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US 2003/0191105 A1Published application
Antibacterial cephalosporins
AssigneeSandoz Ltd.
InventorsGerd Ascher, Johannes Ludescher
Life of this patent
Estimating the term…
Abstract
A compound of formula 1 wherein Ac, R1 and R2 have various meanings, a process for a preparation thereof and its use as a pharmaceutical, i.e. as antibacterial agent.
Claims23
A compound of formula
- 199
- wherein
- R1 denotes hydrogen or an ester moiety,
- R2 denotes a group of formula
- 200
- wherein
- Y denotes hydrogen, alkyl, alkenyl, acyl, carbamoyl or aryl
- R4 denotes hydrogen, alkyl, alkenyl, cycloalkyl, aryl, acyl or heterocyclyl
- R5 denotes hydrogen, alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl, or a group of formula
- 201
- wherein
- R7 denotes alkyl or aryl
- R8 denotes hydrogen, cycloalkyl or alkyl
- R9 denotes hydrogen or alkyl
- R10 denotes hydrogen, alkyl, hydroxy, amino, phenyl, alkenyl, cycloalkyl, aryl, heterocyclyl or a group of formula
- —N═CH-Phe
- wherein Phe denotes aryl
- R9 and R10 together with the nitrogen atom denote heterocyclyl,
- Z denotes oxygen, sulphur or N—R13, wherein
- R13 denotes hydrogen, alkyl or cycloalkyl
- R11 denotes hydrogen, alkyl, aryl, cycloalkyl or heterocyclyl, or
- R4 and R5 together with the nitrogen atom denote heterocyclyl,
- R6 denotes heterocyclyl, and
- Ac denotes
- (i) a group
- 202
- (ii) a group of formula
- 203
- wherein
- B denotes N or CH
- Z1 denotes aryl, cycloalkyl, 1,4-cyclohexadienyl or heterocyclyl
- Z2 denotes hydrogen, alkyl or —CH2COOZ5, wherein
- Z5 denotes hydrogen, alkyl or cycloalkyl
- Z3 denotes hydrogen or alkyl
- Z4 denotes hydrogen or an organic radical
- D denotes oxygen or CH2.
33 more elements
A compound of anyone of claims 1 to 3 of formula
- 208
- wherein
- R1s is the same as R1 in formula IA,
- Vs is the same as V in formula IA,
- Ws is the same as W in formula IA
- R3s denotes hydrogen, lower acyl;
- unsubstituted alkyl;
- substituted lower alkyl, by carboxyl and/or fluoro;
- and
- R2s denotes a group of formula
- 209
- wherein
- Ys denotes hydrogen;
- unsubstituted lower alkyl;
- or substituted alkyl by carboxyl,
- R4s denotes hydrogen or lower alkyl, and
- R5s denotes hydrogen;
- saturated or unsaturated, unsubstituted heterocyclyl having 5 or 6 ring members and 1 to 3 nitrogen hetero atoms;
- saturated or unsaturated one or several fold substituted heterocyclyl by oxo, lower alkyl, amino or CF3, having 5 or 6 ring members and 1 to 3 nitrogen hetero atoms;
- benzothiazolyl;
- or a group of formula
- 210
- wherein
- Zs is the same as Z in formula I,
- R7s denotes lower alkyl,
- R8s denotes hydrogen, cycloalkyl or lower alkyl,
- R9s denotes hydrogen or lower alkyl,
- R10s denotes hydrogen;
- phenyl;
- allyl;
- cycloalkyl;
- unsubstituted alkyl;
- substituted alkyl by CF3, dialkylamino, trialkylamino, hydroxy, pyridyl or SO3H, and
- R11s denotes hydrogen;
- pyridyl;
- cycloalkyl;
- unsubstituted lower alkyl;
- substituted lower alkyl by pyridyl or trialkylamino;
- saturated or unsaturated heterocyclyl having 5 or 6 ring members and 1 to 3 nitrogen hetero atoms;
- or one or several fold substituted heterocyclyl by lower alkyl and/or thiono, having 5 or 6 ring members and 1 to 3 nitrogen hetero atoms;
- R4s and R5s together with the nitrogen atom denote heterocyclyl selected from saturated, unsubstituted heterocyclyl having 5 or 6 ring members and 1 or 2 nitrogen hetero atoms;
- saturated, one or several fold substituted heterocyclyl by oxo or lower alkyl, having 5 or 6 ring members and 1 or 2 nitrogen hetero atoms;
- and/or
- R9s and R10s together with the nitrogen atom denote saturated, unsubstituted heterocyclyl having 5 or 6 ring members and 1 or 2 nitrogen and/or oxygen hetero atoms;
- unsaturated, one or several fold substituted heterocyclyl by CHO or lower alkyl, having 5 or 6 ring members and 1 or 2 nitrogen and/or oxygen hetero atoms.
42 more elements
7-[[(2-amino-4-thiazolyl)-(Z)-(hydroxyimino)acetyl]amino]-3-[[(aminoiminomethyl)-hydrazono]methyl]-3-cephem-4-carboxylic acid;
- 7-[[(2-amino-4-thiazolyl)-(Z)-(hydroxyimino)acetyl]-amino]-3-[[(piperazino-iminomethyl)-hydrazono]methyl]-3-cephem-4-carboxylic acid;
- 7-[[(5-Amino-1,2,4-thiadiazol-3-yl)-(Z)-(fluormethoxyimino)acetyl]amino]-3-[[(piperazinoiminomethyl)hydrazono]methyl]-3-cephem-4-carboxylic acid.
A compound of formula
- 213
- wherein
- R1p is the same as R1 in formula I,
- Ac is as defined in formula I,
- R2p denotes a group of formulae
- 214
- wherein
- Yp is the same as Y in formula IA,
- R4p is the same as R4 in formula IA, and
- R5p denotes hydrogen, cycloalkyl, lower alkyl or a group of formula
- 215
- wherein
- R8p is the same as R8 in formula IA,
- Zp is the same as Z in formula IA,
- R9p is the same as R9 in formula IA,
- R7p denotes methyl,
- R10p denotes hydrogen, lower alkyl or hydroxy, and
- R4p and R5p and/or R9p and R10p independently of one another together with the nitrogen denote heterocyclyl, and
- a compound of formulae IIbp, IIdp and IIep denote any tautomeric form, in free form, or, where such a form exists, in form of an acid addition salt, inner salt, quaternary salt or hydrate thereof.
16 more elements
A compound of formula
- 216
- wherein
- Ac is as defined in formula I
- R1q is he same as R1 in formula IA, and
- R2q denotes a group of formulae
- 217
- wherein
- Yq is the same as Y in formula IA,
- R4q is the same as R4 in formula IA, and
- R5q denotes hydrogen, cycloalkyl, lower alkyl or a group of formulae
- 218
- wherein
- R7q is the same as R7 in formula IA,
- R8q is the same as R8 in formula IA,
- Zq is the same as Z in formula IA,
- R9q is the same as R9 in formula IA,
- R10q denotes hydrogen, lower alkyl or hydroxy, and
- R4q and R5q and/or R9q and R10q independently of one another together with the nitrogen denote heterocyclyl, and
- a compound of formulae IIbp, IIdp and IIep denote any tautomeric form, in free form, or, where such a form exists, in form of an acid addition salt, inner salt, quaternary salt or hydrate thereof.
16 more elements
A compound of formula
- H2N—R2i IVi
- wherein
- R2i denotes a group of formula
- —N(R4iR5i) IIbi
- wherein
- R4i is the same as R4 in formula I,
- R5i denotes a group of formula
- 221
- wherein
- Zi denotes N—R13i, wherein
- R13i is hydrogen, alkyl or cycloalkyl, and
- R9i and R10i together with the nitrogen atom denote heterocyclyl which is a piperazinyl;
- or
- R4i is the same as R4 in formula I, and
- R5i denotes a group of formula
- 222
- wherein
- R8i denotes alkyl, preferably at least C2 alkyl;
- or cycloalkyl, preferably cyclopropyl, and
- R7i denotes alkyl, preferably methyl;
- and
- R4i is the same as R4 in formula I and
- R5i denotes a group of formula
- 223
- wherein
- Zi denotes N—R13i, wherein
- R13i denotes hydrogen, alkyl or cycloalkyl
- R9i denotes hydrogen and
- R10i denotes CH2CF3, C(CH3)3, OH or an alkyl group having at least 2 carbon atoms which is substituted by dialkyl amine or trialkyl ammonium, hydroxy;
- or
- R4i is the same as R4 in formula I,
- R5i denotes a group of formula
- 224
- wherein
- Z1 denotes N—R13i, wherein
- R13i denotes alkyl, and
- R9i and R10i together with the nitrogen atom denote heterocyclyl which is morpholyl or pyrrolidinyl;
- or
- R4i is the same as R4 in formula I and denotes preferably hydrogen
- R5i denotes a group of formula
- 225
- wherein
- Zi denotes N—R13i, wherein
- R13i denotes hydrogen, alkyl or cycloalkyl,
- R9i denotes hydrogen, and
- R10i denotes cycloalkyl;
- or
- R4i is the same as R4 in formula I,
- R5i denotes a group of formula
- 226
- wherein
- Zi denotes N—R13i, wherein
- R13i denotes hydrogen, alkyl or cycloalkyl,
- R9i denotes hydrogen or alkyl, and
- R10i denotes a group
- —N=CH-Phe
- wherein Phe denotes phenyl or
- R4i is the same as R4 in formula I,
- R5i denotes a group of formula
- 227
- wherein
- Zi denotes N—R13i, wherein
- R13i denotes hydrogen, alkyl or cycloalkyl,
- R11i denotes a dihydroxyphenyl or substituted pyrrolyl by alkyl;
- or
- Zi denotes oxygen and
- R11i denotes the group of formula
- 228
65 more elements
A compound of formulae I, IA, Is, Ip, Iq, IVi, IVa or VIa according to any preceding claim in free form.
A compound of formulae I, IA, Is, Ip, Iq, IVi, IVa or VIa according to any preceding claim in salt form.
A method of treatment of microbial diseases which comprises administering to a subject in need of such treatment an effective amount of a compound of formula I.
Dependencies are inferred from the claim text.