Antimicrobial agents
AssigneeUniversity of Louisville Research Foundation, Inc.
InventorsArno F. Spatola, James Jun Wen, David M. Vogel
Life of this patent
Estimating the term…
Abstract
Antimicrobial compounds of formula I are disclosed: R1—X—R2 wherein X is a group comprising of from about 4 to about 10 amino acids, wherein at least one of the amide (—CONH—) linkages is replaced by —CRaRaRbNRc—; Ra, Rb, and Rc are each independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, (C1-C6)alkoxycarbonyl, aryl, or heterocycle; and R1 and R2 are each independently hydrogen, a saccharide, a lipid, a solubilizing agent, or a suitable protecting group; or a pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions comprising such compounds or salts, and methods of using such compounds or salts to treat a bacterial infection.
Claims12
A method of treating or preventing a bacterial infection in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound of formula I:
- R1—A—B—C—D—E—R2
- wherein each of A, B, C, D, and E is independently an amino acid, wherein at least the amide bond connecting A to B is replaced by —CRaRbNRc—;
- Ra, Rb, and Rc are each independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, (C1-C6)alkoxycarbonyl, aryl, or heterocycle;
- and
- R1 and R2 are each independently hydrogen, a saccharide, a lipid, a solubilizing agent, or a suitable protecting group;
- or a pharmaceutically acceptable salt thereof.
A method of treating or preventing a bacterial infection in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound of formula I:
- R1—A—B—C—D—E—R2
- wherein each of A, B, C, D, and E is independently an amino acid, wherein at least one of the amide (—CONH—) linkages is replaced by —CRaCbRc—, and B is an amino acid selected from the group consisting of lysine, methionine, diethylglycine, aminoisobutyric acid, and isoleucine;
- Ra, Rb, and Rc are each independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, (C1-C6)alkoxycarbonyl, aryl, or heterocycle;
- and
- R1 and R2 are each independently hydrogen, a saccharide, a lipid, a solubilizing agent, or a suitable protecting group;
- or a pharmaceutically acceptable salt thereof.
A method of treating or preventing a bacterial infection in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound of formula I:
- R1—A—B—C—D—E—R2
- wherein each of A, B, C, D, and E is independently an amino acid, wherein at least one of the amide (—CONH—) linkages is replaced by —CRaRbRc—, and C is an amino acid selected from the group consisting of serine, aminoisobutyric acid, phenylalanine, valine, diethylglycine, and aminomethylbenzoic acid;
- Ra, Rb, and Rc are each independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, (C1-C6)alkoxycarbonyl, aryl, or heterocycle;
- and
- R1 and R2 are each independently hydrogen, a saccharide, a lipid, a solubilizing agent, or a suitable protecting group;
- a pharmaceutically acceptable salt thereof.
A method of treating or preventing a bacterial infection in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound of formula I:
- R1—A—B—C—D—E—R2
- wherein each of A, B, C, D, and E is independently an amino acid, wherein at least one of the amide (—CONH—) linkages is replaced by —CRaRbRc, and E is leucine;
- Ra, Rb, and Rc are each independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, (C1-C6)alkoxycarbonyl, aryl, or heterocycle;
- and
- R1 and R2 are each independently hydrogen, a saccharide, a lipid, a solubilizing agent, or a suitable protecting group;
- or a pharmaceutically acceptable salt thereof.
A method of treating or preventing a bacterial infection in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound of formula I:
- R1—A—B—D—E—R2
- wherein each of A, B, C, D, and E is independently an amino acid, at least one of the amide (—CONH—) linkages is replaced by —CRaRbNRc—, and at least one of A, B, C, D, and E is a D-amino acid;
- Ra, Rb, and Rc are each independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, (C1-C6)alkoxycarbonyl, aryl, or heterocycle;
- and
- R1 and R2 are each independently hydrogen, a saccharide, a lipid, a solubilizing agent, or a suitable protecting group;
- or a pharmaceutically acceptable salt thereof.
A compound which is H-Nalψ[CH2NH]Aib-Ser-Pheψ[CH2NH]Leu-OH, H-Nalψ[CH2NH]Aib-Val-Pheψ[CH2NH]Leu-OH, H-Nalψ[CH2NH]Aib-Phe-Pheψ[CH2NH]Leu-OH, H-Nalψ[CH2NH]Lys-Aib-Pheψ[CH2NH]Leu-OH, H-Nalψ[CH2NH]Met-Aib-Pheψ[CH2NH]Leu-OH, H-Nalψ[CH2NH]Ile-Aib-Pheψ[CH2NH]Leu-OH, H-Nalψ[CH2NH]Deg-Ser-Pheψ[CH2NH]Leu-OH, H-Nalψ[CH2NH]Deg-Val-Pheψ[CH2NH]Leu-OH, H-Nalψ[CH2NH]Deg-Phe-Pheψ[CH2NH]Leu-OH, H-Nalψ[CH2NH]Lys-Deg-Pheψ[CH2NH]Leu-OH, H-Nalψ[CH2NH]Met-Deg-Pheψ[CH2NH]Leu-OH, H-Nalψ[CH2NH]Ile-Deg-Pheψ[CH2NH]Leu-OH, H-D-2-Nalψ[CH2NH]Lys-Ser-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NAc]Lys-Ser-Pheψ[CH2NH]Leu-OH, Ac-2-Nalψ[CH2NH]Lys-Ser-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NAc]Met-Aib-Pheψ[CH2NH]Leu-OH, H-2-Nal-Lys-Ser-Phe-Leu-OH (SEQ ID NO:1), H-2-Nalψ[CH2NH]Lys-Ser-Phe-Leu-OH (SEQ ID NO:2), H-2-Nalψ[CH2NH]Lys(Ac)-Ser-Pheψ[CH2NH]Leu-OH, H-D-2-Nalψ[CH2NH]D-Lys-D-Ser-D-Pheψ[CH2NH]D-Leu-OH, H-2-Nalψ[CH2NH]Lys-Ser-Pheψ[CH2NAc]Leu-OH, H-2-Nalψ[CH2NH]Met-Aib-Pheψ[CH2NH]Leu-NH2, H-2-Nalψ[CH2NH]Nle-Aib-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NH]Met-4-AMB-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NH]Met-3-AMB-Pheψ[CH2NH]Leu-OH, H-D-2-Nalψ[CH2NH]D-Met-Aib-D-Pheψ[CH2NH]D-Leu-OH, H-2-Nalψ[CH2NH]Lys-Ser-4-AMBψ[CH2NH]Leu-OH, 4-AMBψ[CH2NH]Lys-Ser-Pheψ[CH2NH]Leu-OH, or 4-AMBψ[CH2 NH]-Lys-Ser-4-AMBψ[CH2NH]Leu-OH, or a pharmaceutically acceptable salt thereof.
A compound which is H-2-Nalψ[CH2NH]Aib-Ser-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NH]Aib-Val-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NH]Aib-Phe-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NH]Lys-Aib-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NH]Met-Aib-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NH]Ile-Aib-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NH]Deg-Ser-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NH]Deg-Val-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NH]Deg-Phe-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NH]Lys-Deg-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NH]Met-Deg-Pheψ[CH2NH]Leu-OH, H-2-Nalψ[CH2NH]Ile-Deg-Pheψ[CH2NH]Leu-OH, or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.