KR19990028543A - Diglycosylated as an analog of sialyl-Lewis X and sialyl-Lewis A 1,2-diol - Google Patents

Abstract

X is a non-glycosidic aliphatic 1,2-diol; R ₁ is S-substituted methyl substituted by one carboxyl moiety and one other substituent; Compounds of the general formula (I) as analogues of sialyl-Lewis X and sialyl-Lewis A wherein R ₂ is hydrogen, C _1-12 alkyl or C ₆ aryl are described.

(I)

Description

Diglycosylated as an analog of sialyl-Lewis X and sialyl-Lewis A 1,2-diol

The present invention is based on the finding that the natural saury analogue neuraminic acid residue is replaced by methyl of the S-configuration substituted by one carboxyl residue and one other substituent, and the N-acetyl-glucosamine residue is replaced by the 1,2- Analogs of sialyl-Lewis X and sialyl-Lewis A which are replaced by non-glycosidic moieties, methods for their preparation and use of these analogs in therapeutic methods.

The complex process of inflammation that occurs in several steps is, for example, the natural reaction of the body to the trauma, if invasion by infectious agents is also present. Under the influence of cytokines, the endothelium that encircles blood vessels expresses adherent proteins on its surface. The P and E selectins perform so-called " rolling " of leukocytes with glycoproteins on the leukocyte membrane and protein-carbohydrate interactions with glycoproteins. The latter is delayed by the process, which activates a specific protein (integrin) on the surface, which strengthens adhesion of the leukocyte to the endothelium. This involves leukocyte migration into the damaged tissue.

If the process occurs in a controlled manner, the damage is removed after a certain time without any major adverse effect remaining. Or, in the case of certain acute and chronic inflammatory processes in which the migration of leukocytes occurs in an uncontrolled manner, this causes severe damage to the body. This is the case of disorders such as cardiogenic shock, myocardial infarction, thrombosis, rheumatism, psoriasis, dermatitis, acute respiratory distress syndrome and metastatic cancer (Dasgupta, F., Rao, B.N.N., Exp. Opin. Invest. Drugs 3: 709-724 (1994)].

Several approaches to developing medicaments at various points in the process that are not desired are already on the market (Dasgupta, F., Rao, BNN, Exp. Opin. Invest. Drugs 3: 709-724 (1994)]. The purpose of one pathway is to prevent the interaction between the P and E selectins and their receptors on the leukocyte membrane using analogues of the corresponding epitope, thereby preventing " rolling ". This also results in inhibition of the subsequent process. One of the minimal carbohydrate epitopes as a ligand for the E-selectin is sialyl-Lewis X [neuraminic acid- alpha - (2 → 3) - galactose - (1 → 4) - (fucose - )) - N-acetylglucosamine (sLe ^x ).

EP-A-0 579 196 is presented as a compound competing with the natural ligand for binding to the E selectin analog of sLe ^x , wherein the neuraminic acid residue is replaced by the lactic acid residue. WO 93/10796 describes compounds comprising a moiety of alpha -hydroxy acid instead of a neuraminic acid residue. WO93 / 23031 describes analogues in which the N-acetylglucosamine residue (GlcNAc residue) is replaced by R, R-1,2-cyclohexanedioxy. However, for all these compounds, it is customary that the binding affinity between these and E-selectin is only small, or actually worsens, compared to that of sLe ^x , and is insufficient for therapeutic effect.

It has now surprisingly been found by the present invention that neuraminic acid residues by methyl of the S-configuration substituted by one carboxyl residue and one other substituent, and N-acetylglucosamine by the non-glycosidic residues of the aliphatic diol By simultaneous replacement of the residues, it has been found that the binding affinity of the analog produced is higher than expected. The novel compounds are also briefly represented in structure and chemistry, the molecular weight is lower, and the synthesis can be obtained in greater amounts in less complex ways.

The present invention relates to compounds of formula (I), including physiologically acceptable salts thereof.

In this formula,

X is a residue of a non-glycosidic aliphatic 1,2-diol;

R ₁ is methyl of the S-configuration substituted by one carboxyl moiety and one other substituent;

R ₂ is hydrogen, aryl C _1-12 alkyl, or C _6, the substituents alkyl and aryl are here OH, _{halogen, C (O) OR s1,} OC (O) R s4, C (O) R s2, nitro , NH _2, cyano, SO ₃ M _{y, y} OSO ₃ M, NR ₂₀ SO ₃ M _y, C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 hetero Aryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 aralkenyl, C _7-10 heteroalkenyl, primary amino, secondary amino Substituted or unsubstituted with at least one substituent selected from the group consisting of a sulfonyl group, a sulfonyl group, a sulfonamide group, a carbamido group, a carbamate group, a sulfone hydrazide group, a carbhydrazide group, a carbohydroxamic acid group and an aminocarbonylamide group , Wherein R _s1 is hydrogen, M _y , C _1-12 alkyl, C _2-12alke C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl; R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 are alkyl or C _6-10 heteroaralkyl, R _s2, and R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _{2 -11} heterocycloalkyl, heteroaryl C _2-11 cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkyl alkenyl Or C _7-10 heteroaralkenyl and wherein said substituent is selected from the group consisting of alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl , Aralkyloxy, heteroaralkyl, aralkenyl and heteroaralkenyl are substituted or unsubstituted by one of the substituents mentioned above, y is 1 and M is a monovalent metal, or y is ½ M is 2 A metal.

Preferred aliphatic residues X are linear or branched C _2-20 -, preferably C _2-12 -, particularly preferably a C _2-6 alkylene and - alkenylene, C _3-12 -, preferably C _{3- 8-} , particularly preferably C _5-7 cycloalkylene and cycloalkenylene, and C _3-11- , preferably C _3-7- , particularly preferably -O-, -S- and -N- C _3-5 -heterocycloalkylene and heterocycloalkenylene having a heteroatom selected from the group consisting of < RTI ID = 0.0 >

The residue X is OH, halogen, C (O) OR _s1 , OC (O) R _s4 , C (O) R _s2 , nitro, NH ₂ , cyano, SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y , C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 hetero cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _{6- 10} heteroaralkyl, _C8-11 aralkenyl, _C7-10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamido, carbamate, sulfone hydrazyl, carb May include substituents such as hydrazide, carbohydroxamic acid and amidocarbonylamide; Wherein R _s1 is selected from the group consisting of hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 hetero Aryl, C _7-11 aralkyl or C _6-10 heteroaralkyl; R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 Aralkyl or C _6-10 heteroaralkyl; R _s2 and R ₂₀ are _{independently selected} from hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocyclo C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl; The substituted alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, ≪ / RTI > alkenyl and heteroaralkenyl are substituted or unsubstituted by one of the substituents mentioned above; y is 1 and M is a monovalent metal, or y is 1/2 and M is a divalent metal.

In a preferred embodiment of the invention, X is a residue of a 1,2-diol corresponding to the formula (II)

In this formula,

R ₅ and R ₆ are each independently selected from the group consisting of hydrogen, C _1-12 alkyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 ar Alkyl or C _6-10 heteroaralkyl; or

R ₅ and R ₆ together with the -CH-CH- group represent a C _3-12 cycloalkylene, a C _3-12 cycloalkenylene, a C _2-11 heteroatom selected from the group consisting of -O-, -S- and -N- is heterocycloalkyl alkylene, or C _3-11 heterocycloalkyl alkenylene, the substituents where the alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkylene, cycloalkylene alkenylene, heterocycloalkyl alkylene and heterocycloalkyl alkenylene is OH, _{halogen, C (O) OR s1,} OC (O) R s4, C (O) R s2, nitro, NH _{2, cyano, SO 3 M y, OSO 3} M y , NR ₂₀ SO ₃ M _y , C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 hetero cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyl, oxy, C _6-10 heteroaralkyl, C _8-11 alkenyl, aralkyl, C _7-10 heteroaralkyl Which is selected from the group consisting of an alkyl group, an alkenyl group, an alkenyl group, an alkenyl group, an alkynyl group, an alkenyl group, an alkynyl group, an alkenyl group, an alkynyl group, It is substituted or unsubstituted by one substituent, where R _s1 is hydrogen, M _y, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _{6 -10} aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 aralkyl and heteroaryl, R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl alkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or a C _6-10 heteroaralkyl, R _s2, and R ₂₀ is hydrogen, C _{1- 12} alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _{5 -9} heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, _C8-11 aralkenyl or _C7-10 heteroaralkenyl, wherein said substituent alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, Aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, aralkenyl and heteroaralkenyl are substituted or unsubstituted by one of the substituents mentioned above, and y is 1 and M is a monovalent metal, y is 1/2, and M is a divalent metal.

The remaining substituents in R ₁ preferably have 1 to 20 carbon atoms, more preferably 1 to 16 carbon atoms, particularly preferably 1 to 12 carbon atoms, and particularly preferably 1 to 8 carbon atoms. The remaining substituents are preferably selected from the group consisting of substituted or unsubstituted C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _{2 -11} hetero cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkyl and C _7-10 alkenyl heteroaralkyl al ≪ / RTI > The remaining substituents are particularly preferably substituted methyl or 2-substituted ethyl or cyclohexyl. Examples of suitable substituents are those mentioned above in the definition of R ₂ , in particular OH, halogen (F, Cl or Br), carboxyl, -SO ₃ H, C (O) OM _y , SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y wherein R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, heteroaryl C _2-11 cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkyl or alkenyl C _7-10 heteroaralkyl or alkenyl, or C _1-12 alkyl, C _1-12 alkoxy, nitro, -NH _2, C 1 -C 20 primary amino, secondary amino, cyano, C having a carbon number of 2 to 30 in _3-8 cycloalkyl, C _3-6 heterocycloalkyl, C _6-10 aryl in, C _3-9 heteroaryl, C _7-16 heteroaralkyl (here, the heteroatoms are selected from O, S and N atoms group ), Carbamides, carbamates, carbhydrazides, sulfonamides, sulfonehydrazides Or an aminocarbonylamide, wherein the N atom is substituted or unsubstituted by a hydrocarbon group or a hydroxy-hydrocarbon group having 1 to 20 carbon atoms. The substituted hydrocarbon group and the heterohydrocarbon group may be substituted or unsubstituted, for example, by C _1-6 alkyl, C _1-6 alkoxy, carboxyl, halogen (F, Cl or Br), -OH, -CN or -NO ₂ .

In a particular embodiment of the compounds of formula I, R < ₁ >

In this formula,

R ₃ is hydrogen or M _y ;

R ₄ is OH, halogen, C (O) OR _s1 , OC (O) R _s4 , C (O) R _s2 , nitro, NH ₂ , cyano, SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y , C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 hetero cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _{6- 10} heteroaralkyl, _C8-11 aralkenyl, _C7-10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamido, carbamate, sulfone hydrazide, carb C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, and the like, which are unsubstituted or substituted by one or more substituents selected from the group consisting of halogen, cyano, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 Reel, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkyl or C _7-10 alkenyl and heterocyclic are alkenyl; Wherein R _s1 is selected from the group consisting of hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 hetero Aryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, and R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl , C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, and R _s2 and R ₂₀ are selected from hydrogen, C _1-12 alkyl, C _2-12 alkenyl , C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroaralkenyl, wherein said substituent alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, hetero Cycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyl Wherein y is 1 and M is a monovalent metal, or y is ½ and M is 2 or 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, heteroaryl, heteroaryl, Is a metal.

For the purpose of the present invention, it is preferable that the metal is selected from the group consisting of an alkali metal (for example, lithium (Li), sodium (Na), potassium (K), rubidium (Rb) and cesium (Mg), calcium (Ca) and strontium (Sr)] or manganese (Mn), iron (Fe), zinc (Zn) or silver (Ag). Physiologically acceptable salts will in particular be understood to mean alkali metal and alkaline earth metal salts, for example sodium, potassium, magnesium and calcium salts. Sodium and potassium ions and their salts are preferred.

Halogen is understood to mean representative of the group consisting of fluorine, chlorine, bromine and iodine. Fluorine, chlorine and bromine are preferred, and fluorine and chlorine are particularly preferred.

Alkyl can be linear or branched and can be branched, preferably once or twice, at the alpha position. Preferred examples of alkyl having 1 to 12 carbon atoms are methyl, ethyl, and isomers of propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl. Preferred alkyl groups are methyl, ethyl, n- and i- and t-butyl.

Examples of alkenyl include alkyl, but-1-en-3-yl or 4-yl, pent-3- or 4- 5-en-1-yl or 2-yl and (C _1-4 alkyl) CH = CH-CH ₂ -.

The cycloalkyl and cycloalkenyl may have a ring carbon number of preferably 5 to 8, particularly preferably 5 or 6. Examples of cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cyclodecyl, and cyclododecyl. Cyclohexyl is a particularly preferred cycloalkyl group. Examples of cycloalkenyl are cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclononenyl, cyclodecenyl, cyclodecenyl, and cyclododecenyl. Cyclohexenyl is a particularly preferred cycloalkenyl group.

Examples of alkylene include ethylene, 1,2-propylene, 1,2- or 2,3-butylene, 1,2- or 2,3-pentylene, 1,2-, 2,3- or 3,4 - hexylene. Examples of the cycloalkylene include 1,2-cyclopropylene, 1,2-cyclobutylene, 1,2-cyclopentylene, 1,2-cyclohexylene, 1,2-cycloheptylene and 1,2- Octylene. Examples of heterocycloalkylene are pyrrolidinylene, piperidinylene, tetrahydrofuranylene, di- and tetrahydropyranylene.

Examples of heterocycloalkyl are derived from pyrrolidine, imidazolidine, oxazolidine, pyrazolidine, piperidine, piperazine and morpholine. Examples of heterocycloalkenyl are derived from 2- and 3-pyrrolines, oxazolines, 2- and 4-imidazolines and 2- and 3-pyrazoles.

For purposes of the present invention, aryl or heteroaryl is a 5-membered or 6-membered ring, or a bicyclic ring consisting of two condensed 6-or 5-membered rings or 1 6-membered and 1 5-membered ring, and in the case of heteroaryl , One or more C atoms may each independently be replaced by an atom selected from the group consisting of oxygen, nitrogen and sulfur. Examples are benzene, naphthalene, indene, furan, pyrrole, pyrazole, imidazole, isoxazole, oxazole, furazan, thiadiazole, thiophene, thiazole, oxadiazole, triazole, indole, indazole, , Benzimidazole, benzoxazole, benzothiazole, pyran, pyridine, pyridazine, triazine, pyrimidine, pyrazine, isoquinoline, cinnoline, phthalazine, quinoline, quinazoline, Quinoxaline. Aryl is preferably naphthyl and phenyl. Phenyl is particularly preferred. Heteroaryl is preferably furanyl, pyridinyl and pyrimidinyl.

Aralkyl preferably has 7 to 12 C atoms and may be phenyl-C _n H _2n -, where n is a number from 1 to 6. Examples are benzyl, phenylethyl or phenylpropyl. Benzyl and 2-phenylethyl are preferred. Are alkenyl is preferably unsubstituted phenyl -CH = CH-CH ₂ - (cinnamyl) and cinnamyl is on the phenyl, OH, halogen, COOH, C (O) OM _y, C _1-12 alkyl, C C _1-6 alkoxy, C _6-10 aryl, SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y wherein R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl , C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroaralkenyl), NO ₂ , C _1-12 primary amino, C _2-20 secondary amino, amino and CN Lt; / RTI > is substituted by a substituent selected from the group consisting of

Heteroaralkyl and heteroaralkenyl are preferably C _4-5 heteroarylmethyl and C _4-5 heteroarylethenyl having 1 or 2 heteroatoms selected from the group of O and N, And may include the aforementioned heteroaryl moieties.

Alkoxy can be linear or branched and can be branched, preferably once or twice, at the alpha position. Examples of a part of alkoxy, preferably containing 1 to 12 C atoms, include methoxy, ethoxy, and propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, Lt; / RTI > and isomers of dodecoxy. Preferred alkoxy groups are methoxy and ethoxy.

Examples of aryloxy and aralkoxy are phenoxy and benzyloxy. Heteroaryloxy is preferably furanyloxy, pyridinyloxy and pyrimidinyloxy.

The primary amino preferably contains 1 to 12, particularly preferably 1 to 6, C atoms. Some examples are methyl-, ethyl-, hydroxyethyl-, n- or i-propyl-, n-, i- or t-butyl-, pentyl-, hexyl-, cyclopentyl-, cyclohexyl-, , Methylphenyl-, benzyl- and methylbenzylamino. The secondary amino preferably contains 2 to 14, particularly preferably 2 to 8, C atoms. Some examples are dimethyl-, diethyl-, methylethyl-, di- n -propyl-, di-i-propyl-, di- n -butyl-, diphenyl-, dibenzylamino, morpholino, Dino and pyrrolidino.

NH ₂ , primary amino, secondary amino, carbamides, carbamates, carbhydrazides, sulfonamides, sulfonehydrazides and aminocarbonylamides are preferably R ₈ C (O) (NH) _p N _{(R 9) -, -C (} O) (NH) p NR 8 R 9, R 8 OC (O) (NH) p N (R 9) -, R 8 R 40 NC (O) (NH) p N _{(R 9) -, -OC (} O) (NH) p NR 8 R 9, -N (R 40) C (O) (NH) p NR 8 R 9, R 8 S (O) 2 (NH) p _{N (R 9) -, -S} (O) 2 (NH) p NR 8 R 9, R 8 R 40 NS (O) 2 N (R 9) - or _{-NR 40 S (O) 2 NR} 8 R 9 Wherein R ₈ , R ₉ and R ₄₀ are each independently selected from the group consisting of hydrogen, OH, C _1-12 alkyl, C _1-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkyl C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-16 aralkyl; C _8-16 aralkenyl having C _2-6 alkenylene and C _6-10 aryl; C _6-15 heteroaralkyl, C _6-15 heteroaralkenyl or di-C _6-10 aryl-C _1-6 alkyl, or R _{8 '} R _9' N, wherein R _{8 '} and R _9' Each independently represent hydrogen, OH, SO ₃ M _y , OSO ₃ M _y , C _1-12 alkyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl , C _7-11 aralkyl, C _6-10 heteroaralkyl; C _8-16 alkenyl, aralkyl having a C _2-6 alkenylene and C _6-10 aryl, or di -C _6-10 aryl -C _1- such groups are OH, _{halogen, C (O) OR s1,} OC (O) R s4, C (O) R s2, nitro, NH _2, cyano, SO ₃ M _y, OSO ₃ M _y, and ₆ alkyl, _{NR 20 SO 3 M y, C} 1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 hetero cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy , C _6-10 heteroaralkyl, C _8-11 alkenyl, C _7-10 heteroaryl Is selected from the group consisting of alkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamido, carbamate, sulfone hydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide Wherein R _s1 is selected from the group consisting of hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, and C _7-11 aralkyl or C _6-10 heteroaralkyl, R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _{3- 12} cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or a C _6-10 heteroaralkyl, R _s2, and R ₂₀ is hydrogen, C C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 ahreu al , C _6-10 heteroaralkyl, C _8-11 aralkyl or C _7-10 alkenyl heteroaralkyl and alkenyl, wherein the substituents alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, hetero cycloalkenyl Aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, aralkenyl and heteroaralkenyl are unsubstituted or substituted by one of the substituents mentioned above; p is 0 or 1, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal; Or R ₈ and R ₉ , or R _{8 '} and R _9' , or R ₈ and R ₄₀ are -NR ₈ R ₉ or -NR _{8 '} R _9' or R ₈ R ₄₀ N-, together with tetramethylene, _{methylene, - (CH 2) 2 -O-} (CH 2) 2 -, - (CH 2) 2 -S- (CH 2) 2 - or _{- (CH 2) 2 -NR 7} - (CH 2) 2 - , Wherein R ₇ is H, C _1-6 alkyl, C _7-11 aralkyl, C (O) R _s2 or sulfonyl.

Sulfonyl substituent is, for example the formula R ₁₀ -SO ₂ - corresponds to, in which R ₁₀ is OH, _{halogen, C (O) OR s1,} OC (O) R s4, C (O) R s2, and nitro, NH _{2, cyano, SO 3 M y, OSO 3} M y, NR 20 SO 3 M y, C 1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, _C2-11 heterocycloalkyl, _C2-11 heterocycloalkenyl, _C6-10aryl , _C6-10aryloxy , _C5-9 heteroaryl, _C5-9 heteroaryl Alkoxy, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl, C _7-10 heteroalkenyl, primary amino, secondary amino, sulfonyl, sulfonamido, C _1-12 alkyl, C ₁₂ alkyl substituted or unsubstituted with one or more substituents selected from the group consisting of a halogen atom, a hydroxyl group, a hydroxyl group, a carboxyl group, a carboxyl group, a carboxyl group, a carboxyl group, a carboxyl group, _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 Interrogating aryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, where R _s1 is hydrogen, M _y, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, and C _7-11 aralkyl or C _6-10 heteroaralkyl, R _s4 is hydrogen, C _1-12 alkyl, C _{2- 12} alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, R _s2 And R ₂₀ is selected from the group consisting of hydrogen, C _1-12 alkyl, C _2-12alkenyl , C _{3-12cycloalkyl} , C _{3-12cycloalkenyl} , C _{2-11heterocycloalkyl} , C _{2-11heterocycloalkenyl} , C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, the substituent alkyl , Alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, Heteroaryl, heteroaryl, heteroaryl, heteroaryl, heteroaryl, heteroaryl, heteroaryl, heteroaryl, heteroaryl, heteroaryl, heteroaryl, heteroaryl, heteroaryloxy, aralkyl, heteroaralkyl, aralkenyl and heteroaralkenyl are unsubstituted or substituted by one of the substituents mentioned above; p is 0 or 1, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal.

Preferred compounds of formula I are those wherein X is a group corresponding to a group of formula II wherein R < ₅ > and R < ₆ >

(a) C _1-12 alkyl, such as methyl, ethyl, or C _1-12 alkoxy, substituted or unsubstituted, for example, by methoxy, ethoxy,

(b) together with the group -CH-CH-, a 5- to 8-membered carbocycle, particularly preferably a 5-membered or 6-membered carbocycle, very particularly preferably R, R-1,2-cyclohexylene Lt; / RTI &

(c) together with the group -CH-CH-, a 5-to 8-membered heterocyclo cycle, particularly preferably a 5-membered or 6-membered heterocyclic ring having nitrogen as a hetero atom, very particularly preferably R, R Piperidylene,

(d) each independently hydrogen, unsubstituted C _1-12 alkyl, or _{-C (O) OR s1, -OC} (O) R s4, -C (O) ONa or -C (O) OK, 1 class C _1-12 alkyl substituted by a substituent selected from the group consisting of amino, secondary amino, C _3-12 cycloalkyl, C _1-6 alkoxy, phenyloxy and benzyloxy; _{Unsubstituted} C _3-12 cycloalkyl or -C (O) OR _s1 , -OC (O) R _s4 , -C (O) ONa or -C C _3-12 cycloalkyl substituted by a substituent selected from the group consisting of C _1-6 alkyl, C _1-6 alkoxy, phenyloxy and benzyloxy; (O) OR _s1 , -OC (O) R _s4 , -C (O) ONa or -C (O) OK, primary amino, secondary amino, C _1-6 alkyl or C _1-6 alkoxy C _6-10 aryl which is substituted or unsubstituted by C _3-9 heteroaryl having 1 or 2 hetero atoms selected from the group consisting of oxygen and nitrogen atoms; (O) OR _s1 , -OC (O) R _s4 , -C (O) ONa or -C (O) OK, primary amino, secondary amino, C _1-6 alkyl or C _1-6 alkoxy Or C _7-12 aralkyl which is unsubstituted or substituted by halogen;

(e) a 5- or 12-membered carbocycle together with the group -CH-CH-, or a 5-or 6-membered heterocarbocycle selected from the group consisting of oxygen and nitrogen atoms; or

(f) group together with the -CH-CH-, C _3-12 cycloalkylene, C _4-12 cycloalkyl alkenylene, or a hetero atom is -O-, -S-, and selected from the group consisting of -N-, C _{2 -11} and hetero cycloalkylene or C _3-11 heterocycloalkyl alkenylene, where said substituent cycloalkylene, cycloalkylene alkenylene, heterocycloalkyl and heterocycloalkyl alkylene alkenylene is OH, halogen, C (O) oR _{s1, OC (O) R s4, C} (O) R s2, nitro, NH _{2, cyano, SO 3 M y, OSO 3} M y, NR 20 SO 3 M y, C 1-12 alkyl, C _2-12 Al alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 alkenyl, aralkyl, C _7-10 heteroaralkyl alkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, Carbamide, carboxylic Formate, sulfone hydrazide, carbalkoxy hydrazide, carbonyl hydroxamic acid and an amino acid which is substituted or unsubstituted by one or more substituents selected from the group consisting of carbonyl amide, where R _s1 is hydrogen, M _y, C ₁ C ₁₂ alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 and heteroaralkyl, R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, , C _7-11 aralkyl or C _6-10 heteroaralkyl, and R _s2 and R ₂₀ are selected from hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cyclo alkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _{8 -11} aralkyl alkenyl or C _7-10 heteroaralkyl alkenyl is , Said substituent alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl Alkenyl and heteroaralkenyl are substituted or unsubstituted by one of the substituents mentioned above, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal.

Particularly preferred compounds are those wherein X corresponds to a group of formula II wherein R ₅ and R ₆ together with the -CH-CH- group represent a C _3-12 cycloalkylene or a C _2-11 heterocycle having nitrogen as a heteroatom Alkylene, wherein said cycloalkylene and heterocycloalkylene are substituted or unsubstituted by one or more of said substituents.

Particularly preferred compounds are those wherein R ₅ and R ₆ together with the -CH-CH- group are C _3-12 cycloalkylene or C _2-11 heterocycloalkylene having nitrogen as a heteroatom. Cycloalkylene and heterocycloalkylene may be optionally substituted with one or more groups selected from OH, C (O) OR _s1 , OC (O) OR _s4 , C (O) R _s2 , NR ₈ R ₉ , C _1-12 alkyl, R ₈ C NH) _p N (R ₉ ) -, -C (O) (NH) _p NR ₈ R ₉ , R ₈ S (O) ₂ (NH) _p N (R ₉ ) -; _{R 8 R 40 NC (O)} (NH) p N (R 9) -, R 8 OC (O) (NH) p N (R 9) -, -OC (O) (NH) p NR 8 R 9 and R ₁₀ -SO ₂ -, wherein R ₈ , R ₉ , R ₁₀ and R ₄₀ are each independently selected from the group consisting of hydrogen, OH, C _1-12 alkyl, C _1-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 hetero Aryl, _C7-16 aralkyl; C _8-16 aralkenyl having C _2-6 alkenylene and C _6-10 aryl; C _6-15 heteroaralkyl, C _6-15 heteroaralkyl alkenyl, or di -C _6-10 aryl, and -C _1-6 alkyl, wherein the substituents OH, _{halogen, C (O) OR s1,} OC (O) _{R s4, C (O) R} s2, nitro, NH _{2, cyano, SO 3 M y, OSO 3} M y, NR 20 SO 3 M y, C 1-12 alkyl, C _2-12 alkenyl, C _{1 -12} alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 alkenyl, aralkyl, C _7-10 heteroaryl Selected from the group consisting of arylalkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamido, carbamate, sulfone hydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide Substituted or unsubstituted by one or more substituents; R _s1 is hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, and R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 heteroaryl, _-10 aryl, C _5-9 heteroaryl, and C _7-11 aralkyl or C _6-10 heteroaralkyl, R _s2, and R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _{3 -12} cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, wherein the substituents alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclo Alkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, heteroaryl Alkyl, aralkyl, alkenyl and heterocyclic are alkenyl is unsubstituted or substituted by one of the substituents mentioned above; p is 0 or 1, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal.

R ₈ and R ₉ are especially each independently hydrogen, C _1-12 alkyl, C _3-12 cycloalkyl, C _6-10 aryl; C _7-16 aralkyl having 1 to 6 carbon atoms in the alkylene group and C _6-10 aryl; C _8-16 aralkenyl having C _2-6 alkenylene and C _6-10 aryl, or di-C _6-10 aryl-C _1-6 alkyl, such as diphenylmethyl or 2,2-diphenyl Ethyl, wherein R ₈ and R ₉ are independently selected from OH, halogen, COOH, C (O) OM _y , C _1-12 alkyl, C _1-6 alkoxy, C _6-10 aryl, C _6-10 aryloxy, SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y , NO ₂ , amino, primary amino, secondary amino and CN; R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, y is 1, M is a monovalent metal, y is 1/2, and M is a divalent metal.

R ₁₀ is especially C _1-12 alkyl; C _3-12 cycloalkyl, C _6-10 aryl, an alkylene group, and C _7-16 aralkyl having 1 to 6 carbon atoms in C _6-10 aryl, C _2-6 alkenylene, and C _6-10 aryl _8-16 aralkenyl; Or di -C _6-10 aryl -C _1-6 alkyl, for example diphenylmethyl or 2,2-phenyl-ethyl, and the substituent OH, halogen, COOH, C (O) OM _y, C _1-12 alkyl, C _1-6 alkoxy, C _6-10 aryl, SO ₃ M _{y, y} OSO ₃ M, NR ₂₀ SO ₃ M _y, NO _2, amino, primary amino, secondary amino, and selected from the group consisting of CN Wherein R ₂₀ is selected from the group consisting of hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 hetero cycloalkyl, hetero C _2-11 cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkyl or C ₇ alkenyl _-10 heteroaralkenyl, y is 1 and M is a monovalent metal, or y is 1/2 and M is a divalent metal.

Also, R ₁₀ is preferably C _1-12 alkyl; OH, halogen, carboxyl, C (O) OM _y, C _1-12 alkyl, C _1-6 alkoxy, C _6-10 aryl, SO ₃ M _y, nitro, amino, primary amino, secondary amino, and cyano a substituted or unsubstituted by one or more substituents selected from the group consisting of a furnace, C _3-12 cycloalkyl, C _6-10 aryl, C _6-10 alkyl group and a C _7-16 ahreu having 1 to 6 carbon atoms in the aryl Alkyl; Or C _8-16 aralkenyl having C _2-6 alkenylene and C _6-10 aryl, or di-C _6-10 aryl-C _1-6 alkyl, such as diphenylmethyl or 2,2-di Phenylethyl.

As preferred aliphatic groups of the compound, R ₅ and R ₆ together with -CH-CH- group are C _3-12 cycloalkylene or C _2-11 heterocycloalkylene having nitrogen as a hetero atom, and the substituent cycloalkyl alkylene and heterocycloalkyl alkylene is _{OH, C (O) OR s1} , OC (O) OR s4, C (O) R s2, NH 2, C 1-12 _{alkyl, R 8 C (O) N} (R 9) -, -C (O) NR ₈ R ₉ , R ₈ S (O) ₂ N (R ₉ ) -, R ₈ OC (O) N (R ₉ ) - and R ₁₀ -SO ₂ - is unsubstituted or substituted by one or more substituents, where R ₉ is hydrogen, R ₈ is C _1-12 alkyl, C _6-10 aryl or a C _7-11 aralkyl, all of which are one or more C _{1- 12} alkoxy; R ₁₀ is C _1-12 alkyl, C _6-10 aryl or C _7-11 aralkyl which is substituted or unsubstituted by one or more C _1-12 alkyl; R _s1 and R _s4 are C _1-12 alkyl; R _s2 is C _1-12 alkyl, C _3-12 cycloalkenyl, C _3-12 cycloalkyl, or C _6-10 aryl, wherein the substituents alkyl, cycloalkenyl, cycloalkyl and aryl are OH, C (O) OR _{s1 '} and OC (O) R _s4' ; _Wherein R _{s1 '} is M _y or C _1-12 alkyl, R _s4' is C _1-12 alkyl, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal.

Particularly preferred compounds within this group are those wherein R < ₅ > and R < ₆ > together with the -CH-CH- group are cyclohexylene.

Another preferred group of compounds are those wherein R < ₅ > and R < ₆ > together with the -CH-CH- group are piperidylenes.

Particularly preferred compounds are those wherein R < ₅ > and R < ₆ > together with the -CH-CH- group are piperidylene; Here, the heteroatom is _{C (O) OR s1, C} (O) OR s2, C (O) NR 8 R 9, NH 2, SO 3 M y, C 1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _6-10 aryloxy , C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 alkenyl, aralkyl, C _{7- 10} heteroaralkyl alkenyl, primary amino, secondary amino, sulfonyl, sulfonamide and sulfone hydrazide is substituted by a substituent selected from the group or unsubstituted and ring, ring C atom more than one is OH, OC (O) consisting of OR _s4 , NH ₂ , OSO ₃ M _y , NR ₂₀ SO ₃ M _y , C _1-12 alkoxy, C _6-10 aryloxy, C _5-9 heteroaryloxy, C _7-11 aralkyloxy, , Secondary amino, sulfonamides, carbamides, carbamates, sulfone hydrazides, carbhydrazides, carbohydroxamines Wherein R _s1 is selected from the group consisting of hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 aralkyl and heteroaryl, R _s4 is hydrogen, C _1-12 alkyl, , C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl ego; R ₈ and R ₉ are each independently hydrogen, OH, C _1-12 alkyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _{7- 16} aralkyl, C _6-15 heteroaralkyl, C _2-6 alkenylene and C _8-16 alkenyl, aralkyl having a C _6-10 aryl, or di -C _6-10 aryl, or -C _1-6 alkyl; Or R ₈ and R ₉ together are tetramethylene, _{pentamethylene, - (CH 2) 2 -O-} (CH 2) 2 -, - (CH 2) 2 -S- (CH 2) 2 - or - (CH ₂ ) ₂ -NR ₇ - (CH ₂ ) ₂ -; R ₇ is H, C _1-6 alkyl, C _7-11 aralkyl, C (O) R _s2 or sulfonyl; R _s2 and R ₂₀ are selected from hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocyclo C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, Substituted alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, And heteroaralkenyl are substituted or unsubstituted by one of the substituents mentioned above, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal.

Particularly preferred compounds are those wherein R < ₅ > and R < ₆ > together with the -CH-CH- group are piperidylene; Wherein the heteroatom is substituted or unsubstituted by a substituent selected from the group consisting of C (O) OR _s1 , C (O) R _s2 , -C (O) NR ₈ R ₉ and R ₁₀ -SO ₂ - ring C atom more than one is _{OH, NH 2, R 8 S} (O) 2 N (R 9) -, R 8 C (O) N (R 9) - and _{R 8 OC (O) N (} R 9) -, wherein R ₉ is hydrogen and R ₈ is C _1-12 alkyl, C _6-10 aryl or C _7-11 aralkyl, wherein R ₉ is hydrogen, Wherein said substitutent alkyl, aryl and aralkyl are substituted or unsubstituted by at least one C _1-12 alkoxy, R ₁₀ is C _1-12 alkyl, substituted or unsubstituted by at least one C _1-12 alkyl, C _6-10 aryl or C _7-11 aralkyl; R _s1 is C _1-12 alkyl and R _s2 is C _1-12 alkyl, C _3-12 cycloalkenyl, C _3-12 cycloalkyl or C _6-10 aryl, wherein said substituent alkyl, cycloalkenyl, Cycloalkyl and aryl are substituted or unsubstituted by one or more substituents selected from the group consisting of OH, C (O) OR _{s1 '} and OC (O) R _S4' , wherein R _{s1 '} is M _y or C ₁ and _-12 alkyl, R _{S4 'is} a C _1-12 alkyl, y is 1 and M is either a monovalent metal or y is ½ and M is a divalent metal.

Another ally of preferred compounds R ₅ and R ₆ are together -CH-CH- groups, OH, C (O) OR s1, OC (O) OR s4, C (O) R s2, NH 2, C 1- _{12 alkyl, R 8 C (O) N} (R 9) -, -C (O) NR 8 R 9, R 8 S (O) 2 N (R 9) -; R ₈ OC (O) N (R ₉ ) -, R ₈ R ₄₀ NC (O) N (R ₉ ) -, -OC (O) NR ₈ R ₉ and R ₁₀ -SO ₂ - Piperidylene which is substituted or unsubstituted by at least one substituent; Wherein R ₉ is hydrogen and R ₈ is C _1-12 alkyl, C _6-10 aryl or C _7-11 aralkyl, wherein said alkyl, aryl and aralkyl are optionally substituted with one or more C _1-12 alkoxy or Substituted or unsubstituted C _7-11 aralkyloxy, R ₁₀ is C _1-12 alkyl, C _6-10 aryl or C _7-11 aralkyl which is substituted or unsubstituted by at least one C _1-12 alkyl alkyl, R ₄₀ is hydrogen, OH, C _1-12 alkyl, C _1-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 hetero cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-16 aralkyl, C _8-16 alkenyl ahreu having a C _2-6 alkenylene and C _6-10 aryl, C _{6- 15} heteroaralkyl, C _6-15 heteroalkenyl, or di-C _6-10 aryl-C _1-6 alkyl; R _s1 and R _s4 are C _1-12 alkyl and R _s2 is C _1-12 alkyl, C _3-12 cycloalkenyl, C _3-12 cycloalkyl or C _6-10 aryl, wherein the substituent alkyl, cycloalkyl Cycloalkyl and aryl are substituted or unsubstituted by one or more substituents selected from the group consisting of OH, C (O) OR _{s1 '} and OC (O) R _s4' , wherein R _{s1 '} is M _y or C _1-12 alkyl, R _{s4 '} is C _1-12 alkyl, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal.

Quite especially preferred compounds of formula (I) X is _{OH, NH 2, C 3 H} 7, -C (O) CH 3, -C (O) C 6 H 5, -C (O) (CH 2) 8 C ( _{O) OCH 3, -C (O} ) [CH (OH)] 2 C (O) ONa, C (O) -C 6 H 8 (OH) 3, -C (O) -C 6 H 11, -C _{(O) OC 3 H 7,} -C (O) NHC 6 H 5, -NHS (O) 2 CH 2 C 6 H 5, -NHC (O) OCH 2 C 6 H 5, -NHC (O) C 6 _{H 3 (OCH 3) 2,} -S (O) 2 -C 4 H 9, -NHC (O) NHC 6 H 5, -S (O) 2 -C 6 H 4 CH 3, -S (O) 2 Cyclohexylene or piperidylene which is substituted or unsubstituted by at least one substituent selected from the group consisting of -CH ₂ C ₆ H ₅ and -S (O) ₂ - (CH) ₂ C ₁₀ H ₇ .

Preferred compounds of compound (I) is to the corresponding R1 is a group of the formula III, where R ₃ is hydrogen or M _y R ₄ is

(a) unsubstituted C _1-12 alkyl; -NH ₂ , primary amino, secondary amino, C _1-12 sulfonyl, carbamido, carbamate, carbhydrazide, sulfonamide, sulfone hydrazide, aminocarbonylamido, C _3-12 cyclo C _1-12 alkyl substituted by one or more substituents selected from the group consisting of alkyl, C _1-6 alkoxy, phenyloxy and benzyloxy; _{Unsubstituted} C _3-12 cycloalkyl; C _3-12 cycloalkyl, C _1-6 alkyl, C _1-6 alkoxy, C _1-12 alkylsulfonyl, phenyloxy and benzyloxy C _3-12 cycloalkyl which is optionally substituted by one or more substituents selected from the group consisting of ; C _6-10 aryl; C _3-9 heteroaryl having 1 or 2 hetero atoms selected from the group consisting of oxygen and nitrogen atoms; C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl; C _1-6 alkyl, and oxygen and has one or two heteroatoms selected from the group consisting of nitrogen, C _4-16 heteroaralkyl having a C _3-10 heteroaryl group whose total number of carbon atoms is 3 to 5; OH, halogen, C _1-12 sulfonyl, carboxyl, C (O) OM _y , C _1-12 alkyl, C _1-6 alkoxy, C _6-10 aryl, SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y, nitro, NH _2, 1 amino, secondary amino, Carbamide, carbamate, sulfonamide and cyano is substituted by one or more substituents selected from the group consisting of a furnace, C _6-10 aryl , C _3-9 heteroaryl having one or two heteroatoms selected from the group consisting of oxygen and nitrogen atoms, C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl, C _1-6 alkyl, And C _3-16 heteroaryl having 1 to 2 heteroatoms selected from the group consisting of oxygen and nitrogen atoms and having C _4-10 heteroaryl having a total carbon number of 3 to 5, y is 1, and M is a monovalent metal Or y is ½ and M is a divalent metal, or

(b) OH, halogen, C (O) OR _s1 , OC (O) R _s4 , C (O) R _s2 , nitro, NH ₂ , cyano, SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y , C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 hetero cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _{6- 10} heteroaralkyl, _C8-11 aralkenyl, _C7-10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamido, carbamate, sulfone hydrazide, carb C _1-12 alkyl or C _7-11 aralkyl which is substituted or unsubstituted by one or more substituents selected from the group consisting of hydrazide, carbohydroxamic acid and aminocarbonylamide, wherein R _S1 is hydrogen, _y M, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl Kiel, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, R _S4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl is hydrogen, C _5-9 heteroaryl, C _7-11 aralkyl or a C _6-10 heteroaralkyl, R _S2 and R ₂₀ , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 Aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, wherein the substituents alkyl, alkenyl, Alkoxy, heteroaralkyl, aralkenyl, and heteroaralkenyl are optionally substituted with one or more substituents independently selected from the group consisting of alkyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, Among the above-mentioned substituents Y is 1 and M is a monovalent metal, y is 1/2, and M is a divalent metal.

In formula (III), R ₃ is hydrogen, K or Na.

The following are preferred for application to group (a) of the definitions for R ₄ :

R ₄ is alkyl, preferably methyl, ethyl, n- or i-propyl and n-, i- or t-butyl. In the case of substituted alkyl, the alkylene group is preferably ethylene, especially methylene. A particularly preferred cycloalkyl group is cyclohexyl. Aryl and aralkyl are preferably naphthyl and phenyl, particularly preferably phenyl and phenyl-C _n H _2n - (where n is a number from 1 to 6), especially benzyl and 2-phenylethyl. When R ₄ is heteroaryl, it is preferably C _4-5 heteroaryl having one or two heteroatoms selected from the group of O and N. Furanyl, pyridinyl and pyrimidinyl are preferred. R ₄ is heteroarylalkyl, preferably C _4-5 heteroarylmethyl having 1 or 2 heteroatoms selected from the group of O and N, wherein the heteroaryl may comprise the above-mentioned heteroaryl groups.

Further preferred compounds are those wherein R ₄ of formula III is C _3-12 cycloalkyl, particularly preferably by cyclohexyl, C _3-12 cycloalkyl or by C _1-4 alkyl, especially by cyclohexyl or methyl C _1-4 alkyl, especially methyl or ethyl, C _6-10 aryl, quite especially phenyl, or R ₄ is C _7-12 aralkyl having C _1-6 alkyl and C _6-10 aryl. Particularly preferred groups for R < ₄ > of said series are benzyl, naphthylmethyl, 2-phenylethyl, 3-phenylpropyl, cyclohexylmethyl, 2-cyclohexylethyl, cyclohexyl and isopropyl.

Carbamic not shown, carbalkoxy Hydra map, sulfone amido, sulfonamido Hydra map, aminocarbonyl amides and carbamates are preferably of formula _{R 8 NHC (O) N (} R 9) as a substituent for R ₄ -, _{R 8 OC (O) N (} R 9) -, R 8 C (O) (NH) P N (R 9) - and _{R 8 S (O) 2 (} NH) P N (R 9) - of the group and , Wherein R ₈ is preferably H, C _1-12 alkyl, C ₅ - or C ₆ cycloalkyl, C ₅ - or C ₆ cycloalkylmethyl or -ethyl-, C ₅ - or C ₆ heterocycloalkyl, C ₅ - or C ₆ heterocycloalkyl, or methyl-ethyl-, phenyl, naphthyl, benzyl, 2-phenylethyl or diphenyl methyl, all of which are -OH, -NH _2, C _1-8 1 amino, C _{2 -14} secondary _{amino, NO 2, -CN, -F,} -Cl, -C (O) OH, -C (O) ONa, -SO 3 H, -OSO 3 Na, NR 20 SO 3 Na ( wherein, R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _{7-1 1} with aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkyl or C _7-10 alkenyl heteroaralkyl alkenyl nilim), and -SO ₃ Na, C _1-4 alkyl, C _1-4 alkoxy, and phenyl R ₉ is H, C alkyl, phenyl, naphthyl, benzyl, 2-phenylethyl or phenyl-CH = CH-CH ₂ -, p is 0 or 1, Or 1.

Within group (a), the carbamido-substituted alkyl substituent for R ₄ is particularly preferably R ₈ -C (O) NR ₉ - (CH ₂ ) _n -, wherein n is 1 or 2 , R ₈ is hydrogen, C _1-12 alkyl, C _3-12 cycloalkyl, C _6-10 aryl, or C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl, said substituent alkyl , cycloalkyl, aryl and aralkyl are OH, halogen, _{carboxyl, -C (O) OM y,} C 1-12 alkyl, C _1-6 alkoxy, C _6-10 aryl, SO ₃ M _y, OSO ₃ M _y , NR ₂₀ SO ₃ M _y , C (O) OR _s1 , OC (O) R _s4 , nitro, amino and cyano; Or C _8-16 aralkenyl having C _2-6 alkenyl and C _6-10 aryl, or di-C _6-10 aryl-C _1-6 alkyl; R ₉ is H, linear or branched C _1-10 alkyl, C ₅ - or C ₆ cycloalkyl, C ₅ - or C ₆ cycloalkylmethyl- or -ethyl, phenyl, naphthyl or benzyl, -CH = CH-CH ₂ -, y is 1 and M is an alkali metal, y is ½ and M is an alkaline earth metal and R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _{3 -12} cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroaralkenyl, R _s1 is hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _{3- 12} cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, R _s4 is hydrogen, C _1-12 Alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _{7 -11} are alkyl or C _6-10 heteroaralkyl. Sulfonamides of the R ₁ - substituted alkyl substituents are particularly preferably _{R 8 -SO 2 NR 9 - (} CH 2) n - , and herein, R _8, R ₉ and n have already been defined for the carbamic shown It means. Aminocarbonyl for R ₁ amide-or carbamate-substituted alkyl substituent is the particularly preferred _{R 9 NH-C (O)} -NH- (CH 2) n or R ₉ OC (O) -NH- ( CH ₂ ) _n , wherein R ₉ is a further defined phenyl and already defined in relation to carbamido, and n has already been defined in relation to carbamido. Carbalkoxy map for the Hydra R ₁ - substituted alkyl substituents are particularly preferably _{R 8 -C (O) -NHNR 9} - (CH 2) n - , and where R _8, R ₉ and n are already carbamic It is defined in relation to Mido. The sulfohydra map-substituted alkyl substituent for R ₄ is particularly preferably R ₈ -SO ₂ -NHNR ₉ - (CH ₂ ) _n , wherein R ₈ , R ₉ and n are already related to the carbamido .

Especially preferred compounds further have the R ₄ in the formula III the amide _{R 8 C (O) N (} R 9) (CH 2) n - or _{R 8 S (O) 2 N} (R 9) (CH 2) n - and , Wherein R ₈ and R ₉ are each independently hydrogen; _{Unsubstituted} C _1-12 alkyl; OH, halogen, carboxyl, -C (O) ONa, C 1-12 alkyl, C _1-6 alkoxy, C _{6-10 aryl, -SO 3 H, OSO 3 Na} , NR 20 SO 3 Na, SO 3 Na , nitro, cyano and C _1-12 alkyl that is optionally substituted by one or more substituents selected from the group consisting of a furnace; _{Unsubstituted} C _3-12 cycloalkyl; C _3-12 cycloalkyl substituted by one or more OH; _{Unsubstituted} C _6-12 aryl, unsubstituted C _6-10 aryl, unsubstituted C _7-12 aralkyl having C _1-6 alkyl and C _6-10 aryl; C _6-10 aryl, or C _7-12 aralkyl having C _1-6 alkyl and C _6-10 aryl, wherein the group is OH, halogen, carboxyl, C (O) ONa, -C (O) OK, C _1-12 alkyl, C _1-6 alkoxy, C _{6-10 aryl, SO 3 Na, OSO 3 Na} , NR 20 SO 3 Na, C (O) OR s1, OC (O) R s4, nitro, Amino and cyano), R ₂₀ is selected from the group consisting of hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl , C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 are alkenyl or C _7-10 heteroaralkyl and alkenyl, R _s1 is hydrogen, M _y, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl; R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 Aralkyl or C _6-10 heteroaralkyl; n is 2, preferably 1.

Particularly preferred compounds are those compounds of formula III wherein R ₄ is an amide R ₈ C (O) N (R ₉ ) (CH ₂ ) _n -, wherein R ₈ is unsubstituted C _1-12 alkyl; C _1-12 alkyl which is substituted by one or more substituents selected from the group consisting of cyclohexyl, OH, halogen, -C (O) OH, -C (O) ONa and phenyl; _{Unsubstituted} C _3-12 cycloalkyl; C _3-12 cycloalkyl substituted by one or more OH; _{Unsubstituted} C _6-10 aryl; Halogen, C (O) ONa, -C (O) OH, C _1-6 alkyl, C _1-6 alkoxy, phenyl, -SO ₃ H, SO ₃ Na, OSO ₃ Na, NHSO ₃ Na, C _6-10 aryl substituted by one or more substituents selected from the group _{consisting of} Or C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl. R ₉ is selected from the group consisting of hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl, or C _2-6 alkenyl and C _6-10 aryl and the C _8-16 alkenyl having ahreu, n is 2, preferably one.

Particularly preferred compounds are those compounds of formula III wherein R ₄ is an amide R ₈ C (O) N (R ₉ ) (CH ₂ ) _n -, wherein R ₈ is unsubstituted C _1-12 alkyl; C _1-12 alkyl which is substituted by one or more substituents selected from the group consisting of cyclohexyl, OH, halogen, -C (O) OH, -C (O) ONa and phenyl; _{Unsubstituted} C _3-12 cycloalkyl; C _3-12 cycloalkyl substituted by one or more OH; _{Unsubstituted} C _6-10 aryl; Halogen, C (O) ONa, -C (O) OH, C _1-6 alkyl, C _1-6 alkoxy, phenyl, -SO ₃ H, SO ₃ Na, OSO ₃ Na, NHSO ₃ Na, C _6-10 aryl substituted by one or more substituents selected from the group _{consisting of} Or C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl. R ₉ is selected from the group consisting of hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl, or C _2-6 alkenyl and C _6-10 aryl and the C _8-16 alkenyl having ahreu, n is 2, preferably one.

Also particularly preferred compounds are those compounds of formula III wherein R ₄ is an amide R ₈ C (O) N (R ₉ ) (CH ₂ ) _n -, wherein R ₈ is unsubstituted C _1-12 alkyl; C _1-4 alkyl substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OH, C (O) ONa and phenyl; _{Unsubstituted} C _3-12 cycloalkyl, especially C ₆ H ₁₁ ; C _3-12 cycloalkyl substituted by one or more OH; _{Unsubstituted} C _6-10 aryl, especially C ₅ H ₅ or C ₁₀ H ₇ ; Halogen, -C (O) OH, C (O) ONa, C _1-6 alkyl, C _1-6 alkoxy, -SO ₃ H, SO ₃ Na, OSO ₃ Na, NHSO ₃ Na, nitro and cyano _{C 6 H 4 Cl, C 6} H 4 (3,4) Cl 2, C 6 H 4 COONa, C 6 H 4 CH 3, C 6 H 4 OCH 3, C 6 H 4 SO 3 Na, C 6 H 4 C _6-10 aryl substituted by one or more substituents selected from the group consisting of NO ₂ or C ₆ H ₄ CN; Or unsubstituted C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl, especially (CH ₂ ) ₂ C ₆ H ₅ ; R ₉ is hydrogen, C _1-4 alkyl, phenyl-CH ₂ -, phenyl-CH ₂ CH ₂ , phenyl- (CH ₂ ) ₃ - or phenyl-CH = CH-CH ₂ - Is one.

Particularly preferred compounds are those compounds of formula III wherein R ₄ is an amide R ₈ C (O) N (R ₉ ) (CH ₂ ) _n -, wherein R ₈ is substituted or unsubstituted C _1-12 alkyl, cyclohexyl , naphthyl, biphenylyl, phenyl, benzyl, phenyl-ethyl or diphenylmethyl, R ₉ is C _1-4 alkyl, phenyl -C _1-6 alkyl, in particular _{CH 2 C 6 H 5, (} CH 2) 2 C ₆ H ₅ or (CH ₂ ) ₃ C ₆ H ₅ ; Or phenyl-C _2-6 alkenyl, especially C ₆ H ₅ -CH = CH-CH ₂ , and n is 2,

Also particularly preferred compounds are those compounds of formula III wherein R ₄ is a sulfonamido R ₈ S (O) ₂ N (R ₉ ) (CH ₂ ) _n -, wherein R ₈ is one or more halogen atoms , Cl, especially F), especially C _1-12 alkyl, especially C _1-6 alkyl, which is substituted or unsubstituted by CF ₃ ; Or one or more C _1-4 alkyl (e.g., methyl or ethyl), C _1-4 alkoxy (e.g., methoxy or ethoxy), C ₆ to be substituted by halogen, -CN or -NO _{2 -10} aryl, especially phenyl or naphthyl, R ₉ is hydrogen or isobutyl, and n is 2, preferably 1.

Also particularly preferred compounds are those compounds of formula III wherein R ₄ is an aminocarbonylamide residue of the formula R ₈ -NH-C (O) -NH (CH ₂ ) _n , wherein R ₈ is halogen, -CN, -NO ₂ , C _1-4 alkyl, C _1-4 alkoxy, C ₅ - or C ₆ cycloalkyl, C _6-10 aryl such as phenyl or naphthyl, or C _6-10 aryl such as benzyl, phenylethyl, _7-12 is a substituted or unsubstituted C _1-12 alkyl or C _6-10 aryl, especially C _1-6 -alkyl by aralkyl, n is 2, preferably one.

Particularly preferred compounds are those compounds of formula III wherein R ₄ is aminoalkyl, preferably R _{8 '} R _9' N (CH ₂ ) _n -, wherein R _{8 '} and R _9' are each independently hydrogen; _{Unsubstituted} C _1-12 alkyl; OH, _{halogen, C (O) OR s1,} OC (O) R s4, C (O) -NR 11 R 12, C 1-12 alkyl, C _1-6 alkoxy, C _6-10 aryl, -SO ₃ H , SO ₃ Na, OSO ₃ Na, NR ₂₀ SO ₃ Na, nitro, amino and cyano C _1-12 alkyl that is optionally substituted by one or more substituents selected from the group consisting of; _{Unsubstituted} C _3-12 cycloalkyl; C _3-12 cycloalkyl substituted by one or more OH; C _6-10 aryl; C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl; Or C _8-16 aralkenyl having C _2-6 alkenyl and C _6-10 aryl, said aryl and said aryl in aralkyl and aralkenyl being optionally substituted with one or more substituents selected from OH, halogen, C (O) OR _s1 , OC _{(O) R s4, -C (} O) ONa, -C (O) OK, -C (O) -NR 11 R 12, C 1-12 alkyl, C _1-6 alkoxy, C _6-10 aryl, - SO ₃ H, SO ₃ Na, OSO ₃ Na, NR ₂₀ SO ₃ Na, nitro, amino and cyano, n is 2, preferably 1, R _s1 is hydrogen, K or Na, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, and R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or a C _6-10 heteroaralkyl, R ₁₁ is H, C _1-4 alkyl, C _2-4 hydroxyalkyl, phenyl yet Is benzyl, R ₁₂ is independently for R ₁₁ , or R ₁₁ and R ₁₂ together are tetramethylene, pentamethylene or -CH ₂ CH ₂ -O-CH ₂ CH ₂ -; R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 alkenyl or C _7-10 heteroalkenyl.

Particularly preferred compounds are also those wherein R ₄ in formula III is aminoalkyl R _{8 '} R _9' NCH ₂ -, wherein R _{8 '} and R _9' are each independently hydrogen; C _1-8 alkyl, cyclopentyl, cyclohexyl, C ₅ - or C ₆ cycloalkylmethyl, phenyl-C _1-4 alkyl, especially -CH ₂ C ₆ H ₅ ; Or phenyl-C _2-4 alkenyl, especially -CH ₂ -CH = CHC ₆ H ₅ .

Particularly preferred compounds are also, R ₄ is an amine R _{8 'R 9'} NCH ₂ in the formula III - is, here in R _{8 'and} R _9' are each independently H, C _1-6 alkyl, phenyl -C ₁ - Or C ₂ alkyl, especially CH ₂ C ₆ H ₅ .

Among the definitions for R ₄ , preferred compounds of group (b) are those wherein R ₄ is selected from the group consisting of NH ₂ , C _3-12 cycloalkyl, primary amino, secondary amino, sulfonamide, carbamido and aminocarbonylamino C _7-11 aralkyl, in particular CH ₂ -C ₆ H _5, and (CH ₂ ) ₂ -C ₆ H ₅ , C _3-12 cycloalkyl or C _1-12 substituted or unsubstituted by one or more selected substituents selected Alkyl. Particularly preferred substituents for C _1-12 alkyl are NH ₂ , cyclohexyl, C _6-10 aryl, R ₈ C (O) N (R ₉ ) -, R ₈ S (O) ₂ N (R ₉ ) _{R 8 NHC (O) NR 9} -, NR 9 C (O) NHR 8 and R _{8 'R 9'} are selected from the group consisting of N-, where R ₈ and R ₉ are independently hydrogen, C _1- each ₁₂ alkyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 aralkyl and heteroaryl, R _{8 '} And R _{9 '} are each independently selected from the group consisting of hydrogen, OH, C _1-12 alkyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 It is aralkyl or C _6-10 heteroaralkyl, all of which are OH, _{halogen, C (O) oR s1,} OC (O) R s4, C (O) R s2, nitro, NH _2, cyano, SO ₃ M _{y , OSO 3 M y, NR 20} SO 3 M y, C 1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _{2- 11} heterocycloalkyl, _C2-11 heterocycloalkenyl, _{C6- 10} aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _{8 -11} aralkyl alkenyl, C _7-10 heteroaralkyl alkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, Carbamide, carbamate, sulfone hydrazide, carbalkoxy hydrazides, carbonate hydroxide Wherein R _s1 is selected from the group consisting of hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 aralkyl and heteroaryl, R _s4 is hydrogen, C _1-12 alkyl, , C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl , R _s2 and R ₂₀ are hydrogen, C _{1 -12} alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C C _1-6 alkenyl, C _5-6 heteroaryl, C _5-8 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl and the substituents alkyl, alkenyl, alkoxy, cycloalkyl Cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, aralkenyl and heteroaralkenyl are as previously described Or Y is 1, M is a monovalent metal, y is ½ and M is a divalent metal, or R _{8 '} and R _9' are substituted or unsubstituted with one of the substituents, p is 0 or 1, together tetramethylene, _{pentamethylene, - (CH 2) 2 -O-} (CH 2) 2 -, - (CH 2) 2 -S- (CH 2) 2 - or _{- (CH 2) 2 -NR 7} - ( CH ₂ ) ₂ -; R ₇ is H, C _1-6 alkyl, C _7-11 aralkyl, C (O) R _s2 or sulfonyl.

Particularly preferred compounds within said group are those wherein R ₄ is NH ₂ , cyclohexyl, C _6-10 aryl, R ₈ C (O) N (R ₉ ) -, R ₈ S (O) ₂ N (R ₉ ) _{R 8 NHC (O) NR 9} -, NR 9 C (O) NHR 8 and R _{8 'R 9'} is substituted or unsubstituted by one or more substituents selected from the group consisting of N-, CH ₂ -C ₆ H ₅ , (CH ₂ ) ₂ -C ₆ H ₅ , cyclohexyl, methyl, ethyl or isopropyl; Wherein R ₈ , R ₉ , R _{8 '} and R _9' are each independently hydrogen, C _1-12 alkyl, C _3-12 cycloalkyl, C _6-10 aryl or C _7-11 aralkyl, OH, halogen, C (O) OM _y, nitro, cyano, SO ₃ M _{y, y} OSO ₃ M, NHSO ₃ M _y, C _1-12 consisting of alkyl, C _1-12 alkoxy and C _6-10 aryl , Y is 1, M is a monovalent metal, y is 1/2, and M is a divalent metal. A particularly preferred compound is _{R 8, R 9, R 8} ' and R _9' are each independently OH, F, Cl, C (O) ONa, nitro, cyano, SO ₃ Na, C _1-6 alkyl, methoxy and substituted or unsubstituted by one or more substituents selected from the group consisting of phenyl, hydrogen, C _1-12 alkyl, cyclohexyl, it is phenyl, naphthyl, or C _7-11 aralkyl.

In a preferred group of compounds of formula I, R ₁ is formula III, where R ₄ is _{C 6 H 11, CH (CH} 3) 2, CH 2 - phenyl, (CH _{2) 2} - phenyl, CH ₂ NHC ( O) - _{phenyl, CH 2 NHC (O) (} CH 2) 3 - _{phenyl, CH 2 NHC (O) (} CH 2) 3 OH, CH 2 NHC (O) CF 3, CH 2 NHC (O) C 6 H _{11, CH 2 NHC (O)} C 11 H 23, CH 2 NHC (O) CH (C 6 H 5) 2, CH 2 HNC (O) NHC 6 H 5, CH 2 NHC (O) C 2 H 4 CO _{2 Na, CH 2 NHC (O} ) C 6 [(1,3,4,5) OH] 4 H 7, CH 2 NHC (O) C 6 H 4 -p-SO 3 Na, CH 2 NHC (O) _{C 6 H 4 Cl, CH 2} NHC (O) C 6 H 4 NO 2, CH 2 NHC (O) C 6 H 4 OCH 3, CH 2 NHC (O) C 6 H 4 (3,4) Cl 2, _{CH 2 NHC (O) C 6} H 4 CH 3, CH 2 NHC (O) C 6 H 4 C 6 H 5, CH 2 NHC (O) C 6 H 4 CN, CH 2 NHC (O) C 10 H 7 _{, CH 2 NHC (O) C} 6 H 4 COONa, CH 2 NHC (O) (CHOH) 2 COONa, CH 2 N (CH 2 CH = CH- phenyl) [C (O) - phenyl], CH ₂ N [ _{CH 2 CH (CH 3) 2} ] [C (O) - _{phenyl], CH 2 N [C (} O) C 6 H 5] CH 2 C 6 H 5, CH 2 N [C (O) C 6 H 5 _{] (CH 2) 3 C 6} H 5, CH 2 C 6 H 11, (CH 2) 2 C 6 H 11, CH 2 NH 2, CH 2 NHCH 2 CH = CH- , phenyl, CH ₂ NHCH ₂ - phenyl, _{CH 2 NHCH 2 CH (CH 3} ) 2, CH 2 N (CH 2 - Fe _{) 2, CH 2 N [CH} 2 CH (CH 3) 2] 2, CH 2 NHSO 2 -p- nitrophenyl, CH ₂ NHSO ₂ -p- _{tolyl, CH 2 NHSO 2 CF 3,} CH 2 NHC (O) NHC ₆ H ₅ or CH ₂ N [SO ₂ -p-nitrophenyl] [CH ₂ CH (CH ₃ ) ₂ ].

R ₂ may preferably contain from 1 to 6 C atoms, particularly preferably from 1 to 4 C atoms, as alkyl. Methyl and ethyl are particularly preferred.

In the case of halogen as a substituent for R ₂ it is preferably -C (O) OM _y , preferably -C (O) ONa or -C (O) OK; Alkyl, preferably C _1-6 , particularly preferably C _1-4 alkyl, such as methyl, ethyl, n- or i-propyl and n-, i- or t-butyl; Alkoxy, preferably C _1-4 alkoxy, such as methoxy and ethoxy; In the case of aryl, preferably phenyl or naphthyl; -SO ₃ M _y , preferably -SO ₃ Na or -SO ₃ K; C _1-12 primary amino groups such as primary amino, preferably methyl-, ethyl-, n- or i-propyl and n-, i- or t-butyl, pentyl, hexyl, cyclohexyl, In the case of; Secondary amino, preferably dimethyl-, diethyl-, methylethyl-, di-n-propyl-, di-i-propyl-, di-n-butyl-, diphenyl-, dibenzylamino, morpholino , For C _2-20 secondary amino, such as thiomorpholino, piperidino and pyrrolidino; -SO ₂ -NR ₈ R _9; And _{-C (O) -NR 8 R 9} ( wherein, R ₈ and R ₉ are independently H, C _1-4 alkyl, C _2-4 hydroxyalkyl, or phenyl or benzyl, or R ₈ and R ₉ each In the case of morpholino, thiomorpholino, pyrrolidino or piperidino, together with the N atom; F, Cl or Br.

R ₈ and R ₉ are alkyl, preferably containing 1 to 6, particularly preferably 1 to 4, C atoms, for example methyl, ethyl, n- or i-propyl or n-, t-butyl. R ₈ and R ₉ are preferably 1 to 6, particularly preferably 1 to 4, C atoms as hydroxyalkyl, and may be, for example, hydroxymethyl or 2-hydroxyethyl . R ₈ and R ₉ are cycloalkyl, preferably cyclopentyl or cyclohexyl. Substituents for R < ₈ > and R < ₉ > are preferably F, Cl, methyl, ethyl, methoxy and ethoxy as phenyl and benzyl.

Preferred groups of compounds of formula I are those wherein R ₂ is hydrogen, unsubstituted C _1-6 alkyl, particularly preferably C _1-4 alkyl, especially methyl or ethyl; Or C (O) OH, -C ( O) ONa, -C (O) OK, -OH, -C (O) -NR 8 R 9 or -SO ₂ -NR C _{1- 8} R ₉ to be substituted by ₆ would alkyl, most preferably C _1-4 alkyl, especially methyl or ethyl, where R ₈ is H, C _1-4 alkyl, C _2-4 hydroxyalkyl, phenyl or benzyl, R ₉ are independently or the meaning of the R _8, or R ₈ and R ₉ together are tetramethylene, pentamethylene or _{-CH 2 CH 2 -O-CH 2} CH 2 - is. Especially preferred compounds R ₂ is hydrogen, methyl, _{ethyl, HO (O) CCH 2 CH} 2 -, NaOC (O) CH 2 CH 2 - or _{R 8 R 9 NC (O)} CH 2 CH 2 - , and, R ₈ And R ₉ are each independently H, C _1-6 alkyl, C _2-4 hydroxyacyl, phenyl, benzyl or together morpholino.

Particularly preferred embodiments of the present invention include compounds of formula (Ia):

In this formula,

R ₃ is hydrogen or M _y ;

R ₄ is selected from the group consisting of C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 alkenyl or C _7-10 heteroaryl Alkenyl;

R ₅ and R ₆ are each independently selected from the group consisting of hydrogen, C _1-12 alkyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 ar Alkyl or C _6-10 heteroaralkyl, or

R ₅ and R _6, together with the -CH-CH- group, are C _3-12 cycloalkylene, C _4-12 cycloalkenylene, or a group having a heteroatom selected from the group consisting of -O-, -S- and -N- C _2-11 heterocycloalkylene and C _3-11 heterocycloalkenylene; From here,

Said alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkylene, cycloalkenylene, heterocycloalkylene and heterocycloalkenylene being optionally substituted by OH, halogen, C (O) OR _{s1, OC (O) R s4} , C (O) R s2, nitro, NH _{2, cyano, SO 3 M y, OSO 3} M y, NR 20 SO 3 M y, C 1-12 alkyl, C _{2- 12} alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _{6 -10} aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 aralkyl alkenyl , C _7-10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamido, carbamido, carbamate, sulfone hydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonyl Amide < / RTI > By a substituent, and ring once or several times substituted or unsubstituted, where R _s1 is hydrogen, M _y, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl , C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _{3 And} R _s2 and R ₂₀ are _{independently selected from the} group consisting of hydrogen, C _1-6 alkyl, C _1-6 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl , C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, the substituents alkyl, alkenyl, alkoxy, Cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryl When, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, aralkyl, alkenyl and heterocyclic are alkenyl is unsubstituted or substituted by one of the substituents mentioned above;

y is 1 and M is a monovalent metal, y is 1/2, and M is a divalent metal.

Preferred compounds of formula Ia are those wherein R ₃ is H, K or Na and R ₅ and R _{6 taken} together with the -CH-CH- group are C _3-12 cycloalkylene, C _4-12 cycloalkenylene, or -O- , -S-, and a C _2-11 heterocycloalkyl C _3-11 alkylene or alkenylene heterocycloalkyl having a heteroatom selected from -N- group, all of which are OH, _{halogen, C (O) oR s1,} OC (O) _s4 OR, C (O) R _s2, nitro, NH _{2, cyano, SO 3 M y, OSO 3} M y, NH 20 SO 3 M y, C 1-12 alkyl, C _2-12 alkenyl, C _{1 -12} alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 alkenyl, aralkyl, C _7-10 heteroaryl Alkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamido, carbamate, sulfone hydrazide, carbhydrazide, Wherein R _s1 is selected from the group consisting of hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, and substituted or unsubstituted aryl or heteroaryl, each of which is optionally substituted once or several times with a substituent selected from the group consisting of alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, R _s4 is hydrogen , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, and R _s2 and R ₂₀ are _{independently selected} from the group consisting of hydrogen, C _1-12 alkyl, C _2-12alkenyl , C _{3-12cycloalkyl} , C _{3-12cycloalkenyl} , C _{2-11heterocyclo} Alkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _{7- 10} heteroaralkyl and alkenyl, wherein the substituents alkyl, alkenyl, alkoxy, Heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, aralkenyl and heteroaralkenyl may be optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, Wherein y is 1 and M is a monovalent metal, y is 1/2, and M is a divalent metal;

(a) R ₄ is a residue R ₁₂ - (CH ₂ ) _n - or cyclohexyl, wherein n is 1 or 2;

Wherein R ₁₂ is C _1-10 alkyl, C _5-8 cycloalkyl, especially cyclohexyl, optionally substituted by C _1-4 alkyl, C _1-4 alkoxy, F, Cl, -CN or -NO ₂ , C _6-10 aryl, preferably phenyl or C _8-12 arylalkenyl, preferably phenyl-C _2-4 alkenyl, or

R ₁₂ is an amino group -NR _{8 '} R _{9' wherein} R _{8 '} and R _9' are C _1-12 alkyl or unsubstituted or C _1-4 alkyl-substituted C ₅ - or C ₆ cycloalkyl, C _6-10 aryl, C _7-12 alkyl or C _8-12 is aralkyl the aralkyl alkenyl, most preferably _{-CH 2 -CH (CH 3) 2} , -CH 2 -C (CH 3) 3, -CH 2 _{-C (CH 3) 2 -C 2} H 5, C 6 H 5 -CH 2 -, C 6 H 5 CH 2 CH 2 -, C 6 H 5 -CH 2 -CH 2 -CH 2 - or C ₆ H ₅ CH = CH-CH ₂ -); or

R ₁₂ is an amino group _{-N (R 9) C (O} ) R 8, -N (R 9) S (O) 2 R 8, -NR 9 C (O) NHR 8 or -NR ₉ C (O) NHR ₈ Wherein R ₈ is C _6-10 aryl optionally substituted by C _1-4 alkyl, especially methyl, C _1-4 alkoxy, especially methoxy, F, Cl, -CN or -NO ₂ , Is C _1-10 alkyl substituted or unsubstituted by phenyl or F or Cl and R ₉ is H, C _1-10 alkyl, C ₅ - or C ₆ cycloalkyl, C ₅ - or C ₆ cycloalkyl-C _1-6 alkyl, phenyl -C _1-6 alkyl or phenyl -C _2-6 alkenyl, in particular H, C _1-6 alkyl, cyclohexyl, cyclohexyl -CH ₂ -, cyclohexyl -CH ₂ CH ₂ -, cyclohexyl _{-CH 2 CH 2 CH 2 -,} C 6 H 5 CH 2, C 6 H 5 CH 2 CH 2 -, C 6 H 5 CH 2 CH 2 CH 2 - and C ₆ H ₅ CHCHCH ₂ -, and, R ₉ is especially H, linear, preferably branched, C _1-6 alkyl, phenyl or phenyl (CH ₂ ) _z - wherein z is a number from 1 to 4, for example methyl, ethyl, n- or i- Or t-butyl, pentyl, isopentyl, hexyl, benzyl, phenylethyl, phenylpropyl And phenyl -CH = CH-CH ₂ -, quite particularly preferably _{CH 2 -CH (CH 3) 2} , benzyl, 2-phenylethyl and 3-phenylpropyl Im) or; or

(b) R ₄ is OH, halogen, C (O) OR _s1 , OC (O) R _s4 , C (O) R _s2 , nitro, NH ₂ , cyano, SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y, C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _{2 -11} hetero cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 aralkenyl, C _7-10 heteroalkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamido, carbamate, sulfone hydrazide , carbalkoxy hydrazide, carbonyl hydroxamic acid and amino acid substituted or unsubstituted by one or more substituents selected from the group consisting of carbonyl amide, C _1-12 alkyl, C _3-12 cycloalkyl or C _7-11 and aralkyl, where R _s1 is hydrogen, M _y, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl Kiel, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 aralkyl and heteroaryl, R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl , R _s2 and R ₂₀ are selected from the group consisting of hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 hetero Cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, The substituted alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, The term " alkenyl " Is unsubstituted or substituted by one of the above-mentioned substituent, y is 1 and M is either a monovalent metal, y is ½ and M is a divalent metal.

Among the compounds of group (a), preferable ally groups include

(i) R ₄ is C ₆ H ₁₁ , C ₆ H ₁₁ -CH ₂ , C ₆ H ₁₁ -CH ₂ CH ₂ -, C ₆ H ₅ -CH ₂ -, C ₆ H ₅ -CH ₂ CH ₂ - or C ₆ H ₅ -CH = CH-CH ₂ -; or

(ii) R ₄ is C ₆ H ₁₁ , C ₆ H ₁₁ -CH ₂ -, C ₆ H ₁₁ -CH ₂ CH ₂ -, C ₆ H ₅ -CH ₂ -, C ₆ H ₅ -CH ₂ CH ₂ - _{, -CH 2 -NR 19 SO 2 R} 18, -CH 2 -NR 19 C (O) R 40, CH 2 NHC (O) NHR 18, -CH 2 NHR 21 or _{CH 2 N (R 21) 2} ( where , R ₁₈ is phenyl substituted by -C ₆ H _5, 1 to 3 methyl or methoxy or -NO ₂ or F or Cl, especially p-CH ₃ -C ₆ H ₄ -, p-CH ₃ OC ₆ H ₄ - or 2,3,5-CH ₃ -C ₆ H ₂ - or pO ₂ NC ₆ H ₄ -, or C _1-4 alkyl substituted by F, -CF ₃ and R ₄₀ is a and 3 methyl or methoxy or -NO _2, or F, or phenyl which is unsubstituted or substituted by Cl, R ₁₉ is H, C _1-6 alkyl, phenyl - (CH _{2) z} - (wherein, z is 1 to 3 Im) phenyl -CH = CH-CH ₂ -, and in particular -CH ₂ -CH (CH _{3) 2} or benzyl, R ₂₁ is _{-CH 2 -CR 22 R 23 R 24} ( wherein, R ₂₂ and R ₂₃ is a methyl, an ethyl or phenyl, R ₂₄ is H, methyl or ethyl and, quite particularly preferably R ₂₂ and R ₂₃ is methyl and R ₂₄ is H ) It will be in.

(b) a preferred spiked compounds of group R ₄ is NH _2, cyclohexyl, C _{6-10 aryl, R 8 C (O) N} (R 9) -, R 8 S (O) 2 N (R 9) C ₆ H ₁₁ , C ₂ -C ₆ H ₅ , (C ₁ -C ₆₎ alkyl, which is unsubstituted or substituted by one or more substituents selected from the group consisting of --NR ₉ C (O) NHR ₈ and R _{8 '} R _{9' CH 2) 2 -C 6 H 5} , methyl, ethyl or isopropyl, and, in which _{R 8, R 9, R 8} ' and R _9' are each independently hydrogen, C _1-12 alkyl, C _3-12 cycloalkyl alkyl, C _6-10 aryl or C _7-11 aralkyl, all of which are OH, halogen, C (O) OM _y, nitro, cyano, SO ₃ M _{y, y} OSO ₃ M, NR ₂₀ SO ₃ M _y, Substituted or unsubstituted with one or more substituents selected from the group consisting of C _1-12 alkyl, C _1-12 alkoxy and C _6-10 aryl, wherein R ₂₀ is hydrogen, C _1-12 alkyl, C _{2- 12} alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _5-9 H. Interrogating aryl, C _7-11 aralkyl, and C _6-10 heteroaralkyl, C _8-11 aralkyl or C _7-10 alkenyl alkenyl heteroaralkyl Al, y is 1 and M is either a monovalent metal, y is ½ And M is a divalent metal. A particularly preferred compound is _{R 8, R 9, R 8} ' and R _9' are each independently OH, F, Cl, C (O) ONa, nitro, cyano, SO ₃ Na, C _1-6 alkyl, methoxy and substituted or unsubstituted by one or more substituents selected from the group consisting of phenyl, hydrogen, C _1-12 alkyl, cyclohexyl, it is phenyl, naphthyl, or C _7-11 aralkyl.

In a preferred group of compounds of formula Ia, R ₄ is _{C 6 H 11, CH (CH} 3) 2, CH 2 - phenyl, (CH _{2) 2} - phenyl, CH ₂ NHC (O) - phenyl, CH ₂ NHC ( O) (CH _{2) 3} - _{phenyl, CH 2 NHC (O) (} CH 2) 3 OH, CH 2 NHC (O) CF 3, CH 2 NHC (O) C 6 H 11, CH 2 NHC (O) C _{11 H 23, CH 2 NHC (} O) CH (C 6 H 6) 2, CH 2 HNC (O) NHC 6 H 6, CH 2 NHC (O) C 2 H 4 CO 2 Na, CH 2 NHC (O) _{C 6 [(1,3,4,5) OH]} 4 H 7, CH 2 NHC (O) C 6 H 4 -p-SO 3 Na, CH 2 NHC (O) C 6 H 4 Cl, CH 2 NHC _{(O) C 6 H 4 NO} 2, CH 2 NHC (O) C 6 H 4 OCH 3, CH 2 NHC (O) C 6 H 4 (3,4) Cl 2, CH 2 NHC (O) C 6 H _{4 CH 3, CH 2 NHC (} O) C 6 H 4 C 6 H 5, CH 2 NHC (O) C 6 H 4 CN, CH 2 NHC (O) C 10 H 7, CH 2 NHC (O) C 6 _{H 4 COONa, CH 2 NHC (} O) (CHOH) 2 COONa, CH 2 N (CH 2 CH = CH- phenyl) [C (O) - _{phenyl], CH 2 N (CH 2} CH (CH 3) 2] [C (O) - _{phenyl], CH 2 N [C (} O) C 6 H 5] CH 2 C 6 H 5, CH 2 N [C (O) C 6 H 5] (CH 2) 3 C 6 H Phenyl, CH ₂ NHCH ₂ -phenyl, CH ₂ NHCH ₂ CH (CH ₃ ) ₅ , CH ₂ C ₆ H ₁₁ , (CH ₂ ) ₂ C ₆ H ₁₁ , CH ₂ NH ₂ , CH ₂ NHCH ₂ CH = ₂ , CH ₂ N (CH ₂ -phenyl) ₂ , CH ₂ N [CH ₂ CH (CH ₃ ) ₂ ] ₂ , CH ₂ NHSO ₂ -p- nitrophenyl, CH ₂ NHSO ₂ -p- _{tolyl, CH 2 NHSO 2 CF 3,} CH 2 NHC (O) NHC 6 H 5 , or CH ₂ N [SO ₂ -p- nitrophenyl] [CH ₂ It is CH (CH _{3) 2].}

The present invention also relates to a process for the preparation of a compound of formula I according to claim 1, which comprises etherifying the 3-OH group of a compound of formula V:

R ₁ -R ₁₃

In this formula,

R ₁ , R ₂ and X have the abovementioned meaning,

R ₁₂ is a protecting group,

R _{12 '} and R _{12 "} are each independently hydrogen or a protecting group,

R ₁₃ is a leaving group.

The leaving group may be a halide, such as chloride, bromide and iodide, and a sulfonic acid, for example, substituted or unsubstituted by C _1-4 alkyl, C _1-4 alkoxy, nitro, cyano or halogen (chlorine, bromine) For example, trifluoroethanesulfonate, aliphatic, alicyclic or aromatic sulfonic acid. Some examples of these acids are methanesulfonic acid, mono-, di- or trifluoromethanesulfonic acid or p-nitrobenzenesulfonic acid. CF ₃ -SO ₂ -O ^- (search also, referred to as triflate) is particularly preferably used. The leaving group is advantageously selected from the group consisting of halogen, and unsubstituted and halogenated R-SO ₂ -, wherein R is C _1-12 alkyl, especially C _1-6 alkyl, C _5-6 cycloalkyl, Phenyl, benzyl, C _1-12 alkylphenyl, especially C _1-4 alkylphenyl, or C _1-12 alkylbenzyl, especially C _1-4 alkylbenzyl such as methane, ethane, propane, butane, benzene, And p-methylbenzenesulfonyl. A preferred leaving group _{Cl, Br, I, -SO 2} CF 3 , and (triflate) and p- nitrobenzene-sulfonyl, -SO ₂ CF ₃ are especially preferred.

Compounds of formula (VI) are known in some cases, or can be prepared according to the literature (Degerbeck, F., Fransson, B., Grehn, L., Ragnarsson, U., J. Chem. Soc. Perkin Trans. 1: 11-14 (1993); Dureault, A. et al., Tranchepain, I., Depezay, J. C., Synthesis 491-493 (1987). Optically pure compounds can be obtained using optically pure starting compounds or chromatographic separation processes, for example in the form of a chiral solid (e. G., Amino acids, alpha -hydroxylic acid).

The compounds of formula V are novel, and the present invention relates to them analogously. These can be obtained by known glycosylation methods starting from known fucosyl and galactosyl donors and from diols of the formula HO-X-OH. The gradual introduction or the reversal of galactose and fucose is also advantageous.

For the preparation of the compound of formula (V), first a pseudo-trisaccharide building block is synthesized. The pseudo-trisaccharides are activated by a glycosidic bond of activated and protected galactose on the fucose-OX-OH building block, or by a glycosidic bond of a suitably protected and activated fucose on the galactose-OX-OH building block Assembled. Glycosylation reactions are known on a large scale and are described in professional literature.

The group R < ₁ > can then be introduced into the pseudosodium salt stream. The resulting compound of formula I can then be modified. Such modifications may involve hydrogenation of an aromatic compound to an alicyclic group, which may occur, for example, simultaneously with the hydrolytic cleavage of the protecting group. In addition, the amino group may be acylated and / or alkylated and / or sulfonated. The preparation of the secondary and tertiary amines can be carried out by reductive amination.

Advantageously, it has been found that the 3-OH group of the galactose residue is activated by etherification. Particularly suitable for this purpose are dialkyltin oxide, dialkyltin alkoxylate and bis (trialkyl) tin oxide. Some examples of are dibutyltin oxide, dibutyltin (O- methyl) ₂ and (tributyltin) ₂ O. The activator is preferably used in stoichiometric amounts. In this case, the reaction is carried out in two steps, a) activation and b) coupling with a compound of formula (VI).

The activation process can be carried out at 40 to 200 캜, preferably 60 to 120 캜.

The compound of formula V and the compound of formula VI may be used in equal amounts. However, it has proved convenient to use the compound of formula (VI) in an excess amount, for example, in an amount of 10 times or less, preferably 5 times or less the amount of the compound of formula (V).

It is also convenient to conduct the reaction in a two-stage reaction in the presence of an inert solvent or a mixture of solvents. Reactive quantum solvents such as alkanols and also acid amides are unsuitable for reaction step b). Non-polar aprotic and polar aprotic or polar protic solvents can be used. These include aliphatic or aromatic hydrocarbons such as pentane, hexane, cyclohexane, methylcyclohexane, benzene, toluene or xylene; Halogenated hydrocarbons such as methylene chloride, chloroform, tetrachloromethane, 1,2-dichloroethane, 1,1,2-trichloroethane, 1,1,2,2-tetrachloroethane and chlorobenzene; Linear or cyclic ethers such as diethyl ether, dibutyl ether, ethylene glycol dimethyl or diethyl ether, tetrahydrofuran and dioxane; N, N -dialkylated carboxamides such as dimethylformamide; N-alkylated lactams such as N-methyl pyrrolidone; Ketones such as acetone and methyl isobutyl ketone; Carboxylic acid esters such as methyl or ethyl acetate; Or an alkanol such as methanol, ethanol, propanol, butanol, and ethylene glycol monoethyl ether. Particularly preferred solvents are methanol, ethanol, benzene and toluene.

Protecting groups and methods for derivatizing hydroxyl groups using such protecting groups are commonly known in the sugar and nucleotide chemistry and are described, for example, in Beaucage, SL Leyer, R., Tetrahedron 48: 2223-2311 (1992) ]. Examples of such protecting groups are benzyl, methylbenzyl, dimethylbenzyl, methoxybenzyl, dimethoxybenzyl, bromobenzyl, 2,4-dichlorobenzyl; Di (methylphenyl) methyl, di (dimethylphenyl) methyl, di (methoxyphenyl) methyl, di (dimethoxyphenyl) methyl, triphenylmethyl, tris-4,4 ' (Methoxyphenyl) methyl, di (methoxyphenyl) phenylmethyl, tri (methoxyphenyl) methyl, , The number of carbon atoms of the alkyl group is 1 to 20, preferably 1 to 12, particularly preferably 1 to 8, and more preferably 1 to 8. The alkyl group of the alkyl group is preferably an alkyl group having 1 to 20 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, Butyldimethylsilyl, t-butyl-diphenylsilyl, n-octyl-dimethylsilyl, (1,1,1- Benzoyl, methoxybenzoyl, chlorobenzoyl, and bromobenzoyl, and the like, with a suitable base such as, for example, acetonitrile, Is C _2-12 -.., In particular a C _2-8 acyl protecting groups which may be the same or may be different from the preferred protecting group is a straight or branched C _1-8 alkyl, especially C _1-4 alkyl, for example, methyl, ethyl, n-propyl, i-propyl, n-, i- and t-butyl, C _7-12 aralkyl such as benzyl, trialkylsilyl having 3 to 20, in particular 3 to 12, Dimethylsilyl, t-butyl-diphenylsilyl, n-octyl-dimethylsilyl, (1,1,2,2- 2-tetramethylethyl) dimethylsilyl; an acetal or ketal from an adjacent hydroxyl group of a sugar or a sugar derivative using an aldehyde and a ketone, and the number of carbon atoms is preferably 2 to 12 or 3 to 12 Methylidene groups such as C _1-12 alkylidene, preferably C _1-6 alkylidene, especially ethylidene, 1,1- and 2,2-propylidene, 1,1- and 2,2- Butylidene, C _1-4 alkylidene such as benzylidene, unsubstituted and halogenated C _2-12 acyl, especially C _2-8 such as acetyl, propanoyl, butanoyl, pentanoyl, hexanoyl, pivaloyl and benzoyl Acyl. ≪ / RTI >

The synthesis preferably takes place using a protecting group for R _{12 '} and R _{12 "} which together form an alkylidene group having 1 to 12 carbon atoms, more preferably 1 to 8 carbon atoms. In this connection, particularly preferred protecting groups are those in which R _{12 '} and R _{12 "} together are an alkylidene group, in particular having 1 to 12 carbon atoms, in which the alkylidene group forms an acetal or ketal using an oxygen atom. These protecting groups can be removed under neutral or slightly acidic conditions. Particularly suitable protecting groups are acyl, benzyl, substituted benzyl, benzyloxymethyl, alkyl and silyl. R _{12 '} and R _{12 "} are particularly preferably alkylidene, for example alkyl- or alkoxy-substituted benzylidene. However, R _{12 '} and R _{12 "} may also be hydrogen, or one of R _12' and R _12" may be a protecting group such as benzyl, and the remaining one of R _{12 '} and R _{12 "} May be hydrogen.

Examples of the carboxylate protecting groups are alkoxy- and aralkoxy group, preferably _{-CO 2 Bn, -CO 2 CH 3} .

The elimination reaction of the protecting group is preferably carried out at 0 to 50 ° C, particularly at room temperature.

Further specifications for the preparation of compounds of formula I are described in the examples.

The alternative synthetic pathway involves glycosidic linking the protected fucose hydroxy ether of a compound of formula VII with a protected galactose of formula VIII and then removing the protecting group from the resulting compound.

In this formula,

R is a leaving group,

R ₁ , R ₂ and X have the meanings given in claim 1,

R < ₁₂ > is a protecting group in formula (VII), in formula (VIII)

Z is O or S.

It is possible to select reaction conditions similar to those satisfying the process already described. For example, the leaving group R can be imidazol -C (= NH) -CCl ₃ or 4-pentenyl. Compounds of formula (VII) can be obtained in a simple manner, if appropriate with glycosidic linkages of a suitably protected fucose with a single protected compound of formula HO-X-OH. Compounds of formula (VIII) can be obtained by etherification of compounds of formula R < ₁ > OH, where appropriate, with protected galactose.

The compounds according to the present invention have anti-inflammatory properties and can therefore be used as medicaments. Use of these agents may alleviate disorders such as cardiogenic shock, myocardial infarction, thrombosis, rheumatism, psoriasis, dermatitis, acute respiratory distress syndrome, asthma, arthritis and metastatic cancer. The invention also relates to a compound according to the invention for use in a method of treatment for the treatment of disorders in warm-blooded animals, including humans. The dose for a warm-blooded animal having a body weight of about 70 kg may be, for example, 0.01 to 1,000 mg / day. Administration is preferably carried out in the form of a pharmaceutical composition, parenterally, for example intravenously or intraperitoneally.

The invention also relates to a pharmaceutical composition comprising an effective amount of a compound according to the invention, alone or, preferably, in combination with a large amount of other active substances, pharmaceutical carriers and, where appropriate, excipients.

The pharmacologically active compound according to the present invention can be used in the form of a composition which can be administered parenterally or as an injectable solution. This type of liquid preparation is an isotonic aqueous solution or suspension in which the latter can be prepared, for example, in the case of a freeze-dried composition which can be prepared by itself, for example, with an active substance, or with a carrier, for example mannitol, prior to use have. May contain a sterilizing agent and / or excipients such as preservatives, stabilizers, wetting agents and / or emulsifiers, solubilizers, salts for controlling osmotic pressure and / or buffers. Pharmaceutical compositions, which may optionally contain other pharmacologically active substances such as antibiotics, are prepared in a manner known per se, for example by a conventional dissolving or lyophilizing process, and contain from about 0.1 to 90%, especially from about 0.5 to < RTI ID = About 30%, for example 1 to 5%, of the active substance (s).

The following examples illustrate the invention.

The following abbreviations are used:

Bz: benzoyl; Bn: benzyl; DMTST: dimethyl (methylthio) sulfonium triflate; FAB: Rapid Atomic Shock Mass Spectroscopy; OTf: triflate; Ph: phenyl; SEt: C ₂ H ₅ S; THG: thioglycerol; THF: tetrahydrofuran; NBA: m-nitrobenzyl alcohol; DMF: N, N-dimethylformamide; DME: 1,2-dimethoxyethane; MeOH: methanol; HRP: horseradish peroxidase; BSA: bovine serum albumin; PAA: polyacrylamide; SA: Streptavidin.

The unconnected hyphen in the formula means methyl.

The molecular sieve is activated at 300 ° C under high vacuum for 12 hours before use. They are used in powder form.

A: Preparation of starting compounds

Example A1 : Preparation of compound A1

3-azido-2-hydroxypropionic acid 28 (Dureault, A., Tranchepain, I., Depezay, JC, Synthesis 491-493 (1987)) at room temperature was added benzyl chloride (660 mL, 5.72 mmol) , Triethylamine (850 mL, 6.1 mmol) and DMF (7.0 mL). The mixture is stirred for 16 hours and then additional triethylamine (850 L, 6.1 mmol) and benzyl chloride (660 L, 5.72 mmol) are added. The reaction mixture is stirred for 2 days and then concentrated under high vacuum. The residue is dissolved in water and the mixture is extracted several times with ethyl acetate. The combined organic phases are washed with saturated NaCl solution, dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The crude product (1 g) was purified by flash chromatography on silica gel (ethyl acetate / hexane 1: 4) to give benzyl R-3-azido-2-hydroxypropionate 29 (0.717 g, 85% Oil.

Trifluoromethane sulfonic anhydride (770 ㎖, 4.41 mmol) a-stirring at 20 ℃, anhydrous CH ₂ Cl ₂ (11.0 ㎖) Alcohol 29 (0.85 g, 3.84 mmol) and of 2,6-di-tert-butyl Pyridine < / RTI > (1.12 mL, 4.99 mmol). The clear, colorless solution is warmed to 0 < 0 > C over 40 minutes and stirred at this temperature for a further 2 hours. The mixture is diluted with CH ₂ Cl ₂ (40 mL) and ₁ M KH ₂ PO ₄ aqueous solution (30 mL) is added with vigorous stirring. The organic phase is separated off and the aqueous phase is extracted twice with CH ₂ Cl ₂ . The combined organic phases are washed with H ₂ O (30 mL), dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The oily residue (2.3 g) was purified by flash chromatography on a silica gel column (ethyl acetate / hexane 1: 7) to give benzyl R-3-azido-2-trifluoromethanesulfonyloxypropionate A1 (1.16 g, 85%) as yellow oil.

Example A2 : Preparation of compound A2

Benzyl (R) -4-phenyl-2-trifluoromethanesulfonyloxybutyrate (A2):

MeOH / H ₂ O: the (R) -2- hydroxy-4-phenylbutyric acid 26 (0.2 g, 1.11 mmol) of (9 1, 1.3 ㎖) is adjusted to pH 8 with 20% Cs ₂ CO ₃ solution. Concentrate the solution in vacuo and ethanol was first and azeotroped using this stand-hexane and then dried under high vacuum to remove residual H ₂ O. The residue is mixed with N, N-dimethylformamide (1.3 mL) and benzyl bromide (132 L, 1.11 mmol) and the mixture is stirred at room temperature for 75 minutes. Additional benzyl bromide (20 [mu] L, 0.168 mmol) is then added and the mixture is stirred for an additional 50 minutes. The white suspension is diluted with CH ₂ Cl ₂ (5 mL), filtered through HyfloSuperCel ^R and concentrated in vacuo. The crude product was purified by flash chromatography on silica (eluent: ethyl acetate / hexane 4: 1) to give benzyl (R) -2-hydroxy-4-phenylbutyrate 27 (0.21 g, 70%). The product (0.3 g, 1.11 mmol) is dissolved in CH ₂ Cl ₂ (4.5 mL), 2,6-di-tert-butylpyridine (323 μL, 1.44 mmol) is added and the mixture is cooled to -20 ° C . Trifluoromethanesulfonic anhydride (222 L, 1.27 mmol) is then added dropwise over 3 minutes and the solution is warmed to 0 C over 45 minutes. After 75 min at 0 C, the mixture is diluted with CH ₂ Cl ₂ (20 mL) and washed with 1 M KH ₂ PO ₄ aqueous solution (15 mL). The aqueous phase is extracted with CH ₂ Cl ₂ (2 x 10 mL) and the combined organic phases are washed with H ₂ O (10 mL), dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The residue was roughly purified by column filtration over silica gel (eluent: ethyl acetate / hexane 1: 9) to give crude triflate A2 (0.311 g, 70%) as an oil. The product is used immediately for the next step (preparation method of B1.18).

Example A3 : Preparation of compound A3

R-hydroxymandelic acid is converted to triflate A3 according to Example A2.

Example A4 : Preparation of compound A4

R-2-Hydroxy-3-methylbutyric acid is converted to triflate A4 according to Example A2.

Example A5 : Preparation of compound A5

R-2-Hydroxy-3-cyclohexylpropionic acid is converted to triflate A5 according to Example A2.

B: Preparation of analog

Example B1 : Preparation of compound B1.1

(5.38 g, 8.40 mmol) (Biessen, EAL, Beuting, DM, Roelen, HCPF, van de Marel, GA, van Boom, JH, van Berkel, TJC, J. Med. Chem. 38: 1538-1546 (1995)] and water component 2 (3.44 g, 6.46 mmol) is dried under high vacuum for 1 hour. The activated 4 A molecular sieve (20 g) and DMTST (4.17 g, 16.14 mmol) followed by CH ₂ Cl ₂ (70 mL) are then added under a nitrogen atmosphere. The yellowish suspension is dried at room temperature and after 3 h, 5 ml of a suspension of DMTST (5.84 g, 22.61 mmol), 4 A molecular sieves (4.0 g) and CH ₂ Cl ₂ (35 ml) is added. An additional 5 ml of the DMTST suspension is added after 30, 45 and 90 minutes, respectively. The brown reaction mixture is then stirred for 15 hours and then filtered through Hyflo Super Cel ^R (filter aid), where it is washed with CH ₂ Cl ₂ (300 mL). The filtrate was first 10% NaHCO ₃ solution and then extracted by shaking with saturated NaCl solution, and dried the organic phase with Na ₂ SO ₄ filtered and concentrated in a vacuum rotary evaporator. The residual brown foam was purified by two column chromatography on silica gel (eluent: ethyl acetate / hexane 1: 4 for primary chromatography; secondary chromatography: ethyl acetate / toluene 1: 9) to give pure product 3 As a colorless solid (4.28 g, 60%) which is used immediately.

A solution of tetrabenzoate 3 (3.38 g, 3.04 mmol) and sodium methoxide (0.165 g, 3.05 mmol) in anhydrous methanol (32 mL) is stirred at room temperature for 3 hours. The mixture is neutralized by the addition of a strong acidic ion exchanger (Amberlyst 15) and then filtered through Hyflo Super Cel ^R , where it is washed with CH ₂ Cl ₂ . The filtrate is concentrated in vacuo and the residual yellow oil is purified by flash chromatography on silica gel (eluent: CH ₂ Cl ₂ / methanol 19: 1) to give pure Tetrol 4 (1.95 g, 92%).

A solution of tetrol 4 (1.0 g, 1.44 mmol), benzaldehyde dimethylacetal (430 mL, 2.86 mmol) and camphorsulfonic acid (0.1 g, 0.43 mmol) in acetonitrile (20 mL) is stirred at room temperature. After 4 hours, additional camphorsulfonic acid (0.15 g, 0.65 mmol) is added and the mixture is stirred at room temperature for an additional 6 hours and then it is heated at 35 DEG C for an additional 6 hours. Additional camphorsulfonic acid (0.06 g, 0.26 mmol) is then added and the solution is stirred at room temperature for 6 hours. The reaction mixture is filtered through Hyflo Super Cel ^R , where it is washed with ethyl acetate. The filtrate is first extracted by shaking with a saturated aqueous NaHCO ₃ solution and then with a saturated solution of NaCl, the organic phase is dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo to give 1.5 g of crude product. The crude product was purified by flash chromatography on silica gel (CH ₂ Cl ₂ / MeOH 39: 1) to give a mixture of less polar byproducts (0.4 g) in addition to the required benzylidene acetal 5 (0.475 g) do. The latter is once again treated and refined under the reaction conditions described above to give an additional 0.08 g of benzylidene acetal 5. The total yield of 5 is 0.555 g (49%):

d)

A mixture of Diol 5 (0.098 g, 0.125 mmol), di-n-butyltin oxide (0.062 g, 0.25 mmol) and methanol (5 mL) is heated under reflux in an argon atmosphere for 2 hours. The reaction mixture is concentrated in vacuo, pentane is added to the residue and it is again concentrated. Anhydrous CsF (dried at 300 [deg.] C under high vacuum, 0.068 g, 0.45 mmol) was added under an argon atmosphere and the mixture was further dried under high vacuum (30 min). After the addition of anhydrous 1,2-dimethoxyethane (1.5 ml), a solution of benzyl R-3-phenyl-2-trifluoromethanesulfonyloxypropionate [see reflux in 1,2-dimethoxyethane : Degerbeck, F., Fransson, B., Grehn, L., Ragnarsson, U., J. Chem. Soc. Perkin Trans. 1: 11-14 (1993)] (0.24 g, 0.62 mmol). The mixture is first stirred vigorously at room temperature for 4 hours and then at 40 < 0 > C for a further 2 hours. After addition of ₁ M KH ₂ PO ₄ aqueous solution, the mixture is diluted with water and extracted three times with ethyl acetate. The combined organic phases are extracted by shaking with dilute KF aqueous solution and then with saturated NaCl solution. The organic phase is dried (Na ₂ SO ₄ ), filtered and concentrated in a vacuum rotary evaporator to give a crude product. Purification by flash chromatography on silica gel (gradient eluent: ethyl acetate / toluene 1: 4 to 100% ethyl acetate), ether 6 (0.045 g, 35%) and the more polar precursor 5 (0.043 g, 44% Lt; / RTI >

Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.03 g) and protected compound 6 (0.03 g, 0.029 mmol) in dioxane (2.5 ml), water (1.2 ml) and glacial acetic acid Lt; / RTI > Flask is flushed and flushed several times with argon. It is then flushed with hydrogen and the black reaction mixture hydrogenated at room temperature under slight hydrogen elevation for 13 hours and then filtered through a cellulose filter (pore size 45 μm). The filtrate is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The residue solution in water is passed through a Dowex50 ion exchanger column (Na ⁺ form, diameter 0.9 cm, length 3.5 cm) and washed with deionized water. Concentrating the clear filtrate was purified by reverse phase chromatography (RP18 silica gel, column diameter 1.4 ㎝, length 7.0 ㎝, gradient eluent: over 45% MeOH / H ₂ O to _{50% MeOH / H 2 O 40} % MeOH / H ₂ O) to give the target molecule B1.1 (0.015 g, 78%) as a colorless solid:

A mixture of tetrol 4 (0.038 g, 0.055 mmol) and di-n-butyltin oxide (0.029 g, 0.117 mmol) in anhydrous methanol (2.0 mL) is heated to reflux in an argon atmosphere. After 2.25 h, the clear, colorless solution is concentrated in vacuo, the residue is mixed with benzene and concentrated several times to remove excess MeOH. It is then dried under high vacuum for 30 minutes and the residue is mixed with CsF (dried at 300 [deg.] C under high vacuum, 0.03 g, 0.197 mmol) and dry 1,2-dimethoxyethane (0.4 ml) under an argon atmosphere. The mixture was cooled to 0 ° C and benzyl R-3-phenyl-2-trifluoromethanesulfonyloxypropionate (Degerbeck, F., Fransson, NJ) in anhydrous 1,2-dimethoxyethane (0.4 ml) B., Grehn, L., Ragnarsson, U., J. Chem. Soc. Perkin Trans. 1: 11-14 (1993)] (0.085 g, 0.219 mmol) was added using a funnel. The reaction mixture is then warmed to room temperature and stirred for 1 hour and then it is stirred at 40 < 0 > C for a further 2 hours. After addition of ₁ M KH ₂ PO ₄ aqueous solution, the mixture is diluted with water and extracted three times with CH ₂ Cl ₂ . The combined organic phases are washed with aqueous KF solution, dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The residue was purified by twice flash chromatography on silica gel (first _{chromatography: 2% MeOH / CHCl 3;} 2 car chromatography: 45% ethyl acetate / toluene), an ether 8-five days (0.013 g, 25 %):

(0.03 g, 0.032 mmol) and Pd / C (0.03 g, Pd content 10%) and then glacial acetic acid (0.1 ml) in 1,4-dioxane / water (2.0 ml of a 4: Lt; / RTI > Flask is flushed and flushed several times with argon. This process is repeated with hydrogen. The mixture was stirred until the test by thin layer chromatography (silica gel plate n-BuOH: H ₂ O: acetone: glacial acetic acid: NH ₄ OH 70: 60: 50: 18: 1.5) indicated the absence of the precursor and intermediate 3.5 hours) under slight hydrogen pressure under vigorous stirring. The black suspension is filtered twice through a cellulose filter (pore size 45 [mu] m) and the filtrate is concentrated in vacuo. The residue is dissolved in water and the solution is passed through an ion exchanger column (Dowex 50, Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The filtrate was concentrated and purified by reverse phase chromatography (RP18 silica gel, column diameter 1.4 ㎝, length 7.0 ㎝, gradient eluent: 45% MeOH / H ₂ O to _{50% MeOH / H 2 O 40} % MeOH / H 2 over the O) to give the target molecule B1.1 (0.015 g, 78%) as a colorless solid.

Example B2 : Preparation of compound B1.2

The aromatic compound B1.1 (0.152 g, 0.256 mmol) and 5% Rh / Al ₂ O ₃ (0.2 g) are dissolved in H ₂ O (5.5 ml), dioxane (3.5 ml) and acetic acid (1.0 ml). The air is first replaced by a plurality of exhausts with argon and then with hydrogen. The black suspension is hydrogenated under slight hydrogen pressure under vigorous stirring for 2 days and then filtered through a cellulose filter (pore size 45 μm). The clear, colorless solution is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The crude product solution in water is filtered through a Dowex 50 ion exchanger column (Na ⁺ type, length: 9 cm, diameter: 1.3 cm), and the column is washed with water. The filtrate was concentrated in vacuo and the residue (0.16 g) was purified on Bio-Gel P2 (65 탆 particle size, 2.5 ㎝ in column diameter, 100 ㎝ in length, eluent: water, 0.55 ml / min at 215 nm detection) Purification by gel filtration and subsequent reverse phase chromatography (Merck RP18 silica gel, eluent: 55% MeOH / H ₂ O) gave the target molecule B1.2 (0.11 g, 73%) as a white fluffy solid ).

Example B3 : Preparation of compound B1.3

A mixture of benzylidene acetal 9 (0.5 g, 1.60 mmol) (EP 671,406), sodium cyanoborohydride (0.9 g, 14.3 mmol), 4 Å active molecular sieve (1.0 g) and anhydrous tetrahydrofuran The suspension is cooled to 0 < 0 > C under a nitrogen atmosphere. The pH of the mixture is carefully adjusted to 1 by adding a saturated solution of HCl gas in anhydrous diethyl ether. The suspension is stirred at 0 < 0 > C and the pH is maintained at 1 by the continuous addition of an ethereal HCl solution. After 10 h, a saturated aqueous NaHCO ₃ solution (30 mL) was added. The organic phase is separated off and the aqueous phase is extracted twice with ethyl acetate (70 ml each time). The combined organic phases are dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo to give 1.3 g of crude product. And, to give the 6-benzyl ether 10 (0.3 g, 60%) and a somewhat less polar byproduct (0.045 g) which requires: purified by flash chromatography on silica gel (1 CHCl ₃ / isopropanol 19):

Pyridine (0.45 mL, 5.56 mmol) and benzoyl chloride (0.49 mL, 4.22 mmol) were added to a solution of triol 10 (0.296 g, 0.941 mmol) in CH ₂ Cl ₂ (3.0 mL) at 0 ° C. The reaction mixture was stirred at 0 ℃ for 3.5 hours and then is added a 1M KH ₂ PO ₄ aqueous solution, The mixture was extracted three times with CH ₂ Cl _2. The combined organic phases are washed with water, dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo to give 1.0 g of crude product. Purification by flash chromatography on silica gel (hexane / ethyl acetate 4: 1) gives tribenzoate 11 as yellowish crystals (0.517 g, 88%).

Anhydrous CH ₂ Cl ₂ (8.0 mL) was added under an argon atmosphere to a solution of thioglycoside 11 (0.377 g, 0.60 mmol), glycosylated Compound 2 (0.32 g, 0.60 mmol) (EP 671,409) ). ≪ / RTI > A suspension of DMTST (0.39 g, 1.51 mmol) and 4 Å activated molecular sieves (0.8 g) in anhydrous CH ₂ Cl ₂ (5.0 mL) is prepared in a second round bottom flask. The two suspensions are stirred at room temperature for 3.5 hours. Three fractions of 1 ml of DMTST suspension are then added to the glycosyl donor / acceptor mixture over 1 hour. The yellowish reaction mixture is stirred at room temperature for an additional 1.5 h, then filtered through Hyflo Super Cel ^R , where it is washed with CH ₂ Cl ₂ . The filtrate NaHCO ₃ aqueous solution, and which is then extracted by shaking with water. The aqueous phase is re-extracted with CH ₂ Cl ₂ , the combined organic phases are dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo to give 0.67 g of crude product. The product 12 (0.404 g, 61%) was colorless and purified by flash chromatography twice on silica gel (primary chromatography: toluene / ethylacetate 14: 1; secondary chromatography: hexane / ethyl acetate 4: 1) Is obtained as a foam.

A solution of tribenzoate 12 (3.42 g, 3.12 mmol) and sodium methoxide (0.169 g, 3.12 mmol) in methanol (65 mL) is stirred at room temperature for 6 hours. Subsequently, the acidic ion-exchange with a base was added (Amberlyst 15) and then neutralized, and the suspension is filtered through Hyflo Super Cel ^R. The filtrate was concentrated in vacuo and the residual yellow oil (3.35 g) was purified by flash chromatography on silica gel (CH ₂ Cl ₂ / MeOH, 19: 1) to give the triol 13 (2.15 g, 88% Is obtained as a foam:

A mixture of triol 13 (0.515 g, 0.656 mmol) and anhydrous di-n-butyltin (0.245 g, 0.984 mmol) in anhydrous methanol (15 mL) is heated under reflux in a nitrogen atmosphere for 2 hours. The clear solution is concentrated in vacuo, dissolved in benzene and concentrated three times to remove excess MeOH. The residue was dried under high vacuum and then dried with anhydrous CsF (0.5 g, 3.29 mmol) at 300 < 0 > C and then with anhydrous 1,2-dimethoxyethane (4.0 ml) and anhydrous 1,2-dimethoxyethane A solution of benzyl R-3-azido-2-trifluoromethanesulfonyloxypropionate A1 (1.16 g, 3.28 mmol) in tetrahydrofuran (8.0 mL) is added under an argon atmosphere. The reaction mixture was stirred at room temperature for 6 hours and then added to aqueous solution of 1M KH ₂ PO ₄ (60 ㎖). The mixture is extracted three times with ethyl acetate and the combined organic phases are washed first with aqueous NaHCO ₃ and then with NaCl solution, dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. Purification of the oily residue (1.15 g) by flash chromatography on silica gel (elution of the product with toluene / ethyl acetate 4: 1 followed by elution of the precursor with CH ₂ Cl ₂ / MeOH 19: 1) 14 (0.488 g, 75%) as a colorless foam and precursor 13 (0.075 g, 15%).

Pt / BaSO ₄ (0.35 g, Pt content: 5%) is added to a solution of azide 14 (0.11 g, 0.111 mmol) in ethyl acetate (12 mL). Flask is flushed and flushed several times with argon. It is then flushed with hydrogen and the mixture is hydrogenated under atmospheric pressure with vigorous stirring. The hydrogenation is stopped after 2.5 hours, the suspension is filtered through a cellulose filter (pore size 45 μm) and the filtrate is concentrated in vacuo. Purification of the residue (0.115 g) by flash chromatography on silica gel _{(CH 2 Cl 2 / MeOH 19} : 1), the amine which requires 16 (0.055 g, 51%) and less polar precursor 14 (0.042 g, 38%). Amine 16 is unstable and is used immediately for further experimentation.

(i) Preparation of benzamide intermediate 17: Diisopropylethylamine (3.5 mL, 0.02 mmol) and benzotriazole-1-yloxytripyrrolidinophosphonium hexaprazole phosphate (PyBOP) (0.012 g, 0.0271 mmol) Is added to a solution of the? -Amino acid derivative 16 (0.013 g, 0.0135 mmol) and benzoic acid (0.0033 g, 0.027 mmol) in dry THF (0.5 mL) at 0 ° C. The reaction mixture was stirred for 45 minutes, the addition of a saturated aqueous solution of NaHCO _3. The mixture was extracted three times with CH ₂ Cl ₂ and the combined organic phases were first washed with aqueous 1M KH ₂ PO ₄ solution (adjusted to pH 1-2 with 1 M aqueous HCl) and then with aqueous NaHCO ₃ , dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (gradient elution: 35% ethyl acetate / toluene to 40% ethyl acetate / toluene) to afford benzamide 17 (0.0098 g, 68%).

(ii) Deprotection of 17: Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.011 g) and benzyl ether 17 (0.1 ml) in dioxane (1.5 ml), water (0.7 ml) and glacial acetic acid (0.0097 g, 0.0091 mmol). Flask is flushed and flushed several times with argon. It is then flushed with hydrogen and the black mixture is hydrogenated under slight elevated pressure with vigorous stirring for 14 hours. The mixture is filtered through a cellulose filter (pore size 45 mu m) and the filtrate is concentrated in vacuo. The residue is dissolved in water and concentrated several times to remove excess acetic acid. The solution of the crude product with a small amount of water is then passed through an ion exchanger column (Dowex 50, Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The filtrate was concentrated in vacuo and the residue (0.007 g) was purified on Bio-Gel P2 (65 탆 particle size, 2.5 ㎝ in column diameter, 35 ㎝ in length, eluent: water, 0.59 ml / min at 230 nm detection) Purification by gel filtration and subsequent reverse phase chromatography (Merck RP 18 silica gel, gradient elution: 37% MeOH / H ₂ O to 45% MeOH / H ₂ O) gave the target molecule B1.3 (3.3 mg, 58% As a white fluffy solid (after lyophilization).

Example B4 : Preparation of compound B1.4

(20 ml, 0.129 mmol) was added at room temperature to a solution of amine 16 (0.032 g, 0.033 mmol), dihydrocinnamic acid (0.015 g, 0.033 mmol) in anhydrous THF , 0.1 mmol) and 1-hydroxybenzotriazole (0.025 g, 0.185 mmol) in DMF (5 mL). The reaction mixture is stirred for 30 minutes and then concentrated in vacuo. The residue (0.09 g) was purified twice by flash chromatography on silica gel (eluent: CH ₂ Cl ₂ / MeOH 39: 1 for primary chromatography, for CH ₂ Cl ₂ / isopropanol 39: 1) and pure amide 19 (0.031 g, 86%).

(b) Removal of 19: Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.035 g) and benzyl ether 19 (2.0 ml) (0.031 g, 0.0283 mmol). Flask is flushed and flushed several times with argon. It is then flushed with hydrogen and the black mixture is hydrogenated under slight hydrogen pressure under vigorous stirring for 18 hours. The mixture is filtered through a cellulose filter (pore size 45 mu m) and the filtrate is concentrated in vacuo. The residue is mixed with toluene (about 2 mL) and concentrated several times to remove excess acetic acid. A solution of the crude product (0.021 g) with a small amount of water is then passed through an ion exchanger column (Dowex 50, Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The filtrate was concentrated in vacuo and the residue (0.02 g) was purified by reverse phase chromatography (Merck RP 18 silica gel, column diameter 1.2 cm, length 6 cm, eluent: 60% MeOH / H ₂ O) The target molecule B1.4 (0.014 g, 74%) was purified by subsequent purification by gel filtration (particle size 65 탆, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, flow rate 0.5 ml / min, detection at 215 nm) As a colorless fluffy solid (after lyophilization).

Example B5 : Preparation of compound B1.5

(16 mL, 0.103 mmol) was added to a solution of amine 16 (0.026 g, 0.027 mmol) in a mixture of dry THF (1.0 mL) and DMF (0.2 mL) mmol), sodium 4-hydroxybutyrate (0.010 g, 0.079 mmol) and 1-hydroxybenzotriazole (0.020 g, 0.148 mmol). After 4 h, additional DMF (dimethylformamide) (0.2 mL) is added and the mixture is stirred for an additional 13 h. The volatile components (including DMF) were distilled off under high vacuum and the residue (0.09 g) was purified by flash chromatography on silica gel (CH ₂ Cl ₂ / MeOH 29: 1) to give amide 21 (0.02 g, 71 %).

(b) Removal of 21: Pd (OH) ₂ / C (Pearlman catalyst, 20% Pd content, 0.04 g) and dioxane (2.0 ml), water (1.0 ml) and glacial acetic acid (0.5 ml) (0.036 g, 0.034 mmol). Flask is flushed and flushed several times with argon. It is then flushed with hydrogen and the black mixture is hydrogenated under slight hydrogen pressure under vigorous stirring for 18 hours. The mixture is filtered through a cellulose filter (pore size 45 mu m) and the filtrate is concentrated in vacuo. The residue is mixed with toluene (about 2 mL) and concentrated several times to remove excess acetic acid. A solution of the crude product (0.022 g) with a small amount of water is then passed through an ion exchanger column (Dowex 50, Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The filtrate was concentrated in vacuo and the residue (0.02 g) was purified by gel filtration on a Bio-Gel P2 (particle size 65 m, column diameter 2.5 cm, length 35 cm, eluent: water, flow 0.5 ml / min, (0.015 g, 70%) of the target molecule B1.5 and purified by a subsequent reverse phase chromatography (Merck RP 18 silica gel, column diameter 1.2 cm, length 6 cm, eluent: MeOH / H ₂ O 1: ) As a colorless fluffy solid (after lyophilization).

Example B6 : Preparation of compound B1.6

Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.03 g) and azide 14 (0.03 g, 0.03 mmol) in dioxane (2.0 ml), water (1.0 ml) and glacial acetic acid Add to the mixture. Flask is flushed and flushed several times with argon. It is then flushed with hydrogen and the black mixture is hydrogenated under slight hydrogen pressure under vigorous stirring for 16 h. The mixture is filtered through a cellulose filter (pore size 45 mu m) and the filtrate is concentrated in vacuo. The residue was purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, 0.55 ml / min at flow rate, detection at 215 nm) and subsequent reverse phase chromatography (Merck RP 18, silica gel, column diameter 1.2 ㎝, length 7 ㎝, _{eluent: 25% MeOH / H 2 O} 1: purification by 4), the target molecule B1.6 (0.011 g, 70%) as a colorless fluffy solid (freeze-dried Lt; / RTI >

Example B7 : Preparation of compound B1.7

Amine B1.6 (0.09 g, 0.176 mmol) was dissolved in anhydrous MeOH (1.5 mL) and CH ₂ Cl ₂ (1.8 mL) and 3 Å active molecular sieves (about 0.2 g), cinnamaldehyde (24 μL, 0.19 mmol) And acetic acid (9 [mu] l). Yellow I stirring the suspension for 2 minutes and then addition of _{NaBH 3 (CN) (0.018 g} , 0.286 mmol). After 1.5 h, the mixture is filtered through a cellulose filter (pore size 45 μm), the filtrate is washed with 1: 1 MeOH / CH ₂ Cl ₂ and the filtrate is concentrated in vacuo. The glassy residue is dissolved in water (5 ml) and the solution is acidified with 1 M hydrochloric acid (0.7 ml) (approx. PH 1-2). The cloudy solution is again filtered through a cellulose filter (pore size 45 μm) and the filtrate is adjusted to pH 7 with 1M sodium hydroxide solution (about 1 ml) and then concentrated. The residue was purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 100 ㎝, eluent: water, flow 0.6 ml / min, detection at 215 nm) and subsequent reverse phase chromatography (Merck RP 18, silica gel, gradient eluent to give 50% MeOH / H ₂ O to _{70% MeOH / H 2 O)} , the target molecule B1.7 (0.03 g, 27%) as a white fluffy solid (after lyophilization) to give do.

Example B8 : Preparation of compound B1.8

1 M NaHCO ₃ (0.1 ㎖) was cooled and a solution of the amino acid B1.7 (0.01 g, 0.0159 mmol) in aqueous solution to 0 ℃, and a 1M solution of benzoyl chloride is added under vigorous stirring in benzene (16.0 ㎕). After an additional 40 minutes, 8.0 [mu] l, after 130 minutes an additional 3.0 [mu] l and a total of 3.5 hours an additional 1.0 [mu] l of benzoyl chloride solution are added. After a total of 4 h, the reaction mixture is diluted with water and extracted with CH ₂ Cl ₂ to remove excess reagent. The aqueous phase was concentrated in vacuo and the residue was purified by gel filtration on a Bio-Gel P2 (particle size 65 占 퐉, column diameter 2.5 cm, length 35 cm, eluent: water, flow rate 0.49 ml / min, detection at 215 nm) Purification by subsequent reverse phase chromatography (Merck RP 18 silica gel, gradient elution: 60% MeOH / H ₂ O to 70% MeOH / H ₂ O) gave the target molecule B1.8 (7.9 g, 66%) as white fluff As a solid (after lyophilization).

Example B9 : Preparation of compounds B1.9 and B1.10

It was freshly distilled benzaldehyde (CH ₂ Cl ₂ 1.0 ㎖ of 0.083 g, 0.1 ㎖, 0.078 mmol ), the Cl ₂ solution of CH ₂ of 3 Å activated molecular sieves (0.1 g) and glacial acetic acid (5 ㎕, 0.087 mmol) MeOH / Was added to a solution of the amino acid B1.6 (0.04 g, 0.078 mmol) in CH ₂ Cl ₂ (1: 1, 1.0 mL). Stir the suspension at room temperature, and after 2 minutes, the addition of _{NaBH 3 (CN) (0.008 g} , 0.129 mmol). After 2.5 h, an additional 15 [mu] l of benzaldehyde solution is added and the mixture is stirred for an additional hour. The reaction mixture is diluted with water, acidified with dilute acetic acid, filtered through a cellulose filter (pore size 45 μm) and the filtrate is adjusted to pH 8-9 with ₁ M NaHCO ₃ solution and concentrated. The residue was purified by gel filtration on Bio-Gel P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water, flow 0.5 ml / min, detection at 215 nm) and subsequent reverse phase chromatography (Merck RP 18, silica gel, gradient eluent: purification by 35% MeOH / H ₂ O to 60% MeOH / H ₂ O), and wherein the eluate is first mono-benzyl-amine B1.9 (0.020 g, 41%), and then, dibenzylamine B1.10 (0.005 g, 9%).

Example B10 : Preparation of compounds B1.11 and B1.12

Amino acids in the: (1, 2.0 ㎖ 1) isobutyramide aldehyde (0.156 ㎖), 3 Å activated molecular sieves (0.2 g) and glacial acetic acid 1M CH ₂ Cl ₂ solution of MeOH / CH ₂ Cl ₂ in (10 ㎕, 0.17 mmol) Is added to a solution of B1.6 (0.08 g, 0.156 mmol). Stir the suspension at room temperature, and after one minute, the addition of _{NaBH 3 (CN) (0.016 g} , 0.258 mmol). After 60 min, the reaction mixture is diluted with water, filtered through a cellulose filter (pore size 45 μm) and the filtrate is adjusted to pH 8-9 with ₁ M aqueous NaHCO ₃ solution and then concentrated. The residue was purified by gel filtration on Bio-Gel P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water, flow 0.5 ml / min, detection at 215 nm) and subsequent reverse phase chromatography (Merck RP 18 silica gel, gradient elution: 35% MeOH / H ₂ O to 50% MeOH / H ₂ O), eluting with mono isobutylamine B1.11 (0.041 g, 46%) and then diisobutylamine Butyl amine B1.12 (0.01 g, 10%).

Example B11 : Preparation of compound B1.13

It was added a 1M solution of benzoyl chloride in toluene (41 ㎕) To a solution of amino acid B1.11 (0.020 g, 0.0339 mmol) of 1M NaHCO ₃ (100 ㎕) at room temperature. The mixture is vigorously stirred and, after 1 hour, additional benzoyl chloride (41 [mu] l of 1 M solution) is added. After the reaction was completed, the volatile components were removed under high vacuum, and the residue was subjected to gel filtration on a Bio-Gel P2 (particle size of 65 mu m, column diameter 2.5 cm, length 35 cm, eluent: water, flow rate 0.5 ml / (Merck RP 18 silica gel, gradient elution: 45% MeOH / H ₂ O) followed by lyophilization to give benzamide B1.13 as a fluffy powder (0.014 g, 59%).

Example B12 : Preparation of compound B1.14

It was added a 1M solution of p- nitrobenzene sulfonyl chloride in toluene (43 ㎕) under vigorous stirring to a solution of the amino acid B1.6 (0.02 g, 0.039 mmol) in 1M NaHCO ₃ aqueous solution (0.2 ㎖). The reaction mixture is stirred at room temperature for 16 hours and then concentrated in vacuo. The residue was dissolved in water (0.3 ml) and purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, flow 0.5 ml / min, detection at 215 nm) do. The crude product (0.025 g) added to the two reverse-phase chromatography with a (Merck RP 18 silica gel, 1st chromatography: _{eluent: 50% MeOH / H 2 O} ; 2 car chromatography: eluent: 40% MeOH / H ₂ O ) And lyophilized to give the target compound as a fluffy powder (0.0105 g, 39%).

Example B13 : Preparation of compound B1.15

It is added to a solution of toluene (22 ㎕) the amino acid B1.6 (0.01 g, 0.02 mmol) in a 1M solution of benzenesulfonyl chloride, p- from 0 ℃ under vigorous stirring 1M NaHCO ₃ aqueous solution (0.1 ㎖). The reaction mixture is stirred at 0 < 0 > C for 90 minutes, then additional p-benzenesulfonyl chloride (10 [mu] l of a 1 M solution) is added. The reaction mixture is then warmed to room temperature, stirred for 18 hours and then concentrated in vacuo. The residue was dissolved in water and subjected to gel filtration on Bio-Gel P2 (particle size of 65 mu m, column diameter 2.5 cm, length 35 cm, eluent: water, flow rate 0.5 ml / min, detection at 215 nm) and subsequent reverse phase chromatography (Merck RP 18 silica gel, eluent: 45% MeOH / H ₂ O) and lyophilized to give the target compound as a fluffy powder (0.004 g, 30%).

Example B14 : Preparation of compound B1.16

Pentafluorophenyl trifluoroacetate (4.5 mL, 0.026 mmol) was added to a solution of isoserine derivative 16 (0.025 g, 0.026 mmol) and triethylamine (0.7 mL, 0.005 mmol) in DMF (100 mL) Solution. After 15 minutes, additional pentafluorophenyltrifluoroacetate (2.5 mL, 0.015 mmol) is added. After 30 minutes, additional triethylamine (2.8 mL, 0.02 mmol) and pentafluorophenyltrifluoroacetate (4.5 mL, 0.026 mmol) are added. The same amount of the latter reagent is added again after 20 minutes. The mixture is stirred for an additional 45 minutes, then a saturated aqueous NaHCO ₃ solution (0.2 mL) is added, the mixture is diluted with water and extracted several times with ethyl acetate. The combined organic phases are dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The crude product (0.04 g) was purified by flash chromatography on silica gel (eluent: ethyl acetate / toluene 1: 3) to afford trifluoroacetamide 24 (0.022 g, 83%).

(Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.02 g) and benzyl ether 24 (0.021 g) in dioxane (1.4 ml), water (0.7 ml) and glacial acetic acid 0.0 > mmol) < / RTI > Flask is flushed and flushed several times with argon. It is then flushed with hydrogen and the black mixture is hydrogenated under slight boost for 3.5 h. The reaction mixture is filtered through a cellulose filter (pore size 45 [mu] m) and the filtrate is concentrated in vacuo. A small amount of the residue solution in water is passed through an ion exchanger column (Dowex 50, Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The filtrate was concentrated in vacuo and the residue was purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, flow 0.5 ml / min, detection at 215 nm) Was purified by reverse phase chromatography (Merck RP 18 silica gel, column diameter 1.2 cm, length 7 cm, gradient elution: 30% MeOH / H ₂ O to 40% MeOH / H ₂ O) to give the target molecule B1.16 g, 68%) as a colorless fluffy solid (after lyophilization).

Example B15 : Preparation of compound B1.17

(0.027 g, 0.028 mmol), cyclohexanecarboxylic acid (0.011 g, 0.086 mmol), and diisopropylcarbodiimide (17 ml, 0.11 mmol) Was added to a mixture of 1-hydroxybenzotriazole (0.021 g, 0.155 mmol) and anhydrous THF (0.9 mL). After 20 minutes, anhydrous DMF (0.4 mL) is added and the mixture is stirred for an additional hour. The reaction mixture is concentrated in vacuo and the remaining DMF is removed under high vacuum. The residue was purified by flash chromatography on silica gel (CH ₂ Cl ₂ / isopropanol 39: 1) to afford amide 26 (0.024 g, 80%).

(b) Removal of 26: Pd (OH) ₂ / C (Pearlman catalyst, 20% Pd content, 0.03 g) and dioxane (2.0 ml), water (1.0 ml) and glacial acetic acid (0.5 ml) (0.024 g, 0.022 mmol). Flask is flushed and flushed several times with argon. It is then flushed with hydrogen and the black mixture is hydrogenated under slight boost for 18 h. The reaction mixture is filtered through a cellulose filter (pore size 45 [mu] m) and the filtrate is concentrated in vacuo. A small amount of water residue solution is passed through an ion exchanger column (Dowex 50, Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The filtrate was concentrated in vacuo and the residue was purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, flow 0.5 ml / min, detection at 215 nm) Was purified by reverse phase chromatography (Merck RP 18 silica gel, column diameter 1.2 cm, length 6 cm, eluent: MeOH / H ₂ O 3: 2) to give the target molecule B1.17 (0.008 g, 56% As a solid (after lyophilization).

Example B16 : Preparation of compound B1.18

A solution of triol 13 (0.129 g, 0.17 mmol) and di-n-butyltin oxide (0.064 g, 0.258 mmol) in anhydrous MeOH (4.0 mL) is boiled under reflux in an argon atmosphere for 2 h. The clear solution is concentrated in vacuo, mixed with the residue pentane (2 mL), concentrated again and dried under high vacuum for 30 min to remove residual MeOH. The residue was treated with anhydrous CsF (0.131 g, 0.86 mmol, measured under argon) and anhydrous 1,2-dimethoxyethane (0.5 mL) and then benzyl ( R) -4-phenyl-2-trifluoromethanesulfonyloxybutyrate (A2) (0.3 g, 0.861 mmol). Then the reaction mixture was stirred at room temperature for 75 minutes and addition of 1M KH ₂ PO ₄ aqueous solution, the mixture was diluted with water and extracted with ethyl acetate (phase separation is promoted by the addition of a small amount of aqueous solution of KF). The organic extracts were combined, dried with Na ₂ SO _4, filtered and concentrated in vacuo to afford, (0.39 g) of the crude product as an oil. Purification by flash chromatography on silica gel (eluent: toluene / ethyl acetate 5: 1) afforded pure ether 30 (0.143 g, 81%).

Benzyl ether 30 (0.14 g, 0.135 mmol) is dissolved in dioxane (4 ml) and water (2 ml), glacial acetic acid (1 ml) and 20% Pd (OH) _{2 /} C (0.14 g) are added. The air in the reaction vessel is initially replaced with argon, followed by hydrogen, by several evaporations and flushes. The black reaction mixture is hydrogenated under slight hydrogen pressure for 90 minutes and then filtered through a cellulose filter (pore size 45 μm), where it is washed with water. The filtrate is concentrated, the residue is dissolved in toluene and concentrated several times to remove any remaining acetic acid. The crude product (0.095 g) is dissolved in a small volume of water and filtered through a Dowex 50 (Na ⁺ ) ion exchanger column. The filtrate was freeze dried and the residue (0.085 g) was purified by reverse gel chromatography (Merck RP 18 silica gel, eluent: 40% MeOH / H ₂ O) and subsequent gel filtration on Bio-Gel P2 2.5 cm, length 35 cm, eluent: water, flow rate 0.5 ml / min, detection at 215 nm) and lyophilized to give the target compound B1.18 as colorless fluffy powder (0.045 g, 55%) .

Example B17 : Preparation of compound B1.19

Is added to an aromatic compound B1.18 (0.02 g, 0.033 mmol) water (1.8 ㎖), dioxane (1.2 ㎖) and glacial acetic acid was dissolved (0.3 ㎖), 5% Rh / Al 2 O 3 (0.04 g) . The air in the reaction vessel is replaced with hydrogen by evaporation and flushed several times and the mixture is hydrogenated under slight hydrogen pressure under vigorous stirring for 1.5 days. It is then filtered through a cellulose filter (pore size 45 μm), washed with water, the filtrate is concentrated, the residue is dissolved in toluene and concentrated several times to remove any remaining acetic acid. The crude product was purified by gel filtration on Bio-Gel P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water, flow 0.5 ml / min, detection at 215 nm) Lt; / RTI > The reaction mixture is then filtered through a cellulose filter (pore size 45 mu m), washed with water, the filtrate is concentrated and the residue is dissolved in toluene and concentrated several times. The crude product was purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, flow 0.5 ml / min, detection at 215 nm) and subsequent reverse phase chromatography (Merck RP18 Silica gel, eluent: 50% MeOH / H ₂ O) and lyophilized to give the desired compound B1.19 (0.01 g, 50%) as a fluffy powder.

Example B18 : Preparation of compound B1.38

And toluene was added to a solution of amino acid B1.11 (0.035 g, 0.0617 mmol) of 1M NaHCO ₃ aqueous solution (315 ㎕) chloride p- nitrobenzene sulfonyl solution under vigorous stirring of the (1M, 150 ㎕). The mixture is vigorously stirred at room temperature and after 17 hours, additional p-nitrobenzenesulfonyl chloride solution (120 [mu] l) is added. The reaction mixture is stirred for an additional 24 h, then diluted with water and washed twice with ethyl acetate. The aqueous phase was concentrated to a volume of 0.5 ml in vacuo and the solution was purified by gel filtration on a Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 100 ㎝, eluent: water, flow 0.5 ml / min, ). ≪ / RTI > The crude product (0.06 g) was further purified three times by reverse phase chromatography (Merck RP 18 silica gel, eluent: 40% MeOH / H ₂ O) and lyophilized to give sulfonamide B1.38 (0.013 g, 27%) as a colorless fluffy powder.

The following compounds are prepared analogously to the above example:

⁽¹⁾ A solution of succinic anhydride in DMF is used as a reagent.

^{(2) Use a} solution of pentafluorophenylbiphenylcarboxylate in dioxane as a reagent.

^{(3) Use a} solution of pentafluorophenyl p-cyanobenzoate in dioxane as reagent.

^{(4) Use a} solution of methylpentafluorophenyl terephthalate in dioxane as reagent. After the amide formation is complete, a 1M aqueous NaOH solution is added to the reaction mixture, which is heated at 65 < 0 > C until the hydrolysis of the methyl ester is complete.

⁽⁵⁾ 1 M NaOH was used instead of 1 M NaHCO ₃ . (+) - di-O-acetyl-L-tartaric anhydride in dioxane was used as a reagent.

^{(6) An} amide was formed using trifluoromethanesulfonic anhydride as a reagent in CH ₂ Cl ₂ at 0 ° C.

Example B19 : Preparation of compound B1.39

A suspension of 13 (0.086 g, 0.11 mmol) and di-n-butyltin oxide (0.05 g, 0.19 mmol) in anhydrous benzene (3.3 mL) is boiled under reflux in an argon atmosphere for 12 h. The reaction mixture is concentrated in vacuo and dried under high vacuum for 1 hour. 0.042 g, 0.274 mmol), followed by anhydrous 1,2-dimethoxyethane (0.6 mL), and anhydrous 1,2-dimethoxyethane (0.4 mL) was added to a solution of CsF (dried at 300 [deg.] C under high vacuum for several hours, Triflate A3 (0.25 g, 0.66 mmol) is added under an argon atmosphere. The reaction mixture is heated to 35-40 < 0 > C and stirred at this temperature for 5 hours. Then, 1M KH ₂ PO ₄ aqueous solution (30 ㎖) concentration during the addition of 15% KF solution in, and the mixture was extracted three times with CH ₂ Cl ₂ and dry the combined organic phases were (Na ₂ SO _4), filtered and vacuum . The oily residue (0.16 g) was purified by column chromatography on silica gel (gradient eluent: toluene / ethyl acetate 80:20 to 75:25 followed by CH ₂ Cl ₂ / MeOH 19: 1), ether 31 g, 44%) as a colorless foam and precursor 13 (0.035 g, 40%).

A solution of Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.028 g) and benzyl ether 31 (0.048 g, 0.047 mmol) in dioxane (2.0 mL), water (1.0 mL) and glacial acetic acid Add to the mixture. Flask is flushed and flushed several times with argon. The flask is then flushed with hydrogen and the black mixture is hydrogenated under slight hydrogen pressure for 17 h and then filtered through a cellulose filter (pore size 45 μm). The filtrate is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The residue solution in water is passed through a Dowex 50 ion exchanger column (Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on a Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, 0.45 ml / min at 230 ㎚ flow rate) Purification by flash chromatography (Merck RP 18 silica gel, eluent: 7: 3 H ₂ O / methanol) gave the target molecule B1.39 (0.014 g, 51%) as a white fluffy solid (after lyophilization).

Example B20 : Preparation of compound B1.40

Coupling of alcohol 13 with triflate A4 is carried out according to Example B19 (preparation of compound 31).

Hydrogenation of the benzyl ether and subsequent purification is carried out according to example B19 (preparation of compound B1.39): < RTI ID = 0.0 >

Example B21 : Preparation of compound B1.41

Prepared from D - (-) - xylulose according to hydroxypiperidine (6.0 g, 34.6 mmol, Ichikawa, Y., Igarashi, Y., Tetrahedron Letters 36: 4585-4586 ) And triethylamine (18.1 mL, 130 mmol) are dissolved in anhydrous tetrahydrofuran (100 mL) and the solution is cooled to -10 DEG C under an argon atmosphere. Allyl chloroformate (3.87 mL, 36.4 mmol) was added slowly over 1 h, at which time a white suspension was formed. The reaction mixture was stirred for an additional hour at -10 ℃, then it is added an aqueous solution of 1M KH ₂ PO ₄ (150 ㎖), and the mixture was extracted three times with CH ₂ Cl _2. The combined organic phases are dried (Na ₂ SO ₄ ) and concentrated in vacuo to give a yellow oil (9 g). Purify by column chromatography on silica gel (hexane / ethyl acetate 1: 1) to give allylcarbamate 34 (7.66 g, 86%).

4 A molecular sieves (dried under high vacuum at 300 캜, 15 g) were added to a solution of water 34 (7.66 g, 29.8 mmol) in anhydrous CH ₂ Cl ₂ (150 mL) under an argon atmosphere and the suspension was stirred at room temperature Lt; / RTI > for 1 hour. In parallel, a suspension of DMTST (15.4 g, 59.6 mmol) and 4 Å molecular sieves (15 g) in anhydrous CH ₂ Cl ₂ (150 mL) is prepared in a second round bottom flask under an argon atmosphere and stirred for 1 hour . The DMTST mixture is then added to the receiver solution over a further 1 hour in 4 portions, and the mixture is then stirred for 1 hour. The reaction mixture is filtered through Hyflo Super Cel ^R , where it is washed thoroughly with CH ₂ Cl ₂ . The filtrate is extracted by shaking with 10% aqueous NaHCO ₃ solution, the aqueous phase is re-extracted three times with CH ₂ Cl ₂ , the combined organic phases are dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The residual yellow oil (36 g) was purified by column chromatography on silica gel (gradient eluent: hexane / ethyl acetate 3: 1 to 3: 2) to give glycoside 35 (13.1 g, 54%).

Acetonide 35 (13.1 g, 15.94 mmol) is dissolved in dioxane (140 mL) and 50% aqueous trifluoroacetic acid (250 mL) is added at room temperature. After 2 hours, the reaction mixture is concentrated under high vacuum and the residue is subjected to column chromatography on silica gel (ethyl acetate / hexane 2: 1) to give diol 36 (11.23 g, 90%).

A mixture of diol 36 (11.63 g, 14.88 mmol), tetra-n-butylammonium bromide (12.7 g, 39.4 mmol) and 4 A molecular sieve (dried under high vacuum at 300 ° C, 22 g) , And then anhydrous CH ₂ Cl ₂ (62 mL) and dimethylformamide (36 mL) are added under an argon atmosphere. The gray suspension is stirred at room temperature for 30 minutes. In parallel, in anhydrous CH ₂ Cl ₂ (49 ㎖) ethyl 2,3,4 tree -O- benzyl-1-thio-pyrano -L- Foucault oxide (7.48 g, 15.62 mmol, described in the reference: Lonn , Prepared according to the method of H. Carbohydr. Res. 139: 105-113 (1985)) was prepared in a second round bottom flask under an argon atmosphere and a solution of bromine in CH ₂ Cl ₂ (25 mL) (2.85 g, Br ₂ , 17.84 mmol). The red solution is stirred at 0 < 0 > C for 30 minutes and excess bromine is ground by addition of 2-3 drops of cyclohexene. The solution is then added to the receiver solution using a needle and the reaction mixture is stirred at room temperature for 40 minutes. The reaction mixture is then filtered through Hyflo Super Cel ^R , washed thoroughly with CH ₂ Cl ₂ , and the filtrate is washed with 10% aqueous NaHCO ₃ solution. The aqueous phase is re-extracted 3 times with CH ₂ Cl ₂ , the combined organic phases are dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The residue is subjected to column chromatography on silica gel (ethyl acetate / hexane 35:65), whereupon the required product 37 (7.85 g, 44%) is eluted.

A solution of ester 37 (2.4 g, 2.0 mmol) and sodium methoxide (0.11 g, 2.0 mmol) in methanol (48 mL) is stirred at room temperature for 8 hours. The clear, colorless solution is then neutralized by the addition of a strong acidic ion exchanger (Amberlyst 15), then filtered through Hyflo Super Cel ^R and concentrated in vacuo. The oily residue was purified by column chromatography on silica gel (gradient eluent: CH ₂ Cl ₂ / methanol 98: 2 to 95: 5) to give triol 38 (1.72 g, 97%).

A suspension of 38 (1.0 g, 1.13 mmol) and di-n-butyltin oxide (0.49 g, 1.98 mmol) in anhydrous benzene (33 mL) is boiled under reflux in an argon atmosphere for 5 h. The reaction mixture is concentrated in vacuo and dried under high vacuum for 1 hour. Then, CsF (dried under high vacuum at 300 < 0 > C for several hours, 0.43 g, 2.82 mmol) was added to a solution of benzyl < RTI ID = 0.0 > -3-phenyl-2-trifluoromethanesulfonyloxypropionate (2.6 g, 6.77 mmol) in dichloromethane is added under an argon atmosphere. The reaction mixture is heated to 35-40 < 0 > C and stirred at this temperature for 3 hours. Then, 1M KH ₂ PO ₄ aqueous solution (100 ㎖) concentration during the addition of 15% KF solution in, and the mixture was extracted three times with CH ₂ Cl ₂ and dry the combined organic phases were (Na ₂ SO _4), filtered and vacuum . The oily residue (3.2 g) was purified by column chromatography on silica gel (eluent: toluene / ethyl acetate 70:30) to give ether 39 (0.98 g, 78%) as a colorless foam.

A solution of Pd (OH) ₂ / C (Pearlman catalyst, Pd 20%, 0.035 g) and benzyl ether 39 (0.038 g, 0.034 mmol) in dioxane (3.5 ml), water (1.7 ml) and glacial acetic acid Add to the mixture. Flask is flushed and flushed several times with argon. The flask is then flushed with hydrogen and the black mixture is hydrogenated at room temperature under slight hydrogen pressure for 24 h and then filtered through a cellulose filter (pore size 45 μm). The filtrate is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The residue solution in water is passed through a Dowex 50 ion exchanger column (Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, 0.45 ml / min, flow rate 215 nm) (0.014 g, 59%) as a white fluffy solid (after lyophilization) to afford the target molecule B1.41 (0.014 g, 59%) as a white fluffy solid (Merck RP 18 silica gel, gradient eluant: H ₂ O / methanol 65:35 to 55:45) .

Example B22 : Preparation of compound B1.42

A suspension of 38 (0.65 g, 0.73 mmol) and di-n-butyltin oxide (0.32 g, 1.28 mmol) in anhydrous benzene (22 mL) is boiled under reflux in an argon atmosphere for 16 h. The reaction mixture is concentrated in vacuo and dried under high vacuum for 1 hour. Subsequently, a solution of CsF (dried at 300 < 0 > C under high vacuum for several hours, 0.28 g, 1.83 mmol) followed by anhydrous 1,2-dimethoxyethane (4.0 ml) and 1,2- dimethoxyethane (2.7 ml) A solution of plate A5 (1.74 g, 4.4 mmol) is added under an argon atmosphere. The reaction mixture is heated to 35-40 < 0 > C and stirred at this temperature for 3 hours. Then, 1M KH ₂ PO ₄ aqueous solution (100 ㎖) concentration during the addition of 15% KF solution in, and the mixture was extracted three times with CH ₂ Cl ₂ and dry the combined organic phases were (Na ₂ SO _4), filtered and vacuum . The oily residue (2.6 g) was purified by column chromatography on silica gel (eluent: toluene / ethyl acetate 3: 1 followed by CH ₂ Cl ₂ / methanol 19: 1), ether 40 (0.33 g, 40% As a colorless foam, partially recovering precursor 38 (0.167 g, 26%).

A solution of Pd (OH) ₂ / C (Pearlman catalyst, Pd 20%, 0.025 g) and benzyl ether 40 (0.036 g, 0.032 mmol) in dioxane (1.2 ml), water (0.6 ml) and glacial acetic acid Add to the mixture. Flask is flushed and flushed several times with argon. The flask is then flushed with hydrogen and the black mixture is hydrogenated at room temperature under slight hydrogen elevation for 8 hours and then filtered through a cellulose filter (pore size 45 μm). The filtrate is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The residue solution in water is passed through a Dowex 50 ion exchanger column (Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, 0.45 ml / min, flow rate 215 nm) Purification by flash chromatography (Merck RP 18 silica gel, gradient eluent: H ₂ O / methanol 1: 1) affords the target molecule B1.42 (0.009 g, 41%) as a white fluffy solid (after lyophilization).

Example B23 : Preparation of compound B1.43

Morpholine (1.1 ㎖) and the addition of _{Pd (PPh 3) 4 (0.071} g, 0.062 mmol) to a solution of the allyl carbamate 39 (0.695 g, 0.618 mmol) in tetrahydrofuran (8.5 ㎖). After exactly 15 minutes the solution is concentrated and the residue is dried under high vacuum for 1 hour. The residue was purified by column chromatography on silica gel (eluent: CH ₂ Cl ₂ / methanol 98: 2, containing 0.3% strength aqueous ammonia solution) initially less polar allylamine 46 (0.24 g, 36% Followed by the more polar piperidine 41 (0.39 g, 60%).

Pyridine (5 L, 0.06 mmol) and acetic anhydride (1.8 L, 0.04 mmol) were added to a solution of piperidine derivative 41 (0.035 g, 0.0336 mmol) in anhydrous CH ₂ Cl ₂ (0.6 mL) . The solution was then eseo han 0 ℃ stirred for 45 minutes and then washed with 5% NaHCO ₃ aqueous solution, and the aqueous phase re-extracted three times with CH ₂ Cl _2. The combined organic phases are dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue (0.05 g) was purified by column chromatography on silica gel (eluent: ethyl acetate / hexane 4: 1) to afford acetylpiperidine 42 (0.033 g, 91%) as a colorless foam.

Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.03 g) and benzyl ether 42 (0.04 g, 0.037 mmol) in dioxane (1.4 ml), water (0.7 ml) and glacial acetic acid Add to the mixture. Flask is flushed and flushed several times with argon. The flask is then flushed with hydrogen and the black reaction mixture is hydrogenated at room temperature under slight hydrogen elevation for 48 hours and then filtered through a cellulose filter (pore size 45 μm). The filtrate is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The residue solution in water is passed through a Dowex 50 ion exchanger column (Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, 0.45 ml / min, flow rate 215 nm) Purification by flash chromatography (Merck RP 18 silica gel, gradient elution: methanol / H ₂ O 2: 3, 1: 1 to 3: 2) afforded the target molecule B1.43 (0.014 g, 64%) as a white fluffy solid (After lyophilization).

Example B24 : Preparation of compound B1.44

Compound 43 is prepared from piperidine 41 (0.02 g, 0.019 mmol) and benzoyl chloride (2.5 l, 0.021 mmol) analogously to the method for acetylpiperidine 42 (example B23). The yield is 0.02 g (90%).

The target compound B1.44 is prepared analogously to acetyl derivative B1.43 by hydrogenation of benzyl ether 43 (0.042 g, 0.0367 mmol) and subsequent purification. The product is obtained as a colored fluffy solid after lyophilization. Yield: 0.015 g (57%): MS (FAB, THG) 716 (M + H), 694 (M + 2H-Na).

Example B25 : Preparation of compound B1.45

The target compound B1.45 is prepared from piperidine derivative 41 analogously to Example 23 (preparation of compound B1.43): < RTI ID = 0.0 >

Example B26 : Preparation of compound B1.46

To a solution of the piperidine derivative 41 (0.04 g, 0.038 mmol) in anhydrous CH ₂ Cl ₂ (0.7 mL) at 0 ° C was added pyridine (4 μL, 0.05 mmol) and cyclohexanecarbonyl chloride . After 20 minutes, the reaction mixture was washed with 10% NaHCO ₃ solution and the aqueous phase re-extracted three times with CH ₂ Cl _2. The combined organic phases are dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The crude product (0.09 g) was purified by column chromatography on silica gel (eluent: hexane / ethyl acetate 1: 1) to give amide 45 (0.03 g, 68%).

A solution of Pd (OH) ₂ / C (Pearlman catalyst, Pd 20%, 0.05 g) and benzyl ether 45 (0.029 g, 0.025 mmol) in dioxane (1.1 mL), water (0.55 mL) and glacial acetic acid Add to the mixture. Flask is flushed and flushed several times with argon. It is then flushed with hydrogen and the black reaction mixture is hydrogenated at room temperature under slight hydrogen elevation for 24 hours. Then, for the hydrogenation of the aromatic ring, 5% Rh / C (0.02 g) is added and the hydrogenation is continued for 24 hours. The reaction mixture is filtered through a cellulose filter (pore size 45 mu m). The filtrate is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The residue solution in water is passed through a Dowex 50 ion exchanger column (Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, 0.45 ml / min, flow rate 215 nm) Purification by flash chromatography (Merck RP 18 silica gel, gradient elution: methanol / H ₂ O 60:40) affords the target molecule B1.46 (0.012 g, 64%) as a white fluffy solid (after lyophilization).

Example B27 : Preparation of compound B1.47

A solution of Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.03 g) and benzyl ether 46 (0.042 g, 0.039 mmol) in dioxane (1.4 ml), water (0.7 ml) and glacial acetic acid Add to the mixture. Flask is flushed and flushed several times with argon. The flask is then flushed with hydrogen and the black reaction mixture is hydrogenated at room temperature under slight hydrogen elevation for 16 hours and then filtered through a cellulose filter (pore size 45 μm). The filtrate is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The crude product (0.014 g) was subjected to gel filtration on a Bio-Gel P2 (particle size of 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water, flow rate 0.45 ml / min, detection at 215 nm) Purification by flash chromatography (Merck RP 18 silica gel, eluent: methanol / H ₂ O 1: 3) affords the target molecule B1.47 (0.009 g, 36%) as a white fluffy solid (after lyophilization).

Example B28 : Preparation of compound B1.48

(3.7 L, 0.029 mmol) was added to a solution of the piperidine 41 (0.025 g, 0.024 mmol) in CH ₂ Cl ₂ (0.3 mL) Lt; / RTI > After 45 minutes, the reaction mixture was washed with 10% NaHCO ₃ solution and the aqueous phase re-extracted three times with CH ₂ Cl _2. The combined organic phases are dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (eluent: hexane / ethyl acetate 60:40) to afford the sulfonamide 47 (0.022 g, 79%).

A solution of Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.013 g) and benzyl ether 47 (0.027 g, 0.023 mmol) in dioxane (1.0 mL), water (0.5 mL) and glacial acetic acid Add to the mixture. Flask is flushed and flushed several times with argon. The flask is then flushed with hydrogen and the resulting reaction mixture is hydrogenated at room temperature under slight hydrogen elevation for 24 hours and then filtered through a cellulose filter (pore size 45 μm). The filtrate is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The residue solution in water is passed through a Dowex 50 ion exchanger column (Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, 0.45 ml / min, flow rate 215 nm) Purified by flash chromatography (Merck RP 18 silica gel, gradient elution: methanol / H ₂ O 35:65 to 45:55) to give the target molecule B1.48 (0.011 g, 65%) as a white fluffy solid .

Example B29 : Preparation of compound B1.49

The target compound B1.49 is prepared starting from piperidine derivative 41 and p-toluenesulfonyl chloride analogously to Example B28 (preparation of compound B1.48)

Example B30 : Preparation of compound B1.50

A solution of Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.02 g) and benzyl ether 47 (0.041 g, 0.035 mmol) in dioxane (1.5 ml), water (0.75 ml) and glacial acetic acid Add to the mixture. Flask is flushed and flushed several times with argon. It is then flushed with hydrogen and the black reaction mixture is hydrogenated at room temperature under slight hydrogen elevation for 16 hours. Then, to hydrogenate the aromatic ring, 5% Rh / C (0.025 g) is added and the hydrogenation is continued for 16 hours. The reaction mixture is filtered through a cellulose filter (pore size 45 mu m). The filtrate is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The residue solution in water is passed through a Dowex 50 ion exchanger column (Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, 0.45 ml / min, flow rate 215 nm) Photography: to give the (Merck RP 18 silica gel, eluent gradient of methanol / H ₂ O 40:60 to 50:50), the target molecule B1.50 (0.021 g, 82%) as a white fluffy solid (after lyophilization) .

Example B31 : Preparation of compound B1.51

The morpholine (0.37 ㎖) and _{Pd (PPh 3) 4 (0.025} g, 0.021 mmol) was added to a solution of the allyl carbamate 40 (0.24 g, 0.212 mmol) in tetrahydrofuran (2.9 ㎖). After exactly 15 minutes, the solution is concentrated and the residue is dried under high vacuum for 1 hour. The residue (0.38 g) was purified by column chromatography on silica gel (eluent: CH ₃ Cl ₂ / methanol 19: 1, aqueous ammonia solution 0.3%) to give piperidine derivative 49 (0.17 g, 76% do.

(4.6 μL, 0.042 mmol) and diisopropylethylamine (8.5 μL, 0.05 mmol) were added at 0 ° C. to a solution of piperidine derivative 49 (0.04 g, 0.038 mmol) in CH ₂ Cl ₂ Solution. After 90 minutes, the reaction mixture is re-extracted three times the aqueous phase and washed with 1M KH ₂ PO ₄ aqueous solution in CH ₂ Cl _2. The combined organic phases are dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The crude product (0.047 g) was purified by column chromatography on silica gel (eluent: hexane / ethyl acetate 58: 42) to give the urea derivative 50 (0.035 g, 78%).

A solution of Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.018 g) and benzyl ether 50 (0.036 g, 0.031 mmol) in dioxane (1.3 ml), water (0.65 ml) and glacial acetic acid Add to the mixture. Flask is flushed and flushed several times with argon. The flask is then flushed with hydrogen and the black reaction mixture is hydrogenated at room temperature under slight hydrogen elevation for 16 hours and then filtered through a cellulose filter (pore size 45 μm). The filtrate is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The residue solution in water is passed through a Dowex 50 ion exchanger column (Na ⁺ type, column diameter 0.9 cm, length 3.5 cm), where it is washed with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, 0.45 ml / min, flow rate 215 nm) Purification by flash chromatography (Merck RP 18 silica gel, gradient elution: methanol / H ₂ O 1: 1) affords the target molecule B1.51 (0.018 g, 80%) as a white fluffy solid (after lyophilization).

Example B32 : Preparation of compound B1.52

Piperidine derivative 49 is converted to the target compound B1.52 using phenylmethanesulfonyl chloride as reagent analogously to Example B28 (preparation of compound B1.48)

Example B33 : Preparation of compound B1.53

A solution of Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.05 g) and benzyl ether 49 (0.09 g, 0.086 mmol) in dioxane (3.7 ml), water (1.8 ml) and glacial acetic acid Add to the mixture. Flask is flushed and flushed several times with argon. The flask is then flushed with hydrogen and the black reaction mixture is hydrogenated at room temperature under slight hydrogen elevation for 48 hours and then filtered through a cellulose filter (pore size 45 μm). The filtrate is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The crude product (0.044 g) was subjected to gel filtration (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, flow rate 0.45 ml / min, detection at 215 nm) on Bio- (0.04 g, 78%) as a white fluffy solid (after lyophilization) to afford the target molecule B1.53 (0.04 g, 78%) as a white fluffy solid (Merck RP 18 silica gel, gradient elution: methanol / H ₂ O 30:70 to 50:50) .

Example B34 : Preparation of compound B1.54

A 1M solution of 2- (1-naphthyl) ethanesulfonyl chloride in toluene (46 μl) was added to a solution of piperidine derivative B1.53 (0.025 g, 0.042 mmol) in a 1M aqueous NaHCO ₃ solution (0.22 mL) . The mixture is vigorously stirred for 22 hours, then concentrated in vacuo and dried under high vacuum for 15 minutes. The crude product was purified by gel filtration on Bio-Gel P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water, 0.45 mL / min at flow rate, detection at 215 nm) and subsequent reverse phase chromatography (Merck RP 18 silica gel, gradient elution: methanol / H ₂ O 7: 3) to give the target molecule B1.54 (0.011 g, 31%) as a white fluffy solid (after lyophilization).

Example B35 : Preparation of compound B1.55

A 0.5 M solution of acetic anhydride in toluene was added until all of the precursor was consumed (test by thin layer chromatography: silica gel TLC plate, fluid phase: n-butanol / water / acetone / glacial acetic acid / NH ₄ OH 70: : 18: 1.5) is added piperidine derivative B1.53 (0.035 g, in small portions (50 to 100 ㎕) to a solution of 0.059 mmol) of 1M NaHCO ₃ aqueous solution (0.5 ㎖) at room temperature. The reaction is complete after about 1 hour, the mixture is concentrated in vacuo and dried under high vacuum for 15 minutes. The crude product was purified by gel filtration on Bio-Gel P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water, 0.45 mL / min at flow rate, detection at 215 nm) and subsequent reverse phase chromatography (Merck RP 18 silica gel, eluent: methanol / H ₂ O 3: 7) to give the target molecule B1.55 (0.026 g, 67%) as a white fluffy solid (after lyophilization).

Example B36 : Preparation of compound B1.56

(+) - di-O-acetyl-L-tartaric anhydride was dissolved in 1,4-dioxane until all precursors were consumed (test by thin layer chromatography: silica gel TLC plate, butanol / water / acetone / glacial acetic acid _{/ NH 4 OH 70: 60:} 50: 18: 1.5) piperidine derivative B1.53 (0.03 g in little by little (50 to 100 ㎕) 1M NaOH aqueous solution at room temperature (0.15 ㎖), 0.0 > mmol) < / RTI > The mixture is kept basic by periodic addition of 1M NaOH solution throughout the reaction. The starting material is consumed after about 2 hours, then an additional 1M sodium hydroxide solution (0.13 ml) is added and the mixture is heated to 40 < 0 > C to hydrolyze the ester group. After 1 hour, the mixture is concentrated in vacuo and dried under high vacuum for 15 minutes. The crude product was purified by gel filtration on Bio-Gel P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water, 0.45 mL / min at flow rate, detection at 215 nm) and subsequent reverse phase chromatography (Merck RP 18 silica gel, eluent: methanol / H ₂ O 1: 9 to yield), the target molecule B1.56 (0.020 g, 52%) was obtained as a white fluffy solid (after lyophilization): MS (FAB, THG) 794 (M + Na), 772 (M + H), 750 (M + 2H-Na).

Example B37 : Preparation of compound B1.57

N, N-Diisopropylcarbodiimide (11.7 L, 0.075 mmol) was added to a solution of cinchimic acid (0.013 g, 0.075 mmol) in anhydrous N, N-dimethylformamide (0.37 mL) and 1- Is added to a solution of the sol (0.01 g, 0.075 mmol) and the mixture is stirred for 30 minutes. The mixture is then warmed to room temperature and piperidine derivative B1.53 (0.015 g, 0.025 mmol) is added. After 3 hours, the addition of 10% NaHCO ₃ solution and stirred (0.15 ㎖), and the reaction mixture an additional 20 minutes then concentrated under high vacuum. The residue was dissolved in water and filtered through a cellulose filter (pore size 45 탆) and passed through a Dowex 50 ion exchanger column (Na ⁺ -type, column diameter 0.9 cm, length 3.5 cm), with deionized water Wash. The filtrate was concentrated in vacuo and purified by gel filtration on Bio-Gel P2 (particle size 65 쨉 m, column diameter 2.5 ㎝, length 35 ㎝, eluent: water, 0.45 ml / min at flow rate, detection at 215 nm) and subsequent reverse phase chromatography (Merck RP 18 silica gel, gradient elution: methanol / H ₂ O 1: 9) to give the target molecule B1.57 (0.007 g, 33%) as a white fluffy solid (after lyophilization)

Example B38 : Preparation of compound B1.58

N, N- diisopropylcarbodiimide (1.03 g, 8.44 mmol) and p- nitrobenzene sulfonyl alcohol 37 (6.11 g of (1.65 g, 7.44 mmol) to CH ₂ Cl ₂ (35 ㎖) chloride at room temperature, 5.1 mmol). After 52 hours, the reaction mixture was then washed with 10% NaHCO ₃ solution and the aqueous phase re-extracted three times with CH ₂ Cl _2. The combined organic phases are dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The crude product (10 g) was purified by column chromatography on silica gel (eluent: ethyl acetate / hexane 35:65) to yield nosylate 52 (6.58 g, 93%).

Anhydrous N, N- dimethyl heated to formamide (50 ㎖) nosil rate 52 (7.78 g, 5.62 mmol) and anhydrous _{LiN 3 (0.99 g, 20.21 mmol} ) 50 to 60 ℃ under an atmosphere of argon, a solution of. After 16 h, the solvent is removed under high vacuum and the residue is dissolved in CH ₂ Cl ₂ and washed with 10% aqueous NaHCO ₃ solution. The aqueous phase is extracted three times with CH ₂ Cl ₂ and the combined organic phases are dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (eluent: ethyl acetate / hexane 30:70) to elute first the required azide 53 (4.22 g, 61%) followed by alcohol 37 (2.5 g).

A solution of tribenzoate 53 (4.22 g, 3.45 mmol) and sodium methoxide (0.55 g, 10.2 mmol) in methanol (110 mL) and dioxane (5 mL) is stirred at room temperature for 2.5 hours. The pH of the reaction mixture is then made neutral by the addition of a strong acidic ion exchanger (Amberlyst 15, H ⁺ form), the suspension is filtered and the filtrate is concentrated in vacuo. The crude product (4.5 g) was purified by column chromatography on silica gel (eluent: CH ₂ Cl ₂ / methanol 19: 1) to give the triol 54 (2.89 g, 92%).

54 (2.89 g, 3.17 mmol) and di-n-butyltin oxide (1.56 g, 6.27 mmol) in anhydrous benzene (95 mL) are boiled in an argon atmosphere under reflux for 16 h. The reaction mixture is concentrated in vacuo and dried under high vacuum for 1 hour. CsF (dried under high vacuum at 300 < 0 > C for several hours, 1.2 g, 7.9 mmol) was added under an argon atmosphere followed by dry 1,2- dimethoxyethane (80 mL) and anhydrous 1,2-dimethoxy Add triflate A5 (6.3 g, 15.97 mmol) in ethane (50 mL). The reaction mixture is heated to 35-40 < 0 > C and stirred at this temperature for 3 hours. The mixture _{1M KH 2 PO 4 (150 ㎖} ) and washed with 15% KF solution in the aqueous solution and extracted three times the aqueous phase with CH ₂ Cl ₂ and the combined organic phase was dried (Na ₂ SO _4), filtered and vacuum ≪ / RTI > The oily residue (10.9 g) was purified by column chromatography on silica gel (eluent: toluene / ethyl acetate 4: 1 for recovery of the precursor, then CH ₂ Cl ₂ / methanol 19: 1). Ether 55 (1.94 g, 53%) is obtained as a colorless foam and the precursor (1.1 g, 26%) is partially recovered.

Morpholine (215 μl) and Pd (PPh ₃ ) ₄ (0.015 g, 0.013 mmol) are added to a solution of allylcarbamate 55 (0.15 g, 0.13 mmol) in tetrahydrofuran (1.7 ml) under an argon atmosphere. After exactly 15 minutes, the solution is concentrated and the residue is dried under high vacuum for 1 hour. The crude product is purified on a silica gel column (eluent: CH ₂ Cl ₂ / methanol 19: 1, containing 0.3% aqueous ammonia solution) and dried under high vacuum for 1 hour. The solution was then dissolved in anhydrous CH ₂ Cl ₂ (1.7 mL) and the solution was cooled to 0 ° C and triethylamine (43 μL, 0.31 mmol) and n-butane sulfonyl chloride (18 μL, 0.14 mmol) Lt; / RTI > After 15 minutes, the reaction mixture was allowed to warm to room temperature and washed with 10% NaHCO ₃ aqueous solution. The aqueous phase is re-extracted 3 times with CH ₂ Cl ₂ , the organic phases are combined, dried (Na ₂ SO ₄ ), filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (eluent: ethyl acetate / hexane 30:70) to afford the sulfonamide 56 (0.12 g, 77%).

A solution of Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.035 g) and benzyl ether 56 (0.027 g, 0.023 mmol) in dioxane (1.2 ml), water (0.6 ml) and glacial acetic acid Add to the mixture. Flask is flushed and flushed several times with argon. The flask is then flushed with hydrogen and the black reaction mixture is hydrogenated at room temperature under slight hydrogen pressure for 12 h and then filtered through a cellulose filter (pore size 45 μm). The filtrate is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The crude intermediate (0.017 g, lyophilized) was dissolved in a 1 M aqueous NaHCO ₃ solution (0.3 mL) over 5 hours and purified by thin layer chromatography (silica gel TLC plate, fluid phase: n-butanol / water / acetone / ₄ OH dimethoxybenzoyl chloride in toluene was added several times (30-50 μl) in small portions until the test by HPLC ( ₄ : OH 70: 60: 50: 18: 1.5) indicated complete conversion of the intermediate do. The pH of the solution is maintained at a basic level by adding several times solid NaHCO ₃ (approximately 0.025 g overall) during this reaction. Subsequently, the reaction mixture was concentrated in vacuo, the residue was dissolved in a small amount of water and subjected to gel filtration (65 占 퐉 in particle size, 2.5 cm in length, 35 cm in length, eluent: water, 0.45 ml / Purification by subsequent reverse phase chromatography (Merck RP 18 silica gel, gradient elution: methanol / H ₂ O 65:35) afforded the target molecule B1.58 (0.008 g, 39%) as white fluff As a solid (after lyophilization).

Example B39 : Preparation of compound B1.59

Pd (OH) ₂ / C (Pearlman catalyst, Pd content 20%, 0.13 g) and benzyl ether 56 (0.12 g, 0.1 mmol) in dioxane (5.3 ml), water (2.6 ml) and glacial acetic acid Add to the mixture. Flask is flushed and flushed several times with argon. The flask is then flushed with hydrogen and the resulting reaction mixture is hydrogenated at room temperature under slight hydrogen elevation for 24 hours and then filtered through a cellulose filter (pore size 45 μm). The filtrate is concentrated in vacuo, the residue is dissolved in water and concentrated several times to remove excess acetic acid. The crude amine (0.074 g) was dissolved in a small amount of water and subjected to gel filtration on a Bio-Gel P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water, 0.45 ml / ) And the subsequent reverse phase chromatography (Merck RP 18 silica gel, eluent: methanol / H ₂ O 1: 1) to give the target molecule B1.59 (0.052 g, 73%) as a white fluffy solid ).

Example B40 : Preparation of compound B1.60

Amine B1.59 (0.027 g, 0.038 mmol) a 1M NaHCO ₃ aqueous solution (0.35 ㎖) was dissolved in approximately 0.5 M solution of benzoyl chloride in toluene over a period of 4 hours a thin layer chromatography (silica gel TLC plate, the fluidized bed: (30 to 50 ㎕) several times until the test with n-butanol / water / acetone / glacial acetic acid / NH ₄ OH 70: 60: 50: 18: 1.5 indicated complete conversion. The pH of the solution is maintained by addition of small portions of solid NaHCO ₃ (about 0.01 g overall) several times to maintain basicity throughout the reaction. Then, the reaction mixture was concentrated in vacuo, the residue was dissolved in a small amount of water and subjected to gel filtration (65 占 퐉 in particle size, 2.5 cm in column length, 35 cm in length, eluent: water, 0.45 ml / min on Bio- , Detection at 215 nm) and subsequent reverse phase chromatography (Merck RP 18 silica gel, gradient elution: methanol / H ₂ O 1: 1) gave the target molecule B1.60 (0.027 g, 85% As a fluffy solid (after freeze drying)

Example B41 : Preparation of compound B1.61

Carbamate B1.61 is prepared starting from amine B1.59 (0.027 g, 0.038 mmol) using benzyl chloroformate as reagent analogously to Example B40 (preparation of compound B1.60). The yield is 0.007 g (21%).

The following compounds are prepared analogously to the above example:

C. ligand binding assays for determination of IC ₅₀ value conservation use of positive control E-selectin / human IgG chimera (cloned and expressed in accordance with Kolbinger et al., Biochemistry 35: 6385-6392 (1996) 0.01M tris, 0.15M NaCl, 1mM CaCl _2, is incubated at pH 7.4 (tris buffer -Ca ⁺⁺⁾ concentration Falcon Pro bindeu ^brand microtiter plate (plate 1) with the 200 ng per well of. Thus, the plating solution is dispensed as 100 μl per well of 2 μg / ml E-chimer. In column 12, only the buffer is present and left empty. Plate 1 is incubated at 37 ° C for 2 hours. After incubation, 100 μl / well of 2% BSA in Tris Ca ⁺⁺ buffer is added and incubated at room temperature for 1 hour. During incubation the compound (2 x serial dilutions) is titrated in 1% BSA in Tris -Ca ⁺⁺ using a U-shaped low binding microtiter plate (plate 2). The heat is continuously diluted to below the ninth column. Columns 10, 11 and 12 are immediate buffer solutions. A (SLe ^X -Lemieux) and B were used as positive controls for each plate and the first wells contained 5 mM < RTI ID = 0.0 > . PolySLe ^a SA-HRP conjugate was incubated with Sialyl Le ^a -PAA-biotin (cat # 01-044, Glyco Tech Corp., Rockville, Md.) In a 1: 2 molar ratio with streptavidin- PolySLe ^{a is} manufactured. Add 60 μl / well of 1 ng / μl of PolySLe ^a SA-HRP conjugate in 1% BSA in Tris -Ca ⁺⁺ to all wells except plate 11, column 11. Plate 1 is washed four times with Tris-C ⁺⁺ in an automatic plate washer. 100 [mu] l / well is transferred from plate 2 to plate 1 and starting from the lowest concentration of compound. Plate 2 is discarded. Plates are incubated with shaking for 2 hours at room temperature. The plates are washed four times with Tris-Ca ⁺⁺ using an automatic plate washer. Add 100 μl / well of the substrate [mixture 3,3 ', 5,5'-tetramethylbenzidine reagent and H ₂ O ₂ at a ratio of 1: 1] to the 8-channel pipettor from right to left. Plates are incubated at room temperature for 2 minutes. The reaction is stopped by adding 100 μl / well of 1 M H ₃ PO ₄ using 8-channel pipettor from right to left. The left absorbance at 450 nm is measured with a microtiter plate reader.

IC ₅₀ values are calculated by measuring the concentration of compound required to inhibit the maximal binding of the poly-SialyLe ^a SA-HRP conjugate to 50% to immobilize the E-selectin / human IgG chimera. Relative IC ₅₀ values are calculated by measuring the ratio of the IC ₅₀ value of the internal control compound to the IC ₅₀ value of the test compound.

Claims (51)

Claims 1. Compounds of the formula &lt; RTI ID = 0.0 &gt; I &lt; / RTI &gt; (I) In this formula, X is a residue of a non-glycosidic aliphatic 1,2-diol; R ₁ is methyl of the S-configuration substituted by one carboxyl moiety and one other substituent; R ₂ is hydrogen, aryl C _1-12 alkyl, or C _6, the substituents alkyl and aryl are here OH, _{halogen, C (O) OR s1,} OC (O) R s4, C (O) R s2, nitro , NH _2, cyano, SO ₃ M _{y, y} OSO ₃ M, NR ₂₀ SO ₃ M _y, C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 hetero Aryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 aralkenyl, C _7-10 heteroalkenyl, primary amino, secondary amino Substituted or unsubstituted with at least one substituent selected from the group consisting of a sulfonyl group, a sulfonyl group, a sulfonamide group, a carbamido group, a carbamate group, a sulfone hydrazide group, a carbhydrazide group, a carbohydroxamic acid group and an aminocarbonylamide group , Wherein R _s1 is hydrogen, M _y , C _1-12 alkyl, C _2-12alke C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl; R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 are alkyl or C _6-10 heteroaralkyl, R _s2, and R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _{2 -11} heterocycloalkyl, heteroaryl C _2-11 cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkyl alkenyl Or C _7-10 heteroaralkenyl and wherein said substituent is selected from the group consisting of alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl , Aralkyloxy, heteroaralkyl, aralkenyl and heteroaralkenyl are substituted or unsubstituted by one of the substituents mentioned above, y is 1 and M is a monovalent metal, or y is ½ M is 2 A metal. The method according to claim 1, (a) NH _2, 1 amino, secondary amino, Carbamide, carbamate, carbalkoxy hydrazide, sulfonamide, sulfone hydrazide and aminocarbonyl amide is _{R 8 C (O) (NH} ) p N _{(R 9) -, -C (} O) (NH) p NR 8 R 9, R 8 OC (O) (NH) p N (R 9) -, R 8 R 40 NC (O) (NH) p N _{(R 9) -, -OC (} O) (NH) p NR 8 R 9, -N (R 40) C (O) (NH) p NR 8 R 9, R 8 S (O) 2 (NH) p _{N (R 9) -, -S} (O) 2 (NH) p NR 8 R 9, R 8 R 40 NS (O) 2 N (R 9) - , and _{-NR 40 S (O) 2 NR} 8 R 9 Wherein R ₈ , R ₉ and R ₄₀ are each independently selected from the group consisting of hydrogen, OH, C _1-12 alkyl, C _1-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkyl C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-16 aralkyl; C _8-16 aralkenyl having C _2-6 alkenylene and C _6-10 aryl; C _6-15 heteroaralkyl, C _6-15 heteroaralkenyl or di-C _6-10 aryl-C _1-6 alkyl, or R _{8 '} R _9' N, wherein R _{8 '} and R _9' Each independently represent hydrogen, OH, SO ₃ M _y , OSO ₃ M _y , C _1-12 alkyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl , C _7-11 aralkyl, C _6-10 heteroaralkyl; C _8-16 alkenyl, aralkyl having a C _2-6 alkenylene and C _6-10 aryl, or di -C _6-10 aryl -C _{1- 6} is alkyl, wherein said substituent is unsubstituted or substituted by one or more substituents; or R ₈ and R _9, or R _{8 'and} R _9', or R ₈ and R ₄₀ is -NR ₈ R ₉ or -NR _8, tetramethylene, pentamethylene, with the case of the _{'R 9',} or _{R 8 R 40 N- - (CH} 2) 2 -O- (CH 2) 2 -, - (CH 2) 2 -S- (CH 2) ₂ - or - (CH ₂ ) ₂ --NR ₇ - (CH ₂ ) ₂ - wherein R ₇ is H, C _1-6 alkyl, C _7-11 aralkyl, C (O) R _s2 or sulfonyl ego; (b) sulfonyl is formula R ₁₀ -SO ₂ - and a group of the, in which R ₁₀ is OH, _{halogen, C (O) OR s1,} OC (O) R s4, C (O) R s2, nitro, NH _2, cyano, SO ₃ M _{y, y} OSO ₃ M, NR ₂₀ SO ₃ M _y, C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _{3 -12} cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy , C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl, C _7-10 heteroalkenyl, primary amino, secondary amino, sulfonyl, sulfonamido, carbamido , C _1-12 alkyl which is substituted or unsubstituted by at least one substituent selected from the group consisting of carbamates, sulfone hydrazides, carbhydrazides, carbohydroxamic acids and aminocarbonyl amides, C _{3 -12} cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 ahreu A keel or C _6-10 heteroaralkyl, where R _s1 is hydrogen, M _y, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C C _6-12 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, and R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or a C _6-10 heteroaralkyl, R _s2, and R ₂₀ is hydrogen, C _{1 -12} alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C C _1-6 alkenyl, C _5-6 heteroaryl, C _5-8 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl and the substituents alkyl, alkenyl, alkoxy, cycloalkyl , Cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, Interrogating aryloxy, aralkyl, heteroaralkyl, aralkyl, alkenyl and heterocyclic are alkenyl is unsubstituted or substituted by one of the substituents mentioned above; p is 0 or 1, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal. 3. The compound of claim 1 wherein X is selected from the group of straight or branched C _2-20 alkylene, -alkenylene, C _3-12 cycloalkylene, -cycloalkenylene, or -O-, -S- and -N- C _3-11 hetero cycloalkylene or having a selected heteroatom-hetero cyclo alkenylene compounds. A compound according to claim 1, wherein X is OH, halogen, C (O) OR _s1 , OC (O) R _s4 , C (O) R _s2 , nitro, NH ₂ , cyano, SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y , C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 hetero cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyl, Alkoxy, C _6-10 heteroaralkyl, C _8-11 aralkenyl, C _7-10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamido, carbamido, carbamate, sulfone Hydrazide, carbhydrazide, carbohydroxamic acid and amidocarbonyl amide, wherein R _s1 is selected from the group consisting of hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 O Alkyl or C _6-10 heteroaralkyl alkyl; R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 are alkyl or C _6-10 heteroaralkyl, R _s2, and R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _{2 -11} heterocycloalkyl, heteroaryl C _2-11 cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkyl alkenyl Or C _7-10 heteroaralkenyl and wherein said substituent is selected from the group consisting of alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl , Aralkyloxy, heteroaralkyl, aralkenyl and heteroaralkenyl are substituted or unsubstituted by one of the substituents mentioned above, y is 1 and M is a monovalent metal, or y is ½ M is 2 Metal compounds. 2. The compound according to claim 1, wherein X is a residue of a 1,2-diol corresponding to the formula (II). &Lt; In this formula, R ₅ and R ₆ are each independently selected from the group consisting of hydrogen, C _1-12 alkyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 ar Alkyl or C _6-10 heteroaralkyl; or R ₅ and R ₆ together with the -CH-CH- group represent a C _3-12 cycloalkylene, a C _3-12 cycloalkenylene, a C _2-11 heteroatom selected from the group consisting of -O-, -S- and -N- is heterocycloalkyl alkylene, or C _3-11 heterocycloalkyl alkenylene, the substituents where the alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkylene, cycloalkylene alkenylene, heterocycloalkyl alkylene and heterocycloalkyl alkenylene is OH, _{halogen, C (O) OR s1,} OC (O) R s4, C (O) R s2, nitro, NH _{2, cyano, SO 3 M y, OSO 3} M y , NR ₂₀ SO ₃ M _y , C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 hetero cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyl, oxy, C _6-10 heteroaralkyl, C _8-11 alkenyl, aralkyl, C _7-10 heteroaralkyl Which is selected from the group consisting of an alkyl group, an alkenyl group, an alkenyl group, an alkenyl group, an alkynyl group, an alkenyl group, an alkynyl group, an alkenyl group, an alkynyl group, It is substituted or unsubstituted by one substituent, where R _s1 is hydrogen, M _y, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _{6 -10} aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 aralkyl and heteroaryl, R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl alkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or a C _6-10 heteroaralkyl, R _s2, and R ₂₀ is hydrogen, C _{1- 12} alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _{5 -9} heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, _C8-11 aralkenyl or _C7-10 heteroaralkenyl, wherein said substituent alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, Aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, aralkenyl and heteroaralkenyl are substituted or unsubstituted by one of the substituents mentioned above, and y is 1 and M is a monovalent metal, y is 1/2, and M is a divalent metal. The method of claim 5 wherein the R ₅ and R ₆ (a) substituted or unsubstituted by C _1-12 alkyl or C _1-12 alkoxy, (b) together with the group -CH-CH-, is a 5- to 8-membered carbocycle, (c) together with the group -CH-CH-, is a 5- to 8-membered heterocyclic cycle, (d) each independently hydrogen, unsubstituted C _1-12 alkyl, or _{-C (O) OR s1, -OC} (O) R s4, -C (O) ONa or -C (O) OK, 1 class C _1-12 alkyl substituted by a substituent selected from the group consisting of amino, secondary amino, C _3-12 cycloalkyl, C _1-6 alkoxy, phenyloxy and benzyloxy; _{Unsubstituted} C _3-12 cycloalkyl or -C (O) OR _s1 , -OC (O) R _s4 , -C (O) ONa or -C C _3-12 cycloalkyl substituted by a substituent selected from the group consisting of C _1-6 alkyl, C _1-6 alkoxy, phenyloxy and benzyloxy; (O) OR _s1 , -OC (O) R _s4 , -C (O) ONa or -C (O) OK, primary amino, secondary amino, C _1-6 alkyl or C _1-6 alkoxy C _6-10 aryl which is substituted or unsubstituted by C _3-9 heteroaryl having 1 or 2 hetero atoms selected from the group consisting of oxygen and nitrogen atoms; (O) OR _s1 , -OC (O) R _s4 , -C (O) ONa or -C (O) OK, primary amino, secondary amino, C _1-6 alkyl or C _1-6 alkoxy Or C _7-12 aralkyl which is unsubstituted or substituted by halogen; (e) a 5- or 12-membered carbocycle together with the group -CH-CH-, or a 5-or 6-membered heterocarbocycle selected from the group consisting of oxygen and nitrogen atoms; or (f) group together with the -CH-CH-, C _3-12 cycloalkylene, C _4-12 cycloalkyl alkenylene, or a hetero atom is -O-, -S-, and selected from the group consisting of -N-, C _{2 -11} and hetero cycloalkylene or C _3-11 heterocycloalkyl alkenylene, where said substituent cycloalkylene, cycloalkylene alkenylene, heterocycloalkyl and heterocycloalkyl alkylene alkenylene is OH, halogen, C (O) oR _{s1, OC (O) R s4, C} (O) R s2, nitro, NH _{2, cyano, SO 3 M y, OSO 3} M y, NR 20 SO 3 M y, C 1-12 alkyl, C _2-12 Al alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 alkenyl, aralkyl, C _7-10 heteroaralkyl alkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, Carbamide, carboxylic Formate, sulfone hydrazide, carbalkoxy hydrazide, carbonyl hydroxamic acid and an amino acid which is substituted or unsubstituted by one or more substituents selected from the group consisting of carbonyl amide, where R _s1 is hydrogen, M _y, C ₁ C ₁₂ alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 and heteroaralkyl, R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, , C _7-11 aralkyl or C _6-10 heteroaralkyl, and R _s2 and R ₂₀ are selected from hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cyclo alkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _{8 -11} aralkyl alkenyl or C _7-10 heteroaralkyl alkenyl is , Said substituent alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl Alkenyl and heteroaralkenyl are substituted or unsubstituted by one of the substituents mentioned above, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal. The method of claim 6 wherein, R ₅ and R ₆ is a C _2-11 heterocycloalkyl alkylene having with -CH-CH- group, C _3-12 cycloalkylene, or nitrogen as a hetero atom, wherein the cycloalkylene and Wherein said heterocycloalkylene is substituted or unsubstituted by at least one substituent according to claim 6. The method of claim 7, wherein, R ₅ and R ₆ is a C _2-11 heterocycloalkyl alkylene having with -CH-CH- group, C _3-12 cycloalkylene, or nitrogen as a hetero atom, wherein the cycloalkylene and heterocycloalkyl alkylene is _{OH, C (O) OR s1} , OC (O) OR s4, C (O) R s2, NR 8 R 9, C 1-12 _{alkyl, R 8 C (O) (} NH) p N (R ₉ ) -, -C (O) (NH) _p NR ₈ R ₉ , R ₈ S (O) ₂ (NH) _p N (R ₉ ) -; _{R 8 R 40 NC (O)} (NH) p N (R 9) -, R 8 OC (O) (NH) p N (R 9) -, -OC (O) (NH) p NR 8 R 9 and R ₁₀ -SO ₂ -, wherein R ₈ , R ₉ , R ₁₀ and R ₄₀ are each independently selected from the group consisting of hydrogen, OH, C _1-12 alkyl, C _1-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 hetero Aryl, _C7-16 aralkyl; C _8-16 aralkenyl having C _2-6 alkenylene and C _6-10 aryl; C _6-15 heteroaralkyl, C _6-15 heteroaralkyl alkenyl, or di -C _6-10 aryl, and -C _1-6 alkyl, wherein the substituents OH, _{halogen, C (O) OR s1,} OC (O) _{R s4, C (O) R} s2, nitro, NH _{2, cyano, SO 3 M y, OSO 3} M y, NR 20 SO 3 M y, C 1-12 alkyl, C _2-12 alkenyl, C _{1 -12} alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 alkenyl, aralkyl, C _7-10 heteroaryl Selected from the group consisting of arylalkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamido, carbamate, sulfone hydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide Substituted or unsubstituted by one or more substituents; R _s1 is hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, and R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 heteroaryl, _-10 aryl, C _5-9 heteroaryl, and C _7-11 aralkyl or C _6-10 heteroaralkyl, R _s2, and R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _{3 -12} cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, wherein the substituents alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclo Alkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, heteroaryl Alkyl, aralkyl, alkenyl and heterocyclic are alkenyl is unsubstituted or substituted by one of the substituents mentioned above; p is 0 or 1, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal. 9. The compound of claim 8, wherein R ₈ and R ₉ are each independently selected from the group consisting of hydrogen, C _1-12 alkyl, C _3-12 cycloalkyl, C _6-10 aryl; C _7-16 aralkyl having 1 to 6 carbon atoms in the alkylene group and C _6-10 aryl; C _2-6 alkenylene and C _8-16 ahreu and alkenyl, or di -C _6-10 aryl -C _1-6 alkyl having C _6-10 aryl, where R ₈ and R ₉ is OH, halogen, _{COOH, C (O) OM y} , C 1-12 alkyl, C _1-6 alkoxy, C _6-10 aryl, C _{6-10 aryloxy, SO 3 M y, OSO 3} M y, NR 20 SO 3 M y , NO ₂ , amino, primary amino, secondary amino and CN; R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, y is 1, M is a monovalent metal, y is ½ and M is a divalent metal. 9. The _compound of claim 8, wherein R &lt; ₁₀ &gt; C _3-12 cycloalkyl, C _6-10 aryl, an alkylene group, and C _7-16 aralkyl having 1 to 6 carbon atoms in C _6-10 aryl, C _2-6 alkenylene, and C _6-10 aryl _8-16 aralkenyl; Or di -C _6-10 aryl, -C _1-6 alkyl, wherein the substituents OH, halogen, COOH, C (O) OM _y, C _1-12 alkyl, C _1-6 alkoxy, C _6-10 aryl, SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y , NO ₂ , amino, primary amino, secondary amino, and CN, and R ₂₀ is substituted or unsubstituted with one or more substituents selected from the group consisting of hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _{6- 10} aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, y is 1 and M is 1 Or y is ½ and M is a divalent metal. 11. The method of claim 10 wherein, R ₁₀ is C _1-12 alkyl; OH, halogen, carboxyl, C (O) OM _y, C _1-12 alkyl, C _1-6 alkoxy, C _6-10 aryl, SO ₃ M _y, nitro, amino, primary amino, secondary amino, and cyano a substituted or unsubstituted by one or more substituents selected from the group consisting of a furnace, C _3-12 cycloalkyl, C _6-10 aryl, C _6-10 alkyl group and a C _7-16 ahreu having 1 to 6 carbon atoms in the aryl Alkyl; Or C _8-16 aralkenyl having C _2-6 alkenylene and C _6-10 aryl, or di-C _6-10 aryl-C _1-6 alkyl. A compound according to claim 8, wherein R ₅ and R ₆ together with the -CH-CH- group are C _3-12 cycloalkylene or C _2-11 heterocycloalkylene having nitrogen as a heteroatom, and heterocycloalkyl alkylene is _{OH, C (O) OR s1} , OC (O) OR s4, C (O) R s2, NH 2, C 1-12 _{alkyl, R 8 C (O) N} (R 9) - (O) NR ₈ R ₉ , R ₈ S (O) ₂ N (R ₉ ) -, R ₈ OC (O) N (R ₉ ) - and R ₁₀ -SO ₂ - Wherein R ₉ is hydrogen and R ₈ is C _1-12 alkyl, C _6-10 aryl or C _7-11 aralkyl, which may be substituted with one or more C _1-12 Substituted or unsubstituted by alkoxy; R ₁₀ is C _1-12 alkyl, C _6-10 aryl or C _7-11 aralkyl which is substituted or unsubstituted by one or more C _1-12 alkyl; R _s1 and R _s4 are C _1-12 alkyl; R _s2 is C _1-12 alkyl, C _3-12 cycloalkenyl, C _3-12 cycloalkyl, or C _6-10 aryl, wherein the substituents alkyl, cycloalkenyl, cycloalkyl and aryl are OH, C (O) OR _{s1 '} and OC (O) R _s4' ; _Wherein R _{s1 '} is M _y or C _1-12 alkyl, R _s4' is C _1-12 alkyl, y is 1 and M is a monovalent metal, y is ½ and M is a divalent metal . 13. The compound of claim 12 wherein R &lt; ₅ &gt; and R &lt; ₆ &gt; together with the -CH-CH- group are cyclohexylene. 9. The compound of claim 8, wherein R &lt; ₅ &gt; and R &lt; ₆ &gt; together with the -CH-CH- group are piperidinyl. 15. The compound of claim 14, wherein R &lt; ₅ &gt; and R &lt; ₆ &gt; together with the -CH-CH- group are piperidylene; Here, the heteroatom is _{C (O) OR s1, C} (O) OR s2, C (O) NR 8 R 9, NH 2, SO 3 M y, C 1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _6-10 aryloxy , C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 alkenyl, aralkyl, C _{7- 10} heteroaralkyl alkenyl, primary amino, secondary amino, sulfonyl, sulfonamide and sulfone hydrazide is substituted by a substituent selected from the group or unsubstituted and ring, ring C atom more than one is OH, OC (O) consisting of OR _s4 , NH ₂ , OSO ₃ M _y , NR ₂₀ SO ₃ M _y , C _1-12 alkoxy, C _6-10 aryloxy, C _5-9 heteroaryloxy, C _7-11 aralkyloxy, , Secondary amino, sulfonamides, carbamides, carbamates, sulfone hydrazides, carbhydrazides, carbohydroxamines Wherein R _s1 is selected from the group consisting of hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 aralkyl and heteroaryl, R _s4 is hydrogen, C _1-12 alkyl, , C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl ego; R ₈ and R ₉ are each independently hydrogen, OH, C _1-12 alkyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _{7- 16} aralkyl, C _6-15 heteroaralkyl, C _2-6 alkenylene and C _8-16 alkenyl, aralkyl having a C _6-10 aryl, or di -C _6-10 aryl, or -C _1-6 alkyl; Or R ₈ and R ₉ together are tetramethylene, _{pentamethylene, - (CH 2) 2 -O-} (CH 2) 2 -, - (CH 2) 2 -S- (CH 2) 2 - or - (CH ₂ ) ₂ -NR ₇ - (CH ₂ ) ₂ -; R ₇ is H, C _1-6 alkyl, C _7-11 aralkyl, C (O) R _s2 or sulfonyl; R _s2 and R ₂₀ are selected from hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocyclo C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, Substituted alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, And heteroaralkenyl are substituted or unsubstituted by one of the substituents mentioned above, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal. 16. The compound of claim 15 wherein R &lt; ₅ &gt; and R &lt; ₆ &gt; together with the -CH-CH- group are piperidinyl; Wherein the heteroatom is substituted or unsubstituted by a substituent selected from the group consisting of C (O) OR _s1 , C (O) R _s2 , -C (O) NR ₈ R ₉ and R ₁₀ -SO ₂ - ring C atom more than one is _{OH, NH 2, R 8 S} (O) 2 N (R 9) -, R 8 C (O) N (R 9) - and _{R 8 OC (O) N (} R 9) -, wherein R ₉ is hydrogen and R ₈ is C _1-12 alkyl, C _6-10 aryl or C _7-11 aralkyl, wherein R ₉ is hydrogen, Wherein said substitutent alkyl, aryl and aralkyl are substituted or unsubstituted by at least one C _1-12 alkoxy, R ₁₀ is C _1-12 alkyl, substituted or unsubstituted by at least one C _1-12 alkyl, C _6-10 aryl or C _7-11 aralkyl; R _s1 is C _1-12 alkyl and R _s2 is C _1-12 alkyl, C _3-12 cycloalkenyl, C _3-12 cycloalkyl or C _6-10 aryl, wherein said substituent alkyl, cycloalkenyl, Cycloalkyl and aryl are substituted or unsubstituted by one or more substituents selected from the group consisting of OH, C (O) OR _{s1 '} and OC (O) R _S4' , wherein R _{s1 '} is M _y or C _{1 -Alkyl} , R _{S4 '} is C _1-12 alkyl, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal. 10. The method of claim 8 wherein, R ₅ and R ₆ are together -CH-CH- groups, OH, C (O) OR s1, OC (O) OR s4, C (O) R s2, NH 2, C 1-12 Alkyl, R ₈ C (O) N (R ₉ ) -, -C (O) NR ₈ R ₉ , R ₈ S (O) ₂ N (R ₉ ) -; R ₈ OC (O) N (R ₉ ) -, R ₈ R ₄₀ NC (O) N (R ₉ ) -, -OC (O) NR ₈ R ₉ and R ₁₀ -SO ₂ - Piperidylene which is substituted or unsubstituted by at least one substituent; Wherein R ₉ is hydrogen and R ₈ is C _1-12 alkyl, C _6-10 aryl or C _7-11 aralkyl, wherein said alkyl, aryl and aralkyl are optionally substituted with one or more C _1-12 alkoxy or Substituted or unsubstituted C _7-11 aralkyloxy, R ₁₀ is C _1-12 alkyl, C _6-10 aryl or C _7-11 aralkyl which is substituted or unsubstituted by at least one C _1-12 alkyl Alkyl and R ₄₀ is selected from the group consisting of hydrogen, C _1-12 alkyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl; R _s1 and R _s4 are C _1-12 alkyl and R _s2 is C _1-12 alkyl, C _3-12 cycloalkenyl, C _3-12 cycloalkyl or C _6-10 aryl, wherein the substituent alkyl, cycloalkyl Cycloalkyl and aryl are substituted or unsubstituted by one or more substituents selected from the group consisting of OH, C (O) OR _{s1 '} and OC (O) R _s4' , wherein R _{s1 '} is M _y or C _1-12 alkyl, R _{s4 '} is C _1-12 alkyl, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal. The method of claim 1 wherein, X is _{OH, NH 2, C 3 H} 7, -C (O) CH 3, -C (O) C 6 H 5, -C (O) (CH 2) 8 C (O) _{OCH 3, -C (O) [} CH (OH)] 2 C (O) ONa, C (O) -C 6 H 8 (OH) 3, -C (O) -C 6 H 11, -C (O _{) OC 3 H 7, -C (} O) NHC 6 H 5, -NHS (O) 2 CH 2 C 6 H 5, -NHC (O) OCH 2 C 6 H 5, -NHC (O) C 6 H 3 _{(OCH 3) 2, -S (} O) 2 -C 4 H 9, -NHC (O) NHC 6 H 5, -S (O) 2 -C 6 H 4 CH 3, -S (O) 2 -CH ₂ C ₆ H _5, and -S (O) ₂ - (CH ₂ ) C ₁₀ H ₇ , wherein the substituent is cyclohexylene or piperidylene which is substituted or unsubstituted by at least one substituent selected from the group consisting of -S (O) ₂ - The compound according to claim 1, wherein R ₂ is C _1-6 alkyl. The method of claim 1, wherein the substituents on R ₂ a _{halogen, -C (O) OM y,} C 1-6 alkyl, C _1-4 alkoxy, phenyl, naphthyl, -SO ₃ M _y, C _1-12 1 C 2 -C ₂₀ secondary amino, -SO ₂ -NR ₈ R _9, and -C (O) -NR ₈ R ₉ , wherein R ₈ and R ₉ are each independently selected from the group consisting of H, C _1-4 alkyl, C _2-4 hydroxyalkyl, phenyl or benzyl, or R ₈ and R ₉ together with the N atom are morpholino, thiomorpholino, pyrrolidino or piperidino. A compound according to claim 1, wherein R ₂ is hydrogen, unsubstituted C _1-6 alkyl, or is C (O) OH, -C (O) -NR ₈ R ₉ or -SO ₂ -NR a C _1-6 alkyl which is substituted by ₈ R _9, where R ₈ is H, C _1-4 alkyl, C _2-4 hydroxyalkyl, phenyl or benzyl , R ₉ are independently has the meaning of R _8, or R ₈ and R ₉ together are tetramethylene, pentamethylene or _{-CH 2 CH 2 -O-CH 2} CH 2 - a compound. 22. The method of claim 21 wherein, R ₂ is hydrogen, methyl, ethyl, HO (O) C-CH 2 CH 2 -, NaOC (O) -CH 2 CH 2 - or _{R 8 R 9 NC (O)} -CH 2 CH ₂ -, R ₈ and R ₉ are each independently H, C _1-6 alkyl, C _2-4 hydroxyalkyl, phenyl or benzyl, or R ₈ and R ₉ together are morpholino. The compound according to claim 1, wherein the remaining substituents in R ₁ have 1 to 20 carbon atoms. The method of claim 23 wherein the remaining substituents a substituted or unsubstituted C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl , C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl, and C _7-10 Heteroalkenyl, and heteroaralkenyl. 25. The compound of claim 24, wherein the remaining substituents are substituted methyl, or 2-substituted ethyl or cyclohexyl. 3. A compound according to claim 1, wherein R &lt; ₁ &gt; (III) In this formula, R ₃ is hydrogen or M _y ; R ₄ is OH, halogen, C (O) OR _s1 , OC (O) R _s4 , C (O) R _s2 , nitro, NH ₂ , cyano, SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y , C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 hetero cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _{6- 10} heteroaralkyl, _C8-11 aralkenyl, _C7-10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamido, carbamate, sulfone hydrazide, carb C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, and the like, which are unsubstituted or substituted by one or more substituents selected from the group consisting of halogen, cyano, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 Reel, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkyl or C _7-10 alkenyl and heterocyclic are alkenyl; Wherein R _s1 is selected from the group consisting of hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 hetero Aryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, and R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl , C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, and R _s2 and R ₂₀ are selected from hydrogen, C _1-12 alkyl, C _2-12 alkenyl , C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroaralkenyl, wherein said substituent alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, hetero Cycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyl Wherein y is 1 and M is a monovalent metal, or y is ½ and M is 2 or 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, heteroaryl, heteroaryl, Is a metal. 27. The method of claim 26 wherein, R ₃ is hydrogen or M _y R ₄ is (a) unsubstituted C _1-12 alkyl; -NH ₂ , primary amino, secondary amino, C _1-12 sulfonyl, carbamido, carbamate, carbhydrazide, sulfonamide, sulfone hydrazide, aminocarbonylamido, C _3-12 cyclo C _1-12 alkyl substituted by one or more substituents selected from the group consisting of alkyl, C _1-6 alkoxy, phenyloxy and benzyloxy; _{Unsubstituted} C _3-12 cycloalkyl; C _3-12 cycloalkyl, C _1-6 alkyl, C _1-6 alkoxy, C _1-12 alkylsulfonyl, phenyloxy and benzyloxy C _3-12 cycloalkyl which is optionally substituted by one or more substituents selected from the group consisting of ; C _6-10 aryl; C _3-9 heteroaryl having 1 or 2 hetero atoms selected from the group consisting of oxygen and nitrogen atoms; C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl; C _1-6 alkyl, and oxygen and has one or two heteroatoms selected from the group consisting of nitrogen, C _4-16 heteroaralkyl having a C _3-10 heteroaryl group whose total number of carbon atoms is 3 to 5; OH, halogen, C _1-12 sulfonyl, carboxyl, C (O) OM _y , C _1-12 alkyl, C _1-6 alkoxy, C _6-10 aryl, SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y, nitro, NH _2, 1 amino, secondary amino, Carbamide, carbamate, sulfonamide and cyano is substituted by one or more substituents selected from the group consisting of a furnace, C _6-10 aryl , C _3-9 heteroaryl having one or two heteroatoms selected from the group consisting of oxygen and nitrogen atoms, C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl, C _1-6 alkyl, And C _3-16 heteroaryl having 1 to 2 heteroatoms selected from the group consisting of oxygen and nitrogen atoms and having C _4-10 heteroaryl having a total carbon number of 3 to 5, y is 1, and M is a monovalent metal Or y is ½ and M is a divalent metal, or (b) OH, halogen, C (O) OR _s1 , OC (O) R _s4 , C (O) R _s2 , nitro, NH ₂ , cyano, SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y , C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 hetero cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _{6- 10} heteroaralkyl, _C8-11 aralkenyl, _C7-10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamido, carbamate, sulfone hydrazide, carb C _1-12 alkyl or C _7-11 aralkyl which is substituted or unsubstituted by one or more substituents selected from the group consisting of hydrazide, carbohydroxamic acid and aminocarbonylamide, wherein R _S1 is hydrogen, _y M, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl Kiel, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, R _S4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl is hydrogen, C _5-9 heteroaryl, C _7-11 aralkyl or a C _6-10 heteroaralkyl, R _S2 and R ₂₀ , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 Aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, wherein the substituents alkyl, alkenyl, Alkoxy, heteroaralkyl, aralkenyl, and heteroaralkenyl are optionally substituted with one or more substituents independently selected from the group consisting of alkyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, Among the above-mentioned substituents Y is 1, M is a monovalent metal, y is 1/2, and M is a divalent metal. The method of claim 27 wherein the compound of R ₃ is hydrogen, K or Na. A compound according to claim 27, wherein R ₄ is methyl, ethyl, n- or i-propyl, n-, i- or t-butyl, cyclohexyl, Phenylpropyl, cyclohexylmethyl, 2-cyclohexylethyl, furanyl, pyridinyl or pyrimidinyl. 28. The compound according to claim 27, wherein the carbamido, carbhydrazo, sulfonamido, sulphonhydra map, aminocarbonylamide and carbamate as substituents for R ₄ are of the formula R ₈ NHC (O) N (R ₉ ) _{-, R 8 OC (O)} N (R 9) -, R 8 C (O) (NH) P N (R 9) - and _{R 8 S (O) 2 (} NH) P N (R 9) - of Wherein R ₈ is H, C _1-12 alkyl, C ₅ - or C ₆ cycloalkyl, C ₅ - or C ₆ cycloalkylmethyl or -ethyl-, C ₅ - or C ₆ heterocycloalkyl, C ₅ - or C ₆ heterocycloalkyl, or methyl-ethyl-, phenyl, naphthyl, benzyl, 2-phenylethyl or diphenylmethyl, all of which are -OH, -NH _2, C _1-8 1 amino, _{2-C 14} secondary _{amino, NO 2, -CN, -F,} -Cl, -C (O) OH, -C (O) ONa, -SO 3 H, -OSO 3 Na, NR 20 SO 3 Na ( wherein, R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroaralkenyl), and -SO ₃ Na, C _1-4 alkyl, C _1-4 alkoxy and phenyl. Wherein R ₉ is H, C alkyl, phenyl, naphthyl, benzyl, 2-phenylethyl or phenyl-CH = CH-CH ₂ - and p is 0 or 1, . 28. The compound of claim 27, wherein R &lt; ₄ &gt; is (a) carbamic not shown-substituted alkyl group _{R 8 -C (O) NR 9} - (CH 2) n - ( wherein, n is 1 or 2, R ₈ is hydrogen, C _1-12 alkyl, C _{3- 12} cycloalkyl, C _6-10 aryl, or C _1-6 alkyl and C _7-16 aralkyl having a C _6-10 aryl group, the substituents alkyl, cycloalkyl, aryl and aralkyl are OH, halogen, carboxyl _{, -C (O) OM y,} C 1-12 alkyl, C _1-6 alkoxy, C _{6-10 aryl, SO 3 M y, OSO 3} M y, NR 20 SO 3 M y, C (O) OR s1 , OC (O) R _s4 , nitro, amino and cyano; or C _8-16 arylene having C _2-6 alkenyl and C _6-10 aryl is substituted or unsubstituted by one or more substituents selected from the group consisting of alkenyl, or di -C _6-10 aryl -C _1-6 alkyl; R ₉ is H, straight or branched chain C _1-10 alkyl, C ₅ - or C ₆ cycloalkyl, C ₅ - or C ₆ cycloalkyl methyl- or -ethyl, phenyl, naphthyl or benzyl, 2-phenylethyl or phenyl, -CH = CH-CH ₂ -, y is 1 and M are either alkali metal, y is And M is an alkaline earth metal, R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _{2 -11} hetero cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkyl or C _7-10 alkenyl heteroaralkyl al And R _s1 is hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 hetero Aryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, and R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl , C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl); (b) a sulfonamide-substituted alkyl group R ₈ -SO ₂ NR ₉ - (CH ₂ ) _n -, wherein R ₈ , R ₉ and n are as defined in (a) above; (c) an aminocarbonylamide- or carbamate-substituted alkyl group R ₉ NH-C (O) -NH- (CH ₂ ) _n or R ₉ OC (O) -NH- (CH ₂ ) _n , R ₉ is the same meaning as defined in (a) above and further phenyl, and n is as defined in (a) above; (d) a carbhydrazo-substituted alkyl group R ₈ -C (O) -NHNR ₉ - (CH ₂ ) _n -, wherein R ₈ , R ₉ and n have the meaning defined in (a) above; or (e) a sulfone hydra map-substituted alkyl group R ₈ -SO ₂ -NHNR ₉ - (CH ₂ ) _n , wherein R ₈ , R ₉ and n are as defined in (a) above. 28. The compound of claim 27, wherein R &lt; ₄ &gt; is (a) an amide R ₈ C (O) N (R ₉ ) (CH ₂ ) _n- or R ₈ S (O) ₂ N (R ₉ ) (CH ₂ ) _{n- wherein} R ₈ and R ₉ are independently hydrogen, unsubstituted C _1-12 alkyl; OH, halogen, carboxyl, -C (O) ONa, C 1-12 alkyl, C _1-6 alkoxy, C _6-10 aryl, -SO ₃ H, unsubstituted C _{3-12 cycloalkyl;; OSO 3 Na, NR 20} SO 3 Na, SO 3 Na, nitro and cyano C _1-12 alkyl that is optionally substituted by one or more substituents selected from the group consisting of one or more OH substituted C _3-12 cycloalkyl by; unsubstituted C _6-10 aryl, C _1-6 alkyl and C unsubstituted C _7-12 aralkyl having _6-10 aryl; C _6-10 aryl, or C _1-6 alkyl and C _7-12 aralkyl having a C _6-10 aryl group (where the group OH, halogen, carboxyl, C (O) ONa, -C (O) OK, C _1-12 alkyl, , from C _1-6 alkoxy, C _{6-10 aryl, SO 3 Na, OSO 3 Na} , NR 20 SO 3 Na, C (O) OR s1, OC (O) R s4, nitro, amino and cyano group consisting of By one or more substituents selected Hwandoem), R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkyl C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, R _s1 is hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _{7 -11} aralkyl or C _6-10 heteroaralkyl and; R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _{6- 10} aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl; n is 2 or 1; or (b) sulfonamide R ₈ -S (O) ₂ N (R ₉ ) (CH ₂ ) _n - _wherein R ₈ is C _1-12 alkyl which is substituted or unsubstituted by one or more halogen atoms; C _6-10 aryl substituted by one or more C _1-4 alkyl, C _1-4 alkoxy, halogen, -CN or -NO ₂ , R ₉ is hydrogen or isobutyl, and n is 2 or 1. ; or (c) aminocarbonylamide R ₈ -NH-C (O) -NH (CH ₂ ) _{n wherein} R ₈ is halogen, -CN, -NO ₂ , C _1-4 alkyl, C _1-4 alkoxy, C ₅ - or C ₆ cycloalkyl, C _6-10 aryl or C _7-12 aralkyl substituted or unsubstituted C _1-12 alkyl or C _6-10 aryl by alkyl, n is 1 or 2, Im); or (d) aminoalkyl R _{8 '} R _9' N (CH ₂ ) _n - _wherein R _{8 '} and R _9' are each independently hydrogen, unsubstituted C _1-12 alkyl, OH, halogen, C _{) OR s1, OC (O)} R s4, C (O) -NR 11 R 12, C 1-12 alkyl, C _1-6 alkoxy, C _{6-10 aryl, -SO 3 H, SO 3 Na} , OSO 3 Na, NR ₂₀ SO ₃ Na, C _1-12 alkyl substituted by one or more substituents selected from the group consisting of nitro, amino and cyano, unsubstituted C _3-12 cycloalkyl, substituted by one or more OH C _3-12 cycloalkyl; C _6-10 aryl; C with a ₈ or C _2-6 alkenyl, and C _6-10 aryl; C _1-6 alkyl and C _6-10 aryl C _7-16 aralkyl having _-16 aralkyl and alkenyl, aryl-alkenyl wherein the substituents in the aryl group, and aralkyl and aralkyl Al is OH, _{halogen, C (O) OR s1,} OC (O) R s4, -C (O) ONa, -C (O (O) -NR ₁₁ R ₁₂ , C _1-12 alkyl, C _1-6 alkoxy, C _6-10 aryl, -SO ₃ H, SO ₃ Na, OSO ₃ Na, NR ₂₀ SO ₃ Na , Nitro, amino, and cyano. N is 2, preferably 1, and R _s1 is selected from the group consisting of hydrogen, K or Na, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cyclo Alkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, and R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl , R ₁₁ is H, C _1-4 alkyl, C _2-4 hydroxyalkyl, phenyl or benzyl, R ₁₂ is independently for R ₁₁ , or R ₁₁ and R ₁₂ together are tetramethylene, pentamethylene or _{-CH 2 CH 2 -O-CH 2} CH 2 - , and; R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 alkenyl or C _7-10 heteroaralkenyl. A compound according to claim 32, wherein R ₄ is an amide R ₈ C (O) N (R ₉ ) (CH ₂ ) _n- or R ₈ S (O) ₂ N (R ₉ ) (CH ₂ ) _n - R ₈ is unsubstituted C _1-12 alkyl; C _1-8 alkyl substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) ONa and C _6-10 aryl; _{Unsubstituted} C _3-12 cycloalkyl; C _3-8 cycloalkyl substituted by one or more OH; _{Unsubstituted} C _6-10 aryl, or C _7-12 aralkyl having C _1-6 alkyl; Halogen, -C (O) OH, C (O) ONa, C 1-12 alkyl, C _{1-6 alkoxy, -SO 3 H, SO 3 Na} , OSO 3 Na, NR 20 SO 3 Na ( wherein, R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _{6 -10} aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkyl or C _7-10 alkenyl heteroaralkyl alkenyl nilim) and nitro, and cyano group consisting of that is substituted by one or more substituents selected from, C _6-10 aryl, C _1-6 alkyl and C _7-12 aralkyl, or C _2-6 alkenyl, and C _6-10 aryl group having a C _6-10 aryl &_Lt; / RTI &gt; R ₉ is hydrogen; Unsubstituted C _1-6 alkyl, unsubstituted C _6-10 aryl; _{Unsubstituted} C _7-12 aralkyl having C _1-6 alkyl and C _6-10 aryl; Or C _8-16 aralkenyl having C _2-6 alkenyl and C _6-10 aryl; and n is 2 or 1. 33. The method of claim 32, wherein, R ₄ is an amide _{R 8 C (O) N (} R 9) (CH 2) n - , and where R ₈ is unsubstituted C _1-12 alkyl; C _1-12 alkyl which is substituted by one or more substituents selected from the group consisting of cyclohexyl, OH, halogen, -C (O) OH, -C (O) ONa and phenyl; _{Unsubstituted} C _3-12 cycloalkyl; C _3-12 cycloalkyl substituted by one or more OH; _{Unsubstituted} C _6-10 aryl; Halogen, C (O) ONa, -C (O) OH, C _1-6 alkyl, C _1-6 alkoxy, phenyl, -SO ₃ H, SO ₃ Na, OSO ₃ Na, NHSO ₃ Na, C _6-10 aryl substituted by one or more substituents selected from the group _{consisting of} Or C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl. R ₉ is selected from the group consisting of hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl, or C _2-6 alkenyl and C _6-10 aryl &_Lt; / RTI &gt; and n is 2 or 1. 35. The compound of claim 34, wherein R ₈ is unsubstituted C _1-12 alkyl; C _1-4 alkyl substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OH, C (O) ONa and phenyl; _{Unsubstituted} C _3-12 cycloalkyl; C _3-12 cycloalkyl substituted by one or more OH; _{Unsubstituted} C _6-10 aryl; A group consisting of halogen, -C (O) OH, C (O) ONa, C _1-6 alkyl, C _1-6 alkoxy, -SO ₃ H, SO ₃ Na, OSO ₃ Na, NHSO ₃ Na, nitro and cyano C _6-10 aryl substituted by one or more substituents selected from halogen; Or unsubstituted C _7-16 aralkyl having C _1-6 alkyl and C _6-10 aryl; R ₉ is hydrogen, C _1-4 alkyl, phenyl, -CH ₂ -, phenyl-CH ₂ -CH _2, phenyl, - (CH _{2) 3} - or phenyl, -CH = CH-CH ₂ -, n is 2 or 1 compound. 32. The compound of claim 32, wherein R ₄ is aminoalkyl R _{8 '} R _9' NCH ₂ -, wherein R _{8 '} and R _9' are each independently hydrogen, C _1-8 alkyl, cyclopentyl, cyclohexyl, C ₅ - or C ₆ cycloalkylmethyl, phenyl-C _1-4 alkyl or phenyl-C _2-4 alkenyl. 33. The method of claim 32, wherein, R ₄ is an amine _{R 8 'R 9' NCH 2} - , and wherein R _{8 'and} R _9' are each independently H, C _1-6 alkyl, phenyl -C ₁ - ₂ alkyl or C / RTI &gt; 27. The method of claim 26, wherein, R ₄ is optionally substituted by NH _2, C _3-12 cycloalkyl, primary amino, secondary amino, sulfonamide and Carbamide and aminocarbonyl amino least one substituent selected from the group consisting of road Or unsubstituted, C _7-11 aralkyl, C _3-12 cycloalkyl or C _1-12 alkyl. 39. The method of claim 38, cyclohexyl, C _6-10 aryl, the substituent for the C _1-12 alkyl, _{NH 2, R 8 C (O} ) N (R 9) -, R 8 S (O) 2 N (R ₉ ) -, R ₈ NHC (O) NR ₉ - and R _{8 '} R _9' N- wherein R ₈ and R ₉ are each independently selected from the group consisting of hydrogen, C _1-12 alkyl, C ₃ C8 _- cycloalkyl, _C2-11 heterocycloalkyl, _C6-10aryl , _C5-9 heteroaryl, _C7-11 aralkyl or _C6-10 heteroaralkyl, and R8 _' and R9 &_apos; each independently hydrogen, OH, C _1-12 alkyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _{6 -10} and heteroaralkyl, all of which are OH, _{halogen, C (O) OR s1,} OC (O) R s4, C (O) R s2, nitro, NH _2, cyano, SO ₃ M _{y, y} OSO ₃ M , NR ₂₀ SO ₃ M _y , C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 aryl _C7-10 heteroalkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamido, carbamate, sulfone hydrazide, carbhydrazoside, carbohydroxamic acid and aminocarbamate Wherein R _s1 is selected from the group consisting of hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, and C _7-11 aralkyl or C _6-10 heteroaralkyl, R _s4 is hydrogen, C _1-12 alkyl, C _{2- 12} alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, R _s2 And R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl , C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, and the substituents alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, Aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, aralkenyl, and heteroaralkenyl are optionally substituted with one of the above-mentioned substituents , P is 0 or 1, y is 1 and M is a monovalent metal, y is ½ and M is a divalent metal, or R _{8 '} and R _9' together are tetramethylene, penta _{methylene, - (CH 2) 2 -O-} (CH 2) 2 -, - (CH 2) 2 -S- (CH 2) 2 - or _{- (CH 2) 2 -NR 7} - (CH 2) 2 - ego; R ₇ is H, C _1-6 alkyl, C _7-11 aralkyl, C (O) R _s2 or sulfonyl. The method of claim 39, R ₄ is NH _2, cyclohexyl, C _{6-10 aryl, R 8 C (O) N} (R 9) -, R 8 S (O) 2 N (R 9) -, R 8 NHC _{(O) NR 9 -, NR} 9 C (O) NHR 8 and R _{8 'R 9'} is substituted or unsubstituted by one or more substituents selected from the group consisting of _{N-, CH 2 -C 6 H 5} , ( CH ₂ ) ₂ -C ₆ H ₅ , cyclohexyl, methyl, ethyl or isopropyl; Wherein R ₈ , R ₉ , R _{8 '} and R _9' are each independently hydrogen, C _1-12 alkyl, C _3-12 cycloalkyl, C _6-10 aryl or C _7-11 aralkyl, OH, halogen, C (O) OM _y, nitro, cyano, SO ₃ M _{y, y} OSO ₃ M, NHSO ₃ M _y, C _1-12 consisting of alkyl, C _1-12 alkoxy and C _6-10 aryl , Y is 1 and M is a monovalent metal, y is 1/2, and M is a divalent metal. 27. The method of claim 26, wherein, R ₄ is _{C 6 H 11, CH (CH} 3) 2, CH 2 - phenyl, (CH _{2) 2} - phenyl, CH ₂ NHC (O) - phenyl, CH ₂ NHC (O) ( CH _{2) 3} - _{phenyl, CH 2 NHC (O) (} CH 2) 3 OH, CH 2 NHC (O) CF 3, CH 2 NHC (O) C 6 H 11, CH 2 NHC (O) C 11 H 23 _{, CH 2 NHC (O) CH} (C 6 H 5) 2, CH 2 HNC (O) NHC 6 H 5, CH 2 NHC (O) C 2 H 4 CO 2 Na, CH 2 NHC (O) C 6 [ _{(1,3,4,5) OH] 4 H 7} , CH 2 NHC (O) C 6 H 4 -p-SO 3 Na, CH 2 NHC (O) C 6 H 4 Cl, CH 2 NHC (O) _{C 6 H 4 NO 2, CH} 2 NHC (O) C 6 H 4 OCH 3, CH 2 NHC (O) C 6 H 4 (3,4) Cl 2, CH 2 NHC (O) C 6 H 4 CH 3 _{, CH 2 NHC (O) C} 6 H 4 C 6 H 5, CH 2 NHC (O) C 6 H 4 CN, CH 2 NHC (O) C 10 H 7, CH 2 NHC (O) C 6 H 4 COONa _{, CH 2 NHC (O) (} CHOH) 2 COONa, CH 2 N (CH 2 CH = CH- phenyl) [C (O) - _{phenyl], CH 2 N [CH 2} CH (CH 3) 2] [C ( O) - _{phenyl], CH 2 N [C (} O) C 6 H 5] CH 2 C 6 H 5, CH 2 N [C (O) C 6 H 5] (CH 2) 3 C 6 H 5, CH _{2 C 6 H 11, (CH} 2) 2 C 6 H 11, CH 2 NH 2, CH 2 NHCH 2 CH = CH- phenyl, CH ₂ NHCH ₂ - _{phenyl, CH 2 NHCH 2 CH (CH} 3) 2, CH ₂ N (CH ₂ -phenyl) ₂ , CH ₂ N [CH ₂ CH (CH ₃ ) ₂ ] ₂ , CH ₂ NHSO ₂ -p-nitrophenyl, CH ₂ NHSO ₂ -p- _{tolyl, CH 2 NHSO 2 CF 3,} CH 2 NHC (O) NHC 6 H 5 , or CH ₂ N [SO ₂ -p- _{nitrophenyl] [CH 2 CH (CH 3} ) 2] 2 in compound. 2. A compound according to claim 1, corresponding to the formula (Ia) <Formula Ia> In this formula, R ₃ is hydrogen or M _y ; R ₄ is selected from the group consisting of C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 alkenyl or C _7-10 heteroaryl Alkenyl; R ₅ and R ₆ are each independently selected from the group consisting of hydrogen, C _1-12 alkyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 ar Alkyl or C _6-10 heteroaralkyl, or R ₅ and R _6, together with the -CH-CH- group, are C _3-12 cycloalkylene, C _4-12 cycloalkenylene, or a group having a heteroatom selected from the group consisting of -O-, -S- and -N- C _2-11 heterocycloalkylene and C _3-11 heterocycloalkenylene; From here, Said alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkylene, cycloalkenylene, heterocycloalkylene and heterocycloalkenylene being optionally substituted by OH, halogen, C (O) OR _{s1, OC (O) R s4} , C (O) R s2, nitro, NH _{2, cyano, SO 3 M y, OSO 3} M y, NR 20 SO 3 M y, C 1-12 alkyl, C _{2- 12} alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _{6 -10} aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 aralkyl alkenyl , C _7-10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamido, carbamido, carbamate, sulfone hydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonyl Amide &lt; / RTI &gt; By a substituent, and ring once or several times substituted or unsubstituted, where R _s1 is hydrogen, M _y, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl , C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _{3 And} R _s2 and R ₂₀ are _{independently selected from the} group consisting of hydrogen, C _1-6 alkyl, C _1-6 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl , C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, the substituents alkyl, alkenyl, alkoxy, Cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryl When, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, aralkyl, alkenyl and heterocyclic are alkenyl is unsubstituted or substituted by one of the substituents mentioned above; y is 1 and M is a monovalent metal, y is 1/2, and M is a divalent metal. 43. The compound of claim 42, wherein R ₃ is H, K or Na, R ₅ and R ₆ together with the -CH-CH- group represent C _3-12 cycloalkylene, C _4-12 cycloalkenylene, or -O- , -S-, and a C _2-11 heterocycloalkyl C _3-11 alkylene or alkenylene heterocycloalkyl having a heteroatom selected from -N- group, all of which are OH, _{halogen, C (O) oR s1,} OC (O) _s4 OR, C (O) R _s2, nitro, NH _{2, cyano, SO 3 M y, OSO 3} M y, NH 20 SO 3 M y, C 1-12 alkyl, C _2-12 alkenyl, C _{1 -12} alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 alkenyl, aralkyl, C _7-10 heteroaryl Alkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamido, carbamate, sulfone hydrazide, carbhydrazide, carbohydrox Trioxide and aminocarbonyl amide by a substituent selected from the group and the ring once or several times substituted or consisting of, where R _s1 is hydrogen, M _y, C _1-12 alkyl, C _2-12 alkenyl, C _{3 -12} cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or a C _6-10 heteroaralkyl, R _s4 is hydrogen, C _1- C ₁₂ alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 hetero R ₂ and R ₂₀ are _{independently selected} from the group consisting of hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _{2 -11} hetero cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkyl or C _7-10 alkenyl heteroaralkyl al Alkenyl, alkoxy, cycloalkyl, cyano, &lt; RTI ID = 0.0 &gt; Heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, aralkenyl and heteroaralkenyl may be optionally substituted with one or more of the substituents mentioned above Y is 1 and M is a monovalent metal, y is 1/2, and M is a divalent metal; (a) R ₄ is a residue R ₁₂ - (CH ₂ ) _n - or cyclohexyl, wherein n is 1 or 2; R ₁₂ is C _1-4 alkyl, C _1-4 alkoxy, F, Cl, substituted or unsubstituted by -CN or -NO _2, C _1-10 alkyl, C _5-8 cycloalkyl, C _6-10 Aryl or C _8-12 alkenyl, or R ₁₂ is an amino group -NR _{8 '} R _{9' wherein} R _{8 '} and R _9' are C _1-12 alkyl or unsubstituted or C _1-4 alkyl-substituted C ₅ - or C ₆ cycloalkyl, C _6-10 aryl, C _7-12 aralkyl or C _8-12 aralkenyl); or R ₁₂ is an amino group _{-N (R 9) C (O} ) R 8, -N (R 9) S (O) 2 R 8, -NR 9 C (O) NHR 8 or -NR ₉ C (O) NHR ₈ Wherein R ₈ is C _6-10 aryl substituted or unsubstituted by C _1-4 alkyl, C _1-4 alkoxy, F, Cl, -CN or -NO ₂ , or F or Cl, and ring C _1-10 -alkyl, R ₉ is H, C _1-10 alkyl, C ₅ - or C ₆ cycloalkyl, C ₅ - or C ₆ cycloalkyl, -C _1-6 alkyl, phenyl -C _1-6 Alkyl or phenyl-C _2-6 alkenyl; or (b) R ₄ is OH, halogen, C (O) OR _s1 , OC (O) R _s4 , C (O) R _s2 , nitro, NH ₂ , cyano, SO ₃ M _y , OSO ₃ M _y , NR ₂₀ SO ₃ M _y, C _1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _{2 -11} hetero cycloalkenyl, C _6-10 aryl, C _6-10 aryloxy, C _5-9 heteroaryl, C _5-9 heteroaryloxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 aralkenyl, C _7-10 heteroalkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamido, carbamate, sulfone hydrazide , carbalkoxy hydrazide, carbonyl hydroxamic acid and amino acid substituted or unsubstituted by one or more substituents selected from the group consisting of carbonyl amide, C _1-12 alkyl, C _3-12 cycloalkyl or C _7-11 and aralkyl, where R _s1 is hydrogen, M _y, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl Kiel, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 aralkyl and heteroaryl, R _s4 is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 heteroaralkyl , R _s2 and R ₂₀ are selected from the group consisting of hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 hetero Cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, The substituted alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, The term &quot; alkenyl &quot; Mentioned it substituted or unsubstituted by one, and the one of the substituent, y is 1 and M is either a monovalent metal, y is ½ and M is a divalent metal compound. 44. The method of claim 43, (i) R ₄ is C ₆ H ₁₁ , C ₆ H ₁₁ -CH ₂ , C ₆ H ₁₁ -CH ₂ CH ₂ -, C ₆ H ₅ -CH ₂ -, C ₆ H ₅ -CH ₂ CH ₂ - or C ₆ H ₅ -CH = CH-CH ₂ -; or (ii) R ₄ is C ₆ H ₁₁ , C ₆ H ₁₁ -CH ₂ -, C ₆ H ₁₁ -CH ₂ CH ₂ -, C ₆ H ₅ -CH ₂ -, C ₆ H ₅ -CH ₂ CH ₂ - _{, -CH 2 -NR 19 SO 2 R} 18, -CH 2 -NR 19 C (O) R 40, CH 2 NHC (O) NHR 18, -CH 2 NHR 21 or _{CH 2 N (R 21) 2} ( where in, R ₁₈ is -C ₆ H _5, 1 to 3 is methyl or methoxy, or -NO ₂ or F or C _1-4 -alkyl substituted by phenyl, or F is replaced by Cl, R ₄₀ is 1 and to 3 methyl or methoxy or -NO _2, or F, or phenyl which is unsubstituted or substituted by Cl, R ₁₉ is H, C _1-6 alkyl, phenyl - (CH _{2) z} - (wherein, z is 1-3 Im) phenyl _{-CH = CH-CH 2 -,} -CH 2 -CH ( and CH _{3) 2} or benzyl, R ₂₁ is _{-CH 2 -CR 22 R 23 R 24} ( wherein, R ₂₂ and R ₂₃ is methyl, ethyl or phenyl and R ₂₄ is H, ethyl or methyl; or (iii) R ₄ is NH _2, cyclohexyl, C _{6-10 aryl, R 8 C (O) N} (R 9) -, R 8 S (O) 2 N (R 9) -, NR 9 C (O ) NHR _8, and _{R 8, C 6 H 11,} CH 2 -C 6 H 5, (CH 2) 2 -C 6 substituted or unsubstituted by one or more substituents selected from the _{'R 9'} the group consisting of N- H _5, methyl, ethyl or isopropyl, where _{R 8, R 9, R 8} ' and R _9' is alkyl, hydrogen, C _1-12, each independently, C _3-12 cycloalkyl, C _6-10 aryl or a C _7-11 aralkyl, all of which are OH, halogen, C (O) OM _y, nitro, cyano, SO ₃ M _{y, y} OSO ₃ M, NR ₂₀ SO ₃ M _y, C _1-12 alkyl, C _1-12 alkoxy, and unsubstituted or substituted by one or more substituents selected from the group consisting of C _6-10 aryl, where R ₂₀ is hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _{3- 12} cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heteroaryl cycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 Heteroaralkyl, C _8-11 aralkenyl or C _7-10 heteroalkenyl, y is 1 and M is a monovalent metal, y is ½ and M is a divalent metal. 43. The method of claim 42, wherein, R ₄ is _{C 6 H 11, CH (CH} 3) 2, CH 2 - phenyl, (CH _{2) 2} - phenyl, CH ₂ NHC (O) - phenyl, CH ₂ NHC (O) ( CH _{2) 3} - _{phenyl, CH 2 NHC (O) (} CH 2) 3 OH, CH 2 NHC (O) CF 3, CH 2 NHC (O) C 6 H 11, CH 2 NHC (O) C 11 H 23 _{, CH 2 NHC (O) CH} (C 6 H 5) 2, CH 2 HNC (O) NHC 6 H 5, CH 2 NHC (O) C 2 H 4 CO 2 Na, CH 2 NHC (O) C 6 [ _{(1,3,4,5) OH] 4 H 7} , CH 2 NHC (O) C 6 H 4 -p-SO 3 Na, CH 2 NHC (O) C 6 H 4 Cl, CH 2 NHC (O) _{C 6 H 4 NO 2, CH} 2 NHC (O) C 6 H 4 OCH 3, CH 2 NHC (O) C 6 H 4 (3,4) Cl 2, CH 2 NHC (O) C 6 H 4 CH 3 _{, CH 2 NHC (O) C} 6 H 4 C 6 H 5, CH 2 NHC (O) C 6 H 4 CN, CH 2 NHC (O) C 10 H 7, CH 2 NHC (O) C 6 H 4 COONa _{, CH 2 NHC (O) (} CHOH) 2 COONa, CH 2 N (CH 2 CH = CH- phenyl) [C (O) - _{phenyl], CH 2 N [CH 2} CH (CH 3) 2] [C ( O) - _{phenyl], CH 2 N [C (} O) C 6 H 5] CH 2 C 6 H 5, CH 2 N [C (O) C 6 H 5] (CH 2) 3 C 6 H 5, CH _{2 C 6 H 11, (CH} 2) 2 C 6 H 11, CH 2 NH 2, CH 2 NHCH 2 CH = CH- phenyl, CH ₂ NHCH ₂ - _{phenyl, CH 2 NHCH 2 CH (CH} 3) 2, CH ₂ N (CH ₂ -phenyl) ₂ , CH ₂ N [CH ₂ CH (CH ₃ ) ₂ ] ₂ , CH ₂ NHSO ₂ -p-nitrophenyl, CH ₂ NHSO ₂ -p- _{tolyl, CH 2 NHSO 2 CF 3,} CH 2 NHC (O) NHC 6 H 5 , or CH ₂ N [SO ₂ -p- _{nitrophenyl] [CH 2 CH (CH 3} ) 2] 2 in compound. A process for the preparation of a compound of formula I according to claim 1, which comprises etherifying the 3-OH group of a compound of formula V: (V) &Lt; Formula (VI) R ₁ -R ₁₃ In this formula, R ₁ , R ₂ and X have the meanings given in claim 1, R ₁₂ is a protecting group, R _{12 '} and R _{12 "} are each independently hydrogen or a protecting group, R ₁₃ is a leaving group. 9. A process for the preparation of a compound of formula I according to claim 1, which comprises glycosidating a protected fucosehydroxy ether of formula (VII) with protected galactose of formula (VIII) and then removing the protecting group from the resulting compound. (VII) &Lt; Formula (VIII) In this formula, R is a leaving group; R ₁ , R ₂ and X have the meanings given in claim 1; R &lt; ₁₂ &gt; is a protecting group in formula VII, and in formula VIII has the meaning indicated in claim 1; Z is O or S. A compound of formula V: (V) In this formula, X is a residue of a non-glycosidic aliphatic 1,2-diol; R ₂ is hydrogen, aryl C _1-12 alkyl, or C _6, where the substituents alkyl and aryl are OH, _{halogen, C (O) OR s1,} OC (O) R s4, C (O) R s2, nitro, NH _{2, cyano, SO 3 M y, OSO 3} M y, NR 20 SO 3 M y, C 1-12 alkyl, C _2-12 alkenyl, C _1-12 alkoxy, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, _C2-11 heterocycloalkyl, _C2-11 heterocycloalkenyl, _C6-10aryl , _C6-10aryloxy , _C5-9 heteroaryl, _C5-9 heteroaryl C _1-6 alkoxy, C _7-11 aralkyl, C _7-11 aralkyloxy, C _6-10 heteroaralkyl, C _8-11 aralkenyl, C _7-10 heteroalkenyl, primary amino, secondary amino, Substituted or unsubstituted with at least one substituent selected from the group consisting of a sulfonyl group, a sulfonamide group, a carbamido group, a carbamate group, a sulfone hydrazide group, a carbhydrazide group, a carbohydroxamic acid group and an aminocarbonylamide group, Wherein R _s1 is hydrogen, M _y , C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or a C _6-10 heteroaralkyl, R _s4 is hydrogen, C ₁ C ₁₂ alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _2-11 heterocycloalkyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl or C _6-10 R ₂ and R ₂₀ are _{independently selected} from the group consisting of hydrogen, C _1-12 alkyl, C _2-12 alkenyl, C _3-12 cycloalkyl, C _3-12 cycloalkenyl, C _2-11 heterocycloalkyl, C _2-11 heterocycloalkenyl, C _6-10 aryl, C _5-9 heteroaryl, C _7-11 aralkyl, C _6-10 heteroaralkyl, C _8-11 alkenyl or C _7-10 heteroaryl Alkenyl, wherein said substituent is selected from the group consisting of alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaryl Alkyl, alkenyl, and heteroaralkyl Nyl is substituted or unsubstituted by one of the substituents mentioned above, y is 1 and M is a monovalent metal, or y is ½ and M is a divalent metal, R ₁₂ is a protecting group, and each of R _{12 '} and R _{12 "} is independently hydrogen or a protecting group. Initially, the pseudo-trisaccharide building block was suitably protected against the glycosidic bond of activated and protected galactose, or the galactose-OX-OH building block to the fucose-OX-OH building block, 48. A process for the preparation of a compound of formula V according to claim 48 comprising, after synthesis by glycosidic bonds, introducing group R &lt; ₁ &gt; into a pseudo-trisaccharide and modifying the resulting compound in a desired manner. The compound according to claim 1 for use in a method of treating a disorder in a warm-blooded animal, including a human. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 alone or in combination with other active substances, pharmaceutical carriers and, where appropriate, excipients.