| 摘要 |
Use of bicyclic heterocyclic compounds (I) to prepare medicaments for inhibiting beta -lactamase production by pathogenic bacteria. Use of bicyclic heterocyclic compounds of formula (I) and their salts to prepare medicaments for inhibiting beta -lactamase production by pathogenic bacteria. R 1=H, COOH, CN, COOR, CONR 6R 7, (CH 2) xR 5 or C(=NR 6)NHR 7; R=1-6C alkyl (optionally substituted by pyridyl or CONH 2), 3-9C alkenyl, or 6-10C aryl or 7-11C aralkyl (both optionally ring-substituted by OH, NH 2, NO 2, 1-6C alkyl, 1-6C alkoxy or halo); R 6, R 7=H, 1-6C alkyl (optionally substituted by pyridyl), 6-10C aryl or 7-11C aralkyl (both optionally substituted by CONH 2, NHCONH 2 or NMe 2); x=1 or 2; R 5=COOH, CN, OH, NH 2, CONR 6R 7, COOR, OR, OCHO, OCOR, OCOOR, OCONHR, OCONH 2, NHR, NHCOH, NHCOR, NHSO 2R, NHCOOR, NHCONHR or NHCONH 2; R 2=H or (CH 2) yR 5; y=0-2; R 3=H or 1-6C alkyl; A=bond, -CH(R 4)-,=C(R 4)- or -C(R 4)=; R 4=H or (CH 2) yR 5; n=1 or 2; X=-CO-B- bonded to N through the C atom; B=-O(CH 2) z- bonded to CO through the O atom, or -NR 8-(CH 2) z- or -NR 8'-O- bonded to CO through the N atom; z=0 or 1; R 8=OH, R, OR, Y, OY, Y 1, OY 1, Y 2, OY 2, Y 3, OCH 2CH 2SO mR, OSiR aR bR c or SiR aR bR c; R 8'=H, R, Y, Y 1, Y 2, Y 3 or SiR aR bR c; R a, R b, R c=1-6C alkyl or 6-10C aryl; m=0-2; Y=COH, COR, COOR, CONH 2, CONHOH, CONHSO 2R, CH 2COOH, CH 2COOR, CH 2CONHOH, CH 2CONHCN, CH 2tetrazole (optionally protected), CH 2SO 3H, CH 2SO 2R, CH 2PO(OR) 2, CH 2PO(OR)(OH), CH 2PO(R)(OH) or CH 2PO(OH) 2; Y 1=SO 2R, SO 2NHCOH, SO 2NHCOR, SO 2NHCOOR, SO 2NHCONHR, SO 2NHCONH 2 or SO 3H; Y 2=PO(OH) 2, PO(OR) 2, PO(OH)(OR) or PO(OH)(R); Y 3=tetrazole (optionally substituted by R), NH or NR tetrazole (optionally substituted by R), NHSO 2R or NRSO 2R; and provided that R 1-R 3 are not all H when R 4 is H and X is COO, COOCH 2, CON(iPr)CH 2, CONH or CON(Ph). An independent claim is also included for compositions comprising a compound (I) and a beta -lactamine drug. [Image] ACTIVITY : Antibacterial. MECHANISM OF ACTION : Bacterial beta -Lactamase Production Inhibitor. Benzyl trans-3-benzoyl-2-oxo-1,3-diazabicyclo[2.2.1]heptane-6-carboxylate (Ia) had IC 50 values of 55 nM against Tem1 beta -lactamase and 17 nM against P99 beta -lactamase. |
