RU2001130169A - Derivatives of carbamic acid and their use as ligands of metabotropic glutamate receptors - Google Patents

Claims (19)

1. Compounds of the general formula

where R ¹ means hydrogen or (C ₁ -C ₇ ) alkyl; R ² , R ^{2 ′ are} independently hydrogen, (C ₁ -C ₇ ) alkyl, (C ₁ -C ₇ ) alkoxy, halogen or trifluoromethyl; X is O, S, or two hydrogen atoms that do not form a bridge; A ¹ / A ² mean independently phenyl or a 6-membered heterocycle containing 1 or 2 nitrogen atoms; B is a group of the formula

where R ³ means (C ₁ -C ₇ ) alkyl, (C ₁ -C ₇ ) alkenyl, (C ₁ -C ₇ ) alkynyl, benzyl, (C ₁ -C ₇ ) alkylcycloalkyl, (C ₁ -C ₇ ) alkylcyano group , (C ₁ -C ₇ ) alkyl pyridinyl, (C ₁ -C ₇ ) alkyl- (C ₁ -C ₇ ) alkoxyphenyl, (C ₁ -C ₇ ) alkylphenyl optionally substituted with a (C ₁ -C ₇ ) alkoxy group, or phenyl optionally substituted with a (C ₁ -C ₇ ) alkoxy group, or (C ₁ -C ₇ ) alkylthienyl, cycloalkyl, (C ₁ -C ₇ ) alkyl trifluoromethyl or (C ₁ -C ₇ ) alkyl morpholinyl, Y is —O—, —S— or a bond; Z is —O— or —S—; or B means a 5-membered heterocyclic group of the formulas

where R ⁴ and R ^{5 are} hydrogen, (C ₁ -C ₇ ) alkyl, (C ₁ -C ₇ ) alkoxy, cyclohexyl, (C ₁ -C ₇ ) alkylcyclohexyl or trifluoromethyl, provided that at least one from R ⁴ or R ⁵ must be hydrogen; and their pharmaceutically acceptable salts, with the exception of N- (diphenylacetyl) thiobenzamide, N-benzoyldiphenylacetamide, N-phenoxycarbonyl-α, α-diphenylacetamide and N-phenoxycarbonyl-α-2-pyridylacetamide. 2. The compounds of formula IA according to claim 1

where B is a group of the formula

and the remaining substituents are as defined in claim 1. 3. The compounds of formula IB according to claim 1

where B is a 5-membered heterocyclic group of the formulas

and the remaining substituents are as defined in claim 1. 4. The compounds of formula IA according to claim 2, where A is phenyl, X is 2 hydrogen atoms not forming a bridge, and Z is —O—. 5. The compound of claim 4, which is diphenylacetylcarbamic acid butyl ether, diphenylacetylcarbamic acid ethyl ester, or diphenylacetylcarbamic acid pent-4-ylyl ester. 6. The compounds of formula IA according to claim 2, wherein A is phenyl, X is —O— or –S—, and Z is —O—. 7. The compounds of formula IA according to claim 6, which are carbamic acid ethyl ester (9H-xanthene-9-carbonyl), carbamic acid butyl ether (9H-xanthene-9-carbonyl) or (9H-thioxanthen-9- butyl ether) carbonyl) carbamic acid. 8. The compounds of formula IB according to claim 3, in which A is phenyl, X is 2 hydrogen atoms that do not form a bridge, and Z is —O—. 9. The compounds of formula IB of claim 8, which are N- (5-ethyloxazol-2-yl) -2,2-diphenylacetamide, N- (5-methyloxazol-2-yl) -2,2-diphenylacetamide, 2 , 2-diphenyl-N- (5-propyl- [1,3,4] oxadiazol-2-yl) acetamide, N- [5- (2-methoxyethyl) - [1,3,4] oxadiazol-2-yl ] -2,2-diphenylacetamide, N- (3-methyl- [1,2,4] oxadiazol-5-yl) -2,2-diphenylacetamide, N- (3-cyclopropyl- [1,2,4] oxadiazole -5-yl) -2,2-diphenylacetamide or N- (5-methyl- [1,2,4] oxadiazol-3-yl) -2,2-diphenylacetamide. 10. The compounds of formula IB according to claim 3, wherein A is phenyl, X is —O— and Z is —O—. 11. The compounds of formula IB of claim 10, which are 9H-xanthene-9-carboxylic acid oxazol-2-ylamide, 9H-xanthene- (5-propyl- [1,3,4] oxadiazol-2-yl) amide 9-carboxylic acid, (5-ethyloxazol-2-yl) amide 9H-xanthene-9-carboxylic acid, (5-methyloxazol-2-yl) amide 9H-xanthene-9-carboxylic acid, (5-propyloxazole-2- il) amide of 9H-xanthene-9-carboxylic acid, (5-ethyl- [1,3,4] oxadiazol-2-yl) amide of 9H-xanthene-9-carboxylic acid, (5-cyclopropylmethyl- [1,3, 4] oxadiazol-2-yl) amide of 9H-xanthene-9-carboxylic acid, (4-methyloxazol-2-yl) amide of 9H-xanthene-9-carboxylic acid, (3-methyl- [1,2,4] ox diazol-5-yl) amide of 9H-xanthene-9-carboxylic acid, (5-trifluoromethyl- [1,3,4] oxadiazol-2-yl) amide of 9H-xanthene-9-carboxylic acid, (5-methoxymethyl- [ 1,3,4] oxadiazol-2-yl) amide of 9H-xanthene-9-carboxylic acid, (3-cyclopropyl- [1,2,4] oxadiazol-5-yl) amide of 9H-xanthene-9-carboxylic acid or (5-methyl- [1,2,4] oxadiazol-3-yl) amide 9H-xanthene-9-carboxylic acid. 12. A medicament comprising a compound according to any one of claims 1 to 11, as well as their pharmaceutically acceptable salts and pharmaceutically acceptable excipients. 13. The drug according to item 12 for the treatment or prevention of acute and / or chronic neurological disorders, limited brain activity caused by bypass surgery or transplantation, poor blood supply to the brain, spinal cord injuries, head injuries, hypoxia caused by pregnancy, heart failure , hypoglycemia, Alzheimer's disease, Huntington’s chorea, amyotrophic lateral sclerosis (ALS), dementia caused by AIDS, eye injuries, retinopathy, cognitive disorders, disorders memory, schizophrenia, Parkinsonism of unknown origin or Parkinsonism caused by drugs, as well as conditions leading to glutamate deficiency reactions, muscle cramps, convulsions, migraines, urinary incontinence, addiction to nicotine, psychoses, opium addiction, anxiety, vomiting, acute and chronic pain, dyskinesia, and depression. 14. The use of compounds according to any one of claims 1 to 11, as well as their pharmaceutically acceptable salts for the treatment or prevention of diseases. 15. The use of compounds of the formula I according to any one of claims 1 to 11 for the preparation of medicines containing compounds of the formula I for the treatment of the diseases stated in paragraph 13. 16. Compounds according to claims 1-11, as well as their pharmaceutically acceptable salts for the treatment or prevention of acute and / or chronic neurological disorders. 17. A method of producing compounds according to any one of claims 1 to 11, as well as their pharmaceutically acceptable salts, which includes a) the interaction of the compounds of formula

with a compound of the formula

with the formation of the compounds of formula

where the substituents have the values given in paragraph 1, or b) reacting a compound of the formula

with a compound of the formula

with the formation of the compounds of formula

where G means a suitable leaving group and the remaining substituents have the meanings given in claim 1, C) or the interaction of the compounds of formula

with a compound of the formula

with the formation of the compounds of formula

where the substituents have the meanings in paragraph 1, or g) the interaction of the compounds of formula

with a compound of the formula

with the formation of the compounds of formula

where the substituents have the meanings given in paragraph 1 above, or d) the interaction of the compounds of formula

with a heterocyclic compound of the formula B-NH ₂ IX with the formation of the compounds of formula

where In means a 5-membered heterocycle of the formulas

G is a leaving group and the remaining substituents have the meanings given in paragraph 1, and, if desired, converting a compound of formula I into a pharmaceutically acceptable salt. 18. Compounds according to claims 1-11, obtained according to the method according to 17. 19. The invention presented in the description.