The present disclosure relates to HIF-2α inhibitors and methods of making and using them for treating cancer. Certain compounds were potent in HIF-2α scintillation proximity assay, luciferase assay, and VEGF ELISA assay, and led to tumor size reduction and regression in 786-O xenograft bearing mice in vivo.

The present disclosure provides an organic compound that has a mother skeleton with a fused-ring structure, an electron-withdrawing group bonded to the mother skeleton, and an electron-donating group bonded to the mother skeleton, wherein the electron-withdrawing group is bonded at a position satisfying the following relationship in the mother skeleton.

Σ|C.sub.H|>Σ|C.sub.L|  (1)

(C.sub.H: 2PZ atomic orbital coefficient of a carbon at a substitution site in the HOMO of the mother skeleton)

(C.sub.L: 2PZ atomic orbital coefficient of the carbon at the substitution site in the LUMO of the mother skeleton)

The present disclosure provides an organic compound that has a mother skeleton with a fused-ring structure, an electron-withdrawing group bonded to the mother skeleton, and an electron-donating group bonded to the mother skeleton, wherein the electron-withdrawing group is bonded at a position satisfying the following relationship in the mother skeleton.

Σ|C.sub.H|>Σ|C.sub.L|  (1)

(C.sub.H: 2PZ atomic orbital coefficient of a carbon at a substitution site in the HOMO of the mother skeleton)

(C.sub.L: 2PZ atomic orbital coefficient of the carbon at the substitution site in the LUMO of the mother skeleton)

The invention generally relates to methods and compounds for treating proliferative disorders, viral infections, or both. In some embodiments, the invention provides an anticancer or antiviral compound including a substituted nitro phenoxy phenyl, a sulfonylurea, and an alkyl group. In some embodiments, the invention provides a method of treating a proliferative disorder or a viral infection including administering an anticancer or antiviral compound that binds to a thromboxane receptor, has preferential binding for either TPalpha (TPα) or TPbeta (TPβ) receptor subtype.

The invention generally relates to methods and compounds for treating proliferative disorders, viral infections, or both. In some embodiments, the invention provides an anticancer or antiviral compound including a substituted nitro phenoxy phenyl, a sulfonylurea, and an alkyl group. In some embodiments, the invention provides a method of treating a proliferative disorder or a viral infection including administering an anticancer or antiviral compound that binds to a thromboxane receptor, has preferential binding for either TPalpha (TPα) or TPbeta (TPβ) receptor subtype.

Described are RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders. ##STR00001##

Described are RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders. ##STR00001##

The present invention provides compounds of Formula (I) and (II) as described herein, and salts thereof and therapeutic uses of these compounds for treatment of disorders associated with Raf kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent.

##STR00001##

The present invention provides compounds of Formula (I) and (II) as described herein, and salts thereof and therapeutic uses of these compounds for treatment of disorders associated with Raf kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent.

##STR00001##

Pyridine carboxamide compounds for inhibiting NaV1.8 and methods for treating a condition, disease, or disorder associated with an increased NaV1.8 activity or expression are disclosed.