New triazolo(4,3-A)pyrido(2,3-D)pyrimidin-5-one derivatives are phosphodiesterase inhibitors used for treating e.g. cancer, acquired immunodeficiency syndrome, and fibrosis

摘要

Triazolo(4,3-A)pyrido(2,3-D)pyrimidin-5-one derivatives (I) are new. Triazolo(4,3-A)pyrido(2,3-D)pyrimidin-5-one derivatives of formula (I), their regioisomers, salts and solvates are new. X = alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl (all optionally substituted by 1-3 halo), H, OH, halo, amino, SH, CN, carboxy, NR3R4, (N-(A))n-CO-Q1-Q2-Q3 or group of formula (i) in which the ring is 3-10 membered and optionally additionally contains 1-3 O, S and/or N, and is optionally bridged by alkyl, gem dialkylated or substituted by 1-3 OH, oxo, alkyl and/or alkoxy or by CO-Q1-Q2-Q3; R = alkyl, alkenyl, alkynyl, 2-, 3- or 4-pyridylalkyl (optionally pyridyl substituted by 1-3 alkyl, alkoxy, OH, halo and/or amino), (CH2)s-Ar(Y1)(Y2)Y3, CH2CH=CH-Ar(Y1)(Y2)Y3 or a group of formula (ii) or (iii); s = 1-4; Ar = 5- or 6-membered aryl additionally containing 1-4 O, S and/or N; Y1-Y3 = H, OH, SH, NH, NO2, halo, C(O)R6, CO2R6, C(O)NR6R7, NR6R7, (CH2)tCN or (CH2)t-C(O)-Q1-Q2-Q3, or alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl (all optionally substituted by 1-3 halo); R1, R2 = alkyl, aralkyl, cycloalkyl or cycloalkyl-alkyl, or NR1R2 = 4-7 membered azacycloalkyl additionally containing 1-3 O, S and/or N optionally bridged by alkyl, gem dialkylated or substituted by 1-3 OH, oxo, alkyl and/or alkoxy or by CO-Q1-Q2-Q3, with 2 of the atoms of the resulting ring optionally forming part of another ring comprising Ph and 4-8 membered heteroaryl additionally containing 1-4 O, S and/or N; t = 0-2; R6,R7 = H or alkyl; or NR6R7 = 4-7 membered azacycloalkyl containing 1-3 O, S and/or N; n = 0 or 1; A = H or CO-Q1-Q2-Q3; Q1 = oxy, NH, N-Q2-Q3 or group of formula (iv); p, p' = 0-3; Z = CH, N or oxy; Q2 = (CH2)q or (CH2-CH2-O)r; q = 0-4; r = 2-4; Q3 = H, or OH, MeO, O-CO-X1, NH2 or N(X1)X2; X1, X2 = alkyl, or NX1X2 = 3-10 membered azabicycloalkyl containing additionally 1-3 O, S and/or N heteroatoms; R3, R4 = H, alkyl (optionally substituted by 1-3 halo, OH, CN or alkoxy), C(O)R5 or (CH2)x-cycloalkyl (optionally substituted by OH, alkoxy, mercapto, alkylthio, amino, alkylamino, N-alkyl, N-alkylamino or 1-4C alkyl); x = 0-4, and R5 = H or alkyl optionally substituted by OH, alkoxy, SH or alkylthio. Independent claims are also included for compounds of formulae (II), (IV) and (V). Hal' = Cl, Br or I.