Tricyclic guanidine derivatives as sodium-proton exchange inhibitors

1. A compound of formula 1

wherein,

R1, R2, R3, R4, R5, R6, R7 and R8 are independently from each other selected from: hydrogen, halogen, hydroxy, hydroxyalkyl, formyl, alkoxy, (C 3 -C 6 )cycloalkoxy, aryloxy, alkylthio, alkylcarbonyl, carboxy, alkylcarboxylate, alkyl, alkenyl, (C 3 -C 6 )cycloalkyl, aryl, aryloxycarbonyl, alkylaminoalkyl, aminocarbonyl, cyano, nitro, amidino, sulfonyl chloride, sulfonyl hydrazide, alkylsulfonyl, heterocyclylsulfonyl, heteroarylsulfonyl, sulfonamide, alkyl-NH—SO 2 —, cycloalkyl-NH—SO 2 —, heterocyclyl-NH—SO 2 —, heteroaryl-NH—SO 2 —, heteroaryl-alkyl-NH—SO 2 —, arylalkyl, heterocyclyl, heteroaryl, guanidino carbonyl, guanidino, —NR′R″and N═R′″;

R′ and R″ are independently from each other selected from: hydrogen, alkyl, (C 3 -C 6 )cycloalkyl, aryl, arylalkyl, haloalkyl, thioalkyl, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, carboxyalkyl, aminoalkyl, mono- or di-alkyl-substituted aminoalkyl, (C 3 -C 6 )cycloalkylaminoalkyl, arylalkylaminoalkyl, alkoxyarylalkyl aminoalkyl, heterocyclylalkyl, heterocyclylaminoalkyl, heterocyclylalkylaminoalkyl, heterocyclylalkyl-N[(alkyl)]-alkyl, heteroarylalkyl, heteroarylalkylaminoalkyl, alkoxyarylalkyl-N[(alkyl)]-alkyl, arylalkyl-N[(alkyl)]-alkyl, alkoxycarbonyl, (C 3 -C 6 )cycloalkylcarbonyl, (C 3 -C 6 )cycloalkylaminocarbonyl, arylcarbonyl, aryloxycarbonyl, aralkoxycarbonyl, heterocyclylcarbonyl, CHO and alkyl carbonyl (where said alkyl is unsubstituted or substituted by one, two or three of the same or different substituents selected from: halo, hydroxy, alkoxy, alkylamino, (C 3 -C 6 )cycloalkyl amino, aryl and heterocyclyl);

R′″ is selected from: heterocyclyl, (C 3 -C 6 )cycloalkyl and alkyl;

where aryl is (C 6 -C 10 )aryl which is unsubstituted or substituted by one or two of the same or different groups selected from: nitro, alkyl, alkoxy, halogen, haloalkyl, amino, mono- or dialkylamino, and heterocyclylalkylaminoalkyl; heteroaryl is a 5 or 6 membered ring system containing one, two or three ring atoms selected from N, O and S, which is unsubstituted or substituted by one or two of the same or different groups selected from: halogen, nitro, amino, alkylamino, alkyl, alkoxy and alkylcarbonyl; heterocyclyl is a 5 or 6 membered ring system containing one, two or three ring atoms selected from N, O and S, which is unsubstituted or substituted by one or two of the same or different groups selected from: alkyl, (C 3 -C 6 )cycloalkyl, hydroxyalkyl, alkylaminoalkyl, (C 3 -C 6 )cycloalkylalkyl, (C 3 -C 6 )cycloalkyl carbonyl, heterocyclylalkyl, heteroarylalkyl, heteroarylcarbonyl, arylalkyl, and oxo; guanidino and guanidinocarbonyl are unsubstituted or substituted by one, two or three of the same or different groups selected from: alkyl and alkylcarbonyl;

with the proviso that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 is guanidino or guanidino carbonyl;

U is C(O), CR a R b , O, NR a , or S(O) m ;

V is CR a R b or NR a ;

W is S(O) m ;

wherein,

R a is H, alkyl, (C 3 -C 6 )cycloalkyl, alkenyl or arylalkyl;

R b is H, alkyl, OH, OR a or OCOR a ; and

m is the integer 0, 1 or 2;

in all its stereoisomeric and tautomeric forms and mixtures thereof in all ratios, and pharmaceutically acceptable salts thereof.

2. A compound of the formula I as defined in claim 1 , wherein R1, R2, R3, R4, R5, R6, R7 and R8 are independently from each other selected from: hydrogen, halogen, hydroxy, cyano, nitro, formyl, carboxy, guanidino, guanidino carbonyl, (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkoxy, (C 3 -C 6 )cycloalkoxy, (C 1 -C 4 )alkylthio, (C 1 -C 4 )alkoxycarbonyl, (C 6 -C 10 )aryloxycarbonyl, (C 6 -C 10 )aryl, (C 6 -C 10 )aryloxy, pyrrolyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, amino, (C 1 -C 4 )alkylamino, thio-(C 1 -C 4 )alkylamino, (C 1 -C 4 )alkoxy-substituted(C 1 -C 4 )alkylamino, di-(C 1 -C 4 -alkyl)amino, chloro(C 1 -C 4 )alkylamino, di-[chloro-(C 1 -C 4 )alkyl]amino, hydroxy(C 1 -C 4 )alkylamino, diqhydroxy-(C 1 -C 4 )alkyl]amino, mono- or di-(C 1 -C 4 -alkyl)substituted-amino-(C 1 -C 4 )alkylamino, (C 6 -C 10 )aryloxy(C 1 -C 4 )alkylamino, (C 6 -C 10 )aryl(C 1 -C 4 )alkoxy(C 1 -C 4 )alkylamino, benzylamino, morpholinyl-(C 1 -C 4 )alkylamino, (C 1 -C 4 )alkylsubstituted-thiophenyl-(C 1 -C 4 )alkylamino, pyrrolidinyl(C 1 -C 4 )alkylamino, pyridyl(C 1 -C 4 )alkylamino, piperidinyl(C 1 -C 4 )alkylamino, 3H-imidazolyl(C 1 -C 4 )alkylamino, piperazinyl(C 1 -C 4 )alkylamino, morpholinyl(C 1 -C 4 )alkylamino(C 1 -C 4 -alkyl), pyrrolidinyl (C 1 -C 4 )alkylamino(C 1 -C 4 -alkyl), piperidinyl(C 1 -C 4 )alkylamino(C 1 -C 4 -alkyl), furanyl(C 1 -C 4 )alkylamino, benzylamino(C 1 -C 4 )alkylamino, morpholinylamino(C 1 -C 4 )alkylamino, (C 3 -C 6 )cycloalkylamino(C 1 -C 4 )alkylamino, furanyl(C 1 -C 4 )alkyl-N[(C 1 -C 4 )alkyl]CH 2 CH 2 —N[(C 1 -C 4 )alkyl]-, thiophenyl(C 1 -C 4 )alkyl-N[(C 1 -C 4 )alkyl]-CH 2 CH 2 —N[(C 1 -C 4 )alkyl]-, benzyl-NRC 1 -C 4 )alkyl]-CH 2 CH 2 —N[(C 1 -C 4 )alkyl]-, (C 1 -C 4 )alkylcarbonylamino, (C 1 -C 4 )alkoxycarbonylamino, (C 6 -C 10 )aryloxycarbonylamino, (C 6 -C 10 )aryl(C 1 -C 4 )alkoxycarbonylamino, morpholinylacetamido, morpholinyl(C 1 -C 4 )alkyl-N[C(O)CH 3 ]-, morpholinyl(C 1 -C 4 )alkyl-N(C(O)CH 2 CH 3 )—, morpholinyl(C 1 -C 4 )alkyl-N[C(O)CH 2 OCH 3 ]-, morpholinyl(C 1 -C 4 )alkyl-N[C(O)-isobutoxy]-, morpholinyl(C 1 -C 4 )alkyl-N[C(O)cyclopropyl]-, pyrrolidinyl(C 1 -C 4 )alkyl-N[C(O)CH 3 ]—, pyrrolidinyl-(C 1 -C 4 )alkyl-N[C(O)CH 2 CH 3 ]—, pyrrolidinyl(C 1 -C 4 )alkyl-N[C(O)isobutoxy]-, pyrrolidinyl(C 1 -C 4 )alkyl-N[C(O)cyclopropyl]-, pyrrolidinyl(C 1 -C 4 )alkyl-N[C(O)CH 2 CH 3 ]—, piperidinyl(C 1 -C 4 )alkyl-N[C(O)—CH 3 ], piperidinyl(C 1 -C 4 )alkyl-N[C(O)—CH 2 OCH 3 ]-, piperidinyl(C 1 -C 4 )alkyl-N[C(O)—CH 2 OH]—, piperidinyl(C 1 -C 4 )alkyl-N[C(O)C(CH 3 ) 3 ]—, piperidinyl(C 1 -C 4 )alkyl-N[C(O)-isobutoxy]-, piperidinyl(C 1 -C 4 )alkyl-N[C(O)-cyclopropyl]-, (C 1 -C 4 )alkylamino(C 1 -C 4 )alkyl-N[C(O)—CH 3 ], (C 1 -C 4 )alkylamino(C 1 -C 4 )alkyl-N[C(O)C(CH 3 ) 3 ], halo(C 1 -C 4 )alkyl-N[C(O)—CH 2 Cl]—, (C 3 -C 6 )cycloalkyl-NH-acetamido, (C 1 -C 4 )alkyl-NH-acetamido, (C 1 -C 4 )alkylamino(C 1 -C 4 )alkylacetamido, pyrrolidinyl acetamido, piperidinyl acetamido, piperazinyl acetamido, phenyl piperazinyl acetamido, imidazolyl acetamido, 1-carboxyalkyl pyrrolidinium-(C 1 -C 4 )alkylamino, 1-carboxy, 4-(C 1 -C 4 -alkyl)piperazinium-(C 1 -C 4 )alkylamino, sulfonylchloride, (C 1 -C 4 )alkylsulfonyl, heterocyclylsulfonyl, heteroarylsulfonyl, sulfonylhydrazide, sulfonamide, (C 1 -C 4 )alkyl-NH—SO 2 —, (C 3 -C 6 )cycloalkyl-NH—SO 2 —, heterocyclyl-NH—SO 2 —, heteroaryl-NH—SO 2 — and heterocyclyl═N—;

where pyrrolyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, furanyl, benzyl and imidazolyl are each unsubstituted or substituted by one or two of the same or different groups selected from: (C 1 -C 4 )alkyl, hydroxy(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, oxo, (C 1 -C 4 )alkylamino(C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylcarbonyl, (C 3 -C 6 )cycloalkylcarbonyl, heterocyclylcarbonyl, heterocyclyl(C 1 -C 4 )alkyl, benzyl (where the benzyl is unsubstituted or substituted by one or two of the same or different groups selected from: (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, amino, mono- or di-substituted amino [where the substituents on the amino group may be independently selected from (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, hydroxy(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy(C 1 -C 4 )alkyl, (C 1 -C 4 )acyl, halo(C 1 -C 4 )acyl, heterocyclyl(C 1 -C 4 )alkyl, heteroaryl(C 1 -C 4 )alkyl, amino(C 1 -C 4 )alkyl and (C 1 -C 4 )alkoxy(C 6 -C 10 )aryl(C 1 -C 4 )alkyl], nitro, halo, halo(C 1 -C 4 )alkyl, and heterocyclyl(C 1 -C 4 )alkylamino(C 1 -C 4 )alkyl;

where alkyl is unsubstituted or substituted by one or two of the same or different groups selected from: halo, hydroxy, mono- or di-substituted amino [where the substituents on the amino group may be independently selected from (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, hydroxy(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy(C 1 -C 4 )alkyl, (C 1 -C 4 )acyl, halo(C 1 -C 4 )acyl, heterocyclyl(C 1 -C 4 )alkyl, heteroaryl(C 1 -C 4 )alkyl, amino(C 1 -C 4 )alkyl and (C 1 -C 4 )alkoxy(C 6 -C 10 )aryl(C 1 -C 4 )alkyl], benzyl amino, pyridyl, piperidinyl, pyrrole, furanyl, morpholinyl, thiophenyl, phenyl, (C 3 -C 6 )cycloalkyl, heterocyclyl and heteroaryl; and

where (C 6 -C 10 )aryl, or each of heteroaryl and heterocyclyl, which is a 5 or 6 membered ring system containing one, two or three ring atoms selected from N, O and S, are independently from each other unsubstituted or substituted by one or two of the same or different groups selected from: (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy and halo(C 1 -C 4 )alkyl;

with the proviso that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 is guanidino or guanidino carbonyl;

in all its stereoisomeric and tautomeric forms and mixtures thereof in all ratios, and its pharmaceutically acceptable salts thereof.

3. A compound of formula 1 as defined in claim 1 , which has the structure of formula 1a

wherein

R1, R2, R3, R4, R5, R6, R7, R8 and W are as defined in claim 1 , with the proviso that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 is guanidino or guanidino carbonyl; and

V is CH 2 , CHCH 3 , C(CH 3 ) 2 , NH or NCH 3 ;

in all its stereoisomeric and tautomeric forms and mixtures thereof in all ratios, and its pharmaceutically acceptable salts thereof.

4. A compound of formula 1 as defined in claim 1 , which has the structure of formula 1b

wherein

R1, R2, R3, R4, R5, R6, R7, R8 and W are as defined in claim 1 , with the proviso that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 is guanidino or guanidino carbonyl;

R a is H, (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl or (C 2 -C 4 )alkenyl; and

V is CH 2 , CHCH 3 , C(CH 3 ) 2 , NH or NCH 3 ;

in all its stereoisomeric and tautomeric forms and mixtures thereof in all ratios, and pharmaceutically acceptable salts thereof.

5. A compound of formula I as defined in claim 1 , wherein U is C(O), CHOH or CH 2 , V is CH 2 , R7 is guanidino carbonyl.

6. The compound of formula 1 as defined in claim 1 , wherein R7 is guanidino or guanidino carbonyl.

7. The compound of formula 1 as defined in claim 1 , wherein W is SO 2 .

8. A compound of formula 1 as defined in claim 1 , wherein R1, R3, R4, R5, R6 and R8 are independently from each other selected from: hydrogen, hydroxyl, halogen, nitro, cyano, amino, (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkylcarbonyl, (C 1 -C 4 )carboxy, phenyl, 5- or 6-membered heterocyclyl, 5- or 6-membered heteroaryl, 5- or 6-membered heterocyclyl(C 1 -C 4 )alkyleneamino, 5- or 6-membered heteroarylamino, and phenyl(C 1 -C 4 )alkylene amino.

9. A compound of formula 1a as defined in claim 3 , selected from:

N-(10,10-Dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(2,4-Dichloro-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(2-Chloro-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(3-Fluoro-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(1-Fluoro-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(2-Fluoro-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Isopropyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Amino-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(10,10-dioxo-4-pyrrol-1-yl-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(2-Methanesulfonyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Chloro-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(10,10-dioxo-7-piperidin-1-yl-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(10,10-dioxo-7-pyrrolidin-1-yl-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Chloro-1-fluoro-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Chloro-2-fluoro-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(10,10-Dioxo-7-pyrrol-1-yl-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Chloro-4-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Methyl-10,10-dioxo-7-pyrrol-1-yl-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Chloro-2-methanesulfonyl-4-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Chloro-4-isopropyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(2,7-Dichloro-10,10-dioxo-10,11-dihydro-5-oxa-1° lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Benzylamino-4-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-7-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4,7-Dimethyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(2-Chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-2-methanesulfonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Isopropyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-6-methyl-2-nitro-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4,6-Dimethyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Isopropyl-6-methyl-2-nitro-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(2-Amino-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(2-Amino-4,6-dimethyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-2-iodo-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-6-methyl-10,10-dioxo-2-pyrrol-1-yl-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-[2-(2,5-Dimethyl-pyrrol-1-yl)-4,6-dimethyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-(2-Dimethylamino-4,6-dimethyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-2-dimethylamino-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-6-methyl-2-methylamino-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(2-[N-Benzyloxycarbonyl-guanidino]-4-Chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-2-isobutylamino-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4,6-Dichloro-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine,

N-(2-Amino-4,6-dichloro-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(6-Chloro-4-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(2-Amino-6-chloro-4-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-2-sulfonic acid amide;

N-(6-chloro-4-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lamda*6*-thia-dibenzo [a,d]cyclopentene-8-carbonyl)-guanidine;

4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-2-sulfonic acid (5-cyclopropyl-[1,3,4]thiadiazol-2-yl)-amide;

4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-2-sulfonic acid (pyridin-3-ylmethyl)-amide;

N-[4-Chloro-6-methyl-10,10-dioxo-2-(piperazine-1-sulfonyl)-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]guanidine;

N-[4-Chloro-6-methyl-2-(4-methyl-piperazine-1-sulfonyl)-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-8-carbonyl]-guanidine;

N-[4-Chloro-6-methyl-2-(morpholine-4-sulfonyl)-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]guanidine;

N-[4-Chloro-2-(4-cyclopropyl-2-oxo-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-[4-Chloro-2-(4-cyclopentyl-2-oxo-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-[4-Chloro-2-(4-isopropyl-2-oxo-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-[2-(4-Benzyl-2-oxo-piperazin-1-yl)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbony]-guanidine;

N-{4-Chloro-6-methyl-242-(4-methylpiperazin-1-yl)-ethylamino]-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

1-Carboxymethyl-1-[2-(4-chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-ylamino)-ethyl]-4-methyl piperazin-1-ium;

N-[4-Chloro-2-(2-imidazol-1-yl-ethylamino)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-[2-(2-Amino-ethylamino)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-[4-Chloro-6-methyl-2-(2-morpholin-4-yl-ethylamino)-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-{4-Chloro-2-[ethyl-(2-morpholin-4-yl-ethyl)-amino]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-N-(2-morpholin-4-yl-ethyl)-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2-methoxy-N-(2-morpholin-4-yl-ethyl)-acetamide;

N-(4-Chloro-2-{2-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-ethylamino}-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-{4-Chloro-6-methyl-2-(2-methylamino-ethylamino)-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-[4-Chloro-6-methyl-10,10-dioxo-2-(2-pyrrolidin-1-yl-ethyl amino)-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-{4-Chloro-2-[ethyl-(2-pyrrolidin-1-yl-ethyl)-amino]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-2-yl)-(2-pyrrolidin-1-yl-ethyl)-carbamic acid isobutylester;

1-Carboxymethyl-1-[2-(4-chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10-lambda*6*-thia-dibenzo[a,d]cycloheptene-2-ylamino)-ethyl]-pyrrolidinium;

Cyclopropanecarboxylic acid (4-chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-(2-pyrrolidin-1-yl-ethyl)-amide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2-methoxy-N-(2-pyrrolidin-1-yl-ethyl)-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-N-(2-pyrrolidin-1-yl-ethyl)-acetamide;

N-{4-Chloro-6-methyl-2-[2-(2-morpholin-4-yl-ethylamino)-ethylamino]-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-{4-Chloro-6-methyl-2-[2-(2-morpholin-4-ylamino)-ethylamino]-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-[4-Chloro-2-(2-cyclopropylamino-ethylamino)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-[4-Chloro-6-methyl-2-(3-morpholin-4-yl-propylamino)-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-{4-Chloro-6-methyl-10,10-dioxo-2-[2-(2-pyridin-2-yl-ethylamino)-ethylamino]-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[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-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-2-{ethyl-[2-(ethyl-furan-2-ylmethyl-amino)-ethyl]-amino-}-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-6-methyl-10,10-dioxo-2-{2-[(thiophen-2-ylmethyl)-amino]-ethylamino}-10,11-dihydro-5-oxa-10lambda*6*thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-2-{ethyl-[2-(ethyl-thiophen-2-ylmethyl-amino)-ethyl]-amino}-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-[2-(2-Benzylamino-ethylamino)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-(2-{[2-(Benzyl-ethyl-amino)-ethyl]-ethyl-amino}-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-{4-Chloro-2-[2-(2-methoxy-benzylamino)-ethylamino]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-(4-Chloro-2-{2-[ethyl-(2-methoxy-benzyl)-amino]-ethylamino}-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-[4-Chloro-6-methyl-10,10-dioxo-2-(2-piperidin-1-yl-ethylamino)-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-(4-Chloro-2-[ethyl-(2-piperidin-1-yl-ethyl)-amino]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10-lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2-hydroxy-N-(2-piperidin-1-yl-ethyl)-acetamide;

Cyclopropanecarboxylic acid (4-chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-2-yl)-(2-piperidin-1-yl-ethyl)-amide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2,2-dimethyl-N-(2-piperidin-1-yl-ethyl)-propionamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-N-(2-piperidin-1-yl-ethyl)-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2-methoxy-N-(2-piperidin-1-yl-ethyl)-acetamide;

N-[4-Chloro-2-(2-dimethylamino-ethylamino)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-8-carbonyl]-guanidine;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-N-(2-dimethylamino-ethyl)-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-N-(2-dimethylamino-ethyl)-2,2-dimethyl-propionamide;

N-[4-Chloro-6-methyl-2-(4-methylpiperazin-1-yl)-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-(4-Chloro-6-methyl-10,10-dioxo-2-piperazin-1-yl-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-[4-Chloro-2-(4-decyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-[4-Chloro-6-methyl-10,10-dioxo-2-(4-pentyl-piperazin-1-yl)-10,11-dihydro-5-oxa-10-lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-[4-Chloro-2-(4-cyclopropanecarbonyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-{4-Chloro-2-[4-(4-dimethylamino-benzyl)-piperazin-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-[4-Chloro-2-[4-(2,4-dichloro-benzyl)-piperazin-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-{4-Chloro-6-methyl-10,10-dioxo-2-[4-(1H-pyrrole-2-carbonyl)-piperazin-1-yl]-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-{4-Chloro-6-methyl-2-[4-(5-methyl-furan-2-ylmethyl)-piperazin-1-yl]-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-{4-Chloro-6-methyl-2-[4-(2-methyl-benzyl)-piperazin-1-yl]-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-{4-Chloro-6-methyl-2-[4-(5-methyl-thiophen-2-ylmethyl)-piperazin-1-yl]-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-{4-Chloro-2-[4-(3,4-dimethoxy-benzyl)-piperazin-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbony}-guanidine;

N-{4-Chloro-6-methyl-10,10-dioxo-2-[4-(4-trifluoromethyl-benzyl)-piperazin-1-yl]-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-{4-Chloro-2-(4-ethyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}guanidine;

N-{4-Chloro-6-methyl-2-morpholin-4-yl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-[2-(4-Benzyl-piperazin-1-yl)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-{4-Chloro-2-[4-(2-dimethylamino-ethyl)-piperazin-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-[4-Chloro-2-(4-isopropyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-{4-Chloro-6-methyl-2-[4-(2-morpholin-4-yl-ethyl)-piperazin-1-yl]-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-{4-Chloro-6-methyl-10,10-dioxo-2-[4-(2-pyrrolidin-1-yl-ethyl)-piperazin-1-yl]-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-[4-Chloro-2-(4-cyclopropylmethyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]guanidine;

N-{4-Chloro-6-methyl-10,10-dioxo-2-[4-(2-piperazin-1-yl-ethyl)-piperazin-1-yl]-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-[4-Chloro-2-(4-cyclopropyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-{2-[4-(3-Amino-benzyl-piperazin-1-yl]-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-[4-Chloro-6-methyl-10,10-dioxo-2-(4-pyridin-3-ylmethyl-piperazin-1-yl)-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-[4-Chloro-2-(4-cyclobutyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-[4-Chloro-2-(4-cyclohexyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-[4-Chloro-6-methyl-10,10-dioxo-2-(4-thiophen-2-ylmethyl-piperazin-1-yl)-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-{4-Chloro-2-[4-(2-methoxy-benzyl-piperazin-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-2-yl)-2-pyperidin-1-yl-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-2-yl)-2-(2,2,2-trifluoro-ethylamino)-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-2-yl)-2-hydroxy-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2-imidazol-1-yl-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2-cyclopropylamino-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2-cyclohexylamino-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2-cyclopentylamino-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2-isopropylamino-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2-dimethylamino-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-2-yl)-2-cycylobutylamino-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2-morpholin-4-yl-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-acetamide,

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclohepten-2-yl)-2-methylamino-acetamide dimesylate;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]-cyclohepten-2-yl)-2-pyrrolidine-1-yl-acetamide;

N-{2-[Bis-(2-hydroxy-ethyl)-amino]-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-(2-Amino-4-chloro-6,11,11-trimethyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-2-yl)-2-cyclopropylamino-N-(2-pyrrolidin-1-yl-ethyl)-acetamide;

N-(4-Chloro-8-guanidinocarbonyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lamda*6*-thia-dibenzo[a,d]cyclopenten-2-yl)-2-(4-methyl-piperazin-1-yl)-acetamide;

N-{4-Chloro-6-methyl-10,10-dioxo-2-[4-(tetrahydro-furan-2-ylmethyl)-piperazin-1-yl]-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-(2-Amino-4-chloro-6-methyl-10-oxo-10,11-dihydro-5-oxa-10lambda*4*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-(6-Methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-11-aza-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine;

N-[4-Chloro-6-methyl-2-(1-methyl-pyrrolidin-2-ylidineamino)-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

2-(4-Benzyl-piperazin-1-yl)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-yl-methylene amino guanidine;

N-[4-Amino-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-[6-Methyl-4-(2-morpholin-4-yl-ethylamino)-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[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-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

N-{4-Chloro-6-methyl-2-[(5-methyl-thiophen-2-ylmethyl)-amino]-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-{4-Chloro-6-methyl-10,10-dioxo-2-[(pyridin-3-ylmethyl)-amino]-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-{4-Chloro-2-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl}-guanidine;

N-(2-Aminomethyl-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-2-diethylaminomethyl-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine,

N-(4-Chloro-6-methyl-10,10-dioxo-2-pyrrol-1-ylmethyl-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl)-guanidine; and

N-[2-(Benzylamino-methyl)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carbonyl]-guanidine;

and -their pharmaceutically acceptable salts.

10. A compound of formula 1b as defined in claim 4 , selected from:

N-(10,10-Dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(2-Chloro-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(3-Chloro-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(1-Chloro-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(3-Fluoro-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(2-Fluoro-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(2-Ethanesulfonyl-4-methyl-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Chloro-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(4,7-Dichloro-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(4-tert-Butyl-7-chloro-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Chloro-4-methyl-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Chloro-1-fluoro-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(2,7-Dichloro-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Chloro-2-fluoro-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Chloro-2-ethanesulfonyl-4-methyl-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(1,7-Dichloro-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Methyl-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(4,7-Dimethyl-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine,

N-(4-Chloro-7-methyl-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(4,6-Dimethyl-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(1-Fluoro-6-methyl-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-6-methyl-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(6-Methyl-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(10,10-Dioxo-7-pyrrol-1-yl-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(7-Benzylamino-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(5-Methyl-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(5-Allyl-10,10-dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(4-Chloro-5,6,11-trimethyl-10,10-dioxo-10,11-dihydro-5H-10lambda*6 *-thia-5-aza-dibenzo[a.d]cycloheptene-8-carbonyl)-guanidine;

N-(10,10-Dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-2-carbonyl)-guanidine; and

N-(10,10-Dioxo-10,11-dihydro-5H-10lambda*6*-thia-5-aza-dibenzo[a.d]cycloheptene-1-carbonyl)-guanidine;

and -their pharmaceutically acceptable salts.

11. A process for the preparation of a compound of the formula 1 as defined in claim 1 ,

wherein

at least one of R1, R2, R3, R4, R5, R6, R7 and R8 is C(O)N═C(NH 2 ) 2 and the remaining groups R1 to R8 and U, V and W are as defined in claim 1 , which comprises reacting a compound of the formula 3

wherein

at least one of R1, R2, R3, R4, R5, R6, R7 and R8 is —C(O)Y, wherein Y is a leaving group, and the remaining groups R1 to R8 and U, V and W are as defined in claim 1 , with guanidine, and optionally treating with an acid or base as appropriate to convert the compound of formula 1 into a pharmaceutically acceptable salt.

12. A pharmaceutical composition, comprising a therapeutically effective amount of a compound of formula 1 as defined in claim 1 , or a tautomer, stereoisomer, pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

13. The compound of claim 3 , wherein R7 is guanidino or guanidino carbonyl.

14. The compound of claim 4 , wherein R7 is guanidino or guanidino carbonyl.

15. The compound of claim 3 , wherein W is SO 2 .

16. The compound of claim 4 , wherein W is SO 2 .