FIELD OF THE INVENTION This invention is directed to compounds that are precursors for the synthesis of monomeric units usefull in the synthesis of polynucleotide analoues which bind to complementary DNA and RNA strands more strongly then corresponding DNA. In particular, the invention concerns compounds for the synthesis of peptide nucleic acids.

BACKGROUND OF THE INVENTION The prevention of gene transcription and/or gene translation at the DNA/mRNA level is a new therapeutic and diagnostic methology. Applications include therapy of cancer (S. Agrawal, Tibtech 10,152 (1992): W. James, Antiviral Chemistry & Chemotherapy 2,191 (1991); B.

Calabretta, Cancer Research 51,4505 (1991)), viral and bacterial infections (L. Good, P. E.

Nielsen, Nature Biotechnology 16,355 (1998)). Besides unmodified oligonucleotides (C. <BR> <BR> <BR> <P>Helene, Anti-Cancer Drug Design 6, 569 (1991) ; E. Uhlmann, A. Peymann, Chemical Reviews 90,543 (1990)) modified oligonucleotides have recently found to be even more attractive for inhibition of gen expression due to higher enzymatic and hydrolytic stability. Most recently much interest was focussed on modified DNA analogues with a peptide backbone which were called peptide nucleic acids (PNAs) (Peter E. Nielsen et al., Science 254,1497-1500 (1991)).

The therapeutic potential of this approach has also been highlighted in the recent patent literature (S. Thomson et al., WO 93/12129).

Preparation of PNAs proceedes via coupling of monomeric units (K. L. Dueholm, M. Egholm, C. Behrens, L. Christensen, H. F. Hansen, T. Vulpius, K. H. Petersen, R. H. Berg, P. E.

Nielsen, O. Buchhard, Journal of Organic Chemistry 59,5767-5773 (1994)). In the most simple case the required monomeric unit for PNA synthesis is 2 [ (2'-Boc-aminoethyl) - (nucleine base acetyl) -amino] acetic acid (Peter E. Nielsen et al., Science 254,1497-1500 (1991)). A number of derivatives of 2 [ (2'-Boc-aminoethyl) - (nucleine base acetyl) -amino] acetic acid have also been used as educts in PNA synthesis (P. Lagriffoule, P. Wittung, M.

Eriksson, K. K. Jensen, B. Norden, 0. Buchardt, and P. E. Nielsen, Chemistry European Journal 3,912-919 (1997)).

In the known synthesis of such monomers required for PNA coupling expensive educts are needed. Furthermore, many steps with a low overall yield was observed in this sequence.

OBJECTS OF THE INVENTION It is an object of this invention to provide compounds usefull as precursors for monomers for PNA coupling with at least one protected carboxylic group.

It is a further object of this invention to provide a simple and efficient one pot synthesis of precursors for monomers for PNA coupling with at least one protected carboxylic group.

It is a further object of this invention to provide methods for the synthesis of monomers for PNA coupling that employ such protected precursors.

SUMMARY OF THE INVENTION The present invention provides precursors of monomers for the synthesis of PNA and PNA analogues with at least one protected carboxylic group. These compounds have a protected carboxylic end belonging to an a-amino acid. Furthermore two different groups are linked to the amino end of mentioned a-amino acid: an acyl residue and a organyl group which is substituted in the -position by a hetero atom.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is an example for the synthesis of a PNA monomer starting with an isocyanide, an oxo compound, an amino compound and a carboxylic acid substituted by a nucleo base (thymine).

Fig. 2 is an example for the synthesis of a PNA monomer starting with an isocyanide, an imine and a carboxylic acid substituted by a protected nucleo base (2-amino-6-benzyloxy purine).

DETAILED DESCRIPTION OF THE INVENTION Compounds having the formula (I) constitute the present invention:

A is selected from the group consisting of a single bond, ortho-phenylene, or a group of formula (II) where n is 1, 2 or 3; each R1 and R2 is independently selected from the group consisting of hydrogen, hydroxy, amino, fluorine, chlorine, bromine, iodine, (Cl-C4) alkyl which may be amino- or hydroxy- or alkoxy- or alkylthio-substituted and (C6-C10) aryl.

B is selected from the group consisting of hydrogen, (Cl-C4) alkyl, naturally occuring nucleobases, non-naturally occuring nucleobases, aromatic moieties, heterocyclic moieties, DNA intercalators, nucleobase-binding groups, reporter ligands, vinyl, chlorine, bromine, iodine, and hydroxy.

D is ortho-phenylene or selected from the group consisting of formula (III) where each R3, R4, R5 and R6 is independently selected from the group consisting of <BR> <BR> <BR> hydrogen, (Cl-Cl3) alkyl, aryl which may both be substituted by alkyl-, hydroxy-, alkoxy-, nitro-, aryl-, alkoxycarbonyl-, halogen-groups and carbohydrate moieties, or R3 and R5 taken together complete an alicyclic system, or R3 and R4 taken together complete an alicyclic system; E is CR7R8, where R7 and R8 is selected independently from the group consisting of <BR> <BR> <BR> hydrogen, (Cl-Cl3) alkyl, aryl which may both be substituted by alkyl-, hydroxy-, alkoxy-, nitro-, aryl-, alkoxycarbonyl-, halogen-groups and carbohydrate moieties, or R7 and R8 taken together complete an alicyclic or heterocyclic system which both may be substituted by alkyl-, hydroxy-, alkoxy-, nitro-, aryl-, alkoxycarbonyl-, halogen-groups.

X is a group of formula (IV)

where each R9, R10 and Rl l is independently selected from the group consisting of <BR> <BR> hydrogen, (Cl-C4) alkyl and aryl, or R9 and R10 taken together with the vinyl group in formula (IV) complete a five or sixmembered alicyclic system which may be substituted by <BR> <BR> (Cl-C4) alkyl or aryl, or R9 and R10 taken together with the vinyl group in formula (IV) complete an aromatic or heteroaromatic system which may both be substituted by nitro-, alkoxy-, and halogen groups.

Y is NR12R13, where R12 and R13 is selected independently from the group consisting of hydrogen and an amino protecting group, or OR14, or SR14 where R14 is selected from the group consisting of hydrogen and a hydroxy or mercapto protecting group.

A preferred embodiment of the invention comprises compounds of formula (I) which are characterized in that A is selected from the group consisting of a single bond, ortho-phenylene, or a group of formula (II) where n is 1, 2 or 3; each R1 and R2 is independently selected from the group <BR> <BR> <BR> consisting of hydrogen, hydroxy, chlorine, bromine, iodine, (Cl-C4) alkyl, and phenyl.<BR> <BR> <BR> <BR> <BR> <P> B is selected from the group consisting of hydrogen, (Cl-C4) alkyl, naturally occuring nucleobases, non-naturally occuring nucleobases, aromatic moieties, heterocyclic moieties, DNA intercalators, nucleobase-binding groups, reporter ligands, vinyl, chlorine, bromine, iodine, and hydroxy.

D is ortho-phenylene or selected from the group consisting of formula (III) where each R3, R4, R5 and R6 is independently selected from the group consisting of hydrogen, (Cl- C6) alkyl, and phenyl or R3 and R5 taken together complete an alicyclic system, or R3 and R4 taken together complete an alicyclic system.

E is CR7R8, where R7 and R8 is selected independently from the group consisting of <BR> <BR> <BR> hydrogen, (Cl-Cl3) alkyl, aryl which may both be substituted by alkyl-, hydroxy-, alkoxy-, nitro-, aryl-, alkoxycarbonyl-, halogen-groups and carbohydrate moieties, or R7 and R8 taken together complete an alicyclic or heterocyclic system which both may be substituted by alkyl-, hydroxy-, alkoxy-, nitro-, aryl-, alkoxycarbonyl-, halogen-groups.

X is a group of formula (IV) where each R9, R10 and R1 l is independently selected <BR> <BR> from the group consisting of hydrogen, (Cl-C4) alkyl and aryl, or R9 and R10 taken together with the vinyl group in formula (IV) complete a five or sixmembered alicyclic system which <BR> <BR> may be substituted by (Cl-C4) alkyl or aryl, or R9 and R10 taken together with the vinyl group in formula (IV) complete an aromatic or heteroaromatic system which may both be substituted by nitro- and alkoxy- groups.

Y is NR12Rl3, where R12 and R13 is selected independently from the group consisting of hydrogen and an amino protecting group, or OR14, where R14 is selected from the group consisting of hydrogen and a hydroxy protecting group.

A further preferred embodiment of the invention comprises compounds of formula (I) which are characterized in that A is selected from the group consisting of ortho-phenylene, or a group of formula (II) where n is 1,2 or 3; each R1 and R2 is independently selected from the group consisting of hydrogen, (Cl-C4) alkyl, and phenyl.

B is selected from the group consisting of naturally occuring nucleobases, non- naturally occuring nucleobases and nucleobase-binding groups.

D is ortho-phenylene or selected from the group consisting of formula (III) where each R3, R4, R5 and R6 is independently selected from the group consisting of hydrogen, and methyl or R3 and R5 taken together complete an alicyclic system.

E is CRR, where R7 and R8 is selected independently from the group consisting of <BR> <BR> <BR> hydrogen, (Cl-Cl3) alkyl, aryl which may both be substituted by alkyl-, hydroxy-, alkoxy-, nitro-, aryl-, alkoxycarbonyl-, halogen-groups and carbohydrate moieties, or R7 and R8 taken together complete an alicyclic or heterocyclic system.

X is a group of formula (IV) where R9 and R10 taken together with the vinyl group in formula (IV) complete a sixmembered alicyclic system which may be substituted by (C1- C4) alkyl or phenyl, or R9 and R10 taken together with the vinyl group in formula (IV) complete an aromatic system which may be substituted by nitro- and methoxy-groups.

Y is NR12R13, where R12 and R13 is selected independently from the group consisting of hydrogen and an amino protecting group.

A further preferred embodiment of the invention comprises compounds of formula (I) which are characterized in that X is cyclohexen-1-yl, alkyl cyclohexen-1-yl or ortho-nitro phenyl.

A further preferred embodiment of the invention comprises compounds of formula (I) which are characterized in that B is thymine or a suitable protected derivative of adenine, cytosine, or guanine.

The invention also provides a method for the production of compounds of the general formula (I) which is characterized in that an oxo compound of the formula (V), where R7 and R8 have the meanings discussed above, a primary amino compound H2N-D-Y, where D and Y are defined as discussed above, and a carboxylic acid B-A-COOH, where A and B are defined as discussed above, are allowed to react with an isocyanide of the formula (VI)

where R9, R10 and R1 l is defined as discussed above.

The synthesis of compounds of the general formula (I) can be performed in a one pot reaction as outlined in figure 1. The reactants may be added in any sequence. The temperature of the reaction is not critical; depending on the reactivity of the components, a temperature range between - 10°C and the boiling point of the particular solvent or solvent mixture is to be selected. The reactions are carried out with advantage at 10°C to 50°C.

In a further embodiment of the invention both, the said oxo compound and the amino compound mav be replaced bv the imine having the formula (VII) : where R7, R8, D and Y are defined as discussed above. In the next step a carboxylic acid B- A-COOH, where A and B are defined as discussed above, and an isocyanide of the formula (VI) where R9, R10 and Rl l is defined as discussed above, are added in any sequence to the imine. For an example of the said reaction sequence see figure 2.

The synthesis of compounds of the general formula (I) preferably takes place in organic solvents such as e. g. alcohols, halogenated hydrocarbons, ethers, carboxylic acid esters, dimethyl sulfoxide, dimethyl formamide, benzene, toluene or mixtures thereof.

The stoichiometry of the reaction components is not critical; depending on the reactivity of the components per mole of said isocyanide there are employd 1.0 to 2.0 mole of said amino compound, 1.0 to 2.0 mole of said carboxylic acid, and 1.0 to 10 mole of said oxo compound.

The reactions are carried out with advantage employing equimolar stoichiometry and exclusion of moisture.

In some cases after the reaction has taken place, the precipitated product is filtered off. In other cases the solvent is distilled off the reaction mixture to give the crude product of the general formula (I) as a solid residue. Such solid residues likewise remain which exhibit sufficient purity directly or after washing, recrystallization or chromatography. The products obtained are then dried at temperatures between 20°C to 70°C.

Compounds of the general formula (I) may be transformed to compounds having the formula

where A, B, D, E, and Y are defined as discussed above, by generally known amide cleaving methods (T. A. Keating, R. W. Armstrong J. Am. Chem. Soc. 1996,118, 2574-2583). The transformation (I) -> (VIII) provides directly monomers for the synthesis of PNA and PNA analogues if B, D or E contain a DNA binding moiety, e. g. a nucleo base, and B, D or E contain a protected amino group or hydroxy group.

Compounds having the formula (VIII) where B, D or E contain no nucleo base but a suitable leaving group, e. g. bromine, hydroxy, that may be replaced by a nucleo base by methods known in the literature (O. Buchardt et al. WO 92/20702; S. Thomson et al., WO 93/12129) can thus be transformed to monomers for the synthesis of PNA and PNA analogues.

General Remarks The following abbrevations are used in the experimental examples: Boc, tert. - butyloxycarbonyl; Z, benzyloxycarbonyl; Ib, isobutyryl.

NMR spectra were recorded on a Bruker AM 300 (300 MHz). Chemical shifts are listed in ppm. The following abbrevations are used in the listing of NMR-data: T-Ac-, N-1- <BR> <BR> thyminacetyl-; C-Z-Ac-, N4-benzyloxycarbonyl-N-l-cytosinacetyl- ; A-Z-Ac, N6- <BR> <BR> <BR> <BR> <BR> benzyloxyzarbonyl-N-9-adeninacetyl- ; G-Z-AC-, N²-benzyloxycarbonyl-N-9-guaninacetyl-;<BR> <BR> <BR> <BR> <BR> G-Bz-Ac-, 2-amino-6-benzyloxy-N-9-purinacetyl ; Th-Ac-, N-7-carboxymethyltheophylline, <BR> <BR> <BR> <BR> <BR> U-Ac-, N-l-carboxymethyluracil.

Melting points were determined using a Dr. Lindstrom melting point apparatus and are uncorrected. C, H, N Elementary analyses was performed on a Fisons Instruments EA 1108 C, H, N-Analysator. TLC was performed on TLC-aluminium sheets (silica gel 60 F254) from Merck.

The following educts were prepared according to literature methods: tert. butyl-4- <BR> <BR> <BR> nitrophenylcarbonate, mono-Boc-ethylendiamine, 3- (N-1-thyminyl) -propionsäure (B. Hyrup, M. Egholm, P. E. Nielsen, P. Wittung, B. Norden, O. Buchardt J. Am. Chem. Soc. 1991, 116, 7964-7970); N-1-carboxymethylthymine, N4-benzyloxycarbonylcytosin, N4-benzyloxy- carbonyl-N-1-carboxymethylcytosine, N6-benzyloxyzarbonyl-N-9-carboxymethyladenine, 2- amino-6-benzyloxy-N 9-carboxymethylpurine (K. L. Dueholm, M. Egholm, C. Behrens, L.

Christensen, H. F. Hansen, T. Vulpius, K. H. Petersen, R. H. Berg, P. E. Nielsen, O. Buchardt

J. Org. Chem. 1994,59 5767-5773); trans-1, 2-mono-Boc-cyclohexylendiamine (P.

Lagriffoule, P. Wittung, M. Eriksson, K. K. Jensen, B. Norden, O. Buchardt, P. E. Nielsen (Chem. Eur. J. 1997,3, 912-919); N-1-carboxymethyluracil (H. L. Wheeler, L. M. Liddle J.

Am. Chem. Soc. 1908,30, 1152-1160); cyclohexenylisocyanide (I. Ugi, K. Rosendahl Liebigs Ann. 1963,666, 65-67); O-benzyl-ethanolamine (T. L. Miller, G. L. Rowley, C. Y. Stewart J.

Am. Chem. Soc. 1966,88, 2299-2304); 4-methoxy-2-nitrophenyl isocyanide (I. Ugi, U. <BR> <BR> <BR> <P>Feker, U. Eholzer, H. Knupfer, K. Offermann Angew. Chem. 1965,77, 492-504); 1 : 2: 3: 4-Di-<BR> <BR> <BR> <BR> <BR> <BR> <BR> O-isopropyliden-cc-D-galacto-hexodialdo-1, 5-pyranose (R. E. Arrick, D. C. Baker, D. Horton Carbohydrate Research 1973,26, 441-447); N2-benzyloxycarbonyl-N>9- carboxymethylguanine (S. A. Thomsen, J. A. Josey, R. Cadilla, M. D. Gaul, C. F. Hassmann, M. J. Luzzio, A. J. Pipe, K. L. Reed, D. J. Ricca, R. W. Wiethe, S. A. Noble Tetrahedron 1995, 22,6179-6194) ; methyl ortho-bromomethylen benzoate (this compound was prepared analogue to a literature method from methyl ortho-methyl benzoate: E. L. Eliel, D. E. Rivard J.

Org. Chem. 1952,17, 1252-1256); methyl rac-2-chlorophenylacetate (A. Mc Kenzie, S.

Barrow J. Chem. Soc. 1911,99, 1916).

The nomenclature used for the PNA precursors is illustrated in formula (IX). The compound <BR> <BR> <BR> <BR> rac-2- [ (2'-Boc-aminoethyl) -uracilacetyl-amino] -2"'-chlorophenylacetic acid-cyclohexen-l"-yl-<BR> <BR> <BR> <BR> <BR> <BR> <BR> amide (see example 44) has the following formula (IX) :

EXAMPLES Example 1 rac-2- (N-1-Thyminyl) -isopropionic acid 10 g (80 mmol) Thymine, 24. 5 g (160 mmol) rac-2-bromopropionic acid and 30 g KOH are dissolved in 200 ml water and heated for twelve hours to 80 °C. After cooling to room temperature the solution is acidified to pH 5 with konc. HC1 and the resulting precipitate (unreacted thymine) is filtered off. The filtrate is adjusted to pH 1 with konc. HC1 and the resulting precipitate is filtered off and dried in vacuo. to give the title compound as a white solid in 3.7 g (23 %) yield.

Mp.: 258-260 °C, MP [L$t] 260-262 °C (M. L. Edwards, R. E. Bambury, H. W. Ritter J. Med.

Chem. 1977,20, 560-563).- ¹H-NMR (CDCl3): # = 1.55 (d, 3H, CH-CHj, 3J= 7.15 Hz), 1.83 (s, 3 H, CH=CCH3), 4.98 (q, 1H, CH-CH3), 7.46 (s, 1H, CH=C), 11.25 (s, IH. NH). - Example 2 4- (N-1-Thyminyl) -butyric acid 12.6 g (0.1 Mol) Thymine and 23.4 g (0.12 Mol) ethyl 4-bromobutyrate are suspended in 200 ml dimethylformamide and 15 g potassium carbonate are added. The suspension is heated untill a clear solution is obtained which is stirred for 24 hours at room temperature. The solution is filtered and the solvent is removed in vacuo. The residue is dissolved in 100 ml water and is extracted with 200 ml dichloromethane three times. After drying the combined organics over MgS04 the solvent is evaporated in vacuo and the resulting coluorless solid is dissolved in 200 ml 2N aqueous NaOH. The solution is heated to reflux for two hours and cooled to room temperature. The solution is acidified to pH 1 with 4N aqueous HCI and the volume of the solution is reduced to 100 ml. The resulting solid is filtered off and dried in vacuo. The title compound is obtained as a colourless solid in 7.0 g (33 %) yield.

Mp.: 198-200 °C.- ¹H-NMR(CDCl3/DMSO- [d6]): # = 1.84 (s, 3H, CH3) , 1.92 (m, 2H, <BR> <BR> CH2), 2.29 (t, 2H, COOH-CH2, 3J =7.7 Hz), 3.72 (t, 2H, NCH2, ³J =7.7 Hz), 7.26 (s, 1H, CH=C), 11.08 (s, 1H, NH). - Example 3 3- (2,4-Dioxo-3, 4-dihydro-2H-pyrimidin-1-yl) -propionic acid The title compuond is prepared as described in example 2 with thymine and ethyl 4- bromobutyrate substituted by 11.4 g (100 mmol) uracil und 15.5 g (120 mmol) ethyl 3- bromopropionate and is obtained as a colourless solid in 13.1 g (71 %) yield.

Mp.: 184-186 °C, MP+ [Ljt] : 188-191 °C (J. M. Brown, C. M. Taylor J. Chem. Soc. Perkin Trans. 1972, 2385-2391). -1H- NMR (DMSO-d6): # = 2.70 (t, 2H, CH2, 3J= 6.6 Hz), 3.91 (t, 2H, NCH2, ³J = 6.6 Hz), 5.58 (d, 1H, NCH=CH, 3J= 7.7 Hz), 7.69 (d, 1H, NCH=CH, ³J = 7.7 Hz), 11.28 (s, 1H, NH). -

Example 4 rac-2- (N-1-Thyminyl) -hexanoic acid 6.3 g (50 mmol) thymine, 10.45 g methyl rac-2-bromocapronate and 7.5 g potassium carbonate are suspended in 250 ml dimethylsulfoxide (abs.) and heated to reflux for two hours. The yellowish solution is stirred for 20 hours at room temperature. The solution is evaporated to dryness in vacuo and the residue is dissolved in 200 ml dichloromethane and 200 ml water. After seperation of the two phases the water phase is extracted with 50 ml dichloromethane three times. The combined organic extracts are dried with MgS04, filtered off and evaporated to dryness in vacuo. The resulting yellowish oil is dissolved in 100 ml 2 N NaOH and heated to reflux for two hours. After cooling to room temperature the solution is adjusted to pH 1 with 4 N HC1. The resulting precipitate is filtered off, washed with ether and dried in vacuo. The product is obtained as a colourless solid in 8.77 g (73 %) yield. <BR> <BR> <P>Mp.: 192 °C. ¹H-NMR (CDCl3/DMSO-d6): 8 = 0.84 [t, 3 H, - (CH2) 3-CH3] , 1. 27 [m, 4 H,<BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> - (CH-)) 2-15 1.79 [s, 3 H, Thyminyl-CH3], 1.95 [m, 2 H, -CH2- (CH2) 2-CH3], 4.97 [q, 1 H, CH], 7.33 [s, 1 H, Thyminyl-H]. - Example 5 rac-2- (N-1-Thyminyl) -phenylacetic acid 5 g (40 mmol) Thymine, 8.30 g methyl rac-2-chloro-phenylacetate and 6 g potassium carbonate are suspended in 150 ml dimethylformamide (abs.) and heated to reflux for two hours. The yellowish solution is stirred overnight at room temperature. The solution is evaporated to dryness in vacuo and the residue is dissolved in 200 ml dichloromethane and 200 ml water. After seperation of the two phases the water phase is extracted with 50 ml dichloromethane three times. The combined organic extracts are dried with MgS04, filtered off and evaporated to dryness in vacuo. The resulting yellowish oil is dissolved in 100 ml 2 N NaOH and heated to reflux for two hours. After cooling to room temperature the solution is adjusted to pH 1 with 4 N HCI. The water phase is extracted three times with 100 ml ethyl acetate and the combined organic extracts are dried with MgS04, filtered off and evaporated to dryness in vacuo. The resulting precipitate is washed with ether. The product is obtained as a colourless solid in 5.79 g (56 %) yield. <BR> <BR> <P> Mp.: 162'C (dec.). - IH-NMR (CDC13/DMSO-d6) : 5 = 1. 76 [s, 3 H, Thyminyl-CH3], 6.32 [s, 1 H, CH-Ph], 6.94 [s, 1 H, Thyminyl-H], 7.38-7. 56 [m, 5 H, ArH]. - Example 6 N-1-Thyminyl-methylen-ortho-benzoic acid 10.1 g (80 mmol) Thymine, 21.28 g methyl ortho-bromomethylen-benzoate and 13 g potassium carbonate are suspended in 300 ml dimethylformamide (abs.) and heated to reflux for two hours. The yellowish solution is stirred for two days at room temperature. ThP

solution is filtered off and the filtrate is evaporated to dryness in vacuo. The residue is dissolved in 150 ml dichloromethane and 150 ml water. After seperation of the two phases the water phase is extracted with 50 ml dichloromethane three times. The combined organic extracts are dried with MgS04, filtered off and evaporated to dryness in vacuo. The resulting yellowish oil is dissolved in 150 ml 2 N NaOH and stirred for two days. The solution is adjusted to pH 1 with 4 N HC1. The resulting precipitate is filtered off, washed with ether and dried in vacuo. The product is obtained as a colourless solid in 6.70 g (32 %) yield.

Mp.: 249°C (dec.). -'H-NMR (CDC13/DMSO-d6) : 5 = 1.81 [s, 3 H, Thyminyl-CH3], 5.30<BR> <BR> <BR> <BR> [s, 2 H, CH2-Ph], 7.14-7. 98 [m, 4 H, ArH]., 7.42 [s, 1 H, Thyminyl-H]. - Example 7 (2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-methylen-ortho-ben zoic acid 3.36 g (30 mmol) Uracil, 8.02 g (35 mmol) methyl ortho-bromomethylen-benzoate and 5 g potassium carbonate are suspended in 150 ml dimethylformamide (abs.) and heated to reflux for three hours. The brown solution is stirred overnight at room temperature. The solution is filtered off and the filtrate is evaporated to dryness in vacuo. The residue is dissolved in 150 ml dichloromethane and 150 ml water. The resulting solid is filtered off, dissolved in 150 ml 2 N NaOH and stirred for two days at room temperature. The solution is adjusted to pH 1 with 4 N HC1. The resulting precipitate is filtered off, washed with ether and dried in vacuo. The product is obtained as a colourless solid in 2.66 g (36 %) yield.

Mp.: 232 °C (dec.).- ¹H-NMR (DMSO-d6): # = 5.21 (s, 2H, phenyl-CH2), 5.59 (d, 1 H, <BR> <BR> <BR> CH=CH-C=O), 7. 06 (d, 1 H, CH=CH-C=O), 7. 39-7. 96 (m, 4 H, ArH), 11.28 (s, 1H, NH).

Example 8 mono-Ib-ortho-phenylendiamine To a well stirred solution of 2.16 g (20 mmol) ortho-phenylendiamine in 150 ml dichloromethane (abs.) is added a mixture of 1.07 g (10 mmol) isobutyryl chloride and 50 ml dichloromethane (abs.) at room temperature via a dropping funnel (time: 30 minutes). The resulting suspension is stirred overnight at room temperature, filtered off and the filtrate is evaporated to dryness in vacuo. The resulting yellowish precipitate is identified as the mono- protected diamine, which contains less than 10 % by-products (detected by'H-NMR- spektroskopy). Yield: 1.48 g (83 %). - ¹H-NMR (CDCl3/DMSO-d6): # = 1.16 [d, 6 H, CH- (CH3) 2], 2.71 [m, 1 H, CH- (CH3) 2], 6.44- 7.42 [m, 4 H, C6H4-], 8.97 [s, 1 H, NH]. - Example 9 <BR> <BR> <BR> rac-1-Boc-amino-2-aminopropane <BR> <BR> <BR> <BR> To a well stirred solution of 62 g (836 mmol) rac-1, 2-propylendiamine in 200 ml dimethylformamide (abs.) are added a solution of 20 g (83,6 mmol) tert. -butyl-4-nitrophenyl-

carbonate in 150 ml dimethylformamide (abs.) at room temperature via a dropping funnel (time: one hour). The yellowish solution is stirred overnight at room temperature. The solution is evaporated to dryness in vacuo and the residue is dissolved in 150 ml water. The solution is adjusted to pH 4 at 0° C and extracted with 50 ml dichloromethane three times.

After extraction the water phase is adjusted to pH 10 and extracted with 50 ml chloroform three times. The combined organic extracts are dried with MgS04, filtered off and evaporated to dryness in vacuo. The resulting yellowish oil is identified as the mono-protected diamine, which contained less than 10 % by-products (detected by IH-NMR-spektroskopy) .

Yield: 5.56 g (38 %) . 1H-NMR (CDC13): 6 = 0.97 [d, 3 H, CH2-CH-CH3], 1.38 [s, 9 H, <BR> <BR> (CH3) 3] , 2.71-3. 10 [m, 3 H, CH2-CH-CH3], 5.18 [s, 1 H, NH1. 13C-NMR (CDCI3, 75<BR> <BR> <BR> <BR> <BR> MHz): 5 = 21.22 [CH2-CH-CH3], 28.20 [ (cl3) 315 46.71 [CTH2-CH-CH3], 48.35 [CH2-CH- CH3], 78.83 [O=C-O-C- (CH3) 3], 156.12 [C=O]. - Example 10 4-ter.-Butyl-1-cyano-1-formamido-cyclohexane 308.5 g (2 mol) 4-tert. -Butylcyclohexanone are dissolved in 150 ml diethylether and a solution of 120.8 g (2.26 mol) NH4CI in 366 ml of water are added. After cooling to 0°C a solution of 101 g (2.1 mol) NaCN in 266 ml of water are added via addition funnel. The suspension is stirred 48 hours at room temperature and is then acidified (pH = 1) with conc. HCI. The precipitate is filtered off and washed with ether. The remaining aqueous solution is washed three times with ether to remove unreacted starting material. The pH is raised to twelve with aqueous 20 % NaOH and the solution extracted three times with ether. The organics are combined and dried over MgS04. Evaporation of the solvent in vacuo gives the amine as a white solid. The precipitated hydrochlorid salt is dissolved in aqueous 2N NaOH and extracted with ether three times. After drying of the organics and evaporation of the solvent the two product portions are combined to give the amine in 323 g (90 %) yield.

The amine is dissolved in 311 ml formic acid and cooled to 0°C. To this stirred solution a mixture of 311 ml formic acid and 184 ml acetic anhydride is added via addition funnel. After stirring for twelve hours at room temperature the reaction is quenched with 40 ml water and most of the solvent is evaporated in vacuo. The remaining residue is dissolved in 1000 ml dichloromethane and washed with pH 10 water. The aqueous phase is extracted two times with dichloromethane and the combined organics are dried over MgS04. Evaporation of the solvent in vacuo gives the title compound in 369.1 g (89 %) yield as a white solid. <BR> <BR> <P> TLC (dichloromethane/methanol, 99: 1): Rf= 0.26. - Mp. : 102-103'C. - IH-NMR (CDC13, due to the existance of two rotamers in a 70: 30 ratio several signals are doubled): 8 = 0.88 (ma.), 0.90 (mi) (s, 9H, tert. -Butyl-CH3), 1.0-2. 5 (m, 9H, CHz, CH), 6.53 (ma.), 7.22 (mi.) (br, 0.3H, NH), 8.14 (ma.), 8.49 (mi.) (d, 0.3H, HC=O, 3J=11. 7 Hz). -

Example 11 1 -Cyano-1 -formamido-4-phenyl-cyclohexane The title compound is prepared as described in example 10 with 348.4 g (2 mol) 4- phenylcyclohexanone being substituted for 4-tert. -butylcyclohexanone. The resulting crude product is recrystallized from dichloromethane to give a white solid in 251 g (55 %) yield. <BR> <BR> <P>TLC (dichloromethane/methanol, 98: 2): Rf= 0. 28. - Mp. : 164-165 °C. IH-NMR (CDC13, due to the existance of two rotamers in a 83: 17 ratio several signals are doubled): 5 = 1.7-2. 7 <BR> <BR> <BR> <BR> (m, 9H, CH+CH2), 5.91 (ma.), 6.54 (mi.) (2br, 1H, NH), 7.2-7. 4 (m, 5H, ArH) , 8.22 (ma.), 8.56 (mi.) (s+d, 1H, HC=O, 3J= 11.8 Hz) - Example 12 <BR> <BR> <BR> <BR> N- (4-tert. -Butyl-cyclohex-1-enyl) -formamide<BR> <BR> <BR> <BR> <BR> <BR> <BR> 43 g (0. 384 mol) Potassium tert. -butoxide and 20.8 g (0.1 mol) 4-tert.-butyl-1-cyano-1- formamido-cyclohexane are suspended in 500 ml abs. tetrahydrofurane. After heating to reflux for twelve hours the reaction mixture is poured into 1.5 1 aqueous 0.5 molar NaC03. The layers are seperated and the aqueous is extracted three times with ethyl acetate. The combined organics are dried over MgS04 and the solvent is removed in vacuo. The remaining yellow solid is recrystallized from n-hexane to give the title compound as a white solid in 14.7 g (81 %) yield.

TLC (dichloromethane/methanol, 98: 2): Rf= 0.44. - Mp. : 108-110 °C. 'H-NMR (CDCI3, due to the existance of two rotamers in a 70: 30 ratio several signals are doubled): 8 =0.86 (ma.), 0.87 (mi.) (2s, 9H, tert. -Butyl-CH3), 1.2-1. 6 (m, 7H, CH, CH2), 5.29 (ma.), 6.09 (mi.) (2m, 1H, C=CH), 6.59 (mi.), 7.74 (ma.) (br, 1H, NH), 8.14 (s, 0.35 H, OCH), 8.32 (d, 0.65H, OCH, 3J= 11.6 Hz). - Example 13 rac-N (4-Phenyl-cyclohexen-1-yl) -formamide The title compound is prepared as described in example 12 with 22.8 g (0.1 mol) 1-cyan-1- formamido-4-phenyl-cyclohexane being substituted 4-tert. -butyl-1-cyano-1-formamido- cyclohexane. The resulting crude product is stirred with hot n-hexane and filtered off after cooling to give a white solid in 16.1 g (80 %) yield. <BR> <BR> <P> TLC (dichloromethane/methanol, 98: 2): Rf= 0. 29. - Mp. : 128-129 °C. 'H-NMR (CDCI3, due to the existance of isomers in a 56: 22: 22 ratio several signals are trebled): 8 = 1.5-2. 8 (m, <BR> <BR> <BR> <BR> 7H, CH+CH2), 5.37 (ma.), 6.18 (mi.), 6.59 (mi.) (3m, 1H, C=CH), 7.1-7.3 (m, 5H, ArH), 7.99 (br, 1H, NH) , 7.76 (mi.), 8.14 (mi.) (s, 0.44H, OCH), 8.36 (d, 0.56H, OCH, 3J= 11.6 Hz). -

Example 14 rac-4-tert. -Butyl-cyclohexen-1-yl-isocyanide 18.1 g (0.1 mol) of compound N- (4-tert. -Butyl-cyclohex-l-enyl) -formamide and 32 ml abs. triethylamine are dissolved in 250 ml dichloromethane. The solution is cooled to 0 °C and 10 g <BR> <BR> <BR> (0. 101 mol) phosgene are introduced in about two minutes. After stirring for one hour at 0 °C 70 ml water are added and the layers are seperated. The organic layer is washed with 70 ml water two times and is dried over MgS04. After evaporation of the solvent in vacuo the residue is applied to flash filtration on silica gel with n-hexane/ethyl acetate, 95: 5 to give the title compound as a colourless oil in 13.04 g (80 %) yield. <BR> <BR> <P>TLC (n-hexan/ethyl acetate, 95: 5): Rf= 0.70. - 1H-NMR (CDC13) : 8 = 0.87 (s, 9H, CH3) , 1.2-1. 4 (m, 7H, cyclohexenyl-CH, CHz), 6.02 (m, 1H, cyclohexenyl-C=CH.- Example 15 <BR> <BR> <BR> rac-4-Phenyl-cyclohexen-1-yl-isocyanide <BR> <BR> <BR> <BR> <BR> The title compound is prepared as described in example 14 with 20.1 g (0.1 mol) rac-N- (4- Phenyl-cyclohexen-l-yl) -formamide being substituted for N- (4-tert. -butyl-cyclohexen-1-yl) - formamide. The resulting crude is applied to flash filtration on silica gel with dichloromethane/methanol, 99: 1 to give the title compound as a yellowish solid in 13.1 g (71 %) yield. <BR> <BR> <P> TLC (n-hexan/ethyl acetate, 95: 5): Rf = 0. 34. -'H-NMR (CDC13) : 5 = 1.8-2. 8 (m, 7H,<BR> <BR> <BR> <BR> <BR> <BR> cyclohexenyl-CH+CH2), 6.10 (m, 1H, cyclohexenyl-C=CH), 7.1-7. 3 (m, SH, ArH). - Example 16 N (2-Nitro-4-methylphenyl) -formamide In 300 ml formic acid 152.2 g (1 mol) 2-nitro-4-methylaniline is dissolved and cooled to 0°C.

To this stirred solution a mixture of 300 ml formic acid and 112 g acetic anhydride is added via addition funnel. After stirring for twelve hours at room temperature the reaction is quenched with 40 ml water and most of the solvent is evaporated in vacuo. 250 ml of 2 N aqueous NaOH solution is added to the remaining residue and the resulting precipitate is collected, washed with 250 ml water three times and dried with ether. Traces of solvants are removed in vacuo to give the title compound in 148.0 g (82 %) yield as a yellow solid.

H-NMR (DMSO-d6) : 5 = 2.30 (s, 3 H, CH3), 7.49 (d, 1 H, 6-H), 7.85 (s, 1 H, 3-H), 7. 98 (m, 1 H, 5-H), 8.39 (s, 1 H, NH), 10.40 (s, 1 H, C (O) H). - Example 17 2-Nitro-4-methylphenyl-isocyanide 27.0 g (0.15 mol) N- (2-Nitro-4-methylphenyl) -formamide and 48 ml abs. triethylamine are dissolved in 350 ml dichloromethane. The solution is cooled to 0 °C and 15 g (0.101 mol) phosgene are introduced in about five minutes. After stirring for one hour at 0 °C 100 ml

water are added and the layers are seperated. The organic layer is washed with 100 ml water twice and is dried over MgS04. After evaporation of the solvent at 20°C in vacuo the title compound is obtained as a dark brown solid in 16.6 g (76 %) yield.

H-NMR (CDCI3) : 5 = 2.49 (s, 3H, CH3), 7.49 (s, 2 H, 6-H, 3-H), 7.90 (s, 1 H, 5-H). - Example 18 2- ( (2'-Boc-aminoethyl) -thyminacetyl-amino] -acetic acid-cyclohexen-1"-yl-amide 0.32 g (2 mmol) mono-Boc-ethylendiamine, 0.37 g (2 mmol) N 1-carboxymethylthymine and 0.06 g (2 mmol) paraformaldehyde are suspended in 7 ml abs. methanol and stirred for 10 min at room temperature. 0.21 g (2 mmol) cyclohexen-1-yl-isocyanide are added in one portion and the resulting suspension is stirred 48 hours at room temperature. The solvent is removed in vacuo and the residue is stirred with dichloromethane. The suspension is filtered and the filtrate is evaporated to dryness in vacuo. The remaining solid is stirred with ether and filtered off to give the title compound as a white solid in 0.70 g (76 %) yield. <BR> <BR> <P>TLC (dichloromethane/methanol, 95: 5): Rf= 0. 38. - Mp. : 154 °C. -¹H-NMR (DMSO-d6, due to the existance of two rotamers in a 60: 40 ratio several signals are doubled): # = 1.32 (s, 9H, Boc-CH3), 1.4-2. 1 (m, 8H, cyclohexyl-CH2), 1.71, 1.73 (2s, 3H, T-Ac-CH3), 2.8-3. 2 (m, <BR> <BR> <BR> 4H, I'-H, 2'-H), 3. 91 (ma.), 4.05 (mi.) (s, 2H, CH2), 4.48 (mi.), 4.62 (ma.) (s, 2H, CH2), 6.00 (ma.), 6.08 (mi.) (m, 0.4H, cyclohexenyl-C=CH), 6.92 (mi.), 7.07 (ma.) (br, 1H, Boc-NH), <BR> <BR> <BR> 7.30 (mi.), 7. 35 (ma.) (s, 1H, T-Ac-C=CH), 8.86 (ma.), 9.25 (mi.) (s, 0.4H, cyclohexenyl- NH), 11.25 (br, IH, T-Ac-NH). - C22H33N5O6 (463.5) Calc. C 57.01 H 7.18 N 15.11 Found C 57.06 H 7.24 N 15. 16.- Example 19 rac-2- [ (2'-Ib-amino-phenyl) -thyminacetyl-amino] -biphenyl-4-yl-acetic acid- cyclohexen-1"-yl-amide 0.33 g (2 mmol) mono-Ib-ortho-phenylendiamine and 0.36 g (2 mmol) 4-phenyl benzaldehyde are evaporated three times with toluene. The residue is dissolved in 7 ml abs. methanol and 0.37 g (2 mmol) N-1-carboxymethylthymine are added. After five minutes stirring at room temperature 0.21 g (2 mmol) cyclohexen-1-yl-isocyanide are added in one portion. The suspension is heated to reflux for five minutes and stirred for 48 hours at room temperature.

The precipitate is filtered off and washed with ether. After flash filtration over silica gel (dichloromethane/methanol, 8: 2) and removal of the solvent in vacuo the title compound is obtained as a white solid in 0.65 g (51 %) yield. <BR> <BR> <P> TLC (dichloromethane/methanol, 95: 5): Rf = 0. 71. - Mp.: >250°C.- ¹H-NMR (DMSO-d6):<BR> <BR> <BR> <BR> <BR> <BR> 1.21 (d, 3H, CH (CH3) 2, 3J= 6.6 Hz), 1.24 (d, 3H, CH (cl3) 2, 3J= 6. 6 Hz), 1.50 (m, 4H, CHz), 1.73 (s, 3H, T-Ac-CH3), 2.08 (m, 4H, CH2), 2.90 (m, 1H, CH (CH3) 2, 3J= 6.6 Hz), 3.92 (d, 1H, T-Ac-CH2, ²J= 16.5 Hz), 4.00 (d, 1H, T-Ac-CH2, ²J= 16.5 Hz), 5.88 (s, 1H, 2-

H), 6.10 (s, 1H, C=CH), 6.7-8. 3 (m, 14H, ArH, T-Ac-C=CH), 9.47 (s, 1H, NH), 11.22 (s, 1H, NH), 11.32 (s, 1H, NH) - C37H39N505 (633.6) Calc. C 70.12 H 6.20 N 11.05 Found C 70.49 H 6.24 N 11. 07. - Example 20 <BR> <BR> rac-2- [ (2'-Boc-aminoethyl) -N4-Z-cytosinacetyl-amino] -para-nitrophenylacetic acid-<BR> <BR> <BR> <BR> <BR> <BR> cyclohexen-1"-yl-amide 0.32 g (2 mmol) mono-Boc-ethylendiamine and 0.30 g (2 mmol) 4-nitro benzaldehyde are evaporated with toluene three times. The residue is dissolved in 7 ml abs. methanol and 0.61 g (2 mmol) N4-Z-N-1-carboxymethyl cytosine are added. After stirring for five minutes 0.21 g cyclohexen-1-yl-isocyanide are added in one portion. The suspension is heated for five minutes to reflux and stirred for 48 hours at room temperature. The precipitate is filtered off <BR> <BR> <BR> and is flash filtered over silica gel (dichloromethane/methanol, 9: 1). After removal of the solvent in vacuo the title compound is obtained as a yellowish solid in 0.50 g (36 %) yield.

TLC (dichloromethane/methanol, 95: 5): Rf= 0.56. - Mp. : zers. 150 °C.- ¹H-NMR (CDC13) : 5= 1.37 (s, 9H, Boc-CH3), 1.58 (m, 4H, cyclohexenyl-CH2), 2.07 (m, 4H, cyclohexenyl-CH2), 2.90 (m, 1H, NCH2CH2), 3.07 (m, 1H, NCH2CH2), 3.21 (m, 1H, <BR> <BR> NCH2CH2), 3.43 (m, 1H, NCH2CH2), 4.46 (d, 1H, C-Z-Ac-CH2, 2J= 15 4 Hz), 5.01 (d, 1H, <BR> <BR> <BR> <BR> <BR> <BR> C-Z-Ac-CH2, 2J = 15. 4 Hz), 5.14 (d, 1H, Z-CH2, ²J = 12.1 Hz), 5.25 (d, 1H, Z-CH2, 2J= 12.1 Hz), 5.62 (br, 1H, Boc-NH), 5.99 (s, 1H, NCH), 6.14 (m, 1H, cyclohexenyl-C=CH), 7.18 (d, 1H, C-Z-Ac-NCH=CH, 3J= 7.2 Hz), 7.37 (m, 5H, Z-ArH), 7.55 (d, 1H, C-Z-Ac- NCH=CH, 3J= 7.2 Hz), 7.56 (d, 2H, ArH, ³J = 8.8 Hz), 8.10 (d, 2H, ArH, 3J= 8.8 Hz), 8.53 (br, 1H, cyclohexenyl-NH).- <BR> <BR> <BR> C35H41N7O9(703.8) Calc. C 59.73 H 5. 87 N 13.93<BR> <BR> <BR> <BR> <BR> Found C 59.75 H 5. 89 N 13. 90. - Example 21 rac-2- [ (2'-Boc-aminoethyl) -N6-Z-adeninacetyl-aminol-ortho-chlorophenylacetic acid- cyclohexen-1"-yl-amide 0.28 g (2 mmol) 2-Chlorobenzaldehyde and 0.32 g (2 mmol) mono-Boc-ethylendiamine are evaporated three times with toluene. The residue is dissolved in 7 ml abs. methanol. 0.65 g (2 mmol) A'6-Z-N-9-carboxymethyl adenine are added. After stirring for five minutes cyclohexen-1-yl-isocyanide are added in one portion. The suspension is shortly heated until a clear solution is obtained and than stirred for 48 hours at room temperature. The precipitate is filtered off and washed with ether. After drying in vacuo the title compound is obtained as a yellowish solid in 0.54 g (38 %) yield. <BR> <BR> <P> TLC (dichloromethane/methanol, 9: 1): Rf = 0.89. -Mp.: 154-155 °C-'H-NMR (DMSO- d6) : 1.33 (s, 9H, Boc-CH3), 1.50 (m, 4H, cyclohexenvl-CHz), 2.02 (m, 4H, cyclohexenyl-

CH2), 2.61 (m, 1H, NCH2CH2), 3.18 (m, 1H, NCH2CH2), 3.34 (m, 1H, NCH2CH2) , 3.54 (m, 1H, NCH2CH2), 5.23 (s, 2H, Z-CH2), 5.46 (s, 2H, cyclohexenyl-C=CH, NCH), 6.02 (d, 1H, <BR> <BR> A-Z-Ac-CH2, ²J= 14.9 Hz), 6.17 (d, 1H, A-Z-Ac-CH2, ²J= 14.9 Hz), 6. 83 (br, 1H, Boc-<BR> <BR> <BR> <BR> <BR> NH), 7. 39 (m, 9H, ArH), 8.42 (s, 1H, A-Z-Ac-N=CH), 8.63 (s, 1H, A-Z-Ac-NCH), 9.63 (s, 1H, cyclohexenyl-NH), 10.63 (br, 1H, Z-NH). - C36H4lN806CI (717. 2) Calc. C 60.29 H 5.76 N 15.62 Found C 60.25 H 5.72 N 15.62.- Example 22 <BR> <BR> 2- [ (//'flM-2'-Boc-aminocyclohexyl) -A'-Z-cytosinacetyl-amino] -3-methyl-propionic acid-<BR> <BR> <BR> <BR> <BR> cyclohexen-1"-yl-amide 0.43 g (2 mmol) trans-1, 2-mono-Boc-cyclohexylendiamine are evaporated three times with acetone. The residue is dissolved in 7 ml abs. methanol and 0.61 g (2 mmol) N4-Z-N-1- carboxymethyl cytosine are added. After stirring for five minutes at room temperature 0.21 g (2 mmol) cyclohexen-1-yl-isocyanide are added in one portion. The suspension is heated for five minutes to reflux and stirred for 48 hours at room temperature. After removal of the solvent in vacuo the solid residue is purified by chromatography on silica gel <BR> <BR> <BR> (dichloromethane/methanol, 95: 5). The product containing fractions are collected and the solvent is removed in vacuo to give the title compound as a white solid in 1.29 g (97 %) yield.

The product exists as a mixture of rotamers in a 73: 17 ratio in CDC13 at room temperature.

TLC (dichloromethane/methanol, 95: 5) ; Rf = 0.44.- Mp.: 113 °C. ¹H-NMR (CDClJDMSO-d6, due to the existance of rotamers in a 73: 27 ratio several signals are doubled): 5= 1.1-2. 2 (m, 16H, CH2), 1.35 (s, 15H, Boc-CH3, NC (CH3) 2), 2.82 (m, 1H, <BR> <BR> <BR> NCH), 3.20 (m, 1H, NCH), 4.25 (ma.) (s, 1.46H, C-Z-Ac-CH2), 4.70 (mi.) (d, 0. 17H, C-Z-Ac- CH2, 2ff= 16.5 Hz), 5.13 (s, 2H, Z-CH2), 5.20 (mi.) (d, 0.17H, C-Z-Ac-CH2, ²J= 16.5 Hz), 5.78 (mi.), 5.99 (m, 1H, cyclohexenyl-C=CH), 6.90 (br, 1H, Boc-NH), 6.94 (ma.), 7.04 (mi.) (d, 1H, C-Z-Ac-CH=CH, 3J= 7.2 Hz), 7.30 (m, 5H, Z-ArH), 7.67 (mi.), 7.78 (d, 1H, C- Z-Ac-CH=CH, 3J= 7.2 Hz). - <BR> <BR> <BR> C35H47N607 (663.8) Calc. C 63.23 H 7. 28 N 12.64<BR> <BR> <BR> <BR> Found C 63.30 H 7.26 N 12.63. - Example 23 rac-[(2'-Ib-amino-phenyl)-thyminacetyl-amino] -4, 8-dimethyl-non-7-enoic acid- cyclohexen-1"-yl-amide 0.36 g (2 mmol) mono-Ib-ortho-phenylendiamine and 0.31 g (2 mmol) rac-citronellal are evaporated three times with toluene. The residue is dissolved in 7 ml abs. methanol and 0. 37 g (2 mmol) N-1-carboxymethylthymine are added. After five minutes of stirring at room temperature 0.21 g (2 mmol) cyclohexen-1-yl-isocyanide are added in one portion. The suspension is shortly heated until a clear solution is obtained and stirred for 48 hours at room

temperature. After removal of the solvent in vacuo the residue is stirred with dichloromethane. The suspension is filtered and the filtrate is concentrated in vacuo. The concentrate was purified by column chromatography on silica gel (dichloromethane/methanol, <BR> <BR> <BR> 9: 1). The product containig fractions were collected and the solvent removed in vacuo to give the title compound as a yellowish solid in 0.98 g (81 %) yield.

TLC (dichloromethane/methanol, 9: 1): Rf= 0.70. ¹H-NMR(CDCl3, due to the possible existance of diastereomers and rotamers several peaks are trebled): 8 = 0.83, 0.90, 0.96 (3d, <BR> <BR> 3H, Ib-CH3, ³J = 6.0, 6.7, 6.7 Hz), 1.2-2. 2 (m, 26H), 2.5-2. 8 (m, 2H, Ib-CH (CH3) 2, CHCH3), <BR> <BR> <BR> <BR> <BR> 3.40, 3. 51, 3. 53 (3d, 1H, T-Ac-CH2, 2J= 15.4, 16.8, 17.4 Hz), 4.24, 4.28, 4.33 (3d, 1H, T-<BR> <BR> <BR> <BR> <BR> AC-CH2, 22= 15.4, 17.4, 16.8 Hz), 4.59 (m, 1H, 2-H), 4.98 (m, 1H, (CH3) C=CH), 6.10 (m,<BR> <BR> <BR> <BR> <BR> <BR> 1H, cyclohexenyl-C=CH), 6.73 (s, 1H, T-Ac-C=CH), 7.1-7. 6 (m, 4H, ArH), 8. 30, 8. 3 5, 8.47 (3m, 1H, cyclohexenyl-NH), 10.60, 10.69, 10.82 (3s, 1H, Ib-NH) .

C34H47N505 (605.8) Calc. C 67.41 H 7. 82 N 11. 56 Found C 67.29 H 7.81 N 11. 59.- Example 24 <BR> <BR> <BR> rac-2- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -3,3-dimethyl-butyric acid-4"-tert. -<BR> <BR> <BR> <BR> <BR> butyl-cyclohexen-l"-yl-amide 0.40 g (2.5 mmol) mono-Boc-ethylendiamine, 0.17 g (2 mmol) pivalaldehyde and 0.46 g (2.5 mmol) N-1-carboxymethylthymine are suspended in 7 ml abs. methanol and stirred for ten minutes at room temperature. 0.33 g (2 mmol) rac-1-Isocyano-4-tert.-butyl-cyclohexene are added in one portion and the suspension is stirred for 48 hours at room temperature. The solvent is removed in vacuo and the residue is purified by column chromatography <BR> <BR> <BR> (dichloromethane/methanol, 95: 5). The product containing fractions are collected and the solvent removed in vacuo to give the title compound as a white solid in 1.09 g (94 %) yield. <BR> <BR> <P> TLC (dichloromethane/methanol, 95: 5): Rf= 0.58. - 1H-NMR (CDC13, due to the existance of diastereomers in a 73: 27 ratio several signals are doubled): 5 = 0.88 (ma.), 0.93 (mi.) (2s, <BR> <BR> <BR> 9H, t. -Butyl-cyclohexenyl-CH3), 1.06 (ma.), 1.13 (mi.) (2s, 9H, NCC (CH3) 3), 1.43 (ma.), <BR> <BR> <BR> <BR> <BR> 1. 46 (mi.) (2s, 9H, Boc-CH3), 1.8-2. 2 (m, 7H, t.-Butyl-cyclohexenyl-CH2, CH), 1.92 (s, 3H, T-Ac-CH3), 3.2-4. 0 (m, 4H, 1'-H, 2'-H), 4.31 (mi.), 4.73 (ma.), 4.86 (ma.), 5.15 (mi.) (4d, 2H, T-Ac-CH2, ²J= 16.5 Hz), 4.75 (ma.), 4.90 (mi.) (2s, 1H, NCH), 6.09 (m, 1H, t. -Butyl- <BR> <BR> <BR> cyclohexenyl-C=CH), 7.06 (s, 1H, T-Ac-C=CH), 8.54 (br, 1H, t. -Butyl-cyclohexenyl-NH), <BR> <BR> <BR> <BR> <BR> 11. 50 (br, 1H, T-Ac-NH).- <BR> <BR> <BR> <BR> <BR> C3oH49N506 (580. 7) Calc. C 62.58 H 8.58 N 12.16 Found C 62.54 H 8.60 N 12. 18.-

Example 25 <BR> <BR> <BR> rac-2- [ (trans-2'-Boc-aminocyclohexyl) -thyminacetyl-aminol-3, 3-dimethyl-butyric acid-<BR> <BR> <BR> <BR> <BR> <BR> 4"-tert. -butyl-cyclohexen-1"-yl-amide 0.54 g (2.5 mmol) trans-1, 2-mono-Boc-cyclohexylendiamine, 0.06 g (2 mmol) pivalaldehyde and 0.46 g (2.5 mmol) N-1-carboxymethylthymine are suspended in 7 ml abs. methanol and stirred for ten minutes at room temperature. 0. 33 g (2 mmol) rac-1-Isocyano-4-tert -butyl cyclohexene are added in one portion and the suspension is stirred for 48 hours at room temperature. The solvent is removed in vacuo and the residue is purified by column <BR> <BR> <BR> chromatography (dichloromethane/methanol, 95: 5). The product containing fractions are collected and the solvent is removed in vacuo to give the title compound as a white solid in 0.91 g (79 %) yield. <BR> <BR> <P>TLC (dichloromethane/methanol, 95: 5) : Rf = 0.28. ¹H-NMR(CDCl3, due to the existance<BR> <BR> <BR> <BR> <BR> <BR> of two diastereomers in a 60: 40 ratio several signals are doubled): 8 = 0.85 (ma.), 0.86 (mi.) (s, 9H, 4-tert. -Butyl-cyclohexenyl-CH3), 1.38 (ma.), 1.41 (mi.) (2s, 9H, Boc-CH3), 1.0-2. 2 (m, <BR> <BR> <BR> 15H, cyclohexyl-CH2, 4-tert. -butyl-cyclohexenyl-CH, CH2) , 1. 81 (s, 3H, T-Ac-CH3), 3.28<BR> <BR> <BR> <BR> <BR> (m, 1H, NCH), 3.40 (m, 1H, NCH) , 3.51-4. 12 (4d, 2H, C2H2, ²J = 16.5 Hz), 4. 37-4. 81 (4d, 2H, T-Ac-CH2, ²J= 16.5 Hz), 5.96 (ma.), 6.05 (2m, 1 H, 4-tert. -Butyl-cyclohexenyl-C=CH), 6.21 (ma.), 6.77 (mi.) (2br, 1H, Boc-NH) , 7.07 (s, 1H, T-Ac-CH), 8.39 (ma.), 9.01 (mi.) (2s, 1H, 4-tert. -Butyl-cyclohexenyl-NH) , 11.12 (mi.), 11.18 (ma.) (2s, 1 H, T-Ac-NH). - C30H47N5O6 (573.7) Calc. C 62.80 H 8.26 N 12.21 Found C 62.81 H 8.29 N 12.20.- Example 26 rac-2- [(2'-Boc-aminoethyl)-brom acetyl-aminoj-para-nitrophenylacetic acid- cyclohexen-1"-yl-amide 0.80 g (5 mmol) mono-Boc-ethylendiamine, 0.69 g (5 mmol) bromoacetic acid and 0.76 g (5 mmol) 4-nitrobenzaldehyde are suspended in 10 ml abs. methanol and stirred for ten min at room temperature. 0.53 g (5 mmol) Cyclohexen-1-yl-isocyanide are added in one portion and the resulting suspension is stirred 48 hours at room temperature. The solvent is removed in vacuo and the residue is stirred with dichloromethane. The suspension is filtered and the filtrate is evaporated to dryness in vacuo. The remaining solid is stirred with ether and filtered off to give the title compound as a white solid in 0.50 g (19 %) yield. <BR> <BR> <P> TLC (dichlormethane/methanol, 98: 2): Rf = 0.40. - 1H-NMR (CDC13) : 8 = 1.45 (s, 9H, Boc- CH3) , 1. 5-2.4 (m, 8H, Cyclohexyl-CH2), 3.1-3. 5 (m, 4H, NCH2CH2N), 4.05 (s, 2H, T-Ac- CH2) , 5. 31 (br, 1H, Boc-NH), 5.59 (s, 1H, 2-H), 6.12 (m, 1H, Cyclohexenyl-C=CH), 7.59 (m, 2H, ArH), 8.22 (m, 2H, ArH). - <BR> <BR> C23H3, BrN406 (539.4) Calc. C 51. 21 H 5.79 N 10.39<BR> <BR> <BR> <BR> <BR> Found C 51.16 H 5.81 N 10. 41. -

Example 27 <BR> <BR> <BR> 2- [ (2'-Boc-aminoethyl) -bromacetyl-amino] -3, 3-dimethyl-butyric acid-4"-tert. -butyl- <BR> <BR> <BR> <BR> <BR> cyclohexen-1"-yl-amide 2.00 g (12.5 mmol) mono-Boc-ethylendiamine, 1.74 g (12.5 mmol) bromoacetic acid and 0.86 g (10 mmol) pivalaldehyde are suspended in 15 ml abs. methanol and stirred for ten min <BR> <BR> <BR> at room temperature. 1.65 g (10 mmol) rac-4-tert. -butyl-cyclohexenylisocyanide are added in one portion and the resulting suspension is stirred 48 hours at room temperature. The solvent is removed in vacuo and the residue is purified by chromatography on silica gel <BR> <BR> (dichlormethane/methanol, 98: 2). The title compound is obtained as a white solid in 4.50 g (85 %) yield. <BR> <BR> <P>TLC (dichlormethane/methanol, 98: 2): Rf = 0.59. - IH-NMR (CDC13) : 8 = 0.87 (s, 9H, 4-<BR> <BR> <BR> <BR> <BR> <BR> tert. -Butyl-cyclohexenyl-CH3), 1.08 (s, 9H, C2-C (CH3) 3), 1.44 (s, 9H, Boc-CH3), 1. 1-2. 2 (m,<BR> <BR> <BR> <BR> <BR> 7H, 4-tert. -Butyl-cyclohexyl-CH, CHZ), 3.1-4. 0 (m, 4H, NCH2CH2N), 4.53 (s, 1H, H-2), 4.88 (m, 2H, T-Ac-CH2), 6.05 (m, 1H, 4-tert.Butyl-cyclohexenyl-C=CH), 7.30 (br, 1H, 4- tert. Butyl-cyclohexenyl-NH). - C25H44BrN3O4 (530.5) Calc. C 56.60 H 8.36 N 7.92 Found C 56.68 H 8.40 N 7.96.- Example 28 rac-2-[(2'-Ib-amino-phenyl)-thyminacetyl-amino]-4,8-dimethyl -non-7-enoic acid 0.90 g (1.5 mmol) rac- [ (2'-Ib-amino-phenyl) -thyminacetyl-amino] -4,8-dimethyl-non-7- enoic acid-cyclohexen-l"-yl-amide are dissolved in 10 ml of a stock solution of 1.7 ml conc.

HCl in 100 ml abs. tetrahydrofurane. The reaction mixture is stirred for twelve hours and neutralized by the addition of solid sodium bicarbonate and then filtered. The solvent is removed in vacuo and the residue is applied to column chromatography on silica gel <BR> <BR> <BR> (dichloromethane/methanol, 95: 5). The product containing fractions are collected and the solvent removed in vacuo to give the title compound as a yellowish solid in 0.73 g (92 %) yield.

TLC (dichloromethane/methanol, 95: 5):Rf=0.21. ¹H-NMR (CDCl3, due to the existance of two diastereomers and two rotamers several signals are multiplied): 5 = 0.86, 0.88 (2d, 3H, Ib-CH3, ³J= 6.1 Hz), 1.0-2. 0 (m, 19H), 1.84 (s, 3H, T-Ac-CH3), 2.85 (m, 1H, Ib-CH) , 3.50, <BR> <BR> 3.60, 3.82, 3.84 (4d, 1H, T-Ac-CH2, 2J= 16.5, 17. 1, 17.1, 16.5 Hz), 4.16, 4.20, 4.27, 4.29 (4d, 1H, T-Ac-CH2, 2J= 16.6, 17.1, 16.5, 17.1 Hz), 4.63 (m, 1H, 2-H), 4.98 (m, 1H, <BR> <BR> <BR> CH=C (CH3) 2), 6.05-6. 27 (br, 1H, COOH) 6.71, 6.74, 6.83 (3s, 1H, T-Ac-C=CH), 7.0-7. 5 (m, 3H, ArH) , 8.43, 8.47, 8.48, 8.56 (4d, 1H, ArH, 3J= 8.3 Hz), 8.92, 8.96, 9.09, 9.13 (4s, 1H, Ib-NH), 10.14, 10.21, 10.70, 10.77 (4s, 1H, T-Ac-NH). - C28H38N406 (526.6) Calc. C 63.86 H 7.27 N 10.64 Found C 63. 91 H 7.30 N 10.69.-

Example 29 <BR> <BR> <BR> 2- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -acetic acid<BR> <BR> <BR> <BR> <BR> <BR> 0.70 g (1. S I mmol) 2- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -acetic acid-cyclohexen-l"-yl- <BR> <BR> <BR> <BR> <BR> <BR> amide are dissolved in 10 ml of a stock solution of 1. 7 ml conc. HCl in 100 ml abs. tetrahydrofurane. The reaction mixture is stirred for twelve hours and neutralized by the addition of solid sodium bicarbonate and then filtered. The solvent is removed in vacuo and the residue is dissolved in 15 ml water and 4 ml aquoues 1N LiOH. The solution is washed with 10 ml dichloromethane three times and cooled to 0 °C. The pH is adjusted to three with aquoues IN HC1 and the solution is extracted with 20 ml ethyl acetate nine times. After drying the combined organic extracts over MgS04 and evaporation of the solvent in vacuo the crude product is recrystallized from dichloromethane to give the acid as a white solid in 0.33 g (57 %) yield. NMR-data are consisting with the literature data (K. L. Dueholm, M. Egholm, C. Behrens, L. Christensen, H. F. Hansen, T. Vulpius, K. H. Petersen, R. H. Berg, P. E.

Nielsen. O. Buchardt, Journal of Organic Chemistry 59,5767 - 5773 (1994)).

Example 30 <BR> <BR> <BR> rac-2- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -phenylacetic acid-cyclohexen-1"-yl- amide The title compound is prepared as described in example 18 with 0.21 g (2 mmol) benzaldehyde being substituted for paraformaldehyde in 0.65 g (60 %) yield as a yellowish solid.

TLC (dichloromethane/methanol, 95: 5): Rf = 0.45. Mp.: 186 °C.- ¹H-NMR (DMSO-d6): # = 1.29 (s, 9H, Boc-CH3), 1.4-2.1 (m, 8H, cyclohexenyl-CH2), 1.79 (s, 3H, T-Ac-CH3), 3.0- 3.4 (m, 4H, 1'-H, 2'-H) , 4.71 (s, 2H, T-Ac-CH2), 5.99 (s, 1H, 2-H), 6.05 (s, 1H, cyclohexenyl-C=CH), 6.80 (br, 1H, Boc-NH), 7.27 (s, 1H, T-Ac-C=CH), 7.4 (m, 5H, ArH), 9.10 (s, 1H, cyclohexenyl-NH), 11.03 (br, 1H, T-Ac-NH).- C28H37N506 (539.6) Calc. C 62.32 H 6.91 N 12.98 Found C 62.45 H 6.94 N 12.89.- Example 31 rac-2- [2'-Boc-aminoethyl) -thyminacetyl-aminol-3-methyl-butyric acid-cyclohexen-1"- yl-amide <BR> <BR> <BR> The title compound was prepared as described in example 18 with 0. 14g (2mmol) isobutyraldehyde being substituted for parformaldehyde in 0.70 g (69 %) yield as a white solid.

TLC (dichloromethane/methanol, 95:5): Rf = 0.47.- Mp.: 155-156 °C.- ¹H-NMR (DMSO- d6, due to the existance of rotamers in a 65: 45 ratio several signals are doubled): 8 = 0.75 (d, <BR> <BR> <BR> 1.95H, CHCH3, ³J = 6.7 Hz), 0.81 (d, 1.95H, CHCH3, ³J = 6.7 Hz), 0.88 (d, 2. 1H, CHCH3, 3J= 6.7 Hz), 1.32 (s, 4.05H, Boc-CH3), 1.34 (s, 5.95H, Boc-CH3), 1.4-2. 2 (m. 9H. CH2,

CHCH3), 1.76 (s, 3H, T-Ac-CH3), 3.0-3. 6 (m, 4H, 1'-H, 2'-H), 3.87 (d, 0.65H, 2-H, 3J= 9. 8<BR> <BR> <BR> <BR> <BR> <BR> Hz), 4.49 (d, 0. 45H, 2-H, ³J = 9.8 Hz), 4.56 (d, 0.65H, T-Ac-CH2, ²J = 16.5 Hz), 4.65 (d, 0.45H, T-Ac-CH2, ²J = 16.5 Hz), 4.78 (d, 1H, T-Ac-CH2, ²J = 16.5 Hz), 5.97 (br, 0.65H, cyclohexenyl-C=CH), 6.04 (br, 0.45H, cyclohexenyl-C=CH), 6.66 (br, 0.45H, Boc-NH), 6.99 (br, 0.65H, Boc-NH), 7.43 (s, 1H, T-Ac-CH), 8.89 (s, 0.65H, NH), 9.28 (s, 0.45H, NH), 11.07 (br, 1 H, T-Ac-NH). - C25H39N506 (505.6) Calc. C 59.39 H 7.77 N 13.85 Found C 59.45 H 7. 85 N 13.90.- Example 32 rac-2- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -3-methyl-butyric acid The title compound was prepared as described in example 29 with 0.70 g (1.4 mmol) rac-2- [2'-Boc-aminoethyl) -thyminacetyl-amino] -3-methyl-butyric acid-cyclohexen-l"-yl-amide <BR> <BR> <BR> being substituted for 2- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -acetic acid-cyclohexen-1"- yl-amide in 0.38 g (65 %) yield as a white solid. <BR> <BR> <P>TLC (dichloromethane/methanol, 95: 5) : Rf = 0. 21. Mp. : 164 °C (dec.).- ¹H-NMR (DMSO-d6, due to the existance of two rotamers in a 60: 40 ratio several signals are doubled): # = 0.76 (d, 1.2H, CHCH3, ³J = 6.7 Hz), 0.88 (m, 4.8H, CHCHj), 1.34 (s, 3.6H, Boc-CH3), 1.36 (s, 5.4H, Boc-CH3), 1.75 (s, 3H, T-Ac-CH3), 2.12 (m, 1H, CHCH3), 3.0-3. 5 (m, 4H, 1'- H, 2'-H), 3.70 (d, 0.4H, 2-H, 3J= 9.8 Hz), 4.38 (d, 0.6H, 2-H, 3J= 9.8Hz), 4.57 (d, 0.4H, T- AC-CH2, 2J= 16.5 Hz), 4.63 (d, 0.6H, T-Ac-CH2, ²J = 16.5 Hz), 4.78 (d, 1H, T-Ac-CH2, 2J= 16.5 Hz), 6.68 (br, 0.4H, Boc-NH), 6.97 (br, 0.6H, Boc-NH), 7.19 (s, 0.4H, T-Ac- C=CH), 7.21 (s, 0.6H, T-Ac-C=CH), 11.27 (s, 1H, T-Ac-NH).- Cl9H3ON407 (426. 5) Calc. C 53.51 H 7. 09 N 13.14 Found C 53.50 H 7.10 N 13.17.- Example 33 1-[2'-Boc-aminoethyl)-(N6-Z-adeninacetyl)-amini]-cyclohexanc arboxylic acid- <BR> <BR> <BR> cyclohexen-1"-yl-amide <BR> <BR> <BR> <BR> <BR> <BR> <BR> The title compound was prepared as described in example 18 with 0. 20 g (2 mmol) cyclohexanone being substituted for paraformaldehyde and 0.65 g (2 mmol) N6-Z-N-9- carboxymethyl adenine being substituted for N-1-carboxymethylthymine in 0.69 g (51 % yield) as a white solid.

TLC (dichloromethane/methanol, 95: 5): Rf= 0. 57. Mp.: 123°C (dec.).- ¹H-NMR <BR> <BR> <BR> (CDC13): # = 1.4-2. 1 (m, 18H, CH2) , 1.41 (s, 9H, Boc-CH3), 3.40 (m, 2H, 1'-H, 2'-H), 3.63 (m, 2H, 1'-H, 2'-H), 5.15 (s, 2H, A-Z-Ac-CH2CO), 5.28 (s, 2H, Z-CH2), 5.3 (br, 1H, Boc- NH), 5.93 (br, 1H, C=CH), 7.2-7. 4 (m, 5H, ArH), 7.87 (br, 1H, Z-NH), 7.96 (s, 1H, CH=N), 8.70 (s, 1H, CH=N), 8.95 (br, 1H. NH). -

C35H46N806 (674. 8) Calc. C 62.30 H 6.87 N 16.61 Found C 62.39 H 6.88 N 16. 64.- Example 34 1- [ (2'-Boc-aminoethyl) -N4-Z-cytosinacetyl-amino] -cyclohexancarboxylic acid- cyclohexen-1"-yl-amide The title compound was prepared analoge to example 18 with 0. 20 g (2 mmol) cyclohexanone being substituted for paraformaldehyde and 0.61 g (2 mmol) N 4 -Z-N-1-carboxymethyl cytosine being substituted for N-1-carboxymethylthymine in 0.65 g (50 %) yield.

TLC (dichloromethane/methanol, 95: 5): Rf= 0.49.- Mp.: 136 °C (dec.).- ¹H-NMR (DMSO-d6): #= 1.2-2. 2 (m, 18H, CH2), 1.38 (s, 9H, Boc-NH), 3.22 (m, 2H, 1'-H, 2'-H) , 3.40 (m, 2H, 1'-H, 2'-H), 4.73 (s, 2H, C-Z-Ac-CHz), 5.18 (s, 2H, Z-CH2), 5.20 (br, 1H, Boc-NH), 5.71 (br, 1H, CH=C), 7.02(d, 1H, C-Z-Ac-CH=CH, 3J= 7.2 Hz), 7.4 (m, 5H, ArH), 7.72 (br, 1H, Z-NH), 7.91 (d, 1H, C-Z-Ac-CH=CH, 3J= 7.2 Hz), 10.7 (br, 1H, NH).- C34H46N607 (650.8) Calc. C 62.75 H 7.12 N 12.91 Found C 62.89 H 7.15 N 12. 97. - Example 35 rac-2- [ (2'-Ib-amino-phenyl) -thyminacetyl-amino] -biphen-4"'-yl-acetic acid The title compound was prepared as described in example 29 with 0.35 g (0.55 mmol) rac-2- [(2'-Ib-amino-phenyl)-thyminacetyl-amino]-biphenyl-4-yl-acet ic acid-cyclohexen-1"-yl-amide <BR> <BR> <BR> being substituted for 2- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -acetic acid-cyclohexen-1"- yl-amide in 0.20 g (66 %) yield as a yellowish solid. <BR> <BR> <P> TLC (dichloromethane/methanol, 95: 5): RJ= 0.29. - Mp. : >250 °C. ¹H-NMR (CDCl3):<BR> <BR> <BR> <BR> § = 1.21 (d, 6H, CH (cl3) 2, 3J= 6.6 Hz), 1. 73 (s, 3H, T-Ac-CH3), 2.91 (m, 1H, CH (CH3)2, ³J = 6.6 Hz), 3.91 (d, 1H, T-Ac-CH2, 2J= 16.5 Hz), 4.00 (d, 1H, T-Ac-CH2, ²J = 16.5 Hz), 5.86 (s, 1H, NCH), 6.7-8. 5 (m, 15H, ArH, T-Ac-C=CH, COOH), 11.22 (s, 1H, T-Ac-NH), 11.65 (s, 1H, NH-Ib).- C3lH3ON406 (554.6) Calc. C 67.14 H 5.45 N 10.10 Found C 67.18 H 5.29 N 10.03.- Example 36 <BR> <BR> <BR> rac-2- [ (2'-Ib-amino-phenyl) -thyminacetyl-amino] -ortho-bromophenylacetic acid-<BR> <BR> <BR> <BR> cyclohexen-1"-yl-amide The title compound was prepared as described in example 19 with 0.37 g (2 mmol) 2-bromo benzaldehyde being substituted for 4-phenylbenzaldehyde as a yellowish solid in 0.56 g (44 %) yield. <BR> <BR> <P> TLC (dichloromethane/methanol, 95: 5): Rf= 0.48.- Mp.: 234-235°C. - IH-NMR (DMSO- d6):# = 1.20 (d, 3H, Ib-CH3, ³J = 6.6 Hz), 1.22 (d, 3H, Ib-CH3, ³J = 6.6 Hz), 1.54 (m, 4H,

cyclohexenyl-CH2), 1.74 (s, 3H, T-Ac-CH3), 2.20 (m, 4H, cyclohexenyl-CH2), 2.92 (m, 1H, Ib-CH, 3J= 6.6 Hz), 3.98 (d, 1H, T-Ac-CH2, ²J = 16.5 Hz), 4.07 (d, 1H, T-Ac-CH2, ²J = 16.5 Hz), 6.06 (s, 1H, cyclohexenyl-C=CH), 6.20 (s, 1H, NCH), 6.8-7. 6 (m, 8H, ArH, T-Ac- C=CH), 8.27 (d, 1H, ArH, ³J = 7.7 Hz), 9.71 (s, 1H, cyclohexenyl-NH), 11.00 (br, 1H, Ib- NH), 11.50 (s, 1H, T-Ac-NH).- C31H34N5O5Br (636.5) Calc. C 58.49 H 5. 38 N 11.00 Found C 58.56 H 5.42 N 11. 01. - Example 37 <BR> <BR> <BR> 2-[(2'-Boc-aminoethyl)-thyminacetyl-amino]-2-methyl-propioni c acid-cyclohexen-1"- yl-amide The title compound was prepared as described in example 18 with 0.12 g (2 mmol) acetone being substituted for paraformaldehyde as a white solid in 0.60 g (60%) yield. <BR> <BR> <P>TLC (dichloromethane/methanol, 95: 5): Rf= 0.46.- Mp.: 134 °C (dec.). -'H-NMR (CDCl3): # = 1.43 (s, 9H, Boc-CH3), 1.5-2. 05 (m, 8H, CH2) , 1.52 (s, 6H, C(CH3)2), 1.87 (s, 3H, T-Ac-CH=CCH3), 3.41, 3.60 (2m, 4H, 1'-H, 2'-H), 4.57 (s, 2H, T-Ac-CH2), 5.70 (m, 1H, cyclohexenyl-C=CH), 6.02 (b, 1H, Boc-NH), 7.01 (s, 1H, T-Ac-CH=CCH3), 8.01 (s, 1H, T- Ac-NH). - C24H37N5O6 (491.6) Calc. C 58.64 H 7.59 N 14.25 Found C 58.71 H 7.59 N 14.29.- Example 38 1- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -cyclohexancarboxylic acid-cyclohexen- 1"-yl-amide The title compound is prepared as described in example 18 with 0.20 g (2 mmol) cyclohexanone being substituted for paraformaldehyde as a white solid in 0.50 g (47 %) yield.

TLC (dichloromethane/methanol, 95: 5): Rf= 0.39.- Mp.: 154-156 °C. ¹H-NMR (DMSO- d6) : § = 1.37 (s, 9H, Boc-CH3), 1.2-2. 2 (m, 18H, CH2) , 1. 75 (s, 3H, T-Ac-CH=C), 3.2, 3.4 (2m, 4H, 1'-H, 2'-H), 4.59 (s, 2H, T-Ac-CH2), 5.68 (s, 1H, cyclohexenyl-C=CH), 7.02 (b, 1H, Boc-NH), 7.29 (s, 1H, T-Ac-CH=CCH3) , 7.82 (s, 1H, NH), 11.21 (s, 1H, T-Ac-NH).- C27H41N5O6(531.7) Calc. C 61.00 H 7.77 N 13.17 Found C 60.81 H 7.71 N 13. 11- Example 39 <BR> <BR> <BR> 1- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -cyclopentancarboxylic acid-cyclohexen- 1"-yl-amide The title compound was prepared as described in example 18 with 0.17 g (2 mmol) cyclopentanone being substituted for paraformaldehyde as a white solid in 0.69 g (67 %) yield.

TLC (dichloromethane/methanol, 95: 5): Rf= 0. 41. - Mp.: 119-121 °C.- ¹H-NMR (DMSO- d6): # = 1.2-2. 3 (m, 16H, CH2) , 1. 39 (s, 9H, Boc-CH3), 1.73 (s, 3H, T-Ac-CH=C), 3.15, 3.43 (2m, 4H, 1'-H, 2'-H), 4.61 (s, 2H, T-Ac-CH2), 5.71 (s, 1H, cyclohexenyl-C=CH) , 7.00 (b, 1H, Boc-NH), 7.31 (s, 1H, T-Ac-CH=C), 7.69 (b, 1H, cyclohexenyl-NH), 11.23 (s, 1H, T-Ac- <BR> <BR> <BR> NH). - <BR> <BR> <BR> <BR> <BR> <BR> C26H39N5O6 (517.6) Calc. C 60.33 H 7. 59 N 13.53 Found C 60.35 H 8.01 N 13.56.- Example 40 2- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -2-methyl-propionic acid The title compound was prepared as described in example 29 with 0.60 g (1. 2 mmol) 2- [ (2'- Boc-aminoethyl) -thyminacetyl-amino] -2-methyl-propionic acid-cyclohexen-1"-yl-amide being <BR> <BR> <BR> substituted for 2- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -acetic acid-cyclohexen-1"-yl- amide as a white solid in 0.40 g (80 %) yield. <BR> <BR> <P>TLC (dichloromethane/methanol, 95: 5): Rf= 0. 31. Mp.: 124 °C (dec.).- ¹H-NMR (DMSO-d6, due to the existance of two rotamers in a 80: 20 ratio several signals are doubled): <BR> <BR> <BR> 5 = 1.36 (s, 9H, Boc-CH3), 1.76 (s, 3H, CH=CCH3), 3. 15, 3.34 (2m, 4H, 1'-H, 2'-H) , 4.32 (mi.), 4.59 (ma.) (2s, 2H, T-Ac-CH2), 7.0 (b, 1H, BocNH), 7.3 (ma.), 7.48 (mi.) (2s, 1H, T- Ac-CH=C), 11.21 (s, 1H, T-Ac-NH).- C18H28N4O7 (412.4) Calc. C 52.42 H 6.84 N 13.58 Found C 52.38 H 6.84 N 13.62.- Example 41 1- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -cyclohexancarboxylic acid The title compound is prepared as described in example 29 with 0.50 g (0.94 mmol) 1- [ (2'- <BR> <BR> <BR> Boc-aminoethyl) -thyminacetyl-amino] -cyclohexancarboxylic acid-cyclohexen-1"-yl-amide <BR> <BR> <BR> <BR> <BR> being substituted for 2- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -acetic acid-cyclohexen-1"- yl-amide as a white solid in 0.35 g (82 %) yield.

TLC (dichloromethane/methanol, 95: 5): Rf= 0.29.- Mp.: 185 °C (dec.). ¹H-NMR (DMSO-d6, due to the existance of two rotamers in a 70: 30 ratio several signals are doubled): # = 1.41 (s, 9H, Boc-CH3), 1.2-2. 05 (m, 10H, CH2), 1.79 (s, 3H, T-Ac-CH=CCH3), 3.2, 3.57 (2m, 4H, 1'-H, 2'-H), 4.35 (mi.), 4.64 (ma.) (s, 2H, T-Ac-CH2), 6.85 (ma.), 7.19 (mi.) (b, 1H, BocNH), 7.32 (ma.), 7.51 (mi.) (s, 1H, T-Ac-CH=CCH3), 11.18 (ma.), 11.29 (mi.) (s, 1H, T- Ac-NH). - C2lH32N407 (452.5) Calc. C 55.74 H 7.13 N 12. 38 Found C 55.49 H 7.12 N 12.45.-

Example 42 rac-2- [ (2'-Boc-aminoethyl) -N6-Z-adeninacetyl-aminol-ortho-chlorophenylacetic acid The tilte compound is prepared as described in example 29 with 0.30 g (0.42 mmol) rac-2- [ (2'-Boc-aminoethyl)-N6-Z-adeninacetyl-amino]-ortho-chlorophe nylacetic acid-cyclohexen-1"- <BR> <BR> <BR> yl-amide being substituted for 2- [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -acetic acid- cyclohexen-1"-yl-amide as a white solid in 0.21 g (78 %) yield. <BR> <BR> <P>TLC (dichloromethane/methanol, 95: 5): Rf= 0.28. - Mp.:102 °C (dec.).- ¹H-NMR (CDCl3, due to the existance of two rotamers in a 78: 22 ratio several signals are doubled): 8 = 1.36 (ma.), 1.41 (mi.) (2s, 9H, Boc-CH3), 3.1-3. 4 (m, 4H, I'-H, 2'-H), 5.19 (br, 1H, Boc-NH), 5.30 (m, 3H, 2H, Z-CH2), 5.52 (m, 2H, A-Z-Ac-CH2), 7.3-7. 6 (m, 9H, ArH), 7.98 (mi.), 8.17 (ma.) (2s, 1H, A-Z-Ac-N=CH), 8.72 (s, 1H, A-Z-Ac-N=CH), 9.3 (br, 1H, COOH).- C30H32N707Cl (638.1) Calc. C 56.47 H 5.05 N 15.37 Found C 56.49 H 5.04 N 15.30.- Example 43 rac-2- [ (2'-Boc-aminoethyl) -N4-Z-cytosinacetyl-aminol-ortho-chlorophenylacetic acid- cyclohexen-1"-yl-amide The tilte compound is prepared as described in example 20 with 0.28 g (2 mmol) 2- chlorobenzaldehyde being substituted for 4-nitrobenzaldehyde as a white solid in 0.70 g (50 %) yield.

TLC (dichloromethane/methanol, 95: 5): Rf = 0.53. - Mp. : 138 °C (dec.).- ¹H-NMR (CDCl3, due to the existance of two rotamers in a 75: 25 ratio several signals are doubled): 8 = 1.38 (mi.), 1.41 (ma.) (2s, 9H, Boc-CH3), 1.6-2. 1 (m, 8H, cyclohexenyl-CH2), 3.0-3. 5 (m, 4H, <BR> <BR> I'-H, 2'-H), 4.69 (d, 1H, C-Z-Ac-CH2, ²J = 15.4 Hz), 4.82 (d, lH, C-Z-Ac-CH2, 3ff= 15.4 Hz), 5.22 (s, 2H, Z-CH2) 5.38 (mi.), 5.56 (ma.) (2br, 1H, Boc-NH), 6.03 (s, 1H, 2-H), 6.09 (ma.), 6.18 (mi.) (2m, 1H, cyclohexenyl-CH), 7.2-7. 6 (m, 9H, ArH). - C35H41N6O7Cl (693.2) Calc. C 60.64 H 5.96 N 12.12 Found C 60.64 H 5.92 N 12.02.- Example 44 <BR> <BR> <BR> rac-2- [ (2'-Boc-aminoethyl) -uracilacetyl-amino] -ortho-chlorophenylacetic acid-<BR> <BR> <BR> <BR> cyclohexen-1"-yl-amide The tilte compound is prepared analoge to example 21 with 0.34 g (2 mmol) N-1- carboxymethyl uracil being substituted for N6-Z-N-9-carboxymethyl adenine as a white solid in 0.70 g (63 %) yield.

TLC (dichloromethane/methanol, 95: 5): Rf= 0.40. - Mp.: 145°C (dec.).- ¹H-NMR <BR> <BR> (CDC13) : 8 = 1.42 (s, 9H, Boc-CH3), 1. 7-1. 9 (m, 8H, cyclohexenyl-CH2), 2.9-3. 5 (m, 4H, 1'- H, 2'-H), 4.66 (s, 2H, U-Ac-CHz), 5.62 (br, 1H, Boc-NH), 5.71 (d, 1H, U-Ac-NCH=CH) ,

6.02 (s, 1H, 2-H), 6.23 (m, 1H, cyclohexenyl-CH), 7.18 (d, 1H, U-Ac-NCH=CH, ³J = 7.7 <BR> <BR> <BR> Hz), 7. 3-7. 6 (m, 9H, ArH), 9.41 (br, 1H, NH). - <BR> <BR> <BR> <BR> <BR> <BR> C27H34N506CI (560.0) Calc. C 57. 91 H 6.12 N 12. 50 Found C 58.04 H 6.08 N 12. 48.- Example 45 <BR> <BR> rac-2- [ (2'-Boc-aminoethyl) - (2""-amino-6""-benzyloxy-N9-purin acetyl) -aminol-ortho- chlorophenylacetic acid-cyclohexen-1"-yl-amide The tilte compound is prepared as described in example 21 with 0.60 g (2 mmol) 2-amino-6- benzyloxy-N-9-carboxymethyl purin being substituted for N6-Z-N-9-carboxymethyl adenine as a white solid in 0.29 g (21 %) yield. <BR> <BR> <P>TLC (dichloromethane/methanol, 95: 5): Rf = 0. 51. Mp. : 120-121 °C. ¹H-NMR (CDC13): 8 = 1.39 (s, 9H, Boc-CH3), 1.5-2. 0 (m, 8H, cyclohexenyl-CH2), 2.8-3. 6 (m, 4H, 1'-H, 2'-H), 4.84 (d, 2H, G-Bz-Ac-CH2, ³J = 16.5 Hz), 5.02 (m, 2H, G-Bz-Ac-CH2, Boc-NH), 5.49 (s, <BR> <BR> <BR> 2H, Z-CH2), 5.94 (m, 1H, cyclohexenyl-C=CH) , 6.07 (s, 1H, 2-H) , 6.12 (br, 2H, NH2), 7. 1- 7.5 (m, 9H, ArH), 7.86 (s, 1H, G-Bz-Ac-CH). - <BR> <BR> <BR> C35H4lN805CI (689.2) Calc. C 60.99 H 6.00 N 16. 26<BR> <BR> <BR> <BR> <BR> Found C 60.86 H 5.89 N 16. 30- Example 46 <BR> <BR> rac-2- [ (2'-Boc-aminoethyl)-(N4-Z-cytosinacetyl)-amino]-3,3-dimethyl -butyric acid-4"-<BR> <BR> <BR> <BR> <BR> <BR> tert. -butyl-cyclohexen-1"-yl-amide The tilte compound is prepared as described in example 24 with 0.76 g (2.5 mmol) N4-Z-N-1- carboxymethyl cytosine being substituted for N-1-carboxymethyl thymine The crude product is applied to column chromatography on silica gel (dichloromethane/methanol, 95: 5) and is obtained as a white solid in 1.38 g (99 %) yield.

TLC (dichloromethane/methanol, 95: 5): Rf= 0.53.- ¹H-NMR (CDCl3, due to the existance of two diastereomers in a 63: 37 ratio several signals are doubled): 8 = 0.81 (s, 9H, 4-tert. - <BR> <BR> <BR> Butyl-cyclohexenyl-CH3), 0.98 (ma.), 1.07 (mi.) (2s, 9H, C2-C (CH3) 3), 1.35 (mi.), 1.36 (ma.) (2s, 9H, Boc-CH3), 1.7-2. 2 (m, 7H, 4-tert.-Butyl-cyclohexenyl-CH, CH2), 3.1-4.0 (m, 4H, 1'- H, 2'-H), 4.04 (ma.), 4.38 (mi.) (2s, 1H, 2-H) , 4.76 (m, 1H, C-Z-Ac-CH2), 5.07 (m, 1H, C-Z- Ac-CH2), 5.15 (ma.), 5.17 (mi.) (2s, 2H, Z-CH2), 5.94 (ma.), 6.08 (2m, 1 H, 4-tert. -Butyl- cyclohexenyl-C=CH), 7.18 (d, 1H, C-Z-Ac-CH=CH, ³J = 7.0 Hz), 7.32 (m, 5H, ArH), 7.63 (ma.), 7.90 (mi.) (2d, 1H, C-Z-Ac-CH=CH, ³J = 7.0 Hz), 7.97 (br, 1H, 4-tert.-Butyl- cyclohexenyl-NH), 8.6 (br, 1H, Z-NH). - <BR> <BR> C37H54N6O7 (693.2) Calc. C 63.96 H 7. 83 N 12.09<BR> <BR> <BR> <BR> <BR> Found C 63.78 H 7.91 N 12.03. -

Example 47 rac-2-[(2'-Boc-aminoethyl)-(N4-Z-adeninacetyl)-amino]-3,3-di methyl-butyric acid-4"- tert. -butyl-cyclohexen-1"-yl-amide The tilte compound is prepared as described in example 24 with 0.81 g (2.5 mmol) N6-Z-N-9- carboxymethyl adenine being substituted for N 1-carboxymethyl thymine. The crude product is applied to column chromatography on silica gel (dichloromethane/methanol, 95: 5) and is obtained as a white solid in 0.91 g (63 %) yield. <BR> <BR> <P>TLC (dichloromethane/methanol, 95: 5): Rf = 0.26.- ¹H-NMR (CDCl3): # = 0.83 (s, 9H, 4-<BR> <BR> <BR> <BR> <BR> <BR> <BR> tert. -Butyl-cyclohexenyl-CH3), 0.98 (s, 9H, C2-C (CH3) 3), 1.36 (s, 9H, Boc-CH3), 1.2-2. 1 (m,<BR> <BR> <BR> <BR> <BR> 7H, 4-tert. -Butyl-cyclohexenyl-CH, CH2), 3.2-4. 0 (m, 4H, 1'-H, 2'-H) , 4.68 (s, 1 H, 2-I I), 5.20 (d, 1H, A-Z-Ac-CH2, ²J = 16.5 Hz), 5.25 (s, 2H, Z-CH2), 5. 35 (d, 1H, A-Z-Ac-CH2, ²J = <BR> <BR> <BR> 16.5 Hz), 6.01 (m, 1 H, 4-tert. -Butyl-cyclohexenyl-C=CH), 7. 35 (m, 5H, ArH), 7.95 (s, 1H, A-Z-Ac-CH), 8.71 (s, 1H, A-Z-Ac-CH), 8.35 (br, lH, 4-tert. -Butyl-cyclohexenyl-NH) , 9.33 (br, 1H, Z-NH).- C38H54N806 (718.9) Calc. C 63.49 H 7. 57 N 15.59 Found C 63.52 H 7.60 N 15.47.- Example 48 rac-1-[(2'-Boc-aminoethyl)-thyminacetyl-amino]-cyclohexancar boxylic acid-4"-phenyl cyclohexen-1"-yl-amide The title compound is prepared as described in example 24 with 0.20 g (2 mmol) cyclohexanone being substituted for pivalaldehyde and 0.37 g (2 mmol) rac-1-isocyano-4- phenyl-cyclohexene being substituted for rac-1-isocyano-4-tert.-butyl-cyclohexene as a white solid in 1.10 g (90 %) yield. <BR> <BR> <P> TLC (dichloromethane/methanol, 95: 5): Rf = 0.50. - mu. : 115 °C (dec.). -'H-NMR (CDCl3) : 5 = 1.45 (s, 9H, Boc-CH3), 1.4-2. 4 (m, 16H, CH2), 1.89 (s, 3H, T-Ac-CH=C), 2.75 <BR> <BR> <BR> <BR> (m, 1H, CH-phenyl), 3. 39 (m, 2H, 2'H), 3. 56 (m, 2H, 1'-H), 4.62 (s, 2H, T-Ac-CH2), 5.51 (m, 1H, Boc-NH), 6.03 (m, 1H, 4"-phenyl-cyclohexenyl-C=CH), 6.98 (s, 1H, T-Ac-CH=CCH3), 7.87 (br, 1H, NH), 9.68 (br, 1H, T-Ac-NH).- C33H4sN506 (607.8) Calc. C 65.22 H 7.46 N 11.52 Found C 65.10 H 7.44 N 11.49.- Example 49 2 [ (2'-Boc-aminoethyl) -thyminacetyl-aminol-isobutyric acid-4"-methoxy-2"- nitrophenylamide 0.32 g (2.00 mmol) mono-Boc-ethylendiamine are solved in 20 ml acetone three times and evaporated. The yellowish residue is solved in 7 ml abs. methanol and 0.36 g (2.00 mmol) 4- methoxy-2-nitrophenylisocyanide and 0.37 g (2.00 mmol) N-1-carboxymethylthymine are added. The reaction mixture is heated for five minutes and stirred for three days at room

temperature with exclusion of moisture. The precipitate is filtered off, washed with diethylether three times and dried in vacuo to give the title compound as a yellow powder in 0.52 g (46 %) yield- <BR> <BR> TLC (dichloromethane: methanol 95: 5): Rf= 0.42. - Mp.: 169°C (dec.).- ¹H-NMR (CDCl3, 300 MHz): 8 [ppm] = 1.45 (s, 9 H, Boc-CH3), 1.61 [s, 6 H, C-2(CH3)2], 1.85 (s, 3 H, T-CH3), 3.42 - 3.51, 3.66 - 3.74 (m, 4 H, 1'-H, 2'-H), 3.85 (s, 3 H, ArOCH3), 4.68 (s, 2 H, T-Ac-CH2), 5.48 (s, 1 H, Boc-NH), 6.92 (s, 1 H, T-CH=C), 7.21 (dd, 1 H, 6"-H), 7.60 (d, 1 H, 3"-H), 8.49 (d, 1 H, 5"-H), 8.99 (s, 1 H, T-NH), 10.31 (s, 1 H, C-1"-NH). - C25H34N609 (562.6) Calc. C 53.37 H 6.06 N 14.94 Found C 53.21 H 5. 98 N 14. 82. - Example 50 1 [ (2'-Boc-aminoethyl) -thyminacetyl-aminol-cyclohexancarboxylic acid-4"-methoxy-2"- nitrophenylamide 0.32 g (2.00 mrnol) mono-Boc-ethylendiamine and 0.19 g (2.00 mmol) cyclohexanone are solved in 20 ml toluene three times and evaporated. The residue is solved in 7 ml abs. methanol and 0.36 g (2.00 mmol) 4-methoxy-2-nitrophenylisocyanide and 0.37 g (2.00 mmol) N-1-carboxymethylthymine are added. The reaction mixture is heated for five minutes and stirred for three days at room temperature with exclusion of moisture. The reaction mixture is evaporated to dryness, diluted with 25 ml diethylether and stirred for 30 minutes. The precipitate is filtered off, washed with diethylether three times and dried in vacuo. The crude product is purified by flash filtration (neutral alumina, dichloromethane/methanol 95: 5) to give the title compound as a yellow-brown powder in 0.64 g (53 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf= 0.49. - Mp.: 145°C (dec.).- ¹H-NMR <BR> <BR> (CDC13, 300 MHz):# [ppm] = 1.45 (s, 9 H, Boc-CH3), 1. 23 - 1.50, 1.60 - 1.99, 2.30 - 2.40 (m, 10 H, 2-H, 3-H, 4-H, 5-H, 6-H), 1.81 (s, 3 H, T-CH3), 3.42 - 3.53, 3.65 - 3.72 (m, 4 H, 1'- H, 2'-H), 3.83 (s, 3 H, ArOCH3), 4.66 (s, 2 H, T-Ac-CH2), 5.50 (s, 1 H, Boc-NH), 6.89 (s, 1 H, T-CH=C), 7.19 (dd, 1 H, 6"-H), 7.59 (d, 1 H, 3"-H), 8.48 (d, 1 H, 5"-H), 9.12 (s, 1 H, T- NH), 10.14 (s, 1 H, C-1"-NH).- C28H38N609 (602.6) Calc. C 55.81 H 6. 36 N 13. 95 Found C 55.79 H 6.41 N 14.03.- Example 51 1 [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -4-phenylcyclohexan-carboxylic acid-4"- <BR> <BR> <BR> methoxy-2"-nitrophenylamide <BR> <BR> <BR> <BR> 0.32 g (2.00 mmol) mono-Boc-ethylendiamine and 0. 35 g (2.00 mmol) 4-phenylcyclohexanone are solved in 20 ml toluene three times and evaporated. The residue is solved in 7 ml abs. methanol and 0. 36 g (2.00 mmol) 4-methoxy-2-nitrophenylisocyanide and 0.37 g (2.00 mmol) N-1-carboxymethylthymine are added. The reaction mixture is heated for five minutes and

stirred for three days at room temperature with exclusion of moisture. The precipitate is filtered off, washed with diethylether three times and dried in vacuo to give the title compound as a yellow powder in 0.88 g (65 %) yield. - TLC (dichloromethane: methanol 95: 5): R= 0.50. - Mp.: 217 °C (dec. ).- ¹H-NMR (CDC13, 300 MHz): 8 [ppm] = 1.49 (s, 9 H, Boc-CH3), 1.65 - 2.30, 2.53 - 2.81 (m, 8 H, 2-H, 3-H, 4-H, 5-H, 6-H), 1.84, 1.90 (2 s, 3 H, T-CH3, isomers), 3.48 - 3.60, 3.71 - 3.82 (m, 4 H, 1'-H, 2'-H), 3.86, 3.87 (2 s, 3 H, ArOCH3, isomers), 4.65, 4.75 (2 s, 2 H, T-Ac-CH2, isomers), 5.31 (s, 1 H, Boc-NH), 6.89, 7.01 (2 s, 1 H, T-CH=C, isomers), 7.18 - 7.48 (m, 6 H, <BR> <BR> <BR> 6 "-H, C-4-Ph), 7.64 (2 d, 1 H, 3"-H, isomers), 8.41 - 8.63 (m, 2 H, 5"-H, T-NH), 10.20, 10.45 (2 s, 1 H, C-1"-NH, isomers).- <BR> <BR> <BR> C34H42N609 (678.7) Calc. C 60.17 H 6.24 N 12. 38 <BR> <BR> <BR> <BR> <BR> <BR> <BR> Found C 60.25 H 6. 38 N 12.45.- Example 52 8 [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -1, 4-dioxaspiro [4.5]decan-8- carboxylic acid-4"-methoxy-2"-nitrophenylamide The title compound is prepared as described in example 51 with 4-phenylcyclohexanone substituted by 0. 31 g (2.00 mmol) 1,4-cyclohexandione monoethylene ketal to give the title compound as a yellow powder in 1.09 g (83 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf= 0.48. - Mp. : 230°C (dec.).- ¹H-NMR <BR> <BR> <BR> (CDC13, 300 MHz): 8 [ppm] = 1.43 (s, 9 H, Boc-CH3), 1.63 - 1.70, 1.95 - 2.18, 2. 34 - 2.40 (m, 8 H, 6-H, 7-H, 9-H, 10-H), 1.79 (s, 3 H, T-CH3), 3.35 - 3.47, 3.53 - 3.62 (m, 4 H, 1'-H, 2'-H), 3.85 (s, 3 H, ArOCH3), 3.93 (s, 4 H, 2-H, 3-H), 4.67 (s, 2 H, T-Ac-CH2), 6.69 (s, I H, Boc-NH), 6.99 (s, I H, T-CH=C), 7.20 (dd, I H, 6"-H), 7.55 (d, 1 H, 3"-H), 7.76 (s, 1 H, T- NH), 8.10 (d, 1 H, 5"-H), 9.48 (s, 1 H, C-1"-NH). - <BR> <BR> <BR> <BR> C3oH4oN6011 (660. 7) Calc. C 54.54 H 6.10 N 12.72<BR> <BR> <BR> <BR> <BR> <BR> <BR> Found C 53.97 H 5.83 N 12. 51- Example 53 2 [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -2-hexyl-octan acid-4"-methoxy-2"- nitrophenylamide 0.32 g (2.00 mmol) mono-Boc-ethylendiamine and 0.40 g (2.00 mmol) dihexylketone are solved in 20 ml toluene three times and evaporated. The residue is solved in 7 ml abs. methanol and 0.36 g (2.00 mmol) 4-methoxy-2-nitrophenylisocyanide and 0.37 g (2. 00 mmol) N-1-carboxymethylthymine are added. The reaction mixture is heated for five minutes and stirred for three days at room temperature with exclusion of moisture. The reaction mixture is evaporated to dryness, diluted with 25 ml diethylether and stirred for 30 minutes. The precipitate is filtered off. The filtrate is evaporated to dryness and the remaining residue is diluted in 20 ml n-hexane and 1 ml methyl-tert. -butylether. After stirring 30 minutes the

precipitate is collected to give the title compound as a yellow powder in 0.60 g (43 %) <BR> <BR> <BR> yield. - <BR> <BR> <BR> <BR> <BR> <BR> TLC (dichloromethane: methanol 95: 5): Rf= 0. 67. - Mp. : 107°C.(dec.).- ¹H-NMR (CDC13, 300 MHz): # [ppm] = 0.89 (m, 6 H, 8-H, hexyl-CH3), 1.28 (m, 16 H, 4-H, 5-H, 6-H, 7-H, hexyl-CH2), 1.48 (s, 9 H, Boc-CH3), 1.67 - 1.85, 2.12 - 2.25 (m, 4 H, 3-H, hexyl-CH2), <BR> <BR> <BR> 1.86 (s, 3 H, T-CH3), 3. 51 - 3.59, 3. 61 - 3.69 (m, 4 H, 1'-H, 2'-H), 3.85 (s, 3 H, ArOCH3), 4.63 (s, 2 H, T-Ac-CH2), 5.32 (s, 1 H, Boc-NH), 6.90 (s, 1 H, T-CH=C), 7.21 (dd, 1 H, 6"- H), 7.64 (d, 1 H, 3"-H), 8.38 (s, 1 H, T-NH), 8.49 (d, 1 H, 5"-H), 10.29 (s, 1 H, C-1"-NH). - <BR> <BR> <BR> C35H54N609 (702. 9) Calc. C 59.81 H 7.74 N 11.96<BR> <BR> <BR> <BR> <BR> <BR> Found C 59.91 H 7. 68 N 11.76.- Example 54 <BR> <BR> <BR> 4 [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -1-benzyl-piperidin-4-carboxylic acid-4"- methoxy-2"-nitrophenylamide The title compound is prepared as described in example 50 with cyclohexanone substituted <BR> <BR> <BR> by 0. 38 g (2.00 mmol) 1-benzyl-4-piperidone to give the title compound as a red-brown powder in 0.80 g (58 %) yield- TLC (dichloromethane: methanol 95: 5): Rf = 0.09.- Mp. : 128°C (dec.).- ¹H-NMR (CDC13, 300 MHz): # [ppm] = 1.43 (s, 9 H, Boc-CH3), 1.82 (2 s, 3 H, T-CH3), 2.08 - 2.19, 2.35 - 2.43, 2.65 - 2.89 (m, 8 H, 2-H, 3-H, 4-H, 5-H, 6-H), 3.42 - 3.53, 3.64 - 3.73 (m, 4 H, <BR> <BR> <BR> 1'-H, 2'-H), 3. 59 (s, 2 H, N-1-CH2-Ph), 3.80 (2 s, 3 H, ArOCH3), 4.68 (s, 2 H, T-Ac-CH2), 5.50 (s, 1 H, Boc-NH), 6.90 (s, 1 H, T-CH=C), 7.19 (dd, 1 H, 6"-H,), 7.23 - 7.48 (m, 5 H, N- 1-Ph), 7.59 (d, 1 H, 3"-H), 8.33 (d, 1 H, 5"-H), 10.18 (s, 1 H, C-1"-NH).- C34H43N709 (693.8) Calc. C 58.86 H 6. 25 N 14.13 Found C 58.92 H 6.19 N 14.00.- Example 55 rac-1 [(trans-2'-Boc-aminocyclohexyl)-thyminacetyl-aminol-cyclohex ancarboxylic acid- 4"-methoxy-2"-nitrophenylamide The title compound is prepared as described in example 50 with mono-Boc-ethylendiamine substituted by 0.43 g (2.00 mmol) trans-1, 2-mono-Boc-cyclohexylendiamine to give the title <BR> <BR> <BR> compound as a yellow-brown powder in 0.64 g (49 %) yield. - <BR> <BR> <BR> <BR> <BR> TLC (dichloromethane: methanol 95: 5): Rf= 0.53. - Mp. : 219°C (dec.). -'H-NMR <BR> <BR> <BR> <BR> <BR> <BR> (CDC13,300 MHz): 8 [ppm] = 1.12, 1.45 (2 s, 9 H, Boc-CH3, rotamers), 1.45 - 1.50, 1. 61 - 2.02, 2.14 - 2.45 (m, 18 H, 2-H, 3-H, 4-H, 5-H, 6-H, 3'-H, 4'-H, 5'-H, 6'-H), 1.85 (s, 3 H, T- CH3), 3.42 - 3.58, 3.70 - 4.00 (m, 2 H, 1'-H, 2'-H), 3.85 (s, 3 H, ArOCH3), 4.49 - 4.89 (4 d, 2 H, T-Ac-CH2, rotamers), 5.16 - 5.49 (s, d, 1 H, Boc-NH, rotamers), 6.96, 7.10 (2 s, 1 H, T- CH=C, rotamers), 7.19 (dd, 1 H, 6"-H), 7.58, 7.66 (2 d, 1 H, 3"-H, rotamers), 7.90, 8.43 (2 d,

1 H, 5"-H, rotamers), 8. 47 - 8.65 (m, 1 H, T-NH, rotamers), 9.83, 10.03 (2 s, 1 H, C-1"-NH, rotamers). - C32H44N609 (656. 7) Calc. C 58.52 H 6. 75 N 12.80 Found C 58.64 H 6.79 N 12.68.- Example 56 rac-8 [(trans-2'-Boc-aminocyclohexyl)-thyminacetyl-amino]-1,4-diox aspiro[4.5]decan-8- carboxylic acid-4"-methoxy-2"-nitrophenylamid The title compound is prepared as described in example 55 with cyclohexanone substituted by 0.31 g (2.00 mmol) 1,4-cyclohexandione monoethylene ketal to give the title compound <BR> <BR> without flash filtration as a yellow-brown powder in 1. 10 g (77 %) yield. - <BR> <BR> <BR> TLC (dichloromethane: methanol 95: 5): Rf= 0. 41. - Mp. : 227°C (dec.). -'H-NMR (CDC13, 300 MHz): 8 [ppm] = 1.10, 1.33 (2 s, 9 H, Boc-CH3, rotamers), 1. 35 - 1.50, 1.58 - 2.05, 2.11 - 2.82 (m, 16 H, 6-H, 7-H, 9-H, 10-H, 3'-H, 4'-H, 5'-H, 6'-H), 1.84 (s, 3 H, T-CH3), 3.40 - 3.50, 3.88 - 4.02, 4.12 - 4.25 (m, 2 H, l'-H, 2'-H, rotamers), 3.84 (s, 3 H, ArOCH3), 3.94 (s, 4 H, 2-H, 3-H), 4.45 - 4.92 (4 d, 2 H, T-Ac-CH2, rotamers), 5.08 - 5.27 (s, d, 1 H, Boc-NH, rotamers), 6.95, 7.13 (2 s, 1 H, T-CH=C, rotamers), 7.19 (dd, 1 H, 6"-H), 7.59, 7.65 (2 d, 1 H, 3"-H, rotamers), 7.88, 8.41 (2 d, 1 H, 5"-H, rotamers), 8.22, 8.53 (2 s, 1 H, T-NH, rotamers), 9.82, 10.06 (2 s, 1 H, C-1"-NH, rotamers). - C34H46N6O11(714.8) Calc. C 57.13 H 6.49 N 11.76 Found C 57.54 H 6.42 N 11.98.- Example 57 rac-1 [(2'-Boc-amino-1'-methyl-ethyl)-thyminacetyl-amino] -cyclohexan-carboxylic acid- 4"-methoxy-2"-nitrophenylamide The title compound is prepared as described in example 55 with trans-1, 2-mono-Boc- <BR> <BR> <BR> cyclohexylendiamine substituted by 0. 35 g (2.00 mmol) rac-l-Boc-amino-2-aminopropane to give the title compound without flash filtration as a yellow-brown powder in 0.81 g (65 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf= 0.39. - Mp. : 137°C (dec.).- ¹H-NMR (CDC13, 300 MHz): 8 [ppm] = 1.29 - 1.50, 1.56 - 1.98, 2. 21 - 2.50 (m, 13 H, 2-H, 3-H, 4-H, 5-H, 6-H, C-l'-CH3), 1.40 (s, 9 H, Boc-CH3), 1.83 (s, 3 H, T-CH3), 3.45 - 3.71 (m, 3 H, 1'-H, 2'-H), 3.85, 3.86 (2 s, 3 H, ArOCH3, rotamers), 4.20 - 4.78, 4.55 - 4.69 (m, 2 H, T-Ac-CH2, rotamers), 5.78, 6.05 (2 s, 1 H, Boc-NH, rotamers), 6.90, 7.09 (2 s, 1 H, T-CH=C, rotamers), <BR> <BR> <BR> 7.20 (dd, 1 H, 6"-H), 7. 58, 7.60 (2 d, 1 H, 3"-H, rotamers), 8.19, 8.72 (2 s, 1 H, T-NH,<BR> <BR> <BR> <BR> rotamers), 8. 30 (d, 1 H, 5"-H), 9. 89, 9.91 (2 s, 1 H, C-1"-NH, rotamers). - C29H40N6O9 (619.7) Calc. C 56.48 H 6.54 N 13.63 Found C 56.32 H 6.47 N 13.42.-

Example 58 <BR> <BR> <BR> rac-8 [ (2'-Boc-amino-l'-methyl-ethyl) -thyminacetyl-aminol-1, 4-dioxaspiro [4.5] decan-8- carboxylic acid-4"-methoxy-2"-nitrophenylamide The title compound is prepared as described in example 57 with cyclohexanone substituted <BR> <BR> <BR> by 0.31 g (2.00 mmol) 1, 4-cyclohexandione monoethylene ketal to give the title compound<BR> <BR> <BR> <BR> <BR> without flash filtration as a yellow-brown powder in 1.09 g (81 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf= 0.32. - Mp.: 106°C (dec.).- ¹H-NMR (CDC13, 300 MHz): 8 [ppm] = 1.25 - 1.48, 1.55 - 1.90, 2.00 - 2. 30, 2.48 - 2.58 (m. 11 H, 6- H, 7-H, 9-H, 10-H, C-1'-CH3), 1.40 (s, 9 H, Boc-CH3), 1.82 (s, 3 H, T-CH3), 3.42 - 3.70 (m, <BR> <BR> <BR> 3 H, 1'-H, 2'-H), 3.85 (s, 3 H, ArOCH3), 3.93 (s, 4H, 2-H, 3-H), 4. 14 - 4.69 (m, 2 H, T-Ac- CH2, rotamers), 5.43, 5.69 (2 s, I H, Boc-NH, rotamers), 6.81 - 7.09 (m, I H, T-CH=C, rotamers), 7.20 (dd, 1 H, 6"-H), 7.58, 7.60 (2 d, 1 H, 3"-H, rotamers), 8.10, 8.60 (2 s, H, T- NH, rotamers), 8.30 (d, 1 H, 5"-H), 9.87, 9.90 (2 s, 1 H, C-1"-NH, rotamers). - C3lH42N6011 (674. 7) Calc. C 55.19 H 6.27 N 12.46 Found C 54.99 H 6.22 N 12.20.- Example 59 rac-1 [ (trans-2'-Boc-aminocyclohexyl) -(N4-Z-cytosinacetyl)-amino]-cyclohexan- carboxylic acid-4"-methoxy-2"-nitrophenylamide The title compound is prepared as described in example 5 5 with N- I -carboxymethylthymine substituted by 0.61 g (2.00 mmol) N4-Z-N-1-carboxymethyl cytosine to give the title compound without flash filtration as a yellow-brown powder in 1. 13 g (73 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf= 0.70. Mp.: 159°C (dec.).- ¹H-NMR (CDC13, 300 MHz): 8 [ppm] = 1.14, 1.31 (2 s, 9 H, Boc-CH3, rotamers), 1.28 - 1.49, 1.58 - <BR> <BR> <BR> 2.05, 2.13 - 2.49 (m, 18 H, 2-H, 3-H, 4-H, 5-H, 6-H, 3'-H, 4'-H, 5'-H, 6'-H), 3.49 - 3. 65, 3.87 - 4.02 (m, 2 H, 1'-H, 2'-H), 3.84 (s, 3 H, ArOCH3), 4.37, 4.60 - 5.10 (m, 2 H, C-Z-Ac- CH2, rotamers), 5.20 (s, 2 H, Z-CH2-Ph), 5.60, 5.80 (2 s, 1 H, Boc-NH, rotamers), 7.10 - 7.19 (m, 2 H, C-Z-CH=CH, 6"-H, rotamers), 7.34 - 7.41 (m, 5 H, Z-Ph), 7.52, 7.63 (2 d, 1 H, 3"- H, rotamers), 7.56 - 7.61 (m, I H, C-Z-CH=CH), 7.92, 8.40 (2 d, 1 H, 5"-H, rotamers), 9.81 - 10.02 (2 s, 1 H, C-1"NH, rotamers). - C39H49N7010 (775.9) Calc. C 60. 38 H 6. 37 N 12.64 Found C 60.52 H 6.54 N 12.87.- Example 60 rac-2 [(trans-2'-Boc-aminocyclohexyl)-thyminacetyl-amino]-acetic acid-4"-methoxy-2"- nitrophenylamide The title compound is prepared as described in example 55 with cyclohexanone substituted by 0.06 g (2.00 mmol) paraformaldehyde to give the title compound without flash filtration as a orange-brown powder in 0.75 g (64 %) yield. -

TLC (dichloromethane: methanol 95: 5): Rf= 0. 41. - Mp. : 130°C (dec.).- ¹H-NMR (CDC13, 300 MHz): 8 [ppm] = 1.34, 1.41 (2 s, 9 H, Boc-CH3, rotamers), 1.25 - 2.19 (m, 8 H, 3'-H, 4'-H, 5'-H, 6'-H), 1.91, 1.93 (2 s, 3 H, T-CH3, rotamers), 3.23 - 3.31, 3.48 - 3.61, 3.70 - <BR> <BR> <BR> 4.05, 4.26, 4. 39 - 4.95, 5.05 - 5.30, 5.35, 5. 46 - 5.59 (m, 7 H, 1'-H, 2'-H, 2-H, T-Ac-CH2, Boc-NH, rotamers), 3.85, 3.87 (2 s, 3 H, ArOCH3, rotamers), 6.98 - 7.11 (m, 1 H, T-CH=C, rotamers), 7.20 - 7.29 (m, 1 H, 6"-H), 7.64, 7.70 (2 d, 1 H, 3"-H, rotamers), 8.50, 8.60 (2 d, 1 <BR> <BR> <BR> H, 5"-H, rotamers), 8.68 - 8.98 (m, 1 H, T-NH, rotamers), 10. 31, 10.39 (2 s, 1 H, C-1"-NH, rotamers). - <BR> <BR> <BR> C27H36N609 (588.6) Calc. C 55.09 H 6.16 N 14. 28 <BR> <BR> <BR> <BR> <BR> Found C 55.18 H 6.12 N 14. 11- Example 61 <BR> <BR> <BR> rac-2 [ (2'-Boc-amino-1'-methyl-ethyl) -thyminacetyl-amino] -acetic acid-4"-methoxy-2"- nitrophenylamide The title compound is prepared as described in example 60 with trans-1, 2-mono-Boc- <BR> <BR> <BR> cyclohexylendiamine substituted by 0. 35 g (2.00 mmol) rac-l-Boc-amino-2-aminopropane <BR> <BR> <BR> <BR> <BR> <BR> to give the title compound as a red powder in 0.60 g (55 %) yield. - <BR> <BR> <BR> <BR> <BR> TLC (dichloromethane: methanol 95: 5): Rf= 0.47. - Mp. : 95°C (dec.). -'H-NMR (CDC13, 300 MHz): b [ppm] = 1. 31, 1.42 (2 d, 3 H, C-l'-CH3, rotamers), 1.50 (s, 9 H, Boc- CH3), 1.90 (s, 3 H, T-CH3), 3.29- 3.31 (m, 2 H, 2'-H), 3.38 - 3.47 (m, 1 H, 1'-H), 3.85 (s, 3 H, ArOCH3), 4.25, 4.36 - 4.82 (m, 5 H, 2-H, T-Ac-CH2, Boc-NH, rotamers), 7.02, 7.09 (2 s, 1 H, T-CH=C, rotamers) , 7.21 (dd, 1 H, 6"-H), 7.62, 7.66 (2 d, 1 H, 3"-H, rotamers), 8.45, 8.58 (d, 1 H, 5"-H), 8.61 (s, 1 H, T-NH), 10.30, 10.38 (2 s, 1 H, C-1"-NH, rotamers). - C24H32N609 (548.6) Calc. C 52.55 H 5. 88 N 15.32 Found C 52. 32 H 5.80 N 15.36.- Example 62 2 [ (2'-benzyloxy-ethyl) -thyminacetyl-amino] -acetic acid-4"-methoxy-2"- nitrophenylamide The title compound is prepared as described in example 60 with trans-1, 2-mono-Boc- cyclohexylendiamine substituted by 0.30 g (2.00 mmol) N-benzyloxy-ethanolamine to give the title compound without flash filtration as a orange-brown powder in 0.93 g (89 %) <BR> <BR> <BR> yield. - <BR> <BR> <BR> <BR> <BR> <BR> TLC (dichloromethane: methanol 95: 5): Rf= 0.45. - 1H-NMR (CDC13, 300 MHz): # [ppm] = 1.85 - 1.95 (m, 3 H, T-CH3, rotamers), 3.74 (d, 2 H, 1'-H), 3.88 (s, 3 H, ArOCH3), 4.22, 4.40 - 4.56 (m, 4 H, 2-H, T-Ac-CH2), 4.82 (s, 2 H, CH2-Ph), 5.49 (d, 2 H, 2'-H), 6.92, 7.00 (2 s, 1 H, T-CH=C, rotamers), 7.13 - 7.40 (m, 6 H, Ph, 6"-H), 7.60, 7.68 (2 d, 1 H, 3"-H, rotamers), 8.42, 8.71 (2 s, 1 H, T-NH, rotamers), 8.52, 8.64 (d, 1 H, 5"-H), 10.27, 10.37 (2 s, 1 H, C-1"-NH, rotamers). -

C25H27N5O8 (525.5) Calc. C 57. 14 H 5.18 N 13.33 Found C 57.28 H 5.21 N 13.14.- Example 63 1 [(2'-benzyloxy-ethyl)-thyminacetyl-amino]-cyclohexan-carboxy lic acid-4"-methoxy- 2"-nitrophenylamide The title compound is prepared as described in example 62 with paraformaldehyde substituted by 0.19 g (2.00 mmol) cyclohexanone to give the title compound as a yellow- orange powder in 0.79 g (67 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf= 0.72. Mp.: 191°C- ¹H-NMR (CDCl3, 300 <BR> <BR> MHz): # [ppm] = 1. 20 - 1.32, 1. 56 - 2.00, 2. 34 - 2.45 (m, 10 H, 2-H, 3-H, 4-H, 5-H, 6-H), 1.78 (s, 3 H, T-CH3), 3.82 (m, 7 H, l'-H, ArOCH3, T-Ac-CH2), 4.58 (s, 2 H, CH2-Ph), 4.65 (s, 2 H, 2'-H), 6.58 (s, 1 H, T-CH=C), 7.19 (dd, 1 H, 6"-H), 7.31 (s, 5 H, Ph), 7.60 (d, 1 H, 3"-H), 8.20 (s, 1 H, T-NH), 8. 35 (d, 1 H, 5"-H), 10.21 (s, 1 H, C-1"-NH).- C30H35N5O8 (593.6) Calc. C 60.70 H 5.94 N 11.80 Found C 60.59 H 5.79 N 11.67.- Example 64 rac-2 [ (2'-benzyloxy-ethyl) -thyminacetyl-aminol-4, 8-dimethyl-non-7-enoic acid-4"- methoxy-2"-nitrophenylamide The title compound is prepared as described in example 62 with paraformaldehyde substituted by 0.31 g (2.00 mmol) rac-citronellal to give the title compound without flash <BR> <BR> <BR> filtration as a yellow-brown powder in 0.94 g (72 %) yield. - <BR> <BR> <BR> <BR> TLC (dichloromethane: methanol 95: 5): Rf= 0.85.- ¹H-NMR (CDCl3, 300 MHz) : 5 <BR> <BR> <BR> <BR> <BR> <BR> [ppm] = 0.94 (m, 3H, C-4CH3, isomers), 1.10 - 1.58, 1. 91 - 2.10, 2.16 - 2.28 (m, 7 H, 3-H, 4- H, 5-H, 6-H), 1.59, 1.69 (2 s, 6 H, 9-H, C-8-CH3), 1.87 (s, 3 H, T-CH3), 3.58 - 3.79 (m, 3 H, 2'-H, 2-H), 3.89 (s, 3 H, ArOCH3), 4.27 - 4.52 (m, 3 H, T-Ac-CH2, 7-H), 4.66 - 4.89 (m, 2 H, <BR> <BR> <BR> CH2-Ph, isomers), 4. 95 - 5.19 (m, 2 H, 2'-H, isomers), 6.89 (2 s, 1 H, T-CH=C, isomers), 7.10 - 7.37 (m, 6 H, 6"-H, Ph), 7.60 (m, I H, 3"-H), 8.40, 8.45 (2 d, 1 H, 5"-H, isomers), 8.65 (br, 1 H, T-NH), 10.22, 10.28 (2 s, 1 H, C-1"-NH).- <BR> <BR> <BR> C34H43N508 (649.7) Calc. C 62.85 H 6. 67 N 10.78<BR> <BR> <BR> <BR> Found C 62.79 H 6.72 N 10. 51 - Example 65 rac-2[(2'-benzyloxy-ethyl) -thyminacetyl-amino] -pentadecan acid-4"-methoxy-2"- nitrophenylamide The title compound is prepared as described in example 62 with paraformaldehyde substituted by 0.42 g (2.00 mmol) tetradecanal to give the title compound as a brown powder in 0.47 g (33 %) yield. -

TLC (dichloromethane: methanol 95: 5): Rf = 0.87. - Mp. : 119°C. ¹H-NMR (CDCl3, 300 MHz):# [ppm] = 0.90 (t, 3 H, 15-H), 1.29 (m, 22 H, 4-H, 5-H, 6-H, 7-H, 8-H, 9-H, 10-H, 11-H, 12-H, 13-H, 14-H), 1.62 - 1.84, 2.10 - 2.20 (m, 2 H, 3-H), 1.88 (s, 3 H, T-CH3), 3.61- <BR> <BR> <BR> 3.76 (m, 3 H, 2'-H, 2-H), 3. 88 (s, 3 H, ArOCH3), 4. 35 - 4.44 (m, 2 H, T-Ac-CH2), 4.70 - 4.79 (m, 2 H, CH2-Ph), 4.80 - 4.88 (m, 2 H, 2'-H), 6.85 (s, 1 H, T-CH=C), 7.12 - 7.35 (m, 6 H, 6"- H, Ph), 7.60 (d, 1 H, 3"-H), 8.41 (d, 1 H, 5"-H), 8.50 (s, 1 H, T-NH), 10.26 (s, 1 H, C-1"- NH).- C38H53N508 (707.9) Calc. C 64.48 H 7.55 N 9. 89 Found C 64.32 H 7.47 N 9.76.- Example 66 2 [(2'-Boc-aminoethyl)-thyminacetyl-aminol-acetic acid-4"-methoxy-2"- nitrophenylamide The title compound is prepared as described in example 50 with cyclohexanone substituted by 0.06 g (2.00 mmol) paraformaldehyde to give the title compound as a red powder in 0.68 g (64 %) yield.- TLC (dichloromethane: methanol 95: 5): Rf= 0.37. ¹H-NMR (CDCl3, 300 MHz): # [ppm] = 1.41, 1.49 (2 s, 9 H, Boc-CH3, rotamers), 1.80, 1.81 (2 s, 3 H, T-CH3, rotamers), 3. 30 - 3.75 (m, 4 H, 1'-H, 2'-H, rotamers), 3.88 (s, 3 H, ArOCH3), 4.28 - 4.50 (m, 2 H, 2-H, rotamers), 4.66 - 4.82 (m, 2 H, T-Ac-CH2, rotamers), 5.15, 5.55 (m, 1 H, Boc-NH, rotamers), 7.07, 7.10 (2 s, 1 H, T-CH=C, rotamers), 7.22 (2 dd, 1 H, 6"-H, rotamers), 7.63 (m, 1 H, 3"- H, rotamers), 8.50, 8.58 (2 d, 1 H, 5"-H, rotamers), 8.86, 9.04 (2 s, 1 H, T-NH, rotamers), 10.30, 10.37 (2 s, 1 H, C-1"-NH, rotamers).- C23H30N6O9 (534.5) Calc. C 51. 68 H 5.66 N 15.72.

Found C 51.53 H 5.79 N 15. 56.- Example 67 2 [ (2'-Boc-aminoethyl)-(N4-Z-cytosinacetyl)-aminol-acetic acid-4"-methoxy-2"- nitrophenylamide The title compound is prepared as described in example 66 with N-1-carboxymethylthymine substituted by 0.61 g (2.00 mmol) N4-Z-N-1-carboxymethyl cytosine to give the title compound as a red-brown powder in 0. 83 g (64 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf= 0.41. ¹H-NMR (CDCl3, 300 MHz): # [ppm] = 1.41 (s, 9 H, Boc-CH3) 3.27 - 3.81 (m, 4 H, 1'-H, 2'-H, rotamers), 3.89 (s, 3 H, ArOCH3), 4.21 - 4.25, 4.45 - 4.76 (m, 2 H, 2-H, rotamers), 4.87 - 4.98 (m, 2 H, C-Z-Ac-CH2, rotamers), 5.20 (s, 2 H, C-Z-CHz-Ph), 5.72, 5.98 (2 s, 1 H, Boc-NH, rotamers), 7.12 - 7.29 (m, 2 H, C-Z-CH=C, 6"-H), 7.36 (s, 5 H, C-Z-Ac-Ph), 7.60 - 7.70 (m, 2 H, 3 "-H, C-Z- C=CH), 8.29 (m, 1 H, C-Z-NH), 8.40 - 8.51 (m, 1 H, 5"-H, rotamers), 10.25 - 10.37 (3 s, 1 H, C-1"-NH, rotamers). -

C3oH35N7010 (653.6) Calc. C 55.13 H 5.40 N 15.00 Found C 55.21 H 5. 38 N 15.12.- Example 68 2 [(2'-Boc-aminoethyl)-uracilacetyl-amino]-acetic acid-4"-methoxy-2"- nitrophenylamide The title compound is prepared as described in example 66 with N-1-carboxymethylthymine substituted by 0.34 g (2.00 mmol) N-1-carboxymethyluracil to give the title compound as a <BR> <BR> <BR> red-brown powder in 0.67 g (64 %) yield. - <BR> <BR> <BR> <BR> <BR> <BR> TLC (dichloromethane: methanol 95: 5): Rf= 0.26. -'H-NMR (CDC13, 300 MHz): # <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> [ppm] = 1.42 (s, 9 H, Boc-CH3), 3. 30 - 3.75 (m, 4 H, 1'-H, 2'-H, rotamers), 3.89 (s, 3 H, ArOCH3), 4.16 - 4.53 (m, 2 H, 2-H, rotamers), 4.67 - 4.98 (m, 2 H, UAc-CH2, rotamers), 5.14, 5.54 (2 s, 1 H, Boc-NH, rotamers), 5.70 - 5.80 (d, 1 H, U-C=CH) 7.19 - 7.28 (m, 2 H, U-CH=C, 6 "-H, rotamers), 7.62 (m, 1 H, 3"-H, rotamers), 8.50, 8.57 (2 d, 1 H, 5"-H, rotamers), 8.94, 9.09 (2 s, 1 H, U-NH, rotamers), 10.29, 10.33 (2 s, 1 H, C-1"-NH, rotamers). - C22H28N609 (520.5) Calc. C 50.77 H 5.42 N 16.15 Found C 50. 79 H 5. 38 N 16. 01 - Example 69 2[(2'-Boc-aminoethyl)-(N6-Z-adeninacetyl)-amino]-acetic acid-4"-methoxy-2"- nitrophenylamide The title compound is prepared as described in example 66 with N-1-carboxymethylthymine substituted by 0.65 g (2.00 mmol) N6-Z-N-9-carboxymethyl adenine to give the title <BR> <BR> <BR> <BR> compound as a red-brown powder in 0.94 g (69 %) yield. - <BR> <BR> <BR> <BR> <BR> <BR> <BR> TLC (dichloromethane: methanol 95: 5): Rf= 0.31. -'H-NMR (CDC13, 300 MHz): b [ppm] = 1.39, 1.40 (2 s, 9 H, Boc-CH3, rotamers), 3.24 - 3.80 (m, 4 H, 1'-H, 2'-H, rotamers), <BR> <BR> <BR> <BR> 3.82 (s, 3 H, ArOCH3), 4.20, 4.22, 4. 39 - 4.48 (m, 2 H, 2-H, rotamers), 4.60 - 5.22 (m, 2 H, A-Z-Ac-CH2, rotamers), 5.28, 5.29 (2 s, 2 H, A-Z-CH2-Ph), 5.34, 5.69 (m, 1 H, Boc-NH, <BR> <BR> <BR> <BR> rotamers), 7.14 - 7.20 (m, 1 H, 6"-H), 7. 30 - 7.40 (m, 5 H, A-Z-Ph, rotamers), 7. 58 - 7.62 (m,<BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 1 H, 3"-H, rotamers), 7. 99, 8.10, 8.12 (3 s, 1 H, A-Z-CH=N, rotamers), 8.42 - 8.50 (2 d, 1 H, 5 "-H, rotamers), 8.60, 8.69, 8.73 (m, 1 H, A-Z-CH=N, rotamers), 8.92 - 9.20 (m, 1 H, A-Z- NH, rotamers), 10.29, 10.36, 10.45 (3 s, 1 H, C-1"-NH, rotamers).- C31H35N9O9 (677. 7) Calc. C 54.94 H 5.21 N 18.60 Found C 54.82 H 5.18 N 18. 51. -

Example 70 rac-2 [ (2'-B oc-aminoethyl) -thyminacetyl-amino] -4-ethoxycarbonyl-2-m ethyl- butyric acid-4"-methoxy-2"-nitrophenylamide The title compound is prepared as described in example 66 with paraformaldehyde substituted by 0.29 g (2.00 mmol) ethyl-laevulinate to give the title compound without flash filtration as a yellow-brown powder in 0.98 g (76 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf= 0.47. - Mp.:147°C (dec.).- ¹H-NMR <BR> <BR> (CDC13, 300 MHz):# [ppm] = 1.25 (t, 3 H, C-4-C (0) 0-CH2-C), 1.41 (s, 9 H, Boc-CH3), 1.60 (s, 3 H, C-2-CH3), 1.84 (s, 3 H, T-CH3), 2.20 - 2.30, 2.39 - 2.53 (m, 4 H, 3-H, 4-H), <BR> <BR> <BR> 3.40 - 3. 77 (m, 4 H, I'-H, 2'-H), 3.85 (s, 3 H, ArOCH3), 4.12 (q, 2 H, C-4-C (O)O-CH2), 4.79 (s, 2 H, T-Ac-CH2), 5.38 (s, 1 H, Boc-NH), 6.91 (s, 1 H, T-CH=C), 7.21 (dd, 1 H, 6"-H), 7.61 (d, 1 H, 3"-H), 8.46 (d, 1 H, 5"-H), 8.65 (s, 1 H, T-NH), 10.29 (s, 1 H, C-1"-NH). - C29H40N6O11 (648.7) Calc. C 53.70 H 6.22 N 12.96 Found C 53.75 H 6. 28 N 12. 88- Example 71 2 [ (2'-Ib-amino-phenyl) -thyminacetyl-amino] -acetic acid-4"-methoxy-2"- nitrophenylamide The title compound is prepared as described in example 66 with mono-Boc-ethylene-diamine substituted by 0.36 g (2.00 mmol) mono-Ib-ortho-phenyendiamine. Flash filtration is performed with silica gel (dichloromethane/methanol 9/1) to give the title compound as a orange-brown powder in 0.66 g (60 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf= 0.48.- ¹H-NMR (CDCl3, 300 MHz): 8 [ppm] = 1.30 (t, 6 H, Ib-CH3), 1.87, 1.92 (2 s, 3 H, T-CH3, rotamers), 2.84 (q, 1 H, Ib-CH), <BR> <BR> <BR> 3. 90 (s, 3 H, ArOCH3), 4. 02 - 4. 10 (m, 2 H, 2-H, rotamers), 4.20, 4. 28, 4. 87, 4.92 (m, 2 H, T- Ac-CH2, rotamers), 6.80, 6.99 (2 s, 1 H, T-CH=C, rotamers), 7.11 - 7.49 (m, 5 H, 6 "-H, 3'-H, 4'-H, 5'-H, 6'-H), 7.56, 7.68 (2 d, 1 H, 3"-H, rotamers), 8.23 - 8.80 (m, 1 H, T-NH, rotamers), 8.55, 8.61 (2 d, 1 H, 5"-H, rotamers), 10.06 (s, 1 H, Ib-NH), 10.36 (s, 1 H, C-1"-NH). - C26H28N608 (552.5) Calc. C 56.52 H 5.11 N 15. 21 Found C 56.48 H 5.18 N 15.19.- Example 72 8[(2'-Boc-aminoethyl)-thyminacetyl-amino]-1,4-dioxaspiro[4.5 ]decane-8- carboxylic acid-4"-methyl-2"-nitrophenylamide <BR> <BR> <BR> 0.32 g (2.00 mmol) mono-Boc-ethylendiamine and 0. 31 g (2.00 mmol) 1,4- cyclohexandione monoethylene ketal are solved in 20 ml toluene three times and evaporated.

The residue is solved in 7 ml abs. methanol and 0.32 g (2.00 mmol) 4-methyl-2- nitrophenylisocyanide and 0. 37 g (2.00 mmol) A'- I -carboxymethylthymine are added. The reaction mixture is heated for five minutes and stirred for three days at room temperature with

exclusion of moisture. The reaction mixture is evaporated to dryness, diluted with 25 ml dichloromethane and stirred for half an hour. The precipitate is filtered off and the filtrate is evaporated to dryness. Afterwards 20 ml diethylether are added and the suspension is stirred for 30 minutes. The precipitate is filtered off, washed with diethylether three times and dried <BR> <BR> <BR> in vacuo to give the title compound as a yellow powder in 0.55 g (43 %) yield. - <BR> <BR> <BR> <BR> <BR> TLC (dichloromethane: methanol 95: 5): Rf= 0.42. - Mp. : 220°C (dec.). -'H-NMR <BR> <BR> <BR> <BR> <BR> (CDC13, 300 MHz): # [ppm] = 1.42 (s, 9 H, Boc-CH3), 1.68 - 1.75, 1.98 - 2.21, 2. 39 - 2.53 (m, 8 H, 6-H, 7-H, 9-H, 10-H), 1.80, 1.88 (2 s, 3 H, T-CH3, rotamers), 2.36 (s, 3 H, ArCH3), 3.48 - 3.55, 3.65 - 3.72 (m, 4 H, 1'-H, 2'-H), 3.93 (s, 4 H, 2-H, 3-H), 4.68 (s, 2 H, T-Ac-CH2), 5.39 (s, I H, Boc-NH), 6.88, 7.09 (2 s, 1 H, T-CH=C, rotamers), 7.42 (dd, 1 H, 6"-H), 7.95 (d, 1 H, 3"-H), 8.40 (d, 1 H, 5 "-H) 8.89 (s, 1 H, T-NH), 10.39 (s, 1 H, C-1"-NH). - C3oH4oN6010 (644.7) Calc. C 55.89 H 6.25 N 13.04 Found C 55.93 H 6. 29 N 13. 11. - Example 73 rac-2 [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -2-anthracen-9"'-yl-acetic acide-4"- methyl-2"-nitrophenylamide <BR> <BR> <BR> The title compound is prepared as described in example 72 with 1, 4- cyclohexandione monoethylene ketal substituted by 0.41 g (2.00 mmol) anthracen-9- <BR> <BR> <BR> carbaldehyde to give the title compound as a yellow-brown powder in 0.37 g (27 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf= 0.69. ¹H-NMR (CDCl3, 300 MHz): # <BR> <BR> <BR> [ppm] = 1. 41 (s, 9 H, Boc-CH3), 1.89, 2.00 (2 s, 3 H, T-CH3, rotamers), 2.35 (s, 3 H, Arcs3), 12 - 3.22, 3.41 - 3.53 (m, 4 H, 1'-H, 2'-H), 4.65, 5.20 (2 d, 2 H, T-Ac-CH), 4.80 (s, 1 H, Boc-NH), 6.10 (s, 1 H, 2-H), 7.20 (2 s, 1 H, T-CH=C, rotamers), 7.42 - 7.59, 8.02 - 8.24 (m, 11 H, 6 "-H, 3"-H,1"'-H, 2 "'-H, 3 "'-H, 4 "'-H, 5 "'-H, 6 "'-H, 7"'-H,8"'-H,10"'-H), 7.69, <BR> <BR> <BR> 8. 59 (d, 1 H, 5"-H), 8.66 (s, 1 H, T-NH), 10.15 (s, 1 H, C-1"-NH). - <BR> <BR> <BR> <BR> <BR> C37H38N6O(694.7) Calc. C 63.97 H 5.51 N 12. 10 Found C 63.79 H 5.34 N 12.19.- Example 74 rac-2 [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -2-phenylacetic acid-4"-methoxy-2"- nitrophenylamide 0.32 g (2.00 mmol) mono-Boc-ethylendiamine and 0.21 g (2.00 mmol) benzaldehyde are solved 7 ml abs. methanol and 0.36 g (2.00 mmol) 4-methoxy-2-nitrophenylisocyanide and 0.37 g (2.00 mmol) N-1-carboxymethylthymine are added. The reaction mixture is heated for five minutes and stirred for three days at room temperature with exclusion of moisture. The reaction mixture is evaporated to dryness, diluted with 25 ml dichloromethane and stirred for half an hour. The precipitate is filtered off and the filtrate is evaporated to dryness.

Afterwards 20 ml diethylether are added and the suspension is stirred for 30 minutes. The

precipitate is filtered off, washed with diethylether three times. The crude product is purified by flash filtration (neutral alumina, dichloromethane/methanol 95: 5) to give the title <BR> <BR> <BR> compound as a red-brown powder in 0.50 g (41 %) yield. - <BR> <BR> <BR> <BR> TLC (dichloromethane: methanol 95 : 5): Rf = 0.73. - Mp. : 115°C. lH-NMR (CDCl3, 300 MHz): 8 [ppm] = 1.42 (s, 9 H, Boc-CH3), 1.90 (s, 3 H, T-CH3), 3.20 - 3.51, 3.79 - 3.89 (m, 4 H, 1'-H, 2'-H), 3.83 (s, 3 H, ArOCH3), 4.59, 4.80 (2 d, 2 H, T-Ac-CH2), 5.49 (s, 1 H, Boc- NH), 5.77 (s, 1 H, 2-H), 7.00 (s, 1 H, T-CH=C), 7.21 (dd, 1 H, 6"-H), 7.44 (s, 5 H, C-2-Ph), 7.60 (d, 1 H, 3"-H), 8.59 (d, 1 H, 5"-H), 8.95 (s, 1 H, T-NH), 10.11 (s, 1 H, C-1"-NH). - C29H34N609 (610.6) Calc. C 57.04 H 5.61 N 13.76 Found C 57.12 H 5.69 N 13.59.- Example 75 <BR> <BR> <BR> rac-2 [ (trans-2'-Boc-aminocyclohexyl) -thyminacetyl-amino] -3,3-dimethyl-butyric acid- 4"-methoxy-2"-nitrophenylamide The title compound is prepared as described in example 74 with benzaldehyde substituted by 0.17 g (2.00 mmol) pivalaldehyde and mono-Boc-ethylendiamine substituted by 0.43 g (2.00 mmol) trans-1, 2-mono-Boc-cyclohexylendiamine to give the title compound as a yellow-brown powder in 0.82 g (64 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf = 0.63. ¹H-NMR (CDCl3, 300 MHz): 8 <BR> <BR> <BR> [ppm] = 1.04, 1.06, 1.22 [m, 9 H, C-3 (CH3) 3, isomers] 1.39, 1.44 (m, 9 H, Boc-CH3, isomers), 1.15 - 2.30 (m, 8 H, 3'-H, 4'-H, 5'-H, 6'-H), 1.89, 1.91, 1.93 (3 s, 3 H, T-CH3, isomers), 3.07 - 3.20, 3.31 - 3.42, 3.50 - 3.75, (m, 2 H, 1'-H, 2'-H, isomers), 3.68, 3.74, 3.80 <BR> <BR> <BR> (m, 1 H, 2-H, isomers), 3.86, 3.87 (m, 3 H, ArOCH3, isomers), 4.19 - 4. 47, 4.69, 4.97 (m, 2<BR> <BR> <BR> <BR> H, T-Ac-CH2, isomers), 5.15 - 5.60 (m, I H, Boc-NH, isomers), 6. 94 - 7.32 (m, 2 H, T- CH=C, 6"-H, isomers), 7.57 - 7.73 (4 d, I H, 3"-H, isomers), 8.25 - 8.33, 8.52, 8.67 (m, I H, <BR> <BR> <BR> 5"-H, isomers), 8.70 - 9.40 (br, 1 H, T-NH), 10.17, 10.24, 10.49, 10. 85, 11.00 (m, 1 H, C-1"- NH, isomers). - C3lH44N609 (644.7) Calc. C 57.75 H 6.88 N 13.04 Found C 57.68 H 6.79 N 12.95.- Example 76 2 [(2'-Boc-aminoethyl)-theophyllinacetyl-amino] -acetic acid-4"-methoxy-2"- nitrophenylamide The title compound is prepared as described in example 73 with anthracen-9-carbaldehyde substituted by 0.06 g (2.00 mmol) paraformaldehyde, 4-methyl-2-nitrophenylisocyanide substituted by 0.36 g (2.00 mmol) 4-methoxy-2-nitrophenylisocyanide and N-1- carboxymethylthymine substituted by 0.48 g (2.00 mmol) N -carboxymethyl theophylline.

The crude product is purified by flash filtration (neutral alumina, dichloromethane/methanol 95 : 5) to give the title compound as a red-brown powder in 0. 68 g (58 %) yield. -

TLC (dichloromethane: methanol 95: 5): Rf = 0.34.- <BR> <BR> ¹H-NMR (CDCl3,300 MHz): b [ppm] = 1.40, 1.49 (2 s, 9 H, Boc-CH3, rotamers), 3. 30 - <BR> <BR> <BR> <BR> <BR> <BR> <BR> 3.79 (m, 4 H, 1'-H, 2'-H, rotamers), 3.22, 3.27 (2 s, 3 H, Th-CH3, rotamers), 3. 55, 3.70 (2 s, 3 H, Th-CH3, rotamers), 3.84, 3.85 (2 s, 3 H, ArOCH3), 4.22, 4.23, 4.39, 4.44, 4.52 - 4.88 (m, 2 H, 2-H, rotamers), 5.10 - 5.32 (m, 2 H, Th-Ac-CH2, rotamers), 5.42, 5.61 (m, 1 H, Boc-NH, <BR> <BR> <BR> rotamers), 7. 18 - 7.29 (m, 1 H, 6"-H, rotamers), 7. 60 - 7.71 (m, 2 H, 3 "-H, Th-CH=N, rotamers), 8.43 (d, 1 H, 5"-H, rotamers), 10.19, 10.38 (2 s, 1 H, C-1"-NH, rotamers). - C25H32N8O9 (588.6) Calc. C 51.02 H 5.48 N 19.04 Found C 51. 12 H 5.42 N 18.89.- Example 77 <BR> <BR> <BR> 6 [(2'-Boc-aminoethyl)-thyminacetyl-amino]-6-deoxy-1,2:3,4-di- O-isopropylidene-α-D- <BR> <BR> <BR> <BR> <BR> <BR> galacto-pyranose-6-carboxylic acid-4"-methoxy-2"-nitrophenylamide The title compound is prepared as described in example 73 with anthracen-9-carbaldehyde <BR> <BR> <BR> substituted by 0. 52 g (2.00 mmol) 1, 2: 3, 4-Di-O-isopropylidene-a-D-galacto-hexodialdo-1, 5- pyranose and 4-methyl-2-nitrophenylisocyanide substituted by 0.36 g (2.00 mmol) 4- methoxy-2-nitrophenylisocyanide. The crude product is purified by flash filtration (neutral alumina, dichloromethane/methanol 95 : 5) to give the title compound as a red-brown powder in 0.63 g (41 %) yield. - <BR> <BR> TLC (dichloromethane: methanol 95 : 5) : Rf= 0.68. - 1H-NMR (CDC13,300 MHz): 8<BR> <BR> <BR> <BR> <BR> <BR> <BR> [ppm] = 1.26, 1.38, 1.39, 1.47 [4 s, 12 H, C (CH3) 2], 1.43 (s, 9 H, Boc-CH3), 1.91 (s, 3 H, T- CH3), 3.10 - 3. 22, 3.43 - 3.80 (m, 5 H, 6 - H, I'-H, 2'-H), 3.84 (s, 3 H, ArOCH3), 4.07, 4.21 (2 d, 2 H, 5-H, 4-H), 4.36 (dd, 1 H, 2-H), 4.65 (dd, 1 H, 3-H), 4.94 - 5.02 (2 d, 2 H, T-Ac- CH2), 5.52, 5.72 (2 d, 1 H, 1-H, isomers), 5. 97 (s, 1 H, Boc-NH), 6.93, 7.02 (2 s, 1 H, T- CH=C, isomers), 7.16 (dd, 1 H, 6"-H), 7.56, 7.60 (2 d, 1 H, 3"-H, isomers), 8.11, 8.41 (2 d, 1 H, 5"-H), 9.08 (s, 1 H, T-NH), 10.48, 10.61 (2 s, 1 H, C-1"-NH, isomers). - C34H46N6O14 (762.8) Calc. C 53.54 H 6.08 N 11.02 Found C 53.48 H 6.12 N 10.89.- Example 78 <BR> <BR> <BR> rac-2 [ (2'-Boc-aminoethyl) -thyminacetyl-aminol-2-anthracen-9'"-yl-acetic acid-4"- <BR> <BR> <BR> <BR> <BR> <BR> methoxy-2"-nitrophenylamide The title compound is prepared as described in example 73 with 4-methyl-2- nitrophenylisocyanide substituted by 0.36 g (2.00 mmol) 4-methoxy-2- nitrophenylisocyanide. The crude product is purified by flash filtration (neutral alumina, dichloromethane/methanol 95: 5) to give the title compound as a orange-brown powder in 0.42 g (30 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf= 0.80- ¹H-NMR (CDC13,300 MHz): # <BR> <BR> [ppm] = 1. 36 (s, 9 H, Boc-CH3), 1.78, 1.99 (2 s, 3 H, T-CH3, rotamers), 3.19 - 3. 38, 3. 46 -

3.59 (m, 4 H, l'-H, 2'-H) , 3.80 (s, 3 H, ArOCH3), 4.60, 5.20 (2 d, 2 H, T-Ac-CH2), 4.86 (s, 1 <BR> <BR> <BR> H, Boc-NH), 7.11 - 7.27 (m, 2 H, T-CH=C, 6"-H), 7.43 - 7. 57, 8.00 - 8.12 (m, 9 H, 1"'-H, 2"'- H, 3 "'-H, 4 "'-H, 5 "'-H, 6 "'-H, 7"'-H, 8"'-H, 10"'-H), 7.69 (s, 1 H, 3"-H), 8.57 (d, 1 H, 5"-H), 8.64 (s, 1 H, T-NH), 9.95 (s, 1 H, C-1"-NH). - C37H3gN609 (710.7) Calc. C 62.53 H 5. 39 N 11.82 Found C 62.49 H 5.24 N 11.78.- Example 79 rac-8 [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -tricyclo [5. 2.1. 0 2,6] decan-8- carboxylic acid-4"-methoxy-2"-nitrophenylamide The title compound is prepared as described in example 78 with athracen-9-carbaldehyde substituted by 0.30 g (2.00 mmol) tricyclo [5.2. 1.0 2,6] decan-8-one to give the title compound <BR> <BR> <BR> as a yellow powder in 0.97 g (74 %) yield. - <BR> <BR> <BR> <BR> <BR> <BR> TLC (dichloromethane: methanol 95: 5): Rf= 0.72. lH-NMR (CDCl3, 300 MHz): 6 [ppm] = 1.43, 1.46 (2 s, 9 H, Boc-CH3, isomers), 0.92 - 2.14, 2.33 - 2.50 (m, 14 H, 2-H, 3-H, 4-H, 5-H, 6-H, 7-H, 9-H, 10-H), 1.86, 1.89 (2 s, 3 H, T-CH3, isomers), 3.17 - 3.80 (m, 4 H, 1'-H, 2'-H), 3.85 (s, 3 H, ArOCH3), 4.18, 4.34, 4.88, 4.95 (4 d, 2 H, T-Ac-CH2, isomers), <BR> <BR> <BR> 5.29, 5.59 (2 s, I H, Boc-NH, isomers), 6.88, 7.02 (2 s, I H, T-CH=C, isomers), 7. 15 - 7.24 (m, I H, 6"-H, isomers), 7.59, 7.66 (2 d, I H, 3"-H, isomers), 8.25, 8.61 (2 d, I H, 5"-H, isomers), 8.77 (s, 1 H, T-NH), 10. 33, 10.64 (2 s, 1 H, C-1"-NH, isomers). - C32H42N609 (654.7) Calc. C 58.70 H 6.47 N 12.84 Found C 58.64 H 6.42 N 12.79.- Example 80 2 [ (2'-Boc-aminoethyl) - (2""-amino-6""-benzyloxy-N9-purin acetyl) -amino] -acetic acid- 4"-methoxy-2"-nitrophenylamide The title compound is prepared as described in example 78 with athracen-9-carbaldehyde substituted by 0.06 g (2.00 mmol) paraformaldehyde and N-1-carboxymethylthymine substituted by 0.60 g (2.00 mmol) 2-amino-6-benzyloxy-N-9-carboxymethyl purine. The crude product is purified by flash filtration (neutral alumina, dichloromethane/methanol <BR> <BR> <BR> 95: 5) to give the title compound as a yellow-brown powder in 0.48 g (37 %) yield. - <BR> <BR> <BR> <BR> <BR> TLC (dichloromethane: methanol 95: 5): Rf= 0. 49. -'H-NMR (CDC13, 300 MHz): 8 [ppm] = 1.38 - 1.49 (m, 9 H, Boc-CH3, rotamers), 3.21 - 3.85 (m, 4 H, 1'-H, 2'-H, rotamers), 3.87 (s, 3 H, ArOCH3), 4.15 - 4.57 (m, 2 H, 2-H, rotamers), 4.74 - 5.19 (m, 3 H, G-Bz-Ac- CH2, Boc-NH, rotamers), 5.45 - 5.85 (m, 2 H, G-Bz-CH2-Ph, rotamers), 7.17 - 7.25 (m, 1 H, 6"-H), 7.29 - 7.40 (m, 5 H, G-Bz-Ph, rotamers), 7.46 - 7.58 (m, 1 H, 3"-H, rotamers), 7.61 - 7.77 (m, 1 H, G-Bz-CH=N, rotamers), 8.39 - 8.62 (m, 1 H, 5"-H, rotamers), 10.32 - 10.42 (m, 1 H, C-1 "-NH, rotamers). -

C3oH35N608 (649.7) Calc. C 55.46 H 5.47 N 19.40 Found C 55.42 H 5.38 N 19. 31. - Example 81 rac-2 [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -2-pyridin-3"'-yl-acetic acid-4"- methoxy-2"-nitrophenylamide The title compound is prepared as described in example 74 with benzaldehyde substituted by 0.21 g (2.00 mmol) pyridin-3-carbaldehyde using the double amount of N-1- carboxymethylthymine (0.74 g (4.00 mmol)) to give the title compound as a yellow-brown <BR> <BR> <BR> powder in 0.33 g (27 %) yield. - <BR> <BR> <BR> <BR> <BR> <BR> TLC (dichloromethane: methanol 95: 5): Rf= 0.23. - Mp. : 98 °C (dec.). -'H-NMR (CDCl3 DMSO-d6,300 MHz): 6 [ppm] = 1.31 (s, 9 H, Boc-CH3), 1.79 (s, 3 H, T-CH3), 2.90 - 3.56 (m, 4 H, 1'-H, 2'-H), 3.80 (s, 3 H, ArOCH3), 4.62, 4.73 (2 d, 2 H, T-Ac-CH2), 5.75 (s, 1 H, 2-H), 6.36 (2 s, 1 H, Boc-NH), 7.10 (s, 1 H, T-CH=C), 7.15 (dd, 1 H, 6"-H), 7.30 (m, 1 H, 5"'-H), 7.47 (d, 1 H, 3"-H), 7.79 (d, 1 H, 5"-H), 8.03 (d, 1 H, 4"'-H), 8.50 - 8.61 (m, 2 H, 2"'-H, 6"'-H), 10.09 (s, 1 H, C-1"-NH), 11.01 (s, 1 H, T-NH). - C28H33N709 (611.6) Calc. C 54.99 H 5.44 N 16.03 Found C 54.96 H 5.46 N 16.12. - Example 82 2 [ (2'-Boc-aminoethyl) - (N2-Z-guanina cetyl) -amino] -acetic acid-4"-methyl-2"- nitrophenylamide 0. 32 g (2.00 mmol) wono-Boc-ethylendiamine and 0.06 g (2.00 mmol) paraformaldehyde are suspened 7 ml abs. methanol and 0. 32 g (2.00 mmol) 4-methyl-2-nitrophenylisocyanide and 0.69 g (2.00 mmol) N2-Z-N-9-carboxymethyl guanine are added. The reaction mixture is stirred for three days at room temperature with exclusion of moisture. The reaction mixture is evaporated to dryness, diluted with 25 ml dichloromethane and stirred for half an hour. The precipitate is filtered off and the filtrate is evaporated to dryness. Afterwards 20 ml diethylether are added and the suspension is stirred for 30 minutes. The precipitate is filtered off, washed with diethylether three times. The crude product is purified by chromatography (silica gel, dichloromethane/methanol 95: 5) to give the title compound as a red-brown powder in 0.15 g (13 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf= 0.26.- 1H-NMR (CDC13,300 MHz): # <BR> <BR> <BR> [ppm] = 1.32, 1.44, 1.50 (3 s, 9 H, Boc-CH3, rotamers), 2.34, 2. 38, (2 s, 3 H, Ar-CH3) , 3. 21 - 3.88 (m, 4 H, 1'-H, 2'-H, rotamers), 4.21 (s, 2 H, 2-H), 4.74, 4.82, 5.07 (3 s, 2 H, G-Z-Ac- CH2, rotamers), 5.20, 5.25 (2 s, 2 H, G-Z-CH2-Ph), 6.09 (s, 1 H, Boc-NH), 7.30 - 7.45 (m, 6 <BR> <BR> <BR> H, G-Z-Ph, 6"-H), 7. 64 - 7.74 (m, 1 H, 3"-H, rotamers), 7.83, 7.89, 7.95 (3 s, 1 H, G-Z-<BR> <BR> <BR> <BR> <BR> <BR> <BR> CH=N, rotamers), 8. 38 - 8.55 (m, 1 H, 5"-H, rotamers), 10. 37 - 10.57 (m, 1 H, C-1"-NH, rotamers). -

C31H35N9O9 (677.7) Calc. C 54.94 H 5.21 N 18.60 Found C 54.87 H 5.11 N 18.79.- Example 83 2 [ (2'-Boc-aminoethyl) -(N²-Z-guaninacetyl)-amino]-acetic acid-4"-methoxy-2"- nitrophenylamide The title compound is prepared as described in example 82 with 4-methyl-2- nitrophenylisocyanide substituted by 0.36 g (2.00 mmol) 4-methoxy-2- nitrophenylisocyanide. The crude product is purified by chromatography (silica gel, dichloromethane/methanol 95: 5) to give the title compound as a yellow-brown powder in 0.27 g (20 %) yield. - <BR> <BR> <BR> TLC (dichloromethane: methanol 95: 5) : Rf= 0.26. - Mp. : 190°C (dec.).- ¹H-NMR (CDC13, 300 MHz): b [ppm] = 1.34, 1.44 (2 s, 9 H, Boc-CH3, rotamers), 3.21 - 3. 32, 3.42 - <BR> <BR> <BR> <BR> 3.60, 3. 68 - 3.77 (m, 4 H, 1'-H, 2'-H), 3.80 (s, 3 H, ArOCH3), 4.19, 4.57 (m, 2 H, 2-H, rotamers), 4.89, 5.04, 5.08 (m, 2 H, G-Z-Ac-CH2, rotamers), 5.20, 5.43 (m, 2 H, G-Z-CH2- Ph), 6.00, 6.08 (2 s, 1 H, Boc-NH), 7.10 (dd, 1 H, 6"-H), 7.31 - 7.39 (m, 5 H, G-Z-Ph), 7.53 (d, 1 H, 3"-H), 7.70 (s, 1 H, G-Z-CH=N), 8.11, 8.31 (2d, 1 H, 5"-H, rotamers), 9.57, 9.73, <BR> <BR> <BR> <BR> 10.87 (3 s, 1 H, G-Z-NH), 10.20, 10. 35 (2 s, 1 H, C-1"-NH, rotamers), 11.26, 11.31 (2 s, 1 H,<BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> Z-NH) .

C3lH35N9Olo (693.7) Calc. C 53.68 H 5.09 N 18.17 Found C 53.62 H 5.07 N 18.08.- Example 84 rac-2 [ (2'-Hydroxy-ethyl) -thyminacetyl-amino] -3, 3-dimethyl-butyric acid-4"-methoxy- 2"-nitrophenylamide The title compound is prepared as described in example 82 with 4-methyl-2- nitrophenylisocyanide substituted by 0.36 g (2.00 mmol) 4-methoxy-2- nitrophenylisocyanide, mono-Boc-ethylendiamine substituted by 0.12 g (2.00 mmol) ethanolamine, paraformaldehyde substituted by 0.36 g (2.00 mmol) pivalaldehyde and N2-Z- N-9-carboxymethyl guanine substituted by 0.37 g (2.00 mmol) N 1-carboxymethylthymine to give the title compound as a yellow-brown powder in 0.17 g (17 %) yield. - TLC (dichloromethane: methanol 95: 5): Rf= 0.34. - Mp. : 98 °C (dec.). -'H-NMR <BR> <BR> <BR> (CDC13, 300 MHz): # [ppm] = 1.18 [s, 9 H, 4-H, C-3 (CH3) 2], 1.90 (s, 3 H, T-CH3), 2.67 (s, 1 H, OH), 3.59 - 4.05 (m, 5 H, 2-H, 1'-H, 2'-H), 3.85 (s, 3 H, ArOCH3), 4.68, 4.83 (2 d, 2 H, T-Ac-CH2), 7.09 (s, 1 H, T-CH=C), 7.19 (dd, 1 H, 6"-H), 7.57, (d, 1 H, 3"-H), 8.25 (d, 1 H, 5"-H), 9.16 (s, 1 H, T-NH), 10.08 (2 s, 1 H, C-1"-NH, rotamers). - C22H29N508 (491.5) Calc. C 53.76 H 5. 95 N 14.25 Found C 53.78 H 5.91 N 14.37.-

Example 85 <BR> <BR> <BR> 2 [ (2'-Boc-aminoethyl) -hydroxyacetyl-amino] -3, 3-dimethylbutyric acid-4"-methoxy-2"- nitrophenylamide 0.96 g (6.00 mmol) mono-Boc-ethylendiamine and 0.51 g (6.00 mmol) pivalaldehyde are solved 21 ml abs. methanol and 1.08 g (6.00 mmol) 4-methoxy-2-nitrophenylisocyanide and 0.46 g (6.00 mmol) glycolic acid are added. The reaction mixture is stirred for four days at room temperature with exclusion of moisture. The reaction mixture is evaporated to dryness and the remaining crude product is purified by chromatography (silica gel, <BR> <BR> <BR> dichloromethane/methanol 95: 5) to give the title compound as a orange powder in 2. 38 g (82 %) yield. - TLC (n-hexane/ethyl acetate 7: 3): Rf= 0.34. - Mp. :58 °C. ¹H-NMR (CDCl3, 300 <BR> <BR> MHz): 8 [ppm] = 1.15 (s, 9 H, Boc-CH3), 1.31, 1.40 [2 s, 9 H, 4-H, C-3 (CH3) 2, Rotamere], 3.02 - 3.81 (m, 5 H, I'-H, 2'-H, 2-H), 3.89 (s, 3 H, ArOCH3), 4.35, 4.49 (2 d, 2 H, HOAc- CH2), 4.85 (s, 1 H, Boc-NH), 7.23 (dd, 1 H, 6"-H), 7.64 (d, 1 H, 3"-H), 8.40, 8.58 (2 d, 1 H, 5 "-H, Rotamere), 10.23, 10.35 (2 s, 1 H, C-1"-NH, Rotamere). - C22H34N408 (482.5) Calc. C 54.76 H 7.10 N 11.61.

Found C 54.68 H 7.12 N 11. 58. - Example 86 2 [ (2'-Boc-aminoethyl) -acryl-amino] -3, 3-dimethylbutyric acid-4"-methoxy-2"- nitrophenylamide The title compound is prepared as described in example 85 with glycolic acid substituted by 0.35 g (6.00 mmol) acrylic acid to give the title compound as a red solid in 1.37 g (48 %) yield. - TLC (n-hexane/ethyl acetate 7 Rf = 0. 6 l. -'H-NMR (CDC13, 300 MHz): 8 [ppm] = <BR> <BR> <BR> 1.14 (s, 9 H, Boc-CH3), 1.42 [s, 9 H, 4-H, C-3 (CH3) 2] , 2.96 - 3. 48,3. 60 - 3.92 (m, 5 H, 1'-H, 2'-H, 2-H), 3.86 (s, 3 H, ArOCH3), 4.80, 5.14 (s, 1 H, Boc-NH, Rotamere), 5.85, 6.50, 6.90 (3 m, 3 H, H2C=CH), 7.21 (dd, 1 H, 6"-H), 7.66 (d, 1 H, 3"-H), 8.40 (d, 1 H, 5"-H), 10.14 (s, 1 H, C-1"-NH). - <BR> <BR> <BR> C23H34N407 (478.5) Calc. C 57.73 H 7.16 N 23. 43.<BR> <BR> <BR> <BR> <BR> <BR> <P> Found C 57. 78 H 7.14 N 23. 31. - Example 87 2 [ (2'-Boc-aminocyclohexyl) -isobutyryl-aminol-acetic acid-4"-methoxy-2"- nitrophenylamide 2.06 g (9.60 mmol) trans-1, 2-mono-Boc-cyclohexylendiamine and 0.29 g (9.60 mmol) paraformaldehyde are solved in a mixture of 20 ml abs. methanol and 10 ml abs. dichloromethane, stirred at room tmpereture for two hours with exclusion of moisture and mixed with 1.72 g (9.60 mmol) 4-methoxy-2-nitrophenylisocyanide and 0.84 g

(9.60 mmol) isobutyric acid. The reaction mixture is stirred for four days at room temperature with exclusion of moisture. The reaction mixture is evaporated to dryness and the remaining crude product is purified by chromatography (silica gel, n-hexane/ethyl acetate 7: 3) to give <BR> <BR> <BR> the title compound as a orange powder in 3.20 g (68 %) yield. - <BR> <BR> <BR> <BR> TLC (n-hexane/ethyl acetate 7: 3): Rf= 0. 52- Mp. : 128 °C.- ¹H-NMR (CDCl3, 300<BR> <BR> <BR> <BR> MHz): 8 [ppm] = 1.11, 1.21 (2 d, 6 H, Ib-CH3), 1.28, 1. 35 (2 s, 9 H, Boc-CH3, rotamers),<BR> <BR> <BR> <BR> <BR> 1.18 - 2.22 (m, 8 H, 3'-H, 4'-H, 5'-H, 6'-H) , 2. 55, 2.99 (2 sept, 2 H, Ib-CH, rotamers), 3.49, 3.72, 4.56 (3 m, 4 H, 1'-H, 2'-H, rotamers) , 3.83, 3.85 (2 s, 3 H, ArOCH3, rotamers), 3.90 - 4.35 (m, 2 H, 2-H, rotamers), 4.62, 4.74 (2 d, 1 H, Boc-NH, rotamers), 7.18, 7.24 (2 dd, 1 H, 6 "-H, rotamers), 7.62, 7.68 (2 d, 1 H, 3"-H, rotamers), 8.59, 8.65 (2 d, 1 H, 5"-H, rotamers), 10.27, 10.44 (2 s, 1 H, C-1"-NH, rotamers). - <BR> <BR> <BR> C24H36N407 (492.6) Calc. C 58.52 H 7. 37 N 11.37.<BR> <BR> <BR> <BR> <P> Found C 58.63 H 7. 25 N 11. 31- Example 88 rac-2 [ (trans-2'-Boc-aminocyclohexyl) -thyminacetyl-amino] -acetic acid <BR> <BR> <BR> 0.29 g (0.50 mmol) rac-2 [ (trans-2'-Boc-aminocyclohexyl) -thyminacetyl-amino] -acetic acid- 4"-methoxy-2"-nitrophenylamide are solved in 10 ml methanol, six equvalents lithiumhydroxide monohydrate are added and the reaction mixture is heated to reflux until TLC (dichloromethane: methanol 95: 5) indicates being substituted for N-1- carboxymethylthymine no remaing starting material. The reaction mixture is cooled to room temperature, 10 ml water are added and the solution is washed with 20 ml diethylether three times and with 20 ml ethyl acetate. After adding 5 ml saturated amoniumchloride solution, the aquous phase is washed with 20 ml ethyl acetate again, adjusted to pH 2 with concentrated hydrochloric acid and extracted with 20 ml ethyl acetate five times. The combined organic phases are dried over magnesiumsulfate and the solvent is removed under reduced pressure.

The crude product is recrystallized with dichloromethane to give 0.15 g (68 %) of the title compound as a colourless solid.'H-NMR is consistent to literature (P. Lagriffoule, P.

Wittung, M. Eriksson, K. K. Jensen, B. Norden, 0. Buchardt, P. E. Nielsen, Chemistry European Journal 3,912 - 919 (1997)).

Example 89 2 [(2'-Boc-aminoethyl) -thyminacetyl-amino] -acetic acid <BR> <BR> <BR> The title compound is prepared as described in example 88 with rac-2 [ (trans-2'-Boc- <BR> <BR> <BR> <BR> aminocyclohexyl) -thyminacetyl-amino] -acetic acid-4"-methoxy-2"-nitrophenylamide substituted by 0.27 g (0.50 mmol) 2 [ (2'-Boc-aminoethyl) -thyminacetyl-amino] -acetic acid-4"- methoxy-2"-nitrophenylamide to give the title compound without crystallisation as a yellowish solid in 0.14 g (73 %) yield. 1H-NMR is consistent to literature (K. L. Dueholm,

M. Egholm, C. Behrens, L. Christensen, H. F. Hansen, T. Vulpius, K. H. Petersen, R. H.

Berg, P. E. Nielsen. O. Buchardt, Journal of Organic Chemistry 59,5767 - 5773 (1994)).

Example 90 2 ( (2'-Boc-aminoethyl) -uracilacetyl-amino] -acetic acid The title compound is prepared as described in example 89 with 2 [ (2'-Boc-aminoethyl) - thyminacetyl-amino] -acetic acid-4"-methoxy-2"-nitrophenylamide substituted by 0.21 g <BR> <BR> <BR> (0.50 mmol) 2 [ (2'-Boc-aminoethyl) -uracilacetyl-amino] -acetic acid-4"-methoxy-2"-nitro- phenyl-amide to give the title compound as a yellowish solid in 0.08 g (43 %) yield.'H-NMR is consistent to literature (O. Buchardt, P. E. Nielsen, R. H. Berg, WO 92/20702).

Example 91 rac-2 [ (Z'-Boc-aminoethyl) -thyminacetyl-amino] -2-phenylacetic acid The title compound is prepared as described in example 89 with 2 [ (2'-Boc-aminoethyl) - thyminacetyl-amino] -acetic acid-4"-methoxy-2"-nitrophenylamide substituted by 0.25 g (0.40 mmol) rac-2 [(2'-Boc-aminoethyl)-thyminacetyl-amino]-2-phenylacetic acid-4"- methoxy-2 "-nitrophenylamide. The amide is agitated with 50 equvalents lithiumhydroxide monohydrate at room temperature to give the title compound as a yellowish solid in 0.10 g (54 %) yield- <BR> <BR> TLC (tetrahydrofurane: water 95: 5): Rf= 0.75. lH-NMR (DMSO-d6, 300 MHz): 5 [ppm] = 1.34, 1.35 (2 s, 9 H, Boc-CH3, rotamers), 1.77 (s, 3 H, T-CH3), 2.64, 2.88, 3.01, 3.27 (4 m, 4 H, l'-H, 2'-H) , 4.68, 4.76 (2 d, 2 H, T-Ac-CH2), 5.70 (s, I H, 2-H), 6.60, 6.78 (2 s, I H, Boc-NH, rotamers), 6.88 (s, I H, T-CH=C), 7.29 - 7.46 (m, 5 H, C-2-Ph), 11.25, 11.28 (2 s, 1 H, T-NH).- C22H28N407 (460.5) Calc. C 57.38 H 6.13 N 12.17 Found C 57. 41 H 6.21 N 12. 38- Example 92 <BR> <BR> 2 [ (2'-Boc-aminoethyl) - (2""-amino-6""-benzyloxy-N9-purin acetyl) -amino] -acetic acid The title compound is prepared as described in example 91 with rac-2 [ (2'-Boc-aminoethyl) - thyminacetyl-amino] -2-phenylacetic acid-4"-methoxy-2"-nitrophenylamide substituted by <BR> <BR> 0.26 g (0.40 mmol) 2 [ (2'-Boc-aminoethyl) - (2""-amino-6""-benzyloxy-N9-purin acetyl) - amino] -acetic acid-4"-methoxy-2"-nitrophenylamide to give the title compound as a yellowish solid in 0.12 g (60 %) yield. 1H-NMR is consistent to literature (K. L. Dueholm, M. Egholm, C. Behrens, L. Christensen, H. F. Hansen, T. Vulpius, K. H. Petersen, R. H. Berg, P. E.

Nielsen. O. Buchardt, Journal of Organic Chemistry 59, 5767 - 5773 (1994)).

Example 93 2- [ (2'-Boc-aminoethyl) -uracilpropionyl-aminol-acetic acid-cyclohexen-1"-yl-amide 0. 32 g (2 mmol) mono-Boc-ethylendiamine, 0.37 g (2 mmol) 3- (2,4-dioxo-3, 4-dihydro-2H- pyrimidin-l-yl) -propionic acid and 0.10 g paraformaldehyde are suspended in 7 ml methanol (abs.) and stirred for ten minutes at room temperature. 0.21 g (2 mmol) cyclohex-1-en-1-yl isocyanide are added via a syringe. The suspension is heated to reflux for five minutes and finally stirred for 48 hours at room temperature. The solvent is removed in vacuo and the residue is stirred in dichloromethane. The suspension is filtered and the filtrate is evaporated to dryness in vacuo. The remaining solid is stirred with ether and filtered off to give the title compound as a yellowish solid in 0.58 g (63 %) yield.

TLC (dichloromethane/methanol 95: 5): Rf= 0.46.- Mp.: 163-167 °C (dec.).- ¹H-NMR (CDC13) : (The title compound exists as a 50: 50-mixture of rotamers in CDC13 at room temperature) 8 = 1.35, 1.38 [2 s, 9 H, Boc-CH3], 1.44-1. 63,2. 03 [2 m, 8 H, cyclohexenyl- CH2], 2.78-2. 89 [m, 2 H, U-CH2-CH2], 3.20-3. 41 [m, 4 H, 1'-H, 2'-H], 3.86, 3.96 [2 m, 4 H, U-CH2-CH2, C2-CH2], 5.62 [m, 1 H, -CH=CH-C=O], 5.99 [br, 1 H, cyclohexenyl-C=CH], 7.46 [d, 1 H, -CH--CH-C=O], 9.21 [br, 1 H, cyclohexenyl-NH]. - <BR> <BR> <BR> C22H33N506 (463.53) Calc. C 57.01 H 7.18 N 15. 11<BR> <BR> <BR> <BR> <BR> Found C 57.18 H 6. 99 N 15.03.- Example 94 <BR> <BR> <BR> 2- [ (2'-Boc-aminoethyl) -uracilpropionyl-aminol-isobutyric acid-cyclohexen-l"-yl-amide The title compound is prepared as described in example 93 with paraformaldehyde substituted by 0.12 g (2 mmol) acetone as a yellowish solid in 0.56 g (57 %) yield. <BR> <BR> <P> TLC (dichloromethane/methanol 95: 5): Rf = 0.52. - Mp.: 127-129°C (dec.).- ¹H-NMR (CDCI3/DMSO-d6) : (The title compound exists as a 80: 20-mixture of rotamers in CDC13/DMSO-a'6 at room temperature) 5 = 137, 1.39 [2 s, 15 H, Boc-CH3, C2 (CH3)2], 1.48- <BR> <BR> <BR> 1.67, 2.03-2. 19 [2 m, 8 H, cyclohexenyl-CH2], 2.55, 2.95 [2 m, 2 H, U-CHz-CL 3. 05-3.48<BR> <BR> <BR> <BR> <BR> <BR> [m, 4 H, 1'-H, 2'-H], 3.96 [2 m, 2 H, U-CH3-CHZ], 5.48 [2 d, 1 H, -CH=CH C=O], 5. 78,5. 81 [2 br, 1 H, cyclohexenyl-C=CH], 7.54 [2 d, 1 H, -CH=CH-C=O]. - C24H37N506 (491.59) Calc. C 58.64 H 7. 57 N 14.25 Found C 58.70 H 7.64 N 14.54.- Example 95 rac-2- [ (2'-Boc-aminoethyl)-thyminbutyryl-amino]-phenylacetic acid-cyclohexen-1"-yl- amide The title compound is prepared as described in example 93 with paraformaldehyde and 3- (2,4-dioxo-3, 4-dihydro-2H-pyrimidin-1-yl) -propionic acid substituted by 0.21 g (2 mmol) <BR> <BR> <BR> benzaldehyde and 0.45 g (2 mmol) 4- (N-1-thyminyl) -butyric acid as a colourless solid in 0.54 g (48 %) yield.

TLC (dichloromethane/methanol 95: 5): Rf= 0.49.- Mp.: 144-146 °C (dec.).- ¹H-NMR (CDCl3/DMSO-d6): (The title compound exists as a 50 : 50-mixture of rotamers in CDCl3/DMSO-d6 at room temperature) # = 1.39, 1.42 [2 s, 9 H, Boc-CH3], 1.55-1. 68,1. 92- 2-CH2-CH2], 1. 85, 1.86 [2 s, 3 H, Thyminyl-CH3], 3.26-3. 51 [m, 4 H, 1'-H, 2'-H], 3.72 [m, 2 H, T-CH2-CH2-CH2-], 5.97, 6.04, 6.14 [3 br, 2 H, cyclohexenyl-C=CH, 2-H], 7.22 [2 s, 1 H, Thyminyl-H], 7.22-7. 35 [m, 5 H, ArH].- <BR> <BR> <BR> C3oH4lN506 (567.68) Calc. C 63.47 H 7.28 N 12. 34 <BR> <BR> <BR> <BR> <BR> Found C 63.51 H 7. 52 N 12.54.- Example 96 8- [ (2'-Boc-aminoethyl) -thyminpropionyl-amino] -1, 4-dioxaspiro [4.5] decan-8- carboxylic acid-cyclohexen-1"-yl-amide The title compound is prepared as described in example 93 with paraformaldehyde and 3- (2, 4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl) -propionic acid substituted by 0.31 g (2 mmol) <BR> <BR> <BR> 1,4-cyclohexandione monoethylene ketal 0.40 g (2mmol) 3- (N-l-thyminyl) -propionic acid as a yellowish solid in 0.71 g (59 %) yield.

TLC (dichloromethane/methanol 95: 5): Rf = 0.43.- Mp.: 172-175 °C (dec.).- ¹H-NMR (CDC13): (The title compound exists as a 80: 20-mixture of rotamers in CDC13 at room <BR> <BR> <BR> temperature) 8 = 1.31, 1.37 [2 s, 9 H, Boc-CH3], 1.53-1. 61,1. 93-2.10, 2.41-2. 53 [3 m, 16 H,<BR> <BR> <BR> <BR> <BR> <BR> -(CH2)4-), 1.80, 1.83 [2 s, 3 H, Thyminyl-CH3], 2.83 [t, 2 H, T-CHz-C-L 3.25-3. 38 [m, 4 H, 1'-H, 2'-H], 3.84-4. 79 [m, 6 H, T-CH2-CH2-, -O-(CH2)2-O-], 5.77 [br, 1 H, cyclohexenyl- C=CH], 7.26 [br, 1 H, Thyminyl-H]. - <BR> <BR> <BR> <BR> C30H45N5O8 (603.71) Calc. C 59.69 H 7. 51 N 11.60<BR> <BR> <BR> <BR> <BR> <BR> Found C 59.81 H 7. 56 N 11. 61- Example 97 rac-2-[(2'-Boc-aminoethyl) -thyminpropionyl-amino] -3-methyl-butyric acid-cyclohexen- 1"-yl-amide The title compound is prepared as described in example 93 with paraformaldehyde and 3- (2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic acid substituted by 0.14 g (2 mmol) <BR> <BR> <BR> isobutyric acid and 0.40 g (2mmol) 3- (N-1-thyminyl) -propionic acid as a yellowish solid in 0.75 g (72 %) yield.

TLC (dichloromethane/methanol 95: 5): Rf = 0.57.- Mp.: 122-125 °C (dec.).- ¹NMR (CDC13): (The title compound exists as a 60: 40-mixture of rotamers in CDC13 at room temperature) 5 = 0.72, 0.76, 0.97, 1.08 [4 d, 6 H, -CH- (CH3)2], 1.41, 1.43 [2 s, 9 H, Boc- CH3] , 1.56-1. 64,2. 07-2.13 [2 m, 8 H, cyclohexenyl-CH2], 1.87, 1.90 [2 s, 3 H, Thyminyl- <BR> <BR> CH3], 2.80-4. 01 [m, 10 H, T-CHz-C-, T-C-CHz-. l'-H, 2'-H, -CH-(CH3) 2, C2-H], 6.06<BR> <BR> <BR> <BR> <BR> <BR> [br, 1 H, cyclohexenyl-C=CH], 7. 30, 7. 32 [2 s, 1 H, Thyminyl-H]. -

C26H41N5O6 (519.64) Calc. C 60.10 H 7.95 N 13.48 Found C 59.98 H 7.91 N 13. 71 - Example 98 2- [ (2'-Boc-aminoethyl)-(thymin-methylen-ortho-benzoyl)-amino]-a cetic acid- cyclohexen-1"-yl-amide The title compound is prepared as described example 93 with 3- (2,4-dioxo-3, 4-dihydro-2H- pyrimidin-1-yl) -propionic acid substituted by 0.52 g (2 mmol) N-1-thyminyl-methylen- ortho-benzoic acid as a yellowish solid in 0.58 g (54 %) yield.

TLC (dichloromethane/methanol 95: 5): Rf = 0.63.-Mp. : 161-164 °C (dec.).- ¹H-NMR (CDCl3): (The title compound exists as a 60: 40-mixture of rotamers in CDC13 at room temperature) 5 = 1.40, 1.42 [2 s, 9 H, Boc-CH3], 1.55-1. 63,2. 01-2.12 [2 m, 8 H, cyclohexenyl-CH2], 1.83, 1.91 [2 s, 3 H, Thyminyl-CH3], 3.25-3. 51 [2 m, 4 H, 1'-H, 2'-H], 4.04, 4.16 [2 br, 2 H, C2-H], 4.97 [br, 2 H, Ph-CH2-], 6.06 [br, 1 H, cyclohexenyl-C=CH], 7.15-7. 41 [m, 5 H, Thyminyl-H, ArH]. - C28H37N506 (539.30) Calc. C 62.36 H 6.91 N 12.99 Found C 62. 38 H 6.94 N 13. 41 - Example 99 2- [ (2'-Boc-aminoethyl)-(thymin-methylen-ortho-benzoyl)-amino]-4 '"-tert.-butyl- cyclohexan-carboxylic acid-cylcohexen-1"-yl-amide The title compound is prepared as described in example 93 with paraformaldehyde and 3- (2,4-dioxo-3, 4-dihydro-2H-pyrimidin-1-yl) -propionic acid substituted by 0. 31 g (2 mmol) 4- tert. -butyl-cyclohexanone and 0.52 g (2 mmol) N-1-thyminyl-methylen-o-benzoic acid as a colourless solid in 0.70 g (53 %) yield. <BR> <BR> <P>TLC (dichloromethane/methanol 95: 5): Rf = 0.49.- Mp.: 148-149 °C (dec.). --NMR (CDC13) : 6 = 0.86 [s, 9 H, C2-C6H9-C(CH3)3], 1.30 [s, 9 H, Boc-CH3], 0.81-0. 85,1. 31-1.35, <BR> <BR> <BR> <BR> 1.52-1. 69,1. 99-2.10 [4 m, 17 H, cyclohexenyl-CH2-, C2-C6H9-C (CH3) 3], 1.83 [s, 3 H, Thyminyl-CH3], 2.96-3. 40 [m, 4 H.1'-H, 2'-H], 5.20 [s, 2 H, Ph-CH2-], 6.06 [s, 1 H, cyclohexenyl-C=CH], 7.08-7. 46 [m, 5 H, Thyminyl-H, ArH]. - C37H52N506 (662.85) Calc. C 67.04 H 7.91 N 10.51 Found C 67.22 H 7.94 N 10.42.- Example 100 2- [ (2'-Boc-aminoethyl) - (thymin-methylen-ortho-benzoyl) -aminol -4-phenyl- cyclohexan-carboxylic acid-cyclohexen-1"-yl-amide The title compound is prepared as described in example 93 with paraformaldehyde and 3- <BR> <BR> (2,4-dioxo-3, 4-dihydro-2H-pyrimidin-l-yl) -propionic acid substituted by 0.35 g (2 mmol) 4-

phenyl-cyclohexanone and 0.52 g (2 mmol) N-1-thyminyl-methylen-ortho-benzoic acid as a colourless solid in 1.09 g (80 %) yield.

TLC (dichloromethane/methanol 95: 5): Rf = 0.52. - Mp. : 167-169 °C (dec.).- ¹-NMR (CDC13): (The title compound exists as a 90: 10-mixture of rotamers in CDC13 at room temperature) # = 1.37 [s, 9 H, Boc-CH3], 1.60-2. 75 [m, 16 H, cyclohexenyl-CH2, C2-C6H8], 1.89 [s, 3 H, Thyminyl-CH3], 2.94-3. 36 [m, 4 H, 1'-H, 2'-H], 4.80 [s, 1 H, C2-CH-Ph], 4. 89, 5.32 [2 br, 2 H, Ph-CH2-], 6.00, 6.13 [2 br, 1 H, cyclohexenyl-C=CH], 7.23-7. 47 [m, 10 H, Thyminyl-H, ArH].- <BR> <BR> <BR> C39H49N506 (683. 79) Calc. C 68.50 H 7.22 N 10.24<BR> <BR> <BR> <BR> <BR> Found C 68. 34 H 7. 45 N 10.35.- Example 101 2-[(2'-Boc-aminoethyl)-(thymin-methylen-ortho-benzoyl)-amino ]-isobutyric acid- cyclohexen-1"-yl-amide The title compound is prepared as described in example 93 with paraformaldehyde and 3- <BR> <BR> <BR> (2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic acid substituted by 0. 12 g (2 mmol) acetone and 0.52 g (2 mmol) N-1-thyminyl-methylen-ortho-benzoic acid as a colourless solid in 0.80 g (72 %) yield. <BR> <BR> <P>TLC (dichloromethane/methanol 95: 5): Rf = 0.48. - Mp. : 161-162 °C (dec.).- ¹H-NMR <BR> <BR> <BR> <BR> <BR> (CDCl3) : # = 1.41 [s, 9 H, Boc-CH3], 1.56-1. 60 [m, 6 H, C2 (CH3) 21, 1.62-1. 73,2. 06-2.24 [2 m, 8 H, cyclohexenyl-CH2], 1.85 [s, 3 H, Thyminyl-CH3], 3.09-3. 51 [m, 4 H, 1'-H, 2'-H], 5.30 [s, 2 H, Ph-CH2-1, 6.00, [s, 1 H, cyclohexenyl-C=CH], 7.16-7. 50 [m, 5 H, Thyminyl-H, ArH]. - C29H41N5O6 (555.67) Calc. C 62.68 H 7.44 N 12.60 Found C 62.76 H 7.56 N 12.76.- Example 102 <BR> <BR> <BR> rac-2- [ (2'-Boc-aminoethyl) - (thymin-methylen-ortho-benzoyl) -amino] -acetic acid-4"-<BR> <BR> <BR> <BR> <BR> tert. -butyl-cyclohexen-1"-yl-amide The title compound is prepared as described in example 93 with cyclohexen-1-yl-isocyanide and 3- (2,4-dioxo-3, 4-dihydro-2H-pyrimidin-1-yl) -propionic acid substituted by 0.33 g (2 mmol) 4-tert. -butyl-cyclohexen-1-yl-isocyanide and 0.52 g (2 mmol) N-1-thyminyl- methylen-ortho-benzoic acid as a yellowish solid in 0.83 g (71 %) yield. <BR> <BR> <P> TLC (dichloromethane/methanol 95: 5): Rf = 0. 56. - Mp. : 143-145 °C (dec.).- ¹H-NMR <BR> <BR> <BR> <BR> <BR> <BR> (CDC13) : (The title compound exists as a 90: 10-mixture of rotamers in CDC13 at room<BR> <BR> <BR> <BR> temperature) 8 = 0.84 [s, 9 H, 4"- (CH3) 3], 1. 22,1. 87,2. 15 [3 m, 7 H, cyclohexenyl-CH, CH2], <BR> <BR> <BR> <BR> <BR> 1.42 [s, 9 H, Boc-CH3], 1.86 [s, 3 H, Thyminyl-CH3], 3.12-3. 49 [m, 4 H, 1'-H, 2'-H], 4.05,

4.19 [2 s, 2 H, C2-CH2], 5.03, 5.30 [2 br, 2 H, Ph-CH2], 5.71, 6.05, [2 s, 1 H, cyclohexenyl- C=CH], 7.12-7. 49 [m, 5 H, Thyminyl-H, ArH].- C32H45N506 (595.74) Calc. C 64.52 H 7.61 N 11.76 Found C 64.73 H 7.79 N 12.00.- Example 103 <BR> <BR> <BR> rac-2- [ (trans-2'-Boc-aminocyclohexyl) -thyminbutyryl-amino] -3-methyl-butyric acid-<BR> <BR> <BR> <BR> <BR> cyclohexen-1"-yl-amide The title compound is prepared as described in example 93 with paraformaldehyde, mono- Boc-ethylendiamine and 3-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic acid substituted by 0.14 g (2 mmol) isobutyraldehyde, 0.42 g (2 mmol) trans-l- (N-tert. -Boc- <BR> <BR> <BR> amino) -2-amino-cyclohexan and 0.45 g (2 mmol) 4- (N-l-thyminyl) -butyric acid as a colourless solid in 0.19 g (14 %) yield.

TLC (dichloromethane/methanol 95: 5): Rf = 0.61. ¹H-NMR (CDCl3) : # = 0.71-0. 89 [m, 6 <BR> <BR> <BR> H, C2- (CH3)2], 1.12-2. 20 [m, 10 H, cyclohexenyl-CH2, T-CH2-CH2-CH2], 1.28 1.38 [2 s, 9 H, Boc-CH3], 1.76, 1.85 [2 s, 3 H, Thyminyl-CHs], 2.89 [m, 2 H, T-CHz-CHz-CI, 3.45- 3.75 [m, 5 H, 1'-H, 2'-H, T-CH2-CH2-CH2, 2-H], 5.92, 5.98 [2 br, 1 H, cyclohexenyl-C=CH], 7.05, 7.10 [2 s, 1 H, Thyminyl-H].- C31H49N5O6 (587.76) Calc. C 63.35 H 8.40 N 11.92 Found C 63.52 H 8. 57 N 11. 89.- Example 104 (rac) -2- [ (2'-Boc-aminoethyl) - (thymin-methylen-ortho-benzoyl) -aminol- phenylacetic acid-cyclohexen-1"-yl-amide The title compound is prepared as described in example 93 with paraformaldehyde and 3- (2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic acid substituted by 0.21 g (2 mmol) benzaldehyde and 0.52 g (2 mmol) N-1-thymin-methylen-ortho-benzoic acid as a yellowish solid in 0.88 g (71 %) yield. The product was obtained by chromatography on silica gel (dichloromethane/methanol 95: 5).

TLC (dichloromethane/methanol 95: 5): Rf = 0.40.-Mp.: 130-134 °C. - ¹H-NMR (CDCl3): (The title compound exists as a 50: 50-mixture of rotamers in CDC13 at room temperature) 8 = 1.39 [2 s, 9 H, Boc-CH3], 1.41-1. 69,1. 95-2.11 [2 m, 8 H, cyclohexenyl-CH2], 1.80 [2 s, 3 H, Thyminyl-CH3], 2.94-3. 79 [m, 4 H, 1'-H, 2'-H], 5.20-5. 61 [m, 3 H, Ph-CH2, 2-H], 6.00, [2 s, 1 H, cyclohexenyl-C=CH], 7.00-7. 52 [m, 10 H, Thyminyl-H, ArH], 9.50 [2 br, 1 H, cyclohexenyl-NH]. - C34H4lN506 (615.37) Calc. C 66.36 H 6.72 N 11.38 Found C 66.44 H 6.61 N 11.52.-

Example 105 rac-2- [ (2'-Boc-amino-1'-methyl-ethyl) - (thymin-methylen-ortho-benzoyl) -aminol- acetic acid-cyclohexen-1"-yl-amide The title compound is prepared as described in example 93 with mono-Boc-ethylendiamine and 3- (2,4-dioxo-3, 4-dihydro-2H-pyrimidin-1-yl) -propionic acid substituted by 0.35 g (2 mmol) rac-1-Boc-amino-2-aminopropane and 0.52 g (2 mmol) N-1-thyminyl-methylen- ortho-benzoic acid as a yellowish solid in 0.60 g (54 %) yield. The product was obtained by chromatography on silica gel (dichloromethane/methanol 95: 5).

TLC (dichloromethane/methanol 95: 5): Rf = 0.25.- Mp.: 156-158 °C (dec.).- ¹H-NMR (CDC13) : (The title compound exists as a 70: 30-mixture of rotamers in CDC13 at room <BR> <BR> <BR> temperature) 8 = 1. 11-1. 27 [m, 3 H, N-CH (CH3)-CH2-NHBoc], 1.42 [2 s, 9 H, Boc-CH3], 1.47-1. 78,1. 93-2.19 [2 m, 8 H, cyclohexenyl-CH2], 1.80 [2 s, 3 H, Thyminyl-CH3], 3.05- <BR> <BR> <BR> 3.31 [m, 3 H, 1'-H, 2'-H], 3.69-4. 22 [m, 2 H, 2-H], 5.30 [m, 2 H, Ph-CH2], 6.00, 6.03 [2 s, 1 H, cyclohexenyl-C=CH], 7. 05-7.55 [m, 5 H, Thyminyl-H, ArH], 9.50 [1 br, 1 H, cyclohexenyl-NH]. - C29H39N506 (553.66) Calc. C 62.91 H 7.10 N 12.65 Found C 62.79 H 7.21 N 12.77.- Example 106 rac-2- [ (2'-Boc-aminoethyl) - (thymm-methyIen-ort/tO-benzoyl) -ammo] -3, 3-dimethyl- butyric acid-cyclohexen-1"-yl-amide The title compound is prepared as described in example 93 with paraformaldehyde and 3- (2,4-dioxo-3, 4-dihydro-2H-pyrimidin-1-yl) -propionic acid substituted by 0.15 g (2 mmol) pivalaldehyde and 0.52 g (2 mmol) N-1-thyminyl-methylen-ortho-benzoic acid as a yellowish solid in 0.35 g (32 %) yield.

TLC (dichloromethane/methanol 95: 5): Rf = 0.43-Mp.: 164-166 °C (dec.). - ¹H-NMR (CDC13) : (The title compound exists as a 90: 10-mixture of rotamers in CDC13 at room <BR> <BR> <BR> temperature) 8 = 0.99, 1. 15 [2 s, 9 H, C2-CH-C (CH3) 31, 1.32, 1.41 [2 s, 9 H, -C- (CH3) 3], <BR> <BR> <BR> <BR> <BR> <BR> 1.56-1. 65,2. 07-2.18 [2 m, 8 H, -(CH2)4-], 1.80, 1.83 [2 s, 3 H, Thyminyl-CH3], 2. 91-3.96 [m,<BR> <BR> <BR> <BR> <BR> 4 H, 1'-H, 2'-H], 4.82 [br, 1 H, 2-H], 5.00, 5. 30, 5. 51 [3 br, 2 H, Ph-CH2], 6.09, [2 br, 1 H,<BR> <BR> <BR> <BR> <BR> cyclohexenyl-C=CH], 7. 23-7. 58 [m, 5 H, Thyminyl-H, ArH], 8.52 [br, 1 H, cyclohexenyl- NH]. - C28H37N506 (539.30) Calc. C 62.36 H 6.91 N 12.99 Found C 62.31 H 6.94 N 13. 41. -

Example 107 <BR> <BR> <BR> rac-2- [ (2'-Ib-amino-phenyl) -thyminpropionyl-amino] -isobutyric acid-4"-tert. -butyl- <BR> <BR> <BR> <BR> <BR> <BR> cyclohexen-1"-yl-amide The title compound is prepared as described in example 93 with paraformaldehyde, cyclohexen-1-yl-isocyanide, mono-Boc-ethylendiamine and 3- (2,4-dioxo-3, 4-dihydro-2H- <BR> <BR> <BR> pyrimidin-1-yl) -propionic acid substituted by 0.12 g (2 mmol) acetone, 0. 33 g (2 mmol) 4- tert. -butyl-cyclohexen-1-yl-isocyanide, 0.36 g (2 mmol) mono-Ib-ortho-phenylendiamine and <BR> <BR> <BR> 0.40 g (2 mmol) 3- (N-1-thyminyl) -propionic acid as a yellowish solid in 0.29 g (25 %) yield.<BR> <BR> <BR> <BR> <BR> <BR> <P>The product was obtained by chromatography on silica gel (dichloromethane/methanol 95: 5).

TLC (dichloromethane/methanol 95: 5): Rf = 0.42. Mp.: 64-66 °C.- ¹H-NMR (CDCl3) : (The title compound exists as a 80: 20-mixture of rotamers in CDC13 at room temperature) 8 = <BR> <BR> <BR> 0.76, 0.84, 1.05 [3 s, 15 H, (CH3)3, C2- (CH3) 2], 1.05, 1.23 [2 m, 13 H, -CH-(CH3)2, <BR> <BR> <BR> <BR> <BR> <BR> cyclohexenyl-CH2, 4"-H], 1.90, 1.95 [2 s, 3 H, Thyminyl-Cly, 2. 39 [m, 1 H, -CH- (CH3) 21, 2.62, 2.79 [2 m, 2 H, T-CH2-CH2], 3.82, 3.91 [2 m, 2 H, T-CH2-CH2], 5.93, 6.03 [2 br, 1 H, cyclohexenyl-C=CH], 6.71-7. 38 [m, 5 H, Thyminyl-H, ArH], 8.30, 8.55, 8.69 [3 br, 2 H, Ib- NH, cyclohexenyl-NH].- C32H45N505 (579. 74) Calc. C 66.30 H 7. 82 N 12.08 Found C 66.27 H 7.89 N 12. 47.- Example 108 rac-2-[(2'-Ib-amino-phenyl)-thyminpropionyl-amino]-3-methyl- butyric acid-4 "-tert. - butyl-cyclohexen-1"-yl-amide The title compound is prepared as described in example 93 with paraformaldehyde, cyclohexen-1-yl-isocyanide, mono-Boc-ethylendiamine and 3- (2,4-dioxo-3, 4-dihydro-2H- <BR> <BR> <BR> pyrimidin-1-yl) -propionic acid substituted by 0. 14 g (2 mmol) isobutyraldehyde, 0. 33 g (2 mmol) 4-tert.-butyl-cyclohexen-1-yl-isocyanide, 0.36 g (2 mmol) mono-Ib-ortho- <BR> <BR> <BR> phenylendiamine and 0.40 g (2 mmol) 3- (N 1-thyminyl) -propionic acid as a yellowish solid in 0.32 g (27 %) yield. The product purified by chromatography on silica gel (dichloromethane/methanol 95: 5).

TLC (dichloromethane/methanol 95: 5): Rf = 0.32.- ¹H-NMR (CDCl3): (The title compound exists as a 80: 20-mixture of rotamers in CDC13 at room temperature) b =0.89 [s, 9 H, (cl3) 315 <BR> <BR> <BR> <BR> 0. 94, 0.97 [2 d, 6 H, C2-CH- (cl3) 21, 1.22 [m, 13 H, cyclohexenyl-CH2, 4 "-H, CH- (CH3) 21, 1.82, 1.88 [2 s, 3 H, Thyminyl-CH3], 2.12 [m, 2 H, C2-CH- (CH3)2, -CH-(CH3)2], 2.63, 2.79 [2 m, 2 H, T-CH2-CH2], 3.80, 3.95 [2 m, 2 H, T-CH2-CH2], 4.43 [d, 1 H, 2-H], 6.02 [br, 1 H, cyclohexenyl-C=CH], 7.02-7. 43 [m, 5 H, Thyminyl-H, ArH], 8.45 [3 s, 1 H, cyclohexenyl- NH], 9.49 [br, 1 H, Ib-NH] - C33H47N505 (593.78) Calc. C 66.75 H 7. 98 N 11. 79 Found C 66.67 H 7.83 N 11. 87.-

Example 109 rac-2- [ (2'-Boc-amino-1'-methyl-ethyl) - (thymin-methylen-ortho-benzoyl) -amino] -3- methyl-butyric acid-4"-terts -butyl-cyclohexen-1"-yl-amide The title compound is prepared as described in example 93 with paraformaldehyde, cyclohexen-1-yl-isocyanide, mono-Boc-ethylendiamine and 3- (2,4-dioxo-3, 4-dihydro-2H- <BR> <BR> <BR> pyrimidin-1-yl) -propionic acid substituted by 0. 14 g (2 mmol) isobutyraldehyde, 0.33 g (2 mmol) 4-tert. -butyl-cyclohexen-1-yl-isocyanide, 0.35 g (2 mmol) rac-1-Boc-amino-2- aminopropane and 0.52 g (2 mmol) N-1-thyminyl-methylen-ortho-benzoic acid as a colourless solid in 0.56 g (46 %) yield. The product was obtained by chromatography on silica gel <BR> <BR> <BR> (dichloromethane/methanol 95: 5). <BR> <BR> <BR> <BR> <P>TLC (dichloromethane/methanol 95: 5): Rf = 0. 24. - 1H-NMR (CDC13)., 5 = 0.84 [s, 9 H, C4"- <BR> <BR> <BR> <BR> <BR> <BR> (CH3)3], 1.11 [d, 6 H, C2-CH- (cl3) 21, 1.27 [m, 3 H, Cl'-CH3], 1.32-1. 56,2. 02-2.21 [2 m, 18 H, Boc-CH3 C2-CH-(CH3)2, cyclohexenyl-CH2, 4"-H], 1.89, 1.92 [2 s, 3 H, Thyminyl-CH3], 3.09-3. 74 [2 m, 3 H, I'-H, 2'-H], 4. 32, 4.74 [2 s, 1 H, 2-H], 4.90, 5.36 [2 br, 2 H, Ph-CH2], 6.02, 6.09 [2 br, 1 H, cyclohexenyl-C=CH], 7.02-7. 49 [m, 5 H, Thyminyl-H, ArH], 8.79, 9.34, 9.52 [3 br, 2 H, cyclohexenyl-NH]. - C33H44N5O6 (606.74) Calc. C 65.33 H 7. 31 N 11. 54 Found C 65.28 H 7.45 N 11.65.- Example 110 <BR> <BR> <BR> rac-2- [ (2'-Ib-amino-phenyl) - (uracil-methylen-ortho-benzoyl) -amino] -phenylacetic acid-<BR> <BR> <BR> <BR> <BR> <BR> 4"-/ert. -butyl-cyclohexen-l"-yl-amide The title compound is prepared as described in example 93 with paraformaldehyde, cyclohexen-1-yl-isocyanide, mono-Boc-ethylendiamine and 3- (2,4-dioxo-3, 4-dihydro-2H- <BR> <BR> <BR> pyrimidin-1-yl) -propionic acid substituted by 0.21 g (2 mmol) benzaldehyde, 0. 33 g (2 mmol) 4-tert.-butyl-cyclohexen-1-yl-isocyanide, 0.36 g (2 mmol) mono-Ib-ortho-phenylendiamine and 0.49 g (2 mmol) (2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-methylen-ortho-ben zoic acid as a yellowish solid in 0.60 g (44 %) yield. The product was obtained by chromatography on silica gel (dichloromethane/methanol 95: 5).

TLC (dichloromethane/methanol 95: 5): Rf = 0.36.- ¹H-NMR (CDCl3) : 5 = 0.82 [s, 9 H, C4"- <BR> <BR> <BR> (CH3) 3], 1.21 [d, 6 H, -CH- (cl3) 21, 1.29-1. 42,1. 71- 1.92, 2.02-2. 21 [3 m, 7 H, cyclohexenyl- CH2, 4"-H], 2.58 [m, 1 H, -CH- (CH3)2], 4.79-5.20 [4 br, 2 H, Ph-CH2-] , 5.61 [d, 1 H, <BR> <BR> <BR> CH=CH-C=O, 6. 02,6. 09 [2 br, 1 H, cyclohexenyl-C=CH], 6.40, 6.42 [2 s, 1 H, 2-H], 6.70- 7.71 [m, 14 H, CH=CH-C=O, ArH], 8.01, 8.50 [2 br, 1 H, cyclohexenyl-NH]. - C4oH45N505 (675. 82) Calc. C 71.09 H 6.71 N 10.36 Found C 71.14 H 6.85 N 10.45.-

Example 111 rac-2- [ (trans-2'-Boc-aminocyclohexyl)-(α-thymin-phenylacetyl)-amin o]- biphenylacetic acid-cyclohexen-1"-yl-amide 0.36 g (2 mmol) biphenylcarbaldehyde and 0.42 g (2 mmol) trans-1, 2-mono-Boc- cyclohexylendiamine are evaporated three times with toluene. The residue was dissolved in <BR> <BR> <BR> 7 ml methanol (abs.) and 0.52 g (2 mmol) rac-2- (N-1-thyminyl) -phenylacetic acid are added.

After stirring five minutes at room temperature 0.21 g (2 mmol) cyclohexen-1-yl-isocyanide are added via a syringe. The solution is stirred for 48 hours at room temperature and finally evaporated to dryness in vacuo. The residue is stirred with ether, filtered off and dried in vacuo. After flash filtration over silica gel (dichloromethane/methanol, 95: 5) and removal of the solvent in vacuo the title compound was obtained as a yellowish solid in 0.66 g (44 %) yield. <BR> <BR> <P>TLC (dichloromethane/methanol 95: 5): RS= 0.72.- ¹H-NMR (CDCl3): (due to the possible existance of diastereomers and rotamers several peaks are trebled) 8 = 1.18-2. 42 [m, 16 H, <BR> <BR> <BR> - (CH2) 4-13 1.29 1.43, 1.45 [3 s, 9 H, Boc-CH3], 1.78, 1.80, 1.82 [3 s, 3 H, Thyminyl-CH3], <BR> <BR> <BR> <BR> <BR> 3.68 [br, 2 H, 1'-H, 2'-H], 4.89, 4.90, 4.95 [3 s, 1 H, T-CH], 5.96, 5. 98, 6.08 [3 s, 1 H, cyclohexenyl-C=CH], 6.69, 6.78, 6.80 [3 s, 1 H, 2-H], 727-7.63 [m, 15 H, ArH, Thyminyl- H].- <BR> <BR> <BR> C44H51N5O6(745.92) Calc. C 70.85 H 6. 89 N 9. 39 <BR> <BR> <BR> <BR> <BR> Found C 70.61 H 6. 87 N 9. 71- Example 112 rac-2- [ (2'-Boc-aminoethyl) - (a-thymin-hexanoyl) -amino] -ortho-chlorophenyl- acetic acid-cyclohexen-1"-yl-amide The title compound was prepared as described in example 111 with biphenylcarbaldehyde, trans-1, 2-mono-Boc-cyclohexylendiamine and rac-2- (N-1-thyminyl) -phenylacetic acid substituted by 0.28 g (2 mmol) 2-chlorobenzaldehyde, 0.32 g (2 mmol) mono-Boc- <BR> <BR> <BR> ethylendiamine and 0.48 g (2 mmol) rac-2- (N-1-thyminyl) -hexanoic acid as a yellowish solid in 0.49 g (39 %) yield. <BR> <BR> <P> TLC (dichloromethane/methanol 95 : 5) : Rs= 0. 86.- ¹H-NMR(CDCl3) : 8 = 0.81 [m, 3 H, C3H6-CH3]1.12-1.40 [m, 4 H, CH2- (CH2) 2-CH3], 1.31, 1.35 [2 s, 9 H, Boc-CH3], 1.49-1. 68, 1.99-2. 18 [2 m, 8 H, cyclohexenyl-CH2], 1.71-1. 95 [m, 2 H, -CH2- (CH2) 2-CH3], 1.76, 1.81 [2 <BR> <BR> <BR> s, 3 H, Thyminyl-CH3], 2. 89-3. 46 [m, 4 H, 1'-H, 2'-H], 4.86 [m, 1 H, C4H9-CH-], 6.00, 6.02 [2 s, 1 H, cyclohexenyl-C=CH], 6.43, 6.45 [2 s, 1 H, 2-H], 7.29-7. 54 [m, 5 H, Thyminyl-H, ArH]. - C32H44CIN506 (630.18) Calc. C 60.99 H 7.04 N 11.11 Found C 60.62 H 7. 17 N 11.09.-

Example 113 <BR> <BR> <BR> rac-2- [(trans-2'-Boc-aminocyclohexyl)-thyminbutyryl-amino]-phenyla cetic acid<BR> <BR> <BR> <BR> <BR> - cyclohexen-1"-yl-amide The title compound was prepared as described in example 111 with biphenylcarbaldehyde <BR> <BR> <BR> and rac-2- (N-1-thyminyl) -phenylacetic acid substituted by 0.21 g (2 mmol) benzaldehyde, and 0.45 g (2 mmol) 4- (N-1-thyminyl)-butyric acid as a colourless solid in 0.47 g (38 %) yield.

TLC (dichloromethane/methanol 95: 5): Rf. 0. 52. -'H-NMR (DMSO-d6): 8 = 1.12-2. 20 [m, <BR> <BR> <BR> 10 H, cyclohexenyl-CH2, T-CH2-CH2-CH2], 1.31, 1. 35 [2 s, 9 H, Boc-CH3], 1.71, 1.76 [2 s, 3<BR> <BR> <BR> <BR> <BR> <BR> H, Thyminyl-CH3], 2.86 [m, 2 H, T-CH2-CH2-CH2] 3. 25-3. 80 [m, 4 H, 1'-H, 2'-H, T-CH2- CH2-CH2], 5.79, 5.81 [2 br, 1 H, 2-H], 6.00, 6.10 [2 br, 1 H, cyclohexenyl-C=CH], 7.10- 7.51 [m, 6 H, Thyminyl-H, ArH]. - C34H47N5O6 (621.78) Calc. C 65.68 H 7.62 N 11.26 Found C 65.61 H 7. 59 N 11. 41- Example 114 rac-2- [(2'-Ib-phenylenamino)-thyminbutyryl-amino]-4,8-dimethyl-non -7-enoic-acid- cyclohexen-l"-yl-amide The title compound was prepared as described in example 111 with biphenylcarbaldehyde, trans-1,2-mono-Boc-cyclohexylendiamine and rac-2-(N-1-thyminyl)-phenylacetic acid substituted by 0.31 g (2 mmol) benzaldehyde, 0.36 g (2 mmol) mono-lb-ortho- phenylendiamine and 0.40 g (2 mmol) rac-2- (N-1-thyminyl) -propionic acid. The crude product is purified by chromatography on silica gel (dichloromethane/methanol 95: 5) and is obtained as a colourless solid in 0.36 g (29 %) yield. <BR> <BR> <P> TLC (dichloromethane/methanol 95: 5): Rf. 0. 41. - IH-NMR (CDCl3) : # = 0.82-2. 21 [m, 36<BR> <BR> <BR> <BR> <BR> <BR> H, cyclohexenyl-CH2, T-CH (CH3), O=C-CH- (CH3) 2, Thyminyl-CH3, -CH2-CH (CH3) -CH2- <BR> <BR> <BR> <BR> <BR> C//2-CH= (C3) 2], 2.52-2. 86 [m, 1 H O=C-CH- (CH3) 21, 4.50 [m, 1 H, T-CH (CH3)], 4. 81- <BR> <BR> <BR> <BR> <BR> 5.10 [m, 2 H, 2-H, -CH2-CH (CH3) -CH2-CH2-CH= (CH3)2], 6.00, 6.10 [m, 1 H, cyclohexenyl- C=CH], 6.88- 7.46 [m, 5 H, Thyminyl-H, ArH], 8.52-8. 85 [m, 2 H, cyclohexenyl-NH, Ib- NH]. - C35H49N505 (619.80) Calc. C 67.83 H 7.97 N 11.30 Found C 67.81 H 8.10 N 11.53.-