Inhibitors of HBV replication of Formula (I)

##STR00001##

including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein B, R.sub.1, R.sub.2 and R.sub.4 have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HBV inhibitors, in HBV therapy.

Inhibitors of HBV replication of Formula (I)

##STR00001##

including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein B, R.sub.1, R.sub.2 and R.sub.4 have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HBV inhibitors, in HBV therapy.

The present invention relates to bumetanide derivatives of formula (I) as well as pharmaceutical compositions comprising these compounds for use in the treatment or prevention of diseases/disorders involving Na.sup.+K.sup.+2Cl.sup.-cotransporters (NKCCs), and particularly for use in the treatment or prevention of hyperhidrosis.

##STR00001##

The present invention relates to bumetanide derivatives of formula (I) as well as pharmaceutical compositions comprising these compounds for use in the treatment or prevention of diseases/disorders involving Na.sup.+K.sup.+2Cl.sup.-cotransporters (NKCCs), and particularly for use in the treatment or prevention of hyperhidrosis.

##STR00001##

Provided herein are compounds useful in treating a central nervous system disorder associated with neuronal and/or axonal damage, methods for their preparation, and related pharmaceutical compositions. For example provided herein are compounds of Formula (I): and pharmaceutically acceptable salts and compositions including the same.

##STR00001##

Disclosed are compounds and methods for preventing or treating necroinflammation associated with ferroptotic processes. The method includes inhibiting 15 lipoxygenase/phosphatidylethanolamine binding protein (15LOX/PEBP1) complex, wherein the inhibitor exhibits a higher binding affinity or binding activity for 15LOX/PEBP1 complex compared to 15LOX alone. Necroinflammation associated with ferroptotic processes causes several pathogenic conditions including upper or lower respiratory disorders, acute or chronic brain injury, renal injury, injury by radiation, neurodegenerative disorder, among others. The disclosed compounds and methods are useful in subjects diagnosed with one or more of these conditions.

Disclosed are compounds and methods for preventing or treating necroinflammation associated with ferroptotic processes. The method includes inhibiting 15 lipoxygenase/phosphatidylethanolamine binding protein (15LOX/PEBP1) complex, wherein the inhibitor exhibits a higher binding affinity or binding activity for 15LOX/PEBP1 complex compared to 15LOX alone. Necroinflammation associated with ferroptotic processes causes several pathogenic conditions including upper or lower respiratory disorders, acute or chronic brain injury, renal injury, injury by radiation, neurodegenerative disorder, among others. The disclosed compounds and methods are useful in subjects diagnosed with one or more of these conditions.

Identification and evaluation of a set of first-in-class potent inhibitors targeting a new cancer target, Grb2-associated binder-1 (GAB1), which integrates signals from different signaling pathways and is frequently over-expressed in cancer cells. Intensive computational modeling is utilized to understand the structure of the GAB1 pleckstrin homology (PH) domain and screened five million compounds. Upon biological evaluation, several inhibitors were found that induced large conformational changes of the target structure exhibited strong selective binding to GAB1 PH domain. Particularly, these inhibitors demonstrated potent and tumor-specific cytotoxicity in breast cancer cells. This targeting GAB1 signaling may be used for cancer therapy, especially for triple negative breast cancer patients.

Identification and evaluation of a set of first-in-class potent inhibitors targeting a new cancer target, Grb2-associated binder-1 (GAB1), which integrates signals from different signaling pathways and is frequently over-expressed in cancer cells. Intensive computational modeling is utilized to understand the structure of the GAB1 pleckstrin homology (PH) domain and screened five million compounds. Upon biological evaluation, several inhibitors were found that induced large conformational changes of the target structure exhibited strong selective binding to GAB1 PH domain. Particularly, these inhibitors demonstrated potent and tumor-specific cytotoxicity in breast cancer cells. This targeting GAB1 signaling may be used for cancer therapy, especially for triple negative breast cancer patients.

Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.