| 摘要 |
2,4-Diaminopyrimidine derivatives (I) are new. 2,4-Diaminopyrimidine derivatives of formula (I) are new. R 2-R 4H, halo, (halo)alkyl or (halo)alkoxy, provided that one is halo or CF 3; R 5H or halo; Z : CO or SO 2; D : H, cycloalkyl, or alkyl, alkenyl or alkynyl optionally substituted with halo, OR 8 or NR 8R 9, where alkyl can also be substituted with a C-bonded 5-membered heterocycloalkyl group optionally substituted with halo, alkyl or alkoxy; W' : a 4- to 10-membered mono- or bicyclic ring containing O, S, SO, SO 2, NR 10, CO, dioxolane, CF 2, CHOR 8 or CHNR 8R 9, where the ring can have a 1-3C bridge when W contains NR 10; NW'D= 4- to 7-membered azacycloalkyl substituted with R 1 and R 6 on the same C atom, optionally with a 1-3C bridge; R 10H; cycloalkyl; alkyl optionally substituted with naphthyl, halo, OH, alkoxy, aryl, heteroaryl, NR 8R 9, CONR 8R 9, phosphonate, alkylthio, alkylsulfonyl or optionally substituted heterocycloalkyl; or alkenylmethyl or alkynylmethyl optionally substituted with naphthyl, halo, OH, alkoxy, aryl and heteroaryl; R 1X 1R 7, X 2R 7, NRcQ, CH 2NRcQ or CONRcOR'c; R 6H or is R 6' when R 1= X 1R 7; X 1(CH 2) m; R 7optionally substituted heterocycloalkyl, aryl or heteroaryl; R 6'H, OH, (CH 2) nOH, CONRaRb, CH 2NRaRb, COOH or COOR; R : alkyl; X 2O, O(CH 2) m, CH(OH)(CH 2) n, CO, CONRc, CONRcO, CHNRaRb, C=NOH, C=NNH 2, (CH 2) n1NRc(CH 2) n2; Q : H or 1-4C alkyl optionally substituted with PO(OEt) 2, OH, OR, CF 3, CONR 8R 9 and SO 2R; n, n1, n2 : 0-3; m : 1-3; Rc, R'c : H or 1-4C (halo)alkyl; R 8, R 9H; alkyl optionally substituted with halo, OH, alkoxy, NH 2, NHR, NRR, CONH 2, CONHR, CONRR, alkylthio, optionally substituted phenyl or optionally substituted heterocyclyl; or (hetero)cycloalkyl optionally substituted with halo, OH, alkoxy, NH 2, NHR, NRR, CONH 2, CONHR, CONRR; or NR 8R 9 is an optionally substituted cyclic amine containing 0-2 other heteroatoms (O, S, N, NRc); Ra, Rb= H or 1-4C alkyl or cycloalkyl optionally substituted with halo, OH, OR, NH 2, NHR and NRR, or NRaRb is a cyclic amine containing 0-2 other heteroatoms (O, S, N, NRc), optionally substituted with halo or (halo)alkyl; N : all rings are optionally substituted with halo, OH, alkoxy, alkyl, hydroxyalkyl, alkoxyalkyl, CN, CF 3, OCF 3 or NRaRb. Independent claims are also included for two processes for preparing (I). [Image] - ACTIVITY : Antiinflammatory; Antidiabetic; Cytostatic. Unspecified compounds (I) inhibit proliferation of various tumor cell lines with an IC50 of less than 10 mu M. - MECHANISM OF ACTION : Protein kinase IKK inhibitor. |
