Plasma carboxypeptidase b inhibitors

FIELD: organic chemistry, medicine, biochemistry.

SUBSTANCE: invention describes compound of the formula (I): wherein R1 means hydrogen atom (H); R2 means -SH, -S-C(O)-R8, -P(O)(OR5)2, -P(O)(OR5)R6, -P(O)(OR5)-R7-C(O)-R8, -P(O)(OR5)-R7-N(R5)-S(O)2-R9 or -P(O)(OR5)-R7-N(R5)-C(S)-N(R6)2; R3 means tetrazole, -C(O)OR6, -C(O)O-R7-OC(O)R5; R4 means optionally substituted aryl, or R4 means N-heterocyclyl. Also, invention describes compounds of the formula (II): and (III): wherein X means -CH2- or -O-, and pharmaceutical compositions comprising indicated compounds. Proposed compounds possess inhibitory effect on activity of plasma carboxypeptidase B and used as anti-thrombosis agents.

EFFECT: valuable medicinal and biochemical properties of compounds.

34 cl, 19 ex

 

The text descriptions are given in facsimile form.

Caetanina formula (I)

where R1means hydrogen,

R2means-SH, -S-C(O)-R8, -P(O)(OR5)2, -P(O)(OR5R6, -P(O)(OR5R7-C(O)-R8, -P(O)(OR5)-R7-N(R5)-S(O)2-R9or-P(O)(OR5)-R7-N(R5)-C(S)-N(R6)2,

R3means tetrazole, -C(O)OR6, -C(O)O-R7-OC(O)R5,

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -R7-N(R6)-C(O)-R6, -N(R5)-C(NR5)-N(R5)2,

or R4means N-heterocyclyl, where the carbon atom in the N-heterocyclyl optionally substituted by alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -N(R6)-C(O)-R6, -R7-N(R6)-C(O)-R6, -C(O)-N(R6)2, -C(O)-R7-N(R6)2, -N(R5)-C(NR5)-N(R5)2, -N(R5)-C(O)-N(R6)2or-N(R5)-C(O)-R7-N(R6)2or where the nitrogen atom in N-heterocyclyl optionally substituted-C(NR5)-N(R5)2, -C(NR5)-R6, -C(O)-N(R6)2or-C(O)R 7-N(R6)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl, aralkyl,

each R7independent means alkylen straight or branched chain

(optionally substituted by hydroxy group, mercapto, alkylthio, aryl, cycloalkyl, -N(R6)2, -C(O)OR6or-C(O)N(R6)2),

each R8independently mean alkyl, alkenyl, aryl, aralkyl or

aralkyl, and

R9means aryl (optionally substituted by alkyl group, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halogen, halogenoalkane, -N(R6)2, -C(O)OR6, -C(O)N(R6)2or-N(R6)C(O)R6),

or N-heterocyclyl (optional zameshannyj group alkyl, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halogen, halogenoalkane, -N(R6)2, -C(O)OR6, -C(O)N(R6)2or-N(R6)C(O)R6),

if R3means-C(O)HE or, if R4means substituted aryl or substituted N-heterocyclyl, R2does not mean

-P(O)(OR5)-R7-N(H)-C(O)OR8or

- P(O)(OR5)-R7-N(H)-C(O)-R7-N(R5)-C(O)OR8,

as well as its individual stereoisomer, mixture of stereoisomers or racemic mixtures or the ü stereoisomers or pharmaceutically acceptable salt.

2. The compound according to claim 1, where R1means hydrogen,

R2means-SH or-S-C(O)-R8,

R3means tetrazole, -C(O)OR6or-C(O)O-R7-OC(O)R5;

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -N(R6)-C(O)-R6, -N(R5)-C(NR5)-N(R5)2,

or R4means N-heterocyclyl, where the carbon atom in the N-heterocyclyl optionally substituted by alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -N(R6)-C(O)-R6, -R7-N(R6)-C(O)-R6, -C(O)-N(R6)2, -C(O)-R7-N(R6)2, -N(R5)-C(NR5)-N(R5)2, -N(R5)-C(O)-N(R6)2or-N(R5)-C(O)-R7-N(R6)2or where the nitrogen atom in N-heterocyclyl optionally substituted by a group-C(NR5)-N(R5)2, -C(NR5)-R6, -C(O)-N(R6)2or-C(O)-R7-N(R6)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl, aralkyl,

each R7the independent is IMO means alkylen straight or branched chain, optionally substituted by hydroxy group, mercapto, alkylthio, aryl, cycloalkyl, - N(R6)2, -C(O)OR6or-C(O)N(R6)2and each R8independently mean alkyl, alkenyl, aryl, aralkyl or aralkyl.

3. The compound according to claim 2, where R1means hydrogen,

R2means-SH or-S-C(O)-R8,

R3means-C(O)OR6,

R4means aryl, optionally substituted by one or more substituents selected from the group comprising halogen, nitro, -N(R6)2, -R7-N(R6)2and-N(R5)-C(NR5)-N(R5)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl or aralkyl

R7means alkylen straight or branched chain, and

R8means alkyl, alkenyl, aryl, aralkyl or aralkyl.

4. The compound according to claim 3, selected from the group including:

2-(4-guanidinium)-3-mercaptopropionic acid,

2-(3-guanidinium)-3-mercaptopropionic acid,

2-(3-AMINOPHENYL)-3-mercaptopropionic acid and

2-(2-chloro-5-guanidinium)-3-mercaptopropionic acid.

5. The compound according to claim 2, where R1means hydrogen,

R2means-SH or-S-C(O)-R8,

R3means-C(O)OR 6,

R4means 3(4)-piperidinyl, where the nitrogen atom in piperidinyl radical optionally substituted by a group C(NR5)-N(R5)2, -C(NR5)-R6, -C(O)-N(R5)2or-C(O)-R7-N(R6)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl or aralkyl,

R7means alkylen straight or branched chain, optionally substituted by hydroxy group, mercapto, alkylthio, aryl, cycloalkyl, -N(R6)2, -C(O)OR6or-C(O)N(R6)2a

R8independently mean alkyl, alkenyl, aryl, aralkyl or aralkyl.

6. The compound according to claim 5, selected from the group including:

2-(piperidine-4-yl)-3-mercaptopropionic acid,

2-(1-amidinopropane-4-yl)-3-mercaptopropionic acid,

2-(1-(1-aminoethyl)piperidine-4-yl)-3-mercaptopropionic acid,

2-(1-(aminomethylpropanol)piperidine-4-yl)-3-mercaptopropionic acid,

2-(piperidine-3-yl)-3-mercaptopropionic acid and

2-(1-amidinopropane-3-yl)-3-mercaptopropionic acid.

7. The compound according to claim 1, where R1means hydrogen,

R2mean-P(O)(OR5)2, -P(O)(OR5R6or-P(O)(OR5)-R7-C(O)-R8,

R3means tetrazol, -C(O)OR6or-C(O)O-R7-OC(O)R5,

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -R7-N(R6)-C(O)-R6, -N(R5)-C(NR5)-N(R5)2,

or R4means N-heterocyclyl, where the carbon atom in the N-heterocyclyl optionally substituted alkyl group, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -N(R6)-C(O)-R6, -R7-N(R6)-C(O)-R6, -C(O)-N(R6)2, -C(O)-R7-N(R6)2, -N(R5)-C(NR5)-N(R5)2, -N(R5)-C(O)-N(R6)2or-N(R5)-C(O)-R7-N(R6)2or where the nitrogen atom in N-heterocyclyl optionally substituted-C(NR5)-N(R5)2, -C(NR5)-R6, -C(O)-N(R6)2or-C(O)-R7-N(R6)2;

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl, aralkyl,

each R7independent means alkylen straight or branched chain,

optionally substituted by hydroxy group, mercapto, alkylthio, and the sludge

cycloalkyl, -N(R6)2, -C(O)OR6or-C(O)N(R6)2and

each R8independently mean alkyl, alkenyl, aryl, aralkyl or aralkyl.

8. The connection according to claim 7, where R1means hydrogen,

R2mean - P(O)(OR5)2, - P(O)(OR5R6or - P(O)(OR5)-R7-C(O)-R8

R3means-C(O)OR6,

R4means aryl, optionally substituted by one or more substituents selected from the group comprising halogen, nitro, -N(R6)2, -R7-N(R6)2and-N(R5)-C(NR5)-N(R5)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl or aralkyl,

each R7independent means alkylen straight or branched chain,

optionally substituted aryl, - N(R6)2or-C(O)OR6a

each R8means alkyl, alkenyl, aryl, aralkyl or aralkyl.

9. The compound of claim 8 selected from the group including:

2-(3-guanidinium)-3-phosphonopropionic acid, 2-(3-AMINOPHENYL)-3-((phenyl)(hydroxy)phosphinoyl)propionic acid;

2-(3-AMINOPHENYL)-3-((4-phenylbutyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-AMINOPHENYL)-3-((pentyl)(hydroxy)phosphinoyl)PR is the peony acid,

2-(3-guanidinium)-3-((phenyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-guanidinium)-3-((4-phenylbutyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-guanidinium)-3-((pentyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-guanidinium)-3-((4-methylphenyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-guanidinium)-3-((3-phenylpropyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-guanidinium)-3-((3-phenylprop-2-enyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-guanidinium)-3-((phenylmethyl)(hydroxy)phosphinoyl)propionic acid,

methyl ester 2-(3-guanidinium)-3-((pentyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-guanidinium)-3-((ethyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-guanidinium)-3-((2-phenylethyl)(hydroxy)phosphinoyl)propionic acid and

2-(3-guanidinium)-3-((2-(methylcarbamyl)ethyl)(hydroxy)phosphinoyl)propionic acid.

10. The compound according to claim 1,

where R1means hydrogen,

R2mean-P(O)(OR5)-R7-N(R5)-C(S)-N(R6)2,

R3means tetrazole, -C(O)OR6or-C(O)O-R7-OC(O)R5,

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano,-N(R 6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -R7-N(R6)-C(O)-R6, -N(R5)-C(NR5)-N(R5)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl, aralkyl,

each R7means alkylen straight or branched chain, optionally substituted by hydroxy group, mercapto, alkylthio, aryl, cycloalkyl, N(R6)2, -C(O)OR6or-C(O)N(R6)2a

each R8independently mean alkyl, alkenyl, aryl, aralkyl or aralkyl.

11. The compound of claim 10 selected from the group including

tert-butyl ester 2-(3-(tert-butoxycarbonylamino)were)-3-((1-amino-2-methylpropyl)(hydroxy)phosphinoyl)propionic acid and

tert-butyl ester 2-(3-(tert-butoxycarbonylamino)were)-3-((1-amino-2-methylpropyl)(ethoxy)phosphinoyl)propionic acid.

12. The compound according to claim 1,

where R1means hydrogen,

R2mean-P(O)(OR5)-R7-N(R5)-S(O)2-R9,

R3means tetrazole, -C(O)OR6or-C(O)O-R7-OC(O)R5,

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halo is Yong, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -R7-N(R6)-C(O)-R6, -N(R5)-C(NR5)-N(R5)2,

or R4means N-heterocyclyl, where the carbon atom in the N-heterocyclyl optionally substituted by alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -N(R6)-C(O)-R6, -R7-N(R6)-C(O)-R6, -C(O)-N(R6)2, -C(O)-R7-N(R6)2, -N(R5)-C(NR5)-N(R5)2, -N(R5)-C(O)-N(R6)2or-N(R5)-C(O)-R7-N(R6)2or where the nitrogen atom in N-heterocyclyl optionally substituted by a group-C(NR5)-N(R5)2, -C(NR5)-R6, -C(O)-N(R6)2or-C(O)R7-N(R6)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl, aralkyl,

each R7independent means alkylen straight or branched chain (optionally substituted by hydroxy group, mercapto, alkylthio, aryl, cycloalkyl, -N(R6)2, -C(O)OR6or-C(O)N(R6)2),

each R8independently mean alkyl, alkenyl, aryl, aralkyl or aralkyl, and

R9who appoints aryl (optionally substituted by alkyl group, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halogen, halogenoalkane, -N(R6)2, -C(O)OR6, -C(O)N(R6)2or-N(R6)C(O)R6), or N-heterocyclyl (optionally substituted by alkyl group, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halogen, halogenoalkane, N(R6)2, -C(O)OR6, -C(O)N(R6)2or-N(R6)C(O)R6).

13. The connection section 12, where R1means hydrogen,

R2means P(O)(OR5)-R7-N(R5)-S(O)2-R9,

R3means tetrazole, -C(O)OR6or-C(O)O-R7-OC(O)R5,

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8and-N(R5)-C(NR5)-N(R5)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl, aralkyl,

each R7independent means alkylen straight or branched chain (optionally substituted by hydroxy group, mercapto, alkylthio, aryl, cycloalkyl, -N(R6)2, -C(O)OR6or-C(O)N(R6)2),

each R8independently mean alkyl, alkenyl, aryl, shall alkyl or aralkyl, and

R9means aryl (optionally substituted by alkyl group, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halogen, halogenoalkane, -C(R6)2, -C(O)OR6, -C(O)N(R6)2or-N(R6)C(O)R6or N-heterocyclyl (optionally substituted by alkyl group, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halogen, halogenoalkane, N(R6)2, -C(O)OR6, -C(O)N(R6)2or-N(R6)C(O)R6).

14. The connection indicated in paragraph 13, where R1means hydrogen,

R2means P(O)(OR5)-R7-N(R5)-S(O)2-R9,

R3means tetrazole, -C(O)OR6or-C(O)O-R7-OC(O)R5,

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8and-N(R5)-C(NR5)-N(R5)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl, aralkyl,

each R7independent means alkylen straight or branched chain,

optionally substituted by hydroxy group, mercapto, alkylthio, aryl, cycloalkyl, -N(R6)2, -C(O)OR6, -C(O)N(R6 )2or-N(R6)C(O)R6

each R8independently mean alkyl, alkenyl, aryl, aralkyl or aralkyl, and

R9means aryl (optionally substituted by alkyl group, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halogen, halogenoalkane, -N(R6)2, -C(O)OR6, -C(O)N(R6)2or-N(R6)C(O)R6).

15. The connection 14, selected from the group including:

2-(3-(amino)were)-3-((1-(naphthas-1-ylsulphonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-(amino)were)-3-((1-(3-triftormetilfullerenov)amino-2-methylpropyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-(amino)were)-3-((1-(4-interpersonal)amino-2-methylpropyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-(amino)were)-3-((1-(4-acetamidobenzenesulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-(amino)were)-3-((1-(4-phenylenesulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propionic acid and

2-(3-(amino)were)-3-((1-(phenylsulfonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propionic acid.

16. The connection indicated in paragraph 13

where R1means hydrogen,

R2means P(O)(OR5)-R7-N(R5)-S(O)2-R9,

R3means tetrazole, -C(O)OR or-C(O)O-R7-OC(O)R5,

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8; -R7-N(R6)-C(O)OR8, -R7-N(R6)-C(O)-R6and-N(R5)-C(NR5)-N(R5)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl, aralkyl,

each R7independently means a straight or branched alkylenes chain (optionally substituted by hydroxy group, mercapto, alkylthio, aryl, cycloalkyl, -N(R6)2, -C(O)OR6or-C(O)N(R6)2,

each R independently mean alkyl, alkenyl, aryl, aralkyl or aralkyl, and

R9means N-heterocyclyl (optionally substituted by alkyl group, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halogen, halogenoalkane, -N(R6)2, -C(O)OR6, -C(O)N(R6)2or-N(R6)C(O)R6).

17. Connection P16 selected from the group including

2-(3-(amino)were)-3-((1-(Tien-2-ylsulphonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propionic acid,

and 2-(3-(amino)were)-3-((1-(benzothiazolylsulfenamide)amino-2-methylpropyl)(guide is hydroxy)phosphinoyl)propionic acid.

18. The compound of formula (II)

where R1means hydrogen, alkyl, alkenyl, aryl, or aralkyl,

R2mean-P(O)(OR5R6, -P(O)(OR5)-R7-N(R6)2, -P(O)(OR5)-R7-N(R5)-S(O)2-R9or-P(O)(OR5)-R7-N(R5)-C(S)-N(R6)2;

R3means tetrazole, -C(O)OR6, -C(O)O-R7-OC(O)R5,

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8; -R7-N(R6)-C(O)OR8, -R7-N(R6)-C(O)-R6, -N(R5)-C(NR5)-N(R5)2,

or R4means N-heterocyclyl, where the carbon atom in the N-heterocyclyl optionally substituted by alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -N(R6)-C(O)-R6, -R7-N(R6)-C(O)-R6, -C(O)-N(R6)2, -C(O)-R7-N(R6)2, -N(R5)-C(NR5)-N(R5)2, -N(R5)-C(O)-N(R6)2or-N(R5)-C(O)-R7-N(R6)2or where the nitrogen atom in N-heterocyclyl optionally substituted-C(NR5)-N(R6)2, -C(NR5)-R 6, -C(O)-N(R6)2or-C(O)-R7-N(R6)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl, aralkyl,

each R7independent means alkylen straight or branched chain

(optionally substituted by hydroxy group, mercapto, alkylthio, aryl,

cycloalkyl, -N(R6)2, -C(O)OR6or-C(O)N(R6)2),

each R8independently mean alkyl, alkenyl, aryl, aralkyl or aralkyl,and

R9means aryl (optionally substituted by alkyl group, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halogen, halogenoalkane,-N(R6)2, -C(O)OR6or-C(O)N(R6)2or-N(R6)C(O)R6),

aralkyl (where the aryl group optionally substituted by a group of alkyl, aryl,

aralkyl, hydroxy, alkoxy, cyano, nitro, halogen, halogenoalkane, -N(R6)2, -C(O)OR6, -C(O)N(R6)2or-N(R6)C(O)R6), or N-heterocyclyl

(optionally substituted by alkyl group, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halogen, halogenoalkane, -N(R6)2, -C(O)OR6, -C(O)N(R6)2or-N(R6)C(O)R6),

if R3means-C(O)HE or, if R4OSN which includes substituted aryl

or substituted N-heterocyclyl, R2does not mean

-P(O)(OR5)-R7-N(H)-C(O)OR8or

-P(O)(OR5)-R7-N(H)-C(O)-R7-N(R5)-C(O)OR8,

as well as its individual stereoisomer, mixture of stereoisomers or racemic mixture of stereoisomers, or a pharmaceutically acceptable salt.

19. Connection p,

where R1means hydrogen,

R2mean-P(O)(OR5R6, -P(O)(OR5)-R7-N(R6)2or

-P(O)(OR5)-R7-N(R5)-C(S)-N(R6)2,

R3means tetrazole, -C(O)OR6or-C(O)O-R7-OC(O)R5;

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -N(R6)-C(O)-R6, -N(R5)-C(NR5)-N(R5)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl, aralkyl,

each R7means a straight or branched alkylenes chain

(optionally substituted by hydroxy group, mercapto, alkylthio, aryl, cycloalkyl, -N(R6)2, -C(O)OR6or-C(O)N(R6/sup> )2), and

each R8independently mean alkyl, alkenyl, aryl, aralkyl or aralkyl.

20. The connection according to claim 19, selected from the group including:

2-(3-guanidinium)-2-((1-(2-phenylethyl)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid,

2-(3-AMINOPHENYL)-2-((phenyl)(hydroxy)fosfinovoi)acetic acid;

2-(3-guanidinium)-2-((1-amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid and

2-(3-guanidinium)-2-((1-(benzylaminocarbonyl)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid.

21. Connection p, where R1means hydrogen,

R2mean-P(O)(OR5R6, -P(O)(OR5)-R7-N(R6)2, -P(O)(OR5)-R7-N(R5)-S(O)2-R9or-P(O)(OR5)-R7-N(R5)-C(S)-N(R6)2,

R3means tetrazol,

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -N(R6)-C(O)-R6, -N(R5)-C(NR5)-N(R5)2,

or R4means N-heterocyclyl, where the carbon atom in the N-heterocyclyl optionally substituted by alkyl, halogen, nitro, cyano,, -N(R6 )2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -N(R6)-C(O)-R6, -R7-N(R6)-C(O)-R6, -C(O)-N(R6)2, -C(O)-R7-N(R6)2, -N(R5)-C(NR5)-N(R5)2, -N(R5)-C(O)-N(R6)2or-N(R5)-C(O)-R7-N(R6)2or where the nitrogen atom in N-heterocyclyl optionally substituted-C(NR5)-N(R5)2, -C(NR5)-R6, -C(O)-N(R6)2or-C(O)-R7-N(R6)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl, aralkyl,

each R7independently means a straight or branched alkylenes chain

(optionally substituted by hydroxy group, mercapto, alkylthio, aryl,

cycloalkyl,, -N(R6)2, -C(O)OR6or-C(O)N(R6)2),

each R8independently mean alkyl, alkenyl, aryl, aralkyl or aralkyl, and

R9means aryl (optionally substituted by alkyl group, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halogen, halogenoalkane, -N(R6)2, -C(O)OR6, -C(O)N(R6)2or-N(R6)C(O)R6), or N-heterocyclyl (optionally substituted by alkyl group, aryl, aralkyl, hydroxy, alkoxy, cyano, nitro, halogen, who, halogenoalkane, N(R6)2, -C(O)OR6, -C(O)N(R6)2or-N(R6)C(O)R6).

22. Connection item 21, i.e. benzyl ester 2-methyl-1-[1-(3-(3-guanidinium)-1-tetraisopalmitate](hydroxy)postyourproperty.com acid.

23. The compound of formula (III)

where X is-CH2- or-O-,

R1means hydrogen,

R2mean-P(O)(OR5)-R7-N(R5)-C(O)R6, -P(O)(OR5)-R7-N(R5)-C(O)OR8or-P(O)(OR5)-R7-N(R5)-C(O)-N(R5)-C(O)OR8,

R3-C(O)OH,

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8; -R7-N(R6)-C(O)OR8, -N(R6-C(O)-R6, -N(R5)-C(NR5)-N(R5)2,

or R4means N-heterocyclyl, where the carbon atom in the N-heterocyclyl optionally substituted by alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -N(R6)-C(O)-R6, -R7-N(R6)-C(O)-R6, -C(O)-N(R6)2, -C(O)-R7-N(R6)2, -N(R5)-C(NR5)-N(R5)2, -N(R5)-C(O)-N(R6)2or -(R 5)-C(O)-R7-N(R6)2or where the nitrogen atom in N-heterocyclyl optionally substituted-C(NR5)-N(R5)2, -C(NR5)-R6, -C(O)-N(R6)2or-C(O)-R7-N(R6)2,

each R5independently means hydrogen, alkyl or aralkyl,

each R6independently means hydrogen, alkyl, aryl, aralkyl,

each R7independent means alkylen straight or branched chain (optionally substituted by hydroxy group, mercapto, alkylthio, aryl, cycloalkyl, -N(R6)2, -C(O)OR6or-C(O)N(R6)2), a

each R8independently mean alkyl, alkenyl, aryl, aralkyl or aralkyl, as well as its individual stereoisomer, mixture of stereoisomers or racemic mixture of stereoisomers, or a pharmaceutically acceptable salt.

24. Connection item 23, where X is-O-,

R2mean-P(O)(OR5)-R7-N(R5)-C(O)OR8a

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -N(R6)-C(O)-R6, -N(R5)-C(NR5)-N(R5)2.

25. The connection point 24, selected from the group including:

2-(-guanidinium)-2-((1-(benzyloxycarbonyl)aminoethyl)(hydroxy)-fosfinovoi)acetic acid,

2-(3-guanidinium)-2-(((benzyloxycarbonyl)aminomethyl)(hydroxy)-fosfinovoi)acetic acid,

2-(3-guanidinium)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid,

2-(3-guanidinium)-2-((1-(benzyloxycarbonyl)aminohexyl)(hydroxy)-fosfinovoi)acetic acid,

2-(3-AMINOPHENYL)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid,

2-(3-guanidinium)-2-((1-(benzyloxycarbonyl)amino-3-methylbutyl)(hydroxy)fosfinovoi)acetic acid,

2-(2-chloro-3-guanidinium)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid,

2-(3-guanidinium)-2-((1-(benzyloxycarbonyl)amino-1-phenylmethyl)(hydroxy)fosfinovoi)acetic acid,

2-(2-fluoro-3-guanidinium)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid,

2-(3-guanidinium)-2-((1-(benzyloxycarbonyl)amino-1-cyclohexylmethyl)(hydroxy)fosfinovoi)acetic acid,

2-(2-methyl-3-guanidinium)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid,

2-(3-(amino)were)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid,

2-(3-(guanidinate)phenyl)-2-((1-(unselectable)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid,

2-(3-(1-aminoethylaminomethyl))-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid,

2-(3-(tert-butoxycarbonylamino)were)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid,

2-(3-(ethoxycarbonyl)were)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid,

2-(3-(isopropoxycarbonyl)were)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid,

2-(3-(2,2-dimethylpropanolamine)were)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid,

2-(3-guanidinium)-2-((1-(2-phenylethylamine)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid and

2-(3-guanidinium)-2-((1-(2-phenylacetylcarbinol)amino-2-methylpropyl)(hydroxy)fosfinovoi)acetic acid.

26. Connection item 23, where X is-O-,

R2mean-P(O)(OR5)-R7-N(R5)-C(O)-R7-N(R5)-C(O)OR8and

R4means aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -N(R6)-C()-R 6, -N(R5)-C(NR5)-N(R5)2.

27. Connection p selected from the group including

2-(3-guanidinium)-2-[(1-(1-benzyloxycarbonylamino-2-(4-hydroxyphenyl)ethylcarboxyl)amino-2-methylpropyl)(hydroxy)fosfinovoi]acetic acid,

2-(3-guanidinium)-2-[(1-(1-benzyloxycarbonylamino-2-phenylethylamine)amino-2-methylpropyl)(hydroxy)fosfinovoi]acetic acid,

2-(2-fluoro-3-guanidinium)-2-[(1-(1-benzyloxycarbonylamino-2-phenylethylamine)amino-2-methylpropyl)(hydroxy)fosfinovoi]acetic acid,

2-(3-guanidinium)-2-[(1-(1-phenylcarbonylamino-2-phenylethylamine)amino-2-methylpropyl)(hydroxy)fosfinovoi]acetic acid,

2-(3-guanidinium)-2-[(1-(1-ethoxycarbonyl-2-phenylethylamine)amino-2-methylpropyl)(hydroxy)fosfinovoi]acetic acid,

2-(3-guanidinium)-2-[(1-(1-benzyloxycarbonylamino-3-phenylpropionyl)amino-2-methylpropyl)(hydroxy)fosfinovoi]acetic acid and

2-(3-(amino)were)-2-[(1-(1-benzyloxycarbonylamino-3-phenylpropionyl)amino-2-methylpropyl)(hydroxy)fosfinovoi]acetic acid.

28. Connection item 23, where X is-CH2-,

R2mean-P(O)(OR5)-R7-N(R5)-C(O)R6or-P(O)(OR5)-R7-N(R5)-C(O)OR8a

R4means the reel, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R7)-C(O)OR8, -N(R6)-C(O)-R6, -N(R5)-C(NR5)-N(R5)2.

29. Connection p selected from the group including:

2-(3-(amino)were)-3-((1-(methylcarbamoyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-(hydrazinophenyl)phenyl)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-guanidinium)-3-((1-(benzyloxycarbonyl)aminoethyl)-(hydroxy)phosphinoyl)propionic acid,

2-(3-guanidinium)-3-((1-(benzyloxycarbonyl)amino-3-methylbutyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-guanidinium)-3-(((benzyloxycarbonyl)aminomethyl)-(hydroxy)phosphinoyl)propionic acid,

2-(3-guanidinium)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propionic acid,

2-(2-chloro-5-guanidinium)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propionic acid,

2-(3-(amino)were)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyl)propionic acid and

2-(3-(amino)were)-3-((1-(2-phenylethylamine)AMI is about 2 methylpropyl)(hydroxy)phosphinoyl)propionic acid.

30. Connection item 23, where X is-CH2-,

R2mean-P(O)(OR5)-R7-N(R5)-C(O)-R7-N(R5)-C(O)OR8and

R is aryl, optionally substituted by one or more substituents selected from the group comprising alkyl, halogen, nitro, cyano, -N(R6)2, -R7-N(R6)2, -N(R6)-C(O)OR8, -R7-N(R6)-C(O)OR8, -N(R6)-C(O)-R6, -N(R5)-C(NR5)-N(R5)2.

31. Connection item 30, selected from the group including:

2-(3-guanidinium)-3-(((1-benzyloxycarbonylamino-2-phenylethyl)carbonylmethyl)(hydroxy)phosphinoyl)propionic acid and 2-(3-guanidinium)-3-(((1-benzyloxycarbonylamino-2-phenylethyl)carbonylmethyl)(hydroxy)phosphinoyl)propionic acid.

32. Pharmaceutical composition having antimicrobial activity comprising a pharmaceutically acceptable excipient and the compound of formula (I) according to claim 1.

33. Pharmaceutical composition having antimicrobial activity comprising a pharmaceutically acceptable excipient and the compound of formula (II) p.

34. Pharmaceutical composition having antimicrobial activity comprising a pharmaceutically acceptable excipient and the compound of formula (III) in item 23.



 

Same patents:

FIELD: organic chemistry, biochemistry, medicine.

SUBSTANCE: invention relates to phosphonic acid compounds used as inhibitors of serine proteinase of the general formula (I): wherein R1 is chosen from group comprising piperidinyl, pyrrolidinyl and 1,3,8-triazaspiro[4,5]dec-8-yl (wherein heterocyclic ring as added to nitrogen atom in ring) and -N(R7R80 wherein this heterocyclic ring is substituted optionally with one or two substitutes chosen independently from group comprising the following compounds: (a) C1-C8)-alkyl substituted optionally at terminal carbon atom with a substitute chosen from group comprising aryl, heteroaryl; c) phenyl and naphthalenyl; i) benzothiazolyl; R7 is chosen from group comprising hydrogen atom and (C1-C8)-alkyl; R8 is chosen from group comprising: (aa) (C1-C8)-alkyl; (ab) cycloalkyl; (ac) cycloalkenyl, and (ad) heterocyclyl (wherein R8 is added to carbon atom in ring) wherein (ab) cycloalkyl; (ac) cycloalkenyl, and (ad) heterocyclyl (wherein heterocyclyl (ad) comprises at least one cyclic nitrogen atom) substitutes and cycloalkyl moiety (aa) of a substitute is substituted optionally with substitutes chosen independently from group comprising: (ba) (C1-C8)-alkyl substituted at terminal carbon atom with a substitute chosen from group comprising amino-group (with two substitutes chosen independently from group comprising hydrogen atom and (C1-C8)-alkyl); (bb) (C1-C8)-alkoxy-group substituted at terminal carbon atom with a substitute chosen from group comprising carboxyl; (bc) carbonyl substituted with a substitute chosen from group comprising (C1-C8)-alkyl, aryl, aryl-(C2-C8)-alkenyl; (bd) aryl; (be) heteroaryl; (bf) amino-group substituted with two substitutes chosen independently from group comprising hydrogen atom and (C1-C8)-alkyl; (bh) halogen atom; (bi) hydroxy-group; (bk) heterocyclyl wherein (bd) is aryl substitute, and heteroaryl moiety (bc) comprise a substitute (halogen atom)1-3; R4 is chosen from group comprising aryl and heteroaryl wherein heteroaryl comprises halogen atom as a substitute; R2 and R3 are bound with benzene ring and represent hydrogen atom, and R2 and R3 form in common optionally at least one ring condensed with benzene ring forming polycyclic system wherein this polycyclic system is chosen from group comprising (C9-C14)-benzocondensed cycloalkenyl, (C9-C14)-benzocondensed phenyl; R5 is chosen from group comprising hydrogen atom and (C1-C8)-alkyl; R6 is chosen from group comprising (C1-C8)-alkyl and hydroxy-group; Y is absent, and X represents a single substitute that is added by a double bond and represents oxygen atom (O), and Z is chosen from group comprising a bond, hydrogen atom, and its salts. Also, invention relates to a method for synthesis of these compounds, to their composition inhibiting serine proteinase and to a method for its preparing. Proposed invention describes a method for treatment of inflammatory or serine proteinase-mediated disorder.

EFFECT: valuable biochemical and medicinal properties of compounds.

64 cl, 5 tbl, 38 ex

FIELD: chemistry of organophosphorus compounds.

SUBSTANCE: invention relates to the improved method for synthesis phosphorus-chlorine-containing methacrylates that can be used in synthesis of polymeric, among them, uncolored, optically transparent and composition materials with reduced inflammability. Invention describes a method for synthesis of phosphorus-chlorine-containing methacrylates of the general formula:

wherein R means lower alkyl, chloroalkyl, alkoxyl, phenoxyl or group of the formula:

R1 means lower alkoxyl, phenoxyl or group of the formula:

Method involves interaction of phosphoric pentavalent acid chloroanhydrides with methacrylic acid glycidyl ester at heating in the presence of hexamethylenephosphorotriamide or dimethylformamide as a catalyst wherein catalyst is taken in the amount 0.3-0.6% of reagents mass, and process is carried out at rise of temperature from 40°C to 80°C in the presence of compound chosen from the group: alkyl- or alkoxy-substituted phenols taken in the amount 0.03-0.3% of reagents mass. Method provides decreasing water absorption of (co)polymerization products of synthesized phosphorus-chlorine-containing methacrylates and reducing retention time of surface stickiness of fiber glass synthesized on their basis and at retention the level of other properties, among them transparence and colorless.

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

2 tbl, 10 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to acyclic nucleoside phosphonate derivatives of the formula (1): wherein means a simple or double bond; R1 means hydrogen atom; R2 and R3 mean hydrogen atom or (C1-C7)-alkyl; R7 and R8 mean hydrogen atom or (C1-C4)-alkyl; R4 and R5 mean hydrogen atom or (C1-C4)-alkyl possibly substituted with one or more halogen atoms, or -(CH2)m-OC(=O)-R6 wherein m means a whole number from 1 to 5; R6 means (C1-C7)-alkyl or 3-6-membered heterocycle comprising 1 or 2 heteroatoms taken among the group consisting of nitrogen (N) and oxygen (O) atoms; Y means -O-, -CH(Z)-, =C(Z)-, -N(Z)- wherein Z means hydrogen atom, hydroxy-group or halogen atom, or (C1-C7)-alkyl; Q (see the claim invention); its pharmaceutically acceptable salts or stereoisomers. Also, invention proposes methods for preparing compounds of the formula (1) and their using in treatment of hepatitis B or preparing a medicinal agent designated for this aim.

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

16 cl, 10 tbl, 87 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to the improved method for preparing N-phosphonomethylglycine. Method involves interaction of derivative of hexahydrotriazine of the formula (II):

wherein X represents CN, COOZ, CH2OY and others; Z and Y represent hydrogen atom and others with triacylphosphite of the formula: P(OCOR3)3 (III) wherein R3 means (C1-C18)-alkyl or aryl that can be substituted. The prepared product is hydrolyzed and (if X represents CH2OY) oxidized. The proposed method is a simple in realization, economy and provides high degree of the end product purity.

EFFECT: improved preparing method.

19 cl, 11 ex

FIELD: chemistry of organophosphorus compounds.

SUBSTANCE: invention relates to compounds with the bond C-P, namely to phosphorus-boron-containing methacrylate that can be used as inhibitor of combustion of polyvinyl alcohol-base film materials. Invention describes phosphorus-boron-containing methacrylate of the following formula: wherein n = 4-8. Polyvinyl alcohol films modified with indicated phosphorus-boron-containing methacrylate shows the enhanced refractoriness, rupture strength up to 206 kgf/cm2, water absorption up to 240% and relative elongation up to 12%.

EFFECT: valuable properties of substance.

1 tbl, 2 ex

FIELD: organic chemistry, in particular improved method for production of phosphorinated and chlorinated methacrylates.

SUBSTANCE: invention relates to method for production of compounds having general formula , wherein R is lower alkyl and R1 is lower alkoxyl, phenoxyl, or group of formula . Claimed method includes reaction of pentavalent phosphorous acid chloroanhydride with glycydil methacrylate at 20-50°C in presence of titanium tetrachloride as catalyst in amount of 0.02-0.05 % calculated as reagent mass.

EFFECT: one-step method for production of phosphorous and chlorine containing methacrylates with improved water resistance.

2 tbl, 7 ex

The invention relates to new biologically active phosphonate derivative of acyclovir

The invention relates to the chemistry of organophosphorus compounds, and in particular to a new method of obtaining N-substituted phosphorylated of imidates having the structure zenatello group

The invention relates to derivatives of phosphinic and phosphonic acids of the formula (I)

where R1means unsubstituted or substituted phenyl, -O-(C1-C6)-alkyl, R2means hydrogen, RR3mean hydrogen, alkyl, unsubstituted or substituted phenyl, COOH group or - (CH2)2-CH(COOH)-NH-SO2-C6H4-C6H4-Cl(n), t stands for an integer of 1-4, And is a covalent bond, X is a group-CH=CH -, - group,- (CH2)about- where is 0,1,2 or 3, Y1and Y2mean-OH, -(C1-C4)-alkyl, -O-(C1-C4)-alkyl, and/or their stereoisomeric forms and/or physiologically acceptable salts

The invention relates to new derivatives of benzazepine-N-acetic acid, substituted phosphonic acid, which are pharmaceutically active compounds

FIELD: chemistry of organophosphorus compounds, chemical technology.

SUBSTANCE: invention describes a method for synthesis of monohydroperfluoroalkanes, bis-(perfluoroalkyl)phosphinates and perfluoroalkylphosphonates. Method involves treatment of at least one perfluoroalkylphosphorane with at least one base wherein base(s) are chosen from group consisting of alkali-earth metal hydroxides, metalloorganic compound in useful solvent or at least one organic base and an acid in useful reaction medium. Also, invention describes novel perfluoroalkylphosphonates and bis-(perfluoroalkyl)phosphinates, using novel perfluoroalkylphosphonates and bis-(perfluoroalyl)phosphinates as ionic liquids, catalysts of phase transfer or surfactants.

EFFECT: improved method of synthesis.

18 cl, 19 ex

FIELD: chemistry of metalloorganic compounds, chemical technology.

SUBSTANCE: invention relates to a method for preparing copper (II), zinc (II), nickel (II) and cobalt (II) nitrilotri-(methylenephosphonates)(2-) that involves crystallization from aqueous solutions prepared by interaction of metal (II) compound with nitrilotri-(methylenephosphonic) acid or its salt with sodium potassium or ammonium in aqueous medium at temperature from -5°C to 105°C under atmosphere pressure. As a reactive of the metal (II) compound source the waste from manufacturing printing plates and galvanic covers can be used. The end products can be used in preparing the complex electrolytes and solutions for applying metallic covers by electrochemical and chemical methods in aims for inhibition against the equipment corrosion, and for preparing other compounds of metals with nitrilotri-(methylenephosphonic) acid.

EFFECT: improved method of synthesis.

16 cl, 1 tbl, 19 ex

FIELD: organic chemistry, biochemistry, medicine.

SUBSTANCE: invention relates to phosphonic acid compounds used as inhibitors of serine proteinase of the general formula (I): wherein R1 is chosen from group comprising piperidinyl, pyrrolidinyl and 1,3,8-triazaspiro[4,5]dec-8-yl (wherein heterocyclic ring as added to nitrogen atom in ring) and -N(R7R80 wherein this heterocyclic ring is substituted optionally with one or two substitutes chosen independently from group comprising the following compounds: (a) C1-C8)-alkyl substituted optionally at terminal carbon atom with a substitute chosen from group comprising aryl, heteroaryl; c) phenyl and naphthalenyl; i) benzothiazolyl; R7 is chosen from group comprising hydrogen atom and (C1-C8)-alkyl; R8 is chosen from group comprising: (aa) (C1-C8)-alkyl; (ab) cycloalkyl; (ac) cycloalkenyl, and (ad) heterocyclyl (wherein R8 is added to carbon atom in ring) wherein (ab) cycloalkyl; (ac) cycloalkenyl, and (ad) heterocyclyl (wherein heterocyclyl (ad) comprises at least one cyclic nitrogen atom) substitutes and cycloalkyl moiety (aa) of a substitute is substituted optionally with substitutes chosen independently from group comprising: (ba) (C1-C8)-alkyl substituted at terminal carbon atom with a substitute chosen from group comprising amino-group (with two substitutes chosen independently from group comprising hydrogen atom and (C1-C8)-alkyl); (bb) (C1-C8)-alkoxy-group substituted at terminal carbon atom with a substitute chosen from group comprising carboxyl; (bc) carbonyl substituted with a substitute chosen from group comprising (C1-C8)-alkyl, aryl, aryl-(C2-C8)-alkenyl; (bd) aryl; (be) heteroaryl; (bf) amino-group substituted with two substitutes chosen independently from group comprising hydrogen atom and (C1-C8)-alkyl; (bh) halogen atom; (bi) hydroxy-group; (bk) heterocyclyl wherein (bd) is aryl substitute, and heteroaryl moiety (bc) comprise a substitute (halogen atom)1-3; R4 is chosen from group comprising aryl and heteroaryl wherein heteroaryl comprises halogen atom as a substitute; R2 and R3 are bound with benzene ring and represent hydrogen atom, and R2 and R3 form in common optionally at least one ring condensed with benzene ring forming polycyclic system wherein this polycyclic system is chosen from group comprising (C9-C14)-benzocondensed cycloalkenyl, (C9-C14)-benzocondensed phenyl; R5 is chosen from group comprising hydrogen atom and (C1-C8)-alkyl; R6 is chosen from group comprising (C1-C8)-alkyl and hydroxy-group; Y is absent, and X represents a single substitute that is added by a double bond and represents oxygen atom (O), and Z is chosen from group comprising a bond, hydrogen atom, and its salts. Also, invention relates to a method for synthesis of these compounds, to their composition inhibiting serine proteinase and to a method for its preparing. Proposed invention describes a method for treatment of inflammatory or serine proteinase-mediated disorder.

EFFECT: valuable biochemical and medicinal properties of compounds.

64 cl, 5 tbl, 38 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a novel method for synthesis of N-phosphonomethylglycine. Method involves interaction of hexahydrotriazine compound with triacyl phosphite in organic solvent, saponification of formed phosphonic compound after preliminary extraction into aqueous phase, separation of organic phase and precipitation of N-phosphonomethylglycine by pH value control in the range from 0.5 to 2.0. Invention prevents decomposition of an organic solvent in saponification.

EFFECT: improved method of synthesis.

8 cl, 3 tbl, 4 ex

FIELD: chemical industry; methods of production of the water solution of disodium or dipotassium salt of zinc oxyethyledene phosphonate.

SUBSTANCE: the invention is pertaining to the method of production of the water solutions of disodium or dipotassium salt of zinc oxyethyledene phosohonate with concentration of 15-23 % used as the mineral salts sediments inhibitors and as the microfertilizers and having the properties to inhibit corrosion. The method provides for interaction of the water solution of the sodium zincate or the potassium zincate with the 20-60 % water solution of the oxyethyledenephosphonic acid at the temperature of 60-80°С. As a rule, the sodium zincate or the potassium zincate are produced by interaction of 5-20 % water solution of the sodium hydroxide or the potassium hydroxide with zinc oxide at the temperature of 50-75°С at the molar relation of 2:1.

EFFECT: the invention ensures, that as the rule the sodium zincate or the potassium zincate are produced by interaction of the low-concentration water solutions of the sodium hydroxide or the potassium hydroxide with zinc oxide at the temperature of 50-75°С at the molar relation of 2:1.

2 cl, 1 tbl, 11 ex

FIELD: industrial and waste water treatment.

SUBSTANCE: composition contains 10-25% sodium alkylaminophosphonates having general formula: , in which n=9-19, 1-5% sodium chloride, and 70-89% water. Composition is prepared by heat treatment of industrial-grade aliphatic amines with phosphorous acid and formaldehyde. In particular, treatment of aliphatic amines of formula CH3-(CH2)-NH2 (n=9-19) is carried out in presence of hydrochloric acid as catalyst at 95-105°C for 1.5-3.0 h followed by cooling and neutralization with sodium alkali to pH 10.

EFFECT: enhanced treatment efficiency.

2 cl, 1 tbl

FIELD: chemical technology.

SUBSTANCE: invention relates to technology for synthesis of crystalline nitrilotrimethylphosphonic acid sodium salts. For synthesis of nitrilotrimethylphosphonic acid disodium salt monohydrate the method involves preliminary synthesis of nitrilotrimethylphosphonic acid by interaction of phosphorus trichloride, formaldehyde and ammonia or its derivative followed by neutralization with sodium hydroxide in the content in the reaction mass 46-54 wt.-% of nitrilotrimethylphosphonic acid and 6.0-16.0 wt.-% of hydrogen chloride up to pH value 2.5-4.5, and isolation of the end compound by crystallization. The mass part of the main substance in synthesized product is 88-95%, the content of chloride ions is 1.2-2.0%, yield is 50-60% as measured for PCl3. Synthesized compound is recommended for using as chelate compounds as a component of detergents, anti-rheological additive in drilling solutions, plasticizing agents for building concretes, in wine-making industry, as inhibitors of salt depositions in heat and power engineering and others fields.

EFFECT: improved method of synthesis.

2 tbl, 12 ex

FIELD: chemical technology.

SUBSTANCE: invention relates to the improved method for preparing bis-(1-hydroxyethane-1,1-diphosphonate(1-)) zinc (II). Method involves interaction of zinc-containing reagent and 1-hydroxyethane-1,1-diphosphonic acid in a solvent medium, crystallization of the end product from solution, separation of deposit from solution and drying the deposit. Method involves using water-soluble zinc (II) salt with anion of strong acid as a zinc-containing reagent and preparing the solution with the concentration of zinc (II) salt from 0.2 to 2.2 mole/l and the concentration of 1-hydroxyethane-1,1-diphosphonic acid from 0.4 to 5.0 mole/l. The end product prepared by proposed method can be used in preparing phosphonate electrolytes for galvanic zinc-plating, for preparing zinc-phosphate inhibitors of steel corrosion, as trace supplement to vitamin preparations and fodders for animals, as a zinc microfertilizer in agriculture and for preparing other compounds of zinc (II). Invention provides enhancing purity and uniformity of the end product, increasing its yield, improved technological effectiveness of process, utilizing toxic waste in galvanic manufacturing.

EFFECT: improved preparing method.

8 cl, 1 tbl, 6 ex

FIELD: chemistry of organophosphorus compounds, agriculture, pesticides.

SUBSTANCE: invention describes bis-(diethylammonium)-dihydrogen-1-hydroxyethyl-1,1diphosphonate monohydrate of the formula (I) showing properties of stimulator of growth o agricultural root crop plants. Invention provides enhancing productivity of root crops beet and carrot and expanding assortment of agents for this designation.

EFFECT: valuable agricultural properties of agent.

1 tbl, 2 ex

FIELD: organophosphorus compounds, chemical technology.

SUBSTANCE: invention relates to technology of organic substances, in particular, to the improved method for preparing copper (II) bis-(1-hydroxyethane-1,1-diphosphonate (1-)). The final copper (II) bis-(1-hydroxyethane-1,1-diphosphonate (1-)) is prepared by crystallization from aqueous solution with concentrations of copper salt (II) from 0.5 to 2.0 mole/l and 1-hydroxyethane-1,1-diphosphonic acid with concentration from 2.0 to 6.0 mole/l prepared by using copper-containing waste in galvanic and electronic engineering manufacture, or by using a semi-finished product from production of 1-hydroxyethane-1,1-diphosphonic acid. Invention provides reducing cost in production of copper (I) bis-(1-hydroxyethane-1,1-diphosphonate (1-)) in combination with retaining purity, expanded raw base for preparing the end product and utilization of manufacture waste.

EFFECT: improved preparing method.

9 cl, 1 tbl, 8 ex

The invention relates to derivatives of phosphinic and phosphonic acids of the formula (I)

where R1means unsubstituted or substituted phenyl, -O-(C1-C6)-alkyl, R2means hydrogen, RR3mean hydrogen, alkyl, unsubstituted or substituted phenyl, COOH group or - (CH2)2-CH(COOH)-NH-SO2-C6H4-C6H4-Cl(n), t stands for an integer of 1-4, And is a covalent bond, X is a group-CH=CH -, - group,- (CH2)about- where is 0,1,2 or 3, Y1and Y2mean-OH, -(C1-C4)-alkyl, -O-(C1-C4)-alkyl, and/or their stereoisomeric forms and/or physiologically acceptable salts
Up!