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US 7,582,650 B2Granted
Tricyclic opioid modulators
AssigneeJanssen Pharmaceutica NV
InventorsBart DeCorte, Li Liu, Mark McDonnell, Jim McNally
Life of this patent
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Abstract
The invention is directed to compounds of Formula (I) useful as delta and mu opioid receptor modulators. Pharmaceutical and veterinary compositions and methods of treating mild to severe pain and various diseases using compounds of the invention are also described.
Claims17
A compound of Formula 1
- wherein:
- R1 is hydroxy, aminocarbonyl, hydroxyamidino, formylamino;
- C1-4alkanylaminocarbonyl;
- phenyl-aminocarbonyl;
- phenyl(C1-4)alkanylaminocarbonyl;
- and naphthyl- and phenyl- amino wherein the naphthyl and phenyl are optionally substituted with one to two substitutents independently selected from the group consisting of C1-4alkanyl, C1-4alkoxy, halogen, and hydroxy;
- or pyridinylamino;
- R2 is selected from the group consisting of hydrogen, C1-4alkanyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkanyl(C1-4)alkanyl, C1-4alkanyloxy(C1-4)alkanyl, C1-4alkanylthio(C 1-4)alkanyl, hydroxyC1-4alkanyl, thioformyl, phenylimino(C1-4)alkanyl, phenyl(C1-4)alkanyl, and heteroaryl(C1-4)alkanyl wherein heteroaryl is selected from the group consisting of benzo [1,3 ]dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indolyl, indolinyl, isoquinolinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolyl, quinolinyl, benzothiophenyl, tetrazolyl;
- wherein phenyl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkanyloxy and hydroxy;
- or optionally, when phenyl and heteroaryl are optionally substituted with two substituents attached to adjacent carbon atoms, the two substituents together form —O(CH2)1-3O—;
- A is —(CH2)2—;
- Y is O;
- and enantiomers, diastereomers, tautomers, or pharmaceutically acceptable salts thereof.
10 more elements
A compound of Formula (Ia)
- selected from the group consisting of
- a compound of Formula (Ia) wherein R1 is methoxy, A is —(CH2)2—, and R2 is H;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is H;
- a compound of Formula (Ia) wherein R1 is aminocarbonyl, A is —(CH2)2—, and R2 is H;
- a compound of Formula (Ia) wherein R1 is aminocarbonyl, A is —(CH2)2—, and R2 is furan-2-ylmethyl;
- Enant. A, a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is trifluoromethylcarbonyl;
- Enant. B, a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is trifluoromethylcarbonyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is H;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is H;
- a compound of Formula (Ia) wherein R1 is methylaminocarbonyl, A is —(CH2)2—, and R2is H;
- a compound of Formula (Ia) wherein R1 is dimethylaminocarbonyl, A is —(CH2)2—, and R2is H;
- a compound of Formula (Ia) wherein R1 is phenyl-aminocarbonyl, A is —(CH2)2-, and R2is H;
- a compound of Formula (Ia) wherein R1 is phenylmethyl-aminocarbonyl, A is —(CH2)2-, and R2 is H;
- a compound of Formula (Ia) wherein R1 is phenylethyl-aminocarbonyl, A is —(CH2)2-, and R2 is H;
- a compound of Formula (Ia) wherein R1 is (2-dimethylamino-ethyl) aminocarbonyl, A is —(CH2)2—, and R2 is H;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is methyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is pyridin-2-ylmethyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is pyridin-4-ylmethyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is 2-hydroxy-pyridin-4-ylmethyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is thien-2-ylmethyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is furan-3 -ylmethyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is cyclopropylmethyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is 2-methyl-but-2-enyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is 2-phenyl-imidazol-4-ylmethyl;
- a compound of Formula (Ia) wherein R1 is aminocarbonyl, A is —(CH2)2—, and R2 is trifluoromethylcarbonyl
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is phenethyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is pyridin-2-ylmethyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is phenylmethyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is benzothien-3 -ylmethyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is 1H-imidazol-2-ylmethyl;
- a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is isoquinolin-5 -ylmethyl;
- Enant. A, a compound of Formula (Ia) wherein R1 is aminocarbonyl, A is —(CH2)2—, and R2 is trifluoromethylcarbonyl;
- Enant. A, a compound of Formula (Ia) wherein R1 is aminocarbonyl, A is —(CH2)2—, and R2is H;
- Enant. B, a compound of Formula (Ia) wherein R1 is aminocarbonyl, A is —(CH2)2—, and R2 is trifluoromethtylcarbonyl;
- Enant. A, a compound of Formula (Ia) wherein R1 is aminocarbonyl, A is —(CH2)2—, and R2is H;
- a compound of Formula (Ia) wherein R1 is amino, A is —(CH2)2—, and R2 is H;
- Enant. A, a compound of Formula (Ia) wherein R1 is hydroxyamidino, A is —(CH2)2—, and R2 is H;
- a compound of Formula (Ia) wherein R1 is formylamino, A is —(CH2)2—, and R2 is H;
- Enant. A, a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is phenylmethyl;
- Enant. B, a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is phenylmethyl;
- a compound of Formula (Ia) wherein R1 is phenylaminocarbonyl, A is —(CH2)2—, and R2 is H;
- a compound of Formula (Ia) wherein R1 is phenylaminocarbonyl, A is —(CH2)2—, and R2 is H;
- Enant. A, a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is pyridin-3-ylmethyl;
- Enant. B, a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is pyridin-3-ylmethyl;
- Enant. A, a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is methyl;
- Enant. B, a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is methyl;
- Enant. A, a compound of Formula (Ia) wherein R1 is phenylmethylaminocarbonyl, A is —(CH2)2—, and R2 is H;
- Enant. B, a compound of Formula (Ia) wherein R1 is phenylmethylaminocarbonyl, A is —(CH2)2—, and R2 is H;
- Enant. A, a compound of Formula (Ia) wherein R1 is phenethylaminocarbonyl, A is —(CH2)2—, and R2 is H;
- Enant. B, a compound of Formula (Ia) wherein R1 is phenethylaminocarbonyl, A is —(CH2)2—, and R2 is H;
- Enant. B, a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is furan-3-ylmethyl;
- Enant. A, a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is furan-3-ylmethyl;
- Enant. A, a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is pyridin-2-ylmethyl;
- Enant. B, a compound of Formula (Ia) wherein R1 is hydroxy, A is —(CH2)2—, and R2 is pyridin-2-ylmethyl;
- a compound of Formula (Ia) wherein R1 is 4-chioro-phenylamino, A is —(CH2)2—, and R2is H;
- a compound of Formula (Ia) wherein R1 is pyridin-3-ylamino, A is —(CH2)2—, and R2 is H;
- and
- a compound of Formula (Ia) wherein R1 is phenylamino, A is —(CH2)2—, and R2 is H.
55 more elements
Dependencies are inferred from the claim text.