Retinoic acid mimetic anlides

A compound having the formula

• a N-oxide, a pharmaceutically acceptable addition salt or a stereochemically isomeric form thereof, wherein:
• X represents —O—, —S— or —NR3—;
• R1 represents hydrogen, hydroxy, C1-6alkyl or aryl;
• R2 represents hydrogen;
• C1-12alkyl;
• C3-7cycloalkyl;
• C2-8alkenyl;
• aryl;
• Het1;
• or C1-12alkyl substituted with one or two substituents selected from C3-7cycloalkyl, hydroxy, C1-4alkyloxy, cyano, amino, mono- and di(C1-4alkyl)amino, mono- or di(arylC1-4alkyl)amino, di(arylC1-4alkyl)aminocarbonyloxy, (C1-4alkyl) (arylC1-4alkyl)amino, mono- and di(aryl)amino, (C1-4alkyl) (di(C1-4alkyl)aminoC1-4alkyl)amino, pyrrolidinyl, piperidinyl, piperazinyl optionally substituted with C1-4alkyl, morpholinyl, perhydro-azepinyl, carboxyl, C1-4alkyloxycarbonyl, aminocarbonyl, mono- and di(C1-4alkyl)aminocarbonyl, aryl, aryloxy and arylthio;
• R3 represents hydrogen, C1-6alkyl, aryl, Het1 or C1-6alkyl substituted with aryl or Het1;
• R4 represents C1-12alkyl substituted with one, two or three substituents each independently selected from hydroxy, mercapto, C1-6alkyloxy, C1-6alkylthio, aryloxy, arylthio, Het1-oxy, Het1-thio, C3-7cycloalkyl optionally substituted with hydroxycarbonylC1-6alkyl, carboxyl, C1-6alkyloxycarbonyl, arylC1-6alkyloxy, arylC1-6alkylthio, aryl, Het1;
• C2-8alkenyl optionally substituted with one, two or three substituents selected from halo, C3-7cycloalkyl, Het1;
• C2-8alkynyl optionally substituted with halo, C3-7cycloalkyl, aryl;
• C3-7cycloalkyl optionally substituted with C1-6alkyl or aryl;
• C5-7cycloalkenyl optionally substituted with C1-6alkyl or aryl;
• aryl;
• Het1;
• or
• —Alk—NR3R5 (i)
• wherein Alk represents C1-6alkanediyl;
• and
• R5 represents hydrogen, C1-6alkyl, aryl, Het1, (aryl or Het1)C1-6alkyl, (aryl or Het1)carbonyl or (aryl or Het1)C1-6alkyloxycarbonyl;
• aryl represents indanyl, indenyl, naphtyl, 5,6,7,8-tetrahydro-2-naphtalenyl, phenyl;
• said indanyl, indenyl, naphtyl or phenyl may be substituted with one, two, three, four or five substituents each independently selected from hydroxy, halo, nitro, cyallo, amino, azido, mono- or di(C1-6alkyl)-amino, C1-6alkylcarbonylamino, C1-6alkyl, polyhaloC1-6alkyl, hydroxyC1-6alkyl, phenyl, phenyloxy, phenylC1-6alkyloxy, pyridinylC1-6alkyloxy, C1-6alkyloxy, formyl, carboxyl and C1-6alkylcarbonyl;
• or two adjacent carbon atoms on said phenyl may be substituted by a single bivalent radical having the formula C1-12alkanediyl or polyhaloC1-12alkanediyl;
• Het represents an unsaturated heterocycle selected from pyrrolyl, pyrazolyl, imidazolyl, triazolyl, or tetrazolyl;
• each of said unsaturated heterocycles may optionally be substituted with amino, mercapto, C1-6alkyl, C1-6alkylthio or aryl;
• and
• Het1 represents a monocyclic heterocycle selected from pyrrolidinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,3,4-triazolyl, 1,2,4-triazolyl, tetrahydrofuranyl, furanyl, thiolanyl, thienyl, dioxolanyl, isoxazolyl, oxazolyl, isothiazolyl, thiazolyl, isoxazolidinyl, oxazolidinyl, isothiazolidinyl, thiazolidinyl, piperidinyl, pyridinyl, piperazinyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, tetrahydropyranyl, pyranyl, morpholinyl and dioxanyl;
• each of said monocyclic heterocycles may be optionally substituted with one or two substituents each independently selected from C1-4alkyl, hydroxy, amino, halo, aryl, arylcarbonyl or C1-4alkyloxycarbonyl;
• or a bicyclic heterocycle selected from indolinyl, indolyl, indazolyl, benzimidazolyl, benzotriazolyl, benzofuranyl, benzothienyl, 2H-1-benzopyranyl, 3,4-dihydro-2H-1-benzopyranyl, benzthiazolyl, isoquinolinyl, quinolinyl, 3,4-dihydroquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, chromanyl, 1,4-benzodioxinyl, 1,4-benzoxathianyl, benzodioxanyl and benzodioxolanyl;
• each of said bicyclic heterocycles may be substituted with one or two substituents each independently selected from C1-4alkyl, hydroxy, amino, halo, aryl, arylcarbonyl or C1-4alkyloxycarbonyl.