| 摘要 |
<p>Benzo or heterocyclo fused aza-bicycloalkane derivatives (I) are new. Also new are seven classes of intermediates. Benzo or heterocyclo fused aza-bicycloalkane derivatives of formula (I) and their salts with acids or bases are new. [Image] Either (i) R 1H, COOH, CN, COOR, (CH 2) pR 5, CONR 6R 7or -C(=NR 6)NHR 7; and R 3+R 4group completing a fused phenyl or 5 or 6-membered heterocyclic ring containing 1-4 of N, O and S as heteroatom(s), both optionally substituted (os) by one or more R'; or (ii) R 1+R 3group completing a fused ring as defined above; and R 4H or (CH 2) qR 5; R : 1-6C alkyl (os by pyridyl); CH 2-alkenyl having a total of 3-9C; or 6-10C aryl or 7-11C aralkyl (both os in the ring by OH, NH 2, NO 2, 1-6C alkyl, 1-6C alkoxy or one or more halo); R 5COOH, CN, OH, NH 2, CONR 6R 7, COOR, OR, OCHO, OCOR, OCOOR, OCONHR, OCONH 2, NHR, NHCOR, NHCHO, NHSO 2R, NHCOOR, NHCONHR or NHCONH 2; R 6, R 7H, 1-6C alkyl, 6-10C aryl, 7-11C aralkyl or pyridyl-(1-6C) alkyl; p : 1 or 2; q : 0-2; R' : H, 1-6C alkyl, 2-6C alkenyl, halo, NH 2, OH, OR, NHCHO, NHCOR, NHCOOR, COOH, COOR, C(Ph) 3or -CH 2CH 2S(O) mR; m : 0-2; R 2H, halo, R, S(O) mR, OR, NHCOR, NHCOOR or NHSO 2R; X : CO-B- (bonded to N via CO); B : O-(CH 2) r- (bonded to CO via O), NR 8(CH 2) r, NR 8-O (bonded to CO via N); r : 0-1; R 8H, OH, Y, OY, Y 1, OY 1, Y 2, OY 2, Y 3, OCH 2CH 2S(O) mR, SiR aR bR c, or OSiR aR bR c; R a, R b, R c1-6C alkyl or 6-10C aryl; Y : CHO, COR, COOR, CONH 2, CONHR, CONHOH, CONHSO 2R, CH 2COOH, CH 2COOR, CH 2CONHOH, CH 2CONHCN, optionally protected tetrazolylmethyl, CH 2SO 3H, CH 2SO 2R, CH 2P(O)(OR) 2, CH 2P(O)(OR)(OH), CH 2P(O)(R)(OH) or CH 2P(O)(OH) 2; Y 1SO 2R, SO 2NHCHO, SO 2NHCOR, SO 2NHCOOR, SO 2NHCONHR, SO 2NHCONH 2or SO 3H; Y 2P(O)(OH) 2, P(O)(OR) 2, P(O)(OH)(OR) or P(O)(OH)(R); Y 3Tet, squarate, NH-Tet, NR-Tet, NHSO 2R or NRSO 2R; Tet : tetrazolyl (os by R); n : 1 or 2. Independent claims are also included for: (1) preparation of (I); and (2) piperidine or homopiperazine derivative intermediates of formulae (II)-(VIII), their acid-addition salts (specifically the hydrochlorides or trifluoroacetates) and N-protected derivatives of (II). [Image] R' 1-R' 4, R' 8R 1-R 4, R 8, except that any OH, NH 2, NHR, CONHOH, free carboxylic, sulfonic or phosphoric/phosphonic acid, tetrazolyl or squarate groups are protected; Z'H : HO(CH 2) r, HNR' 8(CH 2) ror HNR 8O; either X 1H; and X 2Z'-CO-X 3; or X 1CO-X 3; and X 2Z'H; X 3carbonylating agent residue; A : H or protecting group. ACTIVITY : Antibacterial. 11 Tested compounds (I) (including the sodium salt of 1-methyl-5-(sulfooxy)-5,6,7,8-tetrahydro-4,7-methano-4H-pyrazolo (3,4-e) (1,3)-diazepin-6(1H)-one (Ia)) had MIC values in the following ranges (no specific values for individual compounds given): 1.25 Microg/ml against Staphylococcus aureusSG511 and Exp54146, less than 0.08-20 Microg/ml against Streptococcus pyogenesA561, less than 0.15-10 Microg/ml against Escherichia coliUC1894, less than 0.15 -20 Microg/ml against E. coliUC1894 250HT7 and less than 0.15-40 Microg/ml against Enterobacter cloacae. MECHANISM OF ACTION : None given in the source material.</p> |
