Derivatives of 1-phenyl-benzofuro[3,2]pyridin-2(1H)-one

A compound of formula (I):

• a pharmaceutically acceptable salt or stereoisomeric form thereof,
• wherein
• R1 is cyano;
• X is a bivalent radical O;
• R3 is
• i) a radical of formula
• wherein n is 1, 2 or 3;
• R3a is nitro, cyano, amino, halo, hydroxy, C1-4alkyloxy, hydroxycarbonyl, aminocarbonyl, C1-4alkyloxycarbonyl, mono- or di(C1-4alkyl)aminocarbonyl, C1-4alkylcarbonyl, methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, N-hydroxy-methanimidamidyl or Het1;
• or R3 is
• ii) a monocyclic or bicyclic aromatic heterocyclic ring system, wherein one, two, three or four ring members are heteroatoms each independently selected from the group consisting of nitrogen, oxygen and sulfur, and wherein the remaining ring members are carbon atoms;
• and wherein each of said heterocyclic ring systems may optionally be substituted with one, two, three, four or five substituents each independently selected from halo, cyano, nitro, C1-6alkyl, hydroxyC1-6alkyl, C1-4alkoxyC1-6alkyl, (R5a)(R5b)N—C1-4alkyl, polyhaloC1-6alkyl, C3-7cycloalkyl, arylC1-6alkyl, formyl, C1-6alkylcarbonyl, —COOR4, (R5a)(R5b)N-carbonyl, (R5a)(R5b)N-sulfonyl, hydroxy, C1-6alkyloxy, arylC1-6alkyloxy, polyhaloC1-6alkyloxy, formyloxy, C1-6alkylcarbonyloxy, aryloxy, (R5a)(R5b)N—, formylamino, C1-6alkylcarbonylamino, C1-6alkyloxycarbonylamino C1-6alkylsulfonylamino, mercapto, C1-6alkylthio, arylthio, arylC1-6alkylthio, C1-6alkylsulfinyl, C1-6alkylsulfonyl, aryl, —CH(═N—O—R5a), —C(═NH)—NH—R5a;
• each R4 independently is hydrogen, C1-4alkyl, arylC1-4alkyl;
• each R5a, R5b independently is hydrogen, C1-4alkyl or arylC1-4alkyl;
• -a1=a2-a3=a4- represents a bivalent radical of formula
• —CH═CH—CH═CH— (c-1),
• wherein one, two, three or four of the hydrogen atoms in (c-1) may be replaced by a radical C1-6alkyl, C1-4alkoxy, or hydroxy;
• R20 is hydrogen, hydroxy, C1-4alkyl, arylC1-4alkyl, C1-4alkyloxy, arylC1-4alkyloxy, oxo, spiro(C2-4alkylenedioxy), spiro(diC1-4alkyloxy), —NR5gR5h;
• each R5g or R5h independently is hydrogen, C1-4alkyl or arylC1-4alkyl, or R5g and R5h together with the nitrogen to which they attached form a pyrrolidinyl, piperidinyl, homopiperidinyl, morfolinyl, piperazinyl or 4-C1-4alkylpiperazinyl radical;
• wherein each of said pyrrolidinyl, piperidinyl, homopiperidinyl, morfolinyl, piperazinyl or 4-C1-4alkylpiperazinyl radical may optionally be substituted with hydroxy or oxo;
• R21 is C1-6alkyl;
• aryl is phenyl optionally substituted with one or more substituents each individually selected from the group consisting of C1-6alkyl, C1-4alkoxy, halo, hydroxy, amino, trifluoromethyl, cyano, nitro, hydroxyC1-6alkyl, cyanoC1-6alkyl, mono- or di(C1-4alkyl)amino, aminoC1-4alkyl, mono- or di(C1-4alkyl)aminoC1-4alkyl;
• Het1 is a 5-membered ring system wherein one, two, three or four ring members are heteroatoms each individually and independently selected from the group consisting of nitrogen, oxygen and sulfur, and wherein the remaining ring members are carbon atoms;
• and, where possible, any nitrogen ring member may optionally be substituted with C1-4alkyl;
• any ring carbon atom may, each individually and independently, optionally be substituted with a substituent selected from the group consisting of C1-4alkyl, C2-6alkenyl, C3-7cycloalkyl, hydroxy, C1-4alkoxy, halo, amino, cyano, trifluoromethyl, hydroxyC1-4alkyl, cyanoC1-4alkyl, mono- or di(C1-4alkyl)amino, aminoC1-4alkyl, mono- or di(C1-4alkyl)aminoC1-4alkyl, arylC1-4alkyl, aminoC2-6alkenyl, mono- or di(C1-4alkyl)aminoC2-6alkenyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, aryl, hydroxycarbonyl, aminocarbonyl, C1-4alkyloxycarbonyl, mono- or di(C1-4alkyl)aminocarbonyl, C1-4alkylcarbonyl, oxo, thio;
• and wherein any of the foregoing furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl and triazolyl moieties may optionally be substituted with C1-4alkyl;
• R13 is hydrogen, hydroxy, C1-4alkyl, C1-4alkyloxy, or arylC1-4alkyloxy;
• and
• each R14 independently is hydrogen, C1-4alkyl, aryl C1-4alkyl, aryl, C1-4alkylcarbonyl, —SO3H, —PO3H2.