The present invention provides compounds, compositions thereof, and methods of using the same.

The present invention provides compounds, compositions thereof, and methods of using the same.

Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (IOP) may be achieved.

Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (IOP) may be achieved.

Provided herein are small molecule inhibitors for the targeting or IRE1 protein family members. Binding may be direct or indirect. Further provided herein are methods of using IRE1 small molecule inhibitors for use in treating or ameliorating cancer in a subject. Moreover, IRE1 small molecule inhibitors described herein are for the treatment of cancer, where the cancer is a solid or hematologic cancer.

Provided herein are small molecule inhibitors for the targeting or IRE1 protein family members. Binding may be direct or indirect. Further provided herein are methods of using IRE1 small molecule inhibitors for use in treating or ameliorating cancer in a subject. Moreover, IRE1 small molecule inhibitors described herein are for the treatment of cancer, where the cancer is a solid or hematologic cancer.

The present disclosure provides, inter alia, compounds with MASP-2 inhibitory activity, compositions of such compounds and methods of making and using such compounds.

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): ##STR00001##
or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R.sup.1, R.sup.2a, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, G.sup.1, G.sup.2, L.sup.1, L.sup.2, m.sup.1, m.sup.2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): ##STR00001##
or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R.sup.1, R.sup.2a, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, G.sup.1, G.sup.2, L.sup.1, L.sup.2, m.sup.1, m.sup.2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Described are methods for the preparation of 6-aminoisoquinoline, a useful intermediate compound in the synthesis of kinase inhibitors.