Cytokine Inhibitors

A compound of the formula (I)

• wherein:
• Ar1 is chosen from rings (i), (ii) and (iii) below:
• wherein one of A or B is nitrogen and the other is carbon, R1 is covalently attached to either A or B, and when nitrogen is N—R1 the double bond between A and B is not present;
• R1 is chosen from hydrogen, NO2, —N(Rc)2, J-C(O)—N(Rc)—, J-S(O)m—N(Rc)—, or R1 is chosen from C1-6 alkyl, C3-7 cylcoalkyl, C1-5 alkoxyl or C3-7 cycloalkoxyl, C1-5 alkylthiol or C3-7 cycloalkylthiol, C1-5 acyl, C1-5 alkoxycarbonyl, C1-5 acyloxy, C1-5 acylamino, C2-5 alkenyl, C2-5 alkynyl, heterocycle, heteroaryl and nitrile, each of the aforementioned where possible are optionally partially or fully halogenated or are optionally further substituted with alkylsulfonylamino, alkoxyl, amino, alkylamino, dialkylamino, hydroxyl, oxo, nitro or nitrile;
• or R1 is, where P can be 0, >CR9 or >NR9
• wherein z is 1 to 4;
• R9 is chosen from C1-6 alkyl, C3-7 cylcoalkyl, C1-5 alkoxyl or C3-7 cycloalkoxyl, C1-5 alkylthiol or C3-7 cycloalkylthiol, C1-5 acyl, C1-5 alkoxycarbonyl, C1-5 acyloxy, C1-5 acylamino, C2-5 alkenyl, C2-5 alkynyl, heterocycle, heteroaryl and nitrile, each of the aforementioned where possible are optionally partially or fully halogenated or are optionally further substituted with alkylsulfonylamino, alkoxyl, amino, alkylamino, dialkylamino, hydroxyl, oxo, nitro or nitrile;
• R2 is chosen from hydrogen, halogen, C1-5 alkyl, C1-5 alkoxy, C1-5 alkylC1-5 alkoxy, hydroxy, hydroxy C1-5 alkyl, oxo, C1-5 alkylS(O)m— and amino optionally mono- or di-substituted by C1-5 alkyl, aryl or aryl C1-5 alkyl;
• wherein
• R1′ is chosen from hydrogen, C1-5 alkylS(O)m—, C1-6 alkyl, C3-7 cylcoalkyl, C1-5 alkoxyl or C3-7 cycloalkoxyl, C1-5 alkylthiol C3-7 cycloalkylthiol, C1-5 acyl, C1-5 alkoxycarbonyl, C1-5 acyloxy, C2-5 alkenyl, C2-5 alkynyl, heterocycle, heterocycleC1-6 alkyl, heteroaryl, heteroarylC1-6 alkyl and nitrile, each of the aforementioned where possible are optionally partially or fully halogenated or are optionally further substituted with alkylsulfonylamino, alkoxyl, amino, alkylamino, dialkylamino, hydroxyl, oxo, nitro or nitrile;
• R2′, is chosen from nitrile, C1-5 alkylS(O)m—, J-O—C(O)—O—, NH2—C(O)—(CH2)n—, H, halogen, C1-5 alkyl, C1-5 alkoxy, C1-5 alkylC1-5 alkoxy, hydroxy, hydroxy C1-5 alkyl and amino optionally mono- or di-substituted by C1-5 alkyl, aryl or aryl C1-5 alkyl;
• wherein c is a benzo ring fused to ring d which is a 5-7 membered heterocyclic ring;
• each Rx is chosen from C1-6 alkyl or C3-7 cycloalkyl each being optionally substituted by C1-3 alkyl and optionally partially or fully halogenated, C1-4 acyl, aroyl, C1-4 alkoxy, which may optionally be partially or fully halogenated, halogen, C1-6 alkoxycarbonyl, carbocyclesulfonyl and —SO2—CF3;
• each J is independently chosen from C1-10 alkyl and carbocycle each optionally substituted by Rb;
• Rb is chosen from hydrogen, C1-5 alkyl, hydroxyC1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, carbocycle, heterocycle, heteroaryl, C1-5 alkoxy, C1-5 alkylthio, amino, C1-5 alkylamino, C1-5 dialkylamino, C1-5 acyl, C1-5 alkoxycarbonyl, C1-5 acyloxy, C1-5 acylamino, each of the aforementioned are optionally partially or fully halogenated, or Rb is chosen from C1-5 alkylsulphonylamino, hydroxy, oxo, halogen, nitro and nitrile;
• Q is a N;
• Y is >CRpRv, —CRp═C(Rv)—, —O— or >S(O)m;
• each Rc, Rp, RV and Ry are each independently hydrogen or C1-5 alkyl;
• X is —CH2—, —N(Rc)—, —O— or —S—;
• W is N or CH;
• each m independently 0, 1 or 2;
• n is 1-4;
• each R3, R4 and R5 are independently chosen from hydrogen, C1-6 alkyl and halogen;
• R6 is optionally attached at a position ortho or meta to the N atom of the indicated ring, and is chosen from
• a bond, —O—, —O—(CH2)1-5—, >C(O), —NH—, —C(O)—NH—, —S—, C1-5 alkyl branched or unbranched, C2-5 alkenyl, C1-3 acyl, C1-3 alkyl(OH), heterocycle selected from morpholinyl, piperazinyl, piperidinyl, pyrrolidinyl and tetrahydrofuranyl, heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, thiazolyl, oxazolyl and isothiazolyl or aryl each alkyl, alkenyl, acyl, heterocycle, heteroaryl and aryl are optionally substituted by one to three hydroxy, oxo, C1-3 alkyl, C1-3 alkoxy, C1-5 alkoxycarbonyl, —NR7R8 or NR7R8—C(O)—;
• wherein each R6 is further optionally covalently attached to groups chosen from:
• hydrogen, NR7R8, C1-3 alkyl, C3-6 cycloalkylC0-2alkyl, hydroxy, C1-3 alkoxy, phenoxy, benzyloxy, arylC0-4 alkyl, heteroaryl C0-4 alkyl and heterocycle C0-4alkyl, each above-listed heterocycle, heteroaryl and aryl group is optionally substituted by one to three hydroxy, oxo, C1-4 alkyl, C1-3 alkoxy, C1-5 alkoxycarbonyl, NR7R8—C(O)— or C1-4 acyl;
• each R7 and R8 are independently hydrogen, phenylC0-3alkyl optionally substituted by halogen, C1-3 alkyl or diC1-5 alkyl amino, or R7 and R8 are C1-2 acyl, benzoyl or C1-5 branched or unbranched alkyl optionally substituted by C1-4 alkoxy, hydroxy or mono or diC1-3 alkyl amino;
• or the pharmaceutically acceptable salts and/or isomers thereof.