CA2352045A1

CA2352045A1 - Substituted benzo[de]isoquinoline-1,3-diones

Info

Publication number: CA2352045A1
Application number: CA002352045A
Authority: CA
Inventors: Werner Mederski; Ralf Devant; Gerhard Barnickel; Sabine Bernotat-Danielowski; Guido Melzer; Peter Raddatz; Zhengdong Wu; Daljit Dhanoa; Richard Soll; James Rinker; Todd Graybill
Original assignee: Individual
Current assignee: Merck Patent GmbH
Priority date: 1998-11-25
Filing date: 1999-11-09
Publication date: 2000-06-08
Also published as: KR20010080569A; NO20012544D0; ID28982A; TW473474B; PL348204A1; WO2000032577A2; HUP0104520A3; AU760136B2; HUP0104520A2; AU2660300A; JP2002537225A; CZ20011782A3; CN1330638A; BR9915648A; SK7022001A3; NO20012544L; WO2000032577A3; EP1144381A2

Abstract

Novel compounds of formula (I) in which R, R1 and R2 have the meaning indicated, and their salts or solvates as glycoprotein IbIX antagonists.

Description

F
n .... ' :o DEMANDES OU BREVETS VOLUMINEUX
LA PRESENTE PARTlE DE CETTE DEMANDE OU CE BREVET
COMPREND PLUS D'UN TOME.
CEC! EST LE TOME 'I DE
NOTE: ~ Pour les tomes additionels, veuillez contacter le Bureau canadien des brevets JUMBO APPLICATIONS/PATEIVTS
THiS SECT10N OF THE APPLICATlON/PATENT CONTAINS MORE
THAN ONE VOLUME
THiS !S VOLUME ~ , OF
NOTE: For additional volumes please contact the Canadian Patent Office - 1 - ' Substituted benzo[de]isoquinoline-1,3-diones This application is a continuation-in-part of Serial No. 09/199,413, the entirety of which is incorporated by reference herein.
The invention relates to substituted benzo[de]-isoquinoline-1,3-diones of the formula I

R ~ ~ R
I
i O ' '-O
N

IO in which R is H or NO2, Rl is -Het, -Het-SO2-Ar, -Het-R5, -Het- (CH2) n-Ar, NO2, -N=CH-Ar, NHAlk, NAAlk, NHA' , NA' 2, N N --NH
-Y-D-H, -Y-Ar' -R3, -Y- (CH2) o-R3, -Y- ( CH2 ) n- ( CHR9 ) -R5, -Y-C [ ( CH2 ) o-OH ] 3 r -Y- ( CH2 ) m NA2 r -Y- ( CH2 ) m-NHA' , -Y- ( CH2 ) o-OH, -Y- ( CH2 ) k-Rs r -Y- ( CH2 ) i-Re r -Y- (CH2) n-Het, -Y- (CH2) n-Ar,

2 0 -Y- ( CH2 ) n-Ar' - ( CH2 ) i-R6 r -Y- ( CH2 ) n-D- ( CH2 ) i-R6 -Y- ( CH2 ) n-Het- ( CH2 ) i-R6 r -Y- ( CH2 ) n-NA- ( CH2 ) i-R6 ~
-Y- ( CH2 ) n-NH- ( CH2 ) i-R6 r -Y- ( CH2 ) n-D- ( CH2 ) i-R8 r -Y- ( CH2 ) n-Ar' - ( CH2 ) i-Re r -Y- ( CH2 ) n-NH- ( CH2 ) i-R8 r -Y- ( CH2 ) n-NA- ( CH2 ) i-Re r -Y-(CH2)n N--~
NH
_Y_ [X_0] t_ [X~_0~ u_X2_Rs Or _Y_ [X_NH] u_X1_OHr R2 is -Ar, -Ar' -D-H, -Hetl, -Hetl-Ar, -Ar' -Hetl, -Ar' - ( CH2 ) n-R3. -Ar' -Y- ( CH2 ) n-R3 r -Ar' -Y-C (A ) 2-R3. -Hetl-R3, -Ar' -Hetl-R3, -Ar' - (CH2) ri R6, -Ar' -SO2-Het, -Ar' -NH-SO2-Het, Ar' -SO2-R', -Ar' - (CH2) n- (CO-NH) -- 2 _ _ ( CH2 ) i-R6. -Ar' - ( CH2 ) n- ( CO-NH ) - ( CH2 ) i-Rll. -Ar' -( CHZ ) n-CO-Het , -Ar' - ( CHZ ) n- ( CO-NH ) - ( CH2 ) i-D-H, -Ar' -( CHZ ) n- ( CO-NH ) - ( CHZ ) i-Ar, -Ar' - ( CH2 ) n- ( CO-NH ) -(CH2) i-Hetl, -Ar' - (CH2) "- (CH (CN) ) - (CH2) i-Ar, -Ar' - ( CH2 ) n- ( CO-NH ) - ( CHZ ) i-CH ( Ari ) -Ar2, -Ar' -S-( CH2 ) n- ( CO-NH ) - ( CH2 ) i-Ar, -Ar' -S- ( CH2 ) n- ( CO-NH ) -( CH2 ) i-R11. -Ar' -S- ( CH2 ) n- ( CO-NH ) - ( CH2 ) i-Het 1.
-Ar' -S- ( CHZ ) n- ( CO-NH ) - ( CH2 ) i-CH ( Arl ) -Ar2 or -Ar' -S-( CI"I2 ) n- ( CO-NH ) - ( CH2 ) i-D-H.
R3 is C (0) A, CONH2, CONHA, CONA2, COOH or CODA, R4 is Ph or OH, RS is CH3, CH2C1, CF3 or Ph, R6 is NH2, NHA, NAz, NH (D-H) or NH-C (0)A, R~ i s NA ( D-H ) , NHA, NH ( D-H ) or NA2, RB is -NH- (C=NH) -NH2, -NH- (C=NH) -NHA, -NH- (C=NH) -NA2, -NA- ( C=NH ) -NH2, -NA- ( C=NH ) -NHA or -NA- ( C=NH ) -NA2, Ril is -CH (A) -Ph, Ar' is phenylene, biphenylene, naphthylene or pyrazol 9-yl, which is unsubstituted or mono-, di- or trisubstituted by A, OH, OA, OCF3, Hal, CN, NH2, NHA, NA2, N02, CF3, SOZNH2, S02Ph, S02NAH, S02NA2, Ar, Arl and Ar2 are each independently phenyl, biphenyl, stilbyl, pyridyl, pyrimidyl, quinolyl, 1-imidazolyl, pyrazolyl, indanyl, benzo[1,3]dioxol-5-yl, dibenzofuranyl, 9-H-fluorenyl, 9-H-carbazolyl, [1,1',9',1 " ]terphenyl, anthracenyl, naphthalen-1-yl, naphthalen-2-yl or fluoren-9-on-2-yl, which is unsubstituted or mono-, di- or trisubstituted by A, OH, OA, OCF3, O-Ph, O-Ph-CH3, CH2-Ph, O-CH2-Ph, Hal, CN, NH2, NHA, NA2, NOZ, CF3, S02NH2, SOZPh, S02NAH, S02NA2 or Re, Het is a saturated, partially or completely unsatura ted mono-, bi- or tricyclic heterocyclic radical having 5 to 13 ring members, where 1 or 2 N and/or 1 or 2 S or 0 atoms can be present and the heterocyclic radical can be mono- or disubstituted by CN, Hal, OH, OA, CF3, A, N02, oxo or R5, where pyrazole is not bonded via N,

- 3 - _ Hetl is an unsaturated mono-, bi- or tricyclic heterocyclic radical having 5 to 13 ring members, where 1 or 2 N and/or 1 or 2 S or O atoms can be present and/or can be mono- or disubstituted by Hal, A, OH, OA, oxo or CF3 or piperidine, morpholine, pyrrolidine or pyrrollidin-2-one, A is unbranched or branched alkyl having 1-8 C

atoms, A' is unbranched or branched alkyl having 2-6 C

atoms, Alk is unbranched alkyl having 4-8 C atoms, D is cycloalkylene having 4-7 C atoms or cyclo-hexen-1-yl, Hal is F, C1, Br or I, X, X1,X2 in each case independently of one another are alkylene having 1 to 12 C atoms, Y is 0, S, NH or NA, i is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12, k is 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12, m is 0, 1 or 2, n is 0, 1, 2, 3 or 4, o is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, t is 0, 1 or 2, w is 1 or 2, where if R2 is 4-chlorophenyl, R1 is not -NH-CH2-CH2-OH, and their pharmaceutically tolerable salts and solvates.

Similar compounds having a benzo[de]iso-quinoline-1,3-dione parent structure are disclosed as dyes in US 4,200,752, FR 2 272 215, FR 2 271 216 A, Chemi cal Abstracts, Vol. 73, No. 2, 13 July 1970, Chemi cal Abstracts, Vol. 57, No. 13, 24 December 1962 and Chemical Abstracts, Vol. 111, No. 20, November 1989.

The invention is based on the object of finding novel compounds having valuable properties, in parti-cular those which can be used for the production of medicaments.

- 4 - -It has been found that the compounds of the formula I and their salts or solvates have very valuable pharmacological properties together with good tolerability. They act especially as GPIbIX inhibitors, in particular inhibiting the interaction of this receptor with the ligand von Willebrand factor (vWF).
This action can be demonstrated, for example, by a' method which is described by S. Meyer et al. in J. Biol. Chem. 1993, 268, 20555-20562. Furthermore, the GPIbIX receptor is able to bind alpha-thrombin (N. J.
Greco, Biochemistry 1996, 35, 915-921), it likewise being possible to block this interaction by means of the compounds according to the invention.
The significance of GPIbIX as an adhesion receptor on platelets, which mediates the primary interaction of platelets with an arteriosclerotically modified vascular wall via binding to the vWF expressed there, has been described by many authors (e. g. Z.M. Ruggeri in Thromb. Hemost. 1997, 78, 611-616). The activation of another platelet adhesion receptor,. GPIIbIIIa, following the GPIbIX-vWF interaction, leads to platelet aggregation and thus to thrombotic vascular occlusion.
A GPIbIX antagonist can thus prevent the start of thrombus formation and thus also release of active substances from the platelets which, for example, promote thrombus growth and have an additional trophic action on the vascular wall. This has been shown with inhibitory peptides or antibodies in various experi mental models (e. g. H Yamamoto et al., Thromb. Hemost.
1998, 79, 202-210).
In the case of higher shear forces, the block-ing action of GPIbIX inhibitors exerts its maximum effect, as described by J.J. Sixma et al. in Arteriosclerosis, Thrombosis, and Vascular Biology 1996, 16, 64-71. According to the flow chamber method used there, the compounds of the formula I can be characterized as GPIbIX inhibitors in whole blood.
The inhibition of thrombus formation of the GPIbIX inhibitors can be measured by a modified Born WO 00!32577 PCT/EP99/08561

- 5 - -method (Nature 19fi2, 4832, 927-929) using botrocetin or ristocetin as an aggregation stimulant.
The compounds of the formula I according to the invention can therefore be employed as pharmaceutical active compounds in human and veterinary medicine. They act as adhesion receptor antagonists, in particular as glycoprotein IbIX antagonists, and are suitable for the prophylaxis and/or therapy of thrombotic disorders and sequelae deriving therefrom. The preferentially best action is to be expected in the case of thrombotic disorders in the arterial vascular system, but GPIbIX
inhibitors also have an effect in the case of thrombotic disorders in the venous vascular bed. The disorders are acute coronary syndromes, angina pectoris, myocardial infarct, peripheral circulatory disorders, stroke, transient ischaemic attacks, arteriosclerosis, reocclusion/restenosis after angio-plasty/stent implantation. The compounds can further-more be employed as anti-adhesive substances where the body comes into contact with foreign surfaces such as implants, catheters or cardiac pacemakers.
Comparison medications which may be mentioned are aspirin and GPIIbIIIa antagonists introduced onto the market, in particular ReoPro~.
The invention relates to the compounds of the formula I and their salts and solvates, and to a process for the preparation of these compounds and their salts or solvates, characterized in that a) a compound of the formula I is liberated from one of its functional derivatives by treating with a solvolysing or hydrogenolysing agent, or b) a compound of the formula II
R i ~ R9 f I I
Ow0~0 in which

- 6 - ' R9 is C1, Br, N02 or R1, and R has the meaning indicated in Claim 1 is reacted with a compound of the formula III

in which R2 has the meaning indicated in Claim 1, and, if necessary, the radical R9 is converted into a radical R1, or (c) a radical R and/or R2 and/or R9 is converted into another radical R and/or RZ and/or R9 by, for example - converting an amino group into a guanidino group by reaction with an amidinating agent, - reacting an aryl bromide or iodide to give the corresponding coupling products by means of a Suzuki coupling with boronic acids, - reducing a nitro group, sulfonyl group or sulfoxyl group, - etherifying an OH group or subjecting an OA
group to ether cleavage, - alkylating a primary or secondary amino group, - partially or completely hydrolysing a CN group, - cleaving an ester group or esterifying a carboxylic acid radical, - or carrying out a nucleophilic or electrophilic ~ substitution, and/or (d) a base or acid of the formula I is converted into one of its salts or solvates.
The compounds of the formula I can have a chiral centre and therefore occur in a number of stereoisomeric forms. All these forms (e.g. R and S
forms) and their mixtures (e.g. the RS forms) are included in the formula I.
The compounds according to the invention also include so-called prodrug derivatives, i.e. compounds of the formula I modified with, for example, alkyl or acyl groups, sugars or oligopeptides and which are rapidly cleaved in the body to give the active compounds according to the invention.

7 PCT/EP99/08561 - ,~ -Furthermore, the invention relates to compounds of the formula I in which free amino groups are provided with appropriate conventional "amino protective groups".
Solvates of the compounds of the formula I are understood as meaning adducts of inert solvent molecules to the compounds of the formula I which are formed on account of their mutual pawer of attraction.
Solvates are, for example, mono- or dihydrates or alcoholates.
The abbreviations used have the following meanings:
BOC tert-butoxycarbonyl CBZ benzyloxycarbonyl DCC dicyclohexylcarbodiimide DMF dimethylformamide Et ethyl Fmoc fluorenylmethoxycarbonyl Me methyl Mtr 4-methoxy-2,3,6-trimethylphenylsulfonyl OBut tert-butyl ester OMe methoxy OEt ethoxy POA phenoxyacetyl Ph phenyl tert-bu tert-butyl TFA trifluoroacetic acid In the above formulae, A is alkyl and has 1 to

8, preferably 1, 2, 3, 4 or 5 C atoms. Alkyl is preferably methyl, furthermore ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl, additionally also pentyl, 1-, 2- or 3-methylbutyl, 1,1-, 1,2- or 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-, 2-, 3- or 4-methylpentyl, 1,1-, 1,2-, 1,3-, 2,2-, 2,3- or 3,3-dimethylbutyl, 1- or 2-ethylbutyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, 1,1,2- or 1,2,2-trimethylpropyl, heptyl, 1-, 2-, 3-, 4-, 5-methylhexyl, 1,1-, 1,2-, 1,3-, 1,4-, 2,2-, 2,3-, 2,4-or 3,3-dimethylpentyl, 1-, 2-, 3-, 4-ethylpentyl, 1, 1, 2-, 1, 1, 3-, 1,1, 4-, 1, 2, 2-, 1, 2, 3-, 1, 2, 4-, 1, 3, 3-, 1,3,4-, 1,4,4- or 2,2,3-trimethylbutyl or octyl.
A' is alkyl and has 2 to 6 C atoms, preferably 2, 3 or 4 C atoms. A' is preferably ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl.
Alk is unbranched alkyl having 4 to 8 carbon atoms, preferably n-butyl, n-pentyl, n-hexyl, n-heptyl or n-octyl.
Ar is preferentially phenyl, preferably - as indicated - monosubstituted phenyl, specifically preferentially phenyl, o-, m- or p-methylphenyl, o-, m or p-ethylphenyl, o-, m- or p-propylphenyl, o-, m- or p-isopropylphenyl, o-, m- or p-tert-butylphenyl, o-, m or p-aminophenyl, o-, m- or p-(N,N-dimethylamino)phenyl, o-, m- or p-sulfonamoylphenyl, o-, m- or p-nitrophenyl, o-, m- or p-hydroxyphenyl, o-, m- or p-methoxyphenyl, o-, m- or p-ethoxyphenyl, o-, m- or p-phenoxyphenyl, o-, m- or p-(phenylmethox)yphenyl, o-, m- or p-(trifluoromethyl)phenyl, o-, m- or p-(trifluoromethoxy)phenyl, o-, m- or p-fluorophenyl, o-, m- or p-chlorophenyl, o-, m- or p-bromophenyl, o-, m- or p-iodophenyl, 4-benzenesulfonyl-phenyl, 4-(4-chloro-phenoxy)-phenyl, furthermore preferentially 2;3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dimethylphenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dimethoxyphenyl, 2,3-, 2,9-, 2,5-, 2,6-, 3,4- or 3,5-dihydroxyphenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-difluorophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dichlorophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dibromophenyl, 2-chloro-3-methyl-, 2-chloro-4-methyl-, 2-chloro-5-methyl-, 2-chloro-6-methyl-, 3-chloro-2-methyl-, 9-chloro-2-methyl-, 5-chloro-2-methyl-, 3-chloro-4-methyl-, 3-chloro-5-methyl-, 4-chloro-3-methylphenyl, 2-bromo-3-methyl-, 2-bromo-4-methyl-, 2-bromo-5-methyl-, 2-bromo-6-methyl-, 3-bromo-2-methyl-, 4-bromo-2-methyl-, 5-bromo-2-methyl-, 3-bromo-4-methyl-, 3-bromo-5-methyl-, 4-bromo-3-methylphenyl, 2-iodo-3-methyl-, 2-iodo-4-methyl-, 2-iodo-5-methyl-, 2-iodo-6-- g - _ methyl-, 3-iodo-2-methyl-, 4-iodo-2-methyl-, 5-iodo-2-methyl-, 3-iodo-4-methyl-, 3-iodo-5-methyl-, 4-iodo-3-methylphenyl, 2-chloro-3-methoxy-, 2-chloro-4-methoxy-, 2-chloro-5-methoxy-, 2-chloro-6-methoxy-, 3-chloro-2-methoxy-, 4-chloro-2-methoxy-, 5-chloro-2-methoxy-, 3-chloro-4-methoxy-, 3-chloro-5-methoxy-, 4-chloro-3-methoxyphenyl, 2-chloro-3-hydroxy-, 2-chloro-4-hydroxy-, 2-chloro-5-hydroxy-, 2-chloro-6-hydroxy-, 3-chloro-2-hydroxy-, 4-chloro-2-hydroxy-, 5-chloro-2-hydroxy-, 3-chloro-4-hydroxy-, 3-chloro-5-hydroxy-, 4-chloro-3-hydroxy-phenyl, 3-fluoro-4-methoxy, 9-fluoro-3-methoxyphenyl, 2-chloro-3-fluoro-, 2-chloro-4-fluoro-, 2-chloro-5-fluoro-, 2-chloro-6-fluoro-, 3-chloro-2-fluoro-, 4-chloro-2-fluoro-, 5-chloro-2-fluoro-, 3-chloro-9-fluoro-, 3-chloro-5-fluoro-, 4-chloro-3-fluorophenyl, 2-fluoro-3-methyl-, 2-fluoro-4-methyl-, 2-fluoro-5-methyl-, 2-fluoro-6-methyl-, 3-fluoro-2-methyl-, 4-fluoro-2-methyl-, 5-fluoro-2-methyl-, 3-fluoro-4-methyl-, 3-fluoro-5-methyl-, 4-fluoro-3-methylphenyl, 2,5- or 3,9-dimethoxyphenyl, 2-cyano-4,5-dimethoxyphenyl, 5-chloro-2,4-dimethoxy-phenyl, 2-cyano-3,4-dimethoxyphenyl or 3,4,5-trimethoxy-phenyl.
Furthermore, however, also preferentially unsubstituted biphenyl - as indicated - or alternatively mono-substituted biphenyl,, specifically preferentially biphenyl-4-yl or biphenyl-3-yl, 2'-methylbiphenyl-4-yl, 3'-methylbiphenyl-4-yl, 4'-methylbiphenyl-4-yl, 2'-methylbiphenyl-3-yl, 3'-methylbiphenyl-3-yl, 4'-methylbiphenyl-3-yl, 2-methylbiphenyl-4-yl, 3-methylbiphenyl-4-yl, 2-methylbiphenyl-3-yl,

9-methylbiphenyl-3-yl, 2'-tert-butylbiphenyl-4-yl, 3'-tert-butylbiphenyl-4-yl, 4'-tert-butylbiphenyl-4-yl, 2'-tert-butylbiphenyl-3-yl, 3'-tert-butylbiphenyl-3-yl, 4'-tert-butylbiphenyl-3-yl, 2-tert-butylbiphenyl-4-yl, 3-tert-butylbiphenyl-4-yl, 2-tertbutylbiphenyl-3-yl, 4-tert-butylbiphenyl-3-yl, 2'-isopropylbiphenyl-4-yl, 3'-isopropylbiphenyl-4-yl, 4'-isopropylbiphenyl-4-yl, 2'-isopropylbiphenyl-3-yl, 3'-isopropylbiphenyl-3-yl,

- 10 -4'-isopropylbiphenyl-3-yl, 2-isopropylbiphenyl-4-yl, 3-isopropylbiphenyl-4-yl, 2-isopropylbiphenyl-3-yl, 4-isopropylbiphenyl-3-yl, 2'-fluorobiphenyl-4-yl, 3'-fluorobiphenyl-9-yl, 9'-fluorobiphenyl-4-yl, 2'-fluorobiphenyl-3-yl, 3'-fluorobiphenyl-3-yl, 4'-fluorobiphenyl-3-yl, 2-fluorobiphenyl-4-yl, 3-fluorobiphenyl-4-yl, 2-fluorobiphenyl-3-yl, 4-fluoro-biphenyl-3-yl, 2'-methoxybiphenyl-4-yl, 3'-methoxy-biphenyl-4-yl, 4'-methoxybiphenyl-4-yl, 2'-methoxybiphenyl-3-yl, 3'-methoxybiphenyl-3-yl, 4'-methoxybiphenyl-3-yl, 2-methoxybiphenyl-4-yl, 3-methoxybiphenyl-4-yl, 2-methoxybiphenyl-3-yl, 4-methoxybiphenyl-3-yl, 2'-nitrobiphenyl-4-yl, 3'-nitrobiphenyl-4-yl, 4'-nitrobiphenyl-4-yl, 2'-nitro-biphenyl-3-yl, 3'-nitrobiphenyl-3-yl, 4'-nitrobiphenyl-3-yl, 2-nitrobiphenyl-4-yl, 3-nitrobiphenyl-4-yl, 2-nitrobiphenyl-3-yl, 4-nitrobiphenyl-3-yl, 2'-trifluoromethylbiphenyl-4-yl, 3'-trifluoromethylbiphenyl-4-yl, 4'-trifluoromethyl-biphenyl-4-yl, 2'-trifluoromethylbiphenyl-3-yl, 3'-trifluoromethylbiphenyl-3-yl, 4'-trifluoromethyl-biphenyl-3-yl, 2-trifluoromethylbiphenyl-4-yl, 3-tri-fluoromethylbiphenyl-4-yl, 2-trifluoromethylbiphenyl-3-yl, 4-trifluoromethylbiphenyl-3-yl, 2'-trifluoromethoxybiphenyl-4-yl, 3'-trifluoromethoxy-biphenyl-4-yl, 4!-trifluoromethoxybiphenyl-4-yl, 2'-trifluoromethoxybiphenyl-3-yl, 3'-trifluoromethoxybiphenyl-3-yl, 4'-tri-fluoromethoxybiphenyl-3-yl, 2-trifluoromethoxybiphenyl-4-yl, 3-trifluoromethoxybiphenyl-4-yl, 2-trifluoromethoxybiphenyl-3-yl, 4-trifluoromethoxybiphenyl-3-yl, furthermore preferentially disubstituted biphenyls, such as 2'-methyl-3'-nitrobiphenyl-4-yl, 2'-methyl-4'-nitro-biphenyl-4-yl, 2'-methyl-5'-nitrobiphenyl-4-yl, 2'-methyl-6'-nitrobiphenyl-4-yl, 3'-methyl-2'-nitrobiphenyl-4-yl, 3'-methyl-4'-nitrobiphenyl-4-yl, 3'-methyl-5'-nitrobiphenyl-4-yl, 3'-methyl-6'-nitrobiphenyl-4-yl, 4'-methyl-2'-nitrobiphenyl-4-yl,

- 11 - -4'-methyl-3'-nitrobiphenyl-4-yl, 2'-methyl-3'-nitrobiphenyl-3-yl, 2'-methyl-4'-nitrobiphenyl-3-yl, 2'-methyl-5'-nitrobiphenyl-3-yl, 2'-methyl-6'-nitro-biphenyl-3-yl, 3'-methyl-2'-nitrobiphenyl-3-yl, 3'-methyl-4'-nitrobiphenyl-3-yl, 3'-methyl-5'-nitrobiphenyl-3-yl, 3'-methyl-6'-nitrobiphenyl-3-yl, 4'-methyl-2'-nitrobiphenyl-3-yl, 4'-methyl-3'-nitrobiphenyl-3-yl, 2'-methoxy-2-methylbiphenyl-4-yl, 3'-methoxy-2-methylbiphenyl-4-yl, 4'-methoxy-2-methylbiphenyl-4-yl, 4'-methoxy-3-nitrobiphenyl-4-yl, 2'-chloro-3'-fluorobiphenyl-4-yl, 2'-chloro-4'-fluorobiphenyl-4-yl, 2'-chloro-5'-fluorobiphenyl-4-yl, 2'-chloro-6'-fluorobiphenyl-4-yl, 3'-chloro-2'-fluorobiphenyl-4-yl, 3'-chloro-4'-fluorobiphenyl-4-yl, 3'-chloro-5'-fluorobiphenyl-4-yl, 3'-chloro-6'-fluorobiphenyl-4-yl, 4'-chloro-2'-fluorobiphenyl-4-yl, 4'-chloro-3'-fluorobiphenyl-4-yl, 2'-chloro-3'-fluorobiphenyl-3-yl, 2'-chloro-4'-fluorobiphenyl-3-yl, 2'-chloro-5'-fluorobiphenyl-3-yl, 2'-chloro-6'-fluorobiphenyl-3-yl, 3'-chloro-2'-fluorobiphenyl-3-yl, 3'-chloro-9'-fluorobiphenyl-3-yl, 3'-chloro-5'-fluorobiphenyl-3-yl, 3'-chloro-6'-fluorobiphenyl-3-yl, 4'-chloro-2'-fluorobiphenyl-3-yl, 4'-chloro-3'-fluorobiphenyl-3-yl, (2',3'-dimethoxy)biphenyl-4-yl, 2',4'-dimethoxy)biphenyl-4-yl, (2',5'-dimethoxy)biphenyl-4-yl, (2',6'-dimethoxy)-biphenyl-4-yl, (3',4'-dimethoxy)biphenyl-9-yl, (3',5'-dimethoxy)biphenyl-4-yl, (2',3'-dimethoxy)-biphenyl-3-yl, (2',4'-dimethoxy)biphenyl-3-yl, (2',5'-dimethoxy)biphenyl-3-yl, (2',6'-dimethoxy)-biphenyl-3-yl, (3',4'-dimethoxy)biphenyl)-3-yl, (3',5'-dimethoxy)biphenyl-3-yl, (2',3'-di(trifluoromethyl))biphenyl-4-yl, (2',4'-di(trifluoromethyl))biphenyl-4-yl, (2',5'-di(trifluoromethyl))biphenyl-4-yl, (2',6'-di(trifluoromethyl))biphenyl-4-yl, (3',4'-di(trifluoromethyl))biphenyl-4-yl, (3',5'-di(trifluoromethyl))biphenyl-4-yl, (2',3'-di(trifluoromethyl))biphenyl-3-yl,

- 12 - -(2',4'-di(trifluoromethyl))biphenyl-3-yl, (2',5'-di(trifluoromethyl))biphenyl-3-yl, (2',6'-di(trifluoromethyl))biphenyl-3-yl, (3',4'-di(trifluoromethyl))biphenyl-3-yl, (3',5'-di(trifluoromethyl)biphenyl-3-yl, (2,2'-dimethyl)biphenyl-4-yl, (2,'3-dimethyl)biphenyl-4-yl, (2,4'-dimethyl)biphenyl-4-yl, (2,2'-dimethyl)biphenyl-3-yl, (2,3'-dimethyl)biphenyl-3-yl or (2,4'-dimethyl)biphenyl-3-yl.
Furthermore, however, also preferentially benzo[1,3]-dioxol-5-yl, 9-H-carbazolyl, quinolyl, dibenzofuranyl, 9-H-fluorenyl, 7-bromo-9H-fluoren-2-yl, 9H-fluoren-9-ol-1-yl, fluoren-9-on-2-yl, imidazolyl, indanyl, 1-imidazolyl, pyrazolyl, 9-H-carbazolyl, [1,1',4',1 " ]terphenyl, anthracenyl, naphthalen-1-yl, naphthalen-2-yl, 4-bromo-naphthalen-1-yl, 4-cyano-naphthalen-1-yl, 4-chloro-naphthalen-1-yl, 4-nitro-naphthalen-1-yl, 4-methoxy-naphthalen-2-yl, 6-hydroxy-naphthalen-1-yl, 7-hydroxy-naphthalen-1-yl, 8-hydroxy-napththalen-1-yl or stilbyl.
Furthermore, Ar is preferentially pyridyl-2-, pyridyl-3-, pyridyl-4-yl, pyrazol-3-yl, pyrazol-4-yl or pyrazol-5-yl, pyrimidin-2-, pyrimidin-4-, pyrimidin-5-yl, which is unsubstituted or substituted by A or Hal particularly preferentially pyridyl-2-, pyridyl-3-yl, 4-chloro-pyridyl-2-yl, 1-methylpyrazol-4-yl or pyrimidin-2-yl.
Ar' is preferentially phenylene, biphenylene, 1-naphthylene or pyrazol-4-yl, which is unsubstituted or monosubstituted by A, OH, OA, CF3, OCF3 or Hal.
Unsubstituted phenylene or 1-naphthylene, 2-methoxyphenylene, 2-methylphenylene, 3-biphenylene, 4-biphenylene or 1-methylpyrazol-4-yl is particularly preferred.
Arl and Ar2 are in each case independently of one another Ar having the preferred meanings indicated beforehand. Phenyl is particularly preferred for Arl and Ar2 independently of one another.

- 13 -In -Ar'-D-H, Ar' is preferentially unsubsti-tuted or substituted phenylene, D having one of the preferred or particularly preferred meanings mentioned below.
is particularly preferred for -Ar'-D-H.
In -Ar'-Hetl, Ar' is preferentially unsubsti tuted or substituted phenylene, Hetl having one of the preferred or particularly preferred meanings mentioned below.
/ \ ~ ~ ~ / \
\ ~
/ \
N
\ ~ ~ /
' ~S ~ CH3 \ ' 'art-butyl tert-butyl / \ ~ ~ / \ ~I
/ \ \ ~ / \
\ / S / \ / S

- 14 - -/ ~ O
/ \
of 01 / \ / \ o or / \ / \ o is particularly preferred for -Ar'-Hetl.
In -Ar'-Y-C(A)2-R3, Ar' is preferentially unsubstituted or substituted biphenylene, where R3 is preferentially an alkyloxycarbonyl group and A has a preferred meaning as mentioned above.
/ \ ~ \ CH3 O
O
H OC2Hs is particularly preferred for -Ar'-Y-C(A)Z-R3.
In -Ar' - (CH2) n-R3, Ar' is preferentially unsubstituted or substituted phenylene, naphthylene, biphenylene or pyrazol-4-yl, where R3 is preferentially an amido group, alkylamido group or dialkylamido group, carboxyl group, alkyloxycarbonyl group or an alkylcarbonyl group and n can be 0, 1, 2, 3 or 4.
(CH2)2~ CH --~O

/ \ NHZ / ~ NH2 O O
/ ~ NH2 / \ NH2 O O
(CHZ}2-~N--C H (CH2)2--~N-C H
/ ~ H 3 7 / ~ H 5 11

- 15 -O- N -C3H~ CO- N -CH3 \ H H
O
(CH2)2 ~ N - CH CH3 ( z)z ~CH

CH3 , O
(CHz)z ~ N - C H
i 3 7 CO-N - (CHz)z ~CH3 H
CH3 , O O
/ \ CH ~IVH / \ (CH2)3-~NH
2 ' 2 O
~ ~OCH3 HOOC
O

O
/ \ CH
OCH3 ' N~CH3 O
NHz O
/ \ / \ COOH / \ / \
U ~_-/ ~OCH3 , O
/ \ / \
OCH3 '

- 16 - ' O _ _ / ~ / ~ ~ /
OH ' , O

O
CH , ~ / ~ / , O

O
/ ~ / ~ / ~ / ~ CH3 3 or H
is particularly preferred for Ar' - (CH2) n-R3.
In Ar' -Y- (CH2) n-R3, Ar' is preferentially unsubstituted or substituted phenylene, where Y is preferentially S or O, R3 is preferentially an amido group, alkylamido group or dialkylamido group, alkyl-oxycarbonyl or an alkylcarbonyl group and n can be 0, 1, 2, 3 or 4.
S-CH2 CONH-(CH2)2-C(CH3)s / ~ S -CH2 CONH-C3H~
O
/ ~ O-CH2-~ or O
/ ~ S-CH2-is particularly preferred for -Ar' -Y- (CH2) n-R3.
In -Ar' -Hetl-R3, Ar' is preferentially unsubstituted or substituted phenylene, where Hetl has one of the meanings preferentially indicated in the following and R3 is preferentially alkylcarbonyl.

- 17 -O O
\ S ( or \ \
is particularly preferred for -Ar'-Hetl-R3.
In -Ar' - (CH2) n-R6, Ar' is preferentially unsubstituted or substituted phenylene or biphenylene, where R6 is preferentially an amino group, alkylamino group, dialkylamino group or alkyloxycarbonylamino group and n can be 0, 1, 2, 3 or 4.
/ ~ / ~ / ~ /
~=-~NH2 ~_ -~NH2 O N,CHs N CH ~ ~ \CH3 N
\ CH3 O
l0 CH3 ~ \ ~ \
O or ~ O
N N

is particularly preferred for -Ar' - (CH2) n-Rs, In -Ar'-SOZ-Het, Ar' is preferentially unsubstituted or substituted naphthylene or phenylene, where Het has one of the meanings preferentially indicated in the following.

- 18 - _ / \
/
SO or ~ ~ SO2 N' ~2 N
is particularly preferred for -Ar'-SOZ-Het.
In -Ar'-NH-S02-Het, Ar' is preferentially unsubstituted or substituted phenylene, where Het is particularly preferred 5-methoxy-pyrimidin-2-yl.
V -N-S02 ~ O
N ~ ~CH3 is particularly preferred for -Ar'-NH-S02-Het.
In -Ar'-SOZ-R', Ar' is preferentially unsub-stituted or substituted naphthylene, where R' is preferentially an alkylamino group, dialkylamino group, cycloalkylamino group or an alkylcycloalkylamino group.
\ ~ / / ~ \ / ~ \
\ / \ /
or /IN TN N
H5(i2 ~ H3C ~ ~C4H9 '"I3C ~ ~(~2H5 is particularly preferred for -Ar'-S02-R'.
In -Ar' - (CH2) "- (CONH) - (CH2) i-R6, Ar' is preferen tially unsubstituted or substituted phenylene, where R6 is preferentially an amino group, alkylamino group, dialkylamino group or a cycloalkylamino group and n can be 0, 1, 2, 3 or 4 and i can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.

- 19 -(CH2)2-CONH-(CH2)3-N(CH3)2 (CH2)2- CONH-(CH2)4-NH2 (CHZ)2- CONH-(CH2)2-NH2 or is particularly preferred for -Ar' - (CHZ) n- (CONH) -( CH2 ) i-R6 .
In -Ar' - ( CHZ ) n- ( CONH ) - ( CHZ ) i-D-H, Ar' i s preferentially unsubstituted or substituted phenylene, where D has one of the preferred meanings mentioned below and n can be 0, 1, 2, 3 or 4 and i can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
(CH2)2-CONH
CONH
CONH -(CH2)2 (CH2)2- CONH-CH2 (CH2)2- CONH-(CHZ)2 or

- 20 -is particularly preferred for -Ar' - (CH2) n- (CONH) -( CH2 ) i-D-H .
In -Ar' -S- (CH2) n- (CONH) - (CHZ) i-D-H, Ar' is preferentially unsubstituted or substituted phenylene, where D has one of the preferred meanings mentioned below and n can be 0, 1, 2, 3 or 4 and i can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
S~HZ CONH
or S-CH2 CONH -(CH2}2 is particularly preferred for -Ar' -S- (CH2) n- (CONH) -( CH2 ) i-D-H .
in -Ar' - (CH2) n- (CONH) - (CH2) i-Rll, Ar' is preferentially unsubstituted or substituted phenylene, where Ril is -CH(A)-Ph, wherein A has one of the preferred meanings mentioned beforehand, Ph is phenyl and n can be 0, 1, 2, 3 or 4 and i can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
(CH2)2- CONH
CH3 or (CH2)2- CONH-CH2 is particularly preferred for -Ar' - (CH2) n- (CONH) - (CH2) t-In -Ar' -S- (CHZ) n- (CONH) - (CHZ) i-Ril, Ar' is preferentially unsubstituted or substituted phenylene, where R11 is -CH(A)-Ph, wherein A has one of the preferred meanings mentioned beforehand, Ph is phenyl

- 21 - _ and n can be 0, 1, 2, 3 or 4 and i can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.

is particularly preferred for -Ar' -S- (CHZ) n- (CONH) -( CH2 ) i-R11.
In -Ar' - (CH2) "- (CO) -Het, Ar' is preferentially unsubstituted or substituted phenylene, where Het has one of the preferred meanings mentioned in the following and n can be 0, 1, 2, 3 or 4.
(CHZ)2-N
is particularly preferred for -Ar' - (CH2) n- (CO) -Het.
In -Ar' - (CH2) n- (CONH) - (CH2) i-Ar, Ar' is preferen-tially unsubstituted or substituted phenylene, where Ar has one of the preferred meanings mentioned beforehand and n can be 0, 1, 2, 3 or 4 and i can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
CONH ~ ~
gr (CH2)2-CONH
r CONH
CN

- 22 -(CH2)2-CONH
CN
(CHZ)2-CONH-(CH2)2 ~ ~ N02 CONH-(CH2)2 ~ ~ N02 (CHZ)2-CONH-CH2 O

O

N
CONH-(CH2)2 -N
(CH2}2-CONH-CH2 \ /
/ \
-N
(CH2}2 -CONH-(CH2)2 (CH2)2 -CONH-CHZ ~ ~ N

- 23 -w ONH-CH2 \ ~ N
/ \
~ CZHS
(CH2)2 -CONH \ / N\C2H5 / \
/ CZHS
CONH \ / N~

CH
(CH2)2-CONH \ / N~

/ \
CH
(CHZ)2-CONH-CH2 \ / N~

/ \
CH
ONH-CH2 \ ~ N~

/ \
(CH2)2 -CONH \ / \ /
/ \
(CH2)2-CONH-(CH2)2 / \ Sp2_NH2 \ / , (CH~2- CONH-CH2 / \ SOZ-NH2 /

- 24 -CONH-CH2 ~ ~ S02-NH2 (CH2)2 -CON

CONH

(CH2)2- CONH ~ ~ CH3 CONH ~ ~ CHs (CH2)2-CONH-(CH2)2 CI
\ /
(CHZ)Z-CONH-CH2 CI
/ , / CI

- 25 -CONH-(CH2)2 CI
(CH2)2-CONH-(CH2)2 / \
- CI
\ /
CI
(CH2)2-CONH / \
\ /
(CH2)2-CONH-CH2 / \
CI
\ / , CI
CONH-(CH2)2 CI
CONH
CI

- 26 -(CH2)2-CONH-(CH2)2 / \ CI
\ /
(CH2)2-CONH-CH2 \ / CI
/ \
CH2)2-CONH / \ C( \ / , CONH-(CH2)2 ~ ~ CI
CONH ~ ~ CI
(CHZ)z- CONH-(CH2)2 ~ ~ CH3 CONH-(CH2)2 ~ ~ CH3 CH2)2- CONH ~ ~ CH3

- 27 -CONH ~ ~ CH3 CH2)2-CONH-CHZ / \
- / \
\ /

(CH2)2-CONH /
CH2)2-CONH-CH2 /
CONH /
(CH2)2-CONH / \ OCH3 - CI
\ /
CONH ~ ~ OCH3 CI

- 28 -(CH2)2- CONH

(CHZ)2- CONH ~ ~ CI
ONH ~ ~ CI

CI
CHZ)2-CONH-CH2 / \
CI
\ /
CI

CI
CI
CH2)2-CONH-(CH~2 ~
CI
CI CI
(CH2)2-CONH-CH2 / \
\ /

- 29 -CI CI

\ /
CI
CONH-CH2 / ~ CI
CI
CONH-(CH2)2 / ~ CI
/
CI
(CH2)2-CONH-CH2 / \
CI
\ /
CI

CI
. ~ / ..
CI
(CH2)2- CONH
CI
/
CI
ONH /
CI
/

- 30 -CI
CHZ)2-CONH / \ CI
\ /

CONH ~ ~ CI

CONH-(CH2 s (CH2)2-CONH-(CH2)3 / \
\ / , (CH2)2-CONH / \
\ /
CONH
/ \
(CH2)2-CONH-CH2 \ / , l0

- 31 -(CH2)2-CONH-(CH2)4 / \
\ /
CONH-(CH2)4 (CH2)2-CONH-(CH2)2 / \ CH3 \ / , CONH-(CH2 2 ~ ~ CH3 (CH2)2-CONH

CONH
CH3 .
CH2)2-CONH / \
\ /
CONH

- 32 -CONH
\ ~ , (CH2)2- CONH
, \ ~ CF3 (CH2)2- CONH-CH2 \ ~ CF3 ONH

(CHZ)2-CONH-CHZ / ~ F
CI
\ /
(CH2)2- CONH ~ ~ F
CI
,

- 33 -CONH-CHZ ~ ~ F
CI
ONH ~ ~ F
CI
(CH2)2- CONH-CH2 ~ ~ F
CI
CONH-CH2 ~ ~ F
CI
(CH2)2- CONH-(CH2)2 /

. 5 (CHZ)2- CONH

(CH2)2-CONH-CH2 /

/ ,

- 34 -ONH-(CHa)2 CONH

(CH2)2-CONH-(CH2)2 / \ OCH3 \ / , ONH-CHZ ~ ~ OCF3 (CH2)2-CONH-CH2 / \ OCF3 \ /
(CH2)2-CONH / \ OCH3 \ /
, CONH ~ ~ OCH3 , CONH-(CH2)z ~ ~ OCH3 , (CH2)2-CONH-(CH2}2 / \ F
\ /

- 35 -CONH-(CH2)2 ~ ~ F
(CHZ)2-CONH-CH2 / \
'- F
\ /

F
CONH
F
F
CH2)2-CONH / \
\ / , CH2)Z- CON
F
CON
Fr OPh CH2)2-CONH
\ / ,

- 36 -OPh CONH /
\ /
CH2)2-CONH / ~ OPh CONH / ~ OPh /
CONH / ~ O ~ ~ CH3 /
CH2)2-CONH / ~ O ~ ~ CH3 /
OCH2Ph (CH2)2- CONH /
/
CONH /
O
/ ~-Ph / \
(CH2)2-CONH-CH2 /
\ /

- 37 -F
(CH2)2-CONH ~ \ OCH3 \ /
CONH ~ ~ OCH3 F
(CH2)2-CONH / \ CH3 \ /
CONH ~ ~ H3 (CH2)2- CONH

CONH

tert-butyl (CHZ)2- CONH
tert-butyl tert-butyl CONH
tert-butyl CONH-(CHZ}2 CH
v CH2)2-CONH

i3 ON
3 ' CONH-(CH2)2 ~ ~ OCH3 CH2)Z- CONH-(CH2)2 or (CH2)2- CONH-(CH2)2 ~ ~ OCH3 is particularly preferred for -Ar' - (CH2) n- (CONH) -( CH2 ) i-Ar .

In -Ar' -S- (CH2) n- (CONH) - (CH2) i-Ar, Ar' is preferentially unsubstituted or substituted phenylene, where Ar has one of the preferred meanings mentioned beforehand and n can be 0, 1, 2, 3 or 4 and i can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
/ \ S-CH2 CONH \ /
Br / \ S-CH2 CONH \ /
CN ' / \ S-CH2 CONH-(CHZ)z \ / NOZ
/ \ S-CH2 CONH-CH2 \ /

N-/ \ S-CH2 CONH-(CH2)2 \ / , -N
\ ~ S-CH2 CONH-CH2 \ / , -N
\ ~ S-CHZ CONH-(CH2)2 \ /
\ ~ S-CH2 CONH-CH2 \ ~N
~'2H5 \ ~ S-CH2 CONH \ / NBC H , 2 s ~ CH3 \ ~ S-CHZ CONH \ / N~ CH

~ CH3 \ ~ S-CH2 CONH-CHZ \ / NCH

S-CH2 CONH-{CHZ)Z ~ ~ S02-NH2 S-CH2 CONH-CHZ ~ ~ SOZ-NH2 S-CH2 CONH ~ \ CH
3 , S-CHZ CONH ~ ~ CH3 S-CH2 CONH-(CH2)2 /
CI

, CI
S- CH2 CONH-(CH2)2 CI

CI

l0 CI
S-CH2 CONH-(CH2)2 ~ ~ CI
S-CH2-CONH-CH2 ~ ~ CI
S-CH2 CONH ~ ~ CI

S-CHZ CONH-(CH2)2 ~ ~ CH3 S-CH2 CONH ~ ~ CH3 , S-CHZ CONH /
S-CH2 CONH ~ ~ OCH3 CI

S-CH2 CONH ~ ~ CI
CI

CI

S-CH2 CONH-(CH2)2 ~
CI
CI CI

to CI
S-CH2 CONH-CH2 ~ ~ CI

CI
S-CH2 CONH-(CH2)2 ~ \ CI
CI
\ ~ S-CH2 CONH-CH2 ~ \
CI
CI
\ ~ S-CHZ CONH ~ ~ , CI
CI
\ / S-CHZ CONH ~ \ CI
\ / S-CH2 CONH-CH2 \
S-CH2 CONH-(CH2 s \
S-CH2 CONH ~ \
\ ~ S-CH2 CONH-(CH2)4 ~ \
S CH2 CONH-(CH2)2 ~ \ CH3 \ ~ S-CH2 CONH ~ ~ CH3 l0 ' \ ~ S-CH2 CONH

S-CH2 CONH ~ \

, CFs S-CH2 CONH-CH2 ~ ~ F
CI
S-CH2 CONH ~ ~ F
CI
S-CH2 CONH-CH2 ~ ~ F
, CI
S- CH2 CONH-(CH2)2 S- CH2 CONH-(CH2)2 ~ ~ OCH3 S- CH2 CONH-CH2 ~ ~ OCF3 , S- CH2 CON ~ ~ OCH3 S- CHZ CONH-(CH2)2 ~ ~ F

, F

F
S- CH2 CON ~ ~
F
OPh , S- CH2 CONH ~ ~ OPh , S- CH2 CONH ~ ~ O ~ ~ CH3 O , l0 S- CH2 CONH-CH2 ~ ~ , F
S- CH2 CONH ~ ~ OCH3 F
S- CH2 CONH ~ ~ CH3 tert-butyl tert-butyl S- CH2 CONH-(CH2)2 or S- CH2 CONH-(CHZ 2 ~ ~ OCH3 In -Ar' - (CH2) n- (CONH) - (CH2) i-Hetl, Ar' is preferentially unsubstituted or substituted phenylene, where Hetl has one of the preferred meanings mentioned in the following and n can be 0, 1, 2, 3 or 4 and i can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.

CONH-(CH2)Z-N
/ , (CH2)2-CONH-(CH2)2 N- ) /
(CH2)2-CONH-(CH2)2 N O
U
/ , O
CONH-(CH2)3-N' /
O
(CHz)z- CONH-(CH2)s-N, / , . CONH-(CH2)2-N' , (CHZ)2-CONH-(CH2)2-N
/ , (CHZ)2-CONH-(CH2)3-N
~N
/
(CH2)2-CONH-CH2 ~ O
/ 'O
, S

S
CH2)2-CONH-CH2 ~ I
O
(CH2)z-CONH-CHZ ~ I
O
CONH-CHZ
of is particularly preferred for -Ar' - (CH2) n- (CONH) - (CH2) i-Heti .
In -Ar' -S- (CH2) n- (CONH) - (CH2) i-Hetl, Ar' is preferentially unsubstituted or substituted phenylene, where Hetl has one of the preferred meanings mentioned in the following and n can be 0, 1, 2, 3 or 4 and i can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
S-CH2 CONH-(CH2)2--O
S-CHZ CONH-(CH2)3-N
S-CH2 CONH-(CH2)2-N' S

or WO 00/32577 PCT/EP99/085151v - 48 - _ O
S-CH2 CONH-CHZ ~ I
is particularly preferred for -Ar'-S-(CH2)n-(CONH)-(CHZ)i-Hetl.
I n -Ar' - ( CH2 ) n- ( CH ( CN ) ) - ( CH2 ) i-Ar, Ar' i s preferentially unsubstituted or substituted phenylene, where Ar has one of the preferred meanings mentioned beforehand and n can be 0, 1, 2, 3 or 4 and i can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
\ / H CH2 \ / N'CH3 II
N
or IH ~
N
is particularly preferred for -Ar' - (CH2) n- (CH (CN) ) -( CH2 ) i-Ar .
In -Ar' - ( CH2 ) n- ( CONH ) - ( CHZ ) i-CH (Arl ) -Ar2, Ar' is preferentially unsubstituted or substituted phenylene, where ArI and Ar2 each independently of one another has one of the preferred meanings mentioned beforehand and n can be 0, 1, 2, 3 or 4 and i can be 0, 1, 2, 3,. 4, 5, 6, 7, 8, 9, 10, 11 or 12.
~I
CONH-(CH2)2-CH /
\
\ /
~I
\

~I
\ / \

i (CH2)2- CONH-(CH2)2-CH / or \i ~i \
(CH2)2- CONH-CH2-CH
~i \
is particularly preferred for -Ar'-(CH2)"-(CONH)-( CH2 ) t-CH (Arl ) -Ar2 .
In -Ar' -S- (CH2) n- (CONH) - (CHZ) i-CH (Arl) -Ar2, Ar' is preferentially unsubstituted or substituted phenylene, where Ari and Ar2 each independently of one another has one of the preferred meanings mentioned beforehand and n can be 0, 1, 2, 3 or 4 and i can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
~i \
S-CH2 CONH-(CH2)2-CH
_ \i or \

i y is particularly preferred for -Ar'-S-(CH2)n-(CONH)-( CH2 ) i-CH ( Arl ) -Arz .
In the above formulae, D is cycloalkylene and has 4 to 7, preferably 5 or 6, C atoms: Cycloalkylene is preferably cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl, particularly preferentially cyclopentyl or cyclohexyl. Furthermore, D is preferentially cyclo-hexen-1-yl.
Hal is preferably F, C1, Br or iodine.
Hetl is preferentially substituted or unsubsti tuted furan-2-yl or furan-3-yl, carbazol-9-yl, thiazol 2-yl, thiazol-4-yl, thiazol-5-yl, [1,3,4]-thiadiazol 2-yl, 1,2-dihydropyrazol-3-on-4-yl, 1,2-dihydropyrazol 3-on-5-yl, benzothiophen-2-yl, benzothiophen-3-yl, 3H
benzotriazol-5-y1, benzothiazol-2-yl, benzofuran-2-yl, benzofuran-3-yl, imidazol-1-yl or benzo[1,3]dioxol-5-yl or piperidine-1-yl, pyrrolidine-1-yl or pyrrolidine-2-on-1-yl. Furthermore furan-2-yl, carbazol-9-yl, 3,6-di-tert-butyl-carbazol-9-yl, thiazol-2-yl, thiazol-3-yl, 5-methyl-[1,3,4]-thiadiazol-2-yl, 5-trifluoromethyl-[1,3,4]-thiadiazol-2-yl, 1,5-dimethyl-1,2-dihydropyrazol-3-on-4-yl, benzofuran-2-yl, 6-methyl-benzothiazol-2-yl, 2,3-dihydro-1H-indol-6-yl, 3H-benzotriazol-5-yl, benzothiophen-2-yl, imidazol-1-yl or benzo[1,3]dioxol-5-yl or piperidine-1-yl, morpholin-4-yl, pyrrolidine-1-yl or pyrrolidine-2-on-1-yl is particularly preferred.
In -Hetl-Ar, Hetl and Ar have one of the preferred meanings indicated above, where Ar is preferably phenyl. 4-phenylthiazol-2-yl, 5-phenyl-[1,3,4]-thiadiazol-2-yl or 1,5-dimethyl-2-phenyl-1;2-dihydropyrazol-3-on-4-yl is particularly preferred for Hetl-Ar.
In -Hetl-R3, Hetl is preferably 2,3-dihydro-1H-indol-6-yl and R3 is preferably CO(A).

is particularly preferred for Hetl-Ar.
Het is preferably substituted or unsubstituted 2- or 3-furyl, 2- or 3-thienyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2-, 3- or WO 00/32577 PC'f/EP99/08561 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, furthermore preferably 1,2,3-triazol-1-, -4- or -5-yl, 1,2,4-triazol-1-, -4- or -5-yl, 1- or 5-tetrazolyl, 1,2,3-oxadiazol-4- or -5-yl, 1,2,4-oxadiazol-3- or -5-yl, 1,3,4-thiadiazol-2- or -5-yl, 1,2,4-thiadiazol-3- or -5-yl, 1,2,3-thiadiazol-4- or -5-yl, 2-, 3-, 4-, 5- or 6-2H-thiopyranyl, 2-, 3- or 4-4H-thiopyranyl, 3- or 4-pyridazinyl, pyrazinyl, 2-, 3-, 4-, 5-, 6- or 7-benzofuryl, 2-, 3-, 4-, 5-, 6- or 7-benzothienyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-1H-indolyl, 1-, 2-, 4- or 5-benzimidazolyl, 1-, 3-, 4-, 5-, 6- or 7-benzopyrazolyl, 2-, 4-, 5-, 6- or 7-benzoxazolyl, 3-, 4-, 5-, 6- or 7-benzisoxazolyl, 2-, 4-, 5-, 6- or 7-benzothiazolyl, 2-, 4-, 5-, 6- or 7-benzisothiazolyl, 4-, 5-, 6- or 7-Benz-2,1,3-oxadiazolyl, 1-, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolinyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolinyl, 1-, 2-, 3-, 4- or 9-carbazolyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridinyl, 3-, 4-, 5-, 6-, 7- or 8-cinnolinyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl. The heterocyclic radicals can also be partially or completely hydrogenated. Het can thus also be 2,3-dihydro-2-, -3-, -4- or -5-furyl, 2,5-dihydro-2-, -3-, -4- or -5-furyl, tetrahydro-2- or -3-furyl, 1,3-dioxolan-4-yl, tetrahydro-2- or -3-thienyl, 2,3-dihydro-1-, -2-, -3-, -4- or -5-pyrrolyl, 2,5-dihydro-1-, -2-, -3-, -4- or -5-pyrrolyl, 1-, 2- or 3-pyrrolidinyl, tetrahydro-1-, -2- or -3-pyrrolyl, tetrahydro-1-, -2- or 4-imidazolyl, 2,3-dihydro-1-, -2-, -3-, -4-, -5-, -6-, -7-1H-indolyl, 2,3-dihydro-1-, -2-, -3-, -4- or -5-pyrazolyl, tetrahydro-1-, -3- or -4-pyrazolyl, 1,4-dihydro-1-, -2-, -3- or -4-pyridyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5- or -6-pyridyl, 1,2,3,6-tetrahydro-1-, -2-, -3-, -4-, -5- or -6-pyridyl, 1-, 2-, 3- or 4-piperidinyl, 1-, 2-, 3- or 4-azepanyl, 2-, 3- or 4-morpholinyl, tetrahydro-2-, -3- or -4-pyranyl, 1,4-dioxanyl, 1,3-dioxan-2-, -4- or -5-yl, hexahydro-1-, -3- or -4-pyridazinyl, hexahydro-1-, -2-, -4- or -5-pyrimidinyl, 1-, 2- or 3-piperazinyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or -8-quinolinyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or -8-isoquinolinyl.
Tetrahydro-1-pyrrolyl, 2,3-dihydro-1H-indol-1-yl, 1-piperidinyl, 2,6-tetramethylpiperidin-4-yl, 4-morpholinyl, 1-piperazinyl, 4-methylpiperazin-1-yl, 4-phenylpiperazin-1-yl, 1,2,3,4-tetrahydroquinolin-1-yl or 1,2,3,4-tetrahydroisoquinolin-1-yl is particularly preferred.
In -Het-S02-Ar, Het and Ar have one of the preferred meanings indicated above, where Het is preferably piperazine-1,4-diyl.
- N N -S02 ~ ~ gr U
is particularly preferred for -Het-S02-Ar.
In -Het-R5, Het has one of the preferred meanings indicated beforehand, where Het is preferably piperazine-1,4-diyl and R5 is preferentially phenyl, methyl, chloromethyl or trifluoromethyl.
- NON
is particularly preferred for -Het-R5.
In -Het- (CH2} n-Ar, Het and Ar have one of the preferred meanings indicated above, where Het is preferably piperazine-1,4-diyl and n can be 0, l, 2, 3 or 4.

-N -CH2 ~ ~ O
U

/--~ N
- N N ~ ~ or U
-N N~N
\--~ N -is particularly preferred for -Het-(CH2)n-Ar.
X and/or X1 and/or X2 is alkylene and is preferably methylene, ethylene, propylene, butylene, furthermore also pentylene or hexylene.
Y is preferably 0, S, NH or NA.
In -Y- (CHz) n-Het, Y is preferably 0, S, NH or NA, where Het has one of the preferred meanings indicated above and n is preferably 0, 1, 2, 3 or 4:
-NH_(CH2)2-N O . -NH-(CH2)3- N-CH3 \--/ U
or _ NH IV
is particularly preferred for -Y-(CH2)n-Het.
In -Y-Ar'-R3, Y is preferably O, S, NH or NA, where Ar' has one of the preferred meanings indicated beforehand and R3 is pzeferentially an alkylcarbonyl group.
O
_NH

is particularly preferred for -Y-Ar'-R3.
In -Y-(CH2)n-Ar, Y is preferably 0, S, NH or NA, where Ar has one of the preferred meanings indicated above and n is preferably 0, 1, 2, 3 or 4.
N- N--NH (CH2)2 \ / , -NH-CH2 \ / ' -NH-(CH2)2 \ > . -NH-(CH2)3-N~N
N ~I
i _ -NH ~ ( , -NH-CHZ \ / OZ-NHZ .

-NH-{CHZ)2 ~ / OH . -NH-CH2 ~ / , -NH-CH2 ~ / NHZ
-NH ~ / CH3 . -NH ~ / F
-NH-(CHZ)2 ~ ~ or OH
-N{CH3)-{CH2)2 / ~~OH
is particularly preferred for -Y-(CH2)n-Ar.
In -Y- (CH2) n-Ar' - (CH2) i-Rs, Y is preferentially O, S, NH or NA, where Ar' has a preferred meaning indicated beforehand, Rs is preferably amino or alkylamino and n is 0, 1, 2, 3 or 4 and i is 0, 1, 2, 3, 9, 5, 6, 7, 8, 9, 10, 11 or 12.

_ NH-CH2 ~ ~ or _ NH-CH2 ~ ~ CH2-NH2 is very particularly preferred for -Y- (CH2) "-Ar' - (CH2) i-Rs.
In -Y- (CH2) n-D- (CH2) i-Rs, Y is preferentially 0, S, NH or NA, where D has a preferred meaning indicated beforehand, Rs is preferably amino or alkylamino and n is 0, 1, 2, 3 or 4 and i is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
H2_ NHZ

or _ NH-CH2 CH2-NH2 is very particularly preferred for -Y- (CH2) n-D- (CH2) i-Rs.

In -Y- (CH2) "-Het- (CH2) i-R6, Y is preferentially 0, S, NH or' NA, where Het has a preferred meaning indicated beforehand, R6 is preferably amino or alkylamino and n is 0, 1, 2, 3 or 9 and i is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
_ NH-(CH2)a - N ~N --(CH2)3 -NH2 is very particularly preferred for -Y- (CH2) n-Het- (CH2) i-R6.
In -Y- (CHZ) n-NA- (CHZ) i-R6, Y is preferentially 0, S, NH or NA, where A has a preferred meaning indicated beforehand, R6 is preferably amino or alkylamino and n is 0, 1, 2, 3 or 4 and i is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12. -NH- (CHZ) 3-N (CH3) - (CH2) 3-NH2 is very particularly preferred for -Y- (CH2) n-NA- (CH2) i-Rs.
In -Y- (CHZ) "-D- (CHZ) i-Re, Y is preferentially O, S, NH or NA, where D has a preferred meaning indicated beforehand, Re is preferably guanidine or alkylguanidino and n is 0, 1, 2, 3 or 4 and i is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
N
CH2- N,~ NH2 H
_ NH-CH2 or N
_ NH-CH2 CH2 - ~ ~ NH2 H
is very particularly preferred for -Y- (CH2) "-D- (CH2) i-Re.
In -Y- (CH2) n-Ar' - (CH2) i-Re, Y is preferentially 0, S, NH or NA, where Ar' has a preferred meaning indicated beforehand, Re is preferably guanidine or alkylguanidino and n is 0, 1, 2, 3 or 4 and i is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
N
CH2 - N,~ NH2 H
_ NH-CH2 ~ ~

N
_ NH-(CH2)2 N,~ NH2 or H
N
_ NH-CHZ CH - N,~ NH2 H
is very particularly preferred for -Y- (CH2) n Ar' - (CHZ) i-Re.
In -Y- (CH2) n-NA- (CHZ) i-Re, Y is preferentially 0, S, NH or NA, where A has a preferred meaning indicated .
beforehand, R8 is preferably guanidino or alkylguanidino and n is 0, 1, 2, 3 or 4 and i is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 . -NH- (CH2) 3-N (CH3) - (CH2) 3-NH-C (=NH} -NH2 is very particularly preferred for -Y- (CH2) n-Ar' - (CHZ} i-Re.
In -Y- [X-0] t- [X1-O] "-X2-R6, Y is preferentially 0, S, NH or NA, where X, X1 and X2 have a preferred meaning indicated beforehand. Furthermore, R6 is preferably amino, alkylamino or dialkylamino, t is 0, 1 or 2 and a is 1 or 2 . -NH- (CHZ) 3-O- (CH2} 4-0- (CH2) 3-NH2 is particularly preferred for -Y- [X-0] t- [X1-O] "-X2-R6.
Furthermore, in -Y-[X-NH]"-Xl-OH, Y is preferentially 0, S, NH or NA, where X and X1 have a preferred meaning indicated beforehand and a can be I
or 2 . -NH- (CH2) 2-NH- (CH2} 2-OH is particularly preferred f or -Y- [X-NH ] u-X1-OH .
R is preferably H or N02.
R1 is preferably -Het, -Het-S02-Ar, -Het-R5, -Het- (CH2) n-Ar, N02, -N=CH-Ar, NHAlk, NAAlk, NHA' , NA' 2, N N --U NH
-Y-D-H, -Y-Ar' -R3, -Y- ( CH2 ) o-R3 r -Y- ( CH2 ) n CHRq -R5, -( ) 2 5 -Y-C [ { CH2 ) o-OH ] 3 r -Y- ( CH2 ) ~ NA2 r -Y- { CH2 ) m NHA' , -Y- ( CH2 ) o-OH, -Y- ( CH2 ) k-R6 i -Y- ( CH2 ) t-Re i -Y- ( CH2 ) n-Het, -Y- { CH2 ) n-Ar, -Y- ( CH2 ) n Ar' - ( CH2 } i-Rs i -Y- ( CH2 ) n D- ( CHy ) i-R6 r -Y- { CHZ } n-Het- ( CHZ } i-R6 r -Y- ( CH2 ) n-NA- ( CH2 ) i-R6 i -Y- ( CHZ ) n-NH- ( CHZ ) i-R6 r -Y- ( CH2 ) n-D- ( CH2 ) i-R8 r 3 0 -Y- ( CHz ) n-Ar' - ( CHZ ) i-Re i -Y- ( CHZ ) n-NH- ( CH2 ) i-Re r -Y- ( CH2 ) n-NA- ( CHZ } i-R8 r _ 5~ --Y-(CH2)n N-.~
NH
-Y- [X-0] t-- [X1-0] "-X2-86 Or -Y- [X-NH] "-X1-OH, where -Het, -Het-S02-Ar, -Het-R5, -Het- ( CH2 ) n-Ar, -Y-Ar' -R3, -Y- ( CH2 ) n-He t , -Y- ( CH2 ) n'Ar, -Y- ( CH2 ) n Ar' - ( CH2 ) i-R6.
-Y- ( CH2 ) n-D- ( CH2 ) i-R6 r -Y- ( CH2 ) n-Het- ( CH2 ) i-R6 r -Y- ( CH2 ) n-NA- ( CH2 ) i-R6 r -Y- ( CH2 ) n-D- ( CH2 ) i-Re r -Y- ( CH2 ) n-Ar' - ( CH2 ) i-R8 r -Y- ( CH2 ) n-NA- ( CH2 ) i-Re r -Y- [X-0] t- [XI-O] "-X2-R6 and -Y- [X-NH] "-X1-OH in particular have the preferred or particularly preferred meanings indicated beforehand.
Furthermore, Ar in -N=CH-Ar is preferably 2-hydroxy-phenyl.
In NHAlk, Alk has a preferred meaning indicated beforehand.
NH- (n-CSH11) is particularly preferred for NHAlk.
In NAAlk, A and Alk have a preferred meaning indicated beforehand, where N (CH3) - (n-C4H9) is particularly preferred for NAAlk.
In NHA', A' has a preferred meaning indicated before-hand. NH-(n-C3H~) is particularly preferred for NHA'.
Furthermore, A' in NA'2 has a preferred meaning indicated beforehand, where N(C2H5)2 is particularly preferred for NA'2.
In -Y-D-H, as a R1 substituent, Y is preferentially 0, S, NH or NA, where D has a preferred meaning indicated beforehand. -NH-C6H11 or -NH-C5H9 is particularly preferred for -Y-D-H.
In -Y- (CH2) o-R3, Y is preferentially 0, S, NH or NA, where R3 is preferably alkyloxycarbonyl and o can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.
-NH- (CH2) 2-COOMe is particularly preferred for -Y- (CH2) o R3.
In -Y- (CH2) n- (CHR4) -R5, Y is preferentially O, S, NH or NA, where R9 is preferably phenyl or hydroxyl, R5 is preferentially methyl, chloromethyl or trifluoromethyl and n is 0, 1, 2, 3 or 4.

- 58 - _ OH
-NH H or -NH-CH2 ~ H

is particularly preferred for -Y- (CHz) n- (CHR4) -R5 In -Y-C [ (CHz) o-OH] 3, Y is preferentially 0, S, NH or NA, where o can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.
-NH-C[CHz-OH]3 is particularly preferred for -Y-C [ ( CHz ) o-OH ] 3 .
In -Y-(CHz)m NAz, Y is preferentially 0, S, NH or NA, where A has a preferred meaning indicated beforehand and m can be 0, 1 or 2.
-NH- (CHz) z-N (CzHs) z or -N (CH3) - (CHz) z-N (CzHs) z is particularly preferred for -Y-(CHz)m-NAz.
In -Y-(CHz)m-NHA', Y is preferentially 0, S, NH or NA, where A' has a preferred meaning indicated beforehand and m can be 0, 1 or 2. -NH- (CHz) z-NH- (C3H~) is particularly preferred for -Y- (CHz),~ NHA' .
In -Y-(CHz)o-OH, Y is preferably 0, S, NH or NA, where o is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. -NH-(CHz)z-OH or -NH-(CHz)5-OH is particularly preferred for -Y- ( CHz ) o-OH .
In -Y- (CHz) k-R6, Y is preferentially 0, S, NH or NA, where R6 is preferably amino, alkylamino, d.ialkylamino or cycloalkylamino and k can be 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 . -NH- (CHz) 3-NHz, -NH- (CH2) 9-NHz, -NH- ( CHz ) s-NHz, -NH- ( CHz ) ~-NHz, -NH- ( CHz ) s-NHz.
2 5 -NH- ( CHz ) 3-N ( CH3 ) z, -NH- ( CHz ) 3-NH ( CH3 ) , -N ( CHs ) - ( CHz ) s-NH ( CH3 ) or -NH-(CH2)s - N
H
is particularly preferred for -Y- (CHz) k-R6.
In -Y- (CHz) i-Re, Y is preferentially 0, S, NH or NA, where RB is preferably -NH-(C=NH)-NHz, -NH-(C=NH)-NHA, -NH-(C=NH)-NAz, -NA-(C=NH)-NHz, -NA-(C=NH)-NHA, -NA-(C=NH)-NAz and i can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 . -NH- (CHz) z-NH-C (=NH) -NHz, -NH- (CH2) 3-NH-C (=NH) -NH2, -NH- (CHZ) 4-NH-C (=NH) -NHZ, -NH- (CH2) 5-NH-C (=NH) -NH2, -NH- (CH2) 6-NH-C (=NH) -NH2, -NH- (CH2) 7-NH-C (=NNH NH2 or -N CH N' _NH
i ( 2)3 is particularly preferred for -Y-(CH2)i-Re.
_ Rs Rs In N N~ and -Y-(CH2)" N-U NH NH
Y is preferentially 0, S, NH or NA, where R6 is preferably amino, alkylamino or dialkylamino and n can be 0, 1, 2, 3 or 4.

N N--~ H and -NH-CH2 N---N NH
is particularly preferred for Rs Rs N~N--~ and -Y-(CH2)~ N--NH NH
R2 is preferably -Ar, -Ar'-D-H, -Hetl, -Hetl-Ar, -Ar' -Hetl, -Ar' - (CH2) n-R3, -Ar' -Y- (CH2) n-R3, -Ar' -Y-C (A) 2-R3, -Hetl-R3, -Ar' -Hetl-R3, -Ar' - (CH2) n R6, -Ar' -S02-Het, -Ar' -NH-S02-Het, Ar' -S02-R7, -Ar' - (CH2) n- (CO-NH ) - ( CH2 ) t-R6 i -Ar' - ( CHZ ) n- ( CC-NH ) - ( CH2 ) i-R11. -Ar' - ( CH2 ) n-CO-Het, -Ar' - ( CH2 ) "- ( CO-NH ) - ( CH2 ) i-D-H, -Ar' - ( CH2 ) n- ( CO-NH ) - ( CH2 ) i-Ar, -Ar' - ( CH2 ) n- ( CO-NH ) - ( CH2 ) i-Hetl, 2 0 -Ar' - ( CHZ ) n- ( CH ( CN ) ) - ( CH2 ) i-Ar, -Ar' - ( CH2 ) "- ( CO-NH
) -( CH2 ) i-CH (Ari ) -Ar2, -Ar' -S- ( CHZ ) n- ( CO-NH ) - ( CH2 ) i-Ar, -Ar' -S- ( CH2 ) n- ( CO-NH ) - ( CH2 ) i-Rii , -Ar' -S- ( CHa ) n ( CO-NH ) -( CH2 ) i-Hetl, -Ar' -S- ( CHZ ) n- ( CO-NH ) - ( CH2 ) i-CH (Arl ) -Ar2 or -Ar' -S- ( CH2 ) n- ( CO-NH ) - ( CHZ ) i-D-H, Ar, Ar' , Arl, Ar2, A, D, Het, Hetl, R3, R6, Rll, Y, n and i in particular have one of the preferred or particularly preferred meanings indicated beforehand.
R3 is preferably C (0) A, CONH2, CONHA, CONA2, COOH or CODA, where A has one of the preferred meanings indicated beforehand.
R4 is preferentially phenyl or hydroxyl.

R5 is preferably methyl, chloromethyl, trifluoromethyl or phenyl.
R6 is preferentially NH2, NHA, NA2, NH (D-H) or NHC(O)A, where A and D have a preferred meaning indicated beforehand.
R' is preferably NA(D-H), NHA, NH(D-H) or NA2, where A and D have a preferred meaning indicated beforehand.
RB is preferentially -NH-(C=NH)-NH2, -NH- ( C=NH ) -NHA, -NH- ( C=NH ) -NA2, -NA- ( C=NH ) -NH2, -NA- (C=NH) -NHA, -NA- (C=NH) -NA2, where A has a preferred meaning indicated beforehand.
R11 is preferentially -CH(A)-Ph, where A has a preferred meaning indicated beforehand.
Some preferred groups of compounds can be expressed by the following subformulae Ia to Iz and I1 to I5, which correspond to the formula I

R ~ ~ R
i I

and in which the radicals not designated in greater detail have the meanings indicated in formula I, but in which:
in Ia R is N02, Rl is N02 and R2 is Ar;
in Ib R is H, R2 is Ar and Rl is -Het, -Het-SOZ-Ar, -Het-R5, N02, NHAlk, NAAlk, NHA', NA'2, -Y-D-H, -Y-Ar'-R3, -Y- ( CH2 ) o-R3 r -Y- ( CH2 ) n- ( CHR4 ) -R5 r -Y-C C ( CH2 ) o-OH ] s. -Y- ( CH2 ) m-NAp i -Y- ( CHZ ) m NHA' , -Y- ( CH2 ) o-OH, -Y- ( CH2 ) x-R6, -Y- ( CH2 ) n-Het , -Y- ( CH2 ) n-Ar, -Y- ( CH2 ) n-Ar' - ( CH2 ) i-R6 r -Y- ( CH2 ) n-Ar' - ( CH2 ) i-R8 r -Y- ( CH2 ) n-D- ( CH2 ) i-R6 r -Y- ( CH2 ) n-Het- ( CH2 ) i-R6 r -Y- ( CH2 ) n-NA- ( CH2 ) i-R6 or -Y- ( CH2 ) n-NH- ( CH2 ) i-R6:
in Ic R is H, R2 is -Hetl and Rl i s NO2 :
in Id R is H, R2 is -Hetl-Ar and Rl is NO2;
in Ie R is H
R2 i s -Ar' - ( CH2 ) n R3 and Ri is -Het, -Het-SO2-Ar, -Het-R5, -Het- (CH2) n-Ar, NO2, NHAlk, NAAlk, NHA' , 2 0 NA' z . -Y-0-H r -Y-Ar' -R3 r -Y- ( CH2 ) o-R3 r -Y- ( CH2 ) n- ( CHR9 ) -R5, -Y-C [ ( CH2 ) o-OH } 3 r -Y- ( CH2 ) m-NA2, -Y- ( CH2 ) m-NHA' , -Y- ( CH2 ) o-OH, -Y- ( CH2 ) x-R6 r -Y- ( CH2 ) n-Het, -Y- ( CH2 ) n-Ar, -Y- ( CH2 ) n-Ar' - ( CH2 ) i-R6 r Y- ( CH2 ) n-~- ( CH2 ) i-R6 r 2 5 -Y- ( CH2 ) n-Het- ( CH2 ) i-Rs r -Y- ( CH2 ) n-NA- ( CH2 ) i-Rs r -Y- ( CH2 ) n-NH- ( CH2 ) i-Rs r _Y_ [X_0} t_ [X1_0} u_X2_R6 Or _Y_ [X_NH} u_Xl_OH:
30 in If R is H, R2 i s -Ar' -Y- ( CH2 ) n-R3 and Rl i s -Y- ( CH2 ) x-Rs r -Y- ( CH2 ) n-Ar' - ( CH2 ) i-R6 or -Y- (CH2) n-Ar~
35 in Ig R is H, R2 is -Ar' -SO2-Het and Rl i s -Y- ( CH2 ) x-R6 or -Y- ( CH2 ) n-Ar' - ( CH2 ) i-R6:

in Ih R is H, R2 is -Ar' -SOZ-R' and Rl i s -Y- ( CH2 ) x-R6 or -Y- ( CH2 ) n-Ar' - ( CH2 ) i-Rs:
in Ii R is H, R2 i s -Ar' - ( CH2 ) n- ( CONH ) - ( CH2 ) i-R6 and Rl is -Y- ( CHZ ) x-R6 or -Y- ( CH2 ) n-Ar' - ( CH2 ) i-Rs:
in Ik R is H, R2 i s -Ar' - ( CH2 ) n- ( CONH ) - ( CH2 ) i-D-H
and Rl 1 S -Y- ( CH2 ) x-R6 r -Y- ( CH2 ) n-Ar' -( CHy ) i-R6 r -Y- ( CH2 ) i-R8 i -Y- ( CH2 ) n-D- ( CH2 ) i-RB i -Y- ( CH2 ) n-Ar' - ( CH2 ) i-Re or -Y- ( CH2 ) n-NA- ( CH2 ) i-R8:

in I1 R is H, RZ i s -Ar' - ( CHz ) n- ( CONH ) - ( CH2 ) i-Ar and Rl 1 s -Y- ( CHZ ) x-R6 ~ -Y- ( CHZ ) n-Ar' -( CH2 ) i-R6.

-Y- ( CH2 ) n-Ar, -Y- ( CHZ ) i-Re.

2 0 -Y- ( CH2 ) n-D- ( CH2 ) i-RB r -Y- ( CH2 ) n-Ar' - ( CH2 ) i-Rs -Y- ( CH2 ) n-NA- ( CH2 ) i-R8 r N N -U NH

Rg or -Y-(CH2)" \N-~ ;

N

in Im R is H, R2 i s -Ar' - ( CH2 ) n- ( CONH ) - ( CH2 ) i-Het 1 and Rl i S -Y- ( CH2 ) i-Re r -Y- ( CH2 ) n-D- ( CH2 ) i-RB r -Y- ( CH2 ) n-Ar' - ( CH2 ) i-Re or 3 0 -Y- ( CH2 ) n-NA- ( CHZ ) i-R8 in In R is H, Rz is -Ar' - ( CHz ) n- ( CH ( CN ) ) - ( CHz ) i-Ar and Rl is -Y- ( CHz ) x-R6' -Y- ( CHz ) n-D- (CHz ) i-R6 or -Y-( CH2 ) n-Ar' - ( CHz ) i-R6:
in Io R is H, Rz i s -Ar' - ( CHz ) n- ( CO-NH ) - ( CHz ) i-CH ( Ar 1 ) -Arz and Rl 1 S -Y- ( CHz ) i-R8 , -Y- ( CH2 ) n-D- ( CH2 ) i-Re i -Y- ( CHz ) n-Ar' - ( CHz ) i-Re or -Y- ( CHz ) n-NA- ( CHz ) i-R8 ;
in Ip R is H, Rz is -Ar' -Hetl and Rl 1 s -Y- ( CHz ) x-R6 ~ -Y- ( CHz ) n-Ar' - ( CHz ) i-R6 ~
-Y- ( CHz ) n-Ar' - ( CHz ) i-R8 or -Y- ( CHz ) n D- ( CHz ) i-R6:
in Iq R is H, Rz is -Ar' -Hetl-R3 and 2 0 Rl i S -Y- ( CHz ) x-R6 or -Y- ( CHz ) n-D- ( CHz ) i-R6:
in Ir R is H
Rz i s -Ar' - ( CHz ) n-R6 and Rl i s -Y- ( CHz ) x-R6 or -Y- ( CHz ) n-D- ( CHz ) i-R6 in Is R is H, Rz i s -Ar' -Y-C ( A ) z-R3 and Rl i s -Y- ( CHz ) x-R6:
in It R is H, RZ is -Ar ~ -NH-SOz-Het and Rl is -Y- (CH=) x-R6;
in Iu R is H, Rz is -Heti-R3 and Rl is -Y- ( CHz ) x-R6;
in Iv R is H, Rz is -Ar' -D-H and ' WO 00/32577 PCT/EP99/08561 Rl i s -Y- ( CHZ ) x-R6:

in Iw R is H, RZ i s -Ar' - ( CH2 ) n- ( CONH ) - ( CHz ) i-Rii and Rl iS -Y- (CHz) n-Ar' - (CH2) i-R6~

in Ix R is H, R2 i s -Ar' - ( CHZ ) "-CO-Het and Rl is -Y- (CH2) n-D- (CH2) i-R6:

in Ty R is H, R2 is -Ar' -S- (CHZ) n- (CO-NH) - (CHZ) i-Ar and Rl i s -Y- ( CH2 ) n-Ar' - ( CHZ ) i-R6 or -Y- ( CH2 ) n-Ar' - ( CH2 ) i-RB

in Iz R is H, RZ is -Ar' -S- (CHa) n- (CO-NH) - (CH2) i-Hetl and R1 i s -Y- ( CH2 ) n-Ar' - ( CH2 ) i-R6 or -Y- ( CH2 ) n-Ar' - ( CH2 ) i-R8 in I1 R is H, RZ is -Ar' -S- (CHZ) n- (CO-NH) - (CHz) i-DH
and Rl i s -Y- ( CHz ) n-Ar' - ( CH2 ) i-R6 or -Y- ( CH2 ) n-Ar' - ( CH2 ) i-Re in I2 R is H, R2 is -Ar' -S- (CHz) n- (CO-NH) - (CH2) i-Rli and Ri i s -Y- ( CH2 ) n-Ar' - ( CH2 ) i-R6 or -Y- ( CH2 ) n-Ar' - ( CHZ ) i-R8 in I3 R is H, R2 is -Ar' -S- (CH2) n- (CO-NH) - (CH2) i-CH-Ar2 (Arl) and R1 i s -Y- ( CH2 ) n-Ar' - ( CHZ ) i-R6 or 3 5 -Y- ( CH2 ) n-Ar' - ( CHZ ) i-Re :

in I4 R is H, R~ is -Ar, -Ar' -Hetl, -Ar' - (CHz)n- (CO-NH) _ ( CHz ) i -Ar and Rl is -Y- ( CH2 ) x-R6. -Y- ( CH2 ) i-R8 ;
-Y- ( CH2 ) n-D- ( CH2 ) i-Re r -Y- ( CH2 ) n-NA- ( CH2 ) i-RB
or -Y- ( CHZ ) n-Ar' - ( CH2 ) i-Re ;
in IS R is H, R2 is -Ar, -Ar' - (CHZ) "- (CO-NH) - (CH2) i-Ar, -Ar' -S- (CHZ) n- (CO-NH) - (CHz) i-Ar, -Ar' - (CHZ) "-(CO-NH) - (CHZ) i-Heti, -Ar' -S- (CH2) n- (CO-NH} -(CHz) i-Hetl, -Ar' - (CHZ) n- (CO-NH) - (CHZ) i-D-H, -Ar' -S- (CHz} n- (CO-NH) - (CH2) i-D-H, -Ar' - (CHZ) n- (CO-NH) - (CHz) i-CH (Ar'} -Arz, -Ar' -S- (CHZ) ~- (CO-NH) - (CHZ) i-CH (Arl) -Ar2, -Ar' - (CHz) "- (CO-NH} - (CHZ) ;-Rll or -Ar' -S-(CH2}n- (CO-NH) - (CHZ) i-Rll and Rl i s -Y- ( CH2 } n-Ar' - ( CH2 ) i-R6 or -Y- ( CHz } n-Ar' - ( CHz ) i-R8 .
Preferred compounds of the formula I are in the following:
3-(3-[6-(4-Guanidinomethyl-benzylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl}-N-[2-(4-sulfamoyl-phenyl}-ethyl]-propionamide;
N-[2-(4-Chloro-phenyl)-ethyl]-3-(3-[6-(4 guanidinomethyl-benzylamino}-1,3-dioxo-1H,3H
benzo[de]isoquinolin-2-yl]-phenyl}-propionamide;
6-(3-Amino-propylamino)-2-(3,4,5-trimethoxy-phenyl)-benzo[de]isoquinoline-1,3-dione;
6-(3-Amino-propylamino}-2-(7-hydroxy-naphthalen-1-yl)-benzo[de]isoquinoline-1,3-dione;
6-[(3-Amino-propylamino}-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-4,5-dimethoxy-benzonitrile;
6-(3-Amino-propylamino}-2-(2,3-dimethoxy-phenyl}-benzo[de]isoquinoline-1,3-dione;

N-[2-(3-Chloro-phenyl)-ethyl]-3-(3-[6-(4-guanidinomethyl-cyclohexylmethyl-amino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl}-propionamide:
N-[2-(4-Chloro-phenyl)-ethyl]-3-(3-[6-(4-guanidinomethyl-cyclohexylmethyl-amino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl}-propionamide:
6-(3-Amino-propylamino)-2-(4'-methoxy-biphenyl-4-yl)-benzo[de]isoquinoline-1,3-dione:
6-(3-Amino-propylamino)-2-(4-carbazol-9-yl-phenyl)-benzo[de]isoquinoline-1,3-dione:
6-(3-Amino-propylamino)-2-(4'-hydroxy-2-methyl-biphenyl-4-yl)-benzo[de]isoquinoline-1,3-dione~
N-(3-([2-(4'Methoxy-biphenyl-4-yl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-ylamino]-methyl}-benzyl)-guanidine 3-(3-[6-(2-Guanidino-ethylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl}-N-(4-phenyl-butyl)-propionamide;
N-(2-(4-Chloro-phenyl)-ethyl]-3-(3-[6-(2-guanidino-ethylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl}-propionamide:
N-(2-(4-Chloro-phenyl)-ethyl]-3-(3-[6-(3-guanidino-propylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl}-propionamide~
N-(2-(9-Chloro-phenyl)-ethyl]-3-[3-(6-(3-[(3-guanidino-propyl)-methyl-amino]-propylamino}-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl}-propionamide;

- 6~ - _ N-(2-(3-Chloro-phenyl)-ethyl]-3-~3-[6-(3-guanidino-propylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl)-propionamide~
6-(3-Amino-propylamino)-2-(4'-methoxy-biphenyl-4-yl)-benzo[de]isoquinoline-1,3-diones N-[3-(~2-[9-(3,6-Di-tert-butyl-carbazol-9-yl)-phenyl]-I,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-ylamino]-methyl)-benzyl]-guanidine and 6-(3-Amino-propylamino)-2-(4-carbazol-9-yl-phenyl)-benzo[de]isoquinoline-1,3-dione.
The compounds of the formula I and also the starting substances for their preparation are otherwise prepared by methods known per se, such as are described in the literature (e.g. in the standard works such as Houben-Weyl, Methoden der organischen Chemie [Methods of Organic Chemistry], Georg-Thieme-Verlag, Stuttgart), namely under reaction conditions which are known and suitable for the reactions mentioned. In this case, use can also be made of variants which are known per se, but not mentioned here in greater detail.
. The starting substances, if desired, can also be formed in situ such that they are not isolated from the reaction mixture, but immediately reacted further to give the compounds of the formula I.
The compounds of the formula I can be obtained by liberating them from their functional derivatives by solvolysis, in particular hydrolysis or by hydrogen olysis.
Preferred starting substances for the solvolysis or hydrogenolysis are those which otherwise correspond to the formula I, but instead of one or more free amino and/or hydroxyl groups contain corresponding protected amino and/or hydroxyl groups, in particular those which instead of an H-N- group carry an R'-N-group, in which R' is an amino protective group and/or those which instead of the H atom of a hydroxyl group carry a hydroxyl protective group, e.g. those which correspond to the formula I, but instead of a group COOH carry a group -COOR", in which R" is a hydroxyl protective group.
A number of - identical or different -protected amino and/or hydroxyl groups can also be present in the molecule of the starting substance. If the protective groups present are different from one another, in many cases they can be removed selectively.
The expression "amino protective group" is generally known and relates to groups which are suitable for protecting (for blocking) an amino group against chemical reactions, but which are easily removable after the desired chemical reaction has been carried out at other positions in the molecule. Typical groups of this type are, in particular, unsubstituted or substituted acyl, aryl, aralkoxymethyl or aralkyl groups. Since the amino protective groups are removed after the desired reaction (or reaction sequence), their nature and size is otherwise not critical;
however, those having 1-20, in particular 1-8, C atoms are preferred. The expression "acyl group" is to be interpreted in the widest sense in connection with the pxesent process. It includes acyl groups derived from aliphatic, araliphatic, aromatic or heterocyclic carboxylic acids or sulfonic acids and, in particular, alkoxycarbonyl groups, aryloxycarbonyl groups and especially aralkoxycarbonyl groups. Examples of acyl groups of this type are alkanoyl such as acetyl, propionyl, butyryl; aralkanoyl such as phenylacetyl;
aroyl such as benzoyl or toluyl: aryloxyalkanoyl such as POA; alkoxycarbonyl such as methoxycarbonyl, ethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, BOC, 2-iodoethoxycarbonyl; aralkyloxycarbonyl such as CBZ
("carbobenzoxy"), 4-methoxybenzyloxycarbonyl, Fmoc;
arylsulfonyl such as Mtr. Preferred amino protective groups are BOC, furthermore CBZ, Fmoc, benzyl and acetyl.

- 69 - ' The expression "hydroxyl protective group" is also generally known and relates to groups which are suitable for protecting a hydroxyl group against chemical reactions, but which are easily removable after the desired chemical reaction has been carried out at other positions in the molecule. Typical groups of this type are the abovementioned unsubstituted or substituted aryl, aralkyl or acyl groups, furthermore also alkyl groups. The nature and size of the hydroxyl protective groups is not critical, since they are removed again after the desired chemical reaction or reaction sequenced groups having 1-20, in particular 1-10 C atoms, are preferred. Examples of hydroxyl protective groups are, inter alia, benzyl, p-nitrobenzoyl, p-toluolsulfonyl, tert-butyl and acetyl, benzyl and tert-butyl being particularly preferred.
The liberation of the compounds of the formula I from their functional derivatives is carried out - depending on the protective group used - for example using strong acids, expediently using TFA or perchloric acid, but also using other strong inorganic acids such as hydrochloric acid or sulfuric acid, strong organic carboxylic acids such as trichloroacetic acid or sulfonic acids such as benzene- or p-toluene-sulfonic acid. The presence of an additional inert solvent is possible, but not always necessary. Suitable inert solvents are preferably organic, for example carboxylic acids such as acetic acid, ethers such as tetrahydrofuran or dioxane, amides such as DMF, halogenated hydrocarbons such as dichloromethane, furthermore also alcohols such as methanol, ethanol or isopropanol, and also water. Furthermore, mixtures of the abovementioned solvents are possible. TFA is preferably used in an excess without addition of a further solvent, perchloric acid in the form of a mixture of acetic acid and 70$ perchloric acid in the ratio 9:1. The reaction temperatures for the cleavage are expediently between approximately 0 and - 70 _ _ approximately 50°C; the reaction is preferably carried out between 15 and 30°C (room temperature).
The groups BOC and Obutyl can preferably be removed, for example, using TFA in dichloromethane or using approximately 3 to 5N HC1 in dioxane at 15-30°C, the Fmoc group using an approximately 5 to 50% solution of dimethylamine, diethylamine or piperidine in DMF at 15-30°C.
Hydrogenolytically removable protective groups (e.g. CBZ or benzyl) can be removed, for example, by treating with hydrogen in the presence of a catalyst (e. g. of a noble metal catalyst such as palladium, expediently on a support such as carbon). Suitable solvents in this case are those indicated above, in particular, for example, alcohols such as methanol or ethanol or amides such as DMF. As a rule, the hydrogenolysis is carried out at temperatures between approximately 0 and 100°C and pressures between approximately 1 and 200 bar, preferentially at 20-30°C
and 1-10 bar. Hydrogenolysis of the CBZ group takes place readily, for example, on 5 to IO% Pd/C in methanol or ammonium formate (instead of hydrogen) on Pd/C in methanol/DMF at 20-30°C.
Compounds of the formula I can also preferably be obtained by reacting-compounds of the formula II
with compounds of the formula III. As a rule, the starting compounds of the formulae II and III are known or commercially available. The unknown compounds, however, can be prepared by methods known per se. The compounds of the formula II are naphthalene-1,8-dicarboxylic anhydride derivatives. They can be prepared in a conventional manner from appropriately substituted 1,8-naphthalenedicarboxylic acids or corresponding derivatives. It is furthermore possible to introduce appropriate substituents into the aromatic by conventional electrophilic or alternatively nucleophilic substitutions.
The compounds of the formula III are primary amines, which, as a rule, are also commercially ' WO 00/32577 PCT/EP99/08561 - 71 - _ available. Furthermore, syntheses for the preparation of primary amines, such as, for example, the Gabriel synthesis, can be used.
As a rule, the reaction is carried out in an inert solvent. Depending on the conditions used, the reaction time is between a few minutes and a number of days, the reaction temperature between approximately 0°
and 150°C, normally between 20° and 130°C. The reactions can be carried out in analogy to the methods indicated in Eur. J. Chem. Chim. Ther. 1981, 16, 207-212 and in J. Med. Chem. 1982, 25, 714-719.
Suitable inert solvents are, for example, hydrocarbons such as hexane, petroleum ether, benzene, toluene or xylene~ chlorinated hydrocarbons such as trichloroethylene, 1,2-dichloroethane, carbon tetrachloride, chloroform or dichloromethane; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol or tert-butanol: ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF) or dioxane~ glycol ethers such as ethylene glycol monomethyl or monoethyl ether (methyl glycol or ethyl glycol), ethylene glycol dimethyl ether (diglyme)~
ketones such as acetone or butanone: amides such as acetamide, N-methylpyrrolidone (NMP), dimethylacetamide or dimethylformamide (DMF): nitriles such as acetonitrile: sulfoxides such as dimethyl sulfoxide (DMSO); carbon disulfide: carboxylic acids such as formic acid or acetic acid; nitro compounds such as nitromethane or nitrobenzene esters such as ethyl acetate or mixtures of the solvents mentioned.
Derivatives having a free primary or an additional secondary amino group are expediently employed in protected form. Possible protective groups are those mentioned beforehand.
For the preparation of compounds of the formula I in which R1 and/or R2 are H2N-C (=NH) -NH-, an appropriate amino-substituted compound can be treated with an amidinating agent. The preferred amidinating agent is 1-amidino-3,5-dimethylpyrazole (DPFN), which - 72 - _ is employed, in particular, in the form of its nitrate, or pyrazole-1-carboxamidine. The reaction is expediently carried out with addition of a base such as triethylamine or ethyldiisopropylamine in an inert solvent or solvent mixture, e.g. DMF at temperatures between 0° and 150°C, preferably between 60° and 120°C.
For the preparation of compounds of the formula I in which R2 is unsubstituted or substituted biphenyl, -Ar' -Hetl, -Ar' -Hetl-R3, -Ar' - (CH2) n-R3 and/or -Ar' - (CH2) n-R6, an appropriate compound of the formula I
in which R2 is aryl bromide or aryl iodide can be reacted with the appropriate boronic acid derivatives in a Suzuki reaction. The Suzuki reaction is expediently carried out in palladium-mediated form, preferably by addition of Pd(PPh3)9, in the presence of a base such as potassium carbonate in an inert solvent or solvent mixture, e.g. DMF at temperatures between 0°
and 150°, preferably between 60° and 120°. Depending on the conditions used, the reaction time is between a few minutes and a number of days. The boronic acid derivatives can be prepared by conventional methods or are commercially available. The reactions can be carried out in analogy to the methods indicated in Suzuki et al., J. Am. Chem. Soc. 1989, 111, 314ff. and Suzuki et al., Chem. Rev. 1995, 95, 2457ff.
For the esterification, an acid of the formula I (R1 = COOH or -Y- (CH2) n-COOH and/or R2 = COOH) can be treated with an excess of an alcohol, expediently in the presence of a strong acid such as hydrochloric acid or sulfuric acid at temperatures between 0° and 100°C, preferably between 20° and 50°C.
Conversely, an ester of the formula I (R1 - COOA or -Y-(CH2)n-COOA and/or RZ - COOA) can be converted into the corresponding acid of the formula I, expediently by solvolysis according to one of the methods indicated above, e.g. using NaOH or KOH in water-dioxane at temperatures between 0° and 40°C, preferably between 10° and 30°C.

Furthermore, free amino groups can be acylated in a customary manner using an acid chloride or anhydride, expediently in an inert solvent such as dichloromethane or THF and/or in the presence of a base such as triethylamine or pyridine at temperatures between -60°C and +30°C.
A base of the formula I can be converted into the associated acid addition salt using an acid, for example by reaction of equivalent amounts of the base and of the acid in an inert solvent such as ethanol and subsequent evaporation. Acids which give physiolo-gically acceptable salts are particularly suitable for this reaction. Thus inorganic acids can be used, e.g.
sulfuric acid, nitric acid, hydrohalic acids such as hydrochloric acid or hydrobromic acid, phosphoric acids such as orthophosphoric acid, sulfamic acid, further-more organic acids, in particular aliphatic, alicyclic, araliphatic, aromatic or heterocyclic mono- or polybasic carboxylic, sulfonic or sulfuric acids, e.g.
formic acid, acetic acid, propionic acid, pivalic acid, diethylacetic acid, malonic acid, succinic acid, pimelic acid, fumaric acid, malefic acid, lactic acid, tartaric acid, malic acid, citric acid, gluconic acid, ascorbic acid, nicotinic acid, isonicotinic acid, methane- or ethanesulfonic acid, p-toluenesulfonic acid, naphthalenemono- and disulfonic acids or laurylsulfuric acid. Salts with physiologically unacceptable acids, e.g. picrates, can be used for the isolation and/or purification of the compounds of the formula I.
On the other hand, compounds of the formula I
with bases (e.g sodium or potassium hydroxide or carbonate) can be converted into the corresponding metal salts, in particular alkali metal or alkaline earth metal salts, or into the corresponding ammonium salts.
All synthesis methods indicated here and all other suitable processes for the preparation of compounds of the formula I can also be carried out by WO 00/32577 PC'T/EP99l08561 74 - _ means of the novel methods of combinatorial chemistry, i.e. by robot- and computer-assisted syntheses, and subjected to mass screening (for this see: US
5,463,564 M. A. Gallop et al., J. Med. Chem. 1994, 37, 1233-1251 and 1385-1401 and M.J. Sofia, Drugs Discovery Today 1996, 1, 27-34).
The invention furthermore relates to pharmaceutical preparations comprising at least one compound of the formula I and/or one of its physiologically acceptable salts, which are prepared, in particular, in an non-chemical way. In this case, the compounds of the formula I can be brought into a suitable dose form together with at least one solid, liquid and/or semi-liquid excipient or auxiliary and, if appropriate, in combination with one or more other active compounds.
These preparations can be used as medicaments in human or veterinary medicine. Possible excipients are organic or inorganic substances which are suitable for enteral (e.g. oral) or parenteral administration or topical application and do not react with the novel compounds, for example water, vegetable oils, benzyl alcohols, alkylene glycols, polyethylene glycols, glyceryl triacetate, gelatin, carbohydrates such as lactose or starch, magnesium stearate, talc and petroleum jelly. Tablets, pills, coated tablets, capsules, powders, granules, syrups, juices or drops are used, in particular, for oral administration, suppositories are used for rectal administration, solutions, preferably oily or aqueous solutions, furthermore suspensions, emulsions or implants, are used for parenteral administration, and ointments, creams or powders are used for topical application. The novel compounds can also be lyophilized and the lyophilizates obtained used, for example, for the production of injection preparations. The preparations indicated can be sterilized and/or can contain auxiliaries such as lubricants, preservatives, stabilizers and/or wetting agents, emulsifiers, salts ' WO 00/32577 PCT/EP99/08561 ~5 _ _ for affecting the osmotic pressure, buffer substances, colourants, flavourings and/or one or more other active compounds, e.g. one or more vitamins.
The compounds of the formula I and their physiologically acceptable salts act as adhesion receptor antagonists, in particular glycoprotein IbIX
antagonists, and can be employed for the prophylaxis and/or therapy of thrombotic disorders and sequelae deriving therefrom. The disorders are acute coronary syndromes, angina pectoris, myocardial infarct, peripheral circulatory disorders, stroke, transient ischaemic attacks, arteriosclerosis and reocclusion/restenosis after angioplasty/stent implantation.
In this case, the substances according to the invention are as a rule administered in the dose of the glycoprotein IIbIIIa antagonist ReoPro~ of preferably between approximately 1 and 500 mg, in particular between 5 and 100 mg, per dose unit. The daily dose is preferably between approximately 0.02 and 10 mg/kg of body weight. The specific dose for each patient depends, however, on all sorts of factors, for example on the efficacy of the specific compound employed, on the age, body weight, general .state of health and sex, on the diet, on the time and route of administration, and on the excretion rate, pharmaceutical combination and severity of the particular disorder to which the therapy applies. Oral administration is preferred.
Above and below, all temperatures are indicated in °C. In the following examples, "customary working up" means: if necessary, water is added, if necessary, depending on the constitution of the final product, the mixture is adjusted to pHs between 2 and 10 and extracted with ethyl acetate or dichloromethane, the organic phase is separated off, dried over sodium sulfate and evaporated, and the residue is purified by chromatography on silica gel and/or by crystallization.
Mass spectrometry (MS) apparatuses Kratos Maldi III and Finnigan LCQ. (M+H)+ values are determined.

_ 76 - _ EXAMPLES
Example 1:
A suspension of 6.6 g of 6,7 dinitrobenzo[de]isochromene-1,3-dione in 100 ml of toluene is treated with 3.3 g of 5-chloropyridin 2-ylamine and the mixture is heated under reflux. After reaction is complete, the reaction mixture is allowed to cool and is worked up as is customary.
2-(5-Chloropyridin-2-yl)-6,7-dinitrobenzo[de]isoquinoline 1,3-dione is obtained.
Example 2:
A suspension of 4 g of 6-chlorobenzo[de]isochromene-1,3-dione in 100 ml of toluene is treated with 4.6 g of 2,5-dichlorophenylamine and heated under reflux. After reaction is complete, the reaction mixture is allowed to cool and is worked up as is customary. 6-Chloro-2-(2,5-dichlorophenyl)benzo[de]isoquinoline-1,3-dione is obtained. This compound is then heated in morpholine until conversion is complete. After cooling the reaction mixture, it is worked up as is customary and 2-(2,5-dichlorophenyl)-6-morpholin-4-ylbenzo[de]iso-quinoline-1,3-dione is obtained. MS: calculated: 426:
found: 427.
Analogously, by reaction of 6-chloro-2-(2,5-dichlorophenyl)benzo[de]isoquinoline-1,3-dione with R1-H, the following compounds of the formula Iba are obtained:
i I
i ~ Iba O "-O
N
Ci l CI

R in R -H and in Iba MS
calculated found H

-N N \ / 501 502 -NH- ( CHZ } 5-OH
-NH- ( CH2 ) 3-N ( CH3 ) 2 4 41 4 4 2 -N CH2 / \
H
-N (CHZ)2 / \
H
-NH- ( CH2 ) 2-COOMe 4 4 2 4 4 3 -N CH2 / \ Sp2NH2 H
-N (CH2)2 / \ pH 476 477 H
~H3 p -N (CH2)2 / \ pH

H

R in R --H and in Iba MS
calculated found '- ~ 424 425 H
i H
/ \ 472 473 -N

--N -- CH / \
H
-N CH2 / \ NH2 H
-N (CHZ)2 %~ \
i H
-N CH2 ~ \
H
-N (CH2)2-N O
H \--~/
-N (CH2)3-N N-CH3 H
-N (CH2)3-H
-NH (CSHli) 426 427 -NH (C3H~) 398 399 -N (CH3) -C4H9 426 427 -N ( CZHS ) 2 412 413 - 79 - _ Example 3:
Analogously to Example 2, 6-chloro-benzo[de)isochromene-1,3-dione is reacted with 3-chlorophenylamine and then with R1-H. The following compounds of the formula Ibb are obtained:

i l i ~ Ibb O ' 'O
N
i I
CI
Rl in Rl-H and in Ibb MS

calculated found 1'h -N ~

H

-N

\ /

-NH-C(CH20H)3 -NH- (CH2) 3-N (CH3) z 407 408 / \

H

/ \

-N (CHZ)2 426 427 H

R' in R'-H and in Ibb MS
calculated found -N CH2 / ~ S02NH2 H
-N (CH2)2 / \ OH 4 4 2 4 4 3 H .
H ~H --N (CH2)2 / \ OH

I
H

H

-H ~ I
/ \
-N
CH2-~ _ -N - CH2 / \
H
-N CH2 / \ NHZ
H
-N -(CH2)2 ~ N _427 428 I
H
~N _ (CH2)2 N \ 42~ _.- 428 I
H

_ 81 - _ Rl in Rl-H and in Ibb MS
calculated found / \

H
-N (CH2)2- p 435 436 H
-N (CH2)3-N N-CH3 i U
H
( n -N CH2)3- ~N 430 431 H
-N ~ \ CH3 H
-N ~ \ F
H
-NH- ( CH2 ) 2-COOCH3 9 0 8 4 0 9 -NH (CSHli) 392 393 -NH ( C3H~ ) -N ( CH3 ) -C9H9 3 92 3 93 -N (CZHS) z 378 379 Example 4 Analogously to Example 2, 6-chloro-benzo[de]isochromene-1,3-dione is reacted with phenylamine and then with R1-H. The following compounds of the formula Ibc are obtained:

R' i I
i ~ Ibc O ' 'O
N
i I
Rl in R -H and in Ibc MS

calculated found Ph H

-N

-N' I 342 393 N

\ /

-NH- (CH2) 3-N (CH3) 2 373 374 / \

H

/ \

-N (CH2)2 392 393 H

/ \

Sp2NH2 H

-N ~CH2}2 / \ pH

H

Rl in Rl-H and in Ibc MS
calculated found H3 vn -N (CH )2 / \ pH

H

H
i I
H
/ \
-N

-N - CH2 ~ \
H
-N CHZ / \ NH
H
N
-N (CH2)2 / ~ 393 394 H
N
-N (CH2)2 ~ \ 393 394 H
-N CH2 ~ \ 379 380 H

R in Rl-H and in Ibc MS
calculated found -N (CH2)2- O 4 01 4 02 H
-N (CH2)3- ~ -CH3 H
n -N (CH2)3- ~ 396 397 H
-NH- ( CHZ ) 2-COOCH3 37 4 37 5 -NH (C5H11) 358 359 -NH (C3H~) 330 331 -N (CH3) -CqH9 358 359 -N (C2H5) 2 344 345 -NH-CH2-CH ( CH2C1 ) -OH
-N=CH ~
HO
-NH- ( CH2 ) 5-OH 37 4 3 7 5 - p 358 359 Example 5:
Analogously to Example 2, 6-chlorobenzo [de]isochromene-1,3-dione is reacted with 3-nitrophenylamine and then with R1-H. The following compounds of the formula Ibd are obtained:

i I
i Ibd O ' 'O
N
i I

Rl in Rl-H and in Ibd MS

calculated found -N

H

-N

\ /

-NH- ( CH2 ) 3-N ( CH3 ) 418 419 -NH- ( CH2 ) 5-OH 4 7 6 4 7 7 -N CH2 / \

H

/ \

-N (CH2)2 437 438 H

-N CH2 / \ S02NH2 H

-N (CH2)2 / ~ OH

H

Ri in R -H and in Ibd MS
calculated found H ,.,. , -N (CH2)2 ~ ~ OH

H
i -H \ ~
/ ~ 449 450 -N

-N-CH / \
H
-N CH2 / ~ NH2 H
-N (CH2)2 / N 438 439 I _ H
-N (CH2)2 ~ ~ 4 3 8 4 3 9 H

H
-N (CH2)2-N p 446 447 H

H

_ 87 _ _ Rl in Rl-H and in Ibd MS
calculated found -N (CH2)3- N N- CH3 H ~--J

-N CH2)3- ~N 441 442 H

-NH- ( CH2 ) 419 4 2 0 -NH (CSHli) 403 404 -NH (CsH~) 375 376 -N (CH3) -C4H9 403 404 -N (C2H5) Z 389 390 U

Example 6:
Analogously to Example 2, 6-chlorobenzo [de]isochromene-1,3-dione is reacted with 3-methoxyphenylamine and then with R1-H. The following compounds of the formula Ibe are obtained:

i w i O ~O
Ibe N
i I

l0 - 88 _ R~ in R1-H and in Ibe MS
calculated found rn --N~CH3 H
-N 386 38?

- N ~ / 463 464 U
-NH- (CH2) 3-N (CH3) z 403 904 -N CH2 / ~ 408 409 H
-N (CH2)2 / ~ 422 423 H
-N CH2 / ~ S02NH2 H
H

-N (CH2)2 / ~ OH

I
H
-N
CH2- NH2 _ _ H

- 89 _ R' in R'-H and in Ibe MS

calculated found -N CH2 ~ ~ NHZ 423 429 H

-N (CH2)2 H

~

-N CH2 ~ 409 410 H

-N (CH2)2-N p 431 432 H

-N
CH
-N N

( 2)3 H

-NH- ( CH2 ) 2-COOCH3 4 0 4 4 0 5 -NH (C3H7) 360 361 -N (CH3) -C4H9 388 389 -N (C2H5) 2 374 375 -NH- {CH2) 5-OH 404 405 O

U

Example 7:
Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with 4-styrylphenylamine and then with R1-H. The following compounds of the formula Ibf are obtained:

Ibf Rl R1-H and in Ibf MS
in calculated found (CH2) (CH3) CH2- N Hz -N CHZ ~ ~ --H

~ ~

H

~ N

-N (CH2)2 495 496 I

H

N (CH2) i H
-N
~

-N CH2 ~ 481 482 H

Rl Rl-H in Ibf MS
in and calculated found -N (CH2)2- N p 503 504 H

N

-N (CH2)3- 530 531 i U

H

-NH-( CHZ
) -N
(CH2)3- ~N 498 499 H

Example 8:
Analogously to Example 2, 6-nitrobenzo [de]isochromene-1,3-dione is reacted with H2N-Ar and then (if necessary) with R1-H. The following compounds of the formula Ibg are obtained:

i i Ibg O ' 'O
N
Ar ~Ar R in R -H and I
IV~
\ ~N - O
U

-N
/ \

- 92 _ Ar R' in Rl-H and Ibg / \ N / \ CH3 CI H
-N
i H
/ \ O
-N
H CHs / \ C~ - ~N-s02 /-\ S~ _-H C -N N
/ \
-NH-C ( CH20H ) 3 / \ CH3 O _NOz / \

/ \

/ \ -N02 / N. - N
Example 9:
Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with 3-chloro-4-methylphenylamine and then with Ri-H. The following compounds of the formula Ibh is obtained:

i i Ibh O ' 'O
N
i l Rl in R -H and in Ibh -NH- ( CH2 ) z-N ( CZHs ) a -N
-N O
U
- ~/ _CH3 -N~CH3 H
-NH- ( CH2 ) 2-OH
Example 10:
Analogously to Example 2, 6-chlorobenzo [deJisochromene-1,3-dione is reacted with H2N-Ar and then with R1-H. The following compounds of the formula Ibi are obtained:

R~
W
Ibg O ' 'O
N
I
Ar Ar R in Rl-H and Ibg MS
calc. fnd.
Q -NH- ( CH2 ) 3-NH2 4 3 5 4 3 6 / \ -NH- ( CHZ ) s-NHZ
-NH- ( CH2 ) ~-NH2 H
-NH- (CH2) 3-NHZ 433 434 / \ -NH- (CHZ) s-NHZ
-NH- (CHZ) ~-NH2 H
V -NH- ( CHz ) 3-NH2 I -NH- (CHZ ) 5-NH2 w / \ -NH- ( CH2 ) ~-NH2 -N -cH2 H
,., ..
- 2 5 -NH- ( CH2 ) 3-NH2 4 62 4 63 \ / -NH- ( CH2 ) s-NHZ 4 90 4 91 -NH- ( CH2 ) ~-NH2 I CH2 NHz ~ ~ 524 524 H

Ar R in Rl-H and Ibg MS

talc. fnd.

-NH- (CHZ) 3-NHZ 395 396 -NH- (CH2) s-NH2 423 424 -NH- ( CHZ ) ~-NH2 4 51 4 52 -N -CHZ

H

~ -NH- (CH2} 3-NH2 395 396 -NH- (CH2} s-NH2 423 424 -NH- ( CHZ } ~-NH2 4 51 4 52 H

-NH- ( CHZ ) 3-NHZ 3 9 6 3 97 -NH- (CH2} s-NHZ 424 425 -NH- ( CH2 } ~-NH2 4 52 4 53 H

~ -NH- (CH2) 3-NH2 396 397 -NH- ( CH2 ) s-NH2 4 2 4 4 2 5 N
-NH- ( CH2 ) ~-NH2 4 52 4 53 H

Example 11:
A suspension of 4 g of 6-nitrobenzo[de]iso chromene-1,3-dione in 100 ml of toluene is treated with 3.1 g of 4-iodophenylamine and the mixture is heated under reflux. After reaction is complete, the reaction mixture is allowed to cool and is worked up as is customary. 6-Nitro-2-(4-iodophenyl)benzo[de]iso-quinoline-1,3-dione is obtained. 1.2 Equivalents of K2C03, 1.2 equivalents of Ph-B-(OH)2 and 10 mol$ of Pd((PPh}3)q are added to a solution of this compound in 80 ml of DMF and it is heated at 80°C until conversion is complete. After filtering off the catalyst and customary working up, 6-nitro-2-biphenyl-9-ylbenzo[de]isoquinoline-1,3-dione is heated with 1,3-diaminopropane until conversion is complete. After cooling the reaction mixture, it is worked up as is customary and 6-(3-aminopropylamino)-2-biphenyl-4-ylbenzo[de]isoquinoline-1,3-dione is obtained.
Analogously, by reaction of 6-nitro-2-(4-iodophenyl)benzo[de]isoquinoline-1,3-dione with Ph-B
(OH)Z and R1-H, the following compounds of the formula Ibk are obtained:

i I
w i Ibk O ' 'O
N
i I
i I
R in R -H and in Ibk -NH- ( CHZ ) s-NH2 -NH- ( CH2 ) ~-NH2 -N 'NH2 H
Example 12:
Analogously to Example 11, 6-nitro 2-(4-iodophenyl)benzo[de]isoquinoline-1,3-dione is reacted with R1°-B- (OH) 2 and R1-H. The following compounds of the formula Ibl are obtained:

R~
/ \
\ I /
Ibl O N O
/
Rio _ 97 _ Rl° R in R -H and Ibl -NH- ( CH2 ) s-NHZ
/
-NH- (CH2) s-NH2 CF3 -NH- ( CHZ ) ~-NH2 -N 'NHZ
H
/ ~ -NH- ( CH2 ) 3-NH2 CF3 _NH- ( CH2 ) s-NHZ
-NH- (CH2) ~-NH2 -N 'NHZ
H
C $ -NH- ( CH2 ) s-NH2 / ~ -NH- ( CH2 ) 5-NH2 -NH- ( CH2 ) ~-NH2 H
/ ~ -NH- ( CH2 ) s-NH2 OCF3 -NH- ( CH2 ) 5-NH2 -NH- ( CH2 ) ~-NH2 -N ~NHZ
H

_ 98 _ Rl" Rr in R -H and Ibl "__._- -NH- ( CHZ ) 3-NHZ
/ \ -NH- ( CH2 ) s-NHZ
-NH- ( CH2 ) ~-NH2 -N 'NH2 H
\ -NH- ( CH2 ) s-NH2 CH3 -NH- ( CH2 ) s-NH2 -NH- ( CH2 ) ~-NH2 -N 'NH2 H
/ \ -NH- ( CH2 ) 3-NHZ
OCH3 -NH- (CHZ) 5-NH2 -NH- ( CHZ ) ~-NH2 -N 'NH2 H
Vl:l-13 -NH- ( CH2 ) 3-NH2 -NH- ( CH2 ) s-NHZ
/ \
OCH3 -NH- ( CH2 ) 7-NHZ
-N 'NH2 H
/ \ -NH- (CH2) 3-NH2 -NH- (CH2) s-NH2 -NH- ( CH2 ) ~-NH2 -N 'NH2 H
-NH- ( CH2 ) 3-NH2 -NH- ( CHZ ) s-NH2 / \ -NH- ( CH2 ) ~-NHZ
-N ~NHZ
H

Rl" R1 in R -H and Ibl -NH- ( CHz ) 3-NHz -NH- ( CHz ) s-NHz N02 -NH- ( CHz ) ~-NHz -N 'NH2 H
/ ~ -NH- ( CHz ) 3-NHz -CH3 _NH_ ( CHz ) s-NHz N02 NH ( CHz ) 7-NHz -N 'NHZ
H
~ -NH- ( CHz ) 3-NHz -NH- ( CHz ) s-NHz -NH- ( CHz ) ~-NHz -N 'NHZ
H
~ -NH- ( CHz ) 3-NHz -NH- ( CHz ) s-NHz CI -NH- ( CHz ) ~-NHz -N 'NHz H
Example 13:
Analogously to Example 11, 6-vitro 2-(3-iodophenyl)benzo[de]isoquinoline-1,3-dione is reacted with R1°-B- (OH) z and R1-H. The following compounds of the formula Ibm are obtained:

WO 00/32577 PCT/EP99/0$561 Ri / \
\
Ibm O " O
N
/
R~ \

Ry" Rl in R -H and Ibm \ -.._ -NH- ( CH2 ) s-NHZ
-NH- ( CH2 ) s-NH2 -NH- ( CH2 ) ~-NH2 -N 'NHZ
H
-NH- ( CH2 ) 3-NH2 _ \
CF3 -NH_ ( CH2 ) s-NH2 -NH- ( CH2 ) ~-NH2 -N 'NHZ
H
~r3 -NH- (CH2) 3-NHZ _ \ -NH- ( CH2 ) s-NHZ
-NH- ( CH2 ) ~-NHZ

H
\ -NH- ( CH2 ) 3-NH2 __ OCF3 _NH_ (CH2) s-NH2 -NH- ( CH2 ) ~-NH2 -N ~NHZ
H

Ry" R~ in Rl-H and Ibm s ~ -NH- ( CHz ) 3-NH2 / \ -NH- ( CH2 } s-NHz -NH- ( CHZ ) ~-NHZ
-N 'NH2 H
-NH- ( CH2 ) 3-NH2 / \ CH3 -NH_ ( CH2 ) s-NH2 -NH- ( CH2 ) ~-NHZ
-N 'NH2 H
/ \ -NH- ( CH2 ) s-NH2 OCH3 _NH_ (cH2) 5-NH2 -NH- ( CH2 ) ~-NH2 -N 'NH2 H
UCal3 -NH- ( CHZ } 3-NH2 -NH- ( CHz ) s-NHZ
/ \
OCH3 -NH- ( CH2 ) ~-NH2 -N 'NHZ
H
/ \ -NH- (CH2) s-NH2 -NH- (CHZ) s-NH2 -NH- ( CH2 ) ~-NHZ
-N 'NH2 H
-NH- ( CHZ ) a-NH2 -NH- ( CHZ ) s-NH2 / \ -NH- ( CH2 ) 7-NH2 -N ~NHZ
H

- 7(72 -Ry" Rl in R -H arid Ibm -NH- ( CHz ) 3-NH2 -NH- ( CHz ) s-NH2 NO2 -NH- (CH2) ~-NHZ
-N 'NH2 H
-NH- ( CH2 ) s-NH2 CH3 _NH_ (CH2) s-NH2 N02 NH (CH2) ~-NHZ
-N 'NH2 H
/ ~ -NH- ( CH2 ) 3-NH2 -NH- ( CH2 ) s-NHZ
-NH- (CH2) ~-NH2 -N 'NH2 H
-NH- ( CH2 ) 3-NH2 _ -NH- ( CH2 ) s-NH2 CI -NH- ( CH2 ) ~-NH2 -N 'NH2 H
~ -NH- ( CH2 ) 3-NH2 -NH- ( CH2 ) s-NH2 -NH- ( CH2 ) ~-NHZ
-N 'NH2 H
Example 14:
Analogously to Example 11, 6-vitro-2-(3-iodo-4-methylphenyl)benzo[de]isoquinoline-1,3-dione is reacted with R1°-B- (OH) 2 and Rl-H. The following compounds of the formula Ibn are obtained:

R~
/
Ibn O ' 'O
N
R~

R R in R -H and Ibn -NH- ( CHz ) s-NH2 -NH- ( CH2 ) s-NH2 -NH- ( CH2 ) ~-NHZ
-N 'NH2 H
-NH- ( CH2 ) s-NH2 OCH3 -NH- (CHZ) s-NH2 -NH- ( CHZ ) ~-NH2 -N 'NH2 H
~ -NH- ( CH2 ) s-NH2 CH3 -NH- ( CH2 ) s-NHz N02 -NH- ( CH2 ) ~-NH2 -N 'NH2 H
/ ~ -NH- ( CHZ ) 3-NH2 -NH- ( CH2 ) s-NH2 H3C -NH- ( CH2 ) 7-NH2 -N 'NHZ
H

Example 15:
Analogously to Example 11, 6-nitro-2-(4-iodo-3-methylphenyl)benzo[de)isoquinoline-1,3-dione is reacted with R1°-B- (OH) 2 and R1-H. The following compounds of the formula Ibo are obtained:
R~
Ibo O " O
N
H3C ~
Rio R R in R -H and Ibo -NH- ( CH2 ) 3-NH2 -NH- (CHZ) s-NHZ

-NH- (CH2) ~-NHZ

-N 'NH2 H

-NH- ( CH2 ) 3-NH2 OCH3 -NH- ( CH2 ) 5-NH2 -NH-~ ( CH2 ) ~-NH2 H

/ ~ -NH- ( CH2 ) 3-NH2 CH3 -NH- ( CH2 ) s-NHZ

N02 -NH- (CH2) ~-NH2 -N 'NH2 H

R " R in R -H and Ibo -NH- ( CH2 ) s-NH2 -NH- ( CH2 ) s-NH2 C -NH- ( CHZ ) ~-NH2 -N 'NH2 H
Example 16:
Analogously to Example 2, 6-nitrobenzo[de]iso chromene-1,3-dione is reacted with H2N-Hetl. The following compounds of the formula Ic are obtained:

i i Ic O ' '-O
N
Het1 Het R in Ic ~N.N _NO2 S

~.N -NO2 Example 17:
Analogously to Example 2, 6-nitrobenzo[de]iso chromene-1,3-dione is reacted with H2N-Hetl-Ar. The following compounds of the formula Id are obtained:

i i Id O ' 'O
N
Het1-Ar Het R in Id S
i I
-NOz N ~ I
S
O / -NOz N
N ~ CH3 Example 18:
Analogously to Example 2, 6-nitrobenzo[de]iso chromene-1,3-dione is reacted with 2-(3-amino phenyl)acetamide and then with R1-H. The following compounds of the formula Iea are obtained:

i I
i lea O ' 'O
N
i I
H2N ~ O

R' in R'-H and in Iea MS

calculated found -N - CH2 ~ \

H

-N (CH2)2 N \
i H

-N CH -N~N 455 456 ( 2)3 H

-NH- (CH2) 3-N (CH3) 430 431 -NH- ( CH2 ) q-NH2 -NH- (CH2) ~-NH2 458 459 -NH- (CHz) 8-NHZ 472 473 N-(CH2)2 -N-C 444 445 H H

Example 19:
Analogously to Example 2, 6-nitrobenzo[de]iso chromene-1,3-dione is reacted with 2-(4-amino phenyl)acetamide and then with R1-H. The following compounds of the formula.Ieb are obtained:
R~
i I
i leb O ' '_O
N
i I
O

Rl in Rl-H and in Ieb MS

calculated found -N \CH3 H

\ /

-NH- ( CH2 ) 5-OH

-NH- ( CH2 ) 3-N ( CH3 ) 4 3 0 4 31 z -N CH2 / \

H

/ \

-N (CH2)2 449 450 H

/ \

H

/ \

-N (CH2)2 H

-N O

U

-NH- ( CH2 ) 2-COOCH3 4 31 4 32 -N -CH2 / \

H

-N CH2 / \ NH

H

Rl in R1-H and in Ieb MS

calculated found .

N \
N (CH2)2 H

-N CH2 N \

i H -~ N
) H

N (C

H

-N (CH2)2-N O 458 459 H

C
-N N

HZ)3 CH3 -N ( -H

n -N (CH2)3- ~ 455 456 H

-NH (CSHli) -NH (C3H~) 387 388 -NH- ( CH2 ) s-NH2 -.NH- ( CH2 ) ~-NH2 4 58 4 5 9 Example 20:
Analogously to Example 2, 6-nitrobenzo[de]iso chromene-1,3-dione is reacted with 3-aminobenzamide and then with R1-H. The following compounds of the formula Iec are obtained:

i I
~ lec O ' \O
N
i O

Rl in Rl-H and in Iec MS
calculated found Nh -N ~CH3 H
-N
-N
\ /
-NH- ( CH2 ) 5-OH
-NH- ( CHZ ) 3-N ( CH3 ) z 416 417 -N CH2 / \
H
-N (CHZ)2 / \
H
-N CH2 / \ S02NH2 H

R in R -H and in Iec MS

calculated found -N (CH2}2 ~ \ OH 4 51 H

-N O

-NH- ( CH2 ) 2-COOCH3 417 418 -N - CH2 ~ \

H

-N CH2 ~ \ NH2 H

\

-N (CH2)2 / 436 437 H

-N CH2 ~ \

H

N (CHZ)2 I

H

'N (CH2)2-N Q 444 445 I
H

-N
CH
N

( 2)3-N

H

-N (CH2}3-N

~
H

-NH ( C5H11 ) WO 00/325'17 PCT/EP99/08561 - ~i~ _ ' R in R -H and in Iec MS
calculated found -NH ( C3H~ ) -NH- ( CHz ) s-NHz -NH- ( CHz ) ~-NHz Example 21:
Analogously to Example 2, 6-nitrobenzo[de]iso chromene-1,3-dione is reacted with 4-(4-amino phenyl)butyramide and then with R1-H. The following compounds of the formula Ied are obtained:

i I
i led O ' '_O
N
i I
(C~2)3 R' in R -H and in Ied MS
calculated found -NH- ( CHz ) 9-NHz -NH- ( CHz ) ~-NHz 9 8 6 4 8 7 -NH- (CHz) e-NHz 500 501 N -(C H2)2 -' N ~ 4 5 8 4 5 9 H H

-NH- ( CHz ) 3-N ( CH3 ) z -N (CH2)3-i H

Rl in Ri-H and in Ied MS
calculated found / \ 478 -479 N (CHZ)2 H
-N -CH / \
H
Example 22:
Analogously to Example 2, 6-nitrobenzo[de]iso chromene-1,3-dione is reacted with 3-(3-aminophenyl) propionamide and then with R1-H. The following compounds of the formula Iee are obtained:

i i lee O ' '-O
N
i Rl in Rl-H and in Ms R in R -H and in Iee Ms talc. fnd. talc.
Iee fnd.

p - 429 430 -NH- (CH2) 3-NH (CH3) 430 -N 427 428 N-(CH2}2 -N--' 444 v -N~ 413 414 -\-/

- N 505 -j N-CH 518 504 ~ \

\ ~ 2 U

R~ in Rl-H and in Ms R in R -H and in Iee Ms calc. fnd. calc.
Iee fnd.

rm ~ iv-_N~CH -N N \ ~

3 \-/
H

-NH- ( CH2 ) 2-COOMe ~ N-N

/ \

NH
CH
-CH

2)3---NH2 5 4 _ 3 2)3 ~N-( -( /
\

-N -(CH2)2 4 gg H

~ \

-N -cH, - 4 4 sozNH~ H- ( CH2 ) 2-NH- ( 6 N CH2 ) 2-H

\

-N -(CHs)z ~ -NH- ( CH2 ) 2-NH ( ~H C3H~ ) H

-NH- ( CH2 ) 5-OH

-NH-(CHz)~-O-(CHz),-O-(CHz)r546 NHz 5 4 -N (CH3) - (CH2) 3- 444 -N (CH3) - (CHZ) 2- 472 NH (CH3) N (C2H5) Z 473 -NH- (CH2) 3-N (CH3) 2 -NH-(CH2)3 N 498 H

1it121V fit -N-CHZ / \ NHs 484 H

CHs-NHi -N-pH, / \ -NH-(CHZ)3-N(CH3)-(CHZ)3-487 R1 R~ and in Ms R in R -H and in Iee Ms in Iee calc. calc.
fnd.

fnd.

-N (CH2)2 ~ ~ 4 64 -NH- ( CHZ ) 2-NH ( 4 30 C2H5 ) -N- (CH2)2 ~ ~ -N
CH
O

( 2)z-N

H H U

-N ~ C
~ --- CH2 450 451 ( 499 HZ)3- ~ -CH3 N

- H

-N- (CH2)3-N

~ 469 470 H N

-H- ( CH2 ) 5-NH2 -NH Hli ) -NH- ( CHz ) ~-NH2 4 72 ( CS

-NH H~ ) -N -CH2 ~
( ~ CH2 NH2 _ H

Example 23:
Analogously to Example 2, 6-nitrobenzo[de]iso-chromene-1,3-dione is reacted with 3-amino-4-methoxybenzarnide and then with R1-H. The following compounds of the formula Ief are obtained:

i I
lef O ' '-O
N

w R1 in R -H and in Ief MS
calculated found -NH- ( CH2 ) q-NH2 -NH- ( CHZ ) ~-NH2 -NH- ( CH2 ) a-NHz 4 8 8 4 8 9 N -(CH2)2- N ---~ 4 6 0 4 61 H H
-NH- ( CHZ ) s-N ( CH3 ) 2 (CH )3 ~
i H
.-N (CH2)2 % \
H

-.N -CH / \
H
Example 24:
Analogously to Example 2, 6-nitrobenzo[de]iso-chromene-1, 3-dione is reacted with H2N-Ar' - (CH2) n-R3 and then (if necessary) with R1-H. The following compounds of the formula Ieg are obtained:
R~
i I
i leg O ' 'O
N
Ar'-(CH2)~ R3 Ar' - (CH2) n-R' R' in Rl-H and in Ieg MS
calc. fnd.

~ N _N02 N-'CH3 -NH- ( CH2 ) ~-NH2 514 515 ~CH2~2~~C3H~ CH2 NH2 H ~ \ 520 521 H

t. (CH2)3-N~/
H
-NH- (CH2) ~-NHZ 542 543 ~CH2~~N-C5H11 / \ H CHZ NH2 H

-N (CH2)3-N~
H

Example 25:
Analogously to Example 11, 6-nitro-2-(3-iodophenyl)benzo[de]isoquinoline-1,3-dione or 6-nitro-2-(4-iodophen;~l)benzo[de]isoquinoline-1,3-dione is reacted with R3- (CH2) n-Ph-B- (OH) z and R1-H. The following compounds of the formula Ieh (Ph-Ph=Ar') are obtained:
R~
i I
i ~ leh ' 'O
N
Ar'-(CH2)~-R3 -Ar' - (CH2) n-R R in R -H and Ieh / \ / \ -NH- ( CH2 ) 3-NH2 COOH
-NH- ( CH2 ) s-NH2 -NH- ( CH2 } ~-NHZ
-N ~NHZ
H
/ \ / \ -NH- ( CH2 ) 3-NH2 COOH
-NH- ( CHa ) s-NH2 -NH- ( CH2 ) ~-NH2 -N ~NH2 H
/ \ / \ " -NH- ( CH2 ) s-NH2 U ~OCH3 -NH- (CH2) s-NH2 -NH- ( CH2 ) ~-NH2 -N ~NHZ
H

-Ar' - (CH2) n-R' R1 in R -H and Ieh / \ / \ -NH- (CHZ ) 3-NH2 OCH3 -NH- ( CH2 ) 5-NH2 -NH- ( CH2 ) ~-NH2 -N 'NH2 H
a -NH- ( CHZ ) 3-NH2 _ ~CH3 -NH- ( CHz ) s-NH2 / \ / \ -NH- ( CH2 ) ~-NH2 a -N 'NH2 H
V -NH- ( CH2 ) a-NH2 ~?CH3 -NH- ( CH2 ) 5-NH2 / \ / \
-NH- ( CH2 ) ~-NH2 -N 'NH2 H
Example 26:
Analogously to Example 2, 6-nitrobenzo[de]iso chromene-1,3-dione is reacted with 2-(4-aminophenyl sulfanyl)acetamide and then with R1-H. The following compounds of the formula Ifa are obtained:
R~
i I
i Ifa O ' 'O
N
i Rl in Rl-H and in Ifa MS

calculated found -NH- (CH2) q-NH2 448 449 -NH- ( CH2 ) ~-NH2 4 90 4 91 -NH- ( CHZ ) e-NH2 N -(C H2)2 '- N '-"'C 4 7 6 4 7 7 H H

-NH- ( CH2 ) s-N ( CH3 ) 2 -N
(CH2)3- ~N 487 488 H

w -N (CH2)2 ~ \
i H

-N - CH2 / \

H

Example 27:
Analogously to Example 2, 6-nitrobenzo[de]iso chromene-1,3-dione is reacted with 2-(4-amino phenoxy)acetaamide and then with R1-H. The following compounds of the formula Ifb are obtained:

i i Ifb O ~O
N
i I

to R' in Rl-H and in Ifb MS
calculated found -NH- ( CH2 ) a-NH2 _ -NH- ( CH2 ) ~-NHZ 4 7 4 4 7 5 -NH- ( CH2 ) e-NH2 4 8 8 4 g 9 N -(CH2)2 N ~ 4 60 4 61 H H
-NH- (CH2) 3-N (CH3) 2 446 447 -N (CH2)3-NON 4 71 H
-N (CH2)2 ~ \
i H

-N - CH2 / \
H
Example 28:
Analogously to Example 2, 6-nitrobenzo[de]iso chromene-1,3-dione is reacted with 5-(piperidine 1-sulfonyl)naphthalen-1-ylamine and then with R1-H. The following compounds of the formula Ig are obtained:

i I
i Ig O N O
i I
i R' in R1-H and in Ig MS

calculated found -NH- (CH2) 3-NH2 542 543 -NH- ( CHZ ) 5-NHZ 57 0 5? 1 -NH- ( CH2 ) ~-NH2 H

Example 29:
Analogously to Example 2, 6-nitrobenzo[de]iso-chromene-1, 3-dione is reacted with H2N-Ar' -S02-R' and then with Rl-H. The following compounds of the formula Ih are obtained:

i I
i Ih O ~O
N
Ar'-S02-R7 WO 00/3257? PCT/EP99/08561 Ar' -S02-R' RI in R -H and in Ih MS
calc. fnd.
-NH- ( CH2 ) 3-NHZ 5 8 4 5 8 5 ~ -NH- ( CHZ ) 5-NH2 612 613 -NH- ( CH2 ) ~-NH2 ~~2 -N-CH2 / \
N H
H~C2 -NH- (CH2) 3-NH2 544 545 ~ -NH- (CHZ) 5-NHZ 572 573 -NH-(CH2)~-NH2 600 601 ~~2 -N-CH2 / \
H
H3C /N\C4H9 -NH- ( CH2 ) 3-NH2 516 517 ~ -NH- (CH2) 5-NH2 594 545 -NH- ( CH2 ) z-NHZ

~~2 -N -CH2 / \
H
H3C /N\C2H5 Example 30:
Analogously to Example 2, 6-nitrobenzo[de]iso chromene-1, 3-dione is reacted with HZN-C6Hq- (CH2) 2-CONH
(CHZ)i-NH2 and then with Rl-H. The following compounds of the formula Ii are obtained:

O' 'nn ~ O
(CH2)2-CONH-(CH2)i-NH2 ~ i Rl in Rl-H and in Ii MS
calc. fnd.
'~ 4 -NH- (CHZ) 7-NH2 543 544 CHZ- NHZ
/ \ 549 550 H
2 -NH- ( CH2 ) ~-NHz 515 516 -N - CH2 / \
H
Example 31:
Analogously to Example 2, 6-nitrobenzo[deJiso-chromene-1, 3-dione is reacted with HZN-C6H4- (CH2) 2-CONH-CH2-C6H11 and then with Ri-H. The following compounds of the formula Ika are obtained:

i i Ika O ' '-O
N
i {CH2)2-CONH-CH2 iR in R -H and in Ika MS
calculated found -NH- (CH2) ~-NH2 568 564 H
Example 32:
Analogously to Example 2, 6-nitrobenzo[de]iso chromene-1, 3-dione is reacted with H2N-C6H4- (CHZ) 2-CONH
(CH2) 2-C6H9 and with H2N- (CH2) 5-NH2. One equivalent of tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl methyl)carbamate is then added to a solution of 3 (3-[6-(5-aminopentylamino)-1,3-dioxo-1H,3H
benzo[de]isoquinolin-2-yl]phenyl)-N-(2-cyclohex-1-enylethyl)propionamide in 60 ml of DMF and, after reaction is complete, the BOC protective groups are removed by addition of TFA in 1,2-dichloroethane.
N-(2-Cyclohex-1-enylethyl)-3-(3-[6-(5-guanidinopentyl-amino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl)propionamide is obtained.
The following compounds of the formula Ikb are obtained analogously by reacting H2N-C6H4- (CH2) 2-CONH-(CH2)2-C6H9 with the appropriate diamine in each case and tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl methyl)carbamate and removing the protective groups:
R~
ikb O ' 'O
N
(CH2)2-CONH-(CHZ 2 R in Ikb -NH- ( CH2 ) 5-NH-C ( =NH ) -NH2 -NH- ( CH2 ) 2-NH-C (=NH } -NH2 --NH- ( CH2 ) ~-NH-C ( =NH ) -NH2 CH2 NI 'NH2 H

H
-N - CH2 ~-~ CH2-N "NH2 i H H
-NH- (CH2) 3-NH-C (=NH) -NH2 -NH- ( CHz ) 3-N ( CH3 ) - ( CHz ) 3-NH-C (=NH ) -NHz -N-CH2 CH2-NI 'NHZ
H H
-NH- ( CH2 ) 6-NH-C (=NH } -NH2 -NH- ( CH2 ) 4-NH-C ( =NH ) -NH2 Example 33:
Analogously to Example 2, 6-nitrobenzo[de]iso chromene-1, 3-dione is reacted with H2N-C6H4- (CH2) 2-CONH
(CH2)i-Ar and then with Rl-H. The following compounds of the formula Ila are obtained:

i i Ila O
i I
(CH2)2-CONH-(CH2)~ Ar -C6H4- (CH2) Z-CONH- R' in Rl-H and in Ila Ms ( CH2 ) i-Ar calc. fnd.
N -NH- (CHZ) ~-NH2 _ _. _ _.
(CH~i -CONH-CHs H

-N (CH2)3-N~
i H
(CH ) -CONH~N~CH~ NH- ( CH2 ) ~-NH2 5 91 5 92 2 2 \ / CHs / \

-N - CHZ
H
(CH2)2-CONH \ / \ / -NH- (CH2) ~-NHZ 624 625 -N - CHZ
H

N (CH2)3 N~
H
-NH- (CH2) ~-NH2 596 597 (CH2)2-CONH-CH2 \ / CI
\ CH2- NH2 H
Example 34:
Analogously to Example 32, 6-nitro benzo [de] isochromene-1, 3-dione is reacted with H2N-C6H4 ( CH2 ) 2-CONH- ( CHZ ) 3-C6H5 i the appropriate diamine in each case and (if necessary) with tert-butyl (tert butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formula Ilb are obtained:

R' i I
w i Ilb O ' '-O
N
i I
/ \
(CH2)2-CONH-(CH2)3 Rl in Ilb MS
calculated found -NH- ( CH2 ) ~-NH2 _ _ CH2- 2 596 597 H
-NH- (CH2) 5-NH-C (=NH) -NH2 604, 8 605, 3 -NH- (CH2) 2-NH-C (=NH) -NH2 562, 7 563, 6 -NH- (CH2 ) ~-NH-C (=NH) -NH2 632, 8 633, 4 NH
CH2 N"NH2 649,8 645,5 . H
-N-CHZ ~ ~ CH2 N~NHZ 638, 8 . 639, 5 H H
-NH- (CH2) 3-NH-C (=NH) -NHZ 5?6, 7 577, 5 -NH- (CHz) 3-N (CH3) - (CHz) 3-NH- 647, 8 648, 4 C(aNH)-NHz -N-CH2 CH2 NI 'NHZ 644, 8 645, 7 H H
-NH- ( CH2 ) 6-NH-C ( =NH ) -NH2 -NH- (CH2) 4-NH-C (=NH) -NH2 590, 7 591, 7 Example 35:
Analogously to Example 32, 6-nitro-benzo [de] isochromene-1, 3-dione is reacted with HZN-C6H4-(CHZ) 2-CONH- (CH2) 2-C6Hq-S02-NH2, the appropriate diamine in each case and tert-butyl (tert-butoxycarbonyl-iminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formula Ilc are obtained:

i I
i Ilc O ' '-O
N
i I
(CH2)2-CONH-(CH2)2 / \ SO -NH
Rl in Ilc MS
calculated found -NH- (CH2} 5-NH-C (=NH) -NHZ 669, 8 670, 5 -NH- (CHZ) 2-NH-C (=NH) -NH2 627, 7 628, 4 -NH- (CH2) ~-NH-C (=NH) -NH2 697, 9 698, 5 rvn CH2 NI 'NHZ
H

H
-N-CH2 ~-~ CH2 N"NH2 H H
-NH- (CH2) 3-NH-C (=NH) -NHZ 641, 8 642, 3 -NH- ( CHZ ) 3-N ( CH3 ) - ( CHZ ) 3-NH-C(=NH)-NHZ
-N-CH2 CH2 N"NHz H H

R' in Ilc MS

calculated found -NH-(CH2)6-NH-C(=NH)-NH2 683,8 684,4 -NH- (CH2) 4-NH-C (=NH) -NHZ 655, 8 656, 4 -N (CH2)3 N NHZ
655,8 656,4 " 703 704 ~ ~ 8 0 N , , -N-(CH ) ~ H
H

iv ri2 - N 653,8 654,5 \..-/ NH

ivn2 -N-CH2 N-~ 681, 8 682, 5 NH

Example 36:
Analogously to Example 32, 6-nitro-benzo [de) isochromene-1, 3-dione is reacted with H2N-C6H4-(CH2)2-CONH-C6H5, the appropriate diamine in each case and tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl-methyl)carbamate. After removal of the protective groups, the following compounds of the formula Ild are obtained:

i w I
i Ild O ' '-O
N
i l / \
(CH2)2-CONH

Rl in Ild MS
calculated found -NH- (CHZ) 5-NH-C (=NH) -NH2 562, 7 563, 3 -NH- (CH2) 2-NH-C (=NH) -NH2 520, 6 521, 3 -NH-(CHZ)~-NH-C(=NH)-NH2 590,7 , 591,4 mn CH2 NI 'NH2 602,7 603,4 H
-N-CH2 ~ ~ CH2 N"NHZ 596, 7 597, 3 i H H
-NH- (CH2) 3-NH-C (=NH) -NHz 534, 6 535, 3 -NH-(CH2}3-N(CH3)-(CHZ)3-NH- 605, 7 606, 4 C(=NH)-NHZ
~ 602,7 603,4 -N-CHZ CH2 N_ 'NH2 H H
-NH- (CH2) 6-NH-C (=NH) -NH2 576, 7 577, 3 -NH- (CHZ) 9-NH-C (=NH) -NH2 548, 6 549, 3 -N (CH ) N~NH 548, 6 549, 5 i 23 ~ 2 w 596,7 597,0 -N - (CH ) / \ N NH2 H H
NH2 _.
-N N--~ 546, 6 547, 7 NH
iv n2 -N-CH2 N--~ 574, 7 575, 5 NH
Example 37:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with / I
CH2)2-CONH-(CH2)i H2N / \
the appropriate diamine and tert-butyl (tert-butoxy-carbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formulae Ilea-Ilef are obtained:

i i Ilea O ' 'O
N
i I
/ \
(CH2)2-CONH-(CH2) CI
Rl in Ilea MS

calculated found -NH- (CH2) 5-NH-C (=NH) -NHZ625, 2 625, 3 ~NH- (CH2) 2-NH-C (=NH) -NH2583, 1 583, 2 -NH- (CH2) ~-NH-C (=NH) -NH2653, 2 653, 3 N"NH

CH2 665,2 665,4 H

~ 659,2 659,3 NI _NH
~ ~

Z

i H H

-NH- (CH2) 3-NH-C (=NH) -NH2597, 1 597, 3 -NH- (CHZ) 3-N (CH3)- (CH2) 668, 2 668, 3 C(=NH)-NHZ

WO 00/32577 PCTlEP99/08561 R' in Ilea MS

calculated found N~
-N~NH
--N-CH 6 , 665, 4 z H H

-NH- (CH2) 6-NH-C (=NH) -NH2 639, 2 639, 4 -NH- (CH2) 9-NH-C (=NH) -NH2 611,1 611, 3 ~

-N CH N 611, 1 611, 6 NH
( 2)3 , I ' 659 659 ~ ~ 2 0 N , , NH
-N - CH
~ 2~2 H H
_ _ __ 609, 1 609, 6 - N-.~ 2 ./ NH

iv n2 -N-CH2 N-~ 637, 2 637, 6 NH

i w I
i Ileb O ' '_O
N
i (CH2)2-CONH-(CH2)2 CI
R~ in Ileb MS

calculated found -NH- (CH2) 5-NH-C (=NH) 625, 2 625, 3 -NH= (CHZ) 2-NH-C (=NH) 583, 1 583, 3 -NHZ

-NH- (CH2) ~-NH-C (=NH) 653, 2 653, 4 Rl in Ileb MS

calculated found CH2-NI 'NHZ
665,2 665,4 H

/ \
-N-CH2~CH2-N NHZ 659, 2 659, 3 H H

-NH- (CH2) 3-NH-C (=NH) -NH2 597, 1 597, 3 -NH- (CHZ) 3-N (CH3) - (CHZ) 668, 2 668, 3 C(=NH)-NHZ

~ 665,2 665,3 -N -CH2 CH2-N- 'NHZ
i H H

-NH- (CHZ) 6-NH-C (=NH) -NH2 639, 2 639, 4 -NH- (CHz) 9-NH-C (=NH) -NH2 611, 1 611, 3 N I~

-N (CH ) N_ _NH 611, 1 611, 6 i 23 , -N - CH ~ ~ N- 'NH 659, 2 659, 2 ~ 2)2 H H

N
-N N-~ 2 609, 1 609, 6 NH

n -N-CH2 N--~ 2 637, 2 637, 6 H NH

R' i i Ilec O "
H-(CH2)2 / ~ CI
Rl ~in Ilec MS
calculated found -NH- (CHZ) 5-NH-C (=NH) -NH2 625, 2 625, 4 -NH- (CH2) 2-NH-C (=NH) -NH2 583, 1 583, 4 -NH- (CH2) ~-NH-C (=NH) -NH2 653, 2 653, 5 CH2 NI 'NHZ
665,2 665,4 -N -CHZ
H
-N-CH2 ~_~ CH2 H NHZ 659, 2 659, 4 H
=NH- (CH2) 3-NH-C (=NH) -NH2 597, 1 597, 3 -NH-(CHZ)3-N(CH3)-(CHz)3-NH- (68,2 668,4 C(=NH)-NHZ
-N-CH2 CH2 NI 'NH2 665, 2 665, 4 i H H
-NH- (CH2) 6-NH-C (=NH) -NH2 639, 2 639, 5 -NH- (CH2) 4-NH-C (=NH) -NHZ 611, 1 611, 4 -N CH N~NH 611,1 612, 4 ~ 2~3 - 1 ~H -Rl in Ilec MS

calculated found / \ N- 'N 2 (CH ) , H 659, 2 H H

-N
-N N-~ 2 609 , , NH

'~' ~2 -N-CH2 N--~ 637, 2 637, 5 NH

R' i I
i Iled O ' 'O
i CI
I
/ \
(CH2)2-CONH
Rl in Iled MS

calculated found =NH- ( CH2 ) 5-NH-C ( =NH
) -NHZ

-NH- (CH2) Z-NH-C (=NH) -NHZ 555, 555, 4 -NH- (CH2) ~-NH-C (=NH) -NH2 625, 625, 3 CH2 N"NH2 637, 637, 4 -N .-CH2 H

-N -CH2 ~ ~ CH2-N"NHZ 631, 631, 3 -NH- (CH2) 3-NH-C (=NH) -NH2 569, 569, 3 -NH-(CHZ}3-N(CH3}-(CHZ)3-NH- 640,2 640,3 C(=NH)-NHZ

R' in Iled MS

calculated found N"NH 637 637 Z , , H H

-NH- (CHZ) 6-NH-C (=NH) -NH2 611, 1 611, 3 -NH- (CH2) 4-NH-C (=NH) -NH2 583, 1 583, 3 -N (CH ) N- _NH 583,1 583, 4 i ~ 631,1 631,2 ~ ~ NI 'NH

-N - CH
( 2)2 H H
_.

NH2 581,1 581, 3 -N N--~

NH

iV t"12 -N-CH2 N-~ 609, 1 609, 3 NH

i i Ilee O ' 'O
N
i I
/ \
(CH2)2-CONH-CH2 CI
R~ in Ilee MS

calculated found -NH-(CH2)5-NH-C(=NH)-NH2 611,1 611,4 -NH- (CH2) 2-NH-C (=NH) -NHz 569, 1 569, 4 -NH- (CH2) ~-NH-C (=NH) -NH2 639, 2 639, 3 N"NH

Z
CHZ 651,2 651,5 H

-N-CH2 ~ 645, 2 645, 4 ~ CH2 NI 'NHZ

_ H H

-NH-(CH2)3-NH-C(=NH)-.NH2. 583,1 583,5 -NH-(CHZ)3-N(CH3}-(CHZ)3-NH- 654,2 654,2 C(=NH)-NHZ

-N -CH2 CH2 NI 'NH2 651, 2 651, 6 H H

-NH- (CHZ} 6-NH-C (=NH) -NH2 625, 2 625, 3 -NH- (CH2) 9-NH-C (=NH) -NH2 597, 1 _ 597, 4 -N
CH
"

( ) N
NH

Rl in Ilee MS
calculated found NH _ _ -N - CH ~ ~ N"NH2 ( 2)2 H
H

~/ '~'~NH
iv n2 NH
R' i I
i clef O ~O
N
(CH2)2-CONH ~ ~ CI
Rl in Ilef MS
calculated found -NH- (CH2) 5-NH-C (=NH) -NH2 597,1 597, 2 -NH- (CH2) 2-NH-C (=NH) -NH2 555, 0 555, 3 -NH- (CH2) ~-NH-C (=NH) -NH2 625, 2 625, 3 CHZ N"NH2 637, 2 637, 2 H
-N-CH2 ~-~ CH2 N NHZ 631, 1 631, 3 H H
-NH- (CH2) 3-NH-C (=NH) -NH2 569, 1 569, 3 -NH-(CH2)3-N(CH3)-(CHZ)3-NH- 640,2 640,2 C(=NH)-NHZ

R in Ilef MS

calculated found -N"NH 637 637 Z , , H H

-NH- (CH2) 6-NH-C (=NH) -NH2 611, 1 611, 3 -NH- (CH2) 9-NH-C (=NH) -NHZ 583, 1 583, 3 Example 38:
Analogously to Example 32, 6-nitro benzo [de] isochromene-1, 3-dione is reacted with H2N-C6Hq (CH2)2-CONH-CH2-Ar, the corresponding diamine and tert butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl) carbamate. After removal of the protective groups, the following compounds of the formula Ilfa are obtained with H2N-C6H9- ( CH2 ) 2-CONH-CH2-CloH~
R~
/ \
\
Ilfa O ' 'O
N
. / [
(CHZ)2-CONH-CH2 R in Ilfa MS

calculated found -NH- ( CH2 ) 5-NH-C (=NH 62 6, 8 62 7 , 3 ) -NH2 -NH- (CH2) 2-NH-C (=NH) 584,7 585, 3 -NH- (CH2) ~-NH-C (=NH) 654, 8 655, 4 R1 in Ilfa MS

calculated found N"NH

CH2 666,8 667,4 H

NH -NI 'NH 660 661 ~ 8 3 ~

Z , , ~
i H H

-NH- (CHZ) 3-NH-C (=NH) -NH2 598, 7 599, 3 -NH- (CHz) 3-N (CH3>- (CHzI3-NH-669, 8 _ -670, 4 C(=NH)-NHz m~
-N"NH 666, 8 667 Z , -H H

-NH- (CH2) 6-NH-C (=NH) -NHz 640, 8 641, 4 -NH- (CH2} 9-NH-C (=NH) -NH2 612, 7 613, 3 -N (CH ) N"NH 61 23 2.7 613,6 ~

" 660 661 ~ ~ 8 0 N , , NH
-N - CH
z ( 2)2 ~
H H

-[ ~ j-.~ 2 610, 7 611, 6 NH

m n2 -N-CH2 N--~ 638, 8 639, 6 NH

After removal of the protective groups, the following compounds of the formula Ilfb are obtained with H2N-C6Hq- (CHZ) 2-CONH-CH2-C9H9:

R~
i~
m o ~o N
i (CH2)2-CONH-CH2 R' in Ilfb MS

calculated found -NH- (CHZ) 5-NH-C (=NH) -NH2602, 7 603, 3 -NH- (CH2) 2-NH-C (=NH) -NH2560, 7 561, 4 -NH- (CH2) ~-NH-C (=NH) -NH2630, 8 631, 3 NI 'NH

Z
CH2 642,8 643,5 H

N"NH 636, 8 637, 3 ~ ~

i H H

-NH- (CH2} 3-NH-C (=NH) -NH2574, 7 575, 6 -NH-(CHz)3-N(CH3)-(CHZ)3-NH-645,8 646,5 C(=NH)-NHZ

N- 'NH 642, 8 643, 5 i i H H

-NH- ( CHZ ) 6-NH-C ( =NH 616, 8 617 , 4 ) -NH2 -NH- (CH2} q-NH-C (=NH) -NH2588, 7 589, 4 - 1d~ -Rl in Ilfb MS

calculated found -N CH N"NH
~ 2~3 CH 2 612, 7 613, 6 -N-(CH ) ~ ~ NI 'NH2 660, 661, 0 i 22 H H

iv n2 -N N-~ 610, 7 611, 6 ./ NH

-N-CH2 N--~ 638. 8 639, 6 H NH , Example 39:
Analogously to Example 32, 6-nitro benzo[de]isochromene-1,3-dione is reacted with 3 (3-aminophenyl)-N-(3-chloro-4-methoxyphenyl)propion amide, the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formula Ilg are obtained:

i I
i Ilg O "-O
N
i I
CH -CONH ~ ~ OCH3 2~2 CI
R in Ilg MS
calculated found I -NH- (CH2) 5-NH-C (=NH) -NH2 627, 1 627, 3 R' in Ilg MS
calculated found -NH- (CHz) z-NH-C (=NH) -NHz 585, 1 585, 2 -NH- (CHz) 7-NH-C (=NH) -NH2 655, 2 655, 3 CH2 N"NHz 667,2 667,3 H
/ ~
-N -CH2-~-CH2 H NHZ 661, 2 661, 2 H
-NH- (CHz) 3-NH-C (=NH) -NHZ 599, 1 599, 2 -NH-(CHZ)3-N(CH3)-(CHZ)3-NH- 670,2 67,3 C(~NH)-NHZ
-N-CH2~CH2- H NHZ 667, 2 667, 3 ~H
-NH- (CHz) 6-NH-C (=NH) -NHz 641, 2 641, 3 -NH-(CHz)q-NH-C(=NH)-NH2 613,1 613,3 -N CH N_ _NH 613 1 613 5 2)3 ~ 2 -N - CH ~ ~ NI 'NH 661, 2 661, 2 ~ 2)2 H z H
NH 611,1 611,4 N tie -N-CH2 N-~ 639, 2 639, 4 NH

Example 40:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with 3-(3-aminophenyl)-N-(4-phenylbutyl)propionamide, the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formula Ilh are obtained:

i I
i Ilh O ' '_O
N
i I
/ \
(CH2)2-CONH-(CH2)4 Rl in Ilh MS

calculated found -NH- ( CHZ ) 5-NH-C (=NH 618 , 8 619, 4 ) -NH2 -NH- (CH2) Z-NH-C (=NH) -NH2576, 7 577, 3 -NH- (CH2) ~-NH-C (=NH) -NHZ646, 8 647, 4 NI 'NH

CH2 658,8 659,4 H

-N- 652, 8 653, 4 N"NH
~ ~

Z

H H

-NH- (CH2) 3-NH-C (=NH) -NHz590, 7 591, 3 -NH- (CH2) 3-N (CH3) - (CH2)~~i, 8 662, 4 C(=NH)-NH2 658, 8 659, 5 -N-CH2 CH2-N- 'NHZ

H H

-NH-(CHZ)6-NH-C(=NH)-NH2 632,8 633,4 Rl in Ilh MS

calculated found -NH- (CHz) 4-NH-C (=NH) -NH2 604, 8 605, 4 N
~

604,8 605,7 -N (CH ) N"NH

i -N 652, 8 653, 3 ~ ~ NI 'N

H
- CH
2~2 H H

- N- C 2 602, 7 603, 8 \--/ NH , rvn2 -N-CH2 N-~ 630, 8 631, 6 NH

Example 41:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with A
CH2)2-CONH-(CH2)i /
H2N ~ \
the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formulae Ilia-Ilic are obtained:

i w I
i Ilia O ~
NH-(CH2)2 / \ CH3 Rl in Ilia MS
calculated found -NH- (CH2) 5-NH-C (=NH) -NH2 604, 8 605, 4 -NH-(CH2)2-NH-C(=NH)-NH2 562,7 563,4 -NH- (CH2) ~-NH-C (=NH) -NH2 632, 8 633, 4 CH2 NI _NHZ
644, 8 645, 5 -N -CHZ
H
-N-CH ~ ~ CH2 N"NH2 638, 8 639,4 i 2~ v H H
-NH-(CHZ)3-N(CH3)-(CHZ)3-NH- 647, 8 648, 4 C(=NH)-NH2 -N-CH2 CH2-NI _NH2 644, 8 645, 5 H
H
-NH- (CH2) 6-NH-C (=NH) -NH2 618, 8 619, 5 -NH- (CH2) 4-NH-C (=NH) -NH2 590, 7 591, 4 -N CH N- _NH 590 7 591 6 ~ 2)3 ~ 2 H CHa _. _ __ _ NH
-N -(CH ) ~ ~ N~NH2 638, 8 639, 3 H H
.N !~ h2 NH 588, 7 589, 8 N~2 -N-CH2 N-~NH 616, 8 617, 7 H

Ilib CONH
R in Ilib MS
calculated found -NH- (CH2) 5-NH-C (=NH) -NHz 604, 8 605, 4 -NH-(CH2)2-NH-C(=NH)-NH2 562,7 563,3 -NH- (CH2) ~-NH-C (=NH) -NH2 632, 8 633, 4 CH2 N"NH2 644,8 645,6 H
/ \
-N-CH2~CHZ N NHZ 638, 8 639, 5 H H
-NH- (CH2) 3-NH-C (=NH} -NH2 576, 7 577, 6 -NH-(CHZ)3-N(CH3)-(CHZ)3-NH- 647, 8 - 648, 4 CiaNH)-NHZ
-N-CH2 CH2 NI 'NHZ 644, 8 645, 7 H H
-NH- ( CH2 ) 6-NH-C (=NH ) -NH2 618 , 8 619, 4 -NH- (CH2) 4-NH-C (=NH) -NH2 590, 7 591, 4 Nh -N (CH N_ _NH 590, 7 591, 8 2~3 S 2 -N - CH ~ ~ NI 'NH 638, 8 639, 3 ~ 2~2 ~ z H H

Rl in Ilib MS
calculated found m n2 -N N--~ 588, 7 589, 6 NH
mn2 _ _ v N CHZ N--~NH 616, 8 . 617, 8 H

i I
i Ilic O ~O
i ~ C2H5 (CH2)2-CONH
Rj in Ilic MS

calculated found -NH- (CH2) 5-NH-C (=NH} -NH2590, 7 591, 3 -.NH- ( CHZ } 2-NH-C (=NH 5 4 8, 6 54 9, 6 } -NH2 -NH- ( CH2 ) ~-NH-C (=NH 618, 8 619, 4 ) -NHZ

NN
N "NH

2 630,8 631,7 H

H

/ \
-N-CH2~CH2-N NHZ 624, 7 625, 4 H H

-NH- (CH2) 3-NH-C (=NH) -NHZ562, 7 563, 5 -NH- (CHZ) 3-N (CH3) - (CHZ)633, 8 634, 4 C(~NH)-NHz Rl in Ilic MS

calculated found 'N~NH 630, 8 631 z , -N-CH2~CH2 H ~--~ H

-NH-(CHZ)6-NH-C(=NH)-NHZ 604,8 605,2 -NH- (CH2) 4-NH-C (=NH) 576, 7 577, 5 -NHZ

Example 42:
A suspension of 4.1 g of 6-nitro benzo[de]isochromene-1,3-dione in 100 ml of glacial acetic acid is treated with 4.3 g of 3-(3 aminophenyl)propionic acid and the mixture is heated under reflux. After reaction is complete, the reaction mixture is allowed to cool and is worked up as is customary. 3-[3-i6-Nitro-1,3-dioxo-2,3-dihydro-1H-phenalen-2-yl)phenyl]propionic acid in 80 ml of THF
is treated with 1.5 equivalents of oxalyl chloride, the mixture is stirred and 1.5 equivalents of 2-p-tolylethylamine are added. After conversion is complete, the mixture is worked up as is customary. A
solution of 3-[3-(6-nitro-1,3-dioxo-2,3-dihydro-1H-phenalen-2-yl)phenyl]-N-(2-p-tolylethyl)propionamide in 80 ml of DMF is treated with one equivalent of propane-1,3-diamine and the mixture is heated under reflux. After customary working up, the amine obtained is heated with 1.5 equivalents of pyrazole-1-carboxamidine and diisopropylethylamine in 80 ml of DMF. After reaction is complete and customary working up, 3-(3-[6-(3-guanidinopropylamino)-1,3-dioxo-2,3-dihydro-1H-phenalen-2-yl]phenyl)-N-(2-p-tolyl-ethyl)propionamide is obtained. MS: calculated: 576.7;
found: 577.4.
Example 43:
Analogously to Example 32, 6-nitrobenzo[de]iso-chromene-1,3-dione is reacted with CI
CH2)2-CONH-(CH2)I
CI

the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formulae Ilka-Ilke are obtained:
A
a CI

CI
R' in Ilka MS
calculated found -NH- (CHZ) 5-NH-C (=NH) -NH2 645, 6 645, 4 -NH- (CHZ) 2-NH-C (=NH) -NH2 603, 5 603, 3 =NH- (CHZ) ~-NH-C (=NH) -NHZ 673, 6 673, 4 N H _..
CH2 N"NHZ 685 7 685 4 H ' ' -N -CHZ
H
-N-CH2 CH2 N NHZ 679, 6 679, 3 H
-NH-(CHZ)3-NH-C(=NH)-NHZ 617,5 617,3 -N-(CHZ)3- N"NH2 631, 6 631, 4 i r Rl in Ilka MS
calculated found 679,6 681,2 -N - (CH2)2 ~-\ N NH2 H H
- N 629,5 630,5 / NH
mn2 -N-CH2---~N--NH
R~
i i Ilkb O ~O
N
CI CI
{CH2)Z-CONH-CH2 ~ \
R' in Ilkb MS
calculated found -NH- (CHz) 5-NH-C (=NH) -NH2 645, 6 645, 3 -NH-(CHZ)Z-NH-C(=NH)-NHZ 603,5 603,3 -NH-(CH2)7-NH-C(=NH)-NHZ 673,6 673,4 CH2 NI 'NHZ 685,7 685,5 H

H
-N -CH2 ~-~ CH2 N"NHZ 67 9, 6 67 9, 3 H H
-NH- ( CHZ ) 3-NH-C (=NH ) -NHZ 617 , 5 617 , 5 Rl in Ilkb MS

calculated found -NH-(CHz)s-N(CHs)-ICHz)s-NH-C(~NH)-NHz688, 7 688, 4 _ 'NH 685, 7 687, 4 Z

H

-NH- (CHZ) 6-NH-C (=NH) 659, 6 659, 9 -NH-(CHZ}4-NH-C(=NH)-NHZ 631,6 633,3 -N-(CHZ)3- N"NH2 631, 6 632, 4 ~~ n - _ 679 679 ~ ~ 6 1 N , , NHz -N-(CH2)2 H H

ivn2 - N 629,5 630,4 NH

w n2 -N-CH2---~~N-~ 657, 6 658, 5 NH
H

Ikc CI
NH-CH2 ~ ~ CI
R1 in Ilkc MS

calculated found -NH- (CH2} 5-NH-C (=NH) 645, 6 645, 6 -NHZ

-NH- (CH2) Z-NH-C (=NH) 603, 5 604, 6 -NHZ

-NH-(CH2)~-NH-C(=NHj-NH2673,6 673,4 Rl in Ilkc MS

calculated found NI 'NH

CH2 685, 7 686, 6 H

-N- 'NH
~ ~

2 679, 6 681, 3 i H H

-NH- ( CH2 ) 3-NH-C ( =NH 617 , 5 618 , 6 ) -NH2 -NH-(CHz)3-N(CH3)-(CHZ)3-NH-688,'7 - 688,5 C(=NH)-NH2 r~rr N"NH 685 686 2 , , H H

-NH- (CH2) 6-NH-C (=NH) -NHZ659, 6 659, 4 -NH- (CH2) 9-NH-C (=NH) -NH2631, 6 633, 3 -N CH N"NH
~ 2~3 ~ 2 _ 631, 6 632, 5 r - 6?9 679 ~ ~ N_ ' 6 NH2 , , I
N-(CH ) H
~ H

-N V~ nz NH 629, 5 630, 4 ~ ~2 -N-CH2 N-~ 657, 6 658, 6 NH
H

R' i I
i Ilkd O ' 'O
N
i I CI
/ \
(CH2)2-CONH-CH2 CI
R' in Ilkd MS
calculated found -NH- (CH2) 5-NH-C (=NH) -NH2 645, 6 645, 3 -NH- (CHZ) 2-NH-C (=NH) -NH2 603, 5 603, 3 -NH- (CH2) ~-NH-C (=NH) -NH2 673, 6 673, 3 CH2 NI 'NH2 685, 7 685, 5 -N -CHz H
-N-CH2 ~-~ CH2-N NHZ 679, 6 679, 3 H H
-NH- ( CH2 ) 3-NH-C (=NH ) -NH2 617 , 5 617 , 4 -NH-(CHZ?3-N(CH3)-(CHZ)3-NH- 68$,7 688,3 C(~NH)-NHZ
-N-CHZ CH2-N"NH2 685, 7 687, 3 H H
-NH- (CH2) 6-NH-C (=NH) -NH2 659, 6 659, 4 -NH- (CH2) 9-NH-C (=NH) -NHZ 631, 6 631, 4 -N (CH ) N_ _NH 631, 6 631, 4 R' in I 1 kd MS

calculated found ~ ~ N I 'NH 67 9 6 67 9,1 -N - CH ) ( 22 H H

U NH 629. 5 629, 4 NNZ

-N-CH2 N--~ 657, 6 658, 4 H NH

R' i i Ilke O ' '-O
N
CI
(CH2)2-CONH ~ ~ CI
R in Ilke MS

calculated found -NH- (CH2) 5-NH-C (=NH) -NHZ 631, 6 631, 2 -NH- (CH2) 2-NH-C (=NH) -NH2 589, 5 589, 1 -NH- (CH2) ?-NH-C (=NH) -NH2 659, 6 659, 2 NI 'NH

CN2 671, 6 671, 2 H

I ' 6 1 ~ ~

NHZ , , H H

-NH- (CH2) 3-NH-C (=NH) -NH2 603, 5 603, 2 -NH-(CHz)3-N(CHs)-(CHi)3-NH-C(NH)-NHi674, 6 674, 2 R1 in Ilke MS

calculated found ~ 671, 6 671, 2 N"NH

i H H

-NH- (CH2) 6-NH-C (=NH) -NH2 645, 6 645, 2 -NH- (CHZ) 4-NH-C (=NH) -NH2 617, 5 619, 2 Example 94:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with 3-(3-aminophenyl)-N-(3-chloro-4-fluorobenzyl)propionamide, the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formula Ilm are obtained:

i I
i ~ Ilm O ' N
i I
(CH2}2-CONH-CH2 ~ ~ F
CI
R1 in Ilm MS

calculated found -NH- ( CH2 ) 5-NH-C (=NH 62 9, 1 62 9, 5 ) -NHZ

-NH- (CHZ) 2-NH-C (=NH) 587, 1 587, 5 -NH- (CH2) ~-NH-C (=NH) 657, 2 657, 3 -NHZ

- 15$ -Rl in Ilm MS
calculated found CH2 N- 'NH2 669, 2 669, 6 H
/ \
-N-CHZ~CH2-N NHZ 663, 2 663, 4 H H
-NH- (CH2) 3-NH-C (=NH) -NH2 601, 1 601, 5 -NH- (CHZ) 3-N (CH3) - (CHZ) 3-NH- 672, 2 672, 3 C(=NH)-NHZ
-N-CH CH -N"NHZ 669 2 2~ 2 ~ . 669, 7 H H
-NH- (CH2) 6-NH-C (=NH) -NH2 643, 2 643, 4 -NH- (CH2) q-NH-C (=NH) -NH2 615, 1 615, 5 ~ 615,1 615,5 -N-(CH ) NI 'NH
i 23 -N - CH ~ ~ NI 'NH 663, 2 663, 2 ~ ~ 2)2 v H H

-N N-~ 613,1 613, 4 NH
~h2 641,1 641, 4 -N-CH2 N-.~
H NH

Example 45:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with CH2)2-CONH-(CH2)I /
H2N / \
the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formulae Ilna-Ilnc are obtained:

i w I
i Ilna O ' '_O
N
i I
/ \
(CH2)2-CONH-CH2 R' in Ilna MS
calculated found -NH- (CH2) 5-NH-C (=NH) -NH2 606, 7 607, 4 -NH- (CH2) 2-NH-C (=NH) -NH2 564, 6 565, 6 -NH- (CH2} ~-NH-C (=NH) -NH2 634, 8 635, 3 CH2 NI 'NH2 646, 8 647, 6 H
/ \
-N-CH2~CH2 N NH2 640, 7 641, 5 H H
-NH- (CH2) 3-NH-C (=NH} -NH2 578, 7 579, 6 -NH- (CHZ) 3-N (CH3) - (CHZ) 3-NH- 64 9, 8 650, 5 C(=NH)-NHZ

R~ in Ilna MS

calculated found -N--N N
~

H2 646, 8 647, 9 ~l H
H

-NH- (CH2) 6-NH-C (=NH} -NH2620, 8 621, 3 -NH- (CHZ) 9-NH-C (=NH) -NHZ592, 7 593, 4 -N (CH ) N"NH
2 3 ~ 2 592,7 593,7 ~ ~ N" 7 NH , 641 2 CH
2)2 ~
H H

-N

NH 590, 7 591, 6 rvn2 v _ _ 618, 7 619, 6 N CH2 N--~

NH
H

~i I
Iinb O ~
H-(CHZ)2 ~ ~ OCH3 Rl in Ilnb MS

calculated found -NH- (CH2) 5-NH-C (=NH) 620, 8 621, 4 -NH- (CH2) Z-NH-C (=NH) 578, 7 579, 4 -NH- (CH2} ~-NH-C (=NH} 648, 8 649, 5 R' in Ilnb calculated found CH2 NI 'NHZ
660,8 661,5 -N -CHZ
H
-N-CH2 ~ ~ CHZ N"NHZ 654, 8 655, 4 H H
-NH- (CH2) 3-NH-C (=NH) -NH2 592, 7 593, 5 -NH-(cH2),-N(cH,)-(cH2),-NH- 663, 8 664, 4 C(=NH)-NHZ
-N -CHZ CH2 N"NHZ 660, 8 661, 9 H H
-NH- (CH2) 6-NH-C (=NH) -NH2 634, 8 635, 4 -NH- (CH2) 9-NH-C (=NH) -NHZ 606, 7 607, 4 -N (CH ) N"NH
i 23 -N - CH ~ ~ N"NH
2~2 H H
-N N , 2 \-./ -~N H
iv n2 -N-CH2 N=-H NH

WO 00/32577 PCf/EP99/08561 R' i i Ilnc O ' 'O
N
i (CH2)2-CON ~ ~ OCH3 Rz in Ilnc MS
calculated found -NH- (CHZ) 5-NH-C (=NH) -NH2 592, 7 593, 3 -NH- (CH2) 2-NH-C (=NH) -NH2 550, 6 551, 4 -NH- (CH2) ~-NH-C (=NH) -NH2 620, 8 621, 3 N
CH2 NI 'NH2 632,8 633,4 H
/ \
-N-CH2~CH2 N NH2 626, 7 627, 3 H H
-NH- (CH2) 3-NH-C (=NH) -NH2 564, 6 565, 3 =NH- (CHZ) 3-N (CH3) - (CHZ) 3-NH- 635, 8 636, 3 C(=NH)-NHZ
NH
-N-CH2 CH2 NI 'NH2 632, 8 633, 4 H H
-NH- (CH2) 6-NH-C (=NH) -NH2 606, 7 607, 3 -NH- (CH2) q-NH-C (=NH) -NHZ 578, 7 579, 4 Example 46:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with / F
CH2)2-CONH-(CH2)i HzN / \
the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formulae Iloa-Iloc are obtained:
R~
/
Iloa O ' 'O
N
/
(CH2)2-CONH-(CH2)2 ~ ~ F
Rl in Iloa MS
calculated found -NH- (CH2) 5-NH-C (=NH) -NH2 608, 7 609, 4 -NH- (CH2) 2-NH-C (=NH) -NHZ 566, 6 567, 5 -NH- (CH2) ~-NH-C (=NH) -NH2 636, 8 637, 3 CH2 N"NH2 H 648,8 649,5 H
-N-CH2 ~_~ CH2-NI 'NHZ 642, 7 643, 4 i H H
-NH-(CH2)3-NH-C(=NH)-NH2 580,7 581,4 -NH- (CH2 ) 3-N (CH3} - (CHZ} 3-NH- 651, 8 652, 4 C(=NH)-NHZ
..r, -N-CH2 CH2 N"NHZ 648, 8 649, 6 H H
-NH- (CH2) 6-NH-C (=NH) -NH2 622, 7 623, 3 Rl in Iloa calculated found -NH- (CH2) 9-NH-C (=NH) -NHZ 594, 7 595, 5 i I
i !!ob O ' '_O
N
i / \
(CH2)2-CONH-CH2 F
Rl in Ilob MS
calculated found -NH- (CH2) 5-NH-C (=NH) -NH2 594, 7 595, 5 -NH- (CH2) 2-NH-C (=NH) -NH2 552, 6 553, 4 -NH-(CH2)~-NH-C(=NH)-NH2 622,7 623,2 CHZ N"NH2 634,8 635,5 =N -CH2 H
/ \
-N-CH2~CH2 N NH2 628, 7 629, 4 H H
-NH- (CH2) 3-NH-C (=NH) -NH2 566, 6 567, 5 -NH-(CHZ)3-N(CH3)-(CHZ)3-NH- 637, 8 638, 3 C(=NH)-NH2 -N-CH2-( J-CH2-N NHZ 634, 8 635, 6 H ~! H
-NH- (CH2) 6-NH-C (=NH) -NH2 608, 7 - 609, 3 -NH- (CH2) q-NH-C (=NH) -NH2 580, 7 581, 4 ra 1 i~w w ~I I i Iloc O'~nn~0 i F
I
/ \
(CH2)2-CON
Rl in Iloc MS
calculated found -NH- (CH2) 5-NH-C (=NH) -NHZ 580, 7 581, 3 -NH- (CH2) 2-NH-C (=NH) -NHZ 538, 6 539, 3 -NH-(CH2)~-NH-C(=NH)-NH2 608,7 609,3 CH2-N"NHZ
620, 7 621, 4 H
-N-CH2 ~ ~ CH2 N' _NHZ 614, 7 615, 2 H H
-NH- (CHZ) 3-NH-C (=NH) -NHZ 552, 6 553, 4 Example 47:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with 3-(3-aminophenyl)-N-(3-phenoxyphenyl)propionamide, the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formula Ilp are obtained:

i I

i Ifp O ~

OPh CONH ~ \
Rl in Ilp MS

calculated found -NH- ( CH2 ) 5-NH-C ( =NH
) -NH2 -NH- (CH2) ~-NH-C (=NH) -NH2 682, 8 683, 3 CHZ-N"NH2 694.8 695,4 H

-NH- ( CH2 ) 2-NH-C (=NH ) -NHZ

/ \
-N-CH2~CH2 N NHZ 6g8~ g 689, 4 H H

-NH- ( CH2 ) 3-NH-C ( =NH 62 6, 7 62 7 , 4 ) -NH2 -NH- (CH2) 3-N (CH3) - (CH2) 697, 8 698, 4 C(=NH)-NHZ

-N-CH2-( J-CHZ-N NH2 694, 8 695, 6 H ~J H

-NH- (CH2) 6-NH-C (=NH) -NHz 668, 8 669, 3 -NH- (CH2) 4-NH-C (=NH) -NH2 640, 7 641, 5 -N CH N- _NH 640. 7 641, 5 i ~ 2~3 -N -(CH2)2 / \ NI 'NH2 688, 8 689, 2 H \~'~ H

Rl in Llp _ _ MS
calculated found -N N~ n2 NH 638, 7 639, 5 -N-CHZ N-~NH 666, 8 667, 5 H
Example 48:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with 3-(3-aminophenyl)-N-(3-benzyloxyphenyl)propionamide, the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formula Ilq are obtained:

i w i Ilq O ~O
. N
i O
(CH2)2-CONH
Rl in Ilq _- MS

calculated found -NH- (CH2) 5-NH-C (=NH) 668, 8 669, 3 -NH- ( CH2 ) 2-NH-C (=NH 62 6, 7 62 7 , 4 ) -NHZ

-NH- (CH2) ~-NH-C (=NH) 696, 8 697, 3 Rl in Ilq MS
calculated found CH2 NI 'NH2 708,9 709,5 H
-N -CH2 ~_~ CH2-N"NHZ
i H H
-NH-(CH2)3-NH-C(=NH)-NH2 640,7 641,5 -N -(CH } ~ ~ N- _NH2 702, 8 703, 0 H H
-N N~ n2 U NH 652,8 653,5 ~h ~ 654,8 655,5 -N (CH ) N"NH

~~en2 -N-CH2 N-~NH 6g0, g 681, 5 i H
Example 49:
Analogously to Example 32, 6-nitro benzo[de]isochromene-1,3-dione is reacted with 3-(3-aminophenyl)-N-naphthalen-2-ylpropionamide, the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formula Ilr are obtained:

R~
~ Ilr O "O
N
\ ~
(CH2)2-CONH-CH2 R in Ilr -NH- ( CH2 )~5-NH-C (=NH ) -NHZ .., '.
-NH- ( CH2 ) 2-NH-C ( =NH ) -NH2 -NH- ( CH2 ) ~-NH-C ( =NH ) -NHz CHZ N"NH2 H

H
-N-CH2 ~_~ CH2-N_ _NHZ
H H
-NH- (CHz) 3-NH-C (=NH) -NH2 -NH- ( CHZ } 3-N ( CH3 } - ( CHz } 3-NH- , C, ( =NH ) -NHZ
N ' -N - CH2 CH2-N"NHZ
H H
-NH- ( CH2 ) 6-NH-C ( =NH ) -NH2 -NH- ( CHZ ) 9-NH-C ( =NH ) -NH2 -N (CH ) N"NH

-N - CH ~ ~ N"NH
i ~ 2~2 H H

Rl in Ilr iv n2 - N-U NH
iv n2 NH
Example 50:
Analogously to Example 32, 6-nitro benzo[de]isochromene-1,3-dione is reacted with 3-(3-aminophenyl)-N-benzylpropionamide, the appropriate diamine and tert-butyl (tert-butoxycarbonyl-iminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formula Its are obtained:
R~
/ ~ \
Its O " O
N
/
\
(CH2)2-CONH-CH2 l0 R1 in Its MS

calculated found -NH- (CHZ) 5-NH-C (=NH) 576, 7 577, 4 -NH- (CH2) z-NH-C (=NH) 534, 6 535, 5 -NH- (CH2) 7-NH-C (=NH) 604, 8 605, 4 -N~NH

616,8 617,5 H

-N - 610, 7 611, 3 N"NH
~ ~

H H

R~ in Its MS
calculated found -NH- (CH2) 3-NH-C (=NH) -NH2 548, 6 549, 5 -NH- (CHZ) 3-N (CH3) - (CH2) 3-NH- 619, 8 620, 3 C ( aNH ) -NHZ
-NH- (CH2) 6-NH-C (=NH) -NH2 590, 7 591, 3 -NH- (CH2) 4-NH-C (=NH) -NH2 562, 7 563, 5 -N CH N "NH
2~3 ~ z H CHs ~ 616, 8 617, 6 -N -CH2 CH2-NI 'NH2 i H H
-N - (CH ) / \ N NH2 H H
m n2 - N-\~/ N H
m n2 NH
Example 51:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with 3-(3-aminophenyl)-N-(3-fluoro-4-methoxyphenyl)propion-amide, the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formula Ilt are obtained:

i i ttt O "

F
CONH ~ ~ OCH3 R in Ilt MS
calculated found -NH- (CH2) 5-NH-C (=NH) -NH2 -NH- (CH2) 2-NH-C (=NH) -NH2 568, 6 569, 3 -NH- (CHZ) ~-NH-C (=NH) -NHz 638, 7 639, 4 CHZ N"NH2 H

H
644,7 645,3 -N -CH2 ~ ~ CH2-N"NH2 H H
-NH- ( CH2 ) 3-NH-C ( =NH ) -NH2 -NH- (CHZ) 3-N (CH3)- (CHZ) 3-NH- 653, 8 654, 3 C(=NH)-NHZ
NH
-N-CH2 CH2 NI 'NHZ 650, 8 651, 8 H H
-NH- (CH2) 6-NH-C (=NH) -NH2 624, 7 625, 3 -NH- (CH2) 9-NH-C (=NH) -NH2 596, 7 597, 5 ivn -N (CH ) N- 'NH 596, 7 597, 7 i 23 -N- CH ~ ~ NI 'NH 644, 7 645, 2 2~2 H H

~Rz in Ilt - MS
calculated found - N 594,6 595,7 NH
wn2 -N-CH2 N--~ 622, 7 623, 5 H NH
Example 52:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with 3-(3-aminophenyl)-N-(3-fluoro-4-methylphenyl)propion-amide, the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formula Ilu are obtained:

i I
i Ilu O ' '-O
N
i F
(CH2)2-CONH ~ ~ CH3 R' in Ilu MS
calculated found -NH- (CH2) 5-NH-C (=NH) -NH2 594, 7 595, 3 -NH- (CH2) 2-NH-C (=NH) -NH2 552, 6 553, 5 -NH- (CH2) ~-NH-C (=NH) -NH2 622, 7 623, 4 CH2 N- 'NHZ
634,8 635,5 -N -CHZ
H

R' in Ilu MS

calculated found -NI _NH 628, 7 629, 3 ~ \

i H H

-NH- (CH2) 3-NH-C (=NH) -NHZ566, 6 567, 5 -NH- (CHZ) 3-N (CH3) - (CHZ)637, 8 638, 3 C(=NH)-NHZ

N"NH 634, 8 635, 6 Z

i N H

-NH- (CHZ) 6-NH-C (=NH) -NH2608, 7 ~ 609, 3 -NH- (CH2) Q-NH-C (=NH) -NH2580, 7 5$1, 4 Example 53:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with CH2)2-CONH-(CH2)i H2N / \
the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formulae Ilva-Ilvb are obtained:

Ilva H2)2-CONH-(CH2)2-~/

Rl in Ilea MS

calculated found -NH-(CH2)5-NH-C(=NH)-NHZ 650,8 651,5 -NH- (CH2) 2-NH-C (=NH) -NH2 608, 7 609, 5 -NH- (CHZ) ~-NH-C (=NH) -NH2 678, 8 679, 4 N- 'NH

CH2 690,8 691,6 -N -CHZ

H

-N-CH2 / \ CH2-N"NHZ 684, 8 685, 5 H H

-NH- (CH2) 3-NH-C (=NH) -NH2 622, 7 623, 5 -NH- (CH2) 3-N (CH3) - (CHZ) 693, 8 694, 4 C(=NH)-NHZ

-N--N NH
~

Z 690, 8 691, 6 /

H ~
H

-NH- ( CH2 ) 6-NH-C (=NH ) 664 , 8 665, 4 -NH- (CH2) q-NH-C (=NH) -NH2 636, 7 637, 5 i w I
i Ilvb O ' 'O
N
i I OCH3 (CH2)2-CONH-(CH2)2 ~ ~ OCH3 Rl in Ilvb MS
calculated found -NH- (CH2) 5-NH-C (=NH) -NH2 650, 8 651, 4 -NH- (CH2) 2-NH-C (=NH) -NH2 608, 7 609, 5 R in Ilvb MS

calculated found -NH- (CHZ) ~-NH-C (=NH) -NH2678, 8 679, 4 NH
NI 'NH

CH2 690,8 691,8 H

~ CH2-N"NH2 684, 8 685, 4 -N-CHZ ~
i -H H

-NH- (CH2) 3-NH-C (=NH) -NH2622, 7 623, 4 -NH-(CHZ)3-N(CH3)-(CHZ)3-NH-693, 8 694, 4 C(=NH)-NHZ

NI 'NH 690 691 Z , , H H

-NH- (CH2) 6-NH-C (=NH) -NH2664, 8 665, 3 -NH- (CH2) 4-NH-C (=NH) -NH2636, 7 637, 4 Example 59:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with CH2)2-CONH-CH2 / \ OCF3 H2N / \
the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formulae Ilw are obtained:

i I
i Ilw O

H-CHZ ~ ~ OCF3 Rl in Ilw -NH- ( CHZ ) 5-NH-C (=NH ) -NH2 -NH- ( CH2 ) 2-NH-C ( =NH ) -NH2 -NH- ( CH2 ) ~-NH-C ( =NH ) -NHZ _ _... ___ _ CH2 NI _NH2 v H
-N -CHZ
H
-N -CH2 ~ ~ CH2 N' \NHZ
i H H
-NH- ( CH2 ) 3-NH-C (=NH ) -NH2 -NH- ( CHZ ) 3-N ( CH3 ) - ( CHZ ) a-NH-C(=NH)-NHZ
NH-.
-N-CH CH -N~NHZ
i 2~ 2 v H H
-NH- (CH2) s-NH-C (=NH) -NH2 _. _---NH- ( CH2 ) q-NH-C (=NH ) -NH2 - __ Example 55:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with O
CH2)2-CONH-CH2 the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formulae Im are obtained:

i I
i Im O ' 'O
N
i O
(CH2)2-CONH-CH2 ~ 1 Rl in Im MS
calculated found -NH- ( CH2 } 5-NH-C ( =NH ) -NH2 -NH- (CH2} 2-NH-C (=NH) -NH2 524, 6 525, 3 -NH- (CH2} ~-NH-C (=NH) -NH2 594, 7 595, 3 CH -N~NH2 606,7 607,3 H
_NH- _ / \
-H-CHZ CH2 H. NHZ 600, 7 601, 2 -NH- (CH2) 3-NH-C (=NH) -NH2 538, 6 539, 4 -NH-(CHZ)3-N(CH3)-(CHZ)3-NH- 609,7 610,3 C(~NH)-NHZ
-N-CH2 CH2 NI 'NHZ 606, 7 607, 9 H
-NH-(CH2)6-NH-C(=NH)-NH2 580,7 581,3 -NH- ( CH2 ) 4-NH-C (=NH ) -NH2 Example 56:
Analogously to Example 2, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with 2-(4-aminophenyl)-3-(4-dimethylaminophenyl)propio-nitrile and then with R1-H. The following compounds of the formula In are obtained:

i I
i ~ In O ' 'O
N
H-CHZ \ / N;CHs N
Rl in R1-H and in In MS

calculated found -NH- ( CH2 ) 5-NH2 54 5 54 6 -NH- (CH2) ~-NH2 573 574 -N - CH / \

H

Example 57:
10 ml of TFA are added at room temperature to a solution of 2.4 g of tert-butyl [3-(2-(4-[1-cyano-2-(4-dimethylaminophenyl)ethyl]phenyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-ylamino)propyl]-carbamate in 40 ml of dichloromethane [obtainable by reaction of 6-nitrobenzo[de]isochromene-1,3-dione with 2-(4-aminophenyl)-3-(4-dimethylaminophenyl)propio-nitrile and H2N-(CH2)3-NHBOC] and the reaction mixture is stirred until removal is complete. After customary working up, 2-(4-[6-(3-aminopropylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl}-3-(4-dimethylamino-phenyl)propionitrile is obtained.
Example 58:
Analogously to Example 32, 6-nitro-benzo[de]isochromene-1,3-dione is reacted with /Ph CH2)2-CONH-(CH2)2-CHI
Ph H2N ~
the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrazol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formula Ioa are obtained:

i i loa O ' '-O
N
i (CH2)2-CON
Rl in Ioa MS
calculated found -NH- (CH2) 5-NH-C (=NH) -NH2 680, 8 681, 4 -NH- (CH2) 2-NH-C (=NH) -NH2 638, 8 639, 6 -NH- (CH2) ~-NH-C (=NH) -NH2 708, 9 709, 4 CH2 NI 'NH2 720,9 721,6 H
-N-CH2 ~ ~ CH2 NI 'NHZ 714, 9 715, 5 H H

R1 in Ioa MS

calculated found -NH- (CH2) 3-NH-C (=NH) -NHZ652, 8 653, 6 -NH-(CHZ)3-N(CH3}-(CHZ}3-NH-723, 9 724, 4 C(=NH)-NHZ

~ 720,9 721,6 NI _NH

Z

i H H

-NH- (CH2) 6-NH-C (=NH) -NHZ694, 9 695, 4 -NH- (CH2) 9-NH-C (=NH) -NH2666, 8 667, 3 Example 59:
Analogously to Example 32, 6-nitrobenzo-[de]isochromene-1,3-dione is reacted with /Ph CH2)2-CONH-CH2-CHI
Ph H2N / \
the appropriate diamine and tert-butyl (tert-butoxycarbonyliminopyrozol-1-ylmethyl)carbamate. After removal of the protective groups, the following compounds of the formula Iob are obtained:
i i lob O ' 'O
N
i i I
(CH2)2-CONH-CH2-CH
i I
Rl in Iob MS
calculated found -NH- (CH2) 5-NH-C (=NH) -NH2 666, 8 667, 3 R in Iob MS
calculated found -NH- ( CHz ) z-NH-C (=NH ) -NHz 62 4 , 7 62 5, 5 -NH- (CHz) 7-NH-C (=NH) -NHz 694, 9 695, 4 -N-CH2 ~_~ CH2 N NHZ 700, 8 701, 4 H H
CH2 N "NHz 706,9 707,6 -N -CHZ
H
-NH- (CHz) 3-NH-C (=NH) -NHz 638, 8 639, 6 Example 60:
Analogously to Example 11, 6-nitrobenzo[de]iso chromene-1,3-dione is reacted with 4-iodophenylamine or 3-iodophenylamine (= I-Ar'-NHz), Hetl-B(OH)z and then with R1-H. The following compounds of the formula Ip are obtained:

i i IP
O ' 'O
N
Ar'-Het1 to -Ar'-Het R in R -H and Ip S . / -NH- ( CHz ) 3-NHz -NH- ( CHz ) s-NHz -NH- ( CHz ) ~-NHz -N 'NHZ
H

-Ar'-Hetl n R -H and Ip -NH- ( CHz ) s-NHz \ ~ -NH- ( CHz ) s-NHz -NH- ( CHz ) z-NHz -N 'NHz H
U -NH- ( CHz ) s-NHz \ I -NH- ( CHz ) s-NHz -NH- ( CHz ) ~-NHz -N 'NH2 H
\ U -NH ( CHz ) 3-NHz \ I -NH- (CHz) s-NHz -NH- ( CHz ) ~-NHz -N 'NHz H
\ S -NH- ( CHz ) s-NHz \ ~ -NH- ( CHz ) s-NHz -NH- ( CHz ) ~-NHz -N 'NHz H
/ ~ b -NH- ( CHz ) 3-NHz \ I -NH- ( CHz ) s-NHz -NH- ( CHz ) ~-NHz -N 'NHz H
/ \ / S NH- ( CHz ) s-NHz -NH- ( CHz ) s-NHz -NH- ( CHz ) ~-NHz -N 'NH2 H

-Ar'-Het R in R -H and Ip / ~ / S NH ( CHZ ) s-NH2 --NH- ( CH2 } s-NHZ
-NH- ( CH2 } ~-NHZ
-N 'NH2 H
/ ~ Q ~ -NH- ( CH2 ) s- NHZ
-NH- ( CHZ ) s-NH2 -NH- ( CH2 } ~-NH2 -N 'NH2 H
Q / -NH- (CH2) 3-NH2 -NH- ( CH2 ) s-NHZ
-NH- (CH2) ~-NHZ
-N 'NH2 H
-NH- ( CHZ } s-NH2 / ~ / ~ p -NH- ( CH2 } s-NH2 -NH- ( CH2 ) ~-NH2 -N 'NH2 H
U\ -NH- ( CH2 ) 3-NHZ
~ / ~ Q -NH- ( CH2 ) s-NH2 -NH- ( CH2 ) ~-NH2 -N 'NH2 H
Example 61:
Analogously to Example 11, 6-nitrobenzo[de]iso chromene-1,3-dione is reacted with 4-iodophenylamine or 3-iodophenylamine (= I-Ar' -NH2) , R3-Hetl-B (OH) 2 and then with Rl-H. The following compounds of the formula Iq are obtained:

R~
i I
i Iq O ' '-O
N
Ar'-Het~-R3 I -Ar' -Hetl-R' Rl in R1-H and Iq a -NH- (CH2) 3-NH2 S I CH3 -NH- ( CH2 ) s-NHZ
-NH- ( CH2 ) 7-NHz -N 'NH2 H
a -NH- ( CHZ ) 3-NH2 CH3 -NH- ( CH2 ) s-NH2 -NH- ( CH2 ) ~-NH2 -N 'NH2 H
Example 62:
Analogously to Example 11, 6-nitrobenzo[de]iso chromene-1,3-dione is reacted with 4-iodophenylamine or 3-iodophenylamine (= I-Ph-NH2) , R6- (CH2) n-Ph-B- (OH) 2 and then with Rl-H (Ph-Ph = Ar'),. The following compounds of the formula Ir are obtained:
R~
i I
i Ir O ' '-O
N
Ar'-(CH2)n-R6 -Ar' - (CH2) n-R° Rl in Rl-H and Ir ~ / ~ -NH- ( CHZ ) 3-NH2 -NH- ( CH2 ) s-NH2 NH2 -NH- ( CH2 ) ~-NH2 -N 'NH2 H
-NH- ( CH2 ) 3-NH2 / ~ / ~ -NH- ( CH2 ) s-NHZ
-NH- ( CH2 ) ~-NHZ

-N 'NH2 H
/ \ / \ -NH- ( CHZ ) s-NH2 -NH- ( CH2 ) s-NHZ
-NH- ( CH2 ) ~-NH2 H CHa -N 'NH2 H
-NH- ( CHz ) s-NH2 / \ -NH- ( CH2 ) s-NH2 -NH- ( CH2 ) ~-NHz N
H CHs -N NH2 H

- 187 - _ Example 63:
Analogously to Example 11, 6-nitro-2-(4-iodophenyl)benzo-[de]isoquinoline-1,3-dione is reacted with R1°-B- (OH) 2, wherein R1° is o-c(cH3)2-co-ocZH5 and Propan-1,3-diamine. 2-(4'-[6-(3-Amino-propylamino)-1,3-dioxo-1H,3H-benzo[dejisoquinolin-2-yl]-biphenyl-4-yloxy)-2-methyl-propionic acid ethyl ester is obtained.
Example 64:
Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with 5-methoxy-pyrimidine-2-sulfonic acid (4-amino-phenyl)-amide and Propan-1,3-diamine. 5-Methoxy-pyrimidine-2-sulfonic acid {4-[6-(3-amino-propylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-ylj-phenyl)-amide is obtained.
Example 65:
Analogously to Example 2, 6-chlorobenzo [de]isochromene-1,3-dione is reacted with 1-(6-amino 2,3-dihydro-indol-1-yl)-ethanone and propan-1,3 diamine. 2-(1-Acetyl-2,3-dihydro-1H-indol-6-yl)-6-(3 amino-propylamino)-benzo[,de]isoquinoline-1,3-dione is obtained.
Exam lp a 66:
Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with 4-(pyrrolidine-1-sulfonyl)-phenylamine and propan-1,3-diamine. 6-(3-Amino-propylamino)-2-[4-(pyrrolidine-1-sulfonyl)-phenyl]-benzo[de]isoquinoline-1,3-dione is obtained.
Example 67:
Analogously to Example 2, 6-chlorobenzo-[dejisochromene-1,3-dione is reacted with 4-cyclohexyl-phenylamine and Propan-1,3-diamine. 6-(3-Amino-- 188 - _ propylamino)-2-(4-cyclohexyl-phenyl)-benzo[de]isoquinoline-1,3-dione is obtained.
Example 68:
Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with 3-(3-amino-phenyl)-N-(2-phenyl-propyl)-propionamide and 3-aminomethyl-benzylamine. 3-{3-[6-(3-Aminomethyl-benzylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl}-N-(2-phenyl-propyl)-propionamide is obtained.
Analogously, by reaction of 6-chlorobenzo-[de]isochromene-1,3-dione with 3-(3-Amino-phenyl)-N-(1-phenyl-ethyl)-propionamide and 3-aminomethyl-benzylamine, 3-{3-[6-(3-aminomethyl-benzylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl}-N-(1-phenyl-ethyl)-propionamideis obtained.
Example 69:
Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with 3-(3-amino-phenyl)-1-(3,4-dihydro-2H-quinolin-1-yl)-propan-1-one and 3-aminomethyl-cyclohexylamine. 6-[(3-Aminomethyl-cyclohexylmethyl)-amino]-2-{3-[3-(3,4-dihydro-2H-quinolin-1-yl)-3-oxo-propyl]-phenyl}-benzo[de]isoquinoline-1,3-dione is obtained.
Example 70:
Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with H2N-Ar'-S-{CH2)n-CONH-(CH2)i-Ar and 3-aminomethyl-benzylamine. The following compounds of the formula Iya are obtained:

L N v Ar'-S-(CH2)"CONH-(CH?); Ar Ar' -S- ( CHz ) n-CONH- ( CHZ ) i-Ar in I a ~ S-CHz-CONH
r ~ S-CHZ CONH ~
CN
S-CHi CONH-(CHi)i ~ ~ N02 ~ S-CHI CONH-CHz ~
~2 N-I ~ S-CHZ CONH-(CHz)z ~ ~ _ _ N
~ S-CHi CONH-CHz N
S-CH2 CONH-(CHi)i ~ S-CHZ CONH-CHz ~ ~ N
~ ~a S-CHi CONH ~ ~ N~
CHs CH
S-CH= CONH ~ ~ N~ s CHs S-CHs CONH-CHs ~ ~ NCH
S-CH=-CONH
S-CHs-CONH-(CHih ~ ~ SOrNH=
S-CHz-CONH-CH= ~ ~ SOz-NN=
S CHz--CONH ~ ~ _ CH' Ar' -S- (CH2) n-CONH- (CH2) i-Ar in Iya ~ S-CHz-CONH ~ ~ CH3 S-CHZ-CONH-(CHZ)z CI

CI
/ S-CHZ CONH-(CHZ)z ~
CI
S-CHZ CONH
CI
S-CHZ-CONH-CH2 ~ ~
CI
~ S-CHZ CONH-(CHZ)2 ~ ~ CI
S-CHZ-CONH-CH2 ~ ~ CI
S-CH2-CONH ~ ~ CI
~ S-CHz -CONH-(CHz)2 ~ ~ CHI
~ S-CHZ-CONH ~ ~ CH3 S-CHZ CONH-CHz ~
S-CHZ -CONH I /
S-CHZ- CONH ~ ~ OCH3 CI

Ar' -S- ( CH2 ) n-CONH- ( CH2 ) i-Ar in I a m 3 / S-CHZ-CONH

/ S-CHZ-CONH ~ ~ CI
CI
S-CHZ-CONH-CHZ
CI
CI
S-CHZ-CONH-(CH2) ~
CI
CI CI
S-CHZ-CONH-CHZ ~
- CI
S-CNZ- CONH-CHZ ~ ~ CI
__ _ CI
S-CHz-CONH-(CFiz)Z ~ ~ C!
Ci CI
_ CI
S-CHZ-CONH ~ ~
CI
CI
S-CHZ- CONH ~ ~ CI
S-CH2-CONH-CH2 ~
S-CHZ-CONH-(CHZ a S-CH2-CONH ~
S-CHZ CONH-(CHz), Ar' -S- (CH2) n-CONH- (CHZ) i-Ar in I ya S-CHI CONH-(CHZ)i ~ ~ CH3 S-CHZ CONH ~ ~ CH3 S-CHZ CONH ~

S-CH2 CONH ~
~Z~ ~5 ~ S-CHZ-CONH

S-CHZ CONH-CHz ~ ~ F
CI
~ S-CH2 CONH ~ ~ F
CI
S-CHZ CONH-CHZ ~ ~ F
CI
S-CHz CONH-(CH=)i S-CHZ CONH-CHz S-CHZ CONH ~

S- CHs-CONH-(CHz)z ~ ~ OCH~
S- CHz CONH-CHz ~ ~ OCF3 Ar' -S- ( CH2 ) "-CONH- ( CH2 ) i-Ar in Iya S- CHZ CON ~ ~ OCH3 S-CH2 CONK-(CHz)2 ~ ~ F

F
S- CH2 CONH ~
F
S- CHZ CON
F
S- CHZ CONH ~
S- CHz CONH ~ ~ OPh S- CHi CONH ~ ~ O ~ / CHI
S- CH2 CONH ~
O
S- CHZ CONH-CHZ
S- CHZ CONH-CHZ
F
S- CHz CONH / ~ OCH3 F
S- CH2 CONH / ~ H~

S- CHZ CONH

- 1gd - _ Ar' -S- (CH2) n-CONH- (CHz) i-Ar in Iya tert-butyl S- CHZ CONH

tert-butyl v. .3 S- CHZ CONH-(CHz)Z

OCH~

__ S- CHZ CONH

... .3 ~ ~

S- CHZ CONH-(CHz z Analogously to example 32, the compounds of the formula Iya as indicated above are reacted with tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl-methyl)carbamate.
After removing of the protection group, the following compounds of the formula Iyb are obtained:
Ar' -S- ( CH2 ) n-CONH- ( CH2 ) i-Ar in I b S-CHZ-CONH
r CN
(r N v Af-S-(CH2)~ CONH-(CH2); Ar Ar' -S- (CH2) n-CONH- (CHZ) i-Ar in Iyb S-CH2 CONH-(CH=)i ~ ~ NOZ
S-CH2 CONH-CHZ ~
~2 N-~ S-CHi CONH-(CH~Z
N
S-CHZ CONH-CHz N
S-CHz CONH-(CHZ)i ~ S-CHz CONH-CHz ~ ~N
S-CH=-CONH ~ ~ N\~Hs CxHs ~ CHI
S-CHI CONH ~ ~ N~
CHI
CH
S-CHz CONH-CHi ~ ~ N~ ' CIi~
S-CH,-CONH
S-CHz-CONH-(CHI ~ ~ SOrNHi S-CHi-CONH-CHi ~ ~ SOz-NH2 S-CHi-CONH ~ \ CH

~ S-CHZ-CONH ~ ~. CH3 _ ~ S-CHZ-CONH-(CHZ)2 CI
~ S-CHZ-CONH-CH2 CI
S- CHz CONH-(CHz)z CI

CI

Ar' -S- (CHz) n-CONH- (CH2) i-Ar in Iyb S-CHZ-CONH-CHZ
CI
~ S-CHZ CONH-(CHz)~ ~ ~ CI
S-CHz-CONH-CHZ ~ ~ CI
S-CHZ-CONH ~ ~ CI
S-CHi -CONH-(CHi)z ~ ~ CHI
S-CHZ-CONH ~ ~ CH3 S-CH2 CONH-CHi _ \
S-CHZ -CONH I /
S-CHZ- CONH ~ ~ OCH~
CI
m 3 / S-CHZ-CONH

v.rs S-CH2-CONH ~ ~ CI
CI __ CI
S-CH2-CONH-(CHI ~
CI
CI CI
S-CHZ-CONH-CHZ ~
S-CHZ- CONH-CHZ ~ ~ CI

Ar' -S- ( CH2 ) n-CONH- ( CH2 ) i-Ar in Iyb cl S-CHz-CONH-(CHz)z ~ ~ CI
CI _ S-CHz-CONH-CHZ ~ ~ .
CI
CI

CI
CI
S-CH2- CONH ~ ~ CI
/ S-CHZ-CONH-CHZ ~
S-CHZ-CONH-(CHZ s S-CH2-CONH ~
S-CH2 CONH-(CH2)4 S-CHs-CONH-(CHz)z ~ ~ CHy S-CHi CONH ~ ~ CH3 S-CHz CONH

2' 'S

~ S-CHi CONH

Ar' -S- ( CH2 ) n-CONH- ( CHZ ) i-Ar in Iyb ~ S-CHZ CONH-CHZ

S-CHz CONH-CHz ~ ~ F
CI
~ S-CHz CONH ~ ~ F
Cl ~ S-CH2 CONH-CHZ ~ ~ F
CI
S-CHz CONH-(CHz)i ~ ~

S-CH2 CONH-CHz ~ S-CHZ CONH

S-Chll CONH-(CHZ)z ~ ~ OCHs S- CHz CONH-CHi ~ ~ OCF~
S- CHZ CON ~ ~ OCH3 _ _.
S- CHZ CONH-(CH~)z ~ ~ F
S- CHZ-CONH-CHZ ~
F

a F

F
,.. ., S- CHZ CONH

Ar' -S- ( CHZ ) "-CONH- ( CH2 ) i-Ar in I b S- CHZ CONH ~ ~ OPh S- CH= CONH ~ ~ O ~ / CHI
S- CHz CONH
O

S- CHZ CONH-CHZ ~
F
S- CHZ CONH / ~ OCH3 F -S-CHz CONH / ~ CH3 S- CHZ CONH

tert-butyl S- CHZ CONH
tert-butyl S- CHi-CONH-(CHi)i OCH~
,r,., ,3 .,. ,, S- CHZ CONH-(CH= z ~ ~ OCH3 Example 71:
Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with H2N-Ar'-S-(CH2)n-CONH-(CHZ)i-Hetl and 3-aminomethyl-benzylamine.
The following compounds of the formula Iza are obtained:
N NHz W
Iza O " O
N
Ar'-S-(CH2)~ CONH-(CH2); Het~
Ar' -S- ( CH2 ) n-CONH- ( CH2 ) i-Hetl in Iza S-CH2 CONH-(CHZ)i S-CHZ-CONH-(CHi)3-N
S-CHZ CONH-(CHz)2-S

O
S-CH2 CONH-CHZ ~ I
Analogously to example 32, the compounds of the formula Iza as indicated above are reacted with tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl-methyl)carbamate.
After removing of the protection group, the following compounds of the formula Izb are obtained:

NH

Cr N v Ar'-S-(CH2)~ CONH-(CH2); Het~
Ar' -S- ( CH2 ) n-CONH- ( CH2 ) i-Hetl in Izb ~ S-CHZ CONH-(CH2)2-Nl ) ~O/
S-CHZ CONH-(CHZ)3-N
~ S-CHZ CONH-(CH2)2-N
S

O

Example 72:
Analogously to Example 2, 6-chlorobenzo [de]isochromene-1,3-dione is reacted with HZN-Ar'-S
(CHZ)n-CONH-(CH2)i-D-H and 3-aminomethyl-benzylamine. The following compounds of the formula Ila are obtained:
Hi Cr N v I
Ar'-S-(CH2)~ CONH-(CH2); D-H

Ar' -S- ( CH2 ) n-CONH-( CH2 ) i-D-H in Ila ~ S- CHZ CONH-(CHZ)z Analogously to example 32, the compounds of the formula I1a as indicated above are reacted with tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl-methyl)carbamate.
After removing of the protection group, the following compounds of the formula Ilb are obtained:
I \ H
N ~ NH2 11b O " O
N
Ar'-S-(CH2)"CONH-(CH2); D-H
Ar' -S- ( CH2 ) n-CONH- ( CH2 ) i-D-H iri Ilb ~ S-CHZ CONH-(CH~~

Example 73 Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with 2-(3-amino-phenylsulfanyl)-N-(2-phenyl-propyl)-acetamide and 3-aminomethyl-benzylamine. 2-(3-[6-(3-Aminomethyl-benzylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenylsulfanyl)-N-(2-phenyl-propyl)-acetamide is obtained.

Analogously to example 32, 2-(3-[6-(3-Aminomethyl-benzylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenylsulfanyl}-N-(2-phenyl-propyl)-acetamide is reacted with tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl-methyl)carbamate. After removing of the protection group 2-(3-[6-(3-guanidinomethyl-benzylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenylsulfanyl}-N-(2-phenyl-propyl)-acetamide is obtained.
Example 74:
Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with H2N-Ar'-S-( CH2 ) n-CONH- ( CH2 ) i-CH (Arl ) -Ar2 and 3-aminomethyl-benzylamine. The following compounds of the formula I3a are obtained:

/ \
13a O ' 'O
N
. ..
Ar'-S-(CH2)~ CONH-(CH2); CH(Ar~)-Ar2 Ar' -S- ( CH2 ) n-CONH- ( CHZ ) i-CH (Arl ) -Ar2 in I3a S-CHZ-CONH-(CH~~-CH

Analogously to example 32, the compounds of the formula I3a as indicated above are reacted with tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl-methyl)carbamate.

After removing of the protection group, the following compounds of the formula I3b are obtained:
NH

(, N
Ar'-S-(CH2)"CONH-(CH2); CH(Ar~)-Ar2 Ar' -S- ( CH2 ) n-CONH- ( CH2 ) i-CH (Arl ) -Ar2 in in I3b S-CHZ-CONH-(CHz)2-CH
\
\
S- CHZ-CONH-CHZ-CH
Example 75:
' Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with 2-(3-amino-phenyl)-N-(4-chloro-benzyl)-acetamide and 9-aminomethyl-cyclohexylmethylamine. 2-(3-~6-[(4-Aminomethyl-cyclohexylmethyl)-amino]-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl}-phenyl)-N-(4-chloro-benzyl)-acetamide is then, analogously to example 32, reacted with tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl-methyl)carbamate. After removing of the protection group N-(4-chloro-benzyl)-2-(3-(6-[(4-guanidinomethyl-cyclohexylmethyl)-amino]-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl}-phenyl)-acetamide is obtained.

Analogously is reacted 6-chlorobenzo[de]isochromene-1,3-dione with 3-(3-amino-phenyl)-N-phenethyl-propionamide and 4-aminomethyl-cylohexylmethylamine and the following product 3-(3-(6-[(4-Aminomethyl-cyclohexylmethyl)-amino]-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl)-phenyl)-N-phenethyl-propionamide with tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl-methyl)carbamate. After removing of the protection group 3-(3-(6-[(4-guanidinomethyl-cyclohexylmethyl)-amino]-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl)-phenyl)-N-phenethyl-propionamide is obtained.
Example 76:
Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with H2N-Ar'-(CH2)n-CONH-(CH2);,-Ar and 3-aminomethyl-benzylamine. The following compounds of the formula I6a are obtained:
Hi Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I6a CONH
r (CH2)2-CONH
r C. N .~
Ar'-(CH2) -CONH-(CH2)i-Ar Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I6a CONH
CN
(CH2)2-CONH \
\ CN
(CHZ)2-CONH-(CHZ)2 ~ ~ NOZ
CONH-(CHZ)2 \ ~ NOZ
(CH2)2-CONH-CHz ~2 \ O

N.
CONH-(CH2)2 \
\
.N
(CH2)2 -CONH-(CH2)Z
(CH2)2 -CONH-CH2 \ ~ N

Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I6a y ONH-CH2 ~ ~ N
/ CZHS
(CHZ)2 -CONH ~ ~ N~
CzHb CONH ~ ~ N~

~ CH3 (CH2)2-CONH-CHZ ~ ~ N~
/ ~ CH3 CH
ONH-CHZ ~ ~ N~

(CHz)Z- CONH-(CH2)Z ~ ~ S02-NHS
(CHZ)z-CONH-CHZ ~ ~ - .SOi-NHz CONH-CH2 ~ ~ S02-NH2 (CHZ)2 -CON
~CH3 CONH

- ~flR -Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I6a (CHz)z- CONH / ~ CH3 CONH ~ ~ CH3 (CHz)2- CONH-(CHz)2 CI
(CH2)2-CONH-CH2 CI

/ CI
CONH-(CH2)2 CI
(CHz)z- CONH-(CHz)z /
CI

Ar' - ( CHZ ) n-CONH- ( CH2 ) i-Ar in I6a CI
(CH2)2- CONH
(CHZ}2- CONH-CH2 CI
CONH-CHZ
CI
CONH-(CH2)2 CI
CONH
CI
(CH~2- CONH-(CHz)i / ~ .CI
CH2)2- CONH ~ ~ Cl Ar' - ( CH2 ) "-CONH- ( CHZ ) i-Ar in I6a CONH-(CH2)2 ~ ~ CI
CONH ~ ~ CI
CH2)2- CONH-(CHZ)2 ~ ~ CH3 CH2)2- CONH ~ ~ CH3 CONH ~ ~ CH3 CONH-(CH2)2 ~ ~ CH3 CONH ~ ~ CH3 CHZ)2- CONH-CH2 ~ ~

- 7'I ~
Ar' - ( CH2 ) "-CONH- ( CHz ) i-Ar in I6a ONH-CHZ
CHZ)2-CONH
CONH /
\
CH2)2-CONH-CHZ I /
(CHZ)2- CONH ~ ~ OCH3 CI
CONH ~ ~ OCH3 CI
(CH2)2- CONH /

Ar' - ( CH2 ) "-CONH- ( CH2 ) f-Ar in I6a m 3 (CH2)2- CONH ~ ~ CI
ONH ~ ~ CI
CI
CHz)2- CONH-CH2 CI
CI

CI
CI
CH2)2-CONH-(CH2)2 ~
CI
CI Ct (CH2)2- CONH-CH2 ~ ~
CI CI

Ar' - ( CH2 ) n-CONH- ( CH2 ) ;-Ar in I6a CONH-(CH2)2 ~ ~ CI
CI
(CH2)Z- CONH-CH2 CI
C( CI
CI -(CHZ)2- CONH
CI
CI
CONH
CI
CH2}2- CONH ~ ~ CI
CONH ~ ~ CI

Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I6a CONH-CH2 \
CONH-(CH2 s \ ~
\
(CH2)2- CONH-(CHZ)s \
(CH2)2- CONH
CONH
(CH2)2- CONH-CH2 (CH2)2- CONH-(CH2)4 \
CONH-(CH2)4 Ar' - ( CHZ ) n-CONH- ( CH2 ) i-Ar in I6a (CHz)z- CONH-(CHz)z ~ ~ CH3 CONH-(CHz z ~ ~ CH3 (CHz)z-CONH
CHI

CONH

CH2)2- CONH
CONH
"2~ ~5 CH2)Z- CONH

Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I6a "2~ ~5 CONH /
/
(CH2)2- CONH
CF
(CHZ)2- CONH-CH2 CONH-CH2 ~

ONH

(CH2)2- CONH-CHZ ~ ~ F
CI
(CH2)2- CONH ~ ~ F
CI
CONH-CH2 / ~ F
CI
/

Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I6a ONH ~ ~ F
CI
(CHz)z- CONH-CHz ~ ~ F
CI
CONH-CH2 ~ ~ F
CI
(CHz)z- CONH-(CHz)z OCH~
(CHz)2- CONH ~

CHz)z- CONH-CHz \ / OCH3 ONH-(CH2)2 /

CON
\OCH3 Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I6a (CHZ)2- CONH-(CHz)2 / ~ OCH3 ONH-CH2 ~ ~ OCF3 (CHz)Z- CONH-CH2 / ~ OCF3 (CHZ)2- CONH ~ ~ OCH3 CON ~ ~ OCH3 CONH-{CH2)2 ~ ~ OCH3 (CH2)2- CONH-(CH2)z ~ ~ F
ONH-(CH2)Z ~ ~ F

- 7'1 A _ Ar' - ( CH2 j n-CONH- ( CH2 j i-Ar in I6a (CH2)2- CONH-CH2 F

F
CONH
F
F
CHz)2- CON
CH2)2- CON
F
CON
Fr vr~~
(CH2)2- CONH

- ~~n -Ar' - ( CH2 ) "-CONH- ( CH2 ) i-Ar in I6a ,., , , CONH
CH2)2-CONH ~ ~ OPh CONH ~ ~ OPh CONH ~ ~ O \ ~ CH3 CHs)i-CONH ~ ~ O ~ ~ CHI
OCH2Ph (CHZ)Z- CONH
CONH
O
~--Ph / \
(CHZ)2- CONH-CHZ /
\ /

Ar' - ( CHZ ) n-CONH- ( CHZ ) i-Ar in I6a F
(CH2)2- CONH ~ ~ OCH, F
CONH ~ ~ OCH3 F
(CH2)2- CONH ~ ~ CH3 F
CONH ~ ~ Hs (CH2)2- CONH

CONH

tent-butyl (CHZ)2- CONH ~
tert-butyl Ar' - (CH2) n-CONH- (CH2) i-Ar in I6a test-butt' CONH
tert-butyl ,.,... .g CHZ)2-CONH ~

ONH

CONH-(CH2)2 ~ ~ OCH3 v. n3 CHz)2- CONH-(CHZ)z t;hz -(CHz)2- CONH-(CHz)2 ~ ~ OCH3 Analogously to example 32, the compounds of the formula I6a as indicated above are reacted with tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl-methyl)carbamate.
After removing of the protection group, the following compounds of the formula I6b are obtained:

Ar' - (CH2 ) n-CONH- ( CH2 ) i-Ar in I 6b CONH
r (CH2)2-CONH
Br CONH
CN
(CH2)2-CONH
CN
(CHZ)z-CONH-(CH2)2 ~ ~ N02 CONH-(CH2)2 ~ ~ N02 (CHZ)2-CONH-CHZ
O

(r N v Ar'-(CH2)~ CONH-(CH2); Ar Ar' - (CH2) n-CONH- (CH2) i-Ar in I6b ONH-CHZ \ ~
\ O
z N_ CONH-(CH2)2 \
/ \
_N
(CHz)z -CONH-CHz \
(CHz)z -CONH-(CHZ)z (CH2)z -CONH-CH2 \ ~ N
"- \
ONH-CH2 \ ~N
\
/.CzHs (CHz)z -CONH ~ / N\C H

CONH \ ~ N~

(CH~z-CONH-CHz ~ / N~
/ ~ CH3 ~ CH3 (CHz)z-CONH ~ / NCH
/ ~ 3 - ~~5 -Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I 6b CH
ONH-CH2 ~ / N~ ' CHI
(CHz)i-CONH-CHZ ~ ~ SOZ-NHZ
CONH-CH2 ~ ~ S02-NHZ
(CH2)2 -CON / ~

CONH

(CH2)2-CONH / ~ CH3 CONH ~ ~ CH3 CI
CONH-(CH2)2 CI

- ?_2H -Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I 6b CI
CONH-(CH2)2 CI
CONH
CI
CONH-(CH~2 ~ ~ CI
CH2)2- CONH-CH2 ~ ~ CI
CONH ~ ~ CI
CH2)2- CONH ~ ~ CH3 CONH ~ ~ CH3 Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I 6b CONH-(CH2)2 / ~ CH

CONH ~ ~ CH3 O N H-CHz CH2)2-CONH
CONH /
CHZ)2-CONH-CH2 CH2)2-CONH
CONH ~ ~ OCH3 CI

Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I 6b m 3 (CH2)2- CONH

w. ~ 3 (CH2)2- CONH ~ ~ CI
/
ONH / ~ CI

CI
CONH-CHZ /
CI
/
CI CI

/
Ct CONH-(CH2)2 ~ ~ CI
CI

CI
/

Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I 6b CI
(CH2)2- CONH ~ \
CI
CI
CONH
CI
CI
CONH ~ ~ CI
CONH-CHZ
\
CONH-(CH2 s \ ~
\
CONH ~ ~ -ONH-(CH2)4 CONH-(CHZ 2 \ ~ CH3 \

- ~~n -Ar' - ( CHz ) n-CONH- ( CHz ) i-Ar in I 6b CH3 ._..
(CHZ)2-CONH ~

CONH /

CONH /
.,z~ ~5 CONH /
/
(CH2)2- CONH
(CHZ)Z- CONH-CHZ

ONH-CHz ONH

- ~~1 -Ar' - ( CH2 ) n-CONH- (CH2 ) i-Ar in I 6b (CH2)2- CONH ~ ~ F
CI
CONH-CH2 ~ ~ F
CI
ONH ~ ~ F
CI
(CH2)2- CONH-CHZ ~ ~ F
CI
CONH-CH2 ~ ~ F
CI
(CHZ)Z- CONH-(CH2)z ~

(CH~2- CONH

ONH-(CH2)z Ar' - ( CH2 ) "-CONH- ( CH2 ) i-Ar in I 6b CON
~OCH3 ONH-CH2 ~ ~ OCF3 CON ~ ~ OCH3 CONH-(CHZ)2 ~ ~ OCH3 (CHp)2- CONH-(CHZ)Z ~ ~ F
ONH-(CH2)2 ~ ~ F

F
CONH
F
CHZ)2- CON
F

Ar' - (CH2) n-CONH- (CH2) i-Ar in I6b CON /
Fr /
CONH
CH2)2-CONH ~ ~ OPh CONH ~ ~ OPh ONH ~ ~ O ~ / CH3 CHz)z-CONH ~ ~ O ~ ~ CHI
CONH
O
/ ~Ph F
CONH ~ ~ OCH3 Ar' - ( CHZ ) n-CONH- ( CHZ ) i-Ar in I 6b F
CONH ~ ~ H3 {CHZ)2- CONH

CONH

tert-butyl {CH2)2- CONH
tent-butyl tert-butyl CONH
tert-butyl ~~~ .3 CH2)Z-CONH ~

_ OCH3 ONH

crl3 CONH-(CH2)2 ~ ~ OCH3 Example 77:
Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with H2N-Ar'-(CH2)n-CONH-(CH2)i-Ar and 3-aminomethyl-cyclohexylmethyl-amine. The following compounds of the formula I7a are obtained:
HZ
G N v Ar'-(CH2)~ CONH-(CH2); Ar Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Ar in I7a (CH2)2-CONH
CI
(CH2)2-CONH ~ ~ P
(CH2)Z-CONH
Example 78:
Analogously to Example 2, 6-chlorobenzo-[de]isochromene-1,3-dione is reacted with H2N-Ar'-(CHZ)n-CONH-(CH2)i-Heti and 3-aminomethyl-benzylamine.
The following compounds of the formula I8a are obtained:

N NHZ
/
18a O N O
Ar'-(CH2)~ CONH-(CH2); Het~
Ar' - ( CH2 ) n-CONH- ( CHZ ) i-Hetl in I8a CONH-(CHZ)z-(CH2)Z-CONH-(CH2)2 (CHZ)2-CONH-(CH2)2 O
CONH-(CH2)3-N' O
CH2)2- CONH-(CH2)3-N' CONH-(CH2)2-N, Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Het 1 in I8a (CH2)2-CONH-(CHZ)z-N
(CHZ)2-CONH-(CHZ)3-N
'=N
(CH2)2-CONH-CHZ ~ O
I
O
S
CONH-CH2 ~ I
S
CH2)2-CONH-CH2 ~ I
O
(CHZ)2-CONH-GH2 ..~ I
O
CONH-CH2 ~ I
Analogously to example 32, the compounds of the formula I8a as indicated above are reacted with tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl-methyl)carbamate.
After removing of the protection group, the following compounds of the formula I8b are obtained:

NH
N ~ NH2 18b O ' 'O
N
Ar'-(CH2)~ CONH-(CHZ)~-Het~
Ar' - ( CH2 ) n-CONH- ( CHZ ) i-Het 1 in I8b CONH-(CH2)2-N
(CH2)2-CONH-(CH2)2 (CH2)2-CONH-(CHZ)2 O
CONH-(CH2)3-N, O
(CH2)2- CONH-(CH2)3-N' CONH-(CH2)2-N, - ~~~ - _ Ar' - ( CH2 ) n-CONH- ( CH2 ) i-Het 1 in I8b (CH2)Z-CONH-(CH2)2-N
(CH2)2-CONH-(CH2)a-N
~N
(cH2)Z-CONH-CH2 ~ O
O
S

S
CH2)2-CONH-CH2 Example 79:
Analogously to Example 2, 6-chlorobenzo [de]isochromene-1,3-dione is reacted with H2N-Ar' (CHZ)n-CONH-(CH2)i-D-H and 3-aminomethyl-benzylamine. The following compounds of the formula I9a are obtained:

Cr N v Ar'-(CH2)"CONH-(CH2)i-D-H

_ yen _ Ar' - ( CH2 ) n-CONH- ( CH2 ) i-D-H in I9a (CH2)2-CONH
CONH
CONH -(CH2)2 Analogously to example 32, the compounds of the formula I9a as indicated above are reacted with tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl-methyl)carbamate.
After removing of the protection group, the following compounds of the formula I9b are obtained:
H
N ~ NH2 ~ 19b O " O
N
Ar'-(CH2)"CONH-(CH~)~-D-H
Ar' - ( CH2 ) n-CONH- ( CH2 ) i-D-H in I9b (CH2)2-CONH

Ar' - ( CH2 ) n-CONH- ( CH2 ) i-D-H in I9b CONH
CONH -(CH2)z (CHZ)2- CONH-CHZ
~ ~/
(CHZ)2- CONH-(CHz)s Example 80:
Analogously to Example 2, 6-chlorobenzo [dejisochromene-1,3-dione is reacted with H2N-Ar' ( CH2 ) n-CONH- ( CH2 ) i-CH (Ari ) -Ar2 and 3-arninomethyl benzylamine. The following compounds of the formula IlOa are obtained:

L N
to Ar'-(CH2)"CONH-(CHZ)~ CH(Ar~)-Ar2 Ar' - ( CH2 ) n-CONH- ( CH2 ) i-CH (Arl ) -Ar2 in IlOa CONH-(CH2)2-CH /
/

\
I
(CH~Z- CONH-(CHZ)2-CH /
(CH2)2- CONH-CHZ-CH
Analogously to example 32, the compounds of the formula IlOa as indicated above are reacted with tert-butyl (tert-butoxycarbonyliminopyrazol-1-yl-methyl)carbamate.
After removing of the protection group, the following compounds of the formula IlOb are obtained:
NH
N p NH2 /
\
110b O " O
N
Ar'-(CH2)"CONH-(CH2); CH(Ar~)-Ar2 _ ~n~ - -Ar' - ( CH2 ) n-CONH- ( CH2 ) i-CH ( Arl ) -Ar2 in IlOb CONH-(CHZ)2-CH /

\
(CHZ)2- CONH-(CH2)2-CH
(CH2)2- CONH-CH2-CH
\
Example 81:
Analogously to Example 2, 6 nitrobenzo[de]isochromene-1,3-dione is reacted with H2N
C6H9- (CH2) n-R3 and then with R1-H. The following compounds of the formula Illa are obtained:
R~
/ \
111a O " O
N
(CH2)ri Rs -C6Hq- (CHx) "-R3 R1 in Rl-H and Illa o -NH- ( CH2 ) 3-NH2 (CH~2 ~NHz / \ -NH- ( CHZ ) s-NH2 -NH- ( CH2 ) ~-NH2 -N 'NH2 H
-N ~ ~NH2 -NH_ ( CHZ ) s-NH2 -NH- ( CH2 ) s-NHZ
(CHz)z ~N-C'H7 / \ H -N NH2 H
-N ~ 'NH2 H I

(CH~2 -,~ -N ,NH2 N C3H' H

-N ~ \ ~NH2 H /
-NH- ( CH2 ) s-NH2 -NH- ( CH21 s-NH2 -NH- ( CH2 ) ~-NH2 H
-N ~ ~NHZ
H /
-NH- ( CHa ) s-NH2 -NH- ( CHZ ) s-NHZ
O- N -CH3 -NH- ( CH2 ) ~-NH2 / ~ H -N NH2 H
-N ~ 'NHZ
H I /

-C6H4- (CHz) n-R3 Rl in Rl-H and Illa -NH- ( CHz ) s-NHz -NH- ( CHz ) s-NHz -NH- ( CHz ) ~-NHz ~", -N ~NH2 N - (CHz~ ~C~ I
H ~CH~ H
-N ~ 'NH2 I/
-NH- ( CHz ) s-NHz -NH- ( CHz ) s-NHz -NH- ( CHz ) ~-NHz CO-N-(CHz)z~CH3 -N ~NH2 H ~CH~ H
-N ~ 'NH2 H ( /
O -NH- ( CHz ) s-NHz -NH- ( CHz ) s-NHz \ OCH3 -NH- ( CHz ) ~-NHz -N 'NHz O H

-N ~ 'NH2 H I /
\ \ -NH- ( CHz ) 3-NHz -NH- ( CHz ) s-NHz HOOC ~ ~ -NH- ( CHz ) ~-NHz -N 'NHZ
H
- N I ~ ' NH2 H /
Analogously to Example 11, 6-nitro-2-(3-ioodophenyl)benzo[de]isoquinoline-1,3-dione or 6-nitro-2-(4-iodophenyl)benzo[de]isoquinoline-1,3-dione is reacted with H2N-ClzHe- (CHz) n-R3 and then with R1-H. The following compounds of the formula Illb are obtained:

R~
111b O "O
N
(CHZ)~ Rs -ClaHB- (CHa) n-R3 Rl in Rl-H and Illb -NH- ( CHa ) 3-NHa CH3 -NH ( CHa ) s-NHa -NH- ( CHa ) ~-NHa -N 'NHa H
-NH- ( CHa ) s-NHa -NH- ( CHa ) s-NHa -NH- (CHa) ~-NHa H C O -N NHa -NH- ( CHa ) 3-NHa CH -NH- ( CHa ) s-NHa -NH- ( CHa ) ~-NHa -N 'NH2 H
-NH- ( CHa ) s-NHa -NH- ( CHa ) s-NHa -NH- ( CHa ) ~-NHa H C O -N NHa H Rl i - (CH Rl-H
) -C

12 n 8 and Illb "

-NH- (CH2) s-NH2 -NH- ( CH2 ) 5-NH2 -NH- ( CH2 ) ~-NHZ

O
HsC -N ,NHZ
H

Example 82:
Analogously to Example 11, 6-nitrobenzo [de]isochromene-1,3-dione is reacted with 4 iodophenylamine or 3-iodophenylamine (= I-Ar'-NH2), Hetl-B (OH) 2 and then with R1-H. The following compounds of the formula Ip are obtained:
R~
\ ~ /
Ip O " O
N
Ar'-Het~
-Ar' -Hetl R1 in R1-H and Ip .'.
. ~ ~ -NH- (CH2) 3-NH2 -NH- ( CH2 ) s-NHZ
-NH- ( CH2 ) ~-NH2 -N 'NH2 H
-N \ ~NH2 -N
H NHZ
'-NH
-N

-Ar' -Hetl R1 in R1-H and Ip -NH- ( CH2 ) 3-NH2 -NH- (CHZ) s-NH2 s I / -N NH
cH3 i H
-N ~ ~NHZ
tert-butyl -NH- ( CHZ ) 3-NH2 -NH- (CHz) s-NH2 -NH- (CH2 ) -r-NHZ
\ ~ -N wNH2 tert-butyl -N ~ ~ ~NH2 H
'-NH
-N ~ -H I / ,~ NHz Example 83:
Analogously to Example 2, 6-nitrobenzo [de] isochromene-1, 3-dione is reacted with R6- (CHz) n-Ph NH2 and then with Rl-H. The following compounds of the formula I12 are obtained:
R~

O ' 'O
N
(CHZ)~ Rs t.
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Claims

What as claimed is:

1. Compounds of the formula I
in which R is H or NO2, R1 is -Het, -Het-SO2-Ar, -Het-R5, -Het-(CH2)n-Ar, NO2, -N=CH-Ar, NHAlk, NAAlk, NHA', NA'2, , -Y-D-H, -Y-Ar'-R3, -Y-(CH2)o-R3, -Y-(CH2)n-(CHR4)-R5, -Y-C[(CH2)o-OH]3, -Y-(CH2)m-NA2, -Y-(CH2 m-NHA', -Y-(CH2)o-OH, -Y-(CH2)k-R6, -Y-(CH2)i-R8, -Y-(CH2)n-Het, -Y-(CH2)n-Ar, -Y-(CH2)n-Ar'-(CH2)i-R6, -Y-(CH2)n-D-(CH2)i-R6, -Y-(CH2)n-Het-(CH2)i-R6, -Y-(CH2)n-NA-(CH2)i-R6, -Y-(CH2)n-NH-(CH2)i-R6, -Y-(CH2)n-D-(CH2)i-R8, -Y-(CH2)n-Ar'-(CH2)i-R8, -Y-(CH2)n-NH-(CH2)i-R8, -Y-(CH2)n-NA-(CH2)i-R8, -Y-[X-O]t-[X1-O]u-X2-R6 or -Y-[X-NH]u-X1-OH, R2 is -Ar, -Ar' -D-H, -Het1, -Het1-Ar, -Ar' -Het1, -Ar'-(CH2)n-R3. -Ar'-Y-(CH2)n-R3. -Ar'-Y-C(A)2-R3. -Het1-R3, -Ar'-Het1-R3, -Ar'-(CH2)n-R6, -Ar'-SO2-Het, -Ar'-NH-SO2-Het, Ar'-SO2-R7, -Ar' - (CH2)n-(CO-NH)-(CH2)i-R6. -Ar'-(CH2)n-(CO-NH)-(CH2)i-R11. -Ar'-(CH2)n-CO-Het, -Ar'-(CH2)n-(CO-NH)-(CH2)i-D-H, -Ar'-(CH2)n-(CO-NH)-(CH2)i-Ar, -Ar'-(CH2)n-(CO-NH)-(CH2)i-Het1, -Ar'-(CH2)n-(CH(CN))-(CH2)i-Ar, -Ar'-(CH2)n-(CO-NH)-(CH2)i-CH(Ar 1)-Ar2, -Ar'-S-(CH2)n-(CO-NH)-(CH2)i-Ar, -Ar'-S-(CH2)n-(CO-NH)-(CH2)i-R11M -Ar' -S-(CH2)n-(CO-NH)-(CH2)i-Het1, -Ar'-S-CH2)n-(CO-NH)-(CH2)i-CH(Ar1)-Ar2 or -Ar'-S-(CH2)n-(CO-NH)-(CH2)i-D-H, R3 is C(O)A, CONH2, CONHA, CONA2, COON or COOA, R4 is Ph or OH, R5 is CH3, CH2Cl, CF3 or Ph, R6 is NH2, NHA, NA2, NH(D-H) or NH-C(O)A, R7 is NA(D-H), NHA, NH(D-H) or NA2, R8 is -NH-(C=NH)-NH2, -NH-(C=NH)-NHA, -NH-(C=NH)-NA2, -NA-(C=NH)-NH2, -NA-(C=NH)-NHA or -NA-(C=NH)-NA2, R11 is -CH(A)-Ph, Ar' is phenylene, biphenylene, naphthylene or pyrazol-4-yl, which is unsubstituted or mono-, di- or trisubstituted by A, OH, OA, OCF3, Hal, CN, NH2, NHA, NA2, NO2, CF3, SO2NH2, SO2Ph, SO2NAH, SO2NA2, Ar, Ar1 and Ar2 are each independently phenyl, biphenyl, stilbyl, pyridyl, pyrimidyl, quinolyl, 1-imidazolyl, pyrazolyl, indanyl, benzo[1,3]dioxol-5-yl, dibenzofuranyl, 9-H-fluorenyl, 9-H-carbazolyl, [1,1',4',1'']terphenyl, anthracenyl, naphthalen-1-yl, naphthalen-2-yl or fluoren-9-on-2-yl, which is unsubstituted or mono-, di- or trisubstituted by A, OH, OA, OCF3, O-Ph, O-Ph-CH3, CH2-Ph, O-CH2-Ph, Hal, CN, NH2, NHA, NA2, NO2, CF3, SO2NH2, SO2Ph, SO2NAH, SO2NA2 or R8, Het is a saturated, partially or completely unsatura-ted mono-, bi- or tricyclic heterocyclic radical having 5 to 13 ring members, where 1 or 2 N and/or 1 or 2 S or O atoms can be present and the heterocyclic radical can be mono- or disubstituted by CN, Hal, OH, OA, CF3, A, NO2, oxo or R5, where pyrazole is not bonded via N, Het1 is an unsaturated mono-, bi- or tricyclic heterocyclic radical having 5 to 13 ring members, where 1 or 2 N and/or 1 or 2 S or O atoms can be present and/or can be mono- or disubstituted by Hal, A, OH, OA, oxo or CF3 or piperidine, morpholine, pyrrolidine or pyrrolidin-2-one, A is unbranched or branched alkyl having 1-8 C
atoms, A' is unbranched or branched alkyl having 2-6 C
atoms, Alk is unbranched alkyl having 4-8 C atoms, D is cycloalkylene having 4-7 C atoms or cyclo-hexen-1-yl, Hal is F, Cl, Br or I, X, X1,X2 in each case independently of one another are alkylene having 1 to 12 C atoms, Y is O, S, NH or NA, i is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12, k is 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12, m is 0, 1 or 2, n is 0, 1, 2, 3 or 4, o is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, t is 0, 1 or 2, u is 1 or 2, where if R2 is 4-chlorophenyl, R1 is not -NH-CH2-CH2-OH, and their pharmaceutically tolerable salts and solvates.

2. Compounds of the formula I according to Claim 1 a) 6-benzylamino-2-(2,5-dichlorophenyl)-3a,9b-dihydro-1H,3H-benzo[de]isoquinoline-1,3-dione;
b) 3-(3-[6-(2-guanidinopropylamino)-1,3-dioxo-3a,9b-dihydro-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl)-N-(2-p-tolylethyl)propionamide:
c) 3-(3-[6-(2-guanidinomethylcyclohexyl-methyl)amino]-1,3-dioxo-3a,9b-dihydro-1H,3H-benzo[de]isoquinolin-2-yl]phenyl}-N-(2-p-tolylethyl)propionamide:
d) 3-(3-[6-(4-Guanidinomethyl-benzylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl}-N-[2-(4-sulfamoyl-phenyl)-ethyl]-propionamide:
e) N-[2-(4-Chloro-phenyl)-ethyl]-3-(3-[6-(4-guanidinomethyl-benzylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl}-propionamide;

f) 6-(3-Amino-propylamino)-2-(3,4,5-trimethoxy-phenyl)-benzo[de]isoquinoline-1,3-dione:
g) 6-(3-Amino-propylamino)-2-(7-hydroxy-naphthalen-1-yl)-benzo[de]isoquinoline-1,3-dione;
h) 6-[(3-Amino-propylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-4,5-dimethoxy-benzonitrile;
i) 6-(3-Amino-propylamino)-2-(2,3-dimethoxy-phenyl)-benzo[de]isoquinoline-1,3-dione;
j) N-[2-(3-Chloro-phenyl)-ethyl]-3-{3-[6-(4-guanidinomethyl-cyclohexylmethyl-amino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl)-propionamide:
k) N-[2-(4-Chloro-phenyl)-ethyl]-3-{3-[6-(4-guanidinomethyl-cyclohexylmethyl-amino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl}-propionamide;
l) 6-(3-Amino-propylamino)-2-(4'-methoxy-biphenyl-4-yl)-benzo[de]isoquinoline-1,3-dione;
m) 6-(3-Amino-propylamino)-2-(4-carbazol-9-yl phenyl)-benzo[de]isoquinoline-1,3-dione;
n) 6-(3-Amino-propylamino)-2-(4'-hydroxy-2-methyl biphenyl-4-yl)-benzo[de]isoquinoline-1,3-dione:
o) N-(3-{[2-(4'Methoxy-biphenyl-4-yl)-1,3-dioxo 2,3-dihydro-1H-benzo[de]isoquinolin-6-ylamino]-methyl)-benzyl)-guanidine:
p) 3-{3-[6-(2-Guanidino-ethylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl)-N-(4-phenyl-butyl)-propionamide:
q) N-(2-(4-Chloro-phenyl)-ethyl]-3-{3-[6-(2-guanidino-ethylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl)-propionamide;
r) N-(2-(4-Chloro-phenyl)-ethyl]-3-{3-[6-(3-guanidino-propylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl}-propionamide;

s) N-(2-(4-Chloro-phenyl)-ethyl]-3-[3-(6-(3-[(3-guanidino-propyl)-methyl-amino]-propylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl)-propionamide;
t) N-(2-(3-Chloro-phenyl)-ethyl]-3-(3-[6-(3-guanidino-propylamino)-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl]-phenyl)-propionamide u) 6-(3-Amino-propylamino)-2-(4'-methoxy-biphenyl-4-yl)-benzo[de]isoquinoline-1,3-dione;
v) N-[3-((2-[4-(3,6-Di-tert-butyl-carbazol-9-yl)-phenyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-ylamino]-methyl)-benzyl]-guanidine:
w) 6-(3-Amino-propylamino)-2-(4-carbazol-9-yl-phenyl)-benzo[de]isoquinoline-1,3-dione.
and their physiologically acceptable salts or solvates.

3. Process for the preparation of the compounds of the formula I according to Claim 1 and their salts or solvates, characterized in that a) a compound of the formula I is liberated from one of its functional derivatives by treating with a solvolysing or hydrogenolysing agent, or b) a compound of the formula II

in which R9 is Cl, Br, NO2 or R1, where R has the meaning indicated in Claim 1 is reacted with a compound of the formula III

H2N~R2 III

in which R2 has the meaning indicated in Claim 1, and, if necessary, the radical R9 is converted into a radical R1, or (c) a radical R and/or R2 and/or R9 is converted into another radical R and/or R2 and/or R9 by, for example - converting an amino group into a guanidino group by reaction with an amidinating agent, - reacting an aryl bromide or iodide to give the corresponding coupling products by means of a Suzuki coupling with boronic acids, - reducing a nitro group, sulfonyl group or sulfoxyl group, - etherifying an OH group or subjecting an OA
group to ether cleavage, - alkylating a primary or secondary amino group, - partially or completely hydrolysing a CN group, - cleaving an ester group or esterifying a carboxylic acid radical, - or carrying out a nucleophilic or electrophilic substitution, and/or (d) a base or acid of the formula I is converted into one of its salts or solvates.

4. A pharmaceutical composition comprising an effective amount of a compound of formula I of claim 1 or a physiologically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

5. A pharmaceutical composition of claim 4 which is effective as a glycoprotein IbIX antagonist.

6. A pharmaceutical composition of claim 5, wherein said glycoprotein IbIX antagonist is effective for the control of thrombotic disorders and sequelae deriving therefrom.

?. A compound of formula I of claim 1, or a physiologically acceptable salt or solvate thereof as a medicament.

8. A compound of formula I of claim 1, or a physiologically acceptable salt or solvate thereof as a glycoprotein IbIX antagonist.

9. Use of compounds of the formula I according to Claim 1 and/or their physiologically acceptable salts or solvates for the production of a medicament for the control of thrombotic disorders and sequelae deriving therefrom or for use as anti-adhesive substances.

10. Use of compounds of the formula I according to Claim 1 and/or their physiologically acceptable salts or solvates in the treatment of illnesses, such as for the prophylaxis and/or therapy of thrombotic disorders, as well as sequelae such as, for example, myocardial infarct, arteriosclerosis, angina pectoris, acute coronary syndromes, peripheral circulatory disorders, stroke, transient ischaemic attacks, reocclusion/restenosis after angioplasty/stent implantations or as anti-adhesive substances for implants, catheters or heart pacemakers.