Albicidin derivatives, their use and synthesis

Patent metadata

Field	Value
Publication number	US-11225465-B2
Application number	US-201716631737-A
Country	US
Kind code	B2
Filing date	Dec 21, 2017
Priority date	Jul 18, 2017
Publication date	Jan 18, 2022
Grant date	Jan 18, 2022

Abstract

A chemical compound is provided according to general formula (1):

First claim

The invention claimed is:

1. A compound having a modular structure as defined by formula (1):

a) with BC being selected from:

with L 1 being a substituted or unsubstituted aromatic heterocycle or a substituted or unsubstituted non-aromatic heterocycle
with Rt being selected from H or C 1 -C 4 alkyl, or
with L 1 and Rt forming a non-aromatic heterocycle, which is optionally substituted,
with L 2 being —H,

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

with R 2 and R 3 being selected 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 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, or a substituted or unsubstituted C 3 -C 10 cycloalkyl,
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,
wherein at least one optional substituent is hydroxy or halogen;

c) with each R 8 being —H, or C 1 -C 4 alkyl, optionally substituted with one or more F,
d) with n of R 10 n and n of R 11 n being independently from each other 0, 1, 2, 3 or 4,
with each R 10 and R 11 being selected independently from any other R 10 and R 11 from:
—OH, —F, —Cl, —Br, —I, —CCH, —CN, —N 3 , or —OC 1 -C 6 alkyl, optionally substituted with OH or F; or
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 , —CH 3 , —CF 3 , —NO 2 , —O—PO 3 H 2 , —O—PO 3 R a H, or —O—PO 3 (R a ) 2 , —OCH 3 , —OC 2 H 5 , —O-i-C 3 H 7 , or —O-n-C 3 H 7 ,
with R a being selected from:
hydrogen,
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, or a C 1 -C 16 haloalkyl, or
a substituted or unsubstituted C 3 -C 10 cycloalkyl or a substituted or unsubstituted C 3 -C 10 halo cycloalkyl;
with m being selected from 0, 1 or 2,

e) with T being selected from:
CO 2 H, —SO 3 H, —C(═O)OR a or —CON(R a ) 2
with R a having the above meaning,

f) with n of R 13 n being 0, 1, 2, 3 or 4, and
with each R 13 being selected independently from any other R 13 from —OH, substituted or unsubstituted —C 1 -C 6 alkyl or substituted or unsubstituted C 1 -C 6 alkoxy.

2. The compound according to claim 1 , wherein moiety L 1 is a five membered or six membered aromatic heterocycle or 3-7 membered non-aromatic heterocycle, that may be substituted or unsubstituted.

3. The compound according to claim 1 , wherein L 1 is a five membered aromatic N-heterocycle selected from a group consisting of substituted or unsubstituted:
pyrroles, imidazoles, pyrazoles, triazoles, tetrazoles;
pyrazolone;
thiadiazoles; and
isoxazoles, oxazoles, and oxadiazoles.

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

5. The compound according to claim 1 , wherein L 1 is a six membered aromatic N-heterocycle selected from a group consisting of substituted or unsubstituted pyridines, pyridazines, pyrimidines, pyrazines, triazines and tetrazines.

6. The compound according to claim 1 , wherein L 1 is a six membered non-aromatic N heterocycle selected from a group consisting of substituted or unsubstituted piperidines and piperazines.

7. The compound according to claim 1 , having a modular structure as defined by the formula (2):

wherein X 1 , BC, R 8 , R 11 , R 10 , R 13 and T have the meaning defined in claim 1 .

8. The compound according to claim 1 , wherein:
X 1 is BA-CONHR 8 —, with BA being BA1, with R 2 and R 3 having the meaning defined in claim 1 , 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, —C 1 , —Br, I, —CCH, —CN, —N 3 , —OCH 3 , —OC 2 H 5 , —OC 3 H 7 , —O-i-Pr, —OCF 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —CH 3 , —CH 2 —CH 3 , —CF 3 , —OCONH 2 , —NO 2 , —OCH 2 O—, —O—PO 3 H 2 , —O—PO 3 R a H, —O—PO 3 (R a ) 2 or —(CH 2 ) m —OR a , with m and R a having the meaning defined in claim 1 .

9. The compound according to claim 1 , wherein:
n of R 10 n and n of R 11 n are 0, 1, 2, 3 or 4, and with each R 10 and with each R 11 independently from any other R 10 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 R a 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 , or —C(CH 3 ) 3 ,
with m being selected from 1 or 2.

10. The compound according to claim 1 , wherein:
T is —CO 2 H, —SO 3 H, —C(═O) OR a or —CONR a ,
with R a 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 , or —C(CH 3 ) 3 .

11. A compound having a modular structure as defined by formula (9):

wherein BC is selected from:

L 3 , L 4 being selected independently from each other from —H, —CH 3 , —CH 2 CH 2 CH 2 NHC(NR c )N(R b )(R a ), —CH 2 CON(R b )(R a ), —CH 2 C(═O)OR a , —CH 2 SR a , —CH 2 CH 2 C(═O)N(R b )(R a ), —CH 2 CH 2 C(═O)OR a , —CH 2 (C 3 H 3 N 2 ), —CH 2 CH 2 CH 2 NH 2 , —CH 2 CH 2 SCH 3 , —CH 2 (C 6 H 5 ), —CH 2 CH 2 CH 2 —, —CH 2 OR a , —CH(OR a )CH 3 , —CH 2 (C 8 H 6 N)OR a , —CH 2 (C 6 H 4 )OR a , —CH(CH 3 ) 2 , —CCH, —CN, —OCH 3 , —CF 3 , —R a , —CH(R b )(R a ), —CH 2 C(═O)R a , —C(═O)OR a , —OC(═O)NR b R a , —C(═O)NR b R a , —CH 2 C(═O)NR b (OR a ), —CH 2 S(O 2 )R a , —S(O 2 )OR a , —CH 2 S(O 2 )OR a , —CH 2 NR b C(═O)R a , —CH 2 NR b S(O 2 )R a , —CH 2 P(═O)(OR b )(OR a ), —CH 2 P(═O)(OR b )(R a ), —CH 2 P(═O)(R b )(R a ) or —CH 2 S(O 2 )NR b R a , and
with R a , R b , and R c being selected independently from each other from:
a substituted or unsubstituted C 1 -C 4 alkyl, a substituted or unsubstituted C 1 -C 4 alkoxy, a substituted or unsubstituted C 1 -C 4 carboxy, a substituted or unsubstituted C 2 -C 4 alkenyl, a substituted or unsubstituted C 2 -C 4 alkynyl, or a C 1 -C 4 haloalkyl, or
a substituted or unsubstituted C 3 -C 10 cycloalkyl or a substituted or unsubstituted C 3 -C 10 halo cycloalkyl, or
a substituted or unsubstituted C 3 -C 10 heterocycle or a substituted or unsubstituted C 3 -C 10 halo heterocycle, or
a substituted or unsubstituted C 5 -C 10 heteroaryl, or
a substituted

Assignees

• Univ Berlin Tech

Inventors

• Suessmuth Roderich
• Kerwat Dennis
• Graetz Stefan
• Behroz Iraj
• Von Eckardstein Leonard
• Durkin Patrick Michael
• Morkunas Marius
• Weston John

Classifications

• C07D213/56

  Amides · CPC title

• C07D249/04

  1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles · CPC title

• C07D233/64 Primary

  with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine · CPC title

• C07C255/28

  containing cyano groups, amino groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton · CPC title

• C07D229/02

  containing three-membered rings · CPC title