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US 2006/0079555 A1Published application
Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof
AssigneeAstraZeneca AB
InventorsWilliam Brown, Andrew Griffin
Life of this patent
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Abstract
Compounds of general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, m and n 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.
Claims18
A compound of formula I, a pharmaceutically acceptable salt thereof, diasteromers, enantiomers, or mixtures thereof:
- wherein
- R1 is hydrogen, C1-6alkyl-O—C(═O)—, C1-6alkyl, substituted C1-6alkyl, C3-6cycloalkyl, and substituted C3-6cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl;
- n is 0, 1 or 2;
- m is 0, 1, or 2;
- R2, R3 and R4 are, independently, selected from hydrogen, C1-6alkyl, substituted C1-6alkyl, C3-6cycloalkyl, and substituted C3-6cycloalkyl;
- R5 and R6 are, independently, selected from —R, —NO2, —OR, —Cl, —Br, —I, —F, —CF3, —C(═O)R, —C(═O)OH, —NH2, —SH, —NHR, —NR2, —SR, —SO3H, —SO2R, —S(═O)R, —CN, —OH, —C(═O)OR, —C(═O)NR2, —NRC(═O)R, and —NRC(═O)—OR, wherein R is, independently, a hydrogen or C1-6alkyl;
- and
- R7 is selected from C1-6alkyl, substituted C1-6alkyl, C3-6cycloalkyl, and substituted C3-6cycloalkyl, optionally substituted C6-10aryl, optionally substituted C3-9heteroaryl, optionally substituted C6-10aryl-C1-6alkyl, and optionally substituted C3-9heteroaryl-C1-6alkyl;
- or R4 and R7 together with nitrogen connected thereto form a portion of a C3-6heterocycle ring.
6 more elements
A compound selected from:
- 4-[[3-(anilinocarbonyl)phenyl](piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- 4-[{3-[(benzylamino)carbonyl]phenyl}(piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- 4-[(3-{[(2-phenethyl)amino]carbonyl}phenyl)(piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- and pharmaceutically acceptable salts thereof.
1 more element
(canceled)
A process for preparing a compound of formula I, comprising:
- reacting a compound of formula II with HNR4R7:
- wherein
- R1 is hydrogen, C1-6alkyl-O—C(═O)—, C1-6alkyl, substituted C1-6alkyl, C3-6cycloalkyl, and substituted C3-6cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl;
- n is 0, 1 or 2;
- m is 0, 1, or 2;
- X is selected from —OH, —OR8, —O—C(═O)—R8, —Cl, —Br and —I, wherein R8 is C1-6alkyl;
- R2, R3 and R4 are, independently, selected from hydrogen, C1-6alkyl, substituted C1-6alkyl, C3-6cycloalkyl, and substituted C3-6cycloalkyl;
- R5 and R6 are, independently, selected from —R, —NO2, —OR, —Cl, —Br, —I, —F, —CF3, —C(═O)R, —C(═O)OH, —NH2, —SH, —NHR, —NR2, —SR, —SO3H, —SO2R, —S(═O)R, —CN, —OH, —C(═O)OR, —C(═O)NR2, —NRC(═O)R, and —NRC(═O)—OR, wherein R is, independently, a hydrogen or C1-6alkyl;
- and
- R7 is C1-6alkyl, substituted C1-6alkyl, C3-6cycloalkyl, and substituted C3-6cycloalkyl, optionally substituted C6-10aryl, optionally substituted C3-9heteroaryl, optionally substituted C6-10aryl-C1-6alkyl, and optionally substituted C3-9heteroaryl-C1-6alkyl;
- or R4 and R7 together with nitrogen connected thereto form a portion of a C3-6heterocycle ring.
8 more elements
A compound of formula IA, a pharmaceutically acceptable salt thereof, diastereomers thereof, enantiomers thereof, or mixtures thereof:
- wherein
- R1 is selected from hydrogen, and C1-6alkyl-O—C(═O)—;
- R4 is selected from hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-6cycloalkyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-6cycloalkyl are optionally substituted with one or more groups selected from —R, —NO2, —OR, —Cl, —Br, —I, —F, —CF3, —C(═O)R, —C(═O)OH, —NH2, —SH, —NHR, —NR2, —SR, —SO3H, —SO2R, —S(═O)R, —CN, —OH, —C(═O)OR, —C(═O)NR2, —NRC(═O)R, and —NRC(═O)—OR, wherein R is, independently, a hydrogen or C1-6alkyl;
- R7 is selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-3alkyl, C6-10aryl, C6-10aryl-C1-3alkyl, C3-6heteroaryl, and C3-6heteroaryl-C1-3alkyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-3alkyl, C6-10aryl, C6-10aryl-C1-3alkyl, C3-6heteroaryl, and C3-6heteroaryl-C1-3alkyl are optionally substituted with one or more groups selected from —R, —NO2, —OR, —Cl, —Br, —I, —F, —CF3, —C(═O)R, —C(═O)OH, —NH2, —SH, —NHR, —NR2, —SR, —SO3H, —SO2R, —S(═O)R, —CN, —OH, —C(═O)OR, —C(═O)NR2, —NRC(═O)R, and —NRC(═O)—OR, wherein R is, independently, a hydrogen or C1-6alkyl;
- or R4 and R7 together with nitrogen connected thereto form a portion of a C3-6heterocycle ring.
2 more elements
A compound selected from:
- COMPOUND 1:
- 4-[[3-(anilinocarbonyl)phenyl](piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- COMPOUND 2:
- 4-[{3-[(benzylamino)carbonyl]phenyl}(piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- COMPOUND 3:
- 4-[(3-{[(2-phenylethyl)amino]carbonyl}phenyl)(piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- COMPOUND 4:
- 4-[{3-[(cyclopentylamino)carbonyl]phenyl}piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- COMPOUND 5:
- 4-[{3-[(cyclohexylamino)carbonyl]phenyl}(piperidin-4-ylidene)methyl]benzoic acid;
- COMPOUND 6:
- 4-[[3-(cyclohexylacetyl)phenyl](piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- COMPOUND 7:
- 4-[(3-{[(2-chlorobenzyl)amino]carbonyl}phenyl)(piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- COMPOUND 8:
- 4-[(3-{[(2-fluorobenzyl)amino]carbonyl}phenyl)(piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- COMPOUND 9:
- 4-[[3-({[(1R)-1-(4-methylphenyl)ethyl]amino}carbonyl)phenyl](piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- COMPOUND 10:
- 4-[(3-{[(4-methyl-1,3-thiazol-2-yl)amino]carbonyl}phenyl)(piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- COMPOUND 11:
- 4-[(3-{[(2,6-dimethylpyridin-3-yl)amino]carbonyl}phenyl)(piperidin-4-ylidene)-N,N-diethylbenzamide;
- COMPOUND 12:
- 4-[{3-[(isobutylamino)carbonyl]phenyl}(piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- COMPOUND 13:
- 4-[(3-{[(1-ethylpropyl)amino]carbonyl}phenyl)(piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- COMPOUND 14:
- 4-[(3-{[methyl(2-phenylethyl)amino]carbonyl}phenyl)(piperidin-4-ylidene)methyl]-N,N-diethylbenzamide;
- COMPOUND 15:
- N,N-diethyl-4-[[3-(piperidin-1-ylcarbonyl)phenyl](piperidin-4-ylidene)methyl]benzamide;
- COMPOUND 16:
- N,N-diethyl-4-{piperidin-4-ylidene[3-(pyrrolidin-1-ylcarbonyl)phenyl]methyl}benzamide;
- and pharmaceutically acceptable salts thereof.
30 more elements
Dependencies are inferred from the claim text.