USRE48335EActiveUtility
Polymyxin derivatives as antimicrobial compounds
Est. expiryApr 1, 2034(~7.7 yrs left)· nominal 20-yr term from priority
Y02A50/30A61K 38/12A61P 43/00A61P 31/04C07K 7/62A61K 38/00
60
PatentIndex Score
1
Cited by
22
References
4
Claims
Abstract
The present invention relates to antimicrobial compounds and their uses, and in particular to peptide antibiotics which may be used in the treatment of bacterial infections such as Gram-negative bacterial infections, particularly those caused by multidrug-resistant (MDR) pathogens.
Claims
exact text as granted — not AI-modifiedThe claims defining the invention are as follows:
1. A compound of formula (IIb):
wherein:
R 1 is selected from hexanoyl, hepatanoyl, octanoyl, nonanoyl, decanoyl, dodecanoyl, 7 methyloctanoyl, S-5-methylheptanoyl, R-5-methylheptanoyl, S,R-5-methylheptanoyl (racemic mixture), 4-biphenylcarboxyl, 4-trifluoromethylbenzoyl, 4-ethylbenzoyl, 3,4-dichlorobenzoyl, 4-chlorobenzoyl, 3-chlorobenzoyl, pentafluorobenzoyl, 4-methylbenzoyl, 4-ethylphenylacetyl, phenylacetyl, 4-methylphenylacetyl, 4-trifluoromethylphenylacetyl, pentafluorophenylacetyl, 3,4-dichlorophenylacetyl, 4-chlorophenylacetyl, 3-chlorophenylacetyl, 2-chlorobenzoyl, 2-fluorobenzoyl, 2-methylbenzoyl, 2-chlorophenylacetyl, 2-fluorophenylacetyl, 2-methylphenylacetyl, 2,3-dichlorobenzoyl, 2,3-dimethylbenzoyl, 2,4-dichlorophenylacetyl, 2,4-dichlorobenzoyl, 2,4-dimethylbenzoyl, 2-chloro-4-methylbenzoyl, 2-chloro-4-trifluoromethylbenzoyl, 3-fluorobenzoyl, 3-methylbenzoyl, 3-trifuoromethylbenzoyl, 3,4-dimethylbenzoyl, 3-fluoro-4-methylbenzoyl, 4-chloro-3-methylbenzoyl, 3,4-dimethylphenylacetyl, 3-chloro-4-methylbenzoyl, 4-chloro-3-fluorobenzoyl, 3-fluoro-4-trifluoromethylbenzoyl, 3-chloro-4-fluorobenzoyl, 4-methyl-3-trifluoromethylbenzoyl, 3-methyl-4-trifluoromethylbenzoyl, 3-methyl-5-trifluoromethylbenzoyl, 3,5-dimethylbenzoyl, 3,5-dichlorobenzoyl, 3,5-bis(trifluoromethyl) benzoyl, 3-fluoro-5-trifluoromethylbenzoyl, 3-chloro-5-methylbenzoyl, 3-chloro-5-fluorobenzoyl, 2,4,6-trimethylbenzoyl, 2,4,6-trichlorobenzoyl, 2-chloro-4-fluorobenzoyl, 4-chloro-2-fluorobenzoyl, 3,4,5-trifluoromethylbenzoyl, 4-chloro-2-trifluoromethylbenzoyl, 2-fluoro-4-trifluoromethylbenzoyl, 3-biphenylcarboxyl, 4-chlorobiphenyl-4-carboxyl, 3-phenylproponyl, 4-phenylbutanoyl, 2,4-dichlorophenylsulfonyl, 4-chloro-3-trifluoromethylbenzoyl, 4-isopropylbenzoyl, 4-chloro-3-fluorobenzoyl, and 3-chloro-4-trifluoromethylbenzoyl;
R 3 represents a side chain of an amino acid selected from leucine, phenylalanine, norleucine, norvaline or t-butylglycine;
R 4 represents a side chain of an amino acid selected from alanine, threonine, serine, valine, t-butylglycine, 2-aminobutyric acid or 2-aminoisobutyric acid; and
k and q are individually selected from 1, 2, or 3; or
pharmaceutically acceptable salts thereof.
2. The compound according to claim 1 , wherein R 4 represents the side chain of an amino acid selected from alanine, threonine, serine, 2-aminobutyric acid, or 2-aminoisobutyric acid.
3. The compound of claim 2, wherein R 3 represents the side chain of D-leucine; R 4 represents the side chain of 2-aminobutyric acid; R 1 is 2,4-dichlorobenzoyl; k is 2; and q is 1.
4. The compound of claim 1, selected from the group consisting of:
Compound
R 1
R 3
R 4
k
q
29
4-BPC
D-Leu
Thr
2
2
30
PA
D-Leu
Thr
2
2
56
4-TFMB
D-Leu
Thr
2
1
57
3,4-DCB
D-Leu
Thr
2
1
61
3-CPA
D-Leu
Thr
2
1
62
2,4-DCPA
D-Leu
Thr
2
1
70
2,4-DCPA
D-Leu
Abu
2
1
71
3,4-DCB
D-Leu
Abu
2
1
72
2-CB
D-Leu
Abu
2
1
73
2-FB
D-Leu
Abu
2
1
74
4-TFMB
D-Leu
Abu
2
1
75
2-MB
D-Leu
Abu
2
1
76
2-MPA
D-Leu
Abu
2
1
77
4-CPA
D-Leu
Abu
2
1
78
PA
D-Leu
Abu
2
1
79
3-CPA
D-Leu
Abu
2
1
80
4-MPA
D-Leu
Abu
2
1
81
3,4-DCPA
D-Leu
Abu
2
1
82
2,4-DCB
D-Leu
Abu
2
1
83
3,4-DMB
D-Leu
Abu
2
1
84
2-CPA
D-Leu
Abu
2
1
85
2-FPA
D-Leu
Abu
2
1
86
3-FB
D-Leu
Abu
2
1
87
3-MB
D-Leu
Abu
2
1
88
3-CB
D-Leu
Abu
2
1
89
2,4-DMB
D-Leu
Abu
2
1
90
2,3-DCB
D-Leu
Abu
2
1
91
2,3-DMB
D-Leu
Abu
2
1
92
2,4,6-TMB
D-Leu
Abu
2
1
93
3,5-DMB
D-Leu
Abu
2
1
94
4-CB
D-Leu
Abu
2
1
95
2,4,6-TCB
D-Leu
Abu
2
1
96
3,5-DCB
D-Leu
Abu
2
1
97
3,5-BTFMB
D-Leu
Abu
2
1
98
4-MB
D-Leu
Abu
2
1
99
4-IPB
D-Leu
Abu
2
1
100
4-EB
D-Leu
Abu
2
1
101
2-C-4-MB
D-Leu
Abu
2
1
102
3-F-4-MB
D-Leu
Abu
2
1
103
3,4-DMPA
D-Leu
Abu
2
1
104
4-C-3-MB
D-Leu
Abu
2
1
105
3-C-4-MB
D-Leu
Abu
2
1
106
3-TFMB
D-Leu
Abu
2
1
107
4-C-3-Fb
D-Leu
Abu
2
1
108
3-F-5-TFMB
D-Leu
Abu
2
1
109
2-C-4-TFMB
D-Leu
Abu
2
1
110
3-C-4-FB
D-Leu
Abu
2
1
111
3-F-4-TFMB
D-Leu
Abu
2
1
112
4-C-3-TFMB
D-Leu
Abu
2
1
113
4-M-3-TFMB
D-Leu
Abu
2
1
114
3-C-5-MB
D-Leu
Abu
2
1
115
3-C-4-TFMB
D-Leu
Abu
2
1
116
3-C-5-FB
D-Leu
Abu
2
1
117
3,5-DCB
D-Leu
Ala
2
1
118
3,5-DCB
D-Leu
Thr
2
1
119
3-M-4-TFMB
D-Leu
Abu
2
1
120
3-M-5-TFMB
D-Leu
Abu
2
1
121
3-TFMB
D-Nle
Abu
2
1
122
3-TFMB
D-Phe
Abu
2
1
123
3-TFMB
D-Nlc
Thr
2
1
124
3-TFMB
D-Phe
Thr
2
1
125
3-TFMB
D-Nlc
Ala
2
1
126
3-TFMB
D-Phe
Ala
2
1
127
4-TFMPA
D-Leu
Abu
2
1
134
4-C-2-FB
D-Leu
Abu
2
1
135
2-C-4-FB
D-Leu
Abu
2
1
136
4-C-2-TFMB
D-Leu
Abu
2
1
137
2-F-4-TFMB
D-Leu
Abu
2
1
138
3-BPC
D-Leu
Abu
2
1
141
3-TFMB
D-Leu
Abu
3
1
142
4-BPC
D-Leu
Abu
2
1
144
4-Cl-BP-4-C
D-Leu
Ala
2
1
145
3-PP
D-Leu
Abu
2
1
146
4-PB
D-Leu
Ala
2
1
147
2,4-DCB
D-Leu
Abu
2
3
148
2,4-DCPS
D-Leu
Abu
2
1,
or pharmaceutically acceptable salts thereof, wherein 4-BPC=4-biphenylcarboxyl, PA=phenylacetyl, 4-TFMPA=4-trifluoromethylphenylacetyl, 2-MB=2-methylbenzoyl, 3-MB=3-methylbenzoyl, 4-MB=4-methylbenzoyl, 3-F-4-MB=3-fluoro-4-methylbenzoyl, 4-C-3-MB=4-chloro-3-methylbenzoyl, 3-C-4-MB=3-chloro-4-methylbenzoyl, 3-C-5-MB=3-chloro-5-methylbenzoyl, 2-FPA=2-fluorophenylacetyl, 3-TFMB=3-trifuoromethylbenzoyl, 4-TFMB=4-trifluoromethylbenzoyl, 2-C-4-TFMB=2-chloro-4-trifluoromethylbenzoyl, 4-C-3-TFMB=4-chloro-3-trifluoromethylbenzoyl, 3-C-4-TFMB=3-chloro-4-trifluoromethylbenzoyl, 3-F-4-TFMB=3-fluoro-4-trifluoromethylbenzoyl, 3-F-5-TFMB=3-fluoro-5-trifluoromethylbenzoyl, 4-M-3-TFMB=4-methyl-3-trifluoromethylbenzoyl, 3-M-4-TFMB=3-methyl-4-trifluoromethylbenzoyl, 3-M-5-TFMB=3-methyl-5-trifluoromethylbenzoyl, 2-F-4-TFMB=2-fluoro-4-trifluoromethylbenzoyl, 4-C-2-TFMB=4-chloro-2-trifluoromethylbenzoyl, 3,5-BTFMB=3,5-bis(trifluoromethyl)benzoyl, 2,4,6-TMB=2,4,6-trimethylbenzoyl, 2,3-DMB=2,3-dimethylbenzoyl, 2,4-DMB=2,4-dimethylbenzoyl, 3,4-DMB=3,4-dimethylbenzoyl, 3,5-DMB=3,5-dimethylbenzoyl, 2-C-4-MB=2-chloro-4-methylbenzoyl, 4-EB=4-ethylbenzoyl, 4-IPB=4-Isopropylbenzoyl, 2,4-DCPA=2,4-dichlorophenylacetyl, 3,4-DCPA=3,4-dichlorophenylacetyl, 2-CPA=2-chlorophenylacetyl, 3-CPA=3-chlorophenylacetyl, 4-CPA=4-chlorophenylacetyl, 2-CB=2-chlorobenzoyl, 3-CB=3-chlorobenzoyl, 4-CB=4-chlorobenzoyl, 2,3-DCB=2,3-dichlorobenzoyl, 2,4-DCB=2,4-dichlorobenzoyl, 3,4-DCB=3,4-dichlorobenzoyl, 3,5-DCB=3,5-dichlorobenzoyl, 2,4,6-TCB=2,4,6-trichlorobenzoyl, 2-FB=2-fluorobenzoyl, 3-FB=3-fluorobenzoyl, 2-C-4-FB=2-chloro-4-fluorobenzoyl, 3-C-4-FB=3-Chloro-4-fluorobenzoyl, 3-C-5-FB=3-chloro-5-fluorobenzoyl, 4-C-2-FB=4-chloro-2-fluorobenzoyl, 4-C-3-FB=4-chloro-3-fluorobenzoyl, 2-MPA=2-methylphenylacetyl, 4-MPA=4-methylphenylacetyl, 3,4-DMPA=3,4-dimethylphenylacetyl, 3-BPC=3-biphenylcarboxyl, 4-C1-BP-4-C=4-chloro-biphenyl-4-carboxyl, 3-PP=3-phenylproponyl, 4-PB=4-phenylbutanoyl, 2,4-DCPS=2,4-dichlorophenylsulfonyl, Abu=2-aminobutyric acid, Phe=phenylalanine, Thr=threonine, Ala=alanine, Leu=leucine, and Nle=norleucine.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.