Substituted oxadiazole derivatives and use thereof as opioid receptor ligands

FIELD: chemistry.

SUBSTANCE: invention relates to substituted oxadiazole derivatives of general formula , where X denotes CH, CH2, CH=CH, CH2CH2, CH2CH=CH or CH2CH2CH2, R1 denotes an unsubstituted or mono- or disubstituted phenyl or pyrrolyl residue or an unsubstituted or mono- or disubstituted phenyl connected through a C1-C3alkyl or a thienyl or indolyl residue, where the said substitutes are selected from a group comprising F, Cl, Br, OCF3, O-C1-C6alkyl or C1-C6alkyl, R2 denotes an unsubstituted or mono- or disubstituted phenyl or thienyl residue or an unsubstituted or mono- or disubstituted phenyl residue connected through a C1-C3alkyl, where the said substitutes are selected from a group comprising F, Cl, and R3 and R4 denote a saturated straight C1-C6alkyl in form of a racemate, diastereomers, mixture of enantiomers and/or diastereomers, or a specific diastereomer, bases and/or salts with physiologically compatible acids. The invention also relates to a method of producing said compounds and a medicinal agent based on said compounds and having affinity to the µ-opioid receptor.

EFFECT: obtaining novel compounds and a medicinal agent based on said compounds, which can be used in medicine to pain killing and for treating depression, enuresis, diarrhoea, skin itching, alcohol and drug abuse, drug induced addiction, aspontaneity or for anxiolyis.

11 cl, 2 tbl, 331 ex

 

The text descriptions are given in facsimile form.

1. Substituted derivatives of oxadiazole General formula I

in which X represents CH, CH2CH=CH, CH2CH2CH CH=CH or CH2CH2CH,
R1denotes unsubstituted or mono - or disubstituted phenyl or pyrrolidinyl balance or attached via C1-C3alkyl group unsubstituted or mono - or disubstituted phenyl or thienyl or indaily balance, where these substituents selected from the group comprising F, Cl, Br, F3O-C1-C6alkyl and C1-C6alkyl,
R2denotes unsubstituted or mono - or disubstituted phenyl or thienyl residue or attached via C1-C3the alkyl chain is unsubstituted or mono - or disubstituted phenyl residue, where these substituents selected from the group comprising F, Cl, and
R3and R4denote unbranched saturated C1-C6alkyl in the form of a racemate, diastereomers, mixtures of enantiomers and/or diastereomers or of an individual diastereoisomer, bases and/or salts with physiologically compatible acids.

2. Substituted derivatives of oxadiazole according to claim 1, in which R1denotes phenyl, pyrrolyl, methylindolin, methylthieno or phenethyl, each of which is not substituted or mono - or dunamase substituents from the group comprising F, Cl, Br, OCF3, O-C1-C6alkyl and C1-C6alkyl.

3. Substituted derivatives of oxadiazole according to claim 2, in which Rsup> 1denotes phenyl, methylindolin, methylthieno or pyrrolyl, each of which is not substituted or mono - or dunamase substituents from the group comprising Cl, Br, och3CH3, F, F3and tert-butyl.

4. Substituted derivatives of oxadiazole according to claim 1, in which R2denotes phenyl which is not substituted or odnosnie atom Cl or F, phenethyl or thienyl.

5. Substituted derivatives of oxadiazole according to claim 1, in which R3and R4denote unbranched saturated With1-C6alkyl.

6. Substituted derivatives of oxadiazole according to claim 5, in which R3and R4denote SN3.

7. Substituted derivatives of oxadiazole according to claim 1, selected from the group including:
43) (4-((3-(4-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)diclohexal)-N,N-dimethyl(phenyl)methanamine,
44) (4-((3-(4-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)-N,N-dimethyl(phenyl)methanamine,
45) ((4-chlorophenyl)-{4-[3-(4-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}methyl)dimethylamine,
46) [{4-[3-(4-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(4-forfinal)methyl]dimethylamine (more polar diastereoisomer),
47) [{4-[3-(4-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(4-forfinal)methyl]dimethylamine (less polar diastereoisomer),
48) ({4-[3-(2,3-dichlorophenyl)-[1,2,4] oxadiazol-5-ylmethylene]cyclohexyl}-phenylethyl)dimethylamine (more polar dust reamer),
49) ({4-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-phenylethyl)dimethylamine (less polar diastereoisomer),
50) [{4-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(3-forfinal)methyl]dimethylamine(more polar diastereoisomer),
51) [{4-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(3-forfinal)methyl]dimethylamine(less polar diastereoisomer),
52) ((4-chlorophenyl)-{4-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (more polar diastereoisomer),
53) ((4-chlorophenyl)-{4-[3-(2,3-dichlorophenyl)-[1,2,4] oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine(less polar diastereoisomer),
54) (1-{4-[3-(2,3-dichlorophenyl)-[1,2,4] oxadiazol-5-ylmethylene]-cyclohexyl}-3-phenylpropyl)dimethylamine,
55) [{4-[3-(2,3-dichlorophenyl)-[1,2,4] oxadiazol-5-ylmethylene]cyclohexyl}-(4-forfinal)methyl]dimethylamine (more polar diastereoisomer),
56) [{4-[3-(2,3-dichlorophenyl)-[1,2,4] oxadiazol-5-ylmethylene]cyclohexyl}-(4-forfinal)methyl]dimethylamine (less polar diastereoisomer),
57) dimethyl(phenyl-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethylene] cyclohexyl }methyl)amine (more polar diastereoisomer),
58) dimethyl(phenyl-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)amine (less polar diastereoisomer),
59) ((3-forfinal)-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethylene] cyclohexyl}methyl)d is methylamine (more polar diastereoisomer),
60) ((3-forfinal)-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (less polar diastereoisomer),
61) ((4-chlorophenyl)-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (more polar diastereoisomer),
62) ((4-chlorophenyl)-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (less polar diastereoisomer),
63) dimethyl-(3-phenyl-1-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}propyl)amine (more polar diastereoisomer),
64) dimethyl-(3-phenyl-1-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl)propyl)amine (less polar diastereoisomer),
65) ((4-forfinal)-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (more polar diastereoisomer),
66) ((4-forfinal)-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (less polar diastereoisomer),
67) dimethyl(thiophene-2-yl-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)amine (more polar diastereoisomer),
68) dimethyl(thiophene-2-yl-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)amine (less polar diastereoisomer),
69) dimethyl{phenyl-[4-(3-phenyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}amine (more polar diastereoisomer),
70) dimetilfenil-[4-(3-phenyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}amine (less polar diastereoisomer),
71) {(3-forfinal)-[4-(3-phenyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}dimethylamine (more polar diastereoisomer),
72) {(3-forfinal)-[4-(3-phenyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}dimethylamine (less polar diastereoisomer),
73) of dimethyl-{3-phenyl-1-[4-(3-phenyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]propyl}amine (more polar diastereoisomer),
74) of dimethyl-{3-phenyl-1-[4-(3-phenyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl] propyl}amine (less polar diastereoisomer),
75) {(4-forfinal)-[4-(3-phenyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}dimethylamine (more polar diastereoisomer),
76) {(4-forfinal)-[4-(3-phenyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl] methyl}dimethylamine (less polar diastereoisomer),
77) [{4-[3-(2,4-differenl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(3-forfinal)methyl]dimethylamine (more polar diastereoisomer),
78) [{4-[3-(2,4-differenl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(3-forfinal)methyl]dimethylamine (less polar diastereoisomer),
79) ({4-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-phenylethyl)dimethylamine (more polar diastereoisomer),
80) ({4-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-phenylethyl)dimethylamine (less polar diastereoisomer),
81) ((3-forfinal)-{4-[3-(4-methoxybenzyl)-[1,2,4] oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (more polar diastereoisomer), 82) ((3-forfinal)-{4-[3-(4-methoxybenzyl)-[1,2,4] oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (less polar diastereoisomer),
83)((4-chlorophenyl)-{4-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (more polar diastereoisomer),
84) ((4-chlorophenyl)-{4-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (less polar diastereoisomer),
85) (1-{4-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-3-phenylpropyl)dimethylamine (more polar diastereoisomer),
86) (1-{4-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-3-phenylpropyl)dimethylamine (less polar diastereoisomer),
87) ((4-forfinal)-{4-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (more polar diastereoisomer),
88) ((4-forfinal)-(4-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (less polar diastereoisomer),
89) ({4-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-phenylethyl)dimethylamine (more polar diastereoisomer),
90) ({4-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-phenylethyl)dimethylamine (less polar diastereoisomer),
91) [{4-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(3-forfinal)methyl]dimethylamine (more polar diastereoisomer),
92) [{4-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(3-forfinal)is ethyl]dimethylamine (less polar diastereoisomer),
93) [{4-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(4-chlorophenyl)methyl]dimethylamine (more polar diastereoisomer),
94) [{4-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(4-chlorophenyl)methyl]dimethylamine (less polar diastereoisomer),
95) (1-{4-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-3-phenylpropyl)dimethylamine (more polar diastereoisomer),
96) (1-{4-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-3-phenylpropyl)dimethylamine(less polar diastereoisomer),
97) [{4-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(4-forfinal)methyl]dimethylamine (more polar diastereoisomer),
98) [{4-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(4-forfinal)methyl]dimethylamine (less polar diastereoisomer),
99) {(3-forfinal)-[4-(3-n-tolyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}dimethylamine,
100) {(4-chlorophenyl)-[4-(3-n-tolyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}dimethylamine,
101) {(4-forfinal)-[4-(3-n-tolyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}dimethylamine (more polar diastereoisomer),
102) {(4-forfinal)-[4-(3-n-tolyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl)dimethylamine (less polar diastereoisomer),
103 ) ({4-[3-(3,4-acid)-[1,2,4] oxadiazol-5-ylmethylene]-cyclohexyl}phenylethyl)dimethylamine (more polar diastereoisomer),
104) ({4-[3-(3,4-acid)-[1,2,4]oxadiazol-ylmethylene]-cyclohexyl}phenylethyl)dimethylamine (less polar diastereoisomer),
105) [{4-[3-(3,4-acid)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-(3-forfinal)methyl] dimethylamine (more polar diastereoisomer),
106) [{4-[3-(3,4-acid)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-(3-forfinal)methyl]dimethylamine (less polar diastereoisomer),
107) ((4-chlorophenyl)-{4-[3-(3,4-acid)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (more polar diastereoisomer),
108) ((4-chlorophenyl)-{4-[3-(3,4-acid)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}methyl)dimethylamine (less polar diastereoisomer),
109) (1-{4-[3-(3,4-acid)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl)-3-phenylpropyl)dimethylamine (more polar diastereoisomer),
110)(1-{4-[3-(3,4-acid)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-3-phenylpropyl)dimethylamine (less polar diastereoisomer),
111) [{4-[3-(3,4-acid)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-(4-forfinal)methyl]dimethylamine (more polar diastereoisomer),
112) [{4-[3-(3,4-acid)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-(4-forfinal)methyl]dimethylamine (less polar diastereoisomer),
113) ({4-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-phenylethyl)dimethylamine (more polar diastereoisomer),
114) ({4-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-phenylethyl)dimethylamine (less polar diastereoisomer),
115)[{4-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]illogical}-(3-forfinal)methyl]dimethylamine (more polar diastereoisomer),
116) [{4-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(3-forfinal)methyl]dimethylamine (less polar diastereoisomer),
117) ((4-chlorophenyl)-{4-[3-(3-chlorophenyl)-[1,2,4] oxadiazol-5-ylmethylene]-cyclohexyl}methyl)dimethylamine (more polar diastereoisomer),
118) ((4-chlorophenyl)-{4-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}methyl)dimethylamine (less polar diastereoisomer),
119) (1-{4-[3-(3-chlorophenyl)-[1,2,4] oxadiazol-5-ylmethylene]cyclohexyl}-3-phenylpropyl)dimethylamine (more polar diastereoisomer),
120) (1-{4-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-3-phenylpropyl)dimethylamine (less polar diastereoisomer),
121) [{4-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethylene]cyclohexyl}-(4-forfinal)methyl]dimethylamine,
122) ({4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}phenylethyl)dimethylamine (more polar diastereoisomer),
123) ({4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}phenylethyl)dimethylamine (less polar diastereoisomer),
124) [{4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-(3-forfinal)methyl]dimethylamine (more polar diastereoisomer),
125) [{4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-(3-forfinal)methyl]dimethylamine (less polar diastereoisomer),
126) [{4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-(4-chlorophenyl)methyl]dimethylamine (more p is regular, the diastereoisomer),
127) [{4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-(4-chlorophenyl)methyl]dimethylamine (less polar diastereoisomer),
128) (1-{4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-3-phenylpropyl)dimethylamine (more polar diastereoisomer),
129) (1-{4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-3-phenylpropyl)dimethylamine (less polar diastereoisomer),
130) [{4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-(4-forfinal)methyl]dimethylamine (more polar diastereoisomer),
131) [{4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}-(4-forfinal)methyl]dimethylamine (less polar diastereoisomer),
132) ({4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}thiophene-2-ylmethyl)dimethylamine (more polar diastereoisomer),
133) ({4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethylene]-cyclohexyl}thiophene-2-ylmethyl)dimethylamine (less polar diastereoisomer),
134) dimethyl{phenyl-[4-(3-m-tolyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}amine (more polar diastereoisomer),
135) dimethyl{phenyl-[4-(3-m-tolyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}amine (less polar diastereoisomer),
136) {(3-forfinal)-[4-(3-m-tolyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}dimethylamine (more polar diastereoisomer),
137) {(3-forfinal)-[4-(3-m-tolyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}is imacillin (less polar diastereoisomer),
138) {(4-chlorophenyl)-[4-(3-m-tolyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}dimethylamine (more polar diastereoisomer),
139) {(4-chlorophenyl)-[4-(3-m-tolyl-[1,2,4]oxadiazol-5-ylmethylene)-cyclohexyl]methyl}dimethylamine (less polar diastereoisomer),
140) ((4-forfinal)-{4-[2-(3-phenyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl} methyl)dimethylamine,
141) [(4-{2-[3-(2,4-differenl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-(4-forfinal)methyl]dimethylamine,
142) [(4-forfinal)-(4-{2-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)methyl]dimethylamine,
143) [(4-{2-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-(4-forfinal)methyl]dimethylamine,
144) dimethyl-(3-phenyl-1-{4-[2-(3-phenyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}propyl)amine,
145) [1-(4-{2-[3-(2,4-differenl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-3-phenylpropyl]dimethylamine,
146) [1-(4-{2-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-3-phenylpropyl]dimethylamine,
147) [1-(4-{2-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-3-phenylpropyl]dimethylamine,
148) dimethyl(phenyl-{4-[2-(3-phenyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl} methyl)amine,
149) [(4-{2-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-phenylmethyl]dimethylamine (more polar diastereoisomer),
150) [(4-{2-[3-(4-Chlorobenzyl)-[1,2,4] oxadiazol-5-yl]vinyl}cyclohexyl)-phenylmethyl]dimethylamine (less polar diastereoisomer),
151) [(4-chlorophenyl)-(4-{2[3-(2,4-differenl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)methyl]dimethylamine,
152) [(4-chlorophenyl)-(4-{2-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)methyl]dimethylamine,
153) [(4-{2-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-(4-chlorophenyl)methyl]dimethylamine,
154) [(4-{2-[3-(4-methoxybenzyl)-[1,2,4] oxadiazol-5-yl]vinyl} -cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
155) [(4-{2-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-thiophene-2-ylmethyl]dimethylamine,
156) ((3-forfinal)-{4-[2-(3-phenyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}methyl)dimethylamine,
157) [(3-forfinal)-(4-{2-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)methyl]dimethylamine,
158) ((4-forfinal)-{4-[2-(3-n-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl} methyl)dimethylamine,
159) [(4-{2-[3-(3,4-acid)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-(4-forfinal)methyl]dimethylamine,
160) dimethyl-(3-phenyl-1-{4-[2-(3-n-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}propyl)amine,
161) [1-(4-{2-[3-(3,4-acid)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-3-phenylpropyl]dimethylamine,
162) dimethyl(phenyl-{4-[2-(3-n-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}methyl)amine,
163) [(4-{2-[3-(3,4-acid)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)phenylmethyl]dimethylamine,
164) ((4-chlorophenyl)-{4-[2-(3-n-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}methyl)dimethylamine,
165) [(4-chlorophenyl)-(4-{2-[3-(3,4-acid)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)methyl]dimethylamine,
166) dimethyl(thio is EN-2-yl-{4-[2-(3-n-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}methyl)amine,
167) [(4-{2-[3-(3,4-acid)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
168) ((3-forfinal)-{4-[2-(3-n-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}methyl)dimethylamine,
169) [(4-{2-[3-(3,4-acid)-[1,2,4] oxadiazol-5-yl]vinyl}-cyclohexyl)-(3-forfinal)methyl]dimethylamine,
170) [(4-{2-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-(4-forfinal)methyl]dimethylamine,
171) [(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-(4-forfinal)methyl]dimethylamine,
172) [(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-(4-forfinal)methyl]dimethylamine,
173) ((4-forfinal)-{4-[2-(3-m-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}methyl)dimethylamine,
174) [1-(4-{2-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-3-phenylpropyl]dimethylamine,
175) [1-(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-3-phenylpropyl]dimethylamine (more polar diastereoisomer),
176) [1-(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-3-phenylpropyl]dimethylamine (less polar diastereoisomer),
177) dimethyl-(3-phenyl-1-{4-[2-(3-m-tolyl-[1,2,4] oxadiazol-5-yl)vinyl]-cyclohexyl}propyl)amine (more polar diastereoisomer),
178) dimethyl-(3-phenyl-1-{4-[2-(3-m-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}propyl)amine (less polar diastereoisomer),
179) [(4-{2-[3-(3-chlorophenyl)-[1,2,4] oxadiazol-5-yl]vinyl}cyclohexyl)-phenylmethy is]dimethylamine,
180) [(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)phenylmethyl]dimethylamine (more polar diastereoisomer),
181) [(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)phenylmethyl]dimethylamine (less polar diastereoisomer),
182) dimethyl(phenyl-{4-[2-(3-m-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}methyl)amine (more polar diastereoisomer),
183) dimethyl(phenyl-{4-[2-(3-m-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}methyl)amine (less polar diastereoisomer),
184) [(4-{2-[3-(4-chlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-phenylmethyl]dimethylamine (more polar diastereoisomer),
185) [(4-{2-[3-(4-chlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-phenylmethyl]dimethylamine (less polar diastereoisomer),
186) [(4-chlorophenyl)-(4-{2-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)methyl]dimethylamine,
187) [(4-{2-[3-(4-tert-butylphenyl]-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-(4-chlorophenyl)methyl]dimethylamine (more polar diastereoisomer),
188) [(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-(4-chlorophenyl)methyl]dimethylamine (less polar diastereoisomer),
189) ((4-chlorophenyl)-{4-[2-(3-m-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl)methyl)dimethylamine (more polar diastereoisomer),
190) ((4-chlorophenyl)-{4-[2-(3-m-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}methyl)dimethylamine (less polar diastereoisomer),
191) [(4-chlorophenyl)-(4-{2-[3-(4-CHL is henyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)methyl]dimethylamine,
192) [(4-{2-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-thiophene-2-ylmethyl]dimethylamine,
193) [(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine (more polar diastereoisomer),
194) [(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine (less polar diastereoisomer),
195) dimethyl(thiophene-2-yl-{4-[2-(3-m-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}methyl)amine,
196) [(4-{2-[3-(4-chlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-thiophene-2-ylmethyl]dimethylamine,
197) [(4-{2-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-(3-forfinal)methyl]dimethylamine,
198) [(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-(3-forfinal)methyl]dimethylamine (more polar diastereoisomer),
199) [(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-(3-forfinal)methyl]dimethylamine (less polar diastereoisomer),
201) ((3-forfinal)-{4-[2-(3-m-tolyl-[1,2,4]oxadiazol-5-yl)vinyl]-cyclohexyl}methyl)dimethylamine,
202) [(4-{2-[3-(4-chlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-(3-forfinal)methyl]dimethylamine,
203) [(4-{2-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-(4-forfinal)methyl]dimethylamine,
204) [(4-forfinal)-(4-{2-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)methyl]dimethylamine,
205) [(4-{2-[3-(3,4-dimethoxybenzyl)-[1,2,4]oxadiazol-5-yl]vinyl-cyclohexyl)-(4-forfinal)methyl]dimethylamine,
206) [(4-{2-[3-(1,5-dimethyl-1H-pyrrol-2-yl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-(4-forfinal)methyl]dimethylamine,
207) [1-(4-{2-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-3-phenylpropyl]dimethylamine,
208)dimethyl-[3-phenyl-1-(4-{2-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)propyl]amine (more polar diastereoisomer),
209) dimethyl-[3-phenyl-1-(4-{2-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)propyl]amine (less polar diastereoisomer),
210) [1-(4-{2-[3-(3,4-dimethoxybenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-3-phenylpropyl]dimethylamine (more polar diastereoisomer),
211) [1-(4-(2-[3-(3,4-dimethoxybenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-3-phenylpropyl]dimethylamine (less polar diastereoisomer),
212) [1-(4-{2-[3-(1,5-dimethyl-1H-pyrrol-2-yl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)-3-phenylpropyl]dimethylamine,
213) [(4-{2-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl)-cyclohexyl)phenylmethyl]dimethylamine,
214) [(4-{2-[3-(3,4-dimethoxybenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)phenylmethyl]dimethylamine (more polar diastereoisomer),
215) [(4-{2-[3-(3,4-dimethoxybenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)phenylmethyl]dimethylamine (less polar diastereoisomer),
217) [(4-{2-[3-(1,5-dimethyl-1H-pyrrol-2-yl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)phenylmethyl]dimethylamine,
218)[(4-chlorophenyl)-(4-{2-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-yl]VI is Il}cyclohexyl)methyl]dimethylamine,
219) [(4-chlorophenyl)-(4-{2-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)methyl]dimethylamine,
220) [(4-chlorophenyl)-(4-{2-[3-(3,4-dimethoxybenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)methyl]dimethylamine,
221) [(4-chlorophenyl)-(4-{2-[3-(1,5-dimethyl-1H-pyrrol-2-yl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)methyl]dimethylamine,
222) [(4-{2-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl)-cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
223) dimethyl[thiophene-2-yl-(4-(2-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)methyl]amine,
224) [(4-{2-[3-(1,5-dimethyl-1H-pyrrol-2-yl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
225) [(4-{2-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-(3-forfinal)methyl]dimethylamine,
226) [(3-forfinal)-(4-{2-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)methyl]dimethylamine (more polar diastereoisomer),
227) [(3-forfinal)-(4-{2-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-yl]vinyl}cyclohexyl)methyl]dimethylamine (less polar diastereoisomer),
228) [(4-{2-[3-(3,4-dimethoxybenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-(3-forfinal)methyl]dimethylamine (more polar diastereoisomer),
229) [(4-{2-[3-(3,4-dimethoxybenzyl)-[1,2,4]oxadiazol-5-yl]vinyl}-cyclohexyl)-(3-forfinal)methyl]dimethylamine (less polar diastereoisomer),
231) [(4-{2-[3-(1,5-dimethyl-1H-pyrrol-2-yl)-[1,2,4]oxadiazol-5-yl] vinyl} cyclohexyl)-(3-f is arvanil)methyl]dimethylamine,
232) {(3-forfinal)-[4-(3-phenyl-[1,2,4]oxadiazol-5-ylmethyl)-cyclohexyl] methyl} dimethylamine,
233) {(4-forfinal)-[4-(3-phenyl-[1,2,4]oxadiazol-5-ylmethyl)-cyclohexyl]methyl}dimethylamine,
234) dimethyl{phenyl-[4-(3-phenyl-[1,2,4]oxadiazol-5-ylmethyl)-cyclohexyl]methyl}amine,
235) [{4-[3-(2,4-differenl)-[1,2,4]oxadiazol-5-ylmethyl]cyclohexyl}-(3-forfinal)methyl]dimethylamine,
236) [{4-[3-(2,4-differenl)-[1,2,4]oxadiazol-5-ylmethyl]cyclohexyl}-(4-forfinal)methyl]dimethylamine,
237) ((3-forfinal)-{4-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-ylmethyl]-cyclohexyl}methyl)dimethylamine,
238) ((4-forfinal)-{4-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-ylmethyl]-cyclohexyl}methyl)dimethylamine,
239) ({4-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-ylmethyl]cyclohexyl}-phenylethyl)dimethylamine,
240) [{4-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-ylmethyl]cyclohexyl}-(3-forfinal)methyl]dimethylamine,
241) [{4-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-ylmethyl] cyclohexyl}-(4-forfinal)methyl]dimethylamine,
242) [{4-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethyl]cyclohexyl}-(4-forfinal)methyl]dimethylamine,
243) ({4-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethyl]cyclohexyl}-phenylethyl)dimethylamine,
244) [{4-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-ylmethyl]cyclohexyl}-(3-forfinal)methyl] dimethylamine,
245) [{4-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-ylmethyl]cyclohexyl}-(4-forfinal)methyl]dimethylamine,
246)({4-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-ylmethyl]illogical}-phenylethyl)dimethylamine,
247) {(3-forfinal)-[4-(3-n-tolyl-[1,2,4]oxadiazol-5-ylmethyl)-cyclohexyl]methyl}dimethylamine,
248) {(4-forfinal)-[4-(3-n-tolyl-[1,2,4]oxadiazol-5-ylmethyl)-cyclohexyl]methyl}dimethylamine,
249) dimethyl{phenyl-[4-(3-n-tolyl-[1,2,4]oxadiazol-5-ylmethyl)-cyclohexyl]methyl}amine,
250) [{4-[3-(3,4-acid)-[1,2,4]oxadiazol-5-ylmethyl]-cyclohexyl}-(3-forfinal)methyl]dimethylamine,
251) [{4-[3-(3,4-acid)-[1,2,4]oxadiazol-5-ylmethyl]-cyclohexyl}-(4-forfinal))methyl]dimethylamine,
252) ({4-[3-(3,4-acid)-[1,2,4]oxadiazol-5-ylmethyl]-cyclohexyl}phenylethyl)dimethylamine,
253) [{4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethyl]-cyclohexyl}-(3-forfinal)methyl]dimethylamine,
254) [{4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethyl]-cyclohexyl} -(4-forfinal)methyl] dimethylamine,
255) ({4-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-ylmethyl]-cyclohexyl}phenylethyl)dimethylamine,
256) {(3-forfinal)-[4-(3-m-tolyl-[1,2,4]oxadiazol-5-ylmethyl)-cyclohexyl]methyl}dimethylamine,
257) {(4-forfinal)-[4-(3-m-tolyl-[1,2,4]oxadiazol-5-ylmethyl)-cyclohexyl]methyl}dimethylamine,
258) dimethyl{phenyl-[4-(3-m-tolyl-[1,2,4]oxadiazol-5-ylmethyl)-cyclohexyl]methyl}amine,
259) [{4-[3-(4-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethyl]cyclohexyl}-(3-forfinal)methyl]dimethylamine,
260)({4-[3-(4-chlorophenyl)-[1,2,4]oxadiazol-5-ylmethyl]cyclohexyl}-phenylethyl)dimethylamine,
261) ((3-forfinal)-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-and the methyl] cyclohexyl}methyl)dimethylamine,
262) ((4-forfinal)-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethyl]cyclohexyl}methyl)dimethylamine,
263) dimethyl(phenyl-{4-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-ylmethyl]cyclohexyl}methyl)amine,
264) ((4-forfinal)-{4-[2-(3-phenyl-[1,2,4]oxadiazol-5-yl)ethyl]-cyclohexyl} methyl)dimethylamine,
265) dimethyl(phenyl-{4-[2-(3-phenyl-[1,2,4]oxadiazol-5-yl)ethyl]-cyclohexyl} methyl)amine,
266) dimethyl-(3-phenyl-1-{4-[2-(3-phenyl-[1,2,4]oxadiazol-5-yl)ethyl]-cyclohexyl}propyl)amine,
267) ((3-forfinal)-{4-[2-(3-phenyl-[1,2,4]oxadiazol-5-yl)ethyl]-cyclohexyl} methyl)dimethylamine,
268) [(4-forfinal)-(4-{2-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)methyl]dimethylamine,
269) [(4-{2-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)phenylmethyl]dimethylamine,
270) [1-(4-{2-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)-3-phenylpropyl]dimethylamine,
271) [(3-forfinal)-(4-{2-[3-(4-methoxybenzyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)methyl]dimethylamine,
272) [(4-{2-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)-(4-forfinal)methyl]dimethylamine,
273) [(4-{2-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)-phenylmethyl]dimethylamine,
274) [1-(4-{2-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)-3-phenylpropyl]dimethylamine,
275) [(4-{2-[3-(4-Chlorobenzyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)-(3-forfinal)methyl]dimethylamine,
276) [(4-{2-[3-(3-chlorophenyl)-[1,2,4] oxadiazol-5-yl]e is Il}cyclohexyl)-(4-forfinal)methyl]dimethylamine,
277) [(4-{2-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)-phenylmethyl]dimethylamine,
278) [1-(4-{2-[3-(3-chlorophenyl)-[1,2,4] oxadiazol-5-yl]ethyl}cyclohexyl)-3-phenylpropyl]dimethylamine,
279) [(4-{2-[3-(3-chlorophenyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)-(3-forfinal)methyl]dimethylamine,
280) [(4-{2-[3-(2,4-differenl)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)-(4-forfinal)methyl]dimethylamine,
281) [(4-{2-[3-(2,4-differenl)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)phenylmethyl]dimethylamine,
282) [(4-{2-[3-(2,4-differenl)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)-(3-forfinal)methyl]dimethylamine,
283) [(4-{2-[3-(3,4-acid)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)-(4-forfinal)methyl]dimethylamine,
284) [(4-{2-[3-(3,4-acid)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)phenylmethyl]dimethylamine,
285) [1-(4-{2-[3-(3,4-acid)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)-3-phenylpropyl]dimethylamine,
286) [(4-{2-[3-(3,4-acid)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)-(3-forfinal)methyl]dimethylamine,
287) ((4-forfinal)-{4-[2-(3-n-tolyl-[1,2,4]oxadiazol-5-yl)ethyl]-cyclohexyl} methyl)dimethylamine,
288) dimethyl(phenyl-{4-[2-(3-n-tolyl-[1,2,4]oxadiazol-5-yl)ethyl]-cyclohexyl} methyl)amine,
289) dimethyl-(3-phenyl-1-{4-[2-(3-n-tolyl-[1,2,4]oxadiazol-5-yl)ethyl]-cyclohexyl} propyl)amine,
290) ((3-forfinal)-{4-[2-(3-n-tolyl-[1,2,4]oxadiazol-5-yl)ethyl]-cyclohexyl} methyl)dimethylamine,
291) [(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadi the ol-5-yl]ethyl}-cyclohexyl)-(4-forfinal)methyl]dimethylamine,
292) [(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)phenylmethyl]dimethylamine,
293) [1-(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)-3-phenylpropyl]dimethylamine,
294) [(4-{2-[3-(4-tert-butylphenyl)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)-(3-forfinal)methyl]dimethylamine,
295) ((4-forfinal)-{4-[2-(3-m-tolyl-[1,2,4] oxadiazol-5-yl)ethyl]-cyclohexyl} methyl)dimethylamine,
296) dimethyl(phenyl-{4-[2-(3-m-tolyl-[1,2,4]oxadiazol-5-yl)ethyl]-cyclohexyl} methyl)amine,
297) dimethyl-(3-phenyl-1-{4-[2-(3-m-tolyl-[1,2,4]oxadiazol-5-yl)ethyl]-cyclohexyl}propyl)amine,
298) ((3-forfinal)-{4-[2-(3-m-tolyl-[1,2,4]oxadiazol-5-yl)ethyl]-cyclohexyl} methyl)dimethylamine,
299) [(4-{2-[3-(4-chlorophenyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)-(4-forfinal)methyl]dimethylamine,
300) [(4-{2-[3-(4-chlorophenyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)-phenylmethyl]dimethylamine,
301) [1-(4-{2-[3-(4-chlorophenyl)-[1,2,4] oxadiazol-5-yl]ethyl} cyclohexyl)-3-phenylpropyl]dimethylamine,
302) [(4-{2-[3-(4-chlorophenyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)-(3-forfinal)methyl]dimethylamine,
303) [(4-{2-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)-(4-forfinal)methyl]dimethylamine,
304) [(4-{2-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-yl]ethyl)-cyclohexyl)phenylmethyl]dimethylamine,
305) [1-(4-{2-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-yl]ethyl}-cyclohexyl)-3-phenylpropyl]dimethylamine,
306) [(4-{2-[3-(2,3-dichlorophenyl)-[1,2,4]oxadiazol-5-yl]ethyl-cyclohexyl)-(3-forfinal)methyl]dimethylamine,
307) [(4-forfinal)-(4-{2-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)methyl]dimethylamine,
308) dimethyl[phenyl-(4-{2-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)methyl]amine,
309) dimethyl-[3-phenyl-1-(4-{2-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-yl]ethyl}cyclohexyl)propyl] amine,
310) [(3-forfinal)-(4-{2-[3-(4-trifloromethyl)-[1,2,4]oxadiazol-5-yl]ethyl} cyclohexyl)methyl]dimethylamine,
311) (4-((3-(4-terbisil)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)(4-forfinal)-N,N-dimethylethanamine,
312) (4-((3-(4-terbisil)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)-N,N-dimethyl(phenyl)methanamine,
313) (4-((3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)(3-forfinal)-N,N-dimethylethanamine,
314) (4-((3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)(4-forfinal)-N,N-dimethylethanamine,
315) (4-((3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)diclohexal)-N,N-dimethyl(phenyl)methanamine,
316) (4-((3-(3-bromophenyl)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)(3-forfinal)-N,N-dimethylethanamine,
317) (4-((3-(3-bromophenyl)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)(4-forfinal)-N,N-dimethylethanamine,
318) (4-((3-(3-bromophenyl)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)-N,N-dimethyl(phenyl)methanamine,
319) (4-((3-(4-bromobenzyl)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)(3-forfinal)-N,N-dimethylethanamine,
320) (4-((3-(4-bromobenzyl)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)(4-forfinal)-N,N-dimethylethanamine, 321)(4-((3-(4-bromobenzyl)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)-N,N-dimethyl(phenyl)methanamine,
322) (3-forfinal)-N,N-dimethyl(4-((3-(thiophene-2-ylmethyl)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)methanamine,
323) (4-forfinal)-N,N-dimethyl(4-((3-(thiophene-2-ylmethyl)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)methanamine,
324) N,N-dimethyl(phenyl)(4-((3-(thiophene-2-ylmethyl)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)methanamine,
325) (4-((3-benzyl-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)(3-forfinal)-N,N-dimethylethanamine,
326) (4-((3-benzyl-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)(4-forfinal)-N,N-dimethylethanamine,
327) (4-((3-benzyl-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)-N,N-dimethyl(phenyl)methanamine,
328) (3-forfinal)-N,N-dimethyl(4-((3-phenethyl-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)methanamine,
329) (4-forfinal)-N,N-dimethyl(4-((3-phenethyl-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)methanamine,
330) N,N-dimethyl(4-((3-phenethyl-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)(phenyl)methanamine and
331) (4-((3-((1H-indol-3-yl)methyl)-1,2,4-oxadiazol-5-yl)methyl)cyclohexyl)(3-forfinal)-N,N-dimethylethanamine.

8. The method of obtaining derivatives of oxadiazole according to claim 1, which consists in the fact that amidoxime General formula D is subjected to interaction in the reaction medium with the addition of a base, for example NaH, saturated or unsaturated esters of the General formula And get proposed in the invention compounds:

9. A drug that has affinity for µ-opioid receptor containing at least one substituted derivative of oxadiazole according to claim 1, optionally in the form of a racemate, diastereomers, mixtures of enantiomers and/or diastereomers or of an individual diastereoisomer, bases and/or salts with physiologically compatible acids, and optionally containing acceptable additives and/or auxiliary substances.

10. The use of substituted derivative of oxadiazole according to claim 1, optionally in the form of the racemate, of the enantiomers, of the diastereomers, mixtures of enantiomers or diastereomers or of an individual enantiomer or diastereoisomer, bases and/or salts with physiologically compatible acids, for preparing a medicinal product intended for analgesic treatment, especially in acute, neuropathic or chronic pain.

11. The use of substituted derivative of oxadiazole according to claim 1, optionally in the form of the racemate, of the enantiomers, of the diastereomers, mixtures of enantiomers or diastereomers or of an individual enantiomer or diastereoisomer, bases and/or salts with physiologically compatible acids, for preparing a medicinal product intended for the treatment of depression, urinary incontinence, diarrhea, pruritus, alcohol and drug is AMI, drug dependence, aspontaneity and/or for anxiolysis.



 

Same patents:

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to pharmaceutical compositions possessing inhibitory effect with respect to MC2R-receptors, for preparing medicinal preparations as tablets, granules, capsules, suspensions, solutions or injections placed into pharmaceutically acceptable package. As active substance the composition comprises azaheterocyclic compound of general formulas (1.1.1) , (1.2.1) or (1.3.1) , wherein R1 in the general formula (1.1.1) represents substituted alkyl, aryl, heteroaryl, heterocyclyl, or R1 in the general formula (1.2.1) represents a substitute of amino-group chosen from hydrogen atom or possibly substituted lower alkyl or lower acyl; each R2, R3 and R4 represents independently of one another a substitute of cyclic system chosen from hydrogen atom, azaheterocyclyl, possibly substituted lower alkyl, possibly substituted hydroxy-group, carboxy-group, cycloalkyl; or R3 and R4 in common with carbon atoms to which they are bound form azaheterocycle, or R1 in common with nitrogen atom to which it is bound, and R3 and R4 in common with carbon atoms to which they are bound form azaheterocycle through R1, R3 and R4; R18 and R19 represent independently of one another substitutes of amino-group chosen from hydrogen atom or lower alkyl substituted with azaheterocycle as their racemates, optically active isomers or their pharmaceutically acceptable salts and/or hydrates; R20 and R21 in common with nitrogen atom to which they are bound form possibly substituted azaheterocycle. Also, invention relates to a method for preparing a pharmaceutical composition and using compounds and compositions for preparing medicinal preparations and for treatment or prophylaxis of diseases associated with enhanced activation of adrenocorticotropic hormone for compounds of general formulas (1.1.1), (1.2.1) and (1.3.1), and for using compounds for experimental investigations of indicated processes in vitro or in vivo also.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions, improved preparing method.

15 cl, 1 dwg, 4 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted oxazole derivatives of general formula I. The disclosed compounds have affinity to the µ-opioid receptor. In general formula I

, n equals 0, 1 or 2, R1 denotes a phenyl residue bonded through a C1-C3alkyl chain, R2 denotes phenyl or thienyl, each of which is unsubstituted or mono-substituted with F or Cl, R3 and R4 independently denote a saturated, branched or straight C1-C6alkyl, phenyl or a phenyl residue bonded through a C1-C3akyl chain, or R3 and R4 together form an unsubstituted five-, six- or seven-member saturated ring which can optionally contain an extra heteroatom selected from a group comprising O or NR9, where R9 denotes phenyl or a phenyl residue bonded through a C1-C3alkyl chain, any of which is unsubstituted or mono-substituted with a substitute selected from a group comprising F, Cl, Br, I and O-C1-C6alkyl, where the ring can be optionally condensed with a phenyl ring, R5 and R6 independently denote a saturated, branched or straight C1-C6alkyl, R7 and R8 independently denote a saturated, branched or straight unsubstituted C1-C6alkyl or a phenyl residue bonded through a C1-C3alkyl chain, or R7 and R8 together form an unsubstituted or mono- or disubstituted five-, six- or seven-member saturated ring, where the substitutes are selected from a group comprising C1-C6alkyl or a phenyl residue bonded through a C1-C3alkyl chain, where the ring can optionally contain an extra heteroatom selected from a group comprising S, O and NR10, where R10 denotes a phenyl or a phenyl residue bonded through a C1-C3alkyl chain, any of which can be unsubstituted or mono-substituted with O-C1-C6alkyl. The invention also relates to methods of producing the disclosed compounds, a medicinal agent containing at least one substituted oxazole derivative of formula I, use of the compounds to prepare a medicinal agent.

EFFECT: improved properties.

13 cl, 1 tbl, 150 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of general formula (I) or to their pharmaceutically acceptable salts exhibiting CCR2B antagonist activity, and to a based pharmaceutical composition. (I) where P represents phenyl optionally substituted by 1 or 2 substitutes independently selected from halogen, C1-4alkyl, cyano, trifluoromethyl, C1-4alkoxy and trifluormethylthio, and R2 has the values specified in the patent claim.

EFFECT: preparation of new compounds of general formula (I) or their pharmaceutically acceptable salts exhibiting CCR2B antagonist activity.

16 cl, 340 ex

FIELD: medicine.

SUBSTANCE: there is described application of 1-hetaryl-2-nitro-2-(3-phenyl-1,2,4-oxadiazole-5-yl)ethanes of general formula I a-m 1a, e, and R1=NO2, R2=H; 1b, f, to R1=NO2, R2=Me; 1c, g, l R1=CO2Et, R2=H; 1d, h, m R1 =CO2Et, R2 =Me; 1a-d R2 =piperidino; 1e-h R3 =1-pyrrolidinyl, 1j-m R3=morpholino as psychotropic substances.

EFFECT: substances are low-toxic and have an evident psychotropic effect on rats.

4 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: compounds can be used for treating neurological conditions, more specifically for treating neurodegenerative conditions, such as Alzheimer's disease. In a compound of formula I R2 represents H or CH2NR1R4 where R1 and R4 are independently selected from H, unsubstituted C1-6alkyl, substituted or unsubstituted C3-6 cycloalkyl, R3 represents H; substituted or unsubstituted C1-4alkyl; substituted or unsubstituted C2-4alkenyl; substituted or unsubstituted 6-members aryl condensed or uncondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl, containing 1-2 nitrogen atoms in a cycle; substituted or unsubstituted saturated or unsaturated 5 or 6-members N-containing heterocycle which can additionally contain nitrogen, oxygen or the sulphur atom condensed or ucondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl containing nitrogen in a cycle; (CH2)nR6 where n is an integer from 1 to 6, and the values of R6 and the values of other radicals are specified in the patent claim.

EFFECT: increased antiamyloidogenic action.

20 cl, 20 tbl, 6 dwg, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds which are methyl-3-azabicyclo[3.3.0]octane-7-carboxylate, N-methyl-3-azabicyclo[3.3.1]nonane-7-carboxamide, N-propyl-3-azabicyclo[3.3.1]nonane-7-carboxamide, or pharmaceutically acceptable salts thereof. The invention also relates to compounds selected from a group, a pharmaceutical composition, methods of treating or preventing central nervous system disorders, as well as use of compounds in any of claims 1-4.

EFFECT: obtaining novel biologically active compounds having activity on neural nicotinic acetylcholine receptor.

11 cl, 14 ex, 7 tbl, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of hetaryl derivatives of 2-nitro-2-(3-phenyl-1,2,4-oxadiazol-5-yl)-ethanes of general formula where, I a,d,i R1=NO2, R2=H; I b,e,k R1=NO2, R2=Me; I v,g,l R1=CO2Et, R2=H; I e,z,m R1=CO2Et, R2=Me; I a-r R3=piperidinyl; I d-z R3=1-pyrrolidinyl, I i-m R3=morpholinyl, based on a nucleophilic substitution reaction of terminal chlorine in 2-nitro-1-chloro-2-(3-phenyl-1,2,4-oxadiazol-5-yl)ethanes of formula IV with 2,5 times excess piperdine, pyrrolidine or morpholine, while heating and stirring in dried ethanol and holding at temperature 25°C for 2 days.

EFFECT: efficient method of producing hetaryl derivatives.

1 cl, 2 tbl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of the 2,9-disubstituted imidazo[1,2-a]benzimidazole family, specifically to water-soluble salts of 9-aminoethyl-substituted 2-(4-fluorophenyl)imidazo[1,2-a]benzimidazole of general formula I:

,

where NR2 = pyrrolidine-, piperidine-, morpholine-; Y=HBr, H2SO4, (CH2COOH)2 and [CH(OH)COOH]2; n=1, 2.

EFFECT: novel compounds have analgesic action.

2 cl, 2 tbl, 15 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: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I): , optical isomers of said compounds, as well as salts thereof having peroxisome proliferator-activated receptor subtype y (PPARy) modulating property. Values of R1, R2, X, Ar1 and Ar2 are given in the formula of invention.

EFFECT: preparation of compositions based on said compounds, as well as use of said compounds in cosmetic and pharmaceutical industry.

11 cl, 30 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted tetracyclic derivatives of tetrahydropyran, pyrrolidine and tetrahydrothiophene of general formula (I), their pharmaceutically acceptable addition salts, their stereochemically isomeric forms, their N-oxide forms, in which all substitutes are defined in claim 1 of the formula of invention. These compounds have binding affinity to serotonin receptors, particularly 5-HT2A and 5-HT2C receptors, and to dopamine receptors particularly D2 dopamine receptors, and have norepiniphrine reuptake inhibition properties. The invention also relates to a pharmaceutical composition containing said compounds, method of preparing said composition and use of said compounds as medicinal agents, particularly for preventing and/or treating several psychiatric and neurological disorders.

EFFECT: new compounds have useful biological properties.

12 cl, 3 tbl, 49 ex

FIELD: chemistry.

SUBSTANCE: described are novel benzofuroxanes of general formula

, where R is phenylamino-, N-[4-methoxyphenyl]amino-, N-piperidyl-, which have fungicidal and bactericidal activity and which can be used in veterinary, medicine and agriculture.

EFFECT: high efficiency of the compositions.

2 cl, 2 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel 3,4-dihydrobenzoxazine compounds of general formula [1] (where X denotes a nitrogen atom or CR3; R1 denotes a hydrogen atom or a halogen atom; R2 denotes a C1-6alkoxy group which can be substituted with 1-5 identical or different substitutes selected from a halogen atom and a hydroxyl group; and R3 denotes a halogen atom. However, R1 denotes a halogen atom when X denotes CR3). Said compounds are effective when treating diseases where activity of vanilloid receptors subtype 1 (VR1) is involved, e.g. pain.

EFFECT: more efficient use of pharmaceutical compositions based on said compounds, more effective treatment or pain killing.

19 cl, 4 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: disclosed compounds have activity and selectivity towards the GABA A receptor subunit α5. In formula I , R1 denotes hydrogen, halogen, phenyl, a 6-member heterocycyl with 2 heteroatoms selected from N, O, a 5-member heteroaryl with 1-2 heteroatoms selected from S, N, cyano, lower alkyl, -(CH2)n-C3-C7-cycloalkyl, -(CH2)n-N(R)2, -(CH2)n-O-lower alkyl or -(CH2)n-OH; equals 0, 1 or 2; R denotes hydrogen or lower alkyl; R2 denotes C3-C7-cycloalkyl, phenyl, 5-6-member heteroaryl with 1 heteroatom selected from N, S or a 9-10-member bicyclic heteroaryl with 1-3 heteroatoms selected from N, which are possibly substituted with one or more substitutes selected from a group comprising halogen, cyano, nitro, oxo group, lower alkyl, lower alkyl substituted with a halogen, lower alkoxy, lower alkoxy substituted with a halogen, -C(O)O-lower alkyl, lower alkylsulphonyl, -NRaRb, -C(O)-NRaRb, -C(O)-(6-member heterocyclyl with 2 heteroatoms selected from N, O), benzyloxy, 6-member heterocyclyl with 1-2 heteroatoms selected from N, S, O, possibly substituted with hydroxy, 1-2 oxo-groups, halogen or lower alkyl, or selected from a 5-6-member heteroaryl with 1-3 heteroatoms selected from N, possibly substituted with lower alkyl; Ra and Rb independently denote hydrogen, lower alkylsulphonyl, -C(O)H, -(CH2)n-N(R)2, -(CH2)n-O-lower alkyl, -(CH2)n-S-lower alkyl, -(CH2)n-S(O)2-lower alkyl, (5-member heteroaryl with 1 heteroatom selected from S)-sulphonyl, lower alkyl, -(CH2)n-(5-6-member heterocyclyl with 1 heteroatom selected from O, N), possibly substituted with lower alkyl, oxo group, or denotes -(CH2)n-C3-C7-cycloalkyl, -(CH2)n-(5-6-member heteroaryl with 1-2 heteroatoms selected from N), possibly substituted with an oxo group, -(CH2)n-OH, -(CO)-R', where R' denotes C3-C7-cycloalkyl, a 5-member heteroaryl with 1 heteroatom selected from S, or lower alkyl; R' denotes a phenyl or a 6-member heteroaryl with 1 heteroatom selected from N which are possibly substituted with a halogen or lower alkyl, optionally substituted with a halogen. The invention also relates to a medicinal agent containing one or more compounds of formula I and use of the disclosed compounds to prepare a medicinal agent.

EFFECT: high effectiveness of derivatives.

16 cl, 145 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof , where D denotes phenyl; n equals 0; A, B and Q denote hydrogen; Z is selected from a group comprising a bond, straight C1-3alkylene; R1 is selected from a group comprising hydrogen, C1-10alkyl, C3-8cycloalkyl, benzyl, a 6-member monocyclic, 9-10-member bicyclic aromatic carbon-containing ring system and a spiro-ring system of formula (V): where X1 and X3 denote O; and where the said alkyl, cycloalkyl or benzyl from the R1 group is optionally substituted with 1-3 substitutes selected from a group comprising C1-3alkyl, cyano, phenyl, wherein the said phenyl is optionally substituted with 1-3 substitutes selected from halogen. The invention also relates to compounds of formulae .

Values of radicals of the said compounds are given in the claim. The invention also relates to a pharmaceutical composition having ORL1 receptor or µ opioid receptor inhibiting properties, containing an effective amount of the disclosed compound, a method of curing pain and a method of modulating pharmacological response from the opioid receptor, including the ORL1 or µ opioid receptor.

EFFECT: improved method.

41 cl, 5 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula as well as separate enantiomers, diastereomers, racemic mixures and pharmaceutically acceptable salts thereof, having mitotic kinesin KSP inhibiting activity, as well as inhibitory action on tumour cells, use thereof in preparing a medicinal agent and a pharmaceutical composition based on said compounds. In said formula, R denotes Z-NR2R3, Z-OH, Ar1 and Ar2 independently denote a phenyl which, if needed, is substituted with one or more groups independently selected from: F, CI, Br, I, OH, Z denotes an alkylene having 1-6 carbon atoms which, if needed, is substituted with C1-6alkyl, and R1 assumes values given in the claim.

EFFECT: improved method.

16 cl, 3 dwg, 124 ex

Iap inhibitors // 2425838

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

, which can inhibit binding of protein Smac with apoptosis protein inhibitor (IAP).

EFFECT: improved properties of the inhibitor.

4 cl, 198 ex

Heterocompound // 2425832

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

or pharmaceutically acceptable salt thereof, where symbols assume the following values; ring denotes

or , X denotes a single bond, -CH2-, -NR3-, -O-, -S-, R1 denotes a halogen; phenyl; pyridyl; (C3-C8)cycloalkyl; or (C1-C6) alkyl or (C2-C6) alkenyl, each of which can contain a halogen, -CONH2, phenyl or (C3-C8)cycloalkyl as a substitute, R2 denotes CN, -O-(C1-C6)alkyl, -C(=O)H, halogen; or (C1-C6)alkyl, which can be substituted with a halogen or -OH, R3 can form morpholino or 1-pyrrolidinyl together with R1 and nitrogen, and when X denotes a single bond, R1 and R2 can jointly form a 5-member ring and additionally contain -(C1-C6)alkyl as a substitute, R4 denotes the following ring: , , , , , , , , , , or , where any one of the bonds in the ring is linked to an oxazole ring, R5 denotes -H, (C1-C6)alkyl, which can be substituted by not less than one group selected from: -C(=O)NRXRY, -NHRX and -ORX- (C2-C6)alkenyl-; -C(=O)H; -C(=O)NRXRY, RX and RY can be identical or different and denote -H; or (C1-C6)alkyl. The invention also relates to a pharmaceutical composition based on said compounds, having SlP1 agonist activity.

EFFECT: compounds and compositions can be used in medicine for preventing and treating rejection during organ transplant, bone marrow or tissue transplant and autoimmune diseases.

16 cl, 84 tbl, 198 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to aryl-isoxazole-4-yl-imidazole derivatives of formula I and to their pharmaceutically acceptable acid addition salts. The compounds of the present invention exhibit GABA A α5 receptor binding site activity and selectivity. In general formula I

each of R1-R3 independently represents hydrogen atom or halogen atom; R4 represents hydrogen atom, lower alkyl, C3-C7cycloalkyl, -(CH2)n-O-lower alkyl or hydroxy substituted lowest alkyl; R5 represents -(CH2)m-phenyl or -(CH2)m-(5-6-members heteroaryl with 1-2 heteroatoms independently seected from N, O) which optionally substituted by one or more substitutes selected from a group consisting of halogen atom, cyano, nitro, lower alkyl, lower alkoxy, lower alkylsulphanyl, lower alkyl substituted by halogen atom, -C(O)-lower alkyl, -C(O)-O-lower alkyl, -NH-C(O)-O-lower alkyl or -C(O)-NH-R' where R' represents the lower alkynyl or hydroxy substituted lower alkyl, or represents -(CH2)n-C3-C7-cycloalkyl, -(CH2)n-(6-members heterocyclyl with 1-2 heteroatoms selected from N, O), -(CH2)n-(5-6-members heteroaryl with 1-2 heteroatoms selected from N, O) or -(CH2)n-phenyl optionally substituted by halogen atom; R6 represents hydrogen atom, -C(O)H, -(CH2)n-O-lower alkyl, -C(O)O-lower alkyl, lower alkyl substituted by hydroxy or halogen atom, or represents C3-C7-cycloalkyl, phenyl, or represents -(CH2)n-O-CH2-phenyl optionally substituted by halogen atom or lower alkyl, or represents -(CH2)n-O-CH2-(6-members heteroaryl with 1 heteroatom selected from N) optionally substituted by lower alkyl or lower alkyl substituted by halogen atoms, or represents -(CH2)n-NH-(CH2)o-(6-members heterocyclyl with 2 heteroatoms selected from N; n means 0, 1, 2 or 3; m means 0 or 1; o means 1, 2 or 3.

EFFECT: presented preparation of a drug containing one or more compound of formula I and application of the compounds for preparing the drug.

31 cl, 168 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted oxazole derivatives of general formula I. The disclosed compounds have affinity to the µ-opioid receptor. In general formula I

, n equals 0, 1 or 2, R1 denotes a phenyl residue bonded through a C1-C3alkyl chain, R2 denotes phenyl or thienyl, each of which is unsubstituted or mono-substituted with F or Cl, R3 and R4 independently denote a saturated, branched or straight C1-C6alkyl, phenyl or a phenyl residue bonded through a C1-C3akyl chain, or R3 and R4 together form an unsubstituted five-, six- or seven-member saturated ring which can optionally contain an extra heteroatom selected from a group comprising O or NR9, where R9 denotes phenyl or a phenyl residue bonded through a C1-C3alkyl chain, any of which is unsubstituted or mono-substituted with a substitute selected from a group comprising F, Cl, Br, I and O-C1-C6alkyl, where the ring can be optionally condensed with a phenyl ring, R5 and R6 independently denote a saturated, branched or straight C1-C6alkyl, R7 and R8 independently denote a saturated, branched or straight unsubstituted C1-C6alkyl or a phenyl residue bonded through a C1-C3alkyl chain, or R7 and R8 together form an unsubstituted or mono- or disubstituted five-, six- or seven-member saturated ring, where the substitutes are selected from a group comprising C1-C6alkyl or a phenyl residue bonded through a C1-C3alkyl chain, where the ring can optionally contain an extra heteroatom selected from a group comprising S, O and NR10, where R10 denotes a phenyl or a phenyl residue bonded through a C1-C3alkyl chain, any of which can be unsubstituted or mono-substituted with O-C1-C6alkyl. The invention also relates to methods of producing the disclosed compounds, a medicinal agent containing at least one substituted oxazole derivative of formula I, use of the compounds to prepare a medicinal agent.

EFFECT: improved properties.

13 cl, 1 tbl, 150 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula (I) in which A means a group of formula or in which * specifies a carbon atom binding site of a pyridinyl ring, and # specifies the a carbon atom binding site of a phenyl ring, R1 means an amino group or a methyl-carbonylamino group, R2 means hydrogen, R3 means hydrogen, R4 means hydrogen, R5 means hydrogen or halogen, R6 means hydrogen or halogen, R7 means hydrogen, R8 means hydrogen, or one of its salts, its solvate or solvate of its salts, to a method of preparing it, to an agent for treatment and/or prevention of viral infections, on the basis of this compound. Also, the invention refers to the application of the compound of formula I for preparing the agent and to the method of viral infection control.

EFFECT: new arylsulfonamides which can are effective as antiviral agents, preferentially for cytomegalovirus control are prepared and described.

9 cl, 5 ex, 2 tbl, 1 dwg

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