	US 7,504,519 B2
	Derivatives of pyrazoline, procedure for obtaining them and use thereof as therapeutic agents
Rosa Cuberes Altisen, Sant Cugat Del Valles (Spain); Jorg Holenz, Vilanova I La Geltru (Spain); Mario Colombo Piñol, Barcelona (Spain); and Mercedes Port De Pol, Barcelona (Spain)
Assigned to Laboratorios Del Dr. Esteve, S.A., Barcelona (Spain)
Appl. No. 11/571,989 PCT Filed Sep. 22, 2004, PCT No. PCT/IB2004/051822 § 371(c)(1), (2), (4) Date Jan. 12, 2007, PCT Pub. No. WO2006/011005, PCT Pub. Date Feb. 02, 2006.
Claims priority of application No. 200401814 (ES), filed on Jul. 16, 2004.
Prior Publication US 2008/0021084 A1, Jan. 24, 2008
Int. Cl. C07D 231/06 (2006.01); C07D 231/00 (2006.01); A61K 31/41 (2006.01); A61K 31/415 (2006.01)

U.S. Cl. 548—379.1 [548/356.1; 514/359; 514/403; 514/406]

45 Claims

1. Pyrazoline derivative of general formula (I)

in which R and R¹are different from each other and are selected from a hydrogen or a

provided that when R¹is hydrogen and R is a

X¹is an alkyl substituted by at least one group selected from a halogen, a hydroxy, an amine, a carboxy, a carboxyalkyl, an acylamine, or a CONH₂; a cycloalkyl, optionally at least monosubstituted; a heterocycle; a —OX²; a

or a heteroaryl, optionally at least monosubstituted;

X²is an alkyl optionally substituted with one or more substituents selected independently from a halogen, a hydroxy, an alkoxyl, a cycloalkyl, optionally at least monosubstituted; a heterocycle; an aryl or a heteroaryl, optionally at least monosubstituted;

X³and X⁴are the same as or different from each other and are selected from a hydrogen; a halogen; an amine; a nitro; a cyano; an alkyl optionally substituted with one or more substituents selected independently from a halogen, a hydroxy or an alkoxyl; a —CO₂X⁵; a —COX⁶; a —SO₂X⁷; an aryl or an heteroaryl, optionally at least monosubstituted;

X⁵is a hydrogen or an alkyl, optionally substituted with one or more substitutents selected independently from a halogen, a hydroxy or an alkoxyl;

X⁶is an alkyl optionally substituted with one or more substituents selected independently from a halogen, a hydroxy or an alkoxyl; a cycloalkyl optionally at least monosubstituted; a heterocycle; an aryl or heteroaryl, optionally at least monosubstituted; and

X⁷is an alkyl; a cycloalkyl; an aryl; or a heteroaryl, optionally at least monosubstituted; and

provided that when R is hydrogen and R¹is a

X¹is an alkyl comprising at least two carbon atoms, optionally substituted with at least one group selected from a halogen, a hydroxy, an amine, a carboxy, a carboxyalkyl, an acylamine or a CONH₂; a cycloalkyl, optionally at least monosubstituted; a heterocycle; a —OX²; a

or a heteroaryl, optionally at least monosubstituted;

X², X³, X⁴, X⁵, X⁶and X⁷are defined above;

and a pharmaceutically acceptable salt thereof, a stereoisomer thereof; a racemate thereof, or a mixture thereof in any mixture ratio.