1. A compound represented by the structural formula (I):
or pharmaceutically acceptable isomers, salts, solvates or esters of the compound of Formula (I), wherein in Formula (I) above:
X, Y and Z can be the same or different and each is independently selected from the group consisting of \u2014CH2\u2014, \u2014CH(alkyl)- and \u2014C(alkyl)2\u2014;
Q1 and Q2 can be the same or different and each is independently selected from the group consisting of H, -G, \u2014(C1-C30 alkylene)-G, \u2014OR6, \u2014OC(O)R6, \u2014OC(O)OR9, \u2014OC(O)NR6R7 and -L-M;
Q3 is 1 to 5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, -G, \u2014(C1-C30 alkylene)-G, \u2014OR6, \u2014(C1-C10 alkylene)-OR6, \u2014C(O)R6, \u2014(C1-C10 alkylene)-C(O)R6, \u2014C(O)OR6, \u2014(C1-C10 alkylene)-C(O)OR6, \u2014OC(O)R6, \u2014(C1-C10 alkylene)-OC(O)R6, \u2014OC(O)OR9, \u2014(C1-C10 alkylene)-OC(O)OR9, \u2014CH\u2550CH\u2014C(O)R6, \u2014CH\u2550CH\u2014C(O)OR6, \u2014C\u2261C\u2014C(O)OR6, \u2014C\u2261C\u2014C(O)R6, \u2014O\u2014(C1-C10 alkylene)-OR6, \u2014O\u2014(C1-C10 alkylene)-C(O)R6, \u2014O\u2014(C1-C10 alkylene)-C(O)OR6, \u2014CN, \u2014O\u2014(C1-C10 alkylene)-C(O)NR6R7, \u2014O\u2014C(O)NR6NR7C(O)OR6, \u2014O\u2014(C1-C10 alkylene)-C(O)NR6NR7C(O)OR6, \u2014O\u2014(C1-C10 alkylene)-C(O)(aryl)-N3, \u2014OC(O)\u2014(C1-C10 alkylene)-C(O)OR6, \u2014C(O)NR6R7\u2014(C1-C10 alkylene)-C(O)NR6R7, \u2014OC(O)NR6R7, \u2014(C1-C10 alkylene)-OC(O)NR6R7, \u2014NO2, \u2014NR6R7, \u2014(C1-C10 alkylene)-NR6R7, \u2014O\u2014(C2-C10 alkylene)-NR6R7, \u2014NR6C(O)R7, \u2014NR6C(O)OR9, \u2014NR6C(O)NR7R8, \u2014NR6S(O)0-2R9, \u2014N(S(O)0-2R9)2, \u2014CHNOR6, \u2014C(O)NR6R7, \u2014C(O)NR6NR6R7, \u2014S(O)0-2NR6R7, \u2014S(O)0-2R9, \u2014O\u2014C(O)\u2014(C1-C10 alkylene)-C(O)NR6R7, \u2014OC(O)\u2014(C1-C10 alkylene)-NR6C(O)O-(alkylaryl), \u2014P(O)(OR10)2, \u2014(C1-C10 alkylene)-OSi(alkyl)3, \u2014CF3, \u2014OCF3, halo, alkoxyalkoxy, alkoxyalkoxyalkoxy, alkoxycarbonylalkoxy, alkoxyarylalkoxy, alkoxyiminoalkyl, alkyldioyl, allyloxy, aryl, arylalkyl, aryloxy, arylalkoxy, aroyl, aroyloxy, aroylaroyloxy, arylalkoxycarbonyl, benzoylbenzoyloxy, heteroaryl, heteroarylalkyl, heteroarylalkoxy, dioxolanyl, heterocyclyl, heterocyclylalkyl, heterocyclylcarbonyl, heterocyclylcarbonylalkoxy and -L-M;
Q4 is 1 to 5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, -G, \u2014(C1-C30 alkylene)-G, \u2014OR6, \u2014(C1-C10 alkylene)-OR6, \u2014C(O)R6, \u2014(C1-C10 alkylene)-C(O)R6, \u2014C(O)OR6, \u2014(C1-C10 alkylene)-C(O)OR6, \u2014OC(O)R6, \u2014(C1-C10 alkylene)-OC(O)R6, \u2014OC(O)OR9, \u2014(C1-C10 alkylene)-OC(O)OR9, \u2014CH\u2550CH\u2014C(O)R6, \u2014CH\u2550CH\u2014C(O)OR6, \u2014C\u2261C\u2014C(O)OR6, \u2014C\u2261C\u2014C(O)R6, \u2014O\u2014(C1-C10 alkylene)-OR6, \u2014O\u2014(C1-C10 alkylene)-C(O)R6, \u2014O\u2014(C1-C10 alkylene)-C(O)OR6, \u2014CN, \u2014O\u2014(C1-C10 alkylene)-C(O)NR6R7, \u2014O\u2014C(O)NR6NR7C(O)OR6, \u2014O\u2014(C1-C10 alkylene)-C(O)NR6NR7C(O)OR6, \u2014O\u2014(C1-C10 alkylene)-C(O)(aryl)-N3, \u2014OC(O)\u2014(C1-C10 alkylene)-C(O)OR6, \u2014C(O)NR6R7, \u2014(C1-C10 alkylene)-C(O)NR6R7, \u2014OC(O)NR6R7, \u2014(C1-C10 alkylene)-OC(O)NR6R7, \u2014NO2, \u2014NR6R7, \u2014(C1-C10 alkylene)-NR6R7, \u2014O\u2014(C2-C10 alkylene)-NR6R7, \u2014NR6C(O)R7, \u2014NR6C(O)OR9, \u2014NR6C(O)NR7R8, \u2014NR6S(O)0-2R9, \u2014N(S(O)0-2R9)2, \u2014CHNOR6, \u2014C(O)NR6R7, \u2014C(O)NR6NR6R7, \u2014S(O)0-2NR6R7, \u2014S(O)0-2R9, \u2014O\u2014C(O)\u2014(C1-C10 alkylene)-C(O)NR6R7, \u2014OC(O)\u2014(C1-C10 alkylene)-NR6C(O)O-(alkylaryl), \u2014P(O)(OR10)2, \u2014(C1-C10 alkylene)-OSi(alkyl)3, \u2014CF3, \u2014OCF3, halo, alkoxyalkoxy, alkoxyalkoxyalkoxy, alkoxycarbonylalkoxy, alkoxyarylalkoxy, alkoxyiminoalkyl, alkyldioyl, allyloxy, aryl, arylalkyl, aryloxy, arylalkoxy, aroyl, aroyloxy, aroylaroyloxy, arylalkoxycarbonyl, benzoylbenzoyloxy, heteroaryl, heteroarylalkyl, heteroarylalkoxy, dioxolanyl, heterocyclyl, heterocyclylalkyl, heterocyclylcarbonyl, heterocyclylcarbonylalkoxy and -L-M;
Q5 is 1 to 5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, -G, \u2014(C1-C30 alkylene)-G, \u2014OR6, \u2014(C1-C10 alkylene)-OR6, \u2014C(O)R6, \u2014(C1-C10 alkylene)-C(O)R6, \u2014C(O)OR6, \u2014(C1-C10 alkylene)-C(O)OR6, \u2014OC(O)R6, \u2014(C1-C10 alkylene)-OC(O)R6, \u2014OC(O)OR9, \u2014(C1-C10 alkylene)-OC(O)OR9, \u2014CH\u2550CH\u2014C(O)R6, \u2014CH\u2550CH\u2014C(O)OR6, \u2014C\u2261C\u2014C(O)OR6, \u2014C\u2261C\u2014C(O)R6, \u2014O\u2014(C1-C10 alkylene)-OR6, \u2014O\u2014(C1-C10 alkylene)-C(O)R6, \u2014O\u2014(C1-C10 alkylene)-C(O)OR6, \u2014CN, \u2014O\u2014(C1-C10 alkylene)-C(O)NR6R7, \u2014O\u2014C(O)NR6NR7C(O)OR6, \u2014O\u2014(C1-C10 alkylene)-C(O)NR6NR7C(O)OR6, \u2014O\u2014(C1-C10 alkylene)-C(O)(aryl)-N3, \u2014OC(O)\u2014(C1-C10 alkylene)-C(O)OR6, \u2014C(O)NR6R7, \u2014(C1-C10 alkylene)-C(O)NR6R7, \u2014OC(O)NR6R7, \u2014(C1-C10 alkylene)-OC(O)NR6R7, \u2014NO2, \u2014NR6R7, \u2014(C1-C10 alkylene)-NR6R7, \u2014O\u2014(C2-C10 alkylene)-NR6R7, \u2014NR6C(O)R7, \u2014NR6C(O)OR9, \u2014NR6C(O)NR7R8, \u2014NR6S(O)0-2R9, \u2014N(S(O)0-2R9)2, \u2014CHNOR6, \u2014C(O)NR6R7, \u2014C(O)NR6NR6R7, \u2014S(O)0-2NR6R7, \u2014S(O)0-2R9, \u2014O\u2014C(O)\u2014(C1-C10 alkylene)-C(O)NR6R7, \u2014OC(O)\u2014(C1-C10 alkylene)-NR6C(O)O-(alkylaryl), \u2014P(O)(OR10)2, \u2014(C1-C10 alkylene)-OSi(alkyl)3, \u2014CF3, \u2014OCF3, halo, alkoxyalkoxy, alkoxyalkoxyalkoxy, alkoxycarbonylalkoxy, alkoxyarylalkoxy, alkoxyiminoalkyl, alkyldioyl, allyloxy, aryl, arylalkyl, aryloxy, arylalkoxy, aroyl, aroyloxy, aroylaroyloxy, arylalkoxycarbonyl, benzoylbenzoyloxy, heteroaryl, heteroarylalkyl, heteroarylalkoxy, dioxolanyl, heterocyclyl, heterocyclylalkyl, heterocyclylcarbonyl, heterocyclylcarbonylalkoxy and -L-M;
wherein optionally one or more carbon atoms of the \u2014(C1-C30 alkylene)-radical of Q1, Q2, Q3, Q4 and Q5 is independently replaced by \u2014O\u2014, \u2014C(O)\u2014, \u2014CH\u2550CH\u2014, \u2014C\u2261C\u2014, \u2014N(alkyl)-, \u2014N(alkylaryl)- or \u2014NH\u2014;
G is selected from the group consisting of a sugar residue, disugar residue, trisugar residue, tetrasugar residue, sugar acid, and amino sugar wherein optionally the sugar residue, disugar residue, trisugar residue, tetrasugar residue, sugar acid, or amino sugar of G is substituted with -L-M;
L is selected from the group consisting of
\u2003wherein Me is methyl;
M is selected from the group of moieties consisting of
\u2003pharmaceutically acceptable salts of the moieties (M1) to (M9) and free acids of the moieties (M1) to (M9);
R2 and R3 can be the same or different and each is independently selected from the group consisting of hydrogen, alkyl and aryl;
R6, R7 and R8 can be the same or different and each is independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl; and
each R9 is independently alkyl, aryl or arylalkyl,
each R10 is independently H or alkyl;
q is 0 or 1;
r is 0 or 1;
m, n and p are independently selected from 0, 1, 2, 3 or 4; provided that at least one of q and r is 1, and the sum of m, n, p, q and r is 1, 2, 3, 4, 5 or 6; and provided that when p is 0 and r is 1, the sum of m, q and n is 1, 2, 3, 4 or 5;
x1 is 1 to 10;
x2 is 1 to 10;
x3 is 1 to 10;
x4 is 1 to 10;
x5 is 1 to 10;
x6 is 1 to 10; and
x7 is 1 to 10;
x8 is 1 to 10;
x9 is 1 to 10;
x10 is 1 to 10; and
x11 is 1 to 10;
with the proviso that at least one of Q1, Q2, Q3, Q4 and Q5 is the sugar residue, disugar residue, trisugar residue, tetrasugar residue, sugar acid, or amino sugar of G is substituted with -L-M, and
wherein each of the above alkyl, alkenyl, alkynyl, alkylene, alkoxyalkoxy, alkoxyalkoxyalkoxy alkoxycarbonylalkoxy, alkoxyarylalkoxy, alkoxyiminoalkyl, alkyldioyl, allyloxy, aryl, arylalkyl, aryloxy, arylalkoxy, aroyl, aroyloxy, aroylaroyloxy, arlalkoxycarbonyl, benzoylbenzoyloxy, heteroaryl, heteroarylalkyl, heteroarylalkoxy, dioxolanyl, heterocyclyl, heterocyclylalkyl, heterocyclylcarbonyl, or heterocyclylcarbonylalkoxy groups, when present, is independently substituted or unsubstituted.
2. The compound according to claim 1, wherein m, n and r are each zero, q is 1, p is 2, and Z is \u2014CH2\u2014.
3. The compound according to claim 1, wherein m, n and r are each zero, q is 1, p is 2, and Z is \u2014CH2\u2014, Q1 is \u2014OR6, wherein R6 is hydrogen and Q5 is fluorine.
4. The compound according to claim 1, wherein R2 and R3 are each hydrogen.
5. The compound according to claim 1, wherein Q1 and Q2 are each independently selected from the group consisting of \u2014OR6, \u2014O(CO)R6, \u2014O(CO)OR9 and \u2014O(CO)NR6R7.
6. The compound according to claim 1, wherein Q4 is halo or \u2014OR6.
7. The compound according to claim 1, wherein Q1 is \u2014OR6 wherein R6 is H.
8. The compound according to claim 1, wherein Q1, Q2, Q3, Q4 or Q5 is -L-M.
9. The compound according to claim 1, wherein Q1, Q2, Q3, Q4 or Q5 is -G or \u2014(C1-C30 alkylene)-G.
10. The compound according to claim 1, wherein G is selected from the group consisting of:
wherein R, Ra and Rb can be the same or different and each is independently selected from the group consisting of H, \u2014OH, halo, \u2014NH2, azido, alkoxyalkoxy or \u2014W\u2014R30;
W is independently selected from the group consisting of \u2014NH\u2014C(O)\u2014, \u2014O\u2014C(O)\u2014, \u2014O\u2014C(O)\u2014N(R31)\u2014, \u2014NH\u2014C(O)\u2014N(R31)\u2014 and \u2014O\u2014C(S)\u2014N(R31)\u2014;
R2a and R6a can be the same or different and each is independently selected from the group consisting of H, alkyl, acetyl, aryl and arylalkyl;
R3a, R4a, R5a, R7a, R3b and R4b can be the same or different and each is independently selected from the group consisting of H, alkyl, acetyl, arylalkyl, \u2014C(O)alkyl and \u2014C(O)aryl;
R30 is independently selected from the group consisting of R32-substituted T, R32-substituted-T-alkyl, R32-substituted-alkenyl, R32-substituted-alkyl, R32-substituted-cycloalkyl and R32-substituted-cycloalkylalkyl;
R31 is independently selected from the group consisting of H and alkyl;
T is independently selected from the group consisting of phenyl, furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, benzothiazolyl, thiadiazolyl, pyrazolyl, imidazolyl and pyridyl;
R32 is 1 to 3 substituents which are each independently selected from the group consisting of H, halo, alkyl, \u2014OH, phenoxy, \u2014CF3, \u2014NO2, alkoxy, methylenedioxy, oxo, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, \u2014N(CH3)2, \u2014C(O)\u2014NHalkyl, \u2014C(O)\u2014N(alkyl)2, \u2014C(O)-alkyl, \u2014C(O)-alkoxy and pyrrolidinylcarbonyl; or R32 is a covalent bond and R31, the nitrogen to which it is attached and R32 form a pyrrolidinyl, piperidinyl, N-methyl-piperazinyl, indolinyl or morpholinyl group, or a alkoxycarbonyl-substituted pyrrolidinyl, piperidinyl, N-methylpiperazinyl, indolinyl or morpholinyl group.
11. The compound according to claim 10, wherein G is selected from:
wherein Ac is acetyl and Ph is phenyl.
12. The compound according to claim 1, wherein optionally one or more carbon atoms of the \u2014(C1-C30 alkylene)- radical of Q1, Q2, Q3, Q4 and Q5 is independently replaced by \u2014O\u2014.
13. The compound according to claim 1, wherein L is
14. The compound according to claim 1, wherein L is
15. The compound according to claim 1, wherein M is
or pharmaceutically acceptable salts thereof.
16. The compound according to claim 1, wherein M is
or pharmaceutically acceptable salts thereof.
17. The compound according to claim 1, wherein M is
or pharmaceutically acceptable salts thereof.
18. The compound according to claim 1, wherein M is
or pharmaceutically acceptable salts thereof.
19. The compound according to claim 1, wherein M is
or pharmaceutically acceptable salts thereof.
20. A pharmaceutical composition for the treatment of atherosclerosis, hypercholesterolemia, sitosterolemia, lowering a concentration of cholesterol, phytosterol or 5\u03b1-stanol in plasma of a mammal, treating demyelination or treating Alzheimer’s disease andor regulating levels of amyloid \u03b2 peptides in a subject comprising a therapeutically effective amount of a compound of claim 1 in a pharmaceutically acceptable carrier.
21. A pharmaceutical composition comprising a cholesterol-lowering effective amount of a compound of claim 1 in a pharmaceutically acceptable carrier.
22. A method of treating atherosclerosis, hypercholesterolemia, sitosterolemia, lowering a concentration of cholesterol, phytosterol or 5\u03b1-stanol in plasma of a mammal, treating demyelination or treating Alzheimer’s disease or regulating a level of an amyloid \u03b2 peptide in a subject comprising the step of administering to a subject in need of such treatment an effective amount of a compound of claim 1.
23. A method of lowering cholesterol level in plasma of a mammal in need of such treatment comprising administering a pharmaceutically effective amount of the compound of claim 1.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A data storage system comprising:
a storage device; and
a data handler coupled to the storage device and operable to:
receive object content;
create metadata associated with the object content, wherein the metadata includes:
a key;
a first authorization field; and
a second authorization field;
create a data object including the object content and the metadata;
store the data object on the storage device;
receive a first access request for the data object;
determine that the first access request includes the key;
determine that the first access request includes information associated with the first authorization field in response to determining that the first access request includes the key;
permit an execution of a first operation on the data object in response to determining that the first access request includes information associated with the first authorization field;
receive a second access request for the data object;
determine that the second access request includes the key;
determine that the second access request includes information associated with the second authorization field in response to determining that the second access request includes the key; and
deny the execution of the first operation on the data object in response to determining that the second access request includes information associated with the second authorization field.
2. The data storage system of claim 1, wherein the first and second authorization fields each include a plurality of operation fields operable to permit a plurality of operations on the data object, the operation fields including at least one of:
a first operation field to enable writing of the data object to the storage device;
a second operation field to enable modifying of the data object on the storage device;
a third operation field to enable reading of the data object from the storage device; and
a fourth operation field to enable deleting of the data object from the storage device.
3. The data storage system of claim 2, wherein:
the first authorization field includes a first type field;
the second authorization field includes a second type field;
in determining that the first access request includes information associated with the first authorization field, the data handler is further operable to determine if the first access request includes the first type field; and
in determining that the second access request includes information associated with the second authorization field, the data handler is further operable to determine if the second access request includes the second type field.
4. The data storage system of claim 3, wherein the first access request corresponds with the first type field when the first access request is received from a user group associated with the first type field.
5. The data storage system of claim 3, wherein the first access request corresponds with the first type field when the first access request is received at a first particular time, wherein the first particular time relative to a second particular time that is indicated by the first type field.
6. The data storage system of claim 5, wherein the first particular time is before the second particular time.
7. The data storage system of claim 5, wherein the first particular time is after the second particular time.
8. The data storage system of claim 1, wherein the data handler is further operable to:
deny an execution of a second operation on the data object in response to determining that the first access request includes information associated with the first authorization field; and
permit the execution of the second operation on the data object in response to determining that the second access request includes information associated with the second authorization field.
9. A method comprising:
receiving object content at a data handler coupled to a storage device;
creating metadata associated with the object content, wherein the metadata includes:
a key;
a first authorization field; and
a second authorization field
creating a data object including the object content and the metadata;
storing the data object on the storage device;
receiving a first access request for the data object;
determining that the first access request includes the key;
determining that the first access request includes information associated with the first authorization field in response to determining that the first access request includes the key;
permitting an execution of a first operation on the data object in response to determining that the first access request includes information associated with the first authorization field
receiving a second access request for the data object;
determining that the second access request includes the key;
determining that the second access request includes information associated with the second authorization field in response to determining that the second access request includes the key; and
denying the execution of the first operation on the data object in response to determining that the second access request includes information associated with the second authorization field.
10. The method of claim 9, wherein the first and second authorization fields each include a plurality of operation fields operable to permit a plurality of operations on the data object, the operation fields including:
a first operation field to enable writing of the data object to the storage device;
a second operation field to enable modifying of the data object on the storage device;
a third operation field to enable reading of the data object from the storage device; and
a fourth operation field to enable deleting of the data object from the storage device.
11. The method of claim 10, wherein:
the first authorization field includes a first type field;
the second authorization field includes a second type field;
in determining that the first access request includes information associated with the first authorization field, the method further comprises determining if the first access request includes the first type field; and
in determining that the second access request includes information associated with the second authorization field, the method further comprises determining if the second access request includes the second type field.
12. The method of claim 11, wherein the first access request corresponds with the first type field when the first access request is received from a user group associated with the first type field.
13. The method of claim 11, wherein the first access request corresponds with the first type field when the first access request is received at a first particular time, wherein the first particular time relative to a second particular time that is indicated by the first type field.
14. The method of claim 9, further comprising:
denying an execution of a second operation on the data object in response to determining that the first access request includes information associated with the first authorization field; and
permitting the execution of the second operation on the data object in response to determining that the second access request includes information associated with the second authorization field.
15. Machine-executable code for an information handling system, wherein the machine-executable code is embedded within a non-transitory medium and includes instructions for carrying out a method, the method comprising:
receiving object content at a data handler coupled to a storage device;
creating metadata associated with the object content, wherein the metadata includes:
a key;
a first authorization field;
creating a data object including the object content and the metadata;
storing the data object on the storage device;
receiving a first access request for the data object;
determining that the first access request includes the key;
determining that the first access request includes information associated with the first authorization field in response to determining that the request includes the key;
permitting an execution of a first operation on the object in response to determining that the first access request includes information associated with the first authorization field;
receiving a second access request for the data object;
determining that the second access request includes the key;
determining that the second access request includes information associated with the second authorization field in response to determining that the second access request includes the key; and
denying the execution of the first operation on the data object in response to determining that the second access request includes information associated with the second authorization field.
16. The machine-executable code of claim 15, wherein:
the first authorization field includes a first type field;
the second authorization field includes a second type field;
in determining that the first access request includes information associated with the first authorization field, the method further comprises determining if the first access request includes the first type field; and
in determining that the second access request includes information associated with the second authorization field, the method further comprises determining if the second access request includes the second type field.
17. The machine-executable code of claim 16, wherein the first access request corresponds with the first type field when the first access request is received from a user group associated with the first type field.
18. The machine-executable code of claim 17, wherein the first access request corresponds with the first type field when the first access request is received at a first particular time, wherein the first particular time relative to a second particular time that is indicated by the first type field.
19. The machine-executable code of claim 15, the method further comprising:
denying an execution of a second operation on the data object in response to determining that the first access request includes information associated with the first authorization field; and
permitting the execution of the second operation on the data object in response to determining that the second access request includes information associated with the second authorization field.