The disclosure relates to substituted fused heteroaromatic tricyclic compounds and the use thereof. Specifically, the disclosure provides compounds of the following Formula I: ##STR00001##
or a pharmaceutically acceptable salt or prodrug thereof, wherein A.sub.1-A.sub.3, B.sub.1-B.sub.3, D.sub.1-D.sub.4 and R.sub.1-R.sub.2 are defined herein. Compounds having Formula I are ATM kinase inhibitors. Therefore, compounds of the disclosure may be used to treat clinical conditions caused by DDR functional defects, such as cancer.

The disclosure relates to substituted fused heteroaromatic tricyclic compounds and the use thereof. Specifically, the disclosure provides compounds of the following Formula I: ##STR00001##
or a pharmaceutically acceptable salt or prodrug thereof, wherein A.sub.1-A.sub.3, B.sub.1-B.sub.3, D.sub.1-D.sub.4 and R.sub.1-R.sub.2 are defined herein. Compounds having Formula I are ATM kinase inhibitors. Therefore, compounds of the disclosure may be used to treat clinical conditions caused by DDR functional defects, such as cancer.

The disclosure describes global transcriptome profiling in human vascular endothelial cells upon THSD1 knockdown and identification from these studies of specific genes and pathways that are THSD1. The analysis highlights a role for THSD1 in regulating endothelial to mesenchymal transition and other pathways. The analysis also demonstrates that endothelial cell injury is the first event of an intracranial aneurysm. The disclosure provides novel cell lines and reagents used for better understanding the molecular mechanism of THSD1 biology.

It is intended to provide a novel method for treating a cancer using an FGFR inhibitor that exhibits a remarkably excellent antitumor effect and has fewer side effects. The present invention provides a combination preparation for the treatment of a malignant tumor comprising a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, and one or more additional compound(s) having an antitumor effect or pharmaceutically acceptable salt(s) thereof, and a pharmaceutical composition comprising both the active ingredients. The present invention also provides an antitumor effect enhancer, an antitumor agent, a kit for malignant tumor treatment, etc. comprising a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof.

It is intended to provide a novel method for treating a cancer using an FGFR inhibitor that exhibits a remarkably excellent antitumor effect and has fewer side effects. The present invention provides a combination preparation for the treatment of a malignant tumor comprising a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, and one or more additional compound(s) having an antitumor effect or pharmaceutically acceptable salt(s) thereof, and a pharmaceutical composition comprising both the active ingredients. The present invention also provides an antitumor effect enhancer, an antitumor agent, a kit for malignant tumor treatment, etc. comprising a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof.

The present disclosure relates to the use of stimulators of soluble guanylate cyclase (sGC), pharmaceutically acceptable salts thereof and pharmaceutical formulations or dosage forms comprising them, alone or in combination with one or more additional agents, for the treatment of various CNS diseases, wherein an increase in sGC stimulation, or an increase in the concentration of nitric oxide (NO), or cyclic guanosine 3′,5′-monophosphate (cGMP) or both, or an upregulation of the NO pathway is desirable.

The present disclosure relates to the use of stimulators of soluble guanylate cyclase (sGC), pharmaceutically acceptable salts thereof and pharmaceutical formulations or dosage forms comprising them, alone or in combination with one or more additional agents, for the treatment of various CNS diseases, wherein an increase in sGC stimulation, or an increase in the concentration of nitric oxide (NO), or cyclic guanosine 3′,5′-monophosphate (cGMP) or both, or an upregulation of the NO pathway is desirable.

The disclosure relates to a series of substituted imidazolecarboxamide compounds of formula I as BTK (Bruton's Tyrosine Kinase) inhibitors, and the methods of using the same for the treatment of autoimmune disease, inflammatory disease, cancer and potentially allergies.

##STR00001##

The present invention relates to 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one for use in the treatment of spinal muscular atrophy (SMA), its pharmaceutical composition to be used in the treatment of SMA, its methods of treatment thereof.

A compound of Formula (I): ##STR00001##
pharmaceutically acceptable salts thereof, deuterated analogs thereof, compositions thereof, and methods of treating disease using a compound thereof, wherein the variable substituents are disclosed herein.