| 摘要 |
Tricyclic diazacycloalkane derivatives (I) are new. Tricyclic diazacycloalkane derivatives of formula (I) are new. A : a 5- to 7-membered ring with 0-2 heteroatoms (O, S, N, NR), where one member can be C=O; R : 1-6C alkyl; n, n' : 0-2, provided that n+n'= 1-3; R 3aryl or heteroaryl; X : 1-6C alkylene, mono- or dioxaalkylene, cycloalkylene, arylene, heteroarylene or SO 2; R 1, R 2H or Q, provided that one is H and the other is Q; Q : YNHSO 2Ar; Y : CO or CH 2; Ar : R 4-substituted 3-R 5-4 R6-phenyl; R 5H; R 6H, NR 7R' 7 or CH 2NR 7R' 7; R 5+R 6groups forming a 5- or 6-membered ring including N para to to the SO 2 group, optionally containing another N atom and/or a SO 2 group, the ring being substituted with R 7; R 7, R' 7H or 1-6C alkyl substituted with aryl, heteroaryl, aryloxy, heteroaryloxy, arylthio, heteroarylthio, heterocycloalkyl or NR 10R' 10; R 10, R' 10H, 1-6C alkyl, 1-6C alkoxy, aryl or heteroaryl, or R 10+R' 10 forms an optionally oxo-substituted mono- or bicyclic group optionally containing another heteroatom; R 4H, NO 2, R 7, SO 2R 9, R or OR; R 9NH 2 or 1-6C (halo)alkyl. Independent claims are also included for: (1) two processes for preparing (I); (2) combination of a compound (I) and an anticancer agent selected from genotoxic agents, mitotic poisons, antimetabolites, proteasome inhibitors and kinase inhibitors. [Image] ACTIVITY : Cytostatic. N-((4aR)-3-(4'-chloro-2-biphenylylmethyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinolin-8-ylcarbonyl)-4-((1R)-3-dimethylamino-1-(phenylthiomethyl)propylamino)-3-nitrobenzenesulfonamide dihydrochloride had an IC50 of 0.305 mu M against H146 tumore cells. MECHANISM OF ACTION : Apoptosis promoter; Caspase 3 promoter. |
