7-(3',4'-DIALKOXYPHENYL)-4,5,6,7-TETRAHYDROPYRAZOLO1,5-APYRIMIDINE COMPOUNDS, PROCESS FOR PREPARING THEREOF, AND PHARMACEUTICAL COMPOSITION FOR TREATING OR PREVENTING ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, ARTHRITIS, ATOPIC DERMATITIS, TUMOR AND DEGENERATIVE BRAIN DISEASES COMPRISING THE SAME

摘要

A novel 7-(3',4'-dialkoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine compound is provided to show excellent inhibitory activity and high enzyme selectivity on PDE-4 enzyme, thereby being used in order to prevent and treat inflammation related diseases, arthritis, atopic dermatitis, tumor, and brain diseases. A 7-(3',4'-dialkoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine compound is represented by a formula(1), wherein each R1 and R2 is independently H, linear or branched saturated or unsaturated C1-7 alkyl, linear or branched saturated or unsaturated C1-7 alkyl including O, N or S, C3-7 cycloalkyl, C3-7 cycloalkyl including O, N or S, (C3-7)cycloalkyl(C1-7)alkyl, 3 to 7-membered saturated or unsaturated heterocycloalkyl including O, N or S in a hetero-ring, phenyl or benzyl, or R1 and R2 may be linked to each other by C1-3 alkylene or C1-3 alkylene including halogen; each R3 and R4 is independently H, formyl, halogen, linear or branched saturated or unsaturated C1-7 alkyl. C1-7 alkoxy, C3-7 cycloalkyl, (C1-7)alkoxy(C1-7)alkyl, C1-7 alkyl ketone, hydroxy(C1-7)alkyl, (C3-7)cycloalkyl(C1-7)alkyl, (C3-7)cycloalkyl(C1-7)alkoxy, C1-7 alkyl carboxyl, carboxy(C1-10)alkylester, carboxyl(C1-10)alkylamide, amino, mono or di(C1-7)alkylamino, mono or di(C1-7)alkylaminocarbonyl, (C3-7)cycloalkylamino, morpholine, morpholine oxide, thio- morpholine, piperidine, piperazine, piperazine oxide, piperidine, piperidine oxide, pyrrolidine, cyano, nitro, carboxyl, guanidine, urea, phenoxy, benzyloxy or aryl represented by Ar; and R5 is H, linear or branched saturated or unsaturated C1-7 alkyl, C3-7 cycloalkyl, (C1-7)alkoxy(C1-7)alkyl, (C3-7)cycloalkyl(C1-7)alkyl, (C3-7)cycloalkyl(C1-7)alkoxy, mono or di(C1-7)alkylamino, carbonyl, cyano, C1-7 alkoxycarbonyl, aminocarbonyl, C1-7 alkylcarbonyl, (C6-10)ar(C1-7)alkylcarbonyl or C6-10 arylcarbonyl. A method for preparing the compound of the formula(1) comprises the steps of: (a) after reacting a 3-amino-5-substituted pyrazole compound represented by a formula(4) with a 3-(dimethylamino)-1-(3,4-dialkoxyphenyl)prophenone compound represented by a formula(5) or a 3-(3,4-dialkoxyphenyl)cinnamic aldehyde compound represented by a formula(6) in the presence of an acetic acid, reducing a reaction producing with NaBH4 to prepare a compound represented by the formula(1); and (b) subjecting the compound of a formula(10) to nucleophilic substitution. A pharmaceutical composition for treating or preventing asthma, chronic obstructive pulmonary disease, arthritis, atopic dermatitis, tumor and degenerative brain diseases comprises the compound of the formula(1) or a pharmaceutically acceptable salt thereof.