| abstract |
(N.B. the claims are not written in the usual way). Antibacterial cpds. are claimed which contain one or more phosphonic acid gps. (esp. geminal or vicinal bisphosphonic acid gp(s). (A) or bisphosphonic acid alkyl ester gps. (B)) as osteotropic molecule fragments; their prodn. and use for the prophylaxis and therapy of infections in the region of bone. Also claimed are gyrase inhibitors (quinolones) of formula (I), sulphonamides of formula (II), and beta -lactam antibiotics (III), where (III) are cpds. with penam, carbapenem or cephem gps., esp. penicillin, oxymethyl penicillin, sulphone penicillin, thienamycin, cephalosporin, oxymethyl cephalosporin, oxacephalosporin gps., and gp(s) (A) and/or (B), such as the cpds. of formula (3) and (4). X, Y, Z = CR2 or N; R1 = alkyl, cycloalkyl, aryl, heteroaryl, (which are opt. substd. by alkyl, NH2, NO2, halo, OH or alkoxy), (pref. Et or cyclopropyl) or R11; R2 = H, halo, NO2, CN, acetyl, COOH, alkoxy or as for R1 (pref. F) or R21; R3 = H, cycloalkyl, aryl, heteroaryl, heterocycloalkyl or alkoxy (pref. F, piperazinyl or N-methylpiperazinyl) or R31; R4 = H or R41; provided at least one of R1-R4 is R11-R41, where the phosphonic acid-substd. gp. may be present as its alkyl ester or alkali metal or ammonium salt; R11 = alkyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl all substd. by Q; Q = CH(PO3H2)2, N(CH2PO3H2)2, C(OH)(PO3H2)2 or C(NH2)(PO3H2)2 R31 = a nitrogen-linked gp. as for R11; R41 = an amide- or ester-linked gp. as for R11. Pref. R11 = CH(PO3H2)2, CMe2CH2CH(PO3H2)2, CHCH2CH(PO3H2)2 (sic), CH(CH2CH(PO3H2)2)2, C6H4CH2PO3H2, esp. C6H4CH(PO3H2)2 or CH2CH2CH(PO3H2)2; R21 is esp. CH(PO3H2)2, CH2(PO3H2); R31 is pref. NHCH(PO3H2)2, NHCH2CH2CH(PO3H2)2, NHCMe2CH2CH(PO3H2)2, NHCHCH2CH(PO3H2)2 (sic), NHCH(CH2CH(PO3H2)2)2, NHC6H4CH(PO3H2)2, NHC6H4NHCH(PO3H2)2, NHC6H4NHCH(PO3H2)2, N(CH2PO3H2)2, esp. piperazinyl substd. on the N by COCH2CH2CH(PO3H2)2 or CH2CH(PO3H2)2; R41 is pref. NHCH(PO3H2)2, NHCH2CH2CH(PO3H2)2, N(CH2PO3H2)2, NHCMe2CH2CH(PO3H2)2, NHCHCH2CH(PO3H2)2 (sic), NHCH(CH2CH(PO3H2)2)2, NHC6H4CH(PO3H2)2, NHC6H4NHCH(PO3H2)2 or OC6H4(PO3H2)2 (sic); A = aryl, heteroaryl (opt. substit. e.g. with alkyl, alkoxy, NO2, NH2, halo, OH), (both with gps. (A) or (B), esp. Q); esp. C6H4CH(PO3H2)2 or C6H4NHCH(PO3H2)2; B = aryl, heteroaryl, cycloheteroaryl all opt. substd., including with Q. |