Antibiotic compositions for the treatment of gram negative infections
AssigneesBioSource Pharm, Inc., Cubist Pharmaceuticals, Inc.
InventorsWilliam V. Curran, Christopher M. Liu, Amy C. D. Bombardier, Richard A. Leese, You Seok Hwang, Blaise S. Lippa, Yanzhi Zhang
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Abstract
Provided herein are novel compounds and novel protected compounds that can be derived from polymyxin, including, e.g., polymyxin A. The novel compounds have antibacterial properties against a diverse range of Gram negative bacteria and reduced toxicity compared to polymyxins such as polymyxin A. Also provided are antibacterial pharmaceutical compositions containing the novel compounds and novel protected compounds, as well as methods for preparing the antibacterial compounds and protected compounds.
Claims9
A method of treating a bacterial infection comprising Gram-negative bacteria, comprising parenterally administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula (Ia):
- or a pharmaceutically acceptable salt thereof.
A process for preparing an antibacterial compound, the process comprising:
- a) treating polymyxin A with an amino protecting group comprising at least one acidic substituent to form a protected compound represented by Structural Formula IVb:
- wherein P is the protecting group;
- b) treating the protected compound with a deacylating agent, to form at least one deacylated protected compound represented by Structural Formula IVc:
- wherein P is the protecting group;
- c) treating the at least one deacylated protected compound with an activated ester of trans-2-phenylcyclopropanecarboxylic acid to form at least one acylated protected compound;
- and
- d) treating the at least one acylated protected compound with an organic base to form an antibacterial compound having Formula (Ia):
Dependencies are inferred from the claim text.