TRICYCLIC GUANIDINE DERIVATIVES AS SODIUM-PROTON EXCHANGE INHIBITORS Russian patent published in 2010 - IPC C07D327/08 C07D411/12 C07D417/12 A61K31/382 A61P9/00 

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), CR^aR^b, O or NR^a; V is CR^aR^b or NR^a; and W is S(O)_m; where R^a is H, alkyl, cycloalkyl or alkenyl; R^b is H, alkyl, OH or OR^a, 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