Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included. ##STR00001##

Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included. ##STR00001##

Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included. ##STR00001##

The present invention relates to novel securinine and norsecurine analogs and their applicapility in treating cellular proliferative disorders.

The present invention relates to novel securinine and norsecurine analogs and their applicapility in treating cellular proliferative disorders.

Novel antibody-drug conjugates (ADCs) and methods of using such ADCs to treat proliferative disorders are described herein. The ADCs may comprise a PARP protein automodified with a plurality of poly-ADP-ribose polymers functionalized with novel NAD.sup.+ analogues. The automodified PARP with functionalized poly-ADP-ribose polymers provide a novel type of drug carrier, which allows facile conjugation of monoclonal antibodies and cytotoxic drug in high ratios.

Novel antibody-drug conjugates (ADCs) and methods of using such ADCs to treat proliferative disorders are described herein. The ADCs may comprise a PARP protein automodified with a plurality of poly-ADP-ribose polymers functionalized with novel NAD.sup.+ analogues. The automodified PARP with functionalized poly-ADP-ribose polymers provide a novel type of drug carrier, which allows facile conjugation of monoclonal antibodies and cytotoxic drug in high ratios.

The present invention describes 3-aza-bicyclo[3.2.1]octane acids of general formula (I), their Salts and Esters, for use as activators of ADAR1 in the treatment of diseases related to acute or chronic inflammations, infective or not., characterized by cytokine storm and/or uncontrolled immune response.

The present invention describes 3-aza-bicyclo[3.2.1]octane acids of general formula (I), their Salts and Esters, for use as activators of ADAR1 in the treatment of diseases related to acute or chronic inflammations, infective or not., characterized by cytokine storm and/or uncontrolled immune response.

Conjugates of an active agent such as DM1 attached to a targeting moiety, such as a somatostatin receptor binding moiety, via a linker, and particles comprising such conjugates have been designed. Such conjugates and particles can provide improved temporospatial delivery of the active agent, improved biodistribution and penetration in tumor, and/or decreased toxicity. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer.