Derivatives of azetidine or their pharmaceutically acceptable salts have antibacterial activity

 

(57) Abstract:

Usage: as substances with antimicrobial activity. The essence of the invention: derivatives of azetidine General formula (I), where A nitrogen atom or the group-CH-, or C-HaI, where HaI is chlorine atom or fluorine; R1lower alkyl or cycloalkyl, lower halogenated or phenyl substituted mono - or Diptera; R2,R3and R5the same or different and signify hydrogen or lower alkyl; R4hydroxyl, amino, aminoalkyl, alkylamino, dialkylamino, pyrrolyl-1 or pyrrolidinyl-1, acylaminoalkyl, trifurcated; R6hydrogen or amino group, or a and R1together form a group and in this case have a chiral center configuration R or S; R7hydrogen or lower alkyl. table 1.

The invention relates to new derivatives of azetidine General formula:

O-R7 (I) where a nitrogen atom or the group-CH-, or C-HaI, where HaI, a chlorine atom or fluorine;

R1lower alkyl or cycloalkyl, lower halogenated or phenyl substituted mono - or Diptera;

R2, R3and R5the same or different and signify hydrogen or lower alkyl;

R4hydroxyl, amino, aminoalkyl, alkylamino, dialkylamino, pyrrolyl-1 or R1together form a group-O-CH2and in this case have a chiral center configuration R or S,

R7hydrogen or lower alkyl,

or their pharmaceutically acceptable salts.

The new compounds (I) azetidinone series exhibit high antimicrobial activity and low toxicity.

The invention is illustrated in the examples.

P R I m e R 1. Getting 1-cyclopropyl-6-fluoro-7-(1-azetidine)-1,4-dihydro-4-oxo - -3-quinoline-carboxylic acid.

In a closed vessel heated at 110aboutC for 2 h in a mixture of 0.6 g (2.2 mmol) of 1-cyclopropyl-6,7-debtor-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid, 0.25 g (4.4 mmol) of azetidine and 1 ml of triethylamine in 8 ml of pyridine. Leave to cool, filtered and washed with water, ethanol and ether. Get 0,275 g 1-cyclopropyl-6-fluoro-7-(1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 291-294aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFAA] IS 8.75 (S, 1H); for 7.78 (d, j=13, 1H); 6,86 (d, j=8 - 1H); 4,22 (t, j=7, 4H); to 3.73 (m, 1H); to 1.15 (m, 6H).

IR (KBr) 1725, 1631, 1479, 1464, 1348 cm-1.

P R I m m e R 2. Getting 1-cyclopropyl-6,8-debtor-7-(3-methyl-3-methylamino-1-AZE - tidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid-incarbone acid, 1.45 g (6.2 mmol) of the hydrochloride of 3-methyl-3-triftoruranmetilidina and 1 ml of triethylamine in 15 ml of pyridine. Evaporated in vacuo, diluted with ice water, filtered and washed with water. Obtain 2.2 g of 1-cyclopropyl-6,8-debtor-7-(3-methyl-3-triptoreline-N-meth - yl-1 - azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 219-294aboutC, which is then hydrolized by heating it in a mixture of 4 ml of 10% sodium hydroxide and 20 ml of water with 1 ml of ethanol for 1 h Exercise hot filtered, acidified with acetic acid, filtered and washed with water. Gain of 1.57 g of 1-cyclopropyl-6,8-debtor-7-(3-methyl-3-meilani - but-1-azetidine)-1,4-dihydro-4-oxo-3 - quinoline-carboxylic acid of melting point > 300oC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] 1,1 (m, 4H); of 1.65 (S, 3H); 2,7 (S, 3H); 4.0 a (m, 1H); 4,5 (AB, j=7, 4H); of 7.75 (d, j= 1H); and 8.6 (S, 1H); 9,4 (advanced, 2H).

IR (KBr) 2918, 1731, 1622, 1470 cm-1.

P R I m e R 3. Getting 1-cyclopropyl-6-fluoro-7-(3-methyl-3-methylamino-1 azetidin - nil)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 2, get 1-cyclopropyl-6-fluoro-7-(3-methyl-3-Triforce-tamido-N-methyl-1-azetidine) -1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point of 210-215aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] of 1.15 (m, 4H); and 1.7 (S, 3H); to 2.75 (S, 3H); 3.75 to (m, 1H); 4,2 (AB, j=7, 4H); 7,0 (d, j=7,6, 1H); a 7.85 (d, I=12,9, 1H); and 8.6 (S, 1H); 9,4 (advanced, 2H).

IR(KBr) 2915, 1731, 1629, 1516, cm-1.

P R I m e R 4. Getting 1-cyclopropyl-6-fluoro-7-(3-dimethyl-amino-3-methyl-1-azet - idini) -1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Heated at reflux for 2 h the mixture of 1.32 g (5 mmol) 1-cyclopropyl-6,7-debtor-1,4-dihydro-4-oxo-3-fineliner - about acid, 1.31 g (7 mmol) of the hydrochloride of 3-methyl-3-dimethylaminopyridine and 3 ml of triethylamine in 10 ml of pyridine. Evaporated, leave to cool, add ice water, filtered and washed with water, ethanol and ether and gain of 11.8 g of 1-cyclopropyl-6-fluoro-7-(3-dimethylamino--3-methyl-1-azetidine) -1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 298-301aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] of 1.16 (m, 4H); to 1.67 (S, 3H); 2,78 (S, 6H); to 3.67 (m, 1H); 4,29 (AB, I=20, I=9,3, 4H); 7,0 (d, j=7,5, 1H); a 7.85 (d, I=12,9, 1H); and 8.6 (S, 1H).

IR (KBr) 1712, 1629, 1521, 1475 cm-1.

P R I m e R 5. Getting 1-cyclopropyl-6,8-debtor-7-(TRANS-2-methyl-3-hydroxy-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working fine karbolovuju acid with a melting point 215-218aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFAA] 8,59 (S, 1H); of 7.69 (d, j=13, 1H); 4,55 (m, 2H); 4,01 (m, 3H); 1,45 (d, j=6,3 H); to 1.16 (d, j=6, 4H).

IR(KBr) 1719, 1628, 1526,1453, 1412 cm-1.

P R I m e R 6. Getting 1-cyclopropyl-6-fluoro-7-(TRANS-2-methyl-3-hydroxy-1-azet - idini)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Work just on example 4 and 1-cyclopropyl-6-fluoro-7-(TRANS-2-methyl-3-hydroxy-1-azetidine)-1,4-dihydro-4 - oxo-3-quinoline-carboxylic acid with a melting point 239-242aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFAA] 8,58 (S, 1H); 7,79 (d, j=13, 1H); 7,01 (d, j=8, 1H); of 4.45 (m, 1H); 4,15 (m, 2H); 3.75 to (m, 2H); of 1.46 (d, j=6, 3H); 1,24 (m, 4H).

IR(KBr) 1708, 1630, 1503, 1474, 1460, 1337 cm-1.

P R I m e R 7. Getting 1-cyclopropyl-6,8-debtor-7-(3-methyl-3)1-pyrrolyl (-1-azetidine)-1,4-dihydro-4-oxo-3-fineliner - oil acid.

Work just on example 4 and 1-cyclopropyl-6,8-debtor-7-(3-methyl-3-) 1-pyrrolyl(-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 249-252aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [Cl3CD] of 1.20 (m, 4H); a 1.96 (S, 3H); 3.9 to (m, 1H); 4,4-5,0 (complex, 4H); and 6.25 (t, j=2, 1H); to 6.88 (t, j=2, 1H); to 7.77 (dd, j= 13, I=2, 1H); 8,66 (S, 1H).

Work just on example 4 and 1-cyclopropyl-6-fluoro-7- (3-ethylaminomethyl-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 200-203aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFAA] CHARGED 8.52 (S, 1H); of 7.69 (d, j=13, 1H); for 6.81 (d, j=8, 1H); 4.26 deaths (m, 2H); 3,95 (m, 2H); 3,68 (m, 1H); 2,84 (S, 2H); of 2.56 (q, j=7, 2H); 1.26 in (m, 4H); was 1.04 (t, j=7, 3H).

IR(KBr) 1710, 1625, 1477, 1323 cm-1.

P R I m e R 9. Getting 1-cyclopropyl-6,8-debtor-7-(TRANS-2-methyl-3-amino-1-AZE - tidine)-1,4- -dihydro-4-oxo-3-quinoline-carboxylic acid.

Work just on example 4 and 1-cyclopropyl-6,8-debtor (7-TRANS-2-methyl-3-amino-1-azetidine)-1,4-dihydro-4-oxo-3-henrikromby Yu acid with a melting point 234-237aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFAA] 8,61 (S, 1H); 8,32 (advanced, 2H); of 7.70 (dd, j=13, I=1,5, 1H); was 4.76 (m, 2H); 4.09 to (m, 2H); and 3.72 (m, 1H); 1,53 (d, j=6, 3H); to 1.16 (d, j=6, 4H).

IR (KBR) 1719, 1630, 1578, 1466, 1402, 1319 cm-1.

P R I m e R 10. Getting 1-cyclopropyl-6-fluoro-7-(TRANS-2-methyl-3-amino-1-azetidine)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid.

Work just on example 4 and 1-cyclopropyl-6-fluoro-(7-TRANS-2-methyl-3-amino-1-azetidine)-1,4-dihydro-4-OK co-3-quinoline-carboxylic keys the [DMSO-TFAA] 8,61 (S, 1H); of 8.37 (advanced, 2H); 7,86 (d, j=13, 1H);? 7.04 baby mortality (d, j=8, 1H); 4.53-in (m, 2H); to 3.92 (m, 3H); and 1.54 (d, j=6, 3H); 1,19 (d, j=8, 4H).

IR(KBr) 1719, 1629, 1479, 1325 cm-1.

P R I m e R 11. Getting 1-cyclopropyl-6-fluoro-7-(3-amino-methyl-1-azetidine) 1,4-dihydro-4 - oxo-3-quinoline-carboxylic acid.

Work exactly according to example 2 and get 1-cyclopropyl-6-fluoro-7-(3-triftormetilfullerenov-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 205-211aboutC, which is then hydrolized to obtain 1-cyclopropyl-6-fluoro-7-(3-aminomethyl-1- -AZE-tidine)-1,4-dihydro-4 - oxo-3-quinoline-carboxylic acid with a melting point 234-239aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] 8,55 (S, 1H); 8.4V (advanced, 2H); of 7.75 (d, j=13, 1H); 6,85 (d, j=7,6, 1H); 4.25 in (m, 2H); 4.0 a (m, 2H); 4.0 a (m, 2H); to 3.45 (m, 1H); 3.15 in (advanced, 3H); 1,11 (m, 4H).

IR(KBr) 3368, 1725, 1630, 1479, 1471 cm-1.

P R I m e R 12. Getting 1-cyclopropyl-6-fluoro-7-(3-methyl-3-hydroxy-1-azeti-dinyl)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid.

Work according to example 4 and 1-cyclopropyl-6-fluoro-7-(3-methyl-3-hydroxy-1-azetidine)-1,4-dihydro-4 - oxo-3-quinoline-carboxylic acid with a melting point 303-308aboutC.

Spectroscopic data:

1N-R4, 1473, 1460 cm-1.

P R I m e p 13. Getting 1-cyclopropyl-6-fluoro-7-(3-ethyl-3-hydroxy-1-azetidin - nil)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6-fluoro-7-(3-ethyl-3-hydroxy-1-azetidine)-1,4-dihydro-4 - oxo-3-quinoline-carboxylic acid with a melting point 284-287aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFAA] 8,55 (S, 1H); 7,73 (d, j=13, 1H); at 6.84 (d, j=7,6, 1H); 4,01 (m, 4H); to 3.64 (m, 1H); 1,74 (q, j=7, 2H); 1,17 (m, 4H); 0,9 (t, j=7, 3H).

IR (KBr) 1725, 1628, 1513, 1465 cm-1.

P R I m e R 14. Getting 1-cyclopropyl-6,8-debtor-7-(3-ethyl-3-hydroxy-1-AZE-tidine)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6,8-debtor-7-(3-ethyl-3-hydro - XI-1-azetidine)-, 4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 257-259aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFAA] CHARGED 8.52 (S, 1H); 7,58 (d, j=13, 1H); 4,20 (advanced, 4H); 3,90 (m, 1H); 1,71 (q, j=7, 2H); of 1.07 (m, 4H); from 0.88 (t, j=7, 3H).

IR (KBr) 1715, 1626, 1460, 1453, 1412 cm-1.

P R I m e R 15. Getting 1-cyclopropyl-6-fluoro-7-(3-amino-3-methyl-1-azetidin - yl)-1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid.

Heated at reflux in t is, ,34 g (2.1 mmol) of the hydrochloride of 3-methyl-3-aminoacridine and 0.5 ml of triethylamine in 10 ml of pyridine. Leave to cool, filtered and washed with water. Obtain 0.52 g of 1-cyclopropyl-6-fluoro-7-(3-amino-3-methyl-1-azeti - dinyl)-1,4-dihydro-4-oxo - 1,8-naphthiridine-3-carboxylic acid with a melting point 285-287aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] 8,59 (S, 1H); 8.4V (advanced, 2H); 8.0 a (d, j= 13, 1H); 4,4 (AB, j=7, 4H); the 3.65 (m, 1H); of 1.65 (S, 3H); 1,1 (m, 4H).

IR (KBr) 2943, 1629, 1447 cm-1.

P R I m e R 16. Getting 1-cyclopropyl-6-fluoro-7-(TRANS-3-amino-2-methyl-1-AZE - tidine)-1,4 - dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid.

Working example 15 and get a 1-cyclopropyl-6-fluoro-(7-TRANS-3-amino-2 - methyl-1-azetidine)-1,4-dihydro - 4-oxo-1,8-naphthiridine-3-carboxylic acid with a melting point 211-218aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] TO 8.6 (S, 1H); 8.4V (advanced, 2H); to 7.95 (d, j= 13, 1H); 4.7 in (m, 2H); 4.25 in (m, 1H); 3,6 (m, 2H); of 1.55 (d, j=6, 3H); 1,1 (m, 4H).

IR (KBr) 2943, 1629, 1629, 1447 cm-1.

P R I m e R 17. Obtain (3S)-(-)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4] benzoxazin-10-(3-amino-1-azetidine)-6-carboxylic acid.

Working example 4, get (3S)-(-) -9-fluoro-3-meth is possible 236-240aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] of 1.41 (d, j=7, 3H); 3.9 to 5,1 (complex, 8H); 7,52 (d, j=13, 1H); 8,35 (advanced, 2H); 8,88 (S, 1H).

IR (KBr) 3350, 1712, 1622, 1536, 1474 cm-1.

[]D20=-78,8 (=4,1, 0.5 N NaOH).

P R I m e R 18. Obtain (3S)-(-)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4] benzoxazin-10-(3-dimethylamino-1-azetidine)-6-carboxylic acid.

Working example 4 and (3S)-(-)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4] benzoxazin-10-(3-dimethylamino-1-azetidine)-6-carboxylic acid with a melting point > 300aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFAA] of 1.41 (d, j=7, 3H); 2,8 (S, 6H); 4,0-5,0 (complex, 8H); 7,52 (d, j=13, 1H); 8,87 (S, 1H).

IR (KBr) 2400, 1712, 1619, 1525, 1442, 1340 cm-1.

[]D20= 79,5 (C=4,06, 0.5 N NaOH).

P R I m e R 19. Obtain (3S)-(-)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4]benzoxazin-10-(3-dimethyl-amino-3-methyl-1-azetidine)-6-carboxylic acid.

Working example 4 and (3S)-(-)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4] benzoxazin-10-(3-dimethylamino-3-methyl-1-azetidine)-6-carb - about acid with a melting point 298-299aboutC.

Spectrosc); 8,76 (S, 1H).

IR (KBr) 2400, 1712, 1617, 1440, 1420, 1325 cm-1.

[]D20=-74,6 (=Was 4.02, 0.5 N NaOH).

P R I m e R 20. Obtain (3R)-(+)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4] benzoxazin-10-(3-amino-1-azetidine)-6-carboxylic acid.

Working example 4 and (3R)-(+)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4] benzoxazin-10-(3-amino-1-azetidine)-6-carboxylic acid with a melting point 236-240aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] of 1.40 (d, j=7, 3H); 3.9 to 5,1 (complex, 8H); 7,51 (d, j=13, 1H); 8,35 (advanced, 2H); 8,87 (S, 1H).

IR (KBr) 3350, 1712, 1622, 1536, 1474 cm-1.

[]D20=+80,1 (C=4,12, 0.5 N NaOH).

P R I m e R 21. Obtain (3R)-(+)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4] benzoxazin-10-(3-dimethylamino-1-azetidine)-6-carboxylic acid.

Working example 4 and (3R)-(+)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4] benzoxazin-10-(3-dimethylamino-1-azetidine)-6-carboxylic acid with a melting point > 300aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFAA] of 1.40 (d, j=7, 3H); 2,8 (S, 6H); 4,0-5,0 (complex, 8H); 7,51 (d, j=13, 1H); 8:88 (S, 1H).

IR (KBr) 2400, 1712, 1619, 1525, 1442, 1340 cm-1.

Working example 4 and (3R)-(+)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4]benzoxazin-10-(3-dimethylamino-3-methyl-1-azetidine)-6-carb - about acid with a melting point 298-299aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] was 1.43 (d, j=6,3, 3H); of 1.62 (S, 3H); of 2.72 (S, 6H); 4,0-5,0 (complex, 7H); 7,51 (d, j=13, 1H); 8,76 (S, 1H).

IR (KBr) 2400, 1712, 1617, 1440, 1420, 1325 cm-1.

[]D20=+72,8 (C=Was 4.02, 0.5 N NaOH).

P R I m e R 23. Getting 1-cyclopropyl-6-fluoro-7-(3-dimethyl-amino-1-azetidin-nil)-1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid.

Working example 15 and get a 1-cyclopropyl-6-fluoro-7-(3-dimethylamino-1-azetidine)-1,4-dihydro-4-oxo - 1,8-naphthiridine-3-carboxylic acid with a melting point 249-251aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] of 1.13 (m, 4H); of 2.86 (S, 6H); 3,66 (m, 1H); of 4.35 (m, 1H); of 4.45 (m, 4H); 8,04 (d, I=11,4, 1H); 8,59 (S, 1H).

IR (KBr) 1716, 1634, 1511, 1452 cm-1.

P R I m e R 24. Getting 1-cyclopropyl-6-fluoro-7-(3-methylamino-1-azetidine)-1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid.

Working example 2 and get 1-cyclopropyl-6-fluoro-7-(3-cryptomelane - tamido-N'-methyl-1-azetidine)- 1,4-dihydro-4-oxo-1,8-naphthiridine-3-CT what-7-(3-methylamino-1- -AZE-tidine)-1,4-dihydro-4-oxo - 1,8-naphthiridine-3-carboxylic acid with a melting point 250-253aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] 1,11 (m, 4H); of 2.64 (S, 3H); the 3.65 (m, 1H); 4,15 (m, 1H); of 4.44 (m, 4H); 7,97 (d, I=11,4, 1H); 8,56 (S, 1H); 9,24 (advanced, 1H).

IR (KBr) 2932, 1631, 1614, 1457, 1276 cm-1.

P R I m e R 25. Getting 1-cyclopropyl-6,8-debtor-7-(TRANS-2,3-dimethyl(R)-3 - hydroxy-1 - azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6,8-debtor-7-(TRANS-2,3-dime - Teal-[R] -3-hydroxy-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 246-251aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] 8,59 (S, 1H); to 7.68 (dd, j=13, I=1,5, 1H); of 4.54 (m, 1H); 4,27 (m, 1H); was 4.02 (m, 2H); of 1.35 (m, 6H); to 1.16 (d, j=6, 4H).

IR (KBr) 3470, 1705, 1626, 1529, 1475, 1458, 1414 cm-1.

P R I m e R 26. Getting 1-cyclopropyl-6-fluoro-7-(TRANS-2,3-dimethyl-/R/-3-guide - Roxy-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6-fluoro-7-(TRANS-2,3-dimethyl-(R)-3-hydroxy-1-azetidine) -1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 284-290aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFAA] TO 8.57 (S, 1H); to 7.77 (d, j=13, 1H); 7,05 (d, j=7, 1H); 4.16 the (m, 2H); 3,81 (m, 2H); 1.32 to (m, 10H).<-7-(3-hydroxy-1-azet - idini)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 5-amino-1-cyclopropyl-6,8-debtor-7-(3-guide-Roxy-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 271-275aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] 8,43 (S, 1H); 6,98 (S, 2H); 4,58 (m, 3H); of 4.05 (m, 3H); of 1.07 (m, 4H).

IR (KBr) 3340, 1690,1540, 1423 cm-1.

P R I m e R 28. Getting 1-cyclopropyl-6,8-debtor-7-(TRANS-3-dimethylamino-2-methyl-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6,8-debtor-7-(TRANS-3-DIMET - ylamino-2-methyl-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 149-151aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] 8,61 (S, 1H); of 7.75 (dd, j=13, I=1,5, 1H); to 4.98 (m, 1H); of 4.67 (m, 1H); 4,34 (m, 1H); to 3.92 (m, 2H); and 2.83 (S, 6H); and 1.54 (d, j=6, 3H); to 1.16 (d, j=6, 4H).

IR (KBr) 1729, 1627, 1523, 1459, 1328 cm-1.

P R I m e R 29. Getting 1-cyclopropyl-6-fluoro-7-(TRANS-3-dimethylamino-2-me-Teal-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6-fluoro-7-(TRANS-3-dimethyl-Mino-2-methyl-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 181-185aboutC.

IR (KBr) 2890, 1727, 1630, 1510, 1468 cm-1< / BR>
P R I m e R 30. Obtain (3S)-(-)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4]-benzoxazin-10-(3-ethylamino-methyl-3-methyl-1-azetidine)-6 carboxylic acid.

Working example 2, get (3S)-(-) -9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-PI - Rideau [1,2,3-de] [1,4]-benzoxazin-10-(3-methyltrifluoroacetamide-N-ethyl-1 - azetidine)-6-carboxylic acid with a melting point 234-238aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFA] to 1.19 (t, j=GHz, 3H); TO 1.31 (S, 3H); 1,45 (d, j= 7 Hz, 3H); 3,44 (m, 2H); 3,66 (S, 2H); 3,90-4,60 (m, 6H); at 4.75 (m, 1H); was 7.45 (d, j=14 Hz, 1H); 8,76 (S, 1H).

IR (KBr) 1718, 1690, 1622, 1466, 1449, 1137 cm-1.

Hydrolyzing the resulting product 10% sodium hydroxide to obtain (3S)-(-)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-Piri-up [1,2,3-de] [1,4]-benzoxazin-10-(3-ethylaminomethyl-3-methyl-1-azetidine)-6 carboxylic acid with a melting point 242-245aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] to 1.22 (t, j=7 Hz, 3H); TO 1.38 (S, 3H); of 1.42 (d, j=8 Hz, 3H); 2.8 to a 3.4 (m, 4H); 3,9-4,6 (m, 6H); 4,84 (m, 1H); of 7.48 (d, j=14 Hz, 1H); 8.34 per (advanced, 1H); 8,86 (S, 1H).

IR (KBr) 2980, 1686, 1621, 1534, 1474, 1459 cm-1.

[]D23=-56,1 (C=4,8, 0.5 N NaOH).

Working example 2 and obtain (3R)-(-)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4]-benzoxazin-10-(3-methyl-3-triftormetilfullerenov-N-ethyl-1 - azetidine)-6-carboxylic acid with a melting point 233-236aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] to 1.19 (t, j=7 Hz, 3H); TO 1.31 (S, 3H); 1,45 (d, j= 7 Hz, 3H); 3,44 (m, 2H); 3,66 (S, 2H); 3,90-4,60 (m, 6H); at 4.75 (m, 1H); was 7.45 (d, j=14 Hz, 1H); 8,76 (S, 1H).

IR (KBr) 1718, 1690, 1622, 1466, 1449, 1137 cm-1.

Hydrolyzing the resulting product 10% sodium hydroxide to obtain (3R)-(-)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-Piri - up [1,2,3-de] [1,4]-benzoxazin-10-(3-ethyl-aminomethyl-3-methyl-1-azetidine)-6-carb - about acid with a melting point 242-245aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] to 1.22 (t, j=7 Hz, 3H); to 1.38 (S, 3H); of 1.42 (d, j=8 Hz, 3H); 2.8 to a 3.4 (m, 4H); 3,9-4,6 (m, 6H); 4,84 (m, 1H); of 7.48 (d, j=14 Hz, 1H); 8.34 per (advanced, 1H); 8,86 (S, 1H).

IR (KBr) 2980, 1686, 1621, 1534, 1474, 1459 cm-1.

[]D23=+55,4 (C=4,5, 0.5 N NaOH).

P R I m e R 32. Getting 1-cyclopropyl-6-fluoro-7-(TRANS-3-aminomethyl-2-methyl-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 222-227aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 8,58 (S, 1H); 8,2 KBr) 3420, 1675, 1629, 1509, 1476 cm-1.

P R I m e R 33. Getting 1-cyclopropyl-6,8-debtor-7-(TRANS-3-aminomethyl-2-methyl-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6,8-debtor-7-(TRANS-3-aminomethyl-2-methyl-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 196-203aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 8,58 (S, 1H); 7,86 (advanced, 1H); of 7.69 (d, 1H, j=13 Hz); 4,58 (m, 1H); Android 4.04 (m, 1H); 3,20 (m, 2H); 2,53 (m, 3H); for 1.49 (d, 3H, j=5.0 Hz); of 1.18 (m, 4H).

IR (KBr) 3400, 1608, 1578, 1475, 1295 cm-1.

P R I m e R 34. Getting 1-cyclopropyl-6-fluoro-7-(TRANS-3-methylamino-2-methyl-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 2 and get 1-cyclopropyl-6-fluoro-7-(TRANS-3-meilani - but-2-methyl-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 208-212aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 9,4 (advanced, 2H); 8,65 (S, 1H); a 7.85 (d, 1H, j= 12 Hz); and 7.1 (d, 1H, j=7,6 Hz); the 4.65 (m, 2H); 4,2 (m, 1H); of 3.85 (m, 2H); and 2.7 (S, 3H), and 1.5 (d, 3H, j=5 Hz); 1,2 (m, 4H).

IR (KBr) 2930, 1626, 1500, 1323, 1286 cm-1.

P R I m e R 35. Getting 1-cyclopropyl-6,8-debtor-7-(TRANS-3-methylamino-2 - mailprofile-6,8-debtor-7-(TRANS-3-methyl - a Mino-2-methyl-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 241-246aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 9,23 (advanced, 2H); 8,65 (S, 1H); to 7.77 (d, 1H, j=13 Hz); 4,87 (m, 2H); of 3.77 (m, 1H); to 2.66 (S, 3H); was 1.58 (d, 3H, j=5 Hz); 1,19 (d, 4H, j=5.6 Hz).

IR (KBr) 2930, 1625, 1461, 1322 cm-1.

P R I m e R 36. Getting 1-cyclopropyl-6-fluoro-7-(TRANS-3-ethylaminomethyl-2-methyl-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6-fluoro-7-(TRANS-3-ethylamino - methyl-2-methyl-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 219-225aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 8,49 (S, 1H, j=14 Hz); 6,94 (d, 1H, j= 6,8 Hz); of 4.35 (m, 2H); 3,55 of 4.1 (m, 3H); of 3.25 (m, 2H); 2.95 and (d, 2H, j= 4,8); to 1.48 (d, 3H, j=5 Hz); 1,2 (m, 7H).

IR (KBr) 1686, 1631, 1520, 1470, 1202 cm-1.

P R I m e R 37. Getting 1-cyclopropyl-6,8-debtor-7-(TRANS-3-ethylaminomethyl- -2-methyl-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6,8-debtor-7-(TRANS-3-ethyl-aminomethyl-2-methyl-1-azetidine) -1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 209-212aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 8,55 )S, 1H); the 7.65 (d, 1H, j=13 Hz); 4,49 (m,/P> P R I m e R 38. Getting 1-cyclopropyl-6,8-debtor-7-(TRANS-3-hydroxy-2-ethyl- -1-azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6,8-debtor-7-(TRANS-3-hydro-XI-3-ethyl-1-azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 259-261aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFA] at 0.7-1.4 (m, 7H); 1,5-2,2 (m, 2H); 3,8-4,4 (m, 5H); the 7.65 (d, I=13,0 Hz, 1H); 8,58 (S, 1H).

IR (KBr) 3406, 1714, 1706, 1628, 1526, 1411 cm-1.

P R I m e R 39. Getting 1-cyclopropyl-6-fluoro-7-(TRANS-3-hydroxy-2-ethyl-1 - azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6-fluoro-7-(TRANS-3-hydroxy-2-ethyl-1-azetidine)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid with a melting point 250-255aboutC.

Spectroscopic data:

1H-NMR spectrum, I= Hz [DMSO-TFA] of 0.97 (t, j=7,3 Hz, 3H); of 1.20 (m, 4H); 1,60-2,00 (m, 2H); and 3.72 (m, 1H); of 4.05 (m, 1H); 4,32 (m, 2H); 4,69 (m, 1H); 6,92 (d, j=8.0 Hz, 1H); 7,74 (d, I=13,0 Hz, 1H); 8,55 (S, 1H).

IR (KBr) 3387, 1706, 1631, 1513, 1473, 1390 cm-1.

P R I m e R 40. Getting 1-cyclopropyl-6,8-debtor-7-[TRANS-3-(triptoreline-N-methyl)-2-methyl-1-azetidine]-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO] 14,1 (S, 1H); and 8.6 (S, 1H); of 7.75 (d, 1H, j=13 Hz); 4,5 (m, 5H); 3,2 (S, 3H).

IR (KBr) 1730, 1704, 1627, 1466 cm-1.

P R I m e R 41. Getting 1-cyclopropyl-6,8-debtor-7-[3-(1-pyrrolidinyl)-1-AZ - yidiny]-1,4-dihydro - 4-oxo-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6,8-debtor-7-[3-(1-pyrrolidin - nil)-1-azetidine] -1,4-dihydro-4-oxo-3 - quinoline-carboxylic acid with a melting point 224-227aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFAA] 10,83 (advanced, 1H); for 7.78 (d, j= 13, 1H); to 4.62 (m, 4H); of 4.35 (m, 1H); 4,06 (m, 1H); to 3.67 (m, 2H); 3.15 in (m, 2H); for 2.01 (m, 4H); to 1.21 (m, 4H).

IR (KBr) 1721, 1627, 1550, 1529, 1474, 1451 cm-1.

P R I m e R 42. Getting 1-cyclopropyl-6,8-debtor-7-(CIS-3-amino-2-methyl-1 - AZE the Il-6,8-debtor-7-(CIS-3-amino-2-methyl-1-azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 215-218aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] to 8.57 (S, 1H); 8,39 (advanced, 2H); of 7.69 (d, j=13, 1H); free 5.01 (m, 1H); 4,39 (m, 3H); 3,99 (m, 1H); to 1.48 (d, j=6, 3H); 1,12 (d, j=6,4 H).

IR (KBr) 3385, 1725, 1626, 1523, 1412, 1337, 803 cm-1.

P R I m e R 43. Getting 1-cyclopropyl-6-fluoro-7-(CIS-3-amino-2-methyl-1-azeti - dinyl)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6-fluoro-7-(CIS-3-amino-2-meth - yl-1-azetidine)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid with a melting point 222-225aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] charged 8.52 (S, 1H); 8,46 (advanced, 2H); of 7.75 (d, j=13, 1H); 6,98 (d, j=8, 1H); of 4.77 (m, 1H); 4.25 in (m, 3H); to 3.64 (m, 1H); for 1.49 (d, j=6, 3H); of 1.18 (d, j=8, 4H).

IR (KBR) 3387, 1725, 1631, 1490, 1466, 1341 cm-1.

P R I m e R 44. Getting 1-cyclopropyl-6,8-debtor-7-(r-3-amino-3-TRANS-2-dim - ethyl-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6,8-debtor-7-(r-3-amino-3-Tr - ANS-2-dimethyl-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 265-268aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFA] 8,63 (S, 1H); to 7.77 (d, j=13, 1H); of 4.83 (m, 1H); 4,33 (m, 2H); of 4.05 (m, 1H); for 1.49 (S, Noel-6-fluoro-7-(r-3-amino-3-TRANS-2-dimethyl- -1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6-fluoro-7-(r-3-amino-3-TRANS-2-dimethyl-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 269-272aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 8,61 (S, 1H); 8,42 (advanced, 2H), 7,86 (d, j=13, 1H); to 7.09 (d, j=8, 1H); of 4.54 (m, 1H); 4,15 (m, 2H); of 3.77 (m, 1H); 1,50 K (S, 3H); of 1.42 (d, j=6, 3H); 1.18 to (d, I=6, 4H).

IR (KBR) 3375, 1629, 1500, 1478, 1326 cm-1.

P R I m e R 46. Getting 1-cyclopropyl-6,8-debtor-7-(CIS-3-hydroxy-2-methyl-1-azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6,8-debtor-7-(CIS-3-hydroxy-2-methyl-1-azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 235-238aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] to 8.57 (S, 1H); 8,39 (advanced, 2H); of 7.69 (d, j=13, 1H); free 5.01 (m, 1H); 4,39 (m, 2H); 3,99 (m, 1H); 1,47 (d, j=7, 3H); 1,11 (d, j=6, 4H).

IR (KBR) 3371, 1708, 1624, 1525, 1476, 1325, 803 cm-1.

P R I m e R 47. Getting 1-cyclopropyl-6-fluoro-7-(CIS-3-hydroxy-2-methyl-1-AZ - yidiny)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6-fluoro-7-(CIS-3-hydroxy-2-methyl-1-azetidine)-1,4-dihydro - 4-oxo-3-healingherbs, , I=Hz [DMSO-TFA] charged 8.52 (S, 1H); 8,45 (advanced, 2H); 7,74 (d, j=13, 1H); 6,98 (d, j=8, 1H); of 4.77 (m, 1H); 4.25 in (m, 2H); to 3.64 (m, 1H); for 1.49 (d, j=6, 3H); to 1.15 (d, j=6, 4H).

IR (KBr) 3446, 1708, 1632, 1514, 1473, 1339 cm-1.

P R I m e R 48. Obtaining the ethyl ester of 1-cyclopropyl-6,8-debtor-7-(3-amino-3-methyl-1-azetidine)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid.

Working example 4 and ethyl ester of 1-cyclo-propyl-6,8-debtor-7-(3-amino-3-methyl-azetidine)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid with a melting point 175-181aboutC.

Spectroscopic data:

1H-NMR-spectrum , [CDCl3] 8,46 (S, 1H); for 7.78(dd, 1H, j=13 Hz); 4,36 (q, 2H, j=7 Hz); 4,3 (d, 2H, j=8 Hz); 3,92 (m, 1H); 1,80 (advanced, 2H); 1,53 (S, 3H); 1.39 in (+, 3H, j=7 Hz); to 1.15 (m, 4H).

IR (KBR) 1727, 1619, 1480, 1318, 800 cm-1.

P R I m e R 49. Obtaining 5-amino-1-cyclopropyl-6,8-debtor-7- (TRANS-3-amino-2-methyl-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4, get 5-amino-1-cyclopropyl-6,8-debtor-7-(TRANS-3-amino-2-methyl-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 206-210aboutC.

Spectroscopic data:

1H-NMR-spectrum , [OMSO-TFA] of 1.05 (m, 4H); of 1.40 (d, j=5 Hz, 3H); 3.46 in (m, 1H); of 3.78 (m, 1H); 4.0 a (m, 1H); 4,59 (m, 4H); 8,25 (advanced, 2H); WITH 8.33 (S, 1H).

Working example 4 and 1-cyclopropyl-6,8-debtor-7-(3-ethylamino-1-azetidine)-1,4-dihydro-4-oxo - 3-quinoline-carboxylic acid with a melting point 222-227aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz, [d6, DMSO-TFAA] 9,29 (advanced, 2H); 8,58 (1, 1H); 7,71 (d, j=13); br4.61 (m, 4H); 4,06 (m, 2H); 3.43 points (m, 2H); 1,19 (m, 7H).

IR (KBr) 1620, 1585, 1472, 1403, 1328 cm-1.

P R I m e R 51. Getting 1-cyclopropyl-6-fluoro-7-(3-ethylamino-1-azetidine)- 1,4-dihydro-4-oxo-3 - quinoline-carboxylic acid.

Working example 2 and get 1-cyclopropyl-6-fluoro-7-(3-ethylamino-1-AZE-tidine)-1,4-dihydro-4-oxo-3 - quinoline-carboxylic acid with a melting point 220-224aboutC.

Spectroscopic data:

H-NMR spectrum , I=Hz, [d6, DMSO-TFAA] of 9.30 (advanced, 2H); AT 8.60 (1, 1H); a 7.85 (d, j= 13, 1H); 6,99 (d, j=7,6, 1H); 4,34 (m, 5); of 3.75 (m, 1H); to 3.02 (m, 2H); of 1.23 (m, 7H).

IR (KBr) 1689, 1630, 1516, 1475, 1185 cm-1.

P R I m e R 52. Getting 1-cyclopropyl-6,8-debtor-7-(CIS-3-amino-2-ethyl-1-AZ - yidiny)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6,8-debtor-7-(CIS-3-amino-2-ethyl-1-azetidine)-1,4-dihydro-4-CSR-acid with melting point 230-234aboutC.

Spectroscopic data:

1H-NMR IS>/P>IR (KBr) 3393, 3318, 1726, 1628, 1544, 1498, 1491, 806 cm-1.

P R I m e R 53. Getting 1-cyclopropyl-6-fluoro-7-(CIS-3-amino-2-ethyl-1-azeti-dinyl)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Working example 4 and 1-cyclopropyl-6-fluoro-7-(CIS-3-amine-2-ethyl-1-azetidine)-1,4-dihydro-4 - oxo-3-quinoline-carboxylic acid with a melting point 236-237aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 0,90-1,50 (m, 7H); to 1.98 (m, 2H); of 3.77 (m, 1H); 4,30 (m, 3H); 4,59 (m, 1H); 7,13 (d, j=8.0 Hz, 1H); 7,81 (d, I=13,0 Hz, 1H); to 8.57 (S, 1H); 9,03 (advanced, 2H).

IR (KBr) 3388, 3318, 1725, 1631, 1509, 1774, 818 cm-1.

P R I m e R 54. Obtain 1-ethyl-6,8-debtor-7-(TRANS-3-amino-2-methyl-1-azetidin - nil)-1,4-dihydro-4-oxo-3-hinolincarbonova - howl acid.

Working example 4 and 1-ethyl-6,8-debtor-7-(TRANS-3-amino-2-methyl-1-azetidine)-1,4-dihydro-4-oxo - 3-quinoline-carboxylic acid with melting point 215-217aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFA] to 1.5 (m, 6H); 3,7 (m, 1H); 4,2 (m, 1H); with 4.65 (m, 4H); 7,8 (d, j=13 Hz, 1H); 8,5 (advanced, 2H); 8,86 (S, 1H).

IR (KBr) 3105, 1625, 1467 cm-1.

P R I m e R 55. Obtain 1-ethyl-6-fluoro-7-(TRANS-3-amino-2-methyl-1-azetidine)-1,4-dihydro-4-oxo - 3-quinoline-carboxylic acid.

Spectroscopic data:

1H-NMR spectrum, I=Hz [DMSO] to 1.38 (m, 6H); 3,5 (m, 4H); 4.0 a (m, 1H); 4.5 m (m, 3H); 6,56 (d, j=7 Hz, 1H); 7,8 (d, j=13 Hz, 1H); 8,83 (S, 1H).

IR (KBr) 3310, 1723, 1630, 1450 cm-1.

P R I m e R 56. Obtain 1-(2,4-differenl)-6,8-debtor-7-(TRANS-3-amino-2-meth - yl-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Just in example 4, get 1-(2,4-differenl)-6,8-debtor-7-(TRANS-3-amino-2-methyl-1-azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 200-204aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFA] 1,4 (d, j=6 Hz, 3H); the 3.65 (m, 1H); to 4.1 (m, 1H); 4,6 (m, 2H); 7,81 (m, 4H); a 8.34 (advanced, 2H); 8,61 (S, 1H).

IR (KBr) 1619, 1509, 1474 cm-1.

P R I m e R 57. Obtain 1-(2,4-differenl)-6-fluoro-7-(TRANS-3-amino-2-methyl-1-azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Just for example 4 get 1-(2,4-differenl)-6-fluoro-7-(TRANS-3-amino-2-methyl-1-azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point of 203-205aboutC.

Spectroscopic data:

1H-NMR spectrum, I=Hz [DMSO-TFA] to 1.32 (d, j=6 Hz, 3H); of 3.78 (m, 2H); 4,3 (m, 2H); 5,78 (d, j=7 Hz, 1H); 8.0 a (m, 4H); 8,3 (advanced, 2H); TO 8.7 (S, 1H).

IR (KBr) 2950, 1628, 1509 cm3.

Just in example 4, get 1-(4-forfinal)-6-fluoro-7-(TRANS-3-amino-2-methyl-1-azetidine)-1,4-dihydro-4 - oxanilate with a melting point 235-239aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 8,64 (S, 1H); 8,25 (advanced, 2H); 8,1 (d, j=13 Hz, 1H); to 7.75 (m, 4H); of 5.84 (d, j=8 Hz, 1H); 4.25 in (m, 2H); 3,81 (m, 2H); to 1.31 (d, j=6 Hz, 3H).

IR (KBr) 3388, 1724, 1630, 1505 cm-1.

P R I m e R 59. Obtain 1-(2-foradil)-6,8-debtor-7-(TRANS-3-amino-2-methyl-1-AZE - tidine)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid.

Just in example 4, get 1-(2-foradil)-6,8-debtor-7-(TRANS-3-amino-2-me - Teal-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 222-224aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFA] of 1.53 (d, j=6 Hz, 3H); 3,7 (m, 1H); 4,27 (m, 2H); 4.7 in (m, 3H); 5,0 (m, 2H); 7,9 (d, j=12 Hz, 1H); 8,44 (advanced, 2H), AND 8.8 (S, 1H).

IR (KBr) 2985, 1632, 1476 cm-1.

P R I m e R 60. Obtain 1-(2-foradil)-6-fluoro-7-(TRANS-3-amino-2-methyl-1-azetidine)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid.

Just in example 4, get 1-(2-foradil)-6-fluoro-7-(TRANS-3-amino-2-methyl-1-azetidine)-1,4-dihydro-4-CSR-carboxylic acid with a melting point 205-220aboutC.

Spectroscopic data is irony, 2H); 8,83 (S, 1H).

IR (KBr) 3100, 1631, 1490, 1341 cm-1.

P R I m e R 61. Obtaining 1-(4-forfinal)-6,8-debtor-7-(TRANS-3-amino-2-methyl-1-azetidine)-1,4-dihydro-4-noncarbonate acid.

Just in example 4, get 1-(4-forfinal)-6,8-debtor-7-(TRANS-3-amino-2-meth - yl-1-azetidine)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid with a melting point 223-229aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] to 8.45 (S, 1H); 8.3 (the advanced, 2H); 7,8 (m, 5H); 4,55 (m, 2H); was 4.02 (m, 1H); to 3.64 (m, 1H); 1,4 (d, j=6 Hz, 3H).

IR (KBr) 3420, 1623, 1578, 1472 cm-1.

P R I m e R 62. Obtaining (-)-(3S)-10-[3-(S)-amino-2-(R)-methyl-1-azetidine] -9-fluoro- -2,3-dihydro-3 - methyl-7-oxo-7H-pyrido [1,2,3-de] [1,4]-benzoxazine-6-carboxylic acid.

Just in example 4, receive (-)-(3S)-10-[3-(S)-amino-2-(R)-methyl-1-azetidine] -9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido [1,2,3-de] [1,4]benzoxazine-6-carboxylic acid with a melting point 217-219aboutC.

[]D20=-106,8 (c=0-31, 0.5 N NaOH).

Spectroscopic data:

1H-NMR spectrum, I=Hz [DMSO-TFA] 1,50 (m, 6H); 3,7 (m, 1H); 4,00-5,10 (m, 6H); 7,58 (d, j=14,0 Hz, 1H); 8,35 (advanced, 3H); OF 8.92 (S, 1H).

IR (KBr) 3425, 2975, 1623, 1472, 1333 cm-1.

P R I m e R 63. Obtain (+)-(3R)-10-[3-(R)-amino-2-(S)-methyl-1-assetid is the emer 4, receive (+)-(3R)-10-[3-(R)-amino-2-(S)-methyl-1-azetidine] -9-fluoro-2,3-dihydro-3 - methyl-7-oxo-7H-pyridine [1,2,3-de] [1,4] benzoxazine-6-carboxylic acid with melting point 215-217aboutC.

[]D20=+104,7 (c=0,25, 0.5 N NaOH).

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 1,50 (m, 6H); 3,7 (m, 1H); 4,00-5,10 (m, 6H); 7,58 (d, j=14,0 Hz, 1H); 8,35 (advanced, 3H); OF 8.92 (S, 1H).

IR (KBr) 3425, 2975,1623, 1472, 1333 cm-1.

P R I m e R 64. Obtain (+)-1-cyclopropyl-6,8-debtor-7-(3(S)-amino-2-(R)-methyl-1-azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Just in example 4, receive (+)-1-cyclopropyl-6,8-debtor-7-[3-(S)-amino-2-(R)- methyl-1-azetidine] -1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 229-231aboutC.

[ ]D20=+9,4 (c=0,26, 0.5 N NaOH).

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 8,61 (S, 1H); 8,32 (advanced, 2H); of 7.70 (dd, j=13, I=1,5, 1H); was 4.76 (m, 2H); 4.09 to (m, 2H); and 3.72 (m, 1H); 1,53 (d, j=6, 3H); to 1.16 (d, j=6, 4H).

IR (KBr) 1719, 1630, 1578, 1466, 1402, 1319 cm-1.

P R I m e R 65. Obtaining (-)-1-cyclopropyl-6,8-debtor-7-[3-(R)-amino-2-(S)-methyl-1 - azetidine]-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Just in example 4, receive (-)-1-cyclopropyl-6,8-debtor-7-[3-(R)-amino-2-(S)- methyl-120=-10,6 (c=0,27, NaOH, 0.5 N).

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 8,61 (S, 1H); 8,32 (advanced, 2H); of 7.70 (dd, j=13, I=1,5, 1H); was 4.76 (m, 2H); 4.09 to (m, 2H); and 3.72 (m, 1H); 1,53 (d, j=6, 3H); to 1.16 (d, j=6, 4H).

IR (KBr) 1719, 1630, 1578, 1466, 1402, 1319 cm-1.

P R I m e R 66. Obtaining (-)-1-cyclopropyl-6-fluoro-7-[3-(S)-amino-2-(R)-methyl-1-AZE - tibinil] -1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid.

Just in example 4, receive (-)-1-cyclopropyl-6-fluoro-7-[3-(S)-amino-2-(R)-methyl-1-azetidine]-1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid with a melting point 236-239aboutC.

[]D20=-7,0 (c=0,37 NaOH, 0.5 N).

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 8,64 (S, 1H); 8,35 (advanced, 2H); 8 (d, j= 13 Hz, 1H); 4.7 in (m, 2H); 4.25 in (m, 1H); the 3.65 (m, 2H); of 1.62 (d, j=6 Hz, 3H); 1,1 (m, 4H).

IR (KBr) 2943,1629, 1447 cm-1.

P R I m e R 67. Obtain (+)-1-cyclopropyl-6-fluoro-7-[3-(R)-amino-2-(S)-methyl-1-AZE - tibinil] -1,4 - dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid.

Just in example 4, receive (+)-1-cyclopropyl-6-fluoro-7-[3-(R)-amino-2-(S)-methyl-1-azetidine]-1,4 - dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid with a melting point of 236 to 249aboutC.

[]D20=+7,6 (c=0,42 0.5 N NaOH).

Spektroskopische (d, I=6 Hz, 3H); 1,1 (m, 4H).

IR (KBr) 2943, 1629, 1447 cm-1.

P R I m e R 68. Obtain (+)-1-cyclopropyl-6-fluoro-7-[3-(S)-amino-2-(R)-methyl-1-AZE - tidal]-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Just in example 4, receive (+)-1-cyclopropyl-6-fluoro-7-[3-(S)-amino-2-(R)-methyl-1-azetidine]-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 242-244aboutC.

[ ]D20=+13,7 (c=0,38 0.5 N NaOH).

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 8,61 (S, 1H); of 8.37 (advanced, 2H); b (d, j=13, 1H);? 7.04 baby mortality (d, j=8, 1H); 4.53-in (m, 2H); to 3.92 (m, 3H); and 1.54 (d, j=6, 3H); 1,19 (d, j=8, 4H).

IR (KBr) 1719, 1629, 1479, 1325 cm-1.

P R I m e R 69. Obtaining (-)-1-cyclopropyl-6-fluoro-7-[3-(R)-amino-2-(S)-methyl-1-AZE - tibinil]-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Just in example 4, receive (-)-1-cyclopropyl-6-fluoro-7-[3-(R)-amino-2-(S)-methyl-1-azetidine]-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 242-244aboutC.

[]D20=margin of 13.3 (c=0.31 in 0.5 N NaOH).

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 8,61 (S, 1H); of 8.37 (advanced, 2H); 7,86 (d, j=13, 1H);? 7.04 baby mortality (d, j=8, 1H); 4.53-in (m, 2H); to 3.92 (m, 3H); and 1.54 (d, j=6, 3H); 1,19 (d, j=8, 4H).

IR (KBr) 1719, 1629, 1479, 1325 cm-1.

P R I m e R 70. Recip is Borovoy acid with a melting point 217-221aboutC.

[]D20=-30,27 (c=0.36 and 0.5 N NaOH).

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] to 1.45 (d, j=7,0 Hz, 3H); of 1.52 (d, j= 6.0 Hz, 3H); 3,66 (m, 1H); 4,00-5,00 (m, 6H); EUR 7.57 (d, I=13,0 Hz, 1H); at 8.36 (advanced, 3H); OF 8.92 (S, 1H).

IR (KBr) 3393, 2962, 1718, 1624, 1529, 1474, 1131, 800 cm-1.

P R I m e R 71. Obtain (+)-(3R)-10-[3-(S)-amino-2-(R)-methyl-1-azetidine] -9-fluoro- -2,3-dihydro-3 - methyl-7-oxo-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6-carboxylic acid.

Just in example 4, receive (+)-(3R)-10-[3-(S)-amino-2-(R)-methyl-1-azetidine] -9 - fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6-carboxylic acid with a melting point 217-219aboutC.

[]D20=-30,60 (c=0.31 in 0.5 N NaOH).

Spectroscopic data:

1H-NMR spectrum ,I=Hz [DMSO-TFA] to 1.45 (d, j=7,0 Hz, 3H); of 1.52 (d, j=6.0 Hz, 3H); 3,66 (m, 1H); 4,00-5,00 (m, 6H); EUR 7.57 (d, I=13,0 Hz, 1H); at 8.36 (advanced, 3H); OF 8.92 (S, 1H).

IR (KBr) 3393, 2962, 1718, 1624, 1529, 1474, 1131, 800 cm-1.

P R I m e R 72. Obtaining (-)-(3S)-9-fluoro-2,3-dihydro-3-methyl-10-(3-methyl-3-methyl - Mino-1-azetidine)- 7-oxo-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6-carboxylic acid.

Just in example 2, get (3S)-9-fluoro-2,3-dihydro-3-methyl-10-(3-methyl-3 - triptoreline-N-methyl - 1-azetidine)-7-oxo-7H-pyrido [1,2,3-de] [1,4]-benzo>H-NMR spectrum , I= Hz [DMSO] of 1.44 (d, j=6.0 Hz, 3H); 1,62 9S, 3H); 3,00 (S, 3H); 4,00-4,70 (m, 6H); of 4.90 (m, 1H); 7,47 (d, I=13,0 Hz, 1H); 8,88 (m, 1H).

IR (KBr) 1726, 1686, 1623, 1476, 1465, 1163, 806 cm-1.

The above product hydrolyzing 10% sodium hydroxide to obtain (-)-(3S)-9-fluoro-2,3-dihydro-3-methyl-10-(3-meth-yl-3-methylamino - 1-azetidine)-7-oxo-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6-carboxylic acid with a melting point 288-289aboutC.

[]D20=-77,4 (c=0.50 in 0.5 N NaOH).

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] of 1.46 (d, j=6.0 Hz, 3H) AND 1.60 (S, 3H) and 1.60 (S, 3H); to 2.65 (S, 3H); 4,10-4,70 (m, 6H); to 4.87 (m, 1H); at 7.55 (d, I=13,0 Hz, 1H); 8,91 (S, 1H); 9,26 (advanced, 2H).

IR (KBr) 3431, 3331, 2956, 1702, 1624, 1540, 1474, 806 cm-1.

P R I m e R 73. Obtain (+)-(3R)-9-fluoro-2,3-dihydro-3-methyl-10-(3-methyl-3-methyl - Mino-1-azetidine)-7-oxo-7H-pyrido [1,2,3-de] [1,4]-benzoxazine-6-carboxylic acid.

Just in example 2, get (3R)-9-fluoro-2,3-dihydro-3-methyl-10-(3-methyl-3-Tr - itterated-N-methyl-1 - azetidine)-7-oxo-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6-carboxylic acid with a melting point > 300aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO] of 1.44 (d, j=6.0 Hz, 3H); OF 1.62 (S, 3H); 3,00 (S, 3H); 4,00-4,70 (m, 6H); of 4.90 (m, 1H); 7,47 (d, I=13,0 Hz, 1H); 8,88 (S, 1H).

IR (KBr) 1726, 1686, (+)-(3R)-9-fluoro-2,3-dihydro-3-methyl-10-(3-meth-yl-3-methylamino-1-azetidine) -7-oxo-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6-carboxylic acid with a melting point 288-289aboutC.

[]D20=+76,8 (c=0.52 in 0.5 N NaOH).

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] of 1.46 (d, j=6.0 Hz, 3H) AND 1.60 (S, 3H) and 1.60 (S, 3H); to 2.65 (S, 3H); 4,10-4,70 (m, 6H); to 4.87 (m, 1H); at 7.55 (d, I=13,0 Hz, 1H); 8,91 (S, 1H); 9,26 (advanced, 2H).

IR (KBr) 3432, 3331, 2956, 1702, 1624, 1540, 1474, 806 cm-1.

P R I m e R 74. Getting 1-cyclopropyl-6-fluoro-7-(3-methyl-3-methylamino-1-AZE - tidine)-1,4-dihydro-4 - oxo-1,8-naphthiridine-3-carboxylic acid.

Just in example 4, get 1-naphthiridine-6-fluoro-7-(3-methyl-3-trifloromethyl - ceramicmetal-1-azetidine) -1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid, which is then hydrolized to obtain 1-cyclopropyl-6-fluoro-7-(3-methyl-3-methylamino-1-azetidine-1,4-dihydro - 4-oxo-1,8-naphthiridine-3-carboxylic acid with a melting point 283-286aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 1,0 (m, 4H); of 1.62 (S, 3H); 2,62 (S, 3H); to 3.73 (m, 1H); to 4.38 (AB, I=7,5 4H); 8 (d, j=11.5 Hz, 1H); 8,54 (S, 1H); 9,34 (advanced, 2H).

IR (KBr) 2900, 1639, 1458 cm-1.

P R I m e R 75. Obtaining 1-(1,1-dimethylethyl)-6-fluoro-7-(3-amino-2-methyl-1-assetid - inyl)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Just in example 4, get 1-(1,1-dimethylethyl)-6-fluoro-7-(3-amino-2-methyl-1-AZ - yidiny)-1,4-dihydro - 4-/BR>1H-NMR spectrum , I=Hz [DMSO-TFA] 8,88 (S, 1H); 8,49 (advanced, 2H); to 7.93 (d, j=13, 1H); 6,85 (d, j=7,6); 4.26 deaths (AB, j=7, 4H); to 1.86 (S, 9H); TO 1.67 (S, 3H).

IR (KBr) 3350, 1718, 1612, 1470 cm-1.

P R I m e R 76. Obtaining 1-(1,1-dimethylethyl)-6-fluoro-7-(3-methyl-3-methylamino-1 - azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Just in example 2, get 1-(1,1-dimethylethyl)-6-fluoro-7-(3-methyl-3-triptoreline-N-methyl-1 - azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 260-263aboutC.

Spectroscopic data:

1H-NMR spectrum, I=Hz. [DMSO-d6; cent to 8.85 (S, 1H); 7,87 (d, j=12 Hz, 1H); to 6.88 (d, j=7, 1H); 4,22 (AB, j=7, 4H); 3.04 from (S, 3H); 1.85 to (S, 9H); OF 1.65 (S, 3H).

IR (KBr) 1712, 1689, 1632, 1510, 1464, 1151 cm-1.

Hydrolyzing the resulting product 10% sodium hydroxide to obtain 1-(1,1-dimethylethyl)-6-fluoro-7-(3-methyl-3-methyl-AMI - but-1-azetidine)-1,4-dihydro-4-oxo-3-hee-noonkanbah acid with a melting point 251-253aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 9.28 are (extended, 2H); 8,87 (S, 1H); of 7.90 (d, j=13, 1H); at 6.84 (d, j=7, 1H); 4.26 deaths (AB, j=8 Hz, 4H); 2,62 (S, 3H); 1,82 (S, 9H); TO 1.61 (S, 3H).

IR (KBr) 1630, 1608, 1474, 1341 cm-1.

P R I m e R 77. Obtain 7-(TRANS-3-amino-2-methyl-1-azetidine)-1,4-(1,1-dimethyl - ethyl)-6-fluoro-1,4-dihydro-4-oxo-3-hin retil)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point of 225-227aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 1,50 (d, j=6.0 Hz, 3H); 1,82 (S, 9H); to 3.9 (m, 2H); 4,49 (m, 2H); of 6.96 (d, j=7,0 Hz, 1H); to $ 7.91 (d, I=13,0 Hz, 1H); 8,31 (advanced, 3H), 8,86 (S, 1H).

IR (KBr) 3387, 3306, 1718, 1630, 1606, 1509, 1405, 1376, 1338 cm-1.

P R I m e R 78. Obtaining 1-(1,1-dimethylethyl)-6-fluoro-7-(TRANS-2-methyl-3-meilani - but-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Just in example 2, get 1-(1,1-dimethylethyl)-6-fluoro-7-(TRANS-2-methyl-3-trif - torsemide-N-methyl-1 - azetidine)-1,4-dihydro-4-oxo-3-Chilingarov acid with melting point 215-217aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] and 1.56 (m, 3H); of 1.88 (S, 9H); 3,18 (S, 3H); 4,20-5,00 (m, 4H); 6,99 (d, j=7,4 Hz, 1H); of 7.96 (d, I=of 12.6 Hz, 1H); of 8.92 (S, 1H).

IR (KBr) 1727, 1697, 1630, 1605, 1509, 1468, 1445, 1337, 1194, 1142 cm-1.

Hydrolyzing the resulting product 10% sodium hydroxide to obtain 1-(1,1-dimethylethyl)-6-fluoro-7-(TRANS-2-methyl-3-METI a melamine - 1-azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point of 194-195aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] of 1.57 (d, j=6,1 Hz, 3H); 1,89 (S, 9H); TO 2.67 (S, 3H); 3.75 to-4,20 (m, 2H); 4,63 (m, 2H); of 6.96 (d, j=7,0 Hz, 1H); 8,00 (d, I=13,0 Hz, 1H); 8,93 (S, 1H); of 9.21 (advanced, 2H).

amino-3-methyl-1-assetid - inyl)-1,4-dihydro-4 - oxo-1,8-naphthiridine-3-carboxylic acid.

Just in example 15, get 1-(1,1-dimethylethyl)-6-fluoro-7-(3-amino-3-methyl-1-azetidine)-1,4-dihydro-4 - oxo-1,8-naphthiridine-3-carboxylic acid with a melting point 230-234aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 8,86 (S, 1H); of 8.47 (advanced, 2H); of 8.09 (d, j=13, 1H); 4,39 (AB, j=7, 4H); to 1.86 (S, 9H); TO 1.67 (S, 3H).

IR (KBr) 3360, 1630, 1467 cm-1.

P R I m e R 80. Obtain 7-(TRANS-3-amino-2-methyl-1-azetidine)-6-fluoro-1-(1,1-di - methylethyl)-1,4 - dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid.

Just in example 15, get 7-(TRANS-3-amino-2-methyl-1-azetidine)-6-fluoro-1- (1,1-dimethylethyl)-1,4-dihydro - 4-oxo-1,8-naphthiridine-3-carboxylic acid with a melting point 223-225aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] to 1.61 (d, j=6.2 Hz, 3H); OF 1.88 (S, 9H); of 3.85 (m, 1H); 4,30 (m, 1H); of 4.66 (m, 2H); to 8.14 (d, j=12.0 Hz, 1H); at 8.36 (advanced, 3H); 8,88 (S, 1H).

IR (KBr) 3425, 2975,1630, 1560, 1466, 1355 cm-1.

P R I m e R 81. Obtaining 1-(1,1-dimethylethyl)-6-fluoro-7-(3-methyl-3-methylamino-1 - azetidine)-1,4 - dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid.

Just in example 2, get 1-(1,1-dimethylethyl)-6-fluoro-7-(3-methyl-3-triflora - lamido-N-methyl-1 - azetidine)-1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid, sa] 8,82 (S, 1H); 7,98 (d, j=11, 1H); 4,34 (AB, I=9, 4H); to 3.02 (S, 3H); of 1.84 (S, 9H); OF 1.62 (S, 3H).

IR (KBr) 1725, 1696, 1633, 1509, 1458, 1420, 1141 cm-1.

The above product hydrolyzing 10% sodium hydroxide to obtain 1-(1,1-dimethylethyl)-6-fluoro-7-(3-methyl-3-meth-yl-amino-1-azetidine)-1,4 - dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid of melting point >300aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 9,24 (advanced, 2H); 8,82 (S, 1H0; 8,0 (d, j=11, 1H); however, 4.40 (AB, I=9, 4H); and 2.26 (S, 3H); 1,82 (S, 9H); OF 1.62 (S, 3H).

IR (KBr) 1629, 1612, 1504, 1442, 1347 cm-1.

P R I m e R 82. Obtaining 1-(1,1-dimethylethyl)-6-fluoro-7-(TRANS-2-methyl-3-meilani - but-1-azetidine(- 1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid.

Just in example 2, get 1-(1,1-dimethylethyl)-6-fluoro-7-(TRANS-2-methyl-3-trif - torsemide-N-methyl - 1-azetidine)-1,4-dihydro-4-oxo-1,8-naphthiridine-3-carbon - new acid with a melting point of 224-226aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] of 1.62 (m, 3H); 1,82 (S, 9H); of 3.12 (m, 3H); 4,30-5,20 (m, 4H); 8,01 (d, I=11,1 Hz, 1H); 8,82 (S, 1H).

IR (KBr) 1725, 1693, 1632, 1449, 1196, 1148 cm-1.

The above product hydrolyzing 10% sodium hydroxide to obtain 1-(1,1-dimethylethyl)-6-fluoro-7-(TRANS-2-methyl-3-methylamino-1-azetidine)-cheskie data:

1H-NMR spectrum , I=Hz [DMSO-TFA] of 1.65 (d, j=6.3 Hz, 3H); 1,90 (S, 9H); TO 2.67 (S, 3H); 3,86 (m, 1H); 4,20-5,00 (m, 3H); 8,13 (d, j=11,6 Hz, 1H); of 8.90 (S, 1H); 9,24 (advanced, 2H).

IR (KBr) 3325, 1728, 1633, 1603, 1504, 1443, 1325 cm-1.

P R I m e R 83. Getting methylsulfonate salt of 6-fluoro-7-(TRANS-2-methyl-3-amino-1-azetidine)-1-cyclopropyl-1,4 - dihydro-4 - oxo-1,8-naphthiridine-3-carboxylic acid.

To a suspension of 0.6 g of 6-fluoro-7-(TRANS-2-methyl-3-amino-1-azetidine)-1-cyclopropyl- -1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid in 20 ml of boiling ethanol is added a solution of methanesulfonic acid in ethanol to slightly acidic pH (6). After cooling, filtering the precipitated solid and washed with cold ethanol and obtain 0.55 g methansulfonate salt of 6-fluoro-7-(TRANS-2-methyl-3-amino-1-azetidine)-1-cyclopropyl-1,4 - dihydro-4-oxo-1,8-naphthiridine-3-carbon - howl acid with a melting point 254-257aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-d6] to 1.14 (m, 4H); and 1.63 (d, j=6 Hz, 3H); 2,3 (S, 3H); 3,5 (m, 2H); to 4.33 (m, 1H); with 4.64 (m, 1H); of 8.06 (d, j=12 Hz, 1H); of 8.37 (advanced, 2H); AND 8.6 (S, 1H).

IR (KBr) 1710, 1648, 1462, 1232, 1162 cm-1.

BIOLOGICAL ACTIVITY

Antimicrobial pharmacological activity of these compounds was investigated in accordance with the technology", so 3, Flammarion Medicine Science, Paris, 1972, and V. B. Hugo, A. D. Rusell, Pharmacentical Microbiology, Blackwell Scientific Publications, London, 1977.

Culture medium and solvent:

Agar antibiotics N 1 (Oxoid CM 327)

Soy solution (Oxoid CM 129)

Physiological ringer's solution 1/4 (Oxoid BR 52)

The dextrose agar (BBL 11165).

P R I m e R 84. Getting 1-cyclopropyl-6,8-debtor-7(3-amino-2,2-dimethyl-1 - azetidine)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid.

In example 4 get 1-cyclopropyl-6,8-debtor-7-(3-amino-2,2-dimethyl-1-azeti - dinyl)-1,4-dihydro-4-oxo-3-hinolinova - new acid with a melting point 214-216aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMCO-d6] to 1.14 (m, 4H); of 1.34 (S, 3H); to 1.48 (S, 3H); 3,25 (advanced, 3H); 4,00 (m, 3H); of 4.44 (m, 1H); to 7.64 (d, I=13,2 Hz, 1H); 8,56 (S, 1H).

IR (KBr) 3393, 3325, 1725, 1627, 1522, 1449 cm-1.

P R I m e R 85. Obtaining 1-(1,1-dimethylethyl)-6,8-debtor-7-(3-methyl-3-amino-1-AZE - tidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Operating according to example 4, get 1-(1,1-dimethylethyl)-6,8-debtor-7-(3-methyl-3-amino-1-azetidine)-1,4-dihydro - 4-OK-3-quinoline-carboxylic acid with a melting point >280aboutC.

Spectroscopic data:

1H-NMR spectrum , I= /SUP>.

P R I m e R 86. Obtain 1-(2,4-differenl)-6-fluoro-7-(3-methyl-3-amino-1-azeti-dinyl)-1,4-dihydro - 4-oxo-1,8-naphthiridine-3-carboxylic acid.

Operating according to example 4, get 1-(2,4-differenl)-6-fluoro-7-(3-methyl-3 - amino-1-azetidine)-1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid with a melting point 244-248aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMCO-TFA] of 1.53 (S, 3H); 4,15 (m,4H); 7,31-7,9 (a.c. 3H); 8,10 (d, j=11 Hz, 1H); of 8.37 (advanced, 2H); 8,82 (S, 1H).

IR (KBr) 2960, 1636, 1512, 1465 cm-1.

P R I m e R 87. Receive ()-1-(2,4-differenl)-6-fluoro-7-(TRANS-2-methyl-3-amino-1-azetidine)- 1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid.

Operating according to example 4, get ()-1-(2,4-differenl)-6-fluoro-7-(tra - NS-2-methyl-3-amino-1-azetidine)- 1,4-dihydro-4-oxo-1,8-naphthiridine-3-carbon - new acid with a melting point of 220aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMCO-TFA] to 1.25 (d, j=6 Hz, 3H); and 3.72 (m, 1H); 4.25 in (m, 3H); 7,15-a 7.85 (a.c. 3H); to 8.14 (d, j=11 Hz, 1H); 8,25 (advanced, 2H); 8,83 (S, 1H).

IR (KBr) 2925, 1632, 1513, 1451 cm-1.

P R I m e R 88. Getting 1-cyclopropyl-6-fluoro-7(3-amino-2,2-dimethyl-1-azeti - dinyl)-1,4-dihydro - 4-oxo-1,8-naphthiridine-3-carboxylic acid.

aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMCO-TFA] of 1.13 (m, 4H); of 1.55 (S,3H); and 1.63 (S, 3H); 3,60 (advanced, 3H); 3,90 (m, 3H); 4,50 (m, 1H); to 7.95 (d, I=to 11.0 Hz, 1H); 8,53 (S, 1H).

IR (KBr) 3393, 3325, 1725, 1630, 1509, 1449 cm-1.

P R I m e R 89. Receive ()-1-(1,1-dimethylethyl)-6,8-debtor-7-(TRANS-2-methyl-3-amino-1-azetidine)- 1,4-dihydro-4-oxo-quinoline-carboxylic acid.

Operating according to example 4, get ()-1-(1,1-dimethylethyl-6,8-debtor-7- (TRANS - 2-methyl-3-amino-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 263-266aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMCO-TFA] is 1.51 (d, j=6 Hz, 3H); AT 1.73 (S, 9H); 3,71 (m, 1H); 4,18 (m, 1H); 4,70 (m, 2H); 7,81 (d, j=12 Hz, 1H); 8,33 (advanced, 2H); 8,96 (S, 1H).

IR (KBr) 2955, 1611, 1470, 1326 cm-1.

P R I m e R 90. Getting 5-amine-1-cyclopropyl-6,8-debtor-7-(3-methyl-3-amino-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Operating according to example 4, get 5-amino-1-cyclopropyl-6,8-debtor-7-(3-me - til-3-amino-1-azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 243-247aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMCO-d6] was 1.04 (m, 4H); to 1.59 (S, 3H); 3.9 to (m, 1H); of 4.35 (m, 4H); 8,42 (S, 1H); 8,48 propyl-6-fluoro-7-(TRANS-2-methyl-3 - amino-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Operating according to example 4, get ()-8-chloro-1-cyclopropyl-6-fluoro-7- (TRANS-2-methyl-3-amino-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 226-230aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMCO-d6-TFA] to 1.11 (m, 4H); and 1.54 (d, I=-6 Hz, 3H); 3,7 (m, 1H); 4.25 in (m, 2H); 5 (d, j=14 Hz, 1H); 8,45 (advanced, 2H); 8,73 (S, 1H).

IR (KBr) 2969, 1625, 1455, 1447 cm-1.

P R I m e R 92. Obtain 8-chloro-1-cyclopropyl-6-fluoro-7-(3-methyl-3-amino-1-azetidine)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid.

Operating according to example 4, to obtain 8-chloro-1-cyclopropyl-6-fluoro-7-(3-methyl-3-amino-1-azetidine)-1,4-dihydro-4-CSR-acid with melting point 284-285aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMCO-d6-TFA] of 1.05 (m, 4H); of 1.57 (S, 3H); 4.25 in (m, 1H); 4,51 (m, 4H), and 7.7 (d, j=14 Hz, 1H); 8,43 (advanced, 2H); TO 8.70 (S, 1H).

IR (KBr) 2945, 1639, 1611, 1444, 1356 cm-1.

P R I m e R 93. Receive ()-8-chloro-1-(2,4-differenl)-6-fluoro-7-(TRANS-2-methyl-3-amino-1-azetidine)-1,4-dihydro-4-oxo- -3-quinoline-carboxylic acid.

Operating according to example 4; get ()-8-chloro-1-(2,4-differenl)-6-fluoro- -7-(TRANS-2-methyl-3-amino-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with dot Hz, 3H); 3,55 (m, 1H); 3,95 (m, 1H); 4,95 (m, 2H); and 7.3 (m, 3H); 7,8 (d, j=13 Hz, 1H); 8,15 (advanced, 2H); AND 8.6 (S, 1H).

IR (KBr) 2930, 1622, 1509, 1445 cm-1.

P R I m e R 94. Obtain 8-chloro-1-(2,4-differenl)-6-fluoro-7-(3-methyl-3-amino-1 - azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Operating according to example 4, to obtain 8-chloro-1-(2,4-differenl)-6-fluoro-7-(3-me-til-3-amino-1-azetidine)-1,4-Digi draw the acid with a melting point 254-258aboutC.

Spectroscopic data:

1H-NMR spectrum, I= Hz [DMCO-TFA] of 1.53 (S, 3H); 4,47 (m, 4H); 7,56 (m, 3H); 7,89 (d, j=13 Hz, 1H); 8,42 (advanced, 2H); TO 8.57 (S, 1H).

IR (KBr) 2932, 1623, 1509, 1448 cm-1.

P R I m e R 95. Receive ()-8-chloro-1-(2-foradil)-6-fluoro-7-(TRANS-2-methyl-3-AMI - but-1-azetidine)-1,4 - dihydro-4-oxo-3-quinoline-carboxylic acid.

Operating according to example 4, get ()-8-chloro-1-(2-fluoro-ethyl)-6-fluoro-7- (TRANS-2-methyl-3-amino-1-azetidine)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 232-236aboutC.

Spectroscopic data:

1H-NMR spectrum, I=Hz [DMCO-TFA] 1,5 (d, j=6 Hz, 3H); 3,7 (m, 1H); 4 (m, 1H); 4.5 m (m, 1H); 5,0 (m, 5H); 7,9 (d, j=13 Hz, 1H); 8.4V (advanced, 2H); TO 8.45 (S, 1H). IR KBr 2940, 1631, 1439, 1302 cm-1.

P R I m e R 96. Obtain 8-chloro-1-(2-foradil)-6-fluoro-7-(3-methyl-3-amino-1-AZE - teenrachel)-6-fluoro-7-(3-methyl-3-amino-1-azetidine)-1,4-dihydro-4 - oxopyrimidine acid with a melting point 275-277aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMCO-TFA] and 1.56 (S, 3H); to 4.52 (m, 5H); 5,0 (m, 2H); 5,3 (m, 1H); 7,8 (d, j=13 Hz, 1H); 8,5 (advanced, 2H); OF 8.8 (S, 1H).

IR (KBr) 2930, 1634, 1611, 1445, 1333 cm-1.

P R I m e R 97. Receive ()-8-chloro-1-ethyl-6-fluoro-7-(TRANS-2-methyl-3-amino-1-AZ - yidiny)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Operating according to example 4, get ()-8-chloro-1-ethyl-6-fluoro-7-(TRANS-2-methyl-3-amino-1-azetidine)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid with a melting point 230-232aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMCO-TFA] of 1.35 (t, j=7 Hz, 3H); 1,47 (d, j=6 Hz, 3H); 3,68 (m, 1H); 4.0 a (m, 1H); 4,6-4,9 (a.c. 4H); to 7.84 (d, j=18 Hz, 1P); a 8.34 (advanced, 2H); 8,80 (S, 1H).

IR (KBr) 2950, 1630, 1615, 1445 cm-1.

P R I m e R 98. Obtain 8-chloro-1-ethyl-6-fluoro-7-(3-methyl-3-amino-1-azetidine)- 1,4-dihydro-4-oxo - 3-quinoline-carboxylic acid.

Operating according to example 4, to obtain 8-chloro-1-ethyl-6-fluoro-7(3-methyl-3-amino-1-azetidine)-1,4-dihydro-4-oxo - 3-quinoline-carboxylic acid with a melting point 280-282aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMCO-TFA] of 1.35 (t, j=7 Hz, 3H); 1,58 (S, advanced N); to 4.52 (m, 3H); 4,6 (q, j=7 Hz, 2H); of 7.75 (d, j=13 Hz, 1H); 8,44 (advanced, 2H); IS 8.75 (S, 1 is the ANS-2-methyl-3 - amino-1-azetidine)-1,4-dihydro-4-oxo-3 - quinoline-carboxylic acid.

Operating according to example 4, get ()-8-chloro-6-fluoro-1-(4-forfinal)-7-(TRANS-2-methyl-3-amino-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 245-247aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] to 1.38 (d, j=6 Hz, 3H); of 3.60 (m, 1H); 4.0 a(m,14); 4,85 (m, 2H); 7,35 (m, 4H); 7,9 (d, j=13 Hz, 1H); 8,30 (advanced, 2H); 8,48 (S, 1H).

IR (KBr) 1727, 1620, 1505, 1432 cm-1.

P R I m e R 100. Obtain 8-chloro-6-fluoro-1-(4-forfinal)-7-(3-methyl-3-amino-1-azetidine)-1,4-dihydro - 4-oxo-3-quinoline-carboxylic acid.

Just for example 4 get 8-chloro-6-fluoro-1-(4-forfinal)-7-(3-methyl-3-amino-1 - azetidine)-1,4-dihydro-4 - oxo-3-quinoline-carboxylic acid with a melting point 256-259aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] is 1.51 (S, 3H); 4,43 (m, 4H); 7,41 (m, 4H); 7,88 (d, j=13 Hz, 1H); at 8.36 (advanced, 2H); 8,46 (S, 1H).

IR (KBr) 2940, 1620, 1441 cm-1.

P R I m e R 101. Receive ()-6-fluoro-1-(2-foradil)-7-(TRANS-2-methyl-3-amino-1-azetidine)-1,4 - dihydro-4-ridin-3-carboxylic acid.

Just for example 4 get ()-6-fluoro-1-(4-foradil)-7-(TRANS-2-methyl-3-amino-1-azetidine)-1,4 - dihydro-4-origin-3-carboxylic acid with a melting point 268-271aboutC.

Spektroskopicheskaya, 2H); 8,79 (S, 1H).

IR (KBr) 1631, 1445, 1336 cm-1.

P R I m e R 102. Getting 6-fluoro-1-(2-foradil)-7-(3-methyl-3-amino-1-azetidin - nil)-1,4-dihydro-4 - oxo-1,8-naphthiridine-3-carboxylic acid.

Just for example 4 get 6-fluoro-1-(2-foradil)-7-(3-methyl-3-amino-1-azetidin - nil)-1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid with a melting point 279-286aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] of 1.53 (S, 3H); 4,4 (m, 6H); 5,2 ( 2H); of 8.09 (d, j=11.5 Hz, 1H); 8,23 (advanced, 2H); 8,8 (m, 1H).

IR (KBr) 1633, 1445, 1315 cm-1.

P R I m e R 103. Receive ()-1-ethyl-6-fluoro-7-(TRANS-2-methyl-3-amino-1-azetidine)-1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid.

Just for example 4 get ()-1-ethyl-6-fluoro-7-(TRANS-2-methyl-3-amino-1-AZ - yidiny)-1,4-dihydro-4-oxo - 1,8-naphthiridine-3-carboxylic acid with a melting point 212-215aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 1,4 (t, j=7 Hz, 3H); 1,6 (d, j=6 Hz, 3H); and 3.8 (m, 1H); 4,3 (m, 1H); 4,6 (m, 4H); and 9.1 (d, j=11.5 Hz, 1H); 8.4V (advanced, 2H); TO 8.94 (S, 1H).

IR (KBr) 1725, 1633, 1472, 1459 cm-1.

P R I m e R 104. Obtain 1-ethyl-6-fluoro-7-(3-methyl-3-amino-1-azetidine)-1,4-Digi - DRO-4-oxo-1,8 - naphthiridine-3-carboxylic acid.

Just p the GTC with a melting point 269-272aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFA] of 1.34 (t, j=7 Hz, 3H); 1,63 (S, 1H); 4,36 (m, 6H); 7,89 (d, j=11.5 Hz, 1H); 8,53 (advanced, 2H); cent to 8.85 (S, 1H).

IR (KBr) 1613, 1617, 1484, 1462 cm-1.

P R I m e R 105. Receive ()-6-fluoro-1-(4-forfinal)-7-(TRANS-2-methyl-3-amino-1-azetidine)-1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid.

Just for example 4 get ()-6-fluoro-1-(4-forfinal)-7-(TRANS-2-methyl-3-amino-1-azetidine)-1,4 - dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid with a melting point 239-244aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] at 1.17 (d, j=6 Hz, 3H); 3,7 (m, 1H); 4,2 (m, 2H); 4,4 (m, 1H); was 7.45 (m, 4H); to 8.12 (d, j=11.5 Hz, 1H); 8,2 (advanced, 2H); 8,67 (S, 1H).

IR (KBr) 1726, 1630, 1504, 1448 cm-1.

P R I m e R 106. Getting 6-fluoro-1-(4-forfinal)-7-(3-methyl-3-amino-1-azetidine)-1,4-dihydro-4 - oxo-1,8-naphthiridine-3-carboxylic acid.

Just for example 4 get 6-fluoro-1-(4-forfinal)-7-(3-methyl-3-amino-1-azeti-dinyl)-1,4-dihydro-4-oxo-1,8-naphthiridine-3-carboxylic acid with a melting point 258-260aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFA] of 1.52 (S, 3H); 4,12 (m, 4H); to 7.4 (m, 4H); 8,1 (d, j=11.5 Hz, 1H); 8,31 (advanced, 2H); 8,64 (S, 1H).

IR (KBr) 2935, 1631, 1460 1,8-naphthiridine-3-carboxylic acid.

Just for example 4 get 6-fluoro-1-(2,4-differenl)-7-(3-amino-1-azetidin - nil)-1,4-dihydro-4-oxo - 1,8-naphthiridine-3-carboxylic acid with a melting point 236-241aboutC.

Spectroscopic data:

1H-NMR spectrum, I=Hz [DMSO-d6-TFA] to 4.1 (m, 5H); 7,5 (m, 3H); 8,07 (d, j= 11.5 Hz, 1H); 8,23 (advanced, 2H); OF 8.8 (S, 1H).

IR (KBr) 1632, 1512, 1459 cm-1.

P R I m e R 108. Getting salt of para-toluenesulfonic acid 6-fluoro-1-(2,4-differenl)-7-(3-amino-1-azetidine)-1,4-dihydro - 4-oxo-1,8 - naphthiridine-3-carboxylic acid.

To a suspension of 0.34 g of 6-fluoro-1-(2,4-differenl)-7-(3-amino-1-azetidine)-1,4-di - hydro-4-oxo-1,8 - naphthiridine-3-carboxylic acid in 10 ml of ethanol is added a solution of 0.2 g of para-toluenesulfonic acid in 2 ml of ethanol, heated at 50aboutC for 30 min, after cooling, collect the solid substance of 0.37 g of salt of p-toluenesulfonic acid with a melting point of 185-187aboutC.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFA], and 2.27 (S, 3H): Android 4.04 (m, 5H); to 7.6 (m, 7H); 8,13 (d, j=11.5 Hz, 1H); 8,2 (advanced, 2H); 8,84 (S, 1H).

IR (KBr) 1728, 1631, 1449 cm-1.

P R I m e R 109. Receive ()-8-chloro-6-fluoro-1-(1,1-dimethyl-ethyl)-7-(TRANS-2-methyl-3-amino-1-azetidine ) -1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Spectroscopic data:

1H-NMR spectrum , I= Hz [DMSO-TFA] of 1.07 (d, j=6 Hz, 3H); 1,78 (S, 9H); and 3.72 (m, 1H); 4.0 a (m, 1H) and 4.9 (m, 2H); 7,8 (d, j=13 Hz, 1H); 8,5 (advanced, 2H); OF 8.8 (S, 1H).

IR (KBr) 2970, 1630, 1611, 1315 cm-1.

P R I m e R 110. Obtain 8-chloro-6-fluoro-1-(1,1-dimethylethyl)-7-(3-methyl-3-AMI - but-1-azetidine)- 1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Just for example 4 get 8-chloro-6-fluoro-1-(1,1-dimethylethyl)-7-(3-methyl-3-AMI - but-1-azetidine)-1,4 - dihydro-4-oxco-3-quinoline-carboxylic acid with a melting point 286-284aboutC.

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] of 1.55 (S, 3H); 1,74 (d, 9H); of 4.45 (m, 4H); 7,83 (d, j=13 Hz, 1H); 8,6 (advanced, 2H); OF 8.8 (S, 1H).

IR (KBr) 2945, 1634, 14562 cm-1.

P R I m e R 111. Obtaining (-)-1-(2,4-differenl)-6,8-debtor-7-[3-(R)-amino-2-(S)-methyl-1-azetidine] -1,4-dihydro-4-oxo-3-quinoline-carboxylic acid.

Just for example 4 receive (-)-1-(2,4-differenl)-6,8-debtor-7-[3-(R)-amino-2-(S)-methyl-1-azetidine] -1,4-dihydro-4-oxo-3-quinoline-carboxylic acid with a melting point 200-204aboutC.

[]D20=-14,0 (c=0,30, 0.5 N NaOH).

Spectroscopic data:

1H-NMR spectrum , I=Hz [DMSO-TFA] 1,4 (d, j=6 Hz, 3H); the 3.65 (m, 1H); to 4.1 (m, 1H); 4,6 (m, 2H); 7,81 (m, 4H); a 8.34 (increasing Trubnaya pharmacological activity of these compounds was investigated in accordance with the sources: Duke J. L. and Shabak I. A. Antimicrobial pharmacological activity. Technique in bacteriology, I. 3. Flammarion Medicine Science, Paris, 1972, and V. B. Hugo, A. D. Rusell, Pharmacevtical Microbiology, Blackwell Scilntific Publications, London, 1977.

Culture medium and solvent:

Agar antibiotics N 1 (Oxoid CM 327)

Soy solution (Oxoid CM 129)

Physiological ringer's solution 1/4 (Oxoid BR 52)

The dextrose agar (BBL 11165)

Microorganisms:

"Bacillus subtilis" ATCC 6633

"Citrobacter freundii" ATCC 112606

"Enterobacter aerogenes" ATCC 15038

"Enterobacter cloacae" ATCC 23355

"Bacillus cereus" ATCC 1178

"Escherichia coli ATCC 10799

"Escherichia coli ATCC 23559

"Klebsiclla pneumoniae" ATCC 10031

"Proteus vulgaris" ATCC 8427

"Morgs have been screaming. morganii" ATCC 8019

"Psendomonas aeruginosa" ATCC 9721

"Psendomonas aeruginosa" ATCC 10145

"Salmonella tiphymurium" ATCC 14028

"Salmonella tiphymurium" ATCC 6539

"Serratia marcescens" ATCC 13880

"Shigella flexnerii" ATCC 12022

"Staphylococcus epidermis" ATCC 155-1

"Staphylococcus aureus" ATCC 25178

"Streptococcus faualis" ATCC 10541

Getting vaccinations

Each microorganism put the strips into tubes with agar antibiotics N 1 and incubated for 20 h at 37aboutC. Then take the link of culture and placed in the soy solution and incubated for 20 h at 37aboutC. the resulting culture was diluted to 1/4 physiological ringer's solution for obtaining the mill is spodnie General formula (I)

On the basis of solution 100 lhs/ml in caustic soda 0,1 N, each product is dissolved in dextrose agar (pre-melted and maintained at 50about(C) by successive digestions to obtain the following concentrations: 64-32-16-8-4-2-1-0,5-0,25-0,125 lhs derived/ml of medium.

Subsequently, each concentration of each product placed in Petri dishes 10 cm in diameter at the rate of 10 ml medium per Cup, while the number of cups corresponds to the number of tested microorganisms.

After cooling medium in cups placed vaccination rate of 0.4 ml of vaccination on the Cup. Their diluted with anastomotic Grignaschi and collect sucks. Filled cups incubated at 37aboutWith over 20 am

The results obtained are shown in the table. Activity of compounds in vitro compared them with the activity norfloxacin. Concentrations are given in lhs/ml.

The structural formula of Norfloxacin has the following form:

< / BR>
The applicant reports that all connections are the subject of this application are compounds of low toxicity.

Derivatives of azetidine General formula

< / BR>
where a nitrogen atom or the group-CH - or-l, where Hal is a chlorine atom or fluorine;

r1>r3and r5the same or different, hydrogen or lower alkyl;

r4hydroxyl, amino, aminoalkyl, alkylamino, dialkylamino, pyrrolyl-1 or pyrrolidinyl-1, acylaminoalkyl, trifurcated;

r6hydrogen or amino group,

or a and r1together form a group and in this case have a chiral center configuration r or S;

r7hydrogen or lower alkyl,

or their pharmaceutically acceptable salts have antibacterial activity.

Priority signs:

16.03.89, when a nitrogen atom or the group-CH - or-Hal, where Hal is a chlorine atom or fluorine, r1cycloalkyl, r2, r3and r5the same or different, hydrogen or lower alkyl, r4hydroxyl, amino, aminoalkyl, alkylamino, dialkylamino, pyrrolyl-1, acylaminoalkyl, r6hydrogen, r7hydrogen

29.06.89 when r4pyrrolidinyl-1, triptorelin, r6amino group, r7lower alkyl;

20.11.89 when r1lower alkyl, lower halogenated or phenyl substituted mono - or Diptera.

 

Same patents:

The invention relates to new derivatives of intellipedia General formula

where R1phenyl substituted by substituents selected from the group consisting of lower alkyl, hydroxyl, protected hydroxyl, halogen or lower alkoxy,

And lower alkylen,

In the lower albaniles, or their pharmaceutically acceptable salts which exhibit anti-allergic effect

The invention relates to new biologically active pyridyl - or pyrimidinediamine derivative of piperazine or 1,4-disallocation, or their pharmacologically active acid additive salts with psychotropic action

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of 5-phenylpyrimidine or their pharmaceutically acceptable acid-additive salts that elicit properties of antagonists of neuropeptide receptor neurokinin-1 (NK-1). This allows their applying for treatment of such diseases as Alzheimer's disease, cerebrospinal sclerosis, attenuating syndrome in morphine withdrawal, cardiovascular alterations and so on. Compounds of invention correspond to the general formula (I):

wherein R1 means hydrogen or halogen; R2 means hydrogen, halogen atom, (lower)-alkyl or (lower)-alkoxy-group; R3 means halogen atom, trifluoromethyl group, (lower)-alkoxy-group or (lower)-alkyl; R4/R4' mean independently hydrogen atom or (lower)-alkyl; R5 means (lower)-alkyl, (lower)-alkoxy-group, amino-group, hydroxyl group, hydroxy-(lower)-alkyl, -(CH2)n-piperazinyl substituted optionally with lower alkyl, -(CH)n-morpholinyl, -(CH2)n+1-imidazolyl, -O-(CH2)n+1-morpholinyl, -O-(CH2)n+1-piperidinyl, (lower)-alkylsulfanyl, (lower)-alkylsulfonyl, benzylamino-group, -NH-(CH2)n+1N(R4'')2, -(CH2)n-NH-(CH2)n+1N(R4'')2, -(CH2)n+1N(R4'')2 or -O-(CH2)n+1N(R4'')2 wherein R4'' means hydrogen atom or (lower)-alkyl; R6 means hydrogen atom; R2 and R6 or R1 and R6 in common with two ring carbon atoms can represent -CH=CH-CH=CH- under condition that n for R1 is 1; n means independently 0-2; X means -C(O)N(R4'')- or -N(R4'')C(O)-. Also, invention relates to a pharmaceutical composition.

EFFECT: valuable medicinal properties of compounds.

15 cl, 4 sch, 86 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a group of new derivatives of 4,5-dihydro-1H-pyrazole of the general formula (I):

wherein R means phenyl, thienyl or pyridyl and these indicated groups can be substituted with (C1-C3)-alkoxy-group or halogen atom; R1 means phenyl that can be substituted with (C1-C3)-alkoxy-group or pyridyl group; R2 means hydrogen atom or hydroxy-group; Aa means one group among the following groups: (i) , (ii) , (iii) , (iv) or (v) ; R4 and R5 mean independently from one another hydrogen atom or (C1-C8)-branched or unbranched alkyl; or R4 means acetamido- or dimethylamino-group or 2,2,2-trifluoroethyl, or phenyl, or pyridyl under condition that R5 means hydrogen atom; R6 means hydrogen atom at (C1-C3)-unbranched alkyl; Bb means sulfonyl or carbonyl; R3 means benzyl, phenyl or pyridyl that can be substituted with 1, 2 or 3 substitutes Y that can be similar or different and taken among the group including (C1-C3)-alkyl or (C1-C3)-alkoxy-group, halogen atom, trifluoromethyl; or R3 means naphthyl, and its racemates, mixtures of diastereomers and individual stereoisomers and as well as E-isomers, Z-isomers and mixture of E/Z-compounds of the formula (I) wherein A has values (i) or (ii), and its salt. These compounds are power antagonists of Cannbis-1 (CB1) receptor and can be used for treatment of psychiatric and neurological diseases. Except for, invention relates to a pharmaceutical composition used for treatment of some diseases mediated by CB1-receptor, to a method for preparing this composition, a method for preparing representatives of compounds of the formula (I) wherein Aa means group of the formulae (i) or (ii), intermediate compounds used for preparing compounds of the formula (I) and to a method for treatment of some diseases mediated by CB1-receptor.

EFFECT: valuable medicinal properties of compounds.

16 cl, 9 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to new derivatives of dihydropyrimidine of the general formula (I):

or its isomeric form of the formula (Ia):

that can be used, for example, for treatment and prophylaxis of hepatitis B. In indicated formulas R1 means unsubstituted phenyl or phenyl substituted once or many times with similar or different substitutes taken among the group including halogen atom, trifluoromethyl group, nitro-, amino-group, hydroxyl and alkyl with 1-6 carbon atoms, or residues of formulas:

, or ; R2 means residue of the formula -XR5 wherein X means a bond or oxygen atom; R5 means alkenyl with 2-4 carbon atoms or alkyl with 1-4 carbon atoms that can be unsubstituted or substituted with phenoxy-group; R3 means amino-group, alkyl with 1-4 carbon atoms or cyclopropyl; R4 means pyridyl that is substituted with up to three times with similar or different substitutes taken among the group including halogen atom, trifluoromethyl group, alkoxy-group with 1-6 carbon atoms and alkyl with 1-6 carbon atoms, and their salts. Also, invention relates to 3,5-difluoro-2-pyridincarboxyimidamide and 3,5-difluoro-2-pyridincarbonitrile that can be sued as intermediates products for preparing compounds of the formula (I) or (Ia) and to a medicinal gent.

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

10 cl, 2 sch, 4 tbl, 9 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of indolylpiperidine of the formula (I): wherein A1 means (C1-C7)-alkylene, (C1-C7)-alkyleneoxy-, (C1-C7)-alkylenethio-, (C1-C7)-alkanoyl, hydroxy-(C1-C7)-alkylene; A2 means a single bond, (C1-C7)-alkylene, (C2-C5)-alkenylene; W means a single bond, phenylene, furanylene that is unsubstituted or substituted with one or more halogen atoms, (C1-C7)-alkoxy- and/or alkyl groups; R1 means hydrogen atom (H), (C1-C7)-alkyl, (C2-C7)-alkenyl, (C2-C7)-alkynyl, (C2-C5)-alkoxyalkyl, (C3-C7)-alkenyloxyalkyl, (C3-C7)-alkynyloxyalkyl, (C3-C7)-alkoxyalkoxyalkyl, phenyl-(C1-C7)-alkyl wherein phenyl is unsubstituted or substituted with one or more halogen atoms, (C1-C7)-alkyl, (C1-C7)-alkoxy- or arylalkoxy- (preferably with phenylalkoxy-) groups, or means (C3-C10)-cycloalkyl-(C1-C7)-alkyl wherein cycloalkyl is unsubstituted or substituted with one or more halogen atoms, (C1-C7)-alkyl, (C1-C7)-alkoxy-groups; R2 means hydrogen atom (H), halogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-; R3 means carboxyl, tetrazolyl, and to their pharmaceutically acceptable salts. Compounds of the formula (I) elicit antihistaminic and anti-allergic activity that allows their using in composition used for treatment of allergic diseases including bronchial asthma, rhinitis, conjunctivitis, dermatitis and nettle rash. Also, invention describes methods for preparing compounds of the formula (I).

EFFECT: valuable medicinal properties of compounds.

15 cl, 2 sch, 3 tbl, 162 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of 1-arenesulfonyl-2-arylpyrrolidine and piperidine of the formula (I):

wherein R1 means hydrogen atom (H), (C1-C7)-alkyl; R2 means furyl, thienyl, pyridyl or phenyl optionally substituted with 1-3 substitutes taken among (C1-C7)-alkyl, (C1-C7)-alkoxy-group, halogen atom, cyano-group, CF3 or -N(R4)2; R3 means naphthyl or phenyl optionally substituted with 1-3 substitutes taken among (C1-C7)-alkyl, (C1-C7)-alkoxy-group, halogen atom, acetyl, cyano-group, hydroxy-(C1-C7)-alkyl, -CH2-morpholine-4-yl, (C1-C7)-alkyloxy-(C1-C7)-alkyl, (C1-C7)-alkyl-N(R4)2 or CF3; R4 means independently of one another hydrogen atom (H), (C1-C7)-alkyl with exception for (RS)-2-phenyl-1-(toluene-4-sulfonyl)pyrrolidine, (RS)-1-(toluene-4-sulfonyl)-2-p-tolylpyrrolidine, N-tosyl-cis-3-methyl-2-phenylpyrrolidine, 3-[1-(toluene-4-sulfonyl)pyrrolidine-2-yl]pyridine and N-tosyl-2-(3,4-dimethoxyphenyl)pyrrolidine, and their pharmaceutically acceptable salts also. Compounds of the formula (I) elicit the effect of agonists or antagonists of metabotropic glutamate receptors that allows their using in pharmaceutical agent useful for treatment or prophylaxis of acute and/or chronic neurological disturbances.

EFFECT: valuable medicinal properties of compounds.

9 cl, 1 tbl, 3 sch, 94 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new antibacterial agents. Invention describes cycloalkyl-substituted derivatives of aminomethylpyrrolidine represented by the general formula (I): wherein each among R1 and R2 represents hydrogen atom; n represents a whole number from 1 to 4; Q represents structural moiety represented by the following formula (Ia): wherein R3 represents cyclic alkyl group comprising from 3 to 6 carbon atoms that can be substituted; R4 represents hydrogen atom; R5 represents hydrogen atom or amino-group; X1 represents halogen or hydrogen atom; A1 represents nitrogen atom or structural moiety represented by the formula (II): wherein X2 represents hydrogen, halogen atom or alkyl group comprising from 1 to 6 carbon atoms, or alkoxyl group comprising from 1 to 6 carbon atoms; X2 and R3 can form a ring structure in common with part of the parent skeleton optionally comprising oxygen, nitrogen or sulfur atom as a ring-forming atoms and optionally comprising alkyl group comprising from 1 to 6 carbon atoms as a substitute; Y represents hydrogen atom. Also, invention describes an antibacterial an agent containing compound by cl. 1. Invention provides preparing new compounds eliciting valuable biological properties.

EFFECT: valuable properties of compounds and agent.

15 cl, 1 tbl, 10 ex

FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: 5-aryl-1H-1,2,4-triazole derivatives of general formula I

, pharmaceutically acceptable salts thereof or pharmaceutical composition containing the same are described. In formula R1 is C1-C6-alkyl, C1-C6-haloalkyl or phenyl; R2 is C3-C8-cycloalkyl; phenyl optionally substituted with one or more substituents selected from C1-C4-alkyl; halogen, hydroxyl, C1-C4-alkoxy, nitro, di-(C1-C4)-alkylamino, C1-C4-alkylsulphonyl, C1-C4- alkylsulphonylamino, and methylenedioxy; phenyl-(C1-C4)-alkyl, wherein phenyl is substituted with C1-C4-alkoxy; or pyridil. New compounds are effective and selective cyclooxygenase-2 (COX-2) inhibitors and useful in treatment of inflammations.

EFFECT: new compounds for inflammation treatment.

10 cl, 36 ex, 1 tbl

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to new 2-aminopyridine derivatives of formula I , wherein R1 is cyano, carboxyl or carbamoyl; R2 is hydrogen, hydroxyl, C1-C6-alkoxy or phenyl; R3 and R4 are aromatic hydrocarbon such as phenyl or naphthyl, 5-14-membered 5-14-membered optionally substituted aromatic group, excepted cases, when (1) R1 is cyano, R2 is hydrogen, and R3 and R4 are simultaneously phenyl;(2) R1 is cyano, R2 is hydrogen, R3 is 4-pyridyl, and R4 is 1-pyridyl; (3) R1 is cyano, R2 is 4-methylphenyl, and R3 and R4 are simultaneously phenyl;(4) R1 is cyano, R2, R3 and R4 are simultaneously phenyl, or salts thereof. Derivatives of present invention have adenosine receptor antagonist activity and are useful in medicine for treatment of irritable bowel syndrome, constipation, and defecation stimulation.

EFFECT: 2-aminopyridine derivatives as adenosine receptor antagonists useful in medicine.

34 cl, 2 tbl, 179 ex

Substituted indoles // 2255087

FIELD: organic chemistry, biochemistry.

SUBSTANCE: invention relates to new substituted indoles of the formula (I): and/or stereoisometic form of compound of the formula (I) and/or physiologically acceptable salt of compound of the formula (I) wherein R3 means residue of the formula (II): wherein D means -C(O)-; R7 means hydrogen atom (H) or -(C1-C4)-alkyl; R8 means (a) typical residue of amino acid among the group: phenylalanine or homophenylalanine wherein phenyl residue is unsubstituted or substituted with halogen atom; or (b) -(C1-C4)-alkyl wherein alkyl is a linear or branched and (b) 1) mono- or multi-substituted independently of one another with pyrrole residue wherein this residue is unsubstituted or substituted with halogen atom; (b) 2) mono- or bi-substituted independently with residue -S(O)x-R10 wherein x = 0, 1 or 2, or (b) 3) mono- or bi-substituted independently of one another -N(R10)2 wherein R10 means (a) hydrogen atom (H); (b) means -(C1-C6)-alkyl wherein alkyl is unsubstituted or substituted with halogen atom from 1 to 3 times; (c) phenyl wherein phenyl is substituted or substituted with halogen atom from 1 to 3 times; in the case (R10)2 residues R10 have values independently of one another (a), (b), (c); Z means (a) residue of heterocycles group comprising benzothiadizine, pyrrole, pyridine, pyrimidine, pyrazine, imidazole, pyrazole, oxazole, isoxazole, thiazole, isothiazole, tetrazole, oxadiazolone, triazole being heterocycles are unsubstituted or substituted with -NH2=, =O, alkoxycarbonyl or aminocarbonyl from 1 to 3 times, or (b) means -C(O)-R11 wherein R11 means 1. -O-R10 or 2. -N(R10)2; R9 means (a) hydrogen atom (H); (b) means (C1-C6)-alkyl wherein alkyl is unbranched or branched and substituted with phenyl or =O independently of one another from 1 to 3 times; (c) phenyl wherein phenyl is unsubstituted or substituted with halogen atom; R1, R2 and R4 mean hydrogen atom (H); R5 means hydrogen atom (H); R6 means (a) phenyl wherein phenyl is unsubstituted or substituted with -NH2; (b) pyridine, or (c) pyrimidine being pyridine or pyrimidine is unsubstituted or substituted with groups -NH2, -NH-CH3. Compounds of the formula (I) are specific inhibitors of IkB kinase.

EFFECT: valuable biochemical properties of compounds.

3 cl, 3 tbl, 29 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes benzamidine derivatives of the general formula (I): wherein R1 means hydrogen atom, halogen atom, (C1-C6)-alkyl or hydroxyl; R2 means hydrogen atom or halogen atom; R3 means (C1-C6)-alkyl possibly substituted with hydroxy-group, alkoxycarbonyl-(C3-C13)-alkylsulfonyl, carboxy-(C2-C7)-alkylsulfonyl; each among R4 and R5 means hydrogen atom, halogen atom, (C1-C6)-alkyl possibly substituted with halogen atom, (C1-C6)-alkoxy-group, carboxy-group, (C2-C7)-alkoxycarbonyl, carbamoyl, mono-(C2-C7)-alkylcarbamoyl, di-(C3-C13)-alkylcarbamoyl; R6 means heterocycle or similar group; each among R7 and R8 means hydrogen atom, (C1-C6)-alkyl or similar group; n = 0, 1 or 2, or their pharmacologically acceptable salts, esters or amides. Compounds elicit the excellent inhibitory activity with respect to activated factor X in blood coagulation and useful for prophylaxis or treatment of diseases associated with blood coagulation.

EFFECT: improved method for prophylaxis and treatment, valuable medicinal properties of compound.

26 cl, 2 tbl, 253 ex

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