Albicidin derivatives, their use and synthesis

Patent metadata

Field	Value
Publication number	US-11358987-B2
Application number	US-201917042815-A
Country	US
Kind code	B2
Filing date	Mar 28, 2019
Priority date	Mar 29, 2018
Publication date	Jun 14, 2022
Grant date	Jun 14, 2022

Abstract

It is provided a chemical compound according to general formula (1)

First claim

The invention claimed is:

1. A compound having a molecular structure as defined by a general formula (1)

a) with XB being independently from each other N or CR 14 ;
b) with XD being independently from each other N or CR 13 ;
c) with XE being independently from each other N or CR 11 ;
d) with XF being independently from each other N or CR 10 ;
wherein at least one of XB, XD, XE and XF must be N;

with each R 10 , R 11 , R 13 and R 14 being selected independently from —H, —OH, —F, —Cl, —Br, —I, —CCH, —CN, —N 3 , —OC 1 -C 6 alkyl that is optionally substituted with OH or F, —OCF 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —C 1 -C 6 alkyl, —(CH 2 )m-OR a , —CHCH 2 , —CH 2 OH, —SO 2 NH 2 , —SO 2 N(CH 3 ) 2 , —SO 2 NHCH 3 , —CF 3 , —NO 2 , —O—PO 3 H 2 , —O—PO 3 R a H, or —O—PO 3 R a2 ,
with R a being
hydrogen,

with m being selected from 0, 1 or 2,
e) with BC being selected from

with L 1 being a five membered or six membered aromatic heterocycle or 3-7 membered non-aromatic heterocycle,
with Rt being selected from H or C 1 -C 4 alkyl,

with L 2 being

f) with X 1 being BA-CONR 8 — with BA being selected from

with R 2 and R 3 being selected, where applicable, independently from each other from —H, —F, —CN, —OH, a substituted or unsubstituted C 1 -C 3 alkyl, a substituted or unsubstituted C 1 -C 3 alkoxy, or a C 1 -C 3 haloalkyl, with R 2 and R 3 optionally being selected, where applicable, independently from each other from —H, —F, —CN, —OH, —CH 3 , —CH 2 CH 3 , —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH(CH 3 ) 2 , —OCF 3 , —CH 2 CF 3 , —CHFCF 3 , —CF 2 CF 3 , —CHF 2 , —CH 2 F or —CF 3 ,
with E being,
a substituted or unsubstituted C 1 -C 16 alkyl, a substituted or unsubstituted C 2 -C 16 alkenyl, a substituted or unsubstituted C 2 -C 16 alkynyl,
a substituted or unsubstituted C 3 -C 10 heterocycle,
a substituted or unsubstituted C 5 -C 10 heteroaryl, or
a substituted or unsubstituted C 6 -C 10 aryl;
f) with each R 8 being H, and
g) with T being
—CO 2 H.

2. The compound according to claim 1 , wherein independently from each other XB, XD, XE and XF are one, two, three or four N and one, two, three or four CR 10 , CR 11 , CR 13 and CR 14 , respectively.

3. The compound according to claim 1 , wherein
one or two of XB is N and none of XD, XE, XF is N, or
one or two of XD is N and none of XB, XE, XF is N, or
one or two of XE is N and none of XB, XD, XF is N, or
one or two of XF is N and none of XB, XD, XE is N.

4. The compound according to claim 1 , wherein
one or two of XB is N and one or two of XD is N and none of XE, XF is N, or
one or two of XB is N and one or two of XE is N and none of XD, XF is N, or
one or two of XB is N and one or two of XF is N and none of XD, XE is N, or
one or two of XD is N and one or two of XE is N and none of XB, XF is N, or
one or two of XD is N and one or two of XF is N and none of XB, XE is N, or
one or two of XE is N and one or two of XF is N and none of XB, XD is N.

5. The compound according to claim 1 , wherein
one or two of XB is N, one or two of XD is N and one or two of XE is N and none of XF is N, or
one or two of XB is N, one or two of XD is N and one or two of XF is N and none of XE is N, or
one or two of XB is N, one or two of XE is N and one or two of XF is N and none of XD is N, or
one or two of XD is N, one or two of XE is N and one or two of XF is N and none of XB is N.

6. The compound according to claim 1 , wherein each R 10 , R 11 , R 13 and R 14 independently from being selected from —OH, —F, —OCH 3 , —OC 2 H 5 , —OC 3 H 7 , —OCF 3 , —CF 3 or —(CH 2 )m-OR a ,
with Ra being selected from hydrogen, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , —C(CH 3 ) 3 , —C 6 H 5 —CH 2 C 6 H 5 , and
with m being selected from 1 or 2.

7. The compound according to claim 1 , wherein moiety L 1 is a five membered aromatic N-heterocycle selected from a group comprising substituted or unsubstituted:
pyrroles, imidazoles, pyrazoles, triazoles, or tetrazoles;
pyrazolones, triazolones, imidazolones, or pyrrolidones,
thiadiazoles, thiazoles, isothiazoles, or thiazolidinediones; or
isoxazoles, oxazoles, or oxadiazoles.

8. The compound according to claim 1 , wherein L 1 is a triazole.

9. The compound according to claim 1 , wherein L 1 is a five membered non-aromatic N-heterocycle selected from a group comprising substituted or unsubstituted:
pyrrolidines or pyrazolidines,
hydantoines, imidazolidinones, isoxazolidines, or oxazolidinones, and
isothiazolidines, or isothiazolinone.

10. The compound according to claim 1 , having a molecular structure as defined by the general formula (5)

11. The compound according to claim 1 , having a molecular structure as defined by the general formula (6)

12. The compound according to claim 1 , wherein X 1 is BA-CONHR 8 —, with BA being BA1, and with E being

with n of R 1 n being 0, 1, 2, 3, 4 or 5, and
with each R 1 independently from any other R 1 being selected from —OH, —F, —Cl, —Br, I, —CCH, —CN, —N 3 , —OCH 3 , —OC 2 H 5 , —OC 3 H 7 .

13. A method of treating a disease of bacterial infections by gram-negative or gram-positive bacterial strains, wherein the bacterial infection is an infection by one of the genus Acinetobacter, Bacillus, Escherichia, Klebisella, Micrococcus, Mycobacterium, Pseudomonas , or Salmonella , the method comprising administering to a subject the compound according to claim 1 .

14. The compound according to claim 1 , wherein:
each R 10 , R 11 , R 13 and R 14 being selected independently from H, —OH, —F, —OCH 3 , —OC 2 H 5 , —OiC 3 H 7 , —OnC 3 H 7 , —OCF 3 or —CF 3 ;
the —C 1 -C 6 alkyl is —CH 3 or —CH 2 CH 3 ;
each R 2 and R 3 being selected independently from each other from —H, —F, —OCH 3 or —CH 3 ; and
with E being:
a substituted or unsubstituted C 1 -C 8 alkyl, a substituted or unsubstituted C 2 -C 8 alkenyl, a substituted or unsubstituted C 2 -C 8 alkynyl, a substituted or unsubstituted C 3 -C 10 cycloalkyl, or a substituted or unsubstituted C 4 -C 10 heterocycle.

15. The compound according to claim 6 , wherein one of R 10 , R 11 and R 13 is —OH, OCH 3 , —OC 2 H 5 or —OiPr.

16. The compound according to claim 7 , wherein L 1 is substituted or unsubstituted: 3H-pyrazol-3-ones, 4H-pyrazol-4-ones, 1,2-dihydro-3H-pyrazol-3-ones, 2,4-dihydro-3H-pyrazol-3-ones, 1,2,4-triazol-3-ones, 1,3,4-thiadiazoles, 1,3,4-oxadiazoles or 1,2,4-oxadiazoles.

17. The compound according to claim 9 , wherein L 1 is substituted or unsubstituted: imidazolidin-4-ones, or 1,3,-oxazolidin-2-ones.

18. The compound according to claim 12 , wherein R1 is OiPr, —OCF3, —NH2, —NHCH3, —N(CH3)2, —CH3, —CH2-CH3, —CF3, —OCONH2, —NO 2 , —OCH2O

Assignees

• Univ Berlin Tech

Inventors

• Suessmuth Roderich
• Graetz Stefan
• Behroz Iraj
• Von Eckardstein Leonard
• Durkin Patrick Michael
• Weston John
• Zborovsky Lieby

Classifications

• C07K7/06 Primary

  having 5 to 11 amino acids · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D401/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D403/14

  containing three or more hetero rings · CPC title