US2008275017A1PendingUtilityA1

Aromatic sulfenates for type i phototherapy

62
Assignee: RAJAGOPALAN RAGHAVANPriority: Jul 3, 2001Filed: Jul 15, 2008Published: Nov 6, 2008
Est. expiryJul 3, 2021(expired)· nominal 20-yr term from priority
A61P 35/00A61K 41/0057
62
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Claims

Abstract

Novel sulfenate derivatives and their bioconjugates for phototherapy of tumors and other lesions. The sulfenates of the present invention are designed to absorb low-energy ultraviolet, visible, or near-infrared (NIR) region of the electromagnetic spectrum. The phototherapeutic effect is caused by direct interaction of free radicals, the reactive intermediate produced upon photofragmentation of the sulfenate moiety, with the tissue of interest.

Claims

exact text as granted — not AI-modified
1 . A method of using a compound, the method comprising:
 administering the compound to a patient; and   exposing the administered compound to light, wherein the compound is of the following formula   
     
       
         
         
             
             
         
       
     
     and wherein:
 E is a somatostatin receptor binding molecule, an ST receptor binding molecule, a neurotensin receptor binding molecule, a bombesin receptor binding molecule, a cholecystokinin receptor binding molecule, a steroid receptor binding molecule, a carbohydrate receptor binding molecule, or dihydroxyindolecarboxylic acid; 
 X is —(R 5 )NOC—, —(R 5 )NOCCH 2 O—, —(R 5 )NOCCH 2 CH 2 O—, or —HNC(═S)NH; 
 each of R 1  to R 5  is independently hydrogen, C1-C10 alkyl, C5-C10 aryl, C1-C10 polyhydroxyalkyl, or C1-C10 polyalkoxyalkyl; 
 Q is a single bond or an alkenyl, aromatic, or heteroaromatic radical derived from an olefin, a benzene, a naphthalene, a naphthoquinone, a fluorene, an anthracene, an anthraquinone, a phenanthrene, a tetracene, a naphthacenedione, a pyridine, a quinoline, an isoquinoline, an indole, an isoindole, a pyrrole, an imidiazole, an oxazole, a thiazole, a pyrazole, a pyrazine, a purine, a benzimidazole, a furan, a benzofuran, a dibenzofuran, a carbazole, an acridine, an acridone, a phenanthridine, a thiophene, a benzothiophene, a dibenzothiophene, a xanthene, a xanthone, a flavone, a coumarin, or an anthracycline; and 
 Ar is an aromatic or heteroaromatic radical derived from a benzene, a naphthalene, a naphthoquinone, a diphenylmethane, a fluorene, an anthracene, an anthraquinone, a phenanthrene, a tetracene, a naphthacenedione, a pyridine, a quinoline, an isoquinoline, an indole, an isoindole, a pyrrole, an imidiazole, an oxazole, a thiazole, a pyrazole, a pyrazine, a purine, a benzimidazole, a furan, a benzofuran, a dibenzofuran, a carbazole, an acridine, an acridone, a phenanthridine, a thiophene, a benzothiophene, a dibenzothiophene, a xanthene, a xanthone, a flavone, a coumarin, or an anthracycline. 
 
   
   
       2 . The method of  claim 1 , wherein E is a somatostatin receptor binding molecule. 
   
   
       3 . The method of  claim 1 , wherein E is an ST receptor binding molecule. 
   
   
       4 . The method of  claim 1 , wherein E is a neurotensin receptor binding molecule. 
   
   
       5 . The method of  claim 1 , wherein E is a bombesin receptor binding molecule. 
   
   
       6 . The method of  claim 1 , wherein E is a cholecystokinin receptor binding molecule. 
   
   
       7 . The method of  claim 1 , wherein E is a steroid receptor binding molecule. 
   
   
       8 . The method of  claim 1 , wherein E is a carbohydrate receptor binding molecule. 
   
   
       9 . The method of  claim 1 , wherein E is dihydroxyindolecarboxylic acid. 
   
   
       10 . The method of  claim 1 , wherein X is —(R 5 )NOC—. 
   
   
       11 . The method of  claim 1 , wherein X is —(R 5 )NOCCH 2 O—. 
   
   
       12 . The method of  claim 1 , wherein X is —(R 5 )NOCCH 2 CH 2 O—. 
   
   
       13 . The method of  claim 1 , wherein X is —HNC(═S)NH. 
   
   
       14 . The method of  claim 1 , wherein Q is a single bond. 
   
   
       15 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from an olefin. 
   
   
       16 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a benzene. 
   
   
       17 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a naphthalene. 
   
   
       18 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a fluorine. 
   
   
       19 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from an anthracene. 
   
   
       20 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from an anthraquinone. 
   
   
       21 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a phenanthrene. 
   
   
       22 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a tetracene. 
   
   
       23 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a naphthacenedione. 
   
   
       24 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a pyridine. 
   
   
       25 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a quinoline. 
   
   
       26 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from an isoquinoline. 
   
   
       27 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from an indole. 
   
   
       28 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from an isoindole. 
   
   
       29 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a pyrrole. 
   
   
       30 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from an imidiazole. 
   
   
       31 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from an oxazole. 
   
   
       32 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a thiazole. 
   
   
       33 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a pyrazole. 
   
   
       34 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a pyrazine. 
   
   
       35 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a purine. 
   
   
       36 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a benzimidazole. 
   
   
       37 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a furan. 
   
   
       38 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a benzofuran. 
   
   
       39 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a dibenzofuran. 
   
   
       40 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a carbazole. 
   
   
       41 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from an acridine. 
   
   
       42 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from an acridone. 
   
   
       43 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a phenanthridine. 
   
   
       44 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a thiophene. 
   
   
       45 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a benzothiophene. 
   
   
       46 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a dibenzothiophene. 
   
   
       47 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a xanthene. 
   
   
       48 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a xanthone. 
   
   
       49 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a flavone. 
   
   
       50 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from a coumarin. 
   
   
       51 . The method of  claim 1 , wherein Q is an alkenyl, aromatic, or heteroaromatic radical derived from an anthracycline. 
   
   
       52 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a benzene. 
   
   
       53 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a naphthalene. 
   
   
       54 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a naphthoquinone. 
   
   
       55 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a diphenylmethane. 
   
   
       56 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a fluorine. 
   
   
       57 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from an anthracene. 
   
   
       58 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a anthraquinone. 
   
   
       59 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a phenanthrene. 
   
   
       60 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a tetracene. 
   
   
       61 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a naphthacenedione. 
   
   
       62 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a pyridine. 
   
   
       63 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a quinoline. 
   
   
       64 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from an isoquinoline. 
   
   
       65 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from an indole. 
   
   
       66 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from an isoindole. 
   
   
       67 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a pyrrole. 
   
   
       68 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from an imidiazole. 
   
   
       69 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from an oxazole. 
   
   
       70 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a thiazole. 
   
   
       71 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a pyrazole. 
   
   
       72 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a pyrazine. 
   
   
       73 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a purine. 
   
   
       74 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a benzimidazole. 
   
   
       75 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a furan. 
   
   
       76 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a benzofuran. 
   
   
       77 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a dibenzofuran. 
   
   
       78 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a carbazole. 
   
   
       79 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from an acridine. 
   
   
       80 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from an acridone. 
   
   
       81 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a phenanthridine. 
   
   
       82 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a thiophene. 
   
   
       83 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a benzothiophene. 
   
   
       84 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a dibenzothiophene. 
   
   
       85 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a xanthene. 
   
   
       86 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a xanthone. 
   
   
       87 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a flavone. 
   
   
       88 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from a coumarin. 
   
   
       89 . The method of  claim 1 , wherein Ar is an aromatic or heteroaromatic radical derived from an anthacyline. 
   
   
       90 . The method of  claim 1 , wherein the light is between about 300 nm and about 950 nm wavelength. 
   
   
       91 . The method of  claim 1 , wherein the compound is administered in a range of about 0.1 mg/kg body weight to about 500 mg/kg body weight. 
   
   
       92 . The method of  claim 1 , wherein the compound is administered in a range of about 0.5 mg/kg body weight to about 2 mg/kg body weight. 
   
   
       93 . The method of  claim 1 , wherein the compound is administered as part of a biocompatible composition. 
   
   
       94 . The method of  claim 92 , wherein the compound is administered at a concentration range of about 1 nM to about 0.5M.

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