US2009227647A1PendingUtilityA1
Compounds, Compositions and Methods for the Treatment of Islet Amyloid Polypeptide (IAPP) Accumulation in Diabetes
Est. expiryMar 5, 2028(~1.6 yrs left)· nominal 20-yr term from priority
A61K 31/4164A61K 31/415A61K 31/18A61K 31/4196A61K 31/167A61P 3/10A61K 31/05
64
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Claims
Abstract
Dihydroxyaryl compounds and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of IAPP or amylin fibril diseases, and the manufacture of medicaments for such treatment.
Claims
exact text as granted — not AI-modified1 . A method of treating the formation, deposition, accumulation, or persistence of IAPP amyloid or amylin/IAPP fibrils, comprising treating the fibrils with an effective amount of a compound selected from the group consisting of:
where R is selected from —C(O)NR′, sulfonamide, a five membered heteroaryl , tricycloalkyl or pharmaceutically acceptable esters or salts thereof, and where R′ is selected from H or CH 3 , and where R 1 , R 2 , R 3 , and R 4 are OH, and
when R is —C(O)NR′ and R′ is H and R 1 and R 2 are in the 3,4-position, R 3 and R 4 are not or when R 3 and R 4 are in the 3,4-position, R 1 and R 2 are not.
2 . The method of claim 1 where R is —C(O)NR′ and R′ is selected from H or CH 3 or pharmaceutically acceptable salts thereof.
3 . The method of claim 2 where R′ is H.
4 . The method of claim 2 where the compound is selected from the group consisting of:
2,3 dihydroxybenzoic acid 3,4 dihydroxyanilide;
3,4 dihydroxybenzoic acid 2,3 dihydroxyanilide; and
2,3 dihydroxybenzoic acid 2,3 dihydroxyanilide.
5 . The method of claim 2 where R′ is CH 3 .
6 . The method of claim 2 where the compound is 3,4 dihydroxybenzoic acid 3,4 dihydroxy N-methyl anilide.
7 . The method of claim 1 where R is sulfonamide.
8 . The method of claim 7 where the sulfonamide is 3,4 dihydroxybenzenesulfonic acid 3,4 dihydroxysulfonamide.
9 . The method of claim 1 where R is a five membered heteroaryl.
10 . The method of claim 9 where the five membered heteroaryl is selected from the group consisting of imidazole, triazole, and pyrazole.
11 . The method of claim 9 where the five membered heteroaryl is selected from the group consisting of:
2,4 bis(3,4 dihydroxyphenyl) imidazole;
3,5 bis(3,4 dihydroxyphenyl) 1,2,4 triazole ; and
3,5 bis(3,4 dihydroxyphenyl)pyrazole.
12 . The method of claim 1 where R is tricycloalkyl.
13 . The method of claim 12 where the tricycloalkyl is 1,3 bis(3,4 dihydroxyphenyl) adamantane.
14 . The method of claim 1 where the compound is selected from the group consisting of
(1) the compounds that are:
2,3 dihydroxybenzoic acid 3,4 dihydroxyanilide,
3,4 dihydroxybenzoic acid 2,3 dihydroxyanilide,
2,3 dihydroxybenzoic acid 2,3 dihydroxyanilide,
3,4 dihydroxybenzoic acid 3,4 dihydroxy N-methyl anilide,
3,4 dihydroxybenzenesulfonic acid 3,4 dihydroxysulfonamide,
2,4 bis(3,4 dihydroxyphenyl) imidazole,
3,5 bis(3,4 dihydroxyphenyl) 1,2,4 triazole,
3,5 bis(3,4 dihydroxyphenyl)pyrazole, and
1,3 bis(3,4 dihydroxyphenyl) adamantane;
(2) the methylenedioxy analogs and pharmaceutically acceptable esters thereof; and
(3) the pharmaceutically acceptable salts of the compounds of (1) and (2).
15 . A method of treating type II diabetes in a mammal suffering therefrom, comprising administration to the mammal of a therapeutically effective amount of a compound selected from the group consisting of:
where R is selected from —C(O)NR′, sulfonamide, a five membered heteroaryl , tricycloalkyl or pharmaceutically acceptable esters or salts thereof, and where R′ is selected from H or CH 3 , and where R 1 , R 2 , R 3 , and R 4 are OH, and
when R is —C(O)NR′ and R′ is H and R 1 and R 2 are in the 3,4-position, then R 3 and R 4 are not, or when R 3 and R 4 are in the 3,4-position, then R 1 and R 2 are not.
16 . The method of claim 15 where R is —C(O)NR′ and R′ is selected from H or CH 3 or pharmaceutically acceptable salts thereof.
17 . The method of claim 16 where R′ is H.
18 . The method of claim 16 where the compound is selected from the group consisting of:
2,3 dihydroxybenzoic acid 3,4 dihydroxyanilide;
3,4 dihydroxybenzoic acid 2,3 dihydroxyanilide; and
2,3 dihydroxybenzoic acid 2,3 dihydroxyanilide.
19 . The method of claim 16 where R′ is CH 3 .
20 . The method of claim 16 where the compound is 3,4 dihydroxybenzoic acid 3,4 dihydroxy N-methyl anilide.
21 . The method of claim 15 where R is sulfonamide.
22 . The method of claim 21 where the sulfonamide is 3,4 dihydroxybenzenesulfonic acid 3,4 dihydroxysulfonamide.
23 . The method of claim 15 where R is a five membered heteroaryl.
24 . The method of claim 23 where the five membered heteroaryl is selected from the group consisting of imidazole, triazole, and pyrazole.
25 . The method of claim 23 where the heteroaryl is selected from the group consisting of:
2,4 bis(3,4 dihydroxyphenyl) imidazole;
3,5 bis(3,4 dihydroxyphenyl) 1,2,4 triazole ; and
3,5 bis(3,4 dihydroxyphenyl)pyrazole.
26 . The method of claim 15 where R is tricycloalkyl.
27 . The method of claim 26 where the tricycloalkyl is 1,3 bis(3,4 dihydroxyphenyl) adamantane.
28 . The method of claim 15 where the compound is selected from the group consisting of
(1) the compounds that are:
2,3 dihydroxybenzoic acid 3,4 dihydroxyanilide,
3,4 dihydroxybenzoic acid 2,3 dihydroxyanilide,
2,3 dihydroxybenzoic acid 2,3 dihydroxyanilide,
3,4 dihydroxybenzoic acid 3,4 dihydroxy N-methyl anilide,
3,4 dihydroxybenzenesulfonic acid 3,4 dihydroxysulfonamide,
2,4 bis(3,4 dihydroxyphenyl) imidazole,
3,5 bis(3,4 dihydroxyphenyl) 1,2,4 triazole,
3,5 bis(3,4 dihydroxyphenyl)pyrazole, and
1,3 bis(3,4 dihydroxyphenyl) adamantane;
(2) the methylenedioxy analogs and pharmaceutically acceptable esters thereof; and
(3) the pharmaceutically acceptable salts of the compounds of (1) and (2).Cited by (0)
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