Patent JP-5368317-B2 (JP)
IPC: A61K31/405
Filed: 2008-01-31
Granted: 2013-12-18
Abstract: Indole derivatives (I) are used to prepare medicaments for treating bacterial diseases. Indoles derivatives of formula (I) are used to prepare medicaments for treating bacterial diseases. R : H, 1-7C (halo)alkyl, 1-7C alkoxy, 7-11C arylmethyl, CH 2NAA', CH 2CH 2NAA', NAA', 6-10C arylsulfonyl, PG, OH, OA" or trialkylsilyl; A, A' : H or 1-4C alkyl; A" : 1-7C alkyl optionally substituted with aryl or NH 2; PG : t-butoxycarbonyl, fluorenylmethoxycarbonyl, benzyloxycarbonyl, trifluoroacetyl or benzoyl; R 3H or halo; R 4-R 7H, 1-4C alkyl, CF 3, OH, 1-7C alkoxy, CH 2OH, CH 2OA", OCF 3, halo or NAA'; R 1= H, 1-6C alkyl, 7-11C arylmethyl, (CH 2) mNH 2 (optionally protected), 6-10C aryl (optionally substituted with NO 2 or OMe), CH 2OH (optionally protected) or CH 2SH (optionally protected); R 2H, OH, O ->, COCH 2ONH 2 (optionally protected), 1-10C acyl, 1-10C alkoxy, benzyloxy, 1-10C alkoxycarbonyl, benzyloxycarbonyl, OCONH 2 or OCSNH 2; B : N-CH(X)Ar, N +>=C(X)Ar, N-PG' or N-A; Ar : phenyl substituted with 1-3 of H, OH, 1-4C alkoxy and NAA'; X : H, 1-4C alkyl, 6-10C aryl, alkoxymethyk, arylmethoxymethyl or trialkylsilyloxymethyl; PG' : t-butoxycarbonyl or benzyloxycarbonyl. Independent claims are also included for: (1) 3-(1,2-di(t-butoxycarbonylamino)ethyl-5-R 5'-6-R 6'-indoles; (2) 3-(1-(N-benzyl-N-hydroxyamino)ethyl)-6-bromoindole, 3-(1-(N-(4-methoxybenzyl)-N-hydroxyamino)ethyl)-5-bromoindole, 3-(1-(N-(4-methoxybenzyl)-N-hydroxyamino)-2-t-butoxycarbonylaminoethy l)-5-bromoindole, 3-(1-(N-t-butoxycarbonyl-N-hydroxyamino)-2-t-butoxy carbonylaminoethyl)-6-bromoindole, 3-(1-benzylaminoethyl)-5-bromoind ole, 3-(1-(N-(4-methoxybenzylidene)-N-oxidoammonio)-2-t-butoxycarbony laminoethyl)-5-bromoindole, 3-(1-hydroxyamino-2-t-butoxycarbonylamino ethyl)-5-bromoindole, 3-(1-hydroxyamino-2-t-butoxycarbonylaminoethyl) -6-bromoindole, 3-(1-amino-2-t-butoxycarbonylaminoethyl)-5-bromoindo le, 3-(1-amino-2-t-butoxycarbonylaminoethyl)-6-bromoindole, 3-(1,2-diaminoethyl)-6-bromoindole dihydrochloride, 3-(1,2-diaminoethyl)-5-methoxyindole dihydrochloride, 3-(1,2-diaminoethyl)-6-methoxyindole dihydrochloride, 3-(2-amino-1-hydroxyaminoethyl)-5-bromoindole dihydrochloride, 3-(2-amino-1-hydroxyaminoethyl)-6-bromoindole dihydrochloride, 3-(1,2-di(t-butoxycarbonylamino)ethyl)indole, 3-(1,2-di(t-butoxycarbonylamino)ethyl)-5-bromoindole, 3-(1,2-di(t-butoxycarbonylamino)ethyl)-6-bromoindole, 3-(1-(N-benzyl-N-hydroxyamino)ethyl)-5-chloroindole, 3-(1-(N-(2,4-dimethoxybenzyl)-N-hydroxyamino)-3-methylbutyl)indole, 3-(1-(N-(4-methoxybenzyl)-N-hydroxyamino)-3-methylbutyl)-5--bromoind ole, 3-(alpha -(N-benzyl-N-hydroxyamino)-4-nitrobenzyl)indole, 3-(1-(N-benzylidene-N-oxidoammonio)ethyl)-5-bromoindole, 3-(1-(N-benzylidene-N-oxidoammonio)propyl)-5-bromoindole; (3) composition comprising a compound (I) and an antibiotic; (4) five processes for preparing various compounds (I). R 5', R 6' : H, 1-4C alkyl, CF 3, OCF 3, OH, 1-7C alkoxy, halo or NAA'. [Image] - ACTIVITY : Antibacterial. The minimum concentration of 3-(1-(N-benzyl-N-hydroxya mino)ethyl)-5-bromoindole capable of restoring the activity of ciprofloxacin (2 mu g/ml) against resistant Staphylococcus aureus strain SA-1199B was 25 mu g/ml. - MECHANISM OF ACTION : None given.