR'COR')CH.sub.3, --CH(CONR'.sub.2)CH.sub.3, --CH(halo)CH.sub.3, or --CH(halo)CH.sub.2 (halo) wherein R' is H, or a hydrocarbon radical (1-6C) optionally substituted with a heteroatom-containing substituent.
- 5. The compound of claim 4 wherein R.sup.5 is vinyl.
- 6. The compound of claim 1 wherein Y and both X are --OH.
- 7. The compound of claim 2 wherein Y and both X are --OH.
- 8. The compound of claim 7 which is the "triacid" of the formula ##STR9##
- 9. The compound of claim 1 wherein Y is --NR.sup.2.sub.2.
- 10. The compound of claim 2 wherein Y is --NR.sup.2.sub.2.
- 11. The compound of claim 3 wherein Y is --NR.sup.2.sub.2.
- 12. The compound of claim 4 wherein Y is --NR.sup.2.sub.2.
- 13. The compound of claim 9 wherein each --NR.sup.2.sub.2 independently comprises methyl, ethyl, propyl, butyl, isobutyl, hexyl, hydroxyalkyl (1-6C), cyclopentyl, cyclopentadienyl, furyl, thienyl, pyrrolyl, isopyrrolyl, pyridyl, pyrazolyl, indolyl, isoindolyl, imidazolyl, isoimidazolyl, triazolyl, furazanyl, isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazolyl, phenyl, cyclohexyl, pyranyl, dioxinyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, piperazinyl, indolyzinyl, pyrrolidinyl, triazinyl, oxazinyl, isoxazinyl, oxathiazinyl, oxadiazinyl, morpholinyl, azepinyl, oxepinyl, thiepinyl, diazepinyl, indenyl, isoindenyl, benzofuranyl, isobenzofuranyl, thionaphthenyl, isothionaphthenyl, indolenyl, isobenzazolyl, pyrano-pyrrolyl, indazolyl, isoindazolyl, indoxazinyl, benzoxazolyl, chromenyl, anthanyl, naphthyl, tetralinyl, decalinyl, benzothienyl, benzyopyranyl, coumarinyl, cinnolinyl, benzopyronyl, quinolinyl, isoquinolinyl, benzodiazinyl, quinolyl, isoquinolyl, quinazolinyl, quinolizinyl, quinoxalinyl, naphthyridinyl, pyrido-pyridinyl, benzoxazinyl, benzisoxazinyl, purinyl, phthalazinyl, naphthyridinyl, pteridinyl, or benzyl.
- 14. The compound of claim 9 wherein both X are --NR.sup.2.sub.2.
- 15. The compound of claim 13 wherein both X are --NR.sup.2.sub.2.
- 16. The compound of claim 1 wherein both X and Y are --OCH.sub.2 CH.sub.2 OH.
- 17. The compound of claim 5 wherein both X and Y are --OCH.sub.2 CH.sub.2 OH.
- 18. The compound of claim 5 wherein Y is OH, both X are --OR.sup.6, wherein R.sup.6 is lower alkyl (1-4C).
- 19. The compound of claim 18 wherein R.sup.6 is methyl.
- 20. The compound of claim 19 wherein R.sup.1 is methyl.
- 21. The compound of claim 20 which is of formula 13 or 14.
- 22. A method to prepare a product compound of the formula ##STR10## and the salts and/or metallated and/or labeled and/or conjugated forms thereof;
- wherein R.sup.1 is alkyl (1-6C);
- n is an integer of 1-6; and
- wherein R.sup.5 is vinyl or a derivative thereof,
- which method comprises treating a more highly esterified form of said product compound or the salt, metallated form, labeled form or conjugated form thereof,
- with a base and solvent for a time sufficient to result in deesterification so as to obtain the product compound.
- 23. The method of claim 22 wherein said treating is conducted in an inert atmosphere that prevents oxidation.
- 24. The method of claim 22 wherein said base is sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, barium hydroxide, chromium hydroxide, or tetraalkyl ammonium hydroxide.
- 25. The method of claim 23 wherein said base is sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, barium hydroxide, chromium hydroxide, or tetraalkyl ammonium hydroxide.
- 26. The method of claim 22 wherein the solvent is DMSO, low molecular weight alcohol, DMF, THF or water or mixtures thereof.
- 27. The method of claim 23 wherein the solvent is DMSO, low molecular weight alcohol, DMF, THF or water or mixtures thereof.
- 28. The method of claim 23 wherein said inert atmosphere is provided by nitrogen, helium or argon gas.
- 29. The method of claim 22 wherein said treating is conducted at a temperature of about 0.degree.-60.degree. C.
- 30. The method of claim 23 wherein said treating is conducted at a temperature of about 0.degree.-60.degree. C.
- 31. The method of claim 22 wherein said treating is conducted at room temperature for about 2-48 hours.
- 32. The method of claim 23 wherein said treating is conducted at room temperature for about 2-48 hours.
- 33. The method of claim 22 which further comprises dissolving any product compound or its salt, metallated form, labeled form or conjugated form in water and adding sufficient acid to precipitate said product compound.
- 34. The method of claim 23 which further comprises dissolving any product compound or its salt, metallated form, labeled form or conjugated form in water and adding sufficient acid to precipitate said product compound.
- 35. A method to prepare a compound of formulas 1-4 or salts or metallated or labeled or conjugated forms thereof, wherein R.sup.1 is alkyl (1-6C); Y and both X are --OR.sup.3 or --NR.sup.2.sub.2 ; n is an integer of 0-6; and R.sup.5 is vinyl or a derivative thereof; which method comprises treating a carboxyl-activated form of a starting compound of the formula ##STR11## and the salts and/or metallated and/or labeled and/or conjugated forms thereof;
- wherein R.sup.1 is alkyl (1-6C);
- n is an integer of 1-6; and
- wherein R.sup.5 is vinyl or a derivative thereof,
- with R.sup.3 OH or HNR.sup.2.sub.2 under conditions which are sufficient to form a compound of formulas 1-4 or the metallated or labeled or conjugated form thereof wherein Y and both X are either --OR.sup.3 or NR.sup.2.sub.2.
- 36. The method of claim 35 wherein the activated carboxyl is obtained by treating free carboxyl groups of said starting compound with an activating agent.
- 37. The method of claim 36 wherein the activating agent is TSTU or BTTU.
- 38. The method of claim 35 wherein Y and both X are --OR.sup.3.
- 39. The method of claim 38 wherein --OR.sup.3 is --OCH.sub.2 CH.sub.2 OH and --R.sup.3 OH is ethylene glycol.
- 40. A pharmaceutical composition comprising the compound of claim 1 in admixture with a pharmaceutically acceptable excipient.
- 41. An improved method to conduct PDT wherein the improvement comprises employing the compound of claim 1 as a photoactive agent.
- 42. A pharmaceutical composition comprising the compound of claim 18 in admixture with a pharmaceutically acceptable excipient.
- 43. An improved method to conduct PDT wherein the improvement comprises employing the compound of claim 18 as a photoactive agent.
Parent Case Info
This application is a continuation-in-part of U.S. Ser. No. 08/852,326, filed 7 May 1997, the contents of which are incorporated herein by reference in their entirety.
US Referenced Citations (6)
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
852326 |
May 1997 |
|