US2008262208A1PendingUtilityA1
6-11 Bridged Oxime Erythromycin Derivatives
Est. expiryMay 3, 2026(expired)· nominal 20-yr term from priority
Inventors:Guoqiang WangLy Tam PhanYat Sun OrYao-Ling QiuDeqiang NiuYulin PengMarina BusuyekYanchun WangSuanne Nakajima
C07H 17/08
62
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Claims
Abstract
The present invention discloses compounds of formula I, or pharmaceutically acceptable salts, esters, or prodrugs thereof: which exhibit antibacterial properties. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject in need of antibiotic treatment. The invention also relates to methods of treating a bacterial infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The invention further includes processes by which to make the compounds of the present invention.
Claims
exact text as granted — not AI-modified1 . A compound represented by formula:
or their racemates, enantiomers, regioisomers, salts, esters or prodrugs thereof, wherein
X and Y are independently selected from the group consisting of: hydrogen, deuterium, halogen, R 1 , OR 1 , S(O) n R 1 , —NR 1 C(O)R 2 , —NR 1 C(O)NR 3 R 4 , —NR 1 S(O) n R 2 , —C(O)NR 3 R 4 , and —NR 3 R 4 ;
Each of R 1 and R 2 is independently selected from the group consisting of: hydrogen, acyl, silane, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, or a substituted or unsubstituted heterocyclic group;
Each of R 3 and R 4 is independently selected from the group consisting of: hydrogen, acyl, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, a substituted, or unsubstituted heterocyclic group; or can be taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted heterocyclic or heteroaromatic ring;
or X and Y, taken together with the carbon atom to which they are attached, are selected from the group consisting of: CO, C═CHR 1 , C═NR 1 , C═NC(O)R 1 , C═NOR 1 , C═NO(CH 2 ) m R 1 , C═NNHR 1 , C═NNHCOR 1 , C═NNHCONR 1 R 2 , C═NNHS(O) n R 1 , C═N—N═CHR 1 , C═N—NO 2 , or C═N—ONO;
one of U or V is hydrogen and the other is independently selected from the group consisting of: R 1 , OR 1 , OC(O)R 1 , OC(O)NR 3 R 4 , S(O) n R 1 ,
or U and V, taken together with the carbon atom to which they are attached, are C═O;
one of J or G is hydrogen and the other is selected from: R 1 , OR 1 , or NR 3 R 4 ;
or, J and G, taken together with the carbon atom to which they are attached, are
selected from: C═O, C═NR 1 , C═NOR 1 , C═NO(CH 2 ) m R 1 , C═NNHR 1 , C═NNHCOR 1 , C═NNHCONR 1 R 2 , C═NNHS(O) n R 1 , or C═N—N═CHR 1 ;
L is selected from the group consisting of: hydrogen, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, or a substituted or unsubstituted heterocyclic group;
M is R 1 ;
W is NR 3 R 4 ;
Z is hydrogen, alkyl or halogen;
R p is hydrogen, hydroxy protecting group or hydroxy prodrug group;
m is an integer; and
n is 0, 1, or 2.
A is
wherein:
Q′ is N, CH or CF;
X 1 is O, N, NR 1 , S, or CR 5 ;
Y 1 is O, N, NR 1 , S, CR 5 , or Se;
Z 1 is O, N, NR 1 , S, or CR 5 ;
R 5 is independently selected from hydrogen, acyl, silane, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, a substituted or unsubstituted heterocyclic group, NR 3 R 4 , OH, NHCOR 1 or NHCONH 2 , and is preferably, NH 2 or NHR 1 .
With the proviso that a compound of Formula I is not selected from the following compound where A, Q, and Z as defined below in the Table A.
TABLE A
Compound
A
Q
Z
01
NAc
H
02
NAc
H
03
NH
H
04
NAc
H
2 . A compound of claim 1 wherein A is:
wherein X 1 and R 5 are as previously defined in claim 1 .
3 . A compound of claim 1 wherein A is:
wherein X 1 is O or S, and R 5 is as previously defined in claim 1 .
4 . A compound of claim 1 wherein A is:
wherein X 1 is O or S, and R 5 is as previously defined in claim 1 .
5 . A compound of claim 1 wherein A is:
wherein R 5 is as previously defined in claim 1 .
6 . A compound of claim 1 wherein A is:
7 . A compound of claim 1 wherein A is selected from the compounds shown in Table B.
TABLE B
Number
A-
01
02
03
04
05
06
07
08
09
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
8 . A compound of claim 1 having the Formula II:
wherein A, Q, and Z are as defined in Table C:
TABLE C
Num-
ber
A
Q
Z
01
NAc
H
02
NAc
F
03
NAc
H
04
NAc
H
05
NAc
H
06
NAc
H
07
NAc
H
08
NAc
F
09
O
H
10
NAc
H
11
O
H
12
NAc
H
13
NAc
H
14
O
H
15
O
H
16
NAc
H
17
NAc
H
18
O
H
19
NAc
H
20
NAc
H
21
NAc
F
22
NAc
F
23
NAc
H
24
O
H
25
NAc
H
26
NAc
H
27
NAc
H
28
O
H
29
NAc
H
30
NAc
H
31
NAc
H
32
NAc
H
33
NAc
H
34
NAc
H
35
NAc
H
36
NAc
H
37
NAc
H
38
NC(O)OCH 3
H
39
NH
H
9 . A compound of claim 1 having the Formula III:
wherein R p , U, V, X, Y, L, W and Z are as previously defined in claim 1 .
10 . A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt, ester or prodrug thereof, in combination with a pharmaceutically acceptable carrier.
11 . A method of treating a bacterial infection in a subject in need of such treatment comprising, administering to said subject a pharmaceutical composition of claim 10 .
12 . A method of treating inflammation in a subject in need of such treatment comprising, administering to said subject a pharmaceutical composition of claim 10 .
13 . A method of treating cystic fibrosis in a subject in need of such treatment comprising, administering to said subject a pharmaceutical composition of claim 10 .
14 . A compound represented by Formula VI:
or any racemates, enantiomers, regioisomers, salts, esters, or prodrugs thereof wherein X, Y, L, W, and R p are as defined previously;
B is independently selected from hydrogen, acyl, silane, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, or a substituted or unsubstituted heterocyclic group.
15 . A compound according to claim 14 represented by Formula VII:
where R p as previously defined in claim 1 .Cited by (0)
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