Substituted oxazole derivatives with analgetic action

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

 

The text descriptions are given in facsimile form.

1. Substituted derivatives of oxazole General formula I

in which n denotes 0, 1 or 2,
R1means attached via C1-C3the alkyl chain of the phenyl residue,
R2denotes phenyl or thienyl, each of which is unsubstituted or one-deputizing F or Cl,
R3and R4independently of one another denote a saturated, branched or non-branched C1-C6alkyl, phenyl or attached via C1-C3the alkyl chain of the phenyl residue, or
R3and R4together form an unsubstituted five-, six - or semiline saturated ring, which optionally may contain an additional heteroatom, you the early group, including O or NR9where R9means phenyl or attached via C1-C3the alkyl chain of the phenyl residue, any of which is unsubstituted or one-deputizing Deputy selected from the group comprising F, Cl, Br, I and O-C1-C6alkyl, where the ring may also be optionally condensed with a phenyl ring,
R5and R6independently of one another denote a saturated, branched or non-branched C1-C6alkyl,
R7and R8independently of one another denote a saturated, branched or unbranched, unsubstituted C1-C6alkyl, or attached via C1-C3the alkyl chain is unsubstituted phenyl residue, or
R7and R8together form an unsubstituted or one - or double-substituted five-, six - or semiline saturated ring, where substituents selected from the group comprising C1-C6alkyl or attached via C1-C3the alkyl chain of the phenyl residue, where the ring may optionally contain an additional heteroatom selected from the group comprising S, O and NR10where R10means phenyl or attached via C1-C3the alkyl chain of the phenyl residue, any of which is unsubstituted or one-deputizing O-C1-C6alkyl is m,
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.

2. Substituted derivatives of oxazole according to claim 1, in which R is benzyl.

3. Substituted derivatives of oxazole according to one of claims 1 and 2, in which R2denotes phenyl, which is unsubstituted or one-deputizing atom Cl or F, or thienyl.

4. Substituted derivatives of oxazole according to claim 1, in which R3and R4independently of one another denote a saturated, branched or non-branched C1-C6alkyl, phenyl, benzyl or phenethyl, or the residues R3and R4together represent CH2CH2OCH2CH2CH2CH2NR9CH2CH2, (CH2)4-5orwhere R9means phenyl or attached via C1-C3the alkyl chain of the phenyl residue, any of which is unsubstituted or one-deputizing Deputy selected from the group comprising F, Cl, Br, I and O-C1-C6alkyl.

5. Substituted derivatives of oxazole according to claim 1, in which R3and R4independently of one another denote phenyl, ethyl or methyl, or the residues R3and R4together represent CH2CH2Och2With the 2CH2CH2NR9CH2CH2, (CH2)4-5or,
where R9denotes a benzyl, 4-F-phenyl or 4-methoxyphenyl.

6. Substituted derivatives of oxazole according to claim 1, in which R5and R6denote SN3.

7. Substituted derivatives of oxazole according to claim 1, in which R7and R8independently of one another denote a saturated, branched or non-branched C1-C6alkyl, benzyl or phenethyl, or the residues R7and R8together represent CH2CH2SCH2CH2CH2CH2Och2CH2, (CH2)5or CH2CH2NR10CH2CH2where individual hydrogen atoms can be replaced With1-C4alkyl or benzyl, where R10denotes phenyl, benzyl or phenethyl, each of which is unsubstituted or one-deputizing group co3.

8. Substituted derivatives of oxazole according to claim 1, in which R7and R8independently of one another denote methyl, ethyl, benzyl or phenethyl, or the residues R7and R8together represent CH2CH2SCH2CH2CH2CH2OCH2CH2, (CH2)4, (CH2)5or CH2CH2NR10CH2CH2where individual hydrogen atoms can be replaced by methyl or benzyl, and R 10denotes phenyl, 4-methoxyphenyl or benzyl.

9. Substituted derivatives of oxazole according to claim 1, selected from the group including
17) [{4-[(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)piperidine-1-ylmethyl]cyclohexyl}-(4-forfinal)methyl]dimethylamine,
18) ((4-benzyl-5-morpholine-4-isoxazol-2-yl)-{4-[dimethylamino-(4-forfinal)methyl]-cyclohexyl}methyl)methylphenylamine,
19) ([4-benzyl-5-(4-methylpiperidin-1-yl)oxazol-2-yl]-{4-[dimethylamino-(4-forfinal)-methyl]cyclohexyl}methyl)methylphenylamine,
20) ([4-benzyl-5-(4-methylpiperidin-1-yl)oxazol-2-yl]-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}methyl)diethylamin,
21) benzyl-[4-benzyl-2-({4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}-diethylaminomethyl)oxazol-5-yl]methylamine,
22) benzyl-{4-benzyl-2-[{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}-(methylphenylimino)methyl]oxazol-5-yl}methylamine,
23) [(4-{[4-benzyl-5-(4-benzylpiperidine-1-yl)oxazol-2-yl]piperidine-1-ylmethyl}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
24) [(4-{[4-benzyl-5-(4-methylpiperidin-1-yl)oxazol-2-yl]piperidine-1-ylmethyl}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
25) benzyl-(4-benzyl-2-{[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]piperidine-1-ylmethyl} oxazol-5-yl)methylamine,
26) [(4-{[4-benzyl-5-(4-phenylpiperazin-1-yl)oxazol-2-yl]piperidine-1-ylmethyl}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
27) {[4-benzyl-5-(4-benzylpiperidine-1-yl)oxazol-2-yl]-[4-(dimethy aminothiophene-2-ylmethyl)cyclohexyl]methyl}diethylamin,
28) {[4-benzyl-5-(4-benzylpiperazine-1-yl)oxazol-2-yl]-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]methyl}diethylamin,
29) {[4-benzyl-5-(4-methylpiperidin-1-yl)oxazol-2-yl]-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]methyl}diethylamin,
30) benzyl-(4-benzyl-2-{diethylamino-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-methyl}oxazol-5-yl)methylamine,
31) {[4-benzyl-5-(4-phenylpiperazin-1-yl)oxazol-2-yl]-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]methyl}diethylamin,
32) ({4-[[4-benzyl-5-(4-benzylpiperidine-1-yl)oxazol-2-yl]-(4-benzylpiperazine-1-yl)methyl]cyclohexyl}thiophene-2-ylmethyl)dimethylamine,
33) [(4-{[4-beisel-5-(3-methylpiperidin-1-yl)oxazol-2-yl]piperidine-1-ylmethyl}-cyclohexyl)-(4-forfinal)methyl]dimethylamine,
34) [4-benzyl-2-(diethylamino-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}-methyl)oxazol-5-yl]methylphenethylamine,
35) [4-benzyl-2-(diethylamino-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}-methyl)oxazol-5-yl]diethylamin,
36) ([4-benzyl-5-(3-methylpiperidin-1-yl)oxazol-2-yl]-{4-[dimethylamino-(4-forfinal)-methyl]cyclohexyl}methyl)diethylamin,
37) ([4-benzyl-5-(3,5-dimethylpiperidin-1-yl)oxazol-2-yl]-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}methyl)methylphenylamine,
38) {4-benzyl-2-[{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}(were-amino)methyl]oxazol-5-yl}methylphenethylamine,
39) [4-benzyl-2-({4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}p is peridin-1-ylmethyl)oxazol-5-yl]diethylamin,
40) [(4-{[4-benzyl-5-(3-methylpiperidin-1-yl)oxazol-2-yl] piperidine-1-ylmethyl}-cyclohexyl)-(4-chlorophenyl)methyl]dimethylamine,
41) ([4-benzyl-5-(3,5-dimethylpiperidin-1-yl)oxazol-2-yl]-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}methyl)diethylamin,
42) ([4-benzyl-5-(3,5-dimethylpiperidin-1-yl)oxazol-2-yl]-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}methyl)methylphenylamine,
43) {4-benzyl-2-[{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}(methylpentylamino)-methyl]oxazol-5-yl}methylphenethylamine,
44) [4-benzyl-2-((4-benzylpiperazine-1-yl)-{4-[(4-chlorophenyl)dimethylaminomethyl]-cyclohexyl}methyl)oxazol-5-yl]diethylamin,
45) [(4-{[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)oxazol-2-yl]piperidine-1-ylmethyl}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
46) (4-benzyl-2-{[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]piperidine-1-ylmethyl}oxazol-5-yl)methylpenicillin,
47) (4-benzyl-2-{[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]piperidine-1-ylmethyl}oxazol-5-yl)diethylamin,
48) ({4-[(4-benzyl-5-thiomorpholine-4-isoxazol-2-yl)piperidine-1-ylmethyl]cyclohexyl}-thiophene-2-ylmethyl)dimethylamine,
49) (4-benzyl-2-{diethylamino-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]methyl}-oxazol-5-yl)methylpenicillin,
50) (4-benzyl-2-{diethylamino-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]methyl}-oxazol-5-yl)diethylamin,
51) {[4-benzyl-5-(3-methylpiperidin-1-yl)oxazol-2-yl]-[4-(dimethylaminopropan-2-ylmethyl)is illogical]methyl}diethylamin,
52) {(4-benzyl-5-thiomorpholine-4-isoxazol-2-yl)-[4-(dimethylaminopropan-2-ylmethyl)-cyclohexyl]methyl}methylphenylamine,
53) ({4-[[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)oxazol-2-yl]-(4-benzylpiperazine-1-yl)methyl]cyclohexyl}thiophene-2-ylmethyl)dimethylamine,
54) (4-benzyl-2-{(4-benzylpiperazine-1-yl)-[4-(dimethylaminopropan-2-ylmethyl)-cyclohexyl]methyl}oxazol-5-yl)methylpenicillin,
55) ({4-[(4-benzylpiperazine-1-yl)-(4-benzyl-5-thiomorpholine-4-isoxazol-2-yl)methyl]-cyclohexyl}thiophene-2-ylmethyl)dimethylamine,
56) [(4-{2-[4-benzyl-5-(4-benzylpiperazine-1-yl)oxazol-2-yl]-2-piperidine-1-ileti}-cyclohexyl)-(4-chlorophenyl)methyl]dimethylamine,
57) [(4-{2-[4-benzyl-5-(4-methylpiperidin-1-yl)oxazol-2-yl]-2-piperidine-1-ileti}-cyclohexyl)-(4-chlorophenyl)methyl]dimethylamine,
58) benzyl-[4-benzyl-2-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]-cyclohexyl}-1-piperidine-1-retil)oxazol-5-yl]methylamine,
59) (1-[4-benzyl-5-(4-benzylpiperidine-1-yl)oxazol-2-yl]-2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}ethyl)diethylamine,
60) (1-[4-benzyl-5-(4-methylpiperidin-1-yl)oxazol-2-yl]-2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}ethyl)diethylamine,
61) benzyl-[4-benzyl-2-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}-1-diethylaminoethyl)oxazol-5-yl]methylamine,
62) [{4-[2-[4-benzyl-5-(4-benzylpiperidine-1-yl)oxazol-2-yl]-2-(4-benzylpiperazine-1-yl)ethyl]cyclohexyl}-(4-chlorophenyl)methyl]dimethylamine,
63) [{4-[2-[4-benzyl-5-(4-gasoline the piperazine-1-yl)oxazol-2-yl]-2-(4-benzylpiperazine-1-yl)ethyl]cyclohexyl}-(4-chlorophenyl)methyl]dimethylamine,
64) [{4-[2-[4-benzyl-5-(4-methylpiperidin-1-yl)oxazol-2-yl]-2-(4-benzylpiperazine-1-yl)ethyl]cyclohexyl}-(4-chlorophenyl)methyl]dimethylamine,
65) [(4-{2-[4-benzyl-5-(4-methylpiperidin-1-yl)oxazol-2-yl]-2-piperidine-1-ileti}-cyclohexyl)-(4-forfinal)methyl]dimethylamine,
66) benzyl-[4-benzyl-2-(2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}-1-piperidine-1-retil)oxazol-5-yl]methylamine,
67) (1-[4-benzyl-5-(4-benzylpiperidine-1-yl)oxazol-2-yl]-2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)diethylamine,
68) (1-[4-benzyl-5-(4-benzylpiperazine-1-yl)oxazol-2-yl]-2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)diethylamine,
69) (1-[4-benzyl-5-(4-methylpiperidin-1-yl)oxazol-2-yl]-2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)diethylamine,
70) benzyl-[4-benzyl-2-(1-diethylamino-2-{4-[dimethylamino-(4-forfinal)methyl]-cyclohexyl}ethyl)oxazol-5-yl]methylamine,
71) [{4-[2-[4-benzyl-5-(4-methylpiperidin-1-yl)oxazol-2-yl]-2-(4-benzylpiperazine-1-yl)ethyl]cyclohexyl}-(4-forfinal)methyl]dimethylamine,
72) [(4-{2-[4-benzyl-5-(4-benzylpiperidine-1-yl)oxazol-2-yl]-2-piperidine-1-ileti}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
73) [(4-{2-[4-benzyl-5-(4-benzylpiperazine-1-yl)oxazol-2-yl]-2-piperidine-1-ileti}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
74) [(4-{2-[4-benzyl-5-(4-methylpiperidin-1-yl)oxazol-2-yl]-2-piperidine-1-ileti}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
75) benzyl-(4-benzyl-2-{2-[4-(di is ethylaminomethyl-2-ylmethyl)-cyclohexyl]-1-piperidine-1-ileti}oxazol-5-yl)methylamine,
76) [(4-{2-[4-benzyl-5-(4-phenylpiperazin-1-yl)oxazol-2-yl]-2-piperidine-1-ileti}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
77) {1-[4-benzyl-5-(4-benzylpiperidine-1-yl)oxazol-2-yl]-2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}diethylamin,
78) {1-[4-benzyl-5-(4-benzylpiperazine-1-yl)oxazol-2-yl]-2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}diethylamin,
79) {1-[4-benzyl-5-(4-methylpiperidin-1-yl)oxazol-2-yl]-2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}diethylamin,
80) benzyl-(4-benzyl-2-{1-diethylamino-2-[4-(dimethylaminopropan-2-ylmethyl)-cyclohexyl]ethyl}oxazol-5-yl)methylamine,
81) ({4-[2-[4-benzyl-5-(4-benzylpiperidine-1-yl)oxazol-2-yl]-2-(4-benzylpiperazine-1-yl)ethyl]cyclohexyl}thiophene-2-ylmethyl)dimethylamine,
82) ({4-[2-[4-benzyl-5-(4-benzylpiperazine-1-yl)oxazol-2-yl]-2-(4-benzylpiperazine-1-yl)ethyl]cyclohexyl}thiophene-2-ylmethyl)dimethylamine,
83) ({4-[2-[4-benzyl-5-(4-methylpiperidin-1-yl)oxazol-2-yl]-2-(4-benzylpiperazine-1-yl)ethyl]cyclohexyl}thiophene-2-ylmethyl)dimethylamine,
84) benzyl-(4-benzyl-2-{1-(4-benzylpiperazine-1-yl)-2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}oxazol-5-yl)methylamine,
85) ({4-[2-[4-benzyl-5-(4-phenylpiperazin-1-yl)oxazol-2-yl]-2-(4-benzylpiperazine-1-yl)ethyl]cyclohexyl}thiophene-2-ylmethyl)dimethylamine,
86) [4-benzyl-2-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}-1-piperidine-1-retil)oxazol-5-yl]methylphenethylamine,
87) [4-benzyl-2-(2-{4-[(4-CHL is henyl)dimethylaminomethyl]cyclohexyl}-1-piperidine-1-retil)oxazol-5-yl]diethylamin,
88) (1-[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)oxazol-2-yl]-2-{4-[(4-chlorophenyl)-dimethylaminomethyl]cyclohexyl}ethyl)diethylamine,
89) [4-benzyl-2-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}-1-diethylamino-ethyl)oxazol-5-yl]methylphenethylamine,
90) [4-benzyl-2-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}-1-diethylamino-ethyl)oxazol-5-yl]diethylamin,
91) (1-(4-benzyl-5-thiomorpholine-4-isoxazol-2-yl)-2-{4-[(4-chlorophenyl)-dimethylaminomethyl]cyclohexyl}ethyl)diethylamine,
92) (1-(4-benzyl-5-thiomorpholine-4-isoxazol-2-yl)-2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}ethyl)methylphenylamine,
93) [4-benzyl-2-(1-(4-benzylpiperazine-1-yl)-2-{4-[(4-chlorophenyl)dimethylaminomethyl]-cyclohexyl}ethyl)oxazol-5-yl]methylphenethylamine,
94) [4-benzyl-2-(1-(4-benzylpiperazine-1-yl)-2-{4-[(4-chlorophenyl)dimethylaminomethyl]-cyclohexyl}ethyl)oxazol-5-yl]diethylamin,
95) [4-benzyl-2-(2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}-1-piperidine-1-retil)oxazol-5-yl]methylphenethylamine,
96) (1-[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)oxazol-2-yl]-2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)diethylamine,
97) [4-benzyl-2-(1-diethylamino-2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}-ethyl)oxazol-5-yl]methylphenethylamine,
98) [4-benzyl-2-(1-diethylamino-2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}-ethyl)oxazol-5-yl]diethylamin,
99) (1-(4-benzyl-5-thiomorpholine-4-isoxazol-2-yl)-2-{4-[dimethylamino-(4-FPO is phenyl)-methyl]cyclohexyl}ethyl)diethylamine,
100) (1-[4-benzyl-5-(3-methylpiperidin-1-yl)oxazol-2-yl]-2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)diethylamine,
101) (1-[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)oxazol-2-yl]-2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)methylphenylamine,
102) {4-benzyl-2-[2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}-1-(methylphenylimino)ethyl]oxazol-5-yl}methylphenethylamine,
103) {4-benzyl-2-[2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}-1-(methylphenylimino)ethyl]oxazol-5-yl}diethylamin,
104) (1-(4-benzyl-5-thiomorpholine-4-isoxazol-2-yl)-2-{4-[dimethylamino-(4-forfinal)-methyl]cyclohexyl}ethyl)methylphenylamine,
105) (1-[4-benzyl-5-(3-methylpiperidin-1-yl)oxazol-2-yl]-2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)methylphenylamine,
106) [{4-[2-[4-benzyl-5-(3-methylpiperidin-1-yl)oxazol-2-yl]-2-(4-benzylpiperazine-1-yl)ethyl]cyclohexyl}-(4-forfinal)methyl]dimethylamine,
107) [(4-{2-[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)oxazol-2-yl]-2-piperidine-1-ileti}cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
108) (4-benzyl-2-{2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-1-piperidine-1-ileti}oxazol-5-yl)methylpenicillin,
109) (4-benzyl-2-{2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-1-piperidine-1-ileti}oxazol-5-yl)diethylamin,
110) ({4-[2-(4-benzyl-5-thiomorpholine-4-isoxazol-2-yl)-2-piperidine-1-ileti]-cyclohexyl}thiophene-2-ylmethyl)dimethylamine,
111) [(4-{2-[4-benzyl-5-(3-methylpiperidin-1-yl)shall xazal-2-yl]-2-piperidine-1-ileti}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
112) {1-[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)oxazol-2-yl]-2-[4-(dimethylamino-thiophene-2-ylmethyl)cyclohexyl]ethyl}diethylamin,
113) (4-benzyl-2-{1-diethylamino-2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-ethyl}oxazol-5-yl)methylpenicillin,
114) (4-benzyl-2-{1-diethylamino-2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-ethyl}oxazol-5-yl)diethylamin,
115) {1-(4-benzyl-5-thiomorpholine-4-isoxazol-2-yl)-2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}diethylamin,
116) {1-[4-benzyl-5-(3-methylpiperidin-1-yl)oxazol-2-yl]-2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}diethylamin,
117) {1-[4-benzyl-5-(3-methylpiperidin-1-yl)oxazol-2-yl]-2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}methylphenylamine,
118) ({4-[2-(4-benzylpiperazine-1-yl)-2-(4-benzyl-5-thiomorpholine-4-isoxazol-2-yl)ethyl]-cyclohexyl}thiophene-2-ylmethyl)dimethylamine,
119) ({4-[2-[4-benzyl-5-(3-methylpiperidin-1-yl)oxazol-2-yl]-2-(4-benzylpiperazine-1-yl)ethyl]cyclohexyl}thiophene-2-ylmethyl)dimethylamine,
120) [{4-[(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)morpholine-4-ylmethyl]cyclohexyl}-(3-forfinal)methyl]dimethylamine,
121) [{4-[(4-benzyl-5-morpholine-4-isoxazol-2-yl)morpholine-4-ylmethyl]cyclohexyl}-(3-forfinal)methyl]dimethylamine,
122) [(4-{(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)-[4-(4-forfinal)piperazine-1-yl]methyl}cyclohexyl)-(3-forfinal)methyl]dimethylamine,
123) [(4-{(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)-[4-(4-methoxyphenyl)-p is perazin-1-yl]methyl}cyclohexyl)-(3-forfinal)methyl]dimethylamine,
124) [(4-{(4-benzyl-5-morpholine-4-isoxazol-2-yl)-[4-(4-methoxyphenyl)-piperazine-1-yl]methyl}cyclohexyl)-(3-forfinal)methyl]dimethylamine,
125) [{4-[(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)-(3,4-dihydro-1H-isoquinoline-2-yl)methyl]cyclohexyl}-(3-forfinal)methyl]dimethylamine,
126) [{4-[(4-benzyl-5-morpholine-4-isoxazol-2-yl)-(3,4-dihydro-1H-isoquinoline-2-yl)methyl]cyclohexyl}-(3-forfinal)methyl]dimethylamine,
127) [{4-[{4-benzyl-5-[4-(4-methoxyphenyl)piperazine-1-yl]oxazol-2-yl}-(3,4-dihydro-1H-isoquinoline-2-yl)methyl]cyclohexyl}-(3-forfinal)methyl]-dimethylamine,
128) [{4-[[4-benzyl-5-(2,6-dimethylmorpholine-4-yl)oxazol-2-yl]-(3,4-dihydro-1H-isoquinoline-2-yl)methyl]cyclohexyl}-(3-forfinal)methyl]-dimethylamine,
129) [{4-[(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)morpholine-4-ylmethyl]cyclohexyl}-(4-chlorophenyl)methyl]dimethylamine,
130) [{4-[(4-benzyl-5-morpholine-4-isoxazol-2-yl)morpholine-4-ylmethyl]cyclohexyl}-(4-chlorophenyl)methyl]dimethylamine,
131) [[4-({4-benzyl-5-[4-(4-methoxyphenyl)piperazine-1-yl]oxazol-2-yl}morpholine-4-ylmethyl)cyclohexyl]-(4-chlorophenyl)methyl]dimethylamine,
132) [(4-{[4-benzyl-5-(2,6-dimethylmorpholine-4-yl)oxazol-2-yl]morpholine-4-ylmethyl}-cyclohexyl)-(4-chlorophenyl)methyl]dimethylamine,
133) [(4-{(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)-[4-(4-forfinal)piperazine-1-yl]methyl}cyclohexyl)-(4-chlorophenyl)methyl]dimethylamine,
134) [(4-{(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)-[4-(4-methoxyphenyl)piperazine-1-yl]methyl}cyclohex who yl)-(4-chlorophenyl)methyl]dimethylamine,
135) [(4-{(4-benzyl-5-morpholine-4-isoxazol-2-yl)-[4-(4-methoxyphenyl)piperazine-1-yl]methyl}cyclohexyl)-(4-chlorophenyl)methyl]dimethylamine,
136) [(4-{[4-benzyl-5-(2,6-dimethylmorpholine-4-yl)oxazol-2-yl]-[4-(4-methoxyphenyl)-piperazine-1-yl]methyl}cyclohexyl)-(4-chlorophenyl)methyl]dimethylamine,
137) [{4-[(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)-(3,4-dihydro-1H-isoquinoline-2-yl)methyl]cyclohexyl}-(4-chlorophenyl)methyl]dimethylamine,
138) ({4-[(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)morpholine-4-ylmethyl]cyclohexyl}-thiophene-2-ylmethyl)dimethylamine,
139) ({4-[(4-benzyl-5-morpholine-4-isoxazol-2-yl)morpholine-4-ylmethyl]cyclohexyl}-thiophene-2-ylmethyl)dimethylamine,
140) {[4-({4-benzyl-5-[4-(4-methoxyphenyl)piperazine-1-yl]oxazol-2-yl}morpholine-4-ylmethyl)cyclohexyl]thiophene-2-ylmethyl}dimethylamine,
141) [(4-{[4-benzyl-5-(2,6-dimethylmorpholine-4-yl)oxazol-2-yl]morpholine-4-ylmethyl}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
142) [(4-{(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)-[4-(4-forfinal)piperazine-1-yl]methyl}cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
143) [(4-{(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)-[4-(4-methoxyphenyl)piperazine-1-yl]methyl}cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
144) [(4-{(4-benzyl-5-morpholine-4-isoxazol-2-yl)-[4-(4-methoxyphenyl)piperazine-1-yl]methyl}cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
145) [(4-{[4-benzyl-5-(2,6-dimethylmorpholine-4-yl)oxazol-2-yl]-[4-(4-methoxyphenyl)-piperazine-1-yl]methyl}cyclohexyl)thiophene-2-and the methyl]dimethylamine,
146) ({4-[(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)-(3,4-dihydro-1H-isoquinoline-2-yl)methyl]cyclohexyl}thiophene-2-ylmethyl)dimethylamine,
147) ({4-[{4-benzyl-5-[4-(4-methoxyphenyl)piperazine-1-yl]oxazol-2-yl}-(3,4-dihydro-1H-isoquinoline-2-yl)methyl]cyclohexyl}thiophene-2-ylmethyl)dimethylamine,
148) ({4-[[4-benzyl-5-(2,6-dimethylmorpholine-4-yl)oxazol-2-yl]-(3,4-dihydro-1H-isoquinoline-2-yl)methyl]cyclohexyl}thiophene-2-ylmethyl)dimethylamine,
149) [{4-[2-(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)-2-morpholine-4-ileti]-cyclohexyl}-(3-forfinal)methyl]dimethylamine,
150) [{4-[2-(4-benzyl-5-morpholine-4-isoxazol-2-yl)-2-morpholine-4-ileti]cyclohexyl}-(3-forfinal)methyl]dimethylamine,
151) [[4-(2-{4-benzyl-5-[4-(4-methoxyphenyl)piperazine-1-yl]oxazol-2-yl}-2-morpholine-4-retil)cyclohexyl]-(3-forfinal)methyl]dimethylamine,
152) [(4-{2-[4-benzyl-5-(2,6-dimethylmorpholine-4-yl)oxazol-2-yl]-2-morpholine-4-ileti}cyclohexyl)-(3-forfinal)methyl]dimethylamine,
153) [(4-{2-[4-benzyl-5-(2,6-dimethylmorpholine-4-yl)oxazol-2-yl]-2-[4-(4-forfinal)-piperazine-1-yl]ethyl}cyclohexyl)-(3-forfinal)methyl]dimethylamine,
154) [(4-{2-(4-benzyl-5-morpholine-4-isoxazol-2-yl)-2-[4-(4-methoxyphenyl)piperazine-1-yl]ethyl}cyclohexyl)-(3-forfinal)methyl]dimethylamine,
155) [(4-{2-{4-benzyl-5-[4-(4-methoxyphenyl)piperazine-1-yl]oxazol-2-yl}-2-[4-(4-methoxyphenyl)piperazine-1-yl]ethyl}cyclohexyl)-(3-forfinal)methyl]dimethylamine,
156) [(4-{2-[4-benzyl-5-(2,6-dimethylmorpholine-4-yl)oxazol-2-yl]-2-[4-(-methoxyphenyl)-piperazine-1-yl]ethyl}cyclohexyl)-(3-forfinal)methyl]dimethylamine,
157) [{4-[2-{4-benzyl-5-[4-(4-methoxyphenyl)piperazine-1-yl]oxazol-2-yl}-2-(3,4-dihydro-1H-isoquinoline-2-yl)ethyl]cyclohexyl}-(3-forfinal)methyl]dimethylamine,
158) ({4-[2-(4-benzyl-5-morpholine-4-isoxazol-2-yl)-2-morpholine-4-ileti]cyclohexyl}-thiophene-2-ylmethyl)dimethylamine,
159) {[4-(2-{4-benzyl-5-[4-(4-methoxyphenyl)piperazine-1-yl]oxazol-2-yl}-2-morpholine-4-retil)cyclohexyl]thiophene-2-ylmethyl}dimethylamine,
160) [(4-{2-[4-benzyl-5-(2,6-dimethylmorpholine-4-yl)oxazol-2-yl]-2-morpholine-4-ileti}-cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
161) [(4-{2-(4-benzyl-5-morpholine-4-isoxazol-2-yl)-2-[4-(4-forfinal)piperazine-1-yl]ethyl}cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
162) [(4-{2-{4-benzyl-5-[4-(4-methoxyphenyl)piperazine-1-yl]oxazol-2-yl}-2-[4-(4-forfinal)piperazine-1-yl]ethyl}cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
163) [(4-{2-(4-benzyl-5-pyrrolidin-1-isoxazol-2-yl)-2-[4-(4-methoxyphenyl)piperazine-1-yl]ethyl}cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
164) [(4-{2-{4-benzyl-5-[4-(4-methoxyphenyl)piperazine-1-yl]oxazol-2-yl}-2-[4-(4-methoxyphenyl)piperazine-1-yl]ethyl}cyclohexyl)thiophene-2-ylmethyl]dimethylamine,
165) [(4-{2-[4-benzyl-5-(2,6-dimethylmorpholine-4-yl)oxazol-2-yl]-2-[4-(4-methoxyphenyl)-piperazine-1-yl]ethyl}cyclohexyl)thiophene-2-ylmethyl]-dimethylamine and
166) ({4-[2-{4-benzyl-5-[4-(4-methoxyphenyl)piperazine-1-yl]oxazol-2-yl}-2-(3,4-dihydro-1H-isoquinoline-2-yl)ethyl]cyclohexyl}thiophene-2-ylmethyl)-dimethylamine.

10. The way polycrystaline derivatives oxazole according to claim 1, namely, that the aldehydes of General formula

subjected to interaction with amines of General formula

and isonitriles General formula

in an organic solvent, for example methanol or ethanol, with heating to a temperature in the range from 30 to 100°C., preferably from 40 to 80°C. for 1-10 hours

11. Drug, with affinitiy to µ-opioid receptor containing at least one substituted derivative oxazole 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, and optionally containing acceptable additives and/or auxiliary substances.

12. The use of substituted derivative oxazole according to claim 1 optionally in 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.

13. Application zamestnanosti oxazole according to claim 1 optionally in the form of a racemate, enantiomers, diastereomers, mixtures of enantiomers or diastereomers or of an individual enantiomer or diastereoisomer, bases and/or salts with physiologically compatible acids for the preparation of medicines intended for the treatment of depression, urinary incontinence, diarrhea, pruritus, alcohol and drug abuse, drug dependence, aspontaneity and/or for anxiolysis.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound of formula I ; or to its pharmaceutically acceptable salts where n represents 0, 1 or 2; Y1 represents a bond or a group C(O); Y2, represents a bond, the groups C(O) or S(O)2; R1 represents hydrogen, halogen, cyano, C1-2alkyl; R2 represents hydrogen, halogen, cyano, C1-4alkyl, C1-3alkoxy, halogen-substituted-C1-3alkyl, halogen-substituted-C1-3alkoxyl, C6aryl-C0alkyl, tetrazolyl, C3-6cycloalkyl-C0alkyl, C6-7heterocycloalkyl-C0-4alkyl where 1 or 2 carbon atoms in the ring are substituted by the groups selected from -O-, -NH-, -S(O) and -SO2-; and phenoxy groups; where said aryl and heterocycloalkyl groups R2 can be substituted by 1 or 2 radicals independently selected from C1-6alkyl; R3 represents hydrogen, halogen, cyano, C1-3alkoxy or halogen-substituted-C1-2alkyl group and a group -NR6aR6b where R6a and R6b are independently selected from hydrogen and C1-4alkyl; R4 represents hydrogen, halogen, cyano, C1-3alkoxy or halogen-substituted-C1-2alkyl group; R5 represents hydrogen or C1-3alkyl group; L represents a bivalent radical selected from ; ; ; ; ; ; ; ; ; ; ; ; and ; where asterisks the junctions of Y2 and R2; where any bivalent radical L can be substituted by 1 or 2 radicals independently selected from halogen, hydroxy, cyano, C1-4alkyl, C1-4alkyl carbonylamino, C1-4alkoxy, C1-4alkoxycarbonyl, halogen-substituted - C1-4alkyl, C1-3alkylsulfonyl, C1-3alkylsulfonyl-amino, cyano-substituted - C1-4alkyl and halogen-substituted -C1-4alkoxy radicals. Also, the invention refers to a method of Hedgehog path inhibition in a cell and to a method of undesired cell proliferation inhibition which involves the interaction of the compound of formula I and the cell.

EFFECT: new substituted imidazole derivatives which can be effective in treatment of some types of cancer are prepared.

13 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel oxadiazole compounds of formula (1) and pharmaceutically acceptable salts thereof, where R1 and R2 assume values given in the description, Y is a single bond. The invention also relates to use of said compounds as DGAT1 inhibitors, for example for treating obesity and diabetes, and a method of inhibiting.

EFFECT: high treatment efficiency.

13 cl, 65 tbl, 712 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound having structure

, radicals are as described in the formula of invention, as well as pharmaceutically-acceptable salt, prodrug, tautomer and stereoisomer thereof. The invention also relates to a composition, a set for modulating PPAR based on said compound, a method of treating a patient suffering from a disease or condition or at risk of a disease or condition, for which PPAR modulation is therapeutically useful.

EFFECT: novel compounds which are active towards PPAR are obtained and described.

41 cl, 622 ex, 8 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 3-(1,3-oxazol-4-yl)pyridin-2(1H)-one derivatives of general formula 1, , where 1a R=Br, R'=CH2OCH3, R"=CH3; 1b R=H, R'=CH2, R"=CH3; 1c R=H, R1=CH2OCH3, R"=Ph; 1d R=H, R'=CH3, R"=Ph; 1e R=Br, R=CH3, R" - fur-2-yl, which can be used as potential biologically active substances and intermediate products for synthesis of novel heterocyclic systems. The method of producing 3 -(2-substituted-1,3 -oxazol-4-yl)pyridin-2( 1 H)-ones of general formula I involves formation of a heterocyclic system of 3-(1,3-oxazol-4-yl)pyridin-2(1H)-one as a result of base-catalysed regrouping of 3-acylamino-2-furfurylfuro[2,3-b]pyridines while boiling said compounds in ethanol for 4-20 hours with addition of 6-7 mmol of potassium hydroxide per 1 mol of the initial 3-acylamino-2-furfurylfuro[2,3-b]pyridine.

EFFECT: high yield.

1 cl, 2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-quinolyloxazoles of formula (I) or pharmaceutically acceptable salts thereof, having PDE4 inhibiting properties, a pharmaceutical composition based on said compounds and use thereof to prepare a medicinal agent which inhibits inflammatory cell recruitment in respiratory tracts. , where is , X is O, R1 is alkyl, R3 and R4 are independently selected from H, R5 and R6 are independently selected from a group comprising H, alkyl, hydroxyalkyl, t equals 1 or 2. Values of substitutes R7-R11, R13 are given in the formula of invention.

EFFECT: high efficiency of using the composition.

24 cl, 1 dwg, 64 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to oxazolidinone derivatives covered by general graphic formula (I) and to their pharmaceutically acceptable salts. In formula (I) R1, R2, R3 and R4 are independently chosen from a group including -H and halogen; A is chosen from a group including R5 and R6 are independently chosen from a group including -H, -F, -CI, -Br, -OH, alkyl(C1-C6), haloalkyl(C1-C6), alkoxygroup(C1-C6); R7 is chosen from a group including -H, alkyl(C1-C6); either R7 and R5 or R6 taken together form a cycle of 2 carbon atoms and include 1 group chosen from O which in turn can be substituted by one substitute chosen from alkyl(C1-C6); R12 is chosen from a group including -H, -COR14, -CSR14, -COOR14; R14 is chosen from a group including alkyl (C1-C6), cycloalkyl(C3-C6), alkenyl(C2-C6), R16, R17 and R18 represent -H; R21 is chosen from a group including -H, alkyl(C1-C6); X is chosen from a group including O, S, and Y is chosen from a group including O, S, SO, SO2, and NR12; and optional substitutes of alkyl(C1-C6) groups can represent one or two groups chosen from the following: -OR21, -CN.

EFFECT: invention refers to methods for preparing the compounds of the invention, to application of oxazolidinone derivatives for preparing a drug for treating bacterial infections and to a pharmaceutical composition for treating bacterial infections, including a therapeutically effective amount of the compound of the invention.

36 cl, 10 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates or tautomers thereof, where substitute M is selected from groups D1 and D2, having structural formulae given below, and R1, E, A and X are as described in the formula of invention. Disclosed also are pharmaceutical compositions which contain these compounds, methods for synthesis of these compounds, intermediate compounds and synthesis methods thereof, as well as use of compounds of formula (I) in preventing or treating diseases mediated by CDK kinases, GSK-3 kinases or Aurora kinases.

EFFECT: high effectiveness of the compounds.

40 cl, 8 dwg, 18 tbl, 84 ex

Aromatic compound // 2416608

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound of general formula (1), where radicals R1, R2, X1, Y and A are as described in claim 1 of the invention. The invention also describes a method of obtaining compounds of formula (1), as well as a pharmaceutical composition based on said compounds, for treating fibrosis.

EFFECT: novel compounds with excellent collagen formation suppression, cause fewer side-effects and which are safer are obtained.

62 cl, 2717 ex, 432 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1, compounds of formula 5 and pharmaceutically acceptable salts thereof. In formulae 1 5 Y denotes -C(O)-, X denotes -N(R11)-, R1 denotes a residue of formula 1a or 1b - for formula 1 or residue of formulae 5a or 5b - for formula 5 1a 1b 5a 5b, R2 and R7 independently denote H, hydroxyl or (C1-C6)alkyl; R3 and R6 each independently denotes H, hydroxyl or (C1-C6)alkyl; R4 and R5 each independently denotes H or (C1-C6)alkyl; the rest of the radicals are described in the formula of invention. The invention also relates to separate compounds given in the formula of invention, a pharmaceutical composition having Bcl bound protein inhibiting properties, which contains a therapeutically effective amount of the disclosed compound, a method of treating a bc1 mediated disorder, involving introduction of a therapeutically effective amount of the disclosed compound and a method of treating a bc1 mediated disorder involving administration to a patient in need of treatment of an effective amount of camptothecin and therapeutically effective amount of the disclosed compound.

EFFECT: high efficiency of the composition.

84 cl, 12 tbl, 1 dwg, 217 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds described by formula in which radical and symbol values are specified in the patent claim, and their pharmaceutically acceptable salts. These compounds inhibit tompomyosine-related kinases (Trk), and can find application in treating a malignant growth, such as breast cancer, rectal cancer and prostate cancer. Also, the invention relates to a method for producing these compounds, a based pharmaceutical composition and to methods of application thereof.

EFFECT: preparation of the pharmaceutical composition which can find application in treating a malignant growth.

18 cl, 134 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: invention relates to novel compounds of the formula (I) where: A is an aryl or a 5-member heteroaryl containing a S heteroatom, possibly substituted with one or two substitutes selected from a group consisting of halogen, C1-6-alkyl or C1-6-alkoxy; n equals 1 or 2; p equals 1, 2, 3 or 4; q equals 1; r equals 0 or 1; R1 is C2-6-alkynyl substituted with aryl, or C1-6-alkyl possibly substituted with one-five substitutes selected from a group consisting of halogen, hydroxy, C1-6-alkyl, C1-6-halogenoalkyl, -OC(O)-C1-6-alkyl, C3-10-cycloalkyl, C1-6-alkoxy, possibly substituted with one, two or three halogens or aryl, aryl which is possibly substituted with a halogen or C1-6-alkoxy, 5-9-member heteroaryl, one, two or three ring atoms of which are heteroatoms selected from N or O, and the rest of the ring atoms are C atoms, possibly substituted with C1-6-alkyl, and phenoxyl, or is C1-6-alkoxy, or is C3-10-cycloalkyl which is possibly substituted with one or more Ra, or is a 5- or 6-member heterocycloalkyl containing one, two or three heteroatoms selected from nitrogen, oxygen or sulphur, possibly substituted with one or more Ra, or is an aryl possibly substituted with one or more Ra, or is a 5-10-member heteraryl, one, two or three ring atoms of which are heteroatoms selected from N, O and S, and the rest of the ring atoms are C atoms, possibly substituted with one or more Ra, or is -NRbRc, where Rb is H or C1-6-alkyl and where Rc is H, C1-6-alkyl or aryl, possibly substituted with one or more Ra, where Ra is selected from: halogen, cyano, oxo, hydroxy, halogenobenzenesulfonyl, C1-6-alkyl, possibly substituted with one, two or three substitutes selected from a group consisting of 5-10-member heterocycloalkyl and aryl, which is possibly substituted with halogen or C1-6-alkoxy, C1-6-halogenoalkyl, C1-6-halogenoalkoxy, C1-6-alkoxy, possibly substituted with aryl or 5-10-member heteroaryl, one, two or three ring atoms of which are heteroatoms selected from N, O and S, and the rest of the ring atoms are C atoms, which is possibly substituted with C1-6-alkyl, aryloxy, -NH(CO)-C1-6-alkyl, -O(CO)-C1-6-alkyl, C1-6-alkylsulfonyl, aryl, 4-6-member heterocycloalkyl containing one, two or three heteroatoms selected from nitrogen, oxygen or sulphur, possibly substituted with hydroxy, C1-6-alkyl or oxo, 5-10-member heteroaryl,one, two or three ring atoms of which are heteroatoms selected from N and O, and the rest of the ring atoms are C atoms, possibly substituted with C1-6-alkyl or oxo, and di(C1-6)alkylamino; R2 is H, OH, C1-6-alkyl or halogen; as well as their pharmaceutically acceptable salts. The invention also relates to medicine and to use of the compounds in any of paragraphs 1-24.

EFFECT: obtaining novel biologically active compounds with affinity to dopamine D3 receptor and to serotonin 5- HT2a receptor.

27 cl, 86 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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