The invention is fused heterocyclic compounds of formula (I), and salts thereof, compositions thereof, and methods of use therefor. In particular, disclosed herein are certain fused heterocyclic compounds that can be useful for inhibiting protein kinase, including Bruton's tyrosine kinase (Btk), and for treating disorders mediated thereby.

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The invention is fused heterocyclic compounds of formula (I), and salts thereof, compositions thereof, and methods of use therefor. In particular, disclosed herein are certain fused heterocyclic compounds that can be useful for inhibiting protein kinase, including Bruton's tyrosine kinase (Btk), and for treating disorders mediated thereby.

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The present invention relates to the following compounds

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wherein the integers are as defined in the description, and where the compounds may be useful as medicaments, for instance for use in the treatment of tuberculosis.

The present invention relates to the following compounds

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wherein the integers are as defined in the description, and where the compounds may be useful as medicaments, for instance for use in the treatment of tuberculosis.

This invention provides heterocyclic compounds that bind to E3 Ubiquitin Ligase (typically through cereblon) (“Degrons”), which can be used as is or linked to a Targeting Ligand for a selected Target Protein for therapeutic purposes and methods of use and compositions thereof as well as methods for their preparation.

This invention provides heterocyclic compounds that bind to E3 Ubiquitin Ligase (typically through cereblon) (“Degrons”), which can be used as is or linked to a Targeting Ligand for a selected Target Protein for therapeutic purposes and methods of use and compositions thereof as well as methods for their preparation.

To identify novel agents to treat carbapenem-resistant Acinetobacter baumannii. the Inventors used a nutrient-depleted medium with serum to mimic the in vivo environment. In RPMI with serum, the screen identified rifabutin (RBT) as being 133-fold more potent than rifampin (RIF) against A. baumannii, with MICs of 0.031 μg/ml and 4 μg/ml respectively. No difference in RBT vs. RIF activity was observed when MHII was used as the culture media. RBT possesses markedly superior in efficacy to RIF in murine models of lethal iv and pneumonia models of infection with a hyper-virulent, clinical lung and blood isolate of extreme-drug resistant (XDR) A. baumannii. In both models, RBT significantly improved survival and lowered bacterial burden compared to RIF. RBT is a promising, novel therapeutic option for A. baumannii infections.

To identify novel agents to treat carbapenem-resistant Acinetobacter baumannii. the Inventors used a nutrient-depleted medium with serum to mimic the in vivo environment. In RPMI with serum, the screen identified rifabutin (RBT) as being 133-fold more potent than rifampin (RIF) against A. baumannii, with MICs of 0.031 μg/ml and 4 μg/ml respectively. No difference in RBT vs. RIF activity was observed when MHII was used as the culture media. RBT possesses markedly superior in efficacy to RIF in murine models of lethal iv and pneumonia models of infection with a hyper-virulent, clinical lung and blood isolate of extreme-drug resistant (XDR) A. baumannii. In both models, RBT significantly improved survival and lowered bacterial burden compared to RIF. RBT is a promising, novel therapeutic option for A. baumannii infections.

To identify novel agents to treat carbapenem-resistant Acinetobacter baumannii. the Inventors used a nutrient-depleted medium with serum to mimic the in vivo environment. In RPMI with serum, the screen identified rifabutin (RBT) as being 133-fold more potent than rifampin (RIF) against A. baumannii, with MICs of 0.031 μg/ml and 4 μg/ml respectively. No difference in RBT vs. RIF activity was observed when MHII was used as the culture media. RBT possesses markedly superior in efficacy to RIF in murine models of lethal iv and pneumonia models of infection with a hyper-virulent, clinical lung and blood isolate of extreme-drug resistant (XDR) A. baumannii. In both models, RBT significantly improved survival and lowered bacterial burden compared to RIF. RBT is a promising, novel therapeutic option for A. baumannii infections.

This invention relates to compounds of formula (I) and methods of treatment using the compounds. The compounds of the invention can be used in combination with antibacterial agents to treat bacterial infections. More specifically, the compounds of formula (I) can be used in combination with a class of antibacterial agents known as carbapenems. The novel compounds of the present invention are enzyme inhibitors and more particularly are metallo-β-lactamase inhibitors.

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