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Ethylene glycol esters as photoactive agentsRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai, Heavy Metal Containing (including Salts), Polycyclo Ring SystemEthylene glycol esters as photoactive agents description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070191329, Ethylene glycol esters as photoactive agents. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] This application is a continuation of U.S. Ser. No. 10/825,270 filed Apr. 14, 2004, which is a continuation of U.S. Ser. No. 09/588,206 filed Jun. 6, 2000 and now U.S. Pat. No. 6,76,396, which is a continuation of Ser. No. 09/313,106 filed May 17, 1999 and now U.S. Pat. No. 6,153,639, which is a continuation of U.S. Ser. No. 09/088,524 filed Jun. 1, 1998 and now U.S. Pat. No. 5,929,105, which is a continuation-in-part of U.S. Ser. No. 08/852,494 filed 7 May 1997 and now abandoned, the contents of which are incorporated herein by reference. TECHNICAL FIELD [0002] The invention relates to compounds useful in photodynamic therapy (PDT) and related applications. In particular, it concerns ethylene glycol esters of monohydrobenzoporphyrins. BACKGROUND ART [0003] Photodynamic therapy (PDT) generally involves the administration of compounds that are capable of absorbing light, typically in the visible range, but also in the near ultraviolet, followed by irradiation of locations in the subject for which a toxic or inhibitory effect is desired. PDT was initially developed using hematoporphyrin and related compounds in the treatment of tumors, as it appeared that these compounds would "home" to locations containing rapidly dividing cells. The tumor could then be irradiated with light absorbed by the hematoporphyrin and destruction of the surrounding tissue resulted. PDT has since been shown to be useful for treatment of atherosclerotic plaques, restenosis, infections in the blood stream, rheumatoid arthritis, psoriasis and in the treatment of ocular conditions not necessarily limited to tumors. [0004] U.S. Pat. No. 5,171,749 and patents issuing on related applications, U.S. Pat. Nos. 5,283,255; 5,399,583; 4,883,790; 4,920,143; and 5,095,030; all of which are incorporated herein by reference, describe and claim a class of photoactive compounds useful in PDT designated the monohydrobenzoporphyrins, or "BPDs." This class is obtained by Diels-Alder reaction of a mono- or disubstituted alkyne with protoporphyrin-IX and the resultant compounds can further be isomerized, reduced, and/or derivatized to obtain a large class of BPDs. As disclosed in these patents, a particularly useful subclass of this group results from hydrolysis or partial hydrolysis of the ester groups of the 2-carboxyethyl side-chains on rings C and D. Esterification as protection of these groups during the Diels-Alder reaction results in initial products which contain 2-carbalkoxyethyl groups. It was found that facile hydrolysis of these esters could readily be conducted, leaving any carbalkoxy groups associated with the Diels-Alder product obtained from a dicarbalkoxyalkyne virtually completely unhydrolyzed. This resulted in four species of compounds, BPD-MA, BPD-MB, BPD-DA and BPD-DB as depicted in FIG. 1; this figure taken from U.S. Pat. No. 5,171,749. In this depiction, R.sup.1 and R.sup.2 are carbalkoxy groups, typically carbomethoxy or carboethoxy, and R is alkyl (1-6C). [0005] BPD-MA was found to have particularly useful properties for PDT and is currently in clinical development. However, there remains a need for additional specific forms of photoactive agents which expand the repertoire of photoactive compounds for the variety of indications to which PDT is applied, as noted above. The present invention provides compounds in which rings C and D contain ethylene glycol esters of the carboxyalkyl substitutents. These compounds have pharmacokinetic properties which are advantageous in certain instances where PDT is employed. DISCLOSURE OF THE INVENTION [0006] The compounds of the invention are useful new additions to the repertoire of compounds that find application in photodynamic therapy and related methodologies that employ photoactive compounds. The presence of ethylene glycol esters in these molecules provides them with characteristics that permit expansion of the scope of conditions under which such photoactive compounds are employed and fine tuning of the treatment. [0007] Thus, in one aspect, the invention is directed to compounds of the formula [0008] and the metallated and/or labeled and or conjugated forms thereof [0009] wherein R.sup.1 is alkyl (1-6C), preferably methyl, n is an integer of 0-6, preferably 2, and R.sup.2 is vinyl or a derivative thereof, preferably vinyl. [0010] The invention also is directed to compounds of the formula [0011] and the metallated and/or labeled and or conjugated forms thereof wherein R.sup.1, n, and R.sup.2 are defined as described above. These analogs are derived from protoporphyrin III and protoporphyrin XIII respectively, in a manner similar to that in which the compounds of formulas 1 and 2 are derived from protoporphyrin IX. The invention also includes isomers of the various forms of formulas 1-4 which result from the unrearranged Diels-Alder condensation products (i.e., the 1,4-diene) as described in U.S. Pat. No. 4,883,790, incorporated herein by reference. These structures are also set forth in FIG. 14. [0012] In other aspects, the invention related to methods of diagnosis and treatment using the compounds of formula 1, 2, 3 or 4 or their 1,4-diene isomers, as shown in FIG. 14, or mixtures thereof. BRIEF DESCRIPTION OF THE DRAWINGS [0013] FIG. 1 shows the compounds of the prior art, BPD-MA, BPD-MB, BPD-DA and BPD-DB. [0014] FIG. 2 shows the kinetics of uptake of B-EA6 by L1210 cells. [0015] FIG. 3 shows the kinetics of release of B-EA6 by L1210 cells. [0016] FIG. 4 shows a graphic depiction of the pharmacokinetics of B-EA6 in vivo. [0017] FIG. 5 shows a comparison of the kinetics of uptake of B-EA6 by normal splenocytes and L1210 cells. [0018] FIG. 6 shows the time course of PDT using B-EA6 in mice as compared to mice treated with BPD-MA and BPD-MB. [0019] FIG. 7 shows the effect of B-EA6 on microvasculature in mice. [0020] FIG. 8 shows a comparison of the spectra in plasma of BPD-MA and B-EA6. Continue reading about Ethylene glycol esters as photoactive agents... Full patent description for Ethylene glycol esters as photoactive agents Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Ethylene glycol esters as photoactive agents patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Ethylene glycol esters as photoactive agents or other areas of interest. ### Previous Patent Application: Isoquinoline compounds Next Patent Application: Polyhydroxylated aromatic compounds for the treatment of amyloidosis and alpha-synuclein fibril diseases Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Ethylene glycol esters as photoactive agents patent info. 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