| abstract |
Useful compounds as PDE4 inhibitors in the treatment of diseases regulated by activation and degranulation especially asthma, chronic bronchitis and chronic lung disease, of the formula: (see formula) where j is 0 ol, k is 0 ol, m is 0 , l, or 2, n is 2, A is selected from the following partial formulas: (see formula) where q is 1, 2, or 3, is -O-; -N (R9) - or -OC (= 0) -; R7 is selected from -H; -C1-C6 alkyl; -alkenyl (C2-C6); or -alkynyl (C2-C6); wherein said alkyl, alkenyl or alkynyl is substituted by 0 to 3 R10 substituents; - (CH2) ucycloalkyl- (C3-C7) where u is 0, 1 or 2, substituted by 0 to 3 R10 substituents; phenyl or benzyl substituted by 0 to 3 R14 substituents; R8 is tetrazol-5-yl; 1,2,4-triazol-3-yl; 1,2,4-triazol-3-on-5-yl; 1,2,3-triazol-5-yl; imidazol-2-yl; imidazol-4-yl; imidazolidin-2-one-4-yl; 1,3,4-oxadiazolyl; 1,3,4-oxadiazol-2-on-5-yl; 1,2,4-oxadiazol-3-yl; 1,2,4-oxadiazol-5-one-3-yl; 1,2,4-oxadiazol-5-yl; 1,2,4-oxadiazol-3-on-5-yl; 1,2,5-thiadiazolyl; 1,3,4-thiadiazolyl; morpholinflo; parathiazinyl; oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; pyrrolyl; pyrazolyl; succinimidyl; glutarimidyl; pyrrolidonyl; 2-piperidonyl; 2-pyridonyl; 4-pyridonyl; pyridazin-3-onayl; pyridyl; pyrimidinyl; pyrazinyl; pyridazinyl; indolyl; indolinyl; isoindolinyl; benzo, [b] furanyl; 2,3-dihydrobenzofuranyl; 1,3-dihydroisobenzofuranyl; 2H-1-benzopyranyl; 2-H-chromenyl; chromanyl; benzothienyl; 1H-indazolyl; benzimidazolyl; benzoxazolyl; benzisoxazolyl; benzothiazolyl; benzotriazolyl; benzotriiazinyl; phthalazinyl; 1,8-naphthyridinyl; quinolinyl; isoquinolinyl; quinazolinyl; quinoxalinyl; pyrazol [3,4- d? pyrimidinyl; pyrimido [4,5-d] pyrimidinyl; imidazo [1,2-a] pyridinyl; pyridopyridinyl; pteridinyl; or 1H-purinyl; or A is selected from phosphorus and sulfur acid groups; W is -O-; -S (= O) t-, where t is 0, 1, or 2; or -N (R3) -; Y is = C (R1a) -, or - [N? (O) k] - where k is 0 or 1; R4, R5 and R6 are - (1) -H; provided that R5 and R6 are not both -H at the same time, -F; - C1; alkynyl of - (C2-C4); R16; -OR16; -S (= 0) pR16; -C (= O) R16; -C (= O) OR16; -OC (= O) R16; - CN; -NO2; -C (= O) NR16R17; -OC (= O) NR16R17; -NR12 BC (= O) NR16R17; -NR12 BC (= NR12) NR15R17; -NR12aC (= NCN) NR16R17; -NR12aC (= N-NO2) NR16R17; - C (= NR12a) NR16R17; -CH2C (= NR12a) NR16R17; -OC (= NR12a) NR16R17; -OC (= N- NO2) NR16R17; -NR16R17; -CH2NR16R17; -NR12aC (= O) R16; -NR12aC (= O) OR16; = NOR16; - NR12aS (= O) pR17 -S (= O) pNR16R17; and -CH2C (= NR12a) NR16R17; - (2) alkyl- (C1-C4) including dimethyl and alkoxy- (C1-C4) substituted with O to 3 substituents -F or ° C1; or 0 or 1 alkoxycarbonyl- (C1-C2) substituent; alkylcarbonyl- (C1-C2); or alkylcarbonyloxy- (C1-C2); or (3) an aryl or heterocyclic portion; or (4) R5 and R6 are taken together to form a portion of the partial formulas (1.3.1) to (1.3.15): (see formula) or a pharmaceutically acceptable salt thereof. |