RU2001126570A

RU2001126570A - Derivatives of 1-arensulfonyl-2-arylpyrrolidine and piperidine for the treatment of disorders of the central nervous system

Info

Publication number: RU2001126570A
Application number: RU2001126570/04A
Authority: RU
Inventors: Венсан МЮТЕЛЬ; Эрик ВИЕЙРА; Юрген ВИХМАНН
Original assignee: Ф.Хоффманн-Ля Рош Аг
Priority date: 1999-03-25
Filing date: 2000-03-18
Publication date: 2003-06-27

Claims

1. Compounds of the general formula

where R ¹ means hydrogen or (C ₁ -C ₇ ) alkyl;

R ² means furyl, thienyl, pyridyl or phenyl, optionally substituted with 1-3 substituents selected from (C ₁ -C ₇ ) alkyl, (C ₁ -C ₇ ) alkoxy, halogen, cyano, CF ₃ or -N (R ⁴ ) ₂ ;

R ³ means naphthyl or phenyl optionally substituted with 1-3 substituents selected from (C ₁ -C ₇ ) alkyl, (C ₁ -C ₇ ) alkoxy, halogen, acetyl, cyano, hydroxy (C ₁ -C ₇ ) alkyl, -CH ₂ -morpholin-4-yl, (C ₁ -C ₇ ) alkyloxy (C ₁ -C ₇ ) alkyl, (C ₁ -C ₇ ) alkyl-N (R ⁴ ) ₂ or CF ₃ ;

R ⁴ means independently hydrogen or (C ₁ -C ₇ ) alkyl, with the exception of (RS) -2-phenyl-1- (toluene-4-sulfonyl) pyrrolidine, (RS) -1- (toluene-4- sulfonyl) -2-p-tolylpyrrolidine, N-tosyl-cis-3-methyl-2-phenylpyrrolidine, 3- [1- (toluene-4-sulfonyl) pyrrolidin-2-yl] pyridine and N-tosyl-2- ( 3,4-dimethoxyphenyl) pyrrolidine, as well as their pharmaceutically acceptable salts.

2. The compounds according to claim 1, where R ¹ means hydrogen or methyl;

R ² is phenyl optionally substituted with halogen, (C ₁ -C ₇ ) alkyl, CF ₃ or —N (CH ₃ ) ₂ , and pharmaceutically acceptable salts thereof.

3. The compounds of claims 1 and 2, which are

(RS) -2- (3-fluorophenyl) -1- (toluene-4-sulfonyl) pyrrolidine,

(RS) -1- (4-chlorobenzenesulfonyl) -2- (3-fluorophenyl) pyrrolidine,

(RS) -1- (4-chlorobenzenesulfonyl) -2-phenylpyrrolidine,

(RS) -2- (4-chlorophenyl) -1- (toluene-4-sulfonyl) pyrrolidine,

(RS) -1- (4-chlorobenzenesulfonyl) -2- (4-fluorophenyl) pyrrolidine,

(RS) -2- (4-fluorophenyl) -1- (toluene-4-sulfonyl) pyrrolidine,

(RS) -1-benzenesulfonyl-2- (4-chlorophenyl) pyrrolidine,

(RS) -1- (4-fluorobenzenesulfonyl) -2- (4-fluorophenyl) pyrrolidine,

(RS) -2- (4-fluorophenyl) -1- (toluene-2-sulfonyl) pyrrolidine,

(RS) -1- (4-chlorobenzenesulfonyl) -2-p-tolylpyrrolidine,

(RS) -1- (4-ethylbenzenesulfonyl) -2- (4-fluorophenyl) pyrrolidine,

(RS) -1- (toluene-4-sulfonyl) -2-m-tolylpyrrolidine,

(RS) -2- (3-chlorophenyl) -1- (toluene-4-sulfonyl) pyrrolidine,

(RS) -2- (3,4-difluorophenyl) -1- (toluene-4-sulfonyl) pyrrolidine,

(RS) -2- (3-chloro-4-fluorophenyl) -1- (toluene-4-sulfonyl) pyrrolidine,

(RS) -1- (4-fluorobenzenesulfonyl) -2- (4-dimethylamino-3-chlorophenyl) pyrrolidine,

(RS) -1- (toluene-4-sulfonyl) -2- (4-fluoromethylphenyl) pyrrolidine,

(RS) -2- (4-chloro-3-methylphenyl) -1- (toluene-4-sulfonyl) pyrrolidine,

(RS) -2- (4-fluorophenyl) -1- (4-trifluoromethylbenzenesulfonyl) pyrrolidine,

(RS) -2- (N, N-dimethylaminophenyl) -1- (4-fluorobenzenesulfonyl) pyrrolidine,

(R) -1- (4-chlorobenzenesulfonyl) -2- (4-fluorophenyl) pyrrolidine,

(S) -1- (4-chlorobenzenesulfonyl) -2- (4-fluorophenyl) pyrrolidine,

(RS) -2- (4-ethylphenyl) -1- (toluene-4-sulfonyl) pyrrolidine,

(RS) -2- (4-ethylphenyl) -1- (4-fluorobenzenesulfonyl) pyrrolidine,

(S) -2- (4-fluorophenyl) -1- (toluene-4-sulfonyl) pyrrolidine,

(R) -2- (4-fluorophenyl) -1- (toluene-4-sulfonyl) pyrrolidine,

(RS) -2- (4-fluorophenyl) -1- (4-methoxymethylbenzenesulfonyl) pyrrolidine and

(2RS, 3RS) -2- (4-fluorophenyl) -3-methyl-1- (toluene-4-sulfonyl) pyrrolidine.

4. The compounds according to claim 1, where R ¹ means hydrogen; and R ² is furyl, thienyl or pyridyl.

5. The compounds of claims 1 and 4, which are (RS) -1- (4-chlorobenzenesulfonyl) -2-thien-2-yl-pyrrolidine, (RS) -2-thien-2-yl-1- (toluene- 4-sulfonyl) pyrrolidine and (RS) -2-thien-3-yl-l- (toluene-4-sulfonyl) pyppolidine.

6. A medicament comprising a compound according to any one of claims 1 to 5 or (RS) -2-phenyl-1- (toluene-4-sulfonyl) pyrrolidine, (RS) -1- (toluene-4-sulfonyl) -2 p-tolylpyrrolidine, N-tosyl-cis-3-methyl-2-phenylpyrrolidine, 3- [1- (toluene-4-sulfonyl) pyrrolidin-2-yl] pyridine or N-tosyl-2- (3,4- dimethoxyphenyl) pyrrolidine, as well as their pharmaceutically acceptable salts and pharmaceutically acceptable excipients.

7. The drug according to claim 6 for the prevention or treatment of acute and / or chronic neurological disorders, such as limited brain function caused by bypass surgery or transplantation, poor blood supply to the brain, spinal cord injury, head injury, hypoxia caused by pregnancy, heart failure, hypoglycemia, Alzheimer's disease, Huntington's chorea, ALS, AIDS dementia, eye injuries, retinopathy, recognition disorders, memory disorders, as well as acute and chronic pain, schizophrenia, parkinson's m of unclear origin or parkinsonism caused by drugs, as well as conditions that lead to reactions associated with glutamate deficiency, such as muscle cramps, convulsions, migraines, urinary incontinence, addiction to nicotine, psychosis, addiction to opium, anxiety, vomiting, dyskinesia, and depression.

8. The use of compounds according to any one of claims 1 to 5 or (RS) -2-phenyl-1- (toluene-4-sulfonyl) pyrrolidine, (RS) -1- (toluene-4-sulfonyl) -2-p- tolylpyrrolidine, N-tosyl-cis-3-methyl-2-phenylpyrrolidine, 3- [1- (toluene-4-sulfonyl) pyrrolidin-2-yl] pyridine or N-tosyl-2- (3,4-dimethoxyphenyl) pyrrolidine and their pharmaceutically acceptable salts for the prevention or treatment of the disease and, accordingly, for the preparation of appropriate medicines.

9. The compounds of claims 1-5 or (RS) -2-phenyl-1- (toluene-4-sulfonyl) pyrrolidine, (RS) -1- (toluene-4-sulfonyl) -2-p-tolyl -pyrrolidine, N-tosyl-cis-3-methyl-2-phenylpyrrolidine, 3- [1- (toluene-4-sulfonyl) pyrrolidin-2-yl] pyridine or N-tosyl-2- (3,4-dimethoxyphenyl) pyrrolidine, as well as their pharmaceutically acceptable salts for the prevention or treatment of acute and / or chronic neurological disorders.

10. The method of obtaining compounds according to any one of claims 1 to 5, as well as their pharmaceutically acceptable salts, comprising reacting a compound of the formula

with a compound of the formula

and, if necessary, converting the functional group in the compound of formula I to another functional group, and, if necessary, converting the compound of formula I into a pharmaceutically acceptable salt.

11. Compounds according to claims 1-5, obtained in accordance with the method of claim 10.

12. The invention as described herein.