Patent ID: 6603005
Filing Date: 2003-08-05
Classification: C07D

Abstract:
A compound of general formula (I): wherein:X1 is >Câ€”Râ€²1; X2 is >Câ€”Râ€²2; X3 is >Câ€”Râ€²3; X4 is >Câ€”Râ€²4; X5 is >Câ€”Râ€²5; and, optionally, one of X1, X2, X3, X4, and X5 is a nitrogen atom; R1, Râ€²1, Râ€²2, Râ€²3, Râ€²4, and Râ€²5 are identical or different, and each independently is: a hydrogen or halogen atom or an alkyl, cycloalkyl, phenyl, phenylthio, mono- or bicyclic aromatic heterocyclyl or heterocyclylthio, hydroxyl, alkyloxy, trifluoromethoxy, alkylthio, trifluoromethylthio, cycloalkyloxy, cycloalkylthio cyano, carboxyl, alkyloxycarbonyl, cycloalkyloxycarbonyl, â€”NRaRb or â€”CONRaRb radical for which Ra and Rb are independently hydrogen, alkyl, cycloalkyl, phenyl, mono- or bicyclic aromatic heterocyclyl, or Ra and Rb form, together with the nitrogen atom to which they are attached, a 5- or 6-membered heterocycle which can optionally contain an additional heteroatom chosen from O, S and N and, when the additional heteroatom is N, the additional heteroatom optionally is substituted with an alkyl, phenyl or mono- or bicyclic aromatic heterocyclyl substituent and, when the additional heteroatom is S, the additional heteroatom optionally is sulfinyl or sulfonyl, or a methylene radical substituted with fluoro, hydroxyl, alkyloxy, alkylthio, cycloalkyloxy, cycloalkylthio, phenyl, mono- or bicyclic aromatic heterocyclyl, carboxyl, alkyloxycarbonyl, cycloalkyloxycarbonyl, â€”NRaRb or â€”CONRaRb for which Ra and Rb are defined as above, and are additionally chosen from phenoxy, heterocyclyloxy, benzyloxy, and heterocyclylmethyloxy, and, optionally, R1 is difluoromethoxy, or a radical of structure â€”CmF2m+1, â€”SCmF2m+1, or â€”OCmF2m+1 wherein m is an integer from 1 to 6; and, optionally, Râ€²5 is trifluoroacetyl; R2 is: carboxyl, alkyloxycarbonyl, cycloalkyloxycarbonyl, cyano, â€”CONRaRb, wherein Ra and Rb are, independently, hydrogen, alkyl, cycloalkyl, phenyl, mono- or bicyclic aromatic heterocyclyl, and optionally, one of Ra and Rb is hydroxyl, alkyloxy, or cycloalkyloxy, or Ra and Rb form, together with the nitrogen atom to which they are attached, a 5- or 6-membered heterocycle which can optionally contain an additional heteroatom chosen from O, S and N and, when the additional heteroatom is N, the additional heteroatom optionally is substituted with an alkyl, phenyl or mono- or bicyclic aromatic heterocyclyl substituent and, when the additional heteroatom is S, the additional heteroatom optionally is sulfinyl or sulfonyl; or R2 is hydroxymethyl, alkyl containing 1 or 2 carbon atoms substituted with carboxyl, alkyloxycarbonyl, cycloalkyloxycarbonyl, cyano, or â€”CONRaRb, wherein Ra and Rb are, independently, hydrogen, alkyl, cycloalkyl, phenyl, mono- or bicyclic aromatic heterocyclyl, and optionally one of Ra and Rb is hydroxyl, alkyloxy, or cycloalkyloxy, or Ra and Rb form, together with the nitrogen atom to which they are attached, a 5- or 6-membered heterocycle which can optionally contain an additional heteroatom chosen from O, S and N and, when the additional heteroatom is N, the additional heteroatom optionally is substituted with an alkyl, phenyl or mono- or bicyclic aromatic heterocyclyl substituent, and, when the additional heteroatom is S, the additional heteroatom optionally is sulfinyl or sulfonyl; or R2 is â€”CF2â€”Rc, â€”C(CH3)2â€”Rc, â€”COâ€”Rc, â€”CHOHâ€”Rc, â€”C(cycloalkyl)-Rc, or â€”CH&boxH;CHâ€”Rc, wherein Rc is carboxyl, alkyloxycarbonyl, cycloalkyloxycarbonyl, or â€”CONRaRb wherein Ra and Rb are, independently, hydrogen, alkyl, cycloalkyl, phenyl, mono- or bicyclic aromatic heterocyclyl, and optionally one of Ra and Rb is hydroxyl, alkyloxy, or cycloalkyloxy, or Ra and Rb form, together with the nitrogen atom to which they are attached, a 5- or 6-membered heterocycle which can optionally contain an additional heteroatom chosen from O, S and N and, when the additional heteroatom is N, the additional heteroatom optionally is substituted with an alkyl, phenyl or mono- or bicyclic aromatic heterocyclyl substituent, and, when the additional heteroatom is S, the additional heteroatom optionally is sulfinyl or sulfonyl; R3 is a phenyl, mono- or bicyclic aromatic heterocyclyl or alk-RÂ°3 radical, wherein alk is an alkyl radical, and RÂ°3 is hydrogen, halogen, hydroxyl, alkyloxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, cycloalkyl, cycloalkyloxy, cycloalkylthio, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylamino, N-cycloalkyl-N-alkylamino, â€”N-(cycloalkyl)2, acyl, cycloalkylcarbonyl, phenyl, phenoxy, phenylthio, phenylsulfinyl, phenylsulfonyl, phenylamino, N-alkyl-N-phenylamino, N-cycloalkyl-N-phenylamino, â€”N-(phenyl)2, phenylalkyloxy, phenylalkylthio, phenylalkylsulfinyl, phenylalkylsulfonyl, phenylalkylamino, N-alkyl-N-phenylaminoalkyl, N-cycloalkyl-N-phenylalkylamino, benzoyl, mono- or bicyclic aromatic heterocyclyl, heterocyclyloxy, heterocyclylthio, heterocyclylsulfinyl, heterocyclylsulfonyl, heterocyclylamino, N-alkyl-N-heterocyclylamino, N-cycloalkyl-N-heterocyclylamino, heterocyclylcarbonyl, heterocyclylalkyloxy, heterocyclylalkylthio, heterocyclylalkylsulfinyl, heterocyclylalkylsulfonyl, heterocyclylalkylamino, N-alkyl-N-heterocyclylaminoalkyl, N-cycloalkyl-N-heterocyclylaminoalkyl, carboxyl, alkyloxycarbonyl, â€”NRaRb, or â€”COâ€”NRaRb, wherein Ra and Rb are, independently, hydrogen, alkyl, cycloalkyl, phenyl, mono- or bicyclic aromatic heterocyclyl, and optionally one of Ra and Rb is hydroxyl, alkyloxy, or cycloalkyloxy, or Ra and Rb form, together with the nitrogen atom to which they are attached, a 5- or 6-membered heterocycle which can optionally contain an additional heteroatom chosen from O, S and N and, when the additional heteroatom is N, the additional heteroatom optionally is substituted with an alkyl, phenyl or mono- or bicyclic aromatic heterocyclyl substituent, and, when the additional heteroatom is S, the additional heteroatom optionally is sulfinyl or sulfonyl, and wherein any heterocyclyl mentioned above is mono- or bicyclic aromatic; or alternatively RÂ°3 is â€”CRâ€²b=CRâ€²c-Râ€²a, wherein Râ€²a is phenyl, phenylalkyl, heterocyclyl, heterocyclylalkyl, phenoxyalkyl, phenylthioalkyl, phenylsulfinylalkyl, phenylsulfonylalkyl, phenylaminoalkyl, N-alkyl-N-phenylaminoalkyl, heterocyclyloxyalkyl, heterocyclylthioalkyl, heterocyclylsulfinylalkyl, heterocyclyl-sulfonylalkyl, heterocyclylaminoalkyl, N-alkyl-N-heterocyclylaminoalkyl, heterocyclylthio, heterocyclylsulfinyl, heterocyclylsulfonyl, phenylthio, phenylsulfinyl, or phenylsulfonyl, wherein any heterocyclyl mentioned above is mono- or bicyclic aromatic, and Râ€²b and Râ€²c are hydrogen, alkyl or cycloalkyl; or alternatively RÂ°3 is a radical â€”Câ‰¡Câ€”Rd wherein Rd is alkyl, phenyl, phenylalkyl, phenoxyalkyl, phenylthioalkyl, N-alkyl-N-phenylaminoalkyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxyalkyl, heterocyclylthioalkyl, heterocyclylaminoalkyl, N-alkyl-N-heterocyclylaminoalkyl, wherein any heterocyclyl mentioned above is mono- or bicyclic aromatic; or alternatively RÂ°3 is a â€”CF2-phenyl, or mono- or bicyclic aromatic â€”CF2-heterocyclyl radical; Y is a radical >CHâ€”Re, wherein Re is hydrogen, fluoro, hydroxyl, alkyloxy, cycloalkyloxy, carboxyl, alkyloxycarbonyl, cycloalkyloxycarbonyl, â€”NRaRb or â€”COâ€”NRaRb, wherein Ra and Rb are, independently, hydrogen, alkyl, cycloalkyl, phenyl, mono- or bicyclic aromatic heterocyclyl, and optionally one of Ra and Rb is hydroxyl, alkyloxy, or cycloalkyloxy, or Ra and Rb form, together with the nitrogen atom to which they are attached, a 5- or 6-membered heterocycle which can optionally contain an additional heteroatom chosen from O, S and N and, when the additional heteroatom is N, the additional heteroatom optionally is substituted with an alkyl, phenyl or mono- or bicyclic aromatic heterocyclyl substituent, and, when the additional heteroatom is S, the additional heteroatom optionally is sulfinyl or sulfonyl, or one of Ra and Rb is a hydrogen atom and the other is an alkyloxycarbonyl, acyl, cycloalkylcarbonyl, benzoyl or heterocyclylcarbonyl radical, wherein any heterocyclyl portion is mono- or bicyclic aromatic; or alternatively Y is a difluoromethylene, carbonyl, hydroxyimino-methylene, alkyloxyiminomethylene, or cycloalkyloxyimino-methylene radical, or a 1,1-cycloalkylene radical containing 3 to 6 carbon atoms; and n is an integer from 0 to 4; wherein any phenyl, benzyl, benzoyl or heterocyclyl radical or portion mentioned above are unsubstituted, or substituted on the ring with 1 to 4 substituents independently chosen from halogen, hydroxyl, alkyl, alkyloxy, alkyloxyalkyl, haloalkyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, carboxyl, alkyloxycarbonyl, cyano, alkylamino, phenyl, hydroxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, and â€”NRaRb wherein Ra and Rb are, independently, hydrogen, alkyl, cycloalkyl, phenyl, mono- or bicyclic aromatic heterocyclyl, and optionally one of Ra and Rb is hydroxyl, alkyloxy, or cycloalkyloxy, or Ra and Rb form, together with the nitrogen atom to which they are attached, a 5- or 6-membered heterocycle which can optionally contain an additional heteroatom chosen from O, S and N and, when the additional heteroatom is N, the additional heteroatom optionally is substituted with an alkyl, phenyl or mono- or bicyclic aromatic heterocyclyl substituent, and, when the additional heteroatom is S, the additional heteroatom optionally is sulfinyl or sulfonyl, or one of Ra and Rb is a hydrogen atom and the other is an alkyloxycarbonyl, acyl, cycloalkylcarbonyl, benzoyl or heterocyclylcarbonyl radical, wherein any heterocyclyl portion is mono- or bicyclic aromatic, wherein any alkyl or acyl radical or portion, unless otherwise indicated, comprises from 1 to 10 carbon atoms in a straight or branched chain, and any cycloalkyl radical comprises from 3 to 6 carbon atoms; in any enantiomeric or diastereoisomeric form, in any syn or anti form, or any salt thereof.