US5622946A
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Radiation sensitization using texaphyrins
Assignee: Pharmacyclics LLC
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Filing: 1995-05-10
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Granted: 1997-04-22
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Expires: 2015-05-10
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
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 11:11
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: 49
Claim 1
Independent Claim
36 words
An improved method for radiation therapy of a patient with a neoplasm or atheroma employing a radiation sensitizer, wherein the improvement comprises treating said patient with an effective amount of a texaphyrin as the radiation sensitizer.
Claim 2
Dependent Claim
36 words
An improved method for radiation therapy of a patient with a neoplasm or atheroma employing a radiation sensitizer, wherein the improvement comprises treating said patient with an effective amount of a texaphyrin as the radiation sensitizer.
Claim 3
Independent Claim
39 words
A method of radiation therapy for a host harboring a neoplasm or atheroma comprising: administering to the host a texaphyrin, said texaphyrin having radiosensitization properties; and administering ionizing radiation to the host in proximity to the neoplasm or atheroma.
Claim 4
Independent Claim
39 words
A method of radiation therapy for a host harboring a neoplasm or atheroma comprising: administering to the host a texaphyrin, said texaphyrin having radiosensitization properties; and administering ionizing radiation to the host in proximity to the neoplasm or atheroma.
Claim 5
Dependent Claim
22 words
The method of claim 2 further comprising the step of determining localization sites in the host by reference to a detectable texaphyrin.
Claim 6
Dependent Claim
13 words
The method of claim 2 wherein the texaphyrin is complexed with a metal.
Claim 7
Dependent Claim
19 words
The method of claim 4 wherein the metal is a paramagnetic metal, a gamma-emitting metal, or a radioactive metal.
Claim 8
Dependent Claim
30 words
The method of claim 4 wherein the metal is selected from the group consisting of Gd(III), Mn(II), Mn(III), Fe(III), Y(III) and all trivalent lanthanides other than La(III), Lu(III) and Pm(III).
Claim 9
Dependent Claim
16 words
The method of claim 3 wherein determining localization sites occurs by observing fluorescence from the texaphyrin.
Claim 10
Dependent Claim
24 words
The method of claim 3 wherein the texaphyrin is complexed with a gamma-emitting metal and determining localization sites occurs by gamma camera body imaging.
Claim 11
Dependent Claim
23 words
The method of claim 3 wherein the texaphyrin is complexed with a paramagnetic metal and determining localization sites occurs by magnetic resonance imaging.
Claim 12
Dependent Claim
11 words
The method of claim 9 wherein the paramagnetic metal is Gd(III).
Claim 13
Dependent Claim
14 words
The method of claim 2 wherein the ionizing radiation is from an external source.
Claim 14
Dependent Claim
29 words
The method of claim 4 wherein the metal is a radioactive metal and the ionizing radiation is from the radioactive metal in combination with radiation from an external source.
Claim 15
Dependent Claim
23 words
The method of claim 2 wherein the texaphyrin is the Gd complex of 4,5-diethyl-10,23-dimethyl-9,24-bis(3-hydroxypropyl)-16,17-bis[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]-13,20,25,26,27-pentaazapentacyclo[20.2.1.1 3 ,6 0.1 8 ,11 0.0 14 ,19 ]-heptacosa-1,3,5,7,9,11(27),12,14(19),15,17,20,22(25),23-tridecaene.
Claim 16
Dependent Claim
23 words
The method of claim 3 wherein the texaphyrin is the Gd complex of 4,5-diethyl-10,23-dimethyl-9,24-bis(3-hydroxypropyl)-16,17-bis[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]-13,20,25,26,27-pentaazapentacyclo[20.2.1.1 3 ,6 0.1 8 ,11 0.0 14 ,19 ]-heptacosa-1,3,5,7,9,11(27),12,14(19),15,17,20,22(25),23-tridecaene.
Claim 17
Dependent Claim
36 words
The method of claim 2 further comprising the steps of administering to the host as a second agent a photosensitive texaphyrin having essentially identical biolocalization property, and administering photoirradiation in proximity to the neoplasm or atheroma.
Claim 18
Dependent Claim
32 words
The method of claim 15, wherein the photosensitive texaphyrin is a texaphyrin complexed to a diamagnetic metal and the diamagnetic metal is selected from the group consisting of Lu(III), La(III) and In(III).
Claim 19
Dependent Claim
171 words
The method of claim 2 where the texaphyrin has structure A or B: ##STR5## wherein M is H, a divalent metal cation or a trivalent metal cation; 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, aminoalkyl, oxyaminoalkyl, 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, aminoalkyl, oxyaminoalkyl, 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; where R 5 and R 10 are other than hydrogen, then R 6 and R 9 are hydrogen, hydroxyl, or halide other than iodide; and N is 0, 1 or 2.
Claim 20
Dependent Claim
21 words
The method of claim 17 where the site-directing molecule is an oligonucleotide, a peptide, protein, steroid, hormone, hormone mimic or macrocycle.
Claim 21
Dependent Claim
85 words
The method of claim 17 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 22
Dependent Claim
28 words
The method of claim 17 where R 4 is methyl and R 1 -R 3 and R 5 -R 10 are as in Table 1 for texaphyrins A1-A38.
Claim 23
Dependent Claim
33 words
The method of claim 17 where R 2 and R 3 are ethyl, R 4 is methyl, and R 1 and R 5 -R 11 are as in Table 2 for texaphyrins B1-B28.
Claim 24
Dependent Claim
65 words
The method of claim 17 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 and R 8 are OCH 2 CH 2 CH 2 OH; and R 11 is methyl.
Claim 25
Dependent Claim
71 words
The method of claim 17 where R 1 is CH 2 CH 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 O(CH 2 CH 2 O) 2 CH 2 CH 2 OCH 3 ; and R 11 is methyl.
Claim 26
Dependent Claim
12 words
The method of claim 20 wherein M is a paramagnetic metal cation.
Claim 27
Dependent Claim
9 words
The method of claim 20 wherein M is Gd(III).
Claim 28
Dependent Claim
126 words
The method of claim 17 wherein the texaphyrin has structure A, 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 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 , or R 7 is H, OCH 3 or O(CH 2 CH 2 O) 2 CH 2 CH 2 OCH 3 and R 8 is a site-directing molecule or a couple to a site-directing molecule; and M is a paramagnetic ion.
Claim 29
Dependent Claim
9 words
The method of claim 26 wherein M is Gd(III).
Claim 30
Dependent Claim
171 words
The method of claim 1 wherein the texaphyrin has structure A or B: ##STR6## wherein, M is H, a divalent metal cation or a trivalent metal cation; 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, aminoalkyl, oxyaminoalkyl, 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, aminoalkyl, oxyaminoalkyl, 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; where R 5 and R 10 are other than hydrogen, then R 6 and R 9 are hydrogen, hydroxyl, or halide other than iodide; and N is zero, 1 or 2.
Claim 31
Independent Claim
181 words
A method of radiation therapy for a host harboring a neoplasm or atheroma comprising: administering to the host a texaphyrin, said texaphyrin having radiosensitization properties; and administering ionizing radiation to the host in proximity to the neoplasm or atheroma; wherein the texaphyrin has the following structure A: ##STR7## where, M is H, a divalent metal cation or a trivalent metal cation; 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, aminoalkyl, oxyaminoalkyl, 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, aminoalkyl, oxyaminoalkyl, carboxyalkyl, carboxyamidealkyl or a couple to a site-directing molecule; where R 6 and R 9 are other than hydrogen, then R 5 and R 10 are hydrogen or methyl; where R 5 and R 10 are other than hydrogen, then R 6 and R 9 are hydrogen, hydroxyl, or halide other than iodide; and N is zero, 1 or 2.
Claim 32
Independent Claim
181 words
A method of radiation therapy for a host harboring a neoplasm or atheroma comprising: administering to the host a texaphyrin, said texaphyrin having radiosensitization properties; and administering ionizing radiation to the host in proximity to the neoplasm or atheroma; wherein the texaphyrin has the following structure A: ##STR7## where, M is H, a divalent metal cation or a trivalent metal cation; 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, aminoalkyl, oxyaminoalkyl, 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, aminoalkyl, oxyaminoalkyl, carboxyalkyl, carboxyamidealkyl or a couple to a site-directing molecule; where R 6 and R 9 are other than hydrogen, then R 5 and R 10 are hydrogen or methyl; where R 5 and R 10 are other than hydrogen, then R 6 and R 9 are hydrogen, hydroxyl, or halide other than iodide; and N is zero, 1 or 2.
Claim 33
Dependent Claim
9 words
The method of claim 29 wherein M is Gd(III).
Claim 34
Dependent Claim
59 words
The method of claim 29 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 35
Dependent Claim
198 words
The method of claim 29 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 36
Dependent Claim
175 words
The method of claim 29 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 37
Dependent Claim
225 words
The method of claim 29 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 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 38
Dependent Claim
25 words
The method of claim 29 wherein the site-directing molecule is an oligonucleotide, a peptide, a protein, asteroid, a hormone, a hormone mimic or a macrocycle.
Claim 39
Dependent Claim
12 words
The method of claim 29 wherein the site-directing molecule is an oligonucleotide.
Claim 40
Dependent Claim
28 words
The method of claim 29 wherein R 4 is methyl, and R 1 -R 3 and R 5 -R 10 are as in Table 1 for texaphyrins A1-A38.
Claim 41
Dependent Claim
128 words
The method of claim 29 wherein R 1 is CH 2 CH 3 or (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; and 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 , or R 7 is H, OCH 3 , OCH 2 CH 2 CH 2 OH or O(CH 2 CH 2 O) 2 CH 2 CH 2 OCH 3 and R 8 is a site-directing molecule or a couple to a site-directing molecule.
Claim 42
Dependent Claim
25 words
The method of claim 38 wherein the site-directing molecule is an oligonucleotide, a peptide, a protein, asteroid, a hormone, a hormone mimic or a macrocycle.
Claim 43
Dependent Claim
12 words
The method of claim 38 wherein the site-directing molecule is an oligonucleotide.
Claim 44
Dependent Claim
9 words
The method of claim 38 wherein M is Gd(III).
Claim 45
Dependent Claim
70 words
The method of claim 29 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 O(CH 2 CH 2 O) 2 CH 2 CH 2 OCH 3 ; and M is Gd(III).
Claim 46
Dependent Claim
59 words
The method of claim 17 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 47
Dependent Claim
198 words
The method of claim 17 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 48
Dependent Claim
175 words
The method of claim 17 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 49
Dependent Claim
225 words
The method of claim 17 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 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.
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