Oxazolidinone antibiotics substituted by cyclopropyl group, and their derivatives

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) and their pharmaceutically acceptable salts. Claimed compounds have antibacterial effect. In formula (I) , X is ; R1 is i) hydrogen, ii) (CH2)nNR5R6, iv) NRCO2R, v) (C1-6alkyl)CN, CN, (CH2)pOH; Y is NR*, O or S(O)p; is phenyl or 5-6-member heteroaryl with N or S as heteroatoms; R3 is NR(C=X2)R12, NR*R12, or -(O)n-5-6-member heteroaryl with 1-3 heteroatoms selected out of N, O, which can be linked over either carbon atom or heteroatom; the indicated 5-6-member heteroaryl can be optionally substituted by 1-3 groups of R7; R4, R4a, R4b and R4c are independently i) hydrogen, ii) halogen; other radicals are defined in the claim.

EFFECT: pharmaceutical composition containing effective volume of the claimed compound.

13 cl, 1 dwg, 194 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

its enantiomer, diastereoisomer or its pharmaceutically acceptable salt, where

X represents

R1represents a

i) hydrogen,

ii) (CH2)nNR5R6,

iv) NRCO2R,

v) (C1-6alkyl)CN, CN, (CH2)pOH;

Y represents NR*, O or S(O)p;

represents phenyl, or 5-6-membered heteroaryl containing the as heteroatoms N or S;

R3represents NR(C=X2R12, NR*R12or -(O)n-5-6-membered heteroaryl containing 1-3 heteroatoms selected from N, O, which may be attached through either a carbon atom or through a heteroatom; and specified 5-6-membered heteroaryl optionally substituted by 1 to 3 groups of R7,

R4, R4a, R4band R4Sindependently represent

i) hydrogen,

ii) halogen,

r and s independently is 1-3, provided that (R4a)s, (R4)r, (R4b)rand (R4c)sdo not simultaneously denote hydrogen, and when R4a)sand (R4)ror (R4b) and (R4c)sattached to the ring Ar or HAr, the sum of r and s is less than or equal to 4;

R5and R6independently represent

i) hydrogen,

R7represents a

i) hydrogen, halogen, CN, CO2R, (CH2)0-3NHAc, HE1-6alkoxy, C1-6alkyl, hydroxy-C1-6alkyl, (CH2)1-3NHC(O)1-6alkyl, (CH2)0-3N(C1-6-alkyl)2, NHCO2R, -OCOC1-6alkyl;

ii) (CH2)namino, (CH2)nC1-6alkylamino, C1-6acylamino, C1-6dialkylamino;

X2represents O, S;

R12represents hydrogen, C1-6Ala is l, NH2OR, CHF2, CHCl2C(R)2Cl, (CH2)nCN, C1-6alkylamino,3-6cycloalkyl, 5-6-membered heteroaryl with 1-3 heteroatoms selected from N, O, where these alkyl and cycloalkyl can be substituted by 1-3 groups selected from halogen, CN, IT, and C1-6alkoxy;

R represents hydrogen or C1-6alkyl;

R* represents hydrogen, CN, C(=O)R14, (CH2)pCO2With1-6alkyl, (CH2)p-5-6-membered heteroaryl containing 1-4 heteroatoms selected from N, S, or C1-6alkyl, with the specified C1-6alkyl and heteroaryl optionally substituted by 1 to 3 groups of R7;

R14represents amino, C1-6alkyl, C3-6cycloalkyl, C1-6halogenated, (CH2)p-5-6-membered heterocyclyl containing 1-3 heteroatoms selected from N, O, (CH2)p-7-10-membered nitrogen cycle containing 2 condensed ring, where these alkyl, cycloalkyl, heterocyclyl optionally substituted by 1 to 3 groups of R7;

p is 0-2 and

n is 0,1.

2. The compound according to claim 1, where Ar and HAr radicals of the formula

independently represent a phenyl, pyridyl and r+s for a and b in the amount of <3.

3. The compound according to claim 1, where Y represents NR* and R1represents N, NR5R 6, CN or (CH2)pOH.

4. The compound according to claim 3, where R1represents CN.

5. The compound according to claim 4, where R3is a 5-6-membered heteroaryl containing 1-3 heteroatoms selected from N, O, and specified heteroaryl optionally substituted by 1-3 groups R7.

6. The compound according to claim 1 of structural formula IV

where R4, R4ahave the above meanings and R3independently represents a 1,2,3-triazole, which may contain 1-3 substituent selected from R7.

7. The connection that represents the

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

hydrochloride of 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]phenyl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

hydrochloride of 1-[5(R)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]phenyl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]-3-forfinal]-2-occaecat the one-5-ylmethyl]-1,2,3-triazole,

hydrochloride of 1-[5(R)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

hydrochloride of 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]phenyl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

the hydrochloride of N-[5(S)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]phenyl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

the hydrochloride of N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl] ndimethylacetamide,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

the hydrochloride of N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]-3-forfinal]-2-oxoa Catholicon-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-pyridine-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

the hydrochloride of N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-tert-butoxycarbonylamino-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-amino-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-tert-butoxycarbonylamino-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-amino-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-tert-butoxycarbonylamino-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

p num="70"> N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-amino-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-tert-butoxycarbonylamino-3-oxabicyclo [3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-amino-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

1-[5(R)-3-[4-[2-1(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]-1-,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl] - for 3,5-differenl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl] - for 3,5-differenl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

the hydrochloride of N-[5(S)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[4-[(1α,5α,6β-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl] - for 3,5-differenl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

the hydrochloride of N-[5(S)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl] - for 3,5-differenl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]phenyl]-3-forfinal]-2-oxoacridine-5-ylmethyl] ndimethylacetamide,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]phenyl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]for 3,5-differenl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]for 3,5-differenl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

hydrochloride of 1-[5(R)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxooxan is lidin-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]phenyl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]phenyl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-tert-butoxycarbonylamino-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-amino-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-tert-butoxycarbonylamino-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-amino-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide, S-oxide,

N-[5()-3-[4-[2-[(1α ,5α,6β)-6-cyano-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide, S,S-dioxide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S-oxide, 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S,S-dioxide, 1-[5(R)-3-[4-[2-1(1α,5α,6β)-6-cyano-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

4-[5(R)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,4-triazole,

4-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,4-triazole,

5(R)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-5-[(isoxazol-3-yl)oxy]methyloxazolidine-2-it,

5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-5-[(isoxazol-3-yl)oxy]methyloxazolidine-2-it,

5(R)-3-[4-[2-[(1α,5α,β )-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-5-[N-(tert-butoxycarbonyl)-N-(isoxazol-3-yl)]aminomethylation-2-it,

5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-5-N-(isoxazol-3-yl)]aminomethylation-2-it,

5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-5-[(isoxazol-3-yl)oxy]methyloxazolidine-2-it,

5(R)-5-[N-(tert-butoxycarbonyl)-N-(isoxazol-3-yl)aminomethyl-3-[4-[2-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]oxazolidin-2-it,

5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-5-[N-(isoxazol-3-yl)]aminomethylation-2-it,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]propionamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]divorcecare,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]cyclopropanecarboxamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-yl is etil]propionamide,

N-5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]propionamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]cyclopropanecarboxamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]cyclopropanecarboxamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]divorcecare,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]divorcecare,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-methyl-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3,6-dicyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3-[(1-tert-butoxycarbonylamino-1-yl)carbonyl]-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3-[(1-aminocyclopropane-1-yl)carbonyl]-6-is iano-3-azabicyclo(3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-[2-(phthalimid-2-yl)ethyl]-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3-(2-amino-ethyl)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-[2-(1.2,4-triazole-4-yl)ethyl]-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3-bromoacetyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-(morpholine-4-yl)acetyl-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-(5-cyano-2-yl)-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-(1,3-Dihydroxypropyl-2-yl)-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3-[((25)-1-tert-butoxycarbonylamino-2-yl)carbonyl]-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5&x003B1; ,6β)-6-cyano-3-[((2S)-pyrrolidin-2-yl)carbonyl]-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3-[((2S,4R)-1-tert-butoxycarbonyl-4-hydroxypyrrolidine-2-yl)carbonyl]-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-[((2S,4R)-4-hydroxypyrrolidine-2-yl)carbonyl]-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3-[((2S,4S)-1-tert-butoxycarbonyl-4-ftorpirimidinu-2-yl)carbonyl]-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-[((2S,4S)-4-ftorpirimidinu-2-yl)carbonyl]-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-(tert-butoxycarbonyl)amino-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

the dihydrochloride of 1-[5(R)-3-[4-[4-[(1α,5α,6β)-6-amino-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3-acetoxyacetyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]PI is one-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-hydroxyacyl-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-(2,2-dichlorocyclopentane)-1-carboxamid,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-(2,2-dichlorocyclopentane)-1-carboxamid,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-(2,2-dichlorocyclopentane)-1-carboxamid,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-(2,2-diversicolor)-1-carboxamid,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-(2,2-diversicolor)-1-carboxamid,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-(2,2-diversicolor)-1-carboxamid,

O-methyl-N-[5(S)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-metil]carbamate,

O-methyl-N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]carbamate,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3,6-dicyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-methyl-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[3-fluoro-4-[2-[(1α,5α,6β)-6-hydroxymethyl-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-4-fluoro-1,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-4-fluoro-1,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-4-fluoro-1,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-5-fluoro-1,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-yl is ethyl]-5-fluoro-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3-(4-tert-butoxycarbonylmethyl-1-yl)acetyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

the dihydrochloride of 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-(piperazine-1-yl)acetyl-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]thiophene-4-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-(piperidine-1-yl)acetyl-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-(pyrrolidin-1-yl)acetyl-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-(4-dimethylaminopyridine-1-yl)acetyl-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-(1α,5α,6β)-3-[((2S)-1-tert-butoxycarbonylamino-2-yl)carbonyl]-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-[((2S)-pyrrolidin-2-yl)carbonyl]-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-OK who oxazolidin-5-ylmethyl]-1,2,3-triazole,

hydrochloride of 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-[((2S,4R)-4-hydroxypyrrolidine-2-yl)carbonyl]-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3-[((2S,4R)-1-tert-butoxycarbonyl-4-hydroxypyrrolidine-2-yl)carbonyl]-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-12-[(1α,5α,6β)-3-[((2S,4S)-1-tert-butoxycarbonyl-4-ftorpirimidinu-2-yl)carbonyl]-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-[((2S,4S)-4-ftorpirimidinu-2-yl)carbonyl]-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-tert-butoxycarbonylamino-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-amino-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S-oxide, 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-tert-butoxycarbonylamino-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S-oxide, 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-amino-3-diabetico[3.1.0]hexane-yl]pyridine-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S,S-dioxide, 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-tert-butoxycarbonylamino-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S,S-dioxide, 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-amino-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-tert-butoxycarbonylamino-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-amino-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S-oxide, 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-tert-butoxycarbonylamino-3-diabetico[3,1 .0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S-oxide, 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-amino-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S,S-dioxide, 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-tert-butoxycarbonylamino-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S,S-dioxide, 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-amino-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

5(R)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxide boil-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-5-[(isoxazol-3-yl)oxy]methyloxazolidine-2-it,

5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-5-[(isoxazol-3-yl)oxy]methyloxazolidine-2-it,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-(4-methylpiperazin-1-yl)acetyl-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S-oxide, 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S,S-dioxide, 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S-oxide, 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

S,S-dioxide, 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-diabetico[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]-1,2 .3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-(1,3-diacetoxybiphenyl-2-yl)-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-reasol,

1-[5(R)-3-[4-[2-[(1A,5A,6β)-3-[(3S,4S)-1-azabicyclo[2.2.1]heptane-3-yl]carbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-(pyridin-2-yl)-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

5(R)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-5-[N-(tert-butoxycarbonyl)-N-(isoxazol-3-yl)aminomethylation-2-it,

5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-5-[N-(isoxazol-3-yl)]aminomethylation-2-it,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-(tetrazol-2-yl)-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]thioacetamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]thioacetamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]isothiocyanate,

O-methyl-N-[5(3)-3-[4-[2-[(1α,5α,6β)-3-tert-butoxycarbonyl-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]THIOCARBAMATE,

O-methyl-N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]THIOCARBAMATE,

or its pharmaceutically acceptable salt.

8. The connection according to claim 7, which is a

1-[5(R)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]phenyl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-amino-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl] - for 3,5-differenl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-reasol,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl] - for 3,5-differenl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl] - for 3,5-differenl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

N-[5(S)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]phenyl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

1-[5(R)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]phenyl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

4-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,4-triazole,

5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-5-[(isoxazol-3-yl)oxy]methyloxazolidine-2-it,

5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-5-[N-(isoxazol-3-yl)]aminomethylation-2-it,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]cyclopropanecarboxamide,

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]divorcecare,

1-[5(R)-3-[4-[2-[(1α,5α,6β)-3-[(1-aminocyclopropane-1-yl)carbonyl]-6-is iano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

or its pharmaceutically acceptable salt.

9. The connection of claim 8, which is a

hydrochloride of 1-[5(R)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

hydrochloride of 1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

the hydrochloride of N-[5(S)-3-[4-[4-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]phenyl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

the hydrochloride of N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

the hydrochloride of N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]-3-forfinal]-3-forfinal]-2-oxoacridine-5-ylmethyl]acetamide

the hydrochloride of N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]ndimethylacetamide.

10. The connection that represents the

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-azabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

or its pharmaceutically acceptable salt.

11. The connection that represents the

1-[5(R)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-about sabillo[3.1.0]hexane-6-yl]pyridin-5-yl]-3-forfinal]-2-oxoacridine-5-ylmethyl]-1,2,3-triazole,

or its pharmaceutically acceptable salt.

12. The connection that represents the

N-[5(S)-3-[4-[2-[(1α,5α,6β)-6-cyano-3-oxabicyclo[3.1.0]hexane-6-yl]pyridin-5-yl]phenyl]-2-oxoacridine-5-ylmethyl]ndimethylacetamide,

or its pharmaceutically acceptable salt.

13. Pharmaceutical composition having antibacterial properties, containing an effective amount of a compound according to claim 1 in combination with a pharmaceutically acceptable carrier.

Priority items:

02.07.2003 according to claims 7 and 8;

24.02.2004 on PP-13.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention concerns benzothiazole derivatives of general formula (1) and their pharmaceutically acceptable acid-additive salts as adenosine receptor ligands with high affinity to A2A adenosine receptor, and based medicine. Compounds can be applied in treatment and prevention of diseases mediated by A2A adenosine receptors, such as Alzheimer's disease, some depressive states, toxicomania, Parkinson's disease. In general formula (I) , R is C5-C6-cycloalkyl non-substituted or substituted by hydroxy group, or is ethyl or isobutyl, or is tetrahydropyrane-4-yl or -(CH2)n-tetrahydrofurane-2 or 3-yl or is 5-hydroxybicyclo[2,2,1]hept-2-yl; X is CH or N; n is 0 or 1.

EFFECT: enhanced efficiency of composition and treatment method.

12 cl, 2 dwg, 14 ex

FIELD: chemistry.

SUBSTANCE: invention concerns method of treatment, alleviation and/or prevention of neurological state, particularly neurodegenerative disorders, involving administration of effective quantity of compound with formula I: . Also invention concerns application of compound of the formula I as neurotherapeutical, neuroprotective or antimyloid agent, pharmaceutical or veterinary composition for treatment, alleviation and/or prevention of neurological states, and compounds of the formula I on the following additional terms: (b) if R3, R and R' are H, and R2 is (CH2)2NR9R10, then both R9 and R10 are not ethyl or methyl; (c) if R3, R and R' are H, and R2 is (CH2)2NR9R10, then both R9 and R10 are not hydrogen or ethyl; (d) if R3, R and R' are H, and R2 is NR11R12, then both R11 and R12 are not hydrogen; (e) if R3, R and R' are H, and R2 is COR6, then R6 is not H, OH or CH2Cl; (f) if R3, R and R' are H, and R2 is not CH3 or CH2Cl; (g) if R3, R and R' are H, and R2 is HCNN R9R10, then both R9 and R10 are not H.

EFFECT: efficient treatment, alleviation and prevention of neurological state.

24 cl, 14 tbl, 21 ex, 14 dwg

FIELD: chemistry.

SUBSTANCE: invention concerns compounds of the formula I , where R0 is 1) monocyclic 6-14-member aryl, where aryl is independently mono-, di- or trisubstituted by R8, 2) heterocyclyl out of group of benzothiazolyl, indazolyl, pyridyl, where the said heterocyclyl is independently non-substituted or mono-, di- or trisubstituted by R8, and other radicals referred to in point 1 of the claim; R8 is halogen; on condition that R8 is at least one halogen atom if R0 is monocyclic 6-14-member aryl; substructure in the formula I is 4-8-member saturated, partly non-saturated or aromatic cyclic group including 0, 1 heteroatom selected out of nitrogen or sulfur, and is non-substituted or substituted 1, 2, 3 times by R3; Q is -(C0-C2)alkylene-C(O)NR10-, methylene; R1 is hydrogen atom, -(C1-C4)alkyl, where alkyl is non-substituted or substituted one to three times by R13; R2 is a direct link; R1-N-R2-V can form 4-8-member cyclic group selected out of piperazine or piperidine group; R14 is halogen, =O, -(C1-C8)alkyl, -CN; V is 1) 6-14-member aryl, where aryl is independently non-substituted or mono-, di- or trisubstituted by R14, and other radicals referred to in point 1 of the claim; G is direct link, -(CH2)m-NR10, where m is 0 and R10 is hydrogen, -(CH2)m-C(O)-(CH2)n-, where m is 0 or 1, and n is 0, -(CH2)m-C(O)-NR10-(CH2)n-, where m is 0 or 1, and n is 0, 1 or 2, -(CH2)m-, where m is 1; M is 1) hydrogen atom, 2) 6-14-member aryl, and other radicals referred to in point 1 of the claim; R3 is 1) hydrogen atom, 2) halogen atom, 3) -(C1-C4)alkyl, where alkyl is non-substituted, and other radicals referred to in point 1 of the claim; R11 and R12 are independently the same or different and are 1) hyfrogen atom, 2) -(C1-C6)alkyl, where alkyl is non-substituted or monosubstituted by R13, and other radicals referred to in point 1 of the claim; or R11 and R12 can form 4-8-member monocyclic heterocyclic ring together with nitrogen atoms to which they are linked, and beside the nitrogen atom the ring can include one or two similar or different ring heteroatoms selected out of oxygen, sulfur and nitrogen; where the said heterocyclic ring is independently non-substituted or mono-, disubstituted by R13; R13 is halogen, =O, -OH, -CF3, -(C3-C8)cycloalkyl, -(C0-C3)alkylene-O-R10; R10 is hydrogen, -(C1-C6)alkyl; R15 and R16 are independently hydrogen, -(C1-C6)alkyl; R17 is -(C1-C6)alkyl, -(C3-C8)cycloalkyl; in all stereoisomer forms and their mixes at any ratio, and physiologically tolerable salts. Compounds of the formula I are reversible inhibitors of enzyme factor Xa (FXa) and/or factor VIIa (FVIIa) of blood clotting, and can be generally applied in states accompanied by undesirable factor Xa and/or factor VIla activity, or supposing factor Xa and/or factor VIla inhibition for treatment or prevention. In addition, invention concerns methods of obtaining compounds of the formula I, their application as agents in pharmaceutical compositions.

EFFECT: obtaining compounds applicable as agents in pharmaceutical compositions.

19 cl, 1 tbl, 169 ex

FIELD: chemistry.

SUBSTANCE: description is given of a piperidine derivative with general formula (I) , where L represents CH or N; M represents CH or N; under the condition that, L and M both do not represent CH; R1 represents phenyl (possibly substituted with a halogen or C1-4alkyl), S(O)2(C1-4alkyl), S(O)2(C1-4fluroalkyl), S(O)2phenyl (possibly substituted with CF3 or OCF3), benzyl, benzoyl (possibly substituted with a halogen) or C(O)NHphenyl (possibly substituted with a halogen); R2 represents phenyl, possibly substituted with a halogen; R3 represents hydrogen or C1-4alkyl; R4 represents methyl or ethyl; R5 represents phenyl-NH, phenyl (C1-2alkyl), phenyl(C1-C2)alkyl-NH or pyridyl(C1-2alkyl). The phenyl can be substituted with a halogen, cyano, C1-4alkyl, C1-4alkoxy, S(O)k(C1-4alkyl) or S(O)2NR8R9; k is equal to 2; R8 and R9 represent hydrogen or its pharmaceutical salts. The compound is a modulator of the activity of the CCR5 receptor. Description is given of the method of obtaining the compound, where L represents N, and the pharmaceutical composition based on a compound with formula (I).

EFFECT: design of a method of obtaining a compound, where L represents N, and a pharmaceutical composition based a compound with formula (I).

7 cl, 7 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to derivatives of 4-[1-arylimidazol-4-yl ethynyl]-2-alkylpyridine and 4-[1-heteroarylimidazol-4-yl ethynyl]-2-alkylpyridine of general formula I having general formula I in which R1 stands for C1-C6alkyl; R2 stands for C1-C6alkyl or C3-C12cycloalkyl; R3 stands for aryl or heteroaryl, where aryl or heteroaryl are unsubstituted or contain substituents, selected from group, including halogen, C1-C6alkyl, S-C1-C6alkyl, C1-C6alkylhlogen, C1-C6alkoxygroup, halogen- C1-C6lkoxygroup, C3-C12cycloalkyl, C2-C11heterocycloakyl, C1-C6alkylminogroup,di- C1-C6alkylaminogroup, C1-C6alkoxyaminogroup, (C1-C6 alkoxy) C1-C6alkylaminogroup, C3-C12cycloalkylaminogroup, benzylaminogroup and cyanogroup, where said "aryl" represents phenyl, and said " heteroaryl" represents aromatic 5- or 6- member ring or one or more condensed rings, containing one or more heteroatoms, selected from group, which includes nitrogen, oxygen and sulfur; and R4 stands for hydrogen, C(O)H or CH2R5 , where R stands for hydrogen or its pharmaceutically acceptable salt. Invention also relates to method of obtaining compounds of general formula I, their application as anxiolytic, to based on them pharmaceutical composition and method of treatment or prevention of disorders, fully or partly mediated by metabotropic glutamate receptor of subtype 5.

EFFECT: obtaining novel heterocyclic compounds possessing useful biological properties.

15 cl, 18 ex

FIELD: medicine; pharmacology.

SUBSTANCE: compounds of this invention possess properties of protein kinase inhibitors. In the general formula p means integer within 0 to 2; R and R1 mean O; A1 and A2 mean single bond, (C1-C6)alkyl; B2 means monocyclic or bicyclic, saturated or unsaturated heterocyclic radical including 1 to several identical or different heteroatoms, chosen among O, S, N and NR7, probably substituted with one or several identical or different substitutes.

EFFECT: inhibiting effect on protein kinase, effective application of compounds of formula for medical products.

49 cl, 1 tbl, 6 dwg, 334 ex

FIELD: chemistry.

SUBSTANCE: in general formula I

R1 is phenyl or 5-6-member heterocycle, containing one N atom and/or one O atom; R2 is imidazole or annelated imidazole, selected from group, including a), b), c), d) and e); and R3 stands for hydrogen, phenyl, 2,3-dihydrobenzo[1,4]dioxin-6-yl, benzo[b]thiophen-3-yl, 3-methylbenzo[b] thiophen-2-yl, thiophen-2-yl or thiophen-2-ylmethyl, R4 is hydrogen or lower alkyl, R5 is hydrogen, lower alkyl, halogen, morpholinyl, -NR'R", piperydinyl, optionally substituted with hydroxy-group, or is pyrrolidin-1-yl; R6 is hydrogen or -(CH2)nO-lower alkyl, R7 is hydrogen, -C(O)O-lower alkyl, -C(O)-C6H4-halogen, -C(O)-C6H4-lower alkyl, -C(O)-lower alkyl, -C(O)-cycloalkyl, -C(O)-NR'R", -C(O)-(CH2)nO-lower alkyl, -S(O)2-lower alkyl, -(CH2)nO-lower alkyl, -C(O)-pyridin-4-yl, whose ring can contain as substituents lower alkyl, halogen-lower alkyl or pyrrolidin-1-ylmethyl or is -(CH2)n-C(O)-NR'R"; R'/R" independently on each other stand for hydrogen, lower alkyl or -(CH2)n-tetrahydropyran-4-yl, X is -CH2-, -NR'''- or -O-; R''' is hydrogen, -C(O)-lower alkyl, -C(O)O-lower alkyl, -C(O)-C6H4CH3 or benzyl; n is 1 or 2.

EFFECT: increase of composition and treatment method efficiency.

14 cl, 56 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to new derivatives of 2-pyridinecarboxamide and their pharmaceutical salts, which have glucokinase activating properties. In formula (I): D represents O or S; R2 and R3 each represents a hydrogen atom; formula (II) represents triazole group, imidazole group, thiazole group and pyridine group, which can have in the ring, 1 or 2 substitutes; formula (III) represents a thiazole group, thiadiazole group, isoxazolyl group, pyrazine group, pyridothiazolyl group or pyridyl group, ring B can have 1 or 2 substitutes. The invention also relates to pharmaceutical compositions based on the invented compounds.

EFFECT: new derivatives can be used for treating such diseases as sugar diabetes.

19 cl, 5 tbl, 165 ex

FIELD: chemistry.

SUBSTANCE: new compounds with formula Ia are proposed, where: P represents pyridine or pyrimidine; R1 represents hydrogen; R2 is chosen from halogen, nitro, C0-6alkylheteroaryl, (CO)OR4, trifluoromethyl, C0-6alkylcyano, C0-6alkylNR4R5, OC1-6alkylNR4R5, C0-6alkylCONR4R5, C0-6alkyl(SO2)NR4R5 and X1R6 group, where X1 represents a direct link; R6 represents a 5- or 6-member heterocyclic group, containing one or two heteroatoms, independently chosen from N, O, and S, for which the given heterocyclic group can be unsaturated and can be substituted with by one substitute, chosen from W; m equals 0, 1, or 2; R3 is chosen from CO(OR4), C0-6alkylNR4R5, C0.6alkylCONR4R5, OC1-6alkylNR4R5 C1-6alkyl(SO2)NR4R5; n equals 1 or 2; R4 is chosen from hydrogen, C1-6alkyl; R5 is chosen from hydrogen, C1-6 alkyl, C0-6 alkyl C3-6 cycloalkyl, C0-6 alkylaryl, C0-6alkylheteroaryl and C1-6alkylNR14R15 or R4 and R5 together can form a 4-, 5-, 6- or 7-member heterocyclic group, containing one or more heteroatoms, independently chosen from N and O, where the given heterocyclic group can be substituted by group Y; and where any C1-6alkyl, indicated in defining R2-R5, can be substituted with one or more one Z group; R14 and R15 together can form a 5-member heterocyclic group, containing one or more heteroatoms, independently chosen from N and O; W and Z are independently chosen from halogen, CN, OR16, C1-6alkyl, trifluoromethyl, trifluoromethoxy, 5-member heterocyclic group, containing one heteroatom, independently chosen from N, for which the given heterocyclic group can be substituted with group Y; Y is chosen from oxo, halogen, C1-6alkyl, C0-6alkylaryl, NR16R17, phenyl, C0-6alkylaryl, where the phenyl and C0-6alkylaryl groups can be substituted with nitro, trifluoromethyl; R16 and R17 are independently chosen from hydrogen and C1-6alkyl, or where R16 and R17 together can form a 5-member heterocyclic group, containing one heteroatom, chosen from N; in form of a free base or pharmaceutical salt. Formula Ia compounds have inhibiting effect to glycogen-synthase-kinase-3 (GSK3). The invention also relates to the method of obtaining the proposed compounds and to new intermediate compounds, used in them, pharmaceutical compositions, containing the given therapeutically active compounds, and use of the given active compounds in therapy for treating conditions, related to GSK3.

EFFECT: new method of obtaining indole derivatives.

33 cl, 1 tbl, 112 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to new compounds with general formula: , where R is -(CH2)n-A, where A: where each of B and C independently represent phenyl or phenyl substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, -OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NH-C(O)-(C1-C6alkyl) and -NO2; or n equals an integer from 0 to 3; n1 equals an integer from 1 to 3; n2 equals an integer from 0 to 4; n3 equals an integer from 0 to 3; n4 equals an integer from 0 to 2; X1 is chosen from a chemical bond -S-, -S(O)2-, -NH-, -NHC(O)- and -C=C-, R1 is chosen from C1-C6alkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, tetrahydropyranyl, CN, -N(C1-C6alkyl)2, phenyl, pyridinyl, pyrimidinyl, furyl, thienyl, naphtyl, morpholinyl, triazolyl, pyrazolyl, piperidinyl, pyrrolidinyl, imidazolyl, piperizinyl, thiazolydinyl, thiomopholinyl, tetrazolyl, benzoxazolyl, imidazolidine-2-thionyl, 7,7-dimethylbicyclo[2.2.1]heptane-2-onyl, benzo[1.2.5]oxadiazolyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and pyrrolyl, each of which can be optionally substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NO2, -SO2(C1-C3alkyl), -SO2NH2, -SO2N(C1-C3alkyl)2, -COOH, -CH2-COOH, pyridyl, 2-methylazolyl, morpholino, 1-chloro-2-methylpropyl, phenyl, (optionally substituted with one or more halogens), benzyloxy, and , X2 selected from -O-, -CH2-, -S-, -SO-, -SO2-, -NH- and , R2 represents a ring group, chosen from a phenyl or thienyl group. Each ring group is substituted with a group with formula -(CH2)n4-CO2H; and besides that, the ring group can optionally be substituted with 1 or 2 extra substitutes, independently chosen from halogen, - C1-C6alkyl and -C1-C6alkoxy; R3 is chosen from H, halogen and -NO2; R4 is chosen from H, halogen and morpholino; or its salt form, used in pharmaceuticals. The invention also relates to pharmaceutical compositions, to methods of treatment, and to compounds with formula (A).

EFFECT: obtaining new biologically active compounds and pharmaceutical compositions based on them, which have inhibiting effect on cytosolic phospholipase A2.

45 cl, 300 ex

FIELD: chemistry.

SUBSTANCE: in compound of formula I , R1 is hydrogen; R2 is phenyl substituted by trifluoromethyl and optionally by other substitute selected out of a group including lower hydroxyl alkyl, lower alkylamino, lower hydroxyl alkylamino, dilower alkylamino, 1H-imidazolyl, lower alkyl-1H-imidazolyl, carbamoyl, lower alkylcarbamoyl, pyrrolidino, piperazino, lower alkylpiperazino, morpholino, lower alkoxy, trilfuoro-lower alkoxy, phenyl, pyridyl and halogenyl; R4 is methyl; where 'lower' prefix denotes radical with up to 7 carbon atoms. Also invention concerns pharmaceutical composition and method of treatment, as well as application of the claimed compounds in obtaining pharmaceutical composition.

EFFECT: improved proteinkinase inhibition properties.

9 cl, 98 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to new macrocyclic compounds with formula (I): (where R3, R6, R7 and R21 can be identical or different from each other, and each of them assume values given in the description), their salts used in pharmacology and their hydrate. Compounds with formula (I) are capable of inhibiting angiogenesis, particularly VEGF production in hypoxic conditions, and can be used as therapeutic means of treating solid malignant tumours. The invention also relates to medicinal agents based on these compounds, prevention and treatment method and use of these compounds in making preparations for preventing and treating cancerous diseases.

EFFECT: obtaining compounds, capable of inhibiting angiogenesis, particularly VEGF production in hypoxic conditions, which can be used as therapeutic means of treating solid malignant tumours.

35 cl, 3 tbl, 147 ex

FIELD: chemistry.

SUBSTANCE: invention concerns compounds of the formula I , where R0 is 1) monocyclic 6-14-member aryl, where aryl is independently mono-, di- or trisubstituted by R8, 2) heterocyclyl out of group of benzothiazolyl, indazolyl, pyridyl, where the said heterocyclyl is independently non-substituted or mono-, di- or trisubstituted by R8, and other radicals referred to in point 1 of the claim; R8 is halogen; on condition that R8 is at least one halogen atom if R0 is monocyclic 6-14-member aryl; substructure in the formula I is 4-8-member saturated, partly non-saturated or aromatic cyclic group including 0, 1 heteroatom selected out of nitrogen or sulfur, and is non-substituted or substituted 1, 2, 3 times by R3; Q is -(C0-C2)alkylene-C(O)NR10-, methylene; R1 is hydrogen atom, -(C1-C4)alkyl, where alkyl is non-substituted or substituted one to three times by R13; R2 is a direct link; R1-N-R2-V can form 4-8-member cyclic group selected out of piperazine or piperidine group; R14 is halogen, =O, -(C1-C8)alkyl, -CN; V is 1) 6-14-member aryl, where aryl is independently non-substituted or mono-, di- or trisubstituted by R14, and other radicals referred to in point 1 of the claim; G is direct link, -(CH2)m-NR10, where m is 0 and R10 is hydrogen, -(CH2)m-C(O)-(CH2)n-, where m is 0 or 1, and n is 0, -(CH2)m-C(O)-NR10-(CH2)n-, where m is 0 or 1, and n is 0, 1 or 2, -(CH2)m-, where m is 1; M is 1) hydrogen atom, 2) 6-14-member aryl, and other radicals referred to in point 1 of the claim; R3 is 1) hydrogen atom, 2) halogen atom, 3) -(C1-C4)alkyl, where alkyl is non-substituted, and other radicals referred to in point 1 of the claim; R11 and R12 are independently the same or different and are 1) hyfrogen atom, 2) -(C1-C6)alkyl, where alkyl is non-substituted or monosubstituted by R13, and other radicals referred to in point 1 of the claim; or R11 and R12 can form 4-8-member monocyclic heterocyclic ring together with nitrogen atoms to which they are linked, and beside the nitrogen atom the ring can include one or two similar or different ring heteroatoms selected out of oxygen, sulfur and nitrogen; where the said heterocyclic ring is independently non-substituted or mono-, disubstituted by R13; R13 is halogen, =O, -OH, -CF3, -(C3-C8)cycloalkyl, -(C0-C3)alkylene-O-R10; R10 is hydrogen, -(C1-C6)alkyl; R15 and R16 are independently hydrogen, -(C1-C6)alkyl; R17 is -(C1-C6)alkyl, -(C3-C8)cycloalkyl; in all stereoisomer forms and their mixes at any ratio, and physiologically tolerable salts. Compounds of the formula I are reversible inhibitors of enzyme factor Xa (FXa) and/or factor VIIa (FVIIa) of blood clotting, and can be generally applied in states accompanied by undesirable factor Xa and/or factor VIla activity, or supposing factor Xa and/or factor VIla inhibition for treatment or prevention. In addition, invention concerns methods of obtaining compounds of the formula I, their application as agents in pharmaceutical compositions.

EFFECT: obtaining compounds applicable as agents in pharmaceutical compositions.

19 cl, 1 tbl, 169 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I), their isomers and pharmaceutically acceptable salts. In the general formula (I) A is (II) ; X1 is methylene; X2 is CN, CHO, C(O)R6; X6 is a link; R1 is R13C(O)-; R2 is hydrogen; R3 is selected out of group including H, phenyl-(C0-6)alkyl, (C1-6)alkyl, optionally substituted by -X6OR9 group; R4 is H or (C1-6)alkyl; or R3 and R4 form (C3-8)cycloalkylene together with carbon atom to which R3, R4 are linked; R5 is (C1-9)alkyl, benzyl. Invention also concerns compounds of formulae (la), (lb), (Ic), and pharmaceutical composition based on the claimed compounds.

EFFECT: new compounds inhibiting cathepsin.

22 cl, 2 dwg, 89 ex

FIELD: chemistry.

SUBSTANCE: description is given of a piperidine derivative with general formula (I) , where L represents CH or N; M represents CH or N; under the condition that, L and M both do not represent CH; R1 represents phenyl (possibly substituted with a halogen or C1-4alkyl), S(O)2(C1-4alkyl), S(O)2(C1-4fluroalkyl), S(O)2phenyl (possibly substituted with CF3 or OCF3), benzyl, benzoyl (possibly substituted with a halogen) or C(O)NHphenyl (possibly substituted with a halogen); R2 represents phenyl, possibly substituted with a halogen; R3 represents hydrogen or C1-4alkyl; R4 represents methyl or ethyl; R5 represents phenyl-NH, phenyl (C1-2alkyl), phenyl(C1-C2)alkyl-NH or pyridyl(C1-2alkyl). The phenyl can be substituted with a halogen, cyano, C1-4alkyl, C1-4alkoxy, S(O)k(C1-4alkyl) or S(O)2NR8R9; k is equal to 2; R8 and R9 represent hydrogen or its pharmaceutical salts. The compound is a modulator of the activity of the CCR5 receptor. Description is given of the method of obtaining the compound, where L represents N, and the pharmaceutical composition based on a compound with formula (I).

EFFECT: design of a method of obtaining a compound, where L represents N, and a pharmaceutical composition based a compound with formula (I).

7 cl, 7 tbl, 16 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns to new diamides of pyrimidine-4,6-dicarboxylic acid of I formula, selective inhibitors of collagenases possessing properties which concern to the metalloproteinase superfamily and the matrix metalloproteinases. The bonds render influence on hyperactivity of the matrix metalloproteinase-13 (MMP-13) and thus do not render influence on MMP-3 and MMP-8. In the formula I R1 means an atom of hydrogen, R2 means - (C1-C6)-alkyl where alkyl is unitary replaced by phenyl where phenyl is replaced 1) -(C0-C6)-alkyl-C(O)-N(R9)-(R10), where R9 and R10 identical or different and independently from each other mean i) atom of hydrogen or ii) - (C1-C6)-alkyl or R9 and R10 together with atom of nitrogen to which they are bound, form 5, 6-links the sated cycle, and instead of one or two other atoms of carbon there can be also a heteroatom from an oxygen row, sulphur and nitrogen, and in case of nitrogen atoms of nitrogen independently from each other can be unsubstituted or substituted with (C1-C6)-alkyl, 2) -(C0-C6)-alkyl-C(O)-NH-SN, 3) -O-(C0-C6)-alkyl-C(O)-N(R9)-(R10) where R9 and R10 have the specified above value, 4) -(C0-C6)-alkyl-C(O)-N (R8)-(C0-C6)-alkyl-N(R9)-(R10) where R8 means hydrogen, R9 and R10 have the specified above value, 5) -(C0-C6)-alkyl-C(O)-N(R8)-(C0-C6)-alkyl-Het, and R8 has the specified above value, and Het means the sated or nonsaturated monocyclic heterocyclic system with number of links from 3 to 6 which contains in a cycle of 1 or 2 identical or different heteroatoms from a number nitrogen, oxygen and sulphur and unsubstituted or one-, two- or triple independently from each other is replaced by halogen, b) hydroxy,) -(C1-C6)-alkyl, and alkyl is unsubstituted or one-, two- or triple is substituted by halogen, d)=0,e)-Het, R4 and R5 or R5 and R6 together with atom of Carboneum to which they are bound, independently from each other form 5 or 6-unit cycle which is sated and contains one or two heteroatoms from an oxygen row.

EFFECT: obtaining of bonds which can find application for treatment of degenerate diseases of joints, such as osteoarthritis, rheumatic disease.

7 cl, 3 tbl, 117 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to derivatives of 4-[1-arylimidazol-4-yl ethynyl]-2-alkylpyridine and 4-[1-heteroarylimidazol-4-yl ethynyl]-2-alkylpyridine of general formula I having general formula I in which R1 stands for C1-C6alkyl; R2 stands for C1-C6alkyl or C3-C12cycloalkyl; R3 stands for aryl or heteroaryl, where aryl or heteroaryl are unsubstituted or contain substituents, selected from group, including halogen, C1-C6alkyl, S-C1-C6alkyl, C1-C6alkylhlogen, C1-C6alkoxygroup, halogen- C1-C6lkoxygroup, C3-C12cycloalkyl, C2-C11heterocycloakyl, C1-C6alkylminogroup,di- C1-C6alkylaminogroup, C1-C6alkoxyaminogroup, (C1-C6 alkoxy) C1-C6alkylaminogroup, C3-C12cycloalkylaminogroup, benzylaminogroup and cyanogroup, where said "aryl" represents phenyl, and said " heteroaryl" represents aromatic 5- or 6- member ring or one or more condensed rings, containing one or more heteroatoms, selected from group, which includes nitrogen, oxygen and sulfur; and R4 stands for hydrogen, C(O)H or CH2R5 , where R stands for hydrogen or its pharmaceutically acceptable salt. Invention also relates to method of obtaining compounds of general formula I, their application as anxiolytic, to based on them pharmaceutical composition and method of treatment or prevention of disorders, fully or partly mediated by metabotropic glutamate receptor of subtype 5.

EFFECT: obtaining novel heterocyclic compounds possessing useful biological properties.

15 cl, 18 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: claimed invention relates to agonist of receptor of glucagone-like peptide-1, which can be applied for treatment of diseases, caused by disturbance of glycometabolism, such as type II diabetes, insensibility to insulin or obesity. In structural formula each of Ar1 and Ar2 independently represents substituted phenyl, and group-substituents represent one, two or three groups selected from C1-C6alkoxyl, C1-C6-alkanoylamino, which is substituted with hydroxyl (which contains groups-substituents, including hydroxyl); C3-C6-cyclolkanoylamino, C2-C6-lkenoylamino; banzoylamino, banzyloxy C1-C6-alkanoylamino, thenoyloxy, tret-butoxyformamido, adamantanformamido; and mandeloylamino; X represents O; Y represents O. Invention also relates to method of obtaining agonist, and to its application for obtaining medication for treatment of diseases caused by disturbance of glycometabolism.

EFFECT: obtaining medication for treatment of diseases caused by disturbance of glycometabolism.

8 cl, 4 ex, 2 tbl, 2 dwg

FIELD: chemistry, pharmacology.

SUBSTANCE: invention relates to novel compounds of formula (I), its pharmaceutically acceptable salts, possessing qualities of chemokine receptor modulators. Compounds can be applied for asthma, allergic rhinitis, COLD, inflammatory intestinal disease, irritated intestine syndrome, osteoarthritis, osteoporosis, rheumatoid arthritis, psoriasis or cancer. In compound of formula (I) , R1 represents group selected from C1-8alkyl, said group is possibly substituted with 1, 2 or 3 substituents, independently selected from -OR4 , -NR5R6 , phenyl, phenyl is possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4,-NR5R6,-SR10,C1-6alkyl and trifluoromethyl; R2 represents group selected from C1-8alkyl, said group is substituted with 1, 2 or 3 substituents, independently selected from hydroxy, amino, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino, N-(C1-6alkyl)-N-(phenyl)amino; R3 represents hydrogen, R4 represents hydrogen or group selected from C1-6alkyl and phenyl, R5 and R6, independently, represent hydrogen or group selected from C1-6alkyl and phenyl, said group being probably substituted with 1, 2 or 3 substituents, independently selected from -OR14, -NR15R16, -COOR14,-CONR15R16, or R5 and R6 together with nitrogen atom, to which they are bound, form 4-7-member saturated heterocyclic ring system, possibly containing additional heteroatom, selected from oxygen and nitrogen atoms, ring possibly being substituted with 1, 2 or 3 substituents, independently selected from -OR14, -COOR14,-NR15R16,CONR15R16 and C1-6alkyl; R10 represents hydrogen or group selected from C1-6alkyl or phenyl; and each from R7, R8, R9, R14, R15, R16 independently represents hydrogen, C1-6alkyl or phenyl; X represents hydrogen, halogeno; Rx represents trifluoromethyl, -NR5 R6 , phenyl, naphtyl, heteroaryl, heteroring can be partly or fully saturated, and one or more ring carbon atoms can form carbonyl group, each phenyl or heteroaryl group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, cyano, -OR4, -NR5R6, -CONR5R6, -COR7, -COOR7, -NR8COR9, -SR10, -SO2R10, -SO2NR5R6, -NR8SO2R9, C1-6alkyl or trifluoromethyl; or Rx represents group selected from C1-6alkyl, said group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4, -NR5R6, phenyl or heteroaryl, where heteroaryl represents monocyclic or bicyclic aryl ring, containing from 5 to 10 ring atoms, from which 1, 2 or 3 ring atoms are selected from nitrogen, sulfur or oxygen. Invention also relates to methods of obtaining compounds, versions, pharmaceutical composition and application for manufacturing medications using compounds of invention.

EFFECT: obtaining novel compounds of formula (I), its pharmaceutically acceptable salts, possessing properties of chemokine receptor moduators.

25 cl, 138 ex

FIELD: medicine; pharmacology.

SUBSTANCE: in formula (I) V represents -N (R1) (R2) or OR4; R4 represents H, C1-6alkyl, C1-6halogenalkyl or (C1-6alkylen)0-1R4' R4' represents C3-7cycloalkyl, phenyl, pyridyl, piperidinyl; and R4' is optionally substituted with 1 or 2 identical or different substitutes chosen from group consisting of C1-4alkyl, amino, C1-3alkylamino, C1-3dialkylamino, phenyl and benzyl; and each R1 and R2 independently represents L1, where L1 is chosen from group consisting from H, C1-6alkyl, C2-6alkenyl, C2-6alkinyl, - adamantyl, pyrrolidinyl, pyridyl, or R1 and R2 together with nitrogen atom to which attached, form X, where X represents pyrrolidinyl, piperazinyl, piperidinyl, morpholino; where X is optionally substituted with Y, where Y represents dioxolanyl, C1-9alkyl, phenyl, furanyl, pyrrolyl, pyridyl, pyrrolidinyl; and where X and Y are optionally split with Z, where Z represents -C1-3alkylen-, C1-3alkylen-. Other radical values are specified in formula of invention.

EFFECT: effective application for treatment of migraine and other headache mediated by action of CGRP-receptors.

34 cl, 11 dwg, 6 tbl, 201 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compound of the formula (I): wherein R1 represents azido, -OR4, -NHR4 wherein R4 represents hydrogen atom or unsubstituted groups chosen from acyl, thioacyl, (C1-C6)-alkoxycarbonyl, (C3-C6)-cycloalkoxythiocarbonyl, (C2-C6)-alkenyloxycarbonyl, (C2-C6)-alkenylcarbonyl, (C1-C6)-alkoxythiocarbonyl, (C2-C6)-alkenyloxythiocarbonyl, -C(=O)-C(=O)-(C1-C6)-alkoxy, -C(C=S)-S-(C1-C6)-alkyl, -(C=S)-NH2, -(C=S)-NH-(C1-C6)-alkyl, -C(=S)-N-((C1-C6)-alkyl)2, -C(=S)-NH-(C2-C6)-alkenyl, -C(C=S)-(C=O)-(C1-C6)-alkoxy, thiomorpholinylthiocarbonyl; R2 and R3 can be similar or different and represent independently hydrogen atom, halogen atom, (C1-C6)-alkyl group, halogen-(C1-C6)-alkyl; heterocyclic moiety represents 5-membered heterocycle wherein Z represents sulfur (S), oxygen (O) atom or -NRb wherein Rb represents hydrogen atom or unsubstituted (C1-C6)-alkyl, (C3-C6)-cycloalkyl, aryl or aryl-(C1-C6)-alkyl; Y1 represents group =O or =S ; Y2 and Y3 represent independently hydrogen atom, and if Y2 and Y3 present in common on adjacent carbon atoms then they form 6-membered aromatic cyclic structure substituted if necessary with (C1-C6)-alkyl, or to its pharmaceutically acceptable salt. Also invention relates to a pharmaceutical composition possessing antibacterial activity and containing as an active compound the compound of the formula (I) taken in the effective dose and a pharmaceutically acceptable carrier, diluting agent, excipient. Also, invention relates to method for synthesis of compound of the formula (I). Method for synthesis of compound of the formula (I) wherein R1 represents group -NHR4 wherein R4 means acyl, (C1-C6)-alkoxycarbonyl, (C2-C6)-alkenyloxycarbonyl, (C2-C6)-alkenylcarbonyl, -C(=O)-C(=O)-(C1-C6)-alkoxy and -(C=S)-S-(C1-C6)-alkyl involves acetylation of compound of the formula (I) wherein R1 represents -NHR4 group wherein R4 represents hydrogen atom and all symbols are given above and using halide. Method for synthesis of compound of the formula (I) wherein R1 represents -NHR4 group wherein R4 means thioacyl, (C3-C6)-cycloalkoxythiocarbonyl, (C1-C6)-alkoxythiocarbonyl, (C2-C6)-alkenyloxythiocarbonyl involves the following steps: (i) conversion of compound of the formula (I) wherein R1 represents -NHR4 wherein R4 represents hydrogen atom, and all symbols are given above to compound of the formula (I) wherein R1 represents isothiocyanate group by reaction with thiophosgene, and (ii) conversion of compound of the formula (I) wherein R1 represents isothiocyanate group to compound of the formula (I) wherein R1 represents -NHR4 wherein R4 represents -C(=S)-OR4d wherein R4d represents (C1-C6)-alkyl, (C3-C6)-cycloalkyl, (C2-C6)-alkenyl, and all symbols are given above, in reaction with alcohol. Compounds of the formula (I) are used in treatment of bacterial infection that involves administration of compound of the formula (I) in a patient needing in this treatment. Invention provides synthesis of oxazolidinone compounds possessing antibacterial activity.

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

7 cl, 1 tbl, 144 ex

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