Tricyclic guanidine derivatives as sodium-proton exchange inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula 1 , where R1, R2, R3, R4, R5, R6, R7 and R8 are independently selected from hydrogen, halogen, alkylcarboxylate, alkyl, alkenyl, cycloalkyl, nitro, sulfonyl chloride, sufonyl hydrazide, alkyl sulfonyl, heterocycylsulfonyl, heteroarylsufonyl, sulfonamide, alkyl-NH-SO2-, cycloalkyl-NH-SO2-, heterocyclyl-NH-SO2-, heteroalkyl-NH-SO2-, heteroarylalkyl-NH-SO2-, heterocyclyl, heteroaryl, guanidinocarbonyl, guanidine, -NR'R" and N=R'"; R' and R" are independently selected from hydrogen, alkyl, cycloalkyl, aryl, aralkyl, halogenalkyl, hydroxyalkyl, alkoxyalkyl, carboxyalkyl, aminoalkyl, mono- or dialkyl substituted aminoalkyl, cycloalkylaminoalkyl, aralkylaminoalkyl, alkoxyaralkylaminoalkyl, heterocyclylalkyl, heterocyclylaminoalkyl, heterocyclylalkylaminoalkyl, heterocyclylalkyl-N(alkyl) alkyl, heteroarylalkyl, heteroaralkylaminoalkyl, alkoxyaralkyl-N(alkyl)alkyl, aralkyl-N(alkyl)alkyl, alkoxycarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl alkylcarbonyl; R'" is selected from heterocyclyl, cycloalkyl and alkyl; where the alkyl is unsubstituted or substituted with 1, 2 or 3 identical or different substitutes selected from halogen, halogen alkyl, hydroxy, alkoxy, alkylamino, carbonyl, cycloalkylamino, nitro, cycloalkyl, aryl, heteroaryl and heterocyclyl; aryl is (C6-C10)aryl which is unsubstituted or substituted with 1-2 identical or different substitutes selected from nitro, alkyl, alkoxy, halogen, halogenalkyl, amino and mono or dialkylamino-; heteroaryl is a 5- or 6-member ring system containing 1, 2 or 3 atoms in the ring selected from N, O and S, which is unsubstituted or substituted with 1-2 identical or different groups selected from halogen, nitro, amino, alkylamino, alkyl, alkoxy and cycloalkyl; heterocyclyl is a 5- or 6-member ring system containing 1, 2 or 3 atoms in the ring selected from N, O and S, which is unsubstituted or substituted with 1-2 identical or different groups selected from alkyl, cycloalkyl, hydroxyalkyl, alkylaminoalkyl, cycloalkylalkyl, cycloalkylcarbonyl, heterocyclylalkyl, heteroarylalkyl, heteroarylcarbonyl, arylalkyl and oxo; and guanidino and guanidinocarbonyl are unsubstituted or substituted with 1, 2 or 3 identical or different groups selected from alkyl and alkylcarbonyl; provided that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 is guanidine or guanidine carbonyl; U is C(O), CRaRb, O or NRa; V is CRaRb or NRa; and W is S(O)m; where Ra is H, alkyl, cycloalkyl or alkenyl; Rb is H, alkyl, OH or ORa, and m equals 1 or 2; or to pharmaceutically acceptable salts thereof. The invention also relates to a method of obtaining formula 1 compounds, to a pharmaceutical composition, as well as to use of the said compounds.

EFFECT: obtaining new biologically active compounds which are sodium/proton exchange (Na+/H+) (NHE) inhibitors.

19 cl, 203 ex, 2 tbl

 

The text descriptions are given in facsimile form.

1. The compound of General formula 1

where R1, R2, R3, R4, R5, R6, R7 and R8 is chosen, independently of one another from among hydrogen, halogen, alkylcarboxylic, alkyl, alkenyl, cycloalkyl, nitro, sulphonylchloride, sulfonylhydrazide, alkylsulfonyl, heterocyclyl the sludge, heteroarylboronic, sulfonamida, alkyl-NH-SO2-cycloalkyl-NH-SO2-, heterocyclyl-NH-SO2-heteroaryl-NH-SO2-heteroallyl-NH-SO2-, heterocyclyl, heteroaryl, guanidiniocarbonyl, guanidino, -NR'r R" and N=R"';
R' and R" are chosen, independently of one another from among hydrogen, alkyl, cycloalkyl, aryl, aralkyl, halogenoalkane, hydroxyalkyl, alkoxyalkyl, carboxyethyl, aminoalkyl, mono - or dialkylamino of aminoalkyl, cycloalkylcarbonyl, aralkylamines, alkoxyalkanols, geterotsiklicheskikh, geterotsiklicheskikh, geterotsiklicheskikh, geterotsiklicheskikh-N(alkyl)alkyl, heteroallyl, heteroarylboronic, alkoxyalkyl-N(alkyl)alkyl, aralkyl-N(alkyl)alkyl, alkoxycarbonyl, cycloalkylcarbonyl, geterotsiklicheskikh and alkylcarboxylic;
R"' is chosen from among heterocyclyl, cycloalkyl and alkyl;
where the alkyl is a substituted or unsubstituted 1, 2 or 3 identical or different substituents selected from halogen, halogenoalkane, hydroxy, alkoxy, alkylamino, carbonyl, cyclooctylamine, nitro, cycloalkyl, aryl, heteroaryl and heterocyclyl;
aryl represents a (C6-C10)aryl, which is substituted or unsubstituted 1-2 are the same or different substituents selected from nitro, alkyl, alkoxy, halogen, halogenate is a, amino, and mono - or dialkylamino-;
heteroaryl represents a 5 - or 6-membered ring system containing 1, 2 or 3 atoms in the ring selected from N, O and S, which is substituted or unsubstituted 1-2 are the same or different groups selected from halogen, nitro, amino, alkylamino, alkyl, alkoxy and cycloalkyl;
heterocyclyl represents a 5 - or 6-membered ring system containing 1, 2 or 3 atoms in the ring selected from N, O and S, which is substituted or unsubstituted 1-2 are the same or different groups selected from alkyl, cycloalkyl, hydroxyalkyl, acylaminoalkyl, cycloalkyl, cycloalkylcarbonyl, geterotsiklicheskikh, heteroallyl, heteroarylboronic, arylalkyl and oxo; and guanidino and guanidiniocarbonyl are substituted or unsubstituted 1, 2 or 3 identical or different groups selected from alkyl and alkylcarboxylic;
provided that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 represents guanidino or guanidiniocarbonyl;
U represents C(O), CRaRb, O or NRa;
V represents CRaRbor NRa;
W represents S(O)m;
where Rarepresents H, alkyl, cycloalkyl or alkenyl;
Rbrepresents H, alkyl, HE or oraand
m is an integer 1 or 2;
or its pharmaceutically acceptable salt.

2. The compound of formula 1 according to claim 1, where R1, R2, R3, R4, R5, R6, R7 and R8, independently of one another, chosen from among hydrogen, halogen, nitro, guanidino, guanidiniocarbonyl, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, pyrrolyl, pyrrolidinyl, piperidinyl, piperazinil, morpholinyl, amino, (C1-C4)-alkylamino, (C1-C4)-alkoxy-substituted(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, chlorine-(C1-C4)-alkylamino, di[chloro-(C1-C4)-alkyl] amino, hydroxy-(C1-C4)-alkylamino, di[hydroxy-(C1-C4)-alkyl] amino, mono - or di-(C1-C4)-alkyl substituted amino-(C1-C4)-alkylamino, benzylamino, morpholinyl-(C1-C4)-alkylamino, (C1-C4)-alkyl substituted thiophenyl-(C1-C4)-alkylamino, pyrrolidinyl-(C1-C4)-alkylamino, pyridyl-(C1-C4)-alkylamino, piperidinyl-(C1-C4)-alkylamino, 3H-imidazolyl-(C1-C4)-alkylamino, piperazinil-(C1-C4)-alkylamino, morpholinyl-(C1-C4)-alkylamino-(C1-C4)-alkyl, pyrrolidinyl-(C1-C4)-alkylamino-(C1-C4)-alkyl, piperidinyl-(C1-C4)-alkylamino-(C1-C4)-alkyl, furanyl-(C1-C4)-alkylamino, benzylamino-(C1-C4 )-alkylamino, morpholinium-(C1-C4)-alkylamino, (C3-C6)-cyclooctylamino-(C1-C4)-alkylamino, furanyl-(C1-C4)-alkyl-N[(C1-C4)-alkyl]CH2CH2-N[(C1-C4)-alkyl]-, thiophenyl-(C1-C4)-alkyl-N[(C1-C4)-alkyl]-CH2CH2-N[(C1-C4)-alkyl]-, benzyl-N[(C1-C4)-alkyl]-CH2CH2-N[(C1-C4)-alkyl]-, (C1-C4)-alkylcarboxylic, (C1-C4)-alkoxycarbonyl, morpholinylcarbonyl, morpholinyl-(C1-C4)-alkyl-N[C(O)CH3]-, morpholinyl-(C1-C4)-alkyl-N(C(O)CH2CH3), morpholinyl-(C1-C4)-alkyl-N[C(O)CH2OCH3]-, morpholinyl-(C1-C4)-alkyl-N[C(O)-isobutoxy], morpholinyl-(C1-C4)-alkyl-N[C(O)-cyclopropyl], pyrrolidinyl-(C1-C4)-alkyl-N[C(O)CH3]-, pyrrolidinyl-(C1-C4)-alkyl-N[C(O)CH2CH3]-, pyrrolidinyl-(C1-C4)-alkyl-N[C(O)-isobutoxy], pyrrolidinyl-(C1-C4)-alkyl-N[C(O)-cyclopropyl], pyrrolidinyl-(C1-C4)-alkyl-N[C(O)CH2Cl]-, piperidinyl-(C1-C4)-alkyl-N{C(O)-CH3]-, piperidinyl-(C1-C4)-alkyl-N[C(O)-CH2OCH3]-, piperidinyl-(C1-C4)-alkyl-N[C(O)-CH2OH]-, piperidinyl-(C1-C 4)-alkyl-H[C(O)C(CH3)3]-, piperidinyl-(C1-C4)-alkyl-N[C(O)-isobutoxy], piperidinyl-(C1-C4)-alkyl-H[C(O)-cyclopropyl]-, (C1-C4)-alkylamino-(C1-C4)-alkyl-N[C(O)-CH3], (C1-C4)-alkylamino-(C1-C4)-alkyl-N[C(O)C(CH3)3], halogen-(C1-C4)-alkyl-N[C(O)-CH2Cl]-, (C3-C6-cycloalkyl-NH-acetamido, (C1-C4)-alkyl-NH-acetamido, (C1-C4)-alkylamino-(C1-C4)-alkylated, pyrrolidinylcarbonyl, piperidinylcarbonyl, piperazinylcarbonyl, phenylpiperazines, imidazolylalkyl, 1 carboxyethylpyrrole-(C1-C4)-alkylamino, 4-(C1-C4)-alkylpiperazine-(C1-C4)-alkylamino, sulphonylchloride, (C1-C4)-alkylsulfonyl, heterocyclization, heteroarylboronic, sulfonylhydrazide, sulfonamida, (C1-C4)-alkyl-NH-SO2-, (C3-C6-cycloalkyl-NH-SO2-, heterocyclyl-NH-SO2-heteroaryl-NH-SO2and heterocyclyl =N-,
where pyrrolyl, pyrrolidinyl, piperidinyl, piperazinil, morpholinyl, furanyl, benzyl and imidazolyl - each are unsubstituted or substituted by one or two identical or different groups selected from (C1-C4)-alkyl, hydroxy-(C1-C4)-is Lila, oxo, (C1-C4)-alkylamino-(C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C3-C6-cycloalkyl-(C1-C4)-alkyl, (C1-C4)-alkylsulphonyl, (C3-C6)-cycloalkylcarbonyl, geterotsiklicheskikh, heterocyclyl-(C1-C4)-alkyl, benzyl, where the benzyl is unsubstituted or substituted by one or two identical or different groups selected from (C1-C4)-alkyl, (C1-C4)-alkoxy, amino, mono - or disubstituted amino [where the substituents of the amino may be selected, independently, from (C1-C4)-alkyl, halogen-(C1-C4)-alkyl, hydroxy-(C1-C4)-alkyl, (C1-C4)-alkoxy-(C1-C4)-alkyl, amino-(C1-C4)-alkyl, nitro, halogen and halogen-(C1-C4)-alkyl;
where the alkyl is unsubstituted or substituted by one or two identical or different groups selected from among halogen, hydroxy, mono - or disubstituted amino [where the substituents of the amino may be selected, independently, from (C1-C4)-alkyl, halogen-(C1-C4)-alkyl, hydroxy-(C1-C4)-alkyl heterocyclyl-(C1-C4)-alkyl, heteroaryl-(C1-C4)-alkyl, amino-(C1-C4)-alkyl and (C1-C4)-alkoxy-(C 6
-C10)-ar-(C1-C4)-alkyl], benzylamino, pyridyl, piperidinyl, pyrrolyl, furanyl, morpholinyl, thiophenyl, phenyl and (C3-C6)-cycloalkyl; and
where aryl, heteroaryl and heterocyclyl represents a 5 - or 6-membered cyclic system containing 1, 2 or 3 atoms in the ring selected from N, O and S, which, independently of one another, are unsubstituted or substituted by one or two identical or different groups selected from (C1-C4)-alkyl, (C1-C4)-alkoxy and halogen-(C1-C4)-alkyl,
provided that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 represents guanidino or guanidiniocarbonyl; or
its pharmaceutically acceptable salt.

3. The compound according to claim 1, having the structure of formula 1A

where R1, R2, R3, R4, R5, R6, R7, R8, and W have the meanings indicated in claim 1, provided that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 represents guanidino or guanidiniocarbonyl; and
V represents CH2, SNSN3, (CH3)2, NH or NCH3;
its pharmaceutically acceptable salt.
4, the Connection according to claim 1, having the structure of formula 1b

where R1, R2, R3, R4, R5, R6, R7, R8, and W have the meanings indicated in claim 1, provided that at least one of R1, R2, R3, R4, R5, R6, R7 or R8, not only is em guanidino or guanidiniocarbonyl;
Rarepresents H, (C1-C4)-alkyl, (C3-C6-cycloalkyl or (C2-C4)-alkenyl; and
V represents CH2, SNSN3, (CH3)2, NH or NCH3;
its pharmaceutically acceptable salt.

5. The compound of formula 1 according to claim 1 or 2, where U represents C(O), SNON or CH2, V represents CH2and R7 represents guanidiniocarbonyl.

6. The compound according to any one of preceding claims 1 to 4, where R7 represents guanidino or guanidiniocarbonyl.

7. The compound according to any one of preceding claims 1 to 6, where W represents the SO2.

8. The compound according to any one of preceding claims 1 to 7, where R1, R2, R3, R4, R5, R6 and R8, independently of one another, chosen from among hydrogen, halogen, nitro, cyano, amino, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, 5 - or 6-membered heterocyclyl, 5 - or 6-membered heteroaryl and phenyl(C1-C4)-alkylamino.

9. The compound of General formula 1A according to claim 3, selected from the group which includes
N-(10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(2,4-dichloro-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d|picogate-8-carbonyl)guanidine;
N-(2-chloro-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-10,10-dioxo-10,11-dig the draw-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(3-fluoro-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(1-fluoro-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant [a,d] cycloheptene-8-carbonyl)guanidine;
N-(2-fluoro-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-isopropyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-amino-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(10,10-dioxo-4-pyrrol-1-yl-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(2-methanesulfonyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-chloro-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(10,10-dioxo-7-piperidine-1-yl-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(10,10-dioxo-7-pyrrolidin-1-yl-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-chloro-1-fluoro-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-chloro-2-fluoro-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(10,10-dioxo-7-PI the roll-1-yl-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-chloro-4-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-methyl-10,10-dioxo-7-pyrrol-1-yl-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-chloro-2-methanesulfonyl-4-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-chloro-4-isopropyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(2,7-dichloro-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-benzylamino-4-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-7-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4,7-dimethyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant [a,d]cycloheptene-8-carbonyl)guanidine;
N-(2-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-2-methanesulfonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-isopropyl-6-methyl-10,10-dioxo-10,11-dihydro-5-the KSA-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-6-methyl-2-nitro-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4,6-dimethyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-isopropyl-6-methyl-2-nitro-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(2-amino-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(2-amino-4,6-dimethyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-2-iodine-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-6-methyl-10,10-dioxo-2-pyrrol-1-yl-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-[2-(2,5-dimethylpyrrole-1-yl)-4,6-dimethyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-(2-amino-4,6-dimethyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-2-dimethylamino-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-6-methyl-2-methylamino-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-2-isobutylamino-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[[a,d]CEC shall hepten-8-carbonyl)guanidine;
N-(4,6-dichloro-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(2-amino-4,6-dichloro-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(6-chloro-4-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(2-amino-6-chloro-4-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
amide 4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-sulfonic acid;
N-(6-chloro-4-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclopenten-2-carbonyl)guanidine;
(5-cyclopropyl[1,3,4]thiadiazole-2-yl)amide of 4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-sulfonic acid;
(pyridine-3-ylmethyl)amide and 4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-sulfonic acid;
N-[4-chloro-6-methyl-10,10-dioxo-2-(piperazine-1-sulfonyl)-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl] guanidine;
N-[4-chloro-6-methyl-2-(4-methylpiperazin-1-sulfonyl)-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-[4-chloro-6-methyl-2-(morpholine-4-sulfonyl)-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepta the n-8-carbonyl]guanidine;
N-[4-chloro-2-(4-cyclopropyl-2-oxopiperidin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-8-carbonic] guanidine;
N-[4-chloro-2-(4-cyclopentyl-2-oxopiperidin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-[4-chloro-2-(4-isopropyl-2-oxopiperidin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-[2-(4-benzyl-2-oxopiperidin-1-yl)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-{4-chloro-6-methyl-2-[2-(4-methylpiperazin-1-yl)ethylamino]-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
1-carboxymethyl-1-[2-(4-chloro-8-guanidiniocarbonyl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-ylamino)ethyl]-4-methylpiperazin-1-s;
N-[4-chloro-2-(2-imidazol-1-ylethylamine)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-[2-(2-aminoethylamino)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-[4-chloro-6-methyl-2-(2-morpholine-4-ylethylamine)-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-{4-chloro-2-[ethyl(2-morpholine-4-retil)amino]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tiatives the[a,d]cycloheptene-8-carbonyl}guanidine;
N-(4-chloro-8-guanidiniocarbonyl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-N-(2-morpholine-4-retil)ndimethylacetamide;
N-(4-chloro-8-guanidiniocarbonyl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-methoxy-(2-morpholine-4-retil)ndimethylacetamide;
N-(4-chloro-{2-[4-(2-hydroxyethyl)piperazine-1-yl]ethylamino}-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-[4-chloro-6-methyl-2-(2-methylaminoethanol)-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-[4-chloro-6-methyl-10,10-dioxo-2-(2-pyrrolidin-1 ylethylamine)-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl] guanidine;
N-{4-chloro-2-[ethyl(2-pyrrolidin-1-retil)amino]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl} guanidine;
isobutyl ether(4-chloro-8-guanidiniocarbonyl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-(2-pyrrolidin-1-retil)carbamino acid;
1-carboxymethyl-1-[2-(4-chloro-8-guanidiniocarbonyl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-ylamino)ethyl]pyrrolidine;
(4-chloro-8-guanidiniocarbonyl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)(2-pyrrolidin-1-retil)amide cyclopropanecarbonyl acids is;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-methoxy-N-(2-pyrrolidin-1-retil)ndimethylacetamide;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-N-(2-pyrrolidin-1-retil)ndimethylacetamide;
N-{4-chloro-6-methyl-2-[2-(2-morpholine-4-ylethylamine)ethylamino]-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-{4-chloro-6-methyl-2-[2-(2-morpholine-4-ylethylamine)ethylamino]-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene - 8-carbonyl}guanidine;
N-[4-chloro-2-(2-cyclopropanemethylamine)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-[4-chloro-6-methyl-2-(3-morpholine-4-ylpropionic)-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-{4-chloro-6-methyl-10,10-dioxo-2-[2-(2-pyridin-2-ylethylamine)ethylamino]-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-(4-chloro-2-{2-[(furan-2-ylmethyl)amino]ethylamino}-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-2-{ethyl[2-(ethylfuran-2-ylmethylamino)ethyl]amino}-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-6-methyl-10,10-dioxo-2-{2-[(thiophene-2-ylmethyl)amino]this is a melamine}-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-2-{ethyl[2-(ethylthiophen-2-ylmethylamino)ethyl]amino}-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-[2-(2-benzylaminopurine)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-(2-{[2-(benzylideneamino)ethyl]ethylamino}-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-{4-chloro-2-[2-(2-methoxybenzylamine)ethylamino]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-{4-chloro-2-[2-(2-methoxybenzylamine)ethylamino]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-[4-chloro-6-methyl-10,10-dioxo-2-(2-piperidine-1-ylethylamine)-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-(4-chloro-2-[ethyl(2-piperidine-1-retil)amino]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-hydroxy-N-(2-piperidine-1-retil)ndimethylacetamide;
(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-(2-piperidine-1-retil)amide cyclopropanecarbonyl acid;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioc the on-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2,2-dimethyl-N-(2-piperidine-1-retil)propionamide;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-N-(2-piperidine-1-retil)ndimethylacetamide;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-methoxy-N-(2-piperidine-1-retil)ndimethylacetamide;
N-[4-chloro-2-(2-diethylaminoethylamine)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-N-(2-dimethylaminoethyl)ndimethylacetamide;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-N-(2-dimethylaminoethyl)-2,2-dimethylpropanamide;
N-[4-chloro-6-methyl-2-(4-methylpiperazin-1-yl)-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-(4-chloro-6-methyl-10,10-dioxo-2-piperazine-1-yl-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-[4-chloro-2-(4-deceleration-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-[4-chloro-6-methyl-10,10-dioxo-2-(4-pentylpyridine-1-yl)-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-[4-chloro-2-(4-cyclopropanecarbonyl-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d] cyclohe the ene-8-carbonyl]guanidine;
N-{4-chloro-2-[4-(4-dimethylaminobenzoyl)piperazine-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl} guanidine;
N-{4-chloro-2-[4-(2,4-dichlorobenzyl)piperazine-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10 lambda*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-{4-chloro-6-methyl-10,10-dioxo-2-[4-(1H-pyrrol-2-carbonyl)piperazine-1-yl]-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-{4-chloro-6-methyl-2-[4-(5-methylfuran-2-ylmethyl)piperazine-1-yl]-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl} guanidine;
N-{4-chloro-6-methyl-2-[4-(2-methylbenzyl)piperazine-1-yl]-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-{4-chloro-6-methyl-2-[4-(5-methylthiophene-2-ylmethyl)piperazine-1-yl]-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant [a,d]cycloheptene-8-carbonyl}guanidine;
N-{4-chloro-2-[4-(3,4-dimethoxybenzyl)piperazine-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl} guanidine;
N-{4-chloro-6-methyl-10,10-dioxo-2-[4-(4-trifloromethyl)piperazine-1-yl]-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-[4-chloro-2-(4-ethylpiperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-(4-chloro-6-methyl-2-morpholine-4-yl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-[2-(4-benzylpiperazine-1-yl)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-{4-chloro-2-[4-(2-dimethylaminoethyl)piperazine-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-[4-chloro-2-(4-isopropylpiperazine-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-{4-chloro-6-methyl-2-[4-(2-morpholine-4-retil)piperazine-1-yl]-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-{4-chloro-6-methyl-10,10-dioxo-2-[4-(2-pyrrolidin-1-retil)piperazine-1-yl]-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-[4-chloro-2-(4-cyclopropylamines-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-{4-chloro-6-methyl-10,10-dioxo-2-[4-(2-piperazine-1-retil)piperazine-1-yl]-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl} guanidine;
N-[4-chloro-2-(4-cyclopropylmethyl-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-{2-[4-(3-aminobenzyl)piperazine-1-yl]-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-[4-chloro-6-methyl-10,10-dioxo-2-(4-pyridine-3-iletileri-1-yl)-10,11-dihydro-5-oxa-Abd*6*-tied the benzo[a,d]cycloheptene-8-carbonyl]guanidine;
N-[4-chloro-2-(4-cyclobutylmethyl-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-[4-chloro-2-(4-cyclohexylpiperazine-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-[4-chloro-6-methyl-10,10-dioxo-2-(4-thiophene-2-iletileri-1-yl)-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-{4-chloro-2-[4-(2-methoxybenzyl)piperazine-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl} guanidine;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-piperidine-1-repeted;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-(2,2,2-triptoreline)ndimethylacetamide;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-hydroxyacetamido;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-imidazol-1-ylacetamide;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-cyclopropylbenzene;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-cyclohe eliminatetime;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-cyclopentylacetic;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-isopropylaminoethyl;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-dimethylaminoacetyl;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-cyclobutylmethyl;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-morpholine-4-ylacetamide;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-[4-(3-triptoreline)piperazine-1-yl]ndimethylacetamide;
dimesylate N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-methylaminoacetaldehyde;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-pyrrolidin-1-ylacetamide;
N-{2-[bis(2-hydroxyethyl)amino]-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-(2-amino-4-chloro-6,11,11-trimethyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten--carbonyl)guanidine;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-cyclopropylamino-M-(2-pyrrolidin-1-retil)ndimethylacetamide;
N-(4-chloro-8-guanidiniocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cyclohepten-2-yl)-2-(4-methylpiperazin-1-yl)ndimethylacetamide;
N-{4-chloro-6-methyl-10,10-dioxo-2-[4-(tetrahydrofuran-2-ylmethyl)piperazine-1-yl]-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-(2-amino-4-chloro-6-methyl-10-oxo-10,11-dihydro-5-oxa-Abd*4*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-thia-11-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-[4-chloro-6-methyl-2-(1-methylpyrrolidine-2-ylideneamino)-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-[4-amino-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-[6-methyl-4-(2-morpholine-4-ylethylamine)-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
N-{4-chloro-2-[(3H-imidazol-4-ylmethyl)amino]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-{4-chloro-6-methyl-2-[(5-methylthiophene-2-ylmethyl)amino]-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-{4-chloro-6-methyl-10,10-dioxo-2-[(PI is one-3-ylmethyl)amino]-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d}cycloheptene-8-carbonyl}guanidine;
N-{4-chloro-2-[4-(2-hydroxyethyl)piperazine-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl}guanidine;
N-(2-aminomethyl-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-2-diethylaminomethyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-6-methyl-10,10-dioxo-2-pyrrol-1-ylmethyl-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl)guanidine;
N-[2-(benzylamino)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-Abd*6*-tudiant[a,d]cycloheptene-8-carbonyl]guanidine;
and their pharmaceutically acceptable salts.

10. The compound of General formula 1b according to claim 4, selected from the group which includes
N-(10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(2-chloro-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(3-chloro-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(1-chloro-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(3-fluoro-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(2-CFT is p-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(2-econsultancy-4-methyl-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-chloro-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4,7-dichloro-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-tert-butyl-7-chloro-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-chloro-4-methyl-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-chloro-1-fluoro-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(2,7-dichloro-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-chloro-2-fluoro-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-chloro-2-econsultancy-4-methyl-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(1,7-dichloro-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-methyl-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4,7-dimethyl-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-7-methyl-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]t is kogepan-8-carbonyl)guanidine;
N-(4,6-dimethyl-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(1-fluoro-6-methyl-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(6-methyl-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(10,10-dioxo-7-pyrrol-1-yl-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(7-benzylamino-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(5-methyl-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(5-allyl-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(4-chloro-5,6,11-trimethyl-10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cycloheptene-8-carbonyl)guanidine;
N-(10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-sediment[a,d]cyclohepten-2-carbonyl)guanidine and
N-(10,10-dioxo-10,11-dihydro-5H-Abd*6*-thia-5-azabenzo[a,d]cyclohepten-1-carbonyl)guanidine;
and their pharmaceutically acceptable salts.

11. The method of obtaining the compounds of formula 1

where at least one of R1, R2, R3, R4, R5, R6, R7 and R8 represents-C(O)N=C(NH2)2and the rest the groups R1-R8 and U, V and W have the meanings indicated in claim 1 or 2, including the interaction of the compounds of formula 3

where at least one of R1, R2, R3, R4, R5, R6, R7 and R8 represents-C(O)Y, where Y represents a group to delete, and the remaining groups R1-R8 and U, V and W have the meanings indicated in claim 1 or 2, with guanidine with obtaining the compounds of formula 1 and, optionally, processing the obtained compounds of formula 1 with an acid or a base in an appropriate case for the conversion of compounds of formula 1 in pharmaceutically acceptable salt.

12. Pharmaceutical composition for the treatment of disorders associated with abnormal Na/H exchange in mammals containing a therapeutically effective amount of the compounds of General formula 1, la or lb according to any one of preceding claims 1 to 10 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier or diluent.

13. The use of the compounds of formula 1, 1a or 1b according to any one of preceding claims 1 to 10 or its pharmaceutically acceptable salt to obtain drugs for inhibiting the activity of Na/H exchange.

14. The use of the compounds of formula 1, 1a or 1b according to any one of preceding claims 1 to 10 or its pharmaceutically acceptable salt for a medicinal product for the treatment of disorders associated with abnormal activity of the sodium-proton about the Jena at a mammal.

15. Use PP or 14, where the disorder associated with abnormal activity of the sodium-proton exchange, include tissue damage caused by ischemia and/or reperfusion injury, which occurs when (i) cardiovascular diseases such as angina, acute coronary syndrome, myocardial infarction, heart attack, arrhythmia, cardiac dysfunction, myocardial remodeling, hypertension, stroke, arteriosclerosis and restenosis of blood vessels, (ii) cardiovascular surgical procedures, such as coronary artery bypass grafting (CABG), percutaneous intraluminal coronary angioplasty (RTSA) or any percutaneous intraluminal coronary intervention (PTCI), transplantation of organs, or other operations not on the heart/blood vessels, and (iii) cerebrovascular disorders such as cerebral ischemic stroke and edema; derebrovascular operations; pulmonary disorders such as pulmonary fibrosis; renal disorders, such as glomerulonephritis; metabolic disorders such as diabetes and its complications; fibrotic diseases; hypertrophy and hyperplasia of the tissue/organ; cell proliferative disorders such as cancer; and thrombosis.

16. The use of the compounds of formula 1, 1a or 1b according to any one of preceding claims 1 to 10 or its pharmaceutically acceptable salt to obtain medicines DL the treatment of ischemic conditions associated with abnormal activity of the sodium-proton exchange in a mammal.

17. The application of article 16, where these ischemic condition include cardiac arrhythmia, myocardial infarction, hypertension, angina, and cardiac hypertrophy.

18. The use of the compounds of formula 1, 1a or 1b according to any one of preceding claims 1 to 10 or its pharmaceutically acceptable salt for a medicinal product for the treatment of damaged tissue in a mammal resulting ischemic conditions.

19. Use p, where the tissue is a tissue of heart, brain, liver, kidney, lung, gut, skeletal muscle, spleen, pancreas, nerve tissue, tissue of the spinal cord, retina, vascular or putting fabric.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: present invention relates to benzazepin derivatives of formula (I), where R1 is unsubstituted cyclobutyl, R2 is 3-pyrazinyl, substituted CON(H)(Me) or 2-pyridinyl-M-pyrrolidinyl, where the said pyrrolidinyl group is substituted with a =O group; which is: methylamide 5-(3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy) pyrazine-2-carboxylic acid

or 1-{6-[(3-cyclbutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-3-pyridinyl}-2-pyrrolidinone

EFFECT: obtaining compounds which have affinity to histamine H3 receptor and pharmaceutical compositons containing said compounds.

11 cl, 288 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) and to their pharmaceutically acceptable salts, optical isomers or their mixture as glucokinase activators. In general formula (I) where R1 is C3-8-cycloalkyl, C3-8-cycloalkenyl, a 6-member heterocyclyl with 1 nitrogen atom, condensed phenyl-C3-8-cycloalkyl, each of which is possibly substituted with one or two substitutes R3, R4, R5 and R6; R2 is C3-8-cycloalkyl, a 5-6-member heterocyclyl with 1-2 heteroatoms selected from N, O, or S, each of which can be substituted with one or two substitutes R30, R31, R32 and R33, and R3, R4, R5, R6, R30, R31, R32 and R33 are independently selected from a group consisting of halogen, hydroxy, oxo, -CF3; or -NR10R12; or C1-6-alkyl, phenyl, C1-6-alkoxy, C1-6-alkyl-C(O)-O-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; or -C(O)-R27, -S(O)2-R27; or two substitutes selected from R3, R4, R5 and R6 or R30, R31, R32 and R33, bonded to the same atom or to neighbouring atoms, together form a -O-(CH2)2-O- radical; R10 and R11 independently represent hydrogen, C1-6-alkyl, -C(O)-C1-6-alkyl, -C(O)-O- C1-6-alkyl, -S(O)2- C1-6-alkyl; R27 is C1-6-alkyl, C1-6-alkoxy, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, phenyl, phenyl-C1-6-alkyl, a 5-6-member heteroaryl with 1-2 heteroatoms selected from N or S, a 6-member heteroaryl-C1-6-alkyl with 1 nitrogen atom, a 6-member heterocyclyl-C1-6-alkyl with 1-2 heteroatoms selected from N or O, R10R11-N- C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; R12 is a halogen, CF3, C1-6-alkoxy, -NR10R11; A is a 5-9-member heteroaryl with 1-3 heteroatoms selected from N, O or S, which is possibly substituted with one or two substitutes independently selected from R7, R8 and R9; R7, R8 and R9 are independently selected from halogen, cyano, -CF3; or C1-6-alkyl, C2-6-alkenyl, C1-6-alkoxy, C1-6-alkylthio, -C(O)-O-C1-6-alkyl, formyl, - C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-O-C(O)-C1-6-alkyl or hydroxy-C1-6-alkyl, each of which is possibly substituted with a substitute independently selected from R16; or phenyl, 5-member heteroaryl-C1-6-alkylthio with 2-4 nitrogen atoms, phenylthio, 5-6-member heteroarylthio with 1-2 nitrogen atoms, each of which is possibly substituted on the aryl or heteroaryl part with one or two substitutes independently selected from R17; or C3-8-cycloalkyl; or a 6-member heterocyclyl with 2 nitrogen atoms, 5-7-member heterocyclyl-C1-6-alkylthio with 1-2 heteroatoms selected from N or O, each of which is possibly substituted with one substitute independently selected from R16; or C1-6-alkyl-NR19R20, -S(O)2-R21 or -S(O)2-NR19R20; or -C(O)NR22R23; R16, R17 and R18 independently represent C1-6-alkyl, carboxy, -C(O)-O-C1-6-alkyl, -NR19R20, -C(O)NR19R20; R19 and R20 independently represent hydrogen, C1-6-alkyl, phenyl, 5-member heteroaryl with 2 heteroatoms selected from N or S, 6-member heterocyclyl with 1 nitrogen atom, -C(O)-O-C1-6-alkyl or -S(O)2-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R24; or R19 and R20 together with a nitrogen atom to which they are bonded form a 5-7-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring possibly contains one additional heteroatom selected from nitrogen, oxygen and sulphur, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R21 is selected from C2-6-alkenyl; or R22 and R23 are independently selected from hydrogen, -C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-S(O)2-C1-6-alkyl, C3-8-cycloalkyl; or R22 and R23 together with a nitrogen atom to which they are bonded form a 6-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R24 is oxo, C1-6-alkyl, carboxy- C1-6-alkyl, a 6-member heterocyclyl with 1 nitrogen atom, -NH-S(O)2R28 or -S(O)2R28, where each cyclic group is possibly substituted with one substitute independently selected from R29; R28 is C1-6-alkyl, -C1-6-alkyl-C(O)-O- C1-6-alkyl or -N(CH3)2; R29 is C1-6-alkyl.

EFFECT: obtaining compounds which can be used for treating and preventing diseases mediated by low glucokinase activity.

21 cl, 1 dwg, 608 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: described are compounds of formula (I)

Values of radicals R1-R6 are given in the formula of invention. The compounds inhibit protein kinase MEK1/2. Also described is a pharmaceutical composition for administration in diseases mediated by MEK1/2.

EFFECT: compounds are highly efficient.

16 cl, 27 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula and their pharmaceutically acceptable salts and esters. The disclosed compounds have cdk4 inhibition properties. In formula (I) n equals 0 or 1; R1 and R2 are each independently selected from a group consisting of H, lower alkyl, CO2R5, SO2R6 and COR6; or alternatively, R1 and R2 can form a ring containing 5-6 atoms in the ring, where the said ring contains carbon atoms, where the said carbon atoms are optionally substituted with oxygen, and the said atoms in the ring are optionally substituted with OR6; R3 is selected from a group consisting of H, lower alkyl, O-lower alkyl, halogen, OH, CN, NO2 and COOH; R4 is selected from a group consisting of H, lower alkyl, C3-C6-cycloalkyl, O-lower alkyl, halogen, NO2, S-lower alkyl, NR5R6, CONR7R8, OH and CN; or alternatively R3 and R4, together with two carbon atoms and the bond between them from the benzene ring, to which R3 and R4 are bonded, can form a ring containing 5-7 atoms, where the said 5-7-member ring contains carbon atoms, where the said carbon atoms are optionally substituted with one or two heteroatoms selected from O and N, and the said atoms in the ring are optionally substituted with CO2R6; R4 represents H or halogen; R5 and R6 are each independently selected from a group consisting of H and lower alkyl; R7 and R8 each represents H. The invention also relates to a pharmaceutical composition for treating or controlling diseases progression of which can be enhanced by inhibiting cdk4, containing an effective amount of the disclosed compound as an active ingredient, to use of disclosed compounds for preparing medicinal agents and method of producing said compounds.

EFFECT: more effective treatment.

30 cl, 1 tbl, 142 ex

Organic compounds // 2382783

FIELD: chemistry.

SUBSTANCE: invention relates to a compound which is 1-[2-(2-ethyl-2H-tetrazol-5-yl)ethyl]-3-[5-(3-fluoro-4-methanesulfonylphenyl)-4-methylthiazol-2-yl]urea in free form or in form of a pharmaceutically acceptable salt.

EFFECT: composition has inhibitory activity on phosphatidylinositol-3-kinase, which contains the disclosed compound as an active ingredient, to use of the compound to prepare a pharmaceutical composition for treating diseases mediated by phosphatidylinositol-3-kinase and synthesis method thereof.

6 cl, 9 tbl, 154 ex

FIELD: chemistry.

SUBSTANCE: invention relates to benzothiazole derivatives with general formula and and their pharmaceutically acceptable acid-addition salts as adenosine receptor ligands and to a pharmaceutical preparation based on said compounds. The compounds can be used for treating and preventing diseases mediated by adenosine A2A receptors, for example Alzheimer's disease, certain depressive conditions, toxicomania and Parkinson's disease. In general formulae (IA) and (IB) R1, R2 independently represent lower alkyl or -(CH2)m-O-lower alkyl, or together with the N atom to which they are bonded form a 5-6-member heterocyclic ring which optionally contains 1 additional oxygen atom; R3 represents hydrogen or lower alkyl; R4 represents lower alkyl; hetaryl represents 3H-imidazole-2,4-diiyl or 1H-pyrazole-1,4-diiyl; n equals 1 or 2 and m equals 1 or 2.

EFFECT: more effective treatment.

12 cl, 36 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I: where A,Y,R and R2 assume values given in the description. The invention also relates to methods of producing compounds of formula I and their intermediate compounds, pharmaceutical compositions and methods of using the compounds and their pharmaceutical compositions for inhibiting caspase.

EFFECT: novel compounds have useful biological properties.

44 cl, 5 tbl, 66 ex

FIELD: chemistry.

SUBSTANCE: novel compound is N-(5-hydroxy-2,4-di-tert-butylphenyl)-4-oxo-1H-quinoline-3-carboxamide or its pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with CFTR activity modulation properties.

2 cl, 485 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula , where Qa is phenyl or heteroaryl, and Qa can possibly carry 1 or 2 substitutes selected from hydroxy, halogen, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; R1 and R2 are each independently selected from hydrogen and (1-6C)alkyl; Qb is phenyl or heteroaryl, and Qb can possibly carry 1 or 2 substitutes selected from hydroxy, halogen, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulfinyl and (1-6C)alkylsulfonyl; where any of the substitutes Qa and Qb defined above, containing a CH2 group which is bonded to 2 carbon atoms, or a CH3 group bonded to a carbon atom, can possibly carry on each of the said CH2 or CH3 group one or more substitutes selected from hydroxy, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; where heteroaryl is an aromatic 5- or 6-member monocyclic ring which can contain up to three heteroatoms selected from oxygen, nitrogen and sulphur, and can be condensed with a benzene ring or a five-member nitrogen-containing ring containing 2 nitrogen atoms; as well as pharmaceutically acceptable salts thereof. The invention also relates to a method of producing formula I compounds, a pharmaceutical composition and use of these compounds for treating conditions mediated by effect of TNF cytokines.

EFFECT: more effective treatment.

13 cl, 3 tbl, 46 ex

FIELD: chemistry.

SUBSTANCE: invention relates to benzothiazole derivatives with general formula (I) and their pharmaceutically acceptable acid addition salts, optically pure enantiomers, racemates and diastereomer mixtures as adenosine receptor ligands and to a pharmaceutical preparation based on said compounds. In general formula (I), R1 represents C3-7cycloalkyl substituted with a OR group, or 2-(7-oxa-bicyclo[2.2.1]hept-1-yl)-ethyl; R represents hydrogen or C(O)-lower alkyl; X represents -CHR'-; and R' represents hydrogen or lower alkyl.

EFFECT: compounds can be used for treating or preventing diseases mediated by adenosine A2A receptors, for example Alzheimer's disease, certain depressive conditions, toxicomania and Parkinson's disease.

8 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: described are derivatives of pyridinecarboxamides with formula (I), where the descriptions of radicals are given in the formula of the invention and its salts.

EFFECT: compounds exhibit insecticide activity.

7 cl, 5 tbl, 21 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to a method for preparing derivatives of indole of the general formula (I):

wherein R1 represents hydroxy-group; R2 represents hydrogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, (C2-C6)-alkoxyalkyl or 4-methoxybenzyl; R3 represents hydrogen atom or (C1-C6)-alkyl; each among R4 and R represents independently hydrogen atom, (C1-C6)-alkyl or (C1-C6)-alkoxy-group; D represents an ordinary bond, (C1-C6)-alkylene, (C2-C6)-alkenylene or (C1-C6)-oxyalkylene; in the group-G-R6 wherein G represents an ordinary bond, (C1-C6)-alkylene; R represents saturated or unsaturated carbocyclic ring (C3-C15) or 4-15-membered heterocyclic ring comprising 1-5 atoms of nitrogen, sulfur and/or oxygen wherein this ring can be substituted. Also, invention describes a method for preparing derivatives of indole and DP-receptor antagonist comprising derivative of the formula (I) as an active component. As far as compounds of the formula (I) bind with DP-receptors and they are antagonists of DP-receptors then they can be useful for prophylaxis and/or treatment of diseases, for example, allergic diseases.

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

11 cl, 7 tbl, 353 ex

The invention relates to sulfhemoglobinemia heterocyclic compound represented by formula (I), its pharmaceutically acceptable salts and their hydrates

where the values of A, B, K, T, W, X, Y, U, V, Z, R1specified in paragraph 1 of the claims

The invention relates to new derivatives of benzopyran formula (I)

where R1and R2each independently represent a hydrogen atom, a C1-6-alkyl group, where this alkyl group may be optionally substituted by a halogen atom, a C1-6-alkoxygroup or a hydroxyl group; R3represents a hydroxyl group or a C1-6-alkylcarboxylic; R4represents a hydrogen atom, or R3and R4together form a bond, m is an integer from 0 to 4, n represents an integer from 0 to 4, Y is absent or represents CR11R12where R11and R12each independently represents a hydrogen atom or a C1-6is an alkyl group, R5represents an aryl group or heteroaryl group, such as thienyl, pyridyl or indolyl, where this aryl group may be optionally substituted(R10), where R10represents a halogen atom, a hydroxyl group, a C1-6-alkyl group, where this alkyl group may be optionally substituted by atom galactography, di-C1-6-alkylamino, C1-6-alkoxycarbonyl group, carboxyl group, q is an integer from 1 to 3, and each R10may be the same or different when q is 2 or 3, R6represents a hydrogen atom or a C1-6is an alkyl group, R10represents a hydrogen atom or a C1-6is an alkyl group, X is absent or represents C=O or SO2; R8represents a hydrogen atom, a C1-6-alkyl group, where this alkyl group may be optionally substituted by a halogen atom, or WITH3-6-cycloalkyl group, and R9represents a halogen atom, a nitro-group, or cyano; or their pharmaceutically acceptable salts, as well as a drug on the basis of these compounds with anti-arrhythmic activity

The invention relates to new biologically active compounds

The invention relates to 2,3,7,8-phenoxythiocarbonyl formula I, which can be used to obtain polyhexamethylene - fluorophores, bifluorophors besed, trifluoroprop

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to cardiology, and concerns normalising functional reactivity of cardiovascular system (CVS) in arterial hypertension, impaired glucose tolerance and abdominal obesity. That is ensured by estimating the condition of functional reactivity of the CVS in psychoemotional load by recording systolic, diastolic, average dynamic pressure and heart rate (HR). These data are used to evaluate a functional responsiveness index (FRI) before and after load by formula: FRI=(BPav.dyn. HR)100(standard units). The post-load FRI increment more than by 20 standard units requires the integrated treatment including individually prescribed hypocaloric diet calculated by considering sex, age and body weight, rationally graduated static and dynamic physical activity, administration of irbesartan 150 mg once a day in the morning and pioglitazone 30 mg once a day in the morning at least within 4 months.

EFFECT: complex drug-induced and drug-free therapy combined with empirically prescribed treatment length provides normalisation of functional reactance of the CVS in the given group of patients due to potentiation of therapeutic effect of separate components of an individual care.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely cardiology, and concerns normalising functional reactivity of cardiovascular system (CVS) in arterial hypertension and impaired glucose tolerance. That is ensured by estimating the condition of functional reactivity of the CVS in psychoemotional load by recording systolic, diastolic, average dynamic pressure (BPav.dyn.) and heart rate (HR). These data are used to evaluate a functional responsiveness index (FRI) before and after stress by formula: FRI=(BPav.dyn. x HR)/100(standard units). The post-load value PFR increased more than by 20 standard units requires the complex therapy including graduated static and dynamic physical activity, and introduction of irbesartan in a dose 150 mg in the morning once a day and pioglitazone in a dose 30 mg in the morning once a day at least within 4 months.

EFFECT: complex of drug-induced therapy combined with physical activity and empirically prescribed treatment length provides normalisation of functional reactivityof the CVS in the given group of the patients due to potentiation of therapeutic effect of the used drugs.

1 ex

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