Carbocyclic nucleosides and their pharmaceutical use and compositions
View Patent ↗Disclosed are compounds of the formula I and the pharmaceutically acceptable salts of such compounds. Also disclosed are processes for the preparation of such compounds, intermediates used in the preparation of such compounds, and the uses of such compounds in treating inflammatory skin diseases.
1. A compound of the formula
wherein R 1 and R 2 are independently selected from hydrogen, CO 2 C 1 -C 4 alkyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl and C 2 -C 6 alkynyl, wherein the alkyl moieties of said alkyl, alkenyl, and alkynyl groups may be linear, branched chain or a combination of linear and branched chain
where n is 0 to 3,
where n is 1 to 2, C 3 -C 7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3-heteroatoms where the heteroatoms are independently selected from N, O and S and where each heterocyclic ring may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from C 1 -C 6 alkoxy, and O—C 1 -C 6 alkyl;
R 3 and R 4 are independently selected from hydrogen and C 1 -C 6 alkyl;
R 5 and R 6 are independently selected from hydrogen and —CO 2 C 4 H 9 ;
A is selected from a covalent bond, O, S, Se, C 1 -C 6 alkyl, and (CH 2 ) n O, where n is an integer from 0 to 3;
X is selected from a covalent bond, O, S and Se;
B is selected from a covalent bond, —CH 2 , —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —, trans-CH═CH—,
cis-CH═CH—, —C≡C—, —CHR 7 —CHR 8 —, cis or trans-CR 7 ═CR 8 —, wherein R 7 and R 8 are independently selected from C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, and C 3 -C 7 cycloalkyl; and
Y is selected from of OH, SH, OR 9 wherein R 9 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl and C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, and (CH 2 ) n OH, wherein n is an integer from 1 to 6 and NR 9 R 10 wherein R 9 and R 10 are independently selected from C 1 -C 6 alkyl and C 3 -C 7 cycloalkyl;
or a pharmaceutically acceptable salt thereof.
2. A compound having the formula
or a pharmaceutically acceptable salt thereof.
3. The compound (−) cis-[4-[2-amino-6-cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-hydroxymethyl acetate according to claim 2 .
4. A pharmaceutically acceptable salt of the compound (−) cis-[4-[2-amino-6-cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-hydroxymethyl acetate according to claim 2 .
5. A pharmaceutical composition for treating inflammatory skin diseases comprising an anti-inflammatory effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.
6. A pharmaceutical composition for treating inflammatory skin diseases comprising an anti-inflammatory effective amount of a compound according to claim 2 and a pharmaceutically acceptable carrier.
7. A pharmaceutical composition according to claim 5 , wherein said composition is in dosage unit form.
8. A pharmaceutical composition according to claim 6 , wherein said composition is in dosage unit form.
9. A pharmaceutical composition for treating psoriasis, eczema, or seborrhiasis comprising an anti-psoriasis, anti-eczema or anti-seborrhiasis effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.
10. A method of treating an inflammatory skin disease in a patient in need of such treatment comprising administering to said patient an amount of a compound according to claim 1 effective to treat said disease.
11. A method according to claim 10 , wherein said compound is (−) cis-[4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-hydroxymethyl acetate (Prurisol) or a pharmaceutically acceptable salt thereof.
12. A method according to claim 10 , wherein said inflammatory disease is psoriasis.
13. A method according to claim 12 , wherein said compound is (−) cis-[4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-hydroxymethyl acetate (Prurisol).
14. A method according to claim 10 , wherein said inflammatory disease is eczema.
15. A method according to claim 14 , wherein said compound is (−) cis-[4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-hydroxymethyl acetate (Prurisol).
16. A method according to claim 10 , wherein said inflammatory disease is seborrhiasis.
17. A method according to claim 16 , wherein said compound is (−) cis-[4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-hydroxymethyl acetate (Prurisol).
18. A compound of the formula
19. A compound of the formula
wherein R 1 , R 5 and R 6 are independently selected from the group consisting of hydrogen and —CO 2 C 4 H 9 .
20. A compound of the formula
wherein R 1 , R 5 and R 6 are independently selected from the group consisting of hydrogen and —CO 2 C 4 H 9 .
21. A compound of the formula
wherein R 1 , R 5 and R 6 are independently selected from the group consisting of hydrogen and —CO 2 C 4 H 9 .