The present invention provides certain lipo-glycopeptide cleavable derivatives and methods for using the same for the treatment of bacterial infections, for example, pulmonary bacterial infections. The LGPC derivatives include a cleavable moiety that in certain embodiments, is designed to allow for cellular uptake and/or a more rapid clearance of the glycopeptide metabolite (i.e., the cleaved glycopeptide) from the site of administration (e.g., the lung) as compared to the uncleaved LGPC.

Vancomycin conjugates of Formula I, its stereoisomers, prodrugs, pharmaceutically acceptable salts, and metal coordination complexes thereof is described in the present disclosure. Further, the present disclosure relates to pharmaceutical compositions comprising vancomycin conjugates, its stereoisomers, prodrugs, pharmaceutically 10 acceptable salts, metal coordination complex thereof with one or more other pharmaceutical compositions or an antibiotic. The present disclosure also describes a process of preparing said conjugates, its stereoisomers, prodrugs, pharmaceutically acceptable salts, and metal coordination complex thereof, and pharmaceutical compositions as described above. Furthermore, the present disclosure describes 15 compositions and methods of treating conditions and diseases that are mediated by bacteria. ##STR00001##

Disclosed is a chromatographic method for separating a mixture of compounds having ionizable groups using a mobile phase comprising (a) a first mobile phase component comprising an aqueous buffer system and an organic solvent mixture miscible with water, and (b) a second mobile phase component comprising an aqueous buffer system and an organic solvent mixture miscible with water, wherein the buffer system and the solvent mixture in the first mobile phase component are different from the buffer system and the solvent mixture in the second mobile phase component and the ratio of the first mobile phase component to the second mobile phase component is varied during the separation. The method can be used for the separation of vancomycin and its degradation products.

A construct comprising: (i) an optionally derivatized glycopeptide antibiotic; (ii) a nanoparticle; and (iii) a first linker connecting (i) and (ii) is provided. The construct may further comprise a second linker located between the first linker and (ii). The nanoparticle may be a separation nanoparticle, such as a magnetic separation nanoparticle. The glycopeptide antibiotic may be selected from the group consisting: of vancomycin; teicoplanin; oritavancin; telavancin; chloroeremomycin; and balhimycin. Also provided are related methods of producing and using the construct, such as methods of separation of bacteria from a sample by binding the bacteria to the construct.

A C-terminus modification to a binding pocket-modified vancomycin introduces a quaternary ammonium salt that provides a binding pocket-modified vancomycin analog with a second mechanism of action that is independent of D-Ala-D-Ala/D-Ala-D-Lac binding. The modification disrupts cell wall integrity and induces cell wall permeability complementary to the glycopeptide inhibition of cell wall synthesis, and provides synergistic improvements in antimicrobial potency (200-fold) against vancomycin-resistant bacteria. Combining the C-terminus and binding pocket modifications with an orthogonal (4-chlorobiphenyl) methyl addition to the vancomycin disaccharide provides even more potent antimicrobial agents whose activity can be attributed to three independent and synergistic mechanisms of action, only one of which requires D-Ala-D-Ala/D-Ala-D-Lac binding. The resulting modified vancomycins display little propensity for acquired resistance through serial exposure of vancomycin-resistant Enterococci and their durability against such challenges as well as their antimicrobial potency follow predicable trends. Methods of treatment with and compositions containing the modified vancomycins are disclosed.

The total synthesis and evaluation of key analogs of vancomycin containing single atom changes in the binding pocket are disclosed as well as their peripherally modified, N-(hydrophobe-substituted) derivatives exemplified by a N-4-(4-chlorobiphenyl)-methyl derivative and their pharmaceutically acceptable salts are disclosed. Their evaluation indicates the combined pocket and peripherally modified analogs exhibit a remarkable spectrum of antimicrobial activity and truly impressive potencies against both vancomycin-sensitive and -resistant bacteria, and likely benefit from two independent and synergistic mechanisms of action. A pharmaceutical composition containing a contemplated compound or its pharmaceutically acceptable salt is disclosed, as is a method of treating a bacterial infection in a mammal by administering an antibacterial amount of a contemplated compound or its salt as above to an infected mammal in need of treatment.

An optimized method for synthesizing dalbavancin is provided in which an organic antisolvent such as tert-butyl methyl ether (TBME) or dimethoxyethane (DME) is used to precipitate the product of the esterification of A-40926.

Drug substance preparations of oritavancin having high purity are disclosed, along with pharmaceutical compositions comprising such oritavancin drug substance preparations, and drug products or dosage forms comprising such pharmaceutical compositions.

Drug substance preparations of oritavancin having high purity are disclosed, along with pharmaceutical compositions comprising such oritavancin drug substance preparations, and drug products or dosage forms comprising such pharmaceutical compositions.

Described herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting bacterial growth. Methods of using the compounds for treating and/or preventing bacterial infection as well as methods of preparing the compounds are also described ##STR00001##