Quinoline derivatives as antibacterial agents

A method for treating methicillin resistant Staphylococcus aureus (MRSA) bacterial infection in a mammal, said method comprising administering an effective amount of a compound of Formula (I) to said mammal:

• a pharmaceutically acceptable acid or base addition salt thereof, or a stereochemically isomeric form thereof wherein:
• R1 is hydrogen, halo, haloalkyl, cyano, hydroxy, Ar, Het, alkyl, alkyloxy, alkylthio, alkyloxyalkyl, alkylthioalkyl, Ar-alkyl or di(Ar)alkyl;
• p is an integer equal to 1, 2 or 3;
• s is an integer equal to zero, 1, 2, 3 or 4;
• R2 is hydrogen;
• halo;
• alkyl;
• hydroxy;
• mercapto;
• alkyloxy optionally substituted with amino or mono or di(alkyl)amino or a radical of formula
• wherein Z is CH2, CH—R8, O, S, N—R8 and t is an integer equal to 1 or 2 and the dotted line represents an optional bond;
• alkyloxyalkyloxy;
• alkylthio;
• mono or di(alkyl)amino wherein alkyl may optionally be substituted with one or two substituents each independently be selected from alkyloxy or Ar or Het or morpholinyl or 2-oxopyrrolidinyl;
• Ar;
• Het or a radical of formula
• wherein Z is CH2, CH—R8, O, S, N—R8;
• t is an integer equal to 1 or 2;
• and the dotted line represents an optional bond;
• R3 is alkyl, Ar, Ar-alkyl, Het or Het-alkyl;
• q is an integer equal to zero, 1, 2, 3 or 4;
• R4 and R5 each independently are hydrogen, alkyl or benzyl;
• or
• R4 and R5 together and including the N to which they are attached may form a radical selected from the group of pyrrolidinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolyl, imidazolidinyl, pyrazolidinyl, 2-imidazolinyl, 2-pyrazolinyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, piperazinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, morpholinyl and thiomorpholinyl, each of said rings optionally being substituted with alkyl, halo, haloalkyl, hydroxy, alkyloxy, amino, mono- or dialkylamino, alkylthio, alkyloxyalkyl, alkylthioalkyl and pyrimidinyl;
• R6 is hydrogen, halo, haloalkyl, hydroxy, Ar, alkyl, alkyloxy, alkylthio, alkyloxyalkyl, alkylthioalkyl, Ar-alkyl or di(Ar)alkyl;
• or
• two vicinal R6 radicals may be taken together to form together with the phenyl ring to which they are attached a naphthyl;
• r is an integer equal to 1, 2, 3, 4 or 5;
• and
• R7 is hydrogen, alkyl, Ar or Het;
• R8 is hydrogen, alkyl, hydroxyl, aminocarbonyl, mono- or di(alkyl)aminocarbonyl, Ar, Het, alkyl substituted with one or two Het, alkyl substituted with one or two Ar, Het-C(═O)— or Ar—C(═O)—;
• alkyl is a straight or branched saturated hydrocarbon radical having from 1 to 6 carbon atoms;
• or is a cyclic saturated hydrocarbon radical having from 3 to 6 carbon atoms;
• or is a cyclic saturated hydrocarbon radical having from 3 to 6 carbon atoms attached to a straight or branched saturated hydrocarbon radical having from 1 to 6 carbon atoms;
• wherein each carbon atom can be optionally substituted with hydroxy, alkyloxy or oxo;
• Ar is a homocycle selected from the group of phenyl, naphthyl, acenaphthyl, tetrahydronaphthyl, each optionally substituted with 1, 2 or 3 substituents, each substituent independently selected from the group of hydroxy, halo, cyano, nitro, amino, mono- or dialkylamino, alkyl, haloalkyl, alkyloxy, haloalkyloxy, carboxyl, alkyloxycarbonyl, alkylcarbonyl, aminocarbonyl, morpholinyl and mono- or dialkylaminocarbonyl;
• Het is a monocyclic heterocycle selected from the group of N-phenoxypiperidinyl, piperidinyl, pyrrolyl, pyrazolyl, imidazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl;
• or a bicyclic heterocycle selected from the group of quinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, quinoxalinyl, indolyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzofuranyl, benzothienyl, 2,3-dihydrobenzo[1,4]dioxinyl or benzo[1,3]dioxolyl;
• each monocyclic and bicyclic heterocycle may optionally be substituted on a carbon atom with 1, 2 or 3 substituents, each substituent independently selected from the group of halo, hydroxy, alkyl or alkyloxy;
• halo is a substituent selected from the group of fluoro, chloro, bromo and iodo and
• haloalkyl is a straight or branched saturated hydrocarbon radical having from 1 to 6 carbon atoms or a cyclic saturated hydrocarbon radical having from 3 to 6 carbon atoms or a cyclic saturated hydrocarbon radical having from 3 to 6 carbon atoms attached to a straight or branched saturated hydrocarbon radical having from 1 to 6 carbon atoms;
• wherein one or more carbon atoms are substituted with one or more halo atoms;
• provided that radical
• is bonded to one of positions 2, 6 or 7 of the quinoline moiety.