Back to results
US 2002/0161012 A1Published application
Isoxazolecarboxamide derivatives
AssigneeRecordati S.A., Chemical and Pharmaceutical Company
InventorsAmedeo Leonardi, Gianni Motta, Carlo Riva, Elena Poggesi
Life of this patent
Estimating the term…
Abstract
The invention relates to novel N-(substituted phenyl)-N′-[(ω-(3-substituted phenyl-4-isoxazolecarbonylamino)alkyl]piperazines, their N-oxides, and pharmaceutically acceptable salts thereof. The compounds are endowed with enhanced selectivity for alpha1-adrenergic receptors and a low activity in lowering blood pressure. The compounds are useful in the treatment of obstructive syndromes of the lower urinary tract, including benign prostatic hyperplasia (BPH), and in the treatment of lower urinary tract symptoms (LUTS) and neurogenic lower urinary tract dysfunction (NLUTD), and other conditions. The compounds may be administered alone or in combination with an anticholinergic compound.
Claims64
A compound having the formula:
- 5
- wherein
- R is selected from the group consisting of alkyl, alkoxy, polyfluoroalkoxy, hydroxy and trifluoromethanesulfonyloxy group,
- each of R1 and R2 is independently selected from the group consisting of hydrogen, halogen, polyfluoroalkoxy and alkoxy group,
- R3 is one or more substituents selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, nitro, amino, acylamino, cyano, alkoxycarbonyl, and carboxamido group,
- R4 represents a hydrogen atom or an alkyl or arylalkyl group, and
- n is 0, 1 or 2, or
- an N-oxide thereof or a pharmaceutically acceptable salt of any of the foregoing.
5 more elements
A compound selected from the group consisting of
- N-{3-[4-(5-Chloro-2-methoxyphenyl)-1-piperazinyl]propyl}-5-methyl-3-phenylisoxazole-4-carboxamide,
- N-{3-[4-(5-Chloro-2-hydroxyphenyl)-1-piperazinyl]propyl}-5-methyl-3-phenylisoxazole-4-carboxamide,
- 5-Methyl-3-phenyl-N-{3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]-propyl}isoxazole-4-carboxamide,
- N-{3-[4-[2-Methoxy-5-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}-5-methyl-3-phenylisoxazole-4-carboxamide,
- N-{3-[4-[5-Fluoro-2(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}-5-methyl-3-phenylisoxazole-4-carboxamide,
- N-{3-[4-[4-Fluoro-2(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}-5-methyl-3-phenylisoxazole-4-carboxamide,
- N-{3-[4-(5-Chloro-2-trifluoromethanesulphonyloxy)-1-piperazinyl]propyl}-5-methyl-3-phenylisoxazole-4-carboxamide,
- 3- (4-Fluorophenyl)-N-{3-[4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}isoxazole-4-carboxamide,
- 3-(2-Chloro-6-fluorophenyl)-N-{3-[4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}-5-methylisoxazole-4-carboxamide,
- 3-(2,6-Dichlorophenyl)-N-{3-[4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}-5-methylisoxazole-4-carboxamide,
- 3-(2-Chlorophenyl)-N-{3-[4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}-5-methylisoxazole-4-carboxamide,
- 3-(2-Chloro-6-fluorophenyl)-5-methyl-N-{3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}isoxazole-4-carboxamide,
- 3-(2-Chlorophenyl)-5-methyl-N-{3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}isoxazole-4-carboxamide,
- 3-(2,6-Dichlorophenyl)-5-methyl-N-{3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}isoxazole-4-carboxamide,
- N-{3-[4-[4-Fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}-3-phenyl-isoxazole-4-carboxamide,
- 3-(4-Fluorophenyl)-N-{3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}isoxazole-4-carboxamide,
- 3-Phenyl-N-{3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}isoxazole-4-carboxamide,
- 3-(4-Fluorophenyl)-N-{3-[4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}-5-methylisoxazole-4-carboxamide,
- 5-Ethyl-3-phenyl-N-{3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}isoxazole-4-carboxamide,
- 5-Ethyl-N-{3-[4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}-3-phenylisoxazole-4-carboxamide,
- 3-(4-Fluorophenyl)-5-methyl-N-{3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}isoxazole-4-carboxamide,
- 3-(2-Fluorophenyl)-N-{3-[4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}-5-methylisoxazole-4-carboxamide,
- 3-(2-Fluorophenyl)-5-methyl-N-{3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}isoxazole-4-carboxamide,
- 3-(3-Fluorophenyl)-N-{3-[4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}-5-methylisoxazole-4-carboxamide,
- 3-(3-Fluorophenyl)-5-methyl-N-{3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}isoxazole-4-carboxamide,
- 3-4(-Methoxyphenyl)-5-methyl-N-[3-[4-[2-(2,2,2-trifluoroethoxy) phenyl]-1 piperazinyl]propyl]isoxazole-4-carboxamide,
- N-{3-[4-[4-Fluoro-2-(2,2,2-trifluoroethoxy)phenyl}-1-piperazinyl]propyl]-3-(4-methoxyphenyl)-5-methylisoxazole-4-carboxamide,
- N-{3-[4-4-Fluoro-2(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}-3-phenyl-5-(2-phenylethyl)isoxazole-4-carboxamide,
- N-{3-[4-[4-Fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl]propyl}-3-phenyl-5-(3-phenylpropyl)isoxazole-4-carboxamide,
- N-{3-[4-[4-Fluoro-2-methoxyphenyl]-1-piperazinyl]propyl}-5-methyl-3-phenylisoxazole-4-carboxamide,
- N-{3-[4-(4-Fluoro-2-methylphenyl)-1-piperazinyl]propyl}-5-methyl-3-phenylisoxazole-4-carboxamide,
- N-{3-[4-(4-Chloro-2-methylphenyl)-1-piperazinyl]propyl}-5-methyl-3-phenylisoxazole-4-carboxamide,
- N-{3-[4-[4-Fluoro-2-(1 methylethoxy)phenyl]-1-piperazinyl]propyl}-5-methyl-3-phenylisoxazole-4-carboxamide,
- N-[3-[4-(4-Chloro-2-methoxyphenyl)-1-piperazinyl]propyl]-5-methyl-3-phenylisoxazole-4-carboxamide,
- N-[3-[4-[4-Chloro-2-(2-methylethoxy)phenyl]-1-piperazinyl]propyl]-5-methyl-3-phenylisoxazole-4-carboxamide, and
- N-[3-[4-(2-Ethoxy-4-fluoro)-1-piperazinyl]propyl]-5-methyl-3-phenylisoxazole-4-carboxamide,
- or an N-oxide or a pharmaceutically acceptable salt of any of the foregoing compound.
34 more elements
Dependencies are inferred from the claim text.