The present disclosure is directed to novel compounds of Formula I and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g. controlling, alleviating, or slowing the progression of) of cancer, including glioblastoma, bone cancer, head and neck cancer, melanoma, basal cell carcinoma, squamous cell carcinoma, adenocarcinoma, oral cancer, esophageal cancer, gastric cancer, intestinal cancer, colon cancer, bladder cancer, hepatocellular carcinoma, renal cell carcinoma, pancreatic cancer, ovarian cancer, cervical cancer, lung cancer, breast cancer, and prostate cancer. The compounds of the disclosure are selective antagonists of the EP4 receptor and useful treatment of various diseases that may be ameliorated with blockade of PGE2-mediated signaling.

The present disclosure is directed to novel compounds of Formula I and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g. controlling, alleviating, or slowing the progression of) of cancer, including glioblastoma, bone cancer, head and neck cancer, melanoma, basal cell carcinoma, squamous cell carcinoma, adenocarcinoma, oral cancer, esophageal cancer, gastric cancer, intestinal cancer, colon cancer, bladder cancer, hepatocellular carcinoma, renal cell carcinoma, pancreatic cancer, ovarian cancer, cervical cancer, lung cancer, breast cancer, and prostate cancer. The compounds of the disclosure are selective antagonists of the EP4 receptor and useful treatment of various diseases that may be ameliorated with blockade of PGE2-mediated signaling.

The present invention relates to a novel compound, and a composition for preventing or treating of respiratory disease comprising the novel compound, E- or Z-isomer thereof, optical isomer thereof, a mixture of two isomers thereof, precursor thereof, pharmaceutically acceptable salt thereof or solvate thereof as an active ingredient.

Compounds of general formula (I): wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5.sup.a, R* X.sup.1, X.sup.2, Z and Y are as defined herein are positive modulators of the calcium-activated chloride channel (CaCC), TMEM16A. The compounds are useful for treating diseases and conditions affected by modulation of TMEM16A, particularly respiratory diseases and conditions. ##STR00001##

Compounds of general formula (I): wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5.sup.a, R* X.sup.1, X.sup.2, Z and Y are as defined herein are positive modulators of the calcium-activated chloride channel (CaCC), TMEM16A. The compounds are useful for treating diseases and conditions affected by modulation of TMEM16A, particularly respiratory diseases and conditions. ##STR00001##

Provided herein are compounds useful as imaging agents. Exemplary compounds provided herein are useful as myeloperoxidase imaging agents using positron emission tomography or fluorescence imaging techniques. Methods for preparing the compounds provided herein and diagnostic methods using radiolabeled and unlabeled compounds are also provided.

This document provides methods and materials for increasing or maintaining NMNAT2 polypeptide levels within cells. For example, compounds (e.g., organic compounds) having the ability to increase or maintain NMNAT2 polypeptide levels within cells, formulations containing compounds having the ability to increase or maintain NMNAT2 polypeptide levels within cells, methods for making compounds having the ability to increase or maintain NMNAT2 polypeptide levels within cells, methods for making formulations containing compounds having the ability to increase or maintain NMNAT2 polypeptide levels within cells, methods for increasing or maintain NMNAT2 polypeptide levels within cells, and methods for treating mammals (e.g., humans) having a condition responsive to an increase in NMNAT2 polypeptide levels are provided (or for preventing said condition).

This document provides methods and materials for increasing or maintaining NMNAT2 polypeptide levels within cells. For example, compounds (e.g., organic compounds) having the ability to increase or maintain NMNAT2 polypeptide levels within cells, formulations containing compounds having the ability to increase or maintain NMNAT2 polypeptide levels within cells, methods for making compounds having the ability to increase or maintain NMNAT2 polypeptide levels within cells, methods for making formulations containing compounds having the ability to increase or maintain NMNAT2 polypeptide levels within cells, methods for increasing or maintain NMNAT2 polypeptide levels within cells, and methods for treating mammals (e.g., humans) having a condition responsive to an increase in NMNAT2 polypeptide levels are provided (or for preventing said condition).

The present invention provides compounds of general Formula I and I′: ##STR00001## ##STR00002##
compositions thereof, and methods of using same to treat Rheb-mediated disorders.

The present disclosure is directed to novel compounds of Formula I and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of cancer, including glioblastoma, bone cancer, head and neck cancer, melanoma, basal cell carcinoma, squamous cell carcinoma, adenocarcinoma, oral cancer, esophageal cancer, gastric cancer, intestinal cancer, colon cancer, bladder cancer, hepatocellular carcinoma, renal cell carcinoma, pancreatic cancer, ovarian cancer, cervical cancer, lung cancer, breast cancer, and prostate cancer. The compounds of the disclosure are selective antagonists of the EP4 receptor and useful treatment of various diseases that may be ameliorated with blockade of PGE2-mediated signaling.