Back to results
US 2021/0332007 A1Published application
Diarylureas as cb1 allosteric modulators
AssigneeResearch Triangle Institute
InventorsYanan ZHANG, Thuy NGUYEN, Nadezhda GERMAN
Life of this patent
Estimating the term…
Abstract
The present invention provides novel diarylurea derivatives (compounds of formula (I)) and their uses. The compounds of the present invention are demonstrated to be allosteric modulators of the CB1 receptor, and therefore useful for the treatment of diseases and conditions mediated by CB1.
Claims29
A compound of Formula (I):
- wherein:
- R1 is O—(C1-6 alkyl), O-(5- to 13-membered cycloalkyl), N(R2)2, (C1-8 alkyl)x-(5- to 13-membered aryl), (C1-8 alkyl)x-(5- to 13-membered heteroaryl), or (C18alkyl)x-(4- to 13-membered heterocyclyl), wherein each of aryl heteroaryl, and heterocyclyl is optionally substituted with one or more of:
- R2,
- OR2,
- C(O)R2,
- C(O)OR2,
- NO2,
- halogen, or
- C1-6 haloalkyl;
- R2 is H, C1-6 alkyl C1-6 alkenyl, C1-6 alkynyl, or 5- to 13-membered aryl;
- R3 is H, C1-6 alkyl, C1-6 alkenyl, C1-6 alkynyl, halogen, C1-6 haloalkyl, NO2, or CN;
- each x is independently 0 or 1;
- and
- n is 1, 2, or 3;
- or a pharmaceutically acceptable salt or solvate thereof.
12 more elements
A compound selected from the group consisting of:
- 3-(4-Chlorophenyl)-1-[3-(6-methoxypyridin-2-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(4-methylpyridin-2-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(2-methoxypyridin-4-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(pyridin-2-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(pyridin-3-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(pyridin-4-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(pyrimidin-5-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-(3-phenylphenyl)urea;
- 3-(4-Chlorophenyl)-1-[3-(3-methoxyphenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(3-hydroxyphenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(3-isopropylphenyl)phenyl]urea;
- 1-[3-(2H-1,3-Benzodioxo1-5-yl)phenyl]-3-(4-chlorophenyl)urea;
- 3-(4-Chlorophenyl)-1-[3-(3-methylphenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(2-methylphenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(3-nitrophenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(4-chlorophenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(3,5-dichlorophenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(3,4-dichlorophenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(2,6-dichlorophenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(4-fluorophenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(2,4-difluorophenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(4-tert-butylphenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(3,5-di-tert-butylphenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(3-phenylphenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(4-phenylphenyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(4-benzoylphenyl)phenyl]urea;
- 1-[3-(1-Benzofuran-5-yl)phenyl]-3-(4-chlorophenyl)urea;
- 3-(4-Chlorophenyl)-1-[3-(naphthalen-2-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(quinolin-2-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(quinolin-3-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(9H-fluoren-2-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(furan-3-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(thiophen-3-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(thiophen-2-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(5-methylthiophen-3-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(5-methylthiophen-2-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(1,3-thiazol-5-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(1,3-thiazol-4-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(1,3-thiazol-2-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-{4-[6-(pyrrolidin-1-yl)pyridin-2-yl]phenyl}urea;
- 3-(4-Chlorophenyl)-1-(4-phenylphenyl)urea;
- tert-Butyl 2-[3-({1-[(4-chlorophenyl)amino]ethenyl}amino)phenyl]-1H-pyrrole-1-carboxylate;
- 3-(4-Chlorophenyl)-1-[3-(1H-pyrrol-2-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(1-methyl-1H-pyrrol-2-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(1H-imidazol-2-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(piperidin-1-yl)phenyl]urea;
- 1-(4-Chlorophenyl)-3-[3-(morpholin-4-yl)phenyl]urea;
- 1-(4-Chlorophenyl)-3-[3-(pyrrolidin-1-yl)phenyl]urea;
- 1-(4-Chlorophenyl)-3-[3-(4-methylpiperazin-1-yl)phenyl]urea;
- 3-[3-(Azetidin-1-yl)phenyl]-1-(4-chlorophenyl)urea;
- 3-(4-Chlorophenyl)-1-[3-(4,4-difluoropiperidin-1-yl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-{3-[(1S,4S)-7-azabicyclo[2.2.1]heptan-7-yl]phenyl}urea;
- 1-[3-(Azepan-1-yl)phenyl]-3-(4-chlorophenyl)urea;
- 3-(4-Chlorophenyl)-1-(3-{2-oxa-6-azaspiro[3.3]heptan-6-yl}phenyl)urea;
- 1-(4-Chlorophenyl)-3-[3-(dimethylamino)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(diethylamino)phenyl]urea;
- 3-(4-Chlorophenyl)-1-[3-(pyrrolidin-1-ylmethyl)phenyl]urea;
- 3-(4-Chlorophenyl)-1-(3-methoxyphenyl)urea;
- and
- 3-(4-Chlorophenyl)-1-[3-(cyclopentyloxy)phenyl]urea,
- and pharmaceutically acceptable salts or solvates thereof.
58 more elements
Dependencies are inferred from the claim text.