SUBSTITUTED ALPHA-ETHYL PHENYLALKYLAMINES
Provided are phenylalkylamines, such as 2,5-disubstituted and 2,4,5-trisubstituted phenylalkylamines. In some embodiments, the phenylalkylamines are asymmetrically substituted. In some embodiments, such compounds modulate the activity of monoamine receptors and/or monoamine transporters. Also provided are methods for the preparation of phenylalkylamines and pharmaceutical compositions thereof. Methods of using the phenylalkylamines, alone or in combination with other therapeutic agents, are provided. In some embodiments, phenylalkylamines are used to treat CNS disorders, such as mental health conditions and neurodegenerative disorders, or are used for the improvement of mental health or functioning.
1 - 82 . (canceled)
83 . A method of treating a medical condition in a subject in need thereof, comprising administering a compound of Formula (A):
or an enantiomer or enantiomerically enriched mixture thereof, or a pharmaceutically acceptable salt, prodrug, hydrate, or solvate of any of the foregoing, wherein:
R 1 is —CH 3 , —CD 3 , or CF 3 ;
R 2 is —CH 3 , —CD 3 , or CF 3 ; and
X is —CH 3 , —CD 3 , or —CF 3 ;
provided that when R 1 and R 2 are both —CH 3 , X is —CD 3 or —CF 3 ; and
wherein the medical condition is selected from a mental health disorder, a neurodegenerative disorder, pain or a pain disorder, and inflammation or an inflammatory disorder.
84 . The method of claim 83 , wherein the compound has the structure of Formula (A-1), (A-2), or (A-3):
85 . The method of claim 83 , wherein the compound has the structure of Formula (A-4), (A-5), or (A-6):
86 . The method of claim 83 , wherein the compound has the structure of Formula (A-7) or (A-8):
87 . The method of claim 83 , wherein the compound has the structure of Formula (A-9):
88 . The method of claim 84 , wherein the compound has the structure of:
89 . The method of claim 84 , wherein the compound has the structure of:
90 . The method of claim 84 , wherein the compound has the structure of:
91 . The method of claim 85 , wherein the compound has the structure of:
92 . The method of claim 85 , wherein the compound has the structure of:
93 . The method of claim 85 , wherein the compound has the structure of:
94 . The method of claim 86 , wherein the compound has the structure of:
95 . The method of claim 86 , wherein the compound has the structure of:
96 . The method of claim 87 , wherein the compound has structure of:
97 . The method of claim 84 , wherein the compound has structure of an (R)-enantiomer of Formula (A-1), (A-2), or (A-3):
98 . The method of claim 83 , wherein the mental health disorder is any of a trauma- or stressor-related disorder, post-traumatic stress disorder (PTSD), acute stress disorder (ASD), an adjustment disorder, an affective disorder, depression, a depressive disorder, major depressive disorder (MDD), treatment-resistant depression (TRD), atypical depression, postpartum depression, catatonic depression, a depressive disorder due to a medical condition, premenstrual dysphoric disorder, seasonal affective disorder, dysthymia (persistent depressive disorder), anxiety, an anxiety disorder, generalized anxiety disorder (GAD), a phobia disorder, binge eating disorder, a body dysmorphic disorder, an addiction disorder, an alcohol or drug abuse or dependence disorder, a substance use disorder, a substance-induced mood disorder, a mood disorder related to another health condition, a disruptive behavior disorder, an eating disorder, an impulse control disorder, obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), a personality disorder, an attachment disorder, and a dissociative disorder.
99 . The method of claim 83 , wherein the neurodegenerative disorder is selected from the group consisting of Alzheimer's disease (AD), corticobasal degeneration (CBD), a form of dementia, Huntington's disease, Lytico-Bodig disease, mild cognitive impairment (MCI), a motor neuron disease, progressive supranuclear palsy (PSP), multiple sclerosis, Parkinson's disease, and traumatic brain injury (TBI).
100 . The method of claim 83 , wherein the pain disorder is selected from the group consisting of arthritis, allodynia, atypical trigeminal neuralgia, trigeminal neuralgia, somatoform disorder, hypoesthesia, hyperalgesia, neuralgia, neuritis, neurogenic pain, phantom limb pain, analgesia, anesthesia dolorosa, causalgia, sciatic nerve pain disorder, degenerative joint disorder, fibromyalgia, visceral disease, chronic pain disorders, headache disorders, migraine headaches, chronic cluster headaches, concussion headache, short-lasting unilateral neuralgiform headache attacks, chronic fatigue syndrome, complex regional pain syndrome, neurodystrophy, plantar fasciitis, or pain associated with cancer.
101 . The method of claim 83 , wherein the inflammatory disorder is characterized by any one or more of skin inflammation, muscle inflammation, tendon inflammation, ligament inflammation, bone inflammation, cartilage inflammation, lung inflammation, heart inflammation, liver inflammation, pancreatic inflammation, kidney inflammation, bladder inflammation, gastric inflammation, intestinal inflammation, neuroinflammation, and brain inflammation.
102 . A method of treating a medical condition in a subject in need thereof, comprising administering a pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 83 , and a pharmaceutically acceptable carrier, diluent, or excipient, wherein the medical condition is selected from a mental health disorder, a neurodegenerative disorder, pain or a pain disorder, and inflammation or an inflammatory disorder.