Thiadiazole derivatives for the treatment of neuro-degenerative diseases

• US 7,960,556 B2
• Filed: 11/22/2007
• Issued: 06/14/2011
• Est. Priority Date: 11/22/2006
• Status: Expired due to Fees

• Current Assignee: Nv Remynd
• Original Assignee: Nv Remynd
• Inventors: Van Damme, Nele, Wera, Stefaan, Gommé, Ellen, Griffioen, Gerard, Duhamel, Hein Roger
• Primary Examiner(s): Saeed; Kamal A
• Assistant Examiner(s): GRAZIER, NYEEMAH A
• Application Number:
  US12/515,824
• Publication Number:
  US 20100144709A1
• Time in Patent Office: 1,300 Days
• Field of Search: None
• US Class Current: 548/128
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07D 285/08 1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

The invention provides novel 1,2,4-thiadiazole derivatives useful for preventing or treating an α-synucleopathy such as Parkinson'"'"'s disease, as well as pharmaceutical compositions including them as biologically active ingredients, and methods for manufacturing them.

Claims

1. A 1,2,4-thiadiazole derivative according to the structural formula (C):

2. The 1,2,4-thiadiazole derivative according to claim 1, wherein Het¹ is selected from the group consisting of furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, cyanoimidazolyl, dicyanoimidazolyl, isoxazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, pyranyl, pyridyl, ethylpyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, tetrazolyl, thiadiazinyl, indolyl, isoindolyl, benzofuryl, benzothienyl, benzothiophenyl, indazolyl, benzimidazolyl, benzthiazolyl, benzisothiazolyl, benzisoxazolyl, purinyl, quinazolinyl, quinolizinyl, quinolinyl, isoquinolinyl, ethylquinolinyl, quinoxalinyl, naphthyridinyl, pteridinyl carbazolyl, azepinyl, diazepinyl, acridinyl, pyrrolinyl, pyrazolinyl, indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, azepinyl, diazepinyl, morpholinyl, thiomorpholinyl, oxazolidinyl, oxazolinyl, oxazepinyl, aziridinyl and tetrahydrofuranyl.

3. The 1,2,4-thiadiazole derivative according to claim 1, wherein the linking moiety X is SO₂.

4. The 1,2,4-thiadiazole derivative according to claim 1, wherein X is a divalent saturated group comprising a carbon atom and a nitrogen atom in the main chain, said carbon atom being substituted with oxo or thioxo.

5. The 1,2,4-thiadiazole derivative according to claim 1, wherein at least two of R₁, R₂, R₃, R₄ and R₅ are hydrogen.

6. The 1,2,4-thiadiazole derivative according to claim 1, wherein at least one of R₁, R₂, R₃, R₄ and R₅ is methoxy.

7. The 1,2,4-thiadiazole derivative according to claim 1, wherein n is 1 or 2.

8. The 1,2,4-thiadiazole derivative according to claim 1, wherein R and R′

are both hydrogen.

9. The 1,2,4-thiadiazole derivative according to claim 1, wherein at least one of R and R′

is methyl.

10. The 1,2,4-thiadiazole derivative according to claim 1, wherein two adjacent substituents selected from the group consisting of R₇, R₈, R₉, R₁₀ and R₁₁ form, together with the phenyl ring carbon atoms to which they are attached, a homocyclic or heterocyclic group fused to said phenyl ring.

11. A pharmaceutical composition comprising a therapeutic effective amount of a 1,2,4-thiadiazole derivative according to claim 1.

12. The pharmaceutical composition according to claim 11, further comprising a therapeutic amount of one or more drugs selected from the group consisting of neuro-protective agents and α

-synuclein deposition inhibitors.

13. A method of treating neurological disorders characterized by cytotoxic α

-synucleopathy, comprising the administration of a therapeutic effective amount of a 1,2,4-thiadiazole derivative according to claim 1, to a patient in need thereof.

14. The method of treatment according to claim 13, wherein said neurological disorders are selected from the group consisting of Parkinson'"'"'s disease, diffuse Lewy body disease, traumatic brain injury, amyotrophic lateral sclerosis, Niemann-Pick disease, Hallervorden-Spatz syndrome, Down syndrome, neuroaxonal dystrophy, multiple system atrophy and Alzheimer'"'"'s disease.

15. The 1,2,4-thiadiazole derivative according to claim 1, being selected from the group consisting of:

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N′

-[4-methoxyphenylsulfonyl]-N-[3-(3-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N-methylethane-1,2-diamine,

N′

-[4-methoxyphenylsulfonyl]-N-[3-(3-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N′

-methylethane-1,2-diamine,

N′

-[4-methoxyphenylsulfonyl]-N-[3-(3-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethylethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-methylbenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-benzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methylbenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-methylbenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methyl-4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-chlorobenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-methylbenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-benzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methylbenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-methylbenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methyl-4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-chlorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-methylbenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-benzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methylbenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-methylbenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methyl-4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-chlorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-benzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methyl-4-fluorobenzyl)-1,2,4-thia-diazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-chlorobenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-benzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methyl-4-fluorobenzyl)-1,2,4-thia-diazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-chlorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-benzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(2-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(3-methyl-4-fluorobenzyl)-1,2,4-thia-diazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[4-methoxyphenylsulfonyl]-N′

-[3-(4-chlorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N′

-[2-thienylsulfonyl]-N-[3-(3-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N-methylethane-1,2-diamine,

N′

-[2-thienylsulfonyl]-N-[3-(3-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N′

-methylethane-1,2-diamine,

N′

-[2-thienylsulfonyl]-N-[3-(3-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethylethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-methylbenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-benzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methylbenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-methylbenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methyl-4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-chlorobenzyl)-1,2,4-thiadiazol-5-yl]-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-methylbenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-benzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methylbenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-methylbenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methyl-4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-chlorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,3-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-methylbenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-benzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methylbenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-methylbenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methyl-4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-chlorobenzyl)-1,2,4-thiadiazol-5-yl]-propane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-benzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methyl-4-fluorobenzyl)-1,2,4-thia-diazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-chlorobenzyl)-1,2,4-thiadiazol-5-yl]-N-methyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-benzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methyl-4-fluorobenzyl)-1,2,4-thia-diazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-chlorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-dimethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-fluorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-benzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-methylbenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(2-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(4-methoxybenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine,

N-[2-thienylsulfonyl]-N′

-[3-(3-methyl-4-fluorobenzyl)-1,2,4-thia-diazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine, and

N-[2-thienylsulfonyl]-N′

-[3-(4-chlorobenzyl)-1,2,4-thiadiazol-5-yl]-N,N′

-diethyl-ethane-1,2-diamine.

16. The pharmaceutical composition of claim 11, further comprising at least one pharmaceutically acceptable carrier.

17. The method of claim 13, wherein said therapeutic effective amount of a 1,2,4-thiadiazole derivative is administered to a patient in combination with one or more pharmaceutically acceptable carriers.

18. The method of claim 13, wherein said therapeutic effective amount of a 1,2,4-thiadiazole derivative is administered to a patient in combination with a therapeutic amount of one or more drugs selected from the group consisting of neuro-protective agents and α

-synuclein deposition inhibitors.