Furoxan compounds, compositions and methods of use
View Patent ↗The invention provides novel furoxan compounds, or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one compound, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The invention also provides methods for (a) treating cardiovascular diseases; (b) inhibiting platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device; (c) treating pathological conditions resulting from abnormal cell proliferation; (d) treating transplantation rejections, (e) treating autoimmune, inflammatory, proliferative, hyperproliferative or vascular diseases; (f) reducing scar tissue or for inhibiting wound contraction; (g) treating diseases resulting from oxidative stress; (h) treating endothelial dysfunctions; and (j) treating diseases caused by endothelial dysfunctions.
1. A furoxan compound of Formula (I), or a pharmaceutically acceptable salt thereof:
wherein the compound of Formula (I) is:
wherein:
R 1 is —C 6 H 4 R 2 , —CN, —S(O) 2 C 6 H 4 R 2 , NO 2 or —C(O)—OR 3 ;
R 2 is hydrogen, —CN, —S(O) 2 R 3 , NO 2 or —C(O)—OR 3 ;
R 3 is an alkyl group or an aryl group;
T is a covalent bond, oxygen, S(O) o or NR 4 ;
o is an integer from 1 to 2;
R 4 is a hydrogen, a lower alkyl group or an aryl group;
X is —(CH 2 ) a —N(R 5 )(R 6 ), —(CHR 7 ) b —CH 2 -T-Z, —(CHR 7 ) b —N(R 5 )(R 6 ) or —CH 2 —C(CH 2 -T-Z) 3 ;
R 5 is a hydrogen, an alkyl group, an aryl group or —(CH 2 ) a -T-Z;
R 6 is a hydrogen, an alkyl group, an aryl group, —(CH 2 ) a -T-Z or —C(CH 2 -T-Z) 3 ;
R 7 is hydrogen or -T-Z;
a is an integer from 2 to 5;
b is an integer from 1 to 6;
Z is
with the proviso that the furoxan compounds of Formula (I) must contain at least one Z group.
2. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
3. The composition of claim 2 , further comprising (i) at least one therapeutic agent; (ii) at least one nitric oxide enhancing compound; or (iii) at least one therapeutic agent and at least one nitric oxide enhancing compound.
4. The composition of claim 3 , wherein the therapeutic agent is a thrombolytic agent, an antimicrobial compound, an antiproliferative agent, an antisecretory agent, an anti-cancer chemotherapeutic agent, a steroid, an immunosuppressive agent, a radiotherapeutic agent, a heavy metal functioning as a radiopaque agent, an aldosterone antagonist, an alpha-adrenergic receptor antagonist, an angiotensin II antagonist, an angiotensin-converting enzyme inhibitor, an antidiabetic compound, an anti-hyperlipidemic compound, an antioxidant, an antithrombotic and vasodilator compound, a β-adrenergic antagonist, a calcium channel blocker, an endothelin antagonist, a hydralazine compound, a H 2 receptor antagonist, an neutral endopeptidase inhibitor, a nonsteroidal antiinflammatory compound, a phosphodiesterase inhibitor, a potassium channel blocker, a platelet reducing agent, a proton pump inhibitor, a renin inhibitor, a selective cyclooxygenase-2 (COX-2) inhibitor, or a combination of two or more thereof.
5. The composition of claim 4 , wherein the therapeutic agent is at least one compound selected from the group consisting of a thrombolytic agent, an antimicrobial compound, an antiproliferative agent, an anti-cancer chemotherapeutic agent, a steroid, an immunosuppressive agents, an antioxidant, an antithrombotic and vasodilator compound, a hydralazine compound and a platelet reducing agent.
6. A kit comprising at least one compound of claim 1 .
7. The kit of claim 6 , further comprising further comprising (i) at least one therapeutic agent; (ii) at least one nitric oxide enhancing compound; or (iii) at least one therapeutic agent and at least one nitric oxide enhancing compound.
8. The kit of claim 7 , wherein the (i) at least one therapeutic agent; (ii) at least one nitric oxide enhancing compound; or (iii) at least one therapeutic agent and at least one nitric oxide enhancing compound are in the form of separate components in the kit.
9. A compound selected from the group consisting of: ethanamine, 2-[[5-oxido-4-(phenylsulfonyl)-1,2,5-oxadiazol-3-yl]oxy]-N,N-bis[2-[[5-oxido-4-(phenylsulfonyl)-1,2,5-oxadiazol-3-yl]oxy]ethyl]-;
ethanamine, 2-[[5-oxido-4-(phenylsulfonyl)-1,2,5-oxadiazol-3-yl]oxy]-N-[2-[[5-oxido-4-(phenylsulfonyl)-1,2,5-oxadiazol-3-yl]oxy]ethyl]-;
ethanol, 2-[bis[2-[[5-oxido-4-(phenylsulfonyl)-1,2,5-oxadiazol-3-yl]oxy]ethyl]amino]-;
1,2,5-oxadiazole, 3,3′,3″-[1,2,3-propanetriyltris(oxy)]tris[4-(phenylsulfonyl)-, 5,5′,5″-trioxide;
1,2,5-oxadiazole, 3,3′-[1,2-ethanediylbis(oxy)]bis[4-(phenylsulfonyl)-, 5,5′-dioxide;
1,2,5-oxadiazole-3-methanamine, 4-methyl-N-[(4-methyl-5-oxido-1,2,5, oxadiazol-3-yl)methyl]-, 5-oxide;
and pharmaceutically acceptable salts thereof.