Albicidin derivatives, their use and synthesis

Patent metadata

Field	Value
Publication number	US-10308595-B2
Application number	US-201414768323-A
Country	US
Kind code	B2
Filing date	Feb 14, 2014
Priority date	Feb 15, 2013
Publication date	Jun 4, 2019
Grant date	Jun 4, 2019

Abstract

Antibiotically active compounds characterized by general formula (I), wherein X1, BB, BC, BD, BE and X2 are building blocks with D1, D2, D3, D4 or D5 being linkers which include carbon, sulphur, nitrogen, phosphor and/or oxygen atoms and which are covalently connecting the moities BA and BB, BB and BC, BC and BD, BD and BE and BE and BF, respectively, and wherein in particular the building block BC comprises an amino acid derivative. The compounds for use in a method of treatment of diseases, in particular for use in a method of treatment of bacterial infections are also disclosed.

First claim

The invention claimed is:

1. A compound having formula (23)

a. with X 1 being BA-D1 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 E being
a substituted or unsubstituted C 1 -C 16 alkyl, a substituted or unsubstituted C 1 -C 16 alkoxy, a substituted or unsubstituted C 1 -C 16 carboxy, 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, —
a substituted or unsubstituted C 3 -C 10 cycloalkyl or a substituted or unsubstituted C 3 -C 10 halo cycloalkyl,

a substituted or unsubstituted C 3 -C 10 heterocycle or a substituted or unsubstituted C 3 -C 10 halo heterocycle,
a substituted or unsubstituted C 5 -C 10 heteroaryl, or

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 the group consisting of —OH, —F, —Cl, —Br, —I, —CCH, —CN, —N3, —OCH3, —OCF3, —NH2, —NHCH3, —N(CH3)2, —CH3, —CH2—CH3, —CF3, —OCONH2 or —NO2, B(ORa)(ORb), —(CH2)m—Ra, —(CH2)m—ORa, —(CH2)m—C(═O)Ra, —(CH2)m—C(═O)ORa, —(CH2)m—OC(═O)Ra, —(CH2)m—OC(═O)ORa, —(CH2)m—OC(═O)NRaRb, —(CH2)m—C(═O)NRaRb, —(CH2)m—C(═O)NRaRb, —(CH2)m—C(═O)NRb(ORa), —(CH2)m—C(═S)Ra, —(CH2)m—C(═S)ORa, —(CH2)m—OC(═S)Ra, —(CH2)m—OC(═S)ORa, —(CH2)m—OC(═S)NRaRb, —(CH2)m—C(═S)NRaRb, —(CH2)m—SRa, —(CH2)m—S(═O)Ra, —(CH2)m—S(O2)Ra, —(CH2)m—S(O2)ORa, —(CH2)m—OS(O2)Ra, —(CH2)m—OS(O2)ORa, —(CH2)m—NRaRb, —(CH2)m—NRcC(═O)Ra, —(CH2)m—NRcC(═O)NRaRb, —(CH2)m—NRcC(═O)ORa, —(CH2)m—NRcC(═S)Ra, —(CH2)m—NRcC(═S)NRaRb, —(CH2)m—NRcC(═S)ORa, —(CH2)m—NRcS(O2)Ra, —(CH2)m—P(═O)(ORb)(ORa), —(CH2)m—P(═O)(ORb)(Ra) or —(CH2)m—S(O2)NRbRa, —(CH2)m—O—C(═O)—(M)—C(═O)OH, —(CH2)m—O—C(═O)—(M)—C(═O)ORa, —(CH2)m—O—C(═O)—(M)—Ra, —(CH2)m—O—(CH2)q—P(═O)(Rba)(Raa), —(CH2)m—C(═O)O—(CH2)q—P(═O)(Rba)(Raa), —(CH2)m—C(═O)O—(CH2)q—S(O2)OH or —(CH2)m—C(═O)O—(CH2)q—S(O2)ORa,
with Raa being selected independently from each other being —Ra or —ORa,
with Rba being selected independently from each other being —Rb or —ORb,
with M being a substituted or unsubstituted C1-C8 alkyl,
with m being selected from 0, 1 or 2,
with q being selected from 0, 1 or 2, and
with each Ra, Rb or Rc being selected independently from each other from
 hydrogen, —CN,
 a substituted or unsubstituted C1-C16 alkyl, a substituted or unsubstituted C1-C16 alkoxy, a substituted or unsubstituted C1-C16 carboxy, a substituted or unsubstituted C2-C16 alkenyl, a substituted or unsubstituted C2-C16 alkynyl, or a C1-C16 haloalkyl, a substituted or unsubstituted C3-C10 cycloalkyl, or a substituted or unsubstituted C3-C10 halo cycloalkyl,
 a substituted or unsubstituted C3-C10 cycloalkyl or a substituted or unsubstituted C3-C10 halo cycloalkyl,
a substituted or unsubstituted C3-C10 heterocycle or a substituted or unsubstituted C3-C10 halo heterocycle,
a substituted or unsubstituted C5-C10 heteroaryl,
a substituted or unsubstituted C6-C10 aryl;

b. with BC being selected from

with Y being selected from —CN, —C(═O)OH, —C(═O)OCH 3 , —C(═O)OCH 2 CH 3 , —C(═O)NHCH 3 , —C(═O)NHCH 2 CH 3 , —C(═O)N(CH 3 ) 2 , —C(═O)N(CH 2 CH 3 ) 2 , —C(═O)N(CH 3 )(CH 2 CH 3 ), —CF 3 or —C(═O)NH 2 , and
with Z being selected from —H, —OH, —CH 3 , —CH 2 CH 3 , —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —N(CH 3 ) 3 + ;

c. with each R 8 being
—H, or, with each R 8 being selected independently from each other from —H, —CH 3 , —CH 2 CH 3 ;

d. with n of R 10 n being 1 or 2; and
with each R 10 independently from any other R 10 being selected from
—OH, —F, —Cl, —Br, I, —CCH, —CN, —N 3 , —OCH 3 , —OCF 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —CH 3 , —CH 2 —CH 3 , —CF 3 , or —NO 2 ;

e. with n of R 11 n being 0, 1, 2, 3 or 4,
with each R 11 being selected independently from any other from any other R 11 from —OH, —F, —Cl, —Br, —I, —CCH, —CN, —N 3 , —OCH 3 , —OCF 3 , NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —CH 3 , —CH 2 CH 3 , —CH 2 OCH 3 , —CHCH 2 , —CH 2 OH, —SO 2 NH 2 , —SO 2 N(CH 3 ) 2 , —SO 2 NHCH 3 , —CH 3 , —CF 3 , or —NO 2 ;

f. with T being selected from
—OH, —F, —Cl, —Br, I, —CCH, —CN, —N 3 , —OCH 3 , —OCF 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —CH 3 , —CH 2 —CH 3 , —CF 3 or —NO 2 ,
—(CH 2 ) m —C(═O)OR a , —(CH 2 ) m —S(O 2 )OR a , with m being selected from 0, 1 or 2, with R a being
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;

g. with D1, D4 and D5 being each independently from each other from

wherein
each R 8 being —H, or with each R 8 being selected independently from each other from —H, —CH 3 , —CH 2 CH 3 , and
V being O;

h. wherein the compounds of formulae (2a) is disclaimed:

wherein R 1 is H or CO(NH 2 ), R 2 ′ is CO(NH 2 ) or CN, R 3 ′ is H or OCH 3 .

2. The compound according to claim 1 having formulae 21

wherein X 1 , BC, R 8 , R 11 n , R 10 n and T have the meaning as recited in claim 1 .

3. The compound according to claim 1 having formulae 25

wherein X 1 , BC, R 8 , R 11 , R 10 and T have the meaning as recited in claim 1 and E is

with n of R 1 n being 0 or 1, and

with each R 1 independently from any other R 1 being selected from —OH or —CH 3 .

4. A compound selected from the group consisting of:

Assignees

• Univ Berlin Tech

Inventors

• Suessmuth Roderich
• Kretz Julian
• Schubert Vivien
• Pesic Alexander
• Huegelland Manuela
• Royer Monique
• Cociancich Stephane
• Rott Philippe
• Kerwat Dennis
• Graetz Stefan

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• A61P31/06

  for tuberculosis · CPC title

• C07D295/14

  substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07C2601/18

  with a ring being at least seven-membered · CPC title

• C07C233/83

  of an acyclic saturated carbon skeleton · CPC title