US5583220A
Expired / Lapsed
US
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Pyrole nitrogen-substituted texaphyrins
Assignee: Pharmacyclics LLC
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Filing: 1995-05-24
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Granted: 1996-12-10
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Expires: 2015-05-24
Abstract
Abstract Texaphyrins are provided for use as radiation sensitizers. Advantageous properties of texaphyrins for use as a radiation sensitizer include: i) a low redox potential which allows radiation-induced hydrated electrons to flow to texaphyrin rather than neutralizing hydroxyl radicals, allowing hydroxyl radicals to cause cellular damage, ii) a relatively stable texaphyrin radical that reacts readily to covalently modify neighboring molecules causing further cellular damage, iii) intrinsic biolocalization, and iv) indifference to the presence or absence of O2. These properties allow texaphyrins to be particularly effective for treating the hypoxic areas of solid neoplasms. Methods of treatment for an individual having a neoplasm or atheroma include the use of a texaphyrin as a radiation sensitizer and as an agent for photodynamic tumor therapy, or the use of a texaphyrin for internal and for external ionizing radiation. Novel texaphyrins are provided.
Inventors
- 👤 Jonathan L. Sessler
- 👤 Anthony M. Harriman
- 👤 Richard A. Miller
- 👤 Tarak D. Mody
- 👤 Gregory W. Hemmi
- 👤 Vladimir A. Kral
- 👤 Darren Magda
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 17:43
CPC Classifications
A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/0474; A61K51/0485; A61K41/00; A61K41/0038; A61K41/0057; A61K41/0076; A61K47/00; A61K47/50; A61K47/51; A61K47/54; A61K47/545; A61K47/546; A61K49/00; A61K49/001; A61K49/0013; A61K49/0017; A61K49/0019; A61K49/0021; A61K49/005; A61K49/0054; A61K49/06; A61K49/08; A61K49/085; A61K49/10; A61K49/101; A61K49/106; A61K49/12; A61K49/126; A61L; A61L2/00; A61L2/02; A61P; A61P35/00; A61P35/02; A61P43/00; B; B01; B01J; B01J31/00; B01J31/16; B01J31/165; B01J31/1658; B01J31/18; B01J31/1805; B01J31/181; B01J31/1815; C; C07; C07D; C07D487/00; C07D487/22; C07H; C07H21/00; A61L2103/00; A61L2103/05; B01J2531/00; B01J2531/02; B01J2531/0238; B01J2531/0241; B01J2531/025; B01J2531/20; B01J2531/23; B01J2531/26; B01J2531/27; B01J2531/28; B01J2531/30; B01J2531/36; B01J2531/37; B01J2531/38; B01J2531/70; B01J2531/72; B01J2531/80; B01J2531/84; B01J2531/842; B01J2531/845; B01J2531/847; B01J2531/90; B01J2531/96; B01J31/02; B01J31/06; B01J31/061
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
141 words
A texaphyrin having the structure: ##STR6## wherein R 1 -R 4 and R 6 -R 9 are independently hydrogen, halide other than iodide, hydroxyl, alkyl, aryl, haloalkyl other than iodoalkyl, nitro, formyl, acyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, carboxy, carboxyalkyl, carboxyamidealkyl, a site-directing molecule or a couple to a site-directing molecule; R 5 and R 10 are independently hydrogen, alkyl, aryl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, carboxyalkyl, carboxyamidealkyl or a couple to a site-directing molecule; R 11 is alkyl, alkenyl, oxyalkyl or hydroxyalkyl having up to about 3 carbon atoms and having rotational flexibility around a first-bound carbon atom; where R 6 and R 9 are other than hydrogen, then R 5 and R 10 are hydrogen or methyl; and where R 5 and R 10 are other than hydrogen, then R 6 and R 9 are hydrogen, hydroxyl, or halide other than iodide.
Claim 2
Dependent Claim
141 words
A texaphyrin having the structure: ##STR6## wherein R 1 -R 4 and R 6 -R 9 are independently hydrogen, halide other than iodide, hydroxyl, alkyl, aryl, haloalkyl other than iodoalkyl, nitro, formyl, acyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, carboxy, carboxyalkyl, carboxyamidealkyl, a site-directing molecule or a couple to a site-directing molecule; R 5 and R 10 are independently hydrogen, alkyl, aryl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, carboxyalkyl, carboxyamidealkyl or a couple to a site-directing molecule; R 11 is alkyl, alkenyl, oxyalkyl or hydroxyalkyl having up to about 3 carbon atoms and having rotational flexibility around a first-bound carbon atom; where R 6 and R 9 are other than hydrogen, then R 5 and R 10 are hydrogen or methyl; and where R 5 and R 10 are other than hydrogen, then R 6 and R 9 are hydrogen, hydroxyl, or halide other than iodide.
Claim 3
Dependent Claim
21 words
The texaphyrin of claim 1 where the site-directing molecule is an oligonucleotide, a peptide, protein, steroid, hormone, hormone mimic or macrocycle.
Claim 4
Dependent Claim
85 words
The texaphyrin of claim 1 where R 1 is (CH 2 ) 2 CH 2 OH; R 2 and R 3 are CH 2 CH 3 ; R 4 is CH 3 ; R 5 , R 6 , R 9 , and R 10 are H; R 7 is H, OCH 3 or O(CH 2 CH 2 O) 2 CH 2 CH 2 OCH 3 ; R 8 is a site-directing molecule, or a couple to a site-directing molecule; and R 11 is methyl.
Claim 5
Dependent Claim
85 words
The texaphyrin of claim 1 wherein R 1 is (CH 2 ) 2 CH 2 OH; R 2 and R 3 are CH 2 CH 3 ; R 4 is CH 3 ; R 5 , R 6 , R 9 , and R 10 are H; R 7 and R 8 are OCH 2 CH 2 CH 2 OH, or R 7 and R 8 are O(CH 2 CH 2 O) 2 CH 2 CH 2 OCH 3 ; and R 11 is methyl.
Claim 6
Dependent Claim
51 words
The texaphyrin of claim 1 where R 2 and R 3 are ethyl; R 4 is methyl; R 5 , R 6 , R 9 and R 10 are H; and R 1 , R 7 , R 8 and R 11 are chosen from the substituents as in Table 2.
Claim 7
Dependent Claim
12 words
The texaphyrin of claim 1 chosen from compounds B1-B28 in Table 2.
Claim 8
Dependent Claim
59 words
The texaphyrin of claim 1 where the oxyhydroxyalkyl is C.sub.(n-x) H.sub.((2n+1)-2x) O x O y or OC.sub.(n-x) H.sub.((2n+1)-2x) O x O y where n is a positive integer from 1 to 10; x is zero or a positive integer less than or equal to n; and y is zero or a positive integer less than or equal to ((2n+1)-2x).
Claim 9
Dependent Claim
198 words
The texaphyrin of claim 1 where the oxyhydroxyalkyl or saccharide is C n H.sub.((2n+1)-q) O y R a q , OC n H.sub.((2n+1)-q) O y R a q or (CH 2 ) n CO 2 R a where n is a positive integer from 1 to 10; y is zero or a positive integer less than or equal to ((2n+1)-q); q is zero or a positive integer less than or equal to (2n+1); and R a is independently H, alkyl, hydroxyalkyl, saccharide, C.sub.(m-w) H.sub.((2m+1)-2w) O w O z , O 2 CC.sub.(m-w) H.sub.((2m+1)-2w) O w O z or N(R)OCC.sub.(m-w) H.sub.((2m+1)-2w) O w O z , where m is a positive integer from 1 to 10, w is zero or a positive integer less than or equal to m, z is zero or a positive integer less than or equal to ((2m+1)-2w), and R is H, alkyl, hydroxyalkyl, or C m H.sub.((2m+1)-r) O z R b r where m is a positive integer from 1 to 10, z is zero or a positive integer less than ((2m+1)-r), r is zero or a positive integer less than or equal to 2m+1, and R b is H, alkyl, hydroxyalkyl, or saccharide.
Claim 10
Dependent Claim
175 words
The texaphyrin of claim 1 where the carboxyamidealkyl is (CH 2 ) n CONHR a , O(CH 2 ) n CONHR a , (CH 2 ) n CON(R a ) 2 , or O(CH 2 ) n CON(R a ) 2 where n is a positive integer from 1 to 10; R a is independently H, alkyl, hydroxyalkyl, saccharide, C.sub.(m-w) H.sub.((2m+1)-2w) O w O z , O 2 CC.sub.(m-w) H.sub.((2m+1)-2w) O w O z or N(R)OCC.sub.(m-w) H.sub.((2m+1)-2w) O w O z , where m is a positive integer from 1 to 10, w is zero or a positive integer less than or equal to m, z is zero or a positive integer less than or equal to ((2m+1)-2w), and R is H, alkyl, hydroxyalkyl, or C m H.sub.((2m+1)-r) O z R b r where m is a positive integer from 1 to 10, z is zero or a positive integer less than ((2m+1)-r), r is zero or a positive integer less than or equal to 2m+1, and R b is H, alkyl, hydroxyalkyl, or saccharide.
Claim 11
Dependent Claim
225 words
The texaphyrin of claim 1 where the carboxyalkyl is C n H.sub.((2n+1)-q) O y R c q or OC n H.sub.((2n+1)-q) O y R c q where n is a positive integer from 1 to 10; y is zero or a positive integer less than or equal to ((2n+1)-q); q is zero or a positive integer less than or equal to (2n+1); and R c is (CH 2 ) n CO 2 R d , (CH 2 ) n CONHR d , or (CH 2 ) n CON(R d ) 2 where n is a positive integer from 1 to 10, and R d is H, alkyl, hydroxyalkyl, saccharide, C.sub.(m-w) H.sub.((2m+1)-2w) O w O z , O 2 CC.sub.(m-w) H.sub.((2m+1)-2w) O w O z or N(R)OCC.sub.(m-w) H.sub.((2m+1)-2w) O w O z , where m is a positive integer from 1 to 10, w is zero or a positive integer less than or equal to m, z is zero or a positive integer less than or equal to ((2m+1)-2w), and R is H, alkyl, hydroxyalkyl, or C m H.sub.((2m+1)-r) O z R b r where m is a positive integer from 1 to 10, z is zero or a positive integer less than ((2m+1)-r), r is zero or a positive integer less than or equal to 2m+1, and R b is H, alkyl, hydroxyalkyl, or saccharide.
Claim 12
Dependent Claim
21 words
The texaphyrin of claim 3 where the site-directing molecule is an oligonucleotide, a peptide, protein, steroid, hormone, hormone mimic or macrocycle.
Claim 13
Dependent Claim
12 words
The texaphyrin of claim 3 where the site-directing molecule is an oligonucleotide.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-12-10 | 2000-06-10 | 2000-12-10 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-12-10 | 2004-06-10 | 2004-12-10 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-12-10 | 2008-06-10 | 2008-12-10 | $7700.00 | Window Closed / Lapsed |