The present invention provides novel derivative of -lactam antibiotics, such as meropenem. The inventive compounds include compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are particles (e.g., nanoparticles) and pharmaceutical compositions thereof that are mucus penetrating. The inventive particles and pharmaceutical compositions may be useful in delivering an inventive compound to the respiratory tract of a subject. The invention further provides methods of using and kits including the inventive compounds, particles thereof, and/or pharmaceutical compositions thereof for treating and/or preventing a pulmonary disease (e.g., a respiratory tract infection).

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The present invention provides novel derivative of -lactam antibiotics, such as meropenem. The inventive compounds include compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are particles (e.g., nanoparticles) and pharmaceutical compositions thereof that are mucus penetrating. The inventive particles and pharmaceutical compositions may be useful in delivering an inventive compound to the respiratory tract of a subject. The invention further provides methods of using and kits including the inventive compounds, particles thereof, and/or pharmaceutical compositions thereof for treating and/or preventing a pulmonary disease (e.g., a respiratory tract infection).

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The present invention includes compositions, methods of making and using novel carbapenem compounds including active agents, compounds, antibacterial agents, pharmaceutically acceptable salts of C1-C1 di-substituted carbapenem compounds, C5 substituted carbapenem compounds, C6-C6 di-substituted carbapenem compounds and combinations thereof.

Provided are a continuous post-treatment method and device for a penem compound. The method includes the following steps: S1, performing continuous extraction on a reaction crude product of a penem compound, to obtain an extraction heavy phase and an extraction light phase; S2, performing continuous solid-liquid separation on the extraction heavy phase, to obtain a liquid phase separation product; S3, performing continuous pH adjustment on the liquid phase separation product until a pH value thereof is 6.1-6.3, to obtain pH-adjusted solution; and S4, performing continuous crystallization treatment on the pH-adjusted solution by a first crystallization solvent, to obtain a penem compound product. The use of the method for the post-treatment of the reaction crude product of the penem compound has the advantages of high treatment speed and high efficiency, and stable material properties and a low deterioration rate during the treatment, and has better control over the yield and purity of a target product.

The present invention provides novel derivative of -lactam antibiotics, such as meropenem. The inventive compounds include compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are particles (e.g., nanoparticles) and pharmaceutical compositions thereof that are mucus penetrating. The inventive particles and pharmaceutical compositions may be useful in delivering an inventive compound to the respiratory tract of a subject. The invention further provides methods of using and kits including the inventive compounds, particles thereof, and/or pharmaceutical compositions thereof for treating and/or preventing a pulmonary disease (e.g., a respiratory tract infection). ##STR00001##

The present invention provides novel derivative of -lactam antibiotics, such as meropenem. The inventive compounds include compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are particles (e.g., nanoparticles) and pharmaceutical compositions thereof that are mucus penetrating. The inventive particles and pharmaceutical compositions may be useful in delivering an inventive compound to the respiratory tract of a subject. The invention further provides methods of using and kits including the inventive compounds, particles thereof, and/or pharmaceutical compositions thereof for treating and/or preventing a pulmonary disease (e.g., a respiratory tract infection). ##STR00001##

New antimicrobials targeting L,D-transpeptidases, non-classical cysteine peptidases, have been developed and their unique chemical structures identified. Carbapenems and penems of the present invention are unique among -lactams as they acylate and inhibit L,D-transpeptidases, which likely results in their superior antimicrobial potency. These new antimicrobial agents can be used alone, or in combination with other classic antimicrobial agents that target D,D transpeptidases, when treating bacterial infections.

The present invention includes a composition, method of making and method of using a novel C5-substituted carbapenem antibiotic of formula 1:

##STR00001## R.sup.1 is H or CH.sub.3 R.sup.2 is not H, and is CH.sub.3, or C1-C6 straight chain, or branched alkyl, or C3-C6 cycloalkyl group, or unsaturated alkenyl, including CCH.sub.2; R.sup.3 is H, CH.sub.3, or a C1-C6 alkyl or cycloalkyl group, a heteroatom-substituted alkyl; and R.sup.4 is a C1 to C6 alkyl, or substituted alkyl group, especially including substituents which possess positive charge, or a hydroxyl group; or R.sup.4 is an SR.sup.a, where R.sup.a is an unsubstituted C1 to C6 alkyl group, a substituted C1 to C6 alkyl group, or a functional group that is positively charged, or which bears a positive charge when in aqueous solution at pH 7; or R.sup.4 is a CH.sub.2OR.sup.b, where R.sup.b=C1 to C6 alkyl or substituted alkyl groups, substituted or unsubstituted aryl, or a heteroaryl groups.

This invention describes an ICE inhibitor prodrug (I) having good bioavailability.

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Compound I is useful for treating IL-1 mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, inflammatory peritonitis, septic shock, pancreatitis, traumatic brain injury, organ transplant rejection, osteoarthritis, asthma, psoriasis, Alzheimer's disease, myocardial infarction, congestive heart failure, Huntington's disease, atherosclerosis, atopic dermatitis, leukemias and related disorders, myelodysplastic syndrome, uveitis or multiple myeloma.

This invention describes an ICE inhibitor prodrug (I) having good bioavailability.

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Compound I is useful for treating IL-1 mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, inflammatory peritonitis, septic shock, pancreatitis, traumatic brain injury, organ transplant rejection, osteoarthritis, asthma, psoriasis, Alzheimer's disease, myocardial infarction, congestive heart failure, Huntington's disease, atherosclerosis, atopic dermatitis, leukemias and related disorders, myelodysplastic syndrome, uveitis or multiple myeloma.