US5504205A
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Reduced sp3 texaphyrins
Assignee: Pharmacyclics LLC
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Filing: 1994-07-26
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Granted: 1996-04-02
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Expires: 2014-07-26
Abstract
Abstract The present invention involves water soluble hydroxy-substituted texaphyrins retaining lipophilicity, the synthesis of such compounds and their uses. These expanded porphyrin-like macrocycles are efficient chelators of divalent and trivalent metal ions. Various metal (e.g., transition, main group, and lanthanide) complexes of the hydroxy-substituted texaphyrin derivatives of the present invention have unusual water solubility and stability. They absorb light strongly in a physiologically important region (i.e. 690-880 nm). They have enhanced relaxivity and therefore are useful in magnetic resonance imaging. They form long-lived triplet states in high yield and act as photosensitizers for the generation of singlet oxygen. Thus, they are useful for inactivation or destruction of human immunodeficiency virus (HIV-1), mononuclear or other cells infected with such virus as well as tumor cells. They are water soluble, yet they retain sufficient lipophilicity so as to have greater affinity for lipid rich areas such as atheroma and tumors. They may be used for magnetic resonance imaging followed by photodynamic tumor therapy in the treatment of atheroma and tumors. These properties, coupled with their high chemical stability and appreciable solubility in water, add to their usefulness.
Inventors
- 👤 Jonathan L. Sessler
- 👤 Gregory W. Hemmi
- 👤 Tarak D. Mody
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 16:14
CPC Classifications
A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/0474; A61K51/0485; A61K41/00; A61K41/0038; A61K41/0057; A61K41/0076; A61K41/10; A61K47/00; A61K47/50; A61K47/51; A61K47/54; A61K47/545; A61K47/546; A61K49/00; A61K49/001; A61K49/0013; A61K49/0017; A61K49/0019; A61K49/0021; A61K49/0036; A61K49/005; A61K49/0058; A61K49/04; A61K49/06; A61K49/08; A61K49/10; A61K49/101; A61K49/106; A61K51/08; A61K51/10; A61K51/1093; A61L; A61L2/00; A61L2/02; A61P; A61P35/00; A61P43/00; C; C07; C07D; C07D487/00; C07D487/22; C07H; C07H17/00; C07H17/02; C07H21/00; A61L2103/00; A61L2103/05
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
153 words
A reduced sp 3 texaphyrin having the structure: ##STR12## where R 1 , R 2 , R 3 , R 4 , and R 5 are independently hydrogen, hydroxyl, alkyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, monosaccharide, carboxyalkyl or carboxyamidealkyl where at least one of R 1 , R 2 , R 3 , R 4 , and R 5 is hydroxyl, oxyhydroxyalkyl, monosaccharide, oxyalkyl, carboxyalkyl, carboxyamidealkyl or hydroxyalkyl and where at least one of R 1 , R 2 , R 3 , R 4 , and R 5 is oxyhydroxyalkyl, monosaccharide, oxyalkyl, carboxyalkyl, carboxyamidealkyl or hydroxyalkyl then at least one of R 1 , R 2 , R 3 , R 4 , and R 5 has at least one hydroxy substituent; and the molecular weight of any one of R 1 , R 2 , R 3 , R 4 , or R 5 is less than or equal to about 1000 daltons.
Claim 2
Dependent Claim
153 words
A reduced sp 3 texaphyrin having the structure: ##STR12## where R 1 , R 2 , R 3 , R 4 , and R 5 are independently hydrogen, hydroxyl, alkyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, monosaccharide, carboxyalkyl or carboxyamidealkyl where at least one of R 1 , R 2 , R 3 , R 4 , and R 5 is hydroxyl, oxyhydroxyalkyl, monosaccharide, oxyalkyl, carboxyalkyl, carboxyamidealkyl or hydroxyalkyl and where at least one of R 1 , R 2 , R 3 , R 4 , and R 5 is oxyhydroxyalkyl, monosaccharide, oxyalkyl, carboxyalkyl, carboxyamidealkyl or hydroxyalkyl then at least one of R 1 , R 2 , R 3 , R 4 , and R 5 has at least one hydroxy substituent; and the molecular weight of any one of R 1 , R 2 , R 3 , R 4 , or R 5 is less than or equal to about 1000 daltons.
Claim 3
Dependent Claim
62 words
The reduced sp 3 texaphyrin of claim 1 wherein 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 4
Dependent Claim
197 words
The reduced sp 3 texaphyrin of claim 1 wherein the oxyhydroxyalkyl or monosaccharide 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 ((2n+1)-q), q is zero or a positive integer less than or equal to 2n+1, R a is independently H, alkyl, hydroxyalkyl, monosaccharide, 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), 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 independently H, alkyl, hydroxyalkyl, or monosaccharide.
Claim 5
Dependent Claim
178 words
The reduced sp 3 texaphyrin of claim 1 wherein 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, monosaccharide, 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), 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 independently H, alkyl, hydroxyalkyl, or monosaccharide.
Claim 6
Dependent Claim
223 words
The reduced sp 3 texaphyrin of claim 1 wherein 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 ((2n+1)-q), q is zero or a positive integer less than or equal to 2n+1, 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, R d is independently H, alkyl, hydroxyalkyl, monosaccharide, 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), 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 independently H, alkyl, hydroxyalkyl, or monosaccharide.
Claim 7
Dependent Claim
97 words
The reduced sp 3 texaphyrin of claim 1 wherein: R 1 , R 2 , R 3 , and R 4 are independently C n H 2n+1 where n is a positive integer from 1 to about 10; R 5 is hydroxyl, hydroxyalkyl, oxyhydroxyalkyl, carboxyalkyl or carboxyamidealkyl and where R 5 is hydroxyalkyl, oxyhydroxyalkyl, carboxyalkyl or carboxyamidealkyl then R 5 has at least one hydroxy substituent; and the molecular weight of any one of R 1 , R 2 , R 3 R 4 , or R 5 is less than or equal to about 1000 daltons.
Claim 8
Dependent Claim
110 words
The reduced sp 3 texaphyrin of claim 1 wherein: R 1 , R 2 , R 3 , and R 4 are independently hydroxyl, alkyl, hydroxyalkyl, oxyhydroxyalkyl, carboxyalkyl or carboxyamidealkyl and at least one of R 1 , R 2 , R 3 , and R 4 is hydroxyalkyl, carboxyalkyl, carboxyamidealkyl or oxyhydroxyalkyl having at least one hydroxy substituent; R 5 is H or C n H 2n+1 where n is a positive integer from 1 to 10; and the molecular weight of any one of R 1 , R 2 , R 3 , R 4 , or R 5 is less than or equal to about 1000 daltons.
Claim 9
Dependent Claim
110 words
The reduced sp 3 texaphyrin of claim 1 wherein: R 1 , R 2 , R 3 and R 4 are independently hydrogen, hydroxyl, alkyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, monosaccharide, carboxyalkyl, or carboxyamidealkyl where at least one of R 1 , R 2 , R 3 and R 4 is oxyhydroxyalkyl, monosaccharide, oxyalkyl, carboxyalkyl, carboxyamidealkyl, or hydroxyalkyl having at least one hydroxy substituent; R 5 is hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, monosaccharide, carboxyalkyl or carboxyamidealkyl having at least one hydroxy substituent; and the molecular weight of any one of R 1 , R 2 , R 3 , R 4 , or R 5 is less than or equal to about 1000 daltons.
Claim 10
Dependent Claim
19 words
The reduced sp 3 texaphyrin of claim 1 wherein R 5 is OCH 2 CH 2 CH 2 OH.
Claim 11
Dependent Claim
41 words
The reduced sp 3 texaphyrin of claim 1 wherein: R 1 , R 2 , and R 3 are CH 2 CH 3 , R 4 is CH 3 , and R 5 is OCH 2 CH 2 CH 2 OH.
Claim 12
Dependent Claim
19 words
The reduced sp 3 texaphyrin of claim 1 wherein R 1 is (CH 2 ) 2 CH 2 OH.
Claim 13
Dependent Claim
39 words
The reduced sp 3 texaphyrin of claim 1 wherein: R 1 is (CH 2 ) 2 CH 2 OH, R 2 and R 3 are CH 2 CH 3 and R 4 and R 5 are CH 3 .
Claim 14
Dependent Claim
30 words
The reduced sp 3 texaphyrin of claim 1 wherein: R 1 is (CH 2 ) 2 CH 2 OH and R 5 is OCH 2 CH 2 CH 2 OH.
Claim 15
Dependent Claim
17 words
The reduced sp 3 texaphyrin of claim 1 wherein R 5 is OCH 2 CHOHCH 2 OH.
Claim 16
Dependent Claim
28 words
The reduced sp 3 texaphyrin of claim 1 wherein: R 1 is (CH 2 ) 2 CH 2 OH and R 5 is OCH 2 CHOHCH 2 OH.
Claim 17
Dependent Claim
17 words
The reduced sp 3 texaphyrin of claim 1 wherein R 2 is CH 2 CH 2 OH.
Claim 18
Dependent Claim
20 words
The reduced sp 3 texaphyrin of claim 1 wherein the oxyalkyl has repeating units of CH 2 CH 2 O.
Claim 19
Dependent Claim
13 words
The reduced sp 3 texaphyrin of claim 1 wherein R 5 is OH.
Claim 20
Dependent Claim
17 words
The reduced sp 3 texaphyrin of claim 1 wherein R 5 is OR' where R' is monosaccharide.
Claim 21
Dependent Claim
17 words
The reduced sp 3 texaphyrin of claim 1 wherein R 5 is OR' where R' is carboxyalkyl.
Claim 22
Dependent Claim
15 words
The reduced sp 3 texaphyrin of claim 20 wherein R 1 is hydroxyalkyl or carboxyalkyl.
Claim 23
Dependent Claim
17 words
The reduced sp 3 texaphyrin of claim 1 wherein R 5 is OR' where R' is carboxyamidealkyl.
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