Application of pyrroloquinoline compounds for killing clinically latent microorganisms

FIELD: medicine.

SUBSTANCE: invention refers to new derivatives of dihydro-pyrroloquinoline of formula I where values of R1, R2, R3a and R3c radicals are specified in cl. 1 of the patent claim. Also the invention refers to a method for making the compound of formula I, to its application, a composite product based on the compound of formula I and a general antimicrobial agent and a pharmaceutical composition based on the compound of formula I.

EFFECT: there are prepared new derivatives of dihydro-pyrroloquinoline exhibiting antibacterial activity.

26 cl, 4 dwg, 11 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula I or its pharmaceutically acceptable salt

where R1represents a
(a) H,
(b) (C1-12alkyl, C3-12cycloalkyl,3-12cycloalkenyl (where the latter three groups optionally are substituted by one or more substituents selected from halogen, nitro, CN, C1-6of alkyl, C2-6alkenyl,2-6the quinil,3-8cycloalkyl (where the latter three groups optionally are substituted by one or more substituents selected from HE, =O, halogen, C1-4the alkyl and C1-4alkoxy), OR4a, S(O)nR4b, S(O)2N(R4c)(R4d), N(R4e)S(O)2R4fN(R4g)(R4h), B1-C(O)-B2-R4i, aryl and Het1and where C3-12cycloalkyl or C4-12cycloalkenyl groups may additionally be substituted by =O),
(c) aryl or
(d) Het2;
R2represents a
(a) H,
(b) C1-12alkyl, C 2-12alkenyl, C2-12quinil, C3-12cycloalkyl or C4-12cycloalkenyl, where the latter five groups optionally are substituted by one or more substituents selected from halogen, nitro, CN, C1-6of alkyl, C1-6alkenyl, C1-6the quinil,3-8cycloalkyl (where the latter three groups optionally are substituted by one or more substituents selected from HE, =O, halogen, C1-4the alkyl and C1-4alkoxy), OR5a, S(O)pR5b, S(O)2N(R5c)(R5d), N(R5e)S(O)2R5fN(R5g)(R5h), B3-C(O)-B4-R51, aryl and Het3and where C3-12cycloalkyl or C4-12cycloalkenyl groups may additionally be substituted by =O,
(c) aryl or
(d) Het4;
R3Aand R3sindependently represent H, OR7aN(H)R7hor Het6provided that R3aand R3cboth are not H;
R4a- R4i, R5a- R5i, R7aand R7hindependently represent in each case
(a) H,
(b) C1-10alkyl, C2-10alkenyl, C2-10quinil (where the last three groups are optionally substituted by one or more Deputy selected halogen, HE, C1-6alkoxy, aryl and Het7),
(c)3-10cycloalkyl, C4-10cycloalkenyl (where the latter two groups is not necessary for the emeny one or more Deputy selected from halogen, HE, =O, C1-6of alkyl, C1-6alkoxy, aryl and Het8),
(d) aryl or
(e) Het9,
provided that R4bor R5bare not H, when n or R, respectively is 1 or 2;
each aryl independently represents a C6-10carbocyclic aromatic group, which may contain one or two rings and may be substituted by one or more Deputy chosen from:
(a) halogen,
(b) CN,
(c) C1-12of alkyl, C2-12alkenyl, C2-12the quinil,3-12cycloalkyl or4-12cycloalkenyl, where the latter five groups optionally are substituted by one or more substituents selected from halogen, nitro, CN, C1-6of alkyl, C2-6alkenyl, C2-6the quinil3-8cycloalkyl (where the latter three groups optionally are substituted by one or more substituents selected from HE, =O, halogen, C1-4the alkyl and C1-4alkoxy), OR9a, S(O)tR9b, S(O)2N(R9c)(R9d), N(R9e)S(O)2R9fN(R9g)(R9h),9-C(O)-10-R9i, phenyl, naphthyl (which latter two groups are optionally substituted by one or more Deputy selected from HE, halogen, C1-4of alkyl, C1-4alkoxy) and Het10and where C3-12cycloalkyl or4-12cycloalkenyl gruppirovat additionally be substituted by =O,
(d) OR10a,
(e) S(O)uR10b,
(f) S(O)2N(R10cR10h,
(g) N(R10e)S(O)2R10f,
(h) N(R10g)(R10h),
(i)11-C(O)-B12-R10i,
(j) phenyl (which latter group may be substituted by one or more Deputy selected from HE, halogen, C1-4of alkyl, C1-4alkoxy) or
(k) Het11;
R9a- R9i, R10a- R10iindependently represent in each case,
(a) H,
(b) C1-12alkyl, C2-12alkenyl, C2-12quinil,3-12cycloalkyl,4-12cycloalkenyl (where the latter five groups optionally are substituted by one or more substituents selected from halogen, HE, C1-6of alkyl, C3-12cycloalkyl, C4-12cycloalkenyl (which latter two groups are optionally substituted by one or more Deputy selected from HE, =O, halogen, C1-4of alkyl, C1-4alkoxy), C1-6alkoxy, NH2N(H)-C1-6of alkyl, N(C1-6alkyl)2, phenyl (which latter group may be substituted by one or more Deputy selected from HE, halogen, C1-4of alkyl, C1-4alkoxy) and Het12and where C3-12cycloalkyl or C4-12cycloalkenyl may additionally be substituted by=O,
(C) phenyl (which latter group may be substituted by one or more Deputy selected from HE, CN, Galaga is a, C1-6of alkyl, C1-6alkoxy) or
(e) Het13,
provided that R9bor R10bare not H, when t or u, respectively, 1 or 2;
Het1-Het4and Het6-Het13independently represent 4-14-membered heterocyclic group containing one or more heteroatoms selected from O, nitrogen and/or sulfur, where the heterocyclic group may contain one, two or three rings and may be substituted by one or more substituents selected from
(a) halogen,
(b) CN,
(c) C1-12of alkyl, C2-12alkenyl, C2-12the quinil,3-12cycloalkyl or C4-12cycloalkenyl, where the latter five groups optionally are substituted by one or more substituents selected from halogen, nitro, CN, C1-6of alkyl, C2-6alkenyl, C2-6the quinil,3-8cycloalkyl (where the latter three groups optionally are substituted by one or more substituents selected from HE, =O, halogen, C1-4the alkyl and C1-4alkoxy), OR11a, S(O)vR11b, S(O)2N(R11c)(R11d), N(R11e)S(O)2R11fN(R11g)(R11h),13-C(O)-14-R11i, phenyl, naphthyl (which latter two groups are optionally are substituted by one or more substituents selected from HE, halogen, C1-4the alkyl and C1-4alkoxy) and Heta and where C3-12cycloalkyl or C4-12cycloalkenyl groups may additionally be substituted by =O,
(d) OR12a,
(e) =O,
(f) S(O)wR12b,
(g) S(O)2N(R12c)(R12d),
(h) N(R12e)S(O)2R12f,
(i) N(R12g)(R12h),
(j) B15-C(O)-B16-R12i,
(k) phenyl (which latter group is optionally may be substituted by one or more substituents selected from HE, halogen, C1-4the alkyl and C1-4alkoxy) or
(l) Hetb;
R11a- R11iand R12a- R12iindependently represent in each case
(a) H,
(b) C1-12alkyl, C2-12alkenyl, C2-12quinil, C3-12cycloalkyl,4-12cycloalkenyl (where the latter five groups optionally are substituted by one or more substituents selected from halogen, HE, C1-6of alkyl, C3-12cycloalkyl, C4-12cycloalkenyl (where the latter two groups optionally are substituted by one or more substituents selected from HE, =O, halogen, C1-4the alkyl and C1-4alkoxy), C1-6alkoxy, phenyl (which latter group is optionally may be substituted by one or more substituents selected from HE, halogen, C1-4the alkyl and C1-4alkoxy) and Hetcand where C3-12cycloalkyl or4-12cycloalkenyl groups can bitopological substituted by =O),
(c) phenyl (which latter group is optionally may be substituted by one or more substituents selected from HE, halogen, C1-4the alkyl and C1-4alkoxy) or
(e) Hetd,
provided that R11bor R12bnot represent H when v or w, respectively, equal to 1 or 2;
B1-B4and B9-B16independently represent a direct bond, O, S, NH or N(R13);
n, R, s, t, u, v and w are independently 0, 1 or 2;
R13represents a
(a) C1-6alkyl,
(b) phenyl (which latter group is optionally may be substituted by one or more substituents selected from HE, halogen, C1-4the alkyl and C1-4alkoxy),
(c)3-7cycloalkyl (where the last group optionally may be substituted by one or more substituents selected from HE, =O, halogen, C1-4the alkyl and C1-4alkoxy) or,
(e) Het6;
Heta-Heteindependently represent a 5 - or 6-membered heterocyclic group containing one to four heteroatoms selected from oxygen, nitrogen and/or sulfur, where the heterocyclic group may be substituted by one or more substituents selected from halogen, =O and C1-6of alkyl; and unless otherwise specified
(i) alkyl, Alchemilla, Alchemilla, cycloalkyl and cycloalkenyl group, and the alkyl part of the Ala is sigroup can be substituted by one or more halogen atoms, and
(ii) cycloalkyl and cycloalkenyl group can include one or two rings and may optionally be condensed with one or two benzene rings,
provided that the compound of formula (I) is not a compound
(a) the following formula

where (i) RArepresents methyl, benzyl or CH2CH2N(C1-2alkyl)2,
RBrepresents H,
RCrepresents H or methyl and
RDrepresents H or one or two substituent selected from HE, and C1-2alkoxy,
(ii) RArepresents benzyl, 1-phenylethyl or phenyl, where the last group substituted in the second position the stands or methoxy, and optionally additionally substituted in the four position by fluorine, HE stands, methoxy or benzyloxy, or in the 6th position of the stands,
RBrepresents H, methyl, ethyl, ISO-propyl or1-2alkyl, ending IT,
RCrepresents H, methyl or hydroxymethyl and
RDis a Deputy to the 6th position for one substitution selected from HE, methoxy, triptoreline, OCH2CH2OH or OCH2CF3,
(iii) RArepresents methyl, 2-hydroxyethyl, phenyl, where the latter group is optionally substituted once in the 2nd position with chlorine or 4-m is ogenyi the stands or methoxy,
RBrepresents H,
RCrepresents methyl,
RDis a Deputy to the 6th position, for one substitution selected from HE, and methoxy,
(iv) RArepresents phenyl, substituted with one or two substituents containing ethyl group at the 4-position, or one or two metoxygroup in the 2nd and/or 4th position,
RBrepresents H,
RCrepresents methyl,
RDrepresents one or two Vice-methoxy for 6th and/or 8th position,
(v) RArepresents methyl or phenyl, where the latter group is optionally substituted by one Deputy, is selected from Cl, F, methyl, trifloromethyl and methoxy, or the two metal groups in position 2 and 6),
RBrepresents H,
RCrepresents H or methyl,
RDrepresents one or two Vice-methoxy; or
b) (i) 6-methoxy-4,5-dimethyl-1-(2-were)-2,3-dihydro-1H-pyrrolo[3,2-C]hyalinum iodide,
(ii) 6,8-dimethoxy-1-(4-ISO-propylphenyl)-4-methyl-2,3-dihydro-1H-pyrrolo [3,2-C]-quinoline,
(iii) 6-methoxy-1-(4-phenoxyphenyl)-4-methyl-2,3-dihydro-1H-pyrrolo [3,2-C]-quinoline,
(iv) 6-methoxy-1-(4-ISO-propylphenyl)-4-methyl-2,3-dihydro-1H-pyrrolo [3,2-C]-quinoline,
(v) 6,8-dimethoxy-1-(4-phenoxyphenyl)-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline, or
(vi) 6,8-dimethoxy-1-(4-hydroxyphenyl)-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline,

2. The compound of formula I as defined in claim 1 provided that it is not:
(vii) 1,4-methoxyphenyl-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(viii) 4-methyl-8-phenoxy-1-(4-phenoxyphenyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(ix) 4-methyl-8-phenoxy-1-(4-ISO-propylphenyl)-2,3-dihydro-1H-pyrrolo [3,2-C]quinoline;
(x) 1-(4-isopropylphenyl)-6-phenoxy-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(xi) 6 phenoxy-1-(4-phenoxyphenyl)-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;or
(xii) 6-phenoxy-1-(4-trifloromethyl)-4-methyl-2,3-dihydro-1H-pyrrolo [3,2-C]quinoline.

3. The compound according to claim 1, where R7ais independently in each case
C1-6alkyl, optionally substituted by one or more Deputy selected from halogen and phenyl, where the latter may be optionally substituted by one or more Deputy selected from halogen, C1-4the alkyl and C1-4alkoxy,
C5-6cycloalkyl, optionally substituted by one or more Deputy selected from halogen, methyl and methoxy,
phenyl, optionally substituted by one or more Deputy selected from halogen, C1-4the alkyl and C1-4alkoxy, or
Het9.

4. The compound according to claim 3, where R7arepresents phenyl, optionally substituted by one or more Deputy selected from halogen, C1-4the alkyl and C1-4alkoxy.

Caetanina according to claim 1, where the compound of formula I represented by the following formula:

where R1and R2as defined in claim 1;
R3a1represents N, and R3c1represents phenoxy,
or, when R1represents a
With1-2alkyl, substituted optionally substituted by phenyl,
With5-6cycloalkyl condensed with benzene ring, or
phenyl, substituted phenoxy,
then R3a1may additionally represent a methoxy or phenoxy, and R3c1may additionally represent H, methoxy, triptoreline or ethoxy,
provided that R3a1and R3c1both do not represent phenoxy.

6. The compound according to claim 1, where R1represents a
C1-5-alkyl, which is optionally substituted C3-5cycloalkyl; phenyl, which, in turn, optionally substituted by one or more Deputy selected from halogen, methyl and methoxy; phenoxy; benzodioxane or benzodioxolyl,
With3-6cycloalkyl, which is optionally condensed with a benzene ring,
phenyl, which is optionally substituted by one or more Deputy selected from halogen; C1-4of alkyl; HE; C1-4alkoxy, the latter, in turn, optionally substituted by N(CH3)2phenoxy, which is unsubstituted or substituted one who does more Deputy selected from methoxy and halogen; pyridyloxy and piperazinil, optionally substituted stands,
pyridyl, optionally substituted by methoxy or phenoxy, or
piperidine, optionally substituted C1-2the alkyl, which is optionally substituted by phenyl.

7. The compound according to claim 1, where R3crepresents H, R3ais not H, HE or methoxy.

8. The compound according to claim 1, which represents the
(1) 6,8-dimethoxy-4-methyl-1-(3-phenoxyphenyl)-2,3-dihydro-1H-pyrrolo [3,2-C]-quinoline;
(2) 6,8-dimethoxy-4-methyl-1-(2-phenoxyethyl)-2,3-dihydro-1H-pyrrolo [3,2-C]-quinoline;
(3) 1-cyclopropyl-6,8-dimethoxy-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(4) 8-methoxy-4-methyl-1-(4-phenoxyphenyl)-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(5) {2-[4-(8-methoxy-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline-1-yl)-phenoxy]ethyl}dimethylamine;
(6) 8-methoxy-4-methyl-1-[4-(pyridine-3-yloxy)phenyl]-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(7) 4-methyl-8-phenoxy-1-phenyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(8) 1-benzyl-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline
(9) 1-(indan-2-yl)-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline
(10) 4-methyl-6-phenoxy-1-phenyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(11) 1-benzyl-4-methyl-6-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(12) 1-(indan-2-yl)-4-methyl-6-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(13) 4-methyl-1-(2-phenylethyl)-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]-hee is Olin;
(14) 8-methoxy-4-methyl-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline-6-ol;
(15) 1-(1-benzyl-piperidine-4-yl)-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(16) 1-(indan-1-yl)-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(17) 1-(benzodioxan-2-ylmethyl)-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(18) 4-methyl-8-phenoxy-1-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(19) 1-cyclohexyl-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(20) 8 ethoxy-4-methyl-1-(4-phenoxyphenyl)-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(21) 1-(4-methoxyphenyl)-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(23) 4-methyl-1-(2-were)methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(24) 4-methyl-8-phenoxy-1-(4-ISO-propylphenyl)-2,3-dihydro-1H-pyrrolo [3,2-C] -quinoline;
(25) 4-methyl-8-phenoxy-1-(1-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(26) 8-methoxy-4-methyl-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(27) 6,8-dimethoxy-1-(4-hydroxyphenyl)-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(28) 6,8-dimethoxy-1-(3-hydroxyphenyl)-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(29) 6,8-dimethoxy-1-(3-hydroxy-5-were)-4-methyl-2,3-dihydro-1H-pyrrolo [3,2-C]quinoline;
(30) 8-methoxy-1-(4-methoxyphenyl)-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(31) 8 triptoreline-1-(4-phenoxyphenyl)-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(32) 6,8-dimethoxy-4-methyl-1-[4-(PI is one-3-yloxy)phenyl]-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(33) 1-benzyl-6,8-dimethoxy-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(34) 6,8-dimethoxy-4-methyl-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo [3,2-C]quinoline;
(35) 4-methyl-1-(2-phenylethyl)-8-triptoreline-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(36) 6,8-dimethoxy-1-(indan-1-yl)-4-methyl-2,3-dihydro-1H-pyrrolo [3,2-C]-quinoline;
(37) 6,8-dimethoxy-4-methyl-1-[(6-phenoxy)pyridine-3-yl]-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(38) 6,8-dimethoxy-1-[(6-methoxy)pyridine-3-yl]-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(39) 1-(benzodioxol-5-ylmethyl)-6,8-dimethoxy-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(40) 6,8-dimethoxy-4-methyl-1-(3-methylbutyl)-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(41) 1-cyclopropylmethyl-6,8-dimethoxy-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(42) 4-methyl-8-(morpholine-4-yl)-1-(4-phenoxyphenyl)-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(43) 8-methoxy-4-methyl-1-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(47) 4-methyl-8-(piperidine-1-yl)-1-[4-(piperidine-1-yl)phenyl]-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(48) 4-methyl-8-(piperidine-1-yl)-1-(3-phenoxyphenyl)-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(49) 1-{4-[2-(N,N-dimethylamino)ethoxy]phenyl}-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(50) 1-[4-(4-pertenece)phenyl]-8-methoxy-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(51) 1-(benzodioxan-2-ylmethyl)-8-methoxy-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(52) 1-cyclohexyl-8-methoxy-4-methyl-2,3-digitron-pyrrolo[3,2-C]quinoline;
(53) 8-methoxy-4-methyl-1-phenyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(54) 4-methyl-8-phenoxy-1-[4-(3-pyridyl)phenyl]-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(55) 4-methyl-8-phenoxy-1-[2-(3-pyridyl)ethyl]-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(56) 4-methyl-8-phenoxy-1-(2-pyridylmethyl)-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(57) 4-methyl-1-(5-methylpyrazine-2-ylmethyl)-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(60) 4-methyl-8-(morpholine-1-yl)-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(62) 1-[3-(4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline-1-yl)propyl]-pyrrolidin-2-he;
(63) 4-methyl-8-phenoxy-1-[2-(2-pyridyl)ethyl]-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(64) ethyl 3-(8-methoxy-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline-1-yl)propionate;
(65) ethyl 4-(4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline-1-yl)butanoate;
(66) methyl 4-(4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline-1-yl)butanoate;
(67) ethyl (4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline-1-yl)acetate;
(68) 4-methyl-1-(1-methylpiperidin-4-yl)-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(69) 1-(1-benzylpyrrolidine-3-yl)-8-methoxy-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(70) methyl 3-(4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline-1-yl)propionate;
(71) 1-((S)-indan-1-yl)-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(72) 1-((R)-indan-1-yl)-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(73) 1-(3-methoxypropyl)-4-methyl-8-Fenox the -2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(74) 4-methyl-8-phenoxy-1-(tetrahydrofuran-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(75) 1-[2-(4-chlorophenyl)ethyl]-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(76) 1-[2-(4-methoxyphenyl)ethyl]-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(77) 4-methyl-8-phenoxy-1-(2-phenylpropyl)-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(79) 8-hydroxy-4-methyl-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
(80) 8 phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(82) 8-methoxy-4-methyl-1-[4-(4-methylpiperazin-1-yl)-3-forfinal]-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline;
(83) 4-methyl-8-phenylamino-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-C]-quinoline;
and its pharmaceutically acceptable salt.

9. The connection of claim 8, representing 8-methoxy-4-methyl-1-(4-phenoxyphenyl)-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline or its pharmaceutically acceptable salt.

10. The connection of claim 8, representing 1-(indan-2-yl)-4-methyl-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline or its pharmaceutically acceptable salt.

11. The connection of claim 8, a 4-methyl-8-phenoxy-1-(1-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-C]quinoline or its pharmaceutically acceptable salt.

12. The method of obtaining the compounds of formula I as defined in any one of claims 1 to 11, including:
(a) the interaction of the compounds of formula II

where L1and L2independently represent is a leaving group, R2, R3aR3c- as defined in any one of claims 1 to 9, with a compound of formula III

where R1as defined in any one of claims 1 to 11, or
(b) removal of a protected derivative of a compound of formula I as defined in any one of claims 1 to 11.

13. The use of the compounds of formula I as defined in any one of claims 1 to 11 for the preparation of medicines for treatment of bacterial infections.

14. Combination product for the treatment of bacterial infections, including:
(A) a compound of formula I as defined in any one of claims 1 to 11, and
(B) a conventional antimicrobial agent,
where each of the components (a) and (b) is prepared in combination with a pharmaceutically acceptable adjuvant, diluent or carrier.

15. The combined product 14, where conventional antimicrobial agent is a penicillin (optional in combination with the inhibitor (β-lactamase), cephalosporins, monobactam, carbapenem (optional in combination with the enzyme inhibitor kidney), 1-oxa-(β-lactam, tetracycline, aminoglycoside, macrolide, ketolide, lincosamide, clindamycin, clindamycin-2-phosphate, fenicol, steroid, glikopeptid oxazolidinone, streptogramin (or a combination of streptogramins), polymyxin, lysostaphin, actinomycin, Aktionen, 7-aminooctanoic D, antimycin a, antipain, bacitracin, cyclosporine a, economizing, gramicidin, myxothiazol, lowlands, paracelsian, valinomycin, viomycin, lipopeptide, sulfonamide (optional in combination with trimethoprim, trimethoprim, isoniazid, rifampicin, rifabutin, pyrazinamide, ethambutol, streptomycin, Dapsone, clofazimine, nitroimidazol, nitrofuran, hinolan, azaserine, bestatin, D-cycloserine, 1,10-phenanthrolin, diazo-5-oxo-L-norleucine, L-alanyl-L-1-aminoethylphosphonic acid, aureoles acid, bethenod, comringtone, irgasan, apiprotocolsupport, cerulenin, glucosamine, staurosporin, macrolactam, taxoid, statin, polyphenolic acid, lasalocid And, ionomycin And, monensin, nigericin, salinomycin, husarova acid, blasticidin S, nikkomycin, nourseothricin, puromycin, adenine-9-β-D-arabinofuranoside, 5-azacytidine, korditsepin, formazin And, tubercidin, tunicamycin, methenamine (hexamine), piericidin And, stigmatella, acticin, anisomycin, apramycin, Copernican A1, L(+)-lactic acid, cytochalasin, emetine, ionomycin,
antifungal azole, antifungal Polian, griseofulvin, caspofungin or flucytosine (the latter two agents are not necessarily applied in combination) or antifungal alamin.

16. Combination product indicated in paragraph 15, where conventional antimicrobial agent is a co-Amoxiclav.

17. Combination product indicated in paragraph 15, where conventional antimicrobial agent is with the battle azithromycin.

18. Combination product indicated in paragraph 15, where conventional antimicrobial agent is telithromycin.

19. Combination product indicated in paragraph 15, where conventional antimicrobial agent is linezolid.

20. Combination product indicated in paragraph 15, where conventional antimicrobial agent represents daptomycin.

21. Combination product indicated in paragraph 15, where conventional antimicrobial agent is a levofloxacin.

22. Combination product indicated in paragraph 15, where conventional antimicrobial agent is a moxifloxacin.

23. The combined product 14 in the form of a kit containing:
(i) a pharmaceutical composition comprising a compound of formula I as defined in any one of claims 1 to 11 in a mixture with a pharmaceutically acceptable adjuvant, diluent or carrier, and
(ii) a pharmaceutical composition comprising a conventional antimicrobial agent as defined in § 15, or its pharmaceutically acceptable salt in a mixture with a pharmaceutically acceptable adjuvant, diluent or carrier
where each component (i) and (ii) are present in a form that is acceptable to the joint application.

24. Pharmaceutical composition comprising a compound of formula (I)as defined in any one of claims 1 to 11, in a mixture with a pharmaceutically acceptable adjuvant, diluent or carrier, for use in the treatment of bacterial infect is I.

25. Combination product according to any one of p-23 for local application.

26. The pharmaceutical composition according to paragraph 24 for local application.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 8-sulphonyl-2,3,4,5-tetrahydro-1H-γ-carbolines of general formula 1 or pharmaceutically acceptable salts thereof, which are ligands with a wider range of simultaneous activity towards alpha adrenoceptors, dopamine receptors, histamine receptors, imidazoline receptors, sigma receptors, norepiniphrine receptors and serotonin receptors. In compounds of general formula 1 R1 is an amino group substitute selected from hydrogen; C1-C3alkyl optionally substituted with phenyl; C1-C4alkyloxycarbonyl; R2 is a cyclic system substitute selected from hydrogen, C1-C3alkyl optionally substituted with phenyl, pyridin-(3- or 4-yl), (6-methylpyridin-3-yl); C1-C3alkenyl substituted with phenyl; or optionally substituted phenylsulphonyl; R3 is an optionally halogen-substituted phenyl, six member aromatic azaheterocycle, mono- or di-C1-C3alkylamino group, phenylamino group which is optionally substituted with halogen atoms on the phenyl ring, or a substituted six member azaheterocycle containing an additional nitrogen atom, substituted with C1-C3alkyl.

EFFECT: compounds can be used in treating and preventing diseases and pathological conditions of the central nervous system, such as anxiety disorders, cognitive disorders, neurodegenerative diseases and depression.

18 cl, 2 dwg, 6 tbl, 23 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula IB , where radicals R1-R5 have values, given in invention formula. In range of claimed invention also described are pharmaceutical compositions, which include compounds of IB formula, and methods of application of such compounds and compositions for treatment of different malfunctions, mainly selected from immune response reactions.

EFFECT: compounds by claimed invention have inhibiting action with respect to proteinkinases and, in particular with respect to JAK-3, ROCK or Aurora kinases.

55 cl, 6 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula: I, where R1 is selected from hydrogen or methoxy; R2 is selected from a group consisting of hydroxy, lower alkoxy, provided that R2 does not denoe methoxy when R1 denotes methoxy, lower alkoxy, mono- or di-substituted with a hydroxy group, benzyloxy, amino, alkylamino, dialkylamino, cyano group, unsubstituted phenyl or tetrazolyl, -O-(CH2)m-C(O)-NR8R9, where m equals 1 or 2, and where R8 and R9 are independently selected from hydrogen, lower alkyl or tetrazolyl, or R8 and R9 together with the nitrogen atom with which they are bonded form morpholinyl or piperazinyl, -O-(CH2)n-COOR10, where n equals 1 or 2 and R10 denotes hydrogen or lower alkyl, -O-(CH2)p-NH-C(O)-OR11, where p equals 1 or 2,and where R11 denotes lower alkyl, -O-SO2-R12, where R12 denotes lower alkyl, -NR13R14, where R13 denotes hydrogen or lower alkyl, and R14 denotes lower alkyl or benzyl, and -NH-CO-(CH2)q-R15, where q equals 1 or 2, and where R5 denotes tetrazolyl; R3 is selected from a group consisting of hydrogen, hydroxy, lower alkoxy, lower alkoxy which is mono- or di-substituted with a hydroxy group, alkoxy or unsubstituted phenyl, and -O-(CH2)m-C(O)-NR8R9, where m equals 1 or 2, and where R8 and R9 are independently selected from hydrogen or lower alkyl, or R8 and R9 together with the nitrogen atom with which they are bonded form morpholinyl or piperazinyl, which can be substituted with lower alkyl; R4 is or , where R5 is selected from lower alkyl; or R5 can also denote hydrogen when selected from a group consisting of -(CH2)m-C(O)-NR8R9, -O-(CH2)p-NH-C(O)-OR11, -O-SO2-R12, -NR13R14, -NH-CO-(CH2)q-R15 and lower alkoxy which is mono- or di-substituted with a group selected from hydroxy, benzyloxy, amino or cyano; R6 is selected from a group consisting of hydrogen and lower alkyl; R7 is selected from a group consisting of lower alkyl and lower halogenalkyl; and to pharmaceutically acceptable salts of said compounds. The invention also pertains to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds having DPP-IV enzyme inhibiting activity.

22 cl, 50 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives of general formula , where R is an optional ortho- or meta-substitute selected from halogen and (C1-4)alkyloxy; R1 is halogen or CF3; R2 is H, (C1-4)alkyloxy or halogen; R3 is H or (CH2)n-NR5R6; R4 is H or (C1-6)alkyl, optionally substituted COOR7 or NR8R9; R5 and R6 independently denote H, (C3-8)cycloalkyl, quinuclidin-3-yl, (C2-6)alkenyl or (C1-6)alkyl, optionally substituted mono-substituted with CF3, (C3-8)cycloalkyl, (C6)aryl, a 5- or 6-member heteroaryl group, OH, (C1-6)alkyloxy, (C6-10)aryloxy, CONR11R12, NR13R14 or NR13SO2(C1-4)alkyl; or R5 and R6 together with a nitrogen atom to which they are bonded form a 4-8-member saturated heterocyclic ring which also contains 1 heteroatom selected from O, SO2 and NR15, where the ring is optionally mono-substituted or di-substituted with oxo, (C1-4)alkyl, (C3-8)cycloalkyl, NR16R17 or CONR18R19; R7 is H or (C1-4)alkyl; R8 and R9 independently denote H, (C1-4)alkyl (optionally substituted di(C1-4)alkylamino) or (C3-8)cycloalkyl; or R8 and R9 together with a nitrogen atom with which they are bonded form a 4-8-member saturated heterocyclic ring which also contains one heteroatom which is O; R11 and R12 independently denote H or (C1-4)alkyl; R13 and R14 independently denote H or (C1-4)alkyl; R15 is H, (C1-4)alkyl (optionally mono-substituted OH, (C1-4)alkyloxy or di(C1-4)alkylamino), phenyl, pyridyl or COR20; R16 and R17 denote (C1-4)alkyl; or R16 and R17 together with a nitrogen atom with which they are bonded from a 4-8-member saturated heterocyclic ring; R18 and R19 denote H; R20 is (C1-4)alkyl, (C3-8)cycloalkyl or furyl; and n equals 0 or 1; or its pharmaceutically acceptable salt. The invention also relates to use of formula I compounds to prepare a medicinal agent and to a pharmaceutical composition based on formula I compound.

EFFECT: novel derivatives have catepsin S and K inhibitory activity.

9 cl, 20 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound which exhibits inhibitory effect on the FAAH enzyme having formula I , where n denotes an integer from 1 to 6; A denotes a group X; where when n equals an integer from 2 to 6, groups A are identical or different; X denotes C1-2-alkylene; R1 denotes a hydrogen atom; R2 denotes a hydrogen atom or a group selected from the following groups: phenyl, phenyloxy; R3 denotes either 2,2,2-trifluoroethyl or phenyl, if necessary substituted with one or more halogen atoms or C1-3-alkyl, C1-3-alkoxy, trifluoromethyl; provided that: the formula 1 compound is not 2,2,2-trifluoroethyl benzylcarbamate, when R3 denotes 2,2,2-trifluoroethyl and group -[A]n- denotes a -CH2- group, when R3 denotes phenyl, if necessary substituted, and group -[A]n-denotes a -CH2-, -CH2CH2-,-CH2CH2CH2- group, then R2 is not a hydrogen atom and is in form of a base, an addition salt with a pharmaceutically acceptable acid, as well as to a method for synthesis of the formula I compound and a pharmaceutical composition having inhibitory effect on FAAH, containing at least one formula I compound.

EFFECT: improved method.

5 cl, 6 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention pertains to novel pyrrolo[3,2-b]pyridine derivatives of formula I , where values of radicals R1-R5 are given in the description. The invention also covers pharmaceutically acceptable salts of these compounds, methods of producing these compounds and pharmaceutical compositions containing these compounds. Pyrrolo[3,2-b]pyridine derivatives and their pharmaceutically acceptable salts can provide proton pump reversible inhibitory effect.

EFFECT: obtaining novel pharmaceutically acceptable salts which can provide proton pump reversible inhibitory effect.

5 cl, 2 tbl, 289 ex

FIELD: medicine.

SUBSTANCE: invention refers to compounds having anxiolytic and antidepressant activity, which are derivatives of the formula 1 (a-b), or formula 2 (a-b) at that compounds of formula 2 (a-b) are intermediate products in synthesis of compounds of the formula , where R-Cl is a compound 1a or R'=COOC2H5 - compound 1b, , where R=COOC2H5 and R'=C1 - compound 2a; R=R-COOC2H5 - compound 2b.

EFFECT: obtaining new biologically active compounds that differ from analogues as intended in low toxicity and lack of side effects.

5 cl, 3 ex, 5 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I and their pharmaceutically acceptable salts. The disclosed compounds have CDK1 and/or CDK2 kinase inhibiting activity. In formula R1 is selected from hydrogen, hydroxy-lower alkyl, C3-C6 cycloalkyl and R2-(X)n; X is selected from lower alkylene, hydroxy-lower alkylene, lower cycloalkylene or lower alkanoyloxy-lower alkylene; R2 is and is selected from phenyl and a 5- or 6-member heteroaromatic ring containing 1 or 2 heteroatoms selected from a group consisting of sulphur and nitrogen; R5 and R6 are independently selected from a group consisting of hydrogen, lower alkyl, halogen and lower alkoxy; and n equals 0 or 1.

EFFECT: design of a pharmaceutical composition for treating and preventing diseases whose condition can be improved by inhibiting CDK1 and/or CDK2 kinase, containing an effective amount of formula I compounds.

47 cl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of formula I. In general formula I A is C or N; B, D and E independently represent CR4, NR5, N, O or S; and a ring containing groups A, B, D, E, selected from thienyl, furan, imidazole, oxazole, isothiazole, thiazole, pyrrol, pyrazole; provided that: b) when A is N, not any of B, D, E can be O or S; and c) when A is C, B is CR4 and one of D or E is N or NR5, when any of D or E cannot be NR5 or N; G is N or C; R1 represents one or more substitutes selected from H, Ra halogen, -OH and -ORa; R2 represents one or more substitutes selected from H, halogen and C1-6-alkyl, and also one of substitutes R2 can be -ORb' , -NRb' Rb', -SRb', -SORb', -SO2Rb', -SO2NRb' Rb'; R3 is H, or Cy, selected from phenyl optionally substituted with one or more substitutes selected from Rc , where Rc independently represents halogen, -ORg', where Rg' independently represents a Rg group, where Rg is C1-6-alkyl; each R4 independently represents H, Re, halogen, -CORe', -CO2Re', -CONRe'Re', -NRe'Re'; R5 independently represents H, Re, -CORe, -CONReRe, -SORe or -SO2Re; each Ra independently represents C1-6-alkyl or halogen- C1-6-alkyl; each R independently represents C1-6-alkyl optionally substituted with one or more substitutes selected from Rd and Rf; each Rb' independently represents H or Rb; each Rc independently represents halogen, -ORg', -CONRg'Rg', -NRg'Rg'; Rd is Cy optionally substituted with one or more Rf substitutes; each Rc independently represents C1-6-alkyl optionally substituted with one or more substitutes selected from Rc and Cy*, or Re is Cy, where any of the groups Cy or Cy* can optionally be substituted with one or more substitutes selected from Rc and Rg ; each Re' independently represents H or Re; each Rf independently represents a halogen, -ORh', -CO2Rh; each Rg independently represents Rd or C1-6-alkyl optionally substituted with one or more substitutes selected from Rd and Rf; each Rg' independently represents H or Rg; each Rh independently represents C1-6-alkyl, halogen-C1-6-alkyl or hydroxy- C1-6-alkyl; each Rh' independently represents H or Rh; and Cy or Cy* given in definitions above is a partially saturated, saturated or aromatic 3-7-member monocyclic carbocyclic ring which optionally contains 1-2 heteroatoms selected from N and O, and where the ring or rings can be bonded to the remaining part of the molecule through a carbon or nitrogen atom.

EFFECT: obtaining formula I compounds with p38-kinase inhibitory properties which can be used in making drugs for treating such diseases as tumour immune and autoimmune diseases etc.

21 cl, 10 dwg, 8 tbl, 57 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of formula where L1 and L2 independently denote a bond, -S-, -NH- or unsubstituted C1-C5alkylene; A1 denotes a 6-member substituted aryl or unsubstituted heteroaryl; A2 denotes aryl or heteroaryl; R1 denotes halogen, -OR5, -NR6R7, -C(Z)R8, -S(O)wR9, -CN, -NO2, -S(O)2NH2, alkyl, aryl or heteroaryl; X1 denotes -C(R2)=, -C(R2)(R3)-, -N(R4)- or -O-; R2 and R3 independently denote hydrogen, -OR5 or alkyl; R4 denotes hydrogen or alkyl; Z denotes O or NH; w is integer from 0 to 2; R5 independently denotes hydrogen or alkyl; R6 and R7 independently denote hydrogen, -S(O)2R11 alkyl or heteroalkyl; R11 denotes hydrogen or alkyl; R8 independently denotes hydrogen, -NR14R15, -OR16, heteroalkyl or cycloalkyl; R14, R15 and R16 independently denote hydrogen, alkyl, cycloalkyl, heteroalkyl or heterocycloalkyl; R9 independently denotes hydrogen or alkyl; and where R6 and R7, R14 and R15 independently and optionally together with the nitrogen atom to which they are bonded form a substituted or unsubstituted heterocycloalkyl. The invention also relates to a method of modulating protein kinase activity, as well as to use of compounds in paragraph 1 and a pharmaceutical composition based on the said compounds.

EFFECT: new compounds which can be useful in treating diseases mediated by kinase activity are obtained and described.

47 cl, 2 ex, 40 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel quinoline derivatives of general formula II, where R1 denotes halogen, R2 denotes halogen, R3 denotes hydroxy, R4, R5 denote C1-C3-alkyl, R6 denotes aryl, R7 denotes aryl, n=1 or 2, as well as to pharmaceutically acceptable acid or base addition salts thereof, having activity towards mycobacteria. The invention also relates to a method for synthesis of formula II compounds.

EFFECT: obtaining novel quinoline derivatives with useful biological activity.

3 cl, 4 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine, namely to chemical-pharmaceutical industry and deals with antituberculosis medication active with respect of drug-resistant strains of tuberculosis mycobacteria. Medication of synergic action contains antituberculosis chemical preparation - isoniaside and silver nanoparticles as potentiating agent, enhancing action of chemical preparation.

EFFECT: invention possesses ability to inhibit drug0resistant strains of tuberculosis mycobacteria and can be used for creation of novel medications for treatment of drug-resistant tuberculosis.

1 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of pharmacology and medicine, namely to new generation of antimicrobial D-cycloserin-based medications of regulated action. Described is medication of anti-microbial action with prolonged release into target organs, characterised in that it represents stable nanoparticles and includes D-cycloserin, PLGA 50/50, D-mannit and polyvinyl alcohol, with the following component ratio, wt %: D-cycloserin from 1 to 15; PLGA 50/50 from 20 to 40; D-mannit from 5 to 40; polyvinyl alcohol from 5 to 15. Described medication has considerably lower neurotoxicity and is able to produce bactericidal effect with respect to Mycobacterium tuberculosis, without producing toxic effect and possessing high therapeutic efficiency.

EFFECT: application of elaborated medication allows to achieve highly selective dosed release of active substance into target organs-cells (macrophages).

5 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention relates to biotechnology and can be used in treatment of diseases, namely oncologic ones. Method is based on sampling from patient immature dendrite cells, their cultivation ex vivo for maturing and formation of allostimulating activity. Cells are additionally collected with antigen and are introduced to the same patient for formation of adaptive immunity. During cultivation ex vivo of immature dendrite cells fragmented allogenic double-stranded genomic DNA with fragments with size 200-6000 bp is introduced into culture medium in amount 5 mcg/ml of medium.

EFFECT: invention allows to extend field of obtained product application with increase of general immune state of patients.

FIELD: medicine.

SUBSTANCE: invention refers to medicine and veterinary science. There is offered a method of treating tuberculosis including administration of Siofor 500 3 times a day, 1 tablet of Delagyl 3 times a day, acetylsalicylic acid three times a day. The 1-year follow-up has shown no recurrence.

EFFECT: method allows intensifying tuberculosis immunity, suppressing tuberculosis and accompanying infection.

1 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine and pharmaceutical industry, namely to method of obtaining poly-DL-lactide-co-glycolide nanoparticles with antituberculosis medications, incapsulated in them, which includes: obtaining lyophilised particles of stable medications, including: stage 1: obtaining lyophilised particles of stable medications, including: stage 2: obtaining lyophilised particles of unstable medications, including: stage 3 combination of lyophilised particles obtained at stages 1 and 2 with obtaining said composition.

EFFECT: claimed is method of obtaining novel nanoparticles.

14 cl, 1 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, and can be used for treatment of tuberculosis of genitor-urinary system. For this purpose from the first days of drug therapy pathologic focus is influenced by wearing paraffin-containing belt "PHYSOMED" at the level of kidneys, prostate.

EFFECT: method allows to activate processes of microcirculation, trophism and cellular metabolism in tissues, which contributes to reduction of spastic and edema components, eliminbation of pain, inflammation and stagnation in kidneys and prostate.

1 dwg, 2 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel benzothiazinone derivatives of formula (I) and their use as antibacterial agents in infectious diseases caused by bacteria, especially mycobacterium tuberculosis (TB) and leprosy, in which R1 and R2 independently denote NO2, CN, CONR7R8, COOR9 CHO, halogen, SO2NR7R8, OCF3, trifluromethyl; R3 and R4 independently denote H or methyl; R5 and R6 independently denote a straight or branched aliphatic radical having 1-8 members in the chain, or R5 and R6 together denote a divalent radical -(CR92)m- or R5 and R6 together denote a divalent radical: R7, R8 and R9 independently denote H or a straight or branched aliphatic radical having 1-7 members in the chain, or phenyl.

EFFECT: design of an efficient method of obtaining benzothiazinone derivatives, a pharmaceutical composition having anti-mycobacterial activity.

12 cl, 6 tbl, 12 ex

FIELD: medicine.

SUBSTANCE: invention belongs to microbiology and biotechnology, notably to tuberculosis anatoxin manufacture for specific prevention of tuberculosis. Tuberculosis anatoxin is made by detoxication of tuberculosis exo- and endotoxins with two detoxifiers - 0.2% formalin solution during 7-9 days at 42-45 C° and 0.5% aethonium solution during 7-9 days at 42-45 C°. Then tuberculosis anatoxin is sorbed on 1-3 mg/ml of aluminium hydroxide, concentration of inactivated toxic allergens is doubled by decantation of 50±5% of supernatant.

EFFECT: usage of anatoxin manufactured by this method gives vaccinated animals immunity to induced by virulent tuberculosis mycobacterium infection due to immune reorganisation of organism; animals acquire moderate sensibility to tuberculin.

4 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of cell biotechnology, veterinary and medicine. Method of treating experimental tuberculosis in mice includes introduction of suspension of bone marrow cells into affected mice. Bone marrow cells are isolated from femoral bone of inbred mice line AKR, resistant to tuberculosis. Introduction is performed into caudal vein once a week in dose 6 mln cells per a mouse during two months. Method allows to reduce number of mycobacteria in organism of experimental animals considerably and guarantees elongation of affected animals life.

EFFECT: invention can be used in veterinary and medicine.

2 tbl

FIELD: medicine, veterinary science.

SUBSTANCE: invention relates to the field of veterinary science. Vaccine contains dissolvent and antigen on the basis of cultures Escherichia coli. As dissolvent, vaccine contains physiological solution, and as antigen - antigen of strain E. coli "B-5" with content of 1.0×106-2.0×106 microbial cells in 1 cm3 of physiological solution.

EFFECT: vaccine has highly immunogenic and protective properties as a result of forming antitoxic immunity.

4 tbl, 3 ex

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