发明公开
- 专利标题: Peptoid compounds
- 专利标题(中): 拟肽连接
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申请号: EP11158209.4申请日: 2002-06-28
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公开(公告)号: EP2343285A3公开(公告)日: 2011-08-10
- 发明人: Bremner, John , Pyne, Stephen , Keller, Paul , Coghlan, Dan , Garas, Adel , Witchard, Helen , Boyle, Tim , Coates, Jonathan
- 申请人: UNIVERSITY OF WOLLONGONG
- 申请人地址: I.P.R. Laboratory, Northfied Avenue Wollongong, NSW 2522 AU
- 专利权人: UNIVERSITY OF WOLLONGONG
- 当前专利权人: UNIVERSITY OF WOLLONGONG
- 当前专利权人地址: I.P.R. Laboratory, Northfied Avenue Wollongong, NSW 2522 AU
- 代理机构: Harrison Goddard Foote
- 优先权: AUPP604401 20010629
- 主分类号: C07D245/04
- IPC分类号: C07D245/04 ; C07D255/04 ; C07D273/08 ; C07D273/02 ; C07D487/02 ; C07D209/18 ; C07D209/88 ; C07C233/31 ; C07K5/06 ; C07K5/08 ; C07K5/10 ; A61K38/12 ; A61K38/06 ; A61P31/04 ; C07D209/86 ; C07D487/04 ; C07C229/36 ; C07C233/47 ; C07C237/22 ; C07C251/24
摘要:
A compound of the formula (I):
wherein
A is an aromatic or heteroaromatic ring system or partially or fully reduced derivatives thereof;
Q is hydrogen, C 1 -C 12 straight chain, branched or cyclic alkyl substituted with one or more hydroxy groups, or a mono- or di-saccharide moiety;
Z is -CR 10 R 11 -, -NR 12 -, -C(O)O-, -C(O)NR 12 - or -O-, where R 10 and R 11 are independently selected from hydrogen, hydroxy, C 1 -C 6 alkyl, C 6 -C 10 aryl, C 1 -C 6 alkoxy and -N(R 13 ) 2 and where each R 13 is independently selected from hydrogen and C 1 -C 6 alkyl, and where R 12 is selected from hydrogen and C 1 -C 6 alkyl; R 1 is selected from hydrogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, -NR(R 13 ) 2 and -N(R 12 )-COR 14 ; where R 12 and R 13 are as defined above, and where R 14 is selected from hydrogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy and -NR 12 ;
R 2 is selected from hydrogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, -N(R 13 ) 2 and -N(R 12 )-COCHR 2a R 2b ; where R 2a and R 2b are selected from hydrogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, -N(R 13 ) 2 and -N(R 12 )-COR 14 ; where R 12 , R 13 and R 14 are as defined above;
R 3 , R 4 and R 5 are independently selected from hydrogen, C 1 -C 6 alkyl and α side chains of α-amino acids or their enantiomers or their derivatives;
R 6 is -CO 2 R 15 , -CONHR 16 , -CONHOR 16 , -CONHNHR 16 , -SO 2 N(R 16 ) 2 , -SO 2 R 17 or -P(O)(OR 18 )(OR 18 ) where each R 15 , R 16 , R 17 and R 18 is independently selected from hydrogen, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl and C 7 -C 10 arylalkyl;
B is an α-amino acid residue, a β-amino acid residue or an α,α-disubstituted amino acid residue, such residue forming amide linkages with the adjacent molecules;
W is -O- or CR 10 R 11 where R 10 and R 11 are as defined above;
Y is an optionally substituted amino group, a moiety containing an optionally substituted amino group or a salt thereof:
------ is a single or double bond;
R 7 and R 8a are hydrogen or are absent if ------ is a double bond; and
R 8b and R 9 are hydrogen, and X is selected from (CR 10 R 11 ) u , -(CR 10 R 11 ) u -CH=CH-, -NR 12 (CR 10 R 11 ) u -, -(CR 10 R 11 ) u NR 12 -, -O(CR 10 R 11 ) u -, -(CR 10 R 11 ) u O- or -O(CR 10 R 11 )CH=CH- where R 10 , R 11 and R 12 are as defined above; or
R 8b and R 9 together form a covalent bond between X and the carbon to which R 8b is attached, and X is selected from (CR 10 R 11 ) x , -NR 12 (CR 10 R 11 ) x -, -(CR 10 R 11 ) x NR 12 -, -O(CR 10 R 11 ) x - or -(CR 10 R 11 ) x O-, where R 10 , R 11 and R 12 are as defined above;
n, m, r and t are independently selected from 0 or 1;
s is an integer selected from 0 to 3;
p is an integer selected from 0 to 6, provided that when W is -O-, p is at least 1; and u, x and q are independently selected from 0 to 4;
and salts and pharmaceutically acceptable derivatives thereof.
The compound of formula (I) are useful in the treatment of bacterial infections.
wherein
A is an aromatic or heteroaromatic ring system or partially or fully reduced derivatives thereof;
Q is hydrogen, C 1 -C 12 straight chain, branched or cyclic alkyl substituted with one or more hydroxy groups, or a mono- or di-saccharide moiety;
Z is -CR 10 R 11 -, -NR 12 -, -C(O)O-, -C(O)NR 12 - or -O-, where R 10 and R 11 are independently selected from hydrogen, hydroxy, C 1 -C 6 alkyl, C 6 -C 10 aryl, C 1 -C 6 alkoxy and -N(R 13 ) 2 and where each R 13 is independently selected from hydrogen and C 1 -C 6 alkyl, and where R 12 is selected from hydrogen and C 1 -C 6 alkyl; R 1 is selected from hydrogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, -NR(R 13 ) 2 and -N(R 12 )-COR 14 ; where R 12 and R 13 are as defined above, and where R 14 is selected from hydrogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy and -NR 12 ;
R 2 is selected from hydrogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, -N(R 13 ) 2 and -N(R 12 )-COCHR 2a R 2b ; where R 2a and R 2b are selected from hydrogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, -N(R 13 ) 2 and -N(R 12 )-COR 14 ; where R 12 , R 13 and R 14 are as defined above;
R 3 , R 4 and R 5 are independently selected from hydrogen, C 1 -C 6 alkyl and α side chains of α-amino acids or their enantiomers or their derivatives;
R 6 is -CO 2 R 15 , -CONHR 16 , -CONHOR 16 , -CONHNHR 16 , -SO 2 N(R 16 ) 2 , -SO 2 R 17 or -P(O)(OR 18 )(OR 18 ) where each R 15 , R 16 , R 17 and R 18 is independently selected from hydrogen, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl and C 7 -C 10 arylalkyl;
B is an α-amino acid residue, a β-amino acid residue or an α,α-disubstituted amino acid residue, such residue forming amide linkages with the adjacent molecules;
W is -O- or CR 10 R 11 where R 10 and R 11 are as defined above;
Y is an optionally substituted amino group, a moiety containing an optionally substituted amino group or a salt thereof:
------ is a single or double bond;
R 7 and R 8a are hydrogen or are absent if ------ is a double bond; and
R 8b and R 9 are hydrogen, and X is selected from (CR 10 R 11 ) u , -(CR 10 R 11 ) u -CH=CH-, -NR 12 (CR 10 R 11 ) u -, -(CR 10 R 11 ) u NR 12 -, -O(CR 10 R 11 ) u -, -(CR 10 R 11 ) u O- or -O(CR 10 R 11 )CH=CH- where R 10 , R 11 and R 12 are as defined above; or
R 8b and R 9 together form a covalent bond between X and the carbon to which R 8b is attached, and X is selected from (CR 10 R 11 ) x , -NR 12 (CR 10 R 11 ) x -, -(CR 10 R 11 ) x NR 12 -, -O(CR 10 R 11 ) x - or -(CR 10 R 11 ) x O-, where R 10 , R 11 and R 12 are as defined above;
n, m, r and t are independently selected from 0 or 1;
s is an integer selected from 0 to 3;
p is an integer selected from 0 to 6, provided that when W is -O-, p is at least 1; and u, x and q are independently selected from 0 to 4;
and salts and pharmaceutically acceptable derivatives thereof.
The compound of formula (I) are useful in the treatment of bacterial infections.
公开/授权文献
- EP2343285B1 Peptoid compounds useful as antibiotics 公开/授权日:2015-02-25
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