Phenyl-Guanidine Derivatives
AssigneesUniversidad Nacional De Quilmes, Chemo Research, S.L.
InventorsPablo Lorenzano Menna, Julieta Comín, Daniel Eduardo Gómez, Daniel Fernando Alonso
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Abstract
Provided herein are phenyl-guanidine derivatives for the inhibition of Rac1 which blocks its interaction with guanosine exchange factors (GEFs) belonging to the DBL family as agents for the treatment of aggressive and/or resistant tumours, as well as pharmaceutical compositions comprising them, their use in therapy and processes for their preparation.
Claims19
A method for treating a condition mediated by Rho-GTPase cell proteins in a human which comprises administering to said human an effective amount of a compound of formula (I):
- or a salt thereof, or any of its stereoisomeric forms or a mixture thereof wherein:
- R1 and R1′ are independently selected from the group consisting of H, (C1-C4)alkyl, CF3, F, Cl, Br, I, —CN, OH, NH2, —OCH3, and NO2;
- with the proviso that at least one of R1 and R1′ is other than H;
- A is a radical selected from linear or branched (C1-C6)alkyl or one of the known carbocyclic or heterocyclic ring systems with 1-2 rings, wherein each of the rings forming the ring system:
- has 5-7 members, each member independently selected from C, N, O, S, CH, CH2, NH;
- and
- is saturated, partially unsaturated or aromatic;
- wherein A is substituted by one or more radicals selected from the group consisting of H, halogen, nitro, cyano, linear or branched (C1-C6)alkyl, halo-(C1-C6)alkyl, linear or branched
- (C2-C6)alkenyl, —OR2, —COR2, —COOR2, —OC(O)R2, —C(O)NR3R4, —NR3R4, —R5NHR6, —SR2, —SO—R2, —SO2—R2, and —SO2NR3R4;
- wherein
- each R2 independently represents H or linear or branched (C1-C4)alkyl,
- each R3 independently represents H or linear or branched (C1-C4)alkyl,
- each R4 independently represents H, linear or branched (C1-C6)alkyl, phenyl, pyridine or quinoline;
- wherein the phenyl, pyridine and quinoline ring system is substituted by one or more radical selected from H, linear or branched (C1-C4)alkyl, and NH2;
- R5 and R6 are independently selected from H, linear or branched (C1-C4)alkyl,
- together with pharmaceutical excipients or carriers.
A compound of formula (II)
- or a salt thereof, or any of its stereoisomeric forms or a mixture thereof wherein:
- A is a radical of one of the known carbocyclic or heterocyclic ring systems with 1-2 rings,
- wherein each of the rings forming the ring system
- has 5-7 members, each member independently selected from C, N, O, S, CH, CH2, NH;
- is saturated, partially unsaturated or aromatic;
- wherein A is substituted by one or more radicals selected from the group consisting of H, F, Cl, Br, I, nitro, cyano, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, —CF3, —CH2CF3, linear or branched (C2-C6)alkenyl, —OH, —OCH3, —OCH2CH3, —COH, —COCH3, —COOH, —COOCH3, —COOCH2CH3, —OC(O)H, —OC(O)CH3, —C(O)NH2, —NH2, —NHCH3, —N(CH3)2, —CH2NH2, —CH2NHCH3, —SH2, —SO—CH3, —SO2—CH3, —SO2NH2, —SO2NHCH3, —SO2NHCH2CH3, —SO2N(CH3)2, —SO2N(CH2CH3)2, —SO2N(CH2CH2CH3)2, —SO2N(CH2CH2CH2CH3)2 and —SO2N(CH2CH2(CH3)2)2;
- with the proviso that the compound is other than N-(4-methyl-6-hydroxy-pyrimidin-2-yl)-N′-(2-trifluoromethylphenyl)guanidine, N-[4,6-bis(methyl)pyrimidin-2-yl]-N′-[2-(trifluoromethyl)phenyl]guanidine or N-[(4-methyl)pyrimidin-2-yl]-N′-[2-(trifluoromethyl)phenyl]guanidine.
Dependencies are inferred from the claim text.