AU5625499A - Novel pyranoses - Google Patents

Description

B666WOO 09991 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 background The International Applications W095/32945, W096/09297, W098/04537 and W099/12918 describe low molecular weight compounds as tryptase inhibitors. The International Application W093/17032 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-A5-K1 M() \B2-A2-B4-A4-B6-A6-K2 in which Al and A2 are identical or different and are -C(O)-, -NH-, -0- (oxygen), -S- (sulfur), -S(0) 2 -, -S(0) 2 -NH-, -NH-S(0) 2 -, -C(0)-NH-, -NH-C(O)-, -0-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are -C(O)-, -0-, -S-, -NH-, -0-C(O)-, -C(0)-0-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group B666WOO 09991 -2 T T T T N N N E NG where E is -0- (oxygen), -S- (sulfur) or -CH 2 - (methylene), G is -0- (oxygen) or -CH 2 - (methylene), and T is the group -C(0)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -0-, -S-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(0)-0-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the following list B666WO0 09991 -3 R4 R4 U R4 R3 R5 R5 R3 5 R3 U R2 R2 R2 WW W R4 U R4 U R5 R3 U W 0W 0W 0 o 0--0 R1 RI RI U R4 R5 U R2 0 R2 0 R1 RI W R3 R2 RI where U and W are identical or different and are -0- (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-I -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)R7-0-], 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 -B11 -X1, K2 is -B8-(C(O))p-B1O-X2, -B8-(C(O))p-B1O-Y2 or -B8-(C(0)),-B1O-Z2-B12-X2, B666WOO 09991 -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 1-4C-alkylene, m is 0 or 1, p is 0 or 1, XI and X2 are identical or different and are selected from the following groups 0 NH NH

-NH

2

NH

2

NH

2 NHOH NH NHH -N4 HN H N NH2

NH

2 N-R8 X N H 0 NH 2 NH NH NH

NH

2 S-R8 H NH 2 NH N-NH

NH

2 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, 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 B666WO0 09991 -5 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 [CH 3 0-C(O)-] and the ethoxycarbonyl radical [CH 3

CH

2 0-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 [CH 3 C(O)-O-I. Ar stands for a phenyl radical which is unsubstituted or mono- or disubstituted by nitro, 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. 1-4C-Alkylene stands for straight-chain or branched 1-4C-alkylene radicals, for example the methylene radical [-CH 2 -], ethylene radical [-CH 2

-CH

2 -], trimethylene radical [-CH 2

-CH

2

-CH

2 -], tetramethylene ra dical [-CH 2

-CH

2

-CH

2

-CH

2 -], 1,2-dimethyethylene radical [-CH(CH 3 )-CH (Cl-I)-], 1,1-dimethylethylene radical [-C(CH 3

)

2

-CH

2 -], 2,2-dimethylethylene radical [-CH 2

-C(CH

3 )2-], isopropylidene radical [-C(CH 3

)

2 -] or the 1-methylethylene radical [-CH(CH3)-CH 2 -l. If m has the meaning 0, the group -(C(O))m- is a bond. If p has the meaning 0, the group -(C(O)),- is a bond.

B666WOO 09991 -6 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 x epimers and P 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. 6 Numbering: 34 5 2 0 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-Heteroaryl 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 0, 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 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 0, 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 B666WO0 09991 -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 0, 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 0, 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 0, 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 B1 1 (-B9-Z1-B11-) or B10 and B12 (-B1O-Z2-B12-). Correspondingly, in the divalent groups mentioned by way of example (e.g. 2,6-indolylene), the first number stands for the linkage site to the group B9 or B10 and the second number for the linkage site to the group B1 1 or B12.

B666WOO 09991 -8 The definitions of M, A3, A4, X1 and X2 contain chemical formulae, such as R4 W N NH R2G NH 2 R1 Bonds not linked on one side in this connection means that the unit is bonded to the rest of the mole cule 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 groups X1 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: B666WOO 09991 -9 0 21 N 2 24 J26 28 29N 30 20 19 0 wN2 27 H H 1 _O - 31 IBnOM -0 0 H HN6 N 8 9 N 12 O

NH

2 0 o 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, maleic acid, lauric acid, malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, embonic acid, stearic acid, toluenesulfonic acid, methanesulfonic 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 1, and also all solvates and in particular all hydrates of the salts of the compounds of the formula 1. Compounds of the formula I to be emphasized are those in which Al and A2 are identical or different and are -C(O)-, -NH-, -0-, -C(O)-NH-, -NH-C(O)-, -0-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are -C(O)-, -0-, -NH-, -O-C(O)-, -C(O)-O-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group B666WOO 09991 -10 T T T T T N NN E N where E is -0- (oxygen), -S- (sulfur) or -CH 2 - (methylene) and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -0-, -C(O)-NH-, -NH-C(O)-, -0-C(O)-, -C(0)-0-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the list below B666WOO 09991 -11 R4 R4 U R4 R3 R5 U R5 R3 R5 R3 U U 0 R2 R2 R2 WW W R4 U R4 U R5 R3R31 o 0 0 W W W RI RI RI U R4 R5 W o 0 R2 R2 RI RI W R3 R2 R1 where U and W are identical or different and are -0- (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 or Ar-I -4C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5), are an alkylenedioxy group [-0-C(R6)R7-0-], 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-B11 -X1, K2 is -B8-(C(0)),-B1O-X2, -B8-(C(0))p-B1O-Y2 or -B8-(C(O)),-B1O-Z2-B12-X2, B666WO0 09991 -12 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 0 NH NH -NH2

NH

2 NH 2 NHOH NH NH H -N N NH 2 H NH 2 N-R8 O NH2 H 0 NH 2 NH NH NH

H-SNH

2

NH

2 S-R8 2 NH

N-NH

2

NH

2 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 B666WOO 09991 -13 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 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. Compounds of the formula I particularly to be emphasized are those in which Al and A2 are identical or different and are -C(O)-, -0-, -C(O)-NH-, -NH-C(O)-, -0-C(O)-, -C(0)-0- or a bond, A3 and A4 are identical or different and are a bond or are selected from the group T T T T T I II N 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(0)-, -0-C(0)-, -C(O)-0-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the list below R4 R4 R3 W U> U 0 0 W R2 RI RI where U and W are identical or different and are -0- (oxygen) or -NH-, RI 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(0))m-B9-X1, -B7-(C(O))m-B9-Y1 or -B7-(C(O))m-B9-Z1 -B11 -X1, K2 is -B8-(C(0)),-B10-X2, -B8-(C(O))p-B10-Y2 or -B8-(C(O))p-B10-Z2-B12-X2, B666WOO 09991 - 14 BI, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, B9, BIO, BI 1 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 0 NH NH

-NH

2 H / -N

NH

2

NH

2 H NH 2 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 zinidazol-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, BI1 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 Al 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 R4 R4 R3 W 0 0 W R2 RI R1 B666WOO 09991 -15 where U and W are identical or different and are -0- (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))mB9-Y1 or -B7-(C(O))m-B9-Z1-B11-X1, K2 is -B8-(C(O)),-B10-Y2 or -B8-(C(0)),-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, B 11 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

-NH

2 / -N

NH

2

NH

2 H NH 2 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 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. Particularly preferred compounds of the formula I are 3,6-di-0-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-0-benzyl-1,2-dideoxy-D glucopyranose; 3,6-di--[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1 -ylcarbonyl]-1,2-dideoxy-D-gluco pyranose; 4-0-benzyl-1,2-dideoxy-3,6-di--[4-(4-guanidinobenzylaminocarbonyl)piperazin-1 -ylcarbonyl]-D-gluco pyranose; B666W00 09991 -16 3,-iO[-tas4aioehlccoeycroy~ieai- -ylcarbonylmethyII-4-O-befl-ll,2-di deoxy-D-glucopyraflose; 3,-iO[-4aioehlezlmncroy~ieai- -ylcarbonyll-4-O-belzyl-l ,2-dideoxy-D glucopyralose; 3,6-di-O-[4-(1 -amidinopiperidifl-4-ylacetyl)piperazin-I -ylcarbonyll-4-O-belzyl-l ,2-dideoxy-D-gluco pyranose; 3,-iO[-tas4aioehlccoeycroy~ieai- -ylcarbonylI-4-O-belzyl-l ,2-dideoxy-D galactopyralose; 3,-iO[-tas4aioeh~ccoeycroy~ieai- -ylcarbonyl]-1 ,2-dideoxy-D-galacto pyranose; 3,-iO[-aiionaol3ycroy~ieai- -ylcarbonyl]-4-O-belzyl-l ,2-dideoxy-D-gluco pyranose; methyl 3,-iO[-tas4aioeh~ccoeycroy~ieai- -ylcarbonyl]-4-O-belzyl- 2 deoxy-a-D-glucopyrafloside; methyl 3,-iO[-tas4aioehlccoeycroy~ieai- -ylcarbonyl-2-deoxy-L-D glucopyranoside; 3,-iO[-tas4aioehlccoeycroy~ieai- -ylcarbonylmethyl]-1 ,2-dideoxy-D glucopyraflose; 6 -O-[4-(4-aminomethylbeflyamiflocarboflyl)piperazin-1lcabnl --4(ras4aioehl cyclohexylcarbolyl)piperazifl-l -ylcarbonyl]-4-O-belY-l,2-dideoxy-D-glucopyralose; benzyl 3,-iO[-tas4aioehlccoeycroy~ieai- -ylcarbonylI-2-deoxy-a-D glucopyranoside; 3,-iO[-4aioehlezlmncroy~ieai- -ylcarbonylmethylI-4-O-bel- 1 ,2 dideoxy-D-glucopyralose; 3,-iO[-4aioehlezlmncroy~ieai- -ylcarbonylmethyll-1 ,2-dideoxy-D-gluco pyranose; 3,-iO[-tas4aioehlccoeycroy~ieai- -ylcarbonyl]-4-O-methyl-l ,2-dideoxy-D galactopyralose; methyl 2,-iO[-tas4aioeh~ccoeycroy~ieai- -ylcarbonyl-cX-D glucopyranoside; methyl 3,-iO[-4aioehybnyaioabnlpieai- labnl-40bny--ex-X D-glucopyranoside; methyl 2,-iO[-4-mnmtybnz mncroylpprzn1ylcarbonyl]-3,4-di-O-belzyl-L-D glucopyranoside; methyl 3,-iO[-4aioehlezlmncroy~ieai- -ylcarbonyl]-2-deoxy-a-D glucopyranoside; 6--4(rn--mnmthlylhxlabnl- -aioetl---4(rn--mnmtycco hexylcarbonyl)piperazifl-l -ylcarbonyl]-4-O-beflzyl-l ,2-dideoxy-D-glucopyralose; 3--4(rn--mnmtyccoeycroy~ieai- -ycroyl60[-2aioehl pyridylcarbonyl)-1 -aminopentyl]-4-O-beflzyl-l ,2-dideoxy-D-gIucopyralose; B666W00 09991 - 17 6--4(rn--mnmtyccoeycroy)4aiouy--xcroyl30[-tas4aio methylcyclohexylcarboflYl)piperazifll -ylcarbonyll-4-O-belzyI-l,2-dideoxy-D-gucopyralose; 6--4(rn--mnmtyccoeycroy)5aioetl---4(rn--mnmtycco hexylcarbonyl)piperazifl-l -ylcarbonyl]-1 ,2-dideoxy-D-glucopyralose; 3,-iO[-tas4aiomtyccoeycroy)5-mnpny 40bny-,2-dideoxy-D-gluco pyra nose; 3,-iO[-tas4aioehlycoeycroy)5aioet -,2-dideoxy-D-glucopyralose; 3,-iO[-3aioehlezy~ieai- -ylcarbonyl]-4-O-bel-1 ,2-dideoxy-D-glucopyralose; 3,-iO[-3aioehlbnolmn~ieii- -ylcarbonyII-4-O-benzyI-l ,2-dideoxy-D-gluco pyra nose; 3,-iO[-3aioehlezlmncroy~ieai- -yI-carbonyl]-4-O-belY-l,2-dideoxy-D glucopyranose; 3,-iO[-3aioehlezlaioabnlmn~ieii- -ylcarbonyl]-4-O-benlZY-l,2-dideoxy D-glucopyralose; 3,-iO[-3aioehlezlmncroy~ieii- -ylcarbonyl]-4-O-belY-l,2-dideoxy-D glucopyraflose; I ,2-dideoxy-D-glucopyralose; 3,-iO[-6aioyii--lehlmn~roy~ieii- -ylcarbonyl]-4-O-belY-I,2-dideoxy-D glucopyralose; 3-O-[4-(4-aminomethylbeflYamfiflocarboflyi)piperazin-1 -ylcarbonyl]-4-O-belY-6-O-1 4

(

6 aminopyridin-3-ylmethylamliflocarboflY)piperidin-I -ylcarbonyl]-1,2-dideoxy-D-glucopyralose; 3-O-[4-(4-aminomethylbelyamliflocarbofl)piperazifll -ylcarbonylI-4-O-befzly-6--4-(6amilo- 2 methylpyridin-3-ylmethylamliflocarboflY)piperidifll -ylcarbonyl]-I ,2-dideoxy-D-glucopyralose; 3-O-[4-(4-aminomethylbeflYamiflocarboflY)piperazin-1 -ylcarbonyl]-4-O-belY-6-O-[ 4

-(

4 aminobenzylaminocarboflyl)piperidifll -ylcarbonyl]-1 ,2-dideoxy-D-glucopyralose; 3-O-[4-(4-aminomethylbelzy~amiflocarboflY)piperazifll -ycarbonyII-4-O-benzyI-6-O-[ 4 -trals-( 6 aminopyridin-3-ylmethylamilocarbofl)cyclohexylmethylaminocarbonyIl] ,2-dideoxy-D-glucopyralose; 3-O-[4-(4-aminomethylbelyamiflocarbofl)piperazif- lcabnll -bny---4trn-6aio 2 -methylpyridin-3-ylmethylamilocarbofl)cycIohexylmethylaminocarbonyIl ,2-dideoxy-D-gluco pyranose; 3-O-[4-(4-aminomethylbelyamliflocarbofl)piperazifll -ycarbonyI]-4-O-befzl~y-6-O-t4-trals-( 4 aminobenzylaminocarboflyl)CYCIohexylmethylaminocarbonYl -,2-dideoxy-D-gucopyralose; 3-O-[4-(4-aminomethylbelYamliflocarboflY)piperazin-1 -ycarbonyI]-4-O-benzyI-6-O-[3-(4-amilo benzylaminocarboflyl)belzylamilocarbofl]lil,2-dideoxy-D-glucopyralose; 3-O-[4-(4-aminomethylbeflYamiflocarbonyl)piperazin-1 -ylcarbonyII-4-O-beflY-6-O-{4-[3-(imlidazol yI)propylaminocarbonyllpiperidifl-I -ylcarbonyl}-1 ,2-dideoxy-D-glucopyralose; 3-O-[4-(4-aminomethylbelamliflocarboflY)piperazifll -ycarbonyII-4-O-benzyI-6-O-{4-[4-(imidazok 1 I yI)butylaminocarboflyllPiPeridifl-l -ylcarbonyl}-l ,2-dideoxy-D-glucopyralose; B666W00 09991 -18 3 -O-I4-(4-aminomethylbeflYImiflocarbony)piperazin-1lcabnl --ezl6--4[-iiao- yI)pentylaminocarbofll]piperidifli -ylcarbonyl}-1 ,2-dideoxy-D-glucopyralose; 3--4(-mnmtybnylmncroy~ieai- -ycarbonylI-4-O-befzly-6--{4-6(imidazoIl yI)hexylaminocarbofllpiperidifll -ylcarbonyl}-1 ,2-dideoxy-D-glucopyralose; 3 -O-[4-(4-aminomethylbelyamliflocarboflY)piperazin-1lcabn ---ezi6--4[-iiao- yI)octylaminocarbofll]piperidifll -ylcarbonyl}-1 ,2-dideoxy-D-glucopyralose; 3--4(-mnprdn3ymthlmncroy~ieii- -ylcarbonyII-6-O-{4-[4-trafls(amilo methyl)cyclohexylcarboflIamiflobutl -yaminocarbonyI}-4-O-benflY1l,2-dideoxy-D-glucopyralose; 3--4(-mnprdn3ymthlmncroy~ieii- -ycarbonyII-6-O-[4-(4-amilomethyI benzylaminocarboflyl)piperazifl-l -ylcarbonyl]-4-O-belY-l,2-dideoxy-D-glucopyralose; 3-O-[4-(4-aminomethylbeflYamiflocarboflY)piperazin-l -ycarbonyl]-6-O-[2-(6-amliflopyridif-l 3 Y methylaminocarboflyl)eth-1 -yI-aminocarbonyI-4-O-belY-l,2-dideoxy-D-gucopyralose; 3-O-[4-(4-aminomethylbeflyamiflocarboflY)piperazin-1 -ycarbonyI]-4O-befzly-6--{3-[(6amidino-I H-indazoI-3-y)carboflamiflo]prop-l -ylaminocarbonyl}-1 ,2-dideoxy-D-glucopyralose; 3-0O 4 -(4-aminomethylbelyamiflocarboflY)piperazin-1 -ylcarbonyI]-4-O-befly-6-O-{3-[(6-amilo carbonyl-1 -H-indazoI-3-yI)carboflamifloIprop-l -ylaminocarboiyl}-l ,2-dideoxy-D-glucopyralose; 3-O-[4-(4-aminomethylbelYamiflocarboflY)piperazin-1 -ylcarbonyI]-6-O-{2-[(6-amilocarbofl-

-H

indol-3-yI)carbonylamileth-1 -ylaminocarbonyl}-l ,2-dideoxy-D-glucopyralose; 3-O-I4-(4-aminomethylbeflyamiflocarboflY)piperazin-1lcabnl -- ezl---3[6aio carbonyl-1 -H-indoI-3-yI)carbonylamliflprop-l -ylaminocarbonyl}-1 ,2-dideoxy-D-gucopyralose; 3-O-[4-(4-aminomethylbelYamliflocarboflY)piperazin-1lcabnl --ezl---4[6aio carbonyl-1 -H-indoI-3-yI)carbonylamilo~but-1 -ylaminocarbonyl}-l ,2-dideoxy-D-glucopyralose; 6--4(-mnprdn3ymthlmncroy~ieii- -ycroy]30[-4tasaioehl cyclohexylcarbonylamilo)eth-1 -ylaminocarbonyll-4-O-belY-l,2-dideoxy-D-glucopyralose; 6--4(-mnprdn3ymthlmncroy~ieii- -ycroyl30[-4tasaioehl cyclohexylcarbonylamilo)prop-l -ylaminocarbonyl-4-O-belY-l,2-dideoxy-D-gucopyralose; 6--4(-mnprdn3ymthlmncroy~ieii- -yicarbonyII-3-O-[4-(4-trafls-amilomethyI cyclohexylcarbonylamilo)but-1 -ylaminocarbonyl]-4-O-belY-l,2-dideoxy-D-glucopyralose; 6-O-[4-(3-aminomethylbefzlZY)piperazif- ll bnl--0[-6aioprdn3y-mtyai carbonyl)piperidifl-1 -ylcarbonyl]-4-O-bel-1 ,2-dideoxy-D-glucopyralose; 6-O-I4-(3-aminomethylbeflzoylamiflo)piperidif- ll bnl---4-6aioyii-3ymtyaio carbonyl)piperidin-1 -ylcarbonyl]-4-O-benzyI-l ,2-dideoxy-D-glucopyralose; 6-O-[4-(3-aminomethylbelYamiflocarboflY)pipeidin-1lcabnl --4(-mioyii--lehl aminocarbonyl)piperidil-1 -ylcarbonyl]-4-O-bel-1 ,2-dideoxy-D-glucopyralose; 6--4tas(-mnmtybnyaioabnlcylhxlehlmncroy]30[-6aio pyridin-3-ylmethylaminocarbofl)piperidifll -ylcarbonyl]-4-O-benlZY-l,2-dideoxy-D-glucopyralose; 6-O0I4(3aminomethylbeflYamiflocarboflY)piperazin-1lcabn ---4(-mioyii--leh ylaminocarbonyl)piperidifl-l -ylcarbonyl]-4-O-belY-l,2-dideoxy-D-glucopyralose; 6-O-[4-(3-aminomethylbelYamliflocarboflYamilo)piperidin-1 -ylcarbony]-3-O-[4-(6-amilopyridil- 3 -ylI methylaminocarboflyl)piperidifl-l -ylcarbonyl]-4-O-belY-1 ,2-dideoxy-D-glucopyralose; B666WOO 09991 - 19 and the salts of these compounds. One embodiment (embodiment a) of the invention are compounds of the formula I, in which Al and A2 are identical or different and are -C(O)-, -NH-, -0- (oxygen), -S- (sulfur), -S(O) 2 -,

-S(O)

2 -NH-, -NH-S(O) 2 -, -C(O)-NH-, -NH-C(O)-, -0-C(O)-, -C(O)-0- or a bond, A3 and A4 are identical or different and are -C(O)-, -0-, -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 I N 1N N N G) where E is -0- (oxygen), -S- (sulfur) or -CH 2 - (methylene), G is -0- (oxygen) or -CH 2 - (methylene), and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -0-, -S-, -C(O)-NH-, -NH-C(O)-, -0-C(0)-, -C(O)-0- or a bond, M is a pyranose unit selected from the following list B666WOO 09991 - 20 R4 R4 U R4 R3 R5 U R5 R3 R5 R3 U U 0 R2 R2 R2 WW W R4 U R4 U R5 R3 3 U W W W RI RI R1 U R4 R5 R2 O R2 0 R1 R1 W R3 R2 RI where U and W are identical or different and are -0- (oxygen), -S- (sulfur) or -NH-, R1 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-I -4C-alkoxy, R2 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-I -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 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)R7-0-], 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(0))m-B9-Z1 -B11 -X1, K2 is -B8-(C(0)),-B1O-X2, -B8-(C(0)),-B10-Y2 or -B8-(C(0)),-B1O-Z2-B12-X2, B666WO0 09991 -21 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 is 0 or 1, p is 0 or 1, XI and X2 are identical or different and are selected from the following groups NH NH

-NH

2

NH

2 NHOH NH NH H -N-H/N NH2

NH

2 N-R8 NH 2 NH NH NH

NH

2 S 8-R H NH 2 NH N-NH

NH

2 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, 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, 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 two carbonyl groups.

B666WOO 09991 - 22 Compounds of embodiment a to be emphasized are those in which Al and A2 are identical or different and are -C(O)-, -NH-, -0-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(0)-0- or a bond, A3 and A4 are identical or different and are -C(O)-, -0-, -NH-, -0-C(O)-, -C(0)-0-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group T T T T T N N N E N where E is -0- (oxygen), -S- (sulfur) or -CH 2 - (methylene) and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -0-, -C(O)-NH-, -NH-C(O)-, -0-C(O)-, -C(0)-0- or a bond, M is a pyranose unit selected from the following list B666WOO 09991 - 23 R4 R4 U R4 R3 R5 R5 R3 R5 R3 U U R2 R2 R2 R4 U R4 U R5 R3 R5 R3U W W W RI RI R1 U R4 W W R5 Us o 0 R2 R2 RI RI W R3 R2 RI where U and W are identical or different and are -0- (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 or Ar-1 -4C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) are an alkylenedioxy group [-0-C(R6)R7-0-], 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(0))m-B9-Y1 or -B7-(C(0))m-B9-Z1 -B11X1, K2 is -B8-(C(0)),-B1O-X2, -B8-(C(O))p-B1O-Y2 or -B8-(C(0)),-B1O-Z2-B12-X2, B666WOO 09991 - 24 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 is 0 or 1, p is 0 or 1, X1 and X2 are identical or different and are selected from the following groups NH NH

-NH

2

NH

2 NHOH NH NH H -N NH2

NH

2 N-R8 = NH H N NH 2 NH NH NH -- SNNH

NH

2 S-R8 NH2 NH

N-NH

2

NH

2 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-y, imidazolidin-4 yl, 2-imidazolin-3-yi, 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 B666WOO 09991 - 25 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 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. Compounds of embodiment a particularly to be emphasized are those in which Al and A2 are identical or different and are -C(O)-, -0-, -C(O)-NH-, -NH-C(O)-, -0-C(O)-, -C(O)-0- or a bond, A3 and A4 are identical or different or are selected from the group T T T T T N NN 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(0)-0- or a bond, M is a pyranose unit selected from the following list R4 R4 R3 W U U 0 0 R2 RI R1 where U and W are identical or different and are -0- (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, B666WOO 09991 - 26 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)),-B10-Y2 or -B8-(C(O)),-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, BI0, B11 and B12 are identical or different and are a bond or 1-3C-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 NH NH

-NH

2 N

NH

2 H NH 2 YI 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-yi, indol-3-yl, ben ziridazol-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 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 Al and A2 is -C(O)-, A3 and A4 are B666WOO 09991 - 27 N N A5 and A6 are identical or different and are -C(O)- or -C(O)-NH-, M is the pyranose unit R4 W 0 R2 R1 where U and W are -0- (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-B1 1-X1, K2 is -B8-(C(O)),-BIO-X2, -B8-(C(O))p-B1O-Y2 or -B8-(C(O))p-B1O-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 bond, B7 and B8 are identical or different and are a bond or 1-3C-alkylene, B9 and B10 are in each case a bond, B 11 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

-NH

2 N

NH

2 H NH 2 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.

B666WOO 09991 - 28 Particularly preferred compounds of embodiment a are 3,6-di-0-[4-(trans-4-aminomethylcyclohexylcarbonyl)-1-piperazinylcarbonyl]-4-0-benzyl-1,2-dideoxy-D glucopyranose; 3,6-di--[4-(trans-4-aminomethylcyclohexylcarbonyl)-1 -piperazinylcarbonyl]-1,2-dideoxy-D-gluco pyranose; 4-0-benzyl-3,6-di-0-[4-(4-guanidinobenzyaminocarbonyl)-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-0-[4-(4-aminomethylbenzylaminocarbonyl)-1-piperazinylcarbonyl]-4-0-benzyl-1,2-dideoxy-D glucopyranose; 3,6-di-O-[4-(l -amidinopiperidin-4-ylacetyl)-l -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 Al and A2 are identical or different and are -C(O)-, -NH-, -0- (oxygen), -(S)- (sulfur), -S(O) 2 -, -S(0) 2 -NH-, -NH-S(0) 2 -, -C(0)-NH-, -NH-C(O)-, -O-C(O)-, -C(O)-O- or a bond, A3 and A4 are identical or different and are -C(O)-, -0-, -S-, -NH-, -0-C(O)-, -C(0)-0-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group II III T T T T T NN N ED- N G where E is -0- (oxygen), -S- (sulfur) or -CH 2 - (methylene), G is -0- (oxygen) or -CH 2 - (methylene), and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -0-, -S-, -C(O)-NH-, -NH-C(O)-, -0-C(O)-, -C(0)-0- or a bond, M is a pyranose unit selected from the following list B666WO0 09991 - 29 R4 R4 U R4 R3 R5 U R5 R3 R5 R3 U 0 R2 R2 R2 o 0 0 WW W R4 U R4 U R5 R5 U 0 0 0 W W W R1 R1 RI U R4 R5 Us 0 0 R2 2 RI RI W R3 R2 RI where U and W are identical or different and are -0- (oxygen), -S- (sulfur) or -NH-, RI is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar- -4C-alkoxy, R2 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyl or Ar- -4C-alkoxy, R3 is hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar- -4C-alkoxy, R4 is hydroxyl, cyano, 1-4C-alkoxy, 1-4C-alkylcarbonyl or Ar- -4C-alkoxy, R5 is hydroxy, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar- -4C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) are an alkylenedioxy group [-0-C(R6)R7-0-], 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 or -B7-(C(O))m-B9-Z-B1I -X1, K2 is -B8-(C(O)),-B1O-X2 or -B8-(C(O)),-B1O-Z2-B12-X2, B666WOO 09991 - 30 B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, B9, B10, B1 1 and B12 are identical or different and are a bond or 1-3C-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 NH NH H H 0NH 2 N-RN NHOH R8 ONH2 NH NH NH

H-SNH

2

NH

2 S-R8 2 NH

N-NH

2 _/ 2

NH

2 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 Al and A2 are identical or different and are -C(O)-, -NH-, -0- (oxygen), -S- (sulfur), -S(0) 2 -, -S(0) 2 -NH-, -NH-S(0) 2 -, -C(O)-NH-, -NH-C(O)-, -0-C(O)-, -C(0)-0- or a bond, A3 and A4 are identical or different and are -C(O)-, -0-, -S-, -NH-, -0-C(O)-, -C(0)-0-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group B666WOO 09991 - 31 T T T T T N N N E NG where E is -0- (oxygen), -S- (sulfur) or -CH 2 - (methylene), G is -0- (oxygen) or -CH 2 - (methylene), and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -0-, -S-, -C(O)-NH-, -NH-C(O)-, -0-C(0)-, -C(0)-0-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the list below B666WOO 09991 - 32 R4 R4 U R4 R3 R5 U R5 R3 R5 R3 U U R2 R2 R2 WW W R4 U R4 U R5 R3 R5 R3 o 0 0 W W W R1 RI R1 U R4 R5 U R2 OR2 O RI RI W R3 R2 R1 where U and W are identical or different and are -0- (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 or Ar-1-4C-alkoxy, or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) are an alkylenedioxy group [-0-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-Z1-B11-X1, K2 is -B8-(C(0)),-B1O-Z2-BI2-X2, B666WOO 09991 - 33 Bi, 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 0 NH NH -- NH O

NH

2

NH

2 NHOH NH NH H -N

NH

2 H NH 2 N-R8 X NH2 H 0 NH 2 NH NH NH -- SN

NH

2 S-R8 NH2 NH N-NH

NH

2 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, 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 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.

B666WO0 09991 -34 Compounds of embodiment c to be emphasized are those in which Al and A2 are identical or different and are -C(O)-, -0-, -C(O)-NH-, -NH-C(O)-, -0-C(O)-, -C(0)-0- or a bond, A3 and A4 are identical or different and are selected from the group T T T T T N N N N where T is the group -C(0)- or a bond, A5 and A6 are identical or different and are -C(O)-, -C(O)-NH-, -NH-C(O)-, -O-C(O)-, -C(0)-0- or a bond, M is a pyranose unit selected from the list below B666WOO 09991 - 35 R4 R4 U R4 R3 R5 R5 R3 R5 R3 U U 0R2 )R2 R2 W W W W R4 U R4 U R5 R3 R5 R3 Us W W 0W 0 o 00 R1 RI RI U R4 R5 U 0 0 R2j R2j R1 RI I W R3 0 U R2 R1 where U and W are identical or different and are -0- (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-B1O-Z2-B12-X2, Bi, 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 is 0 or 1, p is 0 or 1, B666WOO 09991 - 36 X1 and X2 are identical or different and are selected from the following groups NH NH

-NH

2 -N

NH

2 H NH 2 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 B1O 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 Al 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 R4 R4 R3 W U U 0 0 W R2 R1 RI where U and W are identical or different and are -0- (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(0)),-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, B666WOO 09991 - 37 B7, B8, B9 and B10 are identical or different and are a bond or 1-4C-alkylene, B 11 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 O NH NH

-NH

2 / -N

NH

2

NH

2 H NH 2 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 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 embodiment c particularly to be emphasized are 3,6-di-0-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-0-benzyl-1,2-dideoxy-D glucopyranose; 3,6-di-O-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1 -ylcarbonyl]-1,2-dideoxy-D-glucopyra nose; 4-0-benzyl-1,2-dideoxy-3,6-di--[4-(4-guanidinobenzylaminocarbonyl)piperazin-1 -ylcarbonyl]-D-gluco pyranose; 3,6-di-0-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonylmethyl]-4-0-benzyl-1,2-di deoxy-D-glucopyranose; 3,6-di--[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1 -ylcarbonyl]-4-0-benzyl-1,2-dideoxy-D glucopyranose; 3,6-di-O-[4-(1 -amidinopiperidin-4-ylacetyl)piperazin-1 -ylcarbonyl]-4-0-benzyl-1,2-dideoxy-D-gluco pyranose; 3,6-di--[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1 -ylcarbonyl]-4-0-benzyl-1,2-dideoxy-D galactopyranose; 3,6-di-0-[4-(trans-4-aminomethylcyclohexycarbonyl)piperazin-1 -ylcarbonyl]-1,2-dideoxy-D-galacto pyranose; 3,6-di--[4-(amidinoindazol-3-ylcarbonyl)piperazin-1 -ylcarbonyl]-4-0-benzyl-1,2-dideoxy-D-gluco pyranose; B666W00 09991 -38 mehl36d--4(rn--mnmtyccoeycroy~ieai- -ylcarbonyII-4-O-benzyI-2 deoxy-a-D-glucopyraloside; methyl 3,-iO[-tas4aioehlccoeycroy~ieai- -ylcarbonyl]-2-deoxy-L-D glucopyranoside; 3,-iO[-tas4aioehlccoeycroy~ieai- -ylcarbonylmethyl]-1 ,2-dideoxy-D glucopyranose; 6-O-14(4aminomethylbenzylamiflocarboflY)piperazifll -ylcarbonyI-3-O-[4-(trals-4-amiomethyICYClO hexylcarbonyl)piperazifl-1 -ylcarbonyll-4-O-belzyl-1 ,2-dideoxy-D-gluCopyralose; benzyl 3,-iO[-tas4aioeh~ccoeycroy~ieai- -ylcarbonyl]-2-deoxy-L-D glucopyranoside; 3,-iO[-4aioehlezlmncroy~ieai- -ylcarbonylmethyl]-4-O-belzyl-1 ,2-di deoxy-D-glucopyralose; 3,-iO[-4aioehlezlmncroy~ieai- -ylcarbonylmethyll-1 ,2-dideoxy-D-gluco pyranose; 3,-iO[-tas4aioehyccoeycroy ieain- -ylcarbonyl]-4-O-methyl-1 ,2-dideoxy-D galactopyranose; methyl 2,-iO[-tas4aioehlccoeycroy~ieai- -ylcarbonyI-cX-D glucopyranoside; methyl 3,-iO[-4aiomtybnyaioaroy ieai--ylcarbonyl]-4-O-benzyl-2-deoxy-aX D-glucopyranoside; methyl 2,-iO[-4-mnmtybnz mncroylpprzn1ycarbonyl]-3,4-di-O-belzyl-cX-D glucopyranoside; methyl 3,-iO[-4aioehlezlmncroy~ieai- -ylcarbonyl]-2-deoxy-c-D glucopyranoside; 6--4(rn--mnmthlylhxlabnl- -aioetl---4(rn--mnmtycco hexylcarbonyl)piperazifl-l -ylcarbonyl]-4-O-benzyl-1 ,2-dideoxy-D-glucopyralose; 3--4(rn--mnmtyccoeycroy~ieai- -ycroy]60[-2-mnmtyp~dl carbonyl)-l -aminopentyl]-4-O-benzyl-l ,2-dideoxy-D-glucopyranose; 6--4(rn--mnmtyccoeycroy)4aiouy--xcroy]30[-tas4aio methylcyclohexylcarbonyl)piperazifl-1 -ylcarbonyl]-4-O-benzyl-1 ,2-dideoxy-D-glucopyralose; 6--4(rn--mnmtyccoeycroy)5aioetl---4(rn--mnmtycco hexylcarbonyl)piperazin-1 -ylcarbonyl]-1 ,2-dideoxy-D-glucopyranose; 3,-iO[-tas4aiomtyccoeycroy)5-mnpny 40bny-,2-dideoxy-D-gluco pyranose; 3,-iO[-tas4aioehlycoeycroy)5aioetl-,2-dideoxy-D-glucopyralose; 3,-iO[-3aioehlezy~ieai- -ylcarbonyl]-4-O-benzyl-I ,2-dideoxy-D-glucopyralose; 3,-iO[-3aioehlbnolmn~ieii- -ylcarbonyl]-4-O-benzyl-l ,2-dideoxy-D-gluco pyranose; 3,-iO[-3aioehlezlmncroy~ieai- -ylcarbonyl]-4-O-benzyl-l ,2-dideoxy-D glucopyranose; B666W00 09991 - 39 3,-iO[-3aioehlezlaioabnlmn~ieii- -ylcarbonyl]-4-O-benzyl-1 ,2-dideoxy 0-glucopyranose; 3,6-di-O-[4-(3-aminomethylbenzylamilocarbofl)piperidifl-l -ylcarbonyl]-4-O-benzyl-1 ,2-dideoxy-D glucopyranose; 3,-iO[-rn-3aioehlezlmncronlccoeymtyaioabnl---ezl 1 ,2-dideoxy-D-glucopyranose; 3,-iO[-6aioyii--lehlmncroy~ieii- -ylcarbonyl]-4-O-benzyl-1 ,2-dideoxy-D glucopyranose; 3-O-[4-(4-aminomethylbenzylamilocarboflyl)piperazifl-l -ylcarbonyl]-4-O-benzyl-6-O-[4-(6-amilo pyridin-3-ylmethylaminocarbonyl)piperidifl-l -ylcarbonyl]-1 ,2-dideoxy-D-glucopyranose; 3-O-[4-(4-aminomethylbenzylailocarbol)piperazifl-l -ylcarbonyl]-4-O-benzyl-6-O-[4-(6-amilo- 2 methylpyridin-3-ylmethylaminocarboflyl)Piperidil-1 -ylcarbonyl]-1 ,2-dideoxy-D-glucopyranose; 3-O-[4-(4-aminomethylbenzylaminocarboflyl)piPerazil-1 -ylcarbonyl]-4-O-benzyl-6-O-[4-(4-amilo benzylaminocarbonyl)piperidifl-1 -ylcarbonyl]-1 ,2-dideoxy-D-glucopyraflose; 3-O-[4-(4-aminomethylbenzylaminocarboflyI)piperazifl-l -ylcarbonyl]-4-O-benzyl-6-O-[4-trals-(6-amilo pyridin-3-ylmethylaminocarbony)cycohexy~nlethyaiocarboflyl]-l,2-dideoxy-D-glucopyranose; 3-O-[4-(4-aminomethylbenzylaminocarboflyl)piPerazil-1 -ylcarbonyl]-4-O-benzyl-6-O-[4-trans-(6-amilo 2-methylpyridin-3-ylmethylaminocarbony)cycIohexylmethylamilocarboflI-l,2-dideoxy-D-gluco pyranose; 3-O-[4-(4-aminomethylbenzyamiocarbofl)piperazifl-1 -ylcarbonyl]-4-O-benzyl-6-O-[4-trals-(4-amilo benzylaminocarbonyl)cyclohexylmethylaiocarboflyl]-1 ,2-dideoxy-D-glucopyranose; 3-O-[4-(4-aminomethylbenzylaminocarboflyl)piperazifl-1 -ylcarbonyl]-4-O-benzyl-6-O-[3-(4-amino benzylaminocarbonyl)benzylaminocarboflyl]-1 ,2-dideoxy-D-glucopyranose; 3-O-[4-(6-aminopyridin-3-ylmethylaminocarboflyl)piperidil-1 -ylcarbonyll-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-ylmethylaminocarboflyl)piperidil-1 -ylcarbonyl]-6-O-[4-(4-aminomethyl benzylaminocarbonyl)piperazil-1 -ylcarbonyl]-4-O-benzyl-1 ,2-dideoxy-D-glucopyranose; 3-O-[4-(4-aminomethylbenzylaminocarboflyl)piperazifl-1 -ylcarbonyl]-6-O-[2-(6-aminopyridin-3-y methylaminocarbonyl)eth-1 -ylaminocarbonyl]-4-O-benzyl-1 ,2-dideoxy-D-glucopyranose; 3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazil-1 -ylcarbonyll-4-O-benzyl-6-O-3-[(6-amidilo-1 H-indazol-3-yI)carbonylaminolprop-1 -ylaminocarbonyl}-1 ,2-dideoxy-D-glucopyranose; 3-O-[4-(4-aminomethylbenzyaminocarboflyl)piperazil-1 -ylcarbonylj-4-O-benzyl-6-O-{3-[(6-amino carbonyl-1 -H-indazol-3-yI)carbonylamino]prop-1 -ylaminocarbonyl}-1 ,2-dideoxy-D-glucopyranose; 3-O-[4-(4-aminomethylbenzylaminocarboflyl)piperazil-1 -ylcarbonyl]-6-O-{2-[(6-aminocarbonyl-I

-H

indol-3-yl)carbonylamino]eth-1 -ylaminocarbonyl}-1 ,2-dideoxy-D-glucopyranose; 3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazil-1 -ylcarbonyl]-4-O-benzyl-6-O-{3-[(6-amilo carbonyl-1 -H-indol-3-yI)carbonylamino]prop-1 -ylaminocarbonyl}-1 ,2-dideoxy-D-glucopyranose; 3-O-[4-(4-aminomethylbenzyaminocarboflyl)piperazil-1 -ylcarbonyl]-4-O-benzyl-6-O-{4-[(6-amino carbonyl-1 -H-indol-3-yI)carbonylamino]but-1 -ylaminocarbonyl}-1 ,2-dideoxy-D-glucopyranose; and the salts of these compounds.

B666WOO 09991 -40 A further embodiment (embodiment d) of the invention are compounds of the formula I in which Al and A2 are identical or different and are -C(O)-, -NH-, -0- (oxygen), -S- (sulfur), -S(0) 2 -, -S(0) 2 -NH-, -NH-S(0) 2 -, -C(O)-NH-, -NH-C(0)-, -0-C(O)-, -C(O)-0- or a bond, A3 and A4 are identical or different and are -C(O)-, -0-, -S-, -NH-, -0-C(O)-, -C(0)-0-, -C(0)-NH-, -NH-C(O)- or a bond, or are selected from the group T T T T T N N N ED- N G where E is -0- (oxygen), -S- (sulfur) or -CH 2 - (methylene), G is -0- (oxygen) or -CH 2 - (methylene), and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -0-, -S-, -C(O)-NH-, -NH-C(O)-, -0-C(O)-, -C(0)-0-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the following list B666WOO 09991 -41 R4 R4 U R4 R3 R5 U R5 R3 R5 R3 U U R2 R2 R2 W W W W R4 U R4 U R5 R3 R5 R3 Us 0 0 0 W W RI R1 R1 U R4 R5 U R2) R2 O RI RI R3 R2 RI where U and W are identical or different and are -0- (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-I-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)R7-0-], 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, KI is -B7-(C(O))m-B9-Y1, K2 is -B8-(C(O)),-B1O-Y2 or -B8-(C(0)),-B1O-Z2-B12-X2, B666WO0 09991 -42 BI, 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 is 0 or 1, p is 0 or 1, X2 is selected from the following groups 0 NH NH

-NH

2 -N

NH

2

NH

2 H NH 2 Y1 and Y2 are identical or different and are imidazol-1-yl, pyrrolidin-2-yl, imidazolidin-1-yl, imidazolidin 2-yl, irridazolidin-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 Al and A2 are identical or different and are -C(O)-, -NH-, -0- (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)-0- or a bond, A3 and A4 are identical or different and are -C(O)-, -0-, -S-, -NH-, -0-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 hN eG where B666WOO 09991 -43 E is -0- (oxygen), -S- (sulfur) or -CH 2 - (methylene), G is -0- (oxygen) or -CH 2 - (methylene), and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -0-, -S-, -C(O)-NH-, -NH-C(O)-, -0-C(O)-, -C(0)-0- or a bond, M is a pyranose unit selected from the following list R4 R4 U R4 R3UR 3 R3 R3 R5 R3 R5 U U R2 R2 R2 W W W W R4 U R4 U R3 R3 R5 R5 U 0 0 0 W W W R1 RI R1 U R4 R5 112 o 2 0 R2 OR2 O R1 RI W R3 0 R2 RI where U and W are identical or different and are -0- (oxygen), -S- (sulfur) or -NH-, R1 is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy or Ar-I-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, B666WOO 09991 -44 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-], 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-B1O-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 is 0 or 1, p is 0 or 1, Y1 and Y2 are identical or different and are pyrrolidin-2-yl, imidazolidin-1-yl, imidazolidin-2-yl, imida2 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 Al and A2 are identical or different and are -C(O)-, -C(O)-NH-, -C(O)-0- 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 R4 R4 R3 W 0 0 R2 RI R1 where U and W are identical or different and are -0- (oxygen) or -NH-, R1 is hydrogen, methoxy or benzyloxy, R2 is hydrogen, R3 is hydroxyl or benzyloxy, R4 is hydroxyl, methoxy or benzyloxy, B666WOO 09991 -45 K1 is -B7-(C(O))m-B9-Y1, K2 is -B8-(C(O)),-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 BIO 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 0 NH NH

-NH

2 N/

NH

2

NH

2 H NH 2 Y1 is imidazol-1-yl, Z2 is 5,2-pyridinylene, 6-methyl-5,2-pyrdinylene, 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 3-0-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1 -ylcarbonyl]-4-0-benzyl-6-0-{4-[3-(imidazol-1 yl)-propylaminocarbonyl]piperidin-1 -ylcarbonyl}-1,2-dideoxy-D-glucopyranose; 3-0-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1 -ylcarbonyl]-4-0-benzyl-6-0-{4-[4-(imidazol-1 yl)butylaminocarbonyl]piperidin-1 -ylcarbonyl}-1,2-dideoxy-D-glucopyranose; 3-0-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1 -ylcarbonyl]-4-0-benzyl-6-0-{4-[5-(imidazol-1 yl)pentylaminocarbonyl]piperidin-1 -ylcarbonyl}-1,2-dideoxy-D-glucopyranose; 3-0-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1 -ylcarbonyl]-4-O-benzyl-6-0-{4-[6-(imidazol-1 yl)hexylaminocarbonyl]piperidin-1 -ylcarbonyl}-1,2-dideoxy-D-glucopyranose; 3-O-[4-(4-aminomethylbenzylaminocarbonyl)piperazin-1 -ylcarbonyl]-4-0-benzyl-6-0-{4-[8-(imidazol-1 yl)octylaminocarbonyl]piperidin-1 -ylcarbonyl}-1,2-dideoxy-D-glucopyranose; and the salts of these compounds. The compounds of the formula I are composed of a large number of divalent units (M, Al, A2, A3, A4, A5, A6, B1, B2, B3, B4, B5, 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 B666WOO 09991 -46 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 [-0-], thioether [-S-], keto [C(O)-], sulfonyl [-S(0)2-], ester [-O-C(O)-, -C(O)-O-], amide [-C(O)-NH-, -NH-C(O)-], sulfonamide [-S0 2 -NH-, -NH-SO 2 -], carbamate [-NH-C(O)-O-, -0-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 2S04 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 mistry. Correspondingly, sulfonamide bridges can be constructed from sulfonic acid chlorides and pri mary or secondary amines.

B666WOO 09991 -47 Carbamate bridges can be produced, for example, by reaction of chlorocarbonic acid esters with arni 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.

B666WOO 09991 -48 Reaction scheme 1: OAc OH AcO 1.Pd/ C/ H 2 , MeOH HO 0 AcO - HO7 2. NaOMe, MeOH TBDMS-CI (2.4 eq), imidazole BDMS BnBr, NaH, OTBDMS BnO 0 , DMF HO O TBDMSO TBDMSO TBAF, THF OH BnO 0 1. TsCI, Py, RT, (A59) 2. NaN 3 , DMF, 120*C, (A58) 3. LiAIH 4 , THF 1. BrCH 2

CO

2 Me, NaH, THF 2. NaOH, H20, MeOH, 4 h BnOO CO 2 H

NH

2 BnO 7 L BnO : HOCHO A57 B666WOO 09991 -49 Reaction scheme 2: OAc OH 1. LiBr, MeOH, CH 3 CN AcO O Dowex 50 (H+ form) HO 0 AcO - HO 2. NaOMe, MeOH OMe TBDMS-CI (2.4 eq), imidazole, (quant.) OTBDMS BnBr, NaH, OTBDMS BnO O DMF, (95%.) HO 0 TBDMSO TBDMSO OMe OMe TBAF, THF, (88%) OH BnO Carbohydr. Res. 1995, 268 (1), 135-142 OMe OAc OH 1. LiBr, H 2 0, CH 3 CN AcO 0 Dowex 50 (H+ form) HO 0 AcOaL HO 2. BnBr, NaH, DMF HO OBn 1. TBDMS-Cl (2.4 eq), imidazole, (quant.) Chem. Ber. 1980, 113 (8), 2827-2831 2. BnBr, NaH, DMF OH OTBDMS BnO O TBAF, THF, (85%) BnO 0 HO TBDMSO OBn OBn B666WO0 09991 -50 Reaction scheme 3: OH OTBDMS TBDMS-CI (2.0 eq), HO 0 imidazole, DMF, (70 %) HO 0 HO - HO HO OMe TBDMSOOMe BnBr, NaH, DMF OH OTBDMS BnO 0 TBAF, THF BnO 0 BnO BnO HOOMe TBDMSOOMe Bull. Chem. Soc. Jpn. 1983, 56 (4), 1171-1175 Tetrahedron Left. 1984, 25 (36), 4029-4032 Carbohydr. Res. 1982, 102, 207-216 B666WOO 09991 - 51 Reaction scheme 4: OH BnO7 1. COCI 2 , Tol, CH 2 Cl2 2. DIPEA, DMAP, CH 2 Cl 2 , H'N N'o O N NBocB NN OO BnO00 BocN 0 1. HCI, dioxane 2. HOBT, EDC, CH 2 02, Boc N Boc HOOC H 0 - ~ N ON N H BnO O BocN N N H 0 O HCI, dioxane 0 N

NH

2 00 BnO O H2 N x 2HCI \o~o- O B666WOO 09991 - 52 Reaction scheme 5: o Boc N0 N H BnO O Boc, N N N1 H 0 0 Pdl C/ H2 MeOH 0 Boc OI N N HO O Boc- N H 0 HCI, dioxane N NH 2 HO O N N x 2HCI

H

2 NO 0 0 B666WO0 09991 - 53 Reaction scheme 6: N 0 N\- -N-Boc 00 BnO O Boc N 0 1. HCI, dioxane 2. DIPEA, CH2Cl2, BocHN 3. HCI, dioxane 0 N

H

2 N IBHnO\ O ~N NH HN N HN NN n H BnO 0 0 N)>N -- '\ -'<

NH

2 0 0 1. Et 3 N, HgCI 2 , DMF, MeS "I N, o 2.HCI, dioxane NHBoc 0 H HNr N NH H BnO-SI~\N NN N) - N NH 2 x 2HCI H 0 0 3 B666WOO 09991 - 54 Reaction scheme 7: OHO OH O O l BnO 0 Cl CI BnO O BnO BnO HO Py, CH 2 Cl 2 , HOOMe 0 OOMe CI H-N, N0 R R DIPEA, CH 2 Cl2 A2j-3 N.Boc H R O BnO OBn ' Boc N O 0 0 0 MeO 0 N N R HCI, dioxane

-

or 1. Pd/C/H 2 , MeOH 2. HCI, dioxane ROLO R"O OR" R N 0 18: R" = H H ' NH 2 N 20: R" Bn HN N2O

R'

B666WOO 09991 - 55 Reaction scheme 8: O Cl OH 0 0 BnO O CI CI BnOO 0 HO Py, CH 2 ClI 2 , 0 OR" CI R= Me, Bn H.N N R R DIPEA, CH2Cl2 N Bo NBoc OH Bo N yN R R 0 BnO 0 0 OR"' 0 HCI, dioxane Rf - or 1. Pd/C/H 2 , MeOH NH2\2. HCI, dioxane H NH 2 O N 1.) N NeR' R'/ N N R O 10: R" = Bn, R.' = Me OR"' '11 : R" = H, R"= Me O 14: R" = Bn, R" = Bn 2.) 9: R" = Bn, R"' = Me 21: R" = H, R"' = Me B666WOO 09991 - 56 Reaction scheme 9: OH OTBDMS OTBDMS BnO 7 TBDMSCI (1 eq) Bn Cl CI BnO HO HO Py, CH 2 Cl 2 , Cl A53 0 H Boc' N N H A43 O 1. DIPEA, DMAP 2. TBAF Boc-N H OH N 0 j O 0 E 0 N 0 0 A45 B666WOO 09991 - 57 Reaction scheme 10: B00.N H H OH A45N O BnOO N 0 1. CH 2 Cl 2 , r.t. TfO 2 , Py 2. H 2

N-NH

2 x H 2 0, EtOH Ho/\/\^NPht TfO NPht J. Amer. Chem. Soc. 1993, 115 (26), 12550-12568 KPht Boc-N H HOAV NH 2 H2/\ H ONN 0 BnOO 00 N EDC, CH 2 Cl2 O Boc'N H0 R"1 N N OR'OO 0 Boc' N 2.) H HCI, dioxane Boo' N

H

2 N N N R" 22: R'= Bn H2N 0 F: R'2 = H 23: R'= Bn

H

2

N

B666WOO 09991 - 58 Reaction scheme 11: 0 yCI HO OH RO H RO 0 1. TBDMSCI (2 eq) Cd Cl HO 2. Mel or BnBr HO Py, CH 2

C

2 , r.t. cl 3. TBAF O R =Bn, Me H Boc N A4 3 1. DIPEA, DMAP 0 2a. HCI, dioxane 2b. Pd/ C/H 2 , MeOH; HCI, dioxane

H

2 N

NH

2 O N N 7 :R=Bn N RO O 8 :R=H O O 17: R = Me N 0 B666WOO 09991 - 59 Reaction scheme 12: O xCO 2 H BnOOL

HO

2 Cd EDC, CH 2 Cl 2 O N N R N 0 NJ R R NBoc 0 H HCI, dioxane Boc

-

or 1. Pd/C/H 2 , MeOH 2. HCI, dioxane 0 N R O R"O 0 N O R N R 0 2: R" = H NH2 15: R" = Bn H 2 16: R" = H N B666W00 09991 - 60 Reaction scheme 13: OH 0 7 COMe 0 0 -- /C 2 Me BnO BrCH 2

CO

2 Me Bn 0 LI _______ BnO HO NaH HOPC 2

CI

2 , ci-\ A A66 0 A43 ~N -N H Boo \~N1. DIPEA, DMAP 02. NaOH, MeOH Boc N Z" N 0 -,,CO 2 H 0 L-]BnO N -\ 0 1. EDC, CH 2

CI

2 N 2. HCI, dioxane H-NlmsmI>

NH

2

H

2 N H N N 0 L - B n 0 N 0 B666WOO 09991 -61 Reaction scheme 14: HO NH + HO 'Boc 2 O 0 2 EDC /Boc N Boc O O H HO tA ~ H 0 0" N 2 A O A5 NH BnO O :, H BnoA52 COCl 2 HO A57 1. COC1 2 H 2. HCI, dioxane I .H Boc N N H 0

NH

2 N-H OH N- B nO 0_2 O N 0 B666WOO 09991 - 62 Reaction scheme 15: H O N N OH N- -H Boc' N H BnO O HO_\.: 1. COCl 2 , tol N 2. DIPEA, CH 2 Cl 2 O 3. HCI, dioxane 1. EDC, CH 2 Cl 2 , NH DIPEA, DMAP ,N NHZ 2. Pd/ C, H 2 , MeOH N

HO

2 C

NH

2 0 NH 2 HN O N N NH I 0 O N H N N N BnOH N Bn 0 B666WOO 09991 - 63 Reaction scheme 16: OH TfO NPht O NH2 BnO 1. CH 2

C

2 , r.t. BnOO 0 2. H 2

N-NH

2 x H 2 0, EtOH H2N A64 H Boc' CO2H 1. EDC, CH 2

CI

2 2a. HCI, dioxane 2b. Pd/ C/ H2, MeOH; HCI, dioxane

NH

2

H

2 N H R 'O O N\/\V/ 26: R'= Bn 27: R'= H B666WOO 09991 - 64 Reaction scheme 17: 0 C1 \OH COC1 2 _ /C O - HO. 0~- O~ c1 0 1) Ajj2 (AlAl1, Al, Al 16, Ali17 Al 18) 2) HCI/dioxane 0 0 R NO R O N NH2 N N NH 2 29 N 0 N N NH 2 0 N N N2NH 2 N NH2 Na 0 31 N NH2 0 H 32 N -T NH 2 0 33 N NH 2 NHH 34 Ni -S NO )'

NH

2 B666WOO 09991 - 65 Reaction scheme 18: /OH TBSCI OTBS 0 HO - O :2

COC

2 -\0 OTBS c1 0 1 BocHN Al 30 NH 2.) TBAF / \ OH A1 06 BoCHN N N N O y NJ CO" CDI 0 01 NN 0 /c OoN 0 BoHN Q Al105 BOCHN N N NJcN N NJ y 0 B666WOO 09991 - 66 Reaction scheme 19: OH TBSCI OTBS CDI / B OT ABS N N BocH N Al8 NH 1.) H __ 0 2.) TBAF / \ l OH - A109 BocHN N 0 0 CDI 0 N N 0 BocHN N 0 A108 I H N / N 0 B666WOO 09991 - 67 Reaction scheme 20: 0 0 CI N BocHN N 0 BocHN N 0 H H o 1) A120 (23, A124) 0 32) Pd/C, H 2 1.) A 2 (Al 2 l , A2, A 29) 1)Alj8 (Al192, "122) 3) HI, dioxane 2.) HCI/dioxane 2.) HCI/dioxane 0 0

H

2 N N 0 H O N N N 0a o NN"HN2 NH H 42 H N H 2 0NN 0 N HN H N L3 N N 36 INNH N NH 2 N N N N N 37 ' a NH 2 N H 0 2 NH 0~ -- N~ NH, " I_ N oH 2 45 N -N 0 39N,,,e NH N W- N N

NH

2 00 46,#o " NH <H 41 NHN NH 2 B666WOO 09991 -68 Reaction scheme 21: o O O H N N NH2 o C - \ .S :O 01

-

O

H

2 N _NH2 BocHN N 0 BocHN N N H NO0 NN N y BocHN yn= 1;A102 o0 0 HO n =2 A103 AlO 5 /~ = n3; A104 BoHN N OH 0~~ 0 o H 0 N O N N2 A99 (lO, A101) BocHN N O n1.)H 2 /PdDMF A94 (A95 A6) 0 -Yn N

NH

2 H

H

2 N rNAo n =1; 52

-

= 2; 53 0 n = 3; 54 B666WOO 09991 - 69 Reaction scheme 22: 0 N \ N 0 BocHN N O N 0_C 0 O 1 ) A_30(Al 31) 2) HCI, dioxane R= 0 0 f N A O 047 HN H B o c H N O 4 _8 H 2 N N H 2 N N 00 0 - & Al105 BocHN N 0 1)A12 2) HCI, dioxane H - NH 2 I N

-

0 0

H

2 N N 0 B666WOO 09991 - 70 Reaction scheme 23: 0 O ci BocHN N O HNH ON N 0 NH N 0 NBHoc A154 *N.) H2/P , 0 9 (93 N NNH 0 0 b 0 O Or H N& / N / Z

-

0 A97 H N N H 0 1.) H 2 /Pd, DMF -~ &9-2 (A 3 I2.) HCI/dioxane )_H H ~-N N-N 00 NH

H

2 NN N 0 50 0 0 H H H- N-N N y N 00 B666WOO 09991 -71 Reaction scheme 24: o N:N O 0 0 NO + N H H2N H H 0 HN ~N 0 HCH n ~ (C H2)n N O 2 A166 0 3 A167 4 A168 0 -- \ 0 O N H 00 2A157 1 C 2 ) 0 3 A158 4 Al1590 ON HI 0 HCI HCI (H) 0 0 H 2 55 3 .56 4 .57 B666WOO 09991 - 72 Reaction scheme 25: NH 0 OTBDMS NNH + N 0 A118 0 A1 OTBDMS OO N N A177 XO H0 OH 0 N N A173 H NN O 0 N OH / 0 S 0 0 A169 N O H A112 A13/ 116/ A117 A 14 1 A160 A161 Al 62 Al163 Al164 A165 IIII 1 58 59 60 61 62 63 B666WOO 09991 -73 Further suitably substituted pyranose units M which may be mentioned are, for example: benzyl a-D-4 O-benzyl-2-deoxyglucopyranoside (1), methyl a-D-2,4-di-0-benzylglucopyranoside (2), methyl a-D-2,4 di-O-benzylmannopyranoside (3), benzyl a-D-2,4-di-0-benzylmannopyranoside (4), methyl P-D-2,4-di O-benzylgalactopyranoside (5), methyl a-D-2,4-di-0-acetylglucopyranoside (6), methyl p-D-6-amino 3,4-di-O-isopropylidenegalactopyranoside (7), methyl p-D-3,4-di-0-isopropylidenegalactopyranoside (8) and methyl -D-2-amino-3,4-di-0-isopropylidenegalactopyranoside (9). Their preparation is described, for example, in Chem. Ber. 1980, 113, 2827-2831 (1), Chem Pharm. Bull. 1986, 2341; P-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) und 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 a 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 his/her 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 chrorra 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 B666WOO 09991 -74 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 dimethylforrma mide, THF for tetrahydrofuran, PE for petroleum ether, EA for ethyl acetate, DMAP for dimethylamino pyridine, DIPEA for diisopropylethylamine, HOBT for 1-hydroxy-1H-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.

B666WOO 09991 -75 Examples Final compounds: 1. 3.6-Di-0-[4-(trans-4-aminomethlcclohexvicarbonyl)-1 -Diperazinvlcarbonyll-4-0-benzvl 1.2-dideoxy-D-glucopvranose 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 N 2 and washed first with dioxane (2 x 3 ml) and then with CH 2

CI

2 (3 x 3 ml). After drying in vacuo, the title compound (0.72 g) is obtained as colorless crystals. MS: calc.: C 39 HoN 6 0 8 (741.05), found: [MH*] 741.4 2. 3.6-Di-O-[4-(trans-4-aminomethlcclohexvcarbonvl)-1 -piperazinvicarbonvil-1.2-dideoxy D-glucopyranose dihydrochloride A solution of 3,6-di-O-[4-(trans-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 N 2 atmosphere and washed first with dioxane (2 x 1 ml) and then with CH2Cl 2 (3 x 1 ml). After drying in vacuo, the title compound (0.05 g) is obtained as colorless crystals. MS: calc.: C 32

H

54

N

6 0 8 (650.82), found: [MH*] 651.4 3. 4-0-Benzvl-1.2-dideoxy-3.6-di-O-[4-(4-quanidinobenzlaminocarbonyl)-1 -pierazinyl carbonyll-D-glucopvranose 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 Al1) 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 4 and washed first with dioxane (2 x 1 ml) and then with C-2Cl 2 (3 x 1 ml). After drying in vacuo, the title compound (0.04 g) is obtained as colorless crystals. MS: calc.: C 4 1 1H 54

N

12 0 8 (842.96), found: [MH*] 843.4 B666WOO 09991 -76 4. 3.6-Di-O-[4-(trans-4-aminomethlcvclohexvlcarbonvli)-1 -iperazinvlcarbonvimethyll-4-0 benzvl-1.2-dideoxy-D-glucopyranose dihydrochloride 4-O-Benzyl-3,6-di-O-[4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-1-piperazinyl carbonylmethyl]-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 N 2 and washed with dioxane (2 x 1 ml). The residue is coevaporated twice with toluene (20 ml) and then three times with

CH

2 Cl 2 (10 ml). After drying in vacuo, the title compound (0.03 g) is obtained as colorless crystals. MS: calc.: C 4 1

H

64

N

6 08 (769.00), found: [MHW] 769.4 5. 3.6-Di-o-r4-(4-aminomethylbenzvlaminocarbonvl)-1-piperazinvicarbonvIl-4-O-benzyl-1.2 dideoxy-D-glucopyranose 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 N 2 and washed first with dioxane (2 x 1 ml) and then with Et 2 O (3 x 1 ml). The residue is coevaporated with toluene and then with CH2C12 (2 x 10 ml each). After drying in vacuo, the title compound (0.1 g) is obtained as colorless crystals. MS: calc.: C 41

H

54

N

8 08 (786.94), found: [MH*] 787.3 6. 3,6-Di-0-r4-(1-amidinopiperidin-4-vlacetyl)-1-piperazinvlcarbonvll-4-O-benzvl-1.2-dideoxy D-glucopyranose dihydrochloride 4-O-Benzyl-3,6-di-O-{4-[1-(N,N'-bis-tert-butoxycarbonylamidino)piperidin-4-ylacetyl]piperazin-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 N 2 and washed first with dioxane (2 x 1 ml) and then with CH2Cl 2 (3 x 1 ml). The residue is coevaporated with toluene and then with CH 2

CI

2 (2 x 10 ml each). After drying in vacuo, the title compound (0.07 g) is obtained as colorless crystals. MS: calc.: C 3 9 HoN 1 0 0 8 (796.98), found: [MH*] 797.4 B666WOO 09991 - 77 General procedure for the preparation of 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 N 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-[4-(trans-4-aminomethvlcvclohexvlcarbonvl)-1-piperazinvlcarbonvll-4-0-benzvI 1.2-dideoxy-D-qalactopyranose dihydrochloride MS: calc.: C 3 9 HoN 6 0 8 (741.05), found: [MHW] 741.4 8. 3.6-Di-O-r4-(trans-4-aminomethvlcvclohexvcarbonvl)-1-piperazinvicarbonvll-1.2 dideoxy-D-calactopyranose dihydrochloride MS: calc.: C 32

H

5 4

N

6 0 8 (650.82), found: [MH*] 651.3 9. 3.6-Di-o-r4-(amidinoindazol-3-vlcarbonvl)-1-oiperazinvlcarbonvll-4-0-benzvl-1.2 dideoxv-D-alucouvranose The compound prepared according to procedure A24 (0.25 g, 0.182 mmol) is dissolved in a mixture of methanol/dichloromethane (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.: C 4 1

H

4 6

N

12 0 8 (834.90), found: [MH*] 835.4 10. Methyl 3.6-di-O-f4-(trans-4-aminomethvlcvclohexvlcarbonvl)-1-iperazinvicarbonvil-4-O benzvl-2-deoxy-a-D-glucopvranoside dihydrochloride MS: calc.: C 40

H

6 2

N

6 0 9 (770.97), found: [MH*] 771.1 11. Methyl 3.6-di-O-[4-(trans-4-aminomethvlcvclohexvlcarbonvl)-1 -piperazinvlcarbonvll-2 deoxy-a-D-qlucopyranoside dihydrochloride MS: calc.: C 3 3

H

56

N

6 0 9 (680.85), found: [MH*] 681.2 B666W00 09991 - 78 12. 3.6-DI-o-r4(trans4-aminomethvlcvclohexvlcarbonvi)-1 -Diterazinvlcarbonvmethyll-1 .2 dideoxv-D-alucorpvranose dihydrochioride MS: caic.: C 34

H

58

N

6 0 8 (678.88), found: [MH+] 679.4 13. 6-0-r4(4-AminomethvlbenzvlaminocarbonflV)-l -piperazinvicarboflvil-3-O-r4-(trafls-4 aminomethvlcvclohexvlcarbonv)-l -Diperazinvlcarbonvl-4-O-benlZV-1 .2-dideoxv-D cilucoDyraflose dihydrochioride MS: caic.: C 41

H

59

N

7 0 8 (778.00), found: [MI-W] 778.4 14. Benzvl 3.6-di-O-r4-(trans-4-aminomethvlcvclohexvlcarboflyl)-1 -ierazinvlcarbonvll-2 deoxv-a-D-glucopvranoside dihydrochioride MS: caic.: C 46

H

66

N

6 0 9 (847.07), found: [MH+] 847.3 15. 3.6-Di-o-r4-(4-aminomethvlbenzvlaminocarbonv)-1 -Dioerazinvicarbonvlmethvll-4-O benzvl-1 .2-dideoxv-D-clucotvranose dihydrochioride MS: caic.: C 43

H

58

N

8 0 8 (814.99), found: [MH+] 815.4 16. 3.6-Di-O-r4-(4-aminomethvlbenzvlaminocarbonvl)-1 -gierazinvlcarbonvlmethvll-1 .2 dideoxv-D-cllucogvranose dihydrochioride MS: cabc.: C 36

H

52

N

8 0 8 (724.86), found: [MW~] 725.4 17. 3.6-DI-o-r4-(trans-4-aminomethvlcvcIohexvlcarbonvl)-1 -piuperazinvlcarbonvll-4-O-methvl I .2-dideoxv-D-clalactoivranose dihydrochioride MS: caic.: C 33

H

56

N

6 0 8 (664.85), found: [MH-f] 665.4 18. Methyl 2.6-di-O-4-(trans-4-aminomethvlcvclohexvlcarbonvl)-1 -iperazinvicarbonvl-x-D alucoD~vrafloside dihydrochioride MS: caic.: C 33

H

5 6

N

6 0 1 0 (696.85), found: [MH 4 ] 697.4 19. Methyl 3.6-di-04r4-(4-aminomethlbenzvlamiocarboflvl)-1 -piperazinvlcarbonvll-4-O benzyl-2-deoxv-a-D-calucopvranoside dihydrochloride MS: caic.: C 42

H

56

N

8 0 9 (816.96), found: [MW-I] 817.2 B666W00 09991 - 79 20. Methyl 2.6-di-o-r4-(4-aminomethvlbenzvlaminocarbonvI)-1 -iperazinvicarbonv11-3.4-di-O benzvl-cz-D-clucopranoside dihydrochioride MS: caic.: C 49

H

63

N

9 0 9 (922.10), found: [MW~] 923.3 21. Methyl 3.6-di-O-i4-(4-aminomethvlbenzlaminocarboflvl)-1 -piperazinvicarbonv11-2-deoxV cc-D-clucogvranoside dihydrochioride MS: caic.: C 35

H

50

N

8 0 9 (726.80), found: [MH~] 727.2 22. 6-O-i4-(Trans-4-aminomethvlcvclohexvlcarbonv)-1 -aminogentvll-3-O-r4-(trals-4-amilo methvlcvclohexvlcarbonfl)-i -Diierazinvlcarbonvll-4-O-benzvl-1 .2-dideoxv-D-giluco pyranose dihydrochioride MS: caic.: C 39

H

63

N

5 0 7 (713.97), found: [MW~] 714.5 23. 3--4-(Trans-4-aminomethvlcvclohexvlcarbonv)-1 -gierazinvlcarbonvll-6-O-r5-(2 aminomethvlpvridvlcarbonv)-l -aminopentvll-4-O-benzvl-1 .2-dideoxv-D-cllucopvranose trihydrochioride MS: caic.: C 38

H

56

N

6 0 7 (708.91), found: [MW~] 709.4 24. 6-N-i4-(Trans-4-aminomethvlcvclohexvlcarbonv)-4-aminobutl-4-oxvcarboflvil-3-O-4 (trans-4-aminomethvlcvclohexvlcarbonv)-1 -Diperazinvlcarbonvll-4-O-benzvl-1 .2 dideoxy-D-clucopyranose dihydrochioride MS: caic.: C 39

H

62

N

6 0 8 (742.97), found: [MH+] 743.5 25. 6-[-4-(Trans-4-aminomethvlcvclohexvlcarbonv)-5-aminoentl-3--4-(tras-4-ailo methvlcvclohexvlcarbonv)-1 -ierazinvlcarbonvll-1 .2-dideoxy-D-cllucogvranose di hydrochloride MS: caic.: C 32

H

5 7

N

5 0 7 (623.84), found: [MH+] 624.4 26. 3.6-DI-O-r4-(trans-4-aminomethvlcvclohexvlcarbonl)-5-aminoentll-4--benlZV-1 .2 dideoxv-D-cslucomvranose dihydrochioride MS: caic.: C 39

H

66

N

4 0 6 (678.00), found: [MH~] 679.1 B666WOO 09991 - 80 27. 3,6-Di-O-[4-(trans-4-aminomethylcyclohexylcarbony l-5-aminopentyll-1.2-dideoxy-D glucopyranose dihydrochloride MS: calc.: C 32 HoN 4 0 6 (596.96), found: [MH*] 597.5 28. 3.6-Di-O-r4-(3-aminomethylbenzol)piperazin-1-vlcarbonvll-4-0-benzvl-1.2-dideoxv-D glucopyranose dihydrochloride A solution of 3,6-di-O-{4-[3-(tert-butyloxycarbonylaminomethyl)benzoyl]piperazin-1-ylcarbonyl}-4-0 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: calc.: C 39

H

4 8

N

6 0 8 (728.85), found: [MH] 729.2 29. 3.6-Di-O-r4-(3-aminomethylbenzovlamino)piperdin-1 -vlcarbonyll-4-0-benzyl-1.2 dideoxy-D-qlucopyranose dihydrochloride 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: calc.: C 4 1

H

5 2

N

6 0 8 (756.91), found: [MH] 757.3 30. 3.6-Di-0-r4-(3-aminomethylbenzvlaminocarbonl)piperazin-1 -vlcarbonyll-4-O-benzyl-1.2 dideoxy-D-qlucopyranose dihydrochloride A solution of 3,6-di-O-{4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-yl carbonyl}-4-0-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, B666WOO 09991 - 81 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.: C 4 1 1H 5 4

N

8 0 8 (786.94), found: [MH] 787.2 31. 3.6-Di-O-r4-(3-aminomethylbenzvlaminocarboniamino)piperidin-1-vlcarbonyll-4-O 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.: C 4 3

H

58

N

8 0 8 (814.47), found: [MH*] 815.3 32. 3.6-Di-0-r4-(3-aminomethylbenzvlaminocarbonl)piperidin-1 -vlcarbonyll-4-O-benzyl-1.2 dideoxy-D-alucopyranose dihydrochloride A solution of 3,6-di-O-{4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperidin-1-yl carbonyl}-4-0-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.: C 4 3

H

56

N

6 0 8 (784.96), found: [MH] 785.3 33. 3.6-Di-O-r4-trans-(3-aminomethylbenzvlaminocarbonvl)cvclohexvlmethylamino carbonvll-4-O-benzvl-1,2-dideoxy-D-glucopyranose dihydrochloride A solution of 3,6-di-O-{4-trans-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]cyclo hexylmethylaminocarbonyl}-4-0-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.

B666WOO 09991 - 82 MS: calc.: C 4 7

H

4

N

6 0 8 (840.51), found: [MI'] 841.3 34. 3.6-Di-O-r4-(6-aminopyridin-3-vimethylaminocarbonvl)piperidin-1 -vicarbonvil-4-0 benzvl-1.2-dideoxy-D-qlucopyranose dihydrochloride 3,6-Di-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1 -ylcarbonyl]-4-0 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.: C 39

H

5 oN 8

O

8 (758.88), found: [Mi*] 759.3 35. 3-0-[4-(4-Aminomethylbenzvlaminocarbonvlhpiperazin-1 -vicarbonvll-4-O-benzvl-6-O-[4 (6-aminopvridin-3-vimethvlaminocarbonvl)oiperidin-1 -vicarbonvl1-1.2-dideoxv-D-aluco pyranose dihydrochloride 3-0-{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 0 C are obtained (sintering at 140 0 C). MS: calc.: C 4 oH 52

N

8 0 8 (772.9), found: [MH*] 773.2 36. 3-O-[4-(4-Aminomethylbenzvlaminocarbonl)piperazin-1 -vicarbonvill-4-O-benzvl-6-O-[4 (6-amino-2-methvlovridin-3-vimethylaminocarbonvl)piperidin-1 -vicarbonvil-1.2-dideoxv D-qlucopyranose dihydrochloride 3 -0-{ 4

-[

4 -(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-0-benzyl 6 -0-[ 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 0 C). MS: calc.: C 4 1

H

5 4

N

8 0 8 (786.94), found: [MH*] 787.4 B666WO0 09991 -83 37. 3-0-[4-(4-Aminomethylbenzvlaminocarbonl)piperazin-1 -vlcarbonyll-4-O-benzyl-6-0-[4 (4-aminobenzvlaminocarboni)piperidin-1-vlcarbonvll-1.2-dideoxy-D-glucopvranose di hydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 -ylcarbonyl}-4-O-benzyl 6-0-[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. > 2200C are obtained (sintering at 11 0*C). MS: calc.: C 4 1

H

53

N

7 0 8 (771.9), found: [MH*] 772.3 38. 3-0-[4-(4-Aminomethylbenzvlaminocarbonvl)piperazin-1 -vicarbonyll-4-O-benzyl-6-O-[4 trans-(6-aminopyridin-3-vlmethylaminocarbonvl)cvclohexvlmethylaminocarbonll-1,2 dideoxy-D-glucopyranose dihydrochloride 3-O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-0-benzyl 6-0-[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 Itle compound of m.p. > 220*C are obtained (sintering at 1700C). MS: calc.: C 42

H

56

N

8 0 8 (800.96), found: [MHW] 801.4 39. 3-0-[4-4-Aminomethylbenzvlaminocarbonvl)piperazin-1 -vicarbonvll-4-0-benzyl-6-O-[4 trans-(6-amino-2-methylpvridin-3-vlmethylaminocarbonvl)cvclohexvlmethylamino carbonvll-1.2-dideoxy-D-glucopyranose dihydrochloride 3-0-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbony]piperazin-1-ylcarbonyl}-4-0-benzyl 6-0-[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.: C 4 3

H

58

N

8 0 8 (814.99), found: [MH*] 815.4 B666WOO 09991 -84 40. 3-0-f4-(4-Aminomethylbenzvlaminocarbonv)-piperazin-1-vicarbonvll-4-O-benzvl-6-0-[4 trans-(4-aminobenzvlaminocarbonvl)-cyclohexvlmethylaminocarbonvll-1.2-dideoxy-D glucopyranose dihydrochloride 3-0-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbony]piperazin-1 -ylcarbonyl}-4-0-benzyl 6-0-[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 1

H

57

N

7 0 8 (800.0), found: [MH*] 800.2 41. 3-0-[4-(4-Aminomethylbenzvlaminocarbonvl)oiperazin-1 -vlcarbonyll-4-0-benzyl-6-O-[3 (4-aminobenzvlaminocarbonvl)benzvlaminocarbonvll-1.2-dideoxy-D-qlucopyranose di hydrochloride 3-0-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 -ylcarbonyl}-4-0-benzyl 6-0-[3-(4-aminobenzylaminocarbonyl)benzylaminocarbonyl]-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 0 C are obtained. MS: calc.: C 4 3

H

5 1

N

7 0 8 (793.9), found: [MH*] 774.2 42. 3-O-[4-(4-Aminomethylbenzvlaminocarbonyl)piperazin-1-vlcarbonvll-4-O-benzvl-6-0-{4 [3-(imidazol-1-vil)propylaminocarbonvllpiperidin-1-vicarbonvl-1.2-dideoxv-D-gluco pyranose dihydrochloride 3 -O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-0-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.: C 40

H

54

N

8 0 8 (774.9), found: [MH*] 775.4 B666WOO 09991 -85 43. 3-o-r4-(4-Aminomethylbenzvlaminocarbonvlpiperazin-1-vicarbonvil-4-0-benzvl-6-0-4 [4-(imidazol-1 -vil)-butvlaminocarbonvllpiperidin-1 -vicarbonvil-1.2-dideoxv-D-aluco pyranose dihydrochloride 3 -0-{ 4

-[

4 -(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 -ylcarbonyl}-4-0-benzyl -6-0-{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.: C 41

H

56

N

8 0 8 (788.9), found: [MH*] 789.3 44. 3-O-[4-(4-Aminomethylbenzvlaminocarbonl)piperazin-1-vlcarbonvll-4-0-benzvl-6-0-{4 r5-(imidazol-1-vl)pentvlaminocarbonvllpiperidin-1-vlcarbonvil-1.2-dideoxv-D-ciluco pyranose dihydrochloride 3 -0-{ 4

-[

4 -(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 -ylcarbonyl}-4-0-benzyl 6-0-{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. 2020C are obtained (sintering from 1160C). MS: calc.: C 4 2

H

5 8

N

8 0 8 (802.98) found: [MH*] 803.3 45. 3-O-[4-(4-Aminomethylbenzvlaminocarbonv)piperazin-1 -vicarbonvill-4-0-benzvl-6-044 r6-fimidazol-1 -vl)hexvlaminocarbonvilpiperidin-1 -vicarbonvil-1.2-dideoxv-D-aluco pyranose dihydrochloride 3

-O-{

4

-[

4 -(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 -ylcarbonyl}-4-O-benzyl 6-0-{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. 2020C are obtained (sintering from 1250C). MS: calc.: C 4 3 HeoN 8 0 8 (817.0), found: [MH*] 817.4 B666WOO 09991 - 86 46. 3-O-[4-(4-Aminomethylbenzvlaminocarbonl)piperazin-1 -vlcarbonvll-4-0-benzyl-6-044 8-fimidazol-1 -vl)octylaminocarbonvllpiperidin-1 -vlcarbonvil-1.2-dideoxv-D-aluco pyranose dihydrochloride 3 -0-{ 4

-[

4 -(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 -ylcarbonyl}-4-0-benzyl 6-0-{4-[8-(imidazol-1 -yl)octylaminocarbonyl]piperidin-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: calc.: C 4 5

H

4

N

8 0 8 (845.0), found: [MH*] 845.4 47. 3 -0-f 4

-(

6 -Aminopyridin-3-vimethylaminocarbonvl)-iperidin-1 -vicarbonvll-6-0-4-i4 trans-(aminomethvl)cvclohexvlcarbonvllaminobut-1-ylaminocarbonvl-4-0-benzvl-1.2 dideoxy-D-glucopyranose dihydrochloride 3

-O-[

4

-(

6 -tert-Butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-6-0-{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. > 2200C are obtained. MS: calc.: C 39

H

57

N

7 0 8 (751.46), found: [MH] 752.3 48. 3 -0-f 4

-(

6 -Aminooyridin-3-vimethylaminocarbonvl)piperidin- -vicarbonvll-6-0-f4-(4 aminomethylbenzvlaminocarbonvl)piperazinl -vlcarbonvll-4-O-benzvl-1.2-dideoxv-D clucopyranose dhydrochloride 3

-O-[

4

-(

6 -tert-Butyloxycarbonylaminopyridin-3-ylmethylamino-carbonyl)piperidin-1 -ylcarbonyl]-6-0-{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: calc.: C 4 oH 52

N

8 0 8 (772.42), found: [MH*] 773.3 B666WOO 09991 - 87 49. 3-0-4-(4-Aminomethylbenzvlaminocarbonvl)piperazin-1 -vicarbonvll-6-042-(6-amino pvridin-3-vlmethylaminocarbonvl)eth-1 -vI-aminocarbonvll-4-O-benzvl-1.2-dideoxv-D glucopyranose dihydrochloride 3-0-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbony]piperazin-1 -yl-carbonyl}-4-O benzyl-6-0-[2-(6-aminopyridin-3-ylmethylaminocarbonyl)eth-1 -yl-aminocarbonyl]-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 HCL. 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.: C 37

H

48

N

8 0 8 (732.39), found: [MH] 733.3 50. 3-0-44-(4-Aminomethylbenzvlaminocarbonvl)piperazin-1 -vicarbonvill-4-0-benzvl-6-043 [(6-amidino-1 -H-indazol-3-vl)carbonvlaminolprop-1-ylaminocarbonyl}-1.2-dideoxy-D glucopyranose dihydrochloride 3 -0-{ 4

-[

4 -(tert-Butyloxycarbonylaminomethyl)benzylaminocarbony]piperazin-1 -ylcarbonyl}-4-0-benzyl 6-0-{3-[(6-amidino-1 -H-indazol-3-yl)carbonylamino]prop-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.: C 37

H

48

N

8 0 8 (798.38), found: [MH*] 799.3 51. 3-0-r4-(4-Aminomethylbenzvlaminocarbonvl)piperazin-1-vicarbonvil-4-0-benzvl-6-043 r(6-aminocarbonvl-1-H-indazol-3-vl)carbonvlaminolprop-1-vlaminocarbonvl}-1.2-di deoxy-D-glucopyranose dhydrochloride 3

-O-{

4

-[

4 -(tert-Butyloxycarbonylaminomethyl)benzylaminocarbony]piperazin-1 -ylcarbonyl}-4-0-benzyl 6-0-{3-[(6-aminocarbonyl-1 -H-indazol-3-yl)carbonylamino]prop-1 -ylaminocarbonyl}-1,2-dideoxy-D glucopyranose (22 mg, 0.022 mmol, 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.: C 37

H

48

N

8 O8 (799.37), found: [MH] 800.3 B666WOO 09991 - 88 52. 3-0-4-(4-Aminomethylbenzvlaminocarbonvl)Diperazin-1 -vicarbonvill-6-0424(6-amino carbonvl-1 -H-indol-3-vl)carbonvlaminoleth-1 -vlaminocarbonvil-1.2-dideoxy-D-gluco pyranose dihydrochloride 3-0-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 -ylcarbonyl}-6-0-{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: calc.: C 3 7

H

48

N

8 0 8 (694.13), found: [MH*] 695.2 53. 3-0-r4-4-Aminomethylbenzvlaminocarbonvlpiperazin-1 -vcarbonvill-4-0-benzvl-6-043 [(6-aminocarbonvl-1 -H-indol-3-vl)carbonvlaminolprop-1 -vlaminocarbonyll-1.2-dideoxy D-alucopyranose dihydrochloride 3 -0-{ 4

-[

4 -(tert-Butyloxycarbonylaminomethyl)-benzylaminocarbonyl]piperazin-1 -ylcarbonyl}-6-0-{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: calc.: C 3 7 H4 8

N

8 0 8 (798.37), found: [MH'] 799.1 54. 3-0-r4-4-Aminomethylbenzvlaminocarbonv)piperazin-1 -vcarbonvll-4-0-benzyl-6-04 r(6-aminocarbonvl-1 -H-indol-3-vl)carbonvlaminolbut-1 -laminocarbonyl}-1.2-dideoxv-D glucopvranose 3 -O-{4-[4-(tert-Butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 -ylcarbonyl}-4-0-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: calc.: C 3 7 H4 8

N

8

O

8 (812.39), found: [MH*] 813.4 B666WOO 09991 - 89 55. 6-O-[4-(6-Aminopvridin-3-vimethylaminocarbonvl)piperidin-1-vicarbonvl-3-O-[2-(4-trans aminomethvlcvclohexvlcarbonvlamino)eth-1-vlaminocarbonvll-4-O-benzvl-1.2-dideoxy D-glucopyranose dihydrochloride A suspension of 6-0-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-l ylcarbonyl]-3-O-{2-[4-trans-(tert-butyloxycarbonylaminomethyl)cyclohexycarbonylamino]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.: C 37

H

53

N

7 0 8 (723.39), found: [MH*] 724.3 56. 6-0-[4-(6-Aminopyridin-3-vlmethylaminocarbonvl)oioeridin-1 -vcarbonvll-3-O-[3-(4-trans aminomethvlcvclohexvlcarbonlamino)prop-1 -vlaminocarbonvll-4-0-benzvl-1.2-dideoxy D-qlucopyranose dihydrochloride A suspension of 6-0-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1 ylcarbonyl]-3-O-{3-[4-trans-(tert-butyloxycarbonylaminomethyl)cyclohexylcarbonylamino]prop-1 -yl aminocarbonyl}-4-0-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.: C 38

H

55

N

7 0 8 (737.41), found: [MH*] 738.3 57. 6-0-[4-(6-Aminopyridin-3-vimethylaminocarbonvl)piperdin-1 -vicarbonvill-3-0-[4-(4-trans aminomethvlcvclohexvlcarbonvlamino)but-1 -vlaminocarbonvll-4-O-benzvl-1.2-dideoxy D-glucopvranose dihydrochloride A suspension of 6-0-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1 ylcarbonyl]-3-O-{4-[4-trans-(tert-butyloxycarbonylaminomethyl)cyclohexylcarbonylamino]but-1 -yl aminocarbonyl}-4-0-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.: C 39

H

57

N

7 0 8 (751.43), found: [Mf] 752.3 B666WOO 09991 -90 58. 6-0-[4-(3-Aminomethylbenzovl)piperazin-1 -vicarbonvil-3-0-[4-(6-aminopyridin-3-vI methylaminocarbonyl)PiPeridin-1 -vicarbonvll-4-O-benzvl-1.2-dideoxv-D-glucouvranose dihydrochloride A solution of 6-0-{4-[3-(tert-butyloxycarbonylaminomethyl)benzoyl]piperazin-1-ylcarbonyl}-3-0-[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: calc.: C 39

H

49

N

7 0 8 (743.36), found: [MH*] 744.3 59. 6-0-[4-(3-Aminomethylbenzovaminoliperidin-1 -vlcarbonvll-3-0-[4-(6-aminopyridin-3 vimethylaminocarbonvl)oiperidin-1 -vicarbonvil-4-0-benzvl-1.2-dideoxy-D-qluco pyranose dihydrochloride A solution of 6-0-{4-[3-(tert-butyloxycarbonylaminomethyl)benzoylamino]piperidin-1-ylcarbonyl}-3-0-[4 (6-tert-butyloxycarbonylaminopyridin-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: calc.: C 4 oH 51

N

7 0 8 (757.38), found: [MH] 758.2 60. 6-0-r4-(3-Aminomethylbenzvlaminocarbonvl)piperdin-1 -vicarbonvill-3-O-[4-(6-amino ovridin-3-vimethylaminocarbonvilpiperidin-1 -vicarbonvil-4-O-benzvl-1.2-dideoxv-D glucopvranose dihydrochloride A solution of 6-0-{4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperidin-1-ylcarbonyl} 3-0-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1 -ylcarbonyl]-4-0 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 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: calc.: C 4 1

H

53

N

7 0 8 (771.40), found: [MH*] 772.3 B666WOO 09991 - 91 61. 6-0-[4-trans-(3-Aminomethylbenzvlaminocarbonvl)cvclohexvlmethylaminocarbonvll-3 O-[4-(6-aminopyridin-3-vimethylaminocarbonvl)piperidin-1-vicarbonvll-4-O-benzyl-1.2 dideoxv-D-qlucopyranose dihydrochloride A suspension of 6-0-{4-trans-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl] cyclohexylmethylaminocarbonyl}-3-0-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbon yl)piperidin-1-ylcarbonyl]-4-0-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.: C 4 3

H

57

N

7 0 8 (799.43), found: [MH*] 800.3 62. 6-O-f4-(3-Aminomethylbenzvlaminocarbonvl)piperazin-1 -vicarbonvll-3-0-[4-(6-amino pyridin-3-vlmethylaminocarbonvl)piperidin-1 -vicarbonvil-4-O-benzvl-1.2-dideoxv-D glucopyranose dihydrochloride A solution of 6-0-{4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 ylcarbonyl}-3-0-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbony)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.: C 4 0

H

52

N

8 0 8 (772.39), found: [MH] 773.3 63. 6-0-[4-(3-Aminomethylbenzvlaminocarbonvaminopiperidin-1-vicarbonvll-3-0-[4-(6 aminopvridin-3-vlmethylaminocarbonvl)oiperidin-1 -vlcarbonvll-4-O-benzvl-1.2-dideoxy D-qlucopyranose dihydrochloride A solution of 6-0-{4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonylamino]piperidin-1 ylcarbonyl}-3-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbony)piperidin-1 -ylcar bonyl]-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A165, 120 mg, 0.12 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.: C 4 1

H

54

N

8 0 8 (786.41), found: [MH] 787.3 B666WOO 09991 - 92 Starting compounds: Al. 3.6-Di-O-tert-butyldimethylsilyl-1,2-dideoxy-D-glucopvranose 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 NH 4 CI solution (150 ml) and extracted with EA (3 x). The combined organic phases are dried over MgSO 4 , filtered and con centrated in vacuo. Further purification is carried out by means of chromatography [PE/EA (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-0-tert-butyldimethylsilyl-1.2-dideoxy-D-glucopvranose 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 NH 4 CI solu tion and extracted with ethyl acetate (3x). The combined organic phases are dried over MgSO 4 , 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. 4-0-Benzvl-1.2-dideoxy-D-glucopyranose 4-O-Benzyl-3,6-di-0-tert-butydimethylsilyl-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 NH 4 CI solution (25 ml). It is extrac ted with ethyl acetate (3 x) and the combined organic phases are dried over MgSO 4 . The solution is filtered and concentrated in vacuo. After purification by means of chromatography [toluene/acetone (7:3)] on a silica gel column, the title compound (0.37 g) is obtained as colorless crystals. TLC, silica gel (glass plates), [toluene/acetone (7:3)], Rf= 0.28 A4. 4-0-Benzvl-3.6-di-O-4-(N-tert-butoxvcarbonvi)-1-piperazinvicarbonvll-1.2-dideoxv-D-glu cogvranose 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. 4-0-benzyl-1,2-dideoxy-D-glucopyranose (4 g, 16.8 mmol) is dissol ved in CH 2 Cl 2 (10 ml) and slowly added dropwise. The mixture is stirred at RT for 10 min. After the addition of H 2 0 (10 ml), the organic phase is separated off and washed with H20 (1 x). It is dried over B666WOO 09991 - 93 MgSO 4 , filtered and concentrated in vacuo. The residue obtained is dissolved in CH 2 C1 2 (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-tert 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 A1 2 0 3 , washed with CH 2 Cl 2 (2 x 10 ml) and concentrated in vacuo. Further purification by means of chromatography [toluene/acetone (7:3)] on a silica gel column affords the title compound (8.57 g) as a colorless powder. TLC, silica gel (glass plates), [toluene/acetone (7:3)], Rf= 0.5. A5. 4-O-Benzvl-1.2-dideoxy-3.6-di-O-(1-Diperazinvlcarbonvl)-D-qlucopyranose 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 CH 2 Cl 2 (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-[4-(trans-4-N-tert-butoxycarbonvlaminomethylcyclohexvlcarbonl)-1 piperazinvlcarbonvil-1.2-dideoxv-D-alucouvranose trans-4-N-Tert-butoxycarbonyaminomethylcyclohexancarboxylic acid (1.31 g, 5.1 mmol) and HOBT (0.70 g, 5.1 mmol) are added to a solution of 4-0-benzyl-1,2-dideoxy-3,6-di-O-(1-piperazinylcarbonyl) D-glucopyranose dihydrochloride (1.24 g, 2.68 mmol) in CH 2 Cl 2 (25 ml) and Et 3 N (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 A1 2 0 3 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-0-[4-(trans-4-N-tert-butoxvcarbonvlaminomethvlcvclohexvlcarbonyl)-1-piperazinvI carbonyll-1.2-dideoxy-D-glucopvranose 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 [toluene/acetone (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 B666WOO 09991 -94 MS: calc.: C 4 2

H

70

N

6 0 12 (851.06), found: [MH*] 850.9 A8. 4-(N-tert-Butoxvcarbonvlamino)benzvlamine 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 Na 2

CO

3 solution. It is extracted a number of times with

CH

2

C

2 (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), [toluene/acetone (6:4)], Rf= 0.57 A9. 4 -0-Benzvl-3.6-di-044-44-(N-tert-butoxvcarbonvlamino)benzlcarbamov-1-piperazinyl carbonvl}-1.2-dideoxy-D-glucopvranose 4-(N-tert-Butoxycarbonylamino)benzylamine (1.0 g, 4.5 mmol) is dissolved in CH 2

CI

2 (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 CH 2

CI

2 (1 ml) is slowly added dropwise to the reaction solution and the mixture is stirred at RT for 20 min. A solution of 4-0-benzyl-1,2-dideoxy-3,6-di-O-(1-piperazinylcarbonyl)-D-glucopyranose dihydrochloride (1.0 g, 1.87 mmol, starting compound A5) in CH 2 Cl 2 (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 [toluene/acetone (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-[4-(4-aminobenzvlcarbamovl)-1-pipierazinvlcarbonvll-4-O-benzvl-1,2-dideoxy-D qlucopyranose dihydrochloride 4 -0-Benzyl- 3

,

6 -di-O-{4-[4-(N-tert-butoxycarbonylamino)benzylcarbamoylpiperazin-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 l and washed first with dioxane (2 x 1 ml) and then with

CH

2 Cl 2 (3 x 1 ml). After drying in vacuo, the title compound (0.34 g) is obtained as a colorless powder. MS: calc.: C 3 9

H

50

N

8 0 8 (758.88), found: [MH*] 759.34 B666WOO 09991 - 95 All. 4-0-Benzvl-3.6-di-O-[4-(4-(NN'-bis-tert-butoxcarbonylquanidino)benzvlaminocarbonvl)-l Diperazinvicarbonyll- 1.2-dideoxy-D-glucopvranose dihydrochloride A solution of 3,6-di-O-[4-(4-aminobenzylcarbamoyl)piperazin-1-ylcarbonyl]-4-0-benzyl-1,2-dideoxy-D glucopyranose dihydrochloride (0.34 g, 0.41 mmol) in DMF (5.0 ml) and Et 3 N (0.45 ml, 3.28 mmol) is treated with N,N'-bis(tert-butoxycarbonyl)-S-methylisothiourea (0.26 g, 0.9 mmol) and HgCl 2 (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 1-120 (5 x 2 ml), and the organic phase is dried over MgSO 4 , filtered and concentrated 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 (0.30 g) as a pale brown powder. TLC, silica gel (glass plates), [toluene/acetone (1:1)], Rf= 0.43 A12. 4-O-Benzvl-3.6-di-0-(4-tert-butoxvcarbonvl-l-piperazinvlcarbonvlmethyl)-l.2-dideoxy-D glucopyranose 1-tert-Butoxycarbonylpiperazine (1.09 g, 5.8 mmol) and HOBT (0.79 g, 5.8 mmol) are added to a solu tion of 4-0-benzyl-3,6-di-0-carboxymethyl-1,2-dideoxy-D-glucopyranose (0.94 g, 2.65 mmol) in CH2Cl 2 (20 ml) and Et 3 N (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 MgSO 4 , filtered and concentrated in vacuo. Further purification is carried out by means of chromatography [toluene/acetone (7:3)] on a silica gel column and affords the title com pound (0.9 g) as a colorless resin. MS: calc.: CasH 5 4

N

4

O

10 (690.84), found: [MH*] 691.5, [MH 4 *] 708.5 A13. 4-O-Benzvl-1.2-dideoxy-3.6-di-O-(1-piperazinvlcarbonvlmethyl)-D qlucopyranose dihydrochloride 4-0-Benzyl-3,6-di-0-(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 N 2 and washed first with dioxane (2 x 1 ml) and then with Et 2 O (3 x 1 ml). After drying in vacuo, the title compound (0.89 g) is obtained as colorless crystalls. MS: calc.: C 25

H

38

N

4 0 6 (490.6), found: [MH] 491.3 B666WOO 09991 - 96 A14. 4-0-Benzvl-3.6-di-O-[4-(trans-4-N-tert-butoxvcarbonvlaminomethvlcvclohexvlcarbonl)-1 Diperazinvlcarbonvlmethyll-1.2-dideoxv-D-glucouvranose trans-4-(N-tert-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 CH 2 C1 2 (15 ml) and Et 3 N (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 10 ml). The organic phase is dried over MgSO 4 , filtered and concentrated in vacuo. Further purification is carried out by means of chromatography [toluene/acetone (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.: C 5 1 1H 8

N

6 0 12 (969.24), found: [MH*] 969.1 A15. 4-O-Benzvl-1.2-dideoxy-3.6-di-O-methoxvcarbonvlmethyl-D-cilucopvranose 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), [toluene/acetone (8:2)], Rf= 0.53 MS: calc.: C 19

H

26 0 8 (382.41), found: [MNH4*] 400.3 A16. 4-O-Benzvl-3,6-di-O-carboxymethyl-1,2-dideoxy-D-qlucopvranose A solution of 4-0-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 MgSO 4 , filtered and concentrated in vacuo. The title compound (0.94 g) is obtained as a white solid. MS: calc.: C 17

H

2 2 0 8 (354.36), found: [MNH 4 *] 372.2 B666WOO 09991 - 97 A17. 4 -O-Benzvl- 3 .6-di-O-[4-(4-N-tert-butoxcarbonvaminomethylbenzlcarbamovl)-1-pipera zinvlcarbonvil-1.2-dideoxv-D-lucouvranose 4 -N-tert-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 CH 2 Cl 2 (20 ml). The reaction is then treated with Et 3 N (0.12 ml, 0.85 mmol). The mixture is stirred at RT for 2 h. 3,6-Di-O-(1 piperazinylcarbonyl)-4-0-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 Et 3 N (3 ml, 21.8 mmol). The mixture is stirred for 18 h and then washed with saturated aqueous NaHCO 3 solution (2 x 10 ml) and afterward with ice-cold 0.5 N HCI (2 x 5 ml). The organic phase is dried over MgSO 4 , filtered and concentrated in vacuo. Further purification is carried out by means of chromatography [tolue ne/acetone (6:4)] on a silica gel column and affords the title compound (0.15 g) as a pale brown amorphous powder. TLC, silica gel (glass plates), [toluene/acetone (4:6)], Rf= 0.25 MS: calc.: C 51

H

70

N

8 0 12 (987.17), found: [MH*] 986.9 A18. 4 -N-tert-Butoxvcarbonvlaminomethyl-benzvlamine 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 NaHCO 3 . The mixture is extracted with CH 2 Cl 2 (4 x 30 ml) and the combined org. phases are dried over MgSO 4 . The solution is filtered and concentrated in vacuo. Further purification is carried out by means of chromatography [e thyl acetate/methanol/satd. Na-b 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-Benzvl-1.

2 -dideoxy-3.6-di--{4-[4'-N-(9-fluorenlmethoxvcarbonyl) Piperidinvimethvlcarbonvll-l-piperazinvlcarbonvl-D-lucopvranose 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 -0-benzyl-3,6-di-0-(1-piperazinylcarbonyl)-1,2-dideoxy-D glucopyranose dihydrochloride (0.7 g, 1.3 mmol, starting compound A5) in CH 2

CI

2 (15 ml) and Et 3 N (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 MgSO 4 , filtered and concentrated in vacuo. Further purification is carried out by means of chro matography [toluene/acetone (7:3)] on a silica gel column and affords the title compound (0.8 g) as a colorless powder. MS: calc.: C 67

H

76

N

6 0 12 (1157.39), found: [MH*] 1157.3 B666WO0 09991 - 98 A20. 4-0-Benzvl-1.

2 -dideoxv-3.6-di-O-r4-(Diperidin-4-vlacetvl)-1-piperazinvlcarbonvil-D-gluco pyranose dihydrochloride 4-O-Benzyl-1,2-dideoxy-3,6-di-0-{4-[4'-N-(9-fluorenylmethoxycarbonyl)piperidinylmethylcarbonyl] piperazin-1-ylcarbonyl}-D-glucopyranose (0.8 g, 0.7 mmol) is dissolved in CH 2

CI

2 (2 ml), treated at RT with a 20% strength piperidine solution in CH 2 Cl 2 (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 CH 2

CI

2 (10 ml). The combined organic phases are con centrated in vacuo and coevaporated with toluene (2 x 50 ml). The residue is dissolved in CH 2

CI

2 (2 ml) and precipitated with ethereal HCI (2 ml). The precipitate is washed with Et 2 O (3 x 5 ml) and dried in vacuo. The title compound (0.5 g) is obtained as a colorless powder. MS: calc.: C 37

H

56

N

6 0 8 (712.89), found: [MH*] 713.4 A21. 4-O-Benzvl-3.6-di-044-1 -(N.N'-bis-tert-butoxvcarbonylamidino)piperidin-4-vlacetvll-1 piperazinvicarbonvil-1.2-dideoxy-D-Qiucoovranose 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 Et 3 N (0.7 ml, 1.4 mmol) is treated with N,N'-bis(tert-butoxycarbonyl)-S-methylisothiourea (0.41 g, 1.4 mmol) and HgC 2 (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 H 2 0 (5 x 5 ml), and the organic phase is dried over MgSO 4 , 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.: C59H 92

N

10 01 6 (1197.45), found: [MH*] 1197.1 A22. 4-O-Benzvi-3.6-di-O-[4-(trans-4-N-ert-butoxvcarbonvlaminomethylcyclohexvicarbonvl) 1 -piperazinvlcarbonvll-1.

2 -dideoxy-D-galactopyranose 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. 4-0-Benzyl-1, 2 -dideoxy-D-galactopyranose (A63, 0.5 g, 2.10 mmol) is dissolved in CH 2 Cl 2 (3 ml) and the solution is slowly added dropwise. A solution of DIPEA (1.88 ml, 10.5 mmol) in C- 2 C1 2 (13 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

CH

2

C

2 (5 ml), cooled to 0*C and then treated with DIPEA (5 ml) and trans-4-N-tert butoxycarbonylaminomethylcyclohexylcarbonyl-1-piperazine (A43, 1.37 g, 4.20 mmol). The mixture is B666WOO 09991 - 99 stirred at RT overnight. The reaction solution is filtered through A1 2 0 3 , washed with CH 2 Cl 2 (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 [toluene/acetone (8:2)], Rf = 0.25. MS: calc.: C 4 9

H

76

N

6 0 12 (941.15), found: [MH*] 942.0 A23. 3 .6-Di-O-f4-(trans-4-N-tert-butoxvcarbonvlaminomethvlcvclohexvlcarbonvl-1 -Diperazin vicarbonvll-1.2-dideoxv-D-galactopyranose 4-O-Benzyl-3,6-di-O-[4-(trans-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 [toluene/acetone (1:1)] on a silica gel column and affords the title compound (0.14 g) as a colorless resin. TLC, silica gel, glass plates [toluene/acetone (1:1)], Rf = 0.15. MS: calc.: C 4 2

H

7

N

6 0 12 (851.06), found: [MH*] 851.0 A24. 4 -0-Benzvl-3.6-di-O-[4-(N-benzvloxvcarbonvlamidino-1-benzvloxvcarbonvlindazol-3-vl carbonyl)-1 -Diperazinvlcarbonvil-1.2-dideoxv-D-glucopyranose 6-(l-Benzyloxycarbonylamidyl)-1-benzyoxycarbonyl-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-0-(1-piperazinylcarbonyl) D-glucopyranose dihydrochloride (A5, 0.267 g, 0.5 mmol) in dichloromethane (10 ml) and Et 3 N (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 10 ml). The organic phase is dried over MgSO 4 , filtered and concentrated 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 (0.32 g) as a colorless powder. TLC, silica gel, glass plates [toluene/acetone (7:3)], Rf = 0.34. MS: calc.: C 78

H

7 oN 12 0 16 (1371.44), found: [MH*] 1371.2 B666WOO 09991 -100 A25. Methyl 4-0-benzvl-3.6-di-O-[4-(trans-4-N-tert-butoxycarbonvlaminomethvlcvclohexyl carbonv)-1-pipierazinvlcarbonvll-2-deoxy-a-D-glucopyranoside 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 0 C. Methyl 4-O-benzyl-2-deoxy-a-D-glucopyranoside (1.0 g, 3.73 mmol) is dissolved in CH 2

CI

2 (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

CH

2 C1 2 (10 ml), cooled to 0*C and then treated with DIPEA (7 ml) and trans-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 CH 2

CI

2 (20 ml) and extracted (2 x) with semisaturated aqueous NH 4 CI solution (30 ml), dried over MgSO 4 , 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)], Rf = 0.16. MS: calc.: C 5 oH 78

N

6 0 13 (971.34), found: [MH*] 972.0 A26. Methyl 3.6-di-O-[4-(trans-4-N-tert-butoxvcarbonvlaminomethvlcyclohexylcarbonl)-1 piperazinvicarbonvil-2-deoxv-a-D-clucouvranoside Methyl 4 -0-benzyl-3,6-di-O-[4-(trans-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 uniform reaction (TLC checking) and the solution is concentrated in vacuo. Further purification is car ried out by means of chromatography [toluene/acetone (4:6)] on a silica gel column and affords the title compound (0.44 g) as a colorless resin. TLC, silica gel, glass plates [toluene/acetone (4:6)], Rf = 0.37. MS: calc.: C 4 3

H

72

N

6 0 13 (881.1), found: [MH*] 882.1 A27. 3 .6-Di-O-[4-(trans-4-N-tert-butoxycarbonylaminomethvlcyclohexylcarbonl)-I -1ip~erazin vlcarbonvlmethyll-1.2-dideoxv-D-cilucopvranose 4 -O-Benzyl- 3

,

6 -di-O-[4-(trans-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 B666WOO 09991 -101 means of chromatography [CH 2

CI

2 /MeOH (98:2)] on a silica gel column and affords the title compound (0.11 g) as a colorless resin. TLC, silica gel, glass plates [CH 2

CI

2 / MeOH (98:2)], Rf = 0.33. MS: calc.: C 4 4

H

74

N

6 0 12 (878.0), found: [MH*] 879.1 A28. 4 -O-Benzvl- 6 -O-[4-(4-N-tert-butoxcarbonlaminomethylbenzvlaminocarbonvl)-1 -Dipera zinvlcarbonvll-3-O-r4-(trans-4-N-tert-butoxvcarbonvlaminomethvlcyclohexvlcarbonyl)-1 iperazinvlcarbonvil-1.2-dideoxv-D-glucoDvranose HOBT (0.19 g, 1.40 mmol) is added to a solution of 4-0-benzyl-3-0-[4-(trans-4-N-tert butoxycarbonylaminomethylcyclohexylcarbonyl)piperazin-1 -ylcarbonyl]-1,2-dideoxy-6-0-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 CH 2 Cl 2 (8.5 ml) and Et 3 N (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 CH 2

CI

2 (20 ml) and extracted (2 x) with semisaturated aqueous NH 4 Cl solution (15 ml), dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography [CH 2 Cl 2 / 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 [Tol/Ac (4:6)], Rf = 0.31. MS: calc.: C 5 1

H

75

N

7 0 12 (978.2), found: [MH*] 978.1 A29. Benzvl 3 6 -di-O-r 4 -(trans-4-N-tert-butoxvcarbonvlaminomethlcvclohexvlcarbonvl)-1 piperazinvlcarbonvil-2-deoxv-a-D-giucopyranoside 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 CH 2 Cl 2 (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

CH

2 C1 2 (8 ml), cooled to 0*C and then treated with DIPEA (5 ml) and trans-4-N-tert-butoxycarbonyl aminomethylcyclohexylcarbonyl-l-piperazine (A43, 1.42 g, 4.34 mmol). The mixture is stirred at RT overnight. The reaction solution is diluted with Cl-6Cl 2 (15 ml) and extracted (2 x) with semisaturated aqueous NH 4 CI solution (25 ml), dried over MgSO 4 , filtered and concentrated in vacuo. Further purifi cation by means of chromatography [toluene/acetone (6:4)] on a silica gel column affords the title com pound (1.6 g) as a colorless powder. TLC, silica gel, glass plates [toluene/acetone (6:4)], Rf = 0.40. MS: calc.: C 56

H

8 2

N

6 0 13 (1047.4), found: [MH*] 1048.3 B666WOO 09991 -102 A30. 4 -0-Benzl-3.6-di-O-[4-(4-Ntert-butoxvcarbonviaminomethylbenzvlaminocarbonyi)-1 Diperazinvlcarbonvlmethyll-1.

2 -dideoxv-D-glucopyranose HOBT (0.6 g, 4.4 mmol) is added to a solution of 4-0-benzyl-1, 2 -dideoxy-3,6-di-O-carboxymethyl-D glucopyranose (A16, 0.5 g, 1.41 mmol) and 4 -N-tert-butoxycarbonylaminomethylbenzylaminocarbonyl 1-piperazine (1.08 g, 3.1 mmol) in absolute CH 2 Cl 2 (10 ml) and Et 3 N (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 C 2 C1 2 (20 ml) and extracted (2 x) with semisaturated aqueous NH 4 CI solution (15 ml), dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography

[CH

2

C

2 / MeOH (95:5)] on a silica gel column affords the title compound (0.52 g) as a colorless powder. TLC, silica gel, glass plates [CH 2

CI

2 / MeOH (95:5)], Rf = 0.25. MS: calc.: C 53

H

7 4

N

8 0 12 (1015.23), found: [MH*] 1016.2 A31. 3,6-Di-O-[4-(4-N-tert-butoxvcarbonviaminomethylbenzvlaminocarbonyl)-1-piperazinvlcar bonvlmethyll-1.2-dideoxv-D-glucopvranose 4-O-Benzyl-3,6-di-O-[4-(4-N-tert-butoxycarbonylaminomethylbenzylaminocarbonyl)piperazin-1-yl-car bonylmethyl]-1, 2 -dideoxy-D-glucopyranose (A30, 0.30 g, 0.30 mmol) is dissolved in MeOH (14 ml) 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

[CH

2 Cl 2 / 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 [CH 2

C

2 / MeOH (9:1)], Rf = 0.57. MS: calc.: C 4 6

H

8

N

8 0 12 (925.1), found: [MH*] 925.24 A32. 3.6-Di-0--4-(trans-4-N-tert-butoxvcarbonviaminomethylcyclohexvicarbonvil-iperazin vicarbonvil-1.

2 -dideoxv-4-O-methyl-D-cgalactopvranose 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. 4-0- Methyl-1, 2 -dideoxy-D-galactopyranose (A56, 0.5 g, 3.10 mmol) is dissolved in CH 2 Cl 2 (3 ml) and the solution is slowly added dropwise. A solution of DIPEA (3.5 ml) in

CH

2 Cl 2 (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 CH 2 Cl 2 (6 ml), cooled to 00C and then treated with DIPEA (5 ml) and trans-4-N-tert-butoxycarbonyl aminomethylcyclohexylcarbonyl-1-piperazine (A43, 2.01 g, 6.2 mmol). The mixture is stirred at RT overnight. The reaction solution is diluted with CH 2 Cl 2 (25 ml) and extracted (2 x) with semisaturated aqueous NH 4 CI solution (30 ml), dried over MgSO 4 , filtered and concentrated in vacuo. Further purifi- B666WOO 09991 -103 cation by means of chromatography [toluene/acetone (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 acetate/methanol (98:2)], Rf = 0.2. MS: calc.: C 4 3

H

72

N

6 0 12 (865.1), found: [MH*] 866.1 A33. Methyl 2

.

6 -di-O-[ 4 -(trans-4-N-tert-butoxvcarbonvlaminomethvlcvclohexvlcarbonvl)-1 Diperazinvicarbonyll-a-D-aclucouvranoside Methyl 3,4-di-0-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 [EA/MeOH (97:3)], Rf = 0.16. MS: calc.: C 4 3

H

72

N

6 0 14 (896.3), found: [MI] 897.1 A34. Methyl 4-O-benzyl-3,6-di-O-r4-(4-N-tert-butoxvcarbonylaminomethylbenzylaminocarbon vl)-1-piperazinvicarbonvil-2-deoxv-a-D-alucopyranoside A 20% strength solution of phosgene in toluene (10 ml, 23.8 mmol) is initially introduced and cooled to an internal temperature of O'C. Methyl 4 -0-benzyl-2-deoxy-a-D-glucopyranoside (0.5 g, 1.86 mmol) is dissolved in CH 2

CI

2 (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 CH 2 Cl 2 (6 ml), cooled to 0*C and then treated with DIPEA (5 ml) and 4 -N-tert-butoxycarbonylaminomethylbenzylaminocarbonyl-1 piperazine (A43, 2.0 g, 6.2 mmol). The mixture is stirred at RT overnight. The reaction solution is d luted with CH 2 Cl 2 (25 ml) and extracted (2 x) with semisaturated aqueous NH 4 CI solution (20 ml), dried over MgSO 4 , 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.: C 52

H

72

N

8 0 13 (1017.1), found: [MH* 1018.0 B666WOO 09991 - 104 A35. Methyl 3

.

4 -di-O-benzvl-2.6-di-O-[4-(4-N-tert-butoxvcarbonvlaminomethylbenzvlamino carbonyl)-1 -piperazinvlcarbonyll-a-D-glucopyranoside 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 -0-benzyl-a-D-glucopyranoside (0.5 g, 1.33 mmol) is dis solved in CH 2

CI

2 (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 CH 2 Cl 2 (5 ml), cooled to 0*C and then treated with DIPEA (5 ml) and 4 -N-tert-butoxycarbonylaminomethylbenzylaminocarbonyl-l-piperazine (Al 14, 0.93 g, 2.66 mmol). The mixture is stirred at RT overnight. The reaction solution is diluted with

CH

2 Cl 2 (20 ml) and extracted (2 x) with semisaturated aqueous NH 4 Cl solution (15 ml), dried over MgSO 4 , 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.: C 59

H

79

N

9 0 1 3 (1123.0), found: [MH*] 1123.0 A36. Methyl 3 6 -di-O-[4-(4-N-tert-butoxycarbonvlaminomethylbenzvlaminocarbonvl)-1-pipera zinvlcarbonyll-2-deoxy-a-D-glucopyranoside Methyl 4-0-benzyl-3,6-di-0-[4-(4-N-tert-butoxycarbonylaminomethylbenzylaminocarbonyl)-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 [CH 2

CI

2 /MeOH (95:5)] on a silica gel column and affords the title compound (0.3 g) as a colorless resin. TLC, silica gel, glass plates [CH 2

CI

2 / MeOH (95:5)], Rf = 0.38. MS: calc.: C 4 5

H

6

N

8 0 1 3 (927.2), found: [MH-] 928.0 A37. 4 -0-Benzvl- 6 -0-[4-(trans-4-N-tert-butoxvcarbonylaminomethvlcvclohexvlcarbonvl)-5 aminopentyll-3-0-[4-(trans-4-N-tert-butoxvcarbonvlaminomethvlcvclohexvlcarbonvl)-1 Diperazinvlcarbonvil-1.2-dideoxy-D-glucouyranose HOBT (0.11 g, 0.74 mmol) is added to a solution of 6 -0-(5-aminopentyl)-4-0-benzyl-3-0-[4-(trans-4-N tert-butoxycarbonylaminomethylcyclohexylcarbonyl)piperazin-1 -ylcarbonyl]-1,2-dideoxy-D glucopyranose (A49, 0.35 g, 0.74 mmol) and trans-4-N-tert-butoxycarbonylaminomethylcyclo hexylcarboxylic acid (0.14 g, 0.74 mmol) in absolute CH 2

CI

2 (6 ml) and Et 3 N (0.42 ml) and the mixture is stirred at RT for 45 min. EDC (0.15 g, 0.74 mmol) is then added and the mixture is stirred overnight at RT. The reaction solution is diluted with CH 2 C1 2 (15 ml) and extracted (2 x) with semisaturated aque- B666WO0 09991 -105 ous NH 4 CI solution (15 ml), dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography [CH 2 Cl 2 /MeOH (98:2)] on a silica gel column affords the title compound (0.32 g) as a colorless powder. TLC, silica gel, glass plates [CH 2

CI

2 /MeOH (98:2)], Rf = 0.30. MS: calc.: C 49

H

79

N

5 0 11 (914.2), found: [MH*] 914.3 A38. 4 -O-Benzvl- 3 -O-4-(trans-4-N-tert-butoxvcarbonviaminomethvlcvclohexvlcarbonvl)-1 iperazinvlcarbonvil-6-O-r5-(2-N-tert-butoxvcarbonvlaminomethvlpvridvlcarbonvl)-5 aminopentvll-1.2-dideoxv-D-glucouvranose HOBT (0.09 g, 0.45 mmol) is added to a solution of 6-0-(5-aminopentyl)-4-0-benzyl-3-0-[4-(trans-4-N tert-butoxycarbonylaminomethylcyclohexylcarbonyl)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 CH 2 C1 2 (5 ml) and Et 3 N (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 C 2 C1 2 (15 ml) and extracted (2 x) with semisaturated aqueous NH 4 CI solution (15 ml), dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chro matography [CH 2 Cl 2 /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 [CH 2 Cl 2 /MeOH (98:2)], Rf = 0.23. MS: calc.: C 48

H

72

N

6 0 11 (909.14), found: [MH*] 909.2 A39. 4-0-Benzvi-6-N-[4-(trans-4-N-tert-butoxvcarbonvlaminomethylcyclohexvicarbonvi)-4 aminobutvl-1 -oxvcarbonvil-3-O-f4-(trans-4-N-tert-butoxvcarbonvlaminomethylcyclohe xvlcarbonvl)-1 -iperazinvlcarbonvil-1.2-dideoxv-D-glucopvranose A solution of 4-0-benzyl-6-N-[4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-4 aminobutyl-1-oxycarbonyl]-1,2-dideoxy-D-glucopyranose (A52, 0.5 g, 0.85 mmol) in CH2Cl 2 (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 CH 2 C1 2 (1.5 ml), and then treated with DIPEA (1.5 ml) and trans-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 CH 2 Cl 2 (15 ml) and extracted (2 x) with semisaturated aqueous NH 4 CI solution (10 ml), dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography [CH 2 Cl 2 /MeOH (98:2)] on a silica gel column affords the title compound (0.11 g) as a colorless resin. TLC, silica gel, glass plates [CH 2

CI

2 /MeOH (98:2)], Rf = 0.30. MS: calc.: C 49

H

78

N

6 0 12 (943.0), found: [MH*] 943.2 B666WOO 09991 -106 A40. 6 -O-r4-(trans-4-N-tert-Butoxvcarbonviaminomethvlcvclohexvlcarbonvl)-5-aminopentvil 3 -0-[ 4 -(trans-4-N-tert-Butoxvcarbonviaminomethlcvclohexvicarbonvi)1 -piperazinyl carbonvil-1.2-dideoxv-D-alucopvranose 4-O-Benzyl-6-0-[4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)-5-aminopentyl]-3-0

[

4 -(trans- 4 -N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)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

[CH

2 CI2/MeOH (98:2)], Rf = 0.30. MS: calc.: C 4 2

H

7 3

N

5 0 11 (824.08), found: [MH* 824.1 A41. 3

.

6 -Di-O-[4-(trans-4-N-tert-butoxvcarbonlaminomethvlcvclohexvcarbonvl)-5-amino pentvll-1.2-dideoxv-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 [Tol/Ac (1:1)], Rf = 0.29. MS: calc.: C 4 2

H

76

N

4 0 10 (797.1), found: [MH-] 798.2 A42. 4-0-Benzvl-3,6-Di-0-r4-(trans-4-N-ert-butoxvcarbonylaminomethylcyclohexvicarbonvi) 5-aminopentvll-1.

2 -dideoxv-D-glucopvranose 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-butoxycarbonylaminomethyl-cyclohexylcarboxylic acid (1.25 g, 4.8 mmol) in absolute CH 2 Cl 2 (10 ml) and Et 3 N (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 CH 2

CI

2 (25 ml) and extracted (2 x) with semisaturated aqueous NH 4 CI solution (20 ml), dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chro matography [Tol/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, [Tol/ Ac (6:4)], Rf = 0.36.

B666WOO 09991 -107 MS: calc.: C 49

H

82

N

4 0 10 (887.2), found: [MH] 888.3 A43. trans-4-N-tert-Butoxvcarbonvlaminomethvlcvclohexlcarbonl-1-piperazine Benzyl 4-{1 -[trans-4-(N-tert-Butoxycarbonylaminomethyl)cyclohexyl]carbonyl}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 [CH 2

CI

2 / MeOH (9:1)], Rf = 0.10. A44. Benzvl 4414-rtrans-4-(N-tert-butoxvcarbonylaminomethvl)cvclohexvllcarbonvllpiperazin 1-carbonate HOBT (0.16 g, 1.2 mmol) is added to a solution of trans-4-(N-tert-butoxycarbonylaminomethyl) cyclohexanecarboxylic acid (0.40 g, 1.55 mmol) and benzyloxycarbonyl-1-piperazine (0.34 g, 1.55 mmol) in absolute CH 2 Cl 2 (9 ml) and Et 3 N (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 CH2Cl 2 (15 ml) and extracted (2 x) with semisaturated aqueous NH 4 CI solution (15 ml), dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography

[CH

2

CI

2 / MeOH (9:1)] on a silica gel column affords the title compound (0.71 g) as a colorless powder. TLC, silica gel, glass plates [CH 2

CI

2 / MeOH (9:1)], Rf = 0.24. A45. 4 -0-Benzvl- 3 -0-r4-(trans-4-N-tert-butoxvcarbonviaminomethvlcvclohexlcarbonl)-1 Diperazinvlcarbonvll-1,2-dideoxy-D-glucopyranose 4-O-Benzyl-3-0-[4-(trans-4-N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl)piperazin-1-ylcarbon yl]-6-0-tert-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 NH 4 CI solution (15 ml), and the extract is dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography [CH 2

CI

2 /MeOH (7:3)] on a silica gel column affords the title compound (1.15 g) as a colorless powder. TLC, silica gel, glass plates [CH 2

CI

2 / MeOH (7:3)], Rf = 0.39.

B666WOO 09991 - 108 A46. 4-0-Benzyl-3-0-[4-(trans-4-N-tert-butoxvcarbonvlaminomethylcvclohexvicarbonvi)-1 Piperazinvlcarbonvi1-6-O-tert-butvldimethylsilvl-1.2-dideoxv-D-glucouyranose 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 -0-Benzyl-6-0-tert-butyIdimethylsilyl-1, 2 -dideoxy-D-glucopyranose (A53, 3.0 g, 8.51 mmol) is dissolved in CH 2 Cl 2 (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 CH 2

CI

2 (14 ml), and treated with DIPEA (14 ml) and trans-4 N-tert-butoxycarbonylaminomethylcyclohexylcarbonyl-l-piperazine (A43, 3.3 g, 10.21 mmol) . The mixture is stirred at RT overnight. The reaction solution is diluted with CH 2 Cl 2 (20 ml) and extracted (2 x) with semisaturated aqueous NH 4 CI solution (15 ml), dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography [CH 2 CI2/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 [Tol/Ac (95:5)], Rf = 0.21. A47. 4---Benzyl-3-O-[4-(trans-4-N-tert-butoxycarbonvlaminomethylcvclohexylcarbonvi)-1-pi Perazinvicarbonvil-1.

2 -dideoxv-6-0-methvlcarboxvmethyl-D-lucopvranose 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-6-0-methylcarboxymethyl-D-glucopyranose (A66, 0.5 g, 1.6 mmol) is dissolved in CH 2

CI

2 (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 CH 2 Cl 2 (3 ml), and treated with DIPEA (2.5 ml) and trans-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 CH 2

CI

2 (10 ml) and extracted (2 x) with semisaturated aqueous NH 4 CI solution (10 ml), dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography [Tol/Ac (8:2)] on a silica gel column affords the title compound (0.72 g) as a colorless powder. TLC, silica gel, glass plates [Tol/Ac (8:2)], Rf = 0.38. A48. 4-O-Benzyl-3-O-[4-(trans-4-N-tert-butoxvcarbonvlaminomethylcyclohexvicarbonyi)-1 iperazinvicarbonvil-1.

2 -dideoxv-6-O-methlcarboxvmethyl-D-glucouvranose A 5 N aqueous solution of NaOH (0.52 ml) is added to a solution of 4 -0-benzyl-3-0-[4-(trans-4-N-tert butoxycarbonylaminomethylcyclohexycarbonyl)piperazin-1 -ylcarbonyl]-1,2-dideoxy-6-0 methylcarboxymethyl-D-glucopyranose (A47, 0.7 g, 1.06 mmol) in methanol (3 ml) and the mixture is B666WOO 09991 - 109 stirred at RT for 1.5 h. The reaction solution is carefully adjusted to pH 3 using 1 N HCI. It is diluted with ethyl acetate (20 ml) and extracted with -120 (15 ml). After drying over MgSO 4 , the organic phase is concentrated in vacuo. The title compound (0.68 g) is obtained as a colorless powder. TLC, silica gel, glass plates [Tol/ Ac (6:4)], Rf = 0.05. A49. 6 -0-( 5 -Aminopentv)-4-O-benzv-3--O-4-(trans-4-N-tert-butoxvcarbonvlaminomethvl cyclohexvlcarbonvl)-1-oiperazinvlcarbonvll-1,2-dideoxv-D-alucouvranose Hydrazine monohydrate (0.4 ml, 8.2 mmol) is added to a solution of 4 -0-benzyl-3-0-[4-(trans-4-N-tert butoxycarbonylaminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-1,2-dideoxy-6-0-(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 CH 2 Cl 2 (50 ml) and extracted (3 x) with 1 N NaOH (35 ml). The combined organic phases are dried over MgSO 4 , filtered and concentrated in vacuo. The title compound (2.1 g) is obtained as a colorless resin. TLC, silica gel, glass plates [Tol/ Ac (1:1)], Rf = 0.05. A50. 4-O-Benzvi-3-O--4-(trans-4-N-tert-butoxvcarbonvlaminomethylcyclohexvicarbonvi)-1 Diperazinvlcarbonvil-1.

2 -dideoxv- 6 -O-(5-hthalimidopentvl)-D-cglucopvranose 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 CH 2

CI

2 (35 ml) and the mixture is stirred at RT for 10 min. The reaction solution is diluted with CH 2

C

2 (35 ml) and extracted (2x) with an aqueous NaCl solution. The combined organic phases are dried over MgSO 4 , filtered and concentrated in vacuo. The residue obtained is taken up in absolute CH 2

C

2 (35 ml) and 4-O-benzyl-3-O-[4-(trans-4-N-tert-butoxycarbonylaminomethylcyclo hexylcarbony)piperazin-1-yl-carbonyl]-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 NH 4 CI solution (40 ml), extracted (2 x) with CH 2 Cl 2 (50 ml), and the com bined organic phases are dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography [Tol/ Ac (7:3)] on a silica gel column affords the title compound (2.5 g) as a colorless resin. TLC, silica gel, glass plates [Tol/ Ac (75:25)], Rf = 0.26. A51. rtrans-4-(N-tert-Butoxvcarbonlaminomethvl)cvclohexvIcarbonvl14-amino-1-butanol HOBT (1.5 g, 11.1 mmol) is added to a solution of trans- 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

CH

2

CI

2 (90 ml) and Et 3 N (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 CH 2 C1 2 B666WOO 09991 -110 (50 ml) and extracted (2 x) with semisaturated aqueous NH 4 CI solution (60 ml), dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography [CH 2

CI

2 / MeOH (98:2)] on a silica gel column affords the title compound (2.45 g) as a colorless powder. TCL, silica gel, glass plates [CH 2

CI

2 / MeOH (98:2)], Rf = 0.40. A52. 4-0-Benzyl-6-N44-(trans-4-N-tert-butoxvcarbonvlaminomethylcyclohexvicarbonvl)-4 aminobutvl-1 -oxvcarbonvil-1.2-dideoxv-D-alucopvranose A solution of 6-amino-4-O-benzyl-1,2-dideoxy-D-glucopyranose (A57, 0.7 g, 2.13 mmol) in CH 2 C1 2 (3 ml) and DIPEA (1 ml) 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 0 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 CH 2

C

2 (4 ml), and then treated with DIPEA (4 ml) and [trans-4-(N-tert-butoxycarbonylaminomethyl)cyclohexylcarbonyl]-4-amino-1-butanol (A51, 0.51 g, 2.13 mmol). The mixture is stirred overnight at RT. The reaction solution is diluted with CH 2

C

2 (15 ml) and extracted (2 x) with semisaturated aqueous NH 4 CI solution (10 ml), dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography [CH 2

CI

2 /MeOH (98:2)] on a silica gel column affords the title compound (1.8 g) as a colorless resin. TLC, silica gel, glass plates

[CH

2 C2/ MeOH (95:5)], Rf = 0.31. A53. 4 -O-Benzvl-6-0-tert-butyldimethylsilyl-1.2-dideoxy-D-glucopyranose 4 -0-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 NH 4 CI solution (20 ml). The combined organic phases are dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography [Tol/ Ac (9:1)] on a silica gel column affords the title compound (4.02 g) as a colorless resin. TLC, silica gel, glass plates [Tol/ Ac (8:2)], R = 0.64. A54. 3.6-O-tert-Butyldimethylsilyl-1.2-dideoxy-D-galactopyranose 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

NH

4 CI solution (50 ml) and extracted (3 x) with EA (60 ml). The combined organic phases are dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography [PE/EA (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.

B666WOO 09991 - 111 A55. 4 -0-Methyl-3.6-O-tert-butyidimethylsilvi-1, 2 -dideoxy-D-aalactopvranose 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 NH 4 CI solution and extracted with ethyl acetate (3x). The combined organic phases are dried over MgSO 4 , 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 [PE/EA (95:5)], Rf = 0.35. A56. 4-0-Methyl-1.

2 -dideoxy-D-qalactopyranose 4 -0-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 NH 4 CI solution (50 ml). It is extracted with ethyl acetate (3 x) and the combined organic phases are dried over MgSO 4 . The solu tion is filtered and concentrated in vacuo. After purification by means of chromatography [tolue ne/acetone (7:3)] on a silica gel column, the title compound (1.0 g) is obtained as colorless crystals. TLC, silica gel (glass plates), [PE/EA (1:1)], Rf = 0.11. A57. 6-Amino-4-0-benzvl-1, 2 -dideoxy-D-qlucopyranose A solution of 6-azido-4-0-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 LiAIH 4 (3.53 g, 93 mmol) in diethyl ether (100 ml) is slowly added dropwise. After stirring at RT for 2 h, the reaction mixture is cooled to 00C and treated cautously with a semisaturated aqueous NaHCO 3 solution (150 ml). After the separation of the organic phase, the aqueous phase is extracted (3 x) with a mixture of CH 2

CI

2 /MeOH (8:2, 200 ml). The combined or ganic phases are dried over MgSO 4 , filtered and concentrated in vacuo. The title compound (4.7 g) is obtained as a colorless resin. TLC, silica gel, glass plates [Tol/ Ac (1:1)], Rf = 0.14. A58. 6-Azido-4-0-benzyl-1 2 -dideoxy-D-glucopyranose NaNa (3.55 g, 54.3 mmol) is added to a solution of 4-0-benzyl-1, 2 -dideoxy-6-0-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 in ethyl acetate (150 ml) and extracted (2x) with H 2 0. The combined organic phases are dried over MgSO 4 , filtered and concentrated in vacuo. The title compound (4.5 g) is obtained as a colorless resin. TLC, silica gel, glass plates [Tol/ Ac (8:2)], R, = 0.39.

B666WOO 09991 -112 A59. 4-O-Benzvl-1.

2 -dideoxv-6-O-toluenesulfonvl-D.-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 4-0-benzyl-1, 2 -dideoxy-D-glucopyranose (5.0 g, 21.0 mmol) in absolute CH 2 Cl 2 (55 ml) and the mixture is stirred for 2 h. It is then stirred overnight at RT. The reaction solution is d luted with semisaturated aqueous NH 4 CI solution (50 ml). It is extracted with ethyl acetate (3 x) and the combined organic phases are dried over MgSO 4 . 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)], R,= 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 H 2 0 (10 ml), the catalyst is filtered off 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-Butoxvcarbonviaminomethyl)nicotinic acid Et 3 N (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 dioxane/H 2 0 (3.5 ml, 2.5:1) and the mixture is stirred at RT overnight. Further Et 3 N (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 NaHCO 3 solution (10 ml) and extracted with ethyl acetate (15 ml, 3 x). The combined organic phases are dried over MgSO 4 , filtered and concentrated in vacuo. The title compound (0.24 g) is obtained as a colorless solid. TLC, silica gel, glass plates [EtOH/H 2 0 (9:1)], Rf = 0.70. A62. 4-O-Benzv-3,6-di-O-tert-bu

II,

2 -dideoxy-D-galactovranose 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 to 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

NH

4 CI solution and extracted (3x) with ethyl acetate. The combined organic phases are dried over MgSO 4 , filtered and concentrated in vacuo. Further purification by means of chromatography B666WOO 09991 -113 [PE/EA (95:5)] on a silica gel column affords the title compound (7.6 g), as a colorless oil. TLC, silica gel, glass plates [PE/EA (9:1)], Rf = 0.50. A63. 4-O-Benzvl-1.2-dideoxy-D-qalactopyranose 4 -0-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 tetrabutylammonium fluoride (36 ml, 35.9 mmol). The mixture is stirred overnight and then diluted with semisaturated aqueous NH 4 CI solution (50 ml). It is extracted with ethyl acetate (3 x) and the combined organic phases are dried over MgSO 4 . The solu tion is filtered and concentrated in vacuo. After purification by means of chromatography [tolue ne/acetone (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-aminopentvl)-4-0-benzvli-1.2-dideoxv-D-glucopvranose Hydrazine monohydrate (0.38 ml, 7.8 mmol) is added to a solution of 4-O-benzyl-1,2-dideoxy-3,6-di-0 (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 CH 2

CI

2 (30 ml) and extracted (3 x) with 1 N NaOH (15 ml). The combined organic phases are dried over MgSO 4 , filtered and concentrated in vacuo. The title compound (0.9 g) is obtained as a colorless resin. TLC, silica gel, glass plates [Tol/Ac (1:1)], Rf = 0.05. A65. 4-0-Benzvl-1.2-dideoxv-3.6-di-O-(5- hthalimidopentvl)-D-glucouvranose 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 CH 2 C1 2 (25 ml) and the mixture is stirred at RT for 15 min. The reaction solution is diluted with CH 2

CI

2 (35 ml) and extracted (2x) with an aqueous NaCl solution (25 ml). The combined organic phases are dried over MgSO 4 , filtered and concentrated in vacuo. The residue obtained is taken up in absolute CH 2

CI

2 (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 NH 4 CI solution (30 ml), extracted (2 x) with CH 2

CI

2 (50 ml), and the combined organic phases are dried over MgSO 4 , filtered and concentrated in vacuo. Further purifica tion by means of chromatography [Tol/ Ac (8:2)] on a silica gel column affords the title compound (1.3 g) as a colorless resin. TLC, silica gel, glass plates [Tol/ Ac (8:2)], Rf = 0.15.

B666WOO 09991 -114 A66. 4-O-Benzvl-1.

2 .dideoxv-6-0-methvlcarboxvmethyl-D-alucopyranose 4-0-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 chrorma tography [Tol/ Ac (8:2)] on a silica gel column affords the title compound (0.79 g) as a colorless resin. TLC, silica gel, glass plates [Tol/ Ac (8:2)], Rf = 0.47. A67. 3,6-Di-O-4-I'3-(tert-butvloxvcarbonviaminomethyllbenzovil-dideoxvnierazin-1 vicarbonvil-4-0-benzv-1.

2 -dideoxv-D- lucopvranose A solution of 480 mg (2.0 mmol) of 4-0-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.: C 49

H

6 4

N

6 0 12 (928.51) found: [MH*] 929.0 A68. vlaminomethyllbenzovlaminoloineridin-1-vlcarbonvil 4-O-benzvl-1.

2 -dideoxv-D-glucopyranose A solution of 240 mg (1.0 mmol) of 4-0-benzyl-1, 2 -dideoxy-D-glucopyranose and 2.5 ml (14.6 mmol) of diisopropylethylamine in 15 ml of dichloromethane is added dropwise in the course of 40 min to 6.0 ml (11.4 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 h. The reaction mixture is concentrated and coevapo rated with 3 x 20 ml of toluene.

B666WOO 09991 -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) benzoylamino]piperidine (starting compound Al 13) 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.: C 51

H

68

N

6

O

12 (956.54) found: [MH*] 957.0 A69. 3,6-Di-O-4--3-(tert-butyloxvcarbonylaminomethyl)benzvlaminocarbonyllpiperazin-1-vi carbonyl}-4-O-benzvl-1.2-dideoxy-D-glucopyranose A solution of 480 mg (2.0 mmol) of 4-0-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 Al 14) 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.: C 1

H

70

N

8 0 1 2 (986.56) found: [MH] 987.1 A70. 3

.

6 -Di-O-f 4 -[3-(tert-butvloxvcarbonlaminomethl)benzlaminocarbonlaminolpiperidin 1-vi-carbonvil-4-0-benzvl-1.2-dideoxv-D-plucouvranose A solution of 1.02 g (2.8 mmol) of 4

-[

3 -(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl amino]piperidine (starting compound Al 15) in 4 ml of dimethylformamide is combined with a solution of 520 mg (1.2 mmol) of 4-0-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 B666WOO 09991 -116 the solvent and the crude product is purified by chromatography (dichloromethane/methanol = 19:1). 540 mg of the title compound is obtained as a colorless powder. MS: calc.: C 5 3

H

7 4

N

8 0 12 (1014.59), found: [MH*] 1015.1 A71. 3

.

6 -Di-O-f4-r3-(tert-butvloxvcarbonvlaminomethvl)benzvaminocarbonllpiperidin-1-vi carbonyll-4-O-benzvl-1.2-dideoxy-D-glucopyranose A solution of 960 g (2.76 mmol) of 4

-[

3 -(tert-butyloxycarbonylaminomethyl)benzyaminocarbonyl] piperidine (starting compound A116) in 2 ml of dimethylformamide is combined with a solution of 520 mg (1.2 mmol) of 4 -0-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 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 (dichloromethane/methanol = 29:1). 750 mg of the title compound are obtained as a colorless powder. MS: calc.: C 53

H

7 2

N

6 0 12 (984.57), found: [MH] 985.1 A72. 3,6-Di-O-{4-trans-[3-(tert-butyloxvcarbonylaminomethyl)benzylaminocarbonvilcyclo hexvlmethylaminocarbonvl}-4-0-benzvl-1.2-dideoxv-D-alucopvranose A solution of 850 g (2.0 mmol) d 4 -trans-[ 3 -(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl] cyclohexylmethylamine (starting compound Al 17) 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 0 C for 8 days. It is then concentrated to dryness in a rotary evaporator and the residue is purified by chromatography (dichloromethane/methanol = 29:1). 980 mg of the title compound are obtained as a colorless powder. MS: calc.: C 57

H

8 oN 6 0 1 2 (1040.63), found: [MH*] 1041.1 A73. 3.6-Di-O-[4-(6-tert-butvloxvcarbonv-aminopyridin-3-vimethylaminocarbonvlpiperidin-1 vlcarbonvl1-4-O-benzvl-1.2-dideoxv-D-alucouvranose A solution of 200 mg (0.84 mmol) of 4-0-benzy-1, 2 -dideoxy-D-glucopyranose and 2.04 ml (11.7 mmol) of diisopropylethylamine 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 B666WOO 09991 - 117 diisopropylethylamine. A suspension of 620 mg (1.84 mmol) of 4

-(

6 -tert-butyloxycarbonylaminopyridin 3 -ylmethylaminocarbonyl)piperidine (starting compound Al 18) 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. > 2000C are obtained (sintering from 1450C). MS: calc.: C 4 9

H

66

N

8 0 12 (959.1), found: [MH*] 959.2 A74. 3 -0i 4

-

4 -(tert-Butvloxvcarbonvaminomethyl)benzvlaminocarbonllpiperazin-1-vi carbonvil-4-0-benzvl-6-0444(6tert-butvloxvcarbonviaminopyridin-3-vimethylamino carbonvl)Diperidin-1 -vlcarbonvll-1.

2 -dideoxv-D-qlucouvranose A solution of 565 mg (0.92 mmol) of 3

-O-{

4

-[

4 -(tert-butyloxycarbonylaminomethyl) benzylaminocarbonyl]piperazin-1-ylcarbonyl}-4-0-benzyl-1, 2 -dideoxy-D-glucopyranose (starting com pound Al 06) 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 -tert-butyloxycarbonylaminopyridin-3 ylmethylaminocarbonyl)piperidine (starting compound Al 18) 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.: C 5 oH 68

N

8 0 12 (973.1), found: [MH*] 973.2 A75. 3-04444tert-Butvloxvcarbonvlaminom ethylbenzylaminocarbonvilpiperazin-1-vi carbonvl 4 benzvl64(6rt-butloxvcarbonlamino-2-methyloridin-3-vimethv aminocarbonvl)ineridin-1-vicarbonvll-1. 2 -dideoxv-D-lucopvranose A solution of 750 mg (1.22 mmol) of 3

-O-{

4

-[

4 -(tert-butyloxycarbonylaminomethyl) benzylaminocarbonyl]piperazin- -ylcarbonyl}-4-0-benzyl-1, 2 -dideoxy-D-glucopyranose (starting compound A106) and 1.93 ml (10.93 mmol) of diisopropylethylamine in 10 ml of dichloromethane B666WOO 09991 -118 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 Al 19) 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 acetate/methanol/ammonia = 10:0.3:0.2). 440 mg of the title compound are obtained as a colorless foam. MS: calc.: C 51H rN 8 0 12 (987.17), found: [MH*] 987.3 A76. 3 -0 4 4 f 4 tert-Butyloxvcarbonvlaminomethyl)benzvlaminocarbonviltiperazin-1-vi carbonv 4 -benzvl 4(4aminobenzvlamncarbonvl)pieridin-1 -vicarbonvll-1.2 dideoxv-D-lucopyranose 250 mg (0.28 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 ylcarbonyl}-4-0-benzyl-6-0-[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 (toluene/acetone = 1:1) and 100 mg of the title compound are obtained as a pale yellow amorphous solid. MS: calc.: C 39

H

55

N

7 0 1 0 (871.49), found: [MH] 872.0 A77. 3 -0 4 4 -r 4 -tert-Butvloxvcarbonylaminomethvl)benzvlaminocarbonvilpiperazin-1-v carbonvDl- 4 -- benzvl6.r4-(4nitrobenzvlaminocarbonyl)piperidin-l-vicarbonyll-1.2 dideoxv-D-glucopyranose A solution of 860 mg (1.4 mmol) of 3 -0-{ 4

-[

4 -(tert-butyloxycarbonylaminomethyl) benzylaminocarbonylpiperazin-1-ylcarbonyl}-4-0-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 0 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 I h. It is concentrated and the reaction mixture is coevaporated with 3 x 20 ml of toluene.

B666WOO 09991 - 119 The residue is dissolved in 5 ml of dichloromethane and treated with 1.22 ml (7 mmol) of diisopro pylethylamine. A suspension of 505 mg (1.68 mmol) of 1-( 4 -nitrobenzylaminocarbonyl)piperidine in 5 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 (toluene/acetone = 2:1). 260 mg of the title compound are obtained as a yellow oil. MS: calc.: C 4 6

H

5 96N 7 0 12 (902.02), found: [MH*j 902.1 A78. 3 -0 4 4 F44tertButloxcarbonlaminomethyl)benzvlaminocarbon Illierazin-1vIcar bonyl}-4-O-benzyl-6-04-trans(6-tert-butvloxvcarbonviaminopyridin-3-vimethylamino carbonvil)cyclohexvmethylaminocarbonvl- 1.

2 -dideoxv-D-glucouvranose A solution of 400 mg (0.64 mmol) of 3 -0-{ 4 -[4-(tert-butyloxycarbonylaminomethyl) benzylaminocarbonylpiperazin-1-ylcarbonyl}-4-0-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 (toluene/acetone = 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.: C 52

H

7 2

N

8 0 12 1001.2, found: [MH-] 1001.2 A79. 3 -0 44 -r 4 tert-ButoxvcarbonvlaminomethviFbezlaminocarboniip erazin-vi carbonvl 4 Obenz-tr r t carbonylamino-2-m methylaminocarbonvi)cclohexvmethlaminocarbo Il.

2 -dideoxv-D-Olucopyranose A solution of 1.18 g (1.92 mmol) of 3-0-{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 B666WOO 09991 -120 (13.44 mmol) of a 20% strength solution of phosgene in toluene at 0-2 0 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 Al 18) in 30 ml of dichloromethane is added dropwise to this at 0-2 0 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 0 C are obtained (sintering from 130 0 C). MS: calc.: C 53

H

7 4

NBO

12 (1015.23), found: [MH*] 1015.3 A80. 3 -0 4 4

-

4 -(tert-Butloxvcarbonlaminomethv)benzylaminocarbony lliperazin-1-v carbonvl-4-0-benzvi-6-044-trans(4amin laminocarbonvl)cyclohexvimethy aminocarbonvll-1.

2 -dideoxv-D-glucopvranose 530 mg (0.5 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl1piperazin-1 ylcarbonyl}-4-0-benzyl-6-0-[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 acetate/methanol/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 11 0*C) are obtained. MS: calc.: C 48

H

65

N

7 0 10 (900.1), found: [MH*] 900.2 A81. 3

-

4 4 4(tertButvoxvcarbonviaminmethyl)benzylaminocarbonylliperazin-1-vi carbon vil-4-0-ben zvi 4 4tran( ni b lhx methv aminocarbonvl-1.

2 dideoxv-D-alucopyranose A solution of 690 mg (1.12 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl) benzylaminocarbonylpiperazin-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.

B666WOO 09991 - 121 The residue is dissolved in 10 ml of dichloromethane and treated with 1.95 ml (11.2 mmol) of diisopro pylethylamine. A suspension of 360 mg (1.23 mmol) of 4 -trans-(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 acetate/methanol/ammonia = 10:0.3:0.2) and 570 mg of the title compound are obtained as a yellowish oil. MS: calc.: C 4 8

H

63

N

7 0 12 (930.1), found: [MH*] 930.1 A82. 3 -0 4 4 -r 4 -(tert-Butvloxvcarbonviaminomethvl)benzvlaminocarbonvlpiperazin-l-vi carbonvl}-4---benzvi-6-04344-aminobenzvlaminocarbonvl)benzvlaminocarbonvil-1.2 dideoxv-D-alucopyranose 350 mg (0.38 mmol) of 3 -0-{ 4

-[

4 -(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 ylcarbonyl}-4-0-benzyl-6-0-[3-(4-nitrobenzylaminocarbonyl)benzylaminocarbonyl]-1,2-dideoxy-D glucopyranose (starting compound A83) are hydrogenated on palladium/carbon (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 acetate/methanol/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.: C 4 8

H

59

N

7 0 10 (894.05), found: [MH*] 894.1 A83. 3 -0 4 4 -4 4 4 tert-Butvloxvcarbonviaminomethvl)benzvlaminocarbonvl1piperazin-l-vi carbonvll-4-O-benzvl-6-04344-nitrobenzvlaminocarbonvl)benzvlaminocarbonvl-1.2 dideoxv-D-cflucowvranose A solution of 700 mg (1.14 mmol) of 3 -0-{ 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 B666WOO 09991 -122 separated off and the aqueous phase is extracted with 3x 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. 11 5*C are obtained. MS: calc.: C 48

H

57

N

7 0 12 (924.06), found: [MH*] 924.0 A84. 3 -0 4 4 -r 4 -(tert-Butvloxvcarbonvaminomethvl)benzvlaminocarbonvyllpierazin-l-vi carbonvil-4-O-benzvl-6-044r3(imidazol-1-vI)proplaminocarbonvilpperidin-1 vicarbonvil-1.

2 -dideoxy-D-qlucopyranose 530 mg (0.75 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 ylcarbonyl}-4-0-benzyl-6-0-(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 acetate/methanol/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.: C 45

H

6 2

N

8 0 1 0 (875.04), found: [MH] 875.3 A85. Ycarbo'(111B1 III'nlaminomethil)benzvlaminocarbonilliperazin-1-vI carbonvll-4-0-benzvi-6-0444imidazol-1-vl)butvlaminocarbonv1piperidin-1 vicarbonyll-1 2 -dideoxy-D-glucopyranose 800 mg (1.13 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 ylcarbonyl}-4-0-benzyl-6-0-(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.: C 4 6

H

64

N

8

O

1 0 (889.07), found: [MH] 889.3 B666WO0 09991 -123 A86. 3 -0 4 4 4 4 4tert-Butvloxvcarbonvlaminomethvl)benzvlamin carbonvilpiperazin-1-vi carbonvil-4-O-benzvl-6-0.44r5(imidazol- -vl)pentvlaminocarbonvllpiperdin-1 -vi carbonvl}-1, 2 -dideoxy-D-glucopyranose 840 mg (1.19 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 ylcarbonyl}-4-O-benzyl-6-0-(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.: C 4 7

H

66

NO

8 10 (903.1), found: [MH*] 903.3 A87. 3 -0 4 4 44tertButyloxvcarbonvaminomethv1)benzvlaminocarbonl1iperazin-1 -vicar bonvil- 4 -O-benzvl..6..O(4-.I6.midazol-I -vl)hexylaminocarbonyllpiperidin-I -vicarbonvl) 1.

2 -dideoxv-D-alucopvranose 740 mg (1.04 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 ylcarbonyl}-4-0-benzyl-6-0-(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 acetate/methanol/ammonia = 10:1:0.5), 680 mg of the title compound are obtained as a colorless oil. MS: calc.: C 4 8

H

68

N

8 0 10 (917.12), found: [MH] 917.4 A88. 3 -0 4 4 44 tert-Butvloxvcarbonaminomethy l aminocarbonvili.erazin-1-vIcar bonvil-4-O-benzv--444-8(Imidazol1-vloctvlaminocarbonvilpiperidin-1-vicarbonvil 1.

2 -dideoxv-D-glucopyranose 600 mg (0.84 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 ylcarbonyl}-4-O-benzyl-6-0-(imidazol-1-ylcarbonyl)-1, 2 -dideoxy-D-glucopyranose (starting compound Al05) 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 acetate/methanol/ammonia = 10:1:0.5), 680 mg of the title compound are obtained as a colorless foam. MS: calc.: C 50

H

7 2

N

8 0 1 0 (945.18), found: [MH'] 945.4 B666WOO 09991 - 124 A89. 3-0-l'4-(6-tert-Butloxvcarbonviaminopyridin-3-vimethylaminocarbonvilpiperidin-1-vi caronvl--04-r-trns-tet-btyoxvcarbonylaminomethyl)cyclohexylcarbonvilami nobut-1-vlaminocarbonil-4-O-benzv-1. 2 -dideoxv-D-glucopvranose 290 mg (0.37 mmol) of 3-0-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin 1-ylcarbonyl-4-0-benzyl-6-0-(imidazol-1-ylcarbonyl)-1, 2 -dideoxy-D-glucopyranose (starting compound A108) and 145 mg (0.44 mmol) of [ 4

-(

4 -aminobutylaminocarbonyl)cyclohexylmethyl]carbaminic acid tert-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.: C 49

H

73

N

7 0 12 (951.58), found: [MH*] 952.2 A90. 3-- 4-(6-tert-Butloxvcarbonviaminopyvridin-3-vimethylaminocarbonvilpiperidin-1-vi carbonvl- 6 .O-(4-f44tert..buItloxvcarbonylaminomethvl)benzlami ncarbonyllpiperazin 1-vicarbonyl}-4-O-benzvl-1

.

2 -dideoxy-D-alucouvranose 290 mg (0.37 mmol) of 3-0-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin 1-ylcarbonyl]-4-0-benzyl-6-0-(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 (dichloromethane/methanol = 19:1) and crystallization from diethyl ether, 220 mg of the title compound of m.p. 145*C are obtained. MS: calc.: C 50

H

68

N

8 0 12 (972.55), found: [MHW] 973.2 A91. 3

.O

44 r 4 (tertButloxvcarbonvI inomethyl)benzviaminocarbonyll.iperazin-1-vi carbonvl -benzvl6 2(6amyridin-vlmethylaminocarbonyl)eth-1-vlamino carbonvll-1.

2 -dideoxy-D-glucopyranose 485 mg (0.69 mmol) of 3 -0-{ 4

-[

4 -(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperazin-1 ylcarbonyl}-4-0-benzyl-6-0-(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 B666WOO 09991 - 125 magnesium sulfate and concentrated. The crude product is chromatographed on silica gel (ethyl acetate/methanol/ammonia = 10:1:0.5) and the product is crystallized from diisopropyl ether. 480 mg of the title compound are obtained. MS: calc.: C 4 2

H

56

N

8 0 1 0 (832.45), found: [MH] 833.2 A92. 3 -0 44

*

4 tert-Butvloxvcarbonvaminomethl)benzvlaminocarbonlliperazin- -vi carbonvl1-4-0-benzvl6o(3-r(6-amidino-1 -H-indazol-3-vl)carbonvlaminolprop-1 vlaminocarbonvl}-.

2 -dideoxy-D-glucouvranose and A93. 3

-OL-

4 - tert-ButoxvcarbonvlAMInomethvl)benzvlaminocarbon ipiperazin-1 -vicar bonvl)- 4 -o-benzvl4..og(3.r(8.aminocarbonvi-1 -H-indazol-3-vl)carbonvaminoloro.-1 -vi aminocarbonyl}-1, 2 -dideoxy-D-qlucopyranose 410 mg (0.40 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1 ylcarbonyl}-4-0-benzyl-6-0-(3-{[6-(1-benzyloxycarbonylamino-l-iminomethyl)-1-benzyloxycarbon ylaminoindazol-3-yl]carbonylamino}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 8h. 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/methanol/acetic 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: calc.: C 37

H

4 8

N

8 0 8 (898.43), found: [MH*] 899.3 A93: MS: calc.: C 37

H

4 8

N

8 0 8 (899.42), found: [MH*] 900.0 A94. 3 -0 44

-

4 tert-Butloxvcarbonviaminomethvl)benzvlaminocarbonvilpiperazin-1-vi carbonvil-6-042r(6-aminocarbonvi-1 -H-indol-3-vl)carbonviaminoeth-I vlaminocarbonvl}-1 2 -dideoxy-D-glucopyranose 170 mg (0.17 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl)piperazin-1 ylcarbonyl-4-0-benzyl-6-0-{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 palladium/carbon (10%). The catalyst is filtered cf, 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: calc.: C 37

H

4 8

N

8 0 8 (794.36), found: [MH*] 795.0 B666WOO 09991 - 126 A95. 3 -0 44

-

4 44tert-Butloxvcarbonvlaminomethyl)benzvlaminocarbonllpiperazin-1 -vicar bonvfl.

4 -O-benzvl4o43.r(6..aminocarbonvi-1 -H-indol-3-v)carbonviaminolpro-1 -vi aminocarbonvl-1.2-dideoxv-D-glucopyranose 240 mg (0.23 mmol) of 3

-O-{

4

-[

4 -(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl)piperazin-1 ylcarbonyl]-4-0-benzyl-6-0-{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 palladium/carbon (10%). The catalyst is filtered off, the solvent is removed in a high vacuum (bath temp. < 450C) and 180 mg of the title compound are obtained as a colorless foam. MS: calc.: C 37

H

4 8

N

8 0 8 (898.42), found: [MHj 899.0 A96. 3 -0 4 4 r444tert-Butvloxvcarbonvlaminomethyl)benzvlaminocarbonvl iperazin-1-vi carbonyl}-4-O-benzyl-6o-044r(6.-aminocarbonvIl--H-indol-3-v)carbonviamino1but-1 vlaminocarbonvil-1.

2 -dideoxv-D-lucopyranose 300 mg (0.287 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl)piperazin 1-ylcarbonyl]-4-0-benzyl-6-0-{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 palladium/carbon (10%). The catalyst is filtered off, the solvent is removed in a high vacuum (bath temp. < 450C) and 265 mg of the title compound are obtained as a colorless oil. MS: calc.: C 3 7

H

4 8

N

8 0 8 (912.44), found: [MH*] 913.0 A97. 3 -0 44 44tertBuloxvcarbonvilaminomethvl)benzvlaminocarboni iperazin-1 -vicar bonvl}-4-0-benzvi-604341641-benzvloxvcarbonvlamino-1-iminomethvli)-1-benzvloxv carbonalindazolm3carbo1 -vlaminocarbonvl -1.2-dideoxv-D glucopyranose dihydrochloride A solution of 244 mg (0.4 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl] piperazin-1-yl-carbonyl}-4-0-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 of toluene. The residue is dissolved in 5 ml of dichloromethane and added dropwise at 0-2oC to a solution of 0.28 ml (2.0 mmol) of triethylamine and 225 mg (0.4 mmol) of 6 -(l-benzyloxycarbonylamino-1- B666WOO 09991 - 127 iminomethyl)-3-(3-aminopropylaminocarbonyl)-l-benzyloxycarbonylindazole hydrochloride (A156) in 5 ml of dichloromethane. The reaction mixture is stirred at RT for 4 h, concentrated and the crude product is reacted without further purification. A98. 4-O-Befl IlI3.6-dl-imidazocarbonvi)-1. 2 -dideoxy-D-lucopvranose 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

CH

2 C1 2 (10 ml) and the mixture is stirred at RT for 45 min. The reaction solution is diluted with aqueous semisaturated NaCl solution (20 ml) and extracted with

CH

2

CI

2 (20 ml). The organic phase is dried over MgSO 4 and concentrated in vacuo. The title compound thus obtained is employed in the next reaction without further purification. A99. 3 -0 4 4 l'44tertButvIoxvcarbonvlaminomethy l)benzvlamrbonIl iperazin-1-vi carbonvil-16-424(6-aminocarbonvl-1 benzvloxvcarbonvlndol-3-vi)carbonvaminoleth-1 vlaminocarbonvl.-11.

2 -dideoxv-D- lucopyranose A solution of 250 mg (0.36 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylamino carbonyljpiperazin-1-ylcarbonyl}-4-O-benzyl-6-0-(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-benzyloxycarbonylindol-3-carboxylic acid (starting com pound A155), with 74 pl (0.54 mmol) 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 (dichloromethane/methanol = 20:1 -- 10:1). 180 mg of the title compound are obtained as a colorless foam. MS: calc.: C 37

H

48

N

8 0 8 (1018.44), found: [MH] 1019.1 Al 00. 3 -0 4 4 -r4-(tert-ButvloxvcarbonviaminomethylIbenvlaminocarbonv ilpiperazin-vicar bonyl}-4-0-benzvi-6-0436-aminocarbony l--benzvloxvcarbonvlindol-3-vi)carbonvi aminolproD.1-ylaminocarbonvil-1. 2 -dideoxv-D-lucoDyranose A solution of 220 mg (0.31 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylamino carbonyl]piperazin-1-ylcarbonyl}-4-O-benzyl-6-0-(3-aminoprop-1-ylaminocarbonyl)-1,2-dideoxy-D glucopyranose (starting compound A103) in 15 ml of dichloromethane is treated successively with 104 mg (0.31 mmol) of 6 -aminocarbonyl-1-benzyloxycarbonylindol-3-carboxylic acid (starting compound A155), with 64 pl (0.46 mmol) of triethylamine and 89 mg (0.46 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). 240 mg of the title compound are obtained as a colorless foam.

B666WOO 09991 - 128 MS: calc.: C 37

H

4 8

N

8 0 8 (1032.46), found: [MH*] 1033.1 A101. 3 -O-44 4 -(tert-Butyloxvcarbonylaminomethvl)benzvlaminocarbonvllpiperazin-l-vicar bonvil- 4 -O-benzvl-6-O4-4-r(6-aminocarbonvl-1 -benzvloxvcarbonvlindo-3-vl)carbonyl aminolbut-1 -vlaminocarbonvll-1.2-dideoxv-D-alucopyranose A solution of 410 mg (0.56 mmol) of 3 -0-{ 4

-[

4 -(tert-butyloxycarbonylaminomethyl)benzyamino carbonyl]piperazin-1 -ylcarbonyl}-4-0-benzyl-6-0-(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 pl (0.86 mmol) 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.: C 3 7

H

4 8

N

8 0 8 (1046.47), found: [MH-] 1047.1 A102. 3 -0- 4

-

4 (tert-Butvloxvcarbonvaminomethvlbenzvlaminocarbonvilpiperazin- -vicar bonvl}-6-O-(2-aminoeth-1 -viaminocarbonvi)-l.

2 -dideoxy-D-clucopvranose A solution of 356 mg (0.5 mmol) of 3 -0-{ 4

-[

4 -(tert-butyloxycarbonylaminomethyl) benzylaminocarbonyl]piperazin-l-ylcarbonyl}-4-0-benzyl-6-0-(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 4 -r 4 -(tert-Butvloxvcarbonvlaminomethvl)benzvlaminocarbonvilpiperazin-1 -vicar bonvil- 4 -0-benzv-6-O-(3-aminoprogp-1 -vlaminocarbonvi)-l.

2 -dideoxv-D-lucopvranose A solution of 210 mg (0.3 mmol) of 3 -0-{ 4

-[

4 -(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl] piperazin-1-ylcarbonyl}-4-O-benzyl-6-O-(imidazol-1-ylcarbonyl)-1, 2 -dideoxy-D-glucopyranose (starting compound Al 05) 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.

B666WOO 09991 - 129 A104. 3 -o 4 4 -r 4 -(tertButloxvcarbonvlaminomethyl)benzvlaminocarbonvilpiperazin-1-vcar bonyl}- 4 -O-benzyl-6-O-(4-aminobut-1 -vlaminocarbonl) -1, 2 -dideoxy-D-lucopyranose A solution of 510 mg (0.72 mmol) of 3-0-{4-[4-(tert-butyloxycarbonylaminomethyl)benzylamino carbonyl]piperazin-1-ylcarbonyl}-4-0-benzyl-6-0-(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 ml of water, the organic phase is separated off and the aqueous phase is ec 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/methanol/ammonia = 20:4:1). 470 mg of the title compound are obtained. A105. 3 -0 4 4 4(tertBut vloxvcarbonvlaminometh vlaminocarbonlpierazin-vi carbonvl-4-0-benzvl-6-0-(Imidazol-1-vlcarbonvil-1.

2 -dideoxv-D-glucopvranose 3.0 g (49 mmol) of 3 -0-{ 4 -[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl]piperazin-1-yl carbonyl}-4-0-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 -0 4 4 -r4-(tert-Butloxvcarbonvaminomethvl)benzvlaminocarbonvilpiperazin-1-vi carbonvl}-4-O-benzv-1.

2 -dideoxv-D-glucouvranose 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}-4-O-benzyl-6-O-t-butydimethylsilyI-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 3x 200 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.

B666WOO 09991 -130 A107. 3 -0- 4

-

4 -E(tertButvloxvcarbonvlaminomethylienzlaminocarbonvllie n-vi carbonvil-4-O-benzvi-6-O-tert-butvidimethylsilvl-1.

2 -dideoxv-D-glucogvranose 71 ml (135 mmol) of a 20% strength solution of phosgene in toluene are cooled to 0-2 0 C. A solution of 9.5 g (26.95 mmol) of 4-O-benzyl-6-0-tert-butyldimethylsilyl-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)benzylaminocarbonyllpiperazine (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-tert-Butloxvcarbonviaminopyridin-3-vmethlaminocarbonyi

-

carbonvl1-4-O-benzv-6-0-.(imdazol--vicarbonv)-1 ,2-dideoxv-D-glucouvranose 440 g (0.73 mmol) of 3-0-{4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1 ylcarbonyl}-4-0-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. methylaminocarbonyl iperidin1-vi carbonyll-4-0-benzyl-1,. 2 -dideoxv-D-lucopyranose 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 3-0-{4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylamino carbonyl)piperidin-1-ylcarbonyl}-4-O-benzyl-6-0-(tert-butyldimethylsilyl)-1, 2 -dideoxy-D-glucopyranose (starting compound Al 10) 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 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.

B666WOO 09991 -131 A110. v 3

--

4

-(

6 tertButloxvcarbonlaminopvridin-3-vimethylaminocarbonvilpiperidin-l-vi carbonyl1-4-0-benzyl-6-O4tert-butvidimethvlsilvI)-l. 2 -dideoxv-D-glucopvranose 4.08 g (12.2 mmol) of 4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidine (starting compound Al 18) and 4.50 g (10.16 mmol) of 4 -O-benzyl-3-0-(imidazol-1-ylcarbonyl)-6-0 (tert-butyldimethylsilyl)-1, 2 -dideoxy-D-glucopyranose (starting compound Al 11) in 260 ml of DMF are stirred at 80 0 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-Benz l-3-O-(midazol-1-vicarbonl)-6-O-(tert-butvidimethylsilvi)l.2-dideoxv-D glucopyranose 8.8 g (25.0 mmol) of 4 -0-benzyl-6-0-(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-r3-(tert-Butvloxvcarbonvlaminomethl)benzovilpiperazine 7.48 g (16.5 mmol) of benzyl 4-[3-(tert-butyloxycarbonylaminomethyl)benzoyllpiperazine-1-carboxylate (starting compound A133) are hydrogenated on palladium/carbon (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 -r3-(tert-Butvloxvcarbonlaminomethvl)benzovlaminolpiperidine 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 0 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 with 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. 11 3 (tertButvloxvcarbonvlaminomethyl)bnzvlaminoarbonvilpiperazine 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 B666WOO 09991 - 132 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. 4

-

3 -tert-Butvloxvcarbonviaminomethylbenzvlaminocarbon I 2.98 g (6.19 mmol) of 1-benzyl-4-[3-(tert-butyloxycarbonylaminomethyl)benzoylaminocarbonylamino] piperidine (starting compound A136) are hydrogenated on palladium/carbon (5%) at 50 0 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 -r3-(tert-Butvloxvcarbonviaminomethl)benzvlaminocarbonyllpiperidine 2.98 g (6.19 mmol) of benzyl 4-[3-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyllpiperidine 1-carboxylate (starting compound A137) are hydrogenated on palladium/carbon (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 -trans-f3-(tertButvloxvcarbonviaminomethyl)benzvlaminocarbonvllylohexvImethyl amine 5.3 g (10.4 mmol) of benzyl 4-trans-[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-Butvloxvcarbonvlminopyridin-3-vmethylaminocarbonv)piperidine 650 mg (0.81 mmol) of benzyl 4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylamino carbonyl)piperidine-l-carboxylate (starting compound A139) are hydrogenated on palladium/carbon (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. A119. 4

-(

6 -tert-Butvloxvcarbonviamino-2-methylpyridin-3-vimethylaminocarbonvi)piridine 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 B666WOO 09991 -133 (5%) for I 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 -Nitrobenzylaminocarbonlloieridine 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 for 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 -trans46-terit-Butvloxcarbon ylamin in -vimthlaminocarboni yl oh ie thylamine 530 mg (1.07 mmol) of benzyl 4-trans-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl) cyclohexylmethylcarbamate (starting compound A142) are hydrogenated on palladium/carbon (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 0 C are obtained. A122. 4 -trans-(6-tertButvloxcarbonvilamino-2-methl yrdin-3-vlmethylaminocarbonvi)cyclo hexylmethylamine 1.28 g (2.5 mmol) of benzyl 4-trans-(6-tert-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 -trans-(4-Nitrobenzvaminocarboniicyclohexvmethylamine hydrochlorid 1.5 g (3.83 mmol) of tert-butyl 4-trans-(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-Nitrobenzvlaminocarbonvh)benzvlaminehydrochloride 2.1 g (5.4 mmol) of tert-butyl 4-trans-(4-nitrobenzylaminocarbonyl)cyclohexylmethylcarbamate (starting 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.

B666WOO 09991 - 134 A125. 4-[3-(Imidazol-1 -vl)proovlaminocarbonvllpiperidine 2.6 g (7.0 mmol) of benzyl 4

-[

3 -(imidazol-1-yl)propylaminocarbonyl]piperidin-1-carboxylate (starting compound A146) in 50 ml of methanol are hydrogenated for 1 h on palladium/carbon (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-flmidazol-1-vilbutvlaminocarbonvllphieridine 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 palladium/carbon (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-r5-(Imidazol-1-vl)pentvlaminocarbonvllpiperidine 740 mg (1.86 mmol) of benzyl 4-[5-(imidazol-1-yl)pentylaminocarbonyljpiperidine-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-r6-(Imidazol-1-vil)hexvlaminocarbonvlpiperidine 720 mg (1.74 mmol) of benzyl 4

-[

6 -(imidazol-1-yl)hexylaminocarbonyljpiperidine-1-carboxylate (starting compound A149) in 80 ml of methanol are hydrogenated for 1 h on palladium/carbon (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-[8-(Imidazol-1-viloctylaminocarbonvlpiperidine 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 palladium/carbon (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. 1r 4 (tertButloxcarbonvaminomethylbenzvlaminocarbonilp n 41.7 mg (86.4 mmol) of benzyl 1-[4-(tert-butyloxycarbonylaminomethyl)benzylaminocarbonyl] piperazine-1-carboxylate (starting compound A151) in 1.0 1 of methanol are hydrogenated for 4h on B666WOO 09991 - 135 palladium/carbon (5%). The catalyst is filtered off, the solvent is removed and 30.3 g of the title com pound are obtained as a colorless oil. A131. tert-Butvl 4 -trans-(4-aminobutlaminocarbonvl)cclohexvmethvilcarbamate 1.52 g (3.29 mmol) of tert-butyl

[

4

-(

4 -benzyloxycarbonylaminobutylaminocarbonyl)cyclohexylmethyl] carbamate (starting compound A152) in 85 ml of methanol are hydrogenated for 1 h on palla dium/carbon (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-vimethvl)proponamide 390 mg (119 mmol) of benzyl {2-[(6-aminopyridin-3-ylmethyl)aminocarbonyllethyllcarbamate (starting compound A153) in 60 ml of methanol are hydrogenated for 1 h on palladium/carbon (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. Benzvl 1-F3-(tert-butvloxvcarbonvaminomethvl)benzovilp erazine-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-Benzyl-4-f3-(tertbutloxcarbonlaminomethvl)benzovlminolpiperidine 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.

5666WOO 09991 - 136 A135. Benzyl 1-f3-(tert-butloxvcarbonvaminomethy l)benzvlaminocarbonllpiperazine-1 carboxylate 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 RT for 1.5 h. At 00C, 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 (toluene/ethyl 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-Benzyl4f3(tertbutvloxvcarbonvlaminomethvibenzvlaminocarbonIane 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*C, 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. A l137. B enzyl I I ( e. I t 111 111 11 1 carb o l a m o e h l b .

111 A137. hylbenzvlam inocarbonil 1piperidine-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 THF 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.

B666WOO 09991 - 137 A138. Benz 4 trans3tertbutvliaminmeth vllaminocarbonvlcyclohex 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 for 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. Benzi- 4 3-v.methylaminoc)OXcarbonviaminorli ll iperidin-1 carboxylate A solution of 2.11 g (8.01 mmol) of 4 -(benzyloxycarbonyl)piperidine-l-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. Benzyl 4

(

6 -tert-butyloxvcarbonvlamino-2-methylpyridin-3-vimethviaminocarbonyl) piDeridine-1 -carboxylate 700 mg (2.95 mmol) of 6 -tert-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-Butvl 4-( 4 -nitrobenzlaminocarbonl)piperidine-I-carboxylate A solution of 2.0 g (8.72 mmol) of 4 -(tert-butyloxycarbonyl)piperidin-1-carboxylic acid in 60 ml of THF is treated successively with 6.0 ml (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 B666WOO 09991 - 138 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. Benzyl 4 -trans-(6ert-butvloxcarbonylaminopyri din-3-vieth.iaminocarbonvicyclo hexylmethylcarbamate 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 romethane/methanol = 19:1) and crystallization from diethyl ether, 590 mg of the title compound of m.p. 190-192 0 C are obtained. A143. Benzyl 4 trans(6tertbutvloxvcarbonvamino2methld 3 methylamino carbonvl)cvclohexvlmethvlcarbamate 700 mg (2.95 mmol) of 6 -tert-butyloxycarbonylamino-2-methylpyridin-3-ylmethylamine are reacted with 860 mg (2.95 mmol) of 4-trans-(benzyloxycarbonylaminomethyl)cyclohexylmethylcarboxylic acid 2.06 ml (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-Butvl 4 -trans-(4-nitrobenzvlaminocarbonv)chexm thlb te 4.4 g (24 mmol) of 4 -nitrobenzylamine hydrochloride are reacted with 3.0 g (12 mmol) of 4-trans-(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-Butyl 3 n be laminocarbonl)benzlcarbamate 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 triethylamine, 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.

B666WOO 09991 - 139 A146. Benzvi 4-f3-(imidazol-1-vl)3ro viaminocarbonvllpiperidine-1-carboxylate A solution of 3.3 g (12.6 mmol) of 4 -(benzyloxycarbonyl)piperidine-l-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 over magne sium sulfate. The crude product is chromatographed on silica gel (ethyl acetate/methanol/ammonia = 10:1:0.5) and the product is crystallized from diethyl ether, 2.3 g of the title compound of m.p. 98-103 0 C are obtained. A147. Benzvi 4-4-(imidazol-1-vl)butvlaminocarbonviloioeridine-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 mmol) of hydroxybenzotriazole and 3.64 g (19.1 mmol) of EDC hydrochloride analogously to the preparation of A146. After chromatographic purification (ethyl acetate/methanol/ammonia = 10:1:0.5), 3.6 g of the title compound are obtained as a colorless oil. A148. Benzyl 4 -5-(imidazol-l-vi)gentvlaminocarbonvllpiperidin1-carboxylate 1.28 g (8.36 mmol) 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 acetate/methanol/ammonia = 10:1:0.5), 2.49 g of the title compound are obtained as a colorless oil. A149. Benzyl 4-f6-imidazol-1-vl)hexvlaminocarbonvilpioeridine-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 acetate/methanol/ammonia = 10:1:0.5), 2.45 g of the title compound are obtained as a colorless oil. A150. BenzvlI4-8-(Imidazoll v)octylaminocarbonvllpiperidine-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) B666WOO 09991 - 140 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)benzylaminocarbon11piperazi n1 carboxylate 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 O'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 0 C. A152. tert-Butyl I4-trns-(-benzloxvarbonvlaminobutviaminocarbonvi cclohexvimethyl1 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. BenzY ( 2

-(

6 -aminogridin3vlmethv)aminocarbonvllethylcarbamate 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 triethylamine, 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 acetate/methanol/ammonia = 10:1:0.5). After B666WOO 09991 - 141 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-Benzvloxvcarbonvlamino-1-iminomethl)-t-vox aminocarbonyl)-1-benzyloxvcarbonylindazole A solution of 472 mg (1.0 mmol) of 6 -(1-benzyoxycarbonylamino--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-benzvloxvcarbonvlindole-3-carboxvii acid Hydrogen sulfide is passed into a solution of 8.3 g (44.0 mmol) of 6 -cyano1benzyloxycarbonylindole 3-carboxylic acid in 50 ml of pyridine and 50 ml of triethylamine for 20 min. The mixture is allowed to stand at RI for 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 10 HqN 2 0 3 (204.19), found: [MH*] 205 A156. 6-(1-Benzvloxvcarbonvlaminol-imnomethv3(3amnorominocarbonvi)-1-benz vloxvcarbonvlindazole 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 r 4 6ertBu xvcaronvam in 3 i laminocarbon)pieridin y~crboyl- 30444-ras-fertbuyl xva bnyaminomiethyl)cyclohexvicairbonyl aminoleth-l-vlaminocarbonvil-4-0-benzv-1.

2 -dideoxv-D-alucogvranose 3-0-{2-[4-trans-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonylamino eth-1-ylaminocarbonyl}-4 -benzyl-6-0-(imidazol-1-ylcarbonyl)-1,2-dideoxy-D-glucopyranose (A166, 370 mg, 0.48 mmol) and 4 (6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidine (Al 18, 195 mg, 0.58 mmol) 8666WOO 09991 - 142 are stirred at 50 0 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. 1610C are obtained. MS: calc.: C 4 7

H

69

N

7 0 12 (923.50), found: [MH*] 924.2 A158. 6-0446-tert-Butvloxvcarbonvlaminopyridin-3-vimethylaminoca rbony)Diperidin-1 vicarbonvil-3-04344-trans(tert-,tbuloxvcarbonvaminomethviv exvicarbonvi aminolprop-1 -vlaminocarbonvl}4-0-benzyl-1.2-dideoxy-D-glucopyranose 3-0-{3-[4-trans-(tert-Butyloxycarbonylaminomethya)cyclohexylcarbonylaminojprop-1-ylaminocarbonyl} 4 -0-benzyl-6-0-(imidazol-1-ylcarbonyl)-1, 2 -dideoxy-D-glucopyranose (A167, 330 mg, 0.38 mmol) and 4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidine (Al 18, 155 mg, 0.468 mmol) are stirred at 500C 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 (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: calc.: C 4 8

H

71

N

7 0 12 (937.51), found: [MHj 938.2 A159. 6

-

4 6-tertButoxvcaron vid 3 thylaminocarbonii vicarbonvil- 3-04444-trans-ftert-butvloxvcarbonvlaminomnethvi)cyclohlexvlca3rbonvi aminolbut-1 -vlaminocarbonyll-4-0-benzvi-1, 2 -dideox-D-glucopyranose 3-0-{4-[4-trans-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonylamino but-1-ylaminocarbonyl}-4 O-benzyl-6-0-(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 500 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 diethyl ether and 120 mg of the title compound of m.p. 1610C are obtained. MS: calc.: C 4 9

H

73

N

7 01 2 (951.53), found: [MH*] 952.2 Isooovv0o 09991 -143 A160. 6 -0 44 434tert-Butvloxvcarbonvlaminomethvl)benzovilDi erazin-1-vicarbonvl-3-04446 tertbutloxvcarbonlamino Iill ocarbonv)piperidin--vcarbonvl}-4 O-benzvl-1.

2 -dideoxv-D-alucoDvranose A solution of 3-0-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1 ylcarbonyl]-4-0-benzyl-6-0-(imidazol-1-ylcarbonyl)-1, 2 -dideoxy-D-glucopyranose (Al 69, 140 mg, 0.2 mmol) in 1 ml of DMF is combined with a solution of 1-[ 3 -(tert-butyloxycarbonylaminomethyl) benzoyllpiperazine (Al 12, 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 (dichloromethane/methanol = 29:1). 170 mg of the title compound are ob tained. MS: calc.: C 49

H

5

N

7 0 12 (943.47), found: [MH*j 944.1 A161. 6 -044-r34tert-Butyloxvcarbonvaminomethyl)benzoV aminolpiperidin-1-vcarboni-3-0

[

4 6 -tert-buvloxcarbonviaminopyridin-3-vimethylaminocarbon ) -iveridin-I carbonvil-4-O-benzvi.-11. 2 -dideoxv-D-alucopvranose A solution of 3-0-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1 ylcarbonyl]-4-0-benzyl-6-0-(imidazol-1 -ylcarbonyl)-1 2 -dideoxyDglucopyranose (Al 69, 140 mg, 0.2 mmol) in 1 ml of DMF is combined with a solution of 4

-[

3 -(tert-butyloxycarbonylaminomethyl) benzoylamino]piperidine (Al 13, 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 serniconcentrated 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 (dichloromethane/methanol = 19:1). 180 mg of the title compound are obtained. MS: calc.: CsoH 67

N

7 0 12 (957.48), found: [MH*] 958.1 A162. 6 -0 4 4 f34tert-Butloxvcarbonviaminometh vlaminocarbonvilperidin--vi carbonvil-3-04446-tert-butloxvcarbonviaminopyridin-3-vimethylaminocarbonyl) Diperidin-1-vicarbonll4 -benzvideoxv-D e A solution of 3-0-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyI)piperidin-1 ylcarbonyl]-4-0-benzyl-6-0-(imidazol-1 -ylcarbonyl)-1, 2 -dideoxy-D-glucopyranose (Al 69, 140 mg, 0.2 mmol) in 1 ml of DMF is combined with a solution of 4 -[3-(tert-butyloxycarbonylaminomethyl) benzylaminocarbonyllpiperidine (Al 16, 90 mg, 0.26 mmol) in 2 ml of DMF and stirred for 5 days at 5666WOO 09991 -144 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 (dichloromethane/methanol = 19:1). 190 mg of the title compound are obtained. MS: calc.: C 51 HesN 7 0 1 2 (971.50), found: [MH*j 972.2 A163. 6 -0 4 4 -trans43-tert-Butvloxvcarbonvlaminomethl)bnzvlanocrbonvilcyclohex methlaminarbonl344tebul laminopyridin-3-vimethylamino carbonyl))iperidin-1-vcarbonvil-4-0-11benzvi-1

.

2 -dideoxv-D-1alucovranose A solution of 3-O-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyI)piperidin-1-yl carbonyl]-4-O-benzyl-6-0-(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-butyloxycarbony aminomethyl)benzylaminocarbonyllcyclohexylmethylamine (Al 17, 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 (dichloromethane/methanol = 19:1). 150 mg of the title com pound are obtained. MS: calc.: C 53

H

73

N

7 0 1 2 (999.53), found: [MH* 1000.2 A164. 6

-

4 r3(tertButloxvcarbonvaminome nzvlaminocarbnli-erazin--v carbonvl-3-044-(6-tert-butvloxvcarbonylaminopyridin-3-vimethylaminocarbnv) Diperidin-1-vicarbonvll-4-0-benzvl-1.

2 -dideoxv-D-gluco vranose A solution of 3-0-[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 mmol) in 1 ml of DMF is combined with a solution of 1-[3-(tert-butyloxycarbonylaminomethyl) benzylaminocarbonyllpiperazine (Al 14, 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 (dichloromethane/methanol = 19:1). 240 mg of the title compound are obtained. MS: calc.: C 5 OHe 8

N

8 0 12 (972.50), found: [MH* 973.1 bs6WOO 09991 - 145 A165. 6-o-( 4 -r34tert-Butloxvcarbonvlaminomethylibenzvlaminocarbnvlaminolpieidin-vi carbonll3 4 .tebutloxvcan-3-vimethylaminocarbonvi) DiDeridin- -vicarbonvlI-4-O-benzvi-1. 2 -dldeoxv-D-glucopyranose A solution of 3-0-[4-(6-tert-butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-yl carbonyll-4-0-benzyl-6-0-(imidazol-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 (Al 15, 100 mg, 0.26 mmol) in 4 ml of DMF and stirred for 6 days at 50 0 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: calc.: C 51 1H 70

N

8 0 12 (986.51), found: [MH* 987.2 A166. 3-04244-trans-(te t-Butvloxvcarbonv-aminomethyl)cyclohexvicarbonviamino1-eth-1-vi aminocarbo iyl)-4..Oben l-60lmld ol-l -lcarbonyl)-1.

2 -dideoxv-D -lucopyranose 3-0-{2-[4-trans-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonylaminoleth-1-ylaminocarbonyl}-4 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 -0 4 3 44-trans-(tert-Butvloxvcarbonvlaminomethyl)cyclohexvicarbonvlaminorp1-vi aminocarbonvl-4-O-benzvi-6-0-imidazol- -vicarbonvl)-1.

2 -dideoxv-D-lIucopyranose 3-0ac3-[4-trans-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonylaminoprop-1-ylaminocarbonyl} 4-O-benzyl-1 2 -dideoxy-D-glucopyranose (A171, 220 mg, 0.38 mmol) and 95 mg (0.59 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 -0 4 4 44-trans-(tert-Butloxvcarbonvaminomethyl)cyclohexvcarbonvlamino1t -i aminocarbonvil-4-0-benzvl-6-0-(imidazol- -vlcarbonvl)-l.

2 -dideoxv-D-glucopvranose 3-0ac4-[4-trans-(tert-Butyloxycarbonylaminomethyl)cyclohexylcarbonyl]aminobut-1-ylaminocarbonyl} 4 -O-benzyl-1 2 -dideoxy-D-glucopyranose (Al 72, 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 dichlokS656WO0 09991 - 146 romethane. The combined organic phases are dried over magnesium sulfate. 220 mg of the title com pound are obtained as a colorless foam. A169. methylaminocarbonli n vcarbonvi4ben 6 (imidazoll-vcarbonv)-.2-dideoxy-D-gluoranose 3-0-[4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidin-1-ylcarbonyl]-4-0 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. clohexvcarbonylaminoleth-1-vi aminocarbonvl)..4...benzvl-1. 2 -dideoxv-D-glucopvranose 2.6 ml (2.6 mmol) of a 1 M solution of tert-butylammonium fluoride in THF are added dropwise to a solution of 3-0-{2-[4-trans-(tert-butyloxycarbonylaminomethyl)cyclohexylcarbonylamino]eth-1-ylamino carbonyl}-4-0-benzyl-6-0-tert-butyldimethylsilyl-1, 2 -dideoxy-D-glucopyranose (Al 74, 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 -0 4 3 44-trans4tert-Butvloxvcarbonviaminomethyl)cyclohexvicarbonviaminolpro -vi aminocarbo nvll-4.Obenzl v-1.

2 -dideoxy-D-glucopyranose 2.1 ml (2.1 mmol) of a 1 M solution of tert-butylammonium fluoride in THF are added dropwise to a solution of 3-0-{3-[4-trans-(tert-butyloxycarbonylaminomethyl)cyclohexylcarbonylamino prop-1-yl aminocarbonyl}-4-0-benzyl-6-0-tert-butyldimethylsilyl-1,2-dideoyDguoyaoe(15 3 g ~~ ~~-dieoxy-D-glucopyranose (Al175, 730mg 1.05 mmol) in 15 ml of THF. After stirring at RT for 3 h, the mixture is hydrolyzed with water and extracted with 3x 50 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate and concentrated. The crude product is purified by chromatography (dichloromethane/methanol = 19:1). 2 60 mg of the title compound of m.p. 199-202"C are obtained. A172. 3 -0 4 4 44-trans4tert-Butvloxvcarbonviaminomethyl)cyclohexviarbonylaminolb u-vi aminocarbonvrl -4...benzvi-1.

2 -dideoxv-D-glucopvranose 1.7 ml (1.7 mmol) of a 1 M solution of tert-butylammonium fluoride in THF are added dropwise to a solution of 3-0-{4-[4-trans-(tert-butyloxycarbonylaminomethyl)cyclohexylcarbonylamino]but-1-yl- UMUVOO 09991 - 147 aminocarbonyll-4-O-benzyl-6-0-tert-butyldimethylsil

-

2 -dideoxyglucopyran (A76, 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 -04446-tert-Butloxvcarbonvlaminopridin-3-vimethylaminocarboniDierdin-1 carbonll-4-0-benzvi-1. 2 -dideoxv-D-glucopyranose 4.56 ml (4.56 mmol) of a I M solution of tert-butylammonium fluoride in THF are added dropwise to a solution of enz 4-(6-tert-butylox-nopy n -ylmethylaminocarbonyl)piperidn-1 ylabnl---eny -- etbtydmtysli1 2 -dideoxy-o-glucopyranose (Al 77, 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 0 4 2 44-transtert-ButloxvcarbonviaminomethyI)cyclohexvicarbonvlaminoleth--vi aminocarbonvll-4-0-benzv-6-O-tert-butldi ethylsilvi-1.

2 -dideox-D -Qluc vranose tert-Butyl [4-trans-(2-aminoethylaminocarbonyl)cyclohexylmethyl]carbamate (A179 50 1.67 mmol) and 4 -0-benzyl-3-0-(imidazol-1-ylcarbonyl)-6-0-tert-butyldimethylsilyl-1 ,2-dideoxymg glucopyranose (A178, 625 mg, 1.4 mmol) in 10 ml of DMF are stirred at ,C for 5 days. The reaction mixture is largely freed from the solvent and treated with saturated NaCl 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). 990 mg of the title compound are obtained as a colorless glass. A175. 3 -0 4 3 4r4-trans4tert-Butvloxvcarbonvlaminomethl cycohevrbonaIn Po-1 aminocarbonyl}-4-O-benzl-6--ert-butldim thylsilv-1.2-dideoxv-D-lucopyranose tert-Butyl

[

4 -trans-(3-aminopropylaminocarbonyl)cyclohexylmethyl]carbamate (A180 500 1.67 mmol) and 4 -0-benzyl-3-0-(imidazol-1-ylcarbonyl)-6-0-tert-butyldimethylsilyl- 1 2-dideoxy.D glucopyranose (A178, 595 mg, 1.33 mmol) in 10 ml of DMF are stirred at 50 0 C for 5 days. The reaction mixture is largely freed from the solvent and treated with saturated NaCa 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). 790 mg of the title compound are isolated as a colorless foam.

tsubbWOO 09991 - 148 A176. 3

-

44 44-trans(tert-Butloxvcarbonlaminomethyl)cyclohexvcarbonvlaminolbut-1-vi aminocarbonl4 benzvl-6-0-tert-butdh lsilvi-1.

2 -dideoxv-D-glucopvranose tert-Butyl

[

4 -trans-(4-aminobutylaminocarbonyf)cyclohexylmethyl]carbamate (A131 550 1.67 mmol) and 4 -0-benzyl-3-O-(imidazol-1-ylcarbonyl)-6-O-tert-butyldimethylsily 1 1,2-dideoxy

D

glucopyranose (A178, 625 mg, 1.4 mmol) in 10 ml of DMF are stirred at 50 0 C for 5 days. The reaction mixture is largely freed from the solvent and treated with saturated NaCl 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. 3-0-r4-(6-tert-Butyloxvcarbonylaminopyridin-3-vimethylaminocarbonvilpieridin vlcarbonll 1--benvl-6- rtBbutdth iri-.

2 -dideox-D-glucoovranose 4-(6-tert-Butyloxycarbonylaminopyridin-3-ylmethylaminocarbonyl)piperidine (Al 18, 2.7 g, 8.07 mmol) and 4 -0-benzyl-3-0-(imidazol-1-ylcarbonyl)-6-0-tert-butyldimethylsilyl, 2 -dideoxy-D-glucopyranose (Al178, 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 NaCl 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 (toluene/ethyl acetate = 1:1 - ethyl acetate). 1.92 g of the title compound are obtained as a colorless oil A178. 4 -O-Benzv-3-O-(imidazol-l-vicarbonvl)-6-O-tert-butvdimethylsilv-1.2-dideoxv-D-gluco ovranose 8.8 g (25 mmol) of 4 -0-benzyl-6-0-tert-butydimethylsilyl-1, 2 -dideoxy-D-glucopyranose and 5.26 g (32.5 mmol) of carbonydiimidazole 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. Al 79. tert-Buty cvmtranse(2tyacinoethalaminocaabontcleh tert-Butyl [4-trans-(2-benzyloxycarbonylaminoethylaminocarbonyl)cyclohexylmethylcarbamate (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. 11 7-118*C are obtained.

B666WOO 09991 - 149 A180. tert-Butyl

R

4 -trans-(3.-aminopropvlaminocarbonvi)cychexvlmethvllcarbamate tert-Butyl

[

4 -trans-(3-benzyloxycarbonylaminopropylaminocarbonyl)cyclohexylmethylcarbamate (A182 1.42 g, 3.17 mmol) in 70 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. 940 mg of the title compound are obtained. A181. tert-Butvl r4-trans-(2-benzvloxvcarbonvaminoethvla.inocarbonvicyclohexvimethyll 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, 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 diisopropyl ether, 1.58 g of the title compound are obtained as a colorless solid of m.p. 168-1 7000. A182. tert-B etl 4 -trans-(3-benzloxvcarbonvlaminoropylaminocarbonvilcyclohevmethy Sabmate 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 hydroxybenzotrazole 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 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 crystallization from diisopropyl ether, 1.54 g of the title compound are obtained as a colorless solid of m.p. 135-137oC.

5566WOO 09991 - 150 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, ax2, pia, 01b, p2, p3, 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. Nati. Acad. Sci., USA 87 (1990) 3811-3815; Pallaoro et al., J. Biol. Chem. 274 (1999) 3355 3362). Only the P-tryptases (Schwartz et al., J. Clin. Invest. 96 (1995) 2702-2710; Sakai et al., J. Gun. 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". Marcel 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, I80 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 and/or 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 and/or prophylaxis of the diseases mentio ned.

B666WOO 09991 - 151 Furthermore, the invention relates to medicaments for the treatment and/or 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 iv.) is between 0.1 and 10 mg per ki logram per day.

B666WO0 09991 - 152 Biological investigations The documented pathophysiological effects of mast cell tryptase are caused directly by the enzymatic activity of the protease. Accordingly, they are reduced and/or 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 Ki 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. Methodologyi 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 pg/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 Kpp (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/Vo = 1 - {Et+lt+Kapp-(Et+t+Kiapp)2-4EIt]2/ 2 Et In this equation, V and V are the rates in the presence and absence of the inhibitor and Et and It 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, in which the numbers of the compounds correspond to the numbers of the com pounds in the examples.

B666WOO 09991 - 153 Table Inhibition of human tryptase Compound Kiapp (pM) 1 0.13 2 0.16 3 0.0009 4 0.075 5 0.0013 6 0.150 7 0.035 8 0.015 9 0.02 10 0.014 11 0.07 12 0.06 13 0.02 14 0.014 15 0.001 16 0.002 17 0.15 18 0.09 19 0.011 20 0.039 21 0.005 22 0.05 23 0.2 B666WOO 09991 -154 Compound Kipp (pM) 24 0.031 25 0.13 26 0.12 27 0.14 28 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 0.2 44 0.5 50 0.08 52 0.24

Claims (10)

1. A compound of the formula I /B1-Al-B3-A3-B5-A5-K1 M \B2-A2-B4-A4-B6-A6-K2 in which Al and A2 are identical or different and are -C(O)-, -NH-, -0- (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)-0- or a bond, A3 and A4 are identical or different and are -C(O)-, -0-, -S-, -NH-, -0-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 -0- (oxygen), -S- (sulfur) or -CH 2 - (methylene), G is -0- (oxygen) or -CH 2 - (methylene), and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -0-, -S-, -0(O)-NH-, -NH-C(O)-, -0-0(0)-, -C(O)-a-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the following list "6UWO0 09991 -156 R4 R4 UR R5 RR

3 RSR3 R2 R2 0 R2 0 R4 U R4 R5 R 5 R 3 W 0-W 0W 0 R1 RI RI U R4 W U -- R 1W R R5 R2 O R2 RI R1 W R3 R2 O R1 where U and W are identical or different and are -0- (oxygen), -S- (sulfur) or -NH-, RI is hydrogen, hydroxyl, 1-4C-alkoxy, 1-

4 C-alkylcarbonyloxy or Ar-1-4C-alkoxy R2 is hydrogen, hydroxyl, 1-4C-alkoxy, 1- 4 C-alkylcarbonyloxy or Ar-1-4C-alkoxy, R3 is hydroxyl, 1-4C-alkoxy, 1- 4 C-alkylcarbonyloxy or Ar-1-4C-alkoxy R4 is hydroxyl, cyano, 1-4C-alkoxy, 1- 4 C-alkylcarbonyloxy or Ar-1-4C-alkoxy R5 is hydroxyl, 1-4C-alkoxy, 1- 4 C-alkylcarbonyloxy or Ar-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)R7-0-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-Zi-B1 1-X1 K2 is -B 8 -(C(0))p-B1O-X2, -B8-(C(O))p-B1o-Y2 or -B8-(C(o))p-B1o-Z2-B12-X2, 5666W00 09991 -157 B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene B7, B8, B9, BIO, 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 0 NH NH NH 2 NH 2 NH 2 NHOH NH N -N NH NH H NH H NH 2 N-R8 Z N =< 2 H 0 NH 2 --- S NH NH NH ---N NH 2 S--R8 H N H 2 NH N-NH NH 2 where R8 is 1-4C-alkyl, Y1 and Y2 are identical or different and are a 4-11 C-heteroaryl or 2 - 7 C-heterocycloalkyl radical, comprising at least one ring nitrogen, Z1 and Z2 are identical or different and are 5-12C-arylene,

5-1 2 C-heteroarylene, 3 - 8 C-cycloalkylene or 3 - 8 C-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, B4, B5, B6, B7, B8, B9,B 10, B11 or B12 assume the meaning of a bond and direct linkage between two heteroatoms or two carbonyl groups would thereby occur. B666WOO 09991 -158 2. A compound of the formula I as claimed in claim 1, in which Al and A2 are identical or different and are -C(O)-, -NH-, -0-, -C(O)-NH-, -NH-C(O)-, -0-C(O)-, -C(0)-0- or a bond, A3 and A4 are identical or different and are -C(O)-, -0-, -NH-, -0-C(O)-, -C(0)-0-, -C(O)-NH-, -NH-C(O)- or a bond, or are selected from the group II I I I T T T T T II I N N N EN where E is -0- (oxygen), -S- (sulfur) or -CH 2 - (methylene) and T is the group -C(O)- or a bond, A5 and A6 are identical or different and are -C(O)-, -NH-, -0-, -C(O)-NH-, -NH-C(O)-, -0-C(O)-, -C(0)-0-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the list below B666WOO 09991 - 159 R4 R4 U R R3 RU R4 R5 R5 RR5 U R2 R2 R2 0 R4 U R4 R5 R5 U-- 000 WO-W )O I- W * R1 RI RI U R4 R5U R2 O R2 O RI RI W R3 R2 O RI where U and W are identical or different and are -0- (oxygen), -S- (sulfur) or -NH-, R1 is hydrogen, hydroxyl, 1-4C-alkoxy, 1- 4 C-alkylcarbonyloxy or Ar-1-4C-alkoxy R2 is hydrogen, hydroxyl, 1-4C-alkoxy, 1- 4 C-alkylcarbonyloxy or Ar-1-4C-alkoxy R3 is hydroxyl, 1-4C-alkoxy, 1- 4 C-alkylcarbonyloxy or Ar-1-4C-alkoxy R4 is hydroxyl, cyano, 1-4C-alkoxy, 1- 4 C-alkylcarbonyloxy or Ar-1 -4C-alkoxy, R5 is hydroxyl, 1-4C-alkoxy, 1- 4 C-alkylcarbonyloxy or Ar--4C-alkoxy or where two adjacent radicals (R2 and R3, R3 and R4, or R4 and R5) are an alkylenedioxy group [-O-C(R6)R7-0-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-ZI-B11-X1 K2 is -B8-(C(O))p-B1O-X2, -B8-(C(O))p-B1O-Y2 or -B8-(C(O))p-B1O-Z2-B12-X2, 5666WOO 09991 - 160 B1, B2, B3, B4, B5 and B6 are identical or different and are a bond or 1-4C-alkylene, B7, B8, 89, B10, 811 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 0-NH2 NH NH NH 2 NH 2 NHOH NHH -N NH NH H NH2 NH 2 N-R8 H 0 NH 2 S NH NH NH NH 2 S-R8 H NH 2 NH N-NH 2 NH 2 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-y, 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 B666WOO 09991 - 161 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, 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 Al and A2 are identical or different and are -C(O)-, -0-, -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 I I I IT T T T T T N 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)-, -0-C(O)-, -C(O)-a-, -NH-C(O)-NH- or a bond, M is a pyranose unit selected from the list below R4 R4 R3 W 0 U R2 rU WU U RI RI where U and W are identical or different and are -0- (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, KI is - 8 7 -(C(O))m-B9-X1, -B7-(C(O))m-B9-Y1 or -B 7 -(C(O))m-B9-Z1-B11-X1, K2 is -B 8 -(C(O))p-B1O-X2, -B 8 -(C(O))p-B10-Y2 or -B 8 -(C(O))p-BI1o-Z2-B12-X2, tsbuUWOO 09991 - 162 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 1-4C-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 -NH 2 0 NH -N NH NH 2 NH 2 H NH 2 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-y, 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-y, pyrimidin-5-yl, pyrimidin-4-yl, indol-3-yl, ben zirrudazol.4-yl or benzimidazol-5yl, Zi 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, 89, B10, B11 or 812 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 Al 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 I, 4 -cyclohexylene 1, 3 -phenylene or a bond, A5 and A6 are identical or different and are -C(O)-, -C(0)-NH-, -NH-C(O)- or -NH-C(O)-NH-, M is a pyranose unit selected from the following list R4 R4 R3 ' w ~ U> 00 W R2 0 RI R1 B666WOO 09991 -163 where U and W are identical or different and are -0- (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-Bl 1-X1, K2 is -B8-(C(O))p-B1O-Y 2 or -B 8 -(C(O))-B1O-Z2-B12-X2, 61 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 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 O NH N -NH 2 -- N NH NH 2 NH 2 H NH 2 YI 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 612 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-0-[4-(trans-4-aminomethylcyclohexylcarbonyl)piperazin-1-ylcarbonyl]-4-O-benzyl-1,2-dideoxy-D glucopyranose; 3,-iO[-tas4aioehlccoeycroy~ieai- -ylcarbonyl]1 , 2 -dideoxy-D-gluco pyranose; B666W00 09991 -164 4-0benyl-,2-idexy3,6di--[4(4-uanioenzylamnocarbonyl)piperazin-l-yicarbonyll-D-gluco pyranose; 3,-iO[-(rn--mnoeh Ilheycroy)pieai-ylcarbonylmethY1llA-0benzyl 1 ,2-di deoxy-D-glucopyranose; 3,-iO[-4amnmtybnylmncroy)pieai--laboy 40bny-,2-dideoxy-D. glucopyranose; 3,6-di-O-[4-(1 -amidinopiperidin-4ylacetyl)piperazin-1 -ylcarbonyll4O0benzyll , 2 -dideoxy-D-gluco pyranose; 3,-iO[-tas4aioeh ccoeycroy~ieai--ylcarbonyll-4O0benzyll ,2-dideoxy-D galactopyraflose; 3,-iO[-(rn--mnoehlylheycroy)pieai -ylcarbonylj-1 , 2 -dideoxy-D..galacto. pyranose; 3,-iO[-aiionaol3ycroy ieai--ylcarbonyl]-4-0-benzyI1 , 2 -dideoxy-D-gluco pyra nose; methyl 3,-iO[-tan--mnmtycy hxlabnl)pierzi -ylcarbonyII-4-0Obenzyl-2 deoxy-ax-D.glucopyrafloside; methyl 3,-iO[-(rn--mnoehlylheycroy)pieai -ylcarbonyl-2deoxyaD glucopyranoside; 3,-iO[-tas4aioehlccoeycroy~ieai- -ylcarbonylmethyll-1,2-dideoxy-D. glucopyranose; 6 -O-[ 4 -(4-aminomethylbenzyaminocabonyl)pipei1lcabnl---4(ras4aioeh cyclohexylcarbonyl)piperazin- l-ylcarbonyl-40obenzyl-1,2ddoy- lcpyao benzyl3,6diO44(trans4aminom ethlcylohxlcroypiean -ylcarbonylI-2-deoxy-a-D glucopyranoside; 3,-iO[-4aioetybnyaioabnl)pieai- -ylcarbonylmethylII..0-benzyl 1,2 dideoxy-D-glucopyranose; 3,-iO[-4amnmtybnIimncroy)pieai- -ylcarbonylmethylll , 2 -dideoxy-D-gluco pyranose; 3,-iO[-tas4aioehlccoeycroy~ieai- -ylcarbonyll-4o0methyl.1 ,2-dideoxy-D galactopyralose; methy 2,6di-O[4-(tans--amiomtylcyclohexylcarbonyl)piperazin-I -ylcarbonyl]-cX-D glucopyraflosjde; methyl 3 , 6 -di-O-f4(4aminomethylbenzylaminocarboni)pierzi-ylcarbonylI-40-benzyl2deoxy-(.. D-giucopyranoside; methyl 2,-iO[-4aiomtybnyaioaroy ieai--ylcarbonyl-3,4diobenzyI.a-D glucopyraflosjde; methyl 3,-iO[-4aiomtybnyaioaroy ieai--ylcarbonyl]-2-deoxy..-D glucopyrafloside; hexylcarbonyl)piperazin-l-ylcarbonyl].4o0benzyl 1 2 -dideoxy-D-glucopyranose; B666W00 09991 - 165 3 -O-[ 4 -(trans4aminomethycycohexycarbony)pipi-1-ylcarbonyiI-6O0[5-(2aminomethy pyridylcarbonyl)-l-aminopentyll-4O0benzy..1,2ddoy- lcpyao 6 -N-[ 4 (trans4aminomethylcyclohexylcarbony)-4-aiouy--xcroyl30[-tas4ai methylcyclohexylcarbIony)piperazin-1-ylcarbonyI-4-0-benzy.11 ddox--lcoyao 6 -0-[ 4 -(trans-4aminomethycyecaonyl)-amoyI) 5 ilI 3 0[4(rn-amoetyclo hexylcarbonyl)piperazin.1 -ylcarbonyl]-1 . 2 -dideoxy-Doglucopyranose; 3 , 6 -Di-O[4(trans4aminomethycycohexycbonI)-5-aioet -40bny,2-dideoxy-D-gluco pyranose; 3 , 6 -di-O-[4(trans4-aminomethycycohexycbonI)-5-aioenyll 2 -dideoxy-D-glucopyranose; 3,-iO[-3aioehlezy~ieai- -ylcarbonyl-4-O-benzyl 1 2 -dideoxy-D-gucopyranose; 3,-iO[-3aioehlbnolmn~ieii- -ylcarbonyll-4-O-benzyl , 2 -dideoxy-D-gluco pyranose; 3 , 6 -di-O-[4(3aminomethybenzyaminocrbny)pierzi- -yI-carbony]-4-0-.benzyl..1 ,2-dideoxy-D glu copyra nose; 3,-iO[-3aioehlezlaioabnlmn~ieii- -ycarbonyl-4o0benzyl ,2-dideoxy D-glucopyranose; 3,-iO[-3amnmtybnIlmncroy)pieii- -ylcarbonyiI-4-c-benzyI1 ,2-dideoxy-D glucopyranose; l, 2 -dideoxy-D-glucopyranose; 3,-iO[-6ainprdn3ymthlmncroy)pieii- -ylcarbonyl]-40benzyl ,2-dideoxy-D glucopyranose; 3 -O-[ 4 (4aminomethybenzyaminocarbony)piperai- -ycarbonyI]-40benzy6O0[ 4 -( 6 aminopyridin3ylmethylamnocarbonyl)pipeidi- -ylcarbonyl]-i , 2 -dideoxy-D-gucopyranose; 3 -O-[ 4 (4-aminomethybenzyaminocarbony)piperai- -ylcarbonyll.40benzy160 [4-(6-amino-2 methypyridin3ymethylaminocarbonyl)pipidn- -ylcarbonyl]-i , 2 -dideoxy-o-glucopyranose; 3 -O-[ 4 -(4-aminomethybenzyaminocarbony)pipern- -ycarbonyl-40benzy60-[ 4 -( 4 aminobenzylaminocarbonyl)piperidin-1 -ylcarbonylj-1 , 2 -dideoxy-D-ggucopyranose; 3 -O-[ 4 (4aminomethybenzyaminocarbony)piperi- -ylcarbonyI4-0benzy6O0[4-trans-( 6 aminopyridin 3 ylmethylaminocarbonyl)cychlthyainoa nyl1 2 -dideoxy-D-glucopyranose; 3 -O-[ 4 -(4-aminomethylbenzylaminocarbonyl)piai1lcabn --- bny---4trn-6ai 2 -methylpyridin3ylmethylaminocarbonyl)lhxlehlaioaboy]1 2 -dideoxy-D-gluco pyra nose; 3 -O-[ 4 -(4-aminomethybenzyamnocarbony,)piperi- -ylcarbonyI]-4-0benzy6O0[4-trans-( 4 aminobenzylaminocarbony)cyclohexylmthl. ncabnyj 2 -dideoxy-D-glucopyranose; 3 -O-[ 4 (4aminomethybenzyaminocarbony)piperan- -yicarbonyII-40benzyI-6O [3 (4-amino benzylaminocarbonyl)benzylaminocarbonyll-12ddox-- coyaoe 3 -O-[ 4 (4-aminomethybenzyaminocarbony)piperi- -ylcarbonyiI-40benzyI6O {4-[3-(imidazol- 1 yI)propyaminocarbonyllpperidn-1 -ylcarbonyl}-1 , 2 -dideoxy-D-glucopyranose; B666W00 09991 -166 3 -O-[ 4 -( 4 -aminomethylbenzylaminocarbonyl)piperazin-1-YicarbonyII-40-benzy6O{4-[4-(imidazo 1 yI)butylaminocarbonyllpiperidin-1 -yicarbonyl}- 1, 2 -dideoxy-D-glucopyranose; 3 -O- 1 4 -( 4 -aminomethybenzyaminocarbonyl)piperazin-1-yicarbonyI-40-benzyI6O{4-[5(imidazo 1 yI)pentylaminocarbonyj]piperidn-1 -ylcarbonyl}-1 , 2 -dideoxy-D-gucopyranose; 3 -O-[ 4 -( 4 -aminomethylbenzylaminocarbonyl)piperazin-I -ylcarbony]-4O-benzy6O0{4[6-(imidazoI-1 yI)hexylaminocarbonyl]piperidin-1 -ylcarbonyl}- 1,2ddoy--lcpyao 3 -O-[ 4 -(4-aminomethylbenzylaminocarbonyl)piperazin-1 -ylcarbonyI-4O-benzy6o{4-[8-(imidazol-1 yl)octyiaminocarbonyj]piperidinl1 -ylcarbonyl}-1 . 2 -dideoxy-D-glucopyranose; 3 -O-[ 4 -(6-aminopyridin3ylmethylaminocarbonyI)piperidin-1 -ylcarbonyl-6-0{4-44trans(amino methyl)cyclohexylcarbonyllaminobut-1 -ylaminocarbonyl40benzyl1 2 -dideoxy-D-glucopyranose; 3 -O-[ 4 -( 6 -aminopyridin-3-yimethylaminocarbonyI)piperidin-1 -ylcarbonyl-6-0[44(4-aminomethyl benzylaminocarbonyl)piperazinl1 -ylcarbonyl]-4-O-benzyj 1,2ddoy- lcpyaoe 3 -O-[ 4 -( 4 -aminomethylbenzylaminocarbonyl)piperazin-1 -ylcarbony]602(6aminopyrdin-3-yl methylaminocarbonyl)ethl1 -yI-aminocarbonyl]-4-0-benzyl.1,2ddoy- lcpyao 3 -O-[ 4 -( 4 -aminomethylbenzylaminocarbonyl)piperazin- lYcarbony]-40benzyI-6O0{3.{(6-amidino- 1 H-indazol-3-yI)carbonylaminoproplI -ylaminocarbonyi}1 , 2 -dideoxy-D-glucopyranose; 3 -O-[ 4 -(4-aminomethylbenzylaminocarbonyl)piperazin-1 -ylcarbony]-4-0-benzy60{3f(6-amino carbonyl-1 -H-indazol-3-y)carbonylamnolprop-I -ylaminocarbonyi}-1,2ddoy- lcpyao 3 -O-[ 4 -(4-aminomethylbenzylaminocarbonyl)piperazin-1 -ylcarbonyI-60O{2(6-aminocarbonyl-1 -H indol-3-yI)carbonylaminoleth-1 -ylaminocarbonyl}-1,2ddoy- lcpyao 3 -O-[ 4 -( 4 -aminomethylbenzyaminocarbonyl)piperazin-1 -ylcarbony]-4--benzy6O{3-[(6-amino carbonyl-1 -H-indol-3-yI)carbonylaminoprop.1 -ylaminocarbonyl}1 , 2 -dideoxy-o-glucopyranose; 3 -O-[ 4 -(4-aminomethybenzyaminocarbony)piperazin-1 -ylcarbony]40-benzyI6O0{4-[(6-amino carbonyl-1 -H-indol-3-y!)carbonylamino]but.1 -ylaminocarbonyl}-1,2ddoy--lcpyao 6 -O-[ 4 -(6-aminopyridin-3ymethyaminocarbonyl)piperidin-1 -ylcarbonyII-3O4-2(4-trans-aminomethy cyclohexylcarbonylamino)eth-1 -ylaminocarbonyl40benzyll 2ddox--lcoyaoe 6 -O-[ 4 -( 6 -aminopyridin-3ylmethylaminocarbonyI)piperidin-1 -ylcarbonyI-303(4trans-aminomethy cyclohexylcarbonylamino)propl1 -ylaminocarbonyl]4-0benzyl1,2ddoy--lcpyaoe 6 -O-[ 4 -(6-aminopyridin3ylmethyaminocarbony)piperidiIlcabn --- 4(-tasaioehl cyclohexylcarbonylamino)butl1 -yaminocarbonyl]40benzyl1, 2 -dideoxy-D-glucopyranose; 6 -O-1 4 -( 3 -aminomethybenzoyl)piperazin-1lcabnl -- 4(-mnpyii--lmtyaio carbonyl)piperidinl1 -ylcarbonyll-4-O-benzyll 2ddox--lcoyaoe 6 -O-[ 4 -(3-aminomethylbenzoylamino)piperidin-I -ylcarbony]30O4(6aminopyridin-3ylmethylamino carbonyl)piperidinlI -ylcarbonyI]-4-O-benzyI-1 2 -dideoxy-D-glucopyranose; 6 -O-[ 4 -( 3 -aminomethylbenzylaminocarbonyj)piperidin-1 -ylcarbonyII-304(6aminopyridin-3ylmethyl aminocarbonyl)piperidinl1 -ylcarbonyll-4-0-benzyl 12ddox--lcoyao 6 -O-[ 4 trans(3aminomethybenzyaminocarbonyj)cycxlmthainoabn.--0[-6aio pyridin- 3 -yimethylaminocarbonyl)piperidin-1 -ylcarbonyl]-4-0-benzyll , 2 -dideoxy-D-glucopyranose; 6 -O-[ 4 -(3-aminomethylbenzyiaminocarbonyl)piperazin-1 -ylcarbony!I-30[4(6aminopyridin-3ylmeth ylaminocarbonyl)piperidinl1 -yicarbonyll-4--benzyll 2ddox--lcoyaoe B666WOO 09991 - 167 6 -0-[ 4 -( 3 -aminomethylbenzylaminocarbonylamino)piperidin-1 -ylcarbonyl-3-O-[4-(6-aminopyridin-3-yl methylaminocarbonyl)piperidin-1 -ylcarbonyll-4-0-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 -piperazinylcarbonyll-4-0-benzyl-1,2-dideoxy-D glucopyranose; 3, 6 -di-O-[ 4 -(trans-4-aminomethylcyclohexylcarbonyl)-1 -piperazinylcarbonyl]-1,2-dideoxy-D-gluco pyranose; 4 -0-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]-4-0-benzyl-1,2 dideoxy-D-glucopyranose; 3, 6 -di-O-[4-(4-aminomethylbenzylaminocarbonyl)-1 -piperazinylcarbonyll-4-0-benzyl-1,2-dideoxy-D glucopyranose and 3,6-di-O-[4-(1-amidinopiperidin-4-ylacetyl)-l-piperazinylcarbonyl]-4-0-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. B666WOO 09991 -168 Abstract Compounds of the formula I /B1-Al-B3-A3-B5-A5-K1 MB2-A2-B4-A4-B6-A6-K2 in which M, Al, A2, A3, A4, A5, A6, B1, B2, B3, B4, B5, B6, K1 and K2 have the meanings indicated in the description, are novel efficacious tryptase inhibitors.