WATER SOLUBLE AZOLES AS BROAD-SPECTRUM ANTIFUNGALS, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM

摘要

A compound of the formula a N-oxide form, a pharmaceutically acceptable addition salt or a stereochemically isomeric form thereof, wherein L represents a radical of formula wherein each Alk independently represents C1-6 alkanediyl optionally substituted with hydroxy or C1-4 alkyloxy; each n independently is 1, 2 or 3; Y represents O, S or NR2; each R1 independently represents hydrogen, aryl, Het1, or C1-6 alkyl optionally substituted with one, two or three substituents each independently selected from halo, hydroxy, mercapto, C1-4 alkyloxy, C1-4 alkylthio, aryloxy, arylthio, aryl C1-4 alkyloxy, aryl C1-4 alkylthio, cyano, amino, mono- or diC1-4 alkyl)-amino, mono- or di(aryl)amino, mono- or di(aryl C1-4 alkyl)amino, C1-4 alkyloxycarbonylamino, benzyloxycarbonylamino, aminocarbonyl, carboxyl, C1-4 alkyloxycarbonyl, guanidinyl, aryl or Het2; each R2 independently represents hydrogen or C1-6 alkyl; or in case R1 and R2 are attached to the same nitrogen atom, they 2718 י" ב בתשרי התשס" ה - September 27, 2004 may be taken together to form a heterocyclic radical selected from morpholinyl, pyrrolidinyl, piperidinyl, homopiperidinyl or piperazinyl; said heterocyclic radical may optionally be substituted with C1-4 alkyl, aryl, Het2 aryl C1-4 alkyl, Het2 C1-4 alkyl, hydroxy C1-4 alkyl, amino, mono- or di(C1-4 alkyl) amino, amino C1-4 alkyl, mono or di(C1-4 alkyl) amino C1-4 alkyl, carboxy, aminocarbonyl, C1-4 alkyloxycarbonyl, C1-4 alkyloxycarbonylamino or mono- or di(C1-4 alkyl) aminocarbonyl; or they may be taken together to form an azido radical; each R3 indepenently represents hydrogen, hydroxy or C1-4 alkyloxy; aryl represents phenyl, naphthalenyl, 1,2,3,4-tetrahydro- naphthalenyl, indentyl or indanyl; each of said aryl groups may optionally be substituted with one or more substituents selected from halo, C1-4 alkyl, hydroxy, C1-4 alkyloxy, nitro, amino, trifluoromethyl, hydroxy C1-4 alkyl, C1-4 alkyloxy C1-4 alkyl, amino C1-4 alkyl, mono- or di(C1-4 alkyl) amino C1-4 alkyl; Het1 represents a monocyclic or bicyclic heterocyclic radical; said monocyclic heterocyclic radical being selected from the group pyridinyl, piperidinyl, homopiperidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, triazolyl, pyranyl, tetrahydropyranyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, thiazolyl, thiazolidinyl, isothiazolyl, oxazolyl, oxazolidinyl, isoxazolyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, furanyl, tetrahydrofuranyl, thienyl, thiolanyl, dioxolanyl; said bicyclic heterocyclic radical being selected from the group quinolinyl, 1,2,3,4-tetrahydro- quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, phtalazinyl, cinnolinyl, chromanyl, thiochromanyl, 2H-chromenyl, 1,4-benzodioxanyl, indolyl, isoindolyl, indolinyl, indazolyl, purinyl, pyrrolopyridinyl, furanopyridinyl, thienopyridinyl, benzothiazolyl, benzoxazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, benzofuranyl, benzothienyl; whereby each of said mono- or bicyclic heterocycle may optionally be substituted with one or where possible more substituents selected from halo, C1-4 alkyl, hydroxy, C1-4 alkyloxy, nitro, amino, trifluoromethyl, hydroxy C1-4 alkyl, C1-4 alkyloxy-C1-4 alkyl, amino C1-4 alkyl, mono- or di(C1-4 alkyl) amino C1-4 alkyl, aryl or aryl C1-4 alkyl; Het2 is the same as Het1 and may also be a monocyclic heterocycle selected from piperazinyl, homopiperazinyl, 1,4-dioxanyl, morpholinyl, thiomorpholinyl, whereby each of said monocyclic heterocycle may optionally be substituted with one or where possible more substituents selected from halo, C1-4 alkyl, hydroxy, C1-4 alkyloxy, nitro, amino, trifluoromethyl, hydroxy C1-4 alkyl, C1-4 alkyloxy C1-4 alkyl, amino C1-4 alkyl, mono- or di-(C1-4 alkyl) amino C1-4 alkyl, aryl or aryl C1-4 alkyl; R6 represents hydrogen or C1-4 alkyl; R7 represents hydrogen or C1-4 alkyl; or R6 and R7 taken together form a bivalent radical of formula -R6-R7- wherein -R6-R7- is: -N=CH-(i), -CH=N-(ii), -CH=CH-(iii, -CH2-CH2(iv), wherein one hydrogen atom in the radical (i) and (ii) may be replaced with a C1-4 alkyl radical and one or more hydrogen atoms in radicals (iii) and (iv) may be replaced by a C1-4 alkyl radical; D represents hydrogen or a radical of formula 2719 י" ב בתשרי התשס" ה - September 27, 2004 wherein X is N or CH; R4 is hydrogen or halo; R5 is halo; provided that if D is hydrogen R6 and R7 are not hydrogen.