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US 2017/0281532 A1Published application
2 substituted cephem compounds
AssigneesGlaxo Group Limited, Shionogi & Co., Ltd.
InventorsToshiaki AOKI, Hiroki KUSANO, Xiangmin LIAO, Neil David PEARSON, Israil PENDRAK, Jun SATO, Reema K. THALJI, Kenji YAMAWAKI, Katsuki YOKOO
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Abstract
The compounds of the subject invention are related to 2-substituted cephem compounds, which have a wide antimicrobial spectrum, in particular exhibit potent antimicrobial activity against beta-lactamase producing Gram negative bacteria, and pharmaceutical compositions comprising the same.
Claims47
A compound of Formula (I):
- wherein;
- R1 is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group;
- R2A and R2B is selected from:
- a) R2A is hydrogen, optionally substituted amino, —SO3H, optionally substituted amino sulfonyl, carboxyl, optionally substituted (lower alkyl)oxycarbonyl, optionally substituted carbamoyl, hydroxyl, or substituted carbonyloxy;
- and R2B is hydrogen, provided that R2A and R2B are not hydrogen at the same time, or
- b) R2A and R2B are taken together to form optionally substituted methylidene or optionally substituted hydroxyimino;
- R3 is hydrogen, —OCH3 or —NH—CH(═O);
- R5A and R5B is selected from:
- a) R5A and R5B are each independently hydrogen, or lower alkyl and R5A and R5B are not hydrogen at the same time,
- b) R5A and R5B may be taken together with the neighboring atom to form optionally substituted carbocycle or a optionally substituted heterocyclic group, or
- c) R5A and R5B may be taken together to form optionally substituted methylidene;
- L is —CH2—, —CH═CH—, —CH2—CH═CH—, —CH═CH—CH2—, —S—, —CH2—S—, —CH═CH—S— or —CH═CH—CH2—S—;
- E is an optionally substituted divalent group having at least one quaternary ammonium ion;
- R10 is hydrogen or a group represented by the formula (I-B)
- wherein,
- ring A is a benzene ring, monocyclic heterocycle or fused heterocycle;
- n is an integer from 0 to 2;
- each R4 is independently hydrogen, halogen, oxo, —OH, —CN, —NO2, —O—C(═O)—R9, —C(═O)—R9, —C(═O)—OH, —C(═O)—OR9, —OR9′, —NR9R9, —SO2R9, —SR9, —NR9—C(═O)—R9, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
- provided that two hydroxyl groups on ring A bind respectively to carbon atoms each adjacently locates;
- each R9 is independently lower alkyl or halo(lower)alkyl;
- G is a single bond, optionally substituted lower alkylene, optionally substituted alkenylene or optionally substituted alkynylene;
- B is non-existent, a single bond or a 5- or 6-membered heterocyclic group containing at least 1-3 nitrogen atoms;
- D is non-existent, a single bond, —C(═O)—, —O—C(═O)—, —C(═O)—O—, —NR6—, —NR6—C(═O)—, —C(═O)—NR6—, —C(═O)—C(═O)—, —NR6—C(═O)—NR6—, —C(═O)—C(═O)—NR6—, —C(═O)—NR6—C(═O)—, —NR6—C(═O)—C(═O)—, —NR6—NR6—C(═O)—, —C(═O)—NR6—NR6—, —N═N—C(═O)—, —C(═O)—N═N—, —C═N—NR6—C(═O)—, —C═N—C(═O)—, —N═C—C(═O)—, —C═N—C(═O)—NR6—, —NR6—C(═O)—C(═N—OR6)—, —C(═N—OR6)—C(═O)—NR6—, —NR6— C(═N—OR6)—, —C(═N—OR6)—NR6—, —C(═O)—C(═N—OR6)—, —C(═N—OR6)—C(═O)—, —O—, —S—, —S(═O)—, —S(═O)2—NR6—, —NR6—S(═O)2—, —NR6—CH2—, —CH2—NR6— or —S(═O)2—;
- each R6 is independently hydrogen or optionally substituted lower alkyl;
- provided that:
- when R10 is hydrogen, E is an optionally substituted divalent cyclic group having at least one quanternary ammonium ion and at least two hydroxyl groups which bind respectively to carbon atoms each adjacently locates on the cyclic group;
- or
- an ester at carboxyl group, an amino-protected compound when the amino is present on a ring in the 7-side chain;
- or a pharmaceutically acceptable salt thereof.
26 more elements
Dependencies are inferred from the claim text.