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US 2009/0023728 A1Published application
1,2,3,4-Tetrahydroisoquinoline Derivatives, Preparations Thereof and Uses Thereof
AssigneeAstraZeneca AB
InventorsJustin Ripper, Ian Jenkins, Phuc Van Le, Ron Quinn, Christian Janssen
Life of this patent
Estimating the term…
Abstract
Compounds of general formula (I) wherein D, E, R1, R2, R3, R4, R5, R6 and R7 are as defined in the specification, as well as salts, enantiomers thereof and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.
Claims15
A compound of formula I, a pharmaceutically acceptable salt thereof, diastereomers, enantiomers, or mixtures thereof:
- wherein
- R1 is selected from —H and C1-6alkyl;
- R2 and R3 are independently selected from —H and C1-6alkyl;
- R4, R5, R6 and R7 are independently selected from —H, —OH, halogen, —NO2, C1-6alkyl, C6-10aryl, C1-6alkoxy, C3-6cycloalkoxy, C3-6heterocyclyl-oxy, C3-6heterocyclyl-C1-4alkoxy, C6-10aryl-oxy, C6-10aryl-C1-4alkoxy, C1-6alkyl-S(═O)2—O—, C6-10aryl-S(═O)2—O—, C1-6alkyl-NH—S(═O)2—O—, and (C1-6alkyl)2N—S(═O)2—O—;
- or any two adjacent groups selected from R4, R5, R6 and R7 form a portion of a 5 or 6-membered ring that fused with the benzene ring of formula I, wherein said C1-6alkyl, C6-10aryl, C1-6alkoxy, C3-6cycloalkoxy, C3-6heterocyclyl-oxy, C3-6heterocyclyl-C1-4alkoxy, C6-10aryl-oxy, C6-10aryl-C1-4alkoxy, C1-6alkyl-S(═O)2—O—, C6-10aryl-S(═O)2—O—, C1-6alkyl-NH—S(═O)2—O—, and (C1-6alkyl)2N—S(═O)2—O— are optionally substituted with one or more groups selected from halogen, C1-3alkoxy, —OH, —NO2, C1-3alkyl, —NH2, and —CO2—C1-3alkyl;
- E is a 5-membered heterocyclyl optionally substituted with one or more groups selected from halogen, C1-6alkyl, —C(═O)—O—C1-6alkyl, C6-10aryl, C6-10aryl-C1-4alkyl, and C6-10aryl-S(═O)2—;
- and
- D is a divalent group comprising a benzene ring.
5 more elements
A compound selected from:
- COMPOUND 12.1.1:
- N,N-Diethyl-2-{[2-(2-furylmethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl]methoxy}benzamide
- COMPOUND 12.1.2:
- 2-{[6,7-Dimethoxy-2-(thien-3-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]methoxy}-N,N-diethylbenzamide
- COMPOUND 12.1.3:
- N,N-Diethyl-3-{[2-(2-furylmethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl]methoxy}benzamide
- COMPOUND 12.1.4:
- 3-{[6,7-Dimethoxy-2-(thien-3-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]methoxy}-N,N-diethylbenzamide
- COMPOUND 12.1.5:
- N,N-Diethyl-4-{[2-(2-furylmethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl]methoxy}benzamide
- COMPOUND 12.1.6:
- 4-{[6,7-Dimethoxy-2-(thien-3-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]methoxy}-N,N-diethylbenzamide
- COMPOUND 12.1.7:
- 2-({6,7-Dimethoxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}methoxy)-N,N-diethylbenzamide
- COMPOUND 12.1.8:
- 4-({6,7-Dimethoxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}methyl)-N,N-diethylbenzamide
- COMPOUND 12.1.9:
- 4-{6,7-Dimethoxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.10:
- N,N-Diethyl-4-{6-methoxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.11:
- N,N-Diethyl-4-{7-methoxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.12:
- N,N-Diethyl-4-{2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.13:
- 4-{2-[(2-Butyl-1H-imidazol-5-yl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.14:
- 4-{2-[(2-Butyl-4-chloro-1H-imidazol-5-yl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.15:
- 4-{6,7-Dimethoxy-2-[(2-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.16:
- 4-{6,7-Dimethoxy-2-[(3-phenyl-1H-pyrazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.17:
- 4-(6,7-Dimethoxy-2-{[1-(phenylsulfonyl)-1H-pyrrol-2-yl]methyl}-1,2,3,4-tetrahydroisoquinolin-1-yl)-N,N-diethylbenzamide
- COMPOUND 12.1.18:
- N,N-Diethyl-4-{2-[(2-ethyl-4-methyl-1H-imidazol-5-yl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.19:
- 4-{6,7-Dimethoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.20:
- 4-{5,8-Dimethoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.21:
- N,N-Diethyl-4-[1,2,3,4-tetrahydro-6-methoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1-isoquinolinyl]-benzamide
- COMPOUND 12.1.22:
- N,N-Diethyl-4-[2-(1H-imidazol-5-ylmethyl)-6-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl]benzamide
- COMPOUND 12.1.23:
- N,N-Diethyl-4-[2-(1H-imidazol-5-ylmethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl]benzamide
- COMPOUND 12.1.24:
- 4-{6,7-Dimethoxy-2-[(5-phenyl-2-furyl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.25:
- N,N-Diethyl-4-{6-methoxy-2-[(5-phenyl-2-furyl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.26:
- N,N-Diethyl-4-{7-hydroxy-6-methoxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.27:
- N,N-Diethyl-4-{7-hydroxy-6-methoxy-2-[(2-phenyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.28:
- 4-{2-[(1-Benzyl-1H-imidazol-5-yl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.29:
- 4-{6,7-Dimethoxy-2-[(1-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.30:
- 4-{6,7-Dimethoxy-2-[(1-methyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.31:
- 4-({6,7-Dimethoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}methoxy)-N,N-diethylbenzamide
- COMPOUND 12.1.32:
- 4-({6,7-Dimethoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}methyl)-N,N-diethylbenzamide
- COMPOUND 12.1.33:
- 1-{4-[(Diethylamino)carbonyl]phenyl}-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-6-yl methanesulfonate
- COMPOUND 12.1.34:
- 1-{4-[(Diethylamino)carbonyl]phenyl}-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-6-yl methanesulfonate
- COMPOUND 12.1.35:
- 1-{4-[(Diethylamino)carbonyl]phenyl}-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-6-yl dimethylsulfamate
- COMPOUND 12.1.36:
- 1-{4-[(Diethylamino)carbonyl]phenyl}-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-6-yl dimethylsulfamate
- COMPOUND 12.1.37:
- 4-{2-[(2,5-Dimethyl-1,3-thiazol-4-yl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.38:
- 4-{6,7-Dimethoxy-2-[(2-phenyl-1,3-thiazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.39:
- N,N-Diethyl-4-{7-isopropoxy-6-methoxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.40:
- N,N-Diethyl-4-[6-methoxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-7-(2-morpholin-4-ylethoxy)-1,2,3,4-tetrahydroisoquinolin-1-yl]benzamide
- COMPOUND 12.1.41:
- 4-{7-Ethoxy-6-methoxy-2-[(2-phenyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.42:
- N,N-Diethyl-4-{7-isopropoxy-6-methoxy-2-[(2-phenyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.43:
- N,N-Diethyl-4-{6-methoxy-7-(2-morpholin-4-ylethoxy)-2-[(2-phenyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.44:
- N,N-Diethyl-4-{7-methoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.45:
- Methyl 5-{[1-{4-[(diethylamino)carbonyl]phenyl}-6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl]methyl}-1H-imidazole-4-carboxylate
- COMPOUND 12.1.46:
- 1-{4-[(Diethylamino)carbonyl]phenyl}-6-methoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl methanesulfonate
- COMPOUND 12.1.47:
- N,N-Diethyl-4-{6-[(4-methyl-1H-imidazol-5-yl)methyl]-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl}benzamide
- COMPOUND 12.1.48:
- N,N-Diethyl-4-{6-[(2-phenyl-1H-imidazol-5-yl)methyl]-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl}benzamide
- COMPOUND 12.1.49:
- 4-{6-Bromo-7-methoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.50:
- 4-{6-Bromo-7-methoxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.51:
- 4-{6,7-Dimethoxy-3-methyl-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.52:
- N,N-Diethyl-4-[2-(1H-imidazol-5-ylmethyl)-6,7-dimethoxy-3-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl]benzamide
- COMPOUND 12.1.53:
- N,N-Diethyl-4-{6-methoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-7-nitro-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.54:
- N,N-Diethyl-4-{6-methoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-5-nitro-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.55:
- N,N-Diethyl-4-{7-[(4-methyl-1H-imidazol-5-yl)methyl]-6,7,8,9-tetrahydro[1,3]dioxolo[4,5-f]isoquinolin-6-yl}benzamide
- COMPOUND 12.1.56:
- N,N-Diethyl-4-{7-[(2-phenyl-1H-imidazol-5-yl)methyl]-6,7,8,9-tetrahydro[1,3]dioxolo[4,5-f]isoquinolin-6-yl}benzamide
- COMPOUND 12.1.57:
- N,N-Diethyl-4-{5,6,7-trimethoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.58:
- N,N-Diethyl-4-{5,6,7-trimethoxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.59:
- 4-{7-(Cyclobutyloxy)-6-methoxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 12.1.60:
- N,N-Diethyl-4-[6-methoxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-7-(neopentyloxy)-1,2,3,4-tetrahydroisoquinolin-1-yl]benzamide
- COMPOUND 12.1.61:
- N,N-Diethyl-4-{6-fluoro-7-methoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.62:
- N,N-Diethyl-4-{6-fluoro-7-methoxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 12.1.63:
- 1-{4-[(Diethylamino)carbonyl]phenyl}-6-methoxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl dimethylsulfamate
- COMPOUND 13.1.1:
- N,N-Diethyl-4-[6-methoxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-7-(tetrahydro-2H-pyran-4-yloxy)-1,2,3,4-tetrahydroisoquinolin-1-yl]benzamide
- COMPOUND 14.1.1:
- N,N-Diethyl-4-{6-methoxy-7-phenoxy-2-[(2-phenyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 14.1.2:
- N,N-Diethyl-4-{6-methoxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-7-phenoxy-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 14.1.3:
- N,N-diethyl-4-{7-(4-fluorophenoxy)-6-methoxy-2-[(2-phenyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 14.1.4:
- N,N-Diethyl-4-{7-(4-fluorophenoxy)-6-methoxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 14.1.5:
- N,N-Diethyl-4-{6-methoxy-7-(4-methoxyphenoxy)-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 14.1.6:
- N,N-Diethyl-4-[6-methoxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-7-(pyridin-3-yloxy)-1,2,3,4-tetrahydroisoquinolin-1-yl]benzamide
- COMPOUND 15.1.1:
- 4-{7-(Benzyloxy)-6-methoxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 16.4.1:
- N,N-Diethyl-4-{6-methoxy-7-(3-methoxyphenoxy)-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 16.4.2:
- N,N-Diethyl-4-{6-methoxy-7-(4-methoxyphenoxy)-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 16.4.3:
- 1-{4-[(Diethylamino)carbonyl]phenyl}-6-methoxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl benzenesulfonate
- COMPOUND 17.1.1:
- 4-{6,7-Dihydroxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 17.1.2:
- N,N-Diethyl-4-{6-hydroxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 17.1.3:
- N,N-Diethyl-4-{7-hydroxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 17.1.4:
- N,N-Diethyl-4-[1,2,3,4-tetrahydro-6-hydroxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1-isoquinolinyl]-benzamide
- COMPOUND 17.1.5:
- N,N-Diethyl-4-{7-hydroxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 17.1.6:
- N,N-Diethyl-4-{6-hydroxy-7-phenoxy-2-[(2-phenyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 17.1.7:
- N,N-Diethyl-4-{6-hydroxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-7-phenoxy-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 17.1.8:
- N,N-Diethyl-4-{7-(4-fluorophenoxy)-6-hydroxy-2-[(2-phenyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 17.1.9:
- N,N-Diethyl-4-{7-(4-fluorophenoxy)-6-hydroxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 18.1.1:
- 4-{2-[(1,4-Dimethyl-1H-imidazol-5-yl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 18.1.2:
- 4-{2-[(1,5-Dimethyl-1H-imidazol-4-yl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 19.1.1:
- 4-{7-Ethoxy-6-methoxy-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 20.1.1:
- 4-{(1S)-6,7-Dimethoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 20.2.1:
- 4-{(1R)-6,7-Dimethoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}-N,N-diethylbenzamide
- COMPOUND 20.1.2:
- N,N-Diethyl-4-{(1S)-6-methoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 20.2.2:
- N,N-Diethyl-4-{(1R)-6-methoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 20.1.3:
- N,N-Diethyl-4-{(1S)-6-hydroxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 20.2.3:
- N,N-Diethyl-4-{(1R)-6-hydroxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 20.1.4:
- N,N-Diethyl-4-{(1S)-7-isopropoxy-6-methoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 20.2.4:
- N,N-Diethyl-4-{(1R)-7-isopropoxy-6-methoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 20.1.5:
- N,N-Diethyl-4-{(1S)-7-isopropoxy-6-methoxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 20.2.5:
- N,N-Diethyl-4-{(1R)-7-isopropoxy-6-methoxy-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 20.1.6:
- N,N-Diethyl-4-{(1S)-6-methoxy-7-(2-morpholin-4-ylethoxy)-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 20.2.6:
- N,N-Diethyl-4-{(1R)-6-methoxy-7-(2-morpholin-4-ylethoxy)-2-[(2-phenyl-1H-imidazol-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}benzamide
- COMPOUND 20.1.7:
- N,N-Diethyl-4-[(1S)-1,2,3,4-tetrahydro-6-methoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1-isoquinolinyl]-benzamide
- COMPOUND 20.2.7:
- N,N-Diethyl-4-[(1R)-1,2,3,4-tetrahydro-6-methoxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1-isoquinolinyl]-benzamide
- COMPOUND 20.1.8:
- N,N-Diethyl-4-[(1S)-1,2,3,4-tetrahydro-6-hydroxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1-isoquinolinyl]-benzamide
- COMPOUND 20.2.8:
- N,N-Diethyl-4-[(1R)-1,2,3,4-tetrahydro-6-hydroxy-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1-isoquinolinyl]-benzamide;
- and pharmaceutically acceptable salts thereof.
202 more elements
6-7. (canceled)
A process for preparing a compound of formula II,
- comprising of the step of reacting a compound of formula III with a compound of formula IV in the presence of HNR2R3:
- wherein
- R2 and R3 are independently selected from —H and C1-6alkyl;
- R5 and R6 are independently selected from —H, —OH, halogen, —NO2, C1-6alkyl, C6-10aryl, C1-6alkoxy, C3-6cycloalkoxy, C3-6heterocyclyl-oxy, C3-6heterocyclyl-C1-4alkoxy, C6-10aryl-oxy, C6-10aryl-C1-4alkoxy, C1-6alkyl-S(═O)2—O—, C6-10aryl-S(═O)2—O—, C1-6alkyl-NH—S(═O)2—O—, and (C1-6alkyl)2N—S(═O)2—O—;
- or R5 and R6 together form a portion of a 5 or 6-membered ring that fused with the benzene ring of formula I, wherein said C1-6alkyl, C6-10aryl, C1-6alkoxy, C3-6cycloalkoxy, C3-6heterocyclyl-oxy, C3-6heterocyclyl-C1-4alkoxy, C6-10aryl-oxy, C6-10aryl-C1-4alkoxy, C1-6alkyl-S(═O)2—O—, C6-10aryl-S(═O)2—O—, C1-6alkyl-NH—S(═O)2—O—, and (C1-6alkyl)2N—S(═O)2—O— are optionally substituted with one or more groups selected from halogen, C1-3alkoxy, —OH, —NO2, C1-3alkyl, —NH2, and —CO2—C1-3alkyl;
- and
- D is a divalent group comprising a benzene ring.
4 more elements
A process for preparing a compound of formula V,
- comprising of the step of reacting a compound of formula VI with a compound of formula VII in the presence of an acid catalyst:
- wherein
- X is selected from —CH(OEt)2, ═CHOMe and —CHO;
- R1 is selected from —H and C1-6alkyl;
- R2 and R3 are independently selected from —H and C1-6alkyl;
- R4, R5, R5 and R7 are independently selected from —H, —OH, halogen, —NO2, C1-6alkyl, C6-10aryl, C1-6alkoxy, C3-6cycloalkoxy, C3-6heterocyclyl-oxy, C3-6heterocyclyl-C1-4alkoxy, C6-10aryl-oxy, C6-10aryl-C1-4alkoxy, C1-6alkyl-S(═O)2—O—, C6-10aryl-S(═O)2—O—, C1-6alkyl-NH—S(═O)2—O—, and (C1-6alkyl)2N—S(═O)2—O—;
- or any two adjacent groups selected from R4, R5, R6 and R7 form a portion of a 5 or 6-membered ring that fused with the benzene ring of formula I, wherein said C1-6alkyl, C6-10aryl, C1-6alkoxy, C3-6cycloalkoxy, C3-6heterocyclyl-oxy, C3-6heterocyclyl-C1-4alkoxy, C6-10aryl-oxy, C6-10aryl-C1-4alkoxy, C1-6alkyl-S(═O)2—O—, C6-10aryl-S(═O)2—O—, C1-6alkyl-NH—S(═O)2—O—, and (C1-6alkyl)2N—S(═O)2—O— are optionally substituted with one or more groups selected from halogen, C1-3alkoxy, —OH, —NO2, C1-3alkyl, —NH2, and —CO2—C1-3alkyl;
- and
- D is a divalent group comprising a benzene ring.
6 more elements
A process for preparing a compound of formula I,
- comprising:
- reacting a compound of formula VIII with E-CHO:
- wherein
- Y is selected from —H and —C(═O)—O-t-butyl;
- R1 is selected from —H and C1-6alkyl;
- R2 and R3 are independently selected from —H and C1-6alkyl;
- R4, R5, R6 and R7 are independently selected from —H, —OH, halogen, —NO2, C1-6alkyl, C6-10aryl, C1-6alkoxy, C3-6cycloalkoxy, C3-6heterocyclyl-oxy, C3-6heterocyclyl-C1-4alkoxy, C6-10aryl-oxy, C6-10aryl-C1-4alkoxy, C1-6alkyl-S(═O)2—O—, C6-10aryl-S(═O)2—O—, C1-6alkyl-NH—S(═O)2—O—, and (C1-6alkyl)2N—S(═O)2—O—;
- or any two adjacent groups selected from R4, R5, R6 and R7 form a portion of a 5 or 6-membered ring that fused with the benzene ring of formula I, wherein said C1-6alkyl, C6-10aryl, C1-6alkoxy, C3-6cycloalkoxy, C3-6heterocyclyl-oxy, C3-6heterocyclyl-C1-4alkoxy, C6-10aryl-oxy, C6-10aryl-C1-4alkoxy, C1-6alkyl-S(═O)2—O—, C6-10aryl-S(═O)2—O—, C1-6alkyl-NH—S(═O)2—O—, and (C1-6alkyl)2N—S(═O)2—O— are optionally substituted with one or more groups selected from halogen, C1-3alkoxy, —OH, —NO2, C1-3alkyl, —NH2, and —CO2—C1-3alkyl;
- E is a 5-membered heterocyclyl optionally substituted with one or more groups selected from halogen, C1-6alkyl, —C(═O)—O—C1-6alkyl, C6-10aryl, C6-10aryl-C1-4alkyl, and C6-10aryl-S(═O)2—;
- and
- D is a divalent group comprising a benzene ring.
8 more elements
A process for preparing a compound of formula IX,
- comprising:
- reacting a compound of formula X with R12—OH or R12—B(OH)2:
- wherein
- Y is selected from —H and —C(═O)—O-t-butyl;
- R12 is selected from C1-6alkyl, C3-6cycloalkyl, C6-10aryl-C1-4alkyl, C3-6heterocyclyl-C1-4alkyl, C6-10aryl, and C3-6heteroaryl, wherein said C6-10aryl, C3-6heterocyclyl and C3-6heteroaryl are optionally substituted with one or more groups selected from halogen, C1-3alkoxy, —OH, —NO2, C1-3alkyl, —NH2 and —CO2—C1-3alkyl;
- and
- R1 is selected from —H and C1-6alkyl;
- R2 and R3 are independently selected from —H and C1-6alkyl;
- R4, R5, and R7 are independently selected from —H, —OH, halogen, —NO2, C1-6alkyl, C6-10aryl, C1-6alkoxy, C3-6cycloalkoxy, C3-6heterocyclyl-oxy, C3-6heterocyclyl-C1-4alkoxy, C6-10aryl-oxy, C6-10aryl-C1-4alkoxy, C1-6alkyl-S(═O)2—O—, C6-10aryl-S(═O)2—O—, C1-6alkyl-NH—S(═O)2—O—, and (C1-6alkyl)2N—S(═O)2—O—;
- or R4 and R5 together form a portion of a 5 or 6-membered ring that fused with the benzene ring of formula I, wherein said C1-6alkyl, C6-10aryl, C1-6alkoxy, C3-6cycloalkoxy, C3-6heterocyclyl-oxy, C3-6heterocyclyl-C1-4alkoxy, C6-10aryl-oxy, C6-10aryl-C1-4alkoxy, C1-6alkyl-S(═O)2—O—, C6-10aryl-S(═O)2—O—, C1-6alkyl-NH—S(═O)2—O—, and (C1-6alkyl)2N—S(═O)2—O— are optionally substituted with one or more groups selected from halogen, C1-3alkoxy, —OH, —NO2, C1-3alkyl, —NH2, and —CO2—C1-3alkyl;
- and
- D is a divalent group comprising a benzene ring.
9 more elements
A process for preparing a compound of formula XI,
- comprising:
- reacting a compound of formula XII with NsCl, NsBr, or (CF3CO)2O to protect the ═NH group of formula XI;
- reacting the protected compound with R14—Y1 followed by deprotecting the ═NH group:
- wherein
- n is 0, 1, 2 or 3;
- each R13 is independently selected from —H, —OH, halogen, —NO2, C1-6alkyl, C6-10aryl, C1-6alkoxy, C3-6cycloalkoxy, C3-6heterocyclyl-oxy, C3-6heterocyclyl-C1-4alkoxy, C6-10aryl-oxy, C6-10aryl-C1-4alkoxy, C1-6alkyl-S(═O)2—O—, C6-10aryl-S(═O)2—O—, C1-6alkyl-NH—S(═O)2—O—, and (C1-6alkyl)2N—S(═O)2—O—;
- or any two adjacent R13 form a portion of a 5 or 6-membered ring that fused with the benzene ring of formula I, wherein said C1-6alkyl, C6-10aryl, C1-6alkoxy, C3-6cycloalkoxy, C3-6heterocyclyl-oxy, C3-6heterocyclyl-C1-4alkoxy, C6-10aryl-oxy, C6-10aryl-C1-4alkoxy, C1-6alkyl-S(═O)2—O—, C6-10aryl-S(═O)2—O—, C1-6alkyl-NH—S(═O)2—O—, and (C1-6alkyl)2N—S(═O)2—O— are optionally substituted with one or more groups selected from halogen, C1-3alkoxy, —OH, —NO2, C1-3alkyl, —NH2, and —CO2—C1-3alkyl;
- Y1 is halogen;
- R14 is selected from C1-6alkyl-S(═O)2—, C6-10aryl-S(═O)2—, C1-6alkyl-NH—S(═O)2—, and (C1-6alkyl)2N—S(═O)2—;
- R1 is selected from —H and C1-6alkyl;
- R2 and R3 are independently selected from —H and C1-6alkyl;
- and
- D is a divalent group comprising a benzene ring.
10 more elements
Dependencies are inferred from the claim text.