Inhibitors or the magrophage migration inhibition factor and method of identifying them

FIELD: chemistry.

SUBSTANCE: invention pertains to derivatives of quinoline with general formula Ia or Ib their stereoisomers and pharmaceutical salts, where X represents oxygen or sulphur, Z-CH2, Y-NO2, -C(O)OR5, -NR5SO2R5, -SO2R5 (for Ia) and -NO2 or -C(O)OR5 (for Ib). Description is also given of the method of obtaining Ia and Ib compounds, pharmaceutical compositions based on them, and their use when making medicinal preparations.

EFFECT: compounds can be used for treating lesions, related to inhibition of migration of magrophage, for example, during treatment of septic shock or arthritis.

175 cl, 16 tbl, 22 ex, 16 dwg

 

The text descriptions are given in facsimile form.

I. quinoline Derivatives of General formula Ia

their stereoisomers or pharmaceutically acceptable salts, in which

X is oxygen or sulfur;

Y-NO2, -C(O)OR5, -NR5SO2R5-SO2R'5;

Z - CH2-; n=1; R1selected from the group consisting of a possibly substituted by halogen alkyl, aryl, substituted halogen, haloalkyl, group-C(=O)-CH2Br, aryl, arylalkyl substituted by halogen or alkoxy of arylalkyl, heterocycle selected from the group comprising thienyl, furyl, pyridyl, and possibly substituted by halogen, R R"N(CH2)x-where x is an integer from 2 to 4, R' and R" are alkyl; R2and R3- halogen, R5; R4- group C(=O)R7; -CH2R7, R8, R5- alkyl; R'5- aryl; R7- aryl, heterocyclyl, 5-10-membered, saturated or unsaturated and contains from 1 to 3 heteroatoms selected from N, O or S, aryl or heterocyclyl can be substituted by halogen, alkylamino, nitro, haloalkyl, R8- oxazolyl, substituted-C(=O)CH3.

2. The compound according to claim 1 where X is oxygen.

3. The compound according to claim 1, where Y is-C(=O)och2CH3.

4. The compound according to claim 1, where Y is-NO2.

5. The compound according to claim 1, where R4is

or.

6. The compound according to claim 1, where R4is

or.

7. Connection imouse the structure

or a stereoisomer or pharmaceutically acceptable salt,

where X is oxygen or sulfur;

Y is-NO2;

Z is-CH2-;

n = 1;

R1selected from the group consisting of a possibly substituted by halogen alkyl, aryl, substituted halogen, haloalkyl, group-C(=O)-CH2Br, aryl, arylalkyl substituted by halogen or alkoxy of arylalkyl, heterocycle selected from the group comprising thienyl, furyl, pyridyl, and possibly substituted by halogen, R R"N(CH2)x-where x is an integer from 2 to 4, R' and R" are alkyl; R2and R3- halogen, R5; R4- group C(=O)R7; -CH2R7, R8, R5- alkyl; R7- aryl, heterocyclyl, 5-10-membered, saturated or unsaturated and contains from 1 to 3 heteroatoms selected from N, O or S, and the aryl or heterocyclyl can be substituted by halogen, alkylamino, nitro, haloalkyl, R8- oxazolyl, substituted-C(=O)CH3.

8. The connection according to claim 7, where X is oxygen.

9. The connection according to claim 7, where R4is

or.

10. The connection according to claim 7, where R4is

or.

11. With the Association, with the structure

or a stereoisomer or pharmaceutically acceptable salt,

where X is oxygen or sulfur;

Y is C(=O)och2CH3;

Z is-CH2-;

n = 1;

R1selected from the group consisting of a possibly substituted by halogen alkyl, aryl, substituted halogen, haloalkyl, group-C(=O)-CH2Br, aryl, arylalkyl substituted by halogen or alkoxy of arylalkyl, heterocycle selected from the group comprising thienyl, furyl, pyridyl, and possibly substituted by halogen, R R" N(CH2)x-where x is an integer from 2 to 4, R' and R" are alkyl; R2and R3- halogen, R5; R4- group C(=O)R7; -CH2R7, R8, R5- alkyl; R7- aryl, heterocyclyl, 5-10-membered, saturated or unsaturated and contains from 1 to 3 heteroatoms selected from N, O or S, and the aryl or heterocyclyl can be substituted by halogen, alkylamino, nitro, haloalkyl, R8- oxazolyl, substituted-C(=O)CH3.

12. Connection to item 11, where X is oxygen.

13. Connection to item 11, where R4is

or.

14. Connection to item 11, where R4is

/img> or.

15. The compound having the structure

their stereoisomer or pharmaceutically acceptable salt,

where X is oxygen or sulfur;

Y is selected from the group consisting-NO2-C(O)OR5, -NR5SO2R5and S(O)2R'5;

Z is CH2-;

n = 1;

R1selected from the group consisting of a possibly substituted by halogen alkyl, aryl, substituted halogen, haloalkyl, group-C(=O)-CH2Br, aryl, arylalkyl substituted by halogen or alkoxy of arylalkyl, heterocycle selected from the group comprising thienyl, furyl, pyridyl, and possibly substituted by halogen, R R" N(CH2)x-; where x is an integer from 2 to 4, R' and R" are alkyl; R2and R3- halogen, R5, R4is

or; and

R5- alkyl, R'5- aryl.

16. The connection indicated in paragraph 15, where X is oxygen:

17. The connection indicated in paragraph 15, where Y is-C(=O)och2CH3.

18. The connection indicated in paragraph 15, where Y is-NO2.

19. The compound having the structure:

their stereoisomer or pharmaceutically acceptable salt,

where X is oxygen is m or sulfur;

Y is selected from the group consisting-NO2, -C(O)OR5, -NH5SO2R5and S(O)2R'5;

Z is CH2-;

n = 1;

R1selected from the group consisting of a possibly substituted by halogen alkyl, aryl, substituted halogen, haloalkyl, group-C(=O)-CH2Br aryl, arylalkyl substituted by halogen or alkoxy of arylalkyl, heterocycle selected from the group comprising thienyl, furyl, pyridyl, and possibly substituted by halogen, R R" N(CH2)x-where x is an integer from 2 to 4, R' and R" are alkyl; R2and R3- halogen, R5, R4is

or; and

R5- alkyl, R'5- aryl.

20. The connection according to claim 19, where X is oxygen.

21. The connection according to claim 19, where Y is-C(=O)och2CH3.

22. The connection according to claim 19, where Y is-NO2.

23. The compound having the structure:

or a stereoisomer, or a pharmaceutically acceptable salt,

where X is oxygen;

Y is selected from the group consisting of NO2, -C(O)OR5, -NR5-SO2R5and S(O)2R'5;

Z is-CH2;

n = 1;

R1selected from the group status is the present from possibly substituted by halogen alkyl, aryl substituted by halogen, haloalkyl, group-C(=O)-CH2Br aryl, arylalkyl substituted by halogen or alkoxy of arylalkyl, heterocycle selected from the group comprising thienyl, furyl, pyridyl, and possibly substituted by halogen, R R" N(CH2)x-where x is an integer from 2 to 4, R' and R" are alkyl; R2and R3- halogen, or R5, R4- group C(=O)R7; -CH2R7, R8, R5- alkyl; R'5- aryl; R7- aryl, heterocyclyl, 5-10-membered, saturated or unsaturated and contains from 1 to 3 heteroatoms selected from N, O or S, aryl or heterocyclyl can be substituted by halogen, alkylamino, nitro, haloalkyl, R8- oxazolyl, substituted-C(=O)CH3.

24. Connection item 23, where Y is-C(=O)och2CH3.

25. Connection item 23, where Y is-NO2.

26. Connection item 23, where R4is

or

27. Connection item 23, where R4is

or

28. Connection item 21 represents

29. Connection p.22, where the structure is a

30. Connection p.22, where the structure is a

img src="https://img.russianpatents.com/864/8648926-s.jpg" height="79" width="53" >

31. Connection p.22, where the structure is a

32. Connection item 21, where the structure is a

33. Connection item 21, where the structure is a

34. Connection p.22, where the structure is a

35. Connection p.22, where the structure is a

36. Connection p.22, where the structure is a

37. Connection item 21, where the structure is a

38. Connection item 21, where the structure is a

39. Connection item 21, where the structure is a

40. Connection p.22, where the structure is a

41. Connection p.22, where the structure is a

.

42. Connection p.22, where the structure is a

.

43. Connection item 21, where the structure is a

.

44. Connect the tion on p.22, where the structure is a

.

45. Connection item 21, where the structure is a

.

46. Connection item 21, where the structure is a

.

47. Connection item 21, where the structure is a

.

48. Connection item 21, where the structure is a

.

49. Connection item 21, where the structure is a

.

50. The connection 17, where the structure is a

51. The compound according to claim 3, where the structure is a

52. Composition for reducing the activity of MIF, comprising the compound according to claim 1 in combination with a pharmaceutically acceptable carrier or diluent.

53. The use of compounds of the formula Ia according to claim 1 for obtaining a medicinal product for reducing MIF activity.

54. The use of compounds of the formula Ia according to claim 1 for obtaining a medicinal product for the treatment of inflammation.

55. A method of treating septic shock for warm-blooded animals, including the appointment of an animal an effective amount of a compound according to claim 1.

56. A method of treating arthritis is tov for warm-blooded animals, including the appointment of an animal an effective amount of a compound according to claim 1.

57. The use of the compounds of formula Ia according to claim 1 for obtaining a medicinal product for the treatment of cancer.

58. The use of the compounds of formula Ia according to claim 1 for obtaining a medicinal product for the treatment of acute respiratory diseases.

59. The use of the compounds of formula Ia according to claim 1 for obtaining a medicinal product for the treatment of inflammatory diseases.

60. Use p, where the inflammatory disease is selected from the group consisting of progressive deforming arthritis, osteoarthritis, inflammatory bowel disease, and asthma.

61. The use of the compounds of formula Ia according to claim 1 for obtaining a medicinal product for the treatment of autoimmune diseases.

62. Use p, where the autoimmune disease is selected from the group consisting of diabetes, asthma and multiple sclerosis.

63. The use of the compounds of formula Ia according to claim 1 to obtain medication to suppress the immune response in warm-blooded animals.

64. The use of the compounds of formula Ia according to claim 1 for receiving drugs to reduce angiogenesis in a warm-blooded animal.

65. The use of the compounds of formula Ia according to claim 1 for obtaining a medicinal product for the treatment of diseases associated with excessive from what UNAMI glucocorticoid hormone in warm-blooded animals.

66. Use p, where the disease is Cushing disease.

67. Method for detecting an agent that modulates the activity of MIF, including:

contacts containing MIF sample with the agent, and

the detection ability of the agent to modulate MIF by determining the differential ability of antibodies to bind MIF.

68. The method according to p, where the antibody is a monoclonal antibody.

69. The method according to p, where MIF includes fused proteins, mutants or variants.

70. How to use binding antibodies as a surrogate marker for a test agent that modulates the activity of the polypeptide, including:

contacting the polypeptide with the expected modulating agent,

contacting the polypeptide with a monoclonal antibody, and

detection of differential activity of the polypeptide relative to a reference standard.

71. The compound having the structure

or a stereoisomer or pharmaceutically acceptable salt,

where X is oxygen or sulfur;

Y is selected from the group consisting of NO2-C(=O)OR5,

Z is-CH2,

n is 1,

R1is selected from the group consisting of arylalkyl, substituted aryl halide is Qila, R R"N(CH2)x-, where x is an integer from 2 to 4, and where R' and R" are alkyl, substituted alkyl,

R2and R3independently selected from the group consisting of-R5,

R4is selected from the group consisting of C(=O)R7;

R5- alkyl;

R7is selected from the group consisting of substituted halogen or alkoxyaryl, heterocycle selected from the group comprising thienyl and furyl.

72. Connection p, where R1is-NCH2CH2CH2N(CH3)2.

73. Connection p, where X is oxygen.

74. Connection p, where Y is-C(=O)OCH2CH3.

75. Connection p, where Y is-NO2.

76. Connection p, where R4is

or.

77. Connection p, where R4is

or.

78. The compound having the structure

or a stereoisomer or pharmaceutically acceptable salt,

where X is oxygen or sulfur;

Y is-C(=O)och2CH3;

Z is-CH2, n is 1,

R1is selected from the group consisting of arylalkyl substituted by halogen arylalkyl, R R N(CH 2)x-, where x is an integer from 2 to 4, and where R' and R" are alkyl, substituted alkyl,

R2and R3independently selected from the group consisting of-R5,

R4is selected from the group consisting of C(=O)R7;

R5- alkyl;

R7is selected from the group consisting of substituted halogen or alkoxyaryl, heterocycle selected from the group comprising thienyl and furyl.

79. Connection p, where X is oxygen.

80. Connection p, where R4is

or.

81. Connection p, where R4is

or.

82. The compound having the structure

or a stereoisomer or pharmaceutically acceptable salt,

where X is oxygen or sulfur;

Y is selected from the group consisting of NO2, -C(=O)OR5,

Z is-CH2,

n is 1,

R1is-NCH2CH2CH2N(CH3)2;

R2and R3independently selected from the group consisting of-R5,

R4is selected from the group consisting of-C(=O)R7,

R5- alkyl,

R7select the C group, consisting of substituted halogen or alkoxyaryl, heterocycle selected from the group comprising thienyl or furyl.

83. Connection p, where Y is-C(=O)och2CH3.

84. Connection p, where Y is-NO2.

85. Connection p, where R4is

or.

86. Connection p where R4is

or.

87. The compound having the structure

or a stereoisomer or pharmaceutically acceptable salt,

where X is oxygen or sulfur;

Y is-NO2;

Z is-CH2-,

n is 1,

R1is selected from the group consisting of arylalkyl substituted by halogen arylalkyl and R R"N(CH2)x-, where x is an integer from 2 to 4, where R' and R" are alkyl, substituted alkyl;

R2and R3independently selected from the group consisting of-R5,

R4is selected from the group consisting of-C(=O)R7,

R5- alkyl,

R7is selected from the group consisting of substituted halogen or alkoxyl, heterocycle selected from the group comprising furyl or thienyl.

88. Connection p, where R1 is-NCH2CH2CH2N(CH3)2.

89. Connection p, where X is oxygen.

90. Connection p, where R4is

or.

91. Connection p, where R4is

or.

92. The compound having the structure

or a stereoisomer or pharmaceutically acceptable salt,

where X is oxygen or sulfur;

Y is selected from the group consisting of-C(=O)OR5, -NO2;

Z is-CH2-,

n is 1,

R1is selected from the group consisting of arylalkyl substituted by halogen arylalkyl and R R"N(CH2)x-, where x is an integer from 2 to 4, where R' and R" are alkyl, substituted alkyl;

R2and R3independently selected from the group consisting of-R5,

R4is selected from the group consisting of

,,and;

R5- alkyl.

93. Connection p, where R1 is-NCH2CH2CH2N(CH3)2.

94. Connection p, where X is oxygen.

95. Conn is out on p, where Y is-C(=O)och2CH2.

96. Connection p, where Y is - NO2.

97. Connection p, where the structure is:

98. Connection p, where the structure is a

99. Connection p, where the structure is a

.

100. Connection p, where the structure is a

.

101. Connection p, where the structure is a

.

102. Connection p, where the structure is a

.

103. Connection p, where the structure is a

.

104. Connection p, where the structure is a

.

105. Connection p, where the structure is a

.

106. Connection p, where the structure is a

.

107. Connection p, where the structure is a

.

108. Connection p, where the structure is a

.

109. Link is on p, where the structure is a

.

110. Connection p, where the structure is a

.

111. Connection p, where the structure is a

.

112. Connection p, where the structure is a

.

113. Connection p, where the structure is a

.

114. Connection p, where the structure is a

115. The use of compounds according p to obtain drugs for reducing MIF activity.

116. The use of compounds according p to obtain drugs for the treatment of inflammation.

117. A method of treating septic shock for warm-blooded animals, including the appointment of an animal an effective amount of a compound according to claim 7.

118. A method of treatment of arthritis for warm-blooded animals, including the appointment of an animal an effective amount of a compound according to claim 7.

119. The use of compounds according p to the teachings of the medicinal product for the treatment of cancer.

120. The use of compounds according p to obtain drugs for the treatment of acute respiratory diseases.

121. The use of compounds is s on p to obtain drugs for the treatment of inflammatory diseases.

122. Use p, where the inflammatory disease is selected from the group consisting of progressive deforming arthritis, osteoarthritis, inflammatory bowel disease and asthma.

123. The use of compounds according p to obtain drugs for the treatment of autoimmune diseases.

124. Use p, where the autoimmune disease is selected from the group consisting of diabetes, asthma and multiple sclerosis.

125. The use of compounds according p to obtain medication to suppress the immune response in warm-blooded animals.

126. The method of preparation of compounds of formula IV, which includes stages:

reaction of compounds of formula I

with the compound of the formula II

obtaining the compounds of formula III

where R7- aryl, heterocyclyl, 5-10-membered, saturated or unsaturated and contains from 1 to 3 heteroatoms selected from N, O or S, aryl or heterocyclyl can be substituted by halogen, alkylamino, nitro haloalkyl, reaction of compounds of formula III with a compound X-R1where X is selected from the group consisting of CI, Br and J, and where R1matter specified in claim 1 with obtaining the compounds of formula IV

where the compound of formula IV suitable for use as a MIF inhibitor.

127. The method according to p, where the compound of formula IV is a

128. The method of preparation of compounds of formula AIV, which includes stages:

reaction of compounds of formula AI

with the compound of the formula II

obtaining the compounds of formula AIII

where R7matter specified in claim 1, and reacting the compounds of formula AIII connection X-R1where X is selected from the group consisting of Cl, Br and I, and where R1matter specified in claim 1, to obtain the compounds of formula AIV

where the compound of formula AIV suitable for use as inhibition of MIF.

129. The method of preparation of compounds of formula IVa, which includes stages:

reaction of compounds of formula Ia

with the compound of the formula IIa

obtaining the compounds of formula IIIa

and reacting the compounds of formula IIIa with a compound X-R1with what rucenim the compounds of formula IVa

where the compound of formula IVa is suitable for use as a MIF inhibitor, where R1-R5, R7have the meanings indicated in claim 1.

130. The method according to p, where the formula IVa is a

131. The method according to p, where the formula IVa is a

132. The method according to p, where the formula IVa is a

.

133. The method according to p, where the formula IVa is a

.

134. The method according to p, where the formula IVa is a

.

135. The method according to p, where the formula IVa is a

.

136. The method according to p, where the formula IVa is a

.

137. The method according to p, where the formula IVa is a

.

138. The method according to p where the formula IVa is a

.

139. The method according to p, where the formula IVa is a

.

140. The method according to p, where the formula IVa is a

.

141. The method according to p, where the formula IVa is a

< num="351"> .

142. The method according to p, where the formula IVa is a

.

143. The method according to p, where the formula IVa is a

.

144. The method of preparation of compounds of formula AIVa, which includes stages:

reaction of compounds of formula AIa

with the compound of the formula IIa

obtaining the compounds of formula AIIIa

and reacting the compounds of formula AIIIa connection X-R1obtaining the compounds of formula AIVa

where the compound of formula AIVa suitable for use as a MIF inhibitor, and where R1-R4have the meanings indicated in claim 1.

145. The method according to p, where the formula AIVa is a

146. The method according to p, where the formula AIVa is a

147. The method according to p, where the formula AIVa is a

148. The method according to p, where the formula AIVa is a

149. The method according to p, where the formula AIVo is a

150. The method according to p, where the formula AIVa is a

151. The method according to p, where the formula AIVa is a

152. The method according to p, where the formula AIVa is a

153. The method according to p, where the formula AIVa is a

154. The method of preparation of compounds of formula IVb, which includes stages:

reaction of compounds of formula I

with the compound of the formula II

obtaining the compounds of formula III

where R7selected from the group consisting of substituted halogen or alkoxy aryl, heterocycle selected from the group comprising thienyl and furyl, reaction of compounds of formula III with a compound X-R1where X is selected from the group consisting of Cl, Br and I, and where R1has the values listed in p, obtaining the compounds of formula IVb

where the compound of formula IVb is suitable for use as a MIF inhibitor.

155. The method of preparation of compounds of formula AVb, including stage

reaction of compounds of formula AI

with the compound of the formula II

obtaining the compounds of formula AIII

where R7matter specified in p, and reacting the compounds of formula AIII connection X-R1where X is selected from the group consisting of Cl, Br and I, and where R1matter specified in p, obtaining the compounds of formula AIVb

where the compound of formula AIVb suitable for use as a MIF inhibitor.

156. The method of preparation of compounds of formula IVab, which includes stages:

reaction of compounds of formula Ia

with the compound of the formula IIa

obtaining the compounds of formula IIIa

and reacting the compounds of formula IIIa with a compound X-R1obtaining the compounds of formula IVab

where the compound of formula IVab suitable for use as a MIF inhibitor, where R1-R4have the values listed in p.

157. The method according to p, where the formula IVab is a

158. The method according to p, where the formula IVab includes

.

159. The method according to p, where the formula IVab includes

.

160. The method according to p, where the formula IVab includes

.

161. The method according to p, where the formula IVab includes

162. The method according to p, where the formula IVab includes

.

163. The method according to p, where the formula IVab includes

.

164. The method according to p, where the formula IVab includes

165. The method according to p, where the formula IVab includes

166. The method according to p, where the formula IVab includes

167. The method according to p, where the formula IVab includes

168. The method according to p, where the formula IVab includes

.

169. The method according to p, where the formula IVab includes

.

170. The method according to p, where the formula IVab includes

171. The method according to p, where the formula IVab includes

172. The method of preparation of compounds of formula AIVab, which includes stages:

reaction of compounds of formula AIa

with the compound is of formula IIa

obtaining the compounds of formula AIIIa

and reacting the compounds of formula AIII connection X-R1obtaining the compounds of formula AIVab

where the compound of formula AIVab suitable for use as a MIF inhibitor, where R1-R4have the values listed in p.

173. The method according to p, where the formula IVab includes

174. The method according to p, where the formula AIVab includes

175. The method according to p, where the formula AIVab includes



 

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6 cl, 180 ex

FIELD: organic chemistry, medicine, endocrinology.

SUBSTANCE: invention relates to novel compounds representing C-glycoside derivatives and their salts of the formula: wherein ring A represents (1) benzene ring; (2) five- or six-membered monocyclic heteroaryl ring comprising 1, 2 or 4 heteroatoms chosen from nitrogen (N) and sulfur (S) atoms but with exception of tetrazoles, or (3) unsaturated nine-membered bicyclic heterocycle comprising 1 heteroatom representing oxygen atom (O); ring B represents (1) unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (2) saturated or unsaturated five- or six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (3) unsaturated nine-membered bicyclic carbocycle, or (4) benzene ring; X represents a bond or lower alkylene wherein values for ring A, ring B and X correlate so manner that (1) when ring A represents benzene ring then ring B is not benzene ring, or (2) when ring A represents benzene ring and ring B represents unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O and comprising benzene ring or unsaturated nine-membered bicyclic carbocycle comprising benzene ring then X is bound to ring B in moiety distinct from benzene ring comprised in ring B; each among R1-R4 represents separately hydrogen atom, -C(=O)-lower alkyl or lower alkylene-aryl; each R5-R11 represents separately hydrogen atom, lower alkyl, halogen atom, -OH, =O, -NH2, halogen-substituted lower alkyl-sulfonyl, phenyl, saturated six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N and O, lower alkylene-OH, lower alkyl, -COOH, -CN, -C(=O)-O-lower alkyl, -O-lower alkyl, -O-cycloalkyl, -O-lower alkylene-OH, -O-lower alkylene-O-lower alkyl, -O-lower alkylene-COOH, -O-lower alkylene-C(=O)-O-lower alkyl, -O-lower alkylene-C(=O)-NH2, -O-lower alkylene-C(=O)-N-(lower alkyl)2, -O-lower alkylene-CH(OH)-CH2(OH), -O-lower alkylene-NH, -O-lower alkylene-NH-lower alkyl, -O-lower alkylene-N-(lower alkyl)2, -O-lower alkylene-NH-C(=O)-lower alkyl, -NH-lower alkyl, -N-(lower alkyl)2, -NH-lower alkylene-OH or NH-C(=O)-lower alkyl. Indicated derivatives can be used as inhibitor of co-transporter of Na+-glucose and especially as a therapeutic and/or prophylactic agent in diabetes mellitus, such as insulin-dependent diabetes mellitus (diabetes mellitus 1 type) and non-insulin-dependent diabetes mellitus (diabetes mellitus 2 type), and in diseases associated with diabetes mellitus, such as insulin-resistant diseases and obesity.

EFFECT: valuable medicinal properties of compounds.

11 cl, 41 tbl, 243 ex

FIELD: organic chemistry, pharmaceutical chemistry, pharmacology, medicine.

SUBSTANCE: invention relates to novel derivatives of 3-methyl-7-(thietanyl-3)-xanthine of formulae (Ia, b, c, d): wherein R means C2H5, R1 means , n = 1 (Ia); R means n-C3H7, R1 means Br, n = 1 (Ib); R means hydrogen atom (H), R1 means -SCH2CONHNH2, n = 0 (Ic); R means H, R1 means -SCH2CONHNH2, n = 2 (Id). Proposed compounds possess the greater hemorheological activity as compared with that of pentoxyphylline and lower toxicity. Invention provides synthesis of novel and not described previously derivatives of 3-methyl-7-(thietanyl-3)-xanthine of formulae (Ia, b, c, d) possessing hemorheological activity.

EFFECT: improved method of synthesis, valuable medicinal property of compounds.

2 tbl, 4 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes compounds of the formula (I) or their pharmaceutically acceptable salts wherein R1 and R2 are similar or different and chosen independently from group comprising aryl and heteroaryl. Each of them as a substitute comprises optionally from one to sic groups chosen from group comprising the following groups: (a) halogen atom; (b) -OCF3 or -OCHF2; (c) -CF3; (d) -CN; (e) alkyl; (f) R18-heteroaljyl; (k) hydroxyl; (l) alkoxyl comprising cyclopropylmethoxyl, and (s) trifluoroalkoxyl; R3 means hydrogen atom (H); R4, R5, R7 and R8 are similar or different and chosen independently from group comprising H, -OH, alkyl, heteroalkyl and

under condition that if Z and/or X means nitrogen atom (N) then all radicals R4, R5, R7 and R8 don't mean -OH; R6 means -C(O)R15; R9 and R10 mean H; R11 is chosen from group comprising H and alkyl; R12 is chosen from group comprising H and alkyl; R13 is chosen from group comprising alkyl and alkoxyl; R14 means H; R15 is chosen from group comprising -NR16R17, -OR16 and alkyl wherein R16 and R17 are similar or different and chosen independently from group comprising H and alkyl; R18 means a substitute chosen from group comprising lower alkyl, halogen alkyl, halogenalkyl, alkoxycarbonyl, dialkylamino-group and piperidinyl; X and Z are similar or different and chosen independently from carbon atom (C) and N. Proposed compounds possess properties of inhibitor of 17β-hydroxysteroid dehydrogenase of type 3. Also, invention describes a pharmaceutical composition based on compound of the formula (I).

EFFECT: valuable medicinal and biochemical properties of compound and pharmaceutical composition.

16 cl, 23 tbl, 651 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes novel nitrogen-containing aromatic derivatives of the general formula (I): wherein X1 means nitrogen atom (N) or group -CR10= wherein R10 means hydrogen atom (H), halogen atom or -CN; X2 means N or group -CR11= but X1 and X2 can't mean N simultaneously; Y means oxygen atom (O) or group -NRY- wherein RY means hydrogen atom or (C1-C6)-alkyl group; R1 means phenoxy-group, group -NR12aR12b, group , group and other values; each radical among R3, R4, R5, R6 and R11 means hydrogen atom; R7 means hydrogen atom or (C1-C6)-alkyl group; R8 means hydrogen atom or (C1-C6)-alkyl group; R10 means hydrogen atom, halogen atom or cyano-group; R9 means group -NR16aR16b or group of the formula: wherein T2 means pyrrolidine, piperazine ring possibly substituted with (C1-C6)-alkyl group, or morpholine ring; R12a and R12b mean independently hydrogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group; R2 means hydrogen atom or (C1-C6)-alkyl; R16a means hydrogen atom or (C1-C6)-alkyl, and R16b means (C1-C6)-alkyl possibly substituted with phenyl, (C1-C6)-alkoxy-group, (C1-C6)-alkylthio-group or di-(C1-C6)-alkylamino-group, (C3-C6)-alkynyl, (C3-C8)-cycloalkyl, phenyl possibly substituted with halogen atom, thiazolyl or piperidinyl possibly substituted with (C1-C6)-alkyl, and their salts or hydrates. Also, invention describes a pharmaceutical composition, method for treatment or prophylaxis of tumor diseases and using the novel compounds for preparing an agent useful in treatment abovementioned diseases.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method for treatment.

26 cl, 17 tbl, 221 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to compounds of general formula 1 (G1 is group of general formulae 2 G1 is group of general formulae ; meanings of the rest substituents are as described in specification) or pharmaceutically acceptable salts thereof and use thereof in srug production. Said compounds are useful in treatment of male and female sexual disorders.

EFFECT: new oxytocin antagonists.

30 cl, 177 ex

FIELD: chemistry.

SUBSTANCE: invention relates to heterocyclic compounds with general formula (I) or its pharmaceutically acceptable salts; and including its any stereoisomer forms;X and Y are independently N or CR1; Z represents S, O, NR1 or CR12;every R1-R6 represent independently H or not influencing substitute, which is alkyl (C1-10), allkenyl (C2-10), alkynil (C2-10), aryl ("C'5-12), arylalkyl, arylalkenyl or arylalkynil, each of which can not obligatorily contain one or more heteroatoms selected from O, S and N and each of which can be substituted further one; or not obligatorily substituted forms of acyl, arylacyl, alkyl,alkenyl alkynyl or arylsulphonyl or their forms which contain heteroatoms in alkyl,alkynyl or aryl fragments or representing OR, SR, NR2, COOR, CONR2, where R is N or alkyl alkenyl, alkynyl, or aryl not obligatorily substituted, as defined above, when C is a substituted atom not influencing substitute can be a halohen, OOCR, NROCR, where R is H or its substitute shown above, or can equal 0; nl is equal to 0-4; n2 is equal to 0-1, where * means that CR5=CR5 can be substituted by C=C; n3 is equal to 0-4;where nl+n2+n3 exceeds or equals 2; b is equal to 0-2; where the following combinations of R-groups can be associated with cycle formation, which can saturated or unsaturated R2-R2, one R2+R3, R3+ one R4, R4+R4, one R5 + the other R5, one R5 + one R6 and R6+R6; where cycle can not be aromatic, when the cycle formation components are represented by two R5; and where, when n2 is unity 1, neither of n1 nor n3 can be equal to 0, the invention also relates to pharmaceutical composition, based on these compounds, possessing a modulating ability relative to CXCR4- and/or CCRS-receptor; to modulation method CXCR4- and/or CCRS-receptor; to method of treatment of a statec described by unusual activity CXCR4- and/or CCR5-receptor and application of the described compounds for production of pharmaceutical.

EFFECT: new compounds feature useful biological properties.

36 cl, 171 ex

FIELD: chemistry.

SUBSTANCE: invention presents several polymorphous forms and an amorphous form of {2-fluorine-5-[3-((E)-2-pyridine-2-ilvinyl)-1N-indazole-6-ilamine]phenyl}amide 2, 5-dimethyl-2N-pyrazole-3-carbonic acid, a pharmaceutical formula containing such polymorphous or amorphous forms, as well as ways of using such pharmaceutical formulas for therapy of ill conditions mediated by protein kinases such as cancer and other pathological conditions associated with undesirable angiogenesis and/or cell proliferation, as well as the mode of modulating protein kinase receptor activities on the basis of the polymorphous forms.

EFFECT: obtained polymorphous forms possess improved solubility and biological accessibility when taken per os.

22 cl, 40 dwg, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I or pharmaceutically suitable salt or solvate thereof, where dashed line stands for additional bond, а is a number from 0 to 2, b is a number from 0 to 2, n is 2, p is 2, r is 1, М1 stands for nitrogen, М2 stands for С(R3), X stands for either a bond or alkylene group with number of carbon atoms from 1 to 6, Y stands for -С(О)- group, Z stands for a bond, or alkylene group with number of carbon atoms from 1 to 6, or alkenylene group with number of carbon atoms from 1 to 6, or -С(O)-, -CH(CN)-, -SO2- or СН2С(O)NR4- group, R1 stands for groups, R2 stands for six-membered heteroaryl ring with one or two heteroatoms chosen independently of each other from either nitrogen atom or N-O group, other atoms of the cycle being carbon, five-membered heteroaryl ring with one, two, three or four heteroatoms chosen independently of each other from nitrogen, oxygen or sulphur, other atoms of the cycle being carbon, R32 stands for substituded quinoline group, R32 stands for substituted aryl group, heterocycloalkyl group, cycloalkyl group with number of carbon atoms from 3 to 6, alkyl group with number of carbon atoms from 1 to 6, group, where the said six-membered heteroaryl ring or the said five-membered heteroaryl ring may be R6-substituted, R12 independently of others is chosen from an alkyl group with number of carbon atoms from 1 to 6, hydroxyl group or fluorine atom, provided in case R12 stands for hydroxyl or fluorine the rest of R12 cannot be bonded to a nitrogen-bonded carbon atom, or two R12 substituents form an alkyl bridge with number of carbon atoms from 1 to 2, which bonds two non-adjaicent carbon atoms of the ring, R13 independently of the others is chosen from an alkyl group with number of carbon atoms from 1 to 6, hydroxyl group, alcoxy group with number of carbon atoms from 1 to 6, or fluorine atom, provided in case R13 stands for hydroxyl or fluorine the rest of R13 cannot be bonded to a nitrogen-bonded carbon atom, or two R13 substituents form an alkyl bridge with number of carbon atoms from 1 to 2, which bonds two non-adjacent carbon atoms of the ring. See description for meaning of the other structural elements. Invention relates also to pharmaceutical compositions, as well as to application of compounds of formula I.

EFFECT: preparation of novel biologically active substances and pharmaceutical compositions.

20 cl, 659 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to derivatives of quinazoline of the general formula (I): and their pharmaceutically acceptable salts and in vivo hydrolyzed esters as aurorakinase inhibitors and their using, to a method for inhibition and pharmaceutical composition based on thereof, and to a method for their synthesis. In compound of the general formula (I) X represents -NR6 wherein R6 represents hydrogen atom or (C1-C6)-alkyl; R5 represents group of the formula (a): or (b): wherein * means a point for adding to group X in compound of the formula (I); R1, R2, R3 and R4 are chosen independently from hydrogen atom or -X1R9 wherein X1 represents -O-, and R9 is chosen from one of the following groups: (1) hydrogen atom or (C1-C5)-alkyl; (3) (C1-C5)-alkyl-X3R20 wherein X3 represents -O- or -NR25 wherein R25 represents hydrogen atom, (C1-C3)-alkyl or (C1-C3)-alkoxy-(C2-C3)-alkyl, and R20 represents hydrogen atom, (C1-C3)-alkyl, cyclopentyl, cyclohexyl or 5- or 6-membered saturated heterocyclic group with 1 or 2 heteroatoms that are chosen independently from nitrogen atom (N) wherein (C1-C3)-alkyl group can carry 1 or 2 substitutes that are chosen from oxo, hydroxy group, halogen atom and (C1-C4)-alkoxy group, and wherein cyclic group can carry 1 or 2 substitutes that are chosen from (C1-C4)-alkyl; (4) (C1-C5)-alkyl-X4-(C1-C5)-alkyl-X5R26 wherein X4 and X5 can be similar or different, and each means -O- or -NR31- wherein R31 represents hydrogen atom, (C1-C3)-alkyl or (C1-C3)-alkoxy-(C2-C3)-alkyl, and R26 represents hydrogen atom or (C1-C3)-alkyl; (5) R32 wherein R32 represents 5- or 6-membered saturated heterocyclic group added through carbon atom or nitrogen atom with 1 or 2 heteroatoms that are chosen independently from oxygen (O), sulfur (S) and N atoms wherein heterocyclic group can carry 1 or 2 substitutes that are chosen from hydroxy, (C1-C4)-alkyl, (C1-C4)-hydroxyalkyl, (C1-C4)-alkoxy, (C1-C4)-alkoxy-(C1-C4)-alkyl; (6) (C1-C5)-alkyl-R32 wherein R32 is given above; (18) (C1-C5)-alkyl optionally substituted with 1, 2 or 3 halogen atoms; (19) (C1-C5)-alkyl-X10-(C1-C5)-alkyl-X11R90 wherein X10 and X11 that can be similar or different each means -O- or -NR95- wherein R95 represents (C1-C5)-alkyl, (C1-C3)-alkyl substituted with 1, 2 or 3 halogen atoms, (C1-C4)-alkyl or (C1-C4)-alkoxy groups, (and wherein 2 (C1-C4)-alkoxy groups by (C1-C4)-alkyl groups alkoxy can form in common 5- or 6-membered saturated heterocyclic group that comprises 2 oxygen atoms), (C2-C5)-alkenyl, (C2-C5)-alkynyl, (C3-C6)-cycloalkyl, (C3-C6)-cycloalkyl-(C1-C3)-alkyl or (C1-C3)-alkoxy-(C2-C3)-alkyl; R90 represents hydrogen atom or (C1-C3)-alkyl; (22) (C1-C5)-alkyl-R96 wherein R96 represents 5- or 6-membered heterocyclic group that can be saturated or unsaturated (added through carbon or nitrogen atom) with 1 or 2 heteroatoms that are chosen independently from N wherein heterocyclic group can carry 1 or 2 substitutes that are chosen from (C1-C4)-hydroxyalkyl, (C1-C4)-alkyl, hydroxy and (C1-C4)-alkoxy-(C1-C4)-alkyl, and wherein R60 represents hydrogen atom; R61 represents group of the subformula (k): wherein p represents 0 or 1; q represents 1; R'1 and R''1 represent independently hydrogen atom or (C1-C10)-alkyl; T represents C=O; V represents -N(R63)R64 wherein R63 represents -(CH2)q'R70 or phenyl optionally substituted with 1 or 2 groups chosen independently from halogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxy, trifluoromethyl, trifluoromethoxy, nitro, difluoromethyl, difluoromethoxy and cyano group; R64 represents hydrogen atom or (C1-C3)-alkyl; q' = 0; R70 represents -K-J wherein K represents a bond, and J represents phenyl optionally substituted with 1, 2 or 3 groups that are chosen from halogen atom, (C1-C3)-alkyl, cyano, (C1-C3)-alkoxy, and R62 represents hydrogen atom. Proposed compounds can be used in treatment and prophylaxis of diseases mediated by aurorakinase activity, for example, proliferative diseases, such as cancer.

EFFECT: valuable medicinal properties of compounds.

32 cl, 7 tbl, 2 sch, 147 ex

FIELD: organic chemistry, chemical technology, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to a method for synthesis of compound of the formula (I): or its pharmaceutically acceptable salt, ether, ester, amide, hydrate or solvate wherein each R1, R2 and R3 is chosen independently from group consisting of hydrogen atom (H), (C1-C6)-alkyl, (C3-C6)-cycloalkyl, halogen atom, cyano, -CF3, difluoromethoxy, trifluoromethoxy, -O-(C1-C6)-alkyl, -O-(C3-C6)-cycloalkyl and -NR12R13; wherein R4 represents -(CR5R6)mH or -(CR7R8)n (4-10-membered) aromatic or nonaromatic heterocycle comprising one or more heteroatoms each of them is chosen from oxygen (O), sulfurs (S) and nitrogen (N) atoms, and wherein m represents a whole number in the range from 1 to 5, and wherein n represents a whole number in the range from 0 to 5, wherein indicated 4-10-membered aromatic heterocycle is substituted possibly with 1-3 substitutes R9, and wherein indicated 4-10-membered nonaromatic heterocycle is substituted possibly with 1-3 substitutes R10 by any position and substituted possibly with 1-3 substitutes R11 by any position but not adjacent or directly bound to heteroatom; wherein Each R5, R6, R7 and R8 is chosen independently from group consisting of H and (C1-C6)-alkyl; wherein each R9 is chosen independently from H, (C1-C6)-alkyl, (C3-C6)-cycloalkyl, cyano, -CF3, difluoromethoxy, trifluoromethoxy, -O-(C1-C6)-alkyl, -O-(C3-C6)-cycloalkyl and -NR14R15; wherein each R10 is chosen independently from H, (C1-C6)-alkyl and (C3-C6)-cycloalkyl; wherein each R11 is chosen from halogen atom, cyano, -CF3, difluoromethoxy, trifluoromethoxy, -O-(C1-C6)-alkyl, -O-(C3-C6)-cycloalkyl and -NR16R17; wherein R12, R13, R14, R15, R16 and R17 are chosen independently from group consisting of H, (C1-C6)-alkyl and (C3-C6)-cycloalkyl wherein each abovementioned (C1-C6)-alkyl, (C3-C6)-cycloalkyl, -O-(C1-C6)-alkyl and -O-(C3-C6)-cycloalkyl substitutes wherein they present can be substituted independently with substitutes in the amount from 1 to 3 and chosen independently from group consisting of halogen atom, cyano, amino, (C1-C6)-alkylamino, [(C1-C6)-alkyl]-amino, perhalogen-(C1-C6)-alkyl, perhalogen-(C1-C6)-alkoxy, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, hydroxy and (C1-C6)-alkoxy. Method of synthesis involves interaction of compound of the formula (II): wherein BOC represents tert.-butoxycarbonyl, and R1, R2, R3 and R4 are given above for compound of the formula (I) with metal alkoxide in the presence of water to obtain compounds of the formula (I). Invention provides a novel method for synthesis of compounds of the formula (I) that are useful in treatment of cells anomalous growth, such as cancer, in mammals.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds.

12 cl, 7 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to therapeutic agents showing effectiveness in treatment of pain, cancer, cerebrospinal sclerosis, Parkinson's disease, Huntington's chorea and/or Alzheimer's disease. Invention describes compound of the formula (I): or its pharmaceutically acceptable salts wherein RF1 and RF2 represent independently electron-acceptor groups; Z is chosen from O=; R1 is chosen from (C1-C10)-alkyl, heterocyclyl-(C1-C6)-alkyl, substituted heterocyclyl-(C1-C6)-alkyl; R2 is chosen from (C1-C6)-alkyl; X represents bivalent (C1-C10)-group that separates groups added to it by one or two atoms; Ar represents bivalent (C4-C12)-aromatic group, and Y is chosen from =CH=. Also, invention describes fields wherein compounds of the formula (I) are used, a pharmaceutical composition based on thereof, and methods for their synthesis. Invention provides synthesis of novel compounds possessing useful biological properties.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

17 cl, 2 tbl, 35 ex

FIELD: organic chemistry, medicine, pharmacy, chemical technology.

SUBSTANCE: invention relates to novel substituted esters of 1H-indol-3-carboxylic acids of the general formula (1): or their racemates, or their optical isomers, or their pharmaceutical acceptable salts and/or hydrates. Compounds can be used in treatment of such diseases as infectious hepatitis, human immunodeficiency, atypical pneumonia and avian influenza. In compound of the general formula (1) R1, R41 and R42 each represents independently of one another a substitute of amino group chosen from hydrogen atom, optionally linear or branched alkyl comprising 3-12 carbon atoms, optionally substituted cycloalkyl comprising 3-10 carbon atoms, optionally substituted aryl or optionally substituted and possibly an annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 carbon atom in ring with one or some heteroatoms chosen from nitrogen oxygen or sulfur atoms; or R41 and R42 in common with nitrogen atom to which they are bound form 5-10-membered azaheterocycle or guanidyl through R41 and R42; R2 represents an alkyl substitute chosen from hydrogen atom, optionally substituted mercapto group, optionally substituted amino group, optionally substituted hydroxyl; R3 represents lower alkyl; R5 represents a substitute of cyclic system chosen from hydrogen atom, halogen atom, cyano group, optionally substituted aryl or optionally substituted and possibly an annelated heterocycle that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms. Also, invention relates to methods for treatment, drugs and pharmaceutical compositions using compounds of this invention.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method of synthesis.

22 cl, 3 tbl, 8 dwg, 6 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of 3-hydrozy-2-pyridone represented by the formula (I): wherein R1 means aryl optionally substituted with one or more alkyl group; R2 means hydrogen atom; each R3 and R4 is taken independently of one another from hydrogen atom, alkyl, alkylheteroaryl and aralkyl group; or R3 and R4 in common with nitrogen atom bound with them form heteroaryl or heterocycloaryl substitute optionally substituted with one halogen atom, alkoxy group, aryl, heteroaryl and heterocycloalkyl; R5 and R6 mean hydrogen atom. Also, invention relates to using the compound by any claims among 1-7 for preparing pharmaceutical compositions showing antibacterial properties, and to above said pharmaceutical compositions. Invention provides synthesis of novel compounds possessing useful biological properties, and a pharmaceutical composition based on thereof.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

9 cl, 8 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): and/or stereomer form of compound of the formula (I), and/or physiologically compatible salt of compound of the formula (I) wherein X and M are similar or different and mean independently of one another nitrogen atom (N) or -CH; R1 and R11 are similar or different and mean independently of one another: (1.) hydrogen atom; (2.) fluorine (F), chlorine (Cl), iodine (J) or bromine (Br) atom; R2 means: (1.) heteroaryl residue of group comprising 1,3,4-oxadiazole, oxadiazolylidinedione, oxadiazolone, thiazole, and heteroaryl residue is unsubstituted or 1-3-times substituted independently of one another: (1.1.) keto-group; (2) -C(O)-R5 wherein R5 means hydrogen atom or -(C1-C4)-alkyl, or (3.) -C(O)-N(R7)-R8 wherein R7 and R8 mean independently of one another hydrogen atom, -(C1-C4)-alkyl-OH, -O-(C1-C4)-alkyl or -(C1-C4)-alkyl; R3 means hydrogen atom or -(C1-C4)-alkyl; R4 means: (1.) heteroaryl residue of group comprising thiazole, isothiazole, pyridine, pyrazine, pyrimidine wherein heteroaryl residue is unsubstituted or 1-3-times substituted independently of one another with -(C1-C5)-alkyl, halogen atom, trifluoromethyl, or (2.) aryl residue of group comprising phenyl. Also, invention relates to a method for preparing a medicinal agent and to using compounds based on the formula (I) possessing activity with respect to IkB kinase. Invention provides synthesis of novel compounds possessing useful biological properties.

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical agent.

6 cl, 67 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of piperidine of the general formula (I): or their pharmaceutically acceptable salts or isomers wherein Q means nitrogen atom (N); X and Z are chosen independently from group consisting of -CH and N under condition that one or both groups among Q and Z mean N; R, R4, R5, R and R are chosen independently from group consisting of hydrogen atom (H) and (C1-C6)-alkyl; R1 means H, (C1-C6)-alkyl, R9-aryl-(C1-C6)-alkyl-, (C1-C6)-alkyl-SO2-, (C3-C6)-cycloalkyl-SO2-, fluoro-(C1-C6)-alkyl-SO2-, R9-aryl-SO2-, R9-heteroaryl-SO2-, -N(R22)(R23)-SO2-, (C1-C6)-alkyl-C(O)-, (C3-C6)-cycloalkyl-C(O)-, fluoro-(C1-C6)-alkyl-C(O)-, R9-aryl-C(O)-, CH3CH2-NH-C(O)- or R9-aryl-NH-C(O)-; R2 means H or (C1-C6)-alkyl, and R3 means H, (C1-C6)-alkyl, (C1-C6)-alkoxy-(C1-C6)-alkyl-, (C3-C10)-cycloalkyl-, (C3-C10)-cycloalkyl-(C1-C6)-alkyl-, R9-aryl, R9-aryl-(C1-C6)-alkyl- or R9-heteroaryl under condition that each X and X doesn't mean N, or R2 and R3 in common mean =NOR10. Proposed compounds can be used as selective CCR5 antagonists. Compounds are useful in HIV treatment. Also, invention describes a pharmaceutical composition based on compounds thereof and combination with antiviral or anti-inflammatory agent.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

16 cl, 4 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention refers to the method of preparation of 3-halogen-4.5-dihydro-1H-pyrasol compound of the formula , it includes interreaction with HX1of other 4.5-dihydro-1H-pyrasol compound of the formula , in which X1 is halogen and R3, R4, Z, n and X2 have values given in the description. The invention also describes preparation of the compounds of the formula , in which X1, R3, R6, R7, R8a, R8b and n have values, which are indicated in the description, in terms of the formula (Ia) of the compound, prepared according to p.1 of the invention formula.

EFFECT: development of the alternative method of preparation of the compounds with using reagent of relatively low price.

9 cl, 1 tbl, 4 ex, 9 dwg

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