Dialkyl tryptamines and their therapeutic uses

Abstract

The disclosure relates to a compound of formula (I):The disclosure also relates to a compound of formula (Ia):The disclosure relates to compositions comprising, consisting essentially of, or consisting of a compound of formula (I) or formula (Ia) and an excipient. The disclosure also relates to pharmaceutical compositions comprising a therapeutically effective amount of a compound of formula (I) or formula (Ia) where the excipient is a pharmaceutically acceptable carrier. The disclosure further relates to therapeutic uses of compounds of formula (I) or formula (Ia).

1 . A method of administering psilocin comprising:
 administering a therapeutically effective amount of a psilocin prodrug of formula (I) or formula (Ia) to a subject in need thereof,   providing a rate of conversion of the psilocin prodrug of formula (I) or formula (Ia) into psilocin which is increased relative to the rate of conversion of psilocybin into psilocin;   wherein formula (I) is:                         wherein
 R 1  and R 2  are each independently a C 1 -C 6  alkyl or a C 2 -C 6  alkenyl; 
 one of R 3  and R 4  is hydrogen and the other of R 3  and R 4  is chosen from —OR 5 , —OC(O)R 5 , —OC(O)OR 5 , or —OSO 2 R 5 ; 
 R 5  is a C 1 -C 6  alkyl or a substituted or unsubstituted aryl; and 
 R 6 , R 7 , and R 8  are each independently selected from hydrogen or a C 1 -C 6  alkyl; 
   or a pharmaceutically acceptable acid-addition salt thereof; and   formula (Ia) is:                         wherein
 R 1a  and R 2a  are each independently a C 1 -C 6  alkyl or a C 2 -C 6  alkenyl; 
 R 3a  and R 4a  are each independently selected from hydrogen, —OR 5a , —OC(O)R 5a , —OC(O)OR 5a , and —OSO 2 R 5a ; 
 R 5a  is a C 1 -C 6  alkyl or a substituted or unsubstituted aryl; and 
 R 6a , R 7a , and R 8a  are each independently selected from hydrogen or a C 1 -C 6  alkyl; 
 R 9a  is hydrogen; and 
 X 2-  is a pharmaceutically-acceptable dianion. 
   
     
     
         2 . The method of  claim 1 , wherein the therapeutically effective amount of the psilocin prodrug of formula (I) or formula (Ia) is administrated as an oral dosage composition. 
     
     
         3 . The method of  claim 1 , wherein the psilocin prodrug is a psilocin prodrug of formula (I). 
     
     
         4 . The method of  claim 1 , wherein the psilocin prodrug is a psilocin prodrug of formula (Ia). 
     
     
         5 . The method of  claim 3 , wherein the psilocin prodrug of formula (I) is 4-acetoxy-N,N-dimethyltryptamine or a pharmaceutically acceptable salt thereof. 
     
     
         6 . The method of  claim 4 , wherein the psilocin prodrug of formula (Ia) is a pharmaceutically acceptable dianion salt of 4-acetoxy-N,N-dimethyltryptamine. 
     
     
         7 . The method of  claim 1 , wherein 0.1 to 100 mg of the psilocin prodrug of formula (I) or formula (Ia) is administered. 
     
     
         8 . A method of treating a disorder comprising:
 administering a therapeutically effective amount of a psilocin prodrug of formula (I) or formula (Ia) to a subject in need thereof,   providing a rate of conversion of the psilocin prodrug of formula (I) or formula (Ia) into psilocin which is increased relative to the rate of conversion of psilocybin into psilocin,   wherein formula (I) is:                         wherein
 R 1  and R 2  are each independently a C 1 -C 6  alkyl or a C 2 -C 6  alkenyl; 
 one of R 3  and R 4  is hydrogen and the other of R 3  and R 4  is chosen from —OR 5 , —OC(O)R 5 , —OC(O)OR 5 , or —OSO 2 R 5 ; 
 R 5  is a C 1 -C 6  alkyl or a substituted or unsubstituted aryl; and 
 R 6 , R 7 , and R 8  are each independently selected from hydrogen or a C 1 -C 6  alkyl; 
   or a pharmaceutically acceptable acid-addition salt thereof; and   formula (Ia) is:                         wherein
 R 1a  and R 2a  are each independently a C 1 -C 6  alkyl or a C 2 -C 6  alkenyl; 
 R 3a  and R 4a  are each independently selected from hydrogen, —OR 5a , —OC(O)R 5a , —OC(O)OR 5a , and —OSO 2 R 5a ; 
 R 5a  is a C 1 -C 6  alkyl or a substituted or unsubstituted aryl; and 
 R 6a , R 7a  and R 8a  are each independently selected from hydrogen or a C 1 -C 6  alkyl; 
 R 9a  is hydrogen; and 
 X 2-  is a pharmaceutically-acceptable dianion. 
   
     
     
         9 . The method of  claim 8 , wherein the disorder is selected from anxiety, post-traumatic stress disorder, inflammation, pain, and a neurological disorder. 
     
     
         10 . The method of  claim 1 , wherein formula (Ia) is with the proviso that when R 3a  is -OC(O)R 5a  and R 4a , R 6a , R 7a , R 8a , and R 9a  are hydrogen, then R 5a  is not methyl when either both R 1a  and R 2a  are methyl or one of R 1a  and R 2a  is ethyl and the other of R 1a  and R 2a  is propyl; and 
 with the proviso that when R 4a  is —OR 5a  and R 3a , R 6a , R 7a , R 8a , and R 9a  are hydrogen, then R 5a  is not methyl when either both R 1a  and R 2a  are propyl or both R 1a  and R 2a  are allyl. 
 
     
     
         11 . The method of  claim 8 , wherein formula (Ia) is with the proviso that when R 3a  is -OC(O)R 5a  and R 4a , R 6a , R 7a , R 8a , and R 9a  are hydrogen, then R 5a  is not methyl when either both R 1a  and R 2a  are methyl or one of R 1a  and R 2a  is ethyl and the other of R 1a  and R 2a  is propyl; and
 with the proviso that when R 4a  is —OR 5a  and R 3a , R 6a , R 7a , R 8a , and R 9a  are hydrogen, then R 5a  is not methyl when either both R 1a  and R 2a  are propyl or both R 1a  and R 2a  are allyl.