Oxazole derivatives useful as modulators of FAAH
View Patent ↗The present invention is directed to certain Oxazole derivatives which are useful as modulators of Fatty Acid Amide Hydrolase (FAAH) and as FAAH imaging agents. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer Disease, and Parkinson's Disease.
1. A compound of the Formula
wherein:
n is 0, 1 or 2, and
R 1 is selected from the group consisting of:
(1) phenyl, and
(2) pyridyl,
optionally mono or di-substituted with substituents R 4 and R 5 , which are independently selected from the group consisting of
(a) mono, di or tri-halo C 1-4 alkyl,
(b) —C 1-4 alkyl optionally substituted with one or two substituents selected from hydroxyl, —CHF 2 and —CF 3 ,
(c) —S(O) n C 1-4 alkyl,
(d) —C(O)—NR 10 R 11 ,
wherein R 10 and R 11 are each independently selected from H and C 1-4 alkyl,
(e) HET 2 ,
wherein HET 2 is a 5 to 10-membered aromatic, partially aromatic or non-aromatic mono- or bicyclic ring, or N-oxide thereof, said containing 1 to 4 heteroatoms selected from O, S and N, and optionally mono or di-substituted with substituents selected from:
(1) halo,
(2) —OH,
(3) —C 1-4 alkyl optionally substituted with hydroxy, halo or cyano,
(4) —CF 3 ,
(5) —OC 1-4 alkyl optionally substituted with hydroxyl or halo, and
(6) —C(O)O—C 1-3 alkyl; and
R 3 is selected from the group consisting of:
(1) phenyl, and
(3) pyridyl, wherein R 3 is optionally mono or di-substituted with halo, haloC 1-4 alkyl,
or —OC 1-4 alkyl optionally substituted with halo.
2. A compound selected from the group consisting of
No.
Structure
1
2
4
5
6
7
8
9
10
or a pharmaceutically acceptable salt thereof.
3. A compound selected from the group consisting of
No.
Structure
B5.1 1
B5.3 3
9
14
16
17
18
19
20
21
22
24
26
27
28
29
30
31
32
or a pharmaceutically acceptable salt thereof.
4. A pharmaceutical composition which comprises an inert carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.