Acetylenyl-pyrazole-pyrimidine derivatives as mglur2 antagonists

FIELD: chemistry.

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

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

55 cl, 6 dwg, 321 ex

 

The text descriptions are given in facsimile form.

1. The compound of General formula (I):
.
where either E and J are N, G is a C, and L represents N, M represents CH or M represents N, L represents CH;
or L and G are N, E is a C, and J and M are CH;
or J, G, and L are N, E is a C, and M represents CH;
or E and L are N, J and M are CH, and G is a C;
R1represents H, halogen, CF3, CHF2or C1-6-alkyl;
R2represents H, halogen, C1-6-alkyl, C1-6 -alkoxy, CF3or CHF2while R1=R2≠H;
R3represents H; -C(CH3)2HE; linear C1-4-alkyl or C3-4-cycloalkyl, possibly substituted by one or more than one Deputy, selected from the group consisting of 1-3 F and 1-2 IT;
And selected from the group consisting of phenyl or 5 - or 6-membered heteroaryl with in the loop 1-2 heteroatoms selected from nitrogen, sulfur or nitrogen and sulfur in the five-membered ring, and 1-2 nitrogen atoms in the 6-membered ring, possibly substituted by one to three Ra;
Rarepresents halogen; hydroxy; cyano; CF3; NReRf; C1-6-alkyl, possibly substituted amino or hydroxy; C1-6-alkoxy; C3-4-cycloalkyl; CO-NRbRc, SO2-NRbRc; or SO2-Rd;
Rband Rcmay be the same or different and selected from the group consisting of H;
normal or branched C1-6-alkyl, possibly substituted by one or more than one Deputy, selected from the group consisting of
F, cyano, hydroxy, C1-6-alkoxy, -NH-C(O)-O-C1-6-alkyl, amino, (C1-6-alkyl)amino, di(C1-6-alkyl)amino, geterotsiklicheskie having 6 ring atoms, of which 1-2 heteroatoms selected from nitrogen or nitrogen and oxygen, or 6-membered heteroaryl with one heteroatom nitrogen is in the ring;
or 6-membered heteroaryl with one nitrogen heteroatom in the ring;
or Rband Rctogether with the nitrogen atom to which they are attached, may form a heterocyclic ring having 6 members in the ring, of which 1-2 atom selected from nitrogen and/or oxygen, and which may be substituted C1-6-alkyl;
RdHE is a or C1-6-alkyl;
Reand Rfrepresent H, C1-6-alkyl, possibly substituted by hydroxy, -C(O)-C1-6-alkyl; S(O)2-C1-6-alkyl;
as well as its pharmaceutically acceptable salt.

2. The compound of formula I according to claim 1, where
or E and J are N, G is a C, and L represents N, M represents CH or M represents N, L represents CH;
or L and G are N, E is a C, and J and M are CH;
R1represents H, halogen, CF3, CHF2or C1-6-alkyl;
R2represents H, halogen, C1-6-alkyl, C1-6-alkoxy, CF3or CHF2while R1=R2≠H;
R3represents H, -C(CH3)2HE, linear C1-4-alkyl or C3-4-cycloalkyl, possibly substituted by one or more than one Deputy, selected from the group consisting of 1-3 F and 1-2 IT;
And selected from the group consisting of phenyl Il is 5 - or 6-membered heteroaryl, with in the loop 1-2 heteroatoms selected from nitrogen, sulfur or nitrogen and sulfur in the five-membered ring, and 1-2 nitrogen atoms in the 6-membered ring, possibly substituted by one to three Ra;
Rarepresents F, hydroxy, amino, C1-6-alkyl, possibly substituted by hydroxy, C1-6-alkoxy, C3-4-cycloalkyl, SO2-Rdor SO2-NRbRc;
RdHE is a or C1-6-alkyl;
Rband Rcmay be the same or different and selected from the group consisting of H;
normal or branched C1-6-alkyl, possibly substituted by one or more than one Deputy, selected from the group consisting of F, cyano, hydroxy, di(C1-6-alkyl)amino, geterotsiklicheskie having 6 ring atoms, of which 1-2 heteroatoms selected from nitrogen or nitrogen and oxygen, or 6-membered heteroaryl with one nitrogen heteroatom in the ring;
or
6-membered heteroaryl with one nitrogen heteroatom in the ring;
or Rband Rctogether with the nitrogen atom to which they are attached, may form a heterocyclic ring having 6 members in the ring, of which 1-2 atom selected from nitrogen and/or oxygen, and which may be substituted C1-6-alkyl;
as well as its pharmaceutically acceptable salt.

3. The compound of General formula (Ia) according to any one of claim 1 or 2:

where one of L or M represents N and the other represents CH and R1, R2, R3and a are as defined in claim 1.

4. The compound of General formula (I) according to claim 3:

where R1, R2, R3and a are as defined in claim 1.

5. The compound according to claim 4, where a is selected from the group consisting of phenyl, pyridin-2-yl, pyridin-3-yl, pyridine-4-yl, pyrimidine-4-yl, pyrimidine-5-yl, pyridazin-2-yl, pyridazin-3-yl, thiazol-2-yl, thiazol-5-yl and thiophene-2-yl, which may be substituted by one to three Ra.

6. The compound according to claim 5, where a represents phenyl.

7. The connection according to claim 6, where this compound selected from the group consisting of
3-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
N-(2-Hydroxy-1,1-dimethyl-ethyl)-3-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
N-(2-Hydroxy-1,1-dimethyl-ethyl)-2-methoxy-5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
2,4-Debtor-5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
N-tert-Butyl-3-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]feast midin-3-ylethynyl]-2,4-debtor-benzosulfimide;
3-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-hydroxy-1,1-dimethyl-ethyl)-benzosulfimide;
3-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-hydroxy-1-hydroxymethyl-1-methyl-ethyl)-benzosulfimide;
N-(2-Hydroxy-ethyl)-2-methyl-5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
2-Methyl-5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
4-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
3-(3-Methanesulfonyl-phenylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
3-[5-(3-Ethoxy-4-trifluoromethyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-hydroxy-1,1-dimethyl-ethyl)-benzosulfimide;
3-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-hydroxy-1,1-dimethyl-ethyl)-2-methoxy-benzosulfimide;
3-Fluoro-4-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
N-(2-Morpholine-4-yl-ethyl)-3-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
N-(2-Cyano-ethyl)-3-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-pyrimidin-3-ylethynyl]-benzosulfimide;
4-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-3-fluoro-benzosulfimide;
4-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
2-Fluoro-5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
1-{4-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-phenyl}-ethanol;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-2-fluoro-benzosulfimide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-2-methyl-benzosulfimide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-hydroxy-ethyl)-2-methyl-benzosulfimide;
3-Phenylethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
4-[5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
3-[5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-hydroxy-1,1-dimethyl-ethyl)-benzosulfimide;
5-[5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-hydroxy-1,1-dimethyl-ethyl)-2-methoxy-benzosulfimide;
3-[5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
5-[5-(4-Chloro-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-hydroxy-1,1-dimethyl-ethyl)-2-methoxy-bansilal is enamide;
4-[7-Cyclopropyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
5-[7-Cyclopropyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-2,4-debtor-benzosulfimide;
5-[7-Cyclopropyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-hydroxy-1,1-dimethyl-ethyl)-2-methoxy-benzosulfimide;
3-[7-Cyclopropyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
5-[7-Cyclopropyl-5-(3,4-dichloro-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-2,4-debtor-benzosulfimide;
3-[7-Cyclopropyl-5-(3,4-dichloro-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
4-[7-Cyclopropyl-5-(3,4-dichloro-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
5-[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-2,4-debtor-benzosulfimide;
3-[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
4-[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
3-[5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-hydroxy-1,1-dimethyl-ethyl)-benzosulfimide;
5-[5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-2,4-debtor-benzosulfimide;
3-[5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
3-[5-(4-Chloro-what enyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
3-[5-(4-Chloro-3-methyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-hydroxy-1,1-dimethyl-ethyl)-benzosulfimide;
N-(2-Hydroxy-1,1-dimethyl-ethyl)-3-[7-trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
4-[5-(4-Chloro-3-methyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
5-[5-(4-Chloro-3-methyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-2,4-debtor-benzosulfimide;
3-[5-(4-Chloro-3-methyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
4-[7-Trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
2,4-Debtor-5-[7-trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
3-[7-Trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
N,N-Dimethyl-4-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
3-[4-(Morpholine-4-sulfonyl)-phenylethynyl]-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
N-Methyl-4-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
N-(2-Methoxy-ethyl)-4-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
N-(2-Hydroxy-ethyl)-4-[7-trifluoromethyl-5-(4-trifluoromethyl-enyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
N-(2-Dimethylamino-ethyl)-4-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
3-[3-(Morpholine-4-sulfonyl)-phenylethynyl]-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
N-Methyl-3-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
N-(2-Methoxy-ethyl)-3-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
N-(2-Hydroxy-ethyl)-3-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
N-(2-Dimethylamino-ethyl)-3-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-dimethylamino-ethyl)-2,4-debtor-benzosulfimide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-2,4-debtor-N-(2-hydroxy-ethyl)-benzosulfimide;
4-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N,N-dimethyl-benzosulfimide;
7-Deformity-3-[4-(morpholine-4-sulfonyl)-phenylethynyl]-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
4-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-methyl-benzosulfimide;
4-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-methods the si-ethyl)-benzosulfimide;
4-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-hydroxy-ethyl)-benzosulfimide;
7-Deformity-3-[3-(morpholine-4-sulfonyl)-phenylethynyl]-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
3-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-methyl-benzosulfimide;
3-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-methoxy-ethyl)-benzosulfimide;
3-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-hydroxy-ethyl)-benzosulfimide;
3-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-(2-dimethylamino-ethyl)-benzosulfimide;
4-[7-Methyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
3-[7-Methyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
4-[5-(4-Chloro-phenyl)-7-(1-hydroxy-1-methyl-ethyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
4-[5-(4-Chloro-phenyl)-7-hydroxymethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
3-[5-(4-Methyl-piperazine-1-sulfonyl)-thiophene-2-ylethynyl]-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
5-[7-Deformity-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-2,4-debtor-benzosulfimide;
3-[7-Deformity-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]benzosulfimide;
3-[5-(4-Chloro-3-methyl-phenyl)-7-deformity-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
5-[5-(4-Chloro-3-methyl-phenyl)-7-deformity-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
4-[5-(4-Chloro-3-methyl-phenyl)-7-deformity-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
5-[5-(4-Chloro-3-methyl-phenyl)-7-deformity-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-2,4-debtor-benzosulfimide; and
4-[7-Deformity-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
{4-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-phenyl}-methanol;
(2-{5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-2,4-debtor-benzosulfimide}-ethyl)-carbamino acid tert-butyl ether;
1-{4-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-phenyl}-ethylamine;
4-[7-Deformity-5-(3-ethoxy-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
4-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzamide;
3-[7-Deformity-5-(3-ethoxy-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
2-{4-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-phenyl}-propan-2-ol;
{3-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-phenyl}-methanol;
N-{4-7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-phenyl}-ndimethylacetamide;
4-[5-(4-Chloro-phenyl)-7-methyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-benzosulfimide;
2-[5-(4-Chloro-phenyl)-3-(4-hydroxymethyl-phenylethynyl)-pyrazolo[1,5-a]pyrimidine-7-yl]-propan-2-ol;
2-{4-[5-(4-Chloro-phenyl)-7-hydroxymethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-phenyl}-propan-2-ol;
2-{4-[5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-phenyl}-propan-2-ol;
2-{4-[5-(4-Chloro-phenyl)-7-methyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-phenyl}-propan-2-ol and
4-[5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-N-methyl-benzamide.

8. The compound according to claim 5, where a represents pyridin-2-yl.

9. The compound of claim 8 where the compound is a 3-pyridin-2-ylethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine.

10. The compound according to claim 5, where a represents pyridin-3-yl.

11. The compound according to claim 1 where the compound is selected from the group consisting of
3-Pyridin-3-ylethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid amide;
3-(2-Cyclopropyl-pyridine-3-ylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
3-(6-Methyl-pyridine-3-ylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
3-(2-Cyclopropyl-pyridine-5-ylethynyl)-7-trifluoromethyl-5-(4-Tr is formetal-phenyl)-pyrazolo[1,5-a]pyrimidine;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
3-(2-Methyl-pyridine-3-ylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid bis-(2-hydroxy-ethyl)-amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1-hydroxymethyl-1-methyl-ethyl)-amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-nicotinamide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid tert-butylamide;
6-Methoxy-5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
5-(4-Chloro-phenyl)-3-pyridin-3-ylethynyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1,1-bis-hydroxymethyl-ethyl)-amide;
6-Methoxy-5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1-hydroxymethyl-1-methyl-ethyl)-amide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1-hydroxymethyl-1-methyl-ethyl)-amide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1-methyl-ethyl)-amide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid;
3-(5-Methanesulfonyl-pyridine-3-ylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamine;
3-(6-Methoxy-pyridine-3-ylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
3-(5-Methoxy-pyridine-3-ylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-ol;
5-[5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid amide;
5-[5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
5-[5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroc the and-1-hydroxymethyl-1-methyl-ethyl)-amide;
5-[5-(4-Chloro-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid amide;
5-[5-(4-Chloro-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
5-[7-Cyclopropyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
5-[7-Cyclopropyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1-hydroxymethyl-1-methyl-ethyl)-amide;
5-[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1-hydroxymethyl-1-methyl-ethyl)-amide;
3-Pyridin-3-ylethynyl-7-trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
3-Methyl-5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamine;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-3-methyl-pyridine-2-ylamine;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-6-methyl-pyridine-2-ylamine;
3-(6-Fluoro-pyridine-3-ylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamine;
5-[5-(3-Ethoxy-4-trifluoromethyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-lamina;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-3-ylamine;
Methyl-{5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-yl}-amine;
2-{5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamino}-ethanol;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-carboxylic acid amide;
5-[7-Deformity-5-(3-ethoxy-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamine;
N-(Methylsulphonyl)-N-{5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-yl}-methanesulfonamide;
N-{5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-yl}-methanesulfonamide;
2-Amino-5-[7-deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-nicotinanilide;
2-Amino-5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-nicotinanilide;
3-Trifluoromethyl-5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamine;
5-[5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-3-trifluoromethyl-pyridine-2-ylamine;
N-{5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-yl}-ndimethylacetamide;
5-[7-Deformity-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrim the Dean-3-ylethynyl]-pyridine-2-ylamine;
5-[7-Trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamine;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-carbonitrile;
5-[5-(3-Methyl-4-trifluoromethyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamine;
5-[7-Cyclopropyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamine;
5-[5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamine;
5-[5-(4-Chloro-phenyl)-7-methyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamine;
[3-(6-Amino-pyridine-3-ylethynyl)-5-(4-chloro-phenyl)-pyrazolo[1,5-a]pyrimidine-7-yl]-methanol;
5-[5-(4-Chloro-phenyl)-7-ethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamine;
5-[5-(4-Trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamine and
5-[5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridine-2-ylamine.

12. The compound according to claim 5, where a represents pyridin-4-yl.

13. The connection section 12 where the compound is 3-(2-methyl-pyridine-4-ylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine or 3-pyridine-4-ylethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine.

14. The compound according to claim 5, where a represents thiazol-2-yl or thiazol-5-yl.

15. The connection 14, where the connection selected is from the group consisting of
2-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiazole-5-sulfonic acid;
2-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiazole-5-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
2-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiazole-5-sulfonic acid amide;
2-[5-(3-Ethoxy-4-trifluoromethyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiazole-5-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
4-Methyl-2-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiazole-5-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
2-[5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiazole-5-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
2-[7-Cyclopropyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiazole-5-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
2-[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiazole-5-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
2-[5-(4-Chloro-3-methyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiazole-5-sulfonic acid amide;
2-[7-Trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiazole-5-sulfonic acid amide;
2-[7-Trifluoromethyl-5-(3-trif ormetal-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiazole-5-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
N-{5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiazol-2-yl}-ndimethylacetamide.

16. The compound according to claim 5, where a is a thiophene-2-yl.

17. The compound according to claim 1 where the compound is selected from the group consisting of
5-[5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[7-Cyclopropyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[7-Cyclopropyl-5-(3,4-dichloro-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid tert-butylamide;
5-[5-(4-Chloro-3-methyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[5-(4-Chloro-3-methyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid tert-butylamide;
5-[7-Trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]t is open-2-sulfonic acid tert-butylamide;
5-[7-Trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
5-[7-Methyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[5-(4-Chloro-phenyl)-7-(1-hydroxy-1-methyl-ethyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide; and
5-[5-(4-Chloro-phenyl)-7-hydroxymethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-morpholine-4-yl-ethyl)-amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-dimethylamino-ethyl)-amide;
5-[7-Deformity-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[7-Deformity-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid tert-butylamide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid bis-(2-hydroxy-ethyl)-amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-what hydroxy-1-hydroxymethyl-ethyl)-amide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid tert-butylamide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
5-[7-Deformity-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
5-[5-(4-Chloro-3-methyl-phenyl)-7-deformity-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid tert-butylamide;
5-[5-(4-Chloro-3-methyl-phenyl)-7-deformity-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[5-(4-Chloro-3-methyl-phenyl)-7-deformity-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
5-[7-Deformity-5-(3-ethoxy-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
7-Deformity-3-[5-(4-methyl-piperazine-1-sulfonyl)-thiophene-2-ylethynyl]-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
3-[5-(4-Methyl-piperazine-1-sulfonyl)-thiophene-2-ylethynyl]-7-trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
5-[7-Deformity-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic sour is s (2-dimethylamino-ethyl)-amide;
5-[7-Trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-dimethylamino-ethyl)-amide;
7-Deformity-3-[5-(4-methyl-piperazine-1-sulfonyl)-thiophene-2-ylethynyl]-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-dimethylamino-ethyl)-amide;
5-(4-Chloro-3-methyl-phenyl)-7-deformity-3-[5-(4-methyl-piperazine-1-sulfonyl)-thiophene-2-ylethynyl]-pyrazolo[1,5-a]pyrimidine;
5-[5-(4-Chloro-3-methyl-phenyl)-7-deformity-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-dimethylamino-ethyl)-amide;
5-[5-(4-Chloro-3-methyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-dimethylamino-ethyl)-amide;
5-(4-Chloro-3-methyl-phenyl)-3-[5-(4-methyl-piperazine-1-sulfonyl)-thiophene-2-ylethynyl]-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine;
3-[5-(Piperazine-1-sulfonyl)-thiophene-2-ylethynyl]-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
3-[5-(Piperazine-1-sulfonyl)-thiophene-2-ylethynyl]-7-trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
5-[7-Trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-amino-ethyl)-amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulphonic is islote (2-amino-ethyl)-amide;
5-[7-Deformity-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid bis-(2-hydroxy-ethyl)-amide;
5-[7-Deformity-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-hydroxy-1-hydroxymethyl-ethyl)-amide;
5-[7-Trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid bis-(2-hydroxy-ethyl)-amide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid bis-(2-hydroxy-ethyl)-amide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-hydroxy-1-hydroxymethyl-ethyl)-amide;
5-[7-Trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-hydroxy-1-hydroxymethyl-ethyl)-amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (pyridin-4-ylmethyl)-amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (pyridin-3-ylmethyl)-amide;
5-[4-Deformity-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-ylethynyl]-2,4-debtor-benzosulfimide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (pyridin-3-elmet the l)-amide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid pyridin-3-ylamide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid pyridin-4-ylamide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid pyridin-3-ylamide;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid pyridin-4-ylamide;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2,6-dimethyl-pyridine-4-ylmethyl)-amide;
5-[5-(4-Chloro-phenyl)-7-methyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[5-(4-Chloro-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[7-tert-butyl-5-(4-chloro-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[7-Methyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-hydroxy-1-hydroxymethyl-ethyl)-amide;
5-[7-Methyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-hydroxy-ethyl)-amide;
5-[5-(4-Trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid amide and
5-[5-(4-Chloro-phenyl)-7-cyclopropyl-Piras the lo[1,5-a]pyrimidine-3-ylethynyl]-thiophene-2-sulfonic acid (2-pyridin-4-yl-ethyl)-amide.

18. The compound according to claim 5, where a represents pyrimidine-4-yl or pyrimidine-5-yl.

19. Connection p, where this compound selected from the group consisting of
3-Pyrimidine-5-ylethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
3-(2-Chloro-pyrimidine-5-ylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
3-(2-Chloro-pyrimidine-4-ylethynyl)-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyrimidine-2-ylamine;
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyrimidine-2-ylamine;
N-Acetyl-N-{5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyrimidine-2-yl}-ndimethylacetamide;
N-{5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyrimidine-2-yl}-ndimethylacetamide;
5-[5-(3-Methyl-4-trifluoromethyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyrimidine-2-ylamine;
5-[5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyrimidine-2-ylamine;
5-[7-Cyclopropyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyrimidine-2-ylamine;
5-[7-Methyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyrimidine-2-ylamine;
5-[5-(4-Chloro-phenyl)-7-methyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyrimidine-2-ylamine and
5-[5-(4-chlorine is-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyrimidine-2-ylamine.

20. The compound according to claim 5, where a is pyridazin-3-yl.

21. Connection claim 20, where this compound selected from the group consisting of
6-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridazin-3-ylamine and
6-[5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyridazin-3-ylamine.

22. The compound according to claim 5, where a is pyridin-2-yl.

23. The compound according to claim 1 where the compound is selected from the group consisting of
5-[7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyrazin-2-ylamine and
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-ylethynyl]-pyrazin-2-ylamine.

24. The compound of General formula (I) according to claim 1:

where R1, R2, R3and a are as defined in claim 1.

25. The connection point 24, where a represents phenyl.

26. Connection A.25, where this compound selected from the group consisting of
2,4-Debtor-5-[4-trifluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-ylethynyl]-benzosulfimide;
4-[4-Trifluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-ylethynyl]-benzosulfimide;
5-[4-Deformity-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-ylethynyl]-thiophene-2-sulfonic acid amide and
5-[7-Deformity-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]Piri is one-3-ylethynyl]-thiophene-2-sulfonic acid (pyridin-4-ylmethyl)-amide.

27. The connection point 24, where a is a thiophene-2-yl.

28. Connection item 27 where the compound is selected from the group consisting of
5-[4-Trifluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[4-Trifluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-ylethynyl]-thiophene-2-sulfonic acid (2-dimethylamino-ethyl)-amide and
4-[4-Deformity-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-ylethynyl]-benzosulfimide.

29. The connection point 24, where a represents pyridin-3-yl.

30. The connection clause 29, where this compound selected from the group consisting of
8-Pyridin-3-ylethynyl-4-trifluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a] pyrimidine and
5-[4-Trifluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-ylethynyl]-pyridine-2-ylamine.

31. The connection point 24, where a represents pyrimidine-5-yl.

32. The compound according to claim 1 where the compound is 5-[4-trifluoromethyl-2-(4-trifluoromethyl-phenyl)-imidazo[1,5-a]pyrimidine-8-ylethynyl]-pyrimidine-2-ylamine.

33. The compound of General formula (1B) according to claim 1:

where R1, R2, R3and a are as defined in claim 1.

34. Connection p, where a represents phenyl.

35. The connection 34, where this compound selected from the group consisting of
4-[8-Trip ormetal-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-benzosulfimide;
2,4-Debtor-5-[8-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-benzosulfimide;
3-[8-Trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-benzosulfimide;
1-{4-[8-Trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-phenyl}-ethanol and
4-[8-Trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-benzamide.

36. Connection p, where a represents pyridin-3-yl.

37. Connection p, where this compound selected from the group consisting of
3-Pyridin-3-ylethynyl-8-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine;
5-[8-Trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-pyridine-2-ylamine;
5-[8-Methyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-pyridine-2-ylamine;
5-[6-(4-Chloro-phenyl)-8-methyl-imidazo[1,2-a]pyridine-3-ylethynyl]-pyridine-2-ylamine;
3-(6-Amino-pyridine-3-ylethynyl)-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-8-carbonitrile;
5-[8-Methyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
5-[8-Methyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-pyridine-3-sulfonic acid amide;
5-[6-(4-Chloro-phenyl)-8-methyl-imidazo[1,2-a]pyridine-3-ylethynyl]-pyridine-3-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide;
5-[6-(4-Chloro-phenyl)-8-methylimidazo[1,2-a]pyridine-3-ylethynyl]-pyridine-3-sulfonic acid amide;
5-[6-(4-Chloro-phenyl)-8-cyclopropyl-imidazo[1,2-a]pyridine-3-ylethynyl]-pyridine-2-ylamine;
5-[6-(4-Trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-pyridine-2-ylamine;
5-[8-Fluoro-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-pyridine-2-ylamine and
5-[6-(4-Chloro-phenyl)-8-fluoro-imidazo[1,2-a]pyridine-3-ylethynyl]-pyridine-2-ylamine.

38. Connection p, where a is a thiophene-2-yl.

39. Connection § 38, where this compound selected from the group consisting of
5-[8-Trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[6-(4-Chloro-phenyl)-8-methyl-imidazo[1,2-a]pyridine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[8-Methyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[8-Cyano-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-thiophene-2-sulfonic acid amide;
5-[6-(4-Trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-thiophene-2-sulfonic acid amide and
5-[8-Cyclopropyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-thiophene-2-sulfonic acid amide.

40. Connection p, where a represents thiazol-2-yl.

41. Connection p, where this compound is 2-[8-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-thiazole-5-sulfonic acid (2-hydroxy-1,1-dimethyl-uh who yl)-amide.

42. Connection p, where a represents pyrimidine-5-yl.

43. Connection § 42, where the connection is represented by
5-[8-Methyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-pyrimidine-2-ylamine;
5-[6-(4-Chloro-phenyl)-8-methyl-imidazo[1,2-a]pyridine-3-ylethynyl]-pyrimidine-2-ylamine;
3-(2-Amino-pyrimidine-5-ylethynyl)-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-8-carbonitrile;
5-[6-(4-Trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-pyrimidine-2-ylamine;
5-[8-Fluoro-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine-3-ylethynyl]-pyrimidine-2-ylamine and
5-[6-(4-Chloro-phenyl)-8-fluoro-imidazo[1,2-a]pyridine-3-ylethynyl]-pyrimidine-2-ylamine.

44. The compound of General formula (IB) according to claim 1:

where R1, R2, R3and a are as defined in claim 1.

45. Connection item 44, where a represents pyridin-3-yl.

46. Connection § 45, where this compound is 5-[8-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-b]pyridazin-3-ylethynyl]-pyridine-2-ylamine.

47. Connection item 44, where a is a thiophene-2-yl.

48. Connection p, where this compound is 5-[8-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-b]pyridazin-3-ylethynyl]-thiophene-2-sulfonic acid amide.

49. Connection item 44, where a represents pyrimidine-5-yl.

50. Connection § 49, where da is the amount of compound is 5-[8-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-b]pyridazin-3-ylethynyl]-pyrimidine-2-ylamine.

51. The compound of General formula (Iك) according to claim 1:
,
where R1, R2, R3and a are as defined in claim 1.

52. Connection § 51, where a represents pyridin-3-yl.

53. The compound according to claim 1, where the compound is 5-[7-cyclopropyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyridine-3-ylethynyl]-pyridine-2-ylamine or 5-[7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyridine-3-ylethynyl]-pyridine-2-ylamine.

54. A pharmaceutical composition comprising a compound according to any one of claims 1 to 53, for preparing a medicinal product, suitable for the prevention or treatment of a disease or condition in which it is involved, or plays the role of activation of mGluR2.

55. The use of compounds according to any one of claims 1 to 53 in the manufacture of medicaments for treating or preventing the disease or condition in which it is involved, or plays the role of activation of mGluR2.



 

Same patents:

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

Pyrazolepyrimidines // 2412186

FIELD: chemistry.

SUBSTANCE: compounds can be used to treat tumourous diseases, such as solid tumours, breast, lung, large intestine or prostate gland tumours. In compounds of formula

: R1 is selected from a group comprising: (a) saturated cyclic radical containing 3-8 ring atoms, from which 1-3 atoms are N atoms, which can contain up to four substitutes independently selected from a group comprising: (i) lower alkyl; and (ii) CO2R3, OR7 or S(O)nR8; (b) C6-C10aryl, which can contain up to four substitutes independently selected from a group comprising: (i) S(O)nR8, lower alkyl; OR7 and halogen; (c) C3-C8cycloalkyl, which can be substituted with NR5R6; and (d) lower alkyl, which can be substituted: (i) OR7, NR5R6; R2 is selected from a group comprising: (i) H; (ii) lower alkyl; (iii) C6-C10aryl which can be substituted with a halogen, lower alkyl, lower alkoxy group; R3 is selected from a group comprising: (i) H; (ii) lower alkyl; (iv) C3-C8cycloalkyl; R5 and R6 are independently selected from a group comprising: (i) H; (ii) lower alkyl; (iii) C3-C8cycloalkyl; (v) SO2R3; and (vi) CO2R3; R7 is selected from a group comprising H and lower alkyl; R8 is selected from a group comprising: (iii) NR5R6; (iv) lower alkyl; and n equals 1 or 2.

EFFECT: capacity to inhibit activity of cyclin-dependant kinase.

FIELD: chemistry.

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

,

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

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

32 cl, 497 tbl, 1129 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula I and to their pharmaceutically acceptable salts exhibiting inhibitory activity in relation to kinases chosen from Abl, Bcr-Abl, Bmx, BTK, b-RAF, c-RAF, CSK, cSRC, Fes, FGER3, Elt3, 1KKα, 1KKβ, JNK1α1, JNK2α2, Lck, Met, MKK4, MKK6, p70S6K, PAK2, PDGFRα, PKA, PKCα, PKD2, ROCK-II, Ros, Rsk1, SAPK2α, SAPK2β, SAPK3, SAPK4, SGK, Syk, Tie2 and TrkB. In compounds of formula I , n is equal to 1, m is equal to 0, Y1 is chosen from N and CR5, and R5 represents hydrogen, Y2 represents O, R1 represents hydrogen, R2 is chosen from hydrogen and C1-C6alkyl, R3 is chosen from a group including hydrogen, C1-C6alkyl, C1-C6alkoxy, R4 is chosen from NR5C(O)R6 and -C(O)NR5R6 where R5 is chosen from hydrogen and C1-C6 alkyl, and R6 represents phenyl optionally substituted with 1-3 radicals chosen of a group including NR3R3, halogen-substituted C1-C6alkyl, C5-C6heteroaryl(C0-C4)alkyl where heteroaryl contains 1-2 heteroatoms chosen from N and O, C5-C6heterocyclo(C0-C4)alkyl, where heterocyclyl contains 1-2 heteroatoms of N, and C5-C6heterocyclo(C0-C4)alkoxy where heterocyclyl contains 1-2 heteroatoms of N, and any heteroaryl or heterocyclyl contained in R6 is optionally substituted by 1-3 radicals independently chosen from a group including C1-C6alkyl and hydroxy(C1-C6)alkyl.

EFFECT: producing the compounds which can find application for treatment or prevention of diseases or disorders associated with abnormal or unregulated kinase activity, such as proliferative diseases, diseases of immune and nervous system.

8 cl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel chemical compound - 1-(2-isopropoxyethyl)-2-thioxo-1,2,3,5-tetrahydro-pyrrolo [3,2-d]pyrimidin-4-one and pharmaceutically acceptable salts thereof, a pharmaceutical composition containing said compounds and use thereof. Disclosed compound has myeloperoxidase enzyme inhibiting properties.

EFFECT: compounds are especially useful in treating and preventing neuroinflammatory disorders such as Parkinson's disease, cardiovascular disorders and respiratory disorders.

3 cl, 1 tbl, 33 ex

FIELD: chemistry.

SUBSTANCE: described are novel derivatives of genera formula (1) (where A denotes an oxygen or sulphur atom, -CH2- or -NH- group; R1 denotes C1-6alkyl group, possibly substituted ; R1A denotes a hydrogen atom or a C1-6 alkyl group; or these two radicals together with a carbon atom to which they are bonded form a cyclic C3-6 alkyl group; R2 denotes a C1-6 alkyl group or a C3-6 cycloalkyl group; R3 denotes an aryl group or a heteroaryl group, which can be substituted; R4 denotes a hydrogen atom; R5 denotes C1-6 alkyl group, aryl or heteroaryl group, which can be substituted), a pharmaceutical composition containing said derivatives and intermediate compounds. Said compounds (1) can inhibit bonding between SIP and its receptor Edg-1 (SIP1).

EFFECT: possibility of use in medicine.

18 cl, 2 tbl, 28 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

and pharmaceutically acceptable salts thereof, where substitutes R1-R4 are as defined in claim 1. Said compounds have 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) enzyme inhibiting activity.

EFFECT: compounds can be used in form of a pharmaceutical composition.

15 cl, 1 tbl, 94 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new imidazopyrazines of formula where Q1 and R1 have the values specified in the patent claim, and to their pharmaceutically acceptable salts showing IGF-1R enzyme inhibiting activity and applicable for treatment and/or prevention of various diseases and conditions which are sensitive to tyrosine kinase inhibition.

EFFECT: preparation of the compounds showing IGF-1R enzyme inhibiting activity.

27 cl, 294 ex

Chemical compounds // 2405780

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula (I): , in which: R1 and R2 are independently specified from hydrogen, C1-6alkyl, C1-6alkoxy and cyclopropyl; X1, X2 and X3 independently represent =N- or =CR10; R3 and R10 are independently specified from hydrogen, halogen, nitro, cyano, amino, carboxy, carbamoyl, C1-6alkyl, N-(C1-6alkyl)amino, N,N(C1-6alkyl)2amino, C1-6alkanoylamino, C1-6alkoxycarbonyl; R4 represents hydrogen; R5 and R6 are independently specified from hydrogen, hydroxy and C1-6alkyl where R5 and R6 independently can be optionally substituted in carbon atom with one or more R16 where R16 represents hydroxy; A represents a single link or C1-2alkylene; where specified C1-2alkylene can be optionally substituted with one or more R18; the ring C represents a saturated, partially saturated or unsaturated mono- or bicyclic ring containing 5 or 6 atoms in which at least one atom can be specified from nitrogen, sulphur or oxygen which can be linked with carbon or nitrogen atom where the -CH2- group can be optionally substituted with -C(O)- and ring sulphur atom can be optionally oxidised to produce S-oxide; R7 is specified from halogen and C1-6alkyl where R7 can be optionally substituted in carbon atom with halogen; n is equal to 0.1 or 2; where R7 values can be equal or different; and R18 is independently specified from halogen and hydroxy; or its pharmaceutically acceptable salt. Also the invention refers to their pharmaceutical compositions and methods for preparation and application thereof for cancer treatment.

EFFECT: preparation of new compounds which can find application for cancer treatment.

23 cl, 96 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of N-(5-[3-(thiophene-2-carbonyl)-pyrazole[1,5-a]pyrimidin-7-yl]-2-fluoro-phenyl}-N-methyl-acetamide in polymorphic modification B, in which (5-amino-1H-pyrazol-4-yl)-thiophen-2-yl-methanone reacts with N-[5-(3-dimethylamino-acryloyl)-2-fluoro-phenyl]-N-methyl-acetamide in a solvent selected from a group comprising acetic acid, propionic acid and methanoic acid at 50°C until boiling point of the mixture is reached. (C1-C4)-alcohol is then added to the obtained mixture at temperature of 40°C-80°C, after which the obtained mixture is kept for at least 30 minutes a temperature of 30°C- 55°C for initiating crystallisation. The crystalline product is then separated.

EFFECT: method of obtaining a compound in polymorphic modification B, which can be used in medicine in treating and preventing anxiety, epilepsy, sleep disorders and insomnia.

8 cl, 3 dwg, 1 tbl, 1 ex

FIELD: chemistry.

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

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

37 cl, 130 ex

FIELD: chemistry.

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

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

EFFECT: improved properties of the compound.

21 cl, 41 ex

FIELD: chemistry.

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

,

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

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

32 cl, 497 tbl, 1129 ex

Organic compounds // 2411239

FIELD: chemistry.

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

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

11 cl, 338 ex, 1 tbl

FIELD: medicine, pharmaceutics.

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

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

20 cl, 131 ex, 6 tbl

FIELD: chemistry.

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

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

23 cl, 195 ex

FIELD: chemistry.

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

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

11 cl, 49 ex

FIELD: chemistry.

SUBSTANCE: invention relates to systems containing an imidazole ring, which correspond to a substance of formula (I-1): , in which: X denotes alkylene which is facultatively interrupted with one or more -O- groups; Z denotes -C(O)-; R1-1 is selected from a group comprising: hydrogen, alkyl, phenyl, -N(CH3)(OCH3), and phenyl which is substituted with one or more halogens; R2 denotes hydrogen; alkyl; hydroxyalkyl; or alkoxyalkyl; RA and RB taken together form an open phenyl ring, or to pharmaceutically acceptable salts thereof. The invention also relates to pharmaceutical compositions for inducing biosynthesis of cytokine, which contains such substances.

EFFECT: substances can be used in medicine as immunomodulators for inducing or inhibiting biosynthesis of cytokines in animals and when treating diseases, including viral and malignant diseases.

18 cl, 37 ex

FIELD: chemistry.

SUBSTANCE: invention relates to imidazo[1,2-a]pyridine derivatives of formula in which radicals R1, R2, R3 and R4 independently denote a hydrogen atom, a halogen atom, a hydroxyl group, an amino group, a nitro group, a (C1-C12)alkyl radical which can be substituted with one or more halogen atoms or OH, and a O-(C1-C12)alkyl radicalwhich is substituted with phenyl, or two of radicals R1, R2, R3 and R4 can denote part of a phenyl ring; R5 denotes a (C1-C12)alkyl radical which can be substituted with one or more OH, methanesulphanyl, COOH or a halogen atom, (C2-C12)alkenyl radical, (C2-C12)alkynyl radical, (C6-C10)aryl radical, heteroaryl radical, which is an aromatic groupcontaining 5-10 ring members and 1-2 nitrogen or oxygen ring atoms, (C3-C10)cycloalkyl radical, (C1-C12)alkyl(C3-C10)cycloalkyl radical, (C6-C10)aryl(C1-C12)alkyl radical; radicals R6 and R7 independently denote a hydrogen atom or a (C1-C12)alkyl radical, which can be substituted with COOH, (C6-C10)aryl radical; and X denotes a group of formula - CO-NHOH or formula where U denotes a bond, CH2, V denotes O, S, W denotes NH, and Y denotes OH, or pharmaceutically acceptable salts thereof, solvates, hydrates. The invention also relates to the pharmaceutical composition based on the formula I compound and use of the formula I compound.

EFFECT: novel derivatives have peptide deformylase inhibiting activity.

16 cl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) or pharmaceutically acceptable salts thereof, having CRP receptor antagonist activity. In formula (I) R1 denotes C3-C8 alkyl, optionally substituted with hydroxyl; phenyl optionally substituted with 1-3 substitutes selected from halogen, nitro, amino, hydroxyl, C1-C4 alkoxy, C1-C4 alkyl, optionally substituted with hydroxyl or C1-C4 alkylamino; naphthyl; C-bonded 5-6-member heteroaryl with 1-2 heteroatoms selected from S, N or O, optionally substituted with C1-C4 alkyl, C1-C4 alkoxy or acetyl; N-bonded 5-member heteroaryl with 1-2 heteroatoms selected from N, optionally substituted with 1-3 substitutes selected from C1-C4 alkyl or phenyl; R2 denotes phenyl, optionally substituted with 1-3 substitutes selected from C1-C4 alkyl, halogenC1-C4alkyl, C1-C4 alkoxy, halogenC1-C4alkoxy, halogen, hydroxy, di(C1-C4 alkyl)amino or di(C1-C4 alkyl)aminocarbonyl; or a heterocyclic group which is pyridyl, optionally substituted with 1-3 substitutes selected from C1-C4 alkyl, C1-C4 alkoxy or di(C1-C4 alkyl)amino; X denotes -NR3-, where R3 denotes C1-C4 alkyl, optionally substituted with hydroxyl, carboxyl or C1-C4 alkoxycarbonyl; Y1 denotes CR3a, where R3a denotes hydrogen, halogen, cyano, hydroxy, C1-C4 alkyl, optionally substituted with hydroxyl or halogen, C1-C4 alkoxy optionally substituted with halogen; Y2 denotes CR3b, where R3b denotes hydrogen or halogen; Y3 denotes N or CR3c, where R3c denotes hydrogen; and Z denotes O or -NR4-, where R4 denotes hydrogen.

EFFECT: invention also pertains to a method of producing compounds of formula (I), a pharmaceutical composition, an inhibiting method, CRF receptor antagonists and use thereof to prepare a medicinal agent.

25 cl, 9 tbl, 163 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of tetrahydrobenzo[4,5]thiophene[2,3-d]pyrimidine derivatives, including groups of known compounds, having formula (I), for preparing a medicinal agent for treating and/or preventing diseases and disorders which require inhibition of the 17β-hydroxysteroid-dehydrogenase (17β-HSD) enzyme, more preferably which require inhbition of type 1 17β-HSD enzyme, type 2 17β-HSD enzyme or type 3 17β-HSD enzyme. In formula X denotes S or SO2, R1 and R2 are separately selected from a group which includes -C1-C12alkyl, where the alkyl can be straight, cyclic, branched or partially unsaturated, and can be optionally substituted with up to three substitutes, independently selected from a group consisting of hydroxyl, C1-C12alkoxy group, thiol, C1-C12alkylthio-, aryloxy group, -CO-aryl, -CO-OR, -O-COR, -O-CO-heteroaryl and a -N(R)2 group; where the said aryl group is phenyl or naphthyl and can be optionally substituted with up to 3 halogen atoms; where the said heteroaryl group is thienyl, furyl or pyridyl; -aryl and arylC1-C12alkyl, where the aryl is selected from a group consisting of phenyl, biphenyl, naphthyl, indanyl, indenyl and fluorenyl. Other values of substitutes are given in the formula of invention.

EFFECT: high efficiency of using novel compounds in therapy.

32 cl, 3 tbl, 7 dwg, 151 ex

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