US2003073712A1PendingUtilityA1
Cytoprotective compounds, pharmaceutical and cosmetic formulations, and methods
Priority: Jul 23, 2001Filed: Jul 23, 2002Published: Apr 17, 2003
Est. expiryJul 23, 2021(expired)· nominal 20-yr term from priority
Inventors:Bing WangYong-Kang ZhangJian ChenWei ZhangJiangao SongUghetta Del BalzoLesley BrownSekhar BoddupalliSteven Craig BobzinSylvain GilatGuy M. Miller
A61P 5/24A61P 9/04A61P 9/10A61P 43/00A61P 37/06A61P 9/00A61P 37/00A61P 3/10A61P 27/02A61P 29/00A61P 25/02A61P 25/16A61P 25/28A61P 25/18A61P 25/00A61P 21/00A61P 11/00A61P 11/06C07C 49/737C07C 43/23C07F 9/4021C07C 235/42C07C 2603/24C07D 311/72C07D 277/20A61P 15/00C07D 213/30C07C 205/20C07D 213/53C07D 295/26C07C 205/22C07C 205/57A61P 13/12C07C 45/30C07C 255/36C07D 277/24C07C 205/17C07C 45/71C07C 311/29A61P 17/02A61P 17/16A61P 19/02C07C 69/94A61P 17/10A61P 17/00C07C 205/35C07D 231/26A61P 1/04A61P 17/06
51
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Claims
Abstract
Cytoprotective compounds, many of which are phenolic derivatives characterized by a substituted phenol having certain conjugated bonds, are useful in the treatment of certain ischemic or inflammatory conditions, including but not limited to stroke, myocardial infarction, congestive heart failure, and skin disorders characterized by inflammation or oxidative damage. They are also useful in the manufacture of pharmaceutical and cosmetic formulations for the treatment of such conditions.
Claims
exact text as granted — not AI-modifiedWe claim:
1 . A method of treatment for a mammal suffering from a condition characterized by oxidative stress, comprising administering an effective amount of a compound represented by the formula:
wherein:
R is: substituted alkenyl, optionally substituted aryl, (optionally substituted aryl)carbonyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, or nitro;
R′ is: hydrogen or (optionally substituted alkoxy)carbonyl;
R 1 to R 5 are independently selected from: optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkyl, optionally substituted aryl, (optionally substituted alkoxy)carbonyl, carboxy, cyano, halo, optionally substituted heteroaryl, hydrogen, hydroxy, nitro, nitrone, sulfonate; or
two adjacent members of R 1 to R are each O − and together are complexed with carbon or a metal;
provided that at least one of R 1 to R 5 is methoxymethoxy, or H—[CH 2 —(CH 3 )C═CH—CH 2 ] n — where n is an integer from 1 to 4, and
further provided that when R 1 to R 5 is methoxymethoxy, R is phenyl having cyano, nitro, nitroso, hydroxylamino, aminocarbonyl, a lower alkyl ester or a nitrogen-bearing heterocyclyl substituent at its para position,
or by the formula:
wherein:
R″ is: optionally substituted anthracenone, di-cyano, or optionally substituted heterocyclyl selected from: 2,5-(optionally substituted)-2,4-dihydro-pyrazol-3-one; 5-(optionally substituted)-3H-benzofuran-2-one; 2-thioxo-thiazolidin-4-one and thiazolidine-2,4-dione;
R 6 to R 10 are independently selected from: optionally substituted alkenyl, optionally substituted alkoxy, optionally substituted alkyl, optionally substituted aryl, (optionally substituted alkoxy)carbonyl, hydrogen, hydroxy and nitrone; or
two adjacent members of R 6 to R 10 are each O − and together are complexed with carbon or a metal;
provided that at least one of R 6 to R 10 is not hydrogen, and further provided that where R 10 and another of R 6 to R 9 are hydrogen, at least one of R 6 to
R 9 is methoxymethoxy or H—[CH 2 —(CH 3 )C═CH—CH 2 ] n — where n is an integer from 1 to 4,
including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
2 . The method of claim 1 comprising adminstering a compound of Formula I where R′ is hydrogen; and at least one of R 1 to R 5 is methoxymethoxy or H—[CH 2 —(CH 3 )C═CH—CH 2 ] n — where n is an integer from 1 to 2.
3 . The method of claim 2 where at least one of R 1 to R 5 is methoxymethoxy, and another of R 1 to R 5 is H—[CH 2 —(CH 3 )C═CH—CH 2 ] n — where n is an integer from 1 to 2.
4 . The method of claim 1 where R is para-nitro phenyl.
5 . The method of claim 2 , where R is para-nitro phenyl.
6 . A compound represented by the formula:
wherein:
R is: anthraquinone, optionally substituted heteroaryl, optionally substituted heterocyclyl, nitro, or substituted phenyl having:
a substituent in the para position, selected from: cyano, nitro, alkoxycarbonyl, (nitrogen-containing)-heterocyclyl and (nitrogen-containing)-heteroaryl, and/or
a substituent in the meta position selected from: nitro and halo;
R′ is: hydrogen or (optionally substituted alkoxy)-carbonyl;
R 1 to R 5 are independently selected from: optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkyl, optionally substituted aryl, (optionally substituted alkoxy)-carbonyl, carboxy, cyano, halo, optionally substituted heteroaryl, hydrogen, hydroxy, nitro, nitrone, sulfonate;
provided that at least one of R 1 to R 5 is hydrogen, and at least another of R 1 to R 5 is H—[CH 2 —(CH 3 )C═CH—CH 2 ] n — or H—[CH 2 —(CH 3 )C═CH—CH 2 ] n —O— where n is an integer from 1 to 4,
including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
7 . The compound of claim 6 where:
R is: substituted phenyl; and
R′ is: hydrogen.
8 . The compound of claim 7 where at least one of R 1 to R 5 is hydroxy or lower alkoxy.
9 . The compound of claim 8 where at least two of R 1 to R 5 is hydrogen.
10 . The compound of claim 6 where n is 1 or 2.
11 . The compound of claim 7 where n is 1 or 2.
12 . The compound of claim 11 where R 5 is hydrogen.
13 . The compound of claim 6 where R 1 to R 5 are independently selected from: optionally substituted alkoxy, optionally substituted alkenyl, carboxy, cyano, halo, hydrogen, hydroxy, and nitro.
14 . The compound of claim 6 where:
R 5 and another of R 1 to R 4 are hydrogen,
one of R 1 to R 4 is H—[CH 2 —(CH 3 )C═CH—CH 2 ] n —, where n is 1, 2 or 3, and
the others of R 1 to R 4 are selected from hydrogen, hydroxy and lower alkoxy.
15 . The compound of claim 7 where R is phenyl para-substituted with cyano, nitro or alkoxycarbonyl.
16 . The compound of claim 7 where R is phenyl meta-substituted with bromo.
17 . A pharmaceutical or cosmetic formulation comprising a compound of claim 6 admixed with an acceptable excipient.
18 . A compound represented by the formula:
wherein:
R is: (substituted phenyl)-alkenyl;
R′ is: hydrogen;
R 1 to R 5 are independently selected from: optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkyl, optionally substituted aryl, (optionally substituted alkoxy)-carbonyl, carboxy, cyano, halo, optionally substituted heteroaryl, hydrogen, hydroxy, nitro, nitrone, and sulfonate;
provided that (a) at least one of R 1 to R 5 is methoxymethoxy or H—[CH 2 —(CH 3 )C═CH—CH 2 ] n — where n is an integer from 1 to 4, or (b) two adjacent members of R 1 to R 5 are each O − and together are complexed with a metal,
including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
19 . The compound of claim 18 where R is substituted phenyl-vinyl, having:
a substituent in the para position, selected from: cyano, nitro, alkoxycarbonyl, (nitrogen-containing)-heterocyclyl and (nitrogen-containing)-heteroaryl, or
a substituent in the meta position selected from: nitro and halo.
20 . The compound of claim 19 where R is 1-nitro-4-vinyl-benzene.
21 . A compound represented by the formula:
wherein:
R is: (optionally substituted heterocyclyl)-alkenyl
R′ is: hydrogen;
R 1 to R 5 are independently selected from: optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkyl, optionally substituted aryl, (optionally substituted alkoxy)-carbonyl, carboxy, cyano, halo, optionally substituted heteroaryl, hydrogen, hydroxy, nitro, nitrone, and sulfonate, with the proviso that at least one of R 1 to R 5 is hydroxy, methoxymethoxy or H—[CH 2 —(CH 3 )C═CH—CH 2 ] n —, where n is an integer from 1 to 4; or
two adjacent members of R 1 to R 5 are each O − and together are complexed with a metal;
including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
22 . The compound of claim 21 where R is (optionally substituted heterocyclyl)-methylene.
23 . The compound of claim 22 where R is 5-methyl-4-methylene-2-phenyl-2,4-dihydro-pyrazol-3-one or 5-methylene-thiazolidine-2,4-dione.
24 . The compound of claim 22 or 23 , where:
R 5 and another of R 1 to R 4 are hydrogen, and
the others of R 1 to R 4 are selected from alkoxy, hydrogen, hydroxy, methoxymethoxy, and H—[CH 2 —(CH 3 )C═CH—CH 2 ] n —, where n is an integer from 1 to 2.
25 . A pharmaceutical or cosmetic formulation comprising a compound of any of claims 18 or 21 admixed with an acceptable excipient.
26 . A compound represented by the formula:
wherein:
R is: optionally substituted heteroaryl, selected from the group: 1-carboxymethyl-pyridinium-4-yl bromide; 1-(2-carboxy-2-oxo-ethyl)-pyridinium-4-yl bromide; thiazol-2-yl; 6-nitro-benzo[1,3]dioxo-5-yl; and a [2,2′]bipyridin-5-yl metal complex;
R′ is: hydrogen;
R 1 to R 5 are independently selected from: optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkyl, optionally substituted aryl, (optionally substituted alkoxy)carbonyl, carboxy, cyano, halo, optionally substituted heteroaryl, hydrogen, hydroxy, nitro, nitrone, sulfonate; or
two adjacent members of R 1 to R 5 are each O − and together are complexed with a metal;
provided that where R is a [2,2′]bipyridin-5-yl Ru or Pd metal complex, R 3 and R 4 are not both hydroxy,
including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
27 . The compound of claim 26 where:
R 5 and another of R 1 to R 4 are hydrogen,
the others of R 1 to R 4 are selected from: alkoxy, (optionally substituted alkoxy)carbonyl, hydrogen, hydroxy, and H—[CH 2 —(CH 3 )C═CH—CH 2 ] n —, where n is an integer from 1 to 4.
28 . The compound of claim 27 where R 1 is hydrogen, R 2 is hydroxy, R 3 is hydroxy and R 4 is hydrogen.
29 . The compound of claim 27 where R 1 is hydrogen, R 2 is methoxymethoxy, R 3 is methoxymethoxy, and R 4 is hydrogen.
30 . The compound of claim 27 where R 1 is hydrogen, R 2 is hydrogen, R 3 is methoxycarbonyl and R 4 is hydrogen.
31 . The compound of claim 26 where R is [2,2′]bipyridin-5-yl, the nitrogen atoms of which are complexed to a metal having one or more apical ligands.
32 . The compound of claim 31 where the metal is selected from Zn(II), Mn(III) and Cu(II).
33 . The compound of claim 32 where the apical ligand is selected from chloride and acetate.
34 . The compound of claim 31 or 32 where R 1 is hydrogen, R 2 is hydrogen, R 3 is methoxymethoxy, R 4 is methoxymethoxy and R 5 is hydrogen.
35 . The compound of claim 26 selected from the group:
4-(2-[2,2′]bipyridinyl-5-yl-vinyl)-1,2-dimethoxymethoxy-benzene, zinc(II) chloride;
4-(2-[2,2′]bipyridinyl-5-yl-vinyl)-1,2-dimethoxymethoxy-benzene, copper(II) chloride; and
4-(2-[2,2′]bipyridinyl-5-yl-vinyl)-1,2-dimethoxymethoxy-benzene, manganese(III) acetate.
36 . A pharmaceutical or cosmetic formulation comprising a compound of claim 26 admixed with an acceptable excipient.
37 . A compound represented by the formula:
wherein:
R is: substituted alkenyl, optionally substituted aryl, (optionally substituted aryl)-carbonyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, or nitro;
R′ is: hydrogen or (optionally substituted alkoxy)-carbonyl;
three members of R 1 to R 5 are independently selected from: optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkyl, optionally substituted aryl, (optionally substituted alkoxy)-carbonyl, carboxy, cyano, halo, optionally substituted heteroaryl, hydrogen, hydroxy, nitro, nitrone, and sulfonate; and
two adjacent members of R 1 to R 5 are each O − and together are complexed with a metal having one or more apical ligands, said metal optionally being further complexed with a second compound of Formula I,
including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
38 . The compound of claim 37 where R′ is hydrogen.
39 . The compound of claim 38 where R 3 and R 4 are O − and together are complexed with a metal.
40 . The compound of claim 39 where R 1 , R 2 and R 5 are hydrogen.
41 . The compound of claim 37 or 39 , where the metal is selected from Zn(II), Mn(III) and Cu(II).
42 . The compound of claim 41 where the apical ligand is selected from chloride and acetate.
43 . The compound of claim 38 where R is substituted phenyl having:
a substituent in the para position, selected from: cyano, nitro, alkoxycarbonyl, (nitrogen-containing)-heterocyclyl and (nitrogen-containing)-heteroaryl, or
a substituent in the meta position selected from: nitro and halo.
44 . The compound of claim 43 where R is para-alkoxycarbonyl-phenyl.
45 . The compound of claim 43 selected from the group:
4-[2-(phenyl-1,2-diol)-vinyl]-benzoic acid ethyl ester, zinc(II) chloride;
4-[2-(phenyl-1,2-diol)-vinyl]-benzoic acid ethyl ester, copper(II) chloride;
4-[2-(phenyl-1,2-diol)-vinyl]-benzoic acid ethyl ester, manganese(III) acetate; and
bis-{4-[2-(4-methoxycarbonyl-phenyl)-vinyl]-benzene-1,2-diol}, zinc(II) chloride.
46 . The compound of claim 37 selected from Formula III, IV and V:
where:
M is: a metal;
L is: a ligand associated with a remaining free valence on M;
n is: an integer from 1 to 3, corresponding to the remaining free valences on M and the number of associated ligands;
R and R* are independently selected from: optionally substituted anthraquinone, substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, or nitro; and
R 2 , R 4 and R 4* are independently selected from: optionally substituted alkoxy, hydrogen, or hydroxy.
47 . A pharmaceutical or cosmetic formulation comprising a compound of claim 37 admixed with an acceptable excipient.
48 . A compound represented by the formula:
wherein:
R″ is: optionally substituted anthracenone, di-cyano, or optionally substituted heterocyclyl selected from: 2,5-(optionally substituted)-2,4-dihydro-pyrazol-3-one; 5-(optionally substituted)-3H-benzofuran-2-one; 2-thioxo-thiazolidin-4-one and thiazolidine-2,4-dione;
R 6 to R 10 are independently selected from: optionally substituted alkenyl, optionally substituted alkoxy, optionally substituted alkyl, optionally substituted aryl, (optionally substituted alkoxy)carbonyl, hydrogen, hydroxy and nitrone; or
two adjacent members of R 6 to R 9 are each O − and together are complexed with a metal;
provided that at least one of R 6 to R 10 is not hydrogen,
and further provided that where R 10 and another of R 6 to R 9 are hydrogen, at least one of R 6 to R 9 is methoxymethoxy or H—[CH 2 —(CH 3 )C═CH—CH 2 ] n — where n is an integer from 1 to 4,
including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
49 . The compound of claim 48 where R 10 and another of R 6 to R 9 are hydrogen.
50 . The compound of claim 48 where R″ is selected from: anthracenone, dihydroxyanthracenone, di-cyano, 5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one; 3H-benzofuran-2-one; 5-hydroxy-3H-benzofuran-2-one; 2-thioxo-thiazolidin-4-one and thiazolidine-2,4-dione.
51 . The compound of claim 49 where R″ is selected from: anthracenone, dihydroxyanthracenone, di-cyano, 5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one; 3H-benzofuran-2-one; 5-hydroxy-3H-benzofuran-2-one; 2-thioxo-thiazolidin-4-one and thiazolidine-2,4-dione.
52 . The compound of claim 49 where R 6 to R 9 are selected from: hydrogen, hydroxy, methoxymethoxy, t-butyl and H—[CH 2 —(CH 3 )C═CH—CH 2 ] n —, where n is 1 or 2.
53 . The compound of claim 51 where R 6 to R 9 are selected from: hydrogen, hydroxy, methoxymethoxy, t-butyl and H—[CH 2 —(CH 3 )C═CH—CH 2 ] n —, where n is 1 or 2.
54 . The compound of claim 53 where R 6 is hydrogen and:
R 7 is hydrogen, R 8 is methoxymethoxy, and R 9 is methoxymethoxy; or
R 7 is methoxymethoxy, R 8 is H—CH 2 —(CH 3 )C═CH—CH 2 —, and R 9 is hydroxy; or
R 7 is hydroxy, R 8 is H—CH 2 —(CH 3 )C═CH—CH 2 —, and R 9 is methoxymethoxy; or
R 7 is hydroxy, R 8 is H—CH 2 —(CH 3 )C═CH—CH 2 —, and R 9 is hydroxy; or
R 7 is H—CH 2 —(CH 3 )C═CH—CH 2 —, R 3 is methoxymethoxy, and R 9 is hydrogen; or
R 7 is H—CH 2 —(CH 3 )C═CH—CH 2 —, R 8 is hydroxy, and R 9 is hydrogen; or
R 7 is H—[CH 2 —(CH 3 )C═CH—CH 2 ] 2 —, R 8 is methoxymethoxy, and R 9 is hydrogen; or
R 7 is H—[CH 2 —(CH 3 )C═CH—CH 2 ] 2 —, R 8 is hydroxy, and R 9 is hydrogen; or
R 7 is 3-methoxy-4-methoxymethoxy-1-(thiazolidine-2,4-dionyl)-benzylidene-5-yl, R 8 is methoxymethoxy, and R 9 is methoxy.
55 . A pharmaceutical or cosmetic formulation comprising a compound of claim 48 admixed with an acceptable excipient.
56 . A compound selected from the group:
4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid methyl ester; 2-methoxy-6-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-phenol; 2-hydroxy-5-[2-(4-nitro-phenyl)-vinyl]-benzoic acid; 3-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol; 4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol; 2-methoxy-4-[4-(4-nitro-phenyl)-buta-1,3-dienyl]-phenol; 2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzoic acid methoxymethyl ester; 3-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol; 2-(3,7-dimethyl-octa-2,6-dienyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 5-{4-[2-(3,4-dihydroxy-phenyl)-vinyl]-phenyl}-2-phenyl-2,4-dihydro-pyrazol-3-one; 4-{2-[3,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester; 4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile; 4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 4-{2-[4-(5-hydroxy-1H-pyrazol-3-yl)-phenyl]-vinyl}-benzene-1,2-diol; 4-{2-[4-(2-nitro-vinyl)-phenyl]-vinyl}-benzene-1,2-diol; 3-[2-(3,4-dimethoxy-phenyl)-vinyl]-4-nitro-phenol; 4-[4-(4-nitro-phenyl)-buta-1,3-dienyl]-benzene-1,2-diol; 2-iodo-6-methoxy-4-[2-(4-nitro-phenyl)-vinyl]-phenol; 4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile; 2-(3,7-dimethyl-octa-2,6-dienyl)-6-methoxy-4-[2-(4-nitro-phenyl)-vinyl]-phenol; 2-bromo-6-methoxy-4-[2-(4-nitro-phenyl)-vinyl]-phenol; 4-{2-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-5-methoxy-phenyl]-vinyl}-benzonitrile; and 2,6-dimethyl-4-[2-(4-nitro-phenyl)-vinyl]-phenol, including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
57 . A compound of claim 56 selected from the group:
2-methoxy-6-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-phenol;
3-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
4-(3-methyl-but-2-enyl)-5,-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol;
2-methoxy-4-[4-(4-nitro-phenyl)-buta-1,3-dienyl]-phenol;
2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzoic acid methoxymethyl ester;
3-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
2-(3,7-dimethyl-octa-2,6-dienyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
5-{4-[2-(3,4-dihydroxy-phenyl)-vinyl]-phenyl}-2-phenyl-2,4-dihydro-pyrazol-3-one;
4-{2-[3,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester;
4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-{2-[4-(5-hydroxy-1H-pyrazol-3-yl)-phenyl]-vinyl}-benzene-1,2-diol;
4-{2-[4-(2-nitro-vinyl)-phenyl]-vinyl}-benzene-1,2-diol;
4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile;
2-(3,7-dimethyl-octa-2,6-dienyl)-6-methoxy-4-[2-(4-nitro-phenyl)-vinyl]-phenol; and
4-{2-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-5-methoxy-phenyl]-vinyl}-benzonitrile,
including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
58 . A compound selected from the group:
3-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol; 4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol; 2-{4-[2-(4-hydroxy-3-methoxy-phenyl)-vinyl]-phenyl}-5-methyl-2,4-dihydro-pyrazol-3-one; 5-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-benzylidene]-thiazolidine-2,4-dione; 2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol; 2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol; 4-[2-(3,4-bis-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-phenyl)-vinyl]-benzoic acid ethyl ester; 2-methoxy-6-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-phenol; 4-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one; 4-[2-(3,4-dihydroxy-phenyl)-vinyl]-N,N-bis-(2-hydroxy-ethyl)-benzamide; 4-[2-(3,4-bis-methoxymethoxy-phenyl)-vinyl]-N,N-bis-(2-hydroxy-ethyl)-benzamide; {4-[2-(3,4-dihydroxy-phenyl}-vinyl]-phenyl-morpholin-4-yl-methanone; 4-[2-(2,5-dimethoxy-3,4-dimethyl-phenyl)-vinyl]-benzoic acid methyl ester; 3,4-bis-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid methyl ester; 4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzenesulfonamide; 4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid 3,7-dimethyl-octa-2,6-dienyl ester; 4-[2-(4-hydroxy-3,5-dimethyl-phenyl)-vinyl]-benzoic acid methyl ester; 4-[2-(4-hydroxy-3-iodo-5-methoxy-phenyl)-vinyl]-benzoic acid methyl ester; 4-bromo-5-methoxy-2-[2-(4-nitro-phenyl)-vinyl]-phenol; 4-[2-(5-bromo-2-hydroxy-4-methoxy-phenyl)-vinyl]-benzoic acid methyl ester; {4-[2-(3,4-dihydroxy-phenyl)-vinyl]-phenyl}-phosphonic acid diisopropyl ester; and (4-methoxyphenyl)-(benzo-1,3-dioxol-5-yl)-ethyne, including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
59 . A compound selected from the group:
5-{2-[4-hydroxy-3-(3-methyl-but-2-enyl)-phenyl]-vinyl}-2-(3-methyl-but-2-enyl)-benzene-1,3-diol; 4-(3,4-dihydroxy-benzylidene)-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one; 4-(3,5-di-tert-butyl-4-hydroxy-benzylidene)-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one; 3-(3,5-di-tert-butyl-4-hydroxy-benzylidene)-5-hydroxy-3H-benzofuran-2-one; 5-{4-[6-hydroxy-2,7,8-trimethyl-2-(4,8,12-trimethyl-tridecyl)-chroman-5-ylmethoxy]-benzylidene}-thiazolidine-2,4-dione; 4-[2-(3,4-dihydroxy-phenyl)-vinyl]-N,N-bis-(2-hydroxy-ethyl)-benzamide; 4-[2-(3,4-bis-methoxymethoxy-phenyl)-vinyl]-N,N-bis-(2-hydroxy-ethyl)-benzamide; {4-[2-(3,4-dihydroxy-phenyl)-vinyl]-phenyl}-morpholin-4-yl-methanone; 4-[2-(2,5-dimethoxy-3,4-dimethyl-phenyl)-vinyl]-benzoic acid methyl ester; 3,4-bis-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid methyl ester; 4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzenesulfonamide; 4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid 3,7-dimethyl-octa-2,6-dienyl ester; 4-[2-(4-hydroxy-3,5-dimethyl-phenyl)-vinyl]-benzoic acid methyl ester; 4-[2-(4-hydroxy-3-iodo-5-methoxy-phenyl)-vinyl]-benzoic acid methyl ester; 4-bromo-5-methoxy-2-[2-(4-nitro-phenyl)-vinyl]-phenol; 4-[2-(5-bromo-2-hydroxy-4-methoxy-phenyl)-vinyl]-benzoic acid methyl ester; and {4-[2-(3,4-dihydroxy-phenyl)-vinyl]-phenyl}-phosphonic acid diisopropyl ester, including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
60 . A pharmaceutical or cosmetic formulation comprising a compound of any of claims 56 , 57 , 58 and 59 and 60 admixed with an acceptable excipient.
61 . A compound is selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol; 4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol; 4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol; 4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile; 4-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one; 5-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-thiazolidine-2,4-dione; 3-(3,5-di-tert-butyl-4-hydroxy-benzylidene)-5-hydroxy-3H-benzofuran-2-one; 4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile; 2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 4-[4-(4-nitro-phenyl)-buta-1,3-dienyl]-benzene-1,2-diol; 5-di-tert-butyl-4-hydroxy-benzylidene)-thiazolidine-2,4-dione; 4-{2-[3,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester; 3-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol; 3-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol; 4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 2-(3,7-dimethyl-octa-2,6-dienyl)-6-methoxy-4-[2-(4-nitro-phenyl)-vinyl]-phenol; 2-(3,7-dimethyl-octa-2,6-dienyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl-benzonitrile; and 2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol, including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
62 . The compound of claim 61 selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol;
2-(3,7-dimethyl-octa-2,6-dienyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-{2-[4-(2-nitro-vinyl)-phenyl]-vinyl}-benzene-1,2-diol; and
4-2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile.
63 . A pharmaceutical or cosmetic formulation for topical application comprising a one or more dermatologically acceptable excipients and a compound of claim 61 or 62 .
64 . A method of treatment for a mammal suffering from a condition characterized by oxidative stress, comprising administering a therapeutically effective amount of a compound of any of claims 6 , 18 , 21 , 26 , 37 , 48 , 56 , 58 , 59 and 60 .
65 . The method of claim 63 comprising treating a cardiovascular, cerebrovascular or neurologic, inflammatory and/or autoimmune, or dermatologic condition.
66 . The method of claim 64 wherein the condition is dermatologic, further comprising a method of promoting a product by directing a user to apply to the skin a pharmaceutical or cosmetic composition incorporating said compound for regulating skin condition, regulating the signs of skin aging, or for treating contact dermatitis, acne, psoriasis, age-related damage or damage resulting from harmful (UV) radiation, stress or fatigue.
67 . A method of treatment for a mammal suffering from a cardiovascular condition characterized by oxidative stress, comprising administering a therapeutically effective amount of a compound represented by Formula I:
wherein:
R is: nitro, nitrogen-containing heteroaryl, or phenyl substituted in the para position with alkoxycarbonyl or a nitrogen-bearing moiety;
R′ is: hydrogen;
R 1 to R 5 are independently selected from: hydrogen, hydroxy, alkoxy, alkenyl or halo, or
two adjacent members of R 1 to R 5 are each O − and together are complexed with a metal; or by Formula II:
wherein:
R″ is: a thiazolidine-2,4-dione or a 2-thioxo-thiazolidin-4-one;
R 6 to R 10 are independently selected from: hydrogen, hydroxy or alkoxy; or
two adjacent members of R 6 to R 10 are each O − and together are complexed with a metal;
including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
68 . The method of claim 67 where:
R is phenyl substituted in the para position with nitro or cyano, or unsubstituted thiazole;
R 1 and R 5 are hydrogen;
R 2 to R 4 are selected from hydrogen, hydroxy, methoxy, methoxymethoxy, prenyl, geranyl and bromo, provided that at least two of R 2 to R 4 are not hydrogen;
R″ is thiazolidine-2,4-dione-5-yl;
R 6 and R 10 are hydrogen; and
at least two of R 7 to R 9 are methoxymethoxy, with the third being hydrogen or methoxymethoxy.
69 . The method of claim 68 comprising administering a compound of Formula I.
70 . The method of claim 69 where at least two of R 2 to R 4 are methoxymethoxy.
71 . The method of claim 69 where one of R 2 to R 4 is methoxy, another of R 2 to R 4 is methoxymethoxy and the third of R 2 to R 4 is prenyl, geranyl or bromo.
72 . The method of claim 67 where the compound is selected from the group:
5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-[2-(4-hydroxy-3,5-dimethyl-phenyl)-vinyl]-benzoic acid methyl ester;
4-[2-(4-hydroxy-3-methoxy-phenyl)-vinyl]-benzonitrile;
4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid;
5-(3,4-dihydroxy-benzylidene)-thiazolidine-2,4-dione;
4-(2-nitro-vinyl)-benzene-1,2-diol;
4-[2-(3,4-bis-methoxymethoxy-phenyl)-vinyl]-N,N-bis-(2-hydroxy-ethyl)-benzamide;
4-[2-(3,4-bis-methoxymethoxy-phenyl)-vinyl]-phthalic acid dimethyl ester;
1-methoxy-2-methoxymethoxy-3-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
1,3-bis-methoxymethoxy-2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
1,3-bis-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
1-bromo-3-methoxy-2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
4-{2-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-5-methoxy-phenyl]-vinyl}-benzonitrile;
2-[2-(3,4-bis-methoxymethoxy-phenyl)-vinyl]-thiazole;
5-(3,4-bis-methoxymethoxy-benzylidene)-thiazolidine-2,4-dione; and
4-{2-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-5-methoxy-phenyl]-vinyl}-benzoic acid methyl ester.
73 . The method of claim 67 where the compound is selected from the group:
5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-[2-(4-hydroxy-3-methoxy-phenyl)-vinyl]-benzonitrile;
4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid;
5-(3,4-dihydroxy-benzylidene)-thiazolidine-2,4-dione;
4-[2-(3,4-bis-methoxymethoxy-phenyl)-vinyl]-N,N-bis-(2-hydroxy-ethyl)-benzamide;
4-[2-(3,4-bis-methoxymethoxy-phenyl)-vinyl]-phthalic acid dimethyl ester;
1-methoxy-2-methoxymethoxy-3-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
1,3-bis-methoxymethoxy-2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
1,3-bis-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
1-bromo-3-methoxy-2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
4-{2-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-5-methoxy-phenyl]-vinyl}-benzonitrile;
2-[2-(3,4-bis-methoxymethoxy-phenyl)-vinyl]-thiazole;
5-(3,4-bis-methoxymethoxy-benzylidene)-thiazolidine-2,4-dione; and
4-{2-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-5-methoxy-phenyl]-vinyl}-benzoic acid methyl ester.
74 . The method of claim 67 where the compound is selected from the group:
5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-[2-(4-hydroxy-3-methoxy-phenyl)-vinyl]-benzonitrile;
4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid;
5-(3,4-dihydroxy-benzylidene)-thiazolidine-2,4-dione;
1-methoxy-2-methoxymethoxy-3-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
1,3-bis-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
4-{2-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-5-methoxy-phenyl]-vinyl}-benzonitrile;
2-[2-(3,4-bis-methoxymethoxy-phenyl)-vinyl]-thiazole; and
4-{2-[3-(3,7-dimethyl octa-2,6-dienyl)-4-hydroxy-5-methoxy-phenyl]-vinyl}-benzoic acid methyl ester.
75 . A method of treatment for a mammal suffering from a cerebrovascular or neurologic condition characterized by oxidative stress, comprising administering a therapeutically effective amount of a compound represented by Formula I:
wherein:
R is: phenyl substituted with an alkoxy, alkoxycarbonyl, hydroxy, a nitrogen-bearing moiety, or nitrogen-bearing heteroaryl;
R′ is: hydrogen;
one or more of R 1 to R 5 is other than hydrogen, selected from hydroxy, alkoxy, alkenyl or halo; or
two adjacent members of R 1 to R 5 are each O − and together are complexed with a metal;
or by Formula II:
wherein:
R″ is: a thiazolidine-2,4-dione or a 2-thioxo-thiazolidin-4-one; and
one or more of R 6 to R 10 are not hydrogen, selected from hydroxy, alkoxy and alkenyl; or
two adjacent members of R 6 to R 10 are each O − and together are complexed with a metal;
including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
76 . The method of claim 75 where:
R is selected from:
optionally substituted pyridinium bromide,
vinyl-5-methyl-2-phenyl-2,4-dihydro-pyraxol-3-one,
phenyl substituted in the para position with nitro or a methyl-, ethyl-, or tetradecyl-ester, and
tri-substituted phenyl having a nitro and a methoxy substituent at the two meta positions and methoxymethoxy or hydroxy at the para position;
R 1 and R 5 are hydrogen;
R 2 to R 4 are selected from hydrogen, hydroxy, methoxymethoxy, and prenyl or geranyl, provided that at least two of R 2 to R 4 are not hydrogen;
R″ is thiazolidine-2,4-dione-5-yl;
R 6 and R 10 are hydrogen; and
two or more of R 7 to R 9 are not hydrogen, selected from hydroxy, methoxymethoxy, prenyl and geranyl.
77 . The method of claim 76 comprising administering a compound of Formula I.
78 . The method of claim 77 where at least one of R 2 to R 4 is prenyl or geranyl.
79 . The method of claim 78 where R is tri-substituted phenyl having a nitro and a methoxy substituent at the two meta positions and methoxymethoxy or hydroxy at the para position.
80 . The method of claim 75 where the compound is selected from the group:
2,6-di-tert-butyl-4-[2-(4-nitro-phenyl)-vinyl]-phenol;
4-{2-[4-(2-nitro-vinyl)-phenyl]-vinyl}-benzene-1,2-diol;
4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzenesulfonamide-4-{2-[4-amino-sulfonyl)-phenyl]-vinyl}-benzene-1,2-diol;
3,4-bis-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid methyl ester;
4-[2-(5-bromo-2-hydroxy-4-methoxy-phenyl)-vinyl]-benzoic acid methyl ester;
4-[2-(2,3,4-trihydroxy-phenyl)-vinyl]-benzonitrile;
2-{4-[2-(4-hydroxy-3-methoxy-phenyl)-vinyl]-phenyl}-5-methyl-2,4-dihydro-pyrazol-3-one;
1-carboxymethyl-4-[2-(3,4-dihydroxy-phenyl)-vinyl]-pyridinium; bromide;
1,3-bis-methoxymethoxy-2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
4-[2-(3,4-bis-methoxymethoxy-phenyl)-vinyl]-benzoic acid tetradecyl ester;
4-[2-(3,4-bis-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-phenyl)-vinyl]-benzoic acid ethyl ester;
4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-bis-methoxymethoxy-phenyl]-vinyl}-benzoic acid methyl ester;
2-methoxymethoxy-1,3-dimethyl-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
1,2-bis-methoxymethoxy-4-[4-(4-nitro-phenyl)-buta-1,3-dienyl]-benzene;
2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzoic acid methoxymethyl ester;
1,5-bis-methoxymethoxy-2-(3-methyl-but-2-enyl)-3-[2-(4-nitro-phenyl)-vinyl]-benzene;
1,3-bis-methoxymethoxy-2-(3-methyl-but-2-enyl)-5-[2-(3-nitro-4-methoxymethoxy-5-methoxy-phenyl)-vinyl]-benzene;
1-iodo-3-methoxy-2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
1-bromo-3-methoxy-2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
4-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one;
5-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-benzylidene]-thiazolidine-2,4-dione;
5-[4-methoxymethoxy-3-(3-methyl-but-2-enyl)-benzyldene]-thiazolidine-2,4-dione;
5-[4-hydroxy-3-(3-methyl-but-2-enyl)-benzylidene]-thiazolidine-2,4-dione;
5-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-benzylidene]-thiazolidine-2,4-dione;
5-[3-(3,7-dim ethyl-octa-2,6-dienyl)-4-methoxymethoxy-benzylidene]-thiazolidine-2,4-dione;
4-{2-[3,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester;
4-{2-[4,5-dihydroxy-2-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester;
2-methoxy-6-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-phenol;
5-[2-(4-hydroxy-3-methoxy-5-nitro-phenyl)-vinyl]-2-(3-methyl-but-2-enyl)-benzene-1,3-diol; and
4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-bis-methoxymethoxy-phenyl]-vinyl}-benzonitrile.
81 . The method of claim 75 where the compound is selected from the group:
4-{2-[4-(2-nitro-vinyl)-phenyl]-vinyl}-benzene-1,2-diol;
3,4-bis-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid methyl ester;
2-{4-[2-(4-hydroxy-3-methoxy-phenyl)-vinyl]-phenyl}-5-methyl-2,4-dihydro-pyrazol-3-one;
1-carboxymethyl-4-[2-(3,4-dihydroxy-phenyl)-vinyl]-pyridinium; bromide;
1,3-bis-methoxymethoxy-2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
4-[2-(3,4-bis-methoxymethoxy-phenyl)-vinyl]-benzoic acid tetradecyl ester;
4-[2-(3,4-bis-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-phenyl)-vinyl]-benzoic acid ethyl ester;
2-methoxymethoxy-1,3-dimethyl-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
5-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-benzylidene]-thiazolidine-2,4-dione;
2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzoic acid methoxymethyl ester;
1,5-bis-methoxymethoxy-2-(3-methyl-but-2-enyl)-3-[2-(4-nitro-phenyl)-vinyl]-benzene;
1,3-bis-methoxymethoxy-2-(3-methyl-but-2-enyl)-5-[2-(3-nitro-4-methoxymethoxy-5-methoxy-phenyl)-vinyl]-benzene;
1-iodo-3-methoxy-2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
1-bromo-3-methoxy-2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
4-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one;
4-{2-[3,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester;
4-{2-[4,5-dihydroxy-2-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester;
2-methoxy-6-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-phenol; and
5-[2-(4-hydroxy-3-methoxy-5-nitro-phenyl)-vinyl]-2-(3-methyl-but-2-enyl)-benzene-1,3-diol.
82 . The method of claim 75 where the compound is selected from the group:
4-{2-[4-(2-nitro-vinyl)-phenyl]-vinyl}-benzene-1,2-diol;
3,4-bis-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid methyl ester;
2-{4-[2-(4-hydroxy-3-methoxy-phenyl)-vinyl]-phenyl}-5-methyl-2,4-dihydro-pyrazol-3-one;
1,3-bis-methoxymethoxy-2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
4-[2-(3,4-bis-methoxymethoxy-phenyl)-vinyl]-benzoic acid tetradecyl ester;
4-[2-(3,4-bis-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-phenyl)-vinyl]-benzoic acid ethyl ester;
5-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-benzylidene-thiazolidine-2,4-dione;
1,3-bis-methoxymethoxy-2-(3-methyl-but-2-enyl)-5-[2-(3-nitro-4-methoxymethoxy-5-methoxy-phenyl)-vinyl]-benzene;
1-bromo-3-methoxy-2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzene;
4-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one;
4-{2-[3,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester;
4-{2-[4,5-dihydroxy-2-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester;
2-methoxy-6-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-phenol; and
5-[2-(4-hydroxy-3-methoxy-5-nitro-phenyl)-vinyl]-2-(3-methyl-but-2-enyl)-benzene-1,3-diol.
83 . The method of claim 75 where the condition is selected from: stroke, cerebral ischemia, retinal ischemia, post-surgical cognitive dysfunctions, peripheral neuropathy spinal chord injury, head injury, surgical trauma, Alzheimer's, dementia and Parkinson's disease.
84 . The method of claim 75 comprising administering said compound about 5 or more hours following an ischemic or oxidative insult.
85 . The method of claim 75 or 84 where the compound is:
4-[2-(4-Nitro-phenyl)-vinyl]-benzene-1,2-diol; or
4-[2-(3,4-Dihydroxy-phenyl)-vinyl]-benzoic acid methyl ester.
86 . A method of treatment for a mammal suffering from a disease characterized by oxidative stress and involving inflammatory and/or autoimmune components, comprising administering a therapeutically effective amount of a compound represented by Formula I:
wherein:
R is: phenyl substituted in the para position with alkoxycarbonyl or a nitrogen-bearing moiety, vinyl-nitrogen-containing heteroaryl, or vinyl-nitrogen-containing heterocyclyl;
R′ is: hydrogen;
one or more of R 1 to R 5 is other than hydrogen, selected from hydroxy, alkoxy, alkoxycarbonyl and alkenyl; or
two adjacent members of R 1 to R 5 are each O − and together are complexed with a metal;
including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
87 . The method of claim 86 where:
R is selected from:
vinyl-thiazolidine-2,4-dione
phenyl substituted in the para position with nitro or cyano, and
vinyl-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one;
R 1 is hydrogen;
R 2 to R 5 are selected from hydrogen, hydroxy, methoxy, methoxymethoxy, methoxymethoxycarbonyl, prenyl or geranyl, provided that at least two of R 2 to R 5 are not hydrogen.
88 . The method of claim 87 where one of R 2 to R 5 is prenyl or geranyl, and two others are selected from hydroxy, methoxy and methoxymethoxy.
89 . The method of claim 88 where R is phenyl substituted in the para position with nitro or cyano.
90 . A method of treatment for a mammal suffering from a disease characterized by oxidative stress and involving inflammatory and/or autoimmune components, comprising administering a therapeutically effective amount of a compound is selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol; 4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid methyl ester; 4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol; 5-methyl-2-(4-styryl-phenyl)-2,4-dihydro-pyrazol-3-one; 2-{4-[2-(3,4-dihydroxy-phenyl)-vinyl]-phenyl}-5-methyl-2,4-dihydro-pyrazol-3-one; 4-(3,5-di-tert-butyl-4-hydroxy-benzylidene)-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one; 4-[3-(4-hydroxy-3-methoxy-phenyl)-allylidene]-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one; 4-{2-[3-methoxy-4-methoxymethoxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester; 4-[2-(3-iodo-5-methoxy-4-methoxymethoxy-phenyl)-vinyl]-benzoic acid methyl ester; 2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzoic acid methoxymethyl ester; 4-[2-(4-methoxymethoxy-3,5-dimethyl-phenyl)-vinyl]-benzoic acid methyl ester; 2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzoic acid methoxymethyl ester; N-{4-[2-(3,4-bis-methoxymethoxy-phenyl)-vinyl]-phenyl}-benzamide; 4-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allyidene]-5-methyl-2-phenyl-2,4-dhydro-pyrazol-3-one; 5-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-thiazolidine-2,4-dione; 3-(3,5-di-tert-butyl-4-hydroxy-benzylidene)-5-hydroxy-3H-benzofuran-2-one; 5-[3,5-bis-methoxymethoxy-4-(3-methyl-but-2-enyl)-benzylidene]-thiazolidine-2,4-dione; 5-[4-methoxymethoxy-3-(3-methyl-but-2-enyl)-benzylidene]-thiazolidine-2,4-dione; 5-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-benzylidene]-thiazolidine-2,4-dione; 5-[3-methoxy-4-methoxymethoxy-5-(3-methoxy-4-methoxymethoxy-1-(thiazolidine-2,4-dionyl)-benzylidene-5-yl)-benzylidene]-thiazolidine-2,4-dione; 4-{2-[3-methoxy-4-methoxymethoxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester; 4-{2-[3,4-dihydroxy-2-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester; 4-{2-[3,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester; 4-{2-[3,5-dihydroxy-2-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester; 4-{2-[3,5-bis-methoxymethoxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester; 4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester; 3-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol; 3-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol; 4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 2-(3,7-dimethyl-octa-2,6-dienyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile; 4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile; 2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol; 5-{2-[4-hydroxy-3-(3-methyl-but-2-enyl)-phenyl]-vinyl}-2-(3-methyl-but-2-enyl)-benzene-1,3-diol; and 5-{3-[3-methoxy-4-(3-methyl-but-2-enyloxy)-phenyl]-allylidene}-thiazolidine-2,4-dione, including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
91 . The method of claim 90 where the compound is selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol;
4-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one;
5-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-thiazolidine-2,4-dione;
3-(3,5-di-tert-butyl-4-hydroxy-benzylidene)-5-hydroxy-3H-benzofuran-2-one;
4-{2-[3,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester;
3-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
3-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl-benzonitrile;
4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile; and
2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol.
92 . The method of claim 91 where the compound is selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol;
3-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol; and
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol.
93 . A method of treatment for a mammal suffering from a dermatologic condition characterized by oxidative stress, comprising administering a therapeutically effective amount of a compound represented by Formula I:
wherein:
R is: phenyl substituted in the para position with a nitrogen-bearing moiety or a lower alkoxycarbonyl, or is phenyl substituted in the meta position with bromo and in the para position with hydroxy;
R′ is: hydrogen;
one or more of R 1 to R 5 is other than hydrogen, selected from hydroxy, alkoxy, alkenyl and halo or
two adjacent members of R 1 to R 5 are each O − and together are complexed with a metal;
including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
94 . The method of claim 93 where:
R is phenyl substituted in the para position with nitro or cyano; and
R 1 is hydrogen.
95 . The method of claim 93 where one or two of R 2 to R 4 is hydroxy, one of R 1 to R 4 is prenyl or geranyl, and the remaining substituents of R 1 to R 5 are hydrogen.
96 . The method of claim 95 where R is phenyl substituted in the para position with nitro or cyano.
97 . A method of treatment for a mammal suffering from a dermatologic condition characterized by oxidative stress, comprising administering a therapeutically effective amount of a compound selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol; 4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid methyl ester; 4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol 2-methoxy-6-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-phenol; 2-hydroxy-5-[2-(4-nitro-phenyl)-vinyl]-benzoic acid; 3-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol; 4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 2,6-di-tert-butyl-4-[2-(4-nitro-phenyl)-vinyl]-phenol; 2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 2-bromo-4-(4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol; 4-(2-nitro-vinyl)-benzene-1,2-diol; 2-methoxy-4-[4-(4-nitro-phenyl)-buta-1,3-dienyl]-phenol; 2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzoic acid methoxymethyl ester; 3-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol; 2-(3,7-dimethyl-octa-2,6-dienyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 5-{4-[2-(3,4-dihydroxy-phenyl)-vinyl]-phenyl}-2-phenyl-2,4-dihydro-pyrazol-3-one; 4-{2-[3,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester; 4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile; 4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol; 4-{2-[4-(5-hydroxy-1H-pyrazol-3-yl)-phenyl]-vinyl}-benzene-1,2-diol; 4-{2-[4-(2-nitro-vinyl)-phenyl]-vinyl}-benzene-1,2-diol; 3-[2-(3,4-dimethoxy-phenyl)-vinyl]-4-nitro-phenol; 4-[4-(4-nitro-phenyl)-buta-1,3-dienyl]-benzene-1,2-diol; 4-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one; 5-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-thiazolidine-2,4-dione; 3-(3,5-di-tert-butyl-4-hydroxy-benzylidene)-5-hydroxy-3H-benzofuran-2-one; 2-iodo-6-methoxy-4-[2-(4-nitro-phenyl)-vinyl]-phenol; 4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile; 2-(3,7-dimethyl-octa-2,6-dienyl)-6-methoxy-4-[2-(4-nitro-phenyl)-vinyl]-phenol; 2-bromo-6-methoxy-4-[2-(4-nitro-phenyl)-vinyl]-phenol; 4-{2-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-5-methoxy-phenyl]-vinyl}-benzonitrile; 2,6-dimethyl-4-[2-(4-nitro-phenyl)-vinyl]-phenol; acetic acid 4-(1-acetoxy-allyl)-phenyl ester; 2-(4-methoxy-phenyl)-1-(3,4,5-trimethoxy-phenyl)-ethanol; acetic acid 4-[2-(4-acetoxy-3-methoxy-phenyl)-vinyl]-2-methoxy-phenyl ester; 3,4,5-trio; 4-(3-ethoxy-propenyl)-phenol; 2,3-bis-(4-acetoxy-3-methoxy-phenyl)-acrylic acid; cis-gnetin; 5-[2-(4-methoxy-phenyl)-vinyl]-benzo[1,3]dioxole; and (4-methoxyphenyl)-(benzo-1,3-dioxol-5-yl)-ethyne, including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
98 . The method of claim 97 where the compound is selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid methyl ester;
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol;
2-hydroxy-5-[2-(4-nitro-phenyl)-vinyl]-benzoic acid;
3-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol;
3-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
2-(3,7-dimethyl-octa-2,6-dienyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-{2-[3,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester;
4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-{2-[4-(2-nitro-vinyl)-phenyl]-vinyl}-benzene-1,2-diol;
3-[2-(3,4-dimethoxy-phenyl)-vinyl]-4-nitro-phenol; and
4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile.
99 . The method of claim 98 where the compound is selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-bromo-4-[4 -hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol;
2-(3,7-dimethyl-octa-2,6-dienyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-{2-[4-(2-nitro-vinyl)-phenyl]-vinyl}-benzene-1,2-diol; and
4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile.
100 . The method of claim 97 comprising topically administering a compound is selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol;
4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile;
4-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one;
5-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-thiazolidine-2,4-dione;
3-(3,5-di-tert-butyl-4-hydroxy-benzylidene)-5-hydroxy-3H-benzofuran-2-one;
4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile;
2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-[4-(4-nitro-phenyl)-buta-1,3-dienyl]-benzene-1,2-diol;
5-(3,5-di-tert-butyl-4-hydroxy-benzylidene)-thiazolidine-2,4-dione;
4-{2-[3,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester;
3-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
3-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-(3,7-dimethyl-octa-2,6-dienyl)-6-methoxy-4-[2-(4-nitro-phenyl)-vinyl]-phenol;
2-(3,7-dimethyl-octa-2,6-dienyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile; and
2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol.
101 . The method of claim 100 comprising topically administering a compound is selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol;
4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile;
4-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one;
5-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-thiazolidine-2,4-dione;
3-(3,5-di-tert-butyl-4-hydroxy-benzylidene)-5-hydroxy-3H-benzofuran-2-one;
4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile; and
2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol.
102 . The method of claim 101 comprising topically administering a compound is selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol;
4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile; and
4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile.
103 . The method of any of claims 93 or 97 where the dermatologic condition is selected from: regulating skin condition, regulating the signs of skin aging, contact dermatitis, acne, psoriasis, age-related damage, and damage resulting from harmful (UV) radiation, stress and fatigue.
104 . The method of any of claims 93 or 97 further comprising a method of promoting a product by directing a user to apply to the skin a pharmaceutical or cosmetic composition incorporating said compound for regulating skin condition, regulating the signs of skin aging, or for treating contact dermatitis, acne, psoriasis, age-related damage or damage resulting from harmful (UV) radiation, stress or fatigue.
105 . A product comprising instructions directing the user to apply a composition to the skin for regulating skin condition, regulating the signs of skin aging, or for treating contact dermatitis, acne, psoriasis, age-related damage or damage resulting from harmful (UV) radiation, stress or fatigue, said composition comprising a compound of any of claims 6 , 18 , 21 , 26 , 37 , 48 , 56 , 58 , 59 and 60 ; or a compound of the formula:
wherein:
R is: phenyl substituted in the para position with a nitrogen-bearing moiety or a lower alkoxycarbonyl, or is phenyl substituted in the meta position with bromo and in the para position with hydroxy;
R′ is: hydrogen;
one or more of R 1 to R 5 is other than hydrogen, selected from hydroxy, alkoxy, alkenyl and halo; or
two adjacent members of R 1 to R 5 are each O − and together are complexed with a metal,
or a compound selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid methyl ester;
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol
2-methoxy-6-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-phenol;
2-hydroxy-5-[2-(4-nitro-phenyl)-vinyl]-benzoic acid;
3-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2,6-di-tert-butyl-4-[2-(4-nitro-phenyl)-vinyl]-phenol;
2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol;
4-(2-nitro-vinyl)-benzene-1,2-diol;
2-methoxy-4-[4-(4-nitro-phenyl)-buta-1,3-dienyl]-phenol;
2-methoxymethoxy-5-[2-(4-nitro-phenyl)-vinyl]-benzoic acid methoxymethyl ester;
3-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
2-(3,7-dimethyl-octa-2,6-dienyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
5-{4-[2-(3,4-dihydroxy-phenyl)-vinyl]-phenyl}-2-phenyl-2,4-dihydro-pyrazol-3-one;
4-{2-[3,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester;
4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile;
4-(3-methyl-but-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-{2-[4-(5-hydroxy-1H-pyrazol-3-yl)-phenyl]-vinyl}-benzene-1,2-diol;
4-{2-[4-(2-nitro-vinyl)-phenyl]-vinyl}-benzene-1,2-diol;
3-[2-(3,4-dimethoxy-phenyl)-vinyl]-4-nitro-phenol;
4-[4-(4-nitro-phenyl)-buta-1,3-dienyl]-benzene-1,2-diol;
4-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one;
5-[3-(3-methoxy-4-methoxymethoxy-phenyl)-allylidene]-thiazolidine-2,4-dione;
3-(3,5-di-tert-butyl-4-hydroxy-benzylidene)-5-hydroxy-3H-benzofuran-2-one;
2-iodo-6-methoxy-4-[2-(4-nitro-phenyl)-vinyl]-phenol;
4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile;
2-(3,7-dimethyl-octa-2,6-dienyl)-6-methoxy-4-[2-(4-nitro-phenyl)-vinyl]-phenol;
2-bromo-6-methoxy-4-[2-(4-nitro-phenyl)-vinyl]-phenol;
4-{2-[3-(3,7-dimethyl-octa-2,6-dienyl)-4-hydroxy-5-methoxy-phenyl]-vinyl}-benzonitrile;
2,6-dimethyl-4-[2-(4-nitro-phenyl)-vinyl]-phenol;
acetic acid 4-(1-acetoxy-allyl)-phenyl ester;
2-(4-methoxy-phenyl)-1-(3,4,5-trimethoxy-phenyl)-ethanol;
acetic acid 4-[2-(4-acetoxy-3-methoxy-phenyl)-vinyl]-2-methoxy-phenyl ester;
2-{3-[2-(3,4-dihydroxy-phenyl)-vinyl]-5-hydroxy-phenoxy}-6-hydroxymethyl-tetrahydro-pyran-3,4,5-trio;
4-(3-ethoxy-propenyl)-phenol;
2,3-bis-(4-acetoxy-3-methoxy-phenyl)-acrylic acid;
cis-gnetin;
5-[2-(4-methoxy-phenyl)-vinyl]-benzo[1,3]dioxole; and
(4-methoxyphenyl)-(benzo-1,3-dioxol-5-yl)-ethyne,
including single stereoisomers, mixtures of stereoisomers, and the pharmaceutically acceptable salts thereof.
106 . The product of claim 105 where:
R is phenyl substituted in the para position with nitro or cyano; and
R 1 is hydrogen.
107 . The product of claim 105 where one or two of R 2 to R 4 is hydroxy, one of R 1 to R 4 is prenyl or geranyl, and the remaining substituents of R 1 to R 5 are hydrogen.
108 . The product of claim 107 where R is phenyl substituted in the para position with nitro or cyano.
109 . The product of claim 105 wherein said compound is selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
4-[2-(3,4-dihydroxy-phenyl)-vinyl]-benzoic acid methyl ester;
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol;
2-hydroxy-5-[2-(4-nitro-phenyl)-vinyl]-benzoic acid;
3-(3-methyl-but-2-enyl)-4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol;
3-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2-diol;
2-(3,7-dimethyl-octa-2,6-dienyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-{2-[3,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzoic acid methyl ester;
4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-{2-[4-(2-nitro-vinyl)-phenyl]-vinyl}-benzene-1,2-diol;
3-[2-(3,4-dimethoxy-phenyl)-vinyl]-4-nitro-phenol; and
4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile.
110 . The product of claim 105 wherein said compound is selected from the group:
4-[2-(4-nitro-phenyl)-vinyl]-benzene-1,2,3-triol;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
2-bromo-4-[4-hydroxy-3-(3-methyl-but-2-enyl-phenyl)-vinyl]-phenol;
2-(3,7-dimethyl-octa-2,6-dienyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-{2-[3,5-dihydroxy-4-(3-methyl-but-2-enyl)-phenyl]-vinyl}-benzonitrile;
4-(3-methyl-but-2-enyl)-5-[2-(4-nitro-phenyl)-vinyl]-benzene-1,3-diol;
4-{2-[4-(2-nitro-vinyl)-phenyl]-vinyl}-benzene-1,2-diol; and
4-{2-[4-(3,7-dimethyl-octa-2,6-dienyl)-3,5-dihydroxy-phenyl]-vinyl}-benzonitrile.Join the waitlist — get patent alerts
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