IP Library › Granted Patent US 7,291,641

Granted Patent B2

US 7,291,641 · App. 10/915,001 · Granted Nov 6, 2007

Derivatives of heterocycles with 5 members, their preparation and their use as medicaments

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 7,291,641
App. No.: 10/915,001
Granted: Nov 6, 2007
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

Thiaxozle, oxazole, imidazole, isoxazole and isoxazoline compounds of the formula wherein Het is thiazole, oxazole, imidazole, isoxazole or isoxazoline, n is an integer from 0 to 6, A is selected from the various optionally substituted aromatic radicals defined in the specification, B is hydrogen, alkyl or phenyl, R 1 and R 2 are independently hydrogen, alkyl or cycloalkyl or R 1 and R 2 taken together with the carbon atom which carries them, form a carbocycle with 3 to 7 members and Ω is —NH 46 R 47 or —OR 48 , R 46 and R 47 are independently hydrogen, alkyl, cycloalkyl or —(CH 2 ) k COOR 51 , R 51 is alkyl or haloalkyl and R 48 is hydrogen or alkyl having advantageous pharmacological properties which allow their use in therapeutics, for treating neurodegenerative disorders or pain.

Claims (110)

1. A compound selected from the group consisting of a compound of the formula

in racemic, enantiomeric form or any combination of these forms wherein A is

Q is phenyl optionally substituted with at least one member selected from the group consisting of halogen, —OH, —CN, —NO 2 , alkyl and haloalkyl of 1 to 6 carbon atoms and alkoxy of 1 to 6 carbon atoms; R 19 , R 20 and R 21 are individually selected from the group consisting of hydrogen, halogen, alkyl of 1 to 6 carbon atoms and alkoxy of 1 to 6 carbon atoms; X is NR38; R 38 is hydrogen or alkyl of 1 to 6 carbon atoms; R 1 and R 2 are individually hydrogen or alkyl of 1 to 6 carbon atoms; B is hydrogen or alkyl of 1 to 6 carbon atoms; Ω is

R 46 and R 47 are individually selected from the group consisting of hydrogen, alkyl of 1 to 6 carbon atoms and —(CH 2 ) k —COOR 51 ; k and n are independently integers from 0 to 6; R 51 is hydrogen or alkyl of 1 to 8 carbon atoms or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , which is butyl 2-(4-[1,1′-biphenyl]-4-yl-1H-imidazol-2-yl)ethylcarbamate or a salt thereof.

3. The compound of claim 1 or its salt, which is selected from the group consisting of the following compounds:

butyl 2-(4-[1,1′-biphenyl]-4-yl-1H-imidazol-2-yl)ethylcarbamate;

4-[2-(2-{[butylamino)carbonyl]amino}ethyl)-1H-imidazol-4-yl]-1,1′-biphenyl;

(R,S)-4-(2-{1-[(tert-butoxycarbonyl)amino]pentyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

butyl (4-[1,1′-biphenyl]-4-yl-1H-imidazol-2-yl)methylcarbamate;

4-(2-{[(tert-butoxycarbonyl)amino]methyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{[(tert-butoxycarbonyl)amino]methyl}-1-methyl-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{[(tert-butoxycarbonyl)(methyl)amino]methyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{2-[(tert-butoxycarbonyl)amino]ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{3-[(tert-butoxycarbonyl)amino]propyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-[2-(2-{[(tert-butylamino)carbonyl]amino}ethyl)-1H-imidazol-4-yl]-1,1′-biphenyl;

(R,S)-4-(2-{1-[(tert-butoxycarbonyl)amino]heptyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{(1S)-1-[(tert-butoxycarbonyl)amino]propyl)-1H-imidazol-4-yl)-1,1′-biphenyl;

4-[2-(2-{[(neopentyloxy)carbonyl]amino}ethyl)-1H-imidazol-4-yl]-1,1′-biphenyl;

4-(2-{(1R)-1-[(tert-butoxycarbonyl)amino[butyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-(1-[(butoxycarbonyl)amino]-1-methylethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{2-[(isobutoxycarbonyl)amino]ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{(1S)-1-[(butoxycarbonyl)amino]ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{(1R)-1-[(butoxycarbonyl)amino]ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{2-[(methoxycarbonyl)amino]ethyl)-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{2-[(propoxycarbonyl)amino]ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-(2-[(ethoxycarbonyl)amino]ethyl)-1H-imidazol-4-yl)-1,1′-biphenyl;

hexyl 2-(4-[1,1′-biphenyl]-4-yl-1H-imidazol-2-yl)ethylcarbamate;

4-bromo-4′-(2-{2-[(butoxycarbonyl)amino]ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-[2-(2-{[(2-methoxyethoxy)carbonyl]amino}ethyl)-1H-imidazol-4-yl]-1,1′-biphenyl;

isobutyl 2-[4-(4′-bromo-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

4-methylpentyl 2-[4-(1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

isopentyl 2-[4-(1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

hexyl 2-[4-(4′-bromo-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

3,3-dimethylbutyl 2-[4-(1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

2-phenylethyl 2-[4-(1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(4′-fluoro-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(1,1′-biphenyl-4-yl)-5-methyl-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(4′-methyl-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(4′-chloro-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(2′-fluoro-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(2′,4′-difluoro-1,1-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(3′-chloro-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(3′-fluoro-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(3′-chloro-4′-fluoro-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(3′,4′-dichloro-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(4′-cyano-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-{4-[4′-(trifluoromethyl)-1,1′-biphenyl-4-yl]-1H-imidazol-2-yl}ethylcarbamate;

butyl 2-[4-(1,1′-biphenyl-4-yl)-5-ethyl-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(2′-chloro-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(2′,3′-difluoro-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(2′-bromo-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(3′,5′-difluoro-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(2′-methoxy-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(3′-nitro-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

butyl 2-[4-(2′,5′-difluoro-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate and

butyl 2-[4-(3′-methoxy-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate; and the salts thereof.

4. A pharmaceutical composition containing, as active principle, a compound of formula (I) G2 as defined in claim 1 , or a pharmaceutically acceptable salt of such a compound, and at least one pharmaceutically acceptable excipient.

5. The pharmaceutically composition of claim 4 wherein the active principle is selected from the group consisting of the following compounds:

butyl 2-(4-[1,1′-biphenyl]-4-yl-1H-imidazol-2-yl)ethylcarbamate;

4-[2-(2-{[butylamino)carbonyl]amino}ethyl)-1H-imidazol-4-yl]-1,1′-biphenyl;

(R,S)-4-(2-{1-(tert-butoxycarbonyl)amino]pentyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

butyl (4-[1,1′-biphenyl]-4-yl-1H-imidazol-2-yl)methylcarbamate;

4-(2-{[(tert-butoxycarbonyl)amino]methyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{[(tert-butoxycarbonyl)amino]methyl}-1-methyl-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{[(tert-butoxycarbonyl)(methyl)amino]methyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{2-[(tert-butoxycarbonyl)amino]ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{3-[(tert-butoxycarbonyl)amino]propyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-[2-(2-{[(tert-butylamino)carbonyl]amino}ethyl)-1H-imidazol-4-yl]-1,1′-biphenyl;

(R,S)-4-(2-(1-[(tert-butoxycarbonyl)amino]heptyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{(1S)-1-[(tert-butoxycarbonyl)amino]propyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-[2-(2-{[(neopentyloxy)carbonyl]amino}ethyl)-1H-imidazol-4-yl]-1,1′-biphenyl;

4-(2-{(1R)-1-[(tert-butoxycarbonyl)amino]butyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{1-[(butoxycarbonyl)amino]-1-methylethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{2-[(isobutoxycarbonyl)amino]ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{(1S)-1-[(butoxycarbonyl)amino]ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{(1R)-1-[(butoxycarbonyl)amino]ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{2-[(methoxycarbonyl)amino]ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{2-[(propoxycarbonyl)amino]ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{2-[(ethoxycarbonyl)amino]ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;