Monamine and monoamine derivatives as inhibitors of leukotriene A4 hydrolase
View Patent ↗This present disclosure is directed to compounds of formula (I): where r, q, R 1a , R 1b , R 1c , R 1d , R 1e , R 2 , R 3 , R 4a , R 5a , R 5b , R 6a , R 6b , R 8 , and R 9 are described herein, as single stereoisomers or as mixtures of stereoisomers, or pharmaceutically acceptable salts, solvates, clathrates, polymorphs, ammonium ions, N-oxides or prodrugs thereof; which are leukotriene A 4 hydrolase inhibitors and therefore useful in treating inflammatory disorders. Pharmaceutical compositions including the compounds described herein and methods of preparing the compounds described herein are also provided.
1. A compound having the formula (I):
wherein:
r is 0; q is 0 to 2;
R 1a , R 1b , R 1c , R 1d and R 1e are each independently selected from the group consisting of hydrogen, C 1 -C 6 alkyl, halo, optionally substituted aryl, and optionally substituted heteroaryl;
R 2 is hydrogen or C 1 -C 6 alkyl;
R 8 is benzyl substituted with R 13 —O—R 10 ;
R 3 is methylene;
R 4a is —O—;
R 5a and R 6a are each hydrogen;
R 5b and R 6b are each hydrogen;
R 10 is phenyl substituted with C(O)OR 15 ;
and
each R 13 is a direct bond; and
R 15 is hydrogen or C 1 -C 6 alkyl;
as a single stereoisomer or as a mixture of stereoisomers;
or a pharmaceutically acceptable salt.
2. The compound according to claim 1 , wherein R 1a , R 1b , R 1c , R 1d and R 1e are each independently hydrogen; or a pharmaceutically acceptable salt thereof.
3. The compound according to claim 1 wherein R 2 is hydrogen; or a pharmaceutically acceptable salt thereof.
4. The compound according to claim 1 , wherein the compound is selected from one of the following compounds, or is a pharmaceutically acceptable salt thereof:
5. The compound according to claim 1 , wherein q is 1, or a pharmaceutically acceptable salt thereof.
6. The compound according to claim 1 , wherein R 2 is methyl, or a pharmaceutically acceptable salt thereof.
7. The compound according to claim 1 , wherein R 15 is hydrogen, or a pharmaceutically acceptable salt thereof.
8. The compound according to claim 2 , wherein q is 1, or a pharmaceutically acceptable salt thereof.
9. The compound according to claim 8 , wherein R 2 is methyl, or a pharmaceutically acceptable salt thereof.
10. The compound according to claim 9 , wherein R 15 is hydrogen, or a pharmaceutically acceptable salt thereof.
11. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.