Salts of a heterocyclic compound and crystalline forms, processes for preparing, therapeutic uses, and pharmaceutical compositions thereof

Abstract

The present disclosure relates to salts of (R)-1-(8-fluoroisochroman-1-yl)-N-methylmethanamine, crystalline forms thereof, and methods of preparation thereof, which are useful in the treatment of CNS disorders.

1 . A salt, which is:
 (R)-1-(8-fluoroisochroman-1-yl)-N-methylmethanamine L-tartrate (Compound 1 L-Tartrate);   (R)-1-(8-fluoroisochroman-1-yl)-N-methylmethanamine fumarate (Compound 1 Fumarate); or   (R)-1-(8-fluoroisochroman-1-yl)-N-methylmethanamine citrate (Compound 1 Citrate);   or a hydrate or solvate thereof.   
     
     
         2 . The salt of  claim 1 , wherein the salt is a solid form. 
     
     
         3 - 12 . (canceled) 
     
     
         13 . The salt of  claim 1 , wherein the salt is (R)-1-(8-fluoroisochroman-1-yl)-N-methylmethanamine L-tartrate (Compound 1 L-Tartrate). 
     
     
         14 . The salt of  claim 13 , wherein Compound 1 L-tartrate is crystalline. 
     
     
         15 . The salt of  claim 14  having Form LA, Form LB, or Form LC. 
     
     
         16 . The salt of  claim 15 , wherein:
 A) Form LA has:
 characteristic XRPD peaks in terms of 2θ selected from 12.1°±0.2°, 18.1°±0.2°, and 24.2°±0.2°; 
 an XRPD pattern with characteristic peaks as substantially shown in  FIG. 10  ( FIG. 10 ); 
 endotherm peaks at temperatures of about 89° C. and/or about 138° C.; 
 a DSC thermogram substantially as depicted in  FIG. 11  ( FIG. 11 ); 
 a TGA thermogram substantially as depicted in  FIG. 12  ( FIG. 12 ); or 
 a DVS isotherm substantially as depicted in  FIG. 13  ( FIG. 13 ); or 
   B) Form LB has:
 characteristic XRPD peaks in terms of 2θ selected from 18.7°±0.2°, 25.0°±0.2°, and 31.4°±0.2°; 
 an XRPD pattern with characteristic peaks as substantially shown in  FIG. 14  ( FIG. 14 ); or 
 a DVS isotherm substantially as depicted in  FIG. 15  ( FIG. 15 ); or 
   C) Form LC has:
 characteristic XRPD peaks in terms of 2θ selected from 12.2°±0.2°, 16.5°±0.2°, and 24.8°±0.2°; 
 an XRPD pattern with characteristic peaks as substantially shown in  FIG. 16  ( FIG. 16 ); 
 an endotherm peak at a temperature of about 137° C.; 
 a DSC thermogram substantially as depicted in  FIG. 17  ( FIG. 17 ); 
 a TGA thermogram substantially as depicted in  FIG. 18  ( FIG. 18 ); or 
 a DVS isotherm substantially as depicted in  FIG. 19  ( FIG. 19 ). 
   
     
     
         17 - 27 . (canceled) 
     
     
         28 . The salt of  claim 1 , wherein the salt is (R)-1-(8-fluoroisochroman-1-yl)-N-methylmethanamine fumarate (Compound 1 L-Fumarate). 
     
     
         29 . The salt of  claim 28 , wherein Compound 1 Fumarate is crystalline. 
     
     
         30 . The salt of  claim 29 , having Form FA or Form FB. 
     
     
         31 . The salt of  claim 30 , wherein:
 A) Form FA has:
 characteristic XRPD peaks in terms of 2θ selected from 7.7°±0.2°, 14.2°±0.2°, and 15.2°±0.2°; 
 an XRPD pattern with characteristic peaks as substantially shown in  FIG. 22  ( FIG. 22 ); 
 an endotherm peak at a temperature of about 147° C.; 
 a DSC thermogram substantially as depicted in  FIG. 23  ( FIG. 23 ); 
 a TGA thermogram substantially as depicted in  FIG. 24  ( FIG. 24 ); or 
 a DVS isotherm substantially as depicted in  FIG. 25  ( FIG. 25 ); or 
   B) Form FB has:
 characteristic XRPD peaks in terms of 2θ selected from 6.7°±0.2°, 13.8°±0.2°, and 20.2°±0.2°, 
 an XRPD pattern with characteristic peaks as substantially shown in  FIG. 26  ( FIG. 26 ); 
 an endotherm peak at a temperature of about 96° C., about 139° C., and/or about 146° C.; 
 a DSC thermogram substantially as depicted in  FIG. 27  ( FIG. 27 ); 
 a TGA thermogram substantially as depicted in  FIG. 28  ( FIG. 28 ); or 
 a DVS isotherm substantially as depicted in  FIG. 29  ( FIG. 29 ). 
   
     
     
         32 - 35 . (canceled) 
     
     
         36 . The salt of  claim 1 , wherein the salt is (R)-1-(8-fluoroisochroman-1-yl)-N-methylmethanamine citrate (Compound 1 Citrate). 
     
     
         37 . The salt of  claim 36 , wherein Compound 1 Citrate is crystalline. 
     
     
         38 . The salt of  claim 37 , wherein the salt has:
 characteristic XRPD peaks in terms of 2θ selected from 6.5°±0.2°, 15.5°±0.2°, and 20.4°±0.2°;   an XRPD pattern with characteristic peaks as substantially shown in  FIG. 30  ( FIG. 30 );   an endotherm peak at a temperature of about 142° C.;   a DSC thermogram substantially as depicted in  FIG. 31  ( FIG. 31 );   a TGA thermogram substantially as depicted in  FIG. 32  ( FIG. 32 ); or   a DVS isotherm substantially as depicted in  FIG. 33  ( FIG. 33 ).   
     
     
         39 - 74 . (canceled) 
     
     
         75 . A pharmaceutical composition comprising the salt of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         76 . A method for treating a neurological or psychiatric disease or disorder in a subject in need thereof, comprising administering to said subject an effective amount of the salt of  claim 1 . 
     
     
         77 . The method according to  claim 76 , wherein the neurological or psychiatric disease or disorder is depression, bipolar disorder, pain, schizophrenia, or other psychotic diseases, obsessive compulsive disorder, addiction, social disorder, attention deficit hyperactivity disorder, an anxiety disorder, a movement disorder, epilepsy, autism or cognitive disease or disorder. 
     
     
         78 . The method according to  claim 76 , wherein the neurological or psychiatric disease or disorder is depression. 
     
     
         79 . The method according to  claim 78 , wherein the depression is treatment-resistant depression (TRD), major depressive disorder (MDD), unipolar depression, bipolar depression or depression associated with another disease or disorder. 
     
     
         80 . The method according to  claim 76 , wherein said neurological disease or disorder is selected from Alzheimer's disease and Parkinson's disease. 
     
     
         81 . The method according to  claim 80 , wherein said Alzheimer's disease is Alzheimer's disease with agitation, Alzheimer's disease with aggression, Alzheimer's disease agitation or Alzheimer's disease with agitation aggression. 
     
     
         82 . A method of treating agitation in a subject in need thereof, comprising administering to said subject an effective amount of the salt of  claim 1 . 
     
     
         83 . A method of treating agitation associated with a neurological or psychiatric disease or disorder in a subject in need thereof, comprising administering to said subject an effective amount of the salt  claim 1 . 
     
     
         84 - 129 . (canceled)