| 摘要 |
Compounds of formula (I) and multimers thereof are inhibitors of human neutrophil elastase activity, and of utility in the treatment of, e.g., COPD: wherein A is aryl or heteroaryl; D is oxygen or sulphur; R1, R2 and R3 are independently each hydrogen, halogen, nitro, cyano, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, hydroxy or C1-C6-alkoxy or C2-C6-alkenyloxy, wherein C1-C6-alkyl and C1-C6-alkoxy can be further substituted with one to three identical or different radicals selected from the group consisting of halogen, hydroxy and C1-C4-alkoxy; R and R4 each independently represent a radical of formula -[X]m-[Alk1]p-[Q]n-[Alk2]q-[X1]k-Z wherein k, m, n, p and q are independently 0 or 1; Alk1 and Alk2 each independently represent an optionally substituted C1-C6 alkylene, or C2-C6 alkenylene radical which may optionally contain an ether (O-), thioether (-S-) or amino (-NRA-) link wherein RA is hydrogen or C1-C3 alkyl; Q represents (i) O-, -S-, -S(-O)-, -S(-O)2-, -S+(RA)-, -N(RA)-, -N+(RA)(RB)-, -C(-O)-, -C(-O)O-, -OC(-O)-, -C(-O)NRA-, -NRAC(-O)-, -S(O2)NRA-, -NRAS(O2)-, -NRAC(-O)NRB-, -NRAC(-NRA)NRB-, -C(-NRD)NRE, -NREC(-NRD), wherein RA, RB, RD and RE are independently hydrogen, C1-C6 alkyl, or C3-C6 cycloalkyl, or RA and RB, or RD and RE taken together with the nitrogen to which they are attached form a monocyclic heterocyclic ring of 5 to 7 ring atoms which my contain a further heteroatom selected from N, O and S, or (ii) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 3-6 ring members; X represents -(C-O)-, -S(O2)-, -C(-O)O-, -(C-O)NRA-, or -S(O2)NRA-, wherein RA is hydrogen, C1-C6 alkyl, or C3-C6 cycloalkyl; X1 represents -O-, -S-, or -NH; and Z is hydrogen or an optionally substituted mono- or bicyclic carbocyclic or heterocyclic radical having 3-6 ring members.
|
