Method for decreasing sebum production
View Patent ↗The present invention is directed to the topical application of the malonamide ACAT inhibitors described by Formula I. Other aspects of the invention are directed to topical formulations of these diamides, their use to treat sebaceous gland disorders and their use to alleviate oily skin.
1. A method for alleviating oily skin comprising administering to a patient in need thereof, an effective amount of a compound of the formula:
in which R 1 and R 2 are each independently C 1-6 alkyl;
X is CH 2 ;
R 3 is C 1-6 alkyl or pyridyl;
p is 1;
R 4 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, and SR 7 ;
R 7 is C 1-6 alkyl;
or a pharmaceutically acceptable salt thereof.
2. A method for decreasing sebum secretion comprising administering to a patient in need thereof, an effective amount of a compound of the formula:
in which R 1 and R 2 are each independently C 1-6 alkyl;
X is CH 2 ;
R 3 is C 1-6 aiki or pyridyl;
p is 1;
R 4 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, and SR 7 ;
R 7 is C 1-6 alkyl;
or a pharmaceutically acceptable salt thereof.
3. A method for decreasing sebum secretion comprising administering to a patient in need thereof, an effective amount of a compound of the formula:
in which R 3 is C 1-6 alkyl or pyridyl;
R 4 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, and SR 7 ;
R 7 is C 1-6 alkyl;
or a pharmaceutically acceptable salt thereof.
4. A method according to claim 3 in which said compound is selected from the group consisting of N′-[2,6-bis(1-niethylethyl)phenyl]-N-(1-methylethyl)-N-([4-(methylthio)phenyl]methyl]- propanediamide or pharmaceutically acceptable salt thereof, and N-[2,6-bis(1- methylethyl)pheny]-]β-[[(4-methoxyphenyl)meth)](2-pyridinyl)amino]-]β-oxo-propanamide, or pharmaceutically acceptable salt thereof.
5. A method for treating acne comprising administering to a patient in need thereof, an effective amount of a compound of the formula:
in which R 1 and R 2 are each independently C 1-6 alkyl;
X is CH 2 ;
R 3 is C 1-6 alkyl or pyridyl;
p is 1;
R 4 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, and SR 7 ;
R 7 is C 1-6 alkyl;
or a pharmaceutically acceptable salt thereof.
6. A method according to claim 5 in which said compound is selected from the group consisting of N′-[2,6-bis(1-methylethyl)phenyl]-N-(1-methylethyl)-N-[[4(methylthio)phenyl]methyl]-propanediamide or pharmaceutically acceptable salt thereof, and N-[2,6-bis(1-methylethyl)phenyl]-]β-[[(4-methoxyphenyl)methyl](2-pyridinyl)amino]-]β-oxo-propanamide or pharmaceutically acceptable salt thereof.
7. An article of manufacture comprising a compound of the formula
in which R 1 and R 2 are each independently C 1-6 alkyl;
X is CH 2 ;
R 3 is C 1-6 alkyl or pyridyl;
p is 1;
R 4 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, and SR 7 ;
R 7 is C 1-6 alkyl;
or a pharmaceutically acceptable salt thereof, packaged for retail distribution, which advises a consumer how to utilize the compound to alleviate a condition selected from the group consisting of acne, oily skin, and seborrheic dermatitis.
8. The article according to claim 7 in which said compound is N-Benzyl-N′-(2,6-diisopropyl-phenyl)-N-isopropyl-malonamide or a pharmaceutically acceptable salt thereof.
9. A method for alleviating oily skin comprising administering to a patient in need thereof, an effective amount of a compound of the formula:
in which R 3 is C 1-6 alkyl or pyridyl;
R 4 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, and SR 7 ;
R 7 is C 1-6 alkyl;
or a pharmaceutically acceptable salt thereof.
10. A method according to claim 9 , wherein said compound is selected from the group consisting of N′-[2,6-bis(1-methylethyl)phenyl]-N-(1-methylethyl)-N-[[4-(methylthio)phenyl]methyl]-propanediamide or pharmaceutically acceptable salt thereof, and N-[2,6-bis(1-methylethyl)phenyl]-]β-[[(4-methoxyphenyl)methyl](2-pyridinyl)amino]-]β-oxo-propanamide or pharmaceutically acceptable salt thereof.
11. A method for treating acne comprising administering to a patient in need thereof an effective amount of a compound of the formula:
in which R 3 is C 1-6 alkyl or pyridyi;
R 4 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, and SR 7 ;
R 7 is C 1-6 alkyl;
or a pharmaceutically acceptable salt thereof.
12. A method for treating seborrheic dermatitis comprising administering to a patient in need thereof an effective amount of a compound of the formula:
in which R 1 and R 2 are each independently C 1-6 alkyl;
X is CH 2 ;
R 3 is C 1-6 alkyl or pyridyl;
p is 1;
R 4 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, and SR 7 ;
R 7 is C 1-6 alkyl;
or a pharmaceutically acceptable salt thereof.
13. A method for treating seborrheic dermatitis comprising administering to a patient in need thereof, an effective amount of a compound of the formula:
in which R 3 is C 1-6 alkyl or pyridyl;
R 4 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, and SR 7 ;
R 7 is C 1-6 alkyl;
or a pharmaceutically acceptable salt thereof.
14. A method according to claim 13 , wherein said compound is selected from the group consisting of: N-benzyl-N′-(2,6-diisopropyl-phenyl)-N-isopropyl-malonamide, N′-[2,6-bis(1 -methylethyl)phenyl]-N-(1 -methylethyl)-N-[[4-(methylthio)phenyl]methyl]-propanediamide or pharmaceutically acceptable salt thereof, and N-[2,6-bis(1-methylethyl)phenyl]-]β-[[(4-methoxyphenyl)methyl](2-pyridinyl)amino]-]β-oxo-propanamide or pharmaceutically acceptable salt thereof.
15. An article of manufacture comprision a compound of the formula
in which R 3 is C 1-6 alkyl or pyridyl;
R 4 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, and SR 7 ;
R 7 is C 1-6 alkyl;
or a pharmaceutically acceptable salt thereof, packaged for retail distribution, which advises a consumer how to utilize the compound to alleviate a condition selected from the group consistion of acne, oily skin, and seborrheic dermatits.
16. The article according to claim 14 , wherein said compound is Selected from the group consistion of: N′-[2,6-bis(1-methylethyl)phenyl]-N-(1-methylethyl)-N-[[4-(methylthio)phenyl]methyl]-propanediamide or pharmaceutically acceptable salt thereof, and N-[2,6-bis(1-methylethyl)phenyl]-]β-[[(4-methoxyphenyl)methyl](2-pyridinyl)amino]-]β-oxo-propanamide or pharmaceutically acceptable salt thereof.