3,5-substituted piperidines as renin inhibitors

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described 3,4-substituted piperidines applicable in diagnostics and drug therapy of a warm-blooded animal, preferentially for therapy of a disease which depends on renin activity; application of a compound of such kind for preparing a pharmaceutical composition for therapy of the disease which depends on renin activity; application of the compound of such kind for therapy of the disease which depends on renin activity; the pharmaceutical compositions containing 3,4-substituted piperidine, and/or a therapeutic mode involving administration of 3,4-substituted piperidine, a method for producing 3,4-substituted piperidine. The preferential compound (which also can be presented in the form of salts) are described by formula I' wherein R1, R2, T, R3 and R4 are such as described by the patent claim.

EFFECT: production of the compounds for therapy of the disease which depends on renin activity.

28 cl, 1 tbl, 375 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula I'

in which
R1 denotes a1-C7alkyl, C3-C8cycloalkyl;
R2 denotes panels1-C7alkyl, pyridyl1-C7alkyl, indolyl1-C7alkyl, 1H-pyrrolo[2,3-b]pyridyl1-C7alkyl, fineliners1-C4alkyl, 1H-pyridine-2-IMT-C1-C7alkyl, thiophenols1-C7alkyl, chromanes1-C7alkyl, 2,3-dihydrobenzofuranyl-C1-C7alkyl, phenyl, 4H-benzo[1,4]oxazin-3-IMT, 3,4-dihydro-1H-quinoline-2-IMT, 1,2,3,4-tetrahydroquinoline, where each phenyl, pyridyl, indolyl, pyrrolo[2,3-b]pyridyl, chinoline, 1H-pyridine-2-IMT, thiophenyl, bromanil, 2,3-dihydrobenzofuranyl, 3,4-dihydro-1H-quinoline-2-IMT, 4H-benzo[1,4]oxazin-3-IMT or 1,2,3,4-tetrahydroquinoline specified for R2 above, is unsubstituted or contains as substituents one or more, preferably up to 3 fragments independently selected from the group comprising From1-C7alkyl, C1-C7alkoxy-C1-C7alkyl, Halogens1-C7alkyl, hydroxys1-C7alkyl, phenyl, phenyl which is mono-, di - or tizamidine and contains as substituents halogen, C1-C7/sub> alkoxygroup and/or C1-C7alkyl; halogen, cyano, C1-C7alkoxyl1-C7alkoxyalkyl,1-C7alkoxyl1-C7alkylamino1-C7alkyl, C1-C7alkanolamines,1-C7alkanoyl and C1-C7alkoxyl1-C7alkoxygroup;
R3 denotes hydrogen, C1-C7alkyl;
R4 is selected from the group comprising: a branched C4-C10alkyl which may be unsubstituted or may contain as substituents one or more, for example 1 or 2 fragment selected from the group comprising unsubstituted or substituted phenyl, hydroxy-group, C1-C7alkoxygroup, hydroxys1-C7alkoxygroup,3-C8cycloalkyl, CN, aminocarbonyl(C(O)NH2), heterocyclyl and N,N-di-(C1-C7alkyl)aminocarbonyl; having a linear chain With1-C7alkyl, which may be associated with limit or nekozawa carbon atom and which may be unsubstituted or may contain as substituents one or more, for example 1 or 2 fragment selected from the group comprising From1-C7alkoxygroup, unsubstituted or substituted heterocyclyl - morpholino group, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyridyl, unsubstituted the first or substituted phenyl, unsubstituted or substituted C3-C8cycloalkyl, the hydroxy-group and N,N-di-(C1-C7alkyl)amino group;
unsubstituted or substituted C3-C8cycloalkyl,
unsubstituted or substituted 2,3-dihydro-1H-inden,
unsubstituted or substituted phenyl,
unsubstituted or substituted heterocyclyl - pyridyl or
piperidinyl, or unsubstituted or substituted phenylmethanesulfonyl;
or R3 and R4 together form pyrolidine or piperidino ring, which is unsubstituted or contains as substituents up to 4 fragments selected from the group comprising From1-C7alkyl and hydroxy-group;
R6 denotes hydrogen or a hydroxy-group;
R7 and R8 independently of one another denote hydrogen or halogen; and
T denotes a methylene or carbonyl; or its salt.

2. The compound according to claim 1 having the structure described by formula I

in which
R1 denotes a1-C7alkyl, C3-C8cycloalkyl;
R2 denotes panels1-C7alkyl, pyridyl1-C7alkyl, indolyl1-C7alkyl, 1H-pyrrolo[2,3-b]pyridyl1-C7alkyl, fineliners1-C7alkyl, 1H-pyridine-2-IMT-C1-C7alkyl, thiophenols1-C7alkyl, chromanes1-C7alkyl, 2,3-dihydrobenzofuranyl-C1-C7 alkyl, phenyl, 4H-benzo[1,4]oxazin-3-IMT, 3,4-dihydro-1H-quinoline-2-IMT, 1,2,3,4-tetrahydroquinoline, where each phenyl, pyridyl, indolyl, pyrrolo[2,3-b]pyridyl, chinoline, 1H-pyridine-2-IMT, thiophenyl, bromanil, 2,3-dihydrobenzofuranyl, 3,4-dihydro-1H-quinoline-2-IMT, 4H-benzo[1,4]oxazin-3-IMT or 1,2,3,4-tetrahydroquinoline specified for R2 above, is unsubstituted or contains as substituents one or more, preferably up to 3 fragments independently selected from the group comprising From1-C7alkyl, C1-C7alkoxy-C1-C7alkyl, Halogens1-C7alkyl, hydroxys1-C7alkyl, phenyl, phenyl which is mono-, di - or tizamidine and contains as substituents halogen, C1-C7alkoxygroup and/or C1-C7alkyl; halogen, cyano, C1-C7alkoxyl1-C7alkoxyalkyl,1-C7alkoxyl1-C7alkylamino1-C7alkyl, C1-C7alkanolamines,1-C7alkanoyl and C1-C7alkoxyl1-C7alkoxygroup;
R3 denotes hydrogen, C1-C7alkyl;
R4 is selected from the group including:
branched C4-C10alkyl which may be unsubstituted or may contain as substituents one or more, e.g. what measures 1 or 2 fragment, selected from the group comprising unsubstituted or substituted phenyl, hydroxy-group, With1-C7alkoxygroup, hydroxys1-C7alkoxygroup,3-C8cycloalkyl, CN, aminocarbonyl(C(O)NH2), heterocyclyl and N,N-di-(C1-C7alkyl)aminocarbonyl; having a linear chain With1-C7alkyl, which may be associated with limit or nekonam carbon atom and which may be unsubstituted or may contain as substituents one or more, for example 1 or 2 fragment selected from the group comprising From1-C7alkoxygroup, unsubstituted or substituted heterocyclyl - morpholino group, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyridyl, unsubstituted or substituted phenyl, unsubstituted or substituted C3-C8cycloalkyl, the hydroxy-group and N,N-di(C1-C7alkyl)amino group;
unsubstituted or substituted C3-C8cycloalkyl,
unsubstituted or substituted 2,3-dihydro-1H-inden,
unsubstituted or substituted phenyl,
unsubstituted or substituted heterocyclyl - pyridyl or piperidinyl, or unsubstituted or substituted phenylmethanesulfonyl;
or R3 and R4 together form pyrolidine or piperidino ring, which is unsubstituted or contains as substituents up to 4 fragments, select the R group, include1-C7alkyl and hydroxy-group; and
T denotes a methylene or carbonyl;
or its salt.

3. The compound according to claim 1, in which
R1 denotes a1-C7alkyl, C3-C8cycloalkyl;
R2 denotes panels1-C7alkyl, pyridyl1-C7alkyl, indolyl1-C7alkyl, 1H-pyrrolo[2,3-b]pyridyl1-C7alkyl, fineliners1-C7alkyl, 1H-pyridine-2-IMT-C1-C7alkyl, thiophenols1-C7alkyl, chromanes1-C7alkyl, 2,3-dihydrobenzofuranyl-C1-C7alkyl, phenyl, 4H-benzo[1,4]oxazin-3-IMT, 3,4-dihydro-1H-quinoline-2-IMT, 1,2,3,4-tetrahydroquinoline, where each phenyl, pyridyl, indolyl, pyrrolo[2,3-b]pyridyl, chinoline, 1H-pyridine-2-IMT, thiophenyl, bromanil, 2,3-dihydrobenzofuranyl, 3,4-dihydro-1H-quinoline-2-IMT, 4H-benzo[1,4]oxazin-3-IMT or 1,2,3,4-tetrahydroquinoline specified for R2 above, is unsubstituted or contains as substituents one or more, preferably up to 3 fragments independently selected from the group comprising From1-C7alkyl, C1-C7alkoxy-C1-C7alkyl, Halogens1-C7alkyl, hydroxys1-C7alkyl, phenyl, phenyl which is mono-, di - or tizamidine and contains as substituents halogen, C1-C7alkoxy is the SCP and/or C 1-C7alkyl; halogen, cyano, C1-C7alkoxyl1-C7alkoxyalkyl,1-C7alkoxyl1-C7alkylamino1-C7alkyl, C1-C7alkanolamines,1-C7alkanoyl and C1-C7alkoxyl1-C7alkoxygroup;
R3 denotes hydrogen, C1-C7alkyl;
R4 is selected from the group including:
branched C4-C10alkyl which may be unsubstituted or may contain as substituents one or more, for example 1 or 2 fragment selected from the group comprising unsubstituted or substituted phenyl, hydroxy-group, With1-C7alkoxygroup, hydroxys1-C7alkoxygroup,3-C8cycloalkyl, CN, aminocarbonyl(C(O)NH2), heterocyclyl and N,N-di-(C1-C7alkyl)aminocarbonyl; having a linear chain With1-C7alkyl, which may be associated with limit or nekozawa carbon atom and which may be unsubstituted or may contain as substituents one or more, for example 1 or 2 fragment selected from the group comprising From1-C7alkoxygroup, unsubstituted or substituted heterocyclyl - morpholino group, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyridyl, unsubstituted or substituted Fe is Il, unsubstituted or substituted C3-C8cycloalkyl, the hydroxy-group and N,N-di-(C1-C7alkyl)amino; unsubstituted or substituted C3-C8cycloalkyl, unsubstituted or substituted 2,3-dihydro-1H-inden,
or R3 and R4 together form pyrolidine or piperidino ring, which is unsubstituted or contains as substituents up to 4 fragments selected from the group comprising From1-C7alkyl and hydroxy-group; and
T denotes a carbonyl (C(=O));
or its pharmaceutically acceptable salt.

4. The compound according to claim 1, in which fragments of the T-NR1R2 and NR3R4 are attached in the CIS-configuration relative to the Central piperidine, or its pharmaceutically acceptable salt.

5. The compound according to claim 1, in which fragments of the T-NR1R2 and NR3R4 are attached in the TRANS configuration relative to the Central piperidinium ring, or its pharmaceutically acceptable salt.

6. The compound according to claim 4, which has a configuration represented by the following formula IA or I'a:


or its pharmaceutically acceptable salt, in which R1, R2, T, R3 and R4 are as defined in any one of claims 1 to 4.

7. The compound according to claim 4, which has a configuration represented by the following formula IB or I B:


or its pharmaceutically acceptable salt, in which R1, R2, T, R3 and R4 are as defined in any one of claims 1 to 4.

8. The compound according to claim 5, which has a configuration represented by the following formula IC or I C:


or its pharmaceutically acceptable salt, in which R1, R2, T, R3 and R4 are as defined in any one of claims 1 to 4.

9. The compound of formula I according to claim 5, which has a configuration represented by the following formula ID or I D:


or its pharmaceutically acceptable salt, in which R1, R2, T, R3 and R4 are as defined in any one of claims 1 to 4.

10. The compound according to claim 1, in which R1 denotes a1-C7-alkyl, such as ethyl or isopropyl or3-C8-cycloalkyl, such as cyclopropyl;
R2 denotes a phenyl-C1-C7-alkyl, pyridyl-C1-C7-alkyl, indolyl-C1-C7-alkyl, 1H-pyrrolo[2,3-b]pyridyl-C1-C7-alkyl, chinoline-C1-C7-alkyl, 1H-pyridine-2-IMT-C1-C7-alkyl, thiophenyl-C1-C7-alkyl, chromanol-C1-C7-alkyl, 2,3-dihydrobenzofuranyl-C1-C7-alkyl, phenyl, 4H-benzo[1,4]oxazin-3-IMT, 3,4-dihydro-1H-quinoline-2-IMT, where each phenyl, pyridyl, indolyl, pyrrolo[2,3-b]pyridyl, chinoline 1H-pyridine-2-IMT, thiophenyl, bromanil, 2,3-dihydrobenzofuranyl, 3,4-dihydro-1H-quinoline-2-IMT or 4H-benzo[1,4]oxazin-3-IMT specified for R2 above as substituent or part of a substituent is unsubstituted or contains as substituents one or more, preferably up to 3 fragments independently selected from the group comprising From1-C7-alkyl, C1-C7-alkoxy-C1-C7-alkyl, halogen-(C1-C7-alkyl, hydroxy-C1-C7-alkyl, phenyl, phenyl which is mono-, di - or tizamidine and contains as substituents halogen, C1-C7-alkoxygroup, and/or C1-C7-alkyl; halogen, cyano, C1-C7-alkoxy-C1-C7-alkoxy-C1-C7-alkyl, C1-C7-alkoxy-C1-C7-alkylamino-C1-C7-alkyl, C1-C7-alkanolamines,1-C7-alkanoyl and C1-C7-alkoxy-C1-C7-alkoxygroup;
R3 denotes hydrogen, C1-C7-alkyl, such as methyl;
R4 is selected from the group including:
branched C4-C10-alkyl, which may be unsubstituted or may contain as substituents one or more, for example 1 or 2 fragment selected from the group including:
unsubstituted or substituted, preferably nez is displaced heterocyclyl, preferably pyrrolyl, furanyl, thienyl, thiazolyl, pyrazolyl, triazolyl, tetrazolyl, tetrahydropyranyl, pyridyl or pyrimidinyl, unsubstituted or substituted, preferably unsubstituted phenyl, a hydroxy-group, With1-C7alkoxygroup, hydroxys1-C7alkoxygroup, CN, aminocarbonyl(C(O)]NH2), unsubstituted or substituted, preferably unsubstituted heterocyclyl, and N,N-di(C1-C7alkyl)aminocarbonyl;
having a linear chain With1-C7-alkyl, which may be associated with limit or nekozawa carbon atom and which may be unsubstituted or may contain as substituents one or more, for example 1 or 2 fragment selected from the group including:
unsubstituted or substituted, preferably unsubstituted heterocyclyl, preferably morpholinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyridyl; unsubstituted or substituted, preferably unsubstituted phenyl; unsubstituted or substituted, preferably unsubstituted With3-C8-cycloalkyl, such as cycloheptyl, cyclohexyl or cyclopentyl; a hydroxy-group and N,N-di(C1-C7-alkyl)-amino group;
unsubstituted or substituted C3-C8-cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cyclopropyl,
illegal is ewenny or substituted aryl, such as phenyl and indanyl,
unsubstituted or substituted heterocyclyl, such as pyridyl or piperidinyl, or
unsubstituted or substituted phenylmethanesulfonyl;
or R3 and R4 together form pyrolidine or piperidino ring, which is unsubstituted or as substituents contains up to 4 fragments selected from the group comprising From1-C7-alkyl and hydroxy-group; and
T denotes a carbonyl or methylene;
or its pharmaceutically acceptable salt.

11. The compound according to claim 1, in which R7 and R8 independently of one another denote F.

12. The connection of claim 1, wherein one of R7 and R8 represents hydrogen and the other denotes F.

13. The compound of formula I according to claim 1, selected from among compounds of the formula

presented in the following table:

ExamplesR1R2R3R4
1H
2 H
3N
4N
5N

ExamplesR1R2R3R4
6H
7H
8Me
9Me
10H
11N

ExamplesR1R2R3R4
12 N
13N
14N
15N
16N
17N

ExamplesR1R2R3R4
18H
19H
20H
21H
22H
23 H

ExamplesR1R2R3R4
24H
25N
26H
27N
28 H

ExamplesR1R2R3R4
29H
30N
31N
32N
33 N
34H

ExamplesR1R2R3R4
35N
36N
37N
38N

39H
40N

ExamplesR1R2R3R4
41H
42H
43H
44H

45N
46N

ExamplesR1R2R3R4
47 N
48N
49N

50N
51N
52N

ExamplesR1R2R3R4
53H
54H
55H

56N
57N
58N

ExamplesR1R2R3R4
59H
60H
61H

62 N
63N
64N

ExamplesR1R2R3R4
65H
66H

67 N
68N
69N
70N

ExamplesR1R2R3R4
71N
72 N
73N
74N
75N
76N

ExamplesR1R2R3R4
77 H
78N
79N
80N
81N
82N

ExamplesR1R2R3R4
83N
84H
85H
86H
87H
H

td align="center"> 93
ExamplesR1R2R3R4
89H
90H
91H
92H
H

ExamplesR1R2R3R4
94H
95N
96N
97N
98N

ExamplesR1R2R3R4
99N
100N
101N
102N
103N

ExamplesR1R2R3R4
104N
105N
106N
107N
108N

ExamplesR1R2R3R4
109N
110N
111N
112
113N

ExamplesR1R2R3R4
114N
115H
116H
117 H
118H

ExamplesR1R2R3R4
119H
120N
121N
122N
123N

ExamplesR1R2R3R4
124H
125N
126 N
127N
128N

ExamplesR1R2R3R4
129N
130H
131H
132H
133H

ExamplesR1R2R3R4
134H
135N
136/td> N
137N
138N

ExamplesR1R2R3R4
139N
140H
141 H
142H
143H

ExamplesR1R2R3R4
144H
145N
146img src="https://img.russianpatents.com/1075/10756028-s.jpg" height="22" width="15" /> N
147N
148N

ExamplesR1R2R3R4
149N
150N
151N
152N
153N

ExamplesR1R2R3R4
154N
155H
156H
157H
158H

ExamplesR1R2R3R4
159H
160H
161N
162H
163N

td align="center"> H
ExamplesR1R2R3R4
164H
165
166H
167H
168H

ExamplesR1R2R3R4
169H
170 H
171H
172H
173H

ExamplesR1R2R3R4
174H
175 H
176H
177H

ExamplesR1R2R3R4
178H
179H
180 N
181N

ExamplesR1R2R3R4
182N
183N
184N
185 H

ExamplesR1R2R3R4
186N
187N
188N
189N

Note the ry R1R2R3R4
190N
191N
192N
193N

ExamplesR1R2R3R4
194N
195H
196N
197H

ExamplesR1R2R3R4
198H
19 H
200H
201H

ExamplesR1R2R3R4
202H
203H
204H
205H

ExamplesR1R2R3R4
206N
207N
208the
209N

td align="center"> H
ExamplesR1R2R3R4
210H
211H
212H
213

ExamplesR1R2R3R4
214H
215N
216N
217N

ExamplesR1 R2R3R4
218N
219N
220N
221N

ExamplesR1R2R3R4
222 N
223N
224N
225N

ExamplesR1R2R3R4
226H
227H
228H
229H

ExamplesR1R2R3R4
230H
231H
232img src="https://img.russianpatents.com/1075/10756653-s.jpg" height="47" width="43" /> H
233H

ExamplesR1R2R3R4
234N
235N
236N
237 N

ExamplesR1R2R3R4
238H
239H
240H
241H

Examples R2R3R4
242N
243N
244N
245N

ExamplesR1R2R3R4
246N
247N
248N
249N

ExamplesR1R2R3R4
250N
251 N
252H
253N

ExamplesR1R2R3R4
254H
255H
256H
257H

ExamplesR1R2R3R4
258H
259H
260Nimg src="https://img.russianpatents.com/1075/10756806-s.jpg" height="25" width="29" />
261N

ExamplesR1R2R3R4
262N
263N
264N
265N

ExamplesR1R2R3R4
266N
267N
268H
269H

ExamplesR1R2 R3R4
270H
271H
272H
273H

ExamplesR1R2R3R4
274
275H
276H
277H

H
ExamplesR1R2R3R4
278H
279
280H
281H

ExamplesR1R2R3R4
282H
283H
284 H
285H

ExamplesR1R2R3R4
286H
287N
288N
289 N

ExamplesR1R2R3R4
290H
291H
292H
293H

Examples R2R3R4
294H
295H
296H
297H

ExamplesR1R2R3R4
298 H
299N
300N
301N

ExamplesR1R2R3R4
302N
303N
304H
305H

ExamplesR1R2R3R4
306H
307H
308/td> H
309H

313
ExamplesR1R2R3R4
310N
311N
312N
H

ExamplesR1R2R3R4
314H
315H
316H
317 H

ExamplesR1R2R3R4
318H
319H
320H
321H

ExamplesR1 R2R3R4
322H
323H
324H
325H

ExamplesR1R2R3R4
326 H
327H
328H
329H

ExamplesR1R2R3R4
330H
331 H
332H
333H

ExamplesR1R2R3R4
334H
335H
336 H
337H

ExamplesR1R2R3R4
338H
339N
340N
341 N

ExamplesR1R2R3R4
342H
343H
369H
370H

ExamplesR1R2R3R4
371H
372H


ExamplesR1R2R3,4
344
345

ExamplesR1R3,4
346
347


ExampleR1R2R3R4
348H
349H

ExampleR1R2R3 R4
350H


ExampleR1R2R3R4
351H


ExamplesR1R2R3
352N

ExamplesR1R2R3
353 H
354H
355N
356N
357N


ExampleR1R2R3R4
358N
359H


ExampleR1R2R3R4
360N


ExampleR1R2R3R4
361N


ExampleR1R2 R3R4
362N
363N
364N
365N

ExampleR1R2R3R4
366 H
367H
368H

or its pharmaceutically acceptable salt, respectively.

14. The compound according to claim 1, selected from among compounds of the formula

presented in the following table:

Table
ExamplesR1R2R3R4Data analysis
1NMS: [M+1]+=469 HPLC:AtRet=2,75
2NMS: [M+1]+=483 HPLC:AtRet=2,88

or its pharmaceutically acceptable salt, respectively.

15. The compound according to claim 1, selected from among compounds of the formula

presented in the following table:

ExamplesR1R2R3R4Data analysis
1NMS: [M+1]+=469 HPLC:AtRet=2,15
2HMS: [M+1]+=483 HPLC:AtRet=2,88

or agopermalink acceptable salt, respectively.

16. The compound or its pharmaceutically acceptable salt according to claim 1 intended for use for the diagnosis or medical treatment of a warm-blooded animal.

17. The compound or its pharmaceutically acceptable salt according to claim 1, intended for treatment of a disease that depends on activity of renin, preferably hypertension.

18. The use of compound or its pharmaceutically acceptable salt according to any one of claims 1 to 17 for the manufacture of pharmaceutical compositions intended for the treatment of a disease that depends on activity of renin, preferably hypertension.

19. The use of compound or its pharmaceutically acceptable salt according to any one of claims 1 to 17 for the treatment of a disease that depends on activity of renin, preferably hypertension.

20. Pharmaceutical composition having inhibitory activity against renin, for the treatment of hypertension, comprising the compound or its pharmaceutically acceptable salt according to any one of claims 1 to 17 and at least one pharmaceutically acceptable carrier.

21. A method of treating hypertension, comprising the introduction of a warm-blooded animal, preferably a human, in need of such treatment, a compound or its pharmaceutically acceptable salt according to any one of claims 1 to 17.

22. The method of obtaining the compound or its pharmaceutically acceptable the th salt according to any one of claims 1 to 17, including
a) introducing into the reaction of compounds of formula II

in which T represents a methylene or preferably carbonyl, PG denotes a protective group, and R3 and R4 are as defined for compounds of formula I in any one of claims 1 to 17, or (preferably) an activated derivative with the compound of the formula III

in which R1 and R2 are as defined for compounds of formula I in any one of claims 1 to 12; or
b) introducing into the reaction of compounds of formula IV

in which PG denotes a protective group, and R1 and R2 are as defined for compounds of formula I in any one of claims 1 to 17, or (preferably) an activated derivative with the compound of the formula V

in which R1 and R2 are as defined for compounds of formula IV; and, if necessary, after any one or more of the operations mentioned above, the conversion of the compounds of formula I or a protected form into another compound of formula I, transforming a salt of the obtained compound of formula I into the free compound or into a different salt, transforming the obtained free compounds of formula I in its salt, and/or separation of the mixture of isomers of compounds of formula I into individual isomers;
where in any of the outcome is s substances in addition to these specific protective groups may contain additional protective group, and any protective groups or linked resin is removed at an appropriate stage to obtain the corresponding compound of formula I or its salts.

23. The method of obtaining the compounds of formula VIIa or VIIb

in which PG denotes a protective group, R5 denotes unsubstituted or substituted alkyl or alkenyl, preferably1-C4alkyl, or its pharmaceutical salt,
including the introduction of the compounds of formula VI

in which PG is as defined in formula VIIa or VIIb, in the reaction with alcohol R5OH in the presence of a chiral amine catalyst.

24. The method according to item 23 receipt of the compounds of formula I or its pharmaceutically acceptable salt according to any one of claims 1 to 17.

25. The method of obtaining the compounds of formula I or its pharmaceutically acceptable salt according to any one of claims 1 to 17, comprising the introduction into the reaction of the compounds of formula (VIIa)

in which PG denotes a protective group, and R5 denotes unsubstituted or substituted alkyl or alkenyl, preferably C1-Salkil, or (preferably) an activated derivative with the compound of the formula III

in which R1 and R2 are as defined for compounds of formula I in any one of claims 1 to 17; obtaining the desired amide forms of the crystals VIII

in which the ester fragment is subjected to hydrolysis and obtain the connection formula IX

and this connection or (preferably) an activated derivative, in turn, if necessary, enter into reaction with the compound of the formula V

in which R3 and R4 are as defined for compounds of formula I in any one of claims 1 to 17; obtaining the compounds of formula X

and, if necessary, after any one or more of the operations mentioned above, the conversion of the compounds of formula I or a protected form into another compound of formula I, transforming a salt of the obtained compound of formula I into the free compound or into a different salt, transforming the obtained free compounds of formula I in its salt, and/or separation of the mixture of isomers of compounds of formula I into individual isomers;
where in any of the original substance in addition to these specific protective groups may contain additional protective group, and any protective groups or linked resin is removed at an appropriate stage to obtain the corresponding compound of formula I or its salts.

26. The method of obtaining the compounds of formula I or its pharmaceutically acceptable salt according to any one of p is.1-17, includes introduction to the reaction of the compound of formula (VIIa)

in which PG denotes a protective group, and R5 denotes unsubstituted or substituted alkyl or alkenyl, preferably C1-C4alkyl,
or (preferably) an activated derivative with the compound of the formula V

in which R3 and R4 are as defined for compounds of formula I in any one of claims 1 to 17;
to obtain the desired amide of formula XI

in which the ester fragment is subjected to hydrolysis and obtain the connection formula XI

and this connection or (preferably) an activated derivative, in turn, if necessary, enter into reaction with the compound of the formula III

in which R1 and R2 are as defined for compounds of formula I in any one of claims 1 to 17; obtaining the compounds of formula XIII

and, if necessary, after any one or more of the operations mentioned above, the conversion of the compounds of formula I or a protected form into another compound of formula I, transforming a salt of the obtained compound of formula I into the free compound or into a different salt, transforming the obtained free compounds of formula I in e what about the salt, and/or separation of the mixture of isomers of compounds of formula I into individual isomers;
where in any of the original substance in addition to these specific protective groups may contain additional protective group, and any protective groups or linked resin is removed at an appropriate stage to obtain the corresponding compound of formula I or its salts.

27. The method of obtaining the compounds of formula I or its pharmaceutically acceptable salt according to any one of claims 1 to 17, comprising introducing into the reaction of compounds of formula VIIb

in which PG denotes a protective group, and R5 denotes unsubstituted or substituted alkyl or alkenyl, preferably Ci-Salkil, or (preferably) an activated derivative in the reaction with the compound of the formula III

in which R1 and R2 are as defined for compounds of formula I in any one of claims 1 to 17; obtaining the desired amide of formula XIV

in which the ester fragment is subjected to hydrolysis and obtain the connection formula XV

and this connection or (preferably) an activated derivative, in turn, if necessary, enter into reaction with the compound of the formula V

in which R3 and R4 are such as is designated for the compounds of formula I in any one of claims 1 to 17; obtaining the compounds of formula XIII

and, if necessary, after any one or more of the operations mentioned above, the conversion of the compounds of formula Gili its protected form into another compound of formula I, transforming a salt of the obtained compound of formula I into the free compound or into a different salt, transforming the obtained free compounds of formula I in its salt, and/or separation of the mixture of isomers of compounds of formula I into individual isomers;
where in any of the original substance in addition to these specific protective groups may contain additional protective group, and any protective groups or linked resin is removed at an appropriate stage to obtain the corresponding compound of formula I or its salts.

28. The method of obtaining the compounds of formula I or its pharmaceutically acceptable salt according to any one of claims 1 to 17, comprising introducing into the reaction of compounds of formula VIIb

in which PG denotes a protective group, and R5 denotes unsubstituted or halogen-substituted alkyl or alkenyl, preferably C1-C4alkyl, or (preferably) an activated derivative with the compound of the formula V

in which R3 and R4 are as defined for compounds f is rmula I in any one of claims 1 to 17;
to obtain the desired amide of formula XVI

in which the ester fragment is subjected to hydrolysis and obtain the connection formula XVII

and this connection or (preferably) an activated derivative, in turn, if necessary, enter into reaction with the compound of the formula III

in which R1 and R2 are as defined for compounds of formula I in any one of claims 1 to 17; obtaining the compounds of formula X

and, if necessary, after any one or more of the operations mentioned above, the conversion of the compounds of formula I or a protected form into another compound of formula I, transforming a salt of the obtained compound of formula I into the free compound or into a different salt, transforming the obtained free compounds of formula I in its salt, and/or separation of the mixture of isomers of compounds of formula I into individual isomers;
where in any of the original substance in addition to these specific protective groups may contain additional protective group, and any protective groups or linked resin is removed at an appropriate stage to obtain the corresponding compound of formula I or its salts.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: present invention relates to novel pyrazole derivatives of formula (I) or pharmaceutically acceptable salts thereof, having tyrosine kinase Trk inhibiting properties and used for treating or preventing malignant growths accompanied by high level of Trk, to a method of producing said derivatives, use thereof to prepare a medicinal agent, pharmaceutical compositions based on said derivatives, a method of inhibiting Trk activity and a method of obtaining antiproliferative action. where A denotes a single bond or C1-2alkylene; where the said C1-2alkylene can be optionally substituted with one R22; ring C is a phenyl or a 5-6-member heterocyclic ring with 1-2 heteroatoms selected from N or S. Values of R1-R7, R22 and n are given in the formula of invention.

EFFECT: obtaining pharmaceutically acceptable salts having tyrosine kinase Trk inhibiting properties and used for treating or preventing malignant growths.

20 cl, 5 dwg, 193 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to the following compounds: N-(1-{4-[2-(1-acetylamino-ethyl)-1-ethyl-1H-imidazol-4-yl]-benzyl}-3-hydroxy-propyl)-3-chloro-4-(2,2,2,-trofluoro-1-methyl-ethoxy)-benzamide, N-(1-{4-[2-(1-methyl-1-hydroxy-ethyl)-1-ethyl-1H-imidazole-4-yl}-benzyl}-3-hydroxy-propyl)-3-chloro-4-(,2,2,2-trifluoro-1-methyl-ethoxy)-benzamide, N-(1-{4-[2-(1-hydroxy-1-methyl-ethyl)-1-methyl-1H-imidazole-4-yl]-benzyl}-3-hydroxy-propyl)-3-chloro-4-(2,2,2,-trifluoro-1-methyl-ethoxy)-benzamide, 3-chloro-N-[2-[(N,N-dimethylglicyl)amino]-1-({4-[8-(1-hydroxyethyl)imidazo[1,2-a]pyridine-2-yl]phenyl}methyl)ethyl]-4-[(1-methylethyl)oxy]benzamide, 3-chloro-N-(1-(2-(dimethylamino)acetamido)-3-(4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl)propan-2-yl)-4-isopropoxybenzamide, 3-chloro-N-(2-[(2-methylalanyl)amino]-1-{[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}ethyl)-4-[(1-methylethyl)oxy]benzamide, 3-chloro-N-[(3-hydroxy)-1-({4-[8-(1-hydroxyethyl)imidazo[1,2-a]pyridine-2-yl]phenyl}methyl)propyl]-4-[(1-methylethyl)oxy]benzamide, as well as to their pharmaceutically acceptable salts.

EFFECT: obtained compounds and salts can be used for treatment cell proliferative diseases and disorders by modulating activity of mitotic kinesin CENP-E.

26 cl, 102 ex, 7 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel acetylenyl-pyrazole-pyrimidine derivatives of general formula (I), having mGluR2 (metabotropic glutamate receptor) antogonist properties). In compounds of general formula (I): either E and J denote N, G denotes C and L denotes N, M denotes CH, or M denotes N, L denotes CH; or L and G denote N, E denotes C, and J and M denote CH; or J, G and L denote N, E denotes C, and M denotes CH; or E and L denote N, J and M denote CH, and G denotes C; R1 denotes H, halogen, CF3, CHF2 or C1-6alkyl; R2 denotes H, halogen, C1-6-alkyl, C1-6-alkoxy, CF3 or CHF2, wherein R1=R2≠H; R3 denotes H; -C(CH3)2OH; linear C1-4-alkyl or C3-4-cycloalkyl, which are possibly substituted with one or more substitutes selected from a group comprising 1-3 F and 1-2 OH; A is selected from a group comprising phenyl or a 5- or 6-member heteroaryl having in the ring 1-2 heteroatoms selected from nitrogen, sulphur or nitrogen and sulphur in the 5-member ring, and 1-2 nitrogen atoms i the 6-member ring, and possibly substituted with 1-3 Ra; Ra denotes halogen; hydroxy; cyano; CF3; NReRf; C1-C6-alkyl, possibly substituted amino or hydroxy; ; C1-6-alkoxy; C3-4-cycloalkyl; CO-NRbRc, SO2-NRbRc; or SO2-Rd-; Rb and RC can be identical or different and are selected from a group comprising H; normal or branched C1-6-alkyl, possibly substituted with one or more substitutes selected from a group comprising F, cyano, hydroxy, C1-6-alkoxy, -NH-C(O)-O-C1-6-alkyl, amino, (C1-6-alkyl)amino, di(C1-6-alkyl)amino, heterocycloalkyl having 6 ring atoms, from which 1-2 heteroatoms are selected from nitrogen or nitrogen and oxygen, or a 6-member heteroaryl with one nitrogen heteroatom in the ring; or a 6-membeer heteroaryl with one nitrogen heteroatom in the ring; or Rb and Rc, together with the nitrogen atom with which they are bonded, can form a heterocyclic ring having 6 members in the ring, from which 1-2 atoms are selected from nitrogen and/or oxygen, and which can be substituted with C1-6-alkyl; Rd denotes OH or C1-6-alkyl; Re and Rf denote H, C1-6-alkyl, possibly substituted hydroxy, -C(O)- C1-6-alkyl; S(O)2-C1-6-alkyl.

EFFECT: compounds can be used in preparing medicinal agents for treating central nervous system (CNS) disorders, such as Huntington's chorea, amyotrophic lateral sclerosis, dementia caused by AIDS, parkinsonism etc.

55 cl, 6 dwg, 321 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel derivatives of 1H-imidazo [4,5-c]quinolines of formula II or pharmaceutically acceptable salts thereof, where R3 is selected from a group comprising -Z-Y-R4, -Z-Y-X-Y-R4, -Z-R5, -Z-Het, -Z-Het'-R4, and -Z-Het'-Y-R4; Z is selected from a group which includes C1-C6alkylene; n equals 0; R1 is selected from a group comprising R4, -X-R4 and -X-Y-R4; R2 is selected from a group comprising C1-C6alkyl, C1-C6alkoxy, hydroxyC1-C6alkyl and C1-C6alkoxy-C1-C6alkyl; X is selected from a group comprising C1-C6alkylene, C6arylene, heteroarylene which is thienyl, and heterocyclylene which is piperzinyl, where the alkylene group can be optionally broken by -O- group; Y is selected from a group comprising -S(O)0-2-, -C(R6)-, -C(R6)-O-, -O-C(R6)-, -N(R8)-Q-, -C(R6)-N(R8)-, and R4 is selected from a group comprising hydrogen, C1-C6alkyl, C2alkenyl, C1-C10aryl, C6aryl-C1alkylenyl, and heteroaryl selected from pyridyl, thienyl, benzodioxanyl and others (see claim 1), where C1-C6alkyl, C2alkenyl and C6-C10aryl can be unsubstituted or substituted with one or two substitutes which are independently selected from a group comprising C1-C6alkyl, C1-C4alkoxy, CF3-O-; halogen, nitro, hydroxy, mercapto, cyano, C6-10aryl, C6aryloxy, C6aryl-C1alkyleneoxy, thienyl, morpholinyl, amino, C1alkylamino, di-C1alkylamino, heterocyclyl group and an oxo-group; R5 is selected from a group comprising and R6 is selected from a group comprising =O and =S; R7 is C2-3akylene; R8 is selected from a group comprising hydrogen and C1-C3alkyl; R10 is C4alkylene; A is selected from a group comprising -O-, -C(O)-, -S(O)0-2-, and -N(R4)-; Het is heterocyclyl selected from morpholinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl and others (see claim 1), which can be unsubstituted or substituted with one or more substitutes which are independently selected from a group comprising C1-C2alkyl, hydroxy, hydroxy-C1-C2alkyl, amino, C1-C2alkylamino, di-C1-C2alkylamino, heterocyclyl group and oxo; Het' is heterocyclylene selected from imidazolinyl and piperidinyl; Q is selected from a group comprising a covalent bond, -C(R6)-, -C(R6)-C(R6)-, -S(O)2-, -C(R6)-N(R8)-W-, -S(O)2-N(R8)- and -C(R6)-O-; V is selected from a group comprising -C(R6)-, -O-C(R6)-, -N(R8)-C(R6)-, and -S(O)2-; W is selected from a group comprising a covalent bond, , -C(O)-, and -S(O)2-; a and b are independently integers from 1 to 6, provided that a+b≤7; provided that Z can also denote a covalent bond when R3 is -Z-Het, -Z-Het'-R4, or -Z-Het'-Y-R4, or R3 is -Z-Y-R4 or -Z-Y-X-Y-R4, and Y is selected from a group comprising -S(O)0-2-, -C(R6)-, -C(R6)-O-, -C(R6)-N(R8)- and The invention also relates to a pharmaceutical composition based on the formula II compound, a method of inducing biosynthesis of cytokines, a method of treating a viral disease and an oncological disease using the compound of formula II.

EFFECT: novel derivatives of 1H-imidazo [4,5-c]quinoline, which are useful in treating viral and oncological diseases, are obtained.

37 cl, 130 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) in form of (R) or (S) isomers, separately or in a mixture, as well as their physiologically acceptable salts and hydrates, having vitronectin receptor antagonist properties. In formula (I)

G denotes Het-NH-CO-, Het-NH-CH2-, Het-; Het denotes a mono- or bicyclic system, where each ring is a 5- or 6-member aromatic or non-aromatic ring, where at least one of the rings contains 1-2 nitrogen atoms as heteroatoms, where Het is unsubstituted or substituted with R9 groups; R1 denotes H, (C6-C14)-aryl, (C6-C14)aryl(C1-C4)alkyl; amino, unsubstituted, mono-or disubstituted with alkyl and/or acyl, containing 1-4 C atoms; R2 denotes H, halogen, nitro-group; alkyl containing 1-4 C atoms; amino, unsubstituted, mono- or disubstituted with alkyl and/or acyl containing 1-4 C atoms; a -(CH2)0-2-OR5 group; R3 denotes H, -CO2R5, -SO2R5 or mono- or bicyclic system, where each ring denotes a 5- or 6-member aromatic or non-aromatic ring, where at least one of the rings contains 1-4 heteroatoms selected from N, O or S, unsubstituted or substituted with R9 radicals; R4 denotes OH, (C1-C8)alkoxy-; amino, unsubstituted, mono- or disubstituted with (C1-C4)alkyl; or an aminoacid residue; R5 denotes (C1-C8)alkyl; (C6-C14)aryl; (C6-C14)aryl(C1-C4)alkyl; (C3-C12)cycloalkyl or (C3-C12)cycloalkyl(C1-C4)alkyl; bi- and tricycloalkyl(C1-C4)alkyl. Aryls, alkyls, cycloalkyls are not substituted or substituted with R9 groups; R9 denotes halogen, amino, nitro, hydroxyl, (C1-C4)alkyloxy-, carboxy, (C1-C4)alkyloxycarbonyl-, (C1-C8)alkyl, unsubstituted or substituted with halogen atoms; phenyl. The invention also relates to a methods for synthesis of formula (I) compounds, a medicinal agent and a pharmaceutical composition containing said compounds, as well as use thereof in preparing the medicinal agent.

EFFECT: improved properties of the compound.

21 cl, 41 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula [I-D1] or pharmaceutically acceptable salt thereof,

,

where each symbol is defined in the claim. The invention also relates to pharmaceutical compositions containing said compound and having HCV polymerase inhibiting activity.

EFFECT: disclosed compound exhibits anti-HCV activity, based on HCV polymerase inhibiting activity and is useful as an agent for preventing and treating hepatitis C.

32 cl, 497 tbl, 1129 ex

Organic compounds // 2411239

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I, in which R1 denotes alkyl or cycloalkyl; R2 denotes phenyl-C1-C7-alkyl, di-(phenyl)- C1-C7-alkyl, naphthyl- C1-C7-alkyl, phenyl, naphthyl, pyridyl-C1-C7-alkyl, indolyl- C1-C7-alkyl, 1H-indazolyl- C1-C7-alkyl, quinolyl C1-C7-alkyl, isoquinolyl- C1-C7-alkyl, 1,2,3,4-tetrahydro-1,4-benzoxazinyl- C1-C7-alkyl, 2H-1,4-benzoxazin-3(4H)-onyl-C1-C7-alkyl, 9-xanthenyl-C1-C7-alkyl, 1-benzothiophenyl-C1-C7-alkyl, pyridyl, indolyl, 1H-indazolyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydro-1,4-benzoxazonyl, 2H-1,4-benzoxazin-3(4H)-onyl, 9-xanthenyl, 1-benzothiophenyl, 4H-benzo[1,4]thiazin-3-only, 3,4-dihydro-1H-quinolin-2-onyl or 3H-benzoxazol-2-onyl, where each phenyl, naphthyl, pyridyl, indolyl, 1H-indazolyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydro-1,4-benzoxazonyl, 2H-1,4-benzoxazin-3(4H)-onyl, 1-benzothiophenyl, 4H-benzo[1,4]thiazin-3-only, 3,4-dihydro-1H-quinolin-2-onyl or 3H-benzoxazol-2-onyl are unsubstituted or contain one or up to 3 substitutes independently selected from a group comprising C1-C7-alkyl, hydroxy-C1-C7-alkyl, C1-C7-alkoxy- C1-C7-alkyl, C1-C7-alkoxy- C1-C7-alkoxy-C1-C7-alkoxy- C1-C7-alkyl, C1-C7-alkanoyloxy- C1-C7-alkyl, amino- C1-C7-alkyl, C1-C7-alkoxy- C1-C7-alkylamino- C1-C7-alkyl, C1-C7-alkanoylamino- C1-C7-alkyl, C1-C7-alkylsulphonylamino- C1-C7-alkyl, carboxy- C1-C7-alkyl, C1-C7-alkoxycarbonyl- C1-C7-alkyl, halogen, hydroxy group, C1-C7-alkoxy group, C1-C7-alkoxy- C1-C7-alkoxy group, amino- C1-C7-alkoxy group, N-C1-C7-alkanoylamino-C1-C7-alkoxy group, carbamoyl- C1-C7-alkoxy group, N-C1-C7-alkylcarbamoyl-C1-C7-alkoxy group, C1-C7-alkanoyl, C1-C7-alkoxy-C1-C7-alkanoyl, C1-C7-alkoxy- C1-C7-alkanoyl, carboxyl, carbamoyl and N-C1-C7-alkoxy-C1-C7-alkylcarbamoyl; W denotes a fragment selected from residues of formulae IA, IB and IC, where () indicates the position in which the fragment W is bonded to the carbon atom in position 4 of the piperidine ring in formula I, and where X1, X2, X3, X4 and X5 are independently selected from a group containing carbon and oxygen, where X4 in formula IB and X1 in formula IC can assume one of these values or can be additionally selected from a group comprising S and O, where carbon and nitrogen ring atoms can include a number of hydrogen atoms or substitutes R3 or R4 if contained, taking into account limitations given below, required to bring the number of bonds of the carbon ring atom to 4 and 3 for the nitrogen ring atom; provided that in formula IA at least 2, preferably at least 3 of the atoms X1-X5 denote carbon and in formulae IB and IC at least one of X1-X4 denotes carbon, preferably 2 of the atoms X1-X4 denote carbon; y equals 0 or 1; z equals 0 or 1; R3, which can be bonded with any of the atoms X1, X2, X3 and X4, denotes hydrogen or a C1-C7-alkyloxy-C1-C7-alkyloxy group, phenyloxy-C1-C7-alkyl, phenyl, pyridinyl, phenyl- C1-C7-alkoxy group, phenyloxy group, phenyloxy-C1-C7-alkoxy group, pyridyl-C1-C7-alkoxy group, tetrahydropyranyloxy group, 2H,3H-1,4-benzodioxynyl-C1-C7-alkoxy group, phenylaminocarbonyl or phenylcarbonylamino group, where each phenyl or pyridyl is unsubstituted or contains one or up to 3 substitutes, preferably 1 or 2 substitutes independently selected from a group comprising C1-C7-alkyl, hydroxy group, C1-C7-alkoxy group, phenyl-C1-C7-alkoxy group, where phenyl is unsubstituted or substituted with a C1-C7-alkoxy group and/or halogen; carboxy- C1-C7-alkyloxy group, N-mono- or N,N-di-(C1-C7-alkyl)aminocarbonyl-C1-C7-alkyloxy group, halogen, amino group, N-mono- or N,N-di-(C1-C7-alkyl)amino group, C1-C7-alkanoylamino group, morpholino-C1-C7-alkoxy group, thiomorpholino-C1-C7-alkoxy group, pyridyl-C1-C7-alkoxy group, pyrazolyl, 4- C1-C7-alkylpiperidin-1-yl, tetrazolyl, carboxyl, N-mono- or N,N-di-(C1-C7-alkylamino)carbonyl or cyano group; or denotes 2-oxo-3-phenyltetrahydropyrazolidin-1-yl, oxetidin-3-yl-C1-C7-alkyloxy group, 3-C1-C7-alkyloxetidin-3-yl- C1-C7-alkyloxy group or 2-oxotetrahydrofuran-4-yl- C1-C7-alkyloxy group; provided that if R3 denotes hydrogen, then y and z are equal to 0; R4, if contained, denotes a hydroxy group, halogen or C1-C7-alkoxy group; T denotes carbonyl; and R11 denotes hydrogen, or pharmaceutically acceptable salts thereof. The invention also relates to use of formula I compounds, a pharmaceutical composition, as well as a method of treating diseases.

EFFECT: obtaining novel biologically active compounds having activity towards rennin.

11 cl, 338 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of pyrrolo[3,2-c]pyridine-4-one 2-indolinone of formula (I). Compound of formula (I): , where: represents single or binary bond; X and Y independently on each other are selected from C or N; X and Y represent N, then R5 and R7 are absent; R1 and R2 represent H; R3 is selected from alkyl, trifluormethyl, aryl and aralkyl, where said alkyl, aryl or aralkyl iis substituted by one or more halogens or hydroxyls; R4 is selected from alkyl, cycloalkyl, heterocycloalkyl, -[CH2CH(OH)]rCH2NR9R10 and -(CH2)nNR9R10, where said alkyl or heterocycloalkyl is probably substituted by one or more groups, selected from group, consisting of hydroxyl, amino, aminoalkyl, hydroxyalkyl and -NR9R10; X and Y represent C, then R5, R6, R7, R8 are independently on each other selected from hydrogen, halo, alkyl, heterocycloalkyl, aryl, heteroaryl, hydroxyl, -OR9, -NR9R10, -NSO2R9, -NR9COR10, -NHCO2R10, where said aryl, heteroaryl, heterocycloalkyl are substituted by one or more groups, consisting of alkyl, alkoxyl and halogen; R9 and R10 independently on each other are selected from hydrogen, alkyl, cycloalkyl, where said alkyl, aryl, independently on each other are substituted by one or more groups, consisting of alkyl, aryl, hydroxyl, alkoxyl; R9 and R10 together with atom, to which they are bound, form 4-6-member rings, where 4-6-member rings can, in addition, contain one-two heteroatoms, selected from group, consisting of N and O, and each 4-6-member ring, formed in said way, is probably substituted by one or more groups, consisting of alkyl; n represents 2-6 and their pharmaceutically acceptable salts, where R1, R2, R3, R4, R5, R6, R7, R8, X, Y and -have values given in description. Also described is pharmaceutical composition, containing said compounds and possessing activity of proteinkinase inhibitor, methods of obtaining and pharmaceutical applications.

EFFECT: obtained and described are novel compounds, which can be useful as proteinkinase inhibitors.

20 cl, 131 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula pharmaceutically acceptable salts thereof, where ---- independently denotes a single or double bond; ring Q is imidazole, triazole (for example 1,2,3-triazole or 1,3,4-triazole), tetrazole or oxadiazole; B denotes C(R7)(R8) or C(R7), where if the bond between B and Y is a single bond, B denotes C(R7)(R8), and when the bond between B and Y is a double bond, B denotes C(R7); Y denotes C(R7), C(R7)(R8) or O, where if the bond between B and Y is a single bond, Y denotes C(R7)(R8) or O, and when the bond between B and Y is a double bond, B denotes C(R7); Z1 denotes -CH2-, -(CH2)2-, -CH2CH-CH3-, where Z1 is bonded on the left side to a nitrogen atom or -(CH2)3-; X denotes C(R1) or N; A denotes quinolyl, quinazolinyl or benzofuranyl, any of which is optionally substituted with 1-4 substitutes, which can be identical or different and are selected from a group comprising halogen, cyano, C1-6-alkyl, halogen-C1-6-alkyl, C(O)N(R3)(R4), 5-member heterocyclic ring containing 1-3 heteroatoms selected from N or O. The heterocyclic ring is optionally substituted with C1-6-alkyl; when R is present, each independently denotes halogen, C1-6-alkyl; each R1 denotes hydrogen or methyl; each R2 denotes cyano, C1-6-alkyl, C1-6-alkoxy, halogen-C1-6-alkyl, =O, -C(O)N(R3)(R4), -C(O)N(R3)-C1-6-alkoxy, -C(NOR5)R6, -C(O)R6, -C(O)OR7, -C(O)NHNHC(O)R6, 5-member heterocyclic ring containing 1-3 heteroatoms selected from N or O. The heterocyclic ring is optionally substituted with C1-6-alkyl; R3 and R4 independently denote hydrogen; C1-6-alkyl; C3-7-cycloalkyl; C3-7-cycloalkyl-C1-6-alkyl; or when R3 and R4 are bonded to the same nitrogen atom, they, together with the nitrogen atom, they form a 4-, 5- or 6-member ring which optionally contains one extra O atom in the ring; R5 denotes C1-4-alkyl; R6 denotes C3-7-cycloalkyl or C1-6-alkyl; R7 and R8 independently denote hydrogen or C1-6-alkyl; p equals 0, 1 or 2; r equals 0, 1, 2 or 3; s equals 0, 1, 2 or 3. The invention also relates to 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazin-3-carboxamide, 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperidinyl]ethyl}imidazo-[1,5-a]quinoline-3-carboxamide, dihydrochloride 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperidinyl]ethyl}[1,2,3]triazolo[1,5-a]quinoline-3-carboxamide, 7-methyl-6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4,5-dihydroimidazo[1,5-a]quinoline-3-carboxamide, to use of the compound in any of claims 1-16, as well as a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds, having 5-HT1 receptor mediated activity.

23 cl, 195 ex

FIELD: chemistry.

SUBSTANCE: invention describes dibenzo[b,f]pyrido[1,2-d][1,4]diazepinyl derivatives of general formula I: or pharmaceutically acceptable salts thereof (values of radicals are listed in the claim), which are glucocorticoid receptor modulators.

EFFECT: derivatives can be used in treating immunological and inflammatory diseases.

11 cl, 49 ex

FIELD: medicine.

SUBSTANCE: invention refers to the compound 3-{[5-(azetidine-1-ylcarbonyl)pyrazine-2-yl] oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazine-5-yl)benzamide or to its pharmaceutically acceptable salt. Also, it refers to a pharmaceutical composition for treating insulin-independent diabetes or obesity containing said compound.

EFFECT: there is produced and described a new compound which can be effective in treating insulin-independent diabetes and obesity.

5 cl, 64 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I) , where the dotted line is either absent or denotes a double bond; R1 denotes H or C1-6-alkyl, possibly substituted with a CN group, or denotes a phenyl or sulphonyl phenyl, substituted with one or more B groups, or denotes -(CH2)m-Ra, where Ra denotes: NRiRii, C3-6-cycloalkyl, 6-member heterocycloalkyl, which denotes a univalent saturated group which contains one nitrogen heteroatom, the rest are carbon atoms, aryl, which can be substituted with one or more B groups, or denotes -(CH2)n-(CO)-Rb or -(CH2)n-(SO2)-Rb, where Rb denotes: NRiRii, 5-6-member heterocycloalkyl, which denotes a univalent saturated group containing one or more heteroatoms selected from nitrogen, oxygen, the rest are carbon atoms, aryl or 5- or 6-member heteroaryl, which denotes an aromatic ring containing two heteroatoms as ring members, the said heteroatoms selected from N or O, the rest are carbon atoms; which can possibly be substituted with one or more B groups, R2 denotes one or more H, halo, C1-6-alkyl, C1-6-alkoxy, R3 denotes H or-(CO)-Rc, where Rc denotes: C1-6-alkyl, 5-member heterocycloalkyl, which denotes a univalent saturated group containing one nitrogen heteroatom, the rest are carbon atoms possibly substituted with C1-6-alkyl, or denotes C1-6-alkyl; R4 denotes H; R5 denotes H, C1-6-alkyl, -(CH2)m-NRiRii, -(CH2)n-(CO)-Rb, where Rb denotes NRiRii or a 6-member heterocycloalkyl which denotes a univalent saturated group which contains one nitrogen heteroatom, the rest are carbon atoms, when the dotted line is absent or is absent when the dotted line denotes a double bond; R6 is absent, when the dotted line denotes a double bond; R7 denotes Cl or NReRf, where Re and Rf denotes H or C1-6-alkyl, or Re and Rf together with the nitrogen atom to which they are bonded form a 6-member heterocycloalkyl which denotes a univalent saturated group containing one or two heteroatoms selected from nitrogen, oxygen, the rest are carbon atoms; which can be substituted with C1-6-alkyl, or R6 and R7 together form a C=O group, when the dotted line is absent; B denotes halogen, C1-6-alkoxy, (CRiiiRiv)n-phenyl; Ri and Rii denote H, C1-6-alkyl -C(O)-C1-6-alkyl; Riii and Riv denote C1-6-alkyl; m equals to 1 or 2, n equals 0 or 1; as well as to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition, as well as to use of compounds of formula (I), (I-a) or (1-b).

EFFECT: obtaining novel biologically active compounds having activity on V1a receptor.

12 cl, 48 ex

FIELD: chemistry.

SUBSTANCE: invention relates to oxazolidinone derivatives of formula (I) or pharmaceutically acceptable salts thereof, synthesis method thereof and pharmaceutical compositions containing said derivatives which are used as an antibiotic. Oxazolidinone derivatives, where R1 and R1' independently denote hydrogen or fluorine; R2 denotes -OR7, fluorine, monophosphate or metal phosphate; and R7 denotes hydrogen, C1-3alkyl or an acylated amino acid group, where the amino acid is alanine, glycine, proline, proline, isoleucine, leucine, phenylalanine, β-alanine or valine; R3 denotes hydrogen, a C1-4alkyl group which is unsubstituted or substituted cyano, , -(CH2)m-OR7 (m equals 0, 1, 2, 3, 4) or a ketone group. Oxazolidinone derivatives of formula (I) have antibacterial activity against different human and animal pathogens.

EFFECT: oxazolidinone derivatives, having inhibiting activity towards a wide range of bacteria and having low toxicity.

27 cl, 4 tbl, 73 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrrolidine derivatives of general formula (1) or its pharmaceutically acceptable salts where R101 and R102 values are described by the patent claim. The compounds inhibit serotonin and/or norepinephrine and/or dopamine reabsorption thereby allowing to be used for treating depression and anxiety disorder. A method for preparing thereof is described.

EFFECT: preparation of new pyrrolidine derivatives.

10 cl, 162 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula: or to its pharmaceutically acceptable salt, where: Ar2 represents phenyl or pyridyl, each of which is substituted by 0-4 substituents, independently selected from R2; X and Z represent N; Y represents CRX; D represents N; F represents N, CH or carbon, substituted by substituent, representing R1 or R10; Rx in each case is independently selected from hydrogen, halogen, C1-C4alkyl, amino, cyano and mono- or di-(C1-C4alkyl)amino; R1 represents 0-3 substituents, independently selected from: (a) halogen, cyano and nitro; (b) groups of formula -Q-M-Ry; R10 represents one substituent, selected from: (a) groups of formula -Q-M-Ry; so that R10 is not hydroxy, amino or unsubstituted group, selected from C1-C6alkyl, C2-C6alkenyl, C2-C6alkinyl, C1-C6aloxy, C2-C6alkyl, ether, C2-C6alkanoyl, C3-C6alcanone, C1-C6halogenalkyl, C1-C6halogenoalkoxy, mono- or di-(C1-C6alkyl)amino, C1-C6alkylsulfonyl, mono- or di-(C1-C6alkyl)aminosulfonyl or mono- or di-(C1-C6alkyl)aminocarbonyl; each Q is independently selected from C0-C4alkylene; each M is independently absent or is selected from O, C(=O), OC(=O), C(=O)O, S(O)m, N(RZ), C(=O)N(Rz), C(=NH)N(Rz), N(Rz)C(=O), N(Rz)C(=NH), N(Rz)S(O)m, S(O)mN(Rz) and N[S(O)mRz]S(O)m, where m equals 2; and Rz in each case is independently selected from hydrogen, C1-C8alkyl and groups, which taken together with Ry, form possibly substituted (4-7)-member heterocycle; and each Ry independently represents hydrogen, C1-C8halogenalkyl, C1-C8alkyl, C2-C8alkenyl, (C3-C8carbocycle)C0-C4alkyl, ((4-7)-member heterocycle)C0-C4alkyl or taken together with Rz forms (4-7) member heterocycle, where each alkyl, carbocycle and heterocycle is substituted by 0-4 substituents, independently selected from hydroxy, halogen, amino, cyano, nitro, -COOH, aminocarbonyl, aminosulfonyl, C1-C6alkyl, C3-C7cecloalkyl, C2-C6alkyl ether, C1-C6alkanoyl, C1-C6alkylsulfonyl, C1-C8alkoxy, C1-C8hydroxyalkyl, mono- and di-(C1-C6alkyl)aminocarbonyl, mono- and di-(C1-C6alkyl)aminosulfonyl, mono- and di-(C1-C6alkyl)amino, C1-C6alkanoylamino and phenyl; so that Ry is not hydrogen, if Q represents C0alkyl and M is absent; each R2: (a) is independently selected from (1) hydroxyl, amino, cyano, halogen, -COOH, nitro and (2) C1-C6alkyl, (C3-C8cycloalkyl)C0-C4alkyl, C1-C6halogenalkyl; R3 is selected from: (1) hydrogen; (2) C1-C6alkyl and (C3-C8cycloalkyl)C0-C2alkyl; and (3) groups of formula: where L represents C0-C6alkylene; R5 and R6: (a) are independently selected from C1-C12alkyl, (C3-C8cycloalkyl)C0-C4alkyl; or (b) are combined with formation of (4-6)-member heterocycle, containing one or two heteroatoms independently selected from O and N; and where each of (2) and (3) is substituted by 0-4 substituents, independently selected from: C1-C6alkyl and (C3-C8cycloalkyl)C0-C2alkyl, each of which is substituted by 0-4 secondary substituents, independently selected from hydroxy, C1-C4alkyl and C1-C4alkoxy; and R4 represents 0-2 substituents, independently selected from C1-C3alkyl.

EFFECT: claimed are pharmaceutical compositions for modulation of capsaicin receptor activity and methods of applying said compounds for treatment of such disorders as pain, itch, cough, hiccup, urinary incontinence or obesity.

65 cl, 1 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a sodium salt N-(4-chloro-3-methyl-5-isoxazolyl)-2-[2-methyl-4,5-(methylenedioxy)phenylacetyl]thiophene-3-sulfonamide in form of a polymorph, characterised by peaks on an x-ray powder diffraction (XRD) pattern at approximately 22.38 and 23.38 degrees 2-theta. The invention also relates to methods of producing said polymorph and to a pharmaceutical composition based on said polymorph, having endothelin antagonist activity.

EFFECT: polymorphous form is more stable and can be used in medicine to treat pulmonary hypertension.

17 cl, 9 tbl, 31 dwg, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to thiophene derivatives of formula (I):

where A denotes -CONH-CH2-, -CO-CH=CH-, -CO-CH2CH2-, -CO-CH2-O-, -CO-CH2-NH-, or ; R1 denotes hydrogen, C1-5-alkyl or C1-5-alkoxy; R2 denotes hydrogen, C1-2-alkyl, C1-5-alkoxy, trifluoromethyl or halogen, R3, R31, R32, R33, R34, R4, R5, R6, R7, k, m, n are described in claim 1. The invention also relates to a pharmaceutical composition for preventing or treating diseases and disorders associated with an activated immune system, based on said compounds and to use thereof as therapeutically active compounds for preventing or treating diseases or disorders such as graft rejection, graft versus host reaction and autoimmune syndromes.

EFFECT: improved properties of the compound.

27 cl, 2 tbl, 525 ex

FIELD: chemistry.

SUBSTANCE: disclosed compounds can be used as a medicinal agent which modulates PPARδ (peroxisome proliferator-activated receptor δ). In formula I

, p is equal to 1; L2 is selected from a group which includes -XOX- and -XSX-, where X is independently selected from a group which includes a bond and C1-C4alkylene; R13 is selected from a group which includes halogen, C1-C6alkyl; R14 is selected from a group which includes -XOXC(O)OR17 and -XC(O)OR17, where X denotes a bond or C1-C4alkylene and R17 denotes hydrogen; R15 and R16 are independently selected from a group which includes -R18 and -YR18, where Y is selected from a group which includes C2-C6alkenylene, and R18 is selected from a group which includes C6-C10aryl, pyridinyl, pyrimidinyl, quinolinyl, benzo[b]furanyl, benzoxazolyl, 1,5-benzodioxanyl, 1,4-benzodioxanyl and 3,4-dihydro-2H-benzo[b][1,4]dioxepin; where any of phenyl, pyridinyl, pyrimidinyl, benzoxazolyl in R18 is independently substituted with 1-2 radicals, independently selected from a group which includes halogen, C1-C6alkyl, C2-C7alkenyl, C1-C6alkoxy group, halogen-substituted C1-C6alkyl, halogen-substituted C1-C6alkoxy group, C3-C12cycloalkyl, phenyl, morpholinyl, pyrrolidinyl, piperidinyl, -XNR17R17, -XC(O)NR17R17, -XC(O)R19 and -XOXR19, where X denotes a bond or C1-C4alkylene; R17 is selected from a group which includes C1-C6alkyl, and R19 is selected from a group which includes C3-C12cycloalkyl, piperidinyl and phenyl. The invention also relates to use of the disclosed compounds to prepare a medicinal agent which modulates PPARδ activity, a pharmaceutical composition having PPARδ activity modulating properties, which contains a therapeutically effective amount of the disclosed compound and to use of the pharmaceutical composition in preparing a medicinal agent which modulates PPARδ activity.

EFFECT: improved properties of compounds.

10 cl, 1 tbl, 69 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula 1, its pharmaceutically acceptable salts and stereoisomers: $ (1), where: R1 means H, amidino, C1-C4-alkyl amidino, C1-C4alkanoylamidino, C1-C10-alkyl, C3-C7-cycloalkyl, C6-C10-aryl, 6-members heterocycle with O atom, 5-members heterocycle with two N atoms, 6-members heteroaryl with one or two N atoms, 5-members heteroaryl with two heteroatoms, one of which is N, and the other is S, C1-C6-alkylcarbonyl, C3-C7-cycloalkylcarbonyl, C1-C4-alkoxycarbonyl, C6-C10-aryl-C1-C4-alkoxycarbonyl, -SO2-C1-C4-alkyl, -C(O)-N(R6)(R7) or -C(S)-N(R6)(R7); and, R6, R7 means H, C1-C6-alkyl, C3-C7-cycloalkyl; alkyl, cycloalkyl, heterocycle, aryl or heteroaryl are unsubstituted or substituted; R2 means C6-C10-aryl which is unsubstituted or mono- or disubstituted; R3 means H, CN, C1-C6-alkyl, C3-C7-cycloalkyl, C2-C6-alkenyl, monocyclic 5-members heterocycle with N and O, monocyclic 5-members heteroaryl with two heteroatoms, one of which is N, and the other is O or S, C(O)-R8 or -C(S)-R8; and R8 means OH, C1-C4-alkyl, C1-C4-alkyloxy or N(R9)(R10); R9, R10 mean N, C1-C6-alkyl, C3-C7-cycloalkyl, C1-C4-alkyloxy, phenyl or 5-members heteroaryl with two heteroatoms, one of which is N, and the other is S, 6-members heteroaryl with N; R9, R10 together with N whereto attached can form a single 4-6-members ring which can include in addition O or S; and alkyl, cycloalkyl, heterocycle, phenyl or heteroaryl are unsubstituted or substituted. R4 means C3-C8-cycloalkyl, C6-C10-aryl, 5-members heteroaryl with two heteroatoms, one of which is N, and the other is S, 6-members heteroaryl with N, 6-members heterocycle with O, and C6-C10-aryl or heteroaryl are unsubstituted or mono- or polysubstituted. R5 means N, C1-C6-alkyl, -C(O)-R11, C1-C6-alkylsulphonyl, C6-C10-arylsulphonyl, -(CH2)p-C6-C10-aryl, -(CH2)p-heteroaryl or -(CH2)p-C3-C8-cycloalkyl where heteroaryl means 5-members heteroaryl with O or with N or with S which can contain in addition N. p is equal to 1 or 2; R11 means C1-C10-alkyl, C1-C6-alkenyl, C3-C8-cycloalkyl, C3-C8-cycloalkenyl, NH2, C1-C4alkylamino, (C1-C4-alkyl)(C1-C4-alkyl)amino, C6-C10-aryl, 5-members heteroaryl with N or with O or with 8 which can contain in addition N, 6-members heterocycle with N and O, 5- or 6-members heterocycle with O, and alkyl is unsubstituted or substituted with one substitute. Aryl, heteroaryl, cycloalkyl, cycloalkenyl or heterocycle are unsubstituted or mono- or disubstituted.

EFFECT: compounds are melanocortin receptor agonists so presented to be used in a pharmaceutical composition for treatment and prevention of obesity, diabetes, inflammation, erectile dysfunction.

19 cl, 18 tbl

Organic compounds // 2411239

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I, in which R1 denotes alkyl or cycloalkyl; R2 denotes phenyl-C1-C7-alkyl, di-(phenyl)- C1-C7-alkyl, naphthyl- C1-C7-alkyl, phenyl, naphthyl, pyridyl-C1-C7-alkyl, indolyl- C1-C7-alkyl, 1H-indazolyl- C1-C7-alkyl, quinolyl C1-C7-alkyl, isoquinolyl- C1-C7-alkyl, 1,2,3,4-tetrahydro-1,4-benzoxazinyl- C1-C7-alkyl, 2H-1,4-benzoxazin-3(4H)-onyl-C1-C7-alkyl, 9-xanthenyl-C1-C7-alkyl, 1-benzothiophenyl-C1-C7-alkyl, pyridyl, indolyl, 1H-indazolyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydro-1,4-benzoxazonyl, 2H-1,4-benzoxazin-3(4H)-onyl, 9-xanthenyl, 1-benzothiophenyl, 4H-benzo[1,4]thiazin-3-only, 3,4-dihydro-1H-quinolin-2-onyl or 3H-benzoxazol-2-onyl, where each phenyl, naphthyl, pyridyl, indolyl, 1H-indazolyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydro-1,4-benzoxazonyl, 2H-1,4-benzoxazin-3(4H)-onyl, 1-benzothiophenyl, 4H-benzo[1,4]thiazin-3-only, 3,4-dihydro-1H-quinolin-2-onyl or 3H-benzoxazol-2-onyl are unsubstituted or contain one or up to 3 substitutes independently selected from a group comprising C1-C7-alkyl, hydroxy-C1-C7-alkyl, C1-C7-alkoxy- C1-C7-alkyl, C1-C7-alkoxy- C1-C7-alkoxy-C1-C7-alkoxy- C1-C7-alkyl, C1-C7-alkanoyloxy- C1-C7-alkyl, amino- C1-C7-alkyl, C1-C7-alkoxy- C1-C7-alkylamino- C1-C7-alkyl, C1-C7-alkanoylamino- C1-C7-alkyl, C1-C7-alkylsulphonylamino- C1-C7-alkyl, carboxy- C1-C7-alkyl, C1-C7-alkoxycarbonyl- C1-C7-alkyl, halogen, hydroxy group, C1-C7-alkoxy group, C1-C7-alkoxy- C1-C7-alkoxy group, amino- C1-C7-alkoxy group, N-C1-C7-alkanoylamino-C1-C7-alkoxy group, carbamoyl- C1-C7-alkoxy group, N-C1-C7-alkylcarbamoyl-C1-C7-alkoxy group, C1-C7-alkanoyl, C1-C7-alkoxy-C1-C7-alkanoyl, C1-C7-alkoxy- C1-C7-alkanoyl, carboxyl, carbamoyl and N-C1-C7-alkoxy-C1-C7-alkylcarbamoyl; W denotes a fragment selected from residues of formulae IA, IB and IC, where () indicates the position in which the fragment W is bonded to the carbon atom in position 4 of the piperidine ring in formula I, and where X1, X2, X3, X4 and X5 are independently selected from a group containing carbon and oxygen, where X4 in formula IB and X1 in formula IC can assume one of these values or can be additionally selected from a group comprising S and O, where carbon and nitrogen ring atoms can include a number of hydrogen atoms or substitutes R3 or R4 if contained, taking into account limitations given below, required to bring the number of bonds of the carbon ring atom to 4 and 3 for the nitrogen ring atom; provided that in formula IA at least 2, preferably at least 3 of the atoms X1-X5 denote carbon and in formulae IB and IC at least one of X1-X4 denotes carbon, preferably 2 of the atoms X1-X4 denote carbon; y equals 0 or 1; z equals 0 or 1; R3, which can be bonded with any of the atoms X1, X2, X3 and X4, denotes hydrogen or a C1-C7-alkyloxy-C1-C7-alkyloxy group, phenyloxy-C1-C7-alkyl, phenyl, pyridinyl, phenyl- C1-C7-alkoxy group, phenyloxy group, phenyloxy-C1-C7-alkoxy group, pyridyl-C1-C7-alkoxy group, tetrahydropyranyloxy group, 2H,3H-1,4-benzodioxynyl-C1-C7-alkoxy group, phenylaminocarbonyl or phenylcarbonylamino group, where each phenyl or pyridyl is unsubstituted or contains one or up to 3 substitutes, preferably 1 or 2 substitutes independently selected from a group comprising C1-C7-alkyl, hydroxy group, C1-C7-alkoxy group, phenyl-C1-C7-alkoxy group, where phenyl is unsubstituted or substituted with a C1-C7-alkoxy group and/or halogen; carboxy- C1-C7-alkyloxy group, N-mono- or N,N-di-(C1-C7-alkyl)aminocarbonyl-C1-C7-alkyloxy group, halogen, amino group, N-mono- or N,N-di-(C1-C7-alkyl)amino group, C1-C7-alkanoylamino group, morpholino-C1-C7-alkoxy group, thiomorpholino-C1-C7-alkoxy group, pyridyl-C1-C7-alkoxy group, pyrazolyl, 4- C1-C7-alkylpiperidin-1-yl, tetrazolyl, carboxyl, N-mono- or N,N-di-(C1-C7-alkylamino)carbonyl or cyano group; or denotes 2-oxo-3-phenyltetrahydropyrazolidin-1-yl, oxetidin-3-yl-C1-C7-alkyloxy group, 3-C1-C7-alkyloxetidin-3-yl- C1-C7-alkyloxy group or 2-oxotetrahydrofuran-4-yl- C1-C7-alkyloxy group; provided that if R3 denotes hydrogen, then y and z are equal to 0; R4, if contained, denotes a hydroxy group, halogen or C1-C7-alkoxy group; T denotes carbonyl; and R11 denotes hydrogen, or pharmaceutically acceptable salts thereof. The invention also relates to use of formula I compounds, a pharmaceutical composition, as well as a method of treating diseases.

EFFECT: obtaining novel biologically active compounds having activity towards rennin.

11 cl, 338 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to azole derivatives of formula I , where: A denotes S, O; W denotes -(C=O)-; X are identical or different and denote =C(-R)- or =N-; Y denotes -O- or -NR1-; R denotes hydrogen, halogen, (C1-C6)-alkyl, nitro; R1 denotes hydrogen; R2 denotes (C5-C16)-alkyl, (C1-C4)alkyl-phenyl, where phenyl can be optionally mono- or poly-substituted with (C1-C6)-alkyl; R3 denotes hydrogen; or R2 and R3 together with the nitrogen atom bearing them can form a monocyclic saturated 6-member ring system, where separate members of this ring system can be substituted with 1 group selected from the following: -CHR5-, -NR5-; R5 denotes (C1-C6)-alkyl, trifluoromethyl; and physiologically acceptable salts thereof. The invention also pertains to methods of producing said compounds and a medicinal agent based on said compounds.

EFFECT: novel compounds and a medicinal agent based on said compounds are obtained, which can be used as hormone-sensitive lipase (HSL) or endothelial lipase (EL) inhibitors.

12 cl, 11 ex

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