Deuyerated tryptamine derivative formulations and methods of use

Abstract

The present disclosure is directed to pharmaceutical compositions and to the use of such formulations in the treatment of diseases associated with a serotonin 5-HT2 receptor.

1 . (canceled) 
     
     
         2 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (III-c) 
       
         
           
           
               
               
           
         
         or an optically pure stereoisomer, pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein 
         R 2  is independently selected from hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl, 
         R 6  and R 7  are selected from hydrogen, deuterium, and halogen, 
         R 8  is an unsubstituted or partially or fully deuterated methyl or ethyl, and 
         R 9  is hydrogen, deuterium, or an unsubstituted or partially or fully deuterated methyl or ethyl, 
         wherein the pharmaceutical composition is formulated for subcutaneous administration. 
       
     
     
         3 - 4 . (canceled) 
     
     
         5 . A pharmaceutical composition comprising a polymer and a therapeutically effective amount of a compound,
 wherein the compound is   
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and
 wherein the pharmaceutical composition is formulated for subcutaneous administration. 
 
     
     
         6 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (III-t) 
       
         
           
           
               
               
           
         
         or an optically pure stereoisomer, pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein
 R 2  is independently selected from hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl, 
 R 6  and R 7  are selected from hydrogen, deuterium, and halogen, 
 R 8  is an unsubstituted or partially or fully deuterated methyl or ethyl, and 
 R 9  is hydrogen, deuterium, or an unsubstituted or partially or fully deuterated methyl or ethyl, 
 wherein the pharmaceutical composition is formulated for subcutaneous administration. 
 
       
     
     
         7 . A pharmaceutical composition comprising a therapeutically effective amount of a compound 
       
         
           
           
               
               
           
         
         wherein the pharmaceutical composition is formulated for subcutaneous administration. 
       
     
     
         8 . (canceled) 
     
     
         9 . A method of treating one or more diseases or conditions, comprising administering to a patient or subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (III-c) 
       
         
           
           
               
               
           
         
         or an optically pure stereoisomer, pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein 
         R 2  is independently selected from hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl, 
         R 6  and R 7  are selected from hydrogen, deuterium, and halogen, 
         R 8  is an unsubstituted or partially or fully deuterated methyl or ethyl, and 
         R 9  is hydrogen, deuterium, or an unsubstituted or partially or fully deuterated methyl or ethyl, 
         wherein the pharmaceutical composition is administered to the patient or subject subcutaneously. 
       
     
     
         10 - 11 . (canceled) 
     
     
         12 . A method of treating one or more diseases or conditions, comprising administering to a patient or subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound,
 wherein the compound is   
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and
 wherein the pharmaceutical composition is administered to the patient or subject subcutaneously. 
 
     
     
         13 . A method of treating one or more diseases or conditions, comprising administering to a patient or subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (III-t) 
       
         
           
           
               
               
           
         
         or an optically pure stereoisomer, pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein
 R 2  is independently selected from hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl, 
 R 6  and R 7  are selected from hydrogen, deuterium, and halogen, 
 R 8  is an unsubstituted or partially or fully deuterated methyl or ethyl, and 
 R 9  is hydrogen, deuterium, or an unsubstituted or partially or fully deuterated methyl or ethyl, 
 wherein the pharmaceutical composition is administered to the patient or subject subcutaneously. 
 
       
     
     
         14 . A method of treating one or more diseases or conditions, comprising administering to a patient or subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound 
       
         
           
           
               
               
           
         
         wherein the pharmaceutical composition is administered to the patient or subject subcutaneously. 
       
     
     
         15 . The method of  claim 9 , wherein the one or more diseases or conditions are associated with a serotonin 5-HT 2  receptor. 
     
     
         16 . The method of  claim 9 , wherein the one or more diseases or conditions are selected from the group consisting of central nervous system (CNS) disorders, major depressive disorder (MDD), major depressive disorder (MDD) with suicidal ideation or suicidal behavior, suicidal ideation, suicidal behavior, non-suicidal self-injury disorder (NSSID), treatment-resistant depression (TRD), post-traumatic stress disorder (PTSD), bipolar and related disorders including bipolar I disorder, bipolar II disorder, cyclothymic disorder, obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), social anxiety disorder, substance use disorders, alcohol use disorder, opioid use disorder, amphetamine use disorder, nicotine use disorder, and cocaine use disorder, anorexia nervosa, bulimia nervosa, Alzheimer's disease, cluster headache and migraine, attention deficit hyperactivity disorder (ADHD), pain, neuropathic pain, aphantasia, childhood-onset fluency disorder, major neurocognitive disorder, mild neurocognitive disorder, sexual dysfunction, chronic fatigue syndrome, Lyme Disease, obesity, autonomic nervous system (ANS) disorders, pulmonary disorders and cardiovascular disorders. 
     
     
         17 . The method of  claim 12 , wherein the one or more diseases or conditions are associated with a serotonin 5-HT 2  receptor. 
     
     
         18 . The method of  claim 12 , wherein the one or more diseases or conditions are selected from the group consisting of central nervous system (CNS) disorders, major depressive disorder (MDD), major depressive disorder (MDD) with suicidal ideation or suicidal behavior, suicidal ideation, suicidal behavior, non-suicidal self-injury disorder (NSSID), treatment-resistant depression (TRD), post-traumatic stress disorder (PTSD), bipolar and related disorders including bipolar I disorder, bipolar II disorder, cyclothymic disorder, obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), social anxiety disorder, substance use disorders, alcohol use disorder, opioid use disorder, amphetamine use disorder, nicotine use disorder, and cocaine use disorder, anorexia nervosa, bulimia nervosa, Alzheimer's disease, cluster headache and migraine, attention deficit hyperactivity disorder (ADHD), pain, neuropathic pain, aphantasia, childhood-onset fluency disorder, major neurocognitive disorder, mild neurocognitive disorder, sexual dysfunction, chronic fatigue syndrome, Lyme Disease, obesity, autonomic nervous system (ANS) disorders, pulmonary disorders and cardiovascular disorders. 
     
     
         19 . The method of  claim 13 , wherein the one or more diseases or conditions are associated with a serotonin 5-HT 2  receptor. 
     
     
         20 . The method of  claim 13 , wherein the one or more diseases or conditions are selected from the group consisting of central nervous system (CNS) disorders, major depressive disorder (MDD), major depressive disorder (MDD) with suicidal ideation or suicidal behavior, suicidal ideation, suicidal behavior, non-suicidal self-injury disorder (NSSID), treatment-resistant depression (TRD), post-traumatic stress disorder (PTSD), bipolar and related disorders including bipolar I disorder, bipolar II disorder, cyclothymic disorder, obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), social anxiety disorder, substance use disorders, alcohol use disorder, opioid use disorder, amphetamine use disorder, nicotine use disorder, and cocaine use disorder, anorexia nervosa, bulimia nervosa, Alzheimer's disease, cluster headache and migraine, attention deficit hyperactivity disorder (ADHD), pain, neuropathic pain, aphantasia, childhood-onset fluency disorder, major neurocognitive disorder, mild neurocognitive disorder, sexual dysfunction, chronic fatigue syndrome, Lyme Disease, obesity, autonomic nervous system (ANS) disorders, pulmonary disorders and cardiovascular disorders. 
     
     
         21 . The method of  claim 14 , wherein the one or more diseases or conditions are associated with a serotonin 5-HT 2  receptor. 
     
     
         22 . The method of  claim 14 , wherein the one or more diseases or conditions are selected from the group consisting of central nervous system (CNS) disorders, major depressive disorder (MDD), major depressive disorder (MDD) with suicidal ideation or suicidal behavior, suicidal ideation, suicidal behavior, non-suicidal self-injury disorder (NSSID), treatment-resistant depression (TRD), post-traumatic stress disorder (PTSD), bipolar and related disorders including bipolar I disorder, bipolar II disorder, cyclothymic disorder, obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), social anxiety disorder, substance use disorders, alcohol use disorder, opioid use disorder, amphetamine use disorder, nicotine use disorder, and cocaine use disorder, anorexia nervosa, bulimia nervosa, Alzheimer's disease, cluster headache and migraine, attention deficit hyperactivity disorder (ADHD), pain, neuropathic pain, aphantasia, childhood-onset fluency disorder, major neurocognitive disorder, mild neurocognitive disorder, sexual dysfunction, chronic fatigue syndrome, Lyme Disease, obesity, autonomic nervous system (ANS) disorders, pulmonary disorders and cardiovascular disorders.