| US 7,601,876 B2 | ||
| Compounds, compositions and methods for the treatment of amyloid diseases such as systemic AA amyloidosis | ||
| Alan D. Snow, Lynnwood, Wash. (US); Beth P. Nguyen, Gurnee, Ill. (US); Gerardo M. Castillo, Bothell, Wash. (US); Virginia J. Sanders, San Francisco, Calif. (US); Thomas P. Lake, Snohomish, Wash. (US); Lesley Larsen, Port Chalmers (New Zealand); Rex T. Weavers, Dunedin (New Zealand); Stephen D. Lorimer, Dunedin (New Zealand); David S. Larsen, Port Chalmers (New Zealand); and David L. Coffen, Belcamp, Md. (US); Charlotte Coffen, legal representative | ||
| Assigned to Proteotech, Inc., Kirkland, Wash. (US) | ||
| Filed on Mar. 05, 2007, as Appl. No. 11/714,894. | ||
| Application 11/714894 is a continuation in part of application No. 10/452851, filed on May 30, 2003, granted, now 7,514,583. | ||
| Claims priority of provisional application 60/385144, filed on May 31, 2002. | ||
| Claims priority of provisional application 60/409100, filed on Sep. 09, 2002. | ||
| Claims priority of provisional application 60/412272, filed on Sep. 20, 2002. | ||
| Claims priority of provisional application 60/435880, filed on Dec. 20, 2002. | ||
| Claims priority of provisional application 60/463104, filed on Apr. 14, 2003. | ||
| Prior Publication US 2007/0225362 A1, Sep. 27, 2007 | ||
| This patent is subject to a terminal disclaimer. | ||
| Int. Cl. C07C 33/00 (2006.01); C07C 49/00 (2006.01); C07C 209/00 (2006.01); C07C 211/00 (2006.01); C07C 233/00 (2006.01); C07C 239/00 (2006.01); C07C 275/00 (2006.01); A61K 31/00 (2006.01) | ||
| U.S. Cl. 568—331 [568/807; 568/809; 564/52; 564/158; 564/170; 564/175; 564/179; 564/367; 564/384; 514/598; 514/616; 514/622; 514/649; 514/650; 514/655; 514/685; 514/734] | 36 Claims |
| 1. A method of treating the formation, deposition, accumulation, or persistence of AA amyloid fibrils, comprising treating
the fibrils with an effective amount of
(1) a compound of the formula:
 where:
R is a C1-C10 alkylene group, in which, when the number of carbon atoms is at least 2, there are optionally 1 or 2 non-adjacent double bonds;
1 to 3 non-adjacent methylene groups are optionally replaced by NR′ where R′ is H, alkyl, or acyl, O, or S; and 1 or 2 methylene
groups are optionally replaced by a carbonyl or hydroxymethylene group;
(2) a compound selected from the group consisting of:
3,4,3′,4′-tetrahydroxybenzoin; 3,4,3′,4′-tetrahydroxydesoxybenzoin; 3,4,3′,4′-tetrahydroxydiphenylmethane; 1,2-bis(3,4-dihydroxyphenyl)ethane;
1,3-bis(3,4-dihydroxyphenyl)propane; 3,4,3′,4′-tetrahydroxychalcone; 3,5-bis(3,4-dihydroxyphenyl)-1-methyl-2-pyrazoline; 4,6-bis(3,4-dihydroxyphenyl)-3-cyano-2-methylpyridine;
1,4-bis(3,4-dihydroxybenzyl)piperazine; N,N′-bis(3,4-dihydroxybenzyl)-N,N′-dimethyl-ethylenediamine; 2,5-bis(3,4-dihydroxybenzyl)-2,5-diaza[2.2.1]bicycloheptane;
N,N′-bis(3,4-dihydroxybenzyl)-trans-1,2-diaminocyclohexane; N,N′-bis(3,4-dihydroxybenzyl)-trans-1,4-diaminocyclohexane; N,N′-bis(3,4-dihydroxybenzyl)-cis-1,3-bis(aminomethyl)cyclohexane;
N-(3,4-dihydroxybenzyl)proline 3,4-dihydroxybenzylamide; 2-(3,4-dihydroxybenzyl)isoquinoline-3-carboxylic acid 3,4-dihydroxyphenethylamide;
2,6-bis(3,4-dihydroxybenzyl)cyclohexanone; 3,5-bis(3,4-dihydroxybenzyl)-1-methyl-4-piperidinone; 2,4-bis(3,4-dihydroxybenzyl)-3-tropinone;
tris(3,4-dihydroxybenzyl)methane; α-(3,4-dihydroxybenzamido)-3,4-dihydroxycinnamic acid 3,4-dihydroxybenzyl amide; 4-(3,4-dihydroxybenzylaminomethylene)-2-(3,4-dihydroxyphenyl)oxazolin-5-one;
1,4-bis(3,4-dihydroxybenzoyl)piperazine; N,N′-bis(3,4-dihydroxybenzoyl)-N,N′-dimethylethylenediamine; 2,5-bis(3,4-dihydroxybenzoyl)-2,5-diaza[2.2.1]bicycloheptane;
N,N′-bis(3,4-dihydroxybenzoyl)-trans-1,2-diaminocyclohexane; N,N′-bis(3,4-dihydroxybenzoyl)-cis-1,3-bis(aminomethyl)cyclohexane;
3,6-bis(3,4-dihydroxybenzyl)-2,5-diketopiperazine; 3,6-bis(3,4-dihydroxybenzylidene)-1,4-dimethyl-2,5-diketopiperazine; N-(3,4-dihydroxyphenylacetyl)proline-3,4-dihydroxyanilide;
2,3-bis(3,4-dihydroxyphenyl)butane; 1,3-bis(3,4-dihydroxybenzyl)benzene; 1,4-bis(3,4-dihydroxybenzyl)benzene; 2,6-bis(3,4-dihydroxybenzyl)pyridine;
2,5-bis(3,4-dihydroxybenzyl)thiophene; 2,3-bis(3,4-dihydroxybenzyl)thiophene; 1,2-bis(3,4-dihydroxyphenyl)cyclohexane; 1,4-bis(3,4-dihydroxyphenyl)cyclohexane;
3,7-bis(3,4-dihydroxyphenyl)bicyclo[3.3.0]octane; 2,3-bis(3,4-dihydroxyphenyl)-1,7,7-trimethyl-bicyclo[2.2.1]heptane; 1,2-bis(3,4-dihydroxyphenoxy)ethane;
1,3-bis(3,4-dihydroxyphenoxy)propane; trans-1,2-bis(3,4-dihydroxyphenoxy)cyclopentane; N-(3,4-dihydroxybenzyl)-3-(3,4-dihydroxyphenoxy)-2-hydroxypropylamine;
3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxyanilide; 3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxybenzylamide; 3,4-dihydroxyphenoxyacetic
acid 3,4-dihydroxyphenethylamide; 3,4-dihydroxybenzoic acid p-(3,4-dihydroxyphenoxy)anilide; 3,4-dihydroxybenzoic acid o-(3,4-dihydroxyphenoxy)anilide;
2,6-bis(3,4-dihydroxyphenoxy)pyridine; 3,4-dihydroxybenzoic acid 3,4-dihydroxyanilide; 3,4-dihydroxybenzoic acid 3,4-dihydroxybenzylamide;
3,4-dihydroxybenzoic acid 3,4-dihydroxyphenethylamide; 3,4-dihydroxyphenyl acetic acid 3,4-dihydroxyanilide; 3,4-dihydroxyphenylacetic
acid 3,4-dihydroxybenzylamide; 3,4-dihydroxyphenylacetic acid 3,4-dihydroxyphenethylamide; 3-(3,4-dihydroxyphenyl)propionic
acid 3,4-dihydroxyanilide; 3-(3,4-dihydroxyphenyl)propionic acid 3,4-dihydroxybenzylamide; 3-(3,4-dihydroxyphenyl)propionic
acid 3,4-dihydroxyphenethylamide; 3,4-dihydroxycinnamic acid 3,4-dihydroxyanilide; 3,4-dihydroxycinnamic acid 3,4-dihydroxybenzylamide;
3,4-dihydroxycinnamic acid 3,4-dihydroxyphenethylamide; oxalic acid bis(3,4-dihydroxyanilide); oxalic acid bis(3,4-dihydroxybenzylamide);
oxalic acid bis(3,4-dihydroxyphenethylamide); succinic acid bis(3,4-dihydroxyanilide); succinic acid bis(3,4-dihydroxybenzylamide);
succinic acid bis(3,4-dihydroxyphenethylamide); maleic acid bis(3,4-dihydroxyanilide); maleic acid bis(3,4-dihydroxybenzylamide);
fumaric acid bis(3,4-dihydroxyanilide); fumaric acid bis(3,4-dihydroxybenzylamide); bis(3,4-dihydroxybenzyl)amine; N-(3,4-dihydroxybenzyl)-3,4-dihydroxyphenethylamine;
tris(3,4-dihydroxybenzyl)amine; 1,3-bis(3,4-dihydroxyphenyl)urea; 1-(3,4-dihydroxyphenyl)-3-(3,4-dihydroxybenzyl)urea; 1-(3,4-dihydroxyphenyl)-3-(3,4-dihydroxyphenethyl)urea;
3-deoxy-3-(3,4-dihydroxybenzyl)aminoepicatechin; 3-deoxy-3-(3,4-dihydroxyphenethyl)aminoepicatechin; 2,3,6,7-tetrahydroxy-9,10-epoxy-9,10-dihydroacridine;
10-aminoanthracene-1,2,7,8-tetraol; acridine-1,2,6,7-tetraol; phenoxazine-2,3,7,8,10-pentaol; dibenzo[c,f][2,7]napthyridine-2,3,10,11-tetraol;
and 6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[d,g]quinoline-2,10,11-triol;
(3) a methylenedioxy analog or a pharmaceutically acceptable ester of any one of The compounds of (1) and (2); or
(4) a pharmaceutically acceptable salt of any one of the compounds of (1) to (3).
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