Heteroaryl-substituted spirocyclic diamine urea modulators of fatty acid amide hydrolase
AssigneeJanssen Pharmaceutica NV
InventorsJ. Guy Breitenbucher, John M. Keith, William M. Jone
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Abstract
Certain heteroaryl-substituted spirocyclic diamine urea compounds are described, which are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity, such as anxiety, pain, inflammation, sleep disorders, eating disorders, energy metabolism disorders, and movement disorders (e.g., multiple sclerosis).
Claims23
A composition of matter selected from compounds of Formula (I), pharmaceutically acceptable salts of compounds of Formula (I), and pharmaceutically acceptable prodrugs of compounds of Formula (I),
- wherein
- n1, n2, n3, and n4, in the form of sets [n1,n2,n3,n4], are chosen from the following sets, [2,2,1,2], [2,2,1,1], [2,1,0,3], [1,2,1,2], [2,2,2,2], [1,3,2,1], [1,2,2,2], [1,3,2,2], [2,2,1,3], [1,3,3,1], [1,3,1,1], [1,1,2,2], [1,1,1,1], [2,2,0,3], or [1,1,1,3];
- Ar1 is benzo[1,2,5]oxadiazolyl, benzo[d]isoxazolyl, benzooxazol-yl, benzo[d]thiazolyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-b]pyridazinyl, 1H-indazolyl, isoxazolyl, isoxazolo[4,5-b]pyridinyl, isoxazolo[5,4-b]pyridinyl, phenyl, pyrazolyl, 1H-pyrazolo[3,4-b]pyridinyl, pyridazinyl, pyridyl, pyrimidinyl, 1H-pyrrolo[2,3-b]pyridinyl, quinolinyl, or tetrazolyl, with the point of attachment being any substitutable carbon of the respective heterocycle;
- where each Ar1 is optionally substituted with one or two groups, each said group individually selected from —C1-3alkyl, halo, —CF3, —CN, —OC1-3alkyl, triazolyl, phenyl, morpholinyl, piperidinyl, or pyrazolyl;
- Ar2 is
- (i) phenyl optionally substituted with one or two Ra moieties;
- where each Ra moiety is independently —OH, —CN, halo, —CF3, —O(CH2)0-1CF3, —S(O)(O)C1-4alkyl, —SCF3, —S(O)(O)CF3, or two adjacent Ra moieties taken together form —OCF2O—;
- (ii) phenyl substituted at the 3-position with -L-Ar3,
- where L is a linker selected from the group consisting of —O— or —C≡C—;
- and
- Ar3 is:
- (c) phenyl optionally substituted with one or two Ra moieties;
- or
- (d) quinolinyl;
- or
- (iii) napthyl optionally substituted with —OH.
A pharmaceutical composition comprising:
- (a) a therapeutically effective amount of a chemical entity selected from the group consisting of compounds of Formula (I):
- wherein
- n1, n2, n3, and n4, in the form of sets [n1,n2,n3,n4], are chosen from the following sets, [2,2,1,2], [2,2,1,1], [2,1,0,3], [1,2,1,2], [2,2,2,2], [1,3,2,1], [1,2,2,2], [1,3,2,2], [2,2,1,3], [1,3,3,1], [1,3,1,1], [1,1,2,2], [1,1,1,1], [2,2,0,3], or [1,1,1,3];
- Ar1 is benzo[1,2,5]oxadiazolyl, benzo[d]isoxazolyl, benzooxazol-yl, benzo[d]thiazolyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-b]pyridazinyl, 1H-indazolyl, isoxazolyl, isoxazolo[4,5-b]pyridinyl, isoxazolo[5,4-b]pyridinyl, phenyl, pyrazolyl, 1H-pyrazolo[3,4-b]pyridinyl, pyridazinyl, pyridyl, pyrimidinyl, 1H-pyrrolo[2,3-b]pyridinyl, quinolinyl, or tetrazolyl, with the point of attachment being any substitutable carbon of the respective heterocycle;
- where each Ar1 is optionally substituted with one or two groups, each said group individually selected from —C1-3alkyl, halo, —CF3, —CN, —OC1-3alkyl, triazolyl, phenyl, morpholinyl, piperidinyl, or pyrazolyl;
- Ar2 is
- (i) phenyl optionally substituted with one or two Ra moieties;
- where each Ra moiety is independently —OH, —CN, halo, —CF3, —O(CH2)0-1CF3, —S(O)(O)C1-4alkyl, —SCF3, —S(O)(O)CF3, or two adjacent Ra moieties taken together form —OCF2O—;
- (ii) phenyl substituted at the 3-position with -L-Ar3,
- where L is a linker selected from the group consisting of —O— or —C≡C—;
- and
- Ar3 is:
- (a) phenyl optionally substituted with one or two Ra moieties;
- or
- (b) quinolinyl;
- or
- (iii) napthyl optionally substituted with —OH;
- and pharmaceutically acceptable salts of compounds of Formula (I),
- pharmaceutically acceptable prodrugs of compounds of Formula (I);
- and
- (b) a pharmaceutically acceptable excipient.
Dependencies are inferred from the claim text.