Substituted triazoles and methods relating thereto
Substituted 1,2,3-triazole compounds are disclosed which have utility in the treatment of a variety of neurological disorders. The compounds provided herein have the general structure: wherein R 1 , R 2 , R 3 and n are as defined herein, including stereoisomers, esters, solvates and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound provided herein in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for treating neurological disorders in a subject in need thereof.
1. A method for treating a neurological condition of a subject having said neurological condition, wherein the neurological condition is essential tremor, epilepsy, status epilepticus or nerve agent exposure, comprising administering to the subject an effective amount of a compound having the following structure (A):
or a stereoisomer, ester, solvate, or pharmaceutically acceptable salt thereof,
wherein:
R 1 and R 2 taken together with the N to which they are attached, form a 5-6 member nonaromatic heterocycle wherein the 5-6 member nonaromatic heterocycle may be substituted with 0-3 R 4 ;
R 3 at each occurrence is Cl, F, C 1-4 alkyl, —OC 1-4 alkyl or trifluoromethyl;
R 4 at each occurrence is C 1-4 alkyl; and
n is 0-3.
2. A method for treating a neurological condition of a subject having said neurological condition, wherein the neurological condition is essential tremor, epilepsy, status epilepticus or nerve agent exposure, comprising administering to the subject an effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound having the following structure (A):
or a stereoisomer, ester, solvate, or pharmaceutically acceptable salt thereof,
wherein:
R 1 and R 2 taken together with the N to which they are attached, form a 5-6 member nonaromatic heterocycle wherein the 5-6 member nonaromatic heterocycle may be substituted with 0-3 R 4 ;
R 3 at each occurrence is Cl, F, C 1-4 alkyl, —OC 1-4 alkyl or trifluoromethyl;
R 4 at each occurrence is C 1-4 alkyl; and
n is 0-3.
3. The method of any one of claim 1 or 2 , wherein the neurological condition is essential tremor.
4. The method of any one of claim 1 or 2 , wherein n is 1.
5. The method of any one of claim 1 or 2 , wherein n is 2.
6. The method of any one of claim 1 or 2 , wherein R 3 is Cl, F, or trifluoromethyl.
7. The method of any one of claim 1 or 2 , wherein R 3 is C 1-4 alkyl or —OC 1-4 alkyl.
8. The method of any one of claim 1 or 2 , wherein n is 1 or 2 and R 3 is F.
9. The method of any one of claim 1 or 2 , wherein n is 1 and R 3 is F.
10. The method of any one of claim 1 or 2 , wherein R 4 is absent.
11. The method of any one of claim 1 or 2 , wherein n is 2 and each occurrence of R 3 is F.
12. The method of any one of claim 1 or 2 , wherein R 3 is C 1-4 alkyl, —OC 1-4 alkyl, trifluoromethyl, or Cl.
13. The method of any one of claim 1 or 2 , wherein the heterocycle formed by R 1 and R 2 taken together is piperidine.
14. The method of any one of claim 1 or 2 , wherein the heterocycle formed by R 1 and R 2 taken together is morpholine.
15. The method of any one of claim 1 or 2 , wherein the heterocycle formed by R 1 and R 2 taken together is piperazine, oxazolidine, or pyrrolidine.
16. The method of any one of claim 1 or 2 , wherein R 4 is methyl or ethyl.
17. The method of any one of claim 1 or 2 , wherein the compound is 4-{1-[(2,6-difluorophenyl)methyl]-1H-1,2,3-triazol-4-yl}morpholine.
18. The method of any one of claim 1 or 2 , wherein the compound is 1-[(2,6-difluorophenyl)methyl]-4-(pyrrolidin-1-yl)-1H-1,2,3-triazole.
19. The method of claim 17 , wherein the neurological condition is essential tremor.
20. The method of claim 18 , wherein the neurological condition is essential tremor.