Trisubstituted carbocyclic cyclophilin binding compounds and their use
AssigneeGuilford Pharmaceuticals Inc.
InventorsYong-Qian Wu, Sergei Belyakov, Gregory S. Hamilton, David Limburg, Joseph P. Steiner, Mark Vaal, Ling Wei, Douglas Wilkinson
Life of this patent
Estimating the term…
Abstract
The present invention relates to novel, non-peptidic small organic compounds having an affinity for cyclophilin (CyP)-type immunophilin proteins, and to pharmaceutical compositions comprising one or more of the said compounds. The invention further relates to the uses of these compounds and compositions for binding CyP-type proteins, inhibiting their peptidyl-prolyl isomerase activity, and for research, development, and therapeutic applications in a variety of medical disorders.
Claims7
A compound of the following Formula I:
- and pharmaceutically acceptable derivatives thereof;
- where V is Q-substituted C1-C6 alkyl, or —(CH2)n—W;
- wherein W is Q, or —O—(CH2)m—Q;
- n and m are independently 0-4;
- Z is Q or S;
- and Q is a mono-, bi-, or tricyclic, carbocyclic ring which is saturated, partially saturated, or aromatic, and wherein the individual ring sizes are 5-6 members, and wherein Q is optionally substituted in one or several positions with:
- halo;
- hydroxyl;
- mercaptyl;
- nitro;
- trifluoromethyl;
- aminocarbonyl;
- arylaminocarbonyl in which the aryl is optionally halogenated and optionally substituted with trifluoromethyl or cyano;
- C1-C4 alkylsulfonyl;
- C1-C4 alklylthio;
- oxo;
- cyano;
- C1-C6 alkyl or alkenyl;
- C1-C5 alkoxycarbonyl;
- C1-C4 alkenyloxy;
- phenoxy;
- phenyl;
- cyanophenyl;
- benzyloxy;
- benzyl;
- amino;
- C1-C4 alkylamino;
- di-(C1-C4) alkylamino;
- C1-C4 alkylcarbamoyl;
- di(C1-C4)alkylcarbamoyl;
- or a combination thereof.
A compound of the following formula
- and pharmaceutically acceptable derivatives thereof;
- where V is —CH2—O—Q;
- Z is O or S;
- and Q is a mono-, bi-, or tricyclic, carbocyclic ring which is saturated, partially saturated, or aromatic, and wherein the individual ring sizes are 5-6 members, and wherein Q is optionally substituted in one or several positions with:
- halo;
- hydroxyl;
- mercaptyl;
- nitro;
- trifluoromethyl;
- aminocarbonyl;
- arylaminocarbonyl in which the aryl is optionally halogenated and optionally substituted with trifluoromethyl or cyano;
- C1-C4 alkylsulfonyl;
- C1-C4 alkylthio;
- oxo;
- cyano;
- carboxy;
- C1-C6 alkyl or alkenyl;
- C1-C4 alkoxy;
- C1-C5 alkoxycarbonyl;
- C1-C4 alkenyloxy;
- phenoxy;
- phenyl;
- cyanophenyl;
- benzyloxy;
- benzyl;
- amino;
- C1-C4 alkylamino;
- di-(C1-C4) alkylamino;
- C1-C4 alkylcarbamoyl;
- di(C1-C4)alkylcarbamoyl;
- or a combination thereof.
A compound selected from:
- 5-Naphthalen-1-yl-N,N′-bis-(3-trifluoromethyl-phenyl)isophthalamide;
- (5-(2-naphthyloxy)-3-{N-[3-(trifluoromethyl)phenyl]carbamoyl}phenyl)-N-[3-(trifluoromethyl)phenyl]formamide;
- (5-(2-naphthyl)-3-{N-[3-(trifluoromethyl)phenyl]carbamoyl}phenyl)-N-[3-(trifluoromethyl)phenyl]formamide;
- 1-[(3,4-dichlorophenyl)oxymethyl]-3,5-bis-[(3,5-dichlorophenyl) aminocarbonyl]benzene;
- 1-[4-(2-cyanophenyl)benzy]loxy-3,5-bis-[(3-cyanophenyl) aminocarbonyl]benzene;
- (5-(2-(2-5,6,7,8-tetrahydronaphthyl)ethyl)-3-{N-[3-(trifluoromethyl) phenyl]carbamoyl}phenyl)-N-[3-(trifluoromethyl)phenyl]formamide;
- (5-(2-(2-naphthyl)ethyl)-3-{N-[3-(trifluoromethyl)phenyl]carbamoyl}phenyl)-N-[3-(trifluoromethyl)phenyl]formamide;
- 1-(3,4-dichlorobenzyloxy)-3,5-bis-[(3,4,5-trichlorophenyl) aminocarbonyl]benzene;
- 3-{[(3-Trifluoromethyl-4-chlorophenyl)aminocarbonyl]benzyloxy}-1,5-bis-[(3-trifluoromethyl-4-chlorophenyl)aminocarbonyl]benzene;
- 3-{[(3,4-dichlorophenyl)aminocarbonyl]benzyloxy}-1,5-bis-[(3,4-dichloro-phenyl)aminocarbonyl]benzene;
- 1,3-Bis[(3-trifluoromethylphenyl)aminocarbonyl]-5-[(2-naphthyl) methyloxy]benzene;
- and
- 1,3-Bis-[3,4-dichlorophenyl)aminocarbonyl]-5-(benzyloxy)benzene.
Dependencies are inferred from the claim text.