Hydroxyphenyl derivatives and biological applications thereof

A method of treatment of microbial infection which comprises administering to a patient in need thereof an effective amount of a hydroxyphenyl derivative of formula (I)

• R1 is phenyl or a 6 membered monocyclic nitrogenous heteroaryl of formula
• Z4, Z5, Z6, Z7 and Z8 are independently C or N with a maximum of three N, R1 being possibly substituted by 1 to 3R identical or different, R being selected from the group comprising H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, 5 or 6 membered monocyclic heteroaryl or aliphatic heterocycle containing 1 to 3 heteroatoms selected from N, O and S, COORa, CORa, CONRaRb, OCORa, CN, ORa, NRaRb, CRa═NORb, NRaCORb, NRaCOORb, OCONRaRb, NRaCONRbRc, SRa, SO2Ra, SO2NRaRb, NRaSO2Rb and NRaC(S)NRbRc, all being possibly substituted by R′, or R is C1-C4fluoro-alkyl, or R is fluoro when R1 is phenyl, or R is halogeno when R1 is nitrogenous heteroaryl,
• R2 is phenyl, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C4fluoro-alkyl, C2-C4fluoro-alkenyl, ORa, SRa, all being possibly substituted by 1 to 3 identical or different R′,
• Ra, Rb and Rc, identical or different, are selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, phenyl, heteroaryl and aliphatic heterocycle as defined above for R2, the heteroaryl and the heterocycle being possibly formed with the carbon and nitrogen atoms to which Ra, Rb and Rc are linked,
• R′ is selected from the group comprising heteroaryl and aliphatic heterocycle as defined above for R2, C1-C8 alkyl, CH2CO2R″, CO2R″, COR″, CONR″R′″, OCOR″, OR″, NR″R′″, NR″COR′″, NR″COOR′″, OCONR″R′″, NR″CONR″R′″, NR″SO2R′″, SO2R″, NR″SO2R′″, halogen and CN, R″ and R′″, identical or different, are H, C1-C8 alkyl or form together a 4 to 6 membered heterocycle with 1 to 3 heteroatoms selected from N, O and S,
• Y represents H or a labile chemical group able to regenerate in vivo the free phenol selected from the group consisting of C(O)Ra, C(O)ORa, C(O)NRa, Rb, P(O)(OH)2 and COCHRaNRbRc,
• Z1 and Z3, identical or different, are halogen or H,
• Z2 is fluoro or H,
• provided that
• either Z2 is fluoro and all the other definitions are as defined above,
• or Z6 is a carbon atom substituted by R as defined above, R being different from H, alkyl, halogen, NH2, OH, CONH2 or fluoro alkyl and all the other definitions are as defined above,
• or Z4 or Z5, or Z7 or Z8 are carbon atoms substituted by NRaRb or ORa, ORa being different from OH and all the other definitions are as defined above,
• or Z5, or Z7, is a carbon atom substituted by R, R being different from H and all the other definitions are as defined above,
• or R2 is a C1-C8alkyl-heteroaryl radical or a C1-C8alkyl-ORa radical, ORa being different from OH and all the other definitions are as defined above,
• or a pharmaceutically acceptable organic or mineral salt, as well as the racemic derivatives and each unique not racemic derivatives, in case the derivatives of formula (I) have one or more chiral centers, both the cis (Z) and trans (E) isomers, in cases the derivatives of formula (I) have unsaturated carbon=carbon double bonds, and any N-oxide form of the derivatives.