US2003023104A1PendingUtilityA1
Therapeutic compound - fatty acid conjugates
Est. expiryJan 16, 2015(expired)· nominal 20-yr term from priority
A61P 37/04A61P 31/12A61P 29/00A61K 47/54C07D 489/02C07H 19/06C07K 5/06078C07K 5/00C07H 19/04C07K 7/06A61K 38/00C07D 475/08A61K 47/542C07J 41/005C07C 237/22A61P 25/04
47
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Claims
Abstract
A therapeutic compound of the chlorambucil family conjugated to two or three acyl groups derived from fatty acids. The compound has the following formula. in which X is a member of the chlorambucil family, Y is an optional spacer group, AA is an amino acid, B is H or CH 2 O—R 3 , and n is a number from 0 to 3. X is linked to Y via the carboxyl group. R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
Claims
exact text as granted — not AI-modified1 . A compound of the following formula:
in which X is a member of the corticosterone family of hormones or drugs and is linked to Y via an hydroxyl group
Y is a spacer group
AA is an amino acid; n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 . R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
2 . A compound as claimed in claim 1 in which X is hydrocortisone or cortisone.
3 . A compound as claimed in claim 1 or claim 2 in which Y is a dicarboxylic acid, AA is not present or is glycine or alanine and the linkage is via the hydroxyl group at position 21.
4 . A compound of the following formula:
X—Y—[AA] n —NH—CH 2 —CH 2 O—R 4 in which X is a member of the corticosterone family of hormones or drugs and is linked to Y via an hydroxyl group Y is a spacer group AA is an amino acid; n is a number from 0 to 5, and R 4 is an acyl group derived from a fatty acid.
5 . A compound as claimed in claim 4 in which X is hydrocortisone or cortisone.
6 . A compound as claimed in claim 4 or claim 5 in which Y is a dicarboxylic acid, AA is not present or is glycine or alanine and the linkage is via the hydroxyl group at position 21.
7 . A method of prolonging or altering the activity of a member of the corticosterone family of hormones or drugs comprising administering the compound in the form:
in which X is a member of the corticosterone family of hormones or drugs and is linked to Y via an hydroxyl group
Y is a linker group
AA is an amino acid; n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
8 . A method as claimed in claim 7 in which X is hydrocortisone or cortisone.
9 . A method as claimed in claim 7 or claim 8 in which Y is a dicarboxylic acid, AA is not present or is glycine or alanine and the linkage is via the hydroxyl group at position 21.
10 . A method of prolonging or altering the activity of a member of the corticosterone family of hormones or drugs comprising administering the compound in the form:
X—Y—[AA] n -NH—CH 2 —CH 2 O—R 4 in which X is a member of the corticosterone family of hormones or drugs and is linked to Y via an hydroxyl group Y is a spacer group AA is an amino acid; n is a number from 0 to 5, and R 4 is an acyl group derived from a fatty acid.
11 . A method as claimed in claim 10 in which X is hydrocortisone or cortisone.
12 . A method as claimed in claim 10 or claim 11 in which Y is a dicarboxylic acid, AA is not present or is glycine or alanine and the linkage is via the hydroxyl group at position 21.
13 . A compound of the following formula:
in which X is a member of the morphine family and is linked to Y via an hydroxyl group eg the hydroxyl group at the 3 or 6 position
Y is a spacer group
AA is an amino acid; n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
14 . A compound as claimed in claim 13 in which X is morphine modified at the 3 or 6 position, Y is a dicarboxylic acid and AA is not present or is glycine or alanine.
15 . A compound of the following formula:
X—Y—[AA] n —NH—CH 2 —CH 2 O—R 4 in which X is a member of the morphine family and is linked to Y via an hydroxyl group at the 3 or 6 position Y is a spacer group AA is an amino acid; n is a number from 0 to 5, and R 4 is an acyl group derived from a fatty acid.
16 . A compound as claimed in claim 15 in which X is morphine modified at the 3 or 6 position, Y is a dicarboxylic acid and AA is not present or is glycine or alanine.
17 . A method of prolonging or altering the activity of a compound of the morphine family comprising administering the compound in the form:
in which X is a member of the morphine family and is linked to Y via an hydroxyl group at the 3 or the 6 position
Y is a linker group
AA is an amino acid; n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
18 . A method as claimed in claim 17 in which X is morphine modified at the 3 or 6 position, Y is a dicarboxylic acid and AA is not present or is glycine or alanine.
19 . A method of prolonging or altering the activity of a compound of the morphine family comprising administering the compound in the form:
X—Y—[AA] n —NH—CH 2 —CH 2 O—R 4 in which X is a member of the morphine family and is linked to Y via an hydroxyl group at the 3 or the 6 position Y is a spacer group AA is an amino acid; n is a number from 0 to 5, and R 4 is an acyl group derived from a fatty acid.
20 . A method as claimed in claim 20 in which X is morphine modified at the 3 or 6 position. Y is a dicarboxylic acid and AA is not present or is glycine or alanine.
21 . A compound of the following formula:
in which X is an antiviral nucleoside and is linked to Y via an hydroxyl group
Y is a spacer group
AA is an amino acid: n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
22 . A compound as claimed in claim 21 in which X is AZT.
23 . A compound as claimed in claim 21 or 22 in which Y is a dicarboxylic acid and AA is not present or is glycine or alanine.
24 . A compound of the following formula:
X—Y—[AA] n —NH—CH 2 —CH 2 O—R 4 in which X is an antiviral nucleoside and is linked to Y via an hydroxyl group Y is a spacer group AA is an amino acid; n is a number from 0 to 5, and R 4 is an acyl group derived from a fatty acid.
25 . A compound as claimed in claim 24 in which X is AZT.
26 . A compound as claimed in claim 24 or 25 in which Y is a dicarboxylic acid and AA is not present or is glycine or alanine.
27 . A method of prolonging or altering the activity of an antiviral nucleoside comprising administering the antiviral nucleoside in the form:
in which X is an antiviral nucleoside and is linked to Y via an hydroxyl group
Y is a linker group
AA is an amino acid; n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
28 . A method as claimed in claim 27 in which X is AZT.
29 . A method as claimed in claim 27 or 28 in which Y is a dicarboxylic acid and AA is not present or is glycine or alanine.
30 . A method of prolonging or altering the activity of an antiviral nucleoside comprising administering the antiviral nucleoside in the form:
X—Y—[AA] n —NH—CH 2 —CH 2 O—R 4 in which X is an antiviral nucleoside and is linked to Y via an hydroxyl group Y is a spacer group AA is an amino acid; n is a number from 0 to 5, and R 4 is an acyl group derived from a fatty acid.
31 . A method as claimed in claim 30 in which X is AZT.
32 . A method as claimed in claim 30 or 31 in which Y is a dicarboxylic acid and AA is not present or is glycine or alanine.
33 . A compound of the following formula:
in which X is a member of the cyclosporin family of drugs and is linked to Y via an hydroxyl group
Y is a spacer group
AA is an amino acid; n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
34 . A compound as claimed in claim 33 in which X is cyclosporin C.
35 . A compound as claimed in claim 33 or 34 in which Y is a dicarboxylic acid and AA is not present or is glycine or alanine.
36 . A compound of the following formula:
X—Y—[AA] n —NH—CH 2 —CH 2 O—R 4 in which X is a member of the cyclosporin family of drugs and is linked to Y via an hydroxyl group Y is a spacer group AA is an amino acid; n is a number from 0 to 5, and R 4 is an acyl group derived from a fatty acid.
37 . A compound as claimed in claim 36 in which X is cyclosporin C.
38 . A compound as claimed in claim 36 or 37 in which Y is a dicarboxylic acid and AA is not present or is glycine or alanine.
39 . A method of prolonging or altering the activity of a compound of the cyclosporin family of drugs comprising administering the compound in the form:
in which X is a member of the cyclosporin family of drugs and is linked to Y via an hydroxyl group
Y is a linker group
AA is an amino acid; n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
40 . A method as claimed in claim 39 in which X is cyclosporin C.
41 . A method as claimed in claim 39 or 40 in which Y is a dicarboxylic acid and AA is not present or is glycine or alanine.
42 . A method of prolonging or altering the activity of a compound of the cyclosporin family of drugs comprising administering the compound in the form:
X—Y—[AA] n —NH—CH 2 —CH 2 O—R 4 in which X is a member of the cyclosporin family of drugs and is linked to Y via an hydroxyl group Y is a spacer group AA is an amino acid, n is a number from 0 to 5, and R 4 is an acyl group derived from a fatty acid.
43 . A method as claimed in claim 42 in which X is cyclosporin C.
44 . A method as claimed in claim 42 or 43 in which Y is a dicarboxylic acid and AA is not present or is glycine or alanine.
45 . A compound of the following formula:
in which X is a member of the folate antagonist family and is linked to Y via a carboxyl group
Y is an optional spacer group
AA is an amino acid; n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
46 . A compound as claimed in claim 45 in which X is methotrexate, Y is absent, an amino acid, glycolic acid, 3-hydroxypropionic acid or lactic acid, AA is not present or glycine or alanine, and the linkage is either an amide bond or an ester bond preferably to the γ-carboxyl of the glutamyl moiety of methotrexate.
47 . A compound of the following formula:
X—Y—[AA] n —NH—CH 2 —CH 2 O—R 4 in which X is a member of the folate antagonist family and is linked to Y via either a carboxyl group Y is an optional spacer group AA is an amino acid; n is a number from 0 to 5, and R 4 is an acyl group derived from a fatty acid.
48 . A compound as claimed in claim 47 in which X is methotrexate, Y is absent. an amino acid, glycolic acid, 3-hydroxypropionic acid or lactic acid, AA is not present or glycine or alanine, and the linkage is either an amide bond or an ester bond preferably to the γ-carboxyl of the glutamyl moiety of methotrexate.
49 . A method of prolonging or altering the activity of a compound of the folate antagonist family comprising administering the compound in the form:
in which X is a member of the folate antagonist family and is linked to Y via a carboxyl group
Y is an optional spacer group
AA is an amino acid; n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
50 . A method as claimed in claim 49 in which X is methotrexate, Y is absent, an amino acid, glycolic acid, 3-hydroxypropionic acid or lactic acid, AA is not present or glycine or alanine, and the linkage is either an amide bond or an ester bond preferably to the γ-carboxyl of the glutamyl moiety of methotrexate.
51 . A method of prolonging or altering the activity of a compound of the folate antagonist family comprising administering the compound in the form:
X—Y—[AA] n —NH—CH 2 —CH 2 O—R 4 in which X is a member of the folate antagonist family and is linked to Y via a carboxyl group Y is an optional spacer group AA is an amino acid; n is a number from 0 to 5, and R 4 is an acyl group derived from a fatty acid.
52 . A method as claimed in claim 51 in which X is methotrexate, Y is absent. an amino acid, glycolic acid, 3-hydroxypropionic acid or lactic acid, AA is not present or glycine or alanine, and the linkage is either an amide bond or an ester bond preferably to the γ-carboxyl of the glutamyl moiety of methotrexate.
53 . A compound of the following formula:
in which X is a member of the DOPA family and is linked to Y via the carboxyl group or amino group
Y is an optional spacer group
AA is an amino acid; n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
54 . A compound as claimed in claim 53 in which X is DOPA, Y is absent, an amino acid, glycolic acid, 3-hydroxypropionic acid or lactic acid, AA is not present or glycine or alanine, and the linkage is either an amide bond or an ester bond to the carboxyl group.
55 . A compound of the following formula:
X—Y—[AA] n —NH—CH 2 —CH 2 O—R 4 in which X is a member of the DOPA family and is linked to Y via the carboxyl group or amino group Y is an optional spacer group AA is an amino acid; n is a number from 0 to 5, and R 4 is an acyl group derived from a fatty acid.
56 . A compound as claimed in claim 55 in which X is DOPA. Y is absent, an amino acid, glycolic acid, 3-hydroxypropionic acid or lactic acid, AA is not present or glycine or alanine, and the linkage is either an amide bond or an ester bond to the carboxyl group.
57 . A method of prolonging or altering the activity of a compound of the DOPA family comprising administering the compound in the form:
in which X is a member of the DOPA family and is linked to Y via the carboxyl group or amino group
Y is an optional spacer group
AA is an amino acid; n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
58 . A method as claimed in claim 57 in which X is DOPA, Y is absent, an amino acid, glycolic acid, 3-hydroxypropionic acid or lactic acid, AA is not present or glycine or alanine, and the linkage is either an amide bond or an ester bond to the carboxyl group.
59 . A method of prolonging or altering the activity of a compound of the DOPA family comprising administering the compound in the form:
X—Y—[AA] n —NH—CH 2 —CH 2 O—R 4 in which X is a member of the DOPA family and is linked to Y via the carboxyl group or amino group Y is an optional spacer group AA is an amino acid; n is a number from 0 to 5. and R 4 is an acyl group derived from a fatty acid.
60 . A method as claimed in claim 59 in which X is DOPA, Y is absent, an amino acid, glycolic acid, 3-hydroxypropionic acid or lactic acid, AA is not present or glycine or alanine, and the linkage is either an amide bond or an ester bond to the carboxyl group.
61 . A compound of the following formula:
in which X is a member of the chlorambucil family and is linked to Y via the carboxyl group
Y is an optional spacer group
AA is an amino acid; n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
62 . A compound as claimed in claim 61 in which X is chlorambucil, Y is absent, an amino acid, glycolic acid, 3-hydroxypropionic acid or lactic acid, AA is not present or glycine or alanine and the linkage is either an amide bond or an ester bond to the carboxyl group.
63 . A compound of the following formula:
X—Y—[AA] n —NH—CH 2 —CH 2 O—R 4 in which X is a member of the chlorambucil family and is linked to Y via the carboxyl group Y is an optional spacer group AA is an amino acid; n is a number from 0 to 5, and R 4 is an acyl group derived from a fatty acid.
64 . A compound as claimed in claim 63 in which X is chlorambucil, Y is absent. an amino acid, glycolic acid, 3-hydroxypropionic acid or lactic acid, AA is not present or glycine or alanine and the linkage is either an amide bond or an ester bond to the carboxyl group.
65 . A method of prolonging or altering the activity of a compound which is a member of the chlorambucil family comprising administering the compound in the form:
in which X is a member of the chlorambucil family and is linked to Y via the carboxyl group
Y is an optional spacer group
AA is an amino acid; n is a number from 0 to 5
B is H or CH 2 O—R 3
R 1 , R 2 and R 3 are the same or different and are either hydrogen, methyl, ethyl or an acyl group derived from a fatty acid, with the proviso that at least one of R 1 , R 2 and R 3 is an acyl group derived from a fatty acid.
66 . A method as claimed in claim 65 in which X is chlorambucil, Y is absent, an amino acid, glycolic acid, 3-hydroxypropionic acid or lactic acid, AA is not present or glycine or alanine and the linkage is either an amide bond or an ester bond to the carboxyl group.
67 . A method of prolonging or altering the activity of a compound which is a member of the chlorambucil family comprising administering the compound in the form:
X—Y—[AA] n —NH—CH 2 -CH 2 O—R 4 in which X is a member of the chlorambucil family and is linked to Y via the carboxyl group Y is an optional spacer group AA is an amino acid; n is a number from 0 to 5, and R 4 is an acyl group derived from a fatty acid.
68 . A method as claimed in claim 67 in which X is chlorambucil, Y is absent, an amino acid, glycolic acid, 3-hydroxypropionic acid or lactic acid, AA is not present or glycine or alanine and the linkage is either an amide bond or an ester bond to the carboxyl group.Join the waitlist — get patent alerts
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