Cephem compound having pyridinium group

Patent metadata

Field	Value
Publication number	US-9242999-B2
Application number	US-201214129631-A
Country	US
Kind code	B2
Filing date	Jun 26, 2012
Priority date	Jun 27, 2011
Publication date	Jan 26, 2016
Grant date	Jan 26, 2016

Abstract

The present invention provides a novel compound which has a broad antibacterial spectrum and particularly exhibits a high antibacterial activity on β-lactamase-producing gram-negative bacteria. Specifically provided are: a compound represented by formula (I)

wherein the meaning of each symbol is as defined in the description, an amino-group-protected form of a type of the compound which has the amino group on a ring in a position-7 side chain, or a pharmaceutically acceptable salt of the compound or the amino-group-protected form; and a pharmaceutical composition containing the compound, the amino-group-protected form or the pharmaceutically acceptable salt.

First claim

The invention claimed is:

1. A compound of the formula:

or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof, wherein
W is —CH 2 ;
U is —S—, —S(═O)— or —O—;
L is a single bond, an optionally substituted lower alkylene group, an optionally substituted lower alkenylene group or an optionally substituted alkynylene group;
R 1 is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group;
with regard to R 2A and R 2B ,
R 2A and R 2B are taken together to form an optionally substituted methylidene group or an optionally substituted hydroxyimino group;
R 3 is a hydrogen atom, —OCH 3 or —NH—CH(═O);
R 11 is

ring E is an optionally substituted pyridinium ring or an optionally substituted fused ring containing pyridinium ring;

R 10 is a group represented by the formula:

wherein
ring A is a benzene ring, or a 6-membered aromatic heterocyclic group having 1-3 nitrogen atoms;
k is an integer from 2 to 5;
each R 4 is independently a hydrogen atom, halogen, hydroxyl group, —CN, —C(═O)—R 5 , —C(═O)—OH, —C(═O)—OR 5 , or —OR 5 ;
R 5 is a lower alkyl group or halo(lower)alkyl group; and
G is a single bond, an optionally substituted lower alkylene group, an optionally substituted alkenylene group or an optionally substituted alkynylene group;
M is a single bond or a 5- or 6-membered heterocyclic group containing at least 1 nitrogen atom;
D is a single bond, —CO—, —O—CO—, —CO—O—, —NR 6 —, —NR 6 —CO—, —CO—NR 6 —, —NR 6 —CO—NR 6 —, —O—, —S—, —SO—, —SO 2 —NR 6 —, —NR 6 —SO 2 —, —CH 2 —NR 6 —CO— or —SO 2 —;
each R 6 is independently a hydrogen atom or an optionally substituted lower alkyl group;
with the proviso that at least two R 4 are hydroxyl groups which bind respectively to adjacent carbon atoms on ring A.

2. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein G is a single bond, —CH 2 —, —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —, —CH═CH—, —CH═CH—CH 2 —, —CH 2 —CH═CH—, —CH 2 —CH(CH 3 )—, —CH 2 —CH( i Pr)- or —CH 2 —CH(Ph)- wherein i Pr is isopropyl group and Ph is phenyl group.

3. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein M is a single bond or a group represented by the formula:

wherein the bond of the left side is attached to G and the bond of the right side is attached to D.

4. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein D is a single bond, —CO—, —O—CO—, —CO—O—, —NR 6 —, —NR 6 —CO—NR 6 —, —NR 6 —CO— or —CO—NR 6 — wherein R 6 is as defined in claim 1 .

5. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the formula:

wherein each R 4 is independently hydrogen, halogen, hydroxyl group, —CN, —C(═O)—R 5 , —C(═O)—OH, —C(═I)—OR 5 or —OR 5 ; and R 5 is as defined in claim 1 .

6. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 5 , wherein the formula:

7. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 5 , wherein the formula:

8. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the formula:

is selected from

wherein the ring is optionally substituted.

9. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 8 , wherein the formula:

is selected from

wherein the ring is optionally substituted.

10. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 8 , wherein the formula:

wherein the ring is optionally substituted.

11. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein U is —S—.

12. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 3 is a hydrogen atom or —OCH 3 .

13. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R I is an optionally substituted phenyl.

14. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is represented by the formula:

wherein X is N, C(—H) or C(—Cl).

15. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 14 , wherein X is N.

16. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 14 , wherein X is C(—H) or C(—Cl).

17. The compound or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein with regard to R 2A and R 2B ,
b) R 2A and R 2B are taken together to form a substituted methylidene

Assignees

• Nishitani Yasuhiro
• Aoki Toshiaki
• Shionogi & Co

Inventors

• Nishitani Yasuhiro
• Aoki Toshiaki

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• C07D501/59

  with hetero atoms directly attached in position 3 · CPC title

• C07D505/00

  Heterocyclic compounds containing 5-oxa-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: [IMAGE cpc-sch-C07D-0995.gif] , e.g. oxacephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring · CPC title

• C07D501/36 Primary

  Methylene radicals, substituted by sulfur atoms · CPC title

• C07D501/04

  from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents · CPC title