OXYSTEROLS AND METHODS OF USE THEREOF
Compounds are provided according to Formula (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 8 are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
1 .- 63 . (canceled)
64 . A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
65 . (canceled)
66 . A pharmaceutical composition comprising a compound of claim 64 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
67 . A method of inducing sedation or anesthesia comprising administering to a subject an effective amount of a compound of claim 64 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.
68 . A method for treating or preventing a disorder described herein, comprising administering to a subject in need thereof an effective amount of a compound of claim 64 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.
69 . The method according to claim 68 , wherein the disorder is a gastrointestinal (GI) disorder e.g., constipation, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) (e.g., ulcerative colitis, Crohn's disease), a structural disorder affecting the GI tract, an anal disorder (e.g., hemorrhoids, internal hemorrhoids, external hemorrhoids, anal fissures, perianal abscesses, anal fistula), colon polyps, cancer, diabetes, a sterol synthesis disorder, or colitis.
70 . The method according to claim 69 , wherein the disorder is inflammatory bowel disease.
71 . The method according to claim 69 , wherein the disorder is cancer, diabetes, or a sterol synthesis disorder.
72 . A method for treating or preventing a CNS-related condition comprising administering to a subject in need thereof an effective amount of a compound of claim 64 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.
73 . The method according to claim 72 , wherein the CNS-related condition is an adjustment disorder, an anxiety disorder (including obsessive-compulsive disorder, posttraumatic stress disorder, and social phobia), a cognitive disorder (including Alzheimer's disease and other forms of dementia), a dissociative disorder, an eating disorder, a mood disorder (including depression (e.g., postpartum depression), bipolar disorder, dysthymic disorder, suicidality), schizophrenia or an other psychotic disorder (including schizoaffective disorder), a sleep disorder (including insomnia), a substance-related disorder, a personality disorder (including obsessive-compulsive personality disorder), an autism spectrum disorder (including those involving mutations to the Shank group of proteins (e.g., Shank3)), a neurodevelopmental disorder (including Rett syndrome, Tuberous Sclerosis complex), multiple sclerosis, a sterol synthesis disorder, pain (including acute and chronic pain), encephalopathy secondary to a medical condition (including hepatic encephalopathy and anti-NMDA receptor encephalitis), a seizure disorder (including status epilepticus and monogenic forms of epilepsy such as Dravet's disease), stroke, traumatic brain injury, a movement disorder (including Huntington's disease and Parkinson's disease), vision impairment, hearing loss, or tinnitus.
74 . The method according to claim 73 , wherein the disorder is a sterol synthesis disorder.