Derivatives of o-thiocarbamoylation, the retrieval method (variants), pharmaceutical composition, method of treatment (options)

 

The invention relates to a derivative Of thiocarbamoyl-aminoalcohol represented by structural formula (VI), in the form of racemates or enantiomers and their pharmaceutically acceptable salts in order to apply them for the treatment of diseases of the nervous system; where Ardenotes a phenyl group described by formula (1); in which R is chosen from the group consisting of hydrogen, lower alkyl containing 1-8 carbon atoms, halogen selected from F, Cl, Br and J, alkoxygroup containing 1-3 carbon atoms, coalcorp containing 1-3 carbon atoms, nitro, hydroxyl or tripterygiidae group, and x = 1, 2, 3, provided that R is the same or different when x = 2 or 3. R1and R2and R3and R4respectively may be the same or may differ from each other and are independently selected from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl 3-7-membered alicyclic compounds, each of 1, m and n denotes 0 or 1; or their pharmaceutically acceptable salts. Describes the various options of method of obtaining compounds, pharmaceutical compositions and methods of treating mammals suffering from disorders of the Central nervous age-break-before:always;">

Tablicy

Claims

1. The racemate O-thiocarbamoylation formula (VI)

in which Andrdenotes a phenyl group,

where R is selected from the group consisting of hydrogen, lower alkyl of 1-8 carbon atoms, halogen selected from F, C1, Br and J, alkoxyl containing 1-3 carbon atoms, thioalkyl containing 1-3 carbon atoms, nitro, hydroxyl, or trifloromethyl, and x denotes an integer from 1 to 3, provided that R is the same or different when x represents 2 or 3;

R1and R2can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered aliphatic compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains directly unbound oxygen atom;

R3and R4can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered alicyclic connection of the CSOs R denotes hydrogen, and its pharmaceutically acceptable salts.

3. Connection on p. 1, in which R denotes hydrogen, R1and R2can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl containing 1-8 carbon atoms, a 3-7-membered aliphatic cyclic (acyclic) compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains an oxygen atom that is not associated directly, R3and R4can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, a 3-7-membered alicyclic compounds, and pharmaceutically acceptable salts.

4. Connection on p. 1, in which x denotes 1, and its pharmaceutically acceptable salts.

5. Connection on p. 1, representing About-thiocarbamoyl-(D)-aminoalcohol formula (VIII)

6. Connection on p. 5, in which R stands for hydrogen, its pharmaceutically acceptable salt.

7. Connection on p. 5, in which R denotes hydrogen, R1and R2can be the same or different from each other and lowly aliphatic cyclic (acyclic) compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains an oxygen atom that is not associated directly, R3and R4can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, a 3-7-membered alicyclic compounds, and pharmaceutically acceptable salts.

8. Connection on p. 5, in which x denotes 1, and its pharmaceutically acceptable salts.

9. Connection on p. 1, representing About-thiocarbamoyl-(L)-aminoalcohol formula (IX)

10. Connection on p. 9, in which R stands for hydrogen, its pharmaceutically acceptable salt.

11. Connection on p. 9, in which R denotes hydrogen, R1and R2can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl containing 1-8 carbon atoms, a 3-7-membered aliphatic cyclic (acyclic) compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains an oxygen atom that is not associated to neposredno is, ostoja from hydrogen, lower alkyl with 1-8 carbon atoms, a 3-7-membered alicyclic compounds, and pharmaceutically acceptable salts.

12. Connection on p. 9, in which x denotes 1, and its pharmaceutically acceptable salts.

13. The racemate 0-thiocarbamoylation formula (X)

where Ardenotes a phenyl group

where R is selected from the group consisting of hydrogen, lower alkyl of 1-8 carbon atoms, halogen selected from F, C1, Br and J, alkoxyl containing 1-3 carbon atoms, thioalkyl containing 1-3 carbon atoms, nitro, hydroxyl, or tripterygiidae, and x denotes an integer from 1 to 3, provided that R is the same or different when x represents 2 or 3;

R1and R2can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered aliphatic compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains directly unbound oxygen atom;

R3and R4may be the same or othered, aryl, 3-7-membered alicyclic compounds and pharmaceutically acceptable salts.

14. Connection on p. 13, in which R stands for hydrogen, its pharmaceutically acceptable salt.

15. Connection on p. 13, in which R denotes hydrogen, R1and R2can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl containing 1-8 carbon atoms, a 3-7-membered aliphatic cyclic (acyclic) compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains an oxygen atom that is not associated directly, R3and R4can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, a 3-7-membered alicyclic compounds, and pharmaceutically acceptable salts.

16. Connection on p. 13, in which x denotes 1, and its pharmaceutically acceptable salts.

17. Connection on p. 13, which represents an About-thiocarbamoyl-(D)-aminoalcohol formula (XI)

where Ardenotes a phenyl group,

R1and R2can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered aliphatic compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains directly unbound oxygen atom;

R3and R4can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered alicyclic compounds and pharmaceutically acceptable salts.

18. Connection on p. 17, in which R stands for hydrogen, its pharmaceutically acceptable salt.

19. Connection on p. 17, in which R denotes hydrogen, R1and R2can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl containing 1-8 the e with the adjacent N-atom form a 6-membered cyclic compound, which optionally contains an oxygen atom that is not associated directly, R3and R4can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, a 3-7-membered alicyclic compounds, and pharmaceutically acceptable salts.

20. Connection on p. 17, in which x denotes 1, and its pharmaceutically acceptable salts.

21. Connection on p. 13, which represents an About-thiocarbamoyl-(L)-aminoalcohol formula(XII)

where Ardenotes a phenyl group,

where R is selected from the group consisting of hydrogen, lower alkyl of 1-8 carbon atoms, halogen selected from F, Cl, Br and J, alkoxyl containing 1-3 carbon atoms, thioalkyl containing 1-3 carbon atoms, nitro, hydroxyl, or tripterygiidae, and x denotes an integer from 1 to 3, provided that R is the same or different when x represents 2 or 3;

R1and R2can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered aliphatic sedimentologist directly contains the unbound oxygen atom;

R3and R4can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered alicyclic compounds,

and its pharmaceutically acceptable salts.

22. Connection on p. 21, in which R stands for hydrogen, its pharmaceutically acceptable salt.

23. Connection on p. 21, in which R denotes hydrogen, R1and R2can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl containing 1-8 carbon atoms, a 3-7-membered aliphatic cyclic (acyclic) compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains an oxygen atom that is not associated directly, R3and R4can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, a 3-7-membered alicyclic compounds, and pharmaceutically acceptable salts.

24. Connection on p. 21, characterized in that x denotes 1, and its pharmaceutically acceptable salts.

25. The racemate Of-tokarno group

where R is selected from the group consisting of hydrogen, lower alkyl of 1-8 carbon atoms, halogen selected from F, C1, Br and J, alkoxyl containing 1-3 carbon atoms, thioalkyl containing 1-3 carbon atoms, nitro, hydroxyl, or tripterygiidae, and x denotes an integer from 1 to 3, provided that R is the same or different when x represents 2 or 3;

R1and R2can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered aliphatic compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains not directly linked oxygen atom;

R3and R4may be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered alicyclic compounds, and R3and R4together with the adjacent N-atom form a 5-7-membered cyclic compound which optionally contains 0-1 additional nitrogen atom with substituent selected from the group SOS is farmacevtichesky acceptable salt.

26. Connection on p. 25, in which R stands for hydrogen, its pharmaceutically acceptable salt.

27. Connection on p. 25, in which R denotes hydrogen, R1and R2can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl containing 1-8 carbon atoms, a 3-7-membered aliphatic cyclic (acyclic) compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains an oxygen atom that is not associated directly, R3and R4can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, a 3-7-membered alicyclic compounds, and pharmaceutically acceptable salts.

28. Connection on p. 25, in which x denotes 1, and its pharmaceutically acceptable salts.

29. Connection on p. 25, which represents an About-thiocarbamoyl-(D)-aminoalcohol formula (XIV)

in which Andrdenotes a phenyl group

where R is selected from the group consisting of hydrogen, lower alkyl of 1-8 atoms ug is 1-3 carbon atoms, nitro, hydroxyl, or tripterygiidae, and x denotes an integer from 1 to 3, provided that R is the same or different when x represents 2 or 3;

R1and R2can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered aliphatic compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains not directly linked oxygen atom;

R3and R4can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered alicyclic compounds,

and its pharmaceutically acceptable salts.

30. Connection on p. 29, in which R stands for hydrogen, its pharmaceutically acceptable salt.

31. Connection on p. 29, in which R denotes hydrogen, R1and R2can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl containing 1-8 carbon atoms, a 3-7-membered aliphatic cyclic (acyclic) compounds, and Rthe spine contains an oxygen atom, not affiliated, R3and R4can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, a 3-7-membered alicyclic compounds, and pharmaceutically acceptable salts.

32. A connection on p. 29, in which x denotes 1, and its pharmaceutically acceptable salts.

33. Connection on p. 25, which represents an About-thiocarbamoyl-(L)-aminoalcohol formula XV

where Ardenotes a phenyl group

where R is selected from the group consisting of hydrogen, lower alkyl of 1-8 carbon atoms, halogen selected from F, Cl, Br and J, alkoxyl containing 1-3 carbon atoms, thioalkyl containing 1-3 carbon atoms, nitro, hydroxyl, or tripterygiidae, and x denotes an integer from 1 to 3, provided that R is the same or different when x represents 2 or 3;

R1and R2can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered aliphatic compounds, and R1and R2together with the adjacent N-atom kislorodny atom;

R3and R4can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered alicyclic compounds and farmatsevticheskii acceptable salt.

34. Connection on p. 33, kotorogo R stands for hydrogen, its pharmaceutically acceptable salt.

35. Connection on p. 33, in which R denotes hydrogen, R1and R2can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl containing 1-8 carbon atoms, a 3-7-membered aliphatic cyclic (acyclic) compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains an oxygen atom that is not associated directly, R3and R4can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, a 3-7-membered alicyclic compounds, and pharmaceutically acceptable salts.

36. Connection on p. 33, in which x denotes 1, and its pharmaceutically acceptable salts.

37. The racemate O-thiocarbamoylation the mg src="https://img.russianpatents.com/img_data/67/678282.gif">

where R is selected from the group consisting of hydrogen, lower alkyl of 1-8 carbon atoms, halogen selected from F, C1, Br and J, alkoxyl containing 1-3 carbon atoms, thioalkyl containing 1-3 carbon atoms, nitro, hydroxyl, or tripterygiidae, and x denotes an integer from 1 to 3, provided that R is the same or different when x represents 2 or 3;

R1and R2can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered aliphatic compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains directly unbound oxygen atom;

R3and R4can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered alicyclic compounds,

and its pharmaceutically acceptable salts.

38. Connection on p. 37, in which R stands for hydrogen, its pharmaceutically acceptable salt.

39. Connection on p. 37, in which R denotes hydrogen, R1and R2there may be one who, terasawa 1-8 carbon atoms, a 3-7-membered aliphatic cyclic (acyclic) compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains an oxygen atom that is not associated directly, R3and R4can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, a 3-7-membered alicyclic compounds, and pharmaceutically acceptable salts.

40. Connection on p. 37, in which x denotes 1, and its pharmaceutically acceptable salts.

41. Connection on p. 37, representing About-thiocarbamoyl-(D)-aminoalcohol formula (XVII)

in which Andrdenotes a phenyl group

where R is selected from the group consisting of hydrogen, lower alkyl of 1-8 carbon atoms, halogen selected from F, Cl, Br and J, alkoxyl containing 1-3 carbon atoms, thioalkyl containing 1-3 carbon atoms, nitro, hydroxyl, or tripterygiidae, and X denotes an integer from 1 to 3, provided that R is the same or different when x represents 2 or 3;

R1and R21and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains directly unbound oxygen atom;

R3and R4can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered alicyclic compounds,

and its pharmaceutically acceptable salts.

42. Connection on p. 41, in which R stands for hydrogen, its pharmaceutically acceptable salt.

43. Connection on p. 41, in which R denotes hydrogen, R1and R2can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl containing 1-8 carbon atoms, a 3-7-membered aliphatic cyclic (acyclic) compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains an oxygen atom that is not associated directly, R3and R4can be the same or different from each other and are selected independently from the group Sottas acceptable salt.

44. Connection on p. 41, in which x denotes 1, and its pharmaceutically acceptable salts.

45. Connection on p. 37, representing About-thiocarbamoyl-(L)-aminoalcohol formula (XVIII)

in which Andrdenotes a phenyl group

where R is selected from the group consisting of hydrogen, lower alkyl of 1-8 carbon atoms, halogen selected from F, Cl, Br and J, alkoxyl containing 1-3 carbon atoms, thioalkyl containing 1-3 carbon atoms, nitro, hydroxyl, or tripterygiidae, and x denotes an integer from 1 to 3, provided that R is the same or different when x represents 2 or 3;

R1and R2can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered aliphatic compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains not directly linked oxygen atom;

R3and R4can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl with >/p>46. Connection on p. 45, in which R stands for hydrogen, its pharmaceutically acceptable salt.

47. Connection on p. 45, in which R denotes hydrogen, R1and R2can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl containing 1-8 carbon atoms, a 3-7-membered aliphatic cyclic (acyclic) compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains an oxygen atom that is not associated directly, R3and R4can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, a 3-7-membered alicyclic compounds, and pharmaceutically acceptable salts.

48. Connection on p. 45, in which x denotes 1, and its pharmaceutically acceptable salts.

49. The racemate Of-thiocarbamoylation formula (XIX)

where Ardenotes a phenyl group

where R is selected from the group consisting of hydrogen, lower alkyl of 1-8 carbon atoms, halogen selected from F, Croczilla, or tripterygiidae, and x denotes an integer from 1 to 3, provided that R is the same or different when x represents 2 or 3;

R1and R2can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered aliphatic compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains not directly linked oxygen atom;

R3and R4can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered alicyclic compounds,

and its pharmaceutically acceptable salts.

50. Connection on p. 49, in which R stands for hydrogen, its pharmaceutically acceptable salt.

51. Connection on p. 49, in which R denotes hydrogen, R1and R2can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl containing 1-8 carbon atoms, a 3-7-membered aliphatic cyclic (acyclic) compounds, and R1and R2together with prod, not affiliated, R3and R4can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, a 3-7-membered alicyclic compounds, and pharmaceutically acceptable salts.

52. Connection on p. 49, in which x denotes 1, and its pharmaceutically acceptable salts.

53. Connection on p. 49, representing About-thiocarbamoyl-(D)-aminoalcohol formula (XX)

in which Andrdenotes a phenyl group

where R is selected from the group consisting of hydrogen, lower alkyl of 1-8 carbon atoms, halogen selected from F, C1, Br and J, alkoxyl containing 1-3 carbon atoms, thioalkyl containing 1-3 carbon atoms, nitro, hydroxyl, or tripterygiidae, and x denotes an integer from 1 to 3, provided that R is the same or different when x represents 2 or 3;

R1and R2can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered aliphatic compounds, and R1and R2together with the adjacent N-atom oxygen atom;

R3and R4can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered alicyclic compounds, and R3and R4together with the adjacent N-atom form a 5-7-membered cyclic compound which optionally contains 0-1 additional nitrogen atom with substituent selected from the group consisting of hydrogen, alkyl and aryl groups, or 0-1 not directly linked to the oxygen atom

and its pharmaceutically acceptable salts.

54. Connection on p. 53, in which R stands for hydrogen, its pharmaceutically acceptable salt.

55. Connection on p. 53, in which R denotes hydrogen, R1and R2can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl containing 1-8 carbon atoms, a 3-7-membered aliphatic cyclic (acyclic) compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains an oxygen atom that is not associated directly, R3and R4may be the same or different from each the alicyclic compounds, and its pharmaceutically acceptable salts.

56. Connection on p. 53, in which x denotes 1, and its pharmaceutically acceptable salts.

57. Connection on p. 49, representing About-thiocarbamoyl-(L)-aminoalcohol formula (XXI)

in which Andrdenotes a phenyl group

where R is selected from the group consisting of hydrogen, lower alkyl of 1-8 carbon atoms, halogen selected from F, Cl, Br and J, alkoxyl containing 1-3 carbon atoms, thioalkyl containing 1-3 carbon atoms, nitro, hydroxyl, or tripterygiidae, and x denotes an integer from 1 to 3, provided that R is the same or different when x represents 2 or 3;

R1and R2can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, aryl, 3-7-membered aliphatic compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains not directly linked oxygen atom;

R3and R4can be the same or different from each other and are independently selected from the group, and its pharmaceutically acceptable salts.

58. Connection on p. 57, in which R stands for hydrogen, its pharmaceutically acceptable salt.

59. Connection on p. 57, in which R denotes hydrogen, R1and R2can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl containing 1-8 carbon atoms, a 3-7-membered aliphatic cyclic (acyclic) compounds, and R1and R2together with the adjacent N-atom form a 6-membered cyclic compound which optionally contains an oxygen atom that is not associated directly, R3and R4can be the same or different from each other and are selected independently from the group consisting of hydrogen, lower alkyl with 1-8 carbon atoms, a 3-7-membered alicyclic compounds, and pharmaceutically acceptable salts.

60. Connection on p. 57, in which x denotes 1, and its pharmaceutically acceptable salts.

61. The method of obtaining the compounds of formula (VI) under item 1, in which aminoalcohol General formula (II)

reacts with di-tert.BUTYLCARBAMATE, forming N-tert.butyloxycarbonyl-aminoalcohol represented by formula (III)

and if the promises (IV)

get On-thiocarbamoyl-N-tert.butyloxycarbonyl-aminoalcohol with the General formula (V)

in which Andr, R1, R2, R3, R4, l, m and n have the meanings specified in paragraph 1;

Vos denotes tert.butyloxycarbonyl radical,

which removed aqueous solution of hydrochloric acid, receiving On-thiocarbamoyl-aminoalcohol with the General formula (VI)

62. The method according to p. 61, characterized in that the compound of formula (VI) without additional purification is transformed into its pharmaceutically acceptable salt of formula (I)

63. The method of obtaining the compounds of formula (VI) under item 1, characterized in that aminoalcohol General formula (II) in which R3and R4not represent hydrogen,

reacts with sodium hydride, carbon disulphide and iodine stands in ether solution followed by treatment of the amine of formula (IV)

giving On-thiocarbamoyl-aminoalcohol with formula (VI)

64. The method according to p. 63, characterized in that the compound of formula (VI) without additional purification of the compounds of formula (VI) under item 1, characterized in that aminoalcohol General formula (II) in which R1denotes H,

reacts with di-tert.BUTYLCARBAMATE, forming N-tert.butyloxycarbonyl-aminoalcohol with formula (III)

which in the subsequent processing isothiocyanato formula (VII)

in galoidovodorodami solution provides On-thiocarbamoyl-N-tert.butyloxycarbonyl-aminoalcohol with the formula V

where Ar, R1, R2, R3, R4, l, m and n have the meanings specified in paragraph 1;

BOC represents a tert. butyloxycarbonyl radical,

which is removed with an aqueous solution of hydrochloric acid, receiving On-thiocarbamoyl-aminoalcohol General formula (VI)

66. The method according to p. 65, characterized in that the compound of formula (VI) without additional purification can be turned in its pharmaceutical acceptable salts of formula (I)

67. The method of obtaining the compounds of formula (VI) under item 1, characterized in that aminoalcohol General formula (II) in which R3and R4are not hydrogen atoms,

68. The method according to p. 67, characterized in that the compound of formula (VI) without additional purification converted into pharmaceutically acceptable salts of formula (I)

69. The method of obtaining the compounds of formula (VIII), which uses a process according to p. 61 using as starting material (D)-aminoalcohol.

70. The method of obtaining the compounds of formula (VIII), which uses a process according to p. 63 using as starting material (D)-aminoalcohol.

71. The method of obtaining the compounds of formula (VIII), which uses a process according to p. 65 using as starting material (D)-aminoalcohol.

72. The method of obtaining the compounds of formula (VIII), which uses a process according to p. 67 using as starting material (D)-aminoalcohol.

73. The method of obtaining the compounds of formula (IX), which uses a process according to p. 61 using as starting material (L)-aminoalcohol.

74. The method of obtaining the compounds of formula (IX), which uses a process according to p. 63 using as starting material (L)-aminoalcohol.

75. The method of obtaining the compounds of formula. the procedure for obtaining compounds of formula (IX), which uses a process according to p. 67 using as starting material (L)-aminoalcohol.

77. Pharmaceutical composition for treating disorders of the Central nervous system containing the compound of the formula (VI) or its pharmaceutically acceptable salt p. 1 and non-toxic pharmaceutically acceptable carrier or diluent.

78. Pharmaceutical composition for treating disorders of the Central nervous system containing the compound of the formula (VI) or its pharmaceutically acceptable salt p. 5 and non-toxic pharmaceutically acceptable carrier or diluent.

79. Pharmaceutical composition for treating disorders of the Central nervous system containing the compound of the formula (IX) or its pharmaceutically acceptable salt according to p. 9 and non-toxic pharmaceutically acceptable carrier or diluent.

80. The method of treatment of a mammal suffering from a disorder of the Central nervous system, which consists in the introduction of the specified mammal is effective for the treatment of Central nervous system number of connections on p. 1.

81. The method of treatment of a mammal suffering from a disorder of the Central nervous system, penned the STV connection on p. 5.

82. The method of treatment of a mammal suffering from a disorder of the Central nervous system, which consists in the introduction of the specified mammal is effective for the treatment of Central nervous system number of connections on p. 9.

83. Compound selected from the group consisting of O-thiocarbamoyl-(DL)-phenylalaninol, 0-thiocarbamoyl-(D)-phenylalaninol and On-thiocarbamoyl-(L)-phenylalaninol, and their non-toxic pharmacologically acceptable salts.

84. Connection on p. 83, representing About-thiocarbamoyl-(D)-phenylalaninol or its pharmaceutically acceptable salt.

85. Connection on p. 83, representing About-thiocarbamoyl-(L)-phenylalaninol or its pharmaceutically acceptable salt.

86. The method of treatment of a mammal suffering from a disorder of the Central nervous system, which consists in the introduction of the specified mammal is effective for the treatment of Central nervous system number of connections on p. 83.

87. The method of treatment of a mammal suffering from a disorder of the Central nervous system, which consists in the introduction of the specified mammal is effective for the treatment of Central nervous system number of connections on p. 84.

88. A method of treating a mammal suffering from ro for treatment of Central nervous system, number of connections on p. 85.

 

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methods for their preparation and their use in pharmaceutical compositions

The invention relates to a new applicable in pharmaceuticals organic compounds and, more specifically, to a chemically pure compounds - monocarbonate and dicarbamate, a derivative of 2-phenyl - 1,2-ethanediol, represented by structural formulas (I) and (II), which dominates one enantiomer and in which the phenyl ring contains as substituents one to five halogen atoms selected from fluorine, chlorine, bromine and iodine, and in which each of R1-R6is selected from hydrogen and linear or branched alkyl groups containing from one to four carbon atoms, possibly substituted phenyl group

The invention relates to medicine and relates to a pharmaceutical composition inhibiting the growth of malignant neoplasms and tumors in mammals, and to a method of treating cancer, and also to a method of treating viral infections in mammals

The invention relates to medicine and relates to a pharmaceutical composition inhibiting the growth of malignant neoplasms and tumors in mammals, particularly in humans and warm-blooded animals, and treatment of cancer

The invention relates to the use of fluorinated derivatives of carbamino acid, namely polyfluoroankyl-N-arylcarbamates General formula

< / BR>
where R and R' = H, o-, m-or p-alkyl (C1-C3, CF3CH3S, Cl, NO2, NHCOOCHR"R"';

R" = H, CF3;

R"' = CF3, (CF2)nH, where n = 2-6, or-CF2NO2except 2.2-debtor-2-nitroethyl-N-phenylcarbamate, 2.2.2-triptorelin-N-p-nitrophenylacetate,

possessing antimicrobial activity

The invention relates to medicine, more specifically to anesthesiology and critical care medicine, and can be used for controlled lowering of blood pressure during surgical procedures under General anesthesia

FIELD: medicine, cosmetology.

SUBSTANCE: one should apply acid composition onto patient's skin scar, moreover, this composition consists of the following ratio of components, weight%: alpha-hydroacid 0.1-70; gamma-lactone of 2,3-dehydro-L-gulonic acid 0.1-10; 1,2,3-propanetriol 1-10; strontium nitrate 0.5-10, water - the rest. Moreover, for steady penetration of this composition for desired depth against scars and surrounding skin one should treat them with alcoholic solution of beta-hydroxyacid for 3-7 d, and for improved regeneration one should lubricate it with an ointment supplemented with hydroxyacid for 7 d.

EFFECT: higher efficiency of therapy.

2 cl, 2 ex

FIELD: organic synthesis.

SUBSTANCE: invention provides compounds of general formula I:

, where R1 represents -CO-Ra, -SO2-Rb, or aryl optionally substituted by lower alkoxy, wherein Ra represents cycloalkyl, cycloalkyl(lower)alkyl, cycloalkyloxy, aryl, aryloxy, aryl(lower)alkyl, aryl(lower)alkoxy, aryloxy(lower)alkyl, aryl-S-(lower)alkyl, aryl(lower)alkenyl, provided that aryl group can be optionally substituted by halogen, lower alkyl, hydroxy, nitro, cyano, lower alkoxy, phenyl, CF3, cyano(lower)alkyl, lower alkyl-C(O)NH, lower alkyl-CO, and lower alkyl-S; heteroaryl, heteroaryl(lower)alkyl, or heteroaryl(lower)alkoxy, provided that heteroaryl group is 5- or 6-membered ring or bicyclic aromatic group constituted by two 5- or 6-membered rings including 1-3 heteroatoms selected from oxygen, nitrogen, and sulfur and that heteroaryl group can be optionally substituted by lower alkoxy; Rb represents aryl, aryl(lower)alkyl, or heteroaryl, aryl group optionally substituted by halogen, cyano, or lower alkyl-C(O)NH; R2 and R3 represent hydrogen atoms; R4 representshydrogen or lower alkyl; R5 represents hydrogen, lower alkyl, cycloalkyl, benzodioxyl, or aryl optionally substituted by lower alkyl, halogen, lower alkoxy, hydroxy, or (lower)alkyl-C(O)O; n is 1 or 2; and pharmaceutically acceptable salts thereof and/or pharmaceutically acceptable esters thereof. Invention also provides a pharmaceutical composition exhibiting inhibitory activity with regard to cysteine proteases of the cathepsin family, which composition comprises compound of formula I, pharmaceutically acceptable recipient, and/or adjuvant.

EFFECT: increased choice of cysteine protease inhibitors.

34 cl, 1 tbl, 13 ex

FIELD: medicine, surgery.

SUBSTANCE: method involves administration of verapamil solution in the amount 20-30 mg by intraperitoneal route by spraying method on visceral and parietal peritoneum on the final stage of operation. Invention promotes to reducing frequency in formation and relapse of post-operative adhesions. Invention can be used for prophylaxis of post-operative adhesions.

EFFECT: improved method for prophylaxis.

2 ex

FIELD: chemico-pharmaceutical industry.

SUBSTANCE: the present innovation deals with applying the compound of formula I

for treating neuropathic pains. This compound I (retigabin) is of high efficiency in treating allodynia, hyperalgesia-conditioned pains, neuropathic pain in case of diabetic neuropathy, neuropathic pain at migraine. The compound suggested is low toxic being of high bioavailability.

EFFECT: higher efficiency of therapy.

6 cl, 1 tbl

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to new compounds of the formula (I) inhibiting tumor growth and angiogenesis wherein each R2 and R3 represents independently hydrogen atom (H), (C1-C4)-alkyl; each X2 and X3 represents independently (C1-C4)-perfluoroalkyl; A represents hydrogen atom (H) or a covalent bond; t represents a whole number 0 or 1 under condition that if A represents hydrogen atom (H) then t = 0, and if A represents a covalent bond then t = 1. Also, invention relates to a pharmaceutical composition and method for inhibition of the tumor growth.

EFFECT: valuable medicinal properties of composition.

32 cl, 3 sch, 5 dwg, 19 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compounds of the formula (I): and formula (II): , and to their esters that can be used for treatment of the cellular proliferation disorders. Also, invention relates to a pharmaceutical composition used for modulation of cellular proliferation and comprising compound of the formula (I) or its ester.

EFFECT: valuable medicinal property of compounds and composition.

62 cl, 2 tbl, 25 dwg, 58 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition possessing capacity to release the therapeutically effective dose of active substance rivastigmin and showing the time-controlled pattern. The pharmaceutical composition is designated for treatment of patients suffering with Alzheimer's diseases dementia from small to middle severity degree. Compositions show safety and time-controlled release pattern of active substance rivastigmin.

EFFECT: valuable medicinal and pharmaceutical properties of composition.

5 cl, 2 tbl, 7 ex

FIELD: organic chemistry, veterinary science.

SUBSTANCE: invention describes using aminoacetonitrile compounds of the formula (I): wherein Ar1 and Ar2 mean independently of one another unsubstituted phenyl or phenyl substituted with halide; Q means -C(R1)(R2) wherein R1 and R2 or independently of one another mean hydrogen atom, or in common with carbon atom to which they are bound form (C2-C6)-alkylene; d = 1; R3 means hydrogen atom, (C1-C6)-alkyl or (C2-C6)-alkynyl; each among R4, R5, R6, R7 and R8 means independently of one another hydrogen atom, (C1-C6)-alkyl or (C3-C6)-cycloalkyl; or R4 and R5 mean in common (C2-C6)-alkylene; W means oxygen atom; a and b mean independently of one another 0 or 1, and optionally of their enantiomers in control of endoparasitic pests in warm-blooded productive cattle and domestic animals. Also, the invention describes the composition and a method for control of endoparasitic pests. Above said compounds are used for control of endoparasites, especially, helminthes in warm-blooded productive cattle and in domestic animals.

EFFECT: valuable properties of compounds.

6 cl, 3 tbl, 5 ex

FIELD: organic chemistry, medicine, clinical pharmacology.

SUBSTANCE: invention relates to agents used in treatment of pain. Method involves administration to a patient the effective dose of enantiomer of compounds of the formula (Ib) or the formula (IIb) or their mixture. Method provides the antihyperanalgesic effect in acute and chronic pain.

EFFECT: valuable medicinal properties of derivatives.

5 cl, 1 tbl

FIELD: veterinary medicine and veterinary pharmacology.

SUBSTANCE: invention relates to application of compounds combining properties of selective antagonists of dopamine D2 receptor and agonists of 5-HT1A receptor, in particular (R)-(-)-2-[5-(4-fluorophenyl)-3-piridylmethylaminomethyl]-chromane or pharmaceutically acceptable salts thereof, or N-(4'-fluoro-3-biphenylmethyl)-N-2-(3-cyanophenoxyethyl)-amine or pharmaceutically acceptable salts thereof. Said compounds are useful in veterinary medicine for treatment of self-directed traumatic disorders, associated with behavioral stress-factors, and/or compulsive disorders, associated with behavioral stress-factors, and/or anxiety, associated with behavioral stress-factors.

EFFECT: effective method for treatment and prophylaxis of disorders, associated with behavioral stress-factors.

6 cl, 3 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new method for production of m- or p-substituted α-arylalkanecarboxylic acids of general formula I

from respective α-hydroxylated derivatives using inexpensive reagents and without converting of any reducible groups such as ester or ketone ones in side chains. In formula R is hydrogen, C1-C6-alkyl; R1 is hydrogen, linear or branched C1-C6-alkyl, phenyl, p-nitrophenyl, alkali or earth-alkali cation or cation of pharmaceutically acceptable ammonia salt: A is C1-C4-alkyl, aryl, optionally substituted with one or more alkyl, hydroxy, etc., aryloxy, arylcarbonyl; A is in m- or p-sites; P - linear or branched C1-C6-flkyl, phenyl, nitrophenyl. Claimed method includes the next steps: a) converting of compounds of formula II to compound of formula III either by reaction of II with compound of formula in presence of organic or inorganic base or by reaction of II with thiophene of formula and followed by reaction of obtained product with HNRaRb, wherein Ra andRb are as defined above; b) thermal rearrangement of III to form IIIb ; c) catalytic dehydration of IIIb to form IIIc ; and d) optional hydrolysis of IIIc to obtain target compound of formula I. Also are disclosed new compounds of formulae III and IIIb.

EFFECT: new α-arylalkanecarboxylic acids and intermediates thereof.

6 cl, 5 ex

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