CA2342855A1 - Novel pyranoses - Google Patents

Abstract

The invention relates to compounds of formula (I), wherein M, A1, A2, A3, A4 , A5, A6, B1, B2, B3, B4, B5, B6, K1 and K2 have the meanings given in the description. Said compounds are novel, effective tryptase inhibitors.</SDOAB >

Description

. -1 -Novel pyranoses Use of the invention The invention relates to novel pyranoses which are used in the pharmaceutical industry for the produc-tion of medicaments.
Known technical back rq ound The International Applications W095132945, W096/09297, W098104537 and W099112918 describe low molecular weight compounds as tryptase inhibitors. The International Application W093117032 describes nonpeptide peptidomimetics whose structure, inter alia, contains a pyranose unit.
Description of the invention It has now been found that the compounds of the formula I described in greater detail below have surprising and particularly advantageous properties.
The invention relates to compounds of the formula I
B1-A1-B3-A3-B5-A~-K1 M (I) ~ B2-A2-B4-A4-B6-A6-K2 in which A1 and A2 are identical or different and are -C(O)-, -NH-, -O- (oxygen), -S-(sulfur), -S(O)2-, -S(O)2-NH-, -NH-S(O)2-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are -C(O)-, -O-, -S-, -NH-, -O-C(O)-, -C(O)-O-, -C(O)-NH-, -NH-C(O)- or a bond; or are selected from the group _ I T
T T T T
N N
N G
where E is -O- (oxygen), -S- (sulfur) or -CH2- (methylene), G is -O- (oxygen) or -CH2- (methylene), and T is the group -C(O}- or a band, A5 and A6 are identical or different and are -C(O}-, -NH-, -O-, -S-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O-, -NH-C(O}-NH- or a bond, M is a pyranose unit selected from the following list W W W W

~ U R3 R3 ~R5 ~ ~R5 O O O
iW iW /W

~.W ~W
' ~R5 ~ ~U~
O O

W

'U~
O

where U and W are identical or different and are -O- (oxygen), -S- (sulfur) or -NH-, R1 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, R2 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, R3 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R4 is hydroxyl, cyano, 1-4.C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, R5 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) are an alkylenedioxy group [-O-C(R6)ER7-O-], in which either orre of the radicals R6 and R7 is hydrogen and the other is methyl, phenyl or p-methoxyphenyl, or in which both radicals R6 and R7 are hydrogen or methyl, K1 is-B7-(C(O))rn-B9-X1, -B7-(C(O))m B9-Y1 or-B7-(C(O))m B9-Z1-B11-X1, K2 is -B8-(C(O))P-B10-X2, -B8-(C(O))P-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2, - 4 - _.
B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-4.C-alkylene, m is0or1, p is0or1, X1 and X2 are identical or different and are selected from the following groups O NH NH

NH NH
H~ NH2 NH2 H-R8 ~N~NH

NH NH NH
S H
NHZ S--Rg NHZ
NH

where R8 is 1-4C-alkyl, Y1 and Y2 are identical or different and are a 4-11 C-heteroaryl or 2-7C-heterocycloalkyl radical, comprising at least one ring nitrogen, Z1 and Z2 are identical or different and are 5-12C-arylene, 5-12C-heteroarylene, 3-8C-cycloalkylene or 3-8C-heterocycloalkylene, where each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocyc-loalkyl can additionally be substituted, for its part, by one, two or three substituents selected from the group consisting of hydroxyl, halogen, vitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl, and in which on the direct route between the terminal nitrogen atoms, 20 to 40, preferably 25 to 40, bonds must be present, r the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroaryle-nes and heterocycloalkylenes comprising a nitrogen atom and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond and direct linkage between two heteroatoms or two carbonyl groups would thereby occur.
1-4C-Alkyl stands for straight-chain or branched alkyl radicals having 1 to 4 carbon atoms. Examples which may be mentioned are the butyl radical, isobutyl radical, sec-butyl radical, tert-butyl radical, pro-pyl radical, isopropyl radical, ethyl radical and the methyl radical.
1-4C-Alkoxy stands for radicals which, in addition to the oxygen atom, contain a straight-chain or bran-ched alkyl radical having 1 to 4 carbon atoms. Examples which may be mentioned are the butoxy radi-cal, isobutoxy radical, sec-butoxy radical, tert-butoxy radical, propoxy radical, isopropoxy radical and preferably the ethoxy radical and methoxy radical.
1-4C-Alkoxycarbonyl stands for a carbonyl group to which one of the abovementioned 1-4C-alkoxy radicals is bonded. Examples which may be mentioned are the methoxycarbonyl radical [CH30-C(O)-]
and the ethoxycarbonyl radical [CH3CH20-C(O)-].
1-4C-Alkylcarbonyloxy stands for a carbonyloxy group to which one of the abovementioned 1-4C-alkyl radicals is bonded. An example which may be mentioned is the acetoxy radical [CH3C(O)-O-].
Ar stands for a phenyl radical which is unsubstituted or mono- or disubstituted by vitro, halogen or methoxy.
Ar-1-4C-alkoxy stands for one of the abovementioned 1-4C-alkoxy radicals substituted by Ar, where Ar has the abovementioned meaning. Examples which may be mentioned are the phenethoxy radical, benzyloxy radcial, p-methoxybenzyloxy radical, 3,4-dimethoxybenzyloxy radical, p-nitrobenzyloxy radi-cal and p-halobenzyloxy radical.
Halogen within the meaning of the invention is bromine, chlorine or fluorine.
w 1-4C-Alkylene stands for straight-chain or branched 1-4C-alkylene radicals, for example the methylene radical [ CHz-], ethylene radical [-CHz-CHz-], trimethylene radical [-CHz-CHz-CHz-], tetramethylene ra-dical [-CHz-CHz-CHz-CHz-], 1,2-dimethyethylene radical (-CH(CH3)-CH (CH3)-], ~1,1-dimethylethylene radical [-C(CH3)z-CHz-], 2,2-dimethylethylene radical [-CHz-C(CH3)z-], isopropylidene radical [-C(CH3)z-1 or the 1-methylethylene radical [-CH(CH3)-CHz-].
If m has the meaning 0; the group -(C(O))m is a bond.
If p has the meaning 0, the group -(C(O))P- is a bond.

The term pyranose unit is understood according to the invention as meaning all 32 stereoisomers which result on account of the 5 stereocenters on the pyranose ring. The isomers of the D form and the L form and also the respective a epimers and (3 epimers are included here.
According to the invention, the term pyranose unit furthermore also comprises all 1-deoxy-, 2-deoxy- and 1,2-dideoxy mono-saccharide units and their stereoisomers which can result on account of the meaning hydrogen for the substituents R1 and R2. Preferred pyranose units with respect to the configuration on the 5 stereo-centers are those which are present in the D-gluco, D-galacto or D-manno configuration; particularly preferred in this connection are the D-gluco-configured pyranose units.
The linkage of the pyranose unit M to the rest of the molecule takes place via the substituents U and W, which can be bonded in the 1, 2, 3, 4 or 6 position of the pyranose ring.
Numbering:
The following possible linkage patterns result from this: 1, 2-, 1, 3-, 1, 4-, 1, 6-, 2, 3-, 2, 4-, 2, 6-, 3, 4-, 3, 6-, 4, 6-, of which 2, 6- and 3, 6- are preferred and 3, 6- is particularly preferred.
If two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) together form an alkylenedioxy group [-O-C(R6)R7-O-], an acetal structure is present. Examples of such an acetal structure which may be mentioned are the methylene acetal, ethylidene acetal, isopropylidene acetal, benzylidene acetal and the p-methoxybenzylidene acetal.

4-11 C-Meteroaryl stands for an - optionally substituted - mono- or bicyclic aromatic hydrocarbon which contains 4 to 11 C atoms and at least one ring nitrogen atom; one or more of the-carbon atoms can additionally be replaced by ring heteroatoms selected from the group consisting of O, N and S. In the case of bicyclic systems, at least one of the rings is aromatic. Pyrid-4-yl, pyrid-3-yl, pyrimidin-5-yl, imi-dazol-1-yl and benzimidazol-5-yl may be mentioned by way of example.
2-7C-Heterocycloalkyl stands for an - optionally substituted - monocyclic saturated or partially satura-f ted hydrocarbon which contains 2 to 7 C atoms and at least one ring nitrogen atom; one or more car-bon atoms can additionally be replaced by ring heteroatoms selected from the group consisting of O, N
and S. Piperid-4-yl, piperazin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl and morpholin-2-yl may be mentioned by way of example.

5-12C-Arylene stands for an - optionally substituted - divalent mono- or bicyclic aromatic hydrocarbon which has 5 to 12 C atoms, where at least one of the rings in the bicyclic aromatic hydrocarbon radicals _7_ is aromatic. The free valencies can both be on the aromatic ring, both on the nonaromatic ring or one on the aromatic ring and one on the nonaromatic ring. 1,4-Phenylene, 1,3-phenylene, 1,4-naphthylene and 2,6-naphthylene may be mentioned by way of example.
9-12C-Arylene - a subset of 5-12C-arylene - stands for an - optionally substituted - divalent bicyclic hydrocarbon radical having 9 to 12 C atoms. At least one of the rings is aromatic. The free valencies can both be on the aromatic ring, both on the nonaromatic ring or one on the aromatic ring and one on the nonaromatic ring. 1,4-Naphthylene, 2,6-naphthylene and 2,5-indanylene may be mentioned by way of example.
5-12C-Heteroarylene stands for an arylene radical, as defined beforehand, in which 1 to 4 C atoms are . replaced by heteroatoms selected from the group consisting of O, N and S.
2,5-Furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,5-benzofuranylene, 2,6-quinolinylene and 4,2-thiazolylene may be mentioned by way of example.
9-12C-Heteroarylene - a subset of 5-12C-heteroarylene - stands for a 9-12C-arylene radical, as defi-ned beforehand, in which 1 to 4 C atoms are replaced by heteroatoms selected from the group con-sisting of O, N and S. 2,5-Indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,6-quinolinylene and 2,5-benzofuranylene may be mentioned by way of example.
3-8C-Cycloalkylene stands for an - optionally substituted - divalent monocyclic saturated or partially saturated hydrocarbon radical which has 3 to 8 C atoms. The 1,3-cyclopentylene radical, the 1,3-cyclohexylene radical and preferably the 1,4-cyclohexylene radical may be mentioned by way of e-xample.
3-8C-Heterocycloalkylene stands for a cycloalkylene radical, as defined beforehand, in which 1 to 3 C
atoms are replaced by heteroatoms selected from the group consisting of O, N
and S. The 1,4-piperidinylene radical, 1,4-piperazinylene radcial, 2,5-pyrrolidinylene radical, 4,2-imidazolidinylene radical and preferably the 4,1-piperidinylene radical may be mentioned by way of example.
Preferred meanings of the groups X1 and X2 are amino, aminocarbonyl, amidino and guanidino.
According to definition, the groups Z1 and Z2 are situated ~ between the groups B9 and B11 (-B9-Z1-B11-) or B10 and B12 (-B10-Z2-B12-). Correspondingly, in the divalent groups mentioned by way of example (e.g. 2;6-indolylene), the first number stands far the linkage site to the group B9 or B10 and the second number for the linkage site to the group B11 or B12.

The definitions of M, A3, A4, X1 and X2 contain chemical formulae, such as ~W
U N NH
O
R2 ~ G NH2 Bonds not linked on one side in this connection means that the unit is bonded to the rest of the mole-cute in this position. Bonds not linked on two sides means that there are several positions in this unit via which the bonding to the rest of the molecule can take place.
The term terminal nitrogen atom in the context of this application in each case means a nitrogen atom in the groups designated by X1, X2, Y1 and Y2.
If the groupsvX1 and X2 contain only one nitrogen atom, this nitrogen atom is the terminal nitrogen atom.
If the groups X1 and X2 contain a number of nitrogen atoms, that nitrogen which is situated furthest from the atom via which the bond is made to the groups B9 (B11) or B10 (B12) is the terminal nitrogen atom.
If the groups Y1 and Y2 only contain one ring nitrogen atom, this ring nitrogen atom is the terminal nitrogen atom.
If the groups Y1 and Y2 contain a number of ring nitrogen atoms, that ring nitrogen atom which is situ-ated furthest from the atom via which the bond is made to the groups B9 and B10 is the terminal nitro-gen atom.
According to the invention, the direct route between the nitrogen atoms which function as terminal nitrogen atoms in the groups defined as X1 (Y1 ) or X2 (Y2) is regarded as that number of bonds which is obtained by counting the bonds which represent the shortest possible connection line between the terminal nitrogen atoms.
The following example( is intended to illustrate the determination of the number of bonds on the direct route between two terminal nitrogen atoms:

_g_ O
21 N 2~24~6 28 \ ~ 29 N 30 7g ~ 2~ ~N 25 N 27 \
H ~ 3~
2 N 3 ~ ~ s N 1, Bn0 ~s ~8 ~ ~ H / N
HN~ a s 7 ~N ~~N 13~a ors NHZ
The direct route here contains 31 bonds.
Suitable salts of compounds of the formula I - depending on substitution - are all acid addition salts or all salts with bases. Particular mention may be made of the pharmacologically tolerable salts of the ,. inorganic and organic acids customarily used in pharmacy. Those suitable are, on the one hand, water-soluble and water-insoluble acid addition salts with acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, 2-(4-hydroxybenzoyl)benzoic acid, butyric acid, sulfosalicylic acid, malefic acid, lauric acid, malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, embonic acid, stearic acid, toluenesulfonic acid, methanesulfovic acid or 3-hydroxy-2-naphthoic acid, where the acids are employed in salt preparation - depending on whether a mono- or polybasic acid is concerned and depending on which salt is desi-red - in an equimolar quantitative ratio or one differing therefrom.
On the other hand, salts with bases are suitable. Examples of salts with bases which may be mentio-ned are alkali metal (lithium, sodium, potassium) or calcium, aluminum, magnesium, titanium, ammoni-um, meglumine or guanidinium salts, where here too the bases can be employed in an equimolar quantitative ratio or one differing therefrom in salt preparation.
Pharmacologically intolerable salts, which can initially be obtained, for example, as process products in the preparation of the compounds according to the invention on an industrial scale, are converted into pharmacologically tolerable salts by processes known to the person skilled in the art.
It is known to the person skilled in the art that the compounds according to the invention and their salts, if, for example, they are isolated in crystalline form, can contain various amounts of solvents. The in-vention therefore includes all solvates and in particular all hydrates of the compounds of the formula I, and also all solvates and in particular all hydrates of the salts of the compounds of the formula I.
Compounds of the formula I to be emphasized are those in which A1 and A2 are identical or different and are -C(O)-, -NH-, -O-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are -C(O)-, -O-, -NH-, -O-C(O)-, -C(O)-O-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group _10_ _ T T T T
N
N
E N
where E is -O- (oxygen), -S- (sulfur) or -CH2- (methylene) and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -O-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the list below ,, R5 \U R5 R3 R5 R3 UW

W W

\ U R3 R3 ~R5 ~ ~R5 O O O
iW iW /W

WW wW
~R5 ~ ~U~
O O

W

_U~
O

where U and W are identical or different and are -O- (oxygen), -S- (sulfur) or -NH-, R1 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, R2 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R3 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R4 is hydroxyl, cyano, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, R5 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4.C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5), are an alkylenedioxy group [-O-C(R6)'R7-O-], in which either one of the radicals R6 and R7 is hydrogen and the other is methyl, phenyl or p-methoxyphenyl, or in which both radicals R6 and R7 are hydrogen or methyl, K1 iS-B7-(C(O))m-B9-X1, -B7-(C(O))rt; B9-Y1'or-B7-(C(O))m B9-Z1-B11-X1, K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))P B10-Y2 or-B8-(C(O))p-B10-Z2-B12-X2, -12_ B1, 82, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, B9, B10, B11 and 812 are identical or different and are a bond or 1-4C-alkylene, m is0or1, p is0or1, X1 and X2 are identical or different and are selected from the following groups O NH ,,NH
N H2 - ~.~/~

NH NH
- H~ NHZ
NHZ H-R8 ~N~NH
\O z NH NH NH
-H

NH
~N-NH2 where R8 is 1-4C-alkyl, Y1 and Y2 are identical or different and are piperid-4-yl, piperid-3-yl, piperazin-1-yl, piperazin-2-yl, morpholin-2-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yi, 2-imidazolin-3-yl, 2-imidazolin-2-yl, imidazol-1-yl, imidazol-2-yl, imidazal-4-yl, pyrid-4-yl, pyrid-3-yl, pyridazin-4=yl, pyrimidin-5-yl, pyrimidin-4-yl, indol-3-yl, benzimidazol-4-yl or benzimidazol-5-yl, Z1 and Z2 are identical or different and are 1,4-phenylene, 1,3-phenylene, 1,4-naphthylene, 2,6-naph-thylene, 1,4-cyclohexylene, 1,3-cyclohexylene, 1,3-cyclopentylene, ~ 1,4-piperazinylene, 4,1-piperidinylene, 1,4-piperidinylene, 2,5-pyrrolidinylene;~ 4,2-imidazolidinylene, 2,5-furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,6-quinolinylene, 2,5-benzofuranylene or 4,2-thiazolylene; v, where each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocyc-loalkyl can additionally be substituted, for its part, by one, two or three substituents selected from the group consisting of hydroxyl, halogen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl, and in which on the direct route between the terminal nitrogen atoms 20 to 40, preferably 25 to 40, bonds must be present, the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroaryle-nes and heterocycioalkylenes comprising a nitrogen atom and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond and a direct linkage would thereby occur between two hetero-atoms or carbonyl groups.
Compounds of the formula I particularly to be emphasized are those in which A1 and A2 are identical or different and are -C(O)-, -O-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are a bond or are selected from the group T
T T N N N
where T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the list below R3 _ \W
O O
~W ~ R2 where U and W are identical or different and are -O- (oxygen) or -NH-, R1 is hydrogen, 1-2C-alkoxy, acetoxy or Ar-methoxy, R2 is hydrogen, hydroxyl, 1-2C-alkoxy, acetoxy or Ar-methoxy, R3 is hydroxyl, 1-2C-alkoxy, acetoxy or Ar-methoxy, R4 is hydroxyl, 1-2C-alkoxy, acetoxy or Ar-methoxy, K1 is-B7-(C(O))m-B9-X1,-B7-(C(O))m-B9-Y1 or-B7-(C(O))m-B9-Z1-B11-X1, K2 - is -B8-(C(O))P-B10-X2, -88-(C(O))P B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2, B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-4.C-alkylene, m is0or1, p is0or1, X1 and X2 are identical or different and are selected from the following groups O NH NH
NHz H

Y1 and Y2 are identical or different and are piperid-4-yl, piperid-3-yl, piperazin-1-yl, piperazin-2-yl, morpholin-2-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, 2-imidazolin-3-yl, 2-imidazolin-2-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, 5-methyl-imidazol-4-yl, pyrid-4-yl, pyrid-3-yl, pyridazin-4-yl, pyrimidin-5-yl, pyrimidin-4-yl, indol-3-yl, ben-zimidazol-4-yl or benzimidazol-5-yl, Z1 and Z2 are identical or different and are 1,4-phenylene, 1,3-phenylene, 1,4-naphthylene, 2,6-naph-thylene, 1,4-cyclohexylene, 1,3-cyclohexylene, 1,3-cyclopentylene, 1,4-piperazinylene, 4,1-piperidinylene, 1,4-piperidinylene, 2,5-pyrrolidinylene, 4,2-imidazolidinylene, 2,5-furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 6-methyl-5,2-pyridinylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,6-quino-linylene, 2,5-benzofuranylene or 4,2-thiazolylene, and in which on the direct route between the terminal nitrogen atoms 20 to 40, preferably 25 to 40, bonds must be present, the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroaryle-nes and heterocycloalkylenes comprising a nitrogen atom and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond and a direct linkage would thereby occur between two hetero-atoms or carbonyl groups.
Preferred compounds of the formula I are those in which A1 and A2 are identical or different and are -C(O)-, -C(O)-NH-, -C(O)-O- or a bond, A3 and A4 are identical or different and are 1,4-piperazinylene, 1,4-piperidinylene, 1,4-cyclohexylene, 1,3-phenylene or a bond, A5 and A6 are identical or different and are -C(O)-, -C(O)-NH-, -NH-C(O)- or -NH-C(O)-NH-, M is a pyranose unit selected from the following list 'U~ ~ ~Uy O
/~ RZ

where U and W are identical or different and are -O- (oxygen) or -NH-, R1 is hydrogen, methoxy or benzyloxy, R2 is hydrogen, R3 is hydroxyl ar benzyloxy, R4 is hydroxyl, methoxy or benzyloxy, K1 is-B7-(C(O))m-B9-Y1 or-B7-(C(O))m B9-Z1-B11-X1, K2 is -B8-(C(O))p B10-Y2 or -B8-(C(O))p B10-Z2-B12-X2, B1 and B2 are identical or different and are a bond or methylene, B3, B4, B5 and B6 are identical or different and are a bond or 1-3C-alkylene, B7, 88, B9 and B10 are identical or different and are a bond or 1-4C-alkylene, B11 and B12 are identical or diffferent and are a bond or methylene, m is 0, p is 0, X1 and X2 are identical or different and are selected from the following groups O NH NH
NH2 ~ H

Y1 and Y2 are imidazol-1-yl, Z1 and Z2 are identical or different and are 5,2-pyridinylene, 6-methyl-5,2-pyridinylene, 4,1-piperidinylene, 3,6-indazolylene, 3,6-indolylene, 1,3-phenylene, 1,4-phenylene, 1,3-cyclohexylene or 1,4-cyclohexylene, and in which on the direct route between the terminal nitrogen atoms 20 to 40, preferably 25 to 40, bonds must be present, the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroaryle-nes and heterocycloalkylenes comprising a nitrogen atom and their salts, where ail those compounds are excluded in which :one or mare of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond and a direct linkage would thereby occur between two hetero-atoms or carbonyl groups.
Particularly preferred compounds of the formula I are 3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(traps-4-arrSinomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-D-gluco-pyranose;
4-O-benzyl-1,2-dideoxy-3,6-di-O-(4-(4-guanidinobenzylaminocarbonyl)piperazin-1-ylcarbonyl]-D-gluco-pyranose;

-16-- i,_ 3,6-di-O-(4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonylmethyl]-4.-O-benzyl-1,2-di-deoxy-D-glucopyranose;
3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-( 1-amidi no pi perid i n-4-ylacetyl) piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-galactopyranose;
3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-D-galacto-pyranose;
3,6-di-O-[4-(amidinoindazol-3-ylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-gluco-pyranose;
methyl 3,6-di-O-[4-(traps-4-aminomethyicyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-2-deoxy-a-D-glucopyranoside;
methyl 3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-2-deoxy-a-D-glucopyranoside;
3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonylmethyl]-1,2-dideoxy-D-glucopyranose;

6-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-3-O-[4-(traps-4-aminomethyl-cyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
benzyl 3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-2-deoxy-a-D-glucopyranoside;
3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonylmethyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonylmethyl]-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-methyl-1,2-dideoxy-D-gafactopyranose; -methyl 2,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-a-D-glucopyranoside;
methyl 3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-2-deoxy-a-D-glucopyranoside; -methyl 2,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-3,4-di-O-benzyl-a-D-glucopyranoside;
methyl 3,6-di-O.-j4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-2-deoxy-a-D-glucopyranoside;
6-O-(4-(traps-4-aminomethylcyclohexylcarbonyl)-1-aminopentyl]-3-O-[4-(traps-4-aminomethylcyclo-hexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-O-{4-(traps-4-aminomethylcyclohexylcarbonyl)~iperazin-1-ylcarbonyi]-6-O-[5-(2-aminomethyl-pyridylcarbonyl)-1-aminopentyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;

-17- a 6-N-[4-(trans-4-aminomethylcyclohexylcaGbonyl)-4-aminobutyl-4-oxycarbonyl]-3-O-[4-(trans-4-amino-methylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)-5-aminopentyl]-3-O-[4-(traps-4-aminomethylcyclo-hexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)-5-aminopentyl]-4-O-benzyl-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-(traps- 4-aminomethylcyclohexylcarbonyl)-5-aminopentyl]-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(3-aminomethylbenzoyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(3-aminomethylbenzoylamino)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-(3-aminomethylbenzylaminocarbonyl)piperazin-1-yl-carbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(3-aminomethylbenzylaminocarbonylamino)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-(4-(3-aminomethylbenzylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-traps-(3-aminomethylbenzylaminocarbonyl)cyclohexylmethylaminocarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-(6-amino-2-methylpyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-(4-aminobenzylaminocarbonyl)piperidin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-(4-traps-(6-aminopyridin-3-ylmethylaminocarbonyl)cyclohexylmethylaminocarbonyl]-1,2-dideoxy.D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-traps-(6-amino-2-methylpyridin-3-ylmethylaminocarbonyl)cyclohexylmethylaminocarbonyl]-1,2-dideoxy-D-gluco-pyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-traps-(4-aminobenzylaminocarbonyl)cyclohexylmethylaminocarbonyl]-1;2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonjil]-4-O-benzyl-6-O-[3-(4-amino-benzylaminocarbonyl)benzylaminocarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylpenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[3-(imidazol-1-yl)propylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[4-(imidazol-1-yl)butylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;

-1$-3-O-[4-(4-aminomethylbenzylaminocarboayl)piperazin-1-ylcarbonyl]-4-0-benzyl-6-O-{4-[5-(imidazol-1-yl)pentylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[6-(imidazol-1-yl)hexylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-{4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[8-(imidazol-1-yl)octylaminocarbonyl]piperidin-1-yicarbonyl}-1,2-dideoxy-D-glucopyranose;
3-0-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-6-O-{4-[4-trans(amino-methyl)cyclohexylcarbonyl]aminobut-1-ylaminocarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-0-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-6-O-[4-(4-aminomethyl-benzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-O-{4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-6-O-[2-(6-aminopyridin-3-yl-methylaminocarbonyl)eth-1-yl-aminocarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-O-{4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{3-[(6-amidino-1-H-indazol-3-yl)carbonylamino]prop-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{3-[(6-amino-carbonyl-1-H-indazol-3-yl)carbonylamino]prop-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-(4-(4-aminomethylbenzylaminocarbonyi)pi perazin-1-ylcarbonyl]-6-O-{2-[(6-aminocarbonyl-1-H-indol-3-yl)carbonylamino]eth-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
3-0-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{3-((6-amino-carbonyl-1-H-indol-3-yl)carbonylamino]prop-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-ami nomethyl benzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[(6-amino-carbonyi-1-H-indol-3-yl)carbonylamino]but-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
6-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-3-O-[2-(4-traps-aminomethyl-cyclohexylcarbonylamino)eth-1-ylaminocarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-3-O-[3-(4-traps-aminomethyl-cyclohexylcarbonylamino)prop-1-ylaminocarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-{4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-3-O-[4-(4-traps-aminomethyl-cyclohexylcarbonylamino)but-1-ylaminocarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-(4-(3-aminomethylbenzoyl)piperazin-1-ylcarbonyl]-3-O-[4-(6-aminopyridin-3-yl-methylamino-carbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-j4-(3-aminomethylbenzoylamino)piperidin-1-ylcarbonyl]-3-O-[4-(6-aminopyridin-3-ylmethylamino-carbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-(3-aminomethylbenzylaminocarbonyl)piperidin-1-ylcarbonyl]-3-O-[4-(6-aminopyridin-3-ylmethyl-aminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-traps-(3-aminomethylbenzylaminocarbonyl)cyclohexylmethylaminocarbonyl]-3-O-[4-(6-amino-pyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-(3-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-3-O-[4-(6-aminopyridin-3-ylmeth-ylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-(3-aminomethylbenzylaminocarbonylamino)piperidin-1-ylcarbonyl]-3-O-[4-(6-aminopyridin-3-yl-methylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;

and the salts of these compounds.
One embodiment (embodiment a) of the invention are compounds of the formula I, in which A1 and A2 are identical or different and are -C(O)-, -NH-, -O- (oxygen), -S-(sulfur), -S(O)2-, -S(O)z-NH-, -NH-S(O)2-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are -C(O)-, -O-, -S-, -NH-, -O-C(O)-, -C(O)-O-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group T I
T T T I T
I N N
/N
E N G
where E is -O- (oxygen), -S- (sulfur) or -CH2- (methylene), G is -O- (oxygen) or -CH2- (methylene), and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -O-, -S-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, M is a pyranose unit selected from the following list R3 R5 U R5 R3 R5 R3 U \
U ~ R2 O R2 ~ R2 O
W ~ W W

\ U R3 R3 _R5 ~ _R5 ~ ~U
/W O /W O W O

\W ~W
~R5 ~ ~U~
O O

W

~U~
O
RZ

where U and W are identical or different and are -O- (oxygen), -S- (sulfur) or -NH-, R1 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4.C-alkylcarbonyloxy orAr-1-4C-alkoxy, R2 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, R3 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, .
R4 is hydroxyl, cyano, 1-4C-alkoxy, 1-4C-alkylcarbonylaxy orAr-1-4C-alkoxy, R5 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy o~Ar-1-4C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) are an alkylenedioxy group [-O-C(R6)R7-O-], in which either one of the radicals R6 and R7 is hydrogen and the other is methyl, phenyl or p-methoxyphenyl, or in which both radicals R6 and R7 are hydrogen or methyl, K1 i5-B7-(C(O))n,-B9-X1,-B7-(C(O))rt,-B9-Y1.or-B7-(C(O))rt,-B9-Z1-B11-X1, K2 is -B8-(C(O))P B10-X2, -B8-(C(O))P B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2, B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4.C-alkylene, B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene, m is0or1, p is0or1, X1 and X2 are identical or different and are selected from the following groups NH NH

NHZ NHOH
NH NH
-H H~ NHZ
NH2 H-R8 \ ~N~NH

NH NH NH
'S ' -H
NHZ S--Rg NH2 NH
~N-NH2 NHZ
where R8 is 1-4C-alkyl, Y1 and Y2 are identical or different and are a 4-11C-heteroaryl or 2-7C-heterocycloalkyl radical, comprising at least one ring nitrogen, Z1 and Z2 are identical or different and are 5-12C-arylene, 5-12C-heteroarylene, 3-8C-cycloalkylene or 3-8C-heterocycloalkylene, where each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocyc-loalkyl can additionally be substituted, for its part, by one, two or three substituents selected from the group consisting of hydroxyl, halogen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl, and in which on the direct route between the terminal nitrogen atoms 25 to 40 bonds must be present, the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroaryle-nes and heterocycloalkylenes comprising a nitrogen atom and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, 84, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond and a direct linkage would thereby occur between two hetero-atoms or two carbonyl groups.

Compounds of embodiment a to be emphasized are those in which A1 and A2 are identical or different and are -C(O)-, -NH-, -O-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are -C(O)-, -O-, -NH-, -O-C(O)-, -C(O)-O-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group T
T T T T
I N N
~ /N
i where E is -O- (oxygen), -S- (sulfur) or -CH2- (methylene) and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -O-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, M is a pyranose unit selected from the following list r R3 ~ U R
'R5 ~' ~R5 R5 U~
O O
,U R2 R
W W

~ U F R3 ''~ ~R5 R5 ~ 'Uw O O
~W ~-. ,W

~W \W
~R5 ~ ~U~
O O

W

-U ~
O

where -U and W are identical or different and are -O- (oxygen), -S- (sulfur) or -NH-, R1 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R2 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R3 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, R4 is hydroxyl, cyano, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, R5 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) are an alkylenedioxy group (-O-C(R6);R7-O-J, in which either one of the radicals R6 and R7 is hydrogen and the other is methyl, phenyl or p-methoxyphenyl, or in which both radicals R6 and R7 are hydrogen or methyl, K1 iS-B7-(C(O))m-B9-X1, -B7-(C(O))m-B9-Y1 :or-B7-(C(O))m-B9-Z1-811-X1, K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or-B8-(C(O))p B10-Z2-B12-X2, - 24 - ~ --- _ B1, B2, B3, B4, B5 and B6 are identical of different and are a bond or 1-4C-alkylene, B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene, m is0or1, p is0or1, X1 and X2 are identical or different and are selected from the following groups ~NH /.NH
-NH ~2 NHz NHOH
NH NH
-H H~ NHz NHz H-R8 ~N~NH
z NH NH NH
S H
NHz S--Rg NH2 NH
~N-NHz NHz where R8 is 1-4C-alkyl, Y1 and Y2 are identical or different and are piperid-4-yl, piperid-3-yl, piperazin-1-yl, piperazin-2-yl, morpholin-2-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, 2-imidazolin-3-yl, 2-imidazolin-2-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, pyrid-4-yl; pyrid-3-yl, pyridazin-4-yl, pyrimidin-5-yl, pyrimidin-4-yl, indol-3-yl, benzimidazol-4-yl or benzimidazol-5-yl, Z1 and Z2 are identical or different and are 1,4-phenylene, 1,3-phenylene, 1,4-naphthylene, 2,6-naph-thylene, 1,4-cyclohexylene, 1,3-cyclohexylene, 1,3-cyclopentylene, ~ 1,4-piperazinylene, 4,1-piperidinylene, 1,4-piperidinylene, 2,5-pyrrolidinylene;- 4,2-imidazolidinylene, 2,5-furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,6-quinolinylene, 2,5-benzofuranylene or 4,2-thiazolylene,'-.
where each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocyc-loalkyl can additionally be substituted, for its part, by one, two or three substituents selected from -25- ._ _ the group consisting of hydroxyl, k~alogen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl, and in which on the direct route between the terminal nitrogen atoms 25 to 40 bonds must be present, the salts of these compounds and the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes comprising a nitrogen atom and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, 810, B11 or B12 assume the meaning of a bond and a direct linkage would thereby occur between two heteroatoms or carbonyl groups.
Compounds of embodiment a particularly to be emphasized are those in which A1 and A2 are identical or different and are -C(O)-, -O-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different or are selected from the group ~ T
T T N N N
where T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, M is a pyranose unit selected from the following list R3 \W
~U~ ~ ~U~
O O
,W R2 R1 R1v where r U and W are identical or different and are -O- (oxygen) or -NH-, R1 is hydrogen, 1-2C-alkoxy, acetoxy or Ar-methoxy, R2 is hydrogen, hydroxyl, 1-2C-alkoxy, acetoxy or Ar-methoxy, R3 is hydroxyl, 1-2C-alkoxy, acetoxy or Ar-methoxy, R4 is hydroxyl, 1-2C-alkoxy, acetoxy orAr-methoxy, K1 is -B7-(C(O))m B9-X1, -B7-(C(O))m B9-Y1 or-B7-(C(O))m B9-Z1-B11-X1, K2 is -B8-(C(O))P B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))P-B10-Z2-B12-X2, B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene, m is0or1, p is0or1, X1 and X2 are identical or different and are selected from the following groups NH /NH
-NHZ --Y1 and Y2 are identical or different and are piperid-4-yl, piperid-3-yl, piperazin-1-yl, piperazin-2-yl, morpholin-2-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, 2-imidazolin-3-yl, 2-imidazolin-2-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, 5-methyl-imidazol-4-yl, pyrid-4-yl, pyrid-3-yl, pyridazin-4-yl, pyrimidin-5-yl, pyrimidin-4-yl, indol-3-yl, ben-zimidazol-4-yl or benzimidazol-5-yl, Z1 and Z2 are identical or different and are 1,4-phenylene, 1,3-phenylene, 1,4-naphthylene, 2,6-naph-thylene, 1,4-cyclohexylene, 1,3-cyclohexylene, 1,3-cyclopentylene, 1,4-piperazinylene, 4,1-piperidinylene, 1,4-piperidinylene, 2,5-pyrrolidinylene, 4,2-imidazolidinylene, 2,5-furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 6-methyl-5,2-pyridinylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,B-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,6-quinolinylene, 2,5-benzofuranylene or 4,2-thiazolylene, and in which on the direct route between the terminal nitrogen atoms 25 to 40 bonds must be present, the salts of these compounds and the N-oxides of the heteroaryls, heterocycloalkyls, heteroarylenes and heterocycloalkylenes comprising a nitrogen atom and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond and a direct linkage would thereby occur between two heteroatoms or carbonyl groups.
Preferred compounds of embodiment a are those in which A1 and A2 is -C(O)-, A3 and A4 are i A5 and A6 are identical or different and are -C(O)- or -C(O)-NH-, M is the pyranose unit \W
~U~
O

where U and W are -O- (oxygen), R1 and R2 are hydrogen, and R4 is hydroxyl or benzyloxy, K1 is-B7-(C(O))m B9-X1, -B7-(C(O))m B9-Y1 or-B7-(C(O))m B9-Z1-B11-X1, K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or-B8-(C(O))p-B10-Z2-B12-X2, B1 and B2 are identical or different and are a bond or methylene, B3, B4, B5 and B6 are in each case a band, B7 and B8 are identical or different and are a bond or 1-3C-alkylene, B9 and B10 are in each case a bond, B11 and B12 are identical or different and are a bond or methylene, m is 0, p is 0, X1 and X2 are identical or different and are selected from the following groups NH NH
-N -H

Y1 and Y2 are piperid-4.-yl., Z1 and Z2 are identical or different and are 4,1-piperidinylene, 3,6-indazolylene, 1,4-phenylene or 1,4-cyclohexylene, and in which on the direct route between the terminal nitrogen atoms 25 to 40 bonds must be present, and salts of these compounds.

- 28 - ~'-Particularly preferred compounds of embodiment a are 3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)-1-piperazinytcarbonyl]-1,2-dideoxy-D-gluco-pyranose;
4-O-benzyl-3,6-di-O-[4-(4-guanidinobenzylaminocarbonyl)-1-piperazinylcarbonyl]-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazinylcarbonylmethyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)-1-piperazinylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(1-amidinopiperidin-4-ylacetyl)-1-piperazinylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-gluco-pyranose;
and the salts of these compounds.
An embodiment (embodiment b) of the invention are compounds of the formula I
in which A1 and A2 are identical or different and are -C(O)-, -NH-, -O- (oxygen), -(S)-(sulfur), -S(O)2-, -S(O)2-NH-, -NH-S(O)2-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are -C(O)-, -O-, -S-, -NH-, -O-C(O)-, -C(O)-O-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group T
T T T I T
I N N
'N
_ N G
where E is -O- (oxygen), -S- (sulfur) or -CH2- (methylene), ' G is -O- (oxygen) or -CH2- (methylene), and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -O-, -S-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, M is a pyranose unit selected from the following list U O R2 ~ R2 O R2 O
W W W W

~ U R3 R3 'R5 ~ 'R5 /W O ./W O W O

wW wW
'R5 ~ ~U~
O O

W

'U~
O

where U and W are identical or different and are -O- (oxygen), -S- (sulfur) or -NH-, R1 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4.C-alkoxy, R2 is hydrogen, hydroxyl, 1-4.C-alkoxy, 1-4C-atkylcarbonyl or Ar-1-4C-alkoxy, R3 is hydroxyl, 1-4.C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R4 is hydroxyl, cyano, 1-4C-alkoxy, 1-4C-alkylcarbonyl or Ar-1-4C-alkoxy, R5 is hydroxy, 1-4.C-alkoxy, 1-4.C-alkylcarbonyloxy or Ar-1-4C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) are an alkylenedioxy group (-O-C(R6).~t7-O-], in which either ogre of the radicals R6 and R7 is hydrogen and the other is methyl, phenyl or p-methoxyphenyl, or in which both radicals R6 and R7 are hydrogen or methyl, K1 _ Is-B7-(C(O))m-B9-X1 or-B7-(C(O))m-B9-Z1-B11-X1, K2 is -B8-(C(O))p B10-X2 or -B8-(C(O))p-B10-Z2-B12-X2, -30- ~ w B1, B2, B3, B4, B5 and B6 are identical of different and are a bond or 1-4.C-alkylene, B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene, rn is0or1, p is0or1, X1 and X2 are identical or different and are selected from the following groups NH NH
H~ NH2 NHOH H--R8 ~N~NH

NH NH NH
S N

NH
~N-NH2 where R8 is 1-4C-alkyl, Z1 and Z2 are identical or different and are 5-12C-arylene, 5-12C-heteroarylene, 3-8C-cycloalkylene or 3-8C-heterocycloalkylene, where each arylene, heteroarylene, cycloalkylene or heterocycloalkylene can additionally be substitu-ted, for its part, by one, two or three substituents selected from the group consisting of hydroxyl, halo-gen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carbo-xyl or aminocarbonyl, and in which on the direct route between the terminal nitrogen atoms 25 to 40 bonds_must be present, and also the salts of these compounds, where all those compounds are excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond and a direct linkage would thereby occur between two heteroatoms or carbonyl groups.
A further embodiment (embodiment c) of the invention are compounds of the formula I in which A1 and A2 are identical or different and are -C(O)-, -NH-, '-O- (oxygen), -S-(sulfur), -S(O)2-, -S(O)2-NH-, -NH-S(O)2-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical br different and are -C(O)-, -O-, -S-, -NH-, -O-C(O)-, -C(O)-O-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group T
T T T T
N N
N
N G
where E is -O- (oxygen), -S- (sulfur) or -CH2- (methylene), G is -O- (oxygen) or -CH2- (methylene), and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -O-, -S-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the list below W

\ U R5 R3 R5 R3 U w /W O ~W O /W O

\W \W
~R5 ~ ~U~
O O

W
R3 _ Uw O

where U and W are identical or different and are -O- (oxygen), -S- (sulfur) or -NH-, R1 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4.C-alkoxy, R2 is hydrogen, hydroxyl, 1-4.C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, R3 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy-, .
R4 is hydroxyl, cyano, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, R5 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy o~Ar-1-4C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) are an alkylenedioxy group [-O-C(R6)R7-O-], in which either one of the radicals R6 and R7 is hydrogen and the other is methyl, phenyl or p-methoxyphenyl, or in which both radicals R6 and R7 are hydrogen or methyl, K1 is -B7-(C(O))~; B9-Z1-811-X1, K2 is -B8-(C(O))p-B10-Z2-B12-X2, - 33 - ' B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-4C-alkylene, m is0or1, p is0or1, X1 and X2 are identical or different and are selected from the following groups O NH NH
NHZ
NHZ NHZ NHOH
NH NH
H~ NHZ
NHZ H-R8 ~N~NH

NH NH NH
S H
NHZ S--Rg NH2 NH

NHZ
where R8 is 1-4C-alkyl, Z1 and Z2 are identical or different and are 5-12C-arylene, 5-12C-heteroarylene, 3-8C-cycloalkylene or 3-8C-heterocycloalkylene, where each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocyc-loalkyl can additionally be substituted, for its part, by one, two or three substituents selected from the group consisting of hydroxyl, halogen, vitro, cyano, amino, 1-4.C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl, and in which on the direct route between the terminal nitrogen atoms 20 to 40, preferably 25 to ~40, bonds must be present, the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroaryle-nes and heterocycloalkylenes comprising a nitrogen atom and their salts, where all those compounds are excluded in which 'one or more of the variables B1, B2, B3, B4, B5, B6, 87, B8, B9, B10, B11 or B12 assume the meaning of a bond and a direct linkage would thereby occur between two hetero-atoms or carbonyl groups.

Compounds of embodiment c to be emphasized are those in which A1 and A2 are identical or different and are -C(O)-, -O-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are selected from the group T T N N N
where T is the group -C(O)- or a band, A5 and A6 are identical or different and are -C(O)-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, M is a pyranose unit selected from the list below R3 R5 U R5 R3 R5 R3 Uw W W i W

~ U R3 R3 'R5 ~ ~R5 O O O
iW ~W /W

WW WW
~R5 ~ ~Uw O O

W

~U~
O

where U and W are identical or different and are -O- (oxygen) or -NH-, R1 is hydrogen, 1-2C-alkoxy, acetoxy or Ar-methoxy, R2 is hydrogen, hydroxyl, 1-2C-alkoxy, acetoxy or Ar-methoxy, R3 is hydroxyl, 1-2C-alkoxy, acetoxy or Ar-methoxy, R4 is hydroxyl, 1-2C-alkoxy, acetoxy or Ar-methoxy, ;.
K1 is -B7-(C(O))m-B9-Z1-B11-X1, K2 is -B8-(C(O))P B10-Z2-B12-X2, B1, B2, B3, B4, B5 and_B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-3C-alkylene, m is0or1, p - is0or1, - 36 - _ X1 and X2 are identical or different and are selected from the following groups -NH /NH -N~/NH
H

Z1 and Z2 are identical or different and are 1,4-naphthylene, 2,6-naphthylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,6-quino-linylene or 2,5-benzofuranylene, and which on the direct route between the terminal nitrogen atoms 25 to 40 bonds must be present, the salts of these compounds, and also the N-oxides of the heteroarylenes comprising a nitrogen atom and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9 or B10 assume the meaning of a bond and a direct linkage would thereby occur between two heteroatoms or carbonyl groups.
Further compounds of embodiment c to be emphasized are those in which A1 and A2 a~~ identical or different and are -C(O)-, -C(O)-NH-, -C(O)-O- or a bond, A3 and A4 are identical or different and are 1,4-piperazinylene, 1,4-piperidinylene, 1,4-cyclohexylene, 1,3-phenylene or a bond, A5 and A6 are identical or different and are -C(O)-, -C(O)-NH-, -NH-C(O)- or -NH-C(O)-NH-, M is a pyranose unit selected from the following list .U\ ~ wU\
O O
R2 ~ _ where U and W are identical or different and are -O- (oxygen) or -NH-, R1 is hydrogen, methoxy or benzyloxy, R2 is hydrogen, R3 is hydroxyl or benzyloxy, R4 is hydroxyl, methoxy or benzyloxy, K1 is -B7-(C(O))m B9-Z1-B11-X1, K2 is -B8-(C(O))p-B10-Z2-B12-X2, B1 and B2 are identical or different and are a bond or methylene, B3, B4, B5 and B6 are identical or different and are a bond or 1-3C-alkylene, -37- _ B7, B8, B9 and B10 are identical or different and are a bond or 1-4C-alkylene, B11 and B12 are identical or dififerent and are a bond or methylene, m is 0, p is 0, X1 and X2 are identical or different and are selected from the following groups O NH NH

Z1 and ZZ are identical or different and are 5,2-pyridinylene, 6-methyl-5,2-pyridinylene, 4,1-piperidinylene, 3,6-indazolylene, 3,6-indolylene, 1,3-phenylene, 1,4-phenylene, 1,3-cyclohexylene or 1,4-cyclohexylene, and in which on the direct route between the terminal nitrogen atoms 20 to 40, preferably 25 to 40, bonds must be present, the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroaryle-nes and heterocycloalkylenes comprising a nitrogen atom and their salts, where all those compounds are excluded~'in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, 810, B11 or B12 assume the meaning of a bond and a direct linkage would thereby occur between two hetero-atoms or carbonyl groups.
Compounds of embodiment c particularly to be emphasized are 3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyra-nose;
4-O-benzyl-1,2-dideoxy-3,6-di-O-[4-{4-guanidinobenzylaminocarbonyl)piperazin-1-ylcarbonyl]-D-gluco-pyranose;
3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonylmethyl]-4-O-benzyl-1,2-di-deoxy-D-giucopyranose;
3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-{1-amidinopiperidin-4-ylacetyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-{traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-galactopyranose;
3,6-di-O-[4-(traps-4-arrtinomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-D-galacto-pyranose;
3,6-di-O-[4-(amidinoindazol-3-ylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-gluco-pyranose;

- gg methyl-3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4'-O-benzyl-2-deoxy-a-D-glucopyranoside;
methyl 3,6-di-O-(4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-2-deoxy-oc-D-glucopyranoside;
3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonylmethyl]-1,2-dideoxy-D-glucopyranose;
6-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-3-O-[4-(traps-4-aminomethylcyclo-hexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
benzyl 3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-2-deoxy-a-D-glucopyranoside;
3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonylmethyl]-4.-O-benzyl-1,2-di-deoxy-D-glucopyranose;
3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonylmethyl]-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-methyl-1,2-dideoxy-D-galactopyranose;
methyl 2,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-a-D-glucopyranoside;
methyl 3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-2-deoxy-a-D-glucopyranoside;
methyl 2,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-3,4-di-O-benzyl-a-D-glucopyranoside;
methyl 3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-2-deoxy-a-D-glucopyranoside;
6-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)-1-aminopentyl]-3-O-[4-(traps-4-aminomethylcyclo-hexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-6-O-[5-(2-aminomethylpyridyl-carbonyl)-1-aminopentyi]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-N-[4-(traps-4-aminomethylcyclohexylcarbonyl)-4.-aminobutyl-4-oxycarbonyl]-3-O-[4-(traps-4-amino-methylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-(traps-4-aminomethylcycfohexylcarbonyl)-5-aminopentyl]-3-O-[4-(traps-4-aminomethylcyclo-hexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose; ' 3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)-5-aminopentyl]-4-O-benzyl-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-(traps-4-aminomethylcyclohexylcarbonyl)-5-aminopentyl]-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(3-aminomethylbenzoyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(3-aminomethylbenzoylamino)piperidin-1-ylcarbonyl]-4.-O-benzyl-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-(3-aminomethylbenzylaminocarbonyi)piperazin-1-yicarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;

3,6-di-O-[4-(3-aminomethylbenzylaminocarbonylamino)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(3-aminomethylbenzylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-traps-(3-aminomethylbenzylaminocarbonyl)cyclohexylmethylaminocarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-(6-amino-pyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-(6-amino-2-methylpyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-(4-amino-benzylaminocarbonyl)piperidin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyf]-4-O-benzyl-6-O-[4-traps-(6-amino-pyridin-3-ylmethylaminocarbonyl)cyclohexylmethylaminocarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-traps-(6-amino-2-methylpyridin-3-ylmethylaminocarbonyl)cyclohexylmethylaminocarbonyl]-1,2-dideoxy-D-gluco-pyranose;
3-O-(4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-traps-(4-amino-benzylaminocarbonyl)cyclohexylmethylaminocarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[3-(4-amino-benzylaminocarbonyl)benzylaminocarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-6-O-{4-(4-traps-(amino-methyl)cyclohexylcarbonyl]aminobut-1-ylaminocarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-6-O-(4-(4-aminomethyl-benzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-6-O-[2-(6-aminopyridin-3-yl-methylaminocarbonyl)eth-1-ylaminocarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{3-[(6-amidino-1-H-indazol-3-yl)carbonylamino]prop-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonylJ-4-O-benzyl-6-O-{3-[(6-amino-carbonyl-1-H-indazol-3-yl)carbonylamino]prop-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-6-O-{2-((6-aminocarbonyl-1-H-indol-3-yl)carbonylamino]eth-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{3-[(6-amino-carbonyl-1-H indol-3-yl)carbonylamino]prop-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[(6-amino-carbonyl-1-H-indol-3-yl)carbonylamino]but-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
and the salts of these compounds.

A further embodiment (embodiment d) of the invention are compounds of the formula I in which A1 and A2 are identical or different and are -C(O)-, -NH-, -O- (oxygen), -S-(sulfur), -S(O)2-, -S(O)2-NH-, -NH-S(O)2-, -C(O)-NH-, -NH-C(O}-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are -C(O)-, -O-, -S-, -NH-, -O-C(O)-, -C(O)-O-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group T
T T T I T
I N N
\ ~N
N G
where E is -O- (oxygen), -S-(sulfur) or -CH2- (methylene), G is -O- (oxygen) or -CH2- (methylene), and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O}-, -NH-, -O-, -S-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the following list - 41 - _.

R5 \U R5 R3 R5 R3 U W

W W

\ U R5 R3 R5 R3 U w O O O
~.W ~.W /W

\W ~.W
~R5 1'' 'Uw O O

W
R3 _ Uw O

where -U and W are identical or different and are -O- (oxygen), -S- (sulfur) or -NH-, R1 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4.C-alkoxy, R2 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4.C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R3 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R4 is hydroxyl, cyano, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, R5 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) are an alkylenedioxy group (-O-C(R6),R7-O-J, in which either one of the radicals R6 and R7 is hydrogen and the other is methyl, phenyl or p-methoxyphenyl, or in which both radicals R6 and R7 are hydrogen or methyl, K1 is -B7-(C(O))m B9'-Y1, K2 is -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2, - ;~ _ B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, B9, B10 and B12 are identical or different and are a bond or 1-4C-alkylene, m is0or1, p is0or1, X2 is selected from the following groups O NH NH
NHz H

Y1 and Y2 are identical or different and are imidazol-1-yl, pyrrolidin-2-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, pyridazin-4-yl, indol-3-yl or morpholin-2-yl, Z2 is 1,4-phenylene, 1,3-phenylene, 1,4-naphthylene, 2,6-naphthylene, 1,4-cyclohexylene, 1,3-cyclohexylene, 1,3-cyclopentylene, 1,4-piperazinylene, 4,1-piperidinylene, 1,4-piperidinylene, 2,5-pyrrolidinylene, 4,2-imidazolidinylene, 2,5-furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 6-methyl-5,2-pyridinylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,6-quinolinylene, 2,5-benzofuranylene or 4,2-thiazolylene, and in which on the direct route between the terminal nitrogen atoms 20 to 40, preferably 25 to 40, bonds must be present, the salts of these compounds, and also the N-oxides of the heteroaryls, heteroarylenes, heterocycloal-kyls and heterocycloalkylenes and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9 or B10 assume the meaning of a bond and a direct linkage would thereby occur between two heteroatoms or carbonyl groups.
Compounds of embodiment d to be emphasized are those in which A1 and A2 are identical or different and are -C(O)-, -NH-, -O- (oxygen), -S-(sulfur), -S(O)2-, -S(O)2-NH-, -NH-S(O)2-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are -C(O)-, -O-, -S-, -NH-, -O-C(O)-, -C(O)-O-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group T T T v) T
N N
~ /N
<( E N G
where E is -O- (oxygen), -S- (sulfur) or -CH2- (methylene), G is -O- (oxygen) or -CH2- (methylene), and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -O-, -S-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, M is a pyranose unit selected from the following list R3 \U R3 R3 -R5 ~ -R5 ~ ~R5 ~ ~U~
,U O R2 O R2 O R2 O
W I W V~V

\ U R3 R3 ~R5 1' ~R5 O O O
~W ~W /W

~W \W
-R5 ~ ~U~
O O

W

-U~
O

where U and W are identical or different and are -O- (oxygen), -S- (sulfur) or -NH-, R1 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, R2 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R3 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R4 is hydroxyl, cyano, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, -~- _ R5 is hydroxyl, 1-4.C-alkoxy, a-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) are an alkylenedioxy group (-O-C(R6)R7-O-], in which either one of the radicals R6 and R7 is hydrogen and the other is methyl, phenyl or p-methoxyphenyl, or in which both radicals R6 and R7 are hydrogen or methyl, K1 is -B7-(C(O})m B9-Y1, K2 is -B8-(C(O))P B10-Y2, B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, B9 and B10 are identical or different and are a bond or 1-3C-alkylene, m is0or1, p is0or1, Y1 and Y2 are identical or different and are pyrrolidin-2-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidaa~-lidin-4-yl, pyridazin-4-yl, indol-3-yl or morpholin-2-yl, and in which on the direct route between the terminal nitrogen atoms 25 to 40 bonds must be present, the salts of these compounds, and also the N-oxides of the heteroaryls and heterocycloalkyls and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9 or B10 assume the meaning of a bond and a direct linkage would thereby occur between two heteroatoms or carbonyl groups.
Compounds of embodiment d further to be emphasized are those in which A1 and A2 are identical or different and are -C(O)-, -C(O)-NH-, -C(O)-O- or a bond, A3 and A4 are identical or different and are 1,4-piperazinylene, 1,4-piperidinylene, 1,4-cyclohexylene, 1,3-phenylene or a bond, A5 and A6 are identical or different and are -C(O)-, -C(O}-NH-, -NH-C(O)- or -NH-C(O)-NH-, M is a pyranose unit selected from the following list _Uw Uw O
/w R2 where U and W are identical or different and are -O- (oxygen) or -NH-, R1 is hydrbgen, methoxy or benzyloxy, R2 is hydrogen, R3 is hydroxyl or benzyloxy, R4 is hydroxyl, methoxy or benzyloXy;

K1 is -B7-(C(O))m B9-Y1, K2 is -B8-(C(O))P B10-Z2-B12-X2, B1 and B2 are identical or different and are a bond or methylene, B3, B4, B5 and B6 are identical or different and are a bond or 1-3C-alkylene, B7, B8, B9 and B10 are identical or different and are a bond or 1-4C-alkylene, B12 is a bond or methylene, m is 0, p is 0, X2 is selected from the following groups O NH NH

Y1 is imidazol-1-yl, Z2 is 5,2-pyridinylene, 6-methyl-5,2-pyridinylene, 4,1-piperidinylene, 3,6-indazolylene, 3,6-indolylene, 1, 3-phenylene, 1,4-phenylene, 1,3-cyclohexylene or 1,4-cyclohexylene, and in which on the direct route between the terminal nitrogen atoms 20 to 40, preferably 25 to 40, bonds must be present, the salts of these compounds, and also the N-oxides of the heteroaryls and heteroarylenes comprising a nitrogen atom and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9 or B10 assume the meaning of a bond and a direct linka-ge would thereby occur between two heteroatoms or carbonyl groups.
Compounds of embodiment d particularly to be emphasized are 3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[3-(imidazol-1-yl)-propylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[4-(imidazol-1-yl)butylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[5-(imidazol-1-yl) pentylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6=O-{4-[6-(imidazol=1-yl)hexylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[8-(imidazol-1-yl)octylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;
and the salts of these r~ompounds.
The compounds of the formula I are composed of a large number of divalent units (M, A1, A2, A3, A4, A5, A6, B1, B2, B3, B4, BS, B6, B7, B8, B9, B10, B11, B12, Z1 and Z2). Their synthesis can in prin-ciple take place starting from any of these units. In the case of compounds of the formula I which are of 1,~.

largely symmetrical construction, synthesis beginning from the pyranose unit M
suggests itself, while in the case of predominantly unsymmetrical compounds of the formula I synthesis starting from one of the end groups K1 or K2 can be advantageous.
The linkage of the units here is always carried out according to the same pattern known per se to the person skilled in the art.
It is known to the person skilled in the art that the compounds of the formula I can be synthesized either unit for unit, or that firstly relatively large fragments consisting of a number of individual units can be prepared, which are then combined to give the entire molecule.
On account of the meanings which the individual units of the compounds of the formula I can assume, amino [-NH-], ether [-O-], thioether [-S-], keto ~C(O)-], sulfonyl [-S(O)2-], ester [-O-C(O)-, -C(O)-O-], amide [-C(O)-NH-, -NH-C(O)-], sulfonamide [-S02-NH-, -NH-S02-], carbamate [-NH-C(O)-O-, -O-C(O)-NH-], carbamide [-NH-C(O)-NH-] or carbonate bridges [-O-C(O)-O-] occur in the compounds of the formula I.
The manner how such bridges are produced is known per se to the person skilled in the art; suitable methods and starting compounds for their preparation are described, for example, in March, Advanced Organic Chemistry, Reactions, Mechanisms and Structure, Third Edition, 1985, John Wiley & Sons.
Ether and thioether bridges can be produced, for example, according to the method of Williamson.
Keto bridges can be introduced, for example, as a constituent of larger units, such as 1,3-dichloro-acetone.
Sulfonyl bridges can be obtained, for example, by oxidation of thioether bridges.
A large number of methods are known for the construction of ester bridges. The reaction of acids with alcohols, preferably using HzS04 or p-toluenesulfonic acid as a catalyst, or with addition of a dehydra-ting agent, such as molecular sieve or a carbodiimide, may be mentioned by way of example here. In addition, the reaction of acid chlorides with alcohols can be mentioned here.
There are also a large number of known methods for the production of amide bridges. An example which may be mentioned here is the reaction of acid chlorides with primary or secondary amines. In addition, reference may also be made to all the methods which have been developed for peptide che f mistry. Correspondingly;,sulfonamide bridges can be constructed from sulfonic acid chlorides and pri-mary or secondary amines.

Carbamate bridges can be produced, for-example, by reaction of chlorocarbonic acid esters with ami-nes. The chlorocarbonic acid esters, for their part, can be synthesized from alcohols and phosgene. A
further variant for the construction of carbamate bridges is the addition of alcohols to isocyanates.
Similarly, as in the case of the carbamate bridges, carbonate bridges can be produced starting from chlorocarbonic acid esters by reaction with alcohols (instead of amines).
Carbamide bridges can be produced, for example, by the reaction of isocyanates with amines.
The preparation of compounds of the formula I may be shown by way of example with the aid of the following reaction schemes. Further compounds of the formula I can be prepared analogously to or using the abovementioned methods known per se to the person skilled in the art.
The reaction schemes 1, 2 and 3 show the synthesis of pyranose units M by way of example. The reaction schemes 4 to 25 show the preparation of compounds of the formula I by way of example.

- 48 - ,'-Reaction scheme 1:
OAc O H
Ac0 O 1. Pdl C/ H2, MeOH HO O
Ac0 ~ HO
2. NaOMe, MeOH
TBDMS-CI (2.4 eq), imidazole OTBDMS Bngr, NaH, OTBDMS
Bn0 O ~ DMF HO O
TBDMSO TBDMSO
TBAF, THF
OH
Bn0 O
HO
1. TsCI, Py, RT, (A59) 2. NaN3, DMF, 120°C, (A58) 3. LiAIH4, THF
1. BrCH2C02Me, NaH, THF
2. NaOH, H20, MeOH, 4 h O~COZH ~ NH2 Bn0 O Bn0 O
O HO
HOzC

- 4g - _ Reaction scheme 2:
OAc O H
1. Liar, MsOH, CH3CN
Ac0 0 Dowex 50 (H+forrr~) HO O
Ac0 ~ HO
2. NaOMe, MeOH
OMe TBDMS-CI (2.4 eq), imidazole, (quant.) OTBDMS gngr, NaH, O~DMS
Bn0 O DMF, (95%.) HO 0 TBDMSO TBDMSO
OMe OMe TBAF, THF, (88%) OH
Bn0 O
HO Carbohydr. Res. 1995, 268 (1), 135-142 OMe OAc 0 H
1. Liar, H20, CH3CN
Ac0 0 Dowex 50 (H+ form)- HO O
Ac0 HO
2. BnBr, NaH, DMF
OBn w 1. TBDMS-CI (2.4 eq), imidazole, (quant.) Chem. Ber. 1980, 113 (8), 2827-2831 2. BnBr, NaH, DMF
OH OTBDMS
Bn0 O TBAF, THF, (85%) Bn0 O
HO TBDMSO
OBn OBn yJo -Reaction scheme 3:
OH OTBDMS
TBDMS-CI (2.0 eq), HO O imidazole, DMF, (70 %) HO O
HO HO
HO OMe TBDMSOOMe BnBr, NaH, DMF
OH OTBDMS
Bn0 O TBAF,THF BnO O
Bn0 Bn0 HOOMe TBDMSOOMe Bull. Chem. Soc. Jpn. 1983, 56 (4), 1171-1175 Tetrahedron Lett. 1984, 25 (36), 4029-4032 Carbohydr. Res. 1982, 702, 207-216 Reaction scheme 4:
OH
Bn0 O
HO
1. COC12, Tol, CH2C12 2. DIPEA, DMAP, CH2C12, ,N
j N~-Boc ' N
O~ ~N...-Boc Bn0 O O
Boc~N~~~ ~O
~N~
~~O
HCI, dioxane HOBT, EDC, CH2C12, Boc HOOC N~H ~ O Boc ~N ~ N\H
O
Bn0 O O
Boc~ N~~~ O
N ~N~
H O O
HCI, dioxane O
N \~w NHZ
O~ ~N
Bn0 O ~~O
HZN N~N O X 2HC1 _O
O

Reaction scheme 5:
O ioc.
N ~.~/~,,~~ N ~
O~ V'"N H
Bn0 O ~~O
B oc ~ N ~..~/~'~ O
N ~N~
H O O
Pdl CI H2, MeOH
O i oc N~ N~
O~ ~N H
HO O \\O
Boc~ N~~~ O
N ~N~
H O O
HCI, dioxane O
N~ NHz O~ V"N 2 HO O O
N~~~ O x2HCl HzN ~N~
O O
r Reaction scheme 6:
N
O~ ~N...Boc Bn0 O O
Boc''N~ O
~N
O
1. HCI, dioxane 2. DIPEA, CH2C12, BocHN
N=C=O
3. HCI, dioxane O
N ~
HzN O ~N~N \
Bn0 O O H
N N ~ O NHz 1~' ~N--~
p o 1. Et3N, HgCl2, DMF, MeS~N
~ Boc 2. HCI, dioxane NHBoc H O
HN~ N N
O ~'N ~N \ NH
H ~ ~
z ~ ~ N Bn0 H ~%'~N
N.~ O I NHz ~N~ x 2HCI H
O O

Reaction scheme 7:
O _ /CI
OH ~O
O
Bn0 O CI"CI
Bn0 O
Bn0 Bn0 Py, CH2C12, HOOMe OOMe O
CI
H
N R
R
DIPEA, CH2C12 A33 ~ N. Boc H
R
// N Bn0 OBn H ~ N,Boc O ~ O A35 ,,~ N ~ , H
N ~ O , O
Me0 O
N
N
~O
R
HCI, dioxane -or-1. PdICIH2, MeOH
2. HCI, dioxane R' N R O O R,.
O~ O
R' N-~ O
.._ 18 : R - H ~ NH2 Me0 O O
N
N~ N
20:R"=Bn '' O
R' Reaction scheme 8:
O ~CI
O H O ~~j'O
O CI' 'CI Bn0 O
Bn0 HO O
PY~ CH2C12, O
O R"' O R"' CI
R"' = Me, Bn H N'.i N R
R _ DIPEA, CH2CI2 1.) , N.Boc Fi w N,Boc O 2.) ~,~N~ H
O\ N~ ~R
N
R O
~N~~ Bn0 O
O
N ~ ~ R", O
HCI, dioxane R, _or_ 1. PdICIH2, MeOH
1.) , NH 2. HCI, dioxane z 2.) N ~ j NHZ O~ N---~
,,i ~ ~ N R
R~~ N O
O// ~ R"O O
N O
10:R"=Bn,R"'=Me ", 1' 11 : R"=H, R"'=Me O~ OR
14: R" = Bn, R"' = Bn 2.) 19:R"=Bn R"'=Me 21: R" = H, R"'~= Me Reaction scheme 9: -OH OTBDMS ~ OTBDMS
Bn0 O TBDMSCI (1 eq) CI CI BnO O
Bn0 O
HO HO Py, CH2C12, A53 ~O
H
I
Boc'N N-A43 '~ IAP
Boc~N
H
OH
N
p ~ Bn0 O
,O
.~\\N
p A45 Reaction scheme 10:
Boc_N
E
OH
_A4 Bn0 O
.O
~'\/N
O
1. CHZCI2, r.t.
Tf02, Py 2, H2N-NHZx H20, EtOH
HO~I~NPht ~" TfO~~~NPht J. Amer. Chem. Soc. 1993, 115 (26), 12550-12568 KPht Boc~N
HO~\~N HZ H
O~\~N HZ
N
O ~ BnO O
O
N
EDC, CH2CI \\2 O
Boc~.N
O
H
R"
O/1~N ~R"
N H H
O ~ R~00 O ~') Boc'N
N
O
~~ z 2.) N
HCI, dioxane i O
O~~~N ~ R"' N H
O ~ R~O O R...
o N
22 : R' = Bn HZN
O 25: R'=H
w 23: R' = Bn- E'rzN I N

Reaction scheme 11:
O\ 'CI
~ RO O
HO OH RO OH CI/ "CI
O 1. TBDMSCI (2 eq) O O
HO 2. Mel or BnBr ' HO PY, CH2CI2, r.t. CIO
3. TBAF \\
O
R = Bn, Me H
I
Boc'N N~N'H
A43 O 1. DIPEA, DMAP
2a. HCI, dioxane 2b. Pd/ CIH2, MeOH;
HCI, dioxane \\
O/'- N O

7 : R = Bn N RO

8 :R=H p ~ O
O
17: R=Me N
\\O
C

Reaction scheme 12:
O~C02H
Bn0 O
O

EDC, CH2C12 O ~~ N -~ ~ R
O
O R"O O
~O
N~ ~ R
~N
R ~ N.Boc O Fi Boc HCI, dioxane H\ J~ H
-or- ~,,N i 1. PdICIH2, MeOH ~
2. HCI, dioxane N _ O ~ II R
O
O R"O O
1, ,0 N~N~ R.
R
12 : R" = H ~ N Hz 15 : R" = Bn H I ~ NHz 16 : R" = H ~'!N

-60- _ Reaction scheme 13:
OH O~C02Me ~ O~COzMe Bn0 O BrCHZCO2Me O CI CI Bn0 O
Bn0 HO NaH HO PY, CHZCI2, CIO
A66 \\O
_A43 ~N~ N~N.H
Boc 1. DIPEA, DMAP
O 2. NaOH, MeOH
Boc~N
Fi O~COZH
p ~ Bn0 O
O
N
~~O
,Boc H ~N
1. EDC, CHZCIz N N ~ I H
2. HCI, dioxane H.
NHZ
HZN H I
N
O O ~N~
N ~N
O ~ Bn0 O
.O
NN

Reaction scheme 14:
HO~NH '+' HO~f~N~Boc ..

EDC ~ Boc Boc N
N H
NHz HO~Ny~ H O O~H ~p H' O A51 ~H
Bn0 O
HO B nO O A52 COCIZ HO -1. COCI2 H
2. HCI, dioxane Boc N N~ N.H

N HZ
H2N O~O~N
H O
N-H
B n00 O 24 O N
O
E

Reaction scheme 15:
H
O N~N.
OH N~ N ~H _N O
Boc~ H
Bn0 O Bn0 O
HO O
1. COC12, tol N
2. DIPEA, CH2CI2 3. HCI, dioxane iH
1. EDC, CH2C12, DIPEA, DMAP ,N \ NHZ
2. Pd/ C, H2, MeOH N

NH" ' ~ NH2 H O\ N~ N ~ ~ ~ NH
N
O ~ Bn00 O g H
N
O

Reaction scheme 16: -O H Tf0/\'~N P ht O!1~~N H2 8n0 O 1. CHzCl2, r.t.
Bn0 O
HO 2, HZN-NH2 x H20, EtOH HzN\~~~0 H
,N
Boo ~ COZH
1. EDC, CHZCI2 2a. HCI, dioxane 2b. Pd/ C/ HZ, MeOH;
HCI, dioxane O/~~N O

~,~- O
__~~N\/~~/ 26 : R' = Bn 27: R'=H

Reaction scheme 17:
O
\~ CI
OH COC12 / ~ , O
p .... O
HO O "
CI~

1 ) A112 (A113. A114, A115, A116, A117. A118) 2) HClldioxane O\\~ R
/ ~ '. O -p... O R=
O O
R"O 28 ~N I ~ I NHz NJ \

N

O
30 ~N~N ~ NHZ
N J \
31 N~~H~H
N N ~~~ N HZ
O
_H
32 ~ N ~~ NHZ
N \
O
33 ,' ~N ~ NHz NH~ \
O
34 I N ~ N
- N \ I
NHZ

Reaction scheme 18:
/ \ OH TBSCI / ~ OTBS
p....,.. O
HO 0...",. O
HO

/ \ OTBS
O
O
CI
O
BccHN ( w A130 ~NH A107 . N N
O
2.) TBAF
/ \ off p BocHN ~ ~ ~N O
/ N\ /N J
~O

o _ o /=1 / \ ~CI / \ ~N~N
~~ O
O ,. O
O
BocHN \ ~ A105 N O
BocHN ~N O
N
O

Reaction scheme 19:
I \ OH TBSCI / \ OTBS
O .... ". O
HO 0~~~.". O
HO
CDI
/ \ oTBs o "",.' o ~ A111 N
<~ ~
N
BocHN ~ A118 NH
N~ ~ r", A 110 2.) TBAF
\ off BocHN
\ ~N O
NI /
I
O
CDI
O~N U
I \ O
O
t BocHN \ N' \ O

NI / N
O

Reaction scheme 20:
~~ci NON
O ~ ~ O
0~~,~, ~O O~~"~ ~O
O O
BocHN ~ N- ' O BocHN ~ N-O
/ N ~ / N ~ 'A
O 1) A120 (A123, A_ 124) O
2) PdIC, HZ 1.) A125 (A126, A127, A128, A, 129) 3) HCI, dioxane 1) A118 A( 119, A121, A122) 2.) HClldioxane 2.) HClldioxane O
~~ R
O
O
O
H N ~ N"O
N\ /N J
R=
O
R= ' 0 O NON
35 N / N 42 N~ H N
N \ I
/f \\~~NH
O z O
N /N
36 N / IN 43 H ~
N~ \ N
O NHz O
H
N -~ N N
37 N ~ ~ NH ~ N H ~N
O z H O
3$ N / N NON
NH~. \ I N
NHz 45 ~ H

,,,~N / N O
39 NH~ \ I NON
NHz 46 N H
~'~~~N /
40 NH 1 1 \
~/' NHz O
41 NH ~ '' ~ N
NHz Reaction scheme 21:
o ~1 N ~ N O~ N
p "", ~ ~ ~NHZ
p ~\ N
BocHN ~ N~O ~-1~
n = 0 - 2 BooHN I ~ H ~N O
/~N N J
o ~ n=1;A102 o O
Ho n = 2; A103 ~ w N I / NHz n = 3; A104 o ~0 0 / \
~ Op N~N O /O
O H
N NH2 A99 (A100, A101) Oi~O
BocHN ~ N~O
1.) H2lPd, DMF --~- A94 (A~ A96) 0 2.) HClldioxane ~ Op N ~N ll NHZ
p ",.. O H
0~.~ N O
H
H2N ~ N' 1 o n = 1; 52 '- N J
n=2; 53 o n=3; 54 Reaction scheme 22:

\~N~N
O
O ii~,' O

BocHN \ N O
w N~ / N
I
O
1 ) A130 (A131 2) HCI, dioxane i R=
~-' R ~
/ \ O~ 47 H ~N~N
H I
NHZ
BocHN \ 48 HZN
H ,, N~ / N ~N " \NHZ
O
O, \~~--NON

BocHN ~ \
H
N
1~ ~fO
1) A132 2) HCI, dioxane O N
\ H ~- NHZ
/ \ ~N ,~ !
~ N
~O ~,~" O O
O i~~~
N \ N"O

o Reaction scheme 23:
°~~ci / ~ o ""
o.S~
BOCHN \ N~O
H
I / N NJ
O
H NHZ
~~--./N
O
N ~ ~ ~ N o ~ ~ A154 ~N
0 ~ NH O
O
O
~~~N N N
/ \ , , O
O O'~ O \ I N~O \

~\ NH
BooHN \ N ' O
H
I / N NJ
° 1.) H2IPd, DMF --~- As2 (A93) 2.) HClldioxane O~N
N-N
/-\ , , °
O \ I NHZ _ ~ NH
HZN \ N- 'O _50 H
I / N NJ
O
O~~ N H
/ ~ ' ' ~ ~N N-N
O O O ~ I NHZ
O
\ ~ 51' H N H ~N O
z I / N NJ
O

Reaction scheme 24:
O ~N
°
° ~ ° i ~
/'~~. ~' O N ~ N O' \
O H H O~,O + HN H I i N O
n I N~(CHZ)n\ C' H

O
N O-O w N( ~ ~ °

O/\ N/,',~ -~ O
H H O,,O
N
n o ~(CH2)~~~ O
2 A15 Fi7 O

O N H I N
NHZ
O HCI
/'''~,. ~ ,. O
HzN O,"
HCI
a °
~ ( C HZ)~~ H
n Reaction scheme 25:
O / \
\ --.._ OTBDMS
NH + O ,".
1' O
O N\ / N\/ N O
A118 ~ A178 O H
OTBDMS
O O ,", N N O ~---.-O

N\ / O
-_ H
~H
'\ O H
O
O ""
N N O '~.--O

~~ -~ H
O N\ / O
O~ H
/ \ O
-", O~N~N
O O "" ~ _ N
~1O
O N\ /
O- H

Further suitably substituted pyranose units M which may be mentioned are, for example: benzyl a-D-4-O-benzyi-2-deoxyglucopyranoside (1), methyl a-D-2,4-di-O=benzylglucopyranoside (2), methyl a-D-2,4-di-O-benzylmannopyranoside (3), benzyl a-D-2,4-di-O-benzylmannopyranoside (4), methyl (i-D-2,4-di-O-benzylgalactopyranoside (5), methyl a-D-2,4-di-O-acetylglucopyranoside (6), methyl ~i-D-6-amino-3,4-di-O-isopropylidenegalactopyranoside (7), methyl ~i-D-3,4-di-O-isopropylidenegalactopyranoside (8) and methyl ~i-D-2-amino-3,4-di-O-isopropylidenegalactopyranoside (9).
Their preparation is described, for example, in Chem. Ber. 1980, 113, 2827-2831 (1), Chem Pharm.
Bull. 1986, 2341; (3-D-compound Carbohydr. Res. 1992, 236, 73-88 (2), Tetrahedron 1981, 37, 2779-2786 (3), Tetrahedron 1982, 38, 3721-3728, Carbohydr. Res. 1982, 101, 263-270 (5), Carbohydr. Res.
1980, 85, 298-301 (6), J. Am. Chem. Soc. 1959, 81, 3716-3718 (7), Carbohydr.
Res. 1985, 144, 45-56 (8) and Carbohydr. Res. 1987, 159, 229-254 (9).
Compounds of the formula I can also be converted into further compounds of the formula I by derivati-zation. Thus, for example, compounds of the formula I which have s heteroaryl, heteroarylene, hetero-cycloalkyl or heterocycloalkylene unit comprising a nitrogen atom can be converted into the correspon-ding N-oxides by oxidation.
The N-oxidation is carried out in a manner likewise familiar to the person skilled in the art, e.g. with the aid of hydrogen peroxide in methanol or m-chloroperoxybenzoic acid in dichloromethane at room tem-perature. The person skilled in the art is familiar on the basis of hislher expert knowledge with reaction conditions which are specifically necessary for carrying out the process.
It is moreover known to the person skilled in the art that in the case of a number of reactive centers on a starting or intermediate compound it may be necessary to block one or more reactive centers tempo-rarily by protective groups in order to allow a reaction to proceed specifically at the desired reaction center. A detailed description of the use of a large number of proven protective groups is found, for example, in T.W. Greene, Protective Groups in Organic Synthesis, John Wiley &
Sons, 1991.
The isolation and purification of the substances according to the invention is carried out in a manner known per se, e.g. by distilling off the solvent in vacuo and recrystallizing the resulting residue from a suitable solvent or subjecting it to one of the customary purification methods, such as column chrorr~-tography on suitable support material.
Salts are obtained by dissolving the free compound in a suitable solvent (e.g.
a ketone, such as aceto-ne, methyl ethyl ketone or methyl isobutyl ketone, an ether, such as diethyl ether, tetrahydrofuran or dioxane, a chlorinated hydrocarbon such as methylene chloride or chloroform, or a low molecular weight aliphatic alcohol such as ethanol or isopropanol) which contains the desired acid or base, or to which the desired acid or base is then added. The salts are obtained by filtration, reprecipitation, preci-pitation with a nonsolvent for the addition salt or by evaporation of the solvent. Salts obtained can be converted by alkalization or by acidification into the free compounds, which in turn can be converted into salts. In this manner, pharmacologically nontolerable salts can be converted into pharmacologically tolerable salts.
The following examples serve to illustrate the invention in greater detail without restricting it. Likewise, further compounds of the formula I whose preparation is not explicitly described can be prepared in an analogous manner or in a manner familiar per se to the person skilled in the art using customary pro-cess techniques.
In the following examples, the abbreviation RT stands for room temperature, DMF for dimethylforma-mide, THF for tetrahydrofuran, PE for petroleum ether, EA for ethyl acetate, DMAP for dimethylamino-pyridine, DIPEA for diisopropylethylamine, HOST for 1-hydroxy-1 H-benzotriazole, EDC for N'-(3-dimethylaminopropyl)-N-ethylcarbodiimide, TLC for thin-layer chromatography and MS for mass spectrometry. The compounds mentioned by way of example and their salts are a preferred subject of the invention.

- Examples Final compounds:
1. 3~6-Di-O-f4-(trans-4-aminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyll-4-O-benz~-1,2-dideoxy-D-glucop3rranose dihydrochloride A solution of 4-O-benzyl-3,6-di-O-[4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-piperazin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose (0.81 g, 0.70 mmol, starting compound A6) in dioxane (5 ml) is treated with a saturated solution of HCI in dioxane (3 ml, 13.5 mmol) and stirred at RT
overnight. The resulting precipitate is filtered off under N2 and washed first with dioxane (2 x 3 ml) and then with CH2C12 (3 x 3 ml). After drying in vacuo, the title compound (0.72 g) is obtained as colorless crystals.
MS: calc.: C39H6oN608 {741.05), found: [MH+J 741.4 2. 3,6-Di-.O-f4-(traps-4-aminomethylcyclohexylcarbonyl)-1-piperazin~ilcarbonyll-1 2-dideoxy-D-alucopyranose dihydrochloride A solution of 3,6-di-O-[4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-1-pipera-zinylcarbonyl]-1,2-dideoxy-D-glucopyranose (0.05 g, 0.06 mmol, starting compound A7) in dioxane (0.5 ml) is treated with a saturated solution of HCI in dioxane (0.5 ml, 2.25 mmol) and stirred at RT
overnight. The resulting precipitate is filtered off under an N2 atmosphere and washed first with dioxane (2 x 1 ml) and then with CH2C12 (3 x 1 ml). After drying in vacuo, the title compound (0.05 g) is obtained as colorless crystals.
MS: calc.: C32H54N6O8 (650.82), found: (MH~] 651.4 3. 4-O-Benzyl-1,2-dideoxy-3.6-di-O-f4-(4-auanidinobenzylaminocarbonyl)-1-piperazinyl-carbonvll-D-alucopyranose dihydrochloride 4-O-Benzyl-3,6-di-O-{4-[4-(N,N'-bis-tert-butoxycarbonylguanidino)benzylaminocarbonyl]-1-piperazinyl-carbonyl}-1,2-dideoxy-D-glucopyranose dihydrochloride (0.1 g, 0.076 mmol, starting compound A11) is dissolved in dioxane (0.5 ml) at RT. A saturated solution of HCI in dioxane (2.0 ml, 5.0 mmol) is added to this and the mixture is stirred at RT for 18 h. The resulting precipitate is filtered off under I~ and washed first with dioxane (2 x 1 ml) and then with CH2C12 (3 x 1 ml). After drying in vacuo, the title compound (0.04 g) is obtained as colorless crystals.
MS: calc.: C4~H54N12O8 (842.96), found: (MH+] 843.4 4. 3,6-Di-O-i'4-(traps-4-aminomethyl.cyclohexylcarbonyll-1-piperazin~ilcarboriylmethyll-4-O-benzyl-1.2-dideoxy-D-ctlucopyranose dihydrochloride 4-O-Benzyl-3,6-di-O-[4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-1-piperazinyl-carbonylmethyi]-1,2-dideoxy-D-glucopyranose (0.15 g, 0.16 mmol, starting compound A14) is dissolved in dioxane (1.0 ml) at RT. A saturated solution of HCI in dioxane (1.0 ml, 2.5 mmol) is added to this and the mixture is stirred at RT overnight. The resulting precipitate is filtered off under N2 and washed with dioxane (2 x 1 ml). The residue is coevaporated twice with toluene (20 ml) and then three times with CH2C12 (10 ml). After drying in vacuo, the title compound (0.03 g) is obtained as colorless crystals.
MS: calc.: C4~H64N608 (769.00), found: [MH"] 769.4 5. 3 6-Di-O-f4-(4-aminomethylbenzylaminocarbonyi)-1-piperazinylcarbonyll-4-O-benzyl-1 2-dideoxy-D-alucopyranose dihydrochloride 4-O-Benzyl-3,6-di-O-[4-(4-N-tert-butoxycarbonylaminomethylbenzylaminocarbonyl)-1-piperazinyl-carbonyl]-1,2-dideoxy-D-glucopyranose (0.14 g, 0.14 mmol, starting compound A17) is dissolved in dioxane (1.5 ml) at RT. A saturated solution of HCI in dioxane (1.0 ml, 2.5 mmol) is added to this and the mixture is stirred at RT for 4 h. The resulting precipitate is filtered off under N2 and washed first with dioxane (2 x 1 ml) and then with Et20 (3 x 1 ml). The residue is coevaporated with toluene and then with CH2CI2 (2 x 10 ml each). After drying in vacuo, the title compound (0.1 g) is obtained as colorless crystals.
MS: calc.: C4~H54N808 (786.94), found: [MH~] 787.3 6. 3,6-Di-O-f4-(1-amidinopiperidin-4-ylacetyl)-1-piperazinylcarbonyll-4-O-benz~rl-1,2-dideoxy-D-glucop~rranose dihvdrochloride 4-O-Benzyl-3,6-di-O-{4-[1-(N, N'-bis-tert-butoxycarbonylamidino)piperid in-4-ylacetyl]pi perazin-1-yl-carbonyl}-1,2-dideoxy-D-glucopyranose (0.15 g, 0.13 mmol, starting compound A21) is dissolved in dioxane (2.0 ml) at RT. A saturated solution of HCI in dioxane (2.0 ml, 5.0 mmol) is added to this and the mixture is stirred at RT for 4 h. The resulting precipitate is filtered off under NZ .and washed first with dioxane (2 x 1 ml) and then with CH2CI2 (3 x 1 ml). The residue is coevaporated with toluene and then with CH2CI2 (2 x 10 ml each). After drying in vacuo, the title compound (0.07 g) is obtained as colorless crystals.
MS: calc.: C39H6oN1o08~(796.98), found: [MH+] 797.4 General procedure for the preparation ~f the final compounds 7, 8 and 10-27 A solution of the respective Boc-protected bivalent compound (A22, A23, A25-42; 1.0 mmol) in dioxane (7 ml) is treated with a saturated solution of HCI in dioxane (4.3 ml, 19.4 mmol) and stirred at RT for 2-12 h. The resulting precipitate is filtered off under an NZ atmosphere and washed first with dioxane (2 x 5 ml) and then with diethyl ether (3 x 5 ml). After drying in vacuo, the title compounds (final com-pounds 7, 8, 10-27) are obtained as colorless solids.
7. 3,6-Di-O-f4-(trans-4-aminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyll-4-O-benzyl-1.2-dideoxy-D-c alt actopyranose dihydrochloride MS: calc.: C3sHsoNsOs (741.05), found: [MH~] 741.4 8. 3,6-Di-O-f4-(trans-4-aminomethylcyclohexylcarbonyl)-1-pperazinylcarbonyll-1 dideoxy-D-g,alactopyranose dihydrochloride MS: calc.:,,C3zHs4NsOs (650.82), found: [MH+] 651.3 9. 3.6-Di-O-f4-(amidinoindazol-3-ylcarbonyl)-1-piperazinylcarbon~rll-4-O-benzyl-1 2-dideoxv-D-c~lucopyranose The compound prepared according to procedure A24 (0.25 g, 0.182 mmol) is dissolved in a mixture of methanolldichloromethane (8:4.12 ml) at RT and treated with palladinized carbon (10% Pd, 130 mg). It is stirred at RT for 8 h under a hydrogen atmosphere in a recirculating hydrogenation unit. The catalyst is filtered off after uniform reaction (TLC checking) and the solution is concentrated in vacuo. The title compound (0.11 g) is obtained as a colorless solid.
MS: calc.: C4~H4sN~20s (834.90), found: [MH+] 835.4 10. Methyl 3.6-di-O-f4-(trans-4-aminomethylcyclohexylcarbonvl)-1-piperazinylcarbonyll-4-O-benzyl-2-deoxy-a-D-glucopyranoside dihydrochloride MS: calc.: C4pH62N6~9 (770.97), found: [M H'] 771.1 11. Methyl 3.6-di-O-f4-(trans-4-aminomethylcyclohexylcarbonyl)-1-piperazinylcarbonylj-2-deoxy-a-D-g~lucopyranoside dihydrochloride MS: calc.: C33HssNs~s (680.85), found: [MH~] 681.2 -7$- ;," _ 12. 3 6-Di-O-f4-(traps-4-aminomethylcyclohexy(carbonyl)-1-piperazinylcarbonylmethyll-1 2-dideoxv-D-alucopyranose dihydrochloride MS: calc.: C34HsaNsOa (678.88), found: [MH+] 679.4 13. 6-O-f4-(4-Aminomethylbenzylaminocarbonyll-1-piperazinylcarbonyll-3-O-f4-(traps-4-aminomethvlcyclohexylcarbonyl)-1-piperazinylcarbonyll-4-O-benzyl-1 2-dideoxy-D-Ia ucopyranose dihydrochloride MS: calc.: C4~Hs9N~0a (778.00), found: [MH'] 778.4 14. Benz~l 3.6-di-O-f4-(traps-4-aminomethytcyclohexylcarbonyl)-1-piperazinylcarbonyll-2-deoxy-a,-D-qlucopyranoside dihydrochloride MS: calc.: C4sHssNs~s (847.07), found: [MH'] 847.3 15. 3,6-Di-O-f4-(4-aminomethylbenzylaminocarbonyl)-1-piperazinylcarbonylmethyll-4-O-benzyl-1,2-dideoxy-D-glucopyranose dihydrochloride MS: calc.: C43HSSNsOa (814.99), found: [MH+] 815.4 16. 3,6-Di-O-f4-(4-aminomethylbenzylaminocarbonyll-1-piperazinylcarbonylmethyll-1 2-dideoxv-D-glucopyranose dihydrochloride MS: calc.: C3sHszNa~s (724.86), found: [MH'] 725.4 17. 3 6-Di-O-f4-(traps-4-aminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyll-4-O-meth 1.2-dideoxy-D-aalactopyranose dihydrochloride .
MS: calc.: C33HssNsOa (664.85), found: [MH+] 665.4 18, Methyl 2.6-di-O-f4-(traps-4-aminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyll-a-D-gilucopyranoside dihydrochloride MS: calc.: C33HssNsO~o (696.85), found: [MH+] 697.4 19. Methyl 3,6~ii-O-f4-(4-aminomethylbenzylaminocarbonyl)-1=piperazinylcarbonyll-4-O-benzyl-2-deoxy-a-D-alucopyranoside dihydrochloride MS: calc.: C42H56N8Og (816.96), found: [MH'] 817.2 20. Methyl2.6-di-O-f4-(4-aminomethylbenzylaminocarbonyl)-1-piperazinylcarbonyll-34-di-O-benzyl-a-D-alucopyranoside dihydrochloride MS: calc.: C4sHs3N9Os (922.10), found: [MHt] 923.3 21. Methyl 3,6-di-O-f4-(4-aminomethylbenzylaminocarbon ly 1-1-piperazinylcarbonyll-2-deoxy-a-D-alucopyranoside dihydrochloride MS: calc.: C3sHsoNa~s (726.80), found: [MH'] 727.2 22. 6-O-I4-(Traps-4-aminomethylcyclohexylcarbonyl)-1-aminopentyll-3-O-f4-(traps-4-amino-methvlcyclohexylcarbonyl)-1-piperazinylcarbonyll-4-O-benzyl-1.2-dideoxy-D-aluco-pyranose dihydrochloride MS: calc.:.C3sHs3N50~ (713.97), found: [MH'] 714.5 23. 3-O-f4-(Traps-4-aminomethylcyclohexylcarbonyl)-1-piperazinylcarbon~rll-6-O-f5-(2-aminomethylpyridylcarbonyl)-1-aminopentyll-4-O-benzyl-1.2-dideoxy-D-alucopyranose trihydrochloride MS: calc.: C3aH5sN6O7 (708.91 ), found: [MH'] 709.4 24. 6-N-f4-(Traps-4-aminomethvlcyclohexylcarbonyll-4-aminobutyl-4-oxycarbonvll-3-O-f4-(traps-4-aminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyll-4-O-benzyl-1.2-dideoxv-D-glucopyranose dihvdrochloride MS: caic.: C3sHs2NsOa (742.97), found: [MH+] 743.5 25. 6-O-f4-(Traps-4-aminomethylcyclohexylcarbonyll-5-aminopentyll-3-O-f4-(traps-4-amino-methvlcyclohexyicarbonyll-1-piperazinylcarbonyll-1.2-dideoxy-D-gilucopyranose ~ di-hydrochloride MS: calc.: C32Hs~N50~ (623.84), found: [MH'] 624.4 26. 3.6-Di-O-f4-(traps-4-aminomethylcyclohexylcarbonyl)-5-aminopentyll-4-O-benzyl-1.2-dideoxy-D-alucopyranose dihydrochloride MS: calc.: C3sHssNa~s (678.00), found: [MH~] 679.1 - $O - _ 27. 3,6-Di-O-f4-(trans-4.-aminomethylcyclohexylcarbonyl)-5-aminopentvll-1 2-dideoxv-D-alucopyranose dihydrochloride MS: talc.: C32HsoNaOs (596.96), found: [MH+] 597.5 28. 3,6-Di-O-f4-(3-aminomethylbenzoyl)piperazin-1-ylcarbonyll-4-O-benzyl-1.2-dideoxy-D-glucopyranose dihydrochloride A solution of 3,6-di-O-{4-[3-(tert-butyloxycarbonylaminomethyl)benzoyl]piperazin-1-ylcarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (120 mg, 0.13 mmol, starting compound A67) in 2 ml of dioxane is treated with 0.65 ml (2.58 mmol) of 4 N HCI in dioxane and stirred at RT.
After 6 h, 1.3 ml (5.16 mmol) of 4 N HCI in dioxane are added again and the mixture is stirred for a further 15 h. The reaction mixture is concentrated to dryness in a rotary evaporator and additionally coevaporated in succession with toluene, ethanol and carbon tetrachloride. The residue is crystallized from diethyl ether and 90 mg of the title compound are obtained.
MS: talc.: C39HaaNsOa (728.85), found: [MH'] 729.2 29. 3 6-Di-O-f4-(3-aminomethylbenzoylamino)piperidin-1 ylcarbonyll-4-O-benzyl-1.2-dideoxy-D-qlucopyranose dihvdrochloride A solution of 3,6-di-O-{4-[3-(tert-butyloxycarbonylaminomethyl)benzoylamino]piperidin-1-ylcarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (180 mg, 0.19 mmol, starting compound A68) in 4 ml of dioxa-ne is treated with 0.95 ml (3.8 mmol) of 4 N HCI in dioxane and stirred at RT.
After 4.5 h, it is con-centrated to dryness in a rotary evaporator and 3 ml (12.0 mmol) of 4 N HCI in dioxane are added a-gain and the mixture is stirred for a further 15 h. After repeated concentration of the mixture in a rotary evaporator and addition of 3 ml (12.0 mmol) of 4 N HCI in dioxane, it is stirred for_ a further 6 h. The reaction mixture is then concentrated to dryness in a rotary evaporator and additionally coevaporated in succession with toluene, ethanol and carbon tetrachloride. The residue is crystallized from diethyl ether and 100 mg of the title compound are obtained.
MS: talc.: C4~ Hs2N608 (756.91 ), found: [MH'] 757.3 30. 3.6-Di-O-f4-(3-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyll-4-O-benzyl-1.2-dideoxv-D-Aluconyranose dihvdrochloride A solution of 3,6-di-O-{4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-yl-carbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (300 mg, 0.3 mmol, starting compound A69) in 4 ml of dioxane is treated with 1.52 ml (6.1 mmol) of 4 N HCI in dioxane and stirred at RT. After 20 h, - $1 - _ the reaction mixture is concentrated to dryness in a rotary evaporator and additionally coevaporated in succession with toluene, ethanol and carbon tetrachloride. The residue is crystallized from diethyl ether and 130 mg of the title compound are obtained.
MS: calc.: C4,Hs4N80$ (786.94), found: [MH'] 787.2 31. 3,6-Di-O-t4-(3-aminomethylbenzylaminocarbonylamino)piperidin-1-ylcarbonyll-benzvl-1.2-dideoxy-D-glucopyranose dihydrochloride A solution of 3,6-di-O-{4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonylamino]piperidin-1-ylcarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (200 mg, 0.2 mmol, starting compound A70) in 2 ml of dioxane is treated at RT with 1 ml (4.0 mmol) of 4 N HCI in dioxane and stirred for 3 h. The reaction mixture is concentrated to dryness in a rotary evaporator and coevaporated successively with 2 x 30 ml of toluene and 2 x 30 ml of ethanol. The residue is crystallized from diethyl ether and 100 mg of the title compound are obtained.
MS: calc.:,,C43Hs8N808 (814.47), found: [MH'] 815.3 32. 3.6-Di-O-f4-(3-aminomethylbenzylaminocarbonyl)piperidin-1-ylcarbonyll-4-O-benzyl-1 2-dideoxy-D-gilucopyranose dih~rdtochloride A solution of 3,6-di-O-{4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperidin-1-yl-carbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (200 mg, 0.2 mmol, starting compond A71) in 4 ml of dioxane is treated at RT with 2 ml (4.0 mmol) of 4 N HCI in dioxane and stirred for 6 h. The reaction mixture is concentrated to dryness in a rotary evaporator and additionally coevaporated in succession with toluene, ethanol and carbon tetrachloride. The residue is crystallized from diethyl ether and 140 mg of the title compound are obtained.
MS: calc.: C43HssNsOa (784.96), found: [MH'] 785.3 33. 3.6-Di-O-f4-trans-(3-aminomethylbenzylaminocarbonyl)cyclohexylmethylamino-carbonyll-4-O-benzvl-1.2-dideoxy-D-ctlucopyranose dihydrochloride , A solution of 3,6-di-O-{4-trans-[3-(tert-butyloxycarbonylami~omethyl)benzylaminocarbonyl]cyclo-hexylmethylarninocarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (200 mg, 0.19 mmol, starting compound A72) in 2 ml of dioxane is treated at RT with 0.96 ml (3.84 mmol) of 4 N HCI in dioxane and stirred for 1.5 h. The reaction mixture is concentrated to dryness in a rotary evaporator and coevapo-rated successively with 2 x 30 ml of toluene and 2 x 30 ml of ethanol. The residue is crystallized from diethyl ether and 150 mg of the title compound are obtained.

-$2- -- _ MS: calc.: C47H64N6Og (840.51 ), found; [MH~] 841.3 34. 3,6-Di-O-f4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyll-4-O-benzyl-1,2-dideoxy-D-ylucopyranose dihydrochloride 3,6-Di-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose (120 mg, 0.125 mmol, starting compound A73) is treated with 2.0 ml (8.0 mmol) of a 4 N HCI solution in dioxane. The mixture is stirred at RT for 12 h, concentrated, and the residue is coevaporated with 3 x 5 ml of toluene and crystallized from diethyl ether. 92 mg of the title compound of m.p. 152°C are obtained.
MS: calc.: C3gH5phigOg (758.88), found: [MH'] 759.3 35. 3-O-f4-(4-Aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyll-4-O-benzyl-6-O-f4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyll-1,2-dideoxy-D-gluco-pyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-yl-carbonyl}-4-O-benzyl-6-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose (300 mg, 0.31 mmol, starting compound A74) in 2 ml of dioxane and 2 ml of methanol is treated with 2 ml (8.0 mmol) of a 4 N HCI solution in dioxane.
The mixture is stirred at RT for 17 h, concentrated, and the residue is coevaporated with 3x 5 ml of toluene and crystallized from acetone. 182 mg of the title compound of m.p. 170°C are obtained (sintering at 140°C).
MS: calc.: C4oHs2NsOs (772.9), found: [MH''] 773.2 36. 3-O-f4-(4-Aminomethvlbenzylaminocarbonyl)piperazin-1-ylcarbonyll-4-O-benzyl-6-O-f4-(6-amino-2-meth~lpyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbo ill-1,2-dideoxy-D-glucopyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-[4-(6-tert-butyloxycarbonylamino-2-methylpyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose (400 mg, 0.405 mmol, starting compound A75) in 3 ml of methanol is treated with 7 ml (28.0 mmol) of a 4 N HCI solution in dioxane. The mixture is stirred at RT for 20 h, concentrated, and the residue is coevaporated with 2 x 10 ml of toluene and crystallized from acetone.
270 mg of the title compound of m.p. > 220°C are obtained (sintering at 153°C).
MS: calc.: C4~Hs4N808 (786.94), found: [MH'] 787.4 - 83 - _ 37. 3-O-f4-(4-Aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyll-4-O-benzyl-6-O-f4-4-aminobenzylaminocarbonyllpiperidin-1-ylcarbonyll-1.2-dideoxy-D-g~lucopyranose di-hydroch loride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-[4-(4-aminobenzylaminocarbonyl)piperidin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose (65 mg, 0.083 mmol, starting compound A76) in 2 ml of dioxane is treated with 0.4 ml (1.6 mmol) of a 4 N HCI
solution in dioxane. The mixture is stirred at RT for 17 h, filtered under a nitrogen atmosphere and 62 mg of the title compound of m.p. > 220°C are obtained (sintering at 110°C).
MS: calc.: C4,Hg3N7Og (771.9), found: [MH+] 772.3 38. 3-O-[4-(4-Aminomethylbenzyiaminocarbonyl)piperazin-1-ylcarbonyll-4-O-benzyl-6-O-~4-trans-(6-aminopyrid(n-3-ylmethylaminocarbonyl)cyclohexylmethylaminocarbonyll-1 dideoxy-D-glucopyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-[4-trans-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)cyclohexylmethylamino-carbonyl]-1,2-dideoxy-D-glucopyranose (220 mg, 0.22 mmol, starting compound A78) in 2 ml of dioxa-ne and 2 ml of methanol is treated with 3 ml (12.0 mmol) of a 4 N HCI solution in dioxane. The mixture is stirred at RT for 17 h, concentrated, and the residue is coevaporated with 2 x 4 ml of toluene and crystallized from acetone. 107 mg of the title compound of m.p. > 220°C
are obtained (sintering at 170°C).
MS: calc.: C42HssNs08 (800.96), found: [MH'] 801.4 39. 3-O-C4-(4-Aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyfl-4-O-benzyl-6-O-f4-trans-(6-amino-2-methylpyridin-3-ylmethylaminocarbonyl)cyclohexylm~thylamino-carbonyll-1.2-dideo~r-D-glucopyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4.-O-benzyl-6-O-[4-trans-(6-tert-butyloxycarbonylamino-2-methylpyridin-3-ylmethylaminocarbonyl)cyclohexyl- .
methylaminocarbonyl]-1,2-dideoxy-D-glucopyranose (750 mg, 0.74 mmol, starting compound A79) in 1 ml of methanol is treated with 5 ml (20.0 mmol) of a 4 N HCI solution in dioxane. The mixture is stir-red at RT for 17 h, concentrated, and the residue is coevaporated with 2 x 10 ml of methanol and crystallized from acetone. 550 mg of the title compound of m.p. 206-214°C are obtained.
MS: calc.: C43HsaNeOa (814.99), found: [MH'] 815.4 40. 3-O-f4-(4-Aminomethylbenzylaminocarbonyl)-piperazin-1-ylcarbonyll-4-O-benzyl-6-O-~4-trans-(4-aminobenzylaminocarbonyl)-cyclohexylmethylaminocarbonyll-1 2-dideoxy-D-ctlucopyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-[4-trans-(4-aminobenzylaminocarbonyl)cyclohexylmethylaminocarbonyl]-1,2-dideoxy-D-gluco-pyranose (155 mg, 0.172 mmol, starting compound A80) in 4 ml of dioxane is treated with 0.86 ml (3.44 mmol) of a 4 N HCI solution in dioxane. The mixture is stirred at RT for 2 h, filtered under a nitro-gen atmosphere and 135 mg of the title compound are obtained.
MS: calc.: C43,HS~N~O$ (800.0), found: [MH'] 800.2 41. 3-O-f4-(4-Aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyll-4-O-benzyl-6-O-f3-(4-aminobenzylaminocarbonyllbenzylaminocarbonyll-1,2-dideoxy-D-glucopyranose di-hydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonylJpiperazin-1-ylcarbonyl}-4-O-benzyl-6-O-[3-(4-aminobenzylaminocarbonyl)benzylaminocarbonylJ-1,2-dideoxy- D-glucopyranose (130 mg, 0.145 mmol, starting compound A82) in 3 ml of dioxane is treated with 0.73 ml (2.92 mmol) of a 4 N
HCI solution in dioxane. The mixture is stirred at RT for 2 h, filtered under a nitrogen atmosphere and 121 mg of the title compound of m.p. 190-194°C are obtained.
MS: calc.: C43H51N~08 (793.9), found: [MH+] 774.2 42. 3-O-f4-(4-Aminomethvlbenzylaminocarbonyl)niaerazin-1-ylcarbon~rll-4-O-benzyl-6-O-~4-!3-(imidazol-1-yl)propylaminocarbonyllpiperidin-1-ylcarbonyl3-1,2-dideoxy-D-aluco-pyranose dih~rdrochloride 3-O-[4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-{4-[3-(imidazol-1-yl)propylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose (460 mg, 0.52 mmol, starting compound A84) in 1 ml of dioxane and 2 ml of methanol is treated with 3.9 ml (15.6 mmol) of a 4 N HCI solution in dioxane. The mixture is stirred at RT for 2 h, concentrated, and the residue is coevaporated with 2 x 10 ml of toluene and crystallized from diethyl ether. 350 mg of the title compound are obtained as a colorless oil.
MS: calc.: C4oH54N808 (774.9), found: [MH+] 775.4 -$5- . _ 43. 3-O-f4-(4-Aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyll-4-O-benzyl-6-O-(4-[4-(imidazol-1-y!)-butylaminocarbonvllpiperidin-1-ylcarbonyl~-1.2-dideoxv-D-ctluco-gyranose dihydrochloride 3-O-(4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl -6-O-{4-[4-(imidazol-1-yl)butylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose (500 mg, 0.56 mmol, starting compound A85) is treated with 2.8 ml (11.2 mmol) of a 4 N HCI solution in dioxane. The mixture is stirred at RT for 7 h, concentrated, and the residue is coevaporated with 2 x 10 ml of toluene and crystallized from diethyl ether. 430 mg of the title compound of m.p. 200°C are obtained (sintering from 116°C).
MS: calc.: C4,HS6NgO$ (788.9), found: jMH+] 789.3 44. 3-O-f4-(4-Aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbon~rll-4-O-benzyl-6-O-f4-(5-(imidazol-1-yl)penty(aminocarbonyllpiperidin-1-vlcarbonyf)-1.2-dideoxy-D-gluco-pyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-{4-[5-(imidazol-1-yl)pentylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose (680 mg, 0.75 mmol, starting compound A86) is treated with 3.7 ml (14.8 mmol) of a 4 N HCI solution in dioxane. The mixture is stirred at RT for 7 h, concentrated, and the residue is coevaporated with 2 x 10 ml of toluene and crystallized from diethyl ether. 490 mg of the title compound of m.p. 202°C are obtained (sintering from 116°C).
MS: calc.: C42HS8N80$ (802.98) found: [MH+] 803.3 45. 3-O-f4-(4-Aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyll-4-O-benzvl-6-O-f4-f6-(imidazol-1-yl)hexytaminocarbonyllpiperidin-1-ylcarbon~}-1,2-dideoxy-D-aluco-pyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl}benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-{4-[6-(imidazol-1-yl)hexylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose (600 mg, 0.65 mmol, starting compound A87) is treated with 2.45 ml (9.8 mmol) of a 4 N HCI solution in dioxane. The mixture is stirred at RT for 2 h, concentrated, and the residue is coevaporated with 2 x 10 ml of toluene and crystallized from diethyl ether. 460 mg of the title compound of m.p. 202°C are obtained (sintering from 125°C).
MS: calc.: C43H6oNeOs (817.0), found: [MH+] 817.4 -86- . _ 46. 3-O-f4-(4-Aminomethylbenzylaminocarbonyl)niperazin-1-ylcarbonyll-4-O-benzyl-6-O-~4-[8-(imidazol-1-yl)octylaminocarbonyllpiperidin-1-ylcarbonyl~~-1,2-dideoxy-D-aluco-eyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-{4-[8-(imidazol-1-yl)octylaminocarbonyljpiperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose (520 mg, 0.55 mmol, starting compound A88) is treated with 2.06 ml (8.24 mmol) of a 4 N HCI solution in dioxane. The mixture is stirred at RT for 4 h, concentrated, and the residue is coevaporated with 2 x ml of toluene and crystallized from diethyl ether. 400 mg of the title compound of m.p. 205°C are obtained (sintering from 99°C).
MS: talc.: C4sHsaNsOs (845.0), found: [MH+] 845.4 47. 3-O-f4-(6-Aminopyridin-3-ylmethylaminocarbonyl)-piaeridin-1-ylcarbon~rll-6-O-~4-f4-trans-(aminomethyl)cyclohexylcarbonyllaminobut-1-ylaminocarbon~ll-4-O-benzyl-1 dideoxy-D-dlucopyranose dihydrochloride 3-O-[4-(6-tent-Butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonylj-6-O-{4-[4-trans-(tert-butyloxycarbonylaminomethyl)cyclohexylcarbonyl]aminobut-1-ylaminocarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (110 mg, 0.11 mmol, starting compound A89) is stirred at RT for 3 h in 0.9 ml (3.6 mmol) of 4 N HCI in dioxane. The mixture is concentrated and the residue is coevaporated successively with 2 x 10 ml of toluene and 2 x 10 ml of ethanol. The residue is crystallized from diethyl ether and 61 mg of the title compound of m.p. > 220°C are obtained.
MS: talc.: C39Hs~N~08 (751.46), found: [MH''] 752.3 48. 3-O-f4-(6-Aminopyridin-3-vlmethylaminocarbonyllpiperidin-1-vlcarbon3r11-6-O-[4-(4-aminomethylbenzylaminocarbonyl)piuerazin-1-ylcarbonyll-4-O-benzyl-1-.2-dideoxy-D-alucopyranose dihydrochloride 3-O-[4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethylamino-carbonyl)piperidin-1-ylcarbonyl]-6-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-1,2-di-deoxy-D-glucopyranose (160 mg, 0.164 mmol, starting material A90) is stirred at RT for 4 h in 1.25 ml (5.0 mmol) of 4 N HCI in dioxane. The mixture is concentrated and the residue is coevaporated suc-cessively with 2 x 10 ml of toluene and 2 x 10 ml of ethanol. The residue is crystallized from diethyl ether and 137 mg of the title compound of m.p. > 220°C are obtained.
MS: talc.: C4oHs2NaOa (772.42), found: [MH'] 773.3 49. 3-O-I4-(4-Aminomethylbenzylaminocarbonyl)piperazin-1-ytcarbonyll-6-O-f2-(6-amino-pyridin-3-ylmethylaminocarbonyl)eth-1-yl-aminocarbon~rll-4-O-benzyl-1 2-dideoxy-D-glucopyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyljpiperazin-1-yl-carbonyl}-4-O-benzyl-6-O-[2-(6-aminopyridin-3-ylmethylaminocarbonyl)eth-1-yl-aminocarbonylj-1,2-dideoxy-D-glu-copyranose (350 mg, 0.42 mmol, starting compound A91 ) is stirred at RT for 2.5 h in 2 ml of 4 N HCI.
The mixture is concentrated, and the residue is coevaporated successively with 2 x 10 ml of toluene and with 2 x 10 ml of ethanol and crystallized from diethyl ether. 270 mg of the title compound are ob-tained.
MS: calc.: C37H4gNgOg (732.39), found: [MH'j 733.3 50. 3-O-f4-(4-Aminomethylbenzylaminocarbonyl)piperazin-1-~rlcarbonyll-4-O-benzyl-6-O-f3-[(6-amidino-1-H-indazol-3-yl)carbonylaminolprop-1-ylaminocarbonyl}-1 2-dideoxy-D-alucopyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyljpiperazin-1-ylcarbonyl}-4-O-benzyl-6-O-{3-[(6-amidino-1-H-indazol-3-yl)carbonylaminojprop-1-ylaminocarbonyl}-1,2-dideoxy-D-gluco-pyranose (200 mg, 0.22 mmol, starting compound A92) in 5 ml of methanol is treated with 1 ml (1.0 mmol) of 4 N HCI and stirred at RT for 16 h. The mixture is concentrated, and the residue is coe-vaporated with 2 x 10 ml of toluene and crystallized from acetone. 127 mg of the title compound are obtained.
MS: calc.: C3~H48N808 (798.38), found: [MHFj 799.3 51. 3-O-I4-(4-Aminomethylbenzylaminocarbonyl)piperazin-1-y(carbonyll-4-O-benzyl-6-O-~3-I(6-aminocarbonyl-1-H-indazol-3-yl)carbonylaminolprop-1-ylaminocarbonyt~-1 2-di-deoxy-D-c~lucopyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyljpiperazin-1-ylcarbonyl}-4-O-benzyl-6-O-{3-[(6-aminocarbonyl-1-H indazol-3-yl)carbonylaminojprop-1-ylaminocarbonyt}-1,2-dideoxy-D- .
glucopyranose (22 mg, 0.022 mrnol, starting compound A93) in 2 ml of methanol is treated with 0.5 ml (1.0 mmol) of 4 N HCI and stirred at RT for 16 h. The mixture is concentrated and the residue is coeva-porated with 2 x 10 ml of toluene and crystallized from acetone. 2 mg of the title compound are obtai-ned. , MS: calc.: C3~H48N808 (799.37), found: [MH~] 800.3 - $$ - _ 52. 3-O-[4-(4-Aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyll-6-O-~2-[(6-amino-carbonyl-1-H-indol-3-yllcarbonylaminoleth-1-ylaminocarbonyl)-1 2-dideoxy-D-aluco=
nyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-6-O-{2-((6-aminocarbonyl-1-H-indol-3-yl)carbonylamino]-eth-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose (190 mg, 0.17 mmol, starting compound A94) is stirred at RT for 4 h in 10 ml of 4 N HCI. The mixture is concentrated, and the residue is coevaporated with 2 x 50 ml of toluene and crystallized from diethyl ether. 122 mg of the title compound are obtained.
MS: talc.: C3~H48N80$ (694.13), found: [MH~] 695.2 53. 3-O-[4-(4-Aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyll-4-O-benzyl-6-O-f3-[(6-aminocarbonyl-1-H-indol-3-yl)carbonylamino]prop-1-ylaminocarbonyl}-1 2-dideox rL-D-glucopyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)-benzylaminocarbonyl]piperazin-1-ylcarbonyl}-6-O-{3-[(6-aminocarbonyl-1-H-indol-3-yl)carbonylamino]prop-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose (180 mg, 0.2 mmol, starting compound A95) is stirred at RT for 8 h in 20 ml of 4 N HCI. The mixture is concentrated, and the residue is coevaporated with 2 x 50 ml of toluene and crystallized from diethyl ether. 117 mg of the title compound are obtained.
MS: talc.: C3~H48Na0$ (798.37), found: [MH'] 799.1 54. 3-O-[4-(4-Aminomethylbenzylaminocarbonyl)pinerazin-1-ylcarbonyll-4-O-Benz I-y 6,-O-{4-L(6-aminocarbonyl-1-H-indol-3-yl)carbonylaminolbut-1-ylaminocarbonyl3-1 2-dideoxy-D-glucopyranose 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-{4-((6-aminocarbonyl-1-H-indol-3-yl)carbonylamino]but-1-ylaminocarbonyl}-1,2-dideoxy-D-glu-copyranose (270 mg, 0.29 mmol, starting compound A96) is stirred at RT for 4 h in 20 ml of 4 N HCI .
The mixture is concentrated and the residue is coevaporated with 2 x 50 ml of toluene and crystallized from diethyl ether. 243 mg of the title compound are obtained.
MS: talc.: C3~H4gNgOg (812.39), found: [MH+] 813.4 - 89 _ _ 55. 6-O-(4-(6-Aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyll-3-O-f2-(4-trans-aminomethvlcyclohexylcarbonyiamino)eth-1-ylaminocarbonyll-4-O-benzyl-1 2-dideox,~r-D-alucopyranose dihydrochloride A suspension of 6-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-3-O-{2-[4-trans-(tert-butyioxycarbonylaminomethyl)cyclohexylcarbonylamino]eth-1-yl-aminocarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A157, 170 mg, 0.18 mmol) in 1.4 ml (5.5 mmol) of 4 M HCI in dioxane is stirred at RT for 4 h. The reaction mixture is concentrated to dry-ness and coevaporated in succession with toluene and ethanol. The residue is washed with diethyl ether with stirring and 96 mg of the title compound are obtained.
MS: calc.: C3~H53N~0$ (723.39), found: [MH'] 724.3 56. 6-O-f4-(6-Aminopyridin-3-vlmethylaminocarbonyl)piperidin-1-ylcarbonyll-3-O-f3-(4-trans-aminomethvlcyclohexylcarbonylamino)prop-1 ylaminocarbonyll-4-O-benzyl-1 2-dideoxv-D-g~lucopyranose dihydrochloride A suspension of 6-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-3-O-{3-[4-trans-(tert-butyloxycarbonylaminomethyl)cyclohexylcarbonylamino]prop-1-yl-aminocarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A158, 140 mg, 0.15 mmol) in 1.1 ml (4.4 mmol) of 4 M HCI in dioxane is stirred at RT for 6 h. The reaction mixture is concentrated to dry-ness and coevaporated in succession with toluene and ethanol. The residue is washed with diethyl ether with stirring and 82 mg of the title compound are obtained.
MS: calc.: C38HSSN~O$ (737.41), found: [MH+] 738.3 57. 6-O-f4-(6-Aminopyridin-3-ylmethylaminocarbon~l,]piperidin-1-ylcarbonyll-3-O-f4-(4-trans-aminomethvlcyclohexylcarbonylamino)but-1-ylaminocarbonyll-4-O-benzyl-1 2-dideoxY
D-alucopyranose dihydrochloride A suspension of 6-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-3-O-{4-[4-traps-(tert-butyloxycarbonylaminomethyl)cyclohexylcarbonylamino]but-1-yl-aminocarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A159, 80 mg, 0.084 mmol) in 0.65 ml (2.6 mmol) of 4 M HCI in dioxane is stirred at RT for 6 h. The reaction mixture is concentrated to dry-ness and coevaporated in succession with toluene and ethanol. The residue is washed with diethyl ether with stirring and 38 mg of the title compound are obtained.
MS: calc.: C3gH57N7Og (751.43), found: [MHO] 752.3 58. 6-O-[4-(3-Aminomethylbenzoyl)piperazin-1-ylcarbonyll-3-O-f4-(6-amino~yridin-3-vl-methYlaminocarbonyllaiperidin-1-ylcarbonyll-4-0-benzyl-1 2-dideoxy-D-alucoayranose dihydrochloride A solution of 6-O-{4-[3-(tert-butyloxycarbonylaminomethyl)benzoyl]piperazin-1-ylcarbonyl}-3-O-[4-{6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A160, 110 mg, 0.12 mmol) in 2 ml of dioxane is treated at RT with 2.5 ml (10.0 mmol) of 4 M HCI in dioxane and stirred for 5 h. The reaction mixture is concentrated to dryness and the residue is coevaporated in succession with toluene and ethanol. It is crystallized from diethyl ether and 60 mg of the title compound are obtained.
MS: talc.: C39H49N~08 (743.36), found: [MH+] 744.3 59. 6-O-f4-(3-Aminomethylbenzoylamino)piperidin-1-ylcarbonyll-3-O-f4-(6-aminopyridin-3 ylmethylaminocarbonyl)piperidin-1-ylcarbonyll-4-O-benzyl-1 2-dideoxy-D giluco p~rranose dihydrochloride A solution of 6-O-{4-[3-(tert-butyloxycarbonylaminomethyl)benzoylamino]piperidin-1-ylcarbonyl}-3-O-[4-(6-tert-butyioxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4.-O-benzyl-1,2-dideoxy-D-glucopyranose (A161, 130 mg, 0.14 mmol) in 2 ml of dioxane is treated at RT with 1.7 ml (6.8 mmol) of 4 M HCI in dioxane and stirred for 5.5 h. The reaction mixture is concentrated to dryness and the residue is coevaporated in succession with toluene and ethanol. It is crystallized from diethyl ether and 100 mg of the title compound are obtained.
MS: talc.: C4pH5~N7Og (757.38), found: [MH~] 758.2 60. 6-O-f4-(3-Aminomethylbenzylaminocarbonyl)piperidin-1-ylcarbonyll-3-O-f4-(6-amino-pyridin-3-ylmethylaminocarbonyllpiperidin-1-ylcarboyrll-4-O-benzyl-1 2-dideoxy-D-alucopyranose dihydrochloride A solution of 6-O-{4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperidin-1-ylcarbonyl}-3-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O- .
benzyl-1,2-dideoxy-D-glucopyranose (A162, 150 mg, 0.15 mmol) in 2 ml of dioxane is treated at RT
with 1.6 ml (6.4 mmol) of 4 M HCI in dioxane and stirred for 3 h. The reactian mixture is concentrated to dryness and the residue is coevaporated in succession with toluene and ethanol. It is crystallized from diethyl ether and 100 mg of the title compound are obtained.
MS: talc.: C4~H53N~Og (771.40), found: [MH+] 772.3 61. 6-O-f4-trans-(3-Aminomethvlbenzylaminocarbonyllcyclohexylmethvlaminocarbonvlt-3-O-(4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-~,L,carbonyll-4-O-benzvl-1 2-dideoxy-D-glucopyranose dihydrochloride A suspension of 6-O-{4-trans-[3-{tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]-cyclohexylmethylaminocarbonyl}-3-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbon-yl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A163, 110 mg, 0.11 mmol) in 2 ml of dioxane is treated at RT with 4.4 ml (17.6 mmol) of 4 M HCI in dioxane and stirred for 24 h. The reaction mixture is concentrated to dryness and the residue is coevaporated in succession with toluene and ethanol. It is crystallized from diethyl ether and 70 mg of the title compound are obtained.
MS: calc.: C43HS~N~Oa (799.43), found: [MH+]800.3 62. 6-O-(4-(3-Aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyll-3-O-f4-(6-amino-pyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyll-4-O-bend-1 2-dideoxy-D-alucopyranose dihydrochloride A solution of 6-O-{4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-3-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbon-yl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A164, 130 mg, 0.13 mmol) in 2 ml of dioxane is treated at RT with 1.0 ml (4.0 mmol) of 4 M HCI in dioxane and stirred for 4 h. The reaction mixture is concentra-ted to dryness and the residue is coevaporated in succession with toluene and ethanol. It is crystallized from diethyl ether and 100 mg of the title compound are obtained.
MS: calc.: C4oH52N808 (772.39), found: [MH+] 773.3 63. 6-O-f4-(3-Aminomethylbenzylaminocarbonylamino)piperidin-1-ylcarbon_y11-3-O-f4-(6-aminoayridin-3-ylmethvlaminocarbonyllpiperidin-1-ylcarbonyll-4-O-benzyl-1 2-dideoxy-D-gluco~wranose dihvdrochloride A solution of 6-O-{4-[3-(tent-butyloxycarbonylaminomethyl)benzylaminocarbonylamino]piperidin-1-ylcarbonyl}-3-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcar-bonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A165, 120 mg, ~.12 mmol) in 2 ml of dioxane is trea-ted at RT with 3.0 ml (12.0 mmol) of 4 M HCI in dioxane and stirred for 6 h.
The reaction mixture is concentrated to dryness and the residue is coevaporated in succession with toluene and ethanol. It is crystallized from diethyl ether and 80 mg of the title compound are obtained.
MS: calc.: C4~H$4Ns0$ (786.41), found: [MH+].787.3 -92- .. , Starting compounds: _ A1. 3 6-Di-O-tert-butyldimethylsilyl-1.2-dideoxy-D-alucopyranose 1,2-Dideoxy-D-glucopyranose (3 g, 20.27 mmol) is dissolved in absolute DMF
(150 ml) at RT and treated with imidazole (6.81 g, 100 mmol). tert-Butyldimethylsilyl chloride (7.84 g, 52 mmol) is then added and the mixture is stirred overnight. A little MeOH (10 ml) is slowly added and the mixture is stirred for 15 min. The reaction solution is diluted with semisaturated aqueous NH4CI solution (150 ml) and extracted with EA (3 x). The combined organic phases are dried over MgS04, filtered and con-centrated in vacuo. Further purification is carried out by means of chromatography [PEIEA (20:1)] on a silica gel column and yields the title compound (4.3 g) as a colorless highly liquid oil. TLC, silica gel (glass plates), [PE/EA (19:1)], Rf=0.35 A2. 4-O-Benzvl-3.6-di-O-tert-butyldimethylsilyl-1 2-dideoxy-D-alucoayranose 3,6-Di-O-tert-butyldimethylsilyl-1,2-dideoxy-D-glucopyranose (3.3 g, 8.76 mmol) is dissolved in abs.
DMF (50 ml) at RT. Benzyl bromide (1.65 ml, 14 mmol) and then NaH (0.7 g, 17.5 mmol, 60% strength) are added to this solution. It is stirred at RT for 15 h. Next, 5 ml of MeOH
are added and the mixture is stirred further for 15 min. The reaction mixture is then treated with semisaturated aqueous NH4C1 solu-tion and extracted with ethyl acetate (3x). The combined organic phases are dried over MgS04, filtered and concentrated in vacuo. The title compound (4.62 g), a slightly brown oil, is obtained as a crude product. The title compound is employed in the next stage without further purification.
A3. 4-O-Benzyl-1.2-dideox~r-D-alucopyranose 4-O-Benzyl-3,6-di-O-tert-butyldimethylsilyl-1,2-dideoxy-D-glucopyranose (1.3 g, 2.57 mmol) is dissol-ved in abs.THF (25 ml) at RT and treated with tetrabutylammonium fluoride (5 ml, 5 mmol). The mixtu-re is stirred overnight and then diluted with semisaturated aqueous NH4CI
solution (25 ml). It is extrac-ted with ethyl acetate (3 x) and the combined organic phases are dried over MgS04. The solution is filtered and concentrated in vacuo. After purification by means of chromatography [toluenelacetone (7:3)] on a silica gel column, the title compound (0.37 g) is obtained as colorless crystals. TLC, silica gel (glass plates), [toluenelacetone (7:3)], Rf= 0.28 . .
A4. 4-O-Benzyl-3,6-di-O-f4-(N-tert-butoxycarbonyl)-1-aiaerazinylcarbonyll-1 2-dideoxy-D-alu-copyranose A 20% strength solution of phosgene in toluene (21 ml, 49.5 mmol) is initially introduced and cooled to an internal temperature of-18°C. 4-O-benzyl-1,2-dideoxy-D-glucopyranose (4 g, 16.8 mmol) is dissol-ved in CH2C12 (10 ml) and slowly added dropwise. The mixture is stirred at RT
for 10 min. After the addition of H20 (10 ml), the organic phase is separated off and washed with H20 (1 x). It is dried over MgS04, filtered and concentrated in vacuQ. The residue obtained is dissolved in CH2CI2 (40 ml), cooled to 0°C and then treated with DIPEA (5.6 ml, 32.7 mmol) and DMAP (1.77 g, 14.6 mmol). 1-terk-Butoxycarbonylpiperazine (1.54 g, 8.27 mmol) is then added in portions to the reaction solution. It is stirred at RT overnight. The reaction solution is filtered through AI203, washed with CH2CI2 (2 x 10 ml) and concentrated in vacuo. Furkher purification by means of chromatography [toluenelacetone (7:3)] on a silica gel column affords the title compound (8.57 g) as a colorless powder.
TLC, silica gel (glass plates), [toluenelacetone (7:3)], Rf= 0.5.
A5. 4-O-Benzvl-1,2-dideoxy-3,6-di-O-(1-piperazinylcarbonyl)-D-c~lucopyranose dihydrochloride A solution of 4-O-benzyl-3,6-di-O-[4-(N-tert-butoxycarbonyl)-1-piperazincarbonyl]-1,2-dideoxy-D-glu-copyranose (8 g, 12 mmol) in dioxane (30 ml) is treated with a saturated solution of HCI in dioxane (50 ml, 225 mmol) and stirred overnight at RT. The resulting precipitate is allowed to settle and the supernatant dioxane is decanted off from the reaction mixture. The precipitate is washed a number of times (3 x) with CH2CI2 (7 ml) and then dried in vacuo. The title compound (6.9 g) is obtained as colorless crystalls.
A6. 4-O-Benzvl-3.6-di-O-f4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl.)-1-piperazinylcarbonyll-1.2-dideoxy-D-alucopyranose trans-4-N-Tert-butoxycarbonylaminomethylcyclohexancarboxylic acid (1.31 g, 5.1 mmol) and HOBT
(0.70 g, 5.1 mmol) are added to a solution of 4-O-benzyl-1,2-dideoxy-3,6-di-O-(1-piperazinylcarbonyl)-D-glucopyranose dihydrochloride (1.24 g, 2.68 mmol) in CH2C12 (25 ml) and Et3N
(1.5 ml). The solution is stirred at RT for 10 min, treated with EDC (0.97 g, 5.1 mmol) and stirred for a further 12 h. The reac-tion solution is filtered through AI203 and concentrated in vacuo. The residue is taken up in ethyl ace-tate, undissolved constituents are filtered off and the filtrate is concentrated again in vacuo. Further purification is carried out by means of chromatography [toluene/acetone (7:3)]
on a silica gel column and affords the title compound (1.13 g) as a colorless powder. TLC, silica gel (glass plates), [toluene/
acetone (6:4)], Rf = 0.30 A7. 3.6-Di-O-f4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-1-piperazinyl-carbonvll-1.2-dideoxy-D-ctluconyranose 4-O-Benzyl-3,6-di-O-[4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)piperazin-1-yl-carbonyl]-1,2-dideoxy-D-glucopyranose (0.15 g, 0.16 mmol) is dissolved in abs.
MeOH (10 ml) at RT
and treated with palladinized carbon (10% Pd, 100 mg). The mixture is stirred at RT for 3 h under a hydrogen atmosphere in a recirculating hydrogenation unit. The catalyst is filtered off after uniform reaction (TLC checking) and the solution is concentrated in vacuo. Further purification is carried out by means of chromatography [toluenelacetone (1:1 )] on a silica gel column and affords the title compound (0.08 g) as a colorless resin. TLC, silica gel (glass plates), [toluene/acetone (6:4)], Rf= 0.20 MS: talc.: C42H~oNs0~2 (851.06), found: [MH+] 850.9 A8. 4-(N-tert-Butoxycarbonylamino)benzylamine 4-Aminobenzylamine (20 g, 0.163 mol) is suspended in water (150 ml) at RT, treated with citric acid (34.4 g, 0.179 mol) and stirred for 30 min. A solution of di-tert-butyl dicarbonate (35.7 g, 0.163 mol) in dioxane (60 ml) is added dropwise to this. The mixture is stirred at RT for 2 days. The solution is ad-justed to pH 9.5 using saturated aqueous Na2C03 solution. It is extracted a number of times with CH2CI2 (10 x 20 ml), concentrated in vacuo and coevaporated three times with toluene. The title com-pound (23 g) is obtained as a pale brown amorphous powder. TLC, amino phases (glass plates), [toluenelacetone (6:4)J, Rf= 0.57 A9. 4-O-Benzvl-3,6-di-O-f'4-f4-(N-tert-butoxycarbonylamino'Ibenzylcarbamoylll-1-piperazinyl-carbonyl~-1,2-dideoxy-D-glucoayranose 4-(N-tert-Butoxycarbonylamino)benzylamine (1.0 g, 4.5 mmol) is dissolved in CH2CI2 (10 ml) at RT, treated with triphosgene (0.49 g, 1.65 mmol) and cooled to 0°C. A
solution of DIPEA (0.9 ml, 9.9 mmol) in CH2C12 (1 ml) is slowly added dropwise to the reaction solution and the mixture is stirred at RT for 20 min. A solution of 4-O-benzyl-1,2-dideoxy-3,6-di-O-(1-piperazinylcarbonyl)-D-glucopyranose dihydrochloride (1.0 g, 1.87 mmol, starting compound A5) in CH2C12 (30 ml) and DIPEA (2.0 ml, 22 mmol) is then slowly added dropwise and the mixture is stirred for a further 60 min. The solution is then concentrated in vacuo. Purification by means of chromatography [toluenelacetone (55:45)] on a silica gel column affords the title compound (0.40 g) as a slightly brown solid. TLC, silica gel (glass plates), [toluene/acetone (55:45)], Rf= 0.43 A10. 3.6-Di-O-f4-(4-aminobenz)rlcarbamoyl)-1-aiaerazinylcarbon3r11-4-O-benzyl-1.2-dideox~ D-alucopyranose dihydrochloride _ 4-O-Benzyl-3,6-di-O-{4-[4-(N-tert-butoxycarbonylamino)benzylcarbamoyl]piperazin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose (0.4 g, 0.42 mmol) is dissolved in dioxane (3.0 ml) at RT. A saturated soluti-on of HCI in dioxane (3.0 ml, 7.5 mmol) is added to this and the mixture is stirred at RT for 3 h. The resulting precipitate is filtered off under t~ and washed first with dioxane (2 x 1 ml) and then with CH2C12 (3 x 1 ml). After drying in vacuo, the title compound (0.34 g) is obtained as a colorless powder.
MS: talc.: C39HsoNsOs (758.88), found: [MH+] 759.34 - 95 - _ A11. 4-O-Benzyl-3,6-di-O-f4-(4-(N.N'-bi -tert-butoxycarbonylguanidino)benzylaminocarbonyll-1-p~erazinylcarbonyll-1,2-dideoxy-D-alucoayranose dihydrochloride A solution of 3,6-di-O-[4-(4-aminobenzylcarbamoyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose dihydrochloride (0.34 g, 0.41 mmol) in DMF (5.0 ml) and Et3N
(0.45 ml, 3.28 mmol) is treated with N,N'-bis(tert-butoxycarbonyl)-S-methyiisothiourea (0.26 g, 0.9 mmol) and HgCl2 (0.25 g, 1.0 mmol) at RT. After stirring for 12 h, the reaction solution is diluted with ethyl acetate (2 ml) and filtered off with suction through kieselguhr. The filtrate is extracted with H20 (5 x 2 ml), and the organic phase is dried over MgS04, filtered and concentrated in vacuo. Further purification is carried out by means of chromatography [toluenelacetone (7:3)] on a silica gel column and affords the title compound (0.30 g) as a pale brown powder. TLC, silica gel (glass plates), [toluene/acetone (1:1)], Rf= 0.43 A12. 4-O-Benzyl-3,6-di-O-(4-tert-butoxycarbonyl-1-piperazinylcarbonylmethyl)-1 Z-dideoxy-D-glucopyranose 1-tert-Butoxycarbonylpiperazine (1.09 g, 5.8 mmol) and HOST (0.79 g, 5.8 mmol) are added to a solu-tion of4-O-benzyl-3,6-di-O-carboxymethyl-1,2-dideoxy-D-glucopyranose (0.94 g, 2.65 mmol) in CH2C12 (20 ml) and Et3N (0.8 ml). The solution is stirred at RT for 10 min, treated with EDC (1.12 g, 5.8 mmol) and stirred at RT for a further 3 h. The reaction solution is extracted with water (3 x 5 ml), and the or-ganic phase is dried over MgS04, filtered and concentrated in vacuo. Further purification is carried out by means of chromatography [toluenelacetone (7:3)] on a silica gel column and affords the title com-pound (0.9 g) as a colorless resin.
MS: calc.: C35HsaNaO,o (690.84), found: [MH+] 691.5, [MH4+] 708. 5 A13. 4-O-Benz-1.2-dideoxy-3.6-di-O-(1-pinerazinylcarbonylmethyl)-D-glucoayranose dihydrochloride 4-O-Benzyl-3,6-di-O-(4-tert-butoxycarbonylpiperazin-1-ylcarbonylmethyl)-1,2-dideoxy-D-glucopyranose (0.89 g, 1.23 mmol) is dissolved in dioxane (2.0 ml) at RT. A saturated solution of HCI in dioxane (4.0 ml, 10 mmol) is added to this and the mixture is stirred at RT for 5 h. The resulting precipitate is filtered under N2 and washed first with dioxane (2 x 1 ml) and then with Et20 (3 x 1 ml). After drying in vacuo, the title compound (0.89 g) is obtained as colorless crystalls.
MS: calc.: C25H38N4O6 (490.6), found: [MH+] 491.3 A14. 4-O-Benzyl-3,6-di-O-f4-(traps-4-N=tert-butoxycarbonylaminomethylc clue ohex~rlcarbonyl~-1-piperazinylcarbon~rlmethyll-1,2-dideoxy-D-glucopyranose traps-4-(N-tent-Butoxycarbonylaminomethyl)cyclohexanecarboxylic acid (0.89 g, 3.16 mmol) and HOBT
(0.43 g, 3.16 mmol) are added to a solution of 4-O-benzyl-1,2-dideoxy-3,6-di-O-(1-piperazinylcarbonylmethyl)-D-glucopyranose dihydrochloride (0.89 g, 1.58 mmol) in CH2C12 (15 ml) and Et3N (0.9 ml). The solution is stirred at RT for 10 min, treated with EDC
(0.60 g, 3.16 mmol) and stirred for a further 5 h. The reaction solution is diluted with ethyl acetate (10 ml) and extracted with water (2 x ml). The organic phase is dried over MgS04, filtered and concentrated in vacuo. Further purification is carried out by means of chromatography (toluenelacetone (1:1)] on a silica gel column and affords the title compound (0.50 g) as a colorless powder. TLC, silica gel (glass plates), [toluene/acetone (4:6)], Rf=0.48 MS: calc.: CS~H8oN60~2 (969.24), found: [MH+] 969.1 A15. 4-O-Benzyl-1.2-dideoxy-3.6-di-O-methoxycarbonylmethyl-D-glucopyranose 4-O-Benzyl-1,2-dideoxy-D-glucopyranose (6.0 g, 25.2 mmol) is dissolved in 100 ml of dioxane and, after the addition of NaH (10.0 g, 252 mmol), heated to reflux for 2 h. The mixture is then cooled to 0°C
and methyl bromoacetate (23.1 ml, 252 mmol) is added. The mixture is stirred at RT for 4 days. The reaction solution is then neutralized with methanolic HCI, the precipitate is filtered off and the filtrate is concentrated in vacuo. The residue is taken up in ethyl acetate, undissolved constituents are filtered off and the filtrate is again concentrated in vacuo. Further purification by means of chromatography [to-luene/acetone (8:2)] on a silica gel column affords the title compound (2.30 g) as an orange-yellow oil.
TLC, silica gel (glass plates), [toluenelacetone (8:2)], Rf= 0.53 MS: calc.: C~9H2608 (382.41), found: [MNH4t] 400.3 A16. 4-O-Benzyl-3.6-di-O-carboxymethyl-1.2-dideoxy-D-alucopyranose A solution of 4-O-benzyl-1,2-dideoxy-3,6-di-O-methoxycarbonylmethyl-D-glucopyranose (1.1 g, 2.87 mmol) in MeOH (2 ml) is treated with 2 N NaOH (7.2 ml) and stirred at RT
for 30 min. The mixture is extracted with ethyl acetate (3 x 5 ml), and the combined organic phases are dried over MgS04, filtered and concentrated in vacuo. The title compound (0.94 g) is obtained as a white solid.
MS: calc.: C»H2208 (354.36), found: [MNH4+] 372.2 - 97 - _ A 17. 4-O-Be nzvl-3.6-d i-O-f4-(4-N-tert-b_utoxyca rbonylaminomethyl benz~lca rbamoyll-1-pi pera-zinylcarbonyll-1.2-dideoxy-D-alucopyranose 4-N-tent-Butoxycarbonylaminomethylbenzylamin (0,2 g, 0.85 mmol) is slowly added at a temperature of 0°C to a solution of 4-nitrophenyl chloroformate (0.17 g, 0.85 mmol) in CH2CI2 (20 ml). The reaction is then treated with Et3N (0.12 ml, 0.85 mmol). The mixture is stirred at RT for 2 h. 3,6-Di-O-(1-piperazinylcarbonyl)-4-O-benzyl-1;2-dideoxy-D-glucopyranose dihydrochloride (0.23g, 0.43 mmol, star-ting compound A5) is then added to the reaction solution and it is treated with further Et3N (3 ml, 21.8 mmol). The mixture is stirred for 18 h and then washed with saturated aqueous NaHC03 solution (2 x ml) and afterward with ice-cold 0.5 N HCI (2 x 5 ml). The organic phase is dried over MgS04, filtered and concentrated in vacuo. Further purification is carried out by means of chromatography [tolue-nelacetone (6:4)] on a silica gel column and affords the title compound (0.15 g) as a pale brawn amorphous powder. TLC, silica gel (glass plates), [toluenelacetone (4:6)], Rf=
0.25 MS: calc.: CS,H~oNe0,2 {987.17), found: [MHi] 986.9 A18. 4-N-tert-Butoxvcarbonylaminomethyl-benzylamine 4 molar HCI (18.7 ml, 75 mmol) is added to a solution of 4-aminomethylbenzylamine (10 g, 75 mmol) in dioxane (200 ml). A solution of di-tert-butyl dicarbonate (18.5 g, 75 mmol) in dioxane (100 ml) is added dropwise to this in the course of 1 hour. The mixture is stirred at RT for 12 h, the resulting precipitate is filtered off with suction and the reaction solution is rendered basic using NaHC03. The mixture is extracted with CH2CI2 (4 x 30 ml) and the combined org. phases are dried over MgS04. The solution is filtered and concentrated in vacuo. Further purification is carried out by means of chromatography [e-thyl acetatelmethanol/satd. NaH3 soln. (20:1:0.2)] on a silica gel column and affords the title compound (6.9 g) as a colorless powder.
A19. 4-O-Benzyl-1,2-dideoxy-3.6-di-O-f4-f4'-N-(9-fluorenylrnethox carbons _ piperidinylmethyrlcarbonyll-1-piperazinylcarbonyl,~-D-alucopyranose 1-(9-Fluorenylmethoxycarbonyl)piperidin-4.-ylacetic acid (1.0 g, 2.74 mmol) and HOBT (0.37 g, 2.74 mmol) are added to a solution of 4-O-benzyl-3,6-di-O-(1-piperazinylcarponyl)-1,2-dideoxy-D-glucopyranose dihydrochloride (0.7 g, 1.3 mmol, starting compound A5) in CH2C12 (15 ml) and Et3N
(0.72 ml). The solution is stirred at RT for 10 min, treated with EDC (0.57 g, 3 mmol) and stirred for a further 12 h. The reaction solution is extracted with water (2 x 10 ml), and the organic phase is dried over MgS04, filtered and concentrated in vacuo. Further purification is carried out by means of chro-matography [toluene/acetone (7:3)j on a silica gel column and affords the title compound (0.8 g) as a colorless powder.
MS: calc.: Cs~H~6Ns0~2 (1157.39), found: [MH'] 1157.3 A20. 4-O-Benzyl-1.2-dideoxy-3,6-di-O-I4-(piperidin-4-ylacetyll-1-piperazin~rlcarbonyll-D-aluco-pyranose dihydrochloride 4-O-Benzyl-1,2-dideoxy-3,6-di-O-(4-[4'-N-(9-fluorenylmethoxycarbonyl)piperidinylmethylcarbonyl]-piperazin-1-ylcarbonyl]-D-glucopyranose (0.8 g, 0.7 mmol) is dissolved in CH2CI2 (2 ml), treated at RT
with a 20% strength piperidine solution in CH2C12 (1.5 ml) and stirred for 3 h. The reaction is diluted with toluene (10 ml) and concentrated in vacuo. The residue is taken up in 0.1 N HCI (10 ml) and extracted a number of times with ethyl acetate (3 x 5 ml). The aqueous phase is then adjusted to pH 12 using 1 N NaOH and extracted 10 times with CH2CI2 (10 ml). The combined organic phases are con-centrated in vacuo and coevaporated with toluene (2 x 50 ml). The residue is dissolved in CH2CI2 (2 ml) and precipitated with ethereal HCI (2 ml). The precipitate is washed with Et20 (3 x 5 ml) and dried in vacuo. The title compound (0.5 g) is obtained as a colorless powder.
MS: calc.: C3~H56N608 (712.89), found: [MH~] 713.4 A21. 4-O-Benzyl-3.6-di-O-~4-f1-(N.N'-bis-tert-butoxycarbonylamidino~piperidin-4-ylacet Iv 1;1-piperazinylcarbonyl]h-1.2-dideoxy-D-qlucopyranose A solution of 4-O-benzyl-1,2-dideoxy-3,6-di-O-[4-(piperidin-4-ylacetyl)piperazin-1-ylcarbonyl]-D-glucopyranose dihydrochloride (0.5 g, 0.64 mmol) in DMF (10.0 ml) and Et3N
(0.7 ml, 1.4 mmol) is treated with N,N'-bis(tert-butoxycarbonyl)-S-methylisothiourea (0.41 g, 1.4 mmol) and HgCl2 (0.43 g, 1.6 mmol) at RT. After stirring for 18 h, the reaction solution is diluted with ethyl acetate (2 ml) and filtered through kieselghur. The filtrate is extracted with H20 (5 x 5 ml), and the organic phase is dried over MgS04, filtered and concentrated in vacuo. Further purification is carried out by means of chro-matography [toluene/acetone (65:35)] on a silica gel column and affords the title compound (0.35 g) as a colorless powder.
MS: calc.: CS9H92N~o0~6 (1197.45), found: [MH+] 1197.1 A22. 4-O-Benzyl-3.6-di-O-f4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-1-piperazinylcarbonvll-1.2-dideoxy-D-aalactopyranose A 20% strength solution of phosgene in toluene (4.4 ml, 10.5 mmol) is initially introduced and cooled to an internal temperature of-18°C. 4-O-Benzyl-1,2-dideoxy-D-galactopyranose (A63, 0.5 g, 2.10 mmol) is dissolved in CH2CI2 ~3 ml) and the solution is slowly added dropwise. A
solution of DIPEA (1.88 ml, 10.5 mmol) in CH2C12 (1-3 ml) is then added. The mixture is stirred at RT for 40 min. The reaction solu-tion is concentrated in vacuo and coevaporated with toluene (2x). The residue obtained is dissolved in CH2C12 (5 ml), cooled to 0°C and then , treated with DIPEA (5 ml) and traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl-1-piperazine (A43, 1.37 g, 4.20 mmol). The mixture is stirred at RT overnight. The reaction solution is filtered through AI203, washed with CH2C12 (2 x 10 ml) and concentrated in vacuo. Further purification by means of chromatography [toluene/acetone (8:2)] on a silica gel column affords the title compound (0.6 g) as a colorless powder.
TLC, silica gel glass plates [toluenelacetone (8:2)], Rf = 0.25.
MS: calc.: C49H~6N60~2 (941.15), found: [MH+] 942.0 A23. 3,6-Di-O-f4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-1-aiperazin-ylcarbonvl].1,2-dideoxy-D-aalactopyranose 4-O-Benzyl-3,6-di-O-[4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)piperazin-1-yl-carbonyl]-1,2-dideoxy-D-galactopyranose (A22, 0.16 g, 0.19 mmol) is dissolved in MeOH (13 ml) at RT
and treated with palladinized carbon (10% Pd, 0.14 g). The mixture is stirred at RT for 2 h under a hydrogen atmosphere in a recirculating hydrogenation unit. The catalyst is filtered off after uniform reaction (TLC, checking) and the solution is concentrated in vacuo. Further purification is carried out by means of chromatography [tolueneJacetone (1:1)] on a silica gel column and affords the title compound (0.14 g) as a colorless resin. TLC, silica gel, glass plates [toluenelacetone (1:1)], Rf = 0.15.
MS: calc.: C42H~oNsO~z (851.06), found: [MH+] 851.0 A24. 4-O-Benzvl-3.6-di-O-f4-(N-benzyloxycarbonylamidino-1-benzylox carbon~rlindazol-3-yl-carbonyl)-1-pinerazinylcarbonyll-1,2-dideoxy-D-alucopyranose 6-(1-Benzyloxycarbonylamidyl)-1-benzyloxycarbonyl-3-carboxylindazole (0.5 g, 1.05 mmol) and HOBT
(0.14 g, 1.05 mmol) are added to a solution of 4-O-benzyl-1,2-dideoxy-3,6-di-O-(1-piperazinylcarbonyl)-D-glucopyranose dihydrochloride (A5, 0.267 g, 0.5 mmol) in dichloromethane (10 ml) and Et3N (0.3 ml, 2.0 mmol). The solution is stirred at RT for 10 min, treated with EDC (0.22 g, 1.15 mmol) and stirred for a further 5 h. The reaction solution is diluted with ethyl acetate (10 ml) and extracted with water (3 x ml). The organic phase is dried over MgS04, filtered and concentrated in vacuo. Further purification is carried out by means of chromatography [toluenelacetone (7:3)] on a silica gel column and affords the title compound (0.32 g) as a colorless powder. TLC, silica gel, glass plates [toluenelacetone (7:3)], Rf = 0.34.
MS: calc.: C~$H~oN.~2016 (1371.44), found: [MH+] 1371.2 A25. Methyl 4-O-benzyl-3,6-di-O-f4-(traps-4-N-tert-butoxycarbonylaminorriethylcyclohexyl-carbonyl)-1-niperazinvlcarbonyll-2-deoxy-a-D-glucoayranoside A 20% strength solution of phosgene in toluene (7.8 ml, 18.6 mmol) is initially introduced and cooled to an internal temperature of -14°C. Methyl 4-O-benzyl-2-deoxy-a-D-glucopyranoside (1.0 g, 3.73 mmol) is dissolved in CH2C12 (10 ml) and the solution is slowly added dropwise.
DIPEA (1.28 ml, 7.46 mmol) and a spatula tipful of DMAP are then added. The mixture is stirred at RT for 1.5 h. The reaction soluti-on is concentrated in vacuo and coevaporated with toluene (2x). The residue obtained is dissolved in CH2C(2 (10 ml), cooled to 0°C and then treated with DIPEA (7 ml) and traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl-1-piperazine (A43, 2.7 g, 8.29 mmol). The mixture is stirred at RT overnight. The reaction solution is diluted with CH2C12 (20 ml) and extracted (2 x) with semisaturated aqueous NH4CI solution (30 ml), dried over MgS04, filtered and concentrated in vacuo.
Further purification by means of chromatography [toluene/acetone (1:1 )] on a silica gel column affords the title compound (2.23 g) as a colorless powder. TLC, silica gel, glass plates [toluene/acetone (1:1)j, Rf = 0.16.
MS: calc.:.,CSOH~$N60,3 (971.34), found: [MH+] 972.0 A26. Methyl 3.6-di-O-f4-(traps-4.-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyll-2-deoxy-a-D-alucop~rranoside Methyl 4-O-benzyl-3,6-di-O-[4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl) pipera-zin-1-yl-carbonyl]-1,2-deoxy-a-D-glucopyranoside (A25, 0.6 g, 0.62 mmol) is dissolved in MeOH (28 ml) at RT and treated with palladinized carbon (10% Pd, 0.3 g). The mixture is stirred at RT for 20 min under a hydrogen atmosphere in a recirculating hydrogenation unit. The catalyst is filtered off after uriiform reaction (TLC checking) and the solution is concentrated in vacuo.
Further purification is car-ried out by means of chromatography [toluenelacetone (4:6)] on a silica gel column and affords the title compound (0.44 g) as a colorless resin. TLC, silica gel, glass plates [toluenelacetone (4:6)], Rf = 0.37.
MS: calc.: C43H~2NsO~3 (881.1), found: [MH+] 882.1 A27. 3.6-Di-O-f4-(traps-4.-N-tert-butoxycarbonylaminomethylc~rclohexylcarbonyl)-1-piperazin-ylcarbonylmethyll-1.2-dideoxv-D-alucoayranose 4-O-Benzyl-3,6-di-O-[4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)piperazin-1-yl-carbonylmethyl]-1,2-dideoxy-D-glucopyranose (A14; 0.15 g, 0.15 mmol) is dissolved in MeOH (13 ml) at RT and treated with palladinized carbon (10% Pd, 0.1 g). The mixture is stirred at RT for 1.5 h under a hydrogen atmosphere in a recirculating hydrogenation unit. The catalyst is filtered off after uniform reaction (TLC checking) and the solution is concentrated in vacuo. Further purification is carried out by means of chromatography [CH2CI21MeOt-1~ (98:2)] on a silica gel column and affords the title compound (0.11 g) as a colorless resin. TLC, silica gel, glass plates [CH2C12/ MeOH
(98:2)], R, = 0.33.
MS: talc.: Cø4H7pNsO~2 (878.0), found: [MH~] 879.1 A28. 4-O-Benzyl-6-O-t4-(4-N-tert-butoxycarbonylaminomethylbenz~rlaminocarbonyl)-1-pipera-zinylcarbonyll-3-O-f4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyll-1.2-dideo~-D-ctlucopyranose HOBT (0.19 g, 1.40 mmol) is added to a solution of 4-O-benzyl-3-O-[4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-6-O-methyl-carboxyl-D-glucopyranose (A48, 0.68 g, 1.05 mmol) and 1-[4-N-tert-butoxycarbonylamino-methylbenzylaminocarbonyl]piperazine (A130, 0.44 g, 1.26 mmol) in absolute CH2C12 (8.5 ml) and Et3N (0.8 ml) and the mixture is stirred at RT for 30 min. EDC (0.26 g, 1.36 mmol) is then added and the mixture is stirred overnight at RT. The reaction solution is diluted with CH2C12 (20 ml) and extracted (2 x} with semisaturated aqueous NH4CI solution (15 ml), dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chromatography [CH2C121 MeOH
(95:5)] on a silica gel col-umn affords the title compound (0.45 g) as a colorless powder. TLC, silica gel, glass plates [ToI/Ac (4:6)], Rf = 0.31.
MS: talc.: CS~H~SN~0~2 (978.2), found: [MH~] 978.1 A29. Benzyl 3.6-di-O-f4-(trans-4-N-tart-butoxvcarbonylaminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyll-2-deoxyr-a-D-glucopyranoside A 20% strength solution of phosgene in toluene (5.7 ml, 10.9 mmol) is initially introduced and cooled to an internal temperature of -18°C. Benzyl 4-O-benzyl-2-deoxy-a-D-glucopyranoside (0.75 g, 2.17 mmol) is dissolved in CH2CI2 (8 ml) and the solution is slowly added dropwise. DIPEA (1.88 ml) and a spatular tipful of DMAP are then added. The mixture is stirred at RT for 2 h. The reaction solution is concentrated in vacuo and coevaporated (2x) with toluene. The residue obtained is dissolved in CH2CI2 (8 ml), cooled to 0°C and then treated with DIPEA (5 ml) and trans-4-N-tart-butoxycarbonyl-aminomethylcyclohexylcarbonyl-1-piperazine (A43, 1.42 g, 4.34 mmol). The mixture is stirred at RT
overnight. The reaction solution is diluted with CH2C12 (15 ml) and extracted (2 x) with semisaturated aqueous NH4CI solution (25 ml), dried over MgS04, filtered and concentrated in vacuo. Further purifi-cation by means of chromatography [toluenelacetone (6:4)] on a silica gel column affords the title com-pound (1.6 g) as a colorless powder. TLC, silica gel, glass plates [toluenelacetone (6:4)], Rf = 0.40.
MS: _ talc.: CSSH82N60~3 (1047.4), found: [MH+] 1048.3 A30. 4-O-Benzyl-3.6-di-O-f4-(4-N-tert,butoxycarbonylaminomethylbenzylaminocarbonyl)-1-piperazinylcarbonylmethyll-1.2-dideoxy-D-glucopyranose HOBT (0.6 g, 4.4 mmol) is added to a solution of 4-O-benzyl-1,2-dideoxy-3,6-di-O-carboxymethyl-D-giucopyranose (A16, 0.5 g, 1.41 mmol) and 4-N-tert-butoxycarbonylaminomethylbenzylaminocarbonyl-1-piperazine (1.08 g, 3.1 mmol) in absolute CH2CI2 (10 ml) and Et3N (0.8 ml) and the mixture is stirred at RT for 45 min. EDC (0.9 g, 4.7 mmol) is then added and the mixture is stirred overnight at RT. The reaction solution is diluted with CH2CI2 (20 ml) and extracted (2 x) with semisaturated aqueous NH4CI
solution (15 ml), dried over MgS04, filtered and concentrated in vacuo.
Further purification by means of chromatography [CH2C12/ MeOH (95:5)] on a silica gel column affords the title compound (0.52 g) as a colorless powder. TLC, silica gel, glass plates [CH2CI2/ MeOH (95:5)], Rf =
0.25.
MS: calc.: C53H~4N80~2 (1015.23), found: [MH~] 1016.2 A31. 3 6-Di-O-f4-(4-N-tert-butoxycarbonylaminomethylbenzylaminocarbonyl)-1-piperazinylcar-bonrlmethvll-1.2-dideoxy-D-gilucopyranose 4-O-Benzyl-3,6-di-O-[4-(4-N-tert-butoxycarbonylaminomethylbenzylaminocarbonyl)piperazin-1-yl-car-bonylmethylJ-1,2-dideoxy-D-glucopyranose (A30, 0.30 g, 0.30 mmol) is dissolved in MeOH (14 m1) at RT and treated with palladinized carbon (10% Pd, 0.15 g). The mixture is stirred at RT for 1.5 h under a hydrogen atmosphere in a recirculating hydrogenation unit. The catalyst is filtered off after uniform reaction (TLC checking) and the solution is concentrated in vacuo. Further purification is carried out by means of chromatography [CH2CI21 MeOH (95:5)] on a silica gel column and affords the title compound (0.11 g) as a colorless resin. TLC, silica gel, glass plates [CH2CI21 MeOH
(9:1 )], Rf = 0.57.
MS: calc.: CasHesNsO~z (925.1), found: [MH'] 925.24 A32. 3i6-Di-O-f4-(traps-4-N-tart-butoxycarbonylaminomethylcyclohe~lcarbor~yl)-1-piperazin-ytcarbonyll-1.2-dideoxy-4-O-methyl-D-aalactopyrranose A 20% strength solution of phosgene in toluene (10 ml, 23.9 mmol) is initially introduced and cooled to an internal temperature of-18°C. 4-O- Methyl-1,2-dideoxy-D-galactopyranose (A56, 0:5 g, 3.10 mmol) is dissolved in CH2CI2 (3 ml) and the solution is slowly added dropwise. A
solution of DIPEA (3.5 ml) in CH2CI2 (13 ml) is then added. The mixture is stirred at RT for 3 h.'' The reaction solution is concentrated in vacuo and coevaporated with toluene (2 x). The residue obtained is dissolved in CH2CI2 (6 ml), cooled to 0°C and then treated with DIPEA (5 ml) and traps-4-N-tart-butoxycarbonyl-aminomethylcyclohexylcarbonyl-1-piperazine (A43, 2.01 g, 6.2 mmol). The mixture is stirred at RT
overnight. The reaction solution is diluted with CH2CI2 (25 ml) and extracted (2 x) with semisaturated aqueous NH4CI solution (30 ml), dried over MgS04, filtered and concentrated in vacuo. Further purifi-cation by means of chromatography [toluenelacetone (8:2)] on a silica gel column affords the title com-pound (1.12 g) as a colorless powder. TLC, silica gel, glass plates [methyl acetatelmethanol (98:2)], Rf = 0.2.
MS: calc.: C43H72N6O12 (865.1), found: [MH+] 866.1 A33. Methyl 2,6-di-O-(4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbon 1 piperazinylcarbonyll-a-D~lucoa~rranoside Methyl 3,4-di-O-benzyl-2,6-di-O-[4-(4-N-tert-butoxycarbonylaminomethylbenzylaminocarbonyl)-pipera-zin-1-ylcarbonyl]-a-D-glucopyranosid (A35, 0.5 g, 0.46 mmol) is dissolved in MeOH (20 ml) at RT and treated with palladinized carbon (10% Pd, 0.15 g). The mixture is stirred at RT for 2 h under a hydro-gen atmosphere in a recirculating hydrogenation unit. The catalyst is filtered off after uniform reaction (TLC checking) and the solution is concentrated in vacuo. Further purification is carried out by means of chromatography [EA/MeOH (97:3)] on a silica gel column and affords the title compound (0.25 g) as a colorless resin. TLC, silica gel, glass plates [EAIMeOH (97:3)], Rf = 0.16.
MS: calc.: C43H72N6O~4 (896.3), found: [MH'] 897.1 A34. Methyl 4-O-benzyl-3,6-di-O-f4-(4-N-tert-butoxycarbonylaminomethylbenzylaminocarbon-yl)-1-piperazinylcarboyrll-2-deoxy-a-D-ctlucopyranoside A 20% strength solution of phosgene in toluene (10 ml, 23.8 mmol) is initially introduced and cooled to an internal temperature of 0°C. Methyl 4-O-benzyl-2-deoxy-a-D-glucopyranoside (0.5 g, 1.86 mmol) is dissolved in CH2CI2 (5 ml) and the solution is slowly added dropwise. DIPEA (5 ml) is then added dropwise. The mixture is stirred at RT for 3 h. The reaction solution is concentrated in vacuo and coe-vaporated with toluene (2 x). The residue obtained is dissolved in CH2CIz (6 ml), cooled to 0°C and then treated with DIPEA (5 ml) and 4-N-terk-butoxycarbonylaminomethylbenzylaminocarbonyl-1-piperazine (A43, 2.0 g, 6.2 mmol). The mixture is stirred at RT overnight. The reaction solution is d-luted with CN2CI2 (25 ml) and extracted (2 x) with semisaturated aqueous NH4CI
solution (20 ml), dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chromatography [EA/MeOH (95:5)] on a silica gel column affords the title compound (2.23 g) as a colorless powder.
TLC, silica gel, glass plates [EA/ MeOH (98:2)], Rf = 0.22.
MS: calc.: C5zH~2N80~3 (1017.1 ), found: [MH+] 1018.0 -104- _ A35. Methyl 3.4-di-O-benzyl-2,6-di-O-f4-(4-N-tert-butoxycarbonylaminomethylbenzylamino-carbonyll-1-piperazinylcarbonyll-a.-D-gilucouyranoside A 20% strength solution of phosgene in toluene (10 ml, 23.8 mmol) is initially introduced and cooled to an internal temperature of 0°C. Methyl 3,4-O-benzyl-a-D-glucopyranoside (0.5 g, 1.33 mmol) is dis-solved in CH2C12 (4 ml) and the solution is slowly added dropwise. DIPEA (2.5 ml) is then added drop-wise. The mixture is stirred at RT for 3 h. The reaction solution is concentrated in vacuo and coevapo-rated with toluene (2 x). The residue obtained is dissolved in CH2C12 (5 ml), cooled to 0°C and then treated with DIPEA (5 ml) and 4N-tert-butoxycarbonylaminomethylbenzylaminocarbonyl-1-piperazine (A114, 0.93 g, 2.66 mmol). The mixture is stirred at RT overnight. The reaction solution is diluted with CH2C12 {20 ml) and extracted (2 x) with semisaturated aqueous NH4CI solution (15 ml), dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chromatography [EA/
MeOH (97:3)] on a silica gel column affords the title compound (0.8 g) as a colorless powder. TLC, silica gel, glass plates [EA/MeOH (98:2)], Rf = 0.27.
MS: calc.: CS9H~9N90~3 (1123.0), found: [MH+] 1123.0 A36. Methyl 3,6-di-O-f4-(4-N-tert-butoxycarbonylaminomethylbenzylaminocarbonyll-1-pipera-zinylcarbonyll-2-deoxy-a-D-ctlucop~anoside Methyl 4-O-benzyl-3,6-di-O-[4-(4-N-tert-butoxycarbonylam inomethylbenzylaminocarbonyl)-piperazin-1-ylcarbonyl]-2-deoxy-a-D-glucopyranoside (A34, 0.4 g, 0.39 mmol) is dissolved in MeOH (20 ml) at RT
and treated with palladinized carbon (10% Pd, 0.1 g). The mixture is stirred at RT for 20 min under a hydrogen atmosphere in a recirculating hydrogenation unit. The catalyst is filtered off after uniform reaction (TLC checking) and the solution is concentrated in vacuo. Further purification is carried out by means of chromatography [CH2CI2IMeOH (95:5)] on a silica gel column and affords the title compound (0.3 g) as a colorless resin. TLC, silica gel, glass plates [CH2CI21 MeOH
(95:5)], R, = 0.38.
MS: calc.: C45HssN80~3 (927.2), found: [MH+] 928.0 A37. 4-O-Benzyl-6-O-f4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbon 1~)-5-aminoaentylt-3-O-f4-(traps-4-N-tert-butoxvcarbonylaminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyll-1.2-dideoxy-D-alucohyranose HOST (0.11 g, 0.74 mmol) is added to a solution of 6-O-(5-aminopentyl)-4-O-benzyl-3-O-[4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose (A49, Ø35 g, 0.74 mmol) and traps-4-N-tert-butoxycarbonylaminomethylcyclo-hexylcarboxylic acid (0.14 g, 0.74 mmol) in absolute CH2CI2 (6 ml) and Et3N
(0.42 ml) and the mixture is stirred at RT for 45 min. EDC (0.15 g, 0.74 mtnol) is then added and the mixture is stirred overnight at RT. The reaction solution is diluted with CH2C12 (15 ml) and extracted (2 x) With semisaturated aque-ous NH4CI solution (15 ml), dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chromatography [CH2CI21MeOH (98:2)] on a silica gel column affords the title compound (0.32 g) as a colorless powder. TLC, silica gel, glass plates [CH2C12lMeOH
(98:2)], Rf = 0.30.
MS: calc.: C4gH7gN5O» (914.2), found: [MH'] 914.3 A38. 4-O-Benzyl-3-O-f4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyll-6-O-f5-(2-N-tert-butoxycarbo~laminomethylnyridylcarbonyl)-aminonentyll-1,2-dideoxy-D-g~lucopyranose HOBT (0.09 g, 0.45 mmol) is added to a solution of 6-O-(5-aminopentyl)-4.-O-benzyl-3-O-[4-(traps-4-N-tert-butoxycarbonylamino methylcyciohexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose (A49, 0.30 g, 0.45 mmol) and 6-(N-tert-butoxycarbonylaminomethyl)nicotinic acid (A61, 0.11 g, 0.45 mmol) in absolute CH2C12 (5 ml) and Et3N (0.35 ml) and the mixture is stirred at RT for 40 min. EDC (0.12 g, 0.45 mmol) is then added and the mixture is stirred overnight at RT. The reaction solution is diluted with CH2CI2 (15 ml) and extracted (2 x) with semisaturated aqueous NH4CI solution (15 ml), dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chro-matography [CH2C12/MeOH (98:2)] on a silica gel column affords the title compound (0.2 g) as a color-less powder. TLC, silica gel, glass plates [CH2C121MeOH (98:2)], Rf = 0.23.
MS: calc.: C4gH72NsO~~ (909.14), found: [MH+) 909.2 A39. 4-O-Benzvl-6-N-f4-(traps-4-N-tert-butoxycarbonylaminomethvlcyrclohexylcarbonyl)-4-aminobutvl-1-oxycarbonyll-3-O-t4-(traps-4-N-tert-butox carbonylaminomethylcyclohe-xylcarbonyl)-1-piperazinylcarbonyll-1.2-dideoxy-D-glucopyranose A solution of 4-O-benzyl-6-N-[4-(traps-4.-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-4-aminobutyl-1-oxycarbonyl]-1,2-dideoxy-D-glucopyranose (A52, 0.5 g, 0.85 mmol) in CH2CI2 (2.5 ml) and DIPEA (0.7 ml) is initially introduced. At a temperature of -14°C, a 20% strength solution of phos-gene in toluene (1.34 ml, 2.53 mmol) is added dropwise. After 20 min at -12°C, the mixture is stirred for 2 h at RT. The reaction solution is concentrated in vacuo and coevaporated with toluene (2 x). The residue obtained is dissolved in CH2CI2 (1.5 ml), and then treated with DIPEA
(1.5 ml) and traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl-1-piperazine (A43, 0.33 g, 1.01 mmol). The mixture is stirred overnight at RT. The reaction solution is diluted with CFi2C12 (15 ml) and extracted (2 x) with semisaturated aqueous NH4CI solution (10 ml), dried over MgS04, filtered and concentrated in vacuo.
Further purification by 'means of chromatography [CH2CI21MeOH (98:2)] on a silica gel column affords the title compound (0.11 g) as a colorless resin. TLC, silica gel, glass plates [CH2CI2/MeOH (98:2)], Rf = 0.30.
MS: calc.: C49H~8N60~2 (943.0), found: [MH"] 943.2 A40. 6-O-L4-(traps-4-N-tert-Butoxycarbonylaminomethylcyclohexylcarbonyl)-5-aminopentyll-3-O-f4-(trans-4-N-tert-Butoxycarbonylaminomethylcyclohexylcarbonyl)-1-piperazinyl-carbonyll-1,2-dideoxy-D-alucopyranose 4-O-Benzyl-6-O-[4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-5-aminopentyl]-3-O-[4-(trans-4.-N-tert-butoxycarbonylaminomethylcyclohexylcarbanyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose (A37, 0.3 g, 0.33 mmol) is dissolved in MeOH (10 ml) at RT and treated with palladi-nized carbon (10% Pd, 0.2 g). The mixture is stirred at RT for 1.5 h under a hydrogen atmosphere in a recirculating hydrogenation unit. The catalyst is filtered off after uniform reaction (TLC checking) and the solution is concentrated in vacuo. The title compound (0.32 g) is obtained as a colorless resin. The compound can be employed in the next stage without further purification. TLC, silica gel, glass plates [CH2C12/MeOH (98:2)], Rf = 0.30.
MS: talc.: C42H73NSO» (824.08), found: [MH+j 824.1 A41. 3 6-Di-O-f4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyll-5-amino-pentyll-1.2-dideoxy-D-glucopyranose 4-O-Benzyl-3,6-di-O-(4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-5-aminopentyl]-1,2-dideoxy-D-glucopyranose (A42, 0.28 g, 0.32 mmol) is dissolved in MeOH (8 ml) at RT and treated with palladinized carbon (10% Pd, 0.25 g). The mixture is stirred at RT for 1.5 h under a hydrogen atmosphere in a recirculating hydrogenation unit. The catalyst is filtered off after uniform reaction (TLC
checking) and the solution is concentrated in vacuo. The title compound {0.22 g) is obtained as a colorless solid. The compound can be employed in the next stage without further purification. TLC, silica gel, glass plates [ToI/Ac (1:1 )], Rf = 0.29.
MS: talc.: C42H7gN4O10 (797.1), found: [MH'J 798.2 _ A42. 4-O-Benzyl-3,6-Di-O-[4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-5-aminopentylt-1,2-dideoxy-D-alucopyranose HOBT {0.95 g, 6.4 mmol) is added to a solution of 3,6-di-O-(5-aminopentyl)-4-O-benzyl-1,2-dideoxy-D-glucopyranose (0.9 g, 2.2 mmol) and trans-4-N-tert-butoxycarbtinyiaminomethyl-cyclohexylcarboxylic acid (1.25 g, 4.8 mmol) in absolute CH2CI2 (10 ml) and Et3N (1.7 ml) and the mixture is stirred at RT for 30 min. EDC (1.4 g, 6.9 mmol) is then added and the mixture is stirred overnight at RT. The reaction solution is diluted with C,H2CI2 (25 ml) and extracted (2 x) with semisaturated aqueous NH4CI solution (20 ml), dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chro-matography [ToI/Ac (6:4)] on a silica gel column affords the title compound (1.1 g) as a colorless pow-der. TLC, silica gel, glass plates, [Toll Ac (6:4)J, Rf = 0.36.

MS: calc.: C4gHg2N4O~p (887.2), found: [MH'] 888.3 A43. traps-4-N-tert-Butoxycarbonylaminomethylcyclohexylcarbonyl-1-piperazine Benzyl 4-(1-[traps-4-(N-tert-Butoxycarbonylaminomethyl)cyclohexyljcarbonyl}piperazine-1-carbonate (A44, 0.4 g, 0.87 mmol) is dissolved in MeOH (20 ml) at RT and treated with palladinized carbon (10%
Pd, 0.2 g). The mixture is stirred at RT for 3 h under a hydrogen atmosphere in a recirculating hydro-genation unit. The catalyst is filtered off after uniform reaction (TLC
checking) and the solution is con-centrated in vacuo. The title compound (0.28 g) is obtained as a colorless solid. The compound can be employed in the next stage without further purification. TLC, silica gel, glass plates [CH2C12/ MeOH
(9:1 )], Rf = 0.10.
A44. Benzyl 4-~1-(traps-4-(N-tert-butoxycarbonylaminomethyl)cyclohexyllcarbonyl3piperazin-1-carbonate HOBT (0.16, g, 1.2 mmol) is added to a solution of traps-4-(N-tert-butoxycarbonylaminomethyl)-cyclohexanecarboxylic acid (0.40 g, 1.55 mmol) and benzyloxycarbonyl-1-piperazine (0.34 g, 1.55 mmol) in absolute CH2C12 (9 ml) and Et3N (0.96 ml) and the mixture is stirred at RT for 20 min. EDC
(0.23 g, 1.2 mmol) is then added and the mixture is stirred overnight at RT.
The reaction solution is diluted with CH2CI2 (15 ml) and extracted (2 x) with semisaturated aqueous NH4CI solution (15 ml), dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chromatography [CH2C121 MeOH (9:1 )] on a silica gel column affords the title compound (0.71 g) as a colorless powder.
TLC, silica gel, glass plates [CH2CI2/ MeOH (9:1)], Rf = 0.24.
A45. 4-O-Benzyl-3-O-f4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbon~rl)-1-piperazinylcarbonyll-1.2-dideoxy-D-glucopyranose 4-O-Benzyl-3-O-[4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)piperazin-1-ylcarbon-yl]-6-O-tent-butyldimethylsilyl-1,2-dideoxy-D-glucopyranose (A46, 1.8 g, 2.56 mmol) is dissolved in absolute THF (16 ml) and treated with a solution of tetrabutylammonium fluoride in absolute THF
(4.6 ml (2.56 mmol) of a 1 molar solution]. The reaction solution is stirred at RT for 4 h. It is then diluted with ethyl acetate (20 ml) and extracted (2 x) with semisaturated aqueous NH4CI solution (15 ml), and the extract is dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chromatography [CH2C12IMeOH (7:3)] on a silica gel column affords the title compound (1.15 g) as a colorless powder. TLC, silica gel, glass plates [CH2C121 MeOH (7:3)], Rf =
0.39.

-1~8- _ A46. 4-O-Benzyl-3-O-f4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbon I
p~erazinylcarbonyll-6-O-tert-butyldimethylsilyl-1,2-dideoxy-D-alucopyranose A 20% strength solution of phosgene in toluene (9 ml, 21.42 mmol) is initially introduced and cooled to an internal temperature of -14°C. 4-O-Benzyl-6-O-tert-butyldimethylsilyl-1,2-dideoxy-D-glucopyranose (A53, 3.0 g, 8.51 mmol) is dissolved in CH2C12 (9 ml) and the solution is slowly added dropwise. DIPEA
(3.9 ml) is then added dropwise and the mixture is stirred at -14°C for 15 min. The mixture is then stirred at RT for 2 h. The reaction solution is concentrated in vacuo and coevaporated with toluene (2 x). The residue obtained is dissolved in CH2CI2 (14 ml), and treated with DIPEA (14 ml) and traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl-1-piperazine (A43, 3.3 g, 10.21 mmol) . The mixture is stirred at RT overnight. The reaction solution is diluted with CH2C12 (20 ml) and extracted (2 x) with semisaturated aqueous NH4CI solution (15 ml), dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chromatography [CH2C12/MeOH (98:2)]
on a silica gel col-umn affords the title compound (1.8 g) as a colorless powder. TLC, silica gel, glass plates [ToI/Ac (95:5)], Rf = 0.21.
A47. 4-O-Benzyl-3-O-f4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyll-1-pi-perazinylcarbonyll-1.2-dideoxy-6-O-methylcarboxvmeth~rl-D-dlucopyranose A 20% strength solution of phosgene in toluene (1.7 ml, 4.05 mmol) is initially introduced and cooled to a temperature of -14°C. 4-O-Benzyl-1,2-dideoxy-6-O-methyicarboxymethyl-D-glucopyranose (A66, 0.5 g, 1.6 mmol) is dissolved in CH2C12 (3 ml) and the solution is slowly added dropwise. DIPEA (0.72 ml) is then added dropwise and the mixture is stirred at -14°C for 15 min.
A 20% strength solution of phos-gene in tolune (0.4 mol, 1.0 mmol) and DIPEA (0.17 ml) are added dropwise again and the mixture is stirred at RT for a further 20 min. The reaction solution is then concentrated in vacuo and coevaporated with toluene (2x).
The residue obtained is dissolved in CH2C12 (3 ml), and treated with DIPEA
(2.5 ml) and traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl-1-piperazine (A43, 0.57 g, 1.76 mmol) . The mixture is stirred at RT overnight. The reaction solution is diluted with CH2C12 (10 ml) and extracted (2 x) with semisaturated aqueous NH4CI solution (10 ml), dried over MgS04, filtered and concentrated in vacuo.
Further purification by means of chromatography [ToIIAc (8:2)] on a silica gel column affords the xitle compound (0.72 g) as a colorless powder. TLC, silica gel, glass plates [ToIIAc (8:2)], Rf = 0.38.
A48. 4-O-Benzyl-3-O-f4-(traps-4-N-tent-butoxycarbonylaminomethylcyclohexylcarbonyll-1 piperazinylcarbonyll-1.2-dideox3r-6-O-methylcarboxymethyl-D-glucopyranose A 5 N aqueous solution of NaOH (0.52 ml) is added to a solution of 4-O-benzyl-3-O-[4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-6-O-methylcarboxymethyl-D-glucopyranose (A47, 0.7 g, 1.06 mmol) in methanol (3 ml) and the mixture is stirred at RT for 1.5 h. The reaction solution is carefully adjusted to p-1 3 using 1 N HCI. It is diluted with ethyl acetate (20 ml) and extracted with H20 (15 ml). After drying over MgS04, the organic phase is concentrated in vacuo. The title compound (0.68 g) is obtained as a colorless powder. TLC, silica gel, glass plates [Toll Ac (6:4)], Rf = 0.05.
A49. 6-O-(5-Aminonentyl)-4-O-benzyl-3-O-f4-(traps-4-N-tert-butoxycarbonylaminomethyl-cyclohexylcarbonyll-1-piperazinylcarbonyll-1.2-dideoxy-D-alucop~rranose Hydrazine monohydrate (0.4 ml, 8.2 mmol) is added to a solution of 4-O-benzyl-3-O-[4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonylj-1,2-dideoxy-6-O-(5-phthalimidopentyl)-D-glucopyranose (A50, 2.5 g, 3.11 mmol) in ethanol (50 ml) and the mixture is stirred overnight at RT. The resulting precipitate is then filtered off, rinsed with EtOH (10 ml) and the filtrate is concentrated in vacuo. The residue obtained is taken up in CH2C12 (50 ml) and extracted (3 x) with 1 N NaOH (35 ml). The combined organic phases are dried over MgS04, filtered and concentrated in vacuo. The title compound (2.1 g) is obtained as a colorless resin. TLC, silica gel, glass plates [Toll Ac (1:1 )], Rf = 0.05.
A50. 4-O-Benzvl-3-O-f4-(traps-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyll-1.2-dideoxy-6-O-(5-phthalirnidopent5rl)-D-alucopyranose Trifluoromethanesulfonic anhydride (1.58 ml, 9.46 mmol) is added dropwise (glass syringe) to a solu-tion of 5-phthalimido-1-pentanol (2.21 g, 9.46 mmol) and 2,6-di-tert-butyl-4-methylpyridine (1.95 g, 9.46 mmol) in absolute CH2C12 (35 ml) and the mixture is stirred at RT for 10 min. The reaction solution is diluted with CH2C12 (35 ml) and extracted (2x) with an aqueous NaCI
solution. The combined organic phases are dried over MgS04, filtered and concentrated in vacuo. The residue obtained is taken up in absolute CH2CI2 (35 ml) and 4-O-benzyl-3-O-(4-{traps-4-N-tert-butoxycarbonylaminomethylcyclo-hexylcarbonyl)piperazin-1-yl-carbonylJ-1,2-dideoxy-D-glucopyranose (A45, 1.86 g, 3.15 mmol) is added. NaH (0.9 g, 22.7 mmol, 60% strength) and 15-crown-5 (1 ml) are added successively with stir-ring at RT (reaction solution changes to orange-yellow). After stirring at RT
for 4 h, the reaction mixture is poured onto an aqueous NH4CI solution (40 ml), extracted (2 x) with CH2C12 (50 ml), and the com-bined organic phases are dried over MgS04, filtered and concentrated in vacuo.
Further purification by means of chromatography [Toll Ac (7:3)] on a silica gel column affords the title compound {2.5 g) as a colorless resin. TLC, silica gel, glass plates (Toll Ac (75:25)], Rf = 0.26.
A51. ftrans-4-(N-tert-Butoxycarbonylaminomethyl)cyclohexylcarbonyll-4-amino-1-butanol HOBT (1.5 g, 11.1 mmol) is added to a solution of traps-4-(N-tert-butoxycarbonylaminomethyl)-cyclohexylcarboxylic acid (2.0 g, 7.8 mmol) and 4-amino-1-butanol (0.72 ml, 7.8 mmol) in absolute CH2C12 (90 ml) and Et3N (6.2 ml) and the mixture is stirred at RT for 30 min.
EDC (2.2 g, 11.5 mmol) is then added and the mixture is stirred overnight at RT. The reaction solution is diluted with CH2C12 (50 ml) and extracted (2 x) with semisaturated aqueous NH4C1 solution (60 ml), dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chromatography [CH2C121 MeOH
(98:2)] on a silica gel column affords the title compound (2.45 g) as a colorless powder. TCL, silica gel, glass plates [CH2CI2I MeOH (98:2)], Rf = 0.40.
A52. 4-O-Benzyl-6-N-f4-(traps-4.-N-tert-butoxycarbonytaminometh~rlcyclohexylcarbony(1-4-aminobutyl-1-oxycarbonyll-1.2-dideoxy-D-ctlucopyranose A solution of 6-amino-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A57, 0.7 g, 2.13 mmol) in CH2CI2 (3 ml) and DIPEA (1 mi) is initially introduced. At a temperature of -12°C, a 20% strength solution of phosgene in toluene (2.25 ml, 4.25 mmol) is added dropwise. After 20 min at -12°C, the mixture is stirred for 7 h at RT. The reaction solution is concentrated in vacuo and coevaporated with toluene (2 x). The residue obtained is dissolved in CH2C12 (4 ml), and then treated with DIPEA (4 ml) and [traps-4-(N-tert-butoxycarbonylaminomethyl)cyclohexylcarbonyl]-4-amino-1-butanol (A51, 0.51 g, 2.13 mmvl). The mixture is stirred overnight at RT. The reaction solution is diluted with CH2C12 (15 ml) and extracted (2 x) with semisaturated aqueous NH4CI solution (10 ml), dried over MgS04, filtered and concentrated. in vacuo. Further purification by means of chromatography [CH2C121MeOH (98:2)j on a silica gel column affords the title compound (1.8 g) as a colorless resin.
TLC, silica gel, glass plates [CH2C12I MeOH (95:5)], Rf = 0.31.
A53. 4-O-Benzyl-6-O-tert-butyldimethylsilyl-1.2-dideoxy-D-glucoayranose 4-O-Benzyl-1,2-dideoxy-D-glucopyranose (3.0 g, 12.6 mmol) is dissolved in absolute DMF (24 ml), cooled to 0°C and treated with tert-butyldimethylsilyl chloride (1.9 g, 12.6 mmol). After warming to RT, the reaction solution is stirred for 3 h. It is diluted with ethyl acetate (50 ml) and extracted (3 x) with semisaturated aqueous NH4CI solution (20 ml). The combined organic phases are dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chromatography [Toll Ac (9:1 )] on a silica gel column affords the title compound (4.02 g) as a colorless resin.
TLC, silica gel, glass plates [Toll Ac (8:2)], Rf = 0.64.
A54. 3z6-O-tert-Butyldimethylsilyl-1.2-dideoxy-D-galactoayranose 1,2-Dideoxy-D-galactopyranose (4.48 g, 30.65 mmol) is dissolved in absolute DMF (50 ml) at RT and treated with imidazole (5.22 g, 76.63 mmol). tert-Butyldimethylsilyl chloride (9.24 g, 61.3 mmol) is then added and the mixture is stirred overnight. The reaction solution is diluted with semisaturated aqueous NH4CI solution (50 ml), and extracted (3 x) with EA (60 ml). The combined organic phases are dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chromatography [PEIEA (20:1 )] on a silica gel column affords the title compound (7.0 g) as a colorless solid. TLC, silica gel, glass plates [PE/EA (9:1)], Rf= 0.54.

A55. 4-O-Methyl-3.6-O-tert-butyldimethylsilyl-1,2-dideoxy-D-galactopyranose 3,6-Di-O-tert-butyldimethylsilyl-1,2-dideoxy-D-galactopyranose (A54, 4.0 g, 10.6 mmol) is dissolved in abs. DMF (20 ml) at RT. Methyl iodide (1.06 ml, 17.0 mmol) and then NaH (0.9 g, 22.5 mmol, 60%
strength) are added to this solution. It is stirred at RT for 2 h. The reaction mixture is then treated with semisaturated aqueous NH4C1 solution and extracted with ethyl acetate (3x).
The combined organic phases are dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chromatography [PE/EA (95:5)] on a silica gel column affords the title compound (3.52 g) as a colorless oil. TLC, silica gel, glass plates [PEIEA (95:5)J, Rf = 0.35.
A56. 4-O-Methyl-1.2-dideox~gialactopyranose 4-O-Methyl-3,6-di-O-tert-butyldimethylsilyl-1,2-dideoxy-D-galactopyranose (A55, 3.5 g, 8.96 mmol) is dissolved in abs. THF (39 ml) at RT and treated with tetrabutylammonium fluoride (19 ml, 19.7 mmol).
The mixture is stirred overnight and then diluted with semisaturated aqueous NH4CI solution (50 ml). It is extracted with ethyl acetate (3 x) and the combined organic phases are dried over MgS04. The solu-tion is filtered and concentrated in vacuo. After purification by means of chromatography [tolue-nelacetone (7:3)] on a silica gel column, the title compound (1.0 g) is obtained as colorless crystals.
TLC, silica gel (glass plates), [PEIEA (1:1 )J, Rf= 0.11.
A57. 6-Amino-4-O-benzyl-1,2-dideoxy-D-alucopyranose A solution of 6-azido-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A58, 6.1 g, 23.1 mmol) in diethyl ether (400 ml) is stirred at 0°C and a solution of LiAIH4 (3.53 g, 93 mmoi) in diethyl ether (100 ml) is slowly added dropwise. After stirring at RT for 2 h, the reaction mixture is cooled to 0°C and treated cautously with a semisaturated aqueous NaHC03 solution (150 ml). After the separation of the organic phase, the aqueous phase is extracted (3 x) with a mixture of CH2C12/MeOH (8:2, 200 ml).-The combined or-ganic phases are dried over MgS04, filtered and concentrated in vacuo. The title compound (4.7 g) is obtained as a colorless resin. TLC, silica gel, glass plates [Toll Ac (1:1)], Rf = 0.14.
A58. 6-Azido-4-O-benzyrl-1.2-dideoxy-D-alucop~~ranose NaN3 (3.55 g, 54.3 mmol) is added to a solution of 4-O-benzyl-1,2-dideoxy-6-O-toluenesulfonyl-D-glucopyranose (A59, 7.1 g, 18.1 mmol) in absolute dimethylformamide (500 ml) and the mixture is stirred at 120°C for 3 h. After cooling to RT, the reaction solution is concentrated in vacuo. The residue obtained is taken up irr..ethyl acetate (150 ml) and extracted (2x) with H20, The combined organic phases are dried over MgS04, filtered and concentrated in vacuo. The title compound (4.5 g) is obtained as a colorless resin. TLC, silica gel, glass plates [Toll Ac (8:2)], Rf = 0.39.

A59. 4-O-Benzyl-1.2-dideoxy-6-O-tolt~enesulfonyl-D-g lucopyranose Absolute pyridine (10.5 ml) and p-toluenesulfonyl chloride (4.25 g, 22.3 mmol) are added successively at 0°C to a solution of 4-O-benzyl-1,2-dideoxy-D-glucopyranose (5.0 g, 21.0 mmol) in absolute CH2C12 (55 ml) and the mixture is stirred for 2 h. It is then stirred overnight at RT. The reaction solution is cf-luted with semisaturated aqueous NH4CI solution (50 ml). It is extracted with ethyl acetate (3 x) and the combined organic phases are dried over MgS04. The solid is filtered off and the filtrate is concentrated in vacuo. After purification by means of chromatography [toluene/acetone (8:2)] on a silica gel column, the title compound (7.1 g) is obtained as colorless crystals. TLC, silica gel, (glass plates), [tolu-ene/acetone (8:2)], Rf= 0.30.
A60. 6-Aminomethylnicotinic acid 6-Cyanonicotinic acid (0.2 g, 1.35 mmol) is dissolved in MeOH (10 ml) at RT
and treated with palladi-nized carbon (10% Pd, 0.07 g). The mixture is stirred at RT for 1 h under a hydrogen atmosphere in a recirculating hydrogenation unit. A colorless precipitate deposits from the reaction mixture. The mixture is then diluted with H20 (10 ml), the catalyst is filtered oft and the filtrate is concentrated in vacuo. The title compound (0.2 g) is obtained as a colorless solid. The compound can be employed in the next stage without further purification.
A61. 6-(N-tert-Butoxycarbonylaminomethyl)nicotinic acid Et3N (0.5 ml, 2.63 mmol) and di-tert-butyl dicarbonate (0.29 g, 1.32 mmol) are added successively to a solution of 6-aminomethylnicotinic acid (A60, 0.2 g, 1.31 mmol) in dioxanelH20 (3.5 ml, 2.5:1 ) and the mixture is stirred at RT overnight. Further Et3N (0.2 ml, 1.05 mmol) and di-tert-butyl dicarbonate (0.05 g, 0.23 mmol) are then added and the mixture is stirred at RT for a further 5 h. The reaction mix-ture is diluted with semisaturated aqueous NaHC03 solution (10 ml) and extracted with ethyl acetate (15 ml, 3 x). The combined organic phases are dried over MgS04, filtered and concentrated in vacuo.
The title compound (0.24 g) is obtained as a colorless solid. TLC, silica gel, glass plates [EtOH/H20 (9:1 )], Rf = 0.70.
A62. 4-O-Benzyl-3.6-di-O-tent-butyldimethvlsilyl-1.2-dideoy-D-cialactopyranose 3,6-Di-O-tert-butyldimethylsilyl-1,2-dideoxy-D-galactopyranose (A54, 7.0 g, 18.58 mmol) is dissolved in abs. DMF (80 ml) at RT. Benzyl bromide (3.50 ml, 29.73 mmol) and then NaH (1.5 g, 37.16 mmol, 60%
strength) are then added fo this mixture. It is stirred at RT for 12 h. Next, 5 ml of MeOH are added and the mixture is stirred for a further 15 min. The reaction mixture is then treated with semisaturated aqueous NH4CI solution and extracted (3x) with ethyl acetate. The combined organic phases are dried over MgS04, filtered and concentrated in vacuo. Further purification by means of chromatography [PEIEA (95:5)] on a silica gel column affords the title compound (7.6 g), as a colorless oil. TLC, silica gel, glass plates [PEIEA (9:1)], Rf = 0.50.
A63. 4-O-Benzvl-1.2-dideoxy-D-aalactopyranose 4-O-Benzyl-3,6-di-O-tert-butyldimethylsilyl-1,2-dideoxy-D-galactopyranose (A62, 7.6 g, 16.3 mmol) is dissolved in abs. THF (70 ml) at RT and treated with tetrabutylammanium fluoride (36 ml, 35.9 mmol).
The mixture is stirred overnight and then diluted with semisaturated aqueous NH4C1 solution (50 ml). It is extracted with ethyl acetate (3 x) and the combined organic phases are dried over MgS04. The solu-tion is filtered and concentrated in vacuo. After purification by means of chromatography [tolue-nelacetone (7:3)] on a silica gel column, the title compound (2.88 g) is obtained as colorless crystals.
TLC, silica gel (glass plates), [toluene/acetone (7:3)], Rf= 0.34 A64. 3 6-Di-O-(5-aminopentyl)-4-O-benzyl-1.2-dideoxy-D-alucopyranose Hydrazine monohydrate (0.38 ml, 7.8 mmol) is added to a solution of4-O-benzyl-1,2-dideoxy-3,6-di-O-(5-phthalimidopentyl)-D-glucopyranose (A65, 1.3 g, 1.95 mmol) in ethanol (30 ml) and the mixture is stirred overnight at RT. The resulting precipitate is then filtered off, rinsed with EtOH (10 ml) and the filtrate is concentrated in vacuo. The residue obtained is taken up in CH2C12 (30 ml) and extracted (3 x) with 1 N NaOH (15 ml). The combined organic phases are dried over MgS04, filtered and concentrated in vacuo. The title compound (0.9 g) is obtained as a colorless resin. TLC, silica gel, glass plates (ToIIAc (1:1 )], Rf = 0.05.
A65. 4-O-Benzvl-1,2-dideoxy-3,6-di-O-(5-phthalimidopentyl)-D-glucopyranose Trifluoromethanesulfonic anhydride (2.1 ml, 12. 6 mmol) is added dropwise (glass syringe) to a solution of 5-phthalimido-1-pentanol (2.94 g, 12.6 mmol) and 2,6-di-tert-butyl-4-methylpyridine (2.6 g, 12.6 mmol) in absolute CH2CI2 (25 ml) and the mixture is stirred at RT for 15 min. The reaction solution is diluted with CH2CI2 (35 ml) and extracted (2x) with an aqueous NaCI
solution (25 ml). The combined organic phases are dried over MgS04, filtered and concentrated in vacuo. The residue obtained is taken up in absolute CH2C12 (25 ml) and 4-O-benzyl-1,2-dideoxy-D-glucopyranose (0.5 g, 2.1 mmol) is added. NaH (0.6 g, 15.1 mmol, 60% strength) and 15-crown-5 (1 ml) are added successively with stir-ring at RT (reaction solution changes to orange-yellow). After stirring at RT
for 3.5 h, the reaction mix-ture is poured onto an aqueous NH4C1 solution (30 ml), extracted (2 x) with CH2CI2 (50 ml), and the combined organic phases are dried over MgS04, filtered and concentrated in vacuo. Further purifica-tion by means of chromatography [Toll Ac (8:2)] on a silica gel column affords the title compound (1.3 g) as a colorless resin. TLC, silica gel, glass plates [Toll Ac (8:2)], Rf = 0.15.

A66. 4-O-Benzyl-1,2-dideoxy-6-O-methylcarboxymethrl-D-ctlucopyranose 4-O-Benzyl-1,2-dideoxy-D-glucopyranose (6 g, 25.2 mmol) is dissolved in dioxane (100 ml) and, after the addition of NaH (10.0 g, 252 mmol), the mixture is heated under reflux for 2 h. It is then cooled to 0°C and methyl bromoacetate (23.1 ml, 252 mmol) is added dropwise. The mixture is stirred at RT for 4 days. The reaction solution is then neutralized with methanolic HCI, the precipitate is filtered off and the filtrate is concentrated in vacuo. The residue is taken up in ethyl acetate, undissolved constituents are filtered off and the filtrate is again concentrated in vacuo. Further purification by means of chroma-tography [Toll Ac (8:2)] on a silica gel column affords the title compound (0.79 g) as a colorless resin.
TLC, silica gel, glass plates [Toll Ac (8:2)], Rf = 0.47.
A67. 3,6-Di-O-f4-f3-(tert-butyloxycarbonylaminomethyl)benzoyll-dideoxypiperazin-1-ylcarbonyl~-4-O-benzyl-1,2-dideo~-D-alucopyranose A solution of 480 mg (2.0 mmol) of 4-O-benzyl-1,2-dideoxy-D-glucopyranose and 5.0 ml (29.2 mmol) of diisopropylethylamine in 30 ml of dichloromethane is added dropwise in the course of 60 min to 12.0 ml (22.7 mmol) of a 20% strength solution of phosgene in toluene cooled to 0°C. The mixture is stirred with ice-cooling for 30 min and at RT for 2.5 h. The reaction mixture is concentrated and coevaporated with 3 x 30 ml of toluene.
The residue is dissolved in 30 ml of dichloromethane and treated with 5.0 ml (29.2 mmol) of diisopro-pylethylamine. A solution of 1.29 g (4.0 mmol) of 1-[3-(tert-butyloxycarbonylaminomethyl)benzoyl]-piperazine in 40 ml in dichloromethane is added dropwise to this at 0°C
in the course of 35 min. The mixture is stirred with ice-cooling for 25 min and at RT for 12 h. It is then treated with water, the organic phase is separated off, the aqueous phase is extracted with 3 x 100 ml of dichloromethane and the combined organic phases are dried over magnesium sulfate. After silica gel chromatography (tolu-ene/acetone = 6.5:3.5), 1.12 g of crude product are obtained. By further purification by means of HPLC
(gradient water/acetonitrile = 40:60 -~ 4:96), the title compound of m.p. 106 °C is obtained.
MS: calc.: C4gH64N6O12 (928.51 ) found: [MH~] 929.0 A68. 3.6-Di-O-f'4-f3-(tert-butyloxycarbonylaminomethyl)benzoylaminopiperidin-1-ylcarbonLrl3-4-O-benzyl-1,2-dideoxy-D-glucopyranose A solution of 240 mg (1.0 mmol) of 4-O-benzyl-1,2-dideoxy-D-glucopyranose and 2.5 ml (14.6 mmol) of diisopropylethylamir~e in 15 ml of dichloromethane is added dropwise in the course of 40 min to 6.0 ml (11.4 mmol) of la ,20% strength solution of phosgene in toluene cooled to 0°C. The mixture is stirred with ice-cooling for 30 min and at RT for 2 h. The reaction mixture is concentrated and coevapo-rated with 3 x 20 ml of toluene.

-115 - _ The residue is dissolved in 15 ml of dichloromethane and treated with 2.5 ml (14.6 ~mmol) of diisopro-pylethylamine. A solution of 670 mg (2.0 mmol) of 4-[3-(tert-butyloxycarbonylaminomethyl)-benzoylaminoJpiperidine (starting compound A113) of 20 ml of dichloromethane is added dropwise to this at 0°C in the course of 40 min. The mixture is stirred with ice-cooling for 20 min and at RT for 12 h.
It is then treated with water, the organic phase is separated off and the aqueous phase is extracted with 3 x 30 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate, freed from the solvent and the crude product is purified by chromatography (toluene/acetone = 7:3).
260 mg of the title compound are obtained.
MS: calc.: CS~H68N60~2 (956.54) found: (MH'J 957.0 A69. 3,6-Di-O-~(4-f3-(tent-butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazin-1-yl-carbon~rl~-4.-O-benzyl-1.2-dideoxy-D-g~lucopyranose A solution of 480 mg (2.0 mmol) of 4-O-benzyl-1,2-dideoxy-D-glucopyranose and 5.0 ml (29.2 mmol) of diisopropylethylamine in 30 ml of dichloromethane is added dropwise in the course of 45 min to 12.0 ml (22.7 mmol) of a 20% strength solution of phosgene in toluene cooled to 0°C. The mixture is stirred with ice-cooling for 30 min and at RT for 2.5 h. The reaction mixture is concentrated and coevaporated with 3 x 30 ml of toluene.
The residue is dissolved in 30 ml of dichloromethane and treated with 5.0 ml (29.2 mmol) of diisopro-pylethylamine. A solution of 1.44 g (4.0 mmol) 1-[3-(tert-butyloxycarbonylaminomethyl)-benzylaminocarbonyl]piperazine (starting compound A114) in 40 ml of dichloromethane is added dropwise to this at 0°C in the course of 40 min. The mixture is stirred with ice-cooling for 10 min and at RT for 12 h. It is then treated with water, the organic phase is separated off and the aqueous phase is extracted with 3 x 50 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate, freed from the solvent and the crude product is purified by chromatography (toluene/acetone =
6:4). 700 mg of the title compound are obtained as a nonmobile light yellow oil.
MS: calc.: CSiH~oNe012 (986.56) found: [MH'J 987.1 A70. 33 6-Di-O-d4-t3-(tert-butvloxycarbonylaminomethyl)benzylaminocarbonylaminolaiperidin-1-yl-carbonyl~-4-O-benzyl-1.2-dideoxy-D-ctlucopyranose A solution of 1.02 g (2.8 mmol) of 4-(3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl-amino]piperidine (starting compound A115) in 4 ml of dimethylformamide is combined with a solution of 520 mg (1.2 mmol) ~~ of 4-O-benzyl-3,6-di-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A98) in 1 ml of dimethylformamide. The reaction mixture is stirred at 50°C for 10 days. It is then treated with 25 ml of semiconcentrated sodium chloride solution and extracted by shaking with 25 ml of dichloromethane. The organic phase is dried over magnesium sulfate, freed from the solvent and the crude product is purified by chromatography (dichloromethanelmethanol = 19:1 ).
540 mg of the title compound is obtained as a colorless powder.
MS: calc.: Cg3H74N8O~z (1014.59), found: [MH+J 1015.1 A71. 3,6-Di-O-f4-f3-(tert-buty(oxycarbonylaminomethyl)benzylaminocarbonyllpiperidin-1-yl-carbonyl~-4-O-benzyl-1.2-dideoxy-D-alucopyranose A solution of 960 g (2.76 mmol) of 4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonylJ-piperidine (starting compound A116) in 2 ml of dimethylformamide is combined with a solution of 520 mg (1.2 mmol) of 4-O-benzyl-3,6-di-O-{imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A98) in 1 m! of dimethylformamide. The reaction mixture is stirred at RT for 3 days.
It is then treated with 25 ml of semiconcentrated sodium chloride solution and extracted by shaking with dichloromethane. The organic phase is dried over magnesium sulfate, freed from the solvent and the crude product is purified by chromatography (dichloromethanelmethanol =
29:1 ). 750 mg of the title compound are obtained as a colorless powder.
MS: calc.: C53H~2N60~2 (984.57), found: [MH'] 985.1 A72. 3.6-Di-O-f4-traps-f3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyllcyclo-hexvlmethvlaminocarbonyl~-4-O-benzyl-1.2-dideoxy-D-ctlucopyranose A solution of 850 g (2.0 mmol) cf 4-traps-[3-{tert-butyloxycarbonylaminomethyl)benzylaminocarbonylJ-cyclohexylmethylamine (starting compound A117) in 15 ml of dimethylformamide is combined with a solution of 1.72 g (4.6 mmol) of 4-O-benzyl-3,6-di-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A98) in 10 ml of dimethylformamide. The reaction mixture is stirred at 50°C for 8 days. It is then concentrated to dryness in a rotary evaporator and the residue is purified by chromatography (dichloromethanelmethanol = 29:1 ). 980 mg of the title compound are obtained as a colorless powder.
MS: calc.: CS~H$oN60~2 {1040.63), found: [MH+J 1041.1 A73. 3.6-Di-O-f4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyll-4-O-benzyl-1.2-dideoxy-D-alucopyranose ' A solution of 200 mg (0.84 mmol) of 4-O-benzyl-1,2-dideoxy-D-glucopyranose and 2.04 ml (11.7 mmol) r of diisopropylethylamirie, in 10 ml of dichloromethane is treated with 4.4 ml (8.4 mmol) of a 20%
strength solution of phosgene in toluene at 0-2°C in the course of 10 min. The mixture is allowed to come to RT and is subsequently stirred for 1 h. It is then concentrated and coevaporated with 3 x 5 ml of toluene. The residue is taken up in 8 ml of dichloromethane and treated with 2.04 ml (11.7 mmol) of -117 - _ diisopropylethylamine. A suspension of 620 mg {1.84 mmol) of 4-(6-tart-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidine (starting compound A118) in 20 ml of dichloromethane is added dropwise to this solution at 0-2°C in the course of 15 min. After 15 min, the mixture is allowed to come to RT and is subsequently stirred for 18 h. It is hydrolyzed with 10 ml of a saturated sodium hydrogen-carbonate solution, the organic phase is separated off and the aqueous phase is extracted with 2 x 25 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate. For purification, the crude product is chromatographed on silica gel (ethylacetate/methanol = 10:1). 140 mg of the title compound of m.p. > 200°C are obtained {sintering from 145°C).
MS: calc.: C49HssNaO~z (959.1 ), found: [MH+] 959.2 A74. 3-O-f4-t4-(tart-Butyloxycarbonylaminomethyl)benzylaminocarbonyllaiperazin-1-yl-carbonvl~-4-O-benzyl-6-O-f4-(6-tart-butyloxycarbonylaminopyridin-3 ylmethylamino-carbonyl)aiperidin-1-ylcarbonyll-1,2-dideoxy-D-alucopyranose A solution of 565 mg (0.92 mmol) of 3-O-{4-[4-(tart-butyloxycarbonylaminomethyl)-benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (starting com-pound A106) and 0.96 ml (5.52 mmol) of diisopropylethylamine in 4 ml of dichloromethane cooled to 0-2°C is treated with 2.24 ml (4.24 mmol) of a 20% strength solution of phosgene in toluene. The mixture is stirred with ice-cooling for 15 min and at RT for 30 min. It is concentrated and the reaction mixture is coevaporated with 3 x 10 ml of toluene.
The residue is dissolved in 1 ml of dichloromethane and treated with 0.48 ml (2.26 mmol) of diisopro-pylethylamine. A suspension of 370 mg (1.11 mmol) of 4-(6-tart-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidine (starting compound A118) in 2 ml of dichloromethane is added dropwise to this at 0-2°C. The reaction mixture is stirred at RT for 18 h. It is then treated with water, the organic phase is separated off and the aqueous phase is extracted with 3 x 25 ml of dichloromethane.
The combined organic phases are dried over magnesium sulfate, freed from the solvent and the crude product is purified by chromatography (toluene/acetone = 1:1). It is crystallized from diisopropylether and 370 mg of the title compound of m.p. 140°C are obtained.
MS: calc.: CSOHsBNeO~z (973.1), found: (MH+] 973.2 A75. 3-O-f4-f4-(tart-Butyloxycarbonylaminomethyl)benzylartiinocarbonyllpiperazin-1-yl-carbonvl~-4-O-benzyl-6-O-f4-(6-tart-butyloxycarbonylamino-2-methylpyridin-3-ylmethyl-A solution of 750 mg (1.22 mmol} of 3-O-(4-[4-(tart-butyloxycarbonylaminomethyl)-benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (starting compound A106) and 1.93 ml (10.93 mmol) of diisopropylethylamine in 10 ml of dichloromethane cooled to 0-2°C is treated with 4.5 ml (8.54 mmol) of a 20% strength solution of phosgene in toluene.
The mixture is stirred with ice-cooling for 15 min and at RT for 30 min. It is concentrated and the reaction mixture is coevaporated with 3 x 15 ml of toluene.
The residue is dissolved in 10 ml of dichloromethane and treated with 1.5 ml (8.5 mmol) of diisopro-pylethylamine. A suspension of 510 mg (1.46 mmol) of 4-(6-tert-butyloxycarbonylamino-2-methylpyridin-3-ylmethylaminocarbonyl)piperidine (starting compound A119) in 15 ml of dichlo-romethane is added dropwise to this at 0-2°C. The reaction mixture is stirred at RT for 18 h. It is then treated with water, the organic phase is separated off and the aqueous phase is extracted with 3 x 25 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate, freed from the solvent and the crude product is purified by chromatography (ethyl acetatelmethanollammonia = 10:0.3:0.2). 440 mg of the title compound are obtained as a colorless foam.
MS: calc.: CS~H~oN80~2 (987.17), found: [MH'] 987.3 A76. 3-O-~4-f4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazin-1-yl-carbonvl~-4.-O-benzyl-6-O-f4-(4-aminobenzvlaminocarbonyl)piperidin-1-ylcarbonyll-1 2-dideoxv-D-~ Iq ucopyranose 250 mg (0.28 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-[4-(4-nitrobenzylaminocarbonyl)piperidin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose (starting compound A77) are hydrogenated on palladium/carbon (5%) for 6 h in 50 ml of methanol. The catalyst is filtered off, the filtrate is concentrated and the crude product is chromato-graphed on silica gel (toluenelacetone = 1:1 ) and 100 mg of the title compound are obtained as a pale yellow amorphous solid.
MS: calc.: C39H55N~O~o (871.49), found: [MH'J 872.0 A77. 3-O-~4-f4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazin-1~1-carbonvli-4.-O-benzvl-6-O-f4-(4-nitrobenzylaminocarbonyl)piperidin-1 ~,rlcarbon~rll-1 2-dideoxv-D-alucopyranose A solution of 860 mg (1.4 mmol) of 3-O-{4-[4-(tent-butyloxycarbonylaminomethyl)-benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (starting com-pound A106) and 2.44 ml (14 mmol) of diisopropylethylamine in 10 ml of dichloromethane cooled to -10°C is treated with 3.3 ml (6.3 mmol) of a 20% strength solution of phosgene in toluene. The mixture is stirred with ice-cooling for 15 min and at RT for 1 h. It is concentrated and the reaction mixture is coevaporated with 3 x 20 ml of toluene.

The residue is dissolved in 5 ml of dichloromethane and treated with 1.22 ml (7 mmol) of diisopro-pylethyfamine. A suspension of 505 mg (1.68 mmol) of 1-(4-nitrobenzylaminocarbonyl)piperidine in ml of dichloromethane and 2 ml of DMF is added dropwise to this at 0-2°C. The reaction mixture is stirred at RT for 18 h. It is then treated with water, the organic phase is separated off and the aqueous phase is extracted with 3 x 30 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate, freed from the solvent and the crude product is purified by chromatography on silica gel (toluenelacetone = 2:1 ). 260 mg of the title compound are obtained as a yellow oil.
MS: calc.: C4gl"1596N7O12 (902.02), found: [MH+] 902.1 A78. 3-O-(4-f4-(tert-Butyloxycarbonylaminomethyllbenzylaminocarbonyllpiperazin-1-yicar-bonyl~-4-O-benzyl-6-O-f4-trans-(6-tert-butyloxycarbonylaminopyridin-3~rlmethylamino-carbonvl)cyclohexylmethylaminocarbonyll-1.2-dideoxy-D-qlucopyranose A solution of 400 mg (0.64 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)-benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (starting com-pound A106) and 0.7 ml (3.86 mmol) of diisopropylethylamine in 4 ml of dichloromethane cooled to 0-2°C is treated with 1.56 ml (2.96 mmol) of a 20% strength solution of phosgene in toluene. The mixture is stirred with ice-cooling for 15 min and at RT for 30 min. It is concentrated and the reaction mixture is coevaporated with 3 x 15 ml of toluene.
The residue is dissolved in 5 ml of dichloromethane and treated with 0.35 ml (1.93 mmol) of diisopropylethylamine. A suspension of 280 mg (0.77 mmol) of 4-trans-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)cyclohexylmethylamine (starting compound A121 ) in 5 ml of dichloromethane is added dropwise to this at 0-2°C.
The reaction mixture is stirred at RT for 18 h. It is then treated with water, the organic phase is separated off and the aqueous phase is extracted with 3 x 20 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate, freed from the solvent and the crude product is purified by chromatography on silica gel (toluenelacetone = 2:1 ). It is crystallized from diisopropylether and 250 mg of the title compound of m.p. 160°C are obtained (sintering from 130°C).
MS: calc.: C52H~2N80~2 1001.2, found: [MF-f ] 1001.2 A79. 3-O-~4-f4-(tert-Butyloxycarbonylaminomethvl)benzvlaminocarbonvllpiaerazin-carbonyl~-4-O-benzyl-6-O-f4-trans-(6-tert-butyloxycarbonylamino-2-methylpyridin-3-yl-methvlaminocarbonyllcyclohexylmethylaminocarbonvll-1.2-dideoxv-D-caluconvranose A solution of 1.18 g (1.92 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]-piperazin-1-ylcarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (starting compound A106) and 3.02 ml (17.4 mmol) of diisopropylethylamine in 15 ml of dichloromethane is treated with 7.05 ml (13.44 mmol) of a 20% strength solution of phosgene in toluene at 0-2°C
in the course of 10 min. The mixture is stirred with ice-cooling for 15 min and at RT for 3 h. It is concentrated and the reaction mixture is coevaporated with 3 x 25 ml of toluene.
The residue is dissolved in 10 ml of dichloromethane and treated with 2.35 ml (13.5 mmol) of diisopro-pylethylamine. A suspension of 870 mg (2.31 mmol) of 4-{6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidine (starting compound A118) in 30 ml of dichloromethane is added dropwise to this at 0-2°C. The reaction mixture is stirred at RT for 18 h. It is then treated with water, the organic phase is separated off and the aqueous phase is extracted with 3 x 30 ml of dichloromethane.
The combined organic phases are dried over magnesium sulfate; freed from the solvent and the crude product is purified by chromatography on silica gel (ethyl acetate). It is crystallized from diisopropyl-ether and 840 mg of the title compound of m.p. > 200°C are obtained (sintering from 130°C).
MS: calc.: C53H74NgO~2 (1015.23), found: [MH+J 1015.3 A80. 3-O-f4-t4-(tert-Butyloxycarbonylaminomethvl)benzylaminocarbonvllaiperazin-1-yl-carbonyll-4-O-benzvl-6-O-f4-trans-(4-aminobenzytaminocarbonyl)cyclohexylmethyl-aminocarbonyll-1,2-dideoxy-D-alucopyranose 530 mg {0.5 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-[4-trans-(4-nitrobenzylaminocarbonyl)cyclohexylmethylaminocarbonyl]-1,2-dideoxy-D-glucopyranose (starting compound A81 ) are hydrogenated on palladium/carbon (10%) for 2 h in 20 ml of methanol. The catalyst is filtered off, the solvent is removed and the residue is chro-matographed for purification on silica gel (ethyl acetatelmethanol/ammonia =
10:0.3:0.2). The product is crystallized from diethyl ether and 196 mg of the title compound of m.p.
162°C (sintering from 110°C) are obtained.
MS: calc.: C48H65N,O,o (900.1 ), found: [MH+] 900.2 _ A81. 3-O-f4-(4-(tert-Butyloxvcarbonylaminomethyl)benz,~rlaminocarbony~piperazin-1-carbonvl~-4-O-benzyl-6-O-(4-trans-(4-nitrobenzylaminocarbonyl)cyclohexylmethyrl-aminocarbonvll-1,2-dideoxy-D-alucoayranose A solution of 690 mg {1.12 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)-benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose {starting com-pound A106) and 1.37 ml (7.9 mmol) of diisopropylethylamine in 15 ml of dichloromethane is treated at 0-2°C in the course of'10 min with 3 ml (5.61 mmol) of a 20% strength solution of phosgene toluene.
The mixture is stirred with ice-cooling for 15 min and at RT for 3 h. It is concentrated and the reaction mixture is coevaporated with 3 x 15 ml of toluene.

The residue is dissolved in 10 ml of dichlQromethane and treated with 1.95 ml (11.2 mmol) of diisopro-pylethylamine. A suspension of 360 mg (1.23 mmol) of 4-traps-(4-nitrobenzylaminocarbonyl)-cyclohexylmethylamine hydrochloride (starting compound A123) in 2 ml of dichloromethane is added dropwise to this at 0-2°C. The reaction mixture is stirred at RT for 18 h. It is then treated with water, the organic phase is separated off and the aqueous phase is extracted with 3 x 20 ml of dichloromethane.
The combined organic phases are dried over magnesium sulfate, freed from the solvent and the crude product is purified by chromatography on silica gel (ethyl acetatelmethanol/ammonia = 10:0.3:0.2) and 570 mg of the title compound are obtained as a yellowish oil.
MS: calc.: C48Hfi3N7~12 (930.1 ), found: [MH;] 930.1 A82. 3-O-~4-f4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazin-1-yl-carbonvl~-4-O-benzyl-6-O-f3-(4-aminobenzylaminocarbonyl)benzylaminocarbonyll-1 dideoxv-D-ctlucopyranose 350 mg (0.38 mmol) of 3-O-(4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-{3-(4-nitrobenzylaminocarbonyl)benzylaminocarbonyl]-1,2-dideoxy-D-glucopyranose (starting compound A83) are hydrogenated on palladiumlcarbon (10%) for 1.5 h in 20 ml of methanol. The catalyst is filtered off, the solvent is removed and the residue is chromato-graphed for purification on silica gel (ethyl acetatelmethanol/ammonia =
10:0.3:0.2). The product is crystallized from diethyl ether and 162 mg of the title compound of m.p.
135°C (sintering from 90°C) are obtained.
MS: calc.: C48H59N,O,a (894.05), found: [MH'] 894.1 A83. 3-O-('4-f4-(tert-Butyloxycarbonylaminomet~l)benzyrlaminocarbonyllpiperazin-1-~rl-carbonyl}-4-O-benzvl-6-O-f3-(4-nitrobenzylaminocarbonyl)benzylaminocarbonyll-1 dideoxv-D-glucopyranose _ A solution of 700 mg (1.14 mmol) of 3-O-(4-[4-(tert-butyloxycarbonylaminomethyl)benzylamino-carbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (starting compound A106) and 1.8 ml (10.29 mmol) of diisopropylethylamine in 10 ml of dichloromethane is treated at 0-2°C in.the course of 10 min with 4.14 ml (7.9 mmol) of a 20% strength solution of phosgene in toluene. The mixture is stirred with ice-cooling for 15 min and at RT for 2 h'. It is concentrated and the reaction mixture is coevaporated with 3 x 20 ml of toluene.
The residue is dissolved in 5 ml of dichloromethane and treated with 0.6 ml (3:43 mmol) of diisopro-pylethylamine. A suspension of 400 mg (1.37 mmol) of 3-(4-nitrobenzylaminocarbonyl)benzylamine hydrochloride (starting compound A124) in 2 ml of dichloromethane is added dropwise to this at 0-2°C.
The reaction mixture is stirred at RT for 18 h. It is then treated with water, the organic phase is separated off and the aqueous phase is extracted with 3 x 20 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate, freed from the solvent and the crude product is purified by chromatography on silica gel (toluene/acetone = 1:1 ). It is crystallized from diisopropylether and 420 mg of the title compound of m.p. 115°C are obtained.
MS: calc.: CqgH57N~O~z (924.06), found: (MH~] 924.0 A84. 3-O-f4-f4-(tert-ButyloxycarbonylaminomethY)benzylaminocarbonyllpiperazin-1-yl-carbonvl'~-4-O-benzyl-6-O-~4-f3-(imidazol-1-yllpropylaminocarbonyllpiperidin-1-ytcarbonyl~-1,2-dideoxy-D-glucopyranose 530 mg (0.75 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A105) and 212 mg (0.9 mmol) of 4-(3-(imidazol-1-yl)propylaminocarbonyl]piperidine (starting com-pound A125) are suspended in 15 ml of dichloromethane. The reaction mixture is stirred at RT for 6 days. It is treated with water and saturated sodium chloride solution, and the organic phase is sepa-rated off and, dried over magnesium sulfate. The residue is concentrated and the crude product is chromatographed on silica gel (ethyl acetatelmethanol/ammonia = 10:1:0.5).
After concentration of the product-containing fractions, 470 mg of the title compound are obtained as a colorless oil.
MS: calc.: C45HszNsO,o (875.04), found: [MH+] 875.3 A85. 3-O-~'4-f4-(tart-Butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazin-1-carbonyl~-4-O-benzyl-6-O-('4-f4-(imidazol-1-yl)butylaminocarbonyllpiperidin-1_ ylcarbonyl~-1,2-dideoxy-D-alucopyranose 800 mg (1.13 mmol) of 3-O-{4-(4-(tent-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A105) and 420 mg (1.36 mmol) of 4-[4-(imidazol-1-yl)butylaminocarbonyl]piperidine (starting compound A126) are reacted in 20 ml of dichloromethane analogously to the preparation of A84. After chroma-tographic purification on silica gel (ethyl acetate/methanol/ammonia =
10:1:0.5), 780 mg of the title compound are obtained as a colorless foam.
MS: calc.: C4sHs4NsO,o (889.07), found: [MH'} 889.3 A86. 3-O-~4-f4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarboriyllpiperazin-1-yl-carbonyl~-4-O-benzyl-6-O-(4-f5-(imidazol-1-yl)pentylaminocarbonvllpiperidin-1 yl-carbonyl~-1,2-dideoxy-D-alucopyranose 840 mg (1.19 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A105) and 400 mg (1.42 mmol) of 4-(5-(imidazol-1-yl)pentylaminocarbonyl]piperidine (starting com-pound A127) are reacted in 20 ml of dichloromethane analogously to the preparation of A84. After chromatographic purification on silica gel (ethyl acetate/methanol/ammonia =
10:1:0.5), 850 mg of the title compound are obtained as a colorless foam.
MS: calc.: C4~H66NsO~o (903.1), found: [M H;] 903.3 A87. 3-O-('4-(4-(tert-Butyloxvcarbonylaminomethyl)benzylaminocarbonyllpiperazin-1 ylcar-bonyl~-4-O-benzyl-6-O-d4-f6-(imidazol-1-yl)hexylaminocarbonyllpiperidin-1-ylcarbonyll-1,2-dideox~ D-glucopyranose 740 mg (1.04 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound .
A105) and 380 mg (1.25 mmol) of 4-[6-(imidazol-1-yl)hexylaminocarbonyl]piperidine (starting com-pound A128) are reacted in 20 ml of dichloromethane analogously to the preparation of A84. After chromatographic purification on silica gel (ethyl acetatelmethanollammonia =
10:1:0.5), 680 mg of the title compound are obtained as a colorless oil.
MS: calc.: C4gl-isgNgO~p (917.12), found: [MH+] 917.4 A88. 3-O-!4-f4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazin-1-ylcar-bonyl}-4-O-benzyl-6-O-i4-t8-(imidazol-1-yl)octylaminocarbonrltpiperidirt-1-ylcarbon~~
1,2-dideoxy-D-qlucopyranose 600 mg (0.84 rnmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose , (starting compound A105) and 320 mg (1.01 mmol) of 4-[8-(imidazol-1-yl)octylaminocarbonyl]piperidine (starting compound A129) are reacted in 20 ml of dichloromethane analogously to the preparation of A84. After chroma-tographic purification on silica gel (ethyl acetatelmethanol/ammonia =
10:1:0.5), 680 mg of the title compound are obtained as a colorless foam.
MS: calc.: CSOH~2NeO~o (945.18), found: (MH'] 945.4 -124- w A89. 3-O-f4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)pineridin-1-yl-carbonyll-6-O-f4-f4-traps-(tert-butyloxycarbonylaminomethyrl)cyclohexylcarbonyllami-nobut-1-yiaminocarbonyll-4.-O-benzyl-1,2-dideoxy-D-glucopyranose 290 mg (0.37 mmol) of 3-O-[4-(6-tent-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A108) and 145 mg (0.44 mmol) of [4-(4-aminobutylaminocarbonyl)cyclohexylmethyl]carbaminic acid tent-butyl ester (starting compound A131) in 3 ml of dichloromethane and 2 ml of DMF are stirred at 40°C for 12 h and at RT for 72 h. The mixture is concentrated, treated with water, extracted with 3 x 20 ml of dichloromethane and the combined organic phases are dried over magnesium sulfate.
After chromatographic purification on silica gel (dichloromethane/methanol =
19:1 ) and crystallization from diethyl ether, 170 mg of the title compound of m.p. 156-162°C are obtained.
MS: calc.: C4gH73N7O~2 (951.58), found: [MH'J 952.2 A90. 3-O-C4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-yl-carbonvll-6-O-f4-f4-(tert-butyloxycarbonvlaminomethyllbenzylaminocarbonyllaiperazin-1-ylcarbonyll-4-O-benzyl-1,2-dideoxy-D-glucoayranose 290 mg (0.37 mmol) of 3-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonylJ-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A108) and 160 mg (0.44 mmol) of 4-[4-(tert-butyloxycarbonylaminomethyl)benzyl-aminocarbonyl]piperazine (starting compound A130) in 3 ml of dichloromethane and 2 ml of DMF are stirred at 40°C for 18 h and at RT for 72 h. The mixture is concentrated, treated with water, extracted with 3 x 20 ml of dichloromethane and the combined organic phases are dried over magnesium sulfate.
After chromatographic purification on silica gel (dichloromethanelmethanol =
19:1 ) and crystallization from diethyl ether, 220 mg of the title compound of m.p. 145°C are obtained. _ MS: calc.: C5oHs8Ne0~2 (972.55), found: [Mf-(~] 973.2 A91. 3-O-f4-f4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllpiaerazin-1-yl- , carbonyll-4-O-benzyl-6-O-f2-(6-aminopyridin-3-ylmethylaminocarbonyl)eth-1-ylamino-carbonyll-1,2-dideoxy-D-glucouyranose 485 mg (0.69 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A105) and 160 mg (0.82 mmol) of 3-amino-N-(6-aminopyridin-3-ylmethyl)propionamide (starting compound A132) are stirred at RT for 18 h in 5 ml of DMF. The mixture is concentrated, treated with water and extracted with 3 x 25 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate and concentrated. The crude product is chromatographed on silica gel (ethyl acetatelmethanollammonia = 10:1:0.5) and the product is crystallized from diisopropyl ether. 480 mg of the title compound are obtained.
MS: calc.: C42HssNsO,o (832.45), found: [MH~J 833.2 A92. 3-O-~4-t4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllninerazin-1-yl-carbonvl~-4-O-benzyl-6-O-~3-f(6-am idino-1-H-indazol-3-yl)carbonylaminolarop-1-ylaminocarbon~~-1,2-dideoxy-D-a(ucoayranose and A93. 3-O-f4-f4-(tert-Butyloxycarbonylaminomethyl)benzylarninocarbonyllaiperazin-1-ylcar-bonyll-4-O-benzyl-6-O-f3-f(6-aminocarbonyl-1-H-indazol-3-y1)carbonylaminolprop-1-yl-aminocarbonyt~-1,2-dideoxy-D-alucopyranose 410 mg {0.40 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-(3-{[6-( 1-benzyloxycarbonylamino-1-imi nomethyl)-1-benzyloxycarbon-ylaminoindazol-3-ylJcarbonylamino}prop-1-ylaminocarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A97) in 20 ml of glacial acetic acid are hydrogenated on palladium/carbon (10%) for 8 h.
The catalyst is filtered off, the solvent is removed, and the residue is coevaporated with 50 ml of tolu-ene and 50 ml of methanol. After chromatographic purification of the crude product (EA/methanollacetic acid = 40:10:1- 0:99:1), 200 mg of the title compound A92 are isolated as a color-less foam. As a by-product, 20 mg of the title compound A93 are obtained as a colorless foam.
A92: MS: colt.: C3~H48N80s (898.43), found: [MH''J 899.3 A93: MS: talc.: C3~H4sNsOs (899.42), found: [MH+] 900.0 A94. 3-O-t4-f4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllniperazin-1-yl-carbonyl~-6-O-('2-fy-aminocarbonyl-1-H-indol-3-yl)carbonylaminoleth-1-ylaminocarbonvl~-1,2-dideoxv-D-ulucoayranose 170 mg (0.17 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{2-[(6-aminocarbonyl-1-benzyloxycarbonylindol-3-yl)eth-1-ylamino-carbonyl}-1,2-dideoxy-D-glucopyranose {starting compound A99)'in 80 ml of DMF
are hydrogenated for 8 h on palladiumlcarbon (10%). The catalyst is filtered df, the solvent is removed in a high vacuum (bath temp. < 45°C) and 133 mg of the title compound are obtained as a colorless foam.
MS: talc.: C3~H48N80$ (794.36), found: [MH''] 795.0 A95. 3-O-('4-(4-(tert-Butyloxycarbonytaminomethyl)benzylaminocarbonyllpiperazin-1-ylcar-bonyl}-4-O-benzyl-6-O-~3- ((6-aminocarbonyl-1-H-indol-3-yl)carbonylaminolprop-1-yl-aminocarbonyl3-1,2-dideoxy-D-ctlucopyranose 240 mg (0.23 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{3-[(6-aminocarbonyl-1-benzyloxycarbonylindol-3-yl)carbonylamino]prop-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose (starting compound A100) in 100 ml of DMF are hy-drogenated for 8 h on palladiumlcarbon (10%). The catalyst is filtered off, the solvent is removed in a high vacuum (bath temp. < 45°C) and 180 mg of the title compound are obtained as a colorless foam.
MS: calc.: C3~H48N80a (898.42), found: [MH+] 899.0 A96. 3-O-~4-(4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyltpiperazin-1-yl-carbonyl~-4.-O-benzyl-6-O-t'4-((6-aminocarbonyl-1-H-indol-3-yl)carbonylaminolbut-1-ylaminocarbony_I}-1,2-dideoxy-D-alucopyranose 300 mg (0.287 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[(6-aminocarbonyl-1-benzyloxycarbonylindol-3-yl)carbonylamino]but-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose (starting compound A101) in 100 ml of DMF are hydrogenated for 6 h on palladiumlcarbon (10%). The catalyst is filtered off, the solvent is removed in a high vacuum (bath temp. < 45°C) and 265 mg of the title compound are obtained as a colorless oil.
MS: calc.: C37H4gNgOg (912.44), found: [MH+] 913.0 A97. 3-O-f4-(4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazin-1-ylcar-bonyl~-4-O-benzyl-6-O-(3-t'(6-(1-benzyloxycarbonylamino-1-iminomethyl)-1-benzyloxy-carbonylindazol-3-yllcarbonylamino~prop-1-ylaminocarbonyl)-1,2-dideoxy-D-ctlucopyranose dihydrochloride A solution of 244 mg (0.4 mmol) of 3-O-{4-(4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]
piperazin-1-yf-carbonyl}-4.-O-benzyl-1,2-dideoxy-D-glucopyranose (starting compound A106) and 0.17 ml (1.2 mmol) of triethylamine in 3 ml of dichloromethane cooled to 0-2°C is treated with 0.53 ml (1.0 mmol) of a 20% strength solution of phosgene in toluene. The mixture is stirred with ice-cooling for 30 min and at RT for 90 min. It is concentrated and the reaction mixture is coevaporated with 4 x 10 ml a of toluene.
The residue is dissolved in 5 ml of dichloromethane and added dropwise at 0-2°C to a solution of 0.28 ml (2.0 mmol) of triethylamine and 225 mg (0.4 mmol) of 6-(1-benzyloxycarbonylamino-1--127- _ iminomethyl)-3-(3-aminopropylaminocarbonyl)-1-benzyloxycarbonylindazole hydrochloride (A156) in ml of dichloromethane. l'he reaction mixture is stirred at RT for 4 h, concentrated and the crude product is reacted without further purification.
A98. 4-O-Benzyl-3.6-di-O-(1-imidazocarbonyl)-1.2-dideoxy-D-alucouyranose N,N-Carbonyldiimidazole (1.6 g, 9.9 mmol) is added to a solution of 4-O-benzyl-1,2-dideoxy-glucopyranose (0.8 g, 3.3 mmol) in absolute CI-hCl2 (10 ml) and the mixture is stirred at RT for 45 min.
The reaction solution is diluted with aqueous semisaturated NaCI solution (20 ml) and extracted with CH2C12 (20 ml). The organic phase is dried over MgS04 and concentrated in vacuo. The title compound thus obtained is employed in the next reaction without further purification.
A99. 3-O-(4-f4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazin-1-yl-carbonvl~-6-O-~Z-f(6-aminocarbonvl-1-benzyloxycarbonylindol-3-yl)carbonylaminoleth-1-ylaminocarbonyl~-1.2-dideoxy-D-glucoayranose A solution of 250 mg (0.36 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylamino-carbonyl]piperazin-1-ylcarbonyi}-4-O-benzyl-6-O-(2-aminoeth-1-ylaminocarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A102) in 15 ml of dichloromethane is treated successively with 121 mg (0.36 mmol) of 6-aminocarbonyl-1-benzyloxycarbonylindol-3-carboxylic acid (starting com-pound A155), with 74 NI (0.54 mmoi) of triethylamine and 102 mg (0.54 mmol) of EDC hydrochloride and stirred at RT for 20 h. It is concentrated and the crude product is chromatographed on silica gel (dichloromethanelmethanol = 20:1 -~ 10:1 ). 180 mg of the title compound are obtained as a colorless foam.
MS: calc.: C3~H48N80$ (1018.44), found: [MH'] 1019.1 A100. 3-O-~4-f4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazin-1-ylcar-bonyl}-4-O-benzyl-6-O-t3-f6-aminocarbonyl-1-benzyloxycarbonylindol-3-yl)carbonyl-aminolproa-1-ylaminocarbonY,l~-1.2-dideo~-D-plucopyranose A solution of 220 mg (0.31 mrnol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylamino-carbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-(3-aminoprop-1-ylaminocarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A103) in 15 ml of dichlorornethane is treated successively with 104 mg (0.31 mmol) of 6-aminocarbonyl-1-benzyloxycarbonylindol-3-carboxylic acid (starting compound A155), with 64~p1 (0.46 mmol) of triethylamine and 89 mg (0.46 mmol) of EDC hydrochloride and stirred at RT for 1E;.,h. It is concentrated and the crude product is chromatographed on silica gel (dichloromethane/methanol = 20:1 ~ 10:1 ). 240 mg of the title compound are obtained as a colorless foam.

MS: calc.: C3~H48Na08 (1032.46), found. [MI-f~] 1033.1 A101. 3-O-~4-f4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllaiaerazin-1 ylcar-bonyl)-4-O-benzyl-6-O-f4-f(6-aminocarbonyl-1-benzyloxycarbonylindol-3-yl)carbonyl aminolbut-1-ylaminocarbon~?-1.2-dideoxy-D-ctlucopyranose A solution of 410 mg (0.56 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylamino-carbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-(4-aminobut-1-ylaminocarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A103) in 20 ml of dichloromethane is treated successively with 190 mg (0.56 mmol) of 6-aminocarbonyl-1-benzyloxycarbonylindol-3-carboxylic acid (starting com-pound A155), with 117 NI (0.86 mmoi) of triethylamine and 162 mg (0.86 mmol) of EDC hydrochloride and stirred at RT for 16 h. It is concentrated and the crude product is chromatographed on silica gel (dichloromethane/methanol = 20:1 ~ 10:1). 300 mg of the title compound are obtained as a colorless amorphous powder.
MS: calc.: C3~H48N80$ (1046.47), found: [MH'] 1047.1 A102. 3-O-1'4-f4-(tert-Butyloxycarbonylaminomethvl)benzylaminocarbonyllniperazin-1- IY car-bonvll-6-O-(2-aminoeth-1-ylaminocarbonyl)-1 2-dideoxy-D-plucopyranose A solution of 356 mg (0.5 mmol) of 3-O-{4-[4-(tent-butyloxycarbonylaminomethyl)-benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A105) in 10 ml of dichloromethane is added dropwise to a solution of 0.34 ml (5.0 mmol) of 1,2-diaminoethane in 10 ml of dichloromethane. The mixture is stirred at RT
for 16 h, then treated with 20 ml of water, the organic phase is separated off and the aqueous phase is extracted with 2 x 10 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate and concentrated. 340 mg of the title compound are obtained.
A103. 3-0~4-f4-(tert-Butyloxycarbonylaminomethyl)benz)rlaminocarbonylluiperazin-1-ylcar-bonyl~-4-O-benzyl-6-O-(3-aminoarop-1-ylaminocarbonyl)-1 2-dideoxy-D-alucopyranose A solution of 210 mg (0.3 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]-piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A105) in 10 ml of dichloromethane is added dropwise to a solution of 0.25 ml (3.0 mmol) of 1,3-diaminopropane in 5 ml of dichloromethane. The mixture is stirred at RT
for 16 h, then treated with 20 ml of water, the organic phase is separated off and the aqueous phase is extracted with 10 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate and concentrated.
220 mg of the title compound are obtained.

-129- s A104. 3-O-f4-f4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazin-1-ylcar-bonyl~-4-O-benzyl-6-O-(4-aminobut-1-ylarninocarbonyl)-1 2-dideoxy-D-glucopyranose A solution of 510 mg (0.72 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylamino-carbonyl]piperazin-1-ylcarbonyi}-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (starting compound A105) in 10 ml of dichloromethane is added dropwise to a solution of 0.8 ml (8.0 mmol) of 1,4-diaminobutane in 10 ml of dichloromethane. The mixture is stirred at RT for 20 h, then treated with 20 m( of water, the organic phase is separated off and the aqueous phase is ex-tracted with 2 x 10 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate and concentrated. For purification, the crude product is chromatographed on silica gel (ethyl acetate/me#hanol/ammonia = 20:4:1 ). 470 mg of the title compound are obtained.
A105. 3-O-~4-C4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazin-1-yl-carbonyfl-4-O-benzyl-6-O-(imidazol-1-ylcarbonyll-1.2-dideoxy-D-alucopyranose 3.0 g (49 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-yl-carbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (starting compound A106) and 0.95 g (5.87 mmol) of carbonyldiimidazole are stirred in 50 ml of dichloromethane with ice-cooling for 30 min and at RT for 18 h. The mixture is added to water, the organic phase is separated off and the aqueous phase is ex-tracted with 2 x 50 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate. The filtrate is concentrated and the residue is dried in a high vacuum for 30 min. 3.55 g of the title compound are obtained as a colorless foam.
A106. 3-O-{4-f4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllniaerazin-1-yl-carbon rl -4.-O-benzyl-1.2-dideoxy-D-ctlucopyranose 39.4 ml (39.4 mmol) of a 1 M solution of tert-butylammonium fluoride in THF
are added dropwise to a solution of 14.3 g (19.7 mmol) of 3-O-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]-piperazin-1-ylcarbonyl}~-O-benzyl-6-O-t-butyldimethylsilyl-1,2-dideoxy-D-glucopyranose (starting compound A107) in 100 ml of THF. After 3 h at RT, the mixture is concentrated to dryness, and the residue is hydrolyzed with dilute ammonium chloride solution and extracted with 3x200 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate and concentrated. The crude product is purified by chromatography (ethyl acetate). 11.87 g of'the title compound are obtained as a colorless foam.

A107. 3-O-~4-(4-(tert-Butyloxycarbonylaminomethyl)benz3rlaminocarbonyllpiaerazin-1-yl-carbonyl~-4-O-benzyl-6-O-tert-butyldimethyfsilyl-1,2-dideoxy-D-alucopyranose 71 ml (135 mmol) of a 20% strength solution of phosgene in toluene are cooled to 0-2°C. A solution of 9.5 g (26.95 mmol) of 4-O-benzyl-6-O-tert-butyldimethylsilyi-1,2-dideoxy-D-glucopyranose (starting compound A53) and 33 ml (189 mmol) of diisopropylethylamine in 100 ml of dichloromethane is added dropwise to this over the course of 50 min. The mixture is subsequently stirred, first with ice-cooling (20 min), then at RT (90 min). It is concentrated and coevaporated with 2 x 50 ml of toluene. The resi-due is dissolved in 100 ml of dichloromethane, treated with 33 ml (189 mmol) of diisopropylethylamine and the solution is again cooled to 0-2°C. 9.4 g (26.95 mmol) of 1-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazine (starting compound A130) is added dropwise to this over the course of 20 min and the mixture is subsequently stirred with cooling for 30 min and at RT for 2 h. It is treated with water, the organic phase is separated off and the aqueous phase is extracted with 3 x 200 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate and concentrated. The crude product is purified by chromatography (toluene/ethyl acetate = 1:1 ). 14.34 g of the title compound are obtained as a colorless foam.
A108. 3-O-(4-(6-tent-Butyloxycarbonylaminoayridin-3-ylmethylaminocarbonyl)piperidin-1-carbonvll-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1.2-dideoxy-D-ctlucoayranose 440 g (0.73 mmol) of 3-O-{4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (starting compound A109) and 165 mg (1.0 mmol) of carbonyldiimidazole are stirred in 5 ml of dichloromethane at RT
for 4 h. The mixture is added to water, the organic phase is separated off and the aqueous phase is extracted with 2 x 30 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate. The filtrate is concentrated and the residue is dried in a high vacuum for 30 min. The product is reacted without fur-ther purification.
A109. 3-O-f4-(6-tert-Butvloxycarbonylaminoayridin-3-ylmethylaminocarbonyl)aiperidin-1-yl-carbonyll-4-O-benz~rl-1.2-dideoxy-D-calucopyranose 3.33 ml (3.33 mmol) of a 1 M solution of tert-butylammonium fluoride in THF
are added dropwise to a solution of 1.19 g (1.67 mmol) of 3-O-{4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylamino-carbonyl)piperidin-1-ylcarbonyl}-4-O-benzyl-6-O-(tent-butyldimeth~lsilyl)-1,2-dideoxy-D-glucopyranose (starting compound A110) in 12 ml of THF. After 10 h at RT, the mixture is concentrated to dryness, and the residue is hydrolyzed with water and extracted with 3 x 50 ml of ethyl acetate. The combined a.
organic phases are dried over magnesium sulfate and concentrated. The crude product is purified by chromatography (ethyl acetate -~ ethyl acetate/methanol = 10:1 ). After crystallization from diisopropyl ether, 490 mg of the title compound of m.p. 136-.138°C are obtained.

-131 - ~ -A110. 3-O-f4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-yl carbonyl~-4-O-benzyl-6-O-(tert-butyldimethylsilyll-1,2-dideoxy-D-gilucopyranose 4.08 g (12.2 mmol) of 4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidine (starting compound A118) and 4.50 g (10.16 mmol) of 4-O-benzyl-3-O-(imidazol-1-ylcarbonyl)-6-O-(tert-butyldimethylsilyl)-1,2-dideoxy-D-glucopyranose (starting compound A111 ) in 260 ml of DMF are stirred at 80°C for 3 days. The reaction mixture is largely concentrated, treated with water and ex-tracted with 350 ml of dichloromethane. The combined organic phases are dried over magnesium sul-fate and the crude product is chromatographed on silica gel for purification (toluene/ethyl acetate= 1:2 -~ ethyl acetate). 1.35 g of the title compound are obtained.
A111. 4-O-Benzvl-3-O-(imidazol-1-ylcarbonyl)-6-O-(tert-butyldimethylsilyl)-1,2-dideoxy-D-glucoQyranose 8.8 g (25.0 mmol) of 4-O-benzyl-6-O-(tertbutyldimethylsilyl)-1,2-dideoxy-D-glucopyranose (starting compound A53) and 5.26 g (32.5 mmol) of carbonyldiimidazole are stirred in 100 ml of dichloromethane at RT for 1 h. The mixture is hydrolyzed with water, the organic phase is separated off and the aqueous phase is extracted with 2 x 100 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate. 11.56 g of the title compound are obtained as a colorless oil.
A112. 1-f3-(tert-Butyloxycarbonylaminometh I~enzoyllpiperazine 7.48 g (16.5 mmol) of benzyl 4-[3-(tert-butyloxycarbonylaminomethyl)benzoyl]piperazine-1-carboxylate (starting compound A133) are hydrogenated on palladiumlcarbon (10%) for 2 h in 300 ml of methanol.
The catalyst is filtered off, the solvent is removed and 5.33 g of the title compound are obtained as a nonmobile pale yellow oil.
A113. 4-f3-(tert-Butyfoxycarbonylaminomethyl)benzoylaminolaiperidine 4.66 g (11.0 mmol) of 1-benzyl-4-[3-(tert-butyloxycarbonylaminomethyl)benzoylamino]piperidine (start-ing compound A134) are hydrogenated on palladium/carbon (5%) at 50°C
for 5 h in 360 ml of glacial acetic acid. The catalyst is filtered off and the solvent is removed. The crude product is treated yvith dichloromethane and extracted with 2 x 75 ml of 2 N sodium hydroxide solution.
The combined organic phases are dried over magnesium sulfate and after crystallization from diethyl ether 2.95 g of the title compound are obtained as a colorless solid.
A114. 1-f3-(tert-Butyfoxycarbonvlaminomethyl)benzvlaminocarbonvllpiperazine 13.77 g (28.5 mmol) of benzyl 4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]-piperazine-1-carboxylate (starting compound A135) are hydrogenated on palladium/carbon (10%) for 4 h in 400 ml of methanol. The catalyst is filtered off, the solvent is removed and 10.35 g of the title compound are obtained as a nonmobile oil.
A115. 413-(tert-Butyloxycarbonylaminomethyllbenzylaminocarbonylaminoluiperidine 2.98 g (6.19 mmol) of 1-benzyl-4-[3-(tert-butyloxycarbonylaminomethyl)benzoylaminocarbonylamino]-piperidine (starting compound A136) are hydrogenated on palladiumlcarbon (5%) at 50°C for 3.5 h in 360 ml of glacial acetic acid. The catalyst is filtered off and the solvent is removed. The crude product is treated with 100 ml of dichloromethane and extracted with 2 x 75 ml of 2 N
sodium hydroxide solu-tion. The combined organic phases are dried over magnesium sulfate and after crystallization from diethyl ether 1.94 g of the title compound are obtained as a colorless solid.
A116. 4-f3-(tert-But~xycarbonylaminomethyl)benzylaminocarbonylluiperidine 2.98 g (6.19 mmol) of benzyl 4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperidine-1-carboxylate (starting compound A137) are hydrogenated on palladiumlcarbon (5%) for 1 h in 150 ml of methanol. The catalyst is filtered off, the solvent is removed and 2.2 g of the title compound are ob-tained as a pale yellow nonmobile oil.
A117. 4-traps-f3-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllcyclohexylmethyl-amine 5.3 g (10.4 mmol) of benzyl 4-traps-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]-cyclohexylmethylcarbamate (starting compound A138) are hydrogenated on palladium/carbon (10%) for 32 h in 200 ml of methanol and 200 ml of dichloromethane. The catalyst is filtered off, the solvent is removed and the residue is crystallized from diethyl ether. 3.17 g of the title compound of m.p. > 245°C
are obtained.
A118. 4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethylaminocarbonvllaiperidine 650 mg (0.81 mmol) of benzyl 4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylamino-carbonyl)piperidine-1-carboxylate (starting compound A139) are hydrogenated on palladiumlcarbon (5%) for 1 h in 25 ml of methanol and 25 ml of THF. The catalyst is filtered off, the solvent is removed and the residue is crystallized from diethyl ether. 420 mg of the title compound of m.p. > 240°C are obtained.
r A119. 4-(6-tent-Butyloxycarbonylamino-2-methylnyridin-3-ylmethylaminocarbonyl)piaeridine 960 mg (2.0 mmol) of benzyl 4-(6-tert-butyloxycarbonylamino-2-methylpyridin-3-ylmethylamino-carbonyl)piperidine-1-carboxylate (starting compound A140) are hydrogenated on palladium/carbon (5%) for 1 h in 40 ml of methanol. The catalyst is filtered off, the solvent is removed and 560 mg of the title compound are obtained as a colorless foam.
A120. 1-(4-Nitrobenzylaminocarbonyl)~peridine hydrochloride 2.25 g (8.5 mmol) of tert-butyl 4-(4-nitrobenzylaminocarbonyl)piperidine-1-carboxylate (starting com-pound A141) are dissolved in 30 ml of dioxane and treated with 6 ml (24 mmol) of 4 N HCI in dioxane.
After stirring at RT far 16 h, the solvent is distilled off and the residue is coevaporated with 3 x 30 ml of diethyl ether. 1.79 g of the title compound are obtained.
A121. 4-traps-(6-tert-Butvloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)cyclohexylme-thylamine 530 mg (1.07 mmol) of benzyl 4-traps-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)-cyclohexylmethylcarbamate (starting compound A142) are hydrogenated on palladiumlcarbon (5%) for 1 h in 30 ml of methanol and 40 ml of THF. The catalyst is filtered off, the solvent is removed and the residue is crystallized from diethyl ether. 330 mg of the title compound of m.p. > 245°C are obtained.
A122. 4-traps-(6-tert-Butyloxycarbonylamino-2-methylayridin-3-ylmethylaminocarbonyl)cyclo-hexvlmethvlamine 1.28 g (2.5 mmol) of benzyl 4-traps-(6-tent-butyloxycarbonylamino-2-methylpyridin-3-ylmethylamino-carbonyl)cyclohexylmethylcarbamate (starting compound A143) are hydrogenated on palladium/carbon (5%) for 1 h in 100 ml of methanol. The catalyst is filtered off, the solvent is removed and 910 mg of the title compound are obtained as a colorless oil.
A123. 4-traps-~,4-Nitrobenzylaminocarbonyl)cyclohexylmethylamine hydrochloride 1.5 g (3.83 mmol) of tent-butyl 4-traps-(4-nitrobenzylaminocarbonyl)cyclohexylmethylcarbamate (start-ing compound A144) are dissolved in 50 ml of dioxane and treated with 10 ml (40 mmol) of 4 N HCI in dioxane. After stirring at RT for 16 h, the solvent is distilled off and the residue is coevaporated with 3 x 25 ml of diethyl ether. 1.32 g of the title compound are obtained.
A124. 3-(4-Nitrobenzylaminocarbonyl)benzylamine hydrochloride 2.1 g (5.4 mmol) of tent-butyl 4-traps-(4-nitrobenzylaminocarbonyl)cyclohexylmethylcarbamate (starting a compound A144) are dissolved in 70 ml of dioxane and treated with 12 ml (48 mmol) of 4 N HCI in dioxane. After stirring at RT for 16 h, the solvent is distilled off and the residue is coevaporated with 3 x 25 ml of diethyl ether. 1.52 g of the title compound are obtained.

-134- , A125. 4-[3-(Imidazol-1-yl)prop~rlaminocarbonYljpiperidine 2.6 g (7.0 mmol) of benzyl 4-[3-(imidazol-1-yl)propylaminocarbonylJpiperidin-1-carboxylate (starting compound A146) in 50 ml of methanol are hydrogenated for 1 h on palladiumlcarbon (5%). The cata-lyst is filtered off, the solvent is removed and 1.65 g of the title compound are obtained as a colorless oil.
A126. 4-f4-(Imidazol-1-yl)butylaminocarbonyllpiperidine 860 mg (2.23 mmol) of benzyl 4-[4-(imidazol-1-yl)butylaminocarbonyl]piperidine-1-carboxylate (starting compound A147) in 80 ml of methanol are hydrogenated for 1 h on palladiumlcarbon (5%). The cata-lyst is filtered off, the solvent is removed and 560 mg of the title compound are obtained as a colorless oil.
A127. 4-[5-(Imidazol-1-yl)pentyiaminocarbony(lpiperidine 740 mg (1.86 mmol) of benzyl 4-[5-{imidazol-1-yl)pentylaminocarbonyl]piperidine-1-carboxylate (starting compound A148) in 80 ml of methanol are hydrogenated for 1 h on palladium/carbon (5%).
The catalyst is filtered off, the solvent is removed and 490 mg of the title compound are obtained as a colorless oil.
A128. 4-f6-(Imidazol-1-yl)hexylaminocarbonyllpiperidine 720 mg (1.74 mmol) of benzyl 4-[6-(imidazol-1-yl)hexylaminocarbonyl]piperidine-1-carboxylate (starting compound A149) in 80 ml of methanol are hydrogenated for 1 h on palladiumlcarbon (5%). The cata-lyst is filtered off, the solvent is removed and 482 mg of the title compound are obtained as a colorless oil.
A129. 4-f8-(Imidazol-1-yl)octylaminocarbonyllpiperidine 820 mg (1.86 mmol) of benzyl 4-[8-(imidazol-1-yl)octylaminocarbonyl]piperidine-1-carboxylate (starting compound A150) in 80 ml of methanol are hydrogenated for 1 h on palladiumlcarbon (5%). The cata-lyst is filtered off, the solvent is removed and 580 mg of the title compound are obtained as a colorless oil.
A130. 1-~4-(tert-Butyio~iycarbonylaminomethyl)benzylaminocarbonyllpiperazine 41.7 mg (86.4 mmol) of benzyl 1-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]-piperazine-1-carboxylate (starting compound A151 ) in 1.0 I of methanol are hydrogenated for 4 h on palladiumlcarbon (5%}. The catalyst is filtered off, the solvent is removed arid 30.3-g of the title com-pound are obtained as a colorless oil.
A131. tert-Butvl f4-trans-(4-aminobutylaminocarbonyl)cyclohexylmethyllcarbamate 1.52 g (3.29 mmol) of tert-butyl [4-(4-benzyloxycarbonylaminobutylaminocarbonyl)cyclohexylmethylJ-carbamate (starting compound A152) in 85 ml of methanol are hydrogenated for 1 h on palla-diumlcarbon (5%). The catalyst is filtered off, the solvent is removed and the residue is crystallized from diisopropyl ether. 860 mg of the title compound of m.p. 132°C are obtained.
A132. 3-Amino-N-(6-aminopyridin-3-ylmethyl)propionamide 390 mg (119 mmol) of benzyl {2-[(6-aminopyridin-3-ylmethyl)aminocarbonyl]ethyl}carbamate (starting compound A153) in 60 ml of methanol are hydrogenated for 1 h on palladiumlcarbon (5%). The cata-lyst is filtered off, the solvent is removed and 210 mg of the title compound are obtained as a colorless oil.
A133. Benzyl1-f3-(tent-butyloxycarbonylaminomethvl)benzoylluiperazine-1-carboxylate A solution of 5.0 g (19.5 mmol) of 3-(tert-butyloxycarbonylaminomethyl)benzoic acid in 50 ml of THF is treated successively with 13.6 ml (97.2 mmol) of triethylamine, 4.0 g (29.6 mmol) of hydroxybenzotriazole and 10.0 g (29.6 mmol) of EDC hydrochloride and stirred at RT for 4 h. 4.3 g (19.5 mmol} of benzyl piperazine-1-carboxylate in 50 ml of THF are then added dropwise in the course of 25 min and the mixture is stirred at RT for 20 h. The reaction mixture is freed from the solvent and treated with water. It is extracted with 3 x 120 ml of ethyl acetate and the combined organic phases are dried over magnesium sulfate. After crystallization from diethyl ether, 7.99 g of the title compound are obtained as a colorless solid of m.p. 123°C.
A134. 1-Benzvt-4-f3-(tert-butyloxycarbonylaminomethyl)benzoylaminolpiperidine A solution of 1.6 g (6.36 mmol) of 3-(tert-butyloxycarbonylaminomethyl)benzoic acid in 15 ml of THF is treated successively with 4.45 ml (31.8 mmol) of triethylamine, 1.3 g (9.54 mmol) of hydroxybenzotri-azole and 2.4 g (12.52 mmol) of EDC hydrochloride and stirred at RT for 2 h.
1.22 g (6.36 mmol) of 4-amino-1-benzylpiperidine in 20 ml of THF are then added dropwise in the course of 10 min and the mixture is stirred at RT for 20 h. The reaction mixture is freed from the solvent and treated with water. It is extracted with 3 x 75 ml of ethyl acetate and the combined organic phases are dried over magne-sium sulfate. After crystallization from diisopropyl ether, 2.47 g of the title compound are obtained as a solid of m.p. 137°C.

A135. Benzyl 1-f3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazine-1-carboxvlate 10.0 g (42.3 mmol) of 3-(tert-butyloxycarbonylaminomethyl)benzylamine in 200 ml of dichloromethane are added dropwise at 0°C to a solution of 8.95 g (44.4 mmol) of 4-nitrophenyl chloroformate in 200 ml of dichloromethane and the mixture is subsequently stirred for 60 min. 6.2 g (44.4 mmol) of triethyl-amine in 50 ml of dichloromethane are then added dropwise and the mixture is stirred at RTfor 1.5 h.
At 0°C, first 9.8 g (44.4 mmol) of benzyl piperazine-1-carboxylate in 100 ml of dichloromethane and then 6.2 g (44.4 mmol) of triethylamine in 50 ml of dichloromethane are subsequently added dropwise.
The mixture is stirred at RT for 16 h. The reaction mixture is then freed from the solvent and the crude product is chromatographed on silica gel (toluenelethyl acetate = 1:1) and 13.77 g of the title com-pound are obtained as a colorless solid of m.p. 128°C.
A136. 1-Benzvl-4-f3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonylaminolpiperidine 4.73 g (20.0 mmol) of 3-(tert-butyloxycarbonylaminomethyl)benzylamine in 45 ml of dichloromethane are added dropwise in the course of 60 min at 0°C to a solution of 4.24 g {21.0 mmol) of 4-nitrophenyl chloroformate in 100 ml of dichloromethane and the mixture is subsequently stirred for 40 min. 3.0 ml (21.5 mmol) of triethylamine in 15 ml of dichloromethane are then added dropwise in the course of 10 min and the mixture is stirred at 0°C for 10 min and at RT for 1.5 h.
At 0°G, first 4.0 g (21.0 mmol) of 4-amino-1-benzylpiperidine in 20 ml of dichloromethane and then 3.0 ml (21.5 mmol) of triethylamine in 15 ml of dichloromethane are subsequently added dropwise. The mixture is then stirred at RT for 16 h.
The reaction mixture is then freed from the solvent and the crude product is chromatographed on silica gel (ethyl acetate). After crystallization from diethyl ether, 6.36 g of the title compound are obtained as a colorless solid of m.p. 132°C.
A137. Benzvl 4-f3-(tert-butyloxvcarbonylaminomethyllbenzylaminocarbonyllpiperidine-1-carboxylate A solution of 3.7 g (14.0 mmol) of 4-(benzyloxycarbonyl)piperidine-1-carboxylic acid in 50 ml of THF is treated successively with 9.8 ml (70.0 mmol) of triethylamine, 2.8 g (21.0 mmol) of hydroxybenzotri-azole and 5.4 g (70.0 mmol) of EDC hydrochloride and stirred at RT for 1.5 h.
3.3 g (14.0 mmol) of 3-(tert-butyloxycarbonylaminomethyl)benzylamine in 50 ml of TWF are then added dropwise in the course of 12 min and the mixture is stirred at RT for 20 h. The reaction mixture is freed from the solvent and treated with water. It is extracted with 3 x 100 ml of ethyl acetate and the combined organic phases are dried over magnesium sulfate. The crude product is chromatographed on silica gel (tolu-ene/acetone = 5:1 ) and after crystallization from diethyl ether 3.01 g of the title compound are obtained as a colorless solid of m.p. 121 °C.

A138. Benzyl 4-trans-f3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyllc~rclohexyl-methylcarbamate A solution of 4.1 g (14.0 mmol) of 4-trans-(benzyloxycarbonylaminomethyl)cyclohexanecarboxylic acid in 60 ml of THF is treated successively with 9.8 ml (70.0 mmol) of triethylamine, 2.8 g (21.0 mmol) of hydroxybenzotriazole and 5.4 g (70.0 mmol) of EDC hydrochloride and stirred at RT far 1.5 h. 3.3 g (14.0 mmol) of 3-(tert-butyloxycarbonylaminomethyl)benzylamine in 50 ml of THF
are then added dropwise in the course of 14 min and the mixture is stirred at RT for 20 h after addition of 30 ml of THF.
The reaction mixture is freed from the solvent and treated with water and ethyl acetate. The solid is filtered off and washed with water. After crystallization from diethyl ether, 5.61 g of the title compound are obtained as a colorless solid of m.p. 196°C.
A139. Benzyl 4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyltpiperidin-1-carboxyrlate A solution of 2.11 g (8.01 mmol) of 4-(benzyloxycarbonyl)piperidine-1-carboxylic acid in 30 ml of THF is treated successively with 4.7 ml (33.3 mmol) of triethylamine, 1.35 g (10.0 mmol) of hydroxybenzotri-azole and 2.56 g (13.3 mmol) of EDC hydrochloride and stirred at RT for 2 h.
1.49 g (6.67 mmol) of 6-tert-butyloxycarbonylaminopyridin-3-ylmethylamine in 15 ml of THF are then added dropwise in the course of 20 min and the mixture is stirred at RT for 24 h. The reaction mixture is freed from the solvent and treated with water. It is extracted with 3 x 25 ml of ethyl acetate and the combined organic phases are dried over magnesium sulfate. The crude product is chromatographed on silica gel (ethyl acetate) and 2.0 g of the title compound are obtained as an amorphous solid.
A140. Benzvl 4-(6-tent-butyloxycarbonylamino-2-methvlpyridin-3-ylmethylarninocarbonvl)-piperidine-1-carboxylate 700 mg (2.95 mmol) of 6-terk-butyloxycarbonylamino-2-methylpyridin-3-ylmethylamine are reacted with 776 mg (2.95 mmol) of 4-(benzyloxycarbonyl)piperidine-1-carboxylic acid, 2.06 ml (14.7 mmol) of tri-ethylamine, 600 mg (4:42 mmol) of hydroxybenzotriazole and 1.31 g (5.9 mmol) of EDC hydrochloride analogously to the preparation of A139. After chromatographic purification (ethyl acetate), 1.01 g of the title compound are obtained as a colorless foam.
A141. tert-Butvl4-(4-nitrobenzylaminocarbonyl)piperidine-1=carbox~ate A solution of 2.0 g (8.72 rrimol) of 4-(tert-butyloxycarbonyl)piperidin-1-carboxylic acid in 60 ml of THF is treated successively-., with 6.0 rnl (42.5 mmol) of triethylamine, 1.76 g (13.0 mmol) of hydroxybenzotriazole and 3.36 g (17.5 mmol) of EDC hydrochloride and stirred at RT for 2 h. 3.29 g (8.72 mmol) of 4-nitrobenzylamine hydrochloride are added dropwise in the course of 20 min and the mixture is stirred at RT for 24 h. The reaction mixture is freed from the solvent and treated with water. It l..

is extracted with 3 x 25 ml of ethyl acetate, the combined organic phases are Washed successively with 0.1 N HCI and 0.1 N NaOH, dried over magnesium sulfate and concentrated, and the residue is crystallized from diethyl ether. 2.65 g of the title compound are obtained.
A142. Benzvl 4-trans-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)cyclo-hex Iy meth~rlcarbamate 390 mg (1.74 mmol) of 6-tert-butyloxycarbonylaminopyridin-3-ylmethylamine are reacted with 510 mg (1.74 mmol) of 4-trans-(benzyloxycarbonylaminomethyl)cyclohexylmethylcarboxylic acid, 1.22 ml (8.7 mmol) of triethylamine, 355 mg (2.62 mmol) of hydroxybenzotriazole and 670 g (3.5 mmol) of EDC
hydrochloride analogously to the preparation of A139. After chromatographic purification (dichlo-romethanelmethanol = 19:1) and crystallization from diethyl ether, 590 mg of the title compound of m.p.
190-192°C are obtained.
A143. Benzyl 4-traps-16-tert-butyloxycarbonylamino-2-methylpyridin-3-ylmethylamino-carbonyl)c cy lohexylmethylcarbamate 700 mg (2.95 mmol) of 6-tert-butyloxycarbonylamino-2-methylpyridin-3-ylmethylamine are reacted with 860 mg (2.95 mmol) of 4-traps-(benzyloxycarbonylaminomethyl)cyclohexylmethylcarboxylic acid 2.06 mi (14.7 mmol) of triethylamine, 600 mg {4.42 mmol) of hydroxybenzotriazole and 1.31 g (5.9 mmol) of EDC hydrochloride analogously to the preparation of A139. After chromatographic purifi-cation {dichloromethane/methanol = 19:1) and crystallization from diisopropyl ether, 1.35 g of the title compound of m.p. 159-161°C are obtained.
A144. tert-Butyl4-traps-(4-nitrobenzvlaminocarbonyllcyclohexylmethylcarbamate 4.4 g (24 mmol) of 4-nitrobenzylamine hydrochloride are reacted with 3.0 g (12 mmol) of 4-traps-{tert-butyloxycarbonylaminomethyl)cyclohexylmethylcarboxylic acid, 8 ml (60 mmol) of triethylamine, 2.43 g (18 mmol) of hydroxybenzotriazole and 4.6 g (24 mmol) of EDC hydrochloride analogously to the preparation of A141. 2.'52 g of the title compound are obtained.
A145. tert-Butvl3-(4-nitrobenzylaminocarbonyl)benz)rlcarbamate 3 g (16 mmol) of 4-nitrobenzylamine hydrochloride are reacted with 2.0 g (7.9 mmol) of 3-{tert-butyloxycarbonylaminomethyl)benzoic acid, 6 ml (43 mmol) of triethyiamine, 1.6 g (11.85 mmol) of hydroxybenzotriazole and' 3.0 g (15.8 mmol) of EDC hydrochloride analogously to the preparation of A141. 2.77 g of the title compound are obtained.

A146. Benzvl4-f3-(imidazol-1-yl)propylaminocarbonyllpiperidine-1-carboxylate A solution of 3.3 g (12.6 mmol) of 4-(benzyloxycarbonyl)piperidine-1-carboxylic acid in 40 ml of THF is treated successively with 8.8 ml (62.8 mmol) of triethylamine, 2.54 g (18:9 mmol) of hydroxybenzotri-azole and 4.82 g (25.1 mmol) of EDC hydrochloride and stirred at RT for 2 h.
1.5 ml (12.6 mmol) of 3-(imidazol-1-yl)propylamine in 5 ml of THF are then added dropwise in the course of 10 min and the mixture is stirred at RT for 48 h. The reaction mixture is freed from the solvent and treated with water. It is extracted with 3 x 30 ml of ethyl acetate and the combined organic phases are dried aver magne-sium sulfate. The crude product is chromatographed on silica gel (ethyl acetatelmethanollammonia =
10:1:0.5) and the product is crystallized from diethyl ether. 2.3 g of the title compound of m.p. 98-103°C
are obtained.
A147. Benzvl4-f4-(imidazol-1-yl)butylaminocarbonyllaiperidine-1-carboxylate 1.32 g (9.5 mmol) of 4-(imidazol-1-yl)butylamine are reacted with 2.5 g (9.5 mmol) of 4-(benzyloxycarbonyl)piperidine-1-carboxylic acid, 6.7 ml (47.5 mmol) of triethylamine, 1.93 g (14.2 mrnol) of hydroxybenzotriazole and 3.64 g (19.1 mmol) of EDC
hydrochloride analogously to the preparation of A146. After chromatographic purification (ethyl acetatelmethanollammonia = 10:1:0.5);
3.6 g of the title compound are obtained as a colorless oil.
A148. Benzvl4-f5-(imidazol-1-yllpentylaminocarbonyllpiperidine-1-carboxylate 1.28 g (8.36 mmoi) of 5-(imidazol-1-yl)pentylamine are reacted with 2.2 g (8.36 mmol) of 4-(benzyloxycarbonyl)piperidine-1-carboxylic acid, 5.85 ml (41.8 mmol) of triethylamine, 1.69 g (12.5 mmol) of hydroxybenzotriazole and 3.2 g (16.7 mmol) of EDC hydrochloride analogously to the preparation of A146. After chromatographic purification (ethyl acetatelmethanollammonia = 10:1:0.5), 2.49 g of the title compound are obtained as a colorless oil.
A149. Benzyl4-f6-(imidazol-1-vl)hexylaminocarbonyllpiperidine-1-carboxylate 1.28 g {7.68 mmol) of 6-(imidazol-1-yl)hexylamine are reacted with 2.02 g (7.68 mmol) of 4-(benzyloxycarbonyl)piperidine-1-carboxylic acid, 5.37 ml (38.4 mmol) of triethylamine, 1.56 g (11.5 mmol) of hydroxybenzotriazole and 2.94 g (15.4 mmol) of EDC
hydrochloride analogously to the preparation of A146. After chromatographic purification (ethyl acetatelmethanol/ammonia = 10:1:0.5), 2.45 g of the title compound are obtained as a colorless oil.
A150. Benzvl4-f8-(imidazol-1-yl)octvlaminocarbonyllaiperidine-1-carboxylate 1.37 g (7.0 mmol) of 8-(imidazol-1-yl)octylamine are reacted with 1.84 g (7.0 mmol) of 4-(benzyloxycarbonyl)piperidine-1-carboxylic acid, 4.9 ml (35 mmol) of triethylamine, 1.42 g (10.5 mmol) of hydroxybenzotriazole and 2.68 g (14.0 mmol) of EDC hydrochloride analogously-to the preparation of A146. After chromatographic purification (ethyl acetate/methanol/ammonia =
10:0.3:0.2), 2.04 g of the title compound are obtained as a colorless oil.
A151. Benzyl 4-(4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazine-1-carbo~late 25.0 g (106 mmol) of 4-(tert-butyloxycarbonylaminomethyl)benzylamine in 150 ml of dichloromethane are added dropwise at 0°C to a solution of 22.4 g (111 mmol) of 4-nitrophenyl chloroformate in 200 ml of dichloromethane and the mixture is subsequently stirred for 10 min. 15.6 ml (111 mmol) of triethyl-amine are subsequently added dropwise and the mixture is stirred at RT for 1.5 h. At 0°C, first 24.5 g (111 mmol) of benzyl piperazine-1-carboxylate in 80 ml of dichloromethane and then 15.6 g (111 mmol) of triethylamine are subsequently added dropwise. The mixture is then stirred at RT for 16 h. The reaction mixture is then freed from the solvent and the crude product is chromatographed on silica gel (toluene/ethyl acetate = 1:1 ). After crystallization from diisopropyl ether 41.7 g of the title compound are obtained as a colorless solid of m.p. 108-112°C.
A152. tert-But~rl f4-trans-(4-benzyloxycarbonylaminobutylaminocarbonyl)cyclohexylmethyll-carbamate A solution of 1.2 g (4.66 mmol) of 4-trans-(tert-butyloxycarbonylamino)cyclohexylmethylcarboxylic acid in 30 ml of THF is treated successively with 2.7 ml (19.4 mmol) of triethylamine, 790 mg (5.8 mmol) of hydroxybenzotriazole and 1.45 g (7.8 mmol) of EDC hydrochloride and stirred at RT for 2 h. It is treated with 2.7 ml (7.8 mmol) of triethylamine, 1.0 g (3.88 mmol) of benzyl 4-(aminobutyl)carbamate hydro-chloride in 30 ml of THF is added dropwise in the course of 15 min and it is stirred at RT for 72 h. The reaction mixture is freed from the solvent and treated with water and ethyl acetate. The phases are separated, and the aqueous phase is extracted with 3 x 50 ml of ethyl acetate, dried over magnesium sulfate and chromatographed on silica gel for purification (ethyl acetate).
After crystallization from dii-sopropyl ether, 1.65 g of the title compound are obtained as a colorless solid of m.p. 164-166°C.
A153. Benzyl ~2-f(6-aminopyridin-3-ylmethyl)aminocarbonyllethyl~~carbamate A solution of 590 mg (2.55 mmol) of 3-(benzyloxycarbonylamino)propionic acid in 15 ml of THF is treated successively with 1.07 ml (7.65 mmol) of triethylamine, 520 mg (3.82 mmol) of hydroxybenzo-triazole and 980 mg (5.1 mmol) of EDC hydrochloride and stirred at RT for 2 h.
It is treated with 1.8 ml (12.7 mmol) of triethylamirie, 500 mg (2.55 mmol) of 2-amino-5-aminomethylpyridine dihydrochloride in 30 ml of THF is added'dropwise in the course of 15 min and it is stirred at RT
for 72 h. The reaction mixture is freed from the solvent and treated with water and ethyl acetate.
The phases are separated, and the aqueous phase is extracted with 4 x 50 ml of ethyl acetate, dried over magnesium sulfate and chromatographed on silica gel for purification (ethyl acetatelmethanol/ammonia = 10:1:0.5). After crystallization from diisopropyl ether, 430 mg of the title compound are obtained as a colorless solid of m.p. 158-160°C.
A154. 6-(1-Benzyloxycarbonylamino-1-iminomethyl)-3-(3-tert-butyloxycarbonylaminopropyl-aminocarbony!)-1-benzyloxycarbonylindazole A solution of 472 mg (1.0 mmol) of 6-(1-benzyloxycarbonylamino-1-iminomethyl)-1-benzyloxy-carbonylindazole-3-carboxylic acid in 5 ml of dichloromethane is treated with 0.21 ml (1.25 mmol) of tert-butyl (3-aminopropyl)carbamate and 230 mg (1.2 mmol) of EDC hydrochloride and stirred at RT for 3 h. It is concentrated, precipitated from ethanol and 325 mg of the title compound are obtained:
A155. 6-Aminocarbonyl-1-benzvloxycarbonylindole-3-carboxylic acid Hydrogen sulfide is passed into a solution of 8.3 g (44.0 mmol) of 6-cyano-1-benzyloxycarbonylindole-3-carboxylic acid in 50 ml of pyridine and 50 ml of triethylamine for 20 min.
The mixture is allowed to stand at RT fog 10 days, the solvent is removed in vacuo, the residue is suspended in 200 ml of ace-tone and the mixture is treated with 5.5 ml (88.0 mmol) of methyl iodide. It is first stirred at RT for 16 h and then heated to reflux for 2 h. The solvent is distilled off in vacuo and the residue is heated to reflux for 3 h with 13.6 g (176.0 mmol) of ammonium acetate in 200 ml of methanol.
The solvent is removed in vacuo, and the residue is dissolved in water at 80°C and allowed to crystallize. 5.7 g of the title com-pound are obtained.
MS: calc.: C~oH9N203 (204.19), found: [M H"] 205 A156. 6-(1-Benzytoxycarbonylamino-1-iminomethyl)-3-(3-aminopropylaminocarbonyl)-1-benz-yloxycarbonylindazole hydrochloride 250 mg (0.4 mmol) of 6-(1-benzyloxycarbonylamino-1-iminomethyl)-3-(3-tert-butyloxycarbonylamino-propylaminocarbonyl)-1-benzyloxycarbonylindazole (starting compound A154) are dissolved in 5 ml of dioxane and treated with 1.0 ml (4 mmol) of 4 N HCI in dioxane. After stirring at RT for 4 days, the sol-vent is distilled off and the residue is coevaporated with 25 ml of ethanol.
225 mg of the title compound are obtained.
A157. 6-O-[4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethjilaminocarbonyl)piperidin-1-ylcarbonyll-3-O-f2-f4-trans-(tert-butyloxycarbonylaminomethyl)cyclohexylcarbonyl-aminoleth-1-ylaminocarbonyl~-4-O-benzyl-1.2-dideox5r-D-glucopyranose 3-O-{2-[4-trans-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonylamino)eth-1-ylaminocarbonyl}-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (A166, 370 mg, 0.48 mmol) and 4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidine (A118, 195 mg, 0.58 mmol) are stirred at 50°C for 18 h in 5 ml of DMF. The reaction mixture is largely freed from the solvent, treated with dichloromethane and water, the organic phase is separated off and the aqueous phase is extracted with 2 x 15 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate. The solution is concentrated and the crude product is chromatographed on silica gel (dichlo-romethane/methanol = 19:1). The product is then crystallized from diisopropyl ether and 220 mg of the title compound of m.p. 161°C are obtained.
MS: talc.: C4~H69N~0~2 (923.50), found: [MH+] 924.2 A158. 6-O-f4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyll-3-O-f3-f4-trans-(tert-butyloxycarbonylaminomethyl)cyclohexylcarbonyl-aminolarop-1-ylaminocarbonyl3-4-O-benzyl-1,2-dideoxy-D-alucoayranose 3-O-{3-[4-trans-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonylamino]prop-1-ylaminocarbonyl}-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (A167, 330 mg, 0.38 mmol) and 4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidine (A118, 155 mg, 0.468 mmol) are stirred at 50°C for 18 h in 5 ml of DMF. The reaction mixture is largely freed from the solvent, treated with dichlorornethane and water, the organic phase is separated off and the aqueous phase is extracted with 2 x 15 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate. The solution is concentrated and the crude product is chromatographed on silica gel (dichloromethane/methanol = 19:1 ). The product is then crystallized from diethyl ether and 190 mg of the title compound of m.p. 161 °C are obtained.
MS: talc.: C48H~~N~0~2 (937.51), found: [MH+] 938.2 A159. 6-O-f4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethyrlaminocarbonyi)piperidin-1-ylcarbonyll-3-O-f4-f4-traps-(tert-butyloxycarbonylaminomethylL~~clohexylcarbonyJ-aminolbut-1-ylaminocarbonvll-4-O-benzyl-1.2-dideoxy-D-glucopyranose 3-O-{4-[4-traps-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonylamino]but-1-ylaminocarbonyl}-4 O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (A168, 220 mg, 0.3 mmol) and 4 (6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidine (A118, ,122 mg, 0.36 mmol) are stirred at 50°C for 18 h in 5 ml of DMF. The reaction mixture is largely freed from the solvent, treated with dichloromethane and water, the organic phase is separated off and the aqueous phase is extracted with 2 x 15 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate. The solution is concentrated and the crude product is chromatographed on silica gel (dichlo r romethanelmethanol =''19:1 ). The product is then crystallized from diethyl ether and 120 mg of the title compound of m.p. 161°C are obtained.
MS: talc.: C49H~3N~0~2 (951.53), found: [MH+] 952.2 A160. 6-O-f4-f3-(tert-Butyloxycarbonylaminomethyl)benzoyllpiperazin-1-~rlcarbonyl')-3-O-t4-(6-tert-butvloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl~-4-O-benzyl-1.2-d ideoxy-D-giucopyranose A solution of 3-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (A169, 140 mg, 0.2 mmol) in 1 ml of DMF is combined with a solution of 1-[3-(tert-butyloxycarbonylaminomethyl)-benzoyl]piperazine (A112, 80 mg, 0.25 mmol) in 1 ml of DMF and stirred for 3 days at 50°C. The reac-tion mixture is then concentrated to dryness in a rotary evaporator, treated with 10 ml of semiconcen-trated sodium chloride solution and extracted by shaking with 10 ml of dichloromethane. The organic phase is separated off, dried over magnesium sulfate, freed from the solvent and the crude product is purified by chromatography (dichloromethanelmethanol = 29:1). 170 mg of the title compound are ob-tained.
MS: calc.: C49H65N~0~2 (943.47), found: [MH+] 944.1 A161. 6-O-f4-f3-(tert-Butyloxycarbonylaminomethyl)benzoylaminolpiperidin-1-ylcarbonyl~-3-O-f4-(6-tert-butyloxycarbonylaminouyridin-3-ylmethylaminocarbonyllaiaeridin-1 yl-carbon3rll-4-O-benz~rl-1.2-dideoxy-D-calucopyranose A solution of 3-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4.-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (A169, 140 mg, 0.2 mmol) in 1 ml of DMF is combined with a solution of 4-[3-(tert-butyloxycarbonylaminomethyl)-benzoylamino]piperidine (A113, 90 mg, 0.27 mmol) in 2 ml of DMF and stirred for 4 days at 50°C. The reaction mixture is then concentrated to dryness, treated with 10 ml of semiconcentrated sodium chlo-ride solution and extracted by shaking with 10 ml of dichloromethane. The organic phase is separated off, dried over magnesium sulfate, freed from the solvent and the crude product is purified by chroma-tography (dichloromethanelmethanol = 19:1 ). 180 mg of the title compound are obtained.
MS: calc.: CSOHs~N,0~2 (957.48), found: [MH+] 958.1 A162. 6-O-f4-f3-(tart-Butyloxycarbonylaminomethyl)benzylaminocarbonyllpiaeridin-1-yl-carbonyl~-3-O-f4-(6-tart-butyloxycarbonylaminopyridirf-3-ylmethylaminocarbonyl)-piperidin-1-ylcarbonyll-4-O-benzyl-1.2-dideoxy-D-glucoayranose A solution of 3O-[4-(6-tent-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (A169, 140 mg, 0.2 mmol) in 1 ml of DMF is combined with a solution of 4-[3-(tart-butyloxycarbonylaminomethyl)-benzylaminocarbonyl]piperidine (A116, 90 mg, 0.26 mmol) in 2 ml of DMF and stirred for 5 days at 50°C. The reaction mixture is then concentrated to dryness, treated with 15 ml of semiconcentrated sodium chloride solution and extracted by shaking with 15 ml of dichloromethane. The organic phase is separated off, dried over magnesium sulfate, freed from the solvent and the crude product is purified by chromatography (dichloromethanelmethanol = 19:1). 190 mg of the title compound are obtained.
MS: calc.: CS~H69N~0~2 (971.50), found: [MH+] 972.2 A163. 6-O-!4-trans-f3-(tert-Butyloxycarbonylaminomethyllbenzylaminocarbonyllcyclohexyl-methylaminocarbonyl~-3-O-f4-(6-tert-butyloxycarbonylaminouyridin-3:ylmethylamino-carbonyl)piaeridin-1-ylcarbonyll-4-O-benzyl-1.2-dideox5r-D-alucopyranose A solution of 3-O-[4-(6-tent-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-yl-carbonyl]-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (A169, 120 mg, 0.17 mmol) in 1 ml of DMF is combined with a suspension of 4-trans-[3-(tert-butyloxycarbonyl-aminomethyl)benzylaminocarbonyl]cyclohexylmethylamine (A117, 100 mg, 0.26 mmol) in 2 ml of DMF
and stirred for 9 days at 50°C. The reaction mixture is then concentrated to dryness and the crude product is purified by chromatography (dichloromethanelmethanol = 19:1 ). 150 mg of the title com-pound are obtained.
MS: calc.: C53H73N7O12 (999.53), found: [MH+] 1000.2 A164. 6-O-d4-t3-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyllaiperazin-1-yl-carbonyll-3-O-f4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)-piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose A solution of 3-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-yl-carbonyl]-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (A169, 140 mg, 0.2 mmoi) in 1 ml of DMF is combined with a solution of 1-[3-(tert-butyloxycarbonylaminomethyl)-benzylaminocarbonyl]piperazine (A114, 90 mg, 0.26 mmol) in 1 ml of DMF and stirred for 5 days at 50°C. The reaction mixture is then concentrated to dryness, treated with 15 ml of semiconcentrated sodium chloride solution and extracted by shaking with 15 ml of dichloromethane. The organic phase is separated off, dried over magnesium sulfate, freed from the solvent and the crude, product is purified by chromatography (dichloromethanelmethanol = 19:1 ). 240 mg of the title compound are obtained.
MS: calc.: CSpHggNgO~z (972.50), found: [MH+] 973.1 A165. 6-O-~4-f3-(tert-Butyloxycarbonylaminomethyl)benzylaminocarboriylaminolpiperidin-1-vl carbonvl~-3-O-f4-(6-tent-butyloxycarbonylaminopyridin-3-ylmeth~rlaminocarbonyll piperidin-1 Vlcarbonyll-4-O-benzyl-1.2-dideoxy-D-ctlucop ranose A solution of 3-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-yl-carbonyl]-4-O-benzyl-6-O-(imidazoi-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (A169, 130 mg 0.19 mmol) in 1 ml of DMF is combined with a suspension of 4-[3-(tert-butyloxycarbonylaminomethyl)-benzylaminocarbonylamino]piperidine (A115, 100 mg, 0.26 mmol) in 4 ml of DMF
and stirred for 6 days at 50°C. The reaction mixture is then concentrated to dryness and the crude product is purified by chromatography (dichloromethane/methanol = 19:1 ). 170 mg of the title compound are obtained.
MS: talc.: CS,H~oN80,2 (986.51), found: [MH+] 987.2 A166. 3-O-f2-f4-trans-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonylaminol-eth-1-yl-aminocarbonvl)-4-O-benzyl-6-O-r(imidazol-1-ylcarbonylL1.2-dideoxy-D-glucopyranose 3-O-{2-[4-trans-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonylamino]eth-1-ylaminocarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A170, 270 mg, 0.48 mmol) and 112 mg (0.69 mmol) of car-bonyldiimidazole are stirred at RT for 12 h in 15 ml of dichloromethane. The mixture is added to water, the organic phase is separated off and the aqueous phase is extracted with 2 x 50 ml of dichlo-romethane. The combined organic phases are dried over magnesium sulfate. 370 mg of the title com-pound are obtained as a colorless oil.
A167. 3-O-~'3-f4-trans-ftert-Butyloxycarbonylaminomethyl)cyclohexylcarbonylaminolprop-1-yl-aminocarbonvl~-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1.2-dideoxy-D-glucopyranose 3-O-{3-[4-trans-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonylamino]prop-1-ylaminocarbonyl}- , 4-O-benzyl-1,2-dideoxy-D-glucopyranose (A171, 220 mg, 0.38 mmol) and 95 mg (9.59 mmol) of car-bonyldiimidazole are stirred at RT for 12 h in 20 ml of dichloromethane. The mixture is added to water, the organic phase is separated off and the aqueous phase is extracted with 2 x 50 ml of dichlo-romethane. The combined organic phases are dried over magnesium sulfate. 330 mg of the title com-pound are obtained as a colorless oil.
A168. 3-O~[4-(4-trans-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonylaminolbut-1-yl-aminocarbonyl~-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-alucopyranose 3-O-{4-[4-traps-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonyl]amino]but-1-ylaminocarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A172, 180 mg, 0.3 mmol) and 60 mg (0.39 mmol) of car-bonyldiimidazole are stirred at RT for 12 h in 15 ml of dichloromethane. The mixture is added to water, the organic phase is separated off and the aqueous phase is extracted with 2 x 50 ml of dichlo-romethane. The combined organic phases are dried over magnesium sulfate. 220 mg of the title com-pound are obtained as a colorless foam.
A169. 3-O-(4-(6-tert-Butyloxycarbonylaminonyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyll-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-ulucopyranose 3-O-[4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A173, 920 mg, 1.53 mmol) and 320 mg (1.95 mmol) of carbonyl-diimidazole are stirred at RT for 12 h in 15 ml of dichloromethane. The mixture is added to water, the organic phase is separated off and the aqueous phase is extracted with 2 x 30 ml of dichloromethane.
The combined organic phases are dried over magnesium sulfate. 850 mg of the title compound are obtained as a colorless oil.
A170. 3-O-~2-(4-trans-(tert-Butyloxycarbonylaminomethyt)cyclohexylcarbonylaminoleth-1-yl-aminocarbon~rl~-4-O-benzyl-1.2-dideoxY;D-Aluconyranose 2.6 ml (2.6 mmol) of a 1 M solution of tert-butylammonium fluoride in THF are added dropwise to a solution of 3-O-{2-[4-trans-(tent-butyloxycarbonylaminomethyl)cyclohexylcarbonylamino]eth-1-ylamino-carbonyl}-4-O-benzyl-6-O-tert-butyldimethylsilyl-1,2-dideoxy-D-glucopyranose (A174, 880 mg, 1.3 mmol) in 15 ml of THF. After stirring at RT for 1 h, the mixture is hydrolyzed with water and extracted with 3 x 50 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate and concentrated. The crude product is purified by chromatography (ethyl acetate). 520 mg of the title compound of m.p. 165-167°C are obtained.
A171. 3-O-~'3-(4-trans-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonylaminolarop-1-yl-aminocarbonyl]'~-4-O-benzvl-1.2-dideoxy-D-glucoayranose 2.1 ml (2.1 mmol) of a 1 M solution of tert-butylammonium fluoride in THF are ad-ded dropwise to a solution of 3-O-{3-[4-trans-(tert-butyloxycarbonylaminomethyl)cyclohexylcarbonylamino]prop-1-yl-aminocarbonyl}-4-O-benzyl-6-O-tert-butyldimethylsilyl-1,2-dideoxy-D-glucopyranose (A175, 730 mg, 1.05 mmol) in 15 ml of THF. After stirring at RT for 3 h, the mixture is hydrolyzed with water and extracted with 3 x 50 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate and concentrated. The crude product is purified by chromatography (dichloromethanelmethanol = 19:1 ). 260 mg of the title compound of m.p. 199-202°C are obtained.
A172. 3-O-~4-f4-traps-(tert-Butvloxycarbonylaminomethyl)cyclohexylcarbonylaminolbut-1-yl-aminocarbonvl]~~-4-O-benzyl-1,2-dideoxy-D~lucopvranose 1.7 ml (1.7 mmol) of a 1 M solution of tert-butylammonium fluoride in THF are added dropwise to a solution of 3-O-{4-[4-traps-(tert-butyloxycarbonylaminomethyl)cyclohexylcarbonylamino]but-1-yl-aminocarbonyl}-4-O-benzyl-6-O-tert-butyldimethylsilyl-1,2-dideoxy-D-glucopyranose~: (A176, 600 mg, 0.85 mmol) in 6 ml of THF. After stirring at RT for 8 h, the mixture is hydrolyzed with water and extracted with 3 x 50 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate and concentrated. The crude product is crystallized from diisopropyl ether and 230 mg of the title compound of m.p. 172-174°C are obtained.
A173. 3-O-f4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piaeridin-1-yl-carbonyll-4-O-benzyl-1.2-dideoxy-D-alucopvranose 4.56 ml (4.56 mmol) of a 1 M solution of tert-butylammonium fluoride in THF
are added dropwise to a solution of 3-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-6-O-tert-butyldimethylsilyl-1,2-dideoxy-D-glucopyranose (A177, 1.63 g, 2.28 mmol) in 15 ml of THF. After stirring at RT for 12 h, the mixture is hydrolyzed with Water and extracted with 3 x 50 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate and concentrated. The crude product is purified by chromatography (dichloromethane/methanol = 29:1 ). 1.2 g of the title compound are obtained.
A174. 3-O-f2-f4-trans-(tert-Butyloxycarbonylaminomethvl)cyclohexylcarbonylaminoleth-1-yl-aminocarbonvl~-4-O-benzvl-6-O-tert-butyldimethylsilyl-1.2-dideoxy-D-ulucopyranose tert-Butyl [4-trans-(2-aminoethylaminocarbonyl)cyclohexylmethyl]carbamate (A179, 500 mg, 1.67 mmol) and 4-O-benzyl-3-O-(imidazol-1-ylcarbonyl)-6-O-tert-butyldimethylsilyl-1,2-dideoxy-D-glucopyranose (A178, 625 mg, 1.4 mmol) in 10 ml of DMF are stirred at 50°C for 5 days. The reaction mixture is largely freed from the solvent and treated with saturated NaCI
solution. The mixture is extracted with 3 x 50 ml of ethyl acetate, the combined organic phases are dried over magnesium sulfate and the crude product is purified by chromatography (toluenelethyl acetate = 1:2 -> ethyl acetate). 990 mg of the title compound are obtained as a colorless glass.
A175. 3-O-!3-t4-traps-(tert-Butyloxycarbonylaminomethyl)cyclohexvlcarbonylaminolpron-1-yl-aminocarbonyl~-4-O-benzyl-6-O-tert-butyldimethylsilyl-1,2-dideoxy-D-ctlucon)~ranose tert-Butyl [4-traps-(3-aminopropylaminocarbonyl)cyclohexylmethyl]carbamate (A180, 500 mg, 1.67 mmol) and 4-O-benzyl-3-O-(imidazol-1-ylcarbonyl)-6-O-tert-butyldimethylsilyl-1,2-dideoxy-D
glucopyranose (A178, 595 mg, 1.33 mmol) in 10 ml of DMF are stirred at 50°C for 5 days. The reaction mixture is largely freed from the solvent and treated with saturated NaCI
solution. The mixture is extracted with 3 x 50 ml~'of ethyl acetate, the combined organic phases are dried over magnesium r sulfate and the crude'-product is purified by chromatography (toluene/ethyl acetate = 1:2 --> ethyl acetate). 790 mg of the title compound are isolated as a colorless foam.

A176. 3-O-f4-f4-trans-(tent-Butyloxycarbonylaminomethyl)cyclohex~carbonylaminolbut-1-yl-aminocarbonvll-4-O-benzyl-6-O-tert-butvldimethvlsilyl-1.2-dideoxy-D-alucopyranose tert-Butyl [4-trans-(4-aminobutyfaminocarbonyl)cyclohexylmethyl]carbamate (A131, 550 mg, 1.67 mmol) and 4-O-benzyl-3-O-(imidazol-1-ylcarbonyl)-6-O-tert-bu#yldimethylsilyl-1,2-dideoxy-D-giucopyranose (A178, 625 mg, 1.4 mmol) in 10 ml of DMF are stirred at 50°C for 5 days. The reaction mixture is largely freed from the solvent and treated with saturated NaCI
solution. The mixture is extracted with 3 x 50 ml of ethyl acetate, the combined organic phases are dried over magnesium sulfate and the crude product is purified by chromatography (toluene/ethyl acetate = 1:2 --> ethyl acetate). 670 mg of the title compound are isolated as a colorless foam.
A177. 3-O-f4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl]ipiperidin-1-ylcarbonyll-4-O-benzyl-6-O-tert-butyldimethylsilyl-1.2-dideoxy-D-alucopyranose 4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidine (A118, 2.7 g, 8.07 mmol) and 4-O-benzyl-3-O-(imidazol-1-ylcarbonyl)-6-O-tert-butyldimethylsilyi-1,2-dideoxy-D-glucopyranose (A178, 3.4 g,,7.6 mmol) in 150 ml of DMF are stirred at 50°C for 9 days. The reaction mixture is largely freed from the solvent and treated with semiconcentrated NaCI solution. The mixture is extracted with 100 ml of dichloromethane, the combined organic phases are dried over magnesium sulfate and the crude product is purified by chromatography (toluenelethyl acetate = 1:1 ->
ethyl acetate). 1.92 g of the title compound are obtained as a colorless oil A178. 4-O-Benzyl-3-O-(imidazol-1-ylcarbonyl)-6-O-tert-butyldimethylsiiyl-1,2-dideoxy-D- luco-pyranose 8.8 g (25 mmol) of 4-O-benzyl-6-O-tert-butyldimethylsilyl-1,2-dideoxy-D-glucopyranose and 5.26 g (32.5 mmol) of carbonyldiimidazole in 100 ml of dichloromethane are stirred at RT for 3 h. The mixture is treated with water, the organic phase is separated off and the aqueous phase is extracted with 2 x 50 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate and after removal of the solvent 11.56 g of the title compound are obtained as a colorless oil.
A179. tert-Butvl f4-trans-(2-aminoethvlaminocarbonyl)cvclohexvlmeth~rllcarbamate tert-Butyl [4-trans-(2-benzyloxycarbonylaminoethylaminocarbonyf)cyclohexylmethyl]carbamate (A181, 1.48 g, 3.41 mmol) in 85 ml of methanol are hydrogenated on palladium/carbon (5%) for 1 h. The catalyst is filtered off, the solvent is removed and the residue is crystallized from diisopropyl ether.
930 mg of the title compound of m.p. 117-118°C are obtained.

-149- w A180. tert-Butvl f4-traps-(3-aminopropylaminocarbonyl)cyclohexylmethyl],carbamate tert-Butyl [4-traps-(3-benzyloxycarbonylaminopropylaminocarbonyl)cyclohexylmethyl]carbamate (A182, 1.42 g, 3.17 mmol) in 70 ml of methanol are hydrogenated on palladiumlcarbon (5%) for 1 h. The catalyst is filtered off, the solvent is removed and the residue is crystallized from diisopropyl ether.
940 mg of the title compound are obtained.
A181. tert-Butvl f4-traps-(2-benzyloxycarbonylaminoethylaminocarbonyl)cyclohexylmethyll-carbamate A solution of 1.2 g (4.66 mmol) of 4-traps-(tert-butyloxycarbonylamino)cyclohexylmethylcarboxylic acid in 30 ml of THF is treated successively with 2.7 ml (19.4 mmol) of triethylamine, 790 mg (5.8 mmol) of hydroxybenzotriazole and 1.45 g (7.8 mmol) of EDC hydrochloride and stirred at RT for 2 h. It is treated with 2.7 ml (7.8 mmol) of triethylamine, 890 mg (3.88 mmol) of benzyl 2-aminoethylcarbamate in 30 ml of THF are added dropwise in the course of 15 min and it is stirred at RT for 72 h. The reaction mixture is freed from the solvent and treated with water and ethyl acetate. The phases are separated, and the aqueous phase is extracted with 3 x 50 ml of ethyl acetate, the combined organic phases are dried over magnesium sulfate and chromatographed on silica gel for purification (ethyl acetate). After crystal-lization from diisopropyi ether, 1.58 g of the title compound are obtained as a colorless solid of m.p.
168-170°C.
A182. tert-Butvl f4-traps-(3-benzyloxycarbonylaminopropylaminocarbow,rl~cyclohex~rlmethyll-carbamate A solution of 1.2 g (4.66 mmol) of 4-traps-(tert-butyloxycarbonylamino)cyclohexylmethylcarboxylic acid in 30 ml of THF is treated successively with 2.7 ml (19.4 mmol) of triethylamine, 790 mg (5.8 mmol) of hydroxybenzotriazole and 1.45 g (7.8 mmol) of EDC hydrochloride and stirred at RT for 2 h. It is treated with 2.7 ml (7.8 mmol) of triethylamine, 950 mg (3.88 mmol) of benzyl 3-aminopropylcarbamate in 30 m! of THF are added dropwise in the course of 15 min and it is stirred at RT for 72 h. The reaction mixture is freed from the solvent and treated with water and ethyl acetate.
The phases are separated, and the aqueous phase is extracted with 3 x 50 ml of ethyl acetate, the combined organic phases are dried over magnesium sulfate and chromatographed on silica gel for purification, (ethyl acetate). After crystallization from diisopropyl ether, 1.54 g of the title compound are obtained as a colorless solid of m.p. 135-137°C.
r Commercial Utility As tryptase inhibitors, the compounds according to the invention have valuable pharmacological pro-perties which make them commercially utilizable. Human tryptase is a serine protease, which is the predominantly present protein in human mast cells. Tryptase comprises eight closely related enzymes (a1, a2, (31 a, ~i1 b, (32, (33, mMCP-7-like-1, mMCP-7-like-2; 85 to 99%
sequence identity) (cf. Miller et al., J. Clin. Invest. 84 (1989) 1188-1195; Miller et al., J. Clin. Invest. 86 (1990) 864-870; Vanderslice et al., Proc. Natl. Acad. Sci., USA 87 (1990) 3811-3815; Pallaoro et al., J.
Biol. Chem. 274 (1999) 3355-3362). Only the ~i-tryptases (Schwartz et al., J. Clin. Invest. 96 (1995) 2702-2710; Sakai et al., J. Clin.
Invest. 97 (1996) 988-995), however, are intracellularly activated and stored in catalytically active form in secretary granules. In comparison with other known serine proteases, such as trypsin or chy-motrypsin, tryptase has some special properties (Schwartz et al., Methods Enzymol. 244, (1994), 88-100; G. H. Caughey, "Mast cell proteases in immunology and biology". Marcei Dekker, Inc., New York, 1995). Tryptase from human tissue has a noncovalently linked tetrameric structure, which must be stabilized by heparin or other proteoglycans in order to be proteolytically active. Tryptase is released together with other inflammatory mediators, such as histamine and proteoglycans, when human mast cells are activated. It is therefore presumed that tryptase plays a role in a number of disorders, in parti-cular in allergic and inflammatory disorders, on the one hand on the basis of the importance of the mast cells in such disorders and on the other that an increased tryptase content has been found in a number of disorders of this type. Thus, tryptase, inter alia, is connected with the following diseases:
acute and chronic (in particular inflammatory and allergen-induced) airway disorders of varying genesis (e.g. bronchitis, allergic bronchitis, bronchial asthma, COPD); interstitial lung disorders; disorders which are based on allergic reactions of the upper airways (pharynx, nose) and of the adjacent regions (e.g. paranasal sinuses, conjunctiva), such as allergic conjunctivitis and allergic rhinitis; disorders of the arthritis type (e.g. rheumatoid arthritis); autoimmune disorders such as multiple sclerosis; in addition periodontitis, anaphylaxis, interstitial cystitis, dermatitis, psoriasis, sclerodermia/systemic sclerosis, inflammatory intestinal disorders (Crohn's disease, inflammatory bowel disease) and others. Tryptase in particular appears to be directly connected with the pathogenesis of asthma (Caughey Am. J.
Respir. Cell Mol. Biol. 16 (1997) 621-628; R. Tanaka, "The role of tryptase in allergic inflammation" in:
Protease Inhibitors, IBC Library Series, 1979, section 3.3.1-3.3.23).
The invention further relates to the compounds according to the invention for use in the treatment andlor prophylaxis of diseases, in particular the diseases mentioned.
The invention likewise relates to the use of the compounds according to the invention for the producti-on of medicaments which are employed for the treatment andlor prophylaxis of the diseases mentio-ned.

-151 - _ Furthermore, the invention relates to medicaments far the treatment andlor prophylaxis of the diseases mentioned, which contain one or more of the compounds according to the invention.
The medicaments are produced by processes which are known per se and familar to the person skilled in the art. As medicaments, the compounds according to the invention (= active compounds) are employed either as such, or preferably in combination with suitable pharmaceutical excipients, e.g. in the form of tablets, coated tablets, capsules, suppositories, patches, emulsions, suspensions, gels or solutions, the active compound content advantageously being between 0.1 and 95%.
The person skilled in the art is familiar on the basis of his/her expert knowledge with excipients which are suitable for the desired pharmaceutical formulations. In addition to solvents, gel formers, ointment bases and other active compound carriers, it is possible to use, for example, antioxidants, dispersing agents, emulsifiers, preservatives, solubilizers or permeation promoters.
For the treatment of disorders of the respiratory tract, the compounds according to the invention are preferably also administered by inhalation. For this, these are either administered directly as a powder (preferably in micronized form) or by atomization of solutions or suspensions which contain them. With respect to the preparations and administration forms, reference is made, for example, to the details in European Patent 163 965.
For the treatment of dermatoses, the use of the compounds according to the invention in particular takes place in the form of those medicaments which are suitable for topical application. For the produc-tion of the medicaments, the compounds according to the invention (= active compounds) are prefe-rably mixed with suitable pharmaceutical excipients and processed to give suitable pharmaceutical formulations. Suitable pharmaceutical formulations which may be mentioned are, for example, pow-ders, emulsions, suspensions, sprays, oils, ointments, fatty ointments, creams, pastes, gels or soluti-ons.
The medicaments according to the invention are produced by processes known per se. The dose of the active compounds in the case of systemic therapy (p.o. or i.v.) is between 0.1 and 10 mg per ki-logram per day.

-152- r..._.
Biological investigations The documented pathophysiological effects of mast cell tryptase are caused directly by the enzymatic activity of the protease. Accordingly, they are reduced andlor blocked by inhibitors which inhibit the enzymatic activity of tryptase. A suitable measure of the affinity of a reversible inhibitor for the target protease is the equilibrium dissociation constant K; of the enzyme-inhibitor complex. This K; value can be determined by means of the influence of the inhibitor on the tryptase-induced cleavage of a chro-mogenic peptide p-nitroanilide substrate or of a fluorogenic peptide-aminomethylcoumarin substrate.
Methodoloay The dissociation constants for the tryptase-inhibitor complexes are determined under equilibrium con-ditions corresponding to the general proposals of Bieth (Bieth JG, Pathophysiological Interpretation of kinetic constants of protease inhibitors, Bull. Europ. Physiopath. Resp.
16:183-195, 1980) and the methods of Sommerhoff et al. (Sommerhoff CP et al., A Kazal-type inhibitor of human mast cell trypta-se: Isolation from the medical leech Hirudo medicinalis, characterization, and sequence analysis, Biol.
Chem. Hoppe-Seyler 375: 685-694, 1994).
Human tryptase is prepared in pure form from lung tissue or prepared in recombinant form. The speci-fic activity of the protease determined by means of titration is customarily greater than 85% of the theo-retical value. Constant amounts of tryptase are incubated with increasing amounts of the inhibitors in the presence of heparin (0.1-50 Ng/ml) to stabilize the protease. After establishment of equilibrium bet-ween the reaction components, the remaining enzyme activity is determined after addition of the pepti-de p-nitroanilide substrate tos-Gly-Pro-Arg-pNA, whose cleavage is monitored at 405 nm for 3 min.
Alternatively, the residual enzymatic activity can also be determined using fluorogenic substrates. The apparent dissociation constants K;~~ (i.e. in the presence of substrate) are then determined by means of nonlinear regression by fitting the enzyme rates to the general equation for reversible inhibitors (Mor-rison JF, Kinetics of the reversible inhibition of enzymecatalysed reactions by tight-binding inhibitors, Biochim. Biophys. Acta 185, 269-286, 1969):
V~o = 1 - f Ec+It+Lapp-I(Et+Ic+K~app)2-4Echjtr2}/2Et In this equation, V, and Uo are the rates in the presence and absence of the inhibitor and Et and k are the concentrations of tryptase and of the inhibitor.
The apparent dissociation constants determined for the compounds according to the invention follow from Table A below, ir'i~~.which the numbers of the compounds correspond to the numbers of the com-pounds in the examples.

Table A
Inhibition of human tryptase Compound K;app (NM) 1 ( 0.13 2 0.16 3 0.0009 4 ~ 0.075 0.0013 6 I 0.150 7 0.035 8 0.015 9\ 0.02 0.014 11 0.07 12 0.06 13 0.02 14 I 0.014 0.001 16 ( 0.002 17 0.15 18 0.09 19 0.011 0.039 21 0.005 22 0.05 23 0.2 Compound Kiapp (~rMj 24 0.031 25 0.13 26 ~ 0.12 27 0.14 28 I 0.01 29 0.02 30 0.02 31 0.008 32 ~ 0.0003 34 0.8 35 0.008 36 0.02 37 ~ 0.2 38 0.09 39 0.4 40 ~ 0.15 41 0.4 42 I 0.2 44 0.5 50 0.08 52 0.24

Claims (10)

Claims

1. A compound of the formula I

in which A1 and A2 are identical or different and are -C(O)-, -NH-, -O- (oxygen), -S-(sulfur), -S(O)2-, -S(O)2-NH-, -NH-S(O)2-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are -C(O)-, -O-, -S-, -NH-, -O-C(O)-, -C(O)-O-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group where E is -O- (oxygen), -S- (sulfur) or -CH2- (methylene), G is -O- (oxygen) or -CH2- (methylene), and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -O-, -S-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the following list where U and W are identical or different and are -O- (oxygen), -S- (sulfur) or -NH-, R1 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R2 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R3 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R4 is hydroxyl, cyano, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R5 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy of Ar-1-4C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) are an alkylenedioxy group [-O-C(R6),R7-O-], in which either one of the radicals R6 and R7 is hydrogen and the other is methyl, phenyl or p-methoxyphenyl, or in which both radicals R6 and R7 are hydrogen or methyl, K1 is -B7-(C(O))m-B9-X1, -B7-(C(O))m B9-Y1,or -B7-(C(O))m-89-Z1-B11-X1, K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or-B8-(C(O))p-B10-Z2-B12-X2, B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-4C-alkylene, m is 0 or 1, p is 0 or 1, X1 and X2 are identical or different and are selected from the following groups where R8 is 1-4C-alkyl, Y1 and Y2 are identical or different and are a 4-11C-heteroaryl or 2-7C-heterocycloalkyl radical, comprising at least one ring nitrogen, Z1 and Z2 are identical or different and are 5-12C-arylene, 5-12C-heteroarylene, 3-8C-cycloalkylene or 3-8C-heterocycloalkylene, where each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocyc-loalkyl can additionally be substituted, for its part, by one, two or three substituents selected from the group consisting of hydroxyl, halogen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4.C-alkylcarbonyloxy, carboxyl or aminocarbonyl, and in which on the direct route between the terminal nitrogen atoms, 20 to 40 bonds must be present, the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroaryle-nes and heterocycloalkylenes comprising a nitrogen atom and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, 84, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond and direct linkage between two heteroatoms or two carbonyl groups would thereby occur.

2. A compound of the formula I as claimed in claim 1, in which A1 and A2 are identical or different and are -C(O)-, -NH-, -O-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are -C(O)-, -O-, -NH-, -O-C(O)-, -C(O)-O-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group where E is -O- (oxygen), -S- (sulfur) or -CH2- (methylene) and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -O-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the list below where U and W are identical or different and are -O- (oxygen), -S- (sulfur) or -NH-, R1 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R2 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonytoxy orAr-1-4C-alkoxy, R3 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, R4 is hydroxyl, cyano, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R5 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy orAr-1-4C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) are an alkylenedioxy group [-O-C(R6)R7-O-], in which either one of the radicals R6 and R7 is hydrogen and the other is methyl, phenyl or p-methoxyphenyl, or in which both radicals R6 and R7 are hydrogen or methyl, K1 is-B7-(C(O))m,-B9-X1,-B7-(C(O))m-B9-Y1 or-B7-(C(O))mB9-Z1-B11-X1, K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2, B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-4C-alkylene, m is 0 or 1, p is 0 or 1, X1 and X2 are identical or different and are selected from the following groups where R8 is 1-4C-alkyl, Y1 and Y2 are identical or different and are piperid-4-yl, piperid-3-yl, piperazin-1-yl, piperazin-2-yl, morpholin-2-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, 2-imidazolin-3-yl, 2-imidazolin-2-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4.-yl, pyrid-4-yl, pyrid-3-yl, pyridazin-4-yl, pyrimidin-5-yl, pyrimidin-4-yl, indol-3-yl, benzimidazol-4-yl or benzimidazol-5-yl, Z1 and Z2 are identical or different and are 1,4-phenylene, 1,3-phenylene, 1,4-naphthylene, 2,6-naph-thylene, 1,4-cyclohexylene, 1,3-cyclohexylene; 1,3-cyclopentylene, 1,4-piperazinylene, 4,1-piperidinylene, 1,4-piperidinylene, 2,5-pyrrolidinylene,.4,2-imidazolidinylene, 2,5-furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,6-quinolinylene, 2,5-benzofuranylene or 4,2-thiazolylene, where each arylene, heteroarylene, cycloalkylene, heterocycloalkylene, heteroaryl or heterocyc-loalkyl can additionally be substituted, for its part, by one, two or three substituents selected from the group consisting of hydroxyl, halogen, nitro, cyano, amino, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyloxy, carboxyl or aminocarbonyl, and in which on the direct route between the terminal nitrogen atoms 20 to 40 bonds must be present, the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroaryle-nes and heterocycloalkylenes comprising a nitrogen atom and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond and a direct linkage would thereby occur between two hetero-atoms or carbonyl groups.

3. A compound of the formula I as claimed in claim 1, in which A1 and A2 are identical or different and are -C(O)-, -O-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are a bond or are selected from the group where T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the list below where U and W are identical or different and are -O- (oxygen) or -NH-, R1 is hydrogen, 1-2C-alkoxy, acetoxy or Ar-methoxy, R2 is hydrogen, hydroxyl, 1-2C-alkoxy, acetoxy or Ar-methoxy, R3 is hydroxyl, 1-2C-alkoxy, acetoxy or Ar-methoxy, R4 is hydroxyl, 1-2C-alkoxy, acetoxy or Ar-methoxy, K1 is -B7-(C(O))m-B9-X1, -B7-(C(O))m; B9-Y1 .or -B7-(C(O))m-B9-Z1-B11-X1, K2 is -B8-(C(O))p-B10-X2, -B8-(C(O))p B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2, B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, B9, B10, B11 and B12 are identical or different and are a bond or 1-4C-alkylene, m is 0 or 1, p is 0 or 1, X1 and X2 are identical or different and are selected from the following groups -NH2 Y1 and Y2 are identical or different and are piperid-4-yl, piperid-3-yl, piperazin-1-yl, piperazin-2-yl, morpholin-2-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, 2-imidazolin-3-yl, 2-imidazolin-2-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, 5-methyl-imidazol-4-yl, pyrid-4-yl, pyrid-3-yl, pyridazin-4-yl, pyrimidin-5-yl, pyrimidin-4-yl, indol-3-yl, ben-zimidazol-4-yl or benzimidazol-5-yl, Z1 and Z2 are identical or different and are 1,4-phenylene, 1,3-phenylene, 1,4-naphthylene, 2,6-naph-thylene, 1,4-cyclohexylene, 1,3-cyclohexylene, 1,3-cyclopentylene, 1,4-piperazinylene, 4,1-piperidinylene, 1,4-piperidinylene, 2,5-pyrrolidinylene, 4,2-imidazolidinylene, 2,5-furylene, 2,5-pyrrolylene, 4,2-pyridylene, 5,2-pyridylene, 6-methyl-5,2-pyridinylene, 2,5-indolylene, 2,6-indolylene, 3,5-indolylene, 3,6-indolylene, 3,5-indazolylene, 3,6-indazolylene, 2,6-quino-linylene, 2,5-benzofuranylene or 4,2-thiazolylene, and in which on the direct route between the terminal nitrogen atoms 20 to 40 bonds must be present, the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroaryle-nes and heterocycloalkylenes comprising a nitrogen atom and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond and a direct linkage would thereby occur between two hetero-atoms or carbonyl groups.

4. A compound of the formula I as claimed in claim 1, in which A1 and A2 are identical or different and are -C(O)-, -C(O)-NH-, -C(O)-O- or a bond, A3 and A4 are identical or different and are 1,4-piperazinylene, 1,4-piperidinylene, 1,4-cyclohexylene, 1,3-phenylene or a bond, A5 and A6 are identical or different and are -C(O)-, -C(O)-NH-, -NH-C(O)- or -NH-C(O)-NH-, M is a pyranose unit selected from the following list where U and W are identical or different and are -O- (oxygen) or -NH-, R1 is hydrogen, methoxy or benzyloxy, R2 is hydrogen, R3 is hydroxyl or benzyloxy, R4 is hydroxyl, methoxy or benzyloxy, K1 is-B7-(C(O))m-B9-Y1 or-B7-(C(O))m-B9-Z1-B11-X1, K2 is -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2, B1 and B2 are identical or different and are a bond or methylene, B3, B4, B5 and B6 are identical or different and are a bond or 1-3C-alkylene, B7, B8, B9 and B10 are identical or different and are a bond or 1-4C-alkylene, B11 and B12 are identical or diffferent and are a bond or methylene, m is 0, p is 0, X1 and X2 are identical or different and are selected from the following groups -NH2 Y1 and Y2 are imidazol-1-yl, Z1 and Z2 are identical or different and are 5,2-pyridinylene, 6-methyl-5,2-pyridinylene, 4,1-piperidinylene, 3,6-indazolylene, 3,6-indolylene, 1,3-phenylene, 1,4-phenylene, 1,3-cyclohexylene or 1,4-cyclohexylene, and in which on the direct route between the terminal nitrogen atoms 20 to 40 bonds must be present, the salts of these compounds, and also the N-oxides of the heteroaryls, heterocycloalkyls, heteroaryle-nes and heterocycloalkylenes comprising a nitrogen atom and their salts, where all those compounds are excluded in which one or more of the variables B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11 or B12 assume the meaning of a bond and a direct linkage would thereby occur between two hetero-atoms or carbonyl groups.

5. A compound of the formula I as claimed in one of claims 1 to 4, wherein 25 to 40 bonds must be present on the direct route between the terminal nitrogen atoms.

6. A compound of the formula I as claimed in claim 1 having the chemical name 3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-D-gluco-pyranose;

4-O-benzyl-1,2-dideoxy-3,6-di-O-[4-(4-guanidinobenzylaminocarbonyl)piperazin-1-ylcarbonyl]-D-gluco-pyranose;
3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonylmethyl]-4-O-benzyl-1,2-di-deoxy-D-glucopyranose;
3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-giucopyranose;
3,6-di-O-[4-(1-amidinopiperidin-4-ylacetyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-galactopyranose;
3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-D-galacto-pyranose;
3,6-di-O-[4-(amidinoindazol-3-ylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-gluco-pyranose;
methyl 3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-2-deoxy-.alpha.-D-glucopyranoside;
methyl 3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-2-deoxy-.alpha.-D-glucopyranoside;
3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonylmethyl]-1,2-dideoxy-D-glucopyranose;
6-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-3-O-[4-(trans-4-aminomethyl-cyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
benzyl-3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-2-deoxy-.alpha.-D-glucopyranoside;
3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonylmethyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonylmethyl]-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-methyl-1,2-dideoxy-D-galactopyranose;
methyl 2,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-.alpha.-D-glucopyranoside;
methyl 3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-2-deoxy-.alpha.-D-glucopyranoside;
methyl 2,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-3,4-di-O-benzyl-.alpha.-D-glucopyranoside;
methyl 3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-2-deoxy-.alpha.-D-glucopyranoside;
6-O-[4-(trans-4-aminomethylcyclohexytcarbonyl)-1-aminopentyl]-3-O-[4-(trans-4-aminomethylcyclo-hexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;

3-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-6-O-[5-(2-aminomethyl-pyridylcarbonyl)-1-aminopentyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-N-[4-(trans-4-aminomethylcyclohexylcarbonyl)-4-aminobutyl-4-oxycarbonyl]-3-O-[4-(trans-4-amino-methylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)-5-aminopentyl]-3-O-[4-(trans-4-aminomethylcyclo-hexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose;
3,6-Di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)-5-aminopentyl]-4-O-benzyl-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)-5-aminopentyl]-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(3-aminomethylbenzoyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(3-aminomethylbenzoylamino)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-(3-aminomethylbenzylaminocarbonyl)piperazin-1-yl-carbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(3-aminomethylbenzylaminocarbonylamino)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-(4-(3-aminomethylbenzylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-(4-trans-(3-aminomethylbenzylaminocarbonyl)cyclohexylmethylaminocarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-(6-amino-2-methylpyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-(4-aminobenzylaminocarbonyl)piperidin-1-ylcarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-(4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-trans-(6-aminopyridin-3-ylmethylaminocarbonyl)cyclohexylmethylaminocarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-(4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-trans-(6-amino-2-methylpyridin-3-ylmethylaminocarbonyl)cyclohexylmethylaminocarbonyl]-1,2-dideoxy-D-gluco-pyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[4-trans-(4-aminobenzylaminocarbonyl)cyclohexylmethylaminocarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-(4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-[3-(4-amino-benzylaminocarbonyl)benzylaminocarbonyl]-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[3-(imidazol-1-yl)propylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;

3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[4-(imidazol-1-yl)butylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[5-(imidazol-1-yl)pentylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[6-(imidazol-1-yl)hexylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[8-(imidazol-1-yl)octylaminocarbonyl]piperidin-1-ylcarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-6-O-{4-[4-trans(amino-methyl)cyclohexylcarbonyl]aminobut-1-ylaminocarbonyl}-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-6-O-(4-(4-aminomethyl-benzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-O-(4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-6-O-[2-(6-aminopyridin-3-yl-methylaminocarbonyl)eth-1-yl-aminocarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3-O-(4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{3-[(6-amidino-1-H-indazol-3-yl)carbonylamino]prop-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{3-[(6-amino-carbonyl-1-H-indazol-3-yl)carbonylamino]prop-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-6-O-{2-[(6-aminocarbonyl-1-H-indol-3-yl)carbonylamino]eth-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{3-[(6-amino-carbonyl-1-H-indol-3-yl)carbonylamino]prop-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-6-O-{4-[(6-amino-carbonyl-1-H-indol-3-yl)carbonylamino]but-1-ylaminocarbonyl}-1,2-dideoxy-D-glucopyranose;
6-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-3-O-(2-(4-trans-aminomethyl-cyclohexylcarbonylamino)eth-1-ylaminocarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-3-O-[3-(4-trans-aminomethyl-cyclohexylcarbonylamino)prop-1-ylaminocarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-(6-aminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-3-O-(4-(4-trans-aminomethyl-cyclohexylcarbonylamino)but-1-ylaminocarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-(3-aminomethylbenzoyl)piperazin-1-ylcarbonyl]-3-O-[4-(6-aminopyridin-3-yl-methylamino-carbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-(3-aminomethylbenzoylamino)piperidin-1-ylcarbonyl]-3-O-[4-(6-aminopyridin-3-ylmethylamino-carbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-(3-aminomethylbenzylaminocarbonyl)piperidin-1-ylcarbonyl]-3-O-[4-(6-aminopyridin-3-ylmethyl-aminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-[4-trans-(3-aminomethylbenzylaminocarbonyl)cyclohexylmethylaminocarbonyl]-3-O-[4-(6-amino-pyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
6-O-(4-(3-aminomethylbenzylaminocarbonyl)piperazin-1-ylcarbonyl]-3-O-[4-(6-aminopyridin-3-ylmeth-ylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;

6-O-[4-(3-aminomethylbenzylaminocarbonylamino)piperidin-1-ylcarbonyl]-3-O-[4-(6-aminopyridin-3-yl-methylaminocarbonyl)piperidin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
and the salts of these compounds.

7. A compound of the formula I as claimed in claim 1 having the chemical name 3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyl]-1,2-dideoxy-D-gluco-pyranose;
4-O-benzyl-3,6-di-O-[4-(4-guanidinobenzylaminocarbonyl)-1-piperazinylcarbonyl]-1,2-dideoxy-D-gluco-pyranose;
3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazinylcarbonylmethyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose;
3,6-di-O-[4-(4-aminomethylbenzylaminocarbonyl)-1-piperazinylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose and 3,6-di-O-[4-(1-aminopiperidin-4-ylacetyl)-1-piperazinylcarbonyl]-4-O-benzyl-1,2-dideoxy-D-gluco-pyranose;
and the salts of these compounds.

8. A compound of the formula I as claimed in one of claims 1 to 5, in which the pyranose unit M has the D-gluco, D-galacto or D-manno configuration.

9. A compound of the formula I as claimed in claim 1 for the treatment of diseases.

10. The use of compounds of the formula I as claimed in claim 1 for the production of medicaments for treating airway disorders.