Patent IL-117807-A (IL)
Title: Use of 1,3-dihydro-1-(phenylalkyl)-2h- imidazol-2-one derivatives for the preparation of medicaments, some such novel derivatives, process for their preparation and pharmaceutical compositions containing them
IPC: C07D401/06
Filed: 1996-04-03
Abstract: The use of a compound for the manufacture of a medicament for treating warm-blooded animals suffering from disease states related to an abnormal enzymatic or catalytic activity of phosphodiesterase IV (PDE IV), and/or disease states related to a physiologically detrimental excess of cytokines, said compound having the formula 1302 כ" ג בסיון התשס" א - June 14, 2001 a N-oxide form, a pharmaceutically acceptable acid or base addition salt or a stereochemically isomeric form thereof, wherein: R1 and R2 each independently are hydrogen; C1-6 alkyl; difluoromethyl; trifluoromethyl; C3-6 cycloalkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; bicyclo [2.2.1]-2-heptenyl; bicyclo [2.2.1] heptanyl; C1-6 alkylsulfonyl; arylsulfonyl; or C1-10 alkyl substituted with one or two substituents each independently selected from aryl, pyridinyl, thienyl, furanyl, C3-7 cycloalkyl and a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; R3 is hydrogen, halo or C1-6 alkyloxy; R4 is hydrogen; halo; C1-6 alkyl; trifluoromethyl; C3-6 cycloalkyl; carboxyl; C1-4 alkyloxycarbonyl; C3-6 cycloalkylaminocarbonyl; aryl; Het1; or C1-6 alkyl substituted with cyano, amino, hydroxy, C1-4 alkylcarbonylamino, aryl or Het1; or R4 is a radical of formula: -O-R6(a-1); or -NH-R7(a-2); wherein R6 is hydrogen; C1-6 alkyl; C1-6 alkyl substituted with hydroxy, carboxyl, C1-4 alkyloxycarbonyl, amino, mono- or di(C1-4 alkyl) amino, Het1 or aryl; R7 is hydrogen; C1-6 alkyl; C1-4 alkylcarbonyl; C1-6 alkyl substituted 1303 כ" ג בסיון התשס" א - June 14, 2001 with hydroxy, carboxyl, C1-4 alkyloxycarbonyl, amino, mono- or di(C1-4 alkyl) amino, Het1 or aryl; R5 is hydrogen, halo, hydroxy or C1-6 alkyl; or R4 and R5 taken together may form a bivalent radical of formula: -(CH2)n (b-1); -CH2-CH2-O- CH2CH2- (b-2); -CH2-CH2- N(R8)- CH2-CH2- (b-3); or -CH2-CH=CH-CH2- wherein n is 2, 3, 4 or 5; R8 is hydrogen, C1-6 alkyl, C1-6 alkylsulfonyl or p-toluenesulfonyl; Y is a direct bond, haloC1-4 alkanediyl or C1-4 alkanediyl; -A-B- is a bivalent radical of formula: -CR9=CR10-(c-1); or -CHR9-CHR10-(c-2); wherein each R9 and R10 independently is hydrogen or C1-4 alkyl; and L is hydrogen; C1-6 alkyl; C1-6 alkylcarbonyl; C1-6 alkyloxycarbonyl; C1-6 alkyl substituted with one or two substituents selected from the group consisting of hydroxy, C1-4 alkyloxy, C1-4 alkyloxycarbonyl, mono- and di(C1-4 alkyl) amino, aryl and Het2; C3-6 alkenyl; C3-6 alkenyl substituted with aryl; piperidinyl; piperidinyl substituted with C1-4 alkyl or aryl C1-4 alkyl; C1-6 alkylsulfonyl or arylsulfonyl; aryl is phenyl or phenyl substituted with one, two or three substituents selected from halo, hydroxy, C1-4 alkyl, C1-4 alkyloxy, C3-6 cycloalkyl, trifluoromethyl, amino, nitro, carboxyl, C1-4 alkyloxycarbonyl and C1-4 alkylcarbonylamino; Het1 is pyridinyl; pyridinyl substituted with C1-4 alkyl; furanyl; furanyl substituted with C1-4 alkyl; thienyl; thienyl substituted with C1-4 alkylcarbonylamino; hydroxypyridinyl, hydroxypyridinyl substituted with C1-4 alkyl or C1-4 alkoxy C1-4 alkyl; imidazolyl; imidazolyl substituted with C1-4 alkyl; thiazolyl; thiazolyl substituted with C1-4 alkyl; oxazolyl; oxazolyl substituted with C1-4 alkyl; isoquinolinyl; isoquinolinyl substituted with C1-4 alkyl; quinolinonyl, quinolinonyl substituted with C1-4 alkyl; morpholinyl; piperidinyl; piperidinyl substituted with C1-4 alkyl, C1-4 alkyloxycarbonyl or aryl C1-4 alkyl; piperazinyl; piperazinyl substituted with C1-4 alkyl, C1-4 alkyloxycarbonyl or aryl C1-4 alkyl; and Het2 is morphilinyl; piperidinyl; piperidinyl substituted with C1-4 alkyl or aryl C1-4 alkyl; piperazinyl; piperazinyl substituted with C1-4 alkyl or aryl C1-4 alkyl; pyridinyl; pyridinyl substituted with C1-4 alkyl; furanyl; furanyl substituted with C1-4 alkyl; thienyl or thienyl substituted