Heteroaryl-1-piperidine and piperazines, the pharmaceutical composition based on them, a method of treating psychosis and relief of pain

 

Describes heteroaryl-1-piperidine and piperazines of General formula (I), where X represents O, S, NH or n(R2), R2selected from the group of benzoyl, (C2-C18)alkanoyl and alkoxycarbonyl, p = 1, Y is hydrogen, chlorine, fluorine, Q is piperidinyl or piperazinil, substituted in the 1 position Y2, Y2choose from 21 groups. Also describes a pharmaceutical composition on the basis of these compounds, a method of reducing pain and the treatment of psychosis using the compounds, 1-[4-(3-chloropropoxy)-3-methoxyphenyl]-2-hydroxyethane, which is the starting compound in the synthesis of compounds of formula (I). The technical result - antipsychotic and analgesic properties of the compounds can be used for relief of pain and treatment of psychosis. 13 C. and 112 C. p. F.-ly, 2 PL.

Description text in facsimile form (see graphic part)g

Claims

1. Heteroaryl-1-piperidine and piperazines of the formula (I)where X represents-O-, -S-, -NH - or-N(R2)-; R2selected from the group including benzoyl, (C2-C18) alkanoyl and alkoxycarbonyl; p = 1; Y represents co - or-N-;
Y2selected from the group including

where R1represents-CR24R27-(CR23R24)n-CR24R27- where n = 0, 1, 2 or 3; or-chr24-CH= CH-chr24-, communications-CH= CH - is CIS or TRANS; R23represents hydrogen, (C1-C18) linear alkyl, hydroxy or (C2-C18) alkanoyloxy; R24represents hydrogen or (C1-C18linear alkyl; R27represents hydrogen, or R24and R27taken together with the carbon atom to which they are attached form C= 0;
And represents-C(= 0)-, -C(= S)-, -C(= CH2)-, -C(= O)CH2-, -CR26= N - or-CR25R26-; R25represents hydrogen, hydroxy or (C2-C18) alkanoyloxy; R26represents hydrogen or (C1-C6) alkyl;
one of the Byand Bzrepresents CH or N and the other represents CH;
U represents O or S;
q = 1 or 2;
R4represents hydrogen, lower alkyl, lower alkoxy, hydroxy, three(C1-C6) alkylsilane, amino, (C2-C18) acylamino, (C2-C18) alkanoyl, chlorine, fluorine, -O-C (= O) - (C1-C18direct Il the Bzboth represent CH;

where R1, R4and q are such as described above;
R28represents hydrogen or phenyl;

where R1, R4and q are such as described above;
R29and R30represent hydrogen;
R31and R32represent hydrogen;

where R1, R4, R28, R29, R30, R31, R32and q are such as described above;

where R1, R4, R29, R30, R31, R32and q are such as described above;

where R1and R4such as indicated above;
m - this is as follows;

where R1and R4such as indicated above;
m - this is as follows;

where R1and R4such as indicated above;
m - this is as follows;
(18) -R1-O-R'12
where R'12selected from the group comprising: (C1-C18straight or branched)alkyl; -C(= O)-(C1-C18straight or branched)alkyl; -C(= O) -NR13R14where R13prestly; and

where R4as mentioned above,
m - this is as follows;
(19) -R1-NR18R19
where R18and R19independently selected from the group comprising hydrogen, provided that only one of R18and R19represents hydrogen, -C(= O)-pyridyl, -(C1-C18straight or branched)alkyl; -(C1-C18alkyl) OC (= O) (C1-C18alkyl); and

where NR18R19taken together form a ring structure selected from the group comprising piperidinyl and morpholinyl where piperidinyl ring substituted

where X, Y, R, R1, R4and R28such as indicated above;
m - this is as follows;
(20) -R1-S-R'12
where R1and R'12such as indicated above; and

where R1, R4and R28such as indicated above;
m = 1, 2, or 3;
all of their geometrical, optical and stereo isomers or pharmaceutically acceptable salt accession acids.

2. Connection on p. 1, represented by formula

3. Connection on p. 2, where Y2is sub> represents CH and U represents O.

5. Connection on p. 4, where X represents-O-.

6. Connection on p. 5, representing 2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -2,3-dihydro-3-hydroxy-1H-isoindole-1-he or 2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -3-oxo-2,3-dihydro-1H-isoindole-1-silt ether decanoas acid, or its pharmaceutically acceptable salt accession acids.

7. Connection on p. 4, where X represents-S-.

8. Connection on p. 7, which is 2-[2-[4-(6-fluoro-1,2-benzisothiazol-3-yl)-1-piperidinyl] ethyl] -2,3-dihydro-3-hydroxy-1H-isoindole-1-it, or its pharmaceutically acceptable salt accession acids.

9. Connection on p. 4, where X represents-NH-.

10. Connection on p. 9 representing 2-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperazinil] ethyl] -2,3-dihydro-3-hydroxy-1H-isoindole-1-it, or its pharmaceutically acceptable salt accession acids.

11. Connection on p. 3, where a represents-C(= S)-,yand Inzrepresents CH and U represents O.

12. Connection on p. 11, where X represents-O-.

13. Connection on p. 12 representing N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] leftlimit, and the Oh-C(= S)-,yand Bzrepresents CH and U represents S.

15. Connection on p. 14, where X represents-O-.

16. Connection on p. 15, N represents-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -1,3-bis-leftlimit, or its pharmaceutically acceptable salt accession acids.

17. Connection on p. 3, where a represents- (CH3HE IS, Byand Bzrepresents CH and U represents O.

18. Connection on p. 17, where X represents-O-.

19. Connection on p. 18, which represents a 2,3-dihydro-2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -3-hydroxy-3-methyl-1H-isoindole-1-it, or its pharmaceutically acceptable salt accession acids.

20. Connection on p. 3, where a represents a-CH(CH3)-, Byand Bzrepresents CH and U represents O.

21. Connection on p. 20, where X represents-O-.

22. Connection on p. 21, which represents a 2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -2,3-dihydro-3-methyl-1H-isoindole-1-it, or its pharmaceutically acceptable salt accession acids.

23. Connection on p. 3, where a represents-C(= CH2)-, Byand Bzrepresents CH and U represents the FDS is ihydro-2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -3-methylene-1H-isoindole-1-it, or its pharmaceutically acceptable salt accession acids.

26. Connection on p. 3, where a represents a-CH2-, Byand Inzrepresents CH and U represents O.

27. Connection on p. 26, where X represents-O-.

28. Connection on p. 27, which represents a 2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -2,3-dihydro-1H-isoindole-1-it, or its pharmaceutically acceptable salt accession acids.

29. Connection on p. 3, where a represents-C(= O)CH2-, Byand Bzrepresents CH and U represents O.

30. Connection on p. 29, where X represents-O-.

31. Connection on p. 30, representing N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -1,2,3,4-Tetra-hydroisoquinoline-1,3-dione, or its pharmaceutically acceptable salt accession acids.

32. Connection on p. 3, where a represents-C(= O)-,yrepresents CH, Bzrepresents N and U represents O.

33. Connection on p. 32, where X represents-O-.

34. Connection on p. 33, representing N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -6-pyrrolo[3,4-b] pyridine-5,7-dione, or its pharmaceutically acceptable salt accession to the N and U represents O.

36. Connection on p. 35, where X represents-O-.

37. Connection on p. 36, representing 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -2-methyl-3H-hinzelin-4-one or its pharmaceutically acceptable salt accession acids.

38. Connection on p. 2, where Y2represents a

39. Connection on p. 38, where X represents-O - and Z represents-CH-.

40. Connection on p. 39, selected from the group including:
4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-[3-(2,3-dihydro-lH-isoindole-2-yl)propyl] piperidine, 4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-[(2,3-dihydro-1H-isoindole-2-yl)ethyl] piperidine, 4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-[2-(5-fluoro-2,3-dihydro-1H-isoindole-2-yl)ethyl] piperidine, 4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-[2-(2,3-dihydro-1H-isoindole-2-yl)propyl] piperidine, N-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -2-hydroxy-1-propyl] -2,3-dihydro-1H-isoindole, N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -2,3-dihydro-5-(triisopropylsilyl)oxy-1H-isoindole, N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -2,3-dihydro-5-hydroxy-1H-isoindole and [2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -1-(2,3-dihydro-1H-isoindole-2-yl)Etalon, or its pharmaceutically acceptable salt accession acids.

work a 4-(6-fluoro-lH-indazol-3-yl)-1-[2-(2,3-dihydro-1H-isoindole-2-yl)ethyl] piperidine or 4-(6-fluoro-1H-indazol-3-yl)-1-[2-(5-fluoro-2,3-dihydro-1H-isoindole-2-yl)ethyl] piperidine, or its pharmaceutically acceptable salt accession acids.

43. Connection on p. 38, where X represents-NH - and Z represents-N-.

44. Connection on p. 43, a 4-(1H-indazol-3-yl)-1-[2-(2,3-dihydro-5-fluoro-1H-isoindole-2-yl)ethyl] piperazine, 4-(6-fluoro-1H-indazol-3-yl)-1-[2-(2,3-dihydro-4-methyl-1H-isoindole-2-yl)ethyl] piperazine, 4-(6-fluoro-1H-indazol-3-yl)-1-[2-(2,3-dihydro-5-methyl-1H-isoindole-2-yl)ethyl] piperazine or 4-(6-fluoro-1H-indazol-3-yl)-1-[2-(5-fluoro-2,3-dihydro-1H-isoindole-2-yl)ethyl] piperazine, or its pharmaceutically acceptable salt accession acids.

45. Connection on p. 43, a 4-(1H-indazol-3-yl)-1-[2-(2,3-dihydro-1H-isoindole-2-yl)ethyl] piperazine, 4-(6-fluoro-1H-indazol-3-yl)-1-[2-(2,3-dihydro-1H-isoindole-2-yl)ethyl] piperazine or 4-(6-fluoro-1H-indazol-3-yl)-1-[3-(2,3-dihydro-1H-isoindole-2-yl)propyl] piperazine, or its pharmaceutically acceptable salt accession acids.

46. Connection on p. 38, where X represents-N(R2)-and Z represents-N-.

47. Connection on p. 46, a 4-(1-decanoyl-6-fluoro-1H-indazol-3-yl)-1-[2-(2,3-dihydro-1H-isoindole-2-yl)ethyl] piperazine, or its pharmaceutically acceptable salt accession acids.

48. 6-Fluoro-3-[4-[2-(2,3-dihydro-1H-isoindole-2-yl)ethyl] -1-piperazinil] -N-Fe by p. 2, where Y2represents a

50. Connection on p. 49, where X represents-O - and Z represents-CH-.

51. Connection on p. 50, representing 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -1-(2,3-dihydroindol-1-yl)Etalon, or its pharmaceutically acceptable salt accession acids.

52. Connection on p. 2, where Y2represents a

53. Connection on p. 52, where X represents-O - and Z represents-CH-.

54. Connection on p. 53, which represents a 1-(1,2,3,4-tetrahydro-1H-isoquinoline-2-yl)-2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] Etalon, N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -1,2,3,4-tetrahydroisoquinoline, 2-(1,2,3,4-tetrahydro-1H-isoquinoline-2-yl)-1-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] Etalon, N-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -2-hydroxy-1-propyl] -1,2,3,4-tetrahydroisoquinoline or 6,7-dimethoxy-2-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -2-hydroxy-1-propyl] -1,2,3,4-tetrahydroisoquinoline, or its pharmaceutically acceptable salt accession acids.

55. Connection on p. 52, where X represents-NH - and Z represents-CH-.

56. Connection on p. 55, representing N-[what do join acids.

57. Connection on p. 52, where X represents-NH - and Z represents-N-.

58. Connection on p. 57, N represents-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperazinil] ethyl] -1,2,3,4-tetrahydroisoquinoline or 2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperazinil] -1-(1,2,3,4-tetrahydro-1H-isoquinoline-2-yl)Etalon, or its pharmaceutically acceptable salt accession acids.

59. Connection on p. 2, where Y2represents a

60. Connection on p. 59, where X represents-O - and Z represents-CH-.

61. Connection on p. 60, which represents a 1-(1,2,3,4-tetrahydro-1H-quinoline-1-yl)-2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] Etalon, N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -1,2,3,4-tetrahydroquinolin or N-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -2-hydroxy-1-propyl] -1,2,3,4-tetrahydroquinolin, or its pharmaceutically acceptable salt accession acids.

62. Connection on p. 2, where Y2represents a

63. Connection on p. 62, representing N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] acetyl] -10,11-dihydro-5H-dibenz[b, f] azepin, or its pharmaceutically acceptable salt accession acids.

64. Connection on p. 2, where Y2CH2-.

66. Connection on p. 65, which represents a 6-chloro-2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -1H-Benz[d, e] isoquinoline-1,3(2H)-dione, or its pharmaceutically acceptable salt accession acids.

67. Connection on p. 2, where Y2represents a

68. Connection on p. 67, where R1represents-CH2CH2-.

69. Connection on p. 68, representing N-2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -2,3-naphthalimide, or its pharmaceutically acceptable salt accession acids.

70. Connection on p. 2, where Y2is a-R1-O-R'12.

71. Connection on p. 70, where R'12represents a

72. Connection on p. 71, N represents-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethoxy] phthalimide, or its pharmaceutically acceptable salt accession acids.

73. Connection on p. 2, where Y2is a-R1NR18R19.

74. Connection on p. 73, where R18represents hydrogen and R19represents -(C= O)-pyridyl.

75. Connection on p. 74, representing N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] is in p. 73, where NR18R19forms a ring structure selected from the group comprising piperidinyl where piperidinyl ring substituted

where X, Y and R such as defined above.

77. Connection on p. 76, which represents a 1,2-bis-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethane or 1,2-bis-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -2-hydroxypropan, or its pharmaceutically acceptable salt accession acids.

78. Connection on p. 72, where R18represents hydrogen and R19represents a

79. Connection on p. 78, representing N-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperazinil] ethyl] -3-phenyl-2-khinoksalinona, or its pharmaceutically acceptable salt accession acids.

80. Connection on p. 2, where Y2represents a

81. Connection on p. 80, representing the 2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -2-phenyl-1,3-indandione, or its pharmaceutically acceptable salt accession acids.

82. Heteroaryl-1-piperidine and piperazines of the formula And

where X represents-O-, -S-, -NH - or-N(R2)-;
R2selected from graphische alkoxy;
Q1is:

where Z represents-CH - or-N-;
Y2selected from the group consisting of

where R1represents-CR24R27- (CR23R24)n-CR24R27- where n = 0, 1, 2 or 3; or-chr24-CH= CH-chr24-, communications-CH= CH - is CIS or TRANS; R23represents hydrogen, (C1-C18) linear alkyl, hydroxy or (C2-C18) alkanoyloxy; R24represents hydrogen or (C1-C18linear alkyl; R27represents hydrogen, or R24and R27taken together with the carbon atom to which they are attached, form a C= O;
R and m are such as follows;
provided that R23does not represent hydrogen or (C1-C6linear alkyl when R27represents hydrogen and R24represents hydrogen or (C1-C6linear alkyl; provided that R24does not represent hydrogen or (C1-C6linear alkyl when R27represents hydrogen and n = 0 or when R27represents hydrogen and R23represents hydrogen or (C1-C6) linejet a hydrogen or-och3;

where R1- as mentioned above;
R4represents hydrogen, lower alkyl, lower alkoxy, hydroxy, amino, (C2-C7) acylamino, (C2-C18) alkanoyl, chlorine, fluorine, bromine or-O-C(= O)-(C1-C18straight or branched alkyl);

where R1and R4such as indicated above;

where one of Xyor Xzrepresents-C(= O)-, and the other represents-CH2-;
R'5represents lower alkoxy,
R1- as mentioned above;

where R1- as mentioned above;
R4is a (C1-C6) alkanoyl;

where a represents-C(= O)-;
both Byand Inzrepresent CH;
U represents O;
q = 1 or 2, R1- as mentioned above;
R4represents hydrogen, lower alkyl, lower alkoxy, hydroxy, three(C1-C6) alkylsilane, amino, (C2-C18) acylamino, (C2-C18) alkanoyl, chlorine, fluorine, bromine or-O-C(= O)- (C1-C18straight or branched)al
where R1- as mentioned above;
Q2represents-S-, -NH - or-CH2-;
R and m are such as follows;

where R1- as mentioned above;
(18) -R1-O-R12
where R12selected from the group comprising hydrogen, -C(= O)-(C1-C12straight or branched)alkyl, and-C(= O)-NR13R14where R13selected from the group comprising hydrogen and (C1-C12) alkyl; Ri4selected from the group comprising hydrogen and (C1-C12) alkyl;
R1- as mentioned above;
(19) -R1-NR18R19
where R18and R19independently selected from the group comprising hydrogen, - (C1-C18straight or branched)alkyl, and -(C1-C18alkyl) OC(= O) (C1-C18alkyl);
NR18R19taken together form a ring structure selected from the group consisting of piperidinyl and morpholinyl;
R1- as mentioned above;
(20) -R1-S-R12
where R1and R12such as indicated above;
R represents hydrogen, lower alkyl, lower alkoxy, hydroxyl, bromo, amino, lower mono - or dialkylamino, lower alkylthio, cyano, acylamino, TRIFLUOROACETYL, aminocarb is)-alkyl, a is alkyl (C1-C18) alkyl; W represents CH2or N-R9; R7represents hydrogen, alkyl or (C2-C18) alkanoyl; R9represents a hydroxy, alkoxy or-other10; R10represents hydrogen;
m = 1, 2, or 3;
and, any hydroxyl group attached to an aliphatic or aromatic carbon atom, or any primary or secondary nitrogen atom may be etilirovany (C4-C18)alkanoyloxy group; in addition, any nitrogen atom may alternatively, allyawan (C4-C18) alkoxycarbonyl group;
all geometric, optical and stereoisomers, or its pharmaceutically acceptable salt accession acid.

83. Connection on p. 82 formula

84. Connection on p. 83, where Y2represents a

85. Connection on p. 84, where R1represents-CH2CH(OH)CH2- or-CH2CH[OC(= O)(C1-C18)alkyl] CH2-.

86. Connection on p. 85, where R is independently selected from hydrogen, (C1-C6)alkoxy or (C1-C18)alkanoyl, and m = 1 or 2.

87. Connection on p. 86, where X represents the evil-3-yl)-1-piperidinyl] -2-hydroxy-1-propoxy] fenilmetilovy ether, 4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -2-hydroxy-1-propoxy] -3-methoxyphenylalanine or 1-[(4-Aceto-2-methoxy)phenoxy] -3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -2-Propellerhead, or its pharmaceutically acceptable salt accession acids.

89. Connection on p. 83, where Y2represents a

where a represents-C(= O)-;
Byand Inzboth represent CH;
U represents O;
R1represents-CH2CH(OH)CH2- or-CH2CH[OC(= O)(C1-C18)alkyl] CH2-.

90. Connection on p. 89, where X represents-O - and Z represents-CH-.

91. Connection on p. 90, representing N-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -2-hydroxy-1-propyl] phthalimide or 1-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -3-phthalimido-2-Propellerhead, or its pharmaceutically acceptable salt accession acids.

92. Connection on p. 82, representing N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -4-(1-decanoyl)or N aminophthalimide-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl) -1-piperidinyl] ethyl] -4-(1-decanoyl)exittime, or their pharmaceutically acceptable salts accession acids.

93. Connected is made by a hydrogen.

95. Connection on p. 94, where X represents-O-.

96. 1-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] cyclohexanol or its pharmaceutically acceptable salt accession acids.

97. 1-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] Cyclopentanol or its pharmaceutically acceptable salt accession acids.

98. Connection on p. 83, where Y2is a-R1NR18R19.

99. Connection on p. 98, where R18and R19both represent hydrogen.

100. Connection on p. 99, representing 3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -2-hydroxy-1-Propylamine, or its pharmaceutically acceptable salt accession acids.

101. Ethyl 3-[4-(6-fluoro-1,2-benzisothiazol-3-yl)-1-piperidinyl] propionate, ethyl 3-[4-(6-fluoro-1H-indazol-3-yl)-1-piperazinil] propionate, 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] acetonitrile, 3-[4-(6-fluoro-1,2-benzisoxazol-3-yl) -1-piperidinyl] propionitrile, [4-(6-fluoro-1H-indazol-3-yl)-1-piperazinil] acetonitrile or 1-[4-(3-chloropropoxy)-3-methoxyphenyl] -2-hydroxyethane, or their pharmaceutically acceptable salts accession acids.

102. Connection on p. 82, representing the (S)-6-fluoro-3-[1-(3-methoxyphenyl-2-methylpropyl)-4-piperidinyl] -1,2-benzisoxazol-3-yl)piperidine or pharmaceutically acceptable salt accession acids.

104. 1-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -2-propanone or its pharmaceutically acceptable salt accession acids.

105. 1-phenoxycarbonyl-3-(1-phenoxycarbonyl-4-piperidinyl)-1H-indazol or its pharmaceutically acceptable salt accession acids.

106. Connection on p. 82, representing 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] propoxy] -3-methoxyphenyl] -2-hydroxyethane or its pharmaceutically acceptable salt accession acids.

107. Connection on p. 82, representing hydrochloride N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] phthalimide.

108. Heteroaryl-1-piperidine and piperazines of the formula

where X represents-N(R2)-; R2is (C1-C18)alkoxycarbonyl;
p = 1;
Y represents hydrogen or fluorine;
Q1represents a

where Z represents-CH - or-N-;
Y2selected from the group including
(7)
where a represents-C(= O)-;
U represents O;
Byand Inzrepresent CH;
q = 1;
R1represents-CR24R27- (CR23R24)n-CR2-C18) alkanoyloxy; R24represents hydrogen or (C1-C18linear al Kyl; R27represents hydrogen, or R24and R27taken together with the carbon atom to which they are attached, form a C= O;
R4represents hydrogen, lower alkyl, lower alkoxy, hydroxy, three (C1-C6) alkylsilane, amino, (C2-C18) acylamino, (C2-C18) alkanoyl, chlorine, fluorine, or-O-C(= O) - (C1-C18straight or branched)alkyl,
them all geometric, optical and stereoisomers, or pharmaceutically acceptable salt accession acids.

109. Connection on p. 108, where X represents-N(R2)- and Z represents-N-, where R2is a (C1-C18) alkoxycarbonyl.

110. Connection on p. 109, which is N-[2-[4-(1-decemoctober-6-fluoro-1H-indazol-3-yl)-1-piperazinil] ethyl] phthalimide or N-[2-[4-(1-etoxycarbonyl-6-fluoro-1H-indazol-3-yl)-1-piperazinil] ethyl] phthalimide, or its pharmaceutically acceptable salt accession acids.

111. Pharmaceutical composition containing as active ingredient an effective amount of a compound according to any one of paragraphs. 1, 82 and 108 and tempermentally composition.

113. The compound according to any one of paragraphs. 1, 82, 106, 107 and 108 for the production of pharmaceuticals for the treatment of psychosis and relief of pain.

114. Pharmaceutical composition for p. 111, which is the analgesic pharmaceutical composition.

115. Pharmaceutical composition for p. 111, which is the pharmaceutical depot composition where the compound according to any one of paragraphs. 1, 82 or 108, contains the acylated hydroxy-group, the amino group or the nitrogen in position 1 indazol rings.

116. Pharmaceutical depot-composition by p. 115, where the hydroxy or amino group etilirovany (C4-C18)alkanoyloxy group or (C4-C18)alkoxycarbonyl group.

117. The composition according to p. 115 or 116, containing pharmaceutically acceptable oil.

118. The composition according to p. 117, where the specified oil selected from the group comprising coconut oil, peanut oil, sesame oil, cottonseed oil, corn oil, soybean oil, olive oil, and esters of fatty acids and polyhydric alcohols.

119. Pharmaceutical depot-composition by p. 115, where the compound is selected from the group comprising: 2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -2,3-dihydro-3-hydroxy-1H-isoindole-1-he, 2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]yl] -2-hydroxy-1-propoxy] fenilmetilovy ether, 4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -2-hydroxy-1-propoxy] -3-methoxyphenylalanine, 1-[(4-Aceto-2-methoxy)phenoxy] -3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -2-Propellerhead, N-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -2-hydroxy-1-propyl] phthalimide, 1-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] -3-phthalimido-2-Propellerhead, N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -4-(1-decanoyl)aminophthalimide, N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] ethyl] -4-(1-decanoyl)exittime, N-[2-[4-(1-decemoctober-6-fluoro-1H-indazol-3-yl)-1-piperazinil] ethyl] phthalimide and N-[2-[4-(1-etoxycarbonyl-6-fluoro-1H-indazol-3-yl)-1-piperazinil] ethyl] phthalimid, or their pharmaceutically acceptable salts accession acids.

120. Method of reducing pain and/or treatment of psychosis, including introduction to the mammal effective to alleviate pain or for the treatment of psychosis amount of compound according to any one of paragraphs. 1, 82 or 108.

121. The method according to p. 120, where to ensure long-term antipsychotic effect to a mammal is injected composition according to any one of paragraphs. 115-119, taken in an amount sufficient to create long-term antipsychotic effect.

122. Composition according to any one of paragraphs. 115-119 as the active ingredient is Setenil-2-hydroxyethane.

124. The composition according to p. 119, containing pharmaceutically acceptable oil.

125. The composition according to p. 124, where the specified oil selected from the group comprising coconut oil, peanut oil, sesame oil, cottonseed oil, corn oil, soybean oil, olive oil, and esters of fatty acids and polyhydric alcohols.

Priority items:
28.10.1993 on PP. 1-81 and 108-110;
25.10.1994 on PP. 82-107;
28.10.1993 and 25.10.1994 on PP. 111-125 multiple.

 

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< / BR>
< / BR>
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