(+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione: methods of using and compositions thereof
Stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, substantially free of its (−) isomer, and prodrugs, metabolites, polymorphs, salts, solvates, hydrates, and clathrates thereof are discussed. Also discussed are methods of using and pharmaceutical compositions comprising the (+) enantiomer of 2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione are disclosed. The methods include methods of treating and/or preventing disorders ameliorated by the reduction of levels of TNF-α or the inhibition of PDE4.
1. A method of treating diseases or disorders ameliorated by the inhibition of PDE4 in a patient which comprises administering to a patient in need of such treatment a therapeutically effective amount of stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, or a pharmaceutically acceptable prodrug, polymorph, salt, or solvate thereof.
2. The method of claim 1 further comprising administering to a patient in need of such treatment a therapeutically effective amount of an antihistamine, anti-inflammatory drug, non-steroid anti-inflammatory drug, or steroid.
3. The method of claim 1 wherein the disease or disorder is asthma, allergic rhinitis, inflammation, or chronic pulmonary inflammatory disease.
4. The method of claim 1 wherein the disease or disorder is chronic obstructive pulmonary disease.
5. The method of claim 1 wherein the patient is a mammal.
6. The method of claim 1 wherein the stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, or pharmaceutically acceptable prodrug, polymorph, salt, or solvate thereof is administered parenterally, transdermally, mucosally, nasally, buccally, sublingually, or orally.
7. The method of claim 6 wherein the stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, or pharmaceutically acceptable prodrug, polymorph, salt, or solvate thereof is administered orally.
8. The method of claim 7 wherein the stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, or pharmaceutically acceptable prodrug, polymorph, salt, or solvate thereof is administered orally in a tablet or capsule form.
9. The method of claim 1 wherein the therapeutically effective amount is from about 1 mg to about 1000 mg per day.
10. The method of claim 9 wherein the therapeutically effective amount is from about 5 mg to about 500 mg per day.
11. The method of claim 10 wherein the therapeutically effective amount is from about 10 mg to about 200 mg per day.
12. A method of treating diseases or disorders ameliorated by the inhibition of PDE4 in a patient which comprises administering to a patient in need of such treatment a therapeutically effective amount of stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, or a pharmaceutically acceptable salt, or solvate thereof.
13. The method of claim 1 , wherein the stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione comprises less than about 20% by weight of (−)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
14. The method of claim 13 , wherein the stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione comprises less than about 10% by weight of (−)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
15. The method of claim 14 , wherein the stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione comprises less than about 5% by weight of (−)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
16. The method of claim 15 , wherein the stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione comprises less than about 3% by weight of (−)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
17. The method of claim 12 , which comprises administering stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
18. The method of claim 12 , which comprises administering a pharmaceutically acceptable salt of stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
19. The method of claim 12 , which comprises administering a pharmaceutically acceptable solvate of stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
20. The method of claim 12 , which comprises administering a hydrate of stereomericaily pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
21. A method of treating asthma, allergic rhinitis, inflammation, chronic pulmonary inflammatory disease or chronic obstructive pulmonary disease in a patient, which comprises administering to a patient in need of such treatment a therapeutically effective amount of stereomericaily pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, or a pharmaceutically acceptable prodrug, polymorph, salt, or solvate thereof.
22. The method of claim 1 , 6 , 7 , 8 , 12 , or 21 , wherein said salt is a clathrate.
23. The method of claim 1 , 6 , 7 , 8 , 12 , or 21 , wherein said solvate is a hydrate.