This invention is in the field of medicinal chemistry. In particular, the invention relates to anew class of small-molecules having a tetrahydroindazole structure which function as modulators (e.g., activators or inhibitors) of sigma-1 and/or sigma-2 receptors, and their use as therapeutics for the treatment of cancer and other diseases (e.g., neurological conditions) characterized with sigma-1 and/or sigma-2 receptor activity.

Compounds described herein may be used for the treatment of neurodegenerative diseases linked to protein misfolding, including prion diseases, Alzheimer's disease, Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), and also other neurodegenerative, degenerative, metabolic and ischemic conditions. Indeed, NAD metabolism impairment is also a critical feature in brain ischemia/reperfusion injury, Wallerian degeneration, kidney failure, multiple sclerosis, aging, and metabolic disorders such as diabetes mellitus. Therapies that elevate or stabilize NAD levels may thus have broad potential for treating many severely debilitating neurological and metabolic conditions. Evidence is provided herein with compounds from 8 lead series for NAD restoring properties and for therapeutic efficacy in cellular and/or animal models of prion disease, PD and ALS.

Described herein are compositions and methods of treating gastrointestinal diseases and disorders such as irritable bowel syndrome and small intestinal bacterial overgrowth.

Described herein are compositions and methods of treating gastrointestinal diseases and disorders such as irritable bowel syndrome and small intestinal bacterial overgrowth.

Described herein are compositions and methods of treating gastrointestinal diseases and disorders such as irritable bowel syndrome and small intestinal bacterial overgrowth.

N-(furan-2-ylmethyl)-7H-purin-6-amine, or a pharmaceutically acceptable salt or solvate thereof, for prevention and/or treatment of circadian rhythm disorders, circadian rhythm diseases and/or circadian rhythm dysfunctions is disclosed. The disorders, diseases and dysfunctions include, inter alia, jet-lag, social jet-lag, shift-work disorder, and circadian rhythm disturbance induced by neurodegeneration is also disclosed.

N-(furan-2-ylmethyl)-7H-purin-6-amine, or a pharmaceutically acceptable salt or solvate thereof, for prevention and/or treatment of circadian rhythm disorders, circadian rhythm diseases and/or circadian rhythm dysfunctions is disclosed. The disorders, diseases and dysfunctions include, inter alia, jet-lag, social jet-lag, shift-work disorder, and circadian rhythm disturbance induced by neurodegeneration is also disclosed.

Disclosed herein are combinations of compounds for treating a disease or condition, such as cancer. A combination of compounds for treating a disease or condition can include a SERD inhibitor and a WEE1 inhibitor, along with pharmaceutically acceptable salts of any of the foregoing.

Disclosed herein are combinations of compounds for treating a disease or condition, such as cancer. A combination of compounds for treating a disease or condition can include a SERD inhibitor and a WEE1 inhibitor, along with pharmaceutically acceptable salts of any of the foregoing.

Disclosed herein are combinations of compounds for treating a disease or condition, such as cancer. A combination of compounds for treating a disease or condition can include a SERD inhibitor and a WEE1 inhibitor, along with pharmaceutically acceptable salts of any of the foregoing.