EA001356B1 - Diglycosylated 1,2-diols as mimetics of sialyl-lewis x and sialyl-lewis a - Google Patents

Abstract

1. A compound of the formula I in which: X is the residue of a non-glycosidic aliphatic 1,2-diol; R1 is a group of the formula III R2 is hydrogen, C1-C12alkyl or C6 aryl; R3 is hydrogen or My; R4 is R3 is C1-C12alkyl, C2-C12alkenyl, C1-C12alkoxy, C3-C12cycloalkyl, C3-C12cycloalkenyl, C2-C11heterocycloalkyl, C2-C11heterocycloalkenyl, C6-C10aryl, C6-C10aryloxy, C5-C9heteroaryl, C5-C9heteroaryloxy, C7-C1aralkyl, C7-C11aralkyloxy, C6-C10heteroaralkyl, C8-C11aralkenyl, C7-C10heteroaralkenyl, which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C(O)ORs1, OC(O)R34, C(O)Rs2, nitro, NH2, cyano, SO3My, OSO3My, NR20SO3My, C1-C12alkyl, C2-C12alkenyl, C1-C12alkoxy, C3-C12cycloalkyl, C3-C12cycloalkenyl, C2-C11heterocycloalkyl, C2-C11heterocycloalkenyl, C6-C10aryl, C6-C10aryloxy, C5-C9heteroaryl, C5-C9heteroaryloxy, C7-C11aralkyl, C7-C11aralkyloxy, C6-C10heteroaralkyl, C8-C11aralkenyl, C7-C10heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide; where R31 is hydrogen, My, C1-C12alkyl, C2-C12alkenyl, C3-C12cycloalkyl, C2-C11heterocycloalkyl, C6-C10aryl, C5-C9heteroaryl, C7-C11aralkyl or C6-C10heteroaralkyl; Rs4 is hydrogen, C1-C12alkyl, C2-C12alkenyl, C3-C12cycloalkyl, C2-C11heterocycloalkyl, C6-C10aryl, C5-C9heteroaryl, C7-C11aralkyl or C6-C10heteroaralkyl, and Rs2 and R20 are hydrogen, C1-C12alkyl, C2-C12alkenyl, C3-C12cycloalkyl, C3-C12cycloalkenyl, C2-C11heterocycloalkyl, C2-C11-heterocycloalkenyl, C6-C10aryl, C5-C9heteroaryl, C7-C11aralkyl, C6-C10heteroaralkyl, C8-C11-aralkenyl or C7-C10heteroaralkenyl; y is 1 and M is a monovalent metal or y is 1/2 and M is a divalent metal; wherein and alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, aralkenyl and heteroaralkenyl in turn are unsubstituted or substituted by one of the abovementioned substituents selected from the group consisting of OH, halogen, C(O)ORs1, OC(O)R34, C(O)Rs2, nitro, NH2, cyano, SO3My, OSO3My, NR20SO3My, C1-C12alkyl, C2-C12alkenyl, C1-C12alkoxy, C3-C12cycloalkyl, C3-C12cycloalkenyl, C2-C11heterocycloalkyl, C2-C11heterocycloalkenyl, C6-C10aryl, C6-C10aryloxy, C5-C9heteroaryl, C5-C9heteroaryloxy, C7-C11aralkyl, C7-C11aralkyloxy, C6-C10heteroaralkyl, C8-C11aralkenyl, C7-C10heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide, including its physiologically tolerated salts of said compound. 2. A compound according to claim 1, wherein X is a linear or branched C2-C20-alkylene, -alkenylene, C3-C12-cycloalkylene, -cycloalkenylene, C3-C11-heterocycloalkylene or -heterocycloalkenylene with hetero atoms selected from the group of -O-, -S- and -N-. 3. A compound as claimed in claim 1, wherein X is the residue of a 1,2-diol corresponding to formula II: in which R5 and R6 are, independently of one another, hydrogen, C1-C12alkyI, C3-C12cycloalkyl, C2-C11heterocycloalkyl, C6-C10aryl, C5-C9heteroaryl, C7-C11aralkyl or C6-C10heteroaralkyl; or R5 and R6 are, together with the -CH-CH- group, C3-C12cycloalkylene, C3-C12-cycloalkenylene, C2-C11heterocycloalkylene and C3-C11heterocycloalkenylene with heteroatoms selected from the group -O-, -S- and -N-; where alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkylene, cycloalkenylene, heterocycloalkylene and heterocycloalkenylene are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C(O)OR31, OC(O)Rs4, C(O)Rs2, nitro, NH2, cyano, SO3My, OSO3My, NR20SO3My, C1-C12alkyl, C2-C12alkenyl, C1-C12alkoxy, C3-C12cycloalkyl, C3-C12cycloalkenyl, C2-C11heterocycloalkyl, C2-C11heterocycloalkenyl, C6-C10aryl, C6-C10aryloxy, C5-C9heteroaryl, C5-C9heteroaryloxy, C7-C11aralkyl, C7-C11aralkyloxy, C6-C10heteroaralkyl, C8-C11aralkenyl, C7 C10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide, where Rs1 is hydrogen, My, C1-C12alkyl, C2-C12alkenyl, C3-C12cycloalkyl, C2-C11heterocycloalkyl, C6-C10aryl, C5-C9heteroaryl, C7-C11aralkyl or C6-C10heteroaralkyl, Rs4 is hydrogen, C1-C12alkyl, C2-C12alkenyl, C3-C12cycloalkyl, C2-C11heterocycloalkyl, C6-C10aryl, C5-C9heteroaryl, C7-C11araIkyl or C6-C10heteroaralkyl, and Rs2 and R20 are hydrogen, Ci-C12alkyl, C2-C12alkenyl, C3-C12cycloalkyl, C3-C12cycloalkenyl, C2-C11heterocycloalkyl, C2-C11heterocycloalkenyl, C6-C10aryl, C5-C9heteroaryl, C7-C11aralkyl, C6-C10heteroaralkyl, C8-C11aralkenyl or C7-C10heteroaralkenyl, and alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, aralkenyl and heteroaralkenyl in turn are unsubstituted or substituted by one of the abovementioned substituents; and y is 1 and M is a monovalent metal or y is 1/2 and M is a divalent metal. 4. A compound according to claim 3, wherein R5 and R6 (a) are unsubstituted or substituted by C1-C12alkyl or C1-C12alkoxy; (b) are, together with the group -CH-CH-, a 5- to 8-membered carbocycle; (c) are, together with the group -CH-CH-, a 5- to 8-membered heterocarbocycle; (d) are, independently of one another, hydrogen, unsubstituted C1-C12alkyl or C1-C12alkyl which is substituted by a substituent selected from the group consisting of -C(O)ORs1, -OC(O)Rs4, -C(O)ONa or -C(O)OK, primary amino, secondary amino, C3-C12cycloalkyl, C,-C6alkoxy, phenyloxy and benzyloxy; unsubstituted C3-C12cycloalkyl or C3-C12cycloalkyl which is substituted by a substituent selected from the group consisting of -C(O)ORs1, -OC(O)Rs4, -C(O)ONa or -C(O)OK, primary amino, secondary amino, C1-C6alkyl, C1-C6alk- oxy, phenyloxy and benzyloxy; C6-C10aryl which is unsubstituted or substituted by -C(O)ORs1, -OC(O)Rs4, -C(O)ONa or -C(O)OK, primary amino, secondary amino, C1-C6alkyl or C1-C6alkoxy; C3-C9heteroaryl with 1 or 2 hetero atoms selected from the group consisting of oxygen and nitrogen atoms; or C7-C12aralkyl which is unsubstituted or substituted by -C(O)ORs1, -OC(O)Rs4, -C(O)ONa or -C(O)OK, primary amino, secondary amino, C1-C6alkyl or C1-C6alkoxy; (e) are, together with the group -CH-CH-, a 5- to 12-membered carbocycle or 5- or 6-membered heterocarbocycle with a hetero atom selected from the group consisting of oxygen and nitrogen atoms; or (f) are, together with the -CH-CH- group, C3-C12cycloalkylene, C4-C12cycloalkenylene, C2-C11heterocycloalkylene or C3-C11heterocycloalkenylene with hetero atoms selected from the group of -O-, -S- and -N-; where cycloalkylene, cycloalkenylene, heterocycloalkylene and heterocycloalkenylene are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C(O)ORs1, OC(O)Rs4, C(O)Rs2, nitro, NH2, cyano, SO3My, OSO3My, NR20SO3My, C1-C12alkyl, C2-C12alkenyl, C1-C12alkoxy, C3-C12cycloalkyl, C3-C12cycloalkenyl, C2-C11heterocycloalkyl, C2-C11heterocycloalkenyl, C6-C10aryl, C6-C10aryloxy, C5-C9heteroaryl, C5-C9heteroaryloxy, C7-C11aralkyl, C7-C11aralkyloxy, C6-C10heteroaralkyl, C8-C11aralkenyl, C7 C10heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide, where Rs1 is hydrogen, My, C1-C12alkyl, C2-C12alkenyl, C3-C12cycloalkyl, C2-C11heterocycloalkyl, C6-C10aryl, C5-C9heteroaryl, C7-C11aralkyl or C6-C10heteroaralkyl, Rs4 is hydrogen, C1-C12alkyl, C2-C12alkenyl, C3-C13cycloalkyl, C2-C11heterocycloalkyl, C6-C10aryl, C5-C9heteroaryl, C7-C11aralkyl or C6-C10heteroaralkyl, and Rs2 and R20 are hydrogen, C1-C12alkyl, C2-C12alkenyl, C3-C12cycloalkyl, C3-C12cycloalkenyl, C2-C11heterocycloalkyl, C2-C11-heterocycloalkenyl, C6-C10aryl, C5-C9heteroaryl, C7-C11aralkyl, C6-C10heteroaralkyl, C8-C11-aralkenyl or C7-C10heteroaralkenyl, and alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkyloxy, heteroaralkyl, aralkenyl and heteroaralkenyl in turn are unsubstituted or substituted by one of the abovementioned substituents; and y is 1 and M is a monovalent metal or y is 1/2 and M is a divalent metal. 5. A compound according to claim 4, wherein R5 and R6 are, together with the -CH-CHgroup, C3-C12cycloalkylene or C2-C11heterocycloalkylene with nitrogen as hetero atom; where cycloalkylene and heterocycloalkylene are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, C(O)ORs1, OC(O)Rs4, C(O)Rs2, NR8R9, C1-C12alkyl, R8C(O)(NH)p N(R9)-, -C(O)(NH)pNR8R9, R8S(O)2(NH)pN(R9)-; R8R40NC(O)(NH)pN(R9)-, R8OC(O)(NH)pN(R9)-, -OC(O)(NH)pNR8R9, and R10-SO2-, in which R8, R9, R10 and R40 are, independently of one another, hydrogen, OH, C1-C12alkyl, C1-C12alkenyl, C3-C12cycloalkyl, C3-C12cycloalkenyl, C2-C11heterocycloalkyl, C2-C11heterocycloalkenyl, C6-C10aryl, C5-C9heteroaryl, C7-C16aralkyl, C8-C16aralkenyl with C2-C6alkenylene and C6-C10aryl, C6-C15heteroaralkyl, C6-C15heteroaralkenyl, or di-C6-C10aryl-C1-C6-alkyl, which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C(O)ORs1, OC(O)Rs4, C(O)Rs2, nitro, NH2, cyano, SO3My, OSO3My, NR20SO3My, C1-C12alkyl, C2-C12alkenyl, C1-C12alkoxy, C3-C12cycloalkyl, C3-C12cycloalkenyl, C2-C11heterocycloalkyl, C2-C11heterocycloalkenyl, C6-C10aryl, C6-C10aryloxy, C5-C9heteroaryl, C5-C9heteroaryloxy, C7-C11aralkyl, C7-C11aralkyloxy, C6-C10heteroaralkyl, C8-C11aralkenyl, C7-C10heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide; Rs1 is hydrogen, My

Description

The present invention relates to the pseudo-compounds of sialyl-LEMA X and sialyl-Bemtk A, in which the natural tetrasaccharide, the neuraminic acid residue, is replaced by methyl in the 8-configuration, substituted by one carboxyl residue and one other substituent, and the Ν-acetylglucosamine residue is replaced by a non-glycoside residue 1, 2-diol; to methods for producing these compounds; and the use of these pseudo-compounds in therapeutic methods.

A complex inflammatory process, which has several stages, is a natural reaction of the body to damage, which, for example, is also the defeat of infectious agents. Under the action of cytokines, the endothelium, which lines the blood vessels, expresses adhesive proteins on its surface. The selectins P and E, through the protein-carbohydrate interaction with glycolipids and glycoproteins on the leukocyte membrane, induce the so-called effect of rolling leukocytes. These leukocytes are slowed down in this process, and some proteins (integrins) are activated on their surface, which provide strong adhesion of leukocytes to the endothelium. After this, white blood cells migrate to the damaged tissue.

If the described process occurs in a controlled manner, then after a certain period of time this tissue damage is repaired without any significant adverse effects. Otherwise, that is, in the case of some acute and chronic inflammatory processes in which leukocyte migration occurs in an unregulated manner, these processes lead to serious illnesses of the body. Such cases include cardiogenic shock, myocardial infarction, thrombosis, rheumatism, psoriasis, dermatitis, acute respiratory distress syndrome and cancer with metastases | 1Eaksh.1p1a E., Kao Β.Ν.Ν., Εχρ. Θρίη. Aegis 3: 709-724 (1994)].

Several studies have already been conducted to develop drugs that could in some cases prevent the development of these undesirable processes [Pa8dir1a E., Kao Β.Ν.Ν., Εχρ. Θρίη. Aegis 3: 709-724 (1994)]. One way to prevent the interaction between P- and Eslectin and their receptors on the leukocyte membrane is to prevent the rolling effect by simulating the corresponding epitopes. It also suppresses subsequent processes. One of the smallest carbohydrate epitopes serving as a ligand for E-selectin is the sialyl-Be \\ t5 X [neuraminic acid-a (2-> 3) -galactose β (1 -> 4) - (fucose-a (1- > 3) -№atsetilglyukozamin (8e ^x)].

EP-A-0579196, as compounds competing with natural ligands for binding to E-selectin, mimetic compounds are proposed (keb ^x ) in which the neuraminic acid residue is replaced by a lactic acid residue. XVO 93/10796 describes compounds which, instead of the neuraminic acid residue, contain an α-hydroxy acid residue. In νθ 93/23031, pseudo compounds are described in which the Ν-acetylglucosamine residue (ΟΙοΝΑο residue) is replaced by P.P-1.2cyclohexanedioxy. However, all these compounds are united by the fact that the affinity of binding between them and E-selectin only very slightly exceeds the affinity of binding of natural (8Le ^x ), and sometimes even lower than the affinity of natural compounds, and is insufficient to achieve a therapeutic effect.

Surprisingly, it was found that the simultaneous substitution of the neuraminic acid residue with 8-configured methyl, substituted with one carboxyl residue and one other substituent, and the β-acetylglucosamine residue with a non-glycoside residue of an aliphatic diol leads to an extremely high binding affinity of the obtained compound. In addition, these new compounds are chemically and structurally simpler, have a lower molecular weight and can be obtained in large quantities and simpler methods of chemical synthesis.

The present invention relates to compounds of formula I

wherein

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

Kg represents a group of formula III

K ₂ represents hydrogen, C 1 -C ₂ alkyl or C ₆ aryl;

Of represents hydrogen or M _y ;

K ₄ represents C1-C _{£ 2} alkyl, C ₂ -C _{£ 2} alkenyl, C ₃ -C _{1 2} cycloalkyl, C ₃ -C _{£ 2} cycloalkenyl, C ₂ Cc heterocycloalkyl, C ₂ -Cc heterocycloalkenyl, C ₆ -C _{£ 0} aryl, C ₅ -C ₉ heteroaryl, C ₇ -Caralkyl, C ₆ -C _{£ 0} heteroaralkyl, C ₈ -Caralkenyl or C7-C10 heteroaralkenyl, which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OK _k1 , OS (O) K _k4 , C (O) K _k2 , nitro, ΝΗ ₂ , cyano, 8О ₃ М _у , О8О ₃ М _у , МК. ₂₀ 8О ₃ М _у , С1-С _{£ 2} alkyl, С ₂ -С12 alkenyl, С1-С1 ₂ alkoxy, С ₃ -С ₁₂ cycloalkyl, С ₃ -С ₁₂ cycloalkenyl, С ₂ -С ₁₁ heterocycloalkyl, С ₂ -С ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₆ -C ₁₀ aryloxy, C ₅ -C ₉ heteroaryl, C ₅ -C ₉ heteroaryloxy, C ₇ -C ₁₁ aralkyl, C ₇ -C ₁₁ aralkyloxy, C ₆ C ₁₀ heteroaryl , C ₈ -C ₁₁ aralkenyl, C ₇ -C ₁₀ heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide;

K ₈₁ represents hydrogen, M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7C ₁₁ aralkyl or C ₆ -C ₁₀ heteroaralkyl;

Cd represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl or C ₆ -C ₁₀ heteroalkyl;

K ₂ and Y ₂₀ represent hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl, C ₇ -C ₁₁ aralkyl, C ₆ -C ₁₀ heteroaralkyl, C ₈ C11 aralkenyl or C7-C10 heteroaralkenyl;

y is 1 and M is a monovalent metal or y is 1/2 and M is a divalent metal;

moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl or heteroalkenyl, in turn, are unsubstituted, substituted or more substituted or substituted consisting of OH, halogen, C (O) OK. ₈₁ , OS (O) K ₄ , C (O) K ₂ , nitro, ΝΗ ₂ , cyano, 8О ₃ М _у , О8О ₃ М _y , КГгоЗОзМу, С ₁ -С ₁₂ alkyl, С ₂ -С ₁₂ alkenyl, С1 -S12alkoksi, C3-C12cycloalkyl, C3-C12 cycloalkenyl, C2-S11geterotsikloalkil, C2-C11 heterocycloalkenyl, C6-C10-aryl, C6-S10ariloksi, S9geteroaril-C5, C5-S9geteroariloksi, S7S11aralkil, S11aralkiloksi C7, C6-S10geteroaralkil, C ₈ - C ₁₁ aralkenyl, C ₇ -C ₁₀ heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide, including physiologically acceptable salts, indicated connection.

Compounds are preferred where X is a linear or branched C ₂ -C ₂₀ alkylene, alkenylene, C3-C12 cycloalkylene, cycloalkenylene, C ₃ -C ₁₁ heterocycloalkylene or heterocycloalkenyl with heteroatoms selected from the group consisting of -O-, -8- and -Ν-.

In the compounds of formula I, where X preferably represents the remainder of the 1,2-diol having the formula

wherein

K and K. ₆ independently represent hydrogen, C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C _p heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ - C ₁₁ aralkyl or C ₆ -C ₁₀ heteroalkyl; either J ₅ and K. ₆ . taken together with the group —CH — CH— represent C ₃ -C ₁₂ cycloalkylene, C ₃ -C ₁₂ cycloalkenylene, C ₂ -C ₁₁ heterocycloalkylene and C ₃ -C ₁₁ heterocycloalkenylene with heteroatoms selected from the group consisting of —O—, -8- and -Ν-; where alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkylene, cycloalkenylene, heterocycloalkylene and heterocycloalkenylene are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OK ₄ , C (O) K ₂ , nitro, ΝΗ ₂ , cyano, 8О ₃ М _у , О8О ₃ М _у , NΚ ₂₀ 8О ₃ М _у , С ₁ -С ₁₂ alkyl, С ₂ -С ₁₂ alkenyl, С ₁ - C ₁₂ alkoxy, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C2-S11geterotsikloalkil, C2-C11 heterocycloalkenyl, C6-C10-aryl, C6-S10ariloksi, S9geteroaril-C5, C5-S9geteroariloksi, S7S11a alkyl, C7-S11aralkiloksi, C6-S10geteroaralkil, C ₈ -C ₁₁ aralkenyl, C ₇ -C ₁₀ heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfongidrazid, carbohydrazide, carbohydroxamic acid and aminokarbonilamid where Κ, , ι represents hydrogen, M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocyclo alkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C ₆ -C ₁₀ heteroaralkyl; Κ · ι represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroalkyl; K ₂ and Y ₂₀ represent hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl, C6-C10 heteroaralkyl, C ₈ -C ₁₁ aralkenyl or C ₇ -C ₁₀ heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl or heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1; and M is a monovalent metal; or y = 1/2, and M denotes a divalent metal. Compounds are preferred, wherein K. ₅ and Ye (a) are unsubstituted or substituted with C ₁ -C ₁₂ alkyl or C ₁ -C ₁₂ alkoxy;

(b) together with the group —CH — CH— represent a 5-8 membered carbocycle;

(c) together with the group —CH — CH represent a 5–8 membered heterocarbocycle;

(d) independently, hydrogen, unsubstituted C-C ₁₂ alkyl or C ₁ -C ₁₂ alkyl, which is substituted with a substituent selected from the group consisting of -C (O) OK ₈₁ . -OS (O) k, ₄ . -C (O) OYa or C (O) OK, primary amino, secondary amino, Cs-C ₁₂ cycloalkyl, C ₁ to C ₆ alkoxy, phenyloxy and benzyloxy; unsubstituted C ₃ -C ₁₂ cycloalkyl or C ₃ -C ₁₂ cycloalkyl, which is substituted with a substituent selected from the group consisting of -C (O) OK ₈₁ . -OC (O) K ₈ 4, -C (O) OAa or C (O) OK, primary amino, secondary amino, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, phenyloxy and benzyloxy; C ₆ -C ₁₀ aryl, which is unsubstituted or substituted with -C (O) OK ₈₁ . —OC (O) K ₄ , —C (O) OAa or C (O) OK, primary amino, secondary amino, C ₁ -C ₆ alkyl, or C ₁ C ₆ alkoxy; C ₃ -C ₉ heteroaryl with 1 or 2 heteroatoms selected from the group consisting of oxygen and nitrogen atoms; or C ₇ -C ₁₂ aralkyl, which is unsubstituted or substituted with -C (O) OK ₈₁ . —OC (O) K ₄ , —C (O) OAa or C (O) OK, primary amino, secondary amino, C1-C6 alkyl, or C1C6 alkoxy;

(e) together with the group —CH — CH— represent a 5-12 carbocycle or a 5- or 6-membered heterocarbocycle with a heteroatom selected from the group consisting of oxygen and nitrogen atoms; or (e) together with the group —CH — CH— represent C ₃ -C ₁₂ cycloalkylene, C ₄ -C ₁₂ cycloalkenylene, C ₂ -C ₁₁ heterocycloalkylene or C ₃ -C ₁₁ heterocycloalkenylene with heteroatoms selected from the group consisting of —O -, -8- and -Ν-;

where cycloalkylene, cycloalkenylene, heterocycloalkylene and heterocycloalkenylene are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OK ₈₁ . OS (O) K ₄ , C (O) K ₂ , nitro, ΝΗ ₂ , cyano, 8О ₃ М _у , О8О ₃ М _у , МК ₂₀ 8О ₃ М _у . C ₁ -C ₁₂ alkyl, C ₂ C ₁₂ alkenyl, C ₁ -C ₁₂ alkoxy, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₆ -C ₁₀ aryloxy, C ₅ -C ₉ heteroaryl, C ₅ -C ₉ heteroaryloxy, C ₇ -C ₁₁ aralkyl, C ₇ -C ₁₁ aralkyloxy, C ₆ C10 heteroaralkyl, C8-C11 aralkenyl, C7-C10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carb carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide, where Κ ,, ι represents hydrogen, M _y . C ₁ -C ₁₂ alkyl, C2-C12 alkenyl, C3-C12 cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroaralkyl;

K ,, ₄ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C ₆ - C ₁₀ heteroaralkyl; and K ₂ and K ₂₀ represent hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl Calkyl, C10 C8-C11 aralkenyl or C7-C10 heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl or heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1, and M denotes a monovalent metal; or y = 1/2. and M is a divalent metal.

Preferred are compounds wherein K. ₅ and K ₆ taken together with the —CH — CH— group are C ₃ -C ₁₂ cycloalkylene or C ₂ -C ₁₁ heterocycloalkylene, where the heteroatom is a nitrogen atom, where K ₅ and K ₆ , taken together with the group —CH — CH— represent C ₃ -C ₁₂ cycloalkylene or C ₂ -C ₁₁ heterocycloalkylene, where the heteroatom is a nitrogen atom, said cycloalkylene and heterocycloalkylene being unsubstituted or substituted by one or more substituents selected from the group consisting of OH, C (O) OK ₈₁ , OS (O) k, ₄ . C (O) K2, ΝΚ8Κ9, C1-C12alkyl, VDO) ^^^) -. -C (O) ^) _p Mk8K_9. K88 (O) 2 ^^ (K9) -.

K8K ^ C (O) - ^) _P ^ K9) -. K8OC (O) ^^ (K9) -. -OS (O) ^ H) _| CK.8K.9 ₁ . and K.10-8O2-, where K ^. K9. Kyu and K ₄₀ independently represent hydrogen, OH, C ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C2- C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C16 aralkyl, C8-C16 aralkenyl with C2-C6 alkenylene and C6-C10 aryl, C6-C15 heteroaralkyl, C6-C15 heteroalkenyl-C 1 -l, or are unsubstituted or substituted by one or more substituents selected from the group. including OH, halogen, C (O) OK ₈₁ . OS (O) K ₈₄ . C (O) K, ₇ · nitro, ΝΗ ₂ , cyano, 8О ₃ М _у . O8O ₃ M _at . MK. ₂₀ 8O ₃ M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₁ -C ₁₂ alkoxy, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C6-C10 aryloxy, C5-C9 heteroaryl, C5-C9 heteroaryloxy, C7C11 aralkyl, C6-C10 heteroaralkyl, C8-C11 aralkenyl, amide, C7-C10 heteroaralkenyl-amide, primary carbhydrazide, carbohydroxamic acid and aminocarbonylamide, where K ₈₁ represents hydrogen, M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycle alkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C ₆ -C ₁₀ heteroalkyl; K ,, ₄ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroalkyl; K, ₇ and K ₂₀ represent hydrogen,

C1-C1 ₂ alkyl, C ₂ -C ₂ alkenyl, C ₃ -C ₂ cycloalkyl, C ₃ -C ₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl, C ₆ -C ₁₀ heteroaralkyl, C ₈ -C ₁₁ aralkenyl or C ₇ -C ₁₀ heteroaralkenyl; and the substituents alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroalkyl, aralkenyl and heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1, and M denotes a monovalent metal;

or y = 1/2, and M denotes a divalent metal.

In the above preferred group are compounds where R ₈ and R ₉ independently represent hydrogen, C1C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₆ -C ₁₀ aryl, C ₇ -C ₁₆ aralkyl with 1-6 carbon atoms in the alkylene group, and C ₆ -C ₁₀ aryl, C ₈ -C ₁₆ aralkenyl with C ₂ -C ₆ alkenylene and C6-C10 aryl, or di-C6-C10 aryl-C1-C6 alkyl, where K ₈ and K ₉ are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, COOH, C (O) OM _Y , C ₁ -C ₁₂ alkyl, C ₁ -C ₆ alkoxy, C ₆ -C ₁₀ aryl, C ₆ -C ₁₀ aryloxy, 8О ₃ М _У , О8О ₃ М _У , MK ₂₀ 8О ₃ М _У , ΝΟ ₂ , ami but primary amino, secondary amino, and C ^ a K ₂₀ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C2-C11 heterocycloalkyl, C2 -C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl, C7C11 aralkyl, C6-C10 heteroaralkyl, C8-C11 aralkenyl or C ₇ -C ₁₀ heteroalkenyl; y = 1, and M denotes a monovalent metal, or y = 1/2, and M denotes a divalent metal.

Compounds are also preferred in this group, where K ₁₀ is C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₆ -C ₁₀ aryl, C ₇ -C ₁₆ aralkyl with 1-6 atoms in the alkylene group, and C6 -C10 aryl, which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, carboxyl, C (O) OMU, C1-C12 alkyl, C1-C6 alkoxy, C6C ₁₀ aryl, 8O ₃ M _U , nitro, amino primary amino, secondary amino and cyano; or C8C16aralkenyl with C2-C6 alkenylene and C6C ₁₀ aryl, or di-C ₆ -C ₁₀ aryl-C ₁ -C ₆ alkyl.

Further preferred are compounds wherein K ₅ and Kb taken together with the —CH — CH— group are C ₃ -C ₁₂ cycloalkylene or C ₂ -C ₁₁ heterocycloalkylene having nitrogen as the heteroatom; and where cycloalkylene and heterocycloalkylene are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, C (O) OK ₈₁ , OC (O) 1A. С (О) К ₂ , ΝΗ ₂ , С1-С12 alkyl, ad-О) ВДЫ9) -, -Ο ^ ΝΚΚ, К «15 (О) yes>) -, К8ОС (О) \ (Н.) - and К10 -8O2- where R9 is hydrogen, and K ₈ is C ₁ -C ₁₂ alkyl, C ₆ -C ₁₀ aryl or C ₇ -C ₁₁ aralkyl which are unsubstituted or substituted by one or more C ₁ -C ₁₂ alkoxy; K ₁₀ represents C1-C12 alkyl, C6-C10 aryl or C7-C11 aralkyl, which are unsubstituted or substituted by one or more C1-C12 alkyls; K ₈₁ and K ,, ₄ represent C ₁ -C ₁₂ alkyl, and Kd represents C ₁ -C ₁₂ cycloalkenyl, C ₃ -C ₁₂ cycloalkyl or C6-C10 aryl, and the substituents alkyl, cycloalkenyl, cycloalkyl and aryl, in turn, can be unsubstituted or substituted by one or more substituents selected from the group consisting of OH, C (O) OK, _G and OC (O) K ₄ ′, where Kg is M _U or C ₁ -C ₁₂ alkyl, and K ₄ ′ represents C ₁ C ₁₂ alkyl; y = 1, and M denotes a monovalent metal, or y = 1/2, and M denotes a divalent metal.

Particularly preferred are compounds wherein K ₅ and K ₆ taken together with the —CH — CH— group are cyclohexylene.

Even more preferred compounds are those wherein K ₅ and K ₆ taken together with the —CH — CH— group are piperidylene.

Compounds are preferred, wherein K and K ₆ taken together with the —CH — CH— group are piperidylene; where the heteroatom is an unsubstituted or substituted substituent selected from the group consisting of C (O) OK, 1, C (O) K, 2, C (O ^ KK, ΝΗ2, 8О3Му, С1С ₁₂ alkyl, С ₂ -С ₁₂ alkenyl, C ₁ -C ₁₂ alkoxy, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₂ heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C6-C10 aryloxy, C5-C9 heteroaryl, C5-C9 heteroaryloxy, C7-C11 aralkyl, C7-C11 aralkyloxy, C6-C10 heteroaralkyl, C8-C11 aralkenyl, C7-C10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, sulfonhydrazide; and where one or more C atoms on the ring are nnym or substituted by one or more substituents selected from the group consisting of OH, OC (O) K _4, ΝΗ ₂ O8O M _{3 y} \ _R; ... 8OA1 C ₁ -C ₁₂ alkoxy, C ₆ -C ₁₀ aryloxy, , C ₅ -C ₉ heteroaryloxy, C ₇ C ₁₁ aralkyloxy, primary amino, secondary amino, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide, where K ₈₁ represents hydrogen, M _U , C ₁ -C ₁₂ alkyl , C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C ₆ -C ₁₀ heteroalkyl; K ₄ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroalkyl; K ₈ and K ₉ independently represent hydrogen, OH, C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C _p heterocycloalkyl, C ₆ -C ₁₀ aryl, C5-C9 heteroaryl, C7-C16 aralkyl, C6-C15 heteroalkyl, C8-C16 aralkenyl with C2-C6 alkenylene and C ₆ -C ₁₀ aryl, or di-C ₆ -C ₁₀ aryl-C ₁ -C ₆ alkyl, or K ₈ and K ₉ taken together represent tetramethylene , pentamethylene, - (CH ₂ ) ₂ -O (CH ₂ ) ₂ -, - (CH ₂ ) ₂ -8- (CH ₂ ) ₂ - or - (CH 2) 2-KE ₇ (CH ₂ ) ₂ -, and K ₇ represents H, C 1 -C ₆ alkyl, C ₇ -C ₁₁ aralkyl, C (O) E ₈₂ , or sulfonyl; K ₈₂ and K ₂₀ represent hydrogen, C ₁ -C ₁₂ alkyl, C ₂ C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C _s -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ C ₁₁ aralkyl, C ₆ -C ₁₀ heteroaralkyl, C ₈ -C ₁₁ aralkenyl or C ₇ -C ₁₀ heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl and heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1, and M denotes a monovalent metal; or y = 1/2, and M denotes a divalent metal.

More preferred are compounds wherein K ₅ and K ₆ taken together with the —CH — CH— group are piperidylene; where the heteroatom is an unsubstituted or substituted substituent selected from the group consisting of C (O) OK ₈₁ , C (O) K ₈₂ , C (O) KK ₈ K ₉ and K ₁₀ -8O ₂ -, and one or more C atoms on the ring are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, ΝΗ ₂ , K ₈ 8 (O) ₂ K (K ₉ ) -, K ₈ C (O) K (K ₉ ) -, and K ₈ OS (O ^ (K ₉ ) -, where K ₉ represents hydrogen and K ₈ represents C ₁ -C ₁₂ alkyl, C ₆ -C ₁₀ aryl or C ₇ -C ₁₁ aralkyl, where alkyl, aryl and aralkyl are unsubstituted or substituted one or more C1-C12 alkoxy; K ₁₀ represents C ₁ -C ₁₂ alkyl, C ₁ -C ₁₀ aryl or C7-C11 aralkyl, which are unsubstituted or substituted by one or more C ₁ -C ₆ alkyls; K ₈₁ represents C ₁ -C ₁₂ alkyl and K ₈₂ represents C ₁ -C ₁₂ alkyl, C ₃ C ₁₂ cycloalkenyl, C ₃ -C ₁₂ cycloalkyl or C ₆ -C ₁₀ aryl; and the substituents alkyl, cycloalkenyl, cycloalkyl and aryl, in turn, are unsubstituted or substituted by one or more substituents selected from the group including OH, C (O) K _8G and OC (O) E ₈₄ ', where K _8G represents M _y or C ₁ -C ₁₂ alkyl, and K ₈ t represents C ₁ -C ₁₂ alkyl; y = 1, and M denotes a monovalent metal, or y = 1/2, and M denotes a divalent metal.

Also particularly preferred are compounds wherein X is cyclohexylene or piperidylene, which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, ΝΗ2, C3H7, —C (O) C ₆ H ₅ , —C (O) (CH ₂ ) ₈ C (O) OCH ₃ ,

-C (O) [CH (OH) LC (O) OG C (O) -C6H8 (OH) s,

-С (О) -С6Н _П , -С (О) OSzN7, -С (О) ЯНС6Н ₅ , -ЯН8 (О) 2СН2С6Н5, -ЯНС (О) OSН2С6Н5,

-YANS (O) С6Нз (ОСНз) 2, -8 (О) 2-С4Н9,

-MNS (O) YANS6N5, -8 (O) 2-С6Н4СНз,

-8 (O) 2CH2C6H ₅ ; and -8 (O) 2- (CH2) CCHH7.

Preferred are compounds where K ₂ is C ₁ -C ₆ alkyl, as well as compounds where E ₁ corresponds to a group of formula III

wherein

K _s represents hydrogen or M _y ; and

K ₄ is C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C _s -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C2-S11geterotsikloalkenil, C6-C10-aryl, C6-S9geteroaril, S11aralkil C7, C6-S10geteroaralkil , C8-C11aralkenyl or C7-C10heteroaralkenyl, which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OK ₈₁ , OC (O) K ₈₄ , C (O) K ₈₂ , nitro , ID _2, cyano, 8o _z M _y M _{y of} O8O, NΚ. ₂₀ 8 O ₃ M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₁ -C ₁₂ alkoxy, Cz-C12 cycloalkyl, Cz-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C ₆ -C ₁₀ aryl , C ₆ -C ₁₀ aryloxy, C ₅ C ₉ heteroaryl, C ₅ -C ₉ heteroaryloxy, C ₇ -C ₁₁ aralkyl, C7-C11 aralkyloxy, C6-C10 heteroaralkyl, C8-C11 arakenyl, C7-C10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfongidrazid, carbohydrazide, carbohydroxamic acid and aminokarbonilamid, where R ₈₁ is hydrogen, M _y, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C _s -C ₁₂ cycloalkyl, C ₂ - C _n het rotsikloalkil, C _{6 to} C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl or C ₆ -C ₁₀ heteroaralkyl; By ₈₄ is hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C _s -C ₁₂ cycloalkyl, C ₂ -C _n heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ - C ₁₁ aralkyl or C ₆ -C ₁₀ heteroalkyl; E ₈₂ and K ₂₀ represent hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C _s -C ₁₂ cycloalkyl, C _s -C ₁₂ cycloalkenyl, C ₂ -C _n heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl; C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl, C ₆ -C ₁₀ heteroaralkyl, C ₈ -C ₁₁ aralkenyl or C7-C10 heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl or heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1; and M is a monovalent metal; or y = 1/2, and M denotes a divalent metal.

In a particularly preferred embodiment, the invention relates to a compound which corresponds to formula 1a

wherein

K ₃ represents hydrogen or M _y ;

Cd represents C _g C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ C ₁₁ heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl, C ₆ -C ₁₀ heteroaralkyl, C ₈ -C ₁₁ aralkenyl or C ₇ -C ₁₀ heteroaralkenyl which are unsubstituted or substituted one or more times;

K ₅ and K ₆ independently represent hydrogen, C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ - C ₁₁ aralkyl or C ₆ -C ₁₀ heteroalkyl; or K ₅ and K ₆ taken together with the group —CH — CH represent C ₃ -C ₁₂ cycloalkylene, C ₄ C ₁₂ cycloalkenylene, C ₂ -C ₁₁ heterocycloalkylene and C ₃ -C ₁₁ heterocycloalkenylene with heteroatoms selected from the group including -O-, -8- and -Ν-; where alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkylene, cycloalkenylene, heterocycloalkylene and geterotsikloalkenilen are unsubstituted or substituted one or more times, wherein the substituent is selected from the group consisting of OH, halogen, C (O) OK _P1, OC (O) K _z4 , C (O) K _z2 , nitro, ΝΗ ₂ , cyano, 8О ₃ М _у , О8О ₃ М _у , NК ₂₀ 8О ₃ М _у , С ₁ -С ₁₂ alkyl, С ₂ -С ₁₂ alkenyl , C ₁ -C ₁₂ alkoxy, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₆ -C ₁₀ aryloxy, C ₅ -C ₉ heteroaryl, C ₅ -C ₉ Goethe oariloksi, C ₇ -C ₁₁ aralkyl, C7-S11aralkiloksi, C6-S10geteroaralkil, C ₈ -C ₁₁ aralkenyl, C ₇ -C ₁₀ heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfongidrazid, carbohydrazide, carbohydroxamic acid and aminocarbonylamide, where K _z1 is hydrogen, M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C ₆ C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl or C ₆ C ₁₀ heteroaralkyl; K _z4 represents hydrogen, C ₁ C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ C ₁₁ heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C7-C11 aralkyl or C6 -C10 heteroaralkyl; K _s2 and R ₂₀ represent hydrogen, C ₁ -C ₁₂ alkyl, C ₂ C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ C ₁₁ aralkyl, C ₆ -C ₁₀ heteroaralkyl, C ₈ -C ₁₁ aralkenyl or C ₇ -C ₁₀ heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl and heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1; and M is a monovalent metal; or y = 1/2, and M denotes a divalent metal.

Preferably the compound of formula 1a, where K ₃ represents H, K or Να;

K ₅ and K ₆ taken together with the —CH — CH— group represent C ₃ -C ₁₂ cycloalkylene, C ₄ -C ₁₂ cycloalkenylene, C ₂ -C ₁₁ heterocycloalkylene and C ₃ -C ₁₁ heterocycloalkylene with heteroatoms selected from the group including -O-, -8- and -Ν-, which are unsubstituted or substituted one or more times;

where the substituent is selected from the group consisting of OH, halogen, C (O) OK _z1 , OS (O) K _z4 , C (O) K _z2 , nitro, ΝΗ ₂ , cyano, 8O ₃ M _y , O8O ₃ M _y , NK ₂₀ 8O ₃ M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₁ -C ₁₂ alkoxy, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₆ -C ₁₀ aryloxy, C ₅ -C ₉ heteroaryl, C ₅ -C ₉ heteroaryloxy, C ₇ -C ₁₁ aralkyl, C7-C11 aralkyloxy, C6-C10 heteroaralkyl, C8- C11aralkenyl, C7-C10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carbohydro xamic acid and aminocarbonylamide, where K _z1 is hydrogen, M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C3-C12 cycloalkyl, C2-C11 heterocycloalkyl, C6C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ - C ₁₁ aralkyl or C ₆ C ₁₀ heteroalkyl; K _z4 represents hydrogen, C ₁ C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ C ₁₁ heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C7-C11 aralkyl or C6 -C10 heteroaralkyl; K _s2 and R ₂₀ represent hydrogen, C ₁ -C ₁₂ alkyl, C2-C12alkenyl, C3-C12cycloalkyl, C3-S12tsikloalkenil, S11geterotsikloalkil-C2, C2-C11 heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C7-C11 aralkyl, C6-C10 heteroaralkyl, C8-C11 aralkenyl or C7-C10 heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl and heteroaralkenyl are, in turn, unsubstituted or substituted; and y = 1; and M is a monovalent metal; or y = 1/2, and M denotes a divalent metal;

(a) K ₄ represents the remainder K ₁₂ - (CH ₂ ) _P or cyclohexyl, where n = 1 or 2, and K ₁₂ represents C ₁ -C ₁₀ alkyl, C ₅ -C ₈ cycloalkyl, C ₆ -C ₁₀ aryl, or C 8 -C 12 aralkenyl, which are unsubstituted or substituted with C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxyl, P, C1, ^ Ν or -ΝΌ ₂ ; or K ₁₂ represents an amino group of ΝΚ ₈ Κ ₉ ', and K ₈ ' and K ₉ 'represent C ₁ -C ₁₂ alkyl, either unsubstituted or C ₁ -C ₄ alkyl substituted C ₅ - or C ₆ cycloalkyl, C ₆ -C ₁₀ aryl, C ₇ C ₁₂ aralkyl or C ₈ -C ₁₂ aralkenyl; or K ₁₂ represents an amide group - ^ K ₉ ) C (O) K ₈ ,

-Ν (Κ ₉ ) 8 (Θ) Κ8, -ΝΚ ₉ € (Ο) ΝΗΚ8 or

-ΝΚ ₉ Ο (Θ) ΝΗΚ ₈ , where K ₈ represents C ₆ -C _{1 0} aryl, which is unsubstituted or substituted by C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, E. C1. -ΟΝ or -ΝΟ ₂ , or C ₁ -C ₁₀ alkyl, which is unsubstituted or substituted by E or C1. and K ₉ represents H, C ₁ -C ₁₀ alkyl, C ₅ - or C ₆ cycloalkyl, C ₅ - or C ₆ cycloalkyl-C ₁ -C ₆ alkyl, phenyl-C ₁ -C ₆ alkyl or phenyl-C ₂ - C ₆ alkenyl; or (b) K ₄ represents C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl or C ₇ -C ₁₁ aralkyl, which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C (O ) OK ₈₁ . OS (O) K ₄ . С (О) К ₂ · nitro, ΝΗ ₂ , cyano, ЗО ₃ М _у . O8O ₃ M _U. ХК ₂₀ 8О ₃ М _у C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C1-C12 alkoxy, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C6-C10 aryloxy, C ₅ -C ₉ , C ₅ -C ₉ heteroaryloxy, C ₇ C ₁₁ aralkyl, C ₇ -C ₁₁ aralkyloxy, C ₆ -C ₁₀ heteroaralkyl, C8-C11 aralkenyl, C7-C10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide, where K. _{? 4} represents hydrogen, M _U. C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C ₆ -C ₁₀ heteroaralkyl; K ,, ₄ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroalkyl; K, ₂ and K ₂₀ represent hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl C7-C11 aralkyl, C6-C10 heteroaralkyl, C8-C11 aralkenyl or C7-C10 heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl and heteroaralkenyl are, in turn, unsubstituted or substituted; and y = 1; and M is a monovalent metal; or y = 1/2, and M denotes a divalent metal.

The most preferred are compounds where (ί) K ₄ represents C ₆ H ₁₁ , C ₆ H ₁₁ -CH ₂ , C6H11-CH2CH2-, C6H5-CH2-, C6H5-CH2CH2- or C6H5-CH = CH-CH2- ;

(i) K ₄ represents C ₆ H ₁₁ , C ₆ H ₁₁ —CH ₂ -, C ₆ H ₁₁ —CH ₂ CH ₂ -, C ₆ H ₅ —CH ₂ -, CeH ₅ —CH ₂ CH ₂ -, - CH ₂ -PC. ₁₉ -8O ₂ TO _18-SI; - \ K -C (O) 1C.

-CH ^ HC (O) PNA ₁₈ , CH; \ HH; · or -CH ^ (K ₂₁ ) ₂ . where K ₁₈ represents —C ₆ H ₅ , phenyl, which is substituted with 1-3 methyl or methoxy groups, or ^ O ₂ or E or C1, or C ₁ -C ₄ alkyl, which is substituted by E; K ₄₀ represents phenyl which is unsubstituted or substituted by 1 to 3 metal or methoxy groups, or ^ O ₂ or E or C1;

K ₁₉ represents H, C ₁ -C ₆ alkyl, phenyl (CH ₂ ) ₂ -, where ζ = 1-3; phenyl-CH = CH-CH ₂ , preferably —CH ₂ —CH (CH ₃ ) ₂ or benzyl; and K ₂₁ represents —CH ₂ —CK ₂₂ K ₂₃ K ₂₄ , where K ₂₂ and K ₂₃ are methyl, ethyl or phenyl, and K ₂₄ is H, ethyl or methyl; or (w) K ₄ represents C ₆ H ₁₁ , CH ₂ —CbH ₅ . (CH ₂ ) ₂ -C ₆ H ₅ methyl, ethyl or isopropyl, which are unsubstituted or substituted by one or more substituents selected from the group consisting of ΝΗ ₂ . cyclohexyl, C ₆ -C ₁₀ aryl, K ₈ C (O) MK ₉ ) -. E ₈ 8 (O) ₂ IU ₉ ) -. -ΝΚ ^^ ΝΗΚ ^ and Κ ₈ Κ ₉ Ν-, where K ₈ . K ₉ . K and K ₉ independently represent hydrogen, C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₆ -C ₁₀ aryl, or C7-C11 aralkyl, which are unsubstituted or substituted by one or more substituents selected from the group including OH, halogen, C (O) OM _U. nitro, cyano, 8О ₃ М _у , О8О ₃ М _у NK ₂₀ 8Ο ₃ M _U , C ₁ C ₁₂ alkyl, C ₁ -C ₁₂ alkoxy and C ₆ -C ₁₀ aryl, where K ₂₀ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ C ₁₁ heterocycloalkyl , C2-C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl, C6-C10 heteroaralkyl, C8-C11 aralkenyl or C ₇ -C ₁₀ heteroaralkenyl, y = 1. and M denotes a monovalent metal, or y = 1/2. and M is a divalent metal.

Another preferred compound of formula 1a is a compound wherein K ₄ is SP ||. CH (CH ₃ ) ₂ , CH ₂ phenyl, (CH ₂ ) ₂ phenyl, CH ₂ HHC (O) phenyl, CH ₂ CNS (O) (CH ₂ ) ₃ phenyl, CΗ ₂ NΗC (Ο) (CH ₂ ) ₃ OH, SPHIS (O) ST _; . CH ₂ MHC (O) C ₆ H _{1 L} CH ₂ ONS (O) C ₁₁ H ₂₃ .

No. ₂ ΝΠ ^ Ο ^ Η (^ Η ₅ ) ₂ , ^ Ν ^^ ΝΗΟΗ

СΠ2NΠС (Ο) С _б [(1,3,4,5) ΟΗ] ₄ Η7, СН2NΠС (Ο) С6Η4-п-8ΟзNа, СΠ2NΠС (Ο) С _€ Π4С1, СН2NΠС (Ο) С6Н4NΟ2, СЩ ^ С ^ С ^ OCH

СН2NΠС (Ο) С6Н4 (3,4) С12, СН2NΠС (Ο) С6Π4СНз. SCHNIS ^ SHCHSN CH ₂ NΠС (Ο) С ₆ Н ₄ СN,

С ^ ННС ^ С ^, СЩНИС ^ СЧССОЖ

CH ₂ NΠC (Ο) (СΗΟΗ) ₂ СΟΟNа.

CH ₂ H (CH ₂ CH = CH-phenyl) [C (O) -phenyl], CΗ ₂ N [CΗ ₂ CΗ (CΗ ₃ ) ₂ ] [C (O) -phenyl], CΗ2N [C (Ο) C6Η5 ] СΗ2С6Η5.

СΗ2N- [С (Ο) С6Н5] (СН2) sС ₆ Π5. No.) ΟΗ11.

(CH ^ sup. ΟΗΝΗ * SPH'ISP; SP C11 phenyl, CΗ2NΗCΗ2-phenyl,

BNC-BN-phenylD, BNC-BNC.

С ^ ННЗО ^ p-nitrophenyl, СН ^ Н8О ₂ -p-tolyl, СН2NΠ8Ο2СΕз, С ^ ННСО С ^ or СШЩ8О2п-nitrophenyl] [СН ₂ СН (СН ₃ ) ₂ ].

Preferred aliphatic residues X are linear or branched C ₂ -C ₂₀ -. preferably C ₂ -C ₁₂ -, and particularly preferably C ₂ -C ₆ -alkylene and -alkenylene, C ₃ -C ₁₂ -, preferably C ₃ -C ₈ -. and particularly preferably C3-C7 cycloalkylene and cycloalkenylene, and C ₃ -C ₁₁ -, preferably C ₃ -C ₇ -, and particularly preferably C3-C5 heterocycloalkylene and heterocycloalkenylene with heteroatoms selected from the group of —O—, - atoms 8- and -Ν-.

Residue X may contain substituents, such as OH, halogen, C (O) Ok, |. OS (O) K ₈₄ , C (O) K, ₂ , nitro, ΝΗ ₂ , cyano, 8О ₃ М _у , О8О ₃ М _у , NК ₂₀ 8О ₃ М _у , Ст-С1 ₂ alkyl, С ₂ -С ₁₂ alkenyl, C ₁ -C ₁₂ alkoxy, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₆ -C ₁₀ aryloxy, C ₅ C ₉ heteroaryl , C ₅ -C ₉ heteroaryloxy, C ₇ -C ₁₁ aralkyl, C ₇ -C ₁₁ aralkyloxy, C ₆ -C ₁₀ heteroaralkyl, C ₈ -C ₁₁ aralkenyl, C ₇ -C ₁₀ heteroaralkenyl, primary amino, secondary amino, sulfonyl , sulfonamide, carbamide, carbamate, sulfongidrazid, carbohydrazide, carbohydroxamic acid and aminokarbonilamid, where R ₈₁ represents vodoro , M _y, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10-aryl, C5-S9geteroaril, C7 S11aralkil or C ₆ -C ₁₀ heteroaralkyl ; K ,, ₄ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroalkyl; K ₂ and K ₂₀ represent hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl, C6-C10 heteroaralkyl, C ₈ -C ₁₁ aralkenyl or C ₇ -C ₁₀ heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl or heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1; and M is a monovalent metal; or y = 1/2, and M denotes a divalent metal.

It should be noted that in the context of the present invention, the term metal means an alkali metal, for example, lithium (L1), sodium (Lα), potassium (K), rubidium (Lb) and cesium (Cg); alkaline earth metal, for example, magnesium (MD), calcium (Ca) and strontium (8g); or manganese (Mn), iron (Her), zinc (Ζη) or silver (Hell). The term physiologically acceptable salts means, in particular, salts of alkali metals and alkaline earth metals, for example, salts of sodium, potassium, magnesium and calcium. Preferred are sodium and potassium ions and their salts.

The term halogen means fluoro, chloro, bromo and iodo. Fluorine, chlorine and bromine are preferred, and fluorine and chlorine are particularly preferred.

Alkyl may be linear or branched, preferably branched once or twice in the α-position. Specific examples of alkyl, which preferably contains 1-12 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 isopropyl, n-, iso- and tert.-butyl.

Examples of alkenyl are allyl, but1-en-3-yl or 4-yl, pent-3-or 4-en-1-yl or 2yl, hex-3- or 4- or 5-en-1-yl or -2 -yl and (C ₁ C ₄ alkyl) CH = CH-CH 2 -.

Cycloalkyl and cycloalkenyl may preferably contain 5-8, and particularly preferably 5 or 6 carbon atoms on the ring. Examples of cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl and cyclododecyl. A particularly preferred cycloalkyl group is cyclohexyl. Examples of cycloalkenyl are cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclononenyl, cyclodecenyl, cyclodecenyl and cyclododecenyl. A particularly preferred cycloalkenyl group is cyclohexenyl.

Examples of alkylene are ethylene, 1,2propylene, 1,2- or 2,3-butylene, 1,2- or 2,3pentylene, 1,2-, 2,3- or 3,4-hexylene. Examples of cycloalkylene are 1,2-cyclopropylene, 1,2-cyclobutylene, 1,2-cyclopentylene, 1,2 cyclohexylene, 1,2-cycloheptylene and 1,2 cyclooctylene. Examples of heterocycloalkylene are pyrrolidinylylene, piperidinyl, tetrahydrofuranylene, di- and tetrahydropyranylene.

Examples of heterocycloalkyl are groups derived from pyrrolidine, imidazolidine, oxazolidine, pyrazolidine, piperidine, piperazine and morpholine. Examples of heterocycloalkenyl are groups derived from 2- and 3-pyrroline, oxazoline, 2- and 4-imidazoline and 2- and 3-pyrazoline.

In accordance with the present invention, aryl or heteroaryl are a 5 or 6 membered ring or a bicycle consisting of two fused 6 or 5 membered rings, or one 6-membered and one 5 membered ring, and in the case of such heteroaryl, one or several carbon atoms can be independently replaced by another atom selected from the group consisting of oxygen, nitrogen and sulfur atoms. Examples are groups derived from benzene, naphthalene, indene, furan, pyrrole, pyrazole, imidazole, isoxazole, oxazole, furazan, thiadiazole, thiophene, thiazole, oxadiazole, triazole, indole, indazole, purine, benzimidazole, benzoxazole, benzene , pyridine, pyridazine, triazine, pyrimidine, pyrazine, isoquinoline, cinnoline, phthalazine, quinoline, quinazoline, pteridine, benzotriazine or quinoxaline. Preferred aryl is naphthyl and phenyl. Phenyl is particularly preferred. Preferred heteroaryl are furanyl, pyridinyl and pyrimidinyl.

Aralkyl preferably has 7-12 carbon atoms and can be phenyl-C _n H _2n -, where η is an integer from 1 to 6. Examples are benzyl, phenylethyl or phenylpropyl. Benzyl and 2-phenylethyl are preferred. Aralkenyl is preferably unsubstituted phenyl-CH = CH-CH ₂ - (cinnamyl), or cinnamyl is a phenyl substituted substituent selected from the group consisting of OH, halogen, COOH, C (O) OM _y , C ₁ -C ₁₂ alkyl, C ₁ C ₆ alkoxy, C ₆ -C ₁₀ aryl, 8O ₃ M _y , O8O ₃ M _y , PC ₂₀ 8 O ₃ M _y , where 1 ₂₀ is C ₁ -C ₁₂ alkyl, C2-C12 alkenyl, C3-C12 cycloalkyl, C3 -S12tsikloalkenil, S11geterotsikloalkil-C2, C2-C11 heterocycloalkenyl, C6-C10-aryl, C6-S10ariloksi, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl, C ₆ -C ₁₀ heteroaralkyl, C ₈ -C ₁₁ aralkenyl, C ₇ - C1 ₀ heteroaralkenyl, and ΝΟ ₂ , C1-C1 ₂ primary amino, C ₂ -C ₂₀ secondary amino, amino and SC

Heteroaralkyl and heteroaralkenyl are preferably C ₄ -C ₅ heteroarylmethyl and C ₄ -C ₅ heteroarylethenyl with 1 or 2 heteroatoms selected from the group consisting of O and атом atoms, and heteroaryl may contain the aforementioned heteroaryl residues.

The alkoxy may be linear or branched, preferably branched once or twice at the α-position. Specific examples of alkoxy, which preferably contains 1-12 carbon atoms, are methoxy, ethoxy, and isomers of propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, nonoxy, deoxy, undexoxy and dodeoxy. Preferred alkoxy groups are methoxy and ethoxy.

Examples of aryloxy and aralkoxy are phenoxy and benzyloxy. Preferred heteroaryloxy are furanyloxy, pyridynyloxy and pyrimidinyloxy.

The primary amino preferably contains 1-12, and more preferably 1-6 C atoms. Specific examples are methyl, ethyl, hydroxyethyl, n- or isopropyl, n-, iso- or tert.-butyl, pentyl, hexyl-, cyclopentyl-, cyclohexyl-, phenyl-, methylphenyl-, benzyl- and methylbenzylamino. The secondary amino preferably contains 2-14, and particularly preferably 2-8, C atoms. Specific examples include dimethyl, diethyl, methylethyl, di-n-propyl, diisopropyl, di-n-butyl, diphenyl, dibenzylamino, morpholino , piperidino and pyrrolidino.

ΝΗ ₂ , primary amino, secondary amino, urea, carbamate, carbhydrazide, sulfonamide, sulfohydrazide and aminocarbonylamide are representatively selected from the above groups including Κ ^ (Ο) (ΝΗ) _ρ Ν (Κ ₉ ) -,

-c (0) (kn) _p ka ₈ i ₉ , 1 gos (0) (\ m \ (H.) -.

Κ_ ₈ Κ_40Ν ^ Ο) (ΝΗ) ρΝ (Κ9) -,

-OS (O) (\ H) p \ U11 ..

- \ (1Γ) C (O) (\ H) p \ U1C C ₈ 8 (Ο) 2 (NΗ) ρN (Κ9) -, -δ ^ ΗΝΗ ^ Νϋ ΙΓΙΓ \ 8 (О) ₂ \ (1.) - or -ΝΚ ^ δ ^^ ΝΚ ^, where 1 ₈ , 1 ₉ and 1 ₄₀ independently represent hydrogen, OH, C1-C12 alkyl, C1-C12 alkenyl, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl , C2-C11 heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C7-C16 aralkyl, C8-C16 aralkenyl with C2-C6 alkenylene and C6-C10 aryl, C6-C15 heteroaralkyl, C6-C15 heteroaralkenyl C10 _aryl-C1-C6 alkyl or Κ Κ _{8 9} Ν, where R ₈ and R ₉ independently of one another are hydrogen, OH, 8o M _{3 y,} M _{3 y} O8O, C1-C1 ₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C2-C11 heterocycloalkyl, C6-C 10aril, C5C ₉ heteroaryl, _C7-Cu aralkyl, C ₆ -C ₁₀ heteroaralkyl, C8 S16aralkenil C2-C6 S6alkenilenom and S10arilom, or di-C6-C10-aryl-C1-C6-alkyl, which are unsubstituted or substituted by one or several substituents selected from the group consisting of OH, halogen, C (O) OK, ₁ , OS (O) K _x1 . C (O) K, ₂ . nitro, ΝΗ ₂ , cyano, 8О ₃ М _у , О8О ₃ М _у , МЯ ₂₀ 8О ₃ М _у , С1С12 alkyl, С2-С12 alkenyl, С1-С12 alkoxy, С3-С12 cycloalkyl, С3-С12 cycloalkenyl, С2-С11 heterocycloalkyl, С2-С11 heterocycloalkyl, С2-С11 , C6-C10 aryl, C ₆ -C1 ₀ aryloxy, C ₅ -C ₉ heteroaryl, C ₅ -C ₉ heteroaryloxy, C7-C11 aralkyl, C7-C11 aralkyloxy, C6-C10 heteroaralkyl, C8-C11 aralkenyl, C7-C10 heteroaralkenyl, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide, where 1 ₈₁ is hydrogen, M _y , C1-C12 alkyl, C2-C12 alkenyl, C3-C12 cycle alkyl, C ₂ -C _p heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl or C ₆ -C ₁₀ heteroalkyl; Cr, ₄ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C3-C12 cycloalkyl, C2-C11 heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl or C ₆ -C ₁₀ heteroaralkyl; and K _? , ₂ represent hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl, C ₆ -C ₁₀ heteroaralkyl, C8-C11aralkenyl or C7-C10 heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl or heteroaralkenyl are, in turn, unsubstituted or substituted; p = 0 or 1, y = 1, and M denotes a monovalent metal; or y = 1/2, and M denotes a divalent metal; either K ₈ and K ₉ or K ₈ and K ₉ ', or K ₈ and 1 ₄₀ , taken together with the nitrogen atom, as in the case of -ΝΚ ₈ Κ ₉ or -ΝΚ ₈ ' Κ ₉ or -ΝΚ ₈ Κ ₄₀ Ν- are tetramethylene, pentamethylene, - (CH2) 2-O- (CH2) 2-, - (CH2) 2-8- (CH2) 2- Or

- (CH ₂ ) ₂ -M1 ₇ - (CH ₂ ) ₂ -, and Κ- represents hydrogen,

C ₁ -C ₆ alkyl, C ₇ -Caralkyl, C (O) K ₂ or sulfonyl.

The sulfonyl substituent corresponds, for example, to the above formula K ₁₀ -8 O ₂ -, where K ₁₀ is C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C _p heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ - C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl or C ₆ -C ₁₀ heteroaralkyl, which are unsubstituted or substituted by one or more substituents, wherein said substituents are selected from the group consisting of OH, halogen, C (O) OK ₈₁ , OS (O ) Kz4, C (O) k, ₂ . nitro, ХН ₂ , cyano, 8О ₃ М _у , О8О ₃ М _у , НК ₂₀ 8О ₃ М _у , С ₁ -С ₁₂ alkyl, С ₂ -С ₁₂ alkenyl, С ₁ -С ₁₂ alkoxy, С ₃ -С ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C2-S11geterotsikloalkil, C2-C11 heterocycloalkenyl, C6-C10-aryl, C6-C10 aryloxy, C ₅ -C ₉ heteroaryl, C ₅ -C ₉ heteroaryloxy, C ₇ C _p aralkyl, C ₇ - C ₁₁ aralkyloxy, C ₆ -C ₁₀ heteroaralkyl, C ₈ -C ₁₁ aralkenyl, C ₇ -C ₁₀ heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminoxidone, ₈₁ represents hydrogen, M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C ₆ -C ₁₀ heteroaralkyl; K ₈₄ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroalkyl; and k, ₂ and K ₂₀ are hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C2-C11 heterocycloalkenyl, C6 -C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl, C6-C10 heteroaralkyl, C ₈ -C ₁₁ aralkenyl or C ₇ -C ₁₀ heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl or heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1, and M denotes a monovalent metal; or y = 1/2, and M denotes a divalent metal.

K ₁₀ represents, in particular, C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₆ -C ₁₀ aryl, C ₇ -C ₁₆ aralkyl with 1-6 atoms in the alkylene group, and C6C ₁₀ aryl, C ₈ -C ₁₆ aralkenyl with C ₂ -C ₆ alkenylene and C ₆ -C ₁₀ aryl, or di-C ₆ -C ₁₀ aryl-C ₁ -C ₆ alkyl, for example, diphenylmethyl or 2,2-diphenylethyl, which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, COOH, C (O) OM _y , C ₁ -C ₁₂ alkyl, C ₁ C ₆ alkoxy, C ₆ -C ₁₀ aryl, 8O ₃ M _y , O8O ₃ M _y , HC ₂₀ 8O ₃ M _y , ΝΌ ₂ , amino, primary amino, secondary amino and ί, 'Ν; where K ₂₀ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl,

C5-C9 heteroaryl, C7-C11 aralkyl, C6-C10 heteroaralkyl, C8-C11 aralkenyl or C7-C10 heteroaralkenyl; y = 1, and M denotes a monovalent metal, or y = 1/2, and M denotes a divalent metal.

In addition, it is more preferred that K ₁₀ is C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₆ -C ₁₀ aryl, C ₇ -C ₁₆ aralkyl with 1-6 atoms in the alkylene group, and C ₆ is C ₁₀ aryl, which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, carboxyl, C (O) OM, C ₁ -C ₁₂ alkyl, C ₁ -C ₆ alkoxy, C ₆ -C ₁₀ aryl, 8O ₃ M _y , nitro, amino, primary amino, secondary amino and cyano; S8S ₁₆ aralkenyl or C ₂ -C ₆ alkenylene and C _{6 to} C ₁₀ aryl, or di-C ₆ -C ₁₀ aryl-C ₁ -C ₆ alkyl, for example diphenylmethyl or 2,2-diphenylethyl.

A preferred subgroup of compounds are compounds in which K ₅ and K ₆ taken together with the —CH — CH— group represent piperidylene, which is unsubstituted or substituted by one or more substituents selected from the group consisting of OH, C (O) OK ₈₁ , ОС (О) К ₄ , С (О) К ₂ , ΝΗ ₂ , С1-С12 alkyl, КЗОДВДК) -, -СУ ^ КК

VDO ^ SJ); KYUSYUMYu) -, ΙΜΤ ΝΟί)) Ν (Κ ₉ ) -, -ОС (О) MK ₈ K ₉ and K ₁₀ -8 О ₂ -, where K ₉ represents hydrogen, K ₈ represents C ₁ -C ₁₂ alkyl, C6- C10 aryl or C7-C11 aralkyl which are unsubstituted or substituted by one or more C ₁ -C ₁₂ alkoxy; K ₁₀ represents C ₁ -C ₁₂ alkyl, C ₆ -C ₁₀ aryl or C ₇ -C ₁₁ aralkyl, which are unsubstituted or substituted by one or more C ₁ C ₆ alkyl; K ₄₀ represents hydrogen, C ₁ -C ₁₂ alkyl, C3-C12 cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C10 heteroaryl, C7-C11 aralkyl or C ₆ -C ₁₀ heteroalkyl; K ₈₁ and K ₈₄ are C ₁ -C ₁₂ alkyl, and K: is C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkenyl, C ₃ -C ₁₂ cycloalkyl or C 6 -C 10 aryl; and the substituents alkyl, cycloalkenyl, cycloalkyl and aryl, in turn, are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, C (O) C3 _G and OC (O) K ₈₄₉ where Kg represents M _y or C ₁ C ₁₂ alkyl, and K ₄ 'represents C ₁ -C ₁₂ alkyl; y = 1, and M denotes a monovalent metal; or y = 1/2, and M denotes a divalent metal.

Preferred compounds of formula I are compounds in which K ₁ corresponds to a group of formula III, where K represents hydrogen or M _y and K ₄ represents (a) unsubstituted C ₁ -C ₁₂ alkyl; C ₁ -C ₁₂ alkyl which is substituted by one or more substituents selected from the group consisting of -HH ₂ , primary amino, secondary amino, C ₁ -C ₁₂ sulfonyl, carbamide, carbamate, carbhydrazide, sulfonamide, sulfonhydrazide, aminocarbonylamido, C3- C12 cycloalkyl, C1-6 alkoxy, phenyloxy and benzyloxy; unsubstituted C 3 -C 1 cycloalkyl; C ₃ -C ₁₂ cycloalkyl which is substituted by one or more substituents selected from the group consisting of C ₃ -C ₁₂ cycloalkyl, C ₁ -C ₆ alkyl, C ₁ C ₆ alkoxy, C ₁ -C ₁₂ sulfonyl, phenyloxy and benzyloxy; C ₆ -C ₁₀ aryl; C ₃ -C ₉ heteroaryl with 1 or 2 heteroatoms selected from oxygen and nitrogen atoms; C ₇ -C ₁₆ aralkyl with C ₁ -C ₈ alkyl and C ₆ -C ₁₀ aryl; C ₄ -C ₁₆ heteroalkyl with C ₁ C6 alkyl and C3-C10 heteroaryl having 1 or 2 heteroatoms selected from oxygen and nitrogen atoms, and a total of 3-5 carbon atoms; C ₆ C ₁₀ aryl, C ₃ -C ₉ heteroaryl with 1 or 2 heteroatoms selected from oxygen and nitrogen atoms; C ₇ -C ₁₆ aralkyl with C ₁ -C ₆ alkyl and C ₆ -C ₁₀ aryl; C ₃ -C ₁₆ heteroalkyl with C ₁ -C ₆ alkyl and C ₄ -C ₁₀ heteroaryl having 1 or 2 heteroatoms selected from oxygen and nitrogen atoms and a total of 3-5 carbon atoms which are substituted by one or more substituents selected from the group consisting of OH, halogen, C ₁ -C ₁₂ sulfonyl, carboxyl, C (O) OM _U , C ₁ -C ₁₂ alkyl, C ₁ -C ₆ alkoxy, C ₆ -C ₁₀ aryl, 8O ₃ M _U , O8O M _{3 y 20} HK 8o ₃ M _y, where 1 ₂₀ is hydrogen, C ₁ C12alkyl, C2-C12alkenyl, C3-C12cycloalkyl, S3S12tsikloalkenil, C2-S11geterotsikloalkil, S2S11geterotsikloalkenil, C6-C10-aryl, C5 -C9 heteroaryl, C ₇ -C ₁₁ aralkyl, C ₆ -C ₁₀ Goethe oaralkil, C ₈ C ₁₁ aralkenyl or C ₇ -C ₁₀ heteroaralkenyl, and nitro, ΝΗ _2, primary amino, secondary amino, carbamide, carbamate, sulfonamide and cyano, where y = 1, and M is a monovalent metal or y = 1 / 2, and M denotes a divalent metal, or (b) C ₁ -C ₁₂ alkyl or C ₇ -C ₁₁ aralkyl, which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OV ₈₁ , OS (O) K ₄ , C (O) B, ₂ . nitro, ΝΗ ₂ , cyano, 8О ₃ М _у , О8О ₃ М _У , П1 ₂₀ 8О ₃ М _у , С ₁ -С ₁₂ alkyl, С2-С12 alkenyl, С1-С12 alkoxy, С3-С12 cycloalkyl, С3-С12 cycloalkenyl, С2- S11geterotsikloalkil, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl, C6-S10ariloksi, S9geteroaril C5, C5 -C9 heteroaryloxy, C7 S11aralkil, C7 S11aralkiloksi, C ₆ -C ₁₀ heteroaralkyl, C ₈ -C ₁₁ aralkenyl , C ₇ C ₁₀ heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carboxyhydroxamic acid and aminocarbonylamide, where B ₈₁ is hydrogen, M _U , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alc enyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C ₇ -C ₁₁ aralkyl or C ₆ -C ₁₀ heteroaralkyl; B ₈₄ represents hydrogen, C 1 -C 12 alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl or C ₆ -C ₁₀ heteroalkyl; B, ₂ and B ₂₀ represent hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C6, C7-C6 C10 heteroaralkyl, C8-C11aralkenyl or C7-C10 heteroaralkenyl;

moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl and heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1, and M denotes a monovalent metal; or y = 1/2, and M denotes a divalent metal.

1 ₃ in formula III is preferably hydrogen, K or Να.

Preferred is a group (a) in which

1 to ₄ is alkyl, preferably methyl, ethyl, n- or isopropyl, iso- or tert-butyl. In the case of substituted alkyl, the alkylene group is preferably ethylene, and particularly preferably methylene. A particularly preferred cycloalkyl group is cyclohexyl. Preferred aryl and aralkyl are naphthyl and phenyl, most preferably phenyl and phenylC _n H _2n -, where η is an integer from 1 to 6, and particularly preferably benzyl and 2 phenylethyl. If 1 ₄ is heteroaryl, then C4-C5 heteroaryl is preferred with one or two heteroatoms selected from the group consisting of O and Ν. Furanyl, pyridinyl and pyrimidyl are preferred. If 1 ₄ is heteroaralkyl, then C ₄ -C ₅ heteroarylmethyl is preferred, which has one or two heteroatoms selected from the group consisting of O and Ν, and may contain the aforementioned heteroaryl groups as heteroaryl.

Other preferred compounds are compounds in which the 1 ₄ in formula III is C ₃ -C ₁₂ cycloalkyl, particularly preferably cyclohexyl, C1-C4 alkyl, in particular methyl or ethyl, substituted with C ₃ C ₁₂ cycloalkyl or C ₁ -C ₄ alkyl and in particular cyclohexyl or methyl; C ₆ -C ₁₀ aryl, and particularly preferably phenyl, or 1 ₄ is C ₇ -C ₁₂ aralkyl with C ₁ -C ₆ alkyl and C6-C10 aryl. In this series, especially preferred groups of 1 to ₄ are benzyl, naphthylmethyl, 2-phenylethyl, 3-phenylpropyl, cyclohexylmethyl, 2-cyclohexylethyl, cyclohexyl and isopropyl.

Carbamido, carbhydrazido, sulfonamido, sulfonhydrazido, amino carbonylamide and carbamate, which are present as substituents for 1 to ₄ , preferably represent a group of formulas B ^ HC (O ^ (K ₉ ) -, UOD-VDC,) -, B8C (O) ^ ) _p ^ K_9) - and VDO ^^^ Yu) -, where 1 preferably represents H, C ₁ -C 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 heterocycloalkylmethyl or ethyl, phenyl, naphthyl, benzyl, 2-phenylethyl, diphenyl methyl, which are unsubstituted or substituted by one or more substituents, you selected from the group consisting of OH, -ΝΗ ₂ , C ₁ -C ₈ primary amino, C ₃ -C ₁₃ secondary amino, HO ₂ , ΟΝ, -E, -C1, -C (O) OH, -C (O) О№, -8О3Н, -О8ОЗ. ΝΗ _; δΟ, Να. where Yu represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ C ₁₁ heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl, C ₆ -C ₁₀ heteroaralkyl, C ₈ -C ₁₁ aralkenyl or C ₇ -C ₁₀ heteroaralkenyl, and 8O ₃ Na, C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy and phenyl; and K. ₉ represents H, C ₁ C ₁₀ alkyl, phenyl, naphthyl, benzyl, 2-phenylethyl or phenyl-CH = CH-CH ₂ -, and p = 0 or 1.

In group (a), a particularly preferred urea-substituted alkyl substituent for B ₄ is B ₈ C (O): No. ₉ - (CH ₂ ) _p -, where n = 1 or 2,

K. ₈ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₃ C ₁₂ cycloalkyl, C ₆ -C ₁₀ aryl or C ₇ -C ₁₆ aralkyl with C ₁ -C ₆ alkyl and C ₆ -C ₁₀ aryl, where alkyl, cycloalkyl, aryl and aralkyl are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, carboxyl, C (O) OM _y , C ₁ C ₁₂ alkyl, C ₁ -C ₆ alkoxy, C ₆ -C ₁₀ aryl, 8О ₃ М _у ,

O8O3My, \ N; 8O _; M ,. C (O) OV ₈ 1, OS (O) 1 k. nitro, amino and cyano; or C ₈ -C ₁₆ aralkenyl with C ₂ -C ₈ alkenyl and C ₆ -C ₁₀ aryl, or di-C ₆ -C ₁₀ aryl C ₁ -C ₆ alkyl; and K, ₉ represents H, linear or branched C ₁ -C ₁₀ alkyl, C ₅ - or C ₆ cycloalkyl, C ₅ - or C ₆ cycloalkylmethyl- or -ethyl, phenyl, naphthyl or benzyl, 2-phenylethyl or phenyl-CH = CH-CH ₂ -; y = 1, and M is an alkali metal, or y = 1/2, and M is an alkaline earth metal, B ₂₀ is hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl , C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl, C6-C10 heteroalkenyl, C8-C11 arakenyl or C7-C10 g; B ₈₁ is hydrogen, M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl or C ₆ -C ₁₀ heteroalkyl, and B ₈₄ represents hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C3-C12 cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl ₁₀ heteroalkyl. A particularly preferred sulphonamide-substituted alkyl substituent for B ₄ is 10-30C / NSSC, -, where K. ₈ . K, ₉ and n are as defined above for urea. A particularly preferred aminocarbonylamino- or carbamate-substituted alkyl substituent for B ₄ is B ₉ HH-C (O) -HH- (CH ₂ ) _p or K ₉ OS (Ο) -NΗ- (CH ₂ ) _η , where K, ₉ is such as defined above for urea, and, in addition, K, ₉ represents phenyl, and n is as defined above in the case of urea. A particularly preferred carbhydrazidosubstituted alkyl substituent for B ₄ is B ₈ C (O) -INHMB ₉ - (CH ₂ ) _p , where B ₈ , B ₉ and p are as defined above in the case of urea. A particularly preferred sulfonhydrazide substituted alkyl substituent for B ₄ is Β ₈ -8Ο ₂ -NΗNΒ ₉ (CH ₂ ) _p , where B ₈ , K, ₉ and p are as defined above in connection with urea.

Even more preferred are compounds in which B ₄ in formula III is an amide B ₈ C (O ^ (B ₉ ) (CH ₂ ) _p - or B ₈ 8 (O ₂ ^ (B ₉ ) (CH ₂ ) _p -, where B ₈ and B ₉ independently represent hydrogen, unsubstituted C1-C12 alkyl, which is substituted by one or more substituents selected from the group consisting of OH, halogen, carboxyl, C (O) OH, C ₁ -C ₁₂ alkyl, C ₁ -C ₆ alkoxy, C ₆ C ₁₀ aryl, -8О ₃ Н, О8О ₃ №k NΚ ₂₀ 8О ₃ Na, 8О ₃ На, nitro and cyano; unsubstituted C3-C12 cycloalkyl; C ₃ -C ₁₂ cycloalkyl, substituted one or more OH; unsubstituted C ₆ -C ₁₀ aryl, unsubstituted C ₇ -C ₁₂ aralkyl with C ^ C ₆ alkyl and C6-C10 aryl; C6-C10 aryl or C7-C12 aralkyl with C1-C6 alkyl and C6-C10 aryl, which is substituted by one or more substituents selected from the group consisting of OH, halogen, carboxyl, С (О) О№1. -С (О) К, С ₁ -С ₁₂ alkyl, С ₁ С ₆ alkoxy, С ₆ -С ₁₀ aryl, О8О ₃ №1, 8О ₃ На,: № ₂₀ 8О ₃ № C, O (O) Oyu C (O) Ok, ₃ , nitro, amino and cyano; B ₂₀ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl, C6-C10 heteroalkyl, C8-C11 aralkenyl or C ₇ -C ₁₀ g eteroaralkenyl; B ₃₁ represents hydrogen, M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl , C ₇ -C ₁₁ aralkyl or C ₆ -C _{10 heteroalkyl} , and K. _h3 represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C _p heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroaralkyl; n = 2 or 1.

Particularly preferred are compounds in which B ₄ in formula III is an amide B ₈ C (O) H (B ₉ ) (CH ₂ ) _p - or B ₈ 8 (O ₂ ^ (B ₉ ) (CH ₂ ) _p -, where B ₈ represents unsubstituted C1-C12 alkyl; C1-C8 alkyl which is substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) O # 1, and C ₆ -C ₁₀ aryl; unsubstituted C ₃ -C ₁₂ cycloalkyl; C ₃ -C ₈ cycloalkyl substituted with one or more OH; unsubstituted C ₆ -C ₁₀ aryl or C ₇ -C ₁₂ aralkyl with C ₁ -C ₆ alkyl; C ₆ -C ₁₀ aryl, C ₇ -C ₁₂ aralkyl with C ₁ -C ₆ alkyl and C ₆ -C ₁₀ aryl, or C ₈ -C ₁₆ aralkenyl with C ₂ -C ₆ alkenyl and C ₆ -C ₁₀ aryl, which is substituted by one or more substituents selected from the group consisting of halogen, C (O) OH, C (O) O # ₁ , C ₁ -C ₁₂ alkyl, C ₁ -C ₆ alkoxy , -8О ₃ Н, 8О ₃ На, О8О ₃ №, No. ₂₀ 8О ₃ No., where В ₂₀ represents hydrogen, С1-С12 alkyl, С2

C1 ₂ alkenyl, C ₃ -C _{1 2} cycloalkyl, C ₃ -C _{1 2} cycloalkenyl, C ₂ -C heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ C _p aralkyl, C ₆ -C ₁₀ heteroalkyl, C ₈ -C ₁₁ aralkenyl or C ₇ -C ₁₀ heteroaralkenyl; nitro and cyano; and K ₉ represents hydrogen, unsubstituted C ₁ -C ₆ alkyl, unsubstituted C ₆ -C ₁₀ aryl, unsubstituted C ₇ -C ₁₁ aralkyl with C ₁ -C ₆ alkyl and C ₆ -C ₁₀ aryl; or C ₂ -C ₁₆ aralkenyl with C ₂ -C ₆ alkenyl and C ₆ -C ₁₀ aryl; and p = 2, and preferably 1.

Also particularly preferred are compounds in which Kd in formula III is the amide K ₈ C (O) M (K ₉ ) (CH ₂ ) _P -, where K ₈ is unsubstituted C ₁ -C ₁₂ alkyl; C ₁ -C ₈ alkyl which is substituted with one or more substituents selected from the group consisting of cyclohexyl, OH, halogen, C (O) OH, C (O) Oa, and phenyl; unsubstituted C ₃ C ₁₂ cycloalkyl; C ₃ -C ₁₂ cycloalkyl which is substituted with one or more OH; unsubstituted C ₆ -C ₁₀ aryl; C ₆ -C ₁₀ aryl, which is substituted by one or more substituents selected from the group consisting of halogen, C (O) O # 1. -C (O) OH, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, phenyl, ₃ H -8O, 8o ₃ Na, O8O ₃ Na, Na NN8O _3, nitro and cyano; or C ₇ -C ₁₆ aralkyl with C ₁ -C ₆ alkyl and C ₆ -C ₁₀ aryl, and K ₉ represents hydrogen; unsubstituted C1-C6 alkyl, unsubstituted C7C ₁₆ aralkyl with C ₁ -C ₆ alkyl and C ₆ -C ₁₆ aryl; or C ₈ -C ₁₆ aralkenyl with C ₂ -C ₆ alkenyl and C ₆ -C ₁₀ aryl; and p = 2, and preferably 1.

Even more preferred are compounds in which Kd in formula III is the amide K ₈ C (O) H (K ₉ ) (CH ₂ ) _P -, where K ₈ is unsubstituted C ₁ -C ₁₂ alkyl; C ₁ -C ₄ alkyl which is substituted with one or more substituents selected from the group consisting of OH, halogen, C (O) OH, C (O) OAa, and phenyl; unsubstituted C ₃ -C ₁₂ cycloalkyl, in particular C ₆ H ₁₁ ; C ₃ -C ₁₂ cycloalkyl which is substituted with one or more OH;

unsubstituted C ₆ -C ₁₀ aryl, in particular C6H5 or C10H7; C6-C10 aryl, which is substituted by one or more substituents selected from the group consisting of halogen, —C (O) OH, C (O) OAa, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, phenyl, -8O ₃ H, 8o ₃ Na, O8O ₃ Na, Na NN8O _3, nitro and cyano, in particular C ₆ H ₄ C 1, C ₆ H ₄ (3.4) C1 _2, SbNdSOOYa, S6N4SN3, sc _CW; Ha or S. 1 ECX '; or unsubstituted C ₇ -C ₁₆ aralkyl with C ₁ -C ₆ alkyl and C ₆ -C ₁₀ aryl, in particular (CH ₂ ) ₂ C ₆ H ₅ ; and K ₉ represents hydrogen, C ₁ -C ₄ alkyl, phenylCH ₂ -, phenyl-CH ₂ CH ₂ , phenyl- (CH ₂ ) ₃ - or phenyl CH = CH-CH ₂ ; and p is 2 or 1, preferably 1.

Particularly preferred are compounds in which K ₄ in formula III is an amide K ₈ C (O) H (K ₉ ) (CH ₂ ) _P -, where K ₈ is unsubstituted or substituted C ₁ C ₁₂ alkyl, cyclohexyl, naphthyl, biphenyl phenyl, benzyl, phenylethyl or diphenylmethyl, and K ₉ represents C ₁ -C ₄ alkyl, phenyl-C ₁ -C 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-C2-C6 alkenyl, in particular C6H5CH = CH-CH ₂ ; and n = 2, and preferably 1.

Particularly preferred are compounds in which K ₄ in the formula III is an amide K ₈ C (O) H (K ₉ ) (CH ₂ ) _P -, where it is C ₁ -C ₁₂ alkyl which is unsubstituted or substituted by one or more atoms halogen (for example, C1, and especially E), in particular CE ₃ ;

or C ₆ -C ₁₀ aryl, especially phenyl or naphthyl, which is substituted with one or more substituents, such as C ₁ -C ₄ alkyl (e.g. methyl or ethyl), C ₁ -C ₄ alkoxy (e.g. methoxy or ethoxy), halogen, -ΟΝ or NO ₂ ; and K ₉ represents hydrogen or isobutyl; and n = 2, and preferably 1.

Even more preferred are compounds in which K ₄ in formula III is an amide B ₈ C (O) H (B ₉ ) (CH ₂ ) _P -, where K ₈ is C ₁ -C ₁₂ alkyl or C ₆ -C ₁₀ aryl especially C1-C6alkyl, which is unsubstituted or substituted by halogen, -ΟΝ, ^ O _2, C ₁ -C ₄ alkyl or C ₁ -C 4 alkoxy, or C5- or C6cycloalkyl, S6S10aril, such as phenyl or naphthyl, or S7S12aralkil such as benzyl phenylethyl, phenylpropyl or phenylpropenyl; and n = 2, and preferably 1.

Further particularly preferred are compounds in which K ₄ in formula II is aminoalkyl, preferably K ₈ K ^ (CH ₂ ) _P -, where K ₈ 'and K _{9 are} independently hydrogen; ₁₂ C1C unsubstituted alkyl; C ₁ -C ₁₂ alkyl, which is substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OV ₈₁ , C (O) OK ₈ 4, C (O) -№ _p K12, C1-C12 alkyl , C1C ₆ alkoxy, C ₆ -C ₁₀ aryl, -8О ₃ Н, 8О ₃ №-1, О8О ₃ На, NК ₂₀ 8О ₃ Na, nitro, amino and cyano; unsubstituted C3-C12 cycloalkyl; C3-C12 cycloalkyl which is substituted by one or more OH; C6C ₁₀ aryl; C ₇ -C ₁₆ aralkyl with C ₁ -C ₆ alkyl and C ₆ C ₁₀ aryl; or C ₈ -C ₁₆ aralkenyl with C ₂ C6 alkenyl and C6-C10 aryl, where aryl and aryl in aralkyl and aralkenyl are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OK ₈₁ , C (O) OK ₄ , С (О) О№, -С (О) ОК, -ССО) ^^, С1-С12 alkyl, С ₁ -С ₆ alkoxy, С ₆ -С ₁₀ aryl, -8О ₃ Н, 8О ₃ No., O8O ₃ No. 1. NK ₂₀ 8O ₃ Na, nitro, amino and cyano; where n = 2, and preferably 1; B ₈₁ represents hydrogen, K or No., C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C3-C12 cycloalkyl, C2-C11 heterocycloalkyl, C6C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6C ₁₀ heteroalkyl, K ,, ₄ represents hydrogen, C ₁ C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ C ₁₁ heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C7-C11 aralkyl or C6-C10 heteroaralkyl ; K11 represents H, C1-C4 alkyl, C2-C4 hydroxyalkyl, phenyl or benzyl; K12, irrespective of K11, has the same meanings, either B ₁₁ and K ₁₂ taken together represent tetramethylene, pentamethylene or -CH2CH2-O-CH2CH2-, and K ₂₀ represents hydrogen, C1-C1 ₂ alkyl, C ₂ -C ₂ alkenyl , C ₃ -C _{1 2} cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ C ₁₀ aryl, C5-C9 heteroaryl, C ₇ -C ₁₁ aralkyl, C ₆ C ₁₀ heteroaralkyl, C ₈ -C ₁₁ aralkenyl or C ₇ C ₁₀ heteroalkenyl.

Particularly preferred, in addition, are compounds in which K ₄ in the formula III represents aminoalkyl K ₈ K ₉ 'YCH ₂ -, where K ₈ and independently represent hydrogen; C ₁ -C ₈ alkyl, cyclopentyl, cyclohexyl, C5 or C6 cycloalkylmethyl, phenyl-C1-C4 alkyl, in particular -CH ₂ C ₆ H ₅ -, or phenyl-C ₂ -C ₄ alkenyl, in particular - CH ₂ CH = CHC ₆ H ₅ .

In addition, particularly preferred are compounds in which K ₄ in the formula III is aminoalkyl K ₈ K ₉ ISN ₂ -, where K. ₈ and independently represent hydrogen; C ₁ -C ₆ alkyl, phenyl-C ₁ -, or C ₂ -alkyl, in particular CH ₂ C ₆ H 5.

Preferred compounds of group (b) are compounds in which K ₄ is C ₇ -C ₁₁ aralkyl, in particular CH ₂ -C ₆ H ₅ and (CH ₂ ) ₂ -C ₆ H ₅ -, C ₃ -C ₁₂ cycloalkyl or C ₁ -C ₁₂ alkyl, which is unsubstituted or substituted by one or more substituents selected from the group consisting of ΝΉ ₂ , C ₃ -C ₁₂ cycloalkyl, primary amino, secondary amino, sulfonamide, urea and aminocarbonylamino. Particularly preferred substituents for C ₁ -C ₁₂ alkyl are ΝΉ ₂ , cyclohexyl, C ₆ -C ₁₀ aryl, K ₈ C (O ^ (K ₉ ) -, Κ ₈ 8 (Ο) ₂ Ν (Κ ₉ ) -, K ₈ ANN (O ^ (K ₉ ) -, and Κ ₈ Κ ₉ Ν-, where K. ₈ and K. ₉ independently represent hydrogen, C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl or C ₆ -C ₁₀ heteroaryl, and K. ₈ and K. ₉ independently represent hydrogen, OH, C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10-aryl, C5-S9geteroaril, C ₇ -C ₁₁ aralkyl or C ₆ -C ₁₀ heteroalkyl which is unsubstituted It is substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OK _81, OC (O) u. C (O) K _2, nitro, ΝΉ _2, cyano, 8o ₃ M _y O8O ₃ M _y , PE ₂₀ 8O ₃ M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₁ -C ₁₂ alkoxy, C ₃ -C ₁₂ cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C ₆ -C ₁₀ aryloxy, C ₅ -C ₉ heteroaryl, C ₅ -C ₉ heteroaryloxy, C ₇ -C ₁₁ aralkyl, C ₇ -C ₁₁ aralkyloxy, C ₆ C ₁₀ heteroaralkyl, C ₈ -C ₁₁ aralkenyl, C ₇ -C ₁₀ heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, urea, carbamate, sulfone hydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide, where Ε, ι represents hydrogen, M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10 aryl C5-C9 heteroaryl, C ₇ -C ₁₁ aralkyl or C ₆ -C ₁₀ heteroaralkyl; K ₈₄ represents hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C3-C12 cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C ₆ -C ₁₀ heteroalkyl; E, _2, and K ₂₀ represent hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl, C10-C11, heteroaralkyl, C8-C11aralkenyl or C7-C10 heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl and heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1; and M is a monovalent metal; or y = 1/2, and M denotes a divalent metal; or K. ₈ and K ₉ > together represent tetramethylene, pentamethylene, - (CH2) 2-O- (CH2) 2-,

- (CH ₂ ) ₂ -8- (CH ₂ ) ₂ - or - (CH ₂ ) ₂ -PE ₇ - (CH ₂ ) ₂ -, and K represents H, C ₁ -C ₆ alkyl, C ₇ -C ₁₁ aralkyl, C (O) K ₈₂ or sulfonyl.

Particularly preferred compounds of this group are compounds in which K ₄ is —CH ₂ —C ₆ H ₅ , - (CH ₂ ) ₂ —C ₆ H ₅ , cyclohexyl, methyl, ethyl or isopropyl, which are unsubstituted or substituted with one or more substituents selected from the group consisting of ΝΉ ₂ , cyclohexyl, C ₆ -C ₁₀ aryl, K ₈ C (O ^ (K ₉ ) -, K ₈ 8 (O) ^ (K ₉ ) -, K. ^ HC (O ) MK. ₉ ) - and Κ ₈ Κ ₉ Ν-, where K. ₈ . K. ₉ . K. ₈ and B ₉ independently represent hydrogen, C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₆ -C ₁₀ aryl or C ₇ -C ₁₁ aralkyl, which are unsubstituted or substituted by substituents selected from the group including OH, halogen, C (O) OM _y , nitro, cyano, 8O ₃ M _y , O8O ₃ M _y , PE ₂₀ 8O ₃ M _y , C ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ alkoxy and C ₆ C ₁₀ aryl, where y = 1, and M is a monovalent metal, or y = 1/2, and M is a divalent metal. Particularly preferred are compounds in which K. ₈ . K. ₉ . K. ₈ and K. ₉ independently represent hydrogen, C ₁ -C ₁₂ alkyl, cyclohexyl, phenyl, naphthyl or C ₇ -C ₁₁ aralkyl, which are unsubstituted or substituted by one or more substituents selected from the group including OH, E, C1, C (O) OH. nitro, cyano, 8O ₃ No. 1, C ₁ -C ₆ alkyl, methoxy and phenyl.

In a preferred group of compounds of formula I, B ₁ is a group of formula III, wherein B ₄ is C ₆ H ₁₁ , CH (CH ₃ ) ₂ , CH ₂ CH ₂ K1HC (O) phenyl, phenyl, (CH2) 2-phenyl,

CH ₂ ANN (O) (CH ₂ ) _3- phenyl, CH ₂ ANN (O) (CH ₂ ) ₃ OH, CH ₂ ANN (O) C ₆ H ₁₁ , CH ₂ ANN (O) CH (C ₆ H ₅ ) ₂ ,

CH ₂ YNS (O) CE ₃ ,

CH ₂ ONS (O) C ₁₁ H ₂₃ , SONS

CH ₂ PNS (O) C ₂ H ₄ CO ₂ No.,

СН2ПНС (О) С6 [(1,3,4,5) ОН] 4Н7,

СН2К1НС (О) С6Н4-р-8ОзЖ СН2ЦНС (О) С6Н4С1,

СН2К1НС (О) С6Н4da2, С11, -ΧΙ 1С (О) С..1 ЕОС11 ;.

С11; \ 11С (0) С.Н 4 (3,4) С12, СН2МНС (О) СНН4СН3, С11; \ 11С (0) С.Н 4С6Н5, СН; \ НС (О) СНН, С \.

CH; \ 11C (0) C11. С11; \ 11С (0) С.Н 4СООЫа,

СН2ЫНС (О) (СНОН) 2СООЖ

CH ^ CH2CH = CH-phenyl) [C (O) -phenyl], CH2Y [CH2CH (CH3) 2] [C (0) -phenyl], CH2 ^ C (O) CbH5] CH2CbH5,

CH2SH [C (0) CbH ₄ (CH2) 3CbH5, (CH2) CbH11, (Cn ^ CHc, Csnu scn-snphenyl, CH; \ HCH _; -phenyl. CH ₃ \ HCH ₃ CH (CH3) 2, CH ₂ ^ CH ₂ -phenyl) ₂ , CH ₂ N [CH ₂ CH (CH ₃ ) ₂ ] ₂ ,

СΗ ₂ NΗ8О ₂ -p-nitρο phenyl, СН ₂ IN80 ₂ -p-tolyl, СН ₂ 1МН8О ₂ CE ₃ , СН ^ НС (О) С ₆ Н ₅ or СН ^ [8О ₂ p-nitrophenyl] [СН ₂ СН ( CH ₃ ) ₂ ].

If K ₂ is alkyl, then it may preferably contain from 1 to 6 carbon atoms, and more preferably from 1 to 4 carbon atoms. Especially preferred are methyl and ethyl.

If the substituent for K ₂ is halogen, then it may preferably be E, C1 and Br; in the case of —C (0) M _y , preferred is —C (O) O # 1 or —C (0) OK; in the case of alkyl, C ₁ -C ₆ - is preferred, and particularly preferably C ₁ -C 4 alkyl, such as methyl, ethyl, n- or isopropyl and n-, iso- or tert.-butyl; in the case of alkoxy, then preferably C1-C4 alkoxy, for example methoxy and ethoxy; in the case of aryl, preferably phenyl or naphthyl; in the case of -8O ₃ M _y , preferably -8O ₃ No. 1 or -80 ₃ K; in the case of a primary amine, preferably a C ₁ -C ₁₂ primary amino, such as methyl, ethyl, n- or isopropyl, n-, iso- or tert.-butyl, phenyl, hexyl, cyclohexyl, phenyl or benzylamino; in the case of a secondary amino, preferably a C ₂ -C ₂₀ secondary amino such as dimethyl, diethyl, methylethyl, di-n-propyl, di-isopropyl, di-n-butyl, diphenyl, dibenzylamino, morpholino thiomorpholino, piperidino and pyrrolidino; -8O ₂ -№ ₈ K ₉ ; and C (O) -No ₈ K ₉ , where K ₈ and K ₉ taken together with the Ν atom form morpholino, thiomorpholino, pyrrolidino or piperidino.

If K ₈ and K ₉ are alkyl, then this alkyl preferably contains 1-6, and particularly preferably 1-4 carbon atoms, and may be, for example, methyl, ethyl, n- or isopropyl, or n-, iso or tert .-butyl. If K ₈ and K ₉ are hydroxyalkyl, then this hydroxyalkyl preferably contains

1-6, and particularly preferably 1-4 carbon atoms, and may be, for example, hydroxymethyl or 2-hydroxyethyl. If K ₈ and K ₉ are cycloalkyl, then such cycloalkyl is preferably cyclopentyl or cyclohexyl. Substituents for K ₈ and K ₉ representing phenyl and benzyl are preferably E, C1, methyl, ethyl, methoxy and ethoxy.

A preferred subgroup of compounds of formula I are compounds in which K ₂ is hydrogen, unsubstituted C ₁ -C ₆ alkyl, particularly preferably C ₁ -C ₄ alkyl, and in particular methyl or ethyl, or C ₁ -C ₆ alkyl, particularly preferably C ₁ -C ₄ alkyl in particular methyl or ethyl, which is substituted with C (0) OH-, -C (O) О№, -C (O) OK, -OH, -C (O) ΝΚ ₈ Κ ₉ or -8O ₂ -№ ₈ K ₉ , where K ₈ represents hydrogen, C ₁ -C ₄ alkyl, C ₂ -C ₄ hydroxyalkyl, phenyl or benzyl, and K ₉ independently has the same meanings as K ₈ ; or K ₈ and K ₉ taken together represent tetramethylene, pentamethylene or —CH 2 CH 2 —O — CH 2 CH 2 -. Particularly preferred are compounds in which K ₂ is hydrogen, methyl, ethyl, HO (0) CCH ₂ CH ₂ -, OOC (O) CH ₂ CH ₂ -, K ₈ KYS (O) CH ₂ CH ₂ -, and K ₈ and K ₉ independently represent hydrogen, C ₁ -C ₆ alkyl, C ₂ -C ₄ hydroxyalkyl, phenyl, benzyl, or, taken together, they represent morpholino.

Particularly preferred are compounds in which K ₈ , K ₉ , K ₈ 'and independently of each other are hydrogen, C ₁ C ₁₂ alkyl, cyclohexyl, phenyl, naphthyl or C ₇ Sp aralkyl, which are unsubstituted or substituted by one or more substituents selected from the group including OH, E, C1, C (O) O #. nitro, cyano, 8О ₃ No. C ₁ -C ₅ alkyl, methoxy and phenyl.

In addition, the present invention relates to a method for producing compounds of formula I, which involves the esterification of 3-OH in a compound of formula V

where K ₂ and X have the above meanings, K ₁₂ represents a protective group, and K ₁₂ and K ₁₂ independently represent hydrogen or a protective group by reaction with a compound of formula VI

K1 - K13 (VI) where K ₁ has the above meanings, and E ₁₃ is a leaving group, and with the subsequent removal of the protective groups.

The leaving groups may be halogen atoms such as chlorine, bromine and iodine, and residues of the corresponding sulfonic acids, for example, trifluoromethanesulfonate, aliphatic, cycloaliphatic or aromatic sulfonic acids, which may be unsubstituted or substituted with C ₁ -C ₄ alkyl, C ₁ C ₄ alkoxy, nitro, cyano or halogen (chlorine, bromine). Some examples of such acids include methanesulfonic acid, mono-, di- or trifluoromethanesulfonic acid, or p-nitrobenzenesulfonic acid. It is especially preferred to use CE ₃ -8O ₂ O- (also called triflate). The leaving group is preferably selected from the group consisting of halogen and unsubstituted and halogenated 8O2- K, where K represents a C1-C12 alkyl, in particular C 1 C ₆ alkyl, C ₅ -C ₆ cycloalkyl, phenyl, benzyl, C1-C1 ₂ alkylphenyl, in particular, _C1-C4 alkylphenyl or _C1 to _C12 alkylbenzyl, in particular, C1-S4alkilbenzil, e.g., methane, ethane, propane, butane, benzene, benzyl and pmetilbenzilsulfonil. Preferred leaving groups are C1, Br, I, -O-8O ₂ CE ₃ (triflate) and p-nitrobenzenesulfonyl, with -O8O ₂ CP ₃ being a particularly preferred leaving group.

Some compounds of formula VI are known, or they can be obtained by known methods described by Edegbesque! a1. [Oedegbesk E., Egapkkop V., Szhekp b., Kadpagkop i., 1. Sket. 8os. Regksh Tgapk. 1: 1114 (1993)] and Oiheaii e! a1. [Oyhean N., ^ aps ^ at I., ^ erusezau 1.S., 8n1kek1K 491-493 (1987)]. Optically pure compounds can be prepared using optically pure starting materials (e.g., amino acids, α-hydroxy acids), or by chromatographic separation methods, e.g., using chiral solid phases.

The compounds of formula V are new compounds that are considered in the present invention. They can be obtained by known glycosylation methods using known fucosyl and galactosyl donors and diodes of the formula HOX-OH. In this case, the stepwise administration of galactose and fucose or vice versa is preferable.

To obtain compounds of formula V, pseudotrisaccharide blocks are first synthesized. The synthesis of pseudotrisaccharides is carried out either by glycosidic addition of activated and protected galactose to the resulting fucose-O-X-OH block, or by glycosidic addition of appropriately protected and activated fucose to the resulting galactose-O-X-OH block. The glycosylation reaction is widely known and is described in the specialized literature.

The group K! Can then be introduced into the pseudotrisaccharide. After that, the obtained compounds of formula I can be modified. Such a modification may be halogenation of aromatic compounds to form cycloaliphatic groups, and at the same time, for example, hydrogenolytic deprotection can be carried out. In addition, acylation and / or alkylation and / or sulfonation of the amino group can be carried out. Obtaining secondary and tertiary amines can be carried out by reductive amination.

It is preferred that the 3-OH group of the galactose residue be activated by esterification. Dialkyltin oxides, dialkyltin alkoxides and bis (trialkyl) tin oxides are particularly suitable for this purpose. Dibutyltin oxide, dibutyltin (O-methyl) ₂ and (tributyltin) 2O can serve as some specific examples. Activating agents are preferably used in stoichiometric amounts. In this case, the reaction is carried out in two stages, namely, a) activation and b) the reaction of interaction with compounds of formula VI.

The activation reaction can be carried out at temperatures of 40-200 ° C, and preferably at 60-120 ° C.

The compounds of formula V and formula VI can be used in equimolar amounts. However, it was found that the compound of formula VI is advisable to use in excess quantities, which, for example, up to 10 times, and preferably 5 times, exceed the amount of the compound of formula V.

In addition, both stages of the reaction are preferably carried out in the presence of an inert solvent or mixture of solvents. Reactive protic solvents such as alkanols as well as acid amides are not suitable for use in step b). Non-polar aprotic and polar aprotic or polar protic solvents may be used. Said solvents may be aliphatic or aromatic hydrocarbons such as pentane, hexane, cyclohexane, methylcyclohexane, benzene, toluene or xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1,2-trichloroethane, 1,1,2,2-tetrachloroethane and chlorobenzene; linear or cyclic ethers such as diethyl ether, ethylene glycol dimethyl or diethyl ether, tetrahydrofuran and dioxane; Ν, Ν-dialkylated carboxamides, such as dimethylformamide, Ν-alkylated lactams, such as Ν-methylpyrrolidone; ketones such as acetone and methyl isobutyl ketone;

carboxylic acid esters such as methyl or ethyl acetate; or alkanols, such as methanol, ethanol, propanol, butanol and ethylene glycol monoethyl ether. Particularly preferred solvents are methanol, ethanol, benzene and toluene.

The protective groups and methods used for derivatization of hydroxyl groups are generally known to those skilled in the art of sugar and nucleotide chemistry and are described, for example, Weisade 8. L., K. Hueg, Teiyeigop 48: 2223-2311 (1992). Examples of such protecting groups are benzyl, methylbenzyl, dimethylbenzyl, methoxybenzyl, dimethoxybenzyl, bromobenzyl, 2,4-dichlorobenzyl; diphenylmethyl, di (methylphenyl) methyl, di (dimethylphenyl) methyl, di (methoxyphenyl) methyl, di (dimethoxyphenyl) methyl, triphenylmethyl, tris-4,4 ', 4-tert-butylphenylmethyl, di-p-anisylphenylmethyl, three ( methylphenyl) methyl, tri (dimethylphenyl) methyl, methoxyphenyl (diphenyl) methyl, di (methoxyphenyl) phenylmethyl, tri (methoxyphenyl) methyl, three (dimethoxyphenyl) methyl; triphenylsilyl, alkyldiphenylsilyl, dialkylphenylsilyl and trialkylsilyl with 1-20, preferably 1-12, and especially preferably 1-8, carbon atoms in the alkyl groups, for example, triethylsilyl, trin-propylsilyl, isopropyldimethylsilyl, tert-butyldimethylsilyl, tert.-butylphenyl -octyldimethylsilyl (1,1,2,2-tetramethylethyl) dimethylsilyl; C2-C12-, especially C2-C6 acyl, such as acetyl, propanoyl, butanoyl, pentanoyl, hexanoyl, benzoyl, methylbenzoyl, methoxybenzoyl, chlorobenzoyl and bromobenzoyl. Protecting groups may be the same or different. Preferred protecting groups are selected from the group consisting of linear and branched C ₁ -C ₈ alkyl, in particular C ₁ -C ₄ alkyl, for example methyl, ethyl, n- and isopropyl, n-, iso- and tert.-butyl;

C ₇ -C ₁₂ aralkyl, for example benzyl; trialkylsilyl with 3-20 carbon atoms, in particular with 3-12 carbon atoms, for example triethylsilyl, tri-n-propylsilyl, triisopropylsilyl, isopropyldimethylsilyl, tert-butyl-dimethylsilyl, tert-butyl diphenylsilyl, n-octyldimethylsilyl 1,2,2-tetramethylethyl) dimethylsilyl; substituted methylidene groups, which can be obtained by the formation of acetal or ketal from adjacent hydroxyl groups of sugars or sugar derivatives by their interaction with aldehydes and ketones, which preferably contain

2-12 or 3-12 carbon atoms, for example, C ₁ C ₁₂ alkylidene, preferably C ₁ -

C6 alkylidene, in particular C1-C4 alkylidene such as ethylidene, 1,1- and 2,2-propylidene, 1,1- and

2,2-butylidene, benzylidene; unsubstituted and halogenated C2-C12 acyl, in particular C2C ₈ acyl such as acetyl, propanoyl, butanoyl, pentanoyl, hexanoyl, pivaloyl and benzoyl.

The synthesis is preferably carried out using protecting groups for K ₁₂ and Y ₁₂ , which together form an alkylidene group, preferably with 1-12, and more preferably with 1-8 carbon atoms. Particularly preferred protecting groups are those groups in which K ₁₂ and K ₁₂ taken together represent an alkylidene group, in particular with 1-12 carbon atoms, where the alkylidene group forms an acetal or ketal with oxygen atoms. These protecting groups can be eliminated under neutral or slightly acidic conditions. Particularly suitable protecting groups are acyl, benzyl, substituted benzyl, benzyloxymethyl, alkyl and silyl. It is particularly preferred that K ₁₂ and K ₁₂ ~ taken together represent an alkylidene, for example an alkyl or alkoxy substituted benzylidene. However, K ₁₂ and K12 can also be hydrogen, or one of

K ₁₂ and Ku may be a protecting group, such as benzyl, and the other may be hydrogen.

Examples of protective carboxylate groups are alkoxy and aralkoxycarbonyl groups, preferably —CO ₂ Bp, —CO ₂ CH 3.

The reaction of elimination of the protective groups is preferably carried out at a temperature of from 0 to 50 ° C, and in particular at room temperature.

The preparation of compounds of formula I is described in more detail in the examples.

An alternative synthesis method involves the glycosidic binding of a protected fucose hydroxy ester of formula VII

where Y ₂ and X are as defined above, and Y ₁₂ is a protective group, by reaction with a protected galactose of formula VIII

where K and Y ₁₂ are as defined above, Ζ represents O or 8, and Y is a leaving group, followed by removal of the protective groups from the resulting compound.

The reaction conditions may be similar to the conditions used to carry out the method described above. The leaving group может may be, for example, —C (═I) —CC1 ₃ or 4-pentenyl. Compounds of formula VII can be prepared simply by glycosidic coupling of an appropriately protected fucose to a compound of formula HO-X-OH, which may be mono-protected if necessary. Compounds of formula VIII can be prepared by esterification of compounds of formula Y ₁ OH with galactose, which can be protected if necessary.

The compounds of the present invention have anti-inflammatory properties, and therefore can be used as medicines. In particular, they can be used to treat diseases such as cardiogenic shock, myocardial infarction, thrombosis, rheumatism, psoriasis, dermatitis, acute respiratory distress syndrome and cancer with metastases. In addition, the present invention relates to the compounds described in the present invention and intended for use in a therapeutic method for the treatment of diseases of warm-blooded animals, including humans. A dosage of administration of such a compound to a warm-blooded animal weighing about 70 kg may be, for example, 0.011000 mg per day. The compounds of the present invention are preferably administered parenterally, for example, intravenously or intraperitoneally, in the form of pharmaceutical compositions.

In addition, the present invention relates to a pharmaceutical composition containing an effective amount of a compound of the present invention, taken alone or in combination with other active substances, a pharmaceutical carrier, preferably in significant quantities, and, if necessary, pharmaceutical additives.

The pharmacologically active compounds of the present invention can be used in the form of compositions that can be administered parenterally or in the form of infusion solutions. Such solutions are preferably isotonic aqueous solutions or suspensions, which can be prepared immediately before use, for example, from lyophilized compositions containing the active compound, taken separately or together with a carrier, for example mannitol. The pharmaceutical compositions may be sterilized and / or contain additives, for example, preservatives, stabilizers, wetting agents and / or emulsifiers, stabilizers, salts for regulating the osmotic pressure and / or buffers. Pharmaceutical compositions, which, if necessary, may contain other pharmacologically active substances, such as antibiotics, can be prepared by methods known to Reghe, for example, by conventional dissolution or lyophilization and may contain about 0.190%, in particular from about 0, 5% to about 30%, for example, 1-5% of the active substance (active substances).

The present invention is illustrated in the following examples. The following abbreviations and notation were used in these examples:

Βζ is benzoyl; Bp is benzyl; EMT8T - triflate dimethyl (methylthio) sulfonium; ΕΑΒ - mass spectroscopy by fast atom bombardment; FROM! triflate; PH is phenyl; 8E - C ₂ H ₂ 8; TH6 - thioglycerol; THP (THF) -tetrahydrofuran; ΝΒΑ - m-nitrobenzyl alcohol; OME (DMF) - Ν, Ν-dimethylformamide; OME - 1,2-dimethoxyethane; MeOH - methanol; Н1Р - horseradish peroxidase; Β8Α - bovine serum albumin; RAA - polyacrylamide; 8Α streptavidin. An unbound bond in the formulas means methyl.

Before use, the molecular sieves were activated at 300 ° C under high vacuum for 12 hours. These sieves were used in powder form.

A: Obtaining the starting compounds. Example A1: Preparation of Compound No. A1

Benzyl chloride (660 ml, 5.72 mmol) was added at room temperature to a mixture of P-3azido-2-hydroxypropionic acid 28 [Pigeiai I., TgapeNerat I., ^ erezau N.S., 8Up (Neikh 491-493 (1987) ], triethylamine (850 ml, 6.1 mmol) and DMF (7.0 ml). The mixture was stirred for 16 hours and then another 850 μl (6.1 mmol) of triethylamine and 660 μl (5.72 mmol) were added. benzyl chloride The reaction mixture was stirred for 2 days and then concentrated in high vacuum. The residue was dissolved in water and the mixture was extracted several times with ethyl acetate. The combined organic phases were washed with saturated m №S1 solution, dried (Na ₂ 8o _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-B -3-azido-2-hydroxypropionate 29 (0.717 g, 85%) as an oily product. ¹ H-NMR (250 MHz, SES1 ₃ ) δ 7.36 (m, 5H), 5.25 (s, 2H), 4 39 (q, 1 = 4.2 Hz, 1H), 3.65 (dd, 1 = 3.3, 12.9 Hz, 1H), 3.51 (dd, 1 = 4.3, 12.9 Hz, 1H), 3.20 (d, 1 = 4.0 Hz, 1H).

FROM(

A1

Trifluoromethanesulfonic anhydride (770 ml, 4.41 mmol) was added, while stirring, at -20 ° C to a solution of alcohol 29 (0.85 g, 3.84 mmol) and 2,6-di-tert.-butylpyridine (1.12 ml, 4.99 mmol) in anhydrous CH ₂ Cl ₂ (11.0 ml). The colorless transparent solution was heated to 0 ° C for 40 minutes and stirred at this temperature for another 2 hours. The resulting mixture was diluted with CH ₂ Cl ₂ (40 ml) and, under vigorous stirring, a 1M aqueous solution of KH ₂ PO ₄ (30 ml) was added. The organic phase was separated and the aqueous phase was extracted twice with methylene chloride. The combined organic phases were washed with water (30 ml), dried SchA ₂ 8O ₄ ), filtered and concentrated in vacuo. The oily residue (2.3 g) was purified by flash column chromatography on a short column of silica gel (ethyl acetate / hexane = 1: 7), whereby benzyl-B-azido-2-trifluoromethanesulfonyloxy propionate A1 (1.16 g, 85%) was obtained in the form of a yellowish oily substance. ¹ NNMR (250 MHz, SES13) δ 7.38 (br.s., 5H), 5.32 (d, 1 = 12.1 Hz, 1H), 5.27 (d, 1 = 12.1 Hz, 1H), 5.24 (dd, 1 = 4.2, 5.5 Hz, 1H), 3.90-3.75 (m, 2H); ¹³ NMR (63 MHz, SES13) δ 164.4, 133.9, 129.1, 128.6, 120.9, 81.0, 69.0, 51.5.

Example A2. Obtaining compound No. A2.

Benzyl (K) -4-phenyl-2-trifluoromethanesulfonyloxybutyrate (A2).

A solution of (K) -2-phenyl-2-hydroxy-4-phenylbutyric acid 26 (0.2 g, 1.11 mmol) in MeOH / H ₂ O (9: 1, 1.3 ml) was adjusted to pH 8 by adding a 20% solution of C ₂ CO ₃ . The resulting solution was concentrated in vacuo and subjected to azeotropic distillation, first with ethanol and then with hexane, after which it was dried under high vacuum to remove residual water. The residue was mixed with Ν, Ν-dimethylformamide (1.3 ml) and benzyl bromide (132 μl, 1.11 mmol), and the mixture was stirred at room temperature for 75 minutes. Then another 20 μl (0.168 mmol) of benzyl bromide was added and the resulting mixture was stirred for another 50 minutes. The white suspension was diluted with CH ₂ Cl ₂ (5 ml), filtered through NuDo8regCe1® and concentrated in vacuo. The resulting product was purified by flash chromatography on silica gel (eluent: ethyl acetate / hexane 4: 1) to give benzyl (K) -2-hydroxy-2-phenylbutyrate 27 (0.21 g, 70%). This product (0.3 g, 1.11 mmol) was dissolved in CH ₂ Cl ₂ (4.5 ml), 2,6-di-tert.butylpyridine (323 μl, 1.44 mmol) was added, and the resulting mixture was cooled to -20 ° C. Then, trifluoromethanesulfonic anhydride (222 μl, 1.27 mmol) was added dropwise over 3 minutes, and the solution was heated to 0 ° C for 45 minutes. After incubation for 75 minutes at 0 ° C, the mixture was diluted with CH ₂ Cl ₂ (20 ml) and washed with a 1 molar aqueous solution of KH ₂ PO ₄ (15 ml). The aqueous phase was extracted with CH2C12 (2 x 10 ml), and the combined organic phases were washed with water (10 ml), dried with Scha ₂ 8O ₄ ), filtered and concentrated in vacuo. The residue was subjected to rough purification by filtration on a column of silica gel (eluent: ethyl acetate / hexane 1: 9), whereby a crude triflate A2 (0.311 g, 70%) was obtained as an oily product. This product was directly used in the next step (Preparation B 1.18). ¹ H-NMR (250 MHz, SES1 ₃ ) δ 7.50-7.17 (m, 10H), 5.31 (s, 2H), 5.28 (dd, 1 = 5.5, 11.0 Hz , 1H), 2.82 (m, 2H), 2.41 (m, 2H).

Example A3. Obtaining compound No. A3.

K-Gidromindalnoy acid was converted to triflate A3, as described in example A2.

Example A4. Getting connection No. A4.

K-2-Hydroxy-3-methylbutyric acid was converted to triflate A4, as described in Example A2.

Example A5. Preparation of Compound A5

K-2-G idroxy-3-cyclohexylpropionic acid was converted to triflate A5, as described in Example A2.

B. Obtaining pseudo-compounds.

Example B1 Obtaining compound No. B1.1.

A mixture of thioglycoside 1 (5.38 g, 8.40 mmol) [B1e88ep E.L., VeiNpd Ό.Μ., Koe1ep N.S.R.E., vapor Be Mage1 S.L., vapor Voot Ι .Η., Wap Vegke1 T.1.S., 1. Meb. Sket. 38: 1538-1546 (1995)] and acceptor 2 (3.44 g, 6.46 mmol) were dried for 1 h under high vacuum. Then, activated 4A molecular sieves (20 g) and EMT8T (4.17 g, 16.14 mmol) were added under nitrogen atmosphere, followed by CH ₂ Cl ₂ (70 ml). The yellowish suspension was dried at room temperature and after 3 hours 5 ml of a suspension consisting of EMT8T (5.84 g, 22.61 mmol), 4 A molecular sieves (4.0 g) and CH ₂ Cl ₂ (35 ml) were added. Then after 30, 45 and 90 minutes, respectively, 5-milliliter portions of this EMT8T suspension were added. Then the brown reaction mixture was stirred for 15 h and filtered through NuDo8regSe1® (filter), washing with CH ₂ Cl ₂ (300 ml), the filtrate was extracted by shaking first with a 10% aqueous solution of No. ₁ HCO ₃ , and then with a saturated solution of No. C1, and the organic the phase was drained (No. 6O ₃ ). filtered and concentrated in a vacuum rotary evaporator. The remaining brown foam was purified by two stages of column chromatography on silica gel (eluent for stage 1 chromatography: ethyl acetate / hexane = 1: 4; eluent for stage 2 chromatography: ethyl acetate / toluene = 1: 9), whereby pure product 3 was obtained as a colorless solid (4.28 g, 60%), which was directly used in the next step.

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) was stirred at room temperature for 3 hours. The resulting mixture was neutralized by adding a strongly acidic ion exchanger (AmBe1u1151), and then filtered through NuDo 8pirg Ce1®, washing with CH ₂ Cl ₂ . The filtrate was concentrated in vacuo and the residual yellow oily substance was purified by flash chromatography on silica gel (eluent: CH ₂ Cl ₂ / methanol = 19: 1), whereby pure tetrol 4 (1.95 g, 92%) was obtained.

A solution of tetrol 4 (1.0 g, 1.44 mmol), benzaldehyde dimethyl acetal (430 ml, 2.86 mmol) and camphorsulfonic acid (0.1 g, 0.43 mmol) in acetonitrile (20 ml) was stirred at room temperature . After 4 hours, another 0.15 g (0.65 mmol) of camphorsulfonic acid was added and the resulting mixture was stirred for another 6 hours at room temperature, and then heated at 35 ° C for 6 hours. After adding another 0.06 g (0, 26 mmol) of camphorsulfonic acid, the solution was stirred at room temperature for 6 hours. The reaction mixture was filtered through NuDo 8 Pyre Ce1®, washing with ethyl acetate. The filtrate was extracted by shaking, first with a saturated aqueous NaHCO ₃ solution, and then with a saturated sodium chloride solution, after which the organic phase was dried (No. 8O ₄ ). filtered and concentrated in vacuo to give 1.5 g of a crude product. The crude product was purified by flash chromatography on silica gel (CH ₂ Cl ₂ / MeOH = 39: 1), whereby the desired benzylideneacetal 5 (0.475 g) was obtained, and a mixture of less polar by-products (0.4 g). The latter product was once processed under the reaction conditions as described above and purified, resulting in another 0.08 g of benzylidene acetal 5. The total yield of compound 5 was 0.555 g (49%): ¹ H-NMR (500 MHz, C1) C1 _; ) δ 7.53-7.51 (m, 2H), 7.38-7.19 (m, 18H), 5.62 (s, 1H), 4.83 (d, 1 = 3.8 Hz, 1H), 4.77 (d, 1 = 12.1 Hz, 1H), 4.71 (d, 1 = 11.5 Hz, 1H), 4.70 (m, 1H), 4.66 (d, 1 = 12.0 Hz, 1H), 4.62 (d, 1 = 11.5 Hz, 1H), 4.51 (d, 1 = 11.1 Hz, 1H), 4.36-4.31 ( m, 2H), 4.22 (brd, 1 = 2.8 Hz, 1H), 4.06 (dd, 1 = 1.7, 12.3 Hz, 1H), 3.97 (dd, 1 = 2.9, 10.2 Hz, 1H), 3.92 (d, 1 = 12.0 Hz, 1H), 3.90 (dd, 1 = 3.8, 10.2 Hz, 1H), 3.76-3.68 (m, 3H), 3.53 (ddd, 1 = 4.9, 9.0, 11.0 Hz, 1H), 3.43 (br.s., 1H), 3 37 (d, 1 = 2.5 Hz, 1H),

2.57 (d, 1 = 8.0 Hz, 1H), 2.51 (s, 1H), 2.08 (m, 2H), 1.73 (brd, 1 = 9.5 Hz, 2H), 1.42-1.25 (m, 2H),

1.20 (br t, 1 = 11.2 Hz, 2H); 1.7 (d, 1 = 6.3 Hz, 3H); MS (RAV, TH6) 800 (M + YAN ₄ ), 783 (M + H).

СОО0п

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) was refluxed under argon for 2 hours. The reaction mixture was concentrated in vacuo and pentane was added to the residue, and then concentrated again. After adding dry СЗР (dried under high vacuum at 300 ° С, 0.068 g, 0.45 mmol) in an argon atmosphere, the mixture was again dried under high vacuum (30 min). After adding anhydrous

1,2-dimethoxyethane (1.5 ml), a solution of benzyl-K-3-phenyl-2-trifluoromethanesulfonyloxypropionate was added to the mixture [R. Oedegbesk, R. Przapzop V., Czekpb., Kadpagzop., 1. Sket. 8os. Regkt Tgapz. 1: 11-14 (1993)] (0.24 g, 0.62 mmol) in dry 1,2-dimethoxyethane (1.5 ml). The resulting mixture was intensively stirred at room temperature for 4 hours, and then at 40 ° C for 2 hours. After adding a 1M aqueous solution of KH ₂ PO _{4, the} mixture was diluted with water and extracted 3 times with ethyl acetate. The combined organic phases were extracted by shaking, first with a dilute aqueous solution of KR, and then with a saturated solution of sodium chloride. The organic phase was dried (No. 8O ₄ ). filtered and concentrated in a vacuum rotary evaporator, resulting in a crude product. The product was purified by flash chromatography on silica gel (elution in a gradient of ethyl acetate / toluene (1: 4) with 100% ethyl acetate), whereby ether 6 (0.045 g, 35%) and less polar precursor 5 (0.043 g, 44%) were obtained. ): ¹ H-NMR (250 MHz, COC13 δ 7.49 (broad d, 1 = 6.9, 2H), 7.37-7.05 (m, 28H), 5.36 (s, 1H ), 5.04 (d, 1 = 12.0 Hz, 1H), 4.98 (d, 1 = 12.0 Hz, 1H), 4.72-4.63 (m, 3H), 4.62 -4.48 (m, 4H), 4.31 (d, 1 = 11.2 Hz, 1H), 4.16 (m, 1H), 4.11 (d, 1 = 7.9 Hz, 1H) , 4.07 (d, 1 = 3.4 Hz, 1H), 3.88-3.79 (m, 2H), 3.76 (dd, 1 = 3.4, 10.3 Hz, 1H), 3.66 (d, 1 = 11.3 Hz, 1H), 3.62-3.47 (m, 2H), 3.44-3.35 (m, 1H), 3.36 (dd, 1 = 3.5, 9.6 Hz, 1H), 3.16-3.06 (m, 2H), 3.12 (br.s., 1H), 3.01 (dd, 1 = 8.4, 13 , 9 Hz, 1H), 2.03-1.86 (m, 2H), 1.93 (d, 1 = 2.0 Hz, 1H), 1.71-1.55 (m, 2H), 1.36-1.00 (m, 4H), 0.99 (d, 1 = 7.1 Hz, 3H).

Dioxane (2.5 ml), water (1.2 ml) and glacial acetic acid (0.1 ml) were added to a mixture of Pb (OH) ₂ / C (Reag1tap catalyst, 20% Pb content, 0.0 g) and protected compound 6 (0.0 g, 0.029 mmol). The contents of the flask were pumped out and purged several times with argon. After purging with hydrogen, the black reaction mixture was hydrogenated under slightly reduced hydrogen pressure at room temperature for 1 hour, and then filtered through a cellulose filter (pore size 45 μm). The filtrate was concentrated in vacuo and the residue was dissolved in water, and then concentrated several times again to remove excess acetic acid. A solution of this residue in water was passed through an EO \\ ex 50 ion-exchange column (Form No. +, column diameter 0.9 cm, length h, 5 cm), washing with deionized water. The clear filtrate was concentrated and purified by reverse phase chromatography (BP18 silica gel, column diameter 1.4 cm, length 7.0 cm, elution in a gradient of 40% MeOH / H ₂ O - 45% MeOH / H ₂ O - 50% MeOH / H ₂ O), as a result, the target molecule B1.1 (0.015 g, 78%) was obtained as a colorless solid: ¹ H-NMR (500 MHz, SES1 _s ) δ 7, s8-7, s0 (m, 4H), 7.29-7.2g (m, 1H), 4.92 (d, 1 = 4.0 Hz, 1H), 4.55 (q, 1 = 6.7 Hz, 1H), 4, h5 (q, 1 = 7.8 Hz, 1H), 4.11 (dd, 1 = 4.8, 8.5 Hz, 1H), h, 86 (d, 1 = 3.6 Hz, 1H), h, 84 (dd, 1 = h, h, 10.5 Hz, 1H), h, 74 (d, 1 = h, 5 Hz, 1H), h, 71 (dd, 1 = h, 9, 10, 5 Hz, 1H), h, 69-z, 62 (m, 3H), h, 50 (ddd, 1 = 1.0, 4.5, 7.1 Hz, 1H), h, 48h, 41 (m , 1H), s, 4s (dd, 1 = 8.0, 9.7 Hz, 1H), h, 24 (dd, 1 = h, 5, 9.7 Hz, 1H), h, 09 (dd, 1 = 4.6, 14.0 Hz, 1H), 2, 92 (dd, 1 = 8.8, 14.0 Hz, 1H), 2.06-1.97 (m, 2H),

1.6h (br.s., 2H), 1.24-1.14 (m, 4H), 1.1h (d, 1 = 7.0 Hz, 3H); ^1h-NMR (100.6 MHz, ART, Ό ₂ Θ) δ: 1z9,5 (C _h) 1z0,7 (2CH), 129.9 (2CH), 128.0 (CH), 100.8 (CH), 96.8 (CH), 84.0 (CH), 8h, s (CH), 79.6 (CH), 78.4 (CH), 75.6 (CH), 7h, s ( CH), 71.4 (CH), 70.9 (CH), 69.2 (CH), 67.7 (CH), 67.4 (CH), 62.8 (CH ₂ ), 40.6 ( CH ₂ ), s 0.9 (CH ₂ ), s 0.4 (CH ₂ ), 24.4 ( ₂ CH ₂ ), 16.6 (CH _s ); MS (RAV, THS): 595 (M + N), 573 (M + H).

A mixture of tetrol 4 (0.0-0.8 g, 0.055 mmol) and di-n-butyltin oxide (0.029 g, 0.117 mmol) in dry methanol (2.0 ml) was heated under reflux in an argon atmosphere. After 2.25 hours, a clear, colorless solution was concentrated in vacuo, and the residue was mixed with benzene and concentrated several times to remove excess methanol. After drying for 3 min under high vacuum, the residue was mixed under argon with С8Р (dried under high vacuum at З00 ° С, 0.0 g, 0.197 mmol) and anhydrous 1,2-dimethoxy ethane (0.4 ml). The mixture was cooled to 0 ° C. and a benzyl-K- solution was added via syringe

3-phenyl-2-trifluoromethanesulfonyloxypropionate [R. Gedebesk, Prgapopop V., Scheckp., Wadpagpopop., 1. Sket. 8os. Retksh Tgap 8.1: 11-14 (199z)] (0.085 g, 0.219 mmol) in anhydrous 1,2 dimethoxyethane (0.4 ml). Then the reaction mixture was warmed to room temperature and stirred for 1 h, after which it was stirred at 40 ° C for 2 h. After adding a 1M aqueous solution of KH ₂ PO _{4, the} mixture was diluted with water and extracted with CH ₂ Cl _{2 2} times. The combined organic phases were washed with an aqueous solution of the CD, and then dried (№ ₂ 8o _4), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel in two stages (first stage: 2% MeOH / CHC1 _s ; second stage: 45% ethyl acetate / toluene), whereby ether 8 was obtained as an oily substance (0.01 g, 25%) : ¹ H-NMR (250 MHz, SES 1 _h ) δ 7.407.00 (m, 25H), 5.15 (d, 1 = 11.6 Hz, 1H), 5.09 (d, 1 = 11.6 Hz , 1H), 4.89 (d, 1 = 11.8 Hz, 1H), 4.86 (d, 1 = 3.2 Hz, 1H), 4.77 (d, 1 = 11.6 Hz, 1H ), 4.69 (d, 1 = 12.0 Hz, 2H), 4.57 (d, 1 = 12.0 Hz, 1H), 4.56 (d, 1 = 11.8 Hz, 1H), 4, s5 (q, 1 = 6.5 Hz, 1H), 4.28 (dd, 1 = 4.0, 9.5 Hz, 1H), 4.11 (d, 1 = 7.6 Hz, 1H ), 4.02 s, 88 (m, 2H), s, 79 (dd, 1 = 7, s, 11.9 Hz, 1 H), s, 66 (br.s, 1 H), s, 6 s-z 40 (m, 5H), s, 22 (m, 1H), s, 10 (dd, 1 = 4.0, 14.0 Hz, 1H), s, 09 (br.s, 1H), s , 0h (dd, 1 = h, 5, 9, h Hz, 2H) , 2.90 (dd, 1 = 9.5, 14.0 Hz, 1H), 1.97-1.84 (m, 2H), 1.75 (d, 1 = 1.9 Hz, 1H), 1, 59 (br.s., 2H), 1.29-1.07 (m, 4H), 1.01 (d, 1 = 6.4 Hz, 3H).

B1.1

A mixture of 1,4-dioxane and water (4: 1, 2.0 ml) was added to the protected carbohydrate 8 (0.0z g, 0.0z2 mmol) and Pb / C (0.0z g, 10% Rb content), and then glacial acetic acid (0.1 ml) was added. The contents of the flask were pumped out and purged several times with argon. This procedure was repeated using hydrogen. The resulting mixture was hydrogenated with slightly increased hydrogen pressure and with vigorous stirring until thin layer chromatography (silica gel plates; nViOH: H ₂ O: acetone: glacial acetic acid: NΗ ₄ ΘΗ, 70:60: 50: 18: 1,5 ) did not indicate the absence of a precursor and its intermediates (about 3 hours). The resulting black suspension was filtered twice through a cellulose filter (pore size 45 μm), and then the filtrate was concentrated in vacuo. The residue was dissolved in water and the solution was passed through an ion exchange column (EOHEX 50, form No. +, column diameter 0.9 cm, length h, 5 cm), washing with deionized water. The filtrate was concentrated and purified by reverse phase chromatography (silica gel KR18, column 1.4 cm diameter, length 7.0 cm, eluting with a gradient of 40% MeOH / H ₂ O - 45% MeOH / H ₂ O - 50% MeOH / H ₂ O) as a result, the target molecule B1.1 (0.015 g, 78%) was obtained as a colorless solid.

Example B2. Getting connection No. In 1.2.

The aromatic compound B1.1 (0.152 g, 0.256 mmol) and 5% Vi / A1 ₂ O ₃ (0.2 g) were dissolved in water (5.5 ml), dioxane (3.5 ml) and acetic acid (1.0 ml). Air was replaced by repeated pumping, first with argon, and then with hydrogen. The black suspension was hydrogenated under slightly elevated hydrogen pressure with vigorous stirring for 2 days, and then filtered through a cellulose filter (pore size 45 μm). A clear, colorless solution was concentrated in vacuo, and the residue was dissolved in water and concentrated several times to remove excess acetic acid. A solution of the crude product in water was filtered through an Eo \\ ex 50 ion-exchange column (Form No. +, length 9 cm, diameter 1.3 cm), and then the column was washed with water. The filtrate was concentrated in vacuo, and then the residue (0.16 g) was purified by gel filtration on Vu-Cc1 P2 (particle size 65 μm, column diameter 2.5 cm, length 100 cm, eluent: water; flow rate 0.55 ml / min .; detection at 215 nm), after which it was subjected to reverse phase chromatography (silica gel Megsk KR18, eluent: 55% MeOH / H ₂ O), whereby the target molecule B1.2 (0.11 g, 73%) was obtained in the form of white solid flakes ( after lyophilization). ¹ NNMR (500 MHz, O ₂ O) δ 4.93 (d, 1 = 3.8 Hz, 1H),

4.58 (q, 1 = 6.4 Hz, 1H), 4.43 (d, 1 = 7.5 Hz, 1H),

3.91 (dd, 1 = 3.5. 9.0 Hz, 1H), 3.88-3.83 (m, 2H),

3.75 (d, 1 = 3.3 Hz, 1H), 3.73-3.64 (m, 4H), 3.573.53 (m, 1H), 3.49 (dd, 1 = 7.3. 9.0 Hz, 1H), 3.50-

3.43 (m, 1H), 3.33 (dd, 1 = 3.2. 9.2 Hz, 1Η). 2.101.99 (m, 2H), 1.73 (broad d, 1 = 12.0 Hz, 1H), 1.69-

1.44 (m, 9H), 1.29-1.07 (m, 7H), 1.14 (d, 1 = 6.5 Hz, 3H), 0.96-0.80 (m, 2H); MS (GAV, ΤΗ6) 623 (M + no.). 601 (M + H).

Example B 3. Preparation of compound No. B1.3.

Suspension containing benzylideneacetal 9 (0.5 g, 1.60 mmol) (EP 671406). sodium cyanoborohydride (0.9 g, 14.3 mmol), activated 4A molecular sieves (1.0 g) and dry tetrahydrofuran (30 ml) were cooled to 0 ° С in a nitrogen atmosphere. The pH of the mixture was adjusted to 1 by careful addition of a saturated solution of gaseous hydrogen chloride in anhydrous diethyl ether. The suspension was stirred at 0 ° C, and the pH was maintained at 1 by carefully adding a solution of HCl in ether. After 10 hours, a cold saturated aqueous sodium bicarbonate solution (30 ml) was added. The organic phase was separated and the aqueous phase was extracted twice with ethyl acetate (70 ml each time). The combined organic phases were dried (Na ₂ 8 O ₄ ). filtered and concentrated in vacuo to give 1.3 g of a crude product. This product was purified by flash chromatography on silica gel (chloroform / isopropanol = 19: 1) and the desired 6-benzyl ether 10 (0.3 g, 60%) and some less polar by-product (0.045 g) were obtained: ¹ H-NMR (250 MHz, SES1 ₃ ) δ 7.47-7.33 (m, 5H), 4.64 (s, 2H), 4.37 (d, 1 = 9.3 Hz, 1H), 4.13 (br.s., 1 = 3.0 Hz, 1H), 3.893.69 (m, 4H), 3.64 (dd, 1 = 3.1. 9.0 Hz, 1H), 2.89

2.70 (m, 2H), 1.38 (t, 1 = 7.3 Hz, 3H).

B)

5E1

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 ° C for 3.5 hours, and then a 1M aqueous solution of KH ₂ PO _{4 was} added, and the mixture was extracted 3 times with methylene chloride. The combined organic phases were washed with water, dried (№ ₂ 8o _4), filtered and concentrated in vacuo to give 1.0 g of crude product. The product was purified by flash chromatography on silica gel (hexane / ethyl acetate = 4: 1). as a result, tribenzoate 11 was obtained in the form of yellowish crystals (0.517 g, 88%). ¹ H-NMR (250 MHz, SES1 ₃ ) δ 8.09 (d, 1 = 7.5 Hz, 2Н), 8.02 (d, 1 = 7.5 Hz, 2Н), 7.85 (d, 1 = 7.5 Hz, 2Н ), 7.68 (t, 1 = 7.4 Hz, 1Н), 7.63-7.39 (m, 7Н), 7.38-7.23 (m, 6Н), 6.06 (d, 1 = 3.3 Hz, 1Н), 5.85 ( t, 1 = 10.0 Hz, 1Н), 5.66 (dd, 1 = 3.5. 10.0 Hz, 1Н), 4.88 (d, 1 = 10.0 Hz, 1Н), 4.60 (d, 1 = 11.9 Hz , 1H), 4.49 (d, 1 = 11.9 Hz, 1H), 4.23 (t, 1 = 6.3 Hz, 1H), 3.84-

3.64 (m, 2H), 3.02-2.80 (m, 2H), 1.38 (t, 1 = 7.5 Hz, 3H).

ΟΒζ

Dry methylene chloride (CH ₂ Cl ₂ ) (8.0 ml) was added to a mixture of thioglycoside 11 (0.377 g, 0.60 mmol), glycosyl acceptor 2 (0.32 g, 0.60 mmol) (EP 671409) and activated 4 A molecular sieve (2.5 g) in an argon atmosphere. In a second round bottom flask, a suspension of ΌΜΤ8Τ (0.39 g, 1.51 mmol) and activated 4 A molecular sieves (0.8 g) in anhydrous methylene chloride (5.0 ml) was obtained. Both suspensions were stirred at room temperature for 3.5 h. To a glycosyl donor / acceptor mixture, 1 ml of ΌΜΤ8ΌΜΤ suspension was added in three portions over three hours. The yellowish reaction mixture was stirred at room temperature for another 1.5 hours, and then filtered through NuDo 8 Pyreg Ce1®, washing with CH ₂ Cl ₂ . The filtrate was extracted with shaking with an aqueous solution of No. ₁ HCO ₃ , and then with water. The aqueous phases were again extracted with CH ₂ Cl ₂ , and the combined organic phases were dried (Haa ₂ 8O ₄ ), filtered and concentrated in vacuo, whereby 0.67 g of crude product was obtained. The product was purified 2 times using flash chromatography on silica gel (first chromatography step: toluene / ethyl acetate = 14: 1; second chromatography step: hexane / ethyl acetate = 4: 1), and product 12 (0.404 g, 61%) was obtained as colorless

and sodium methoxide (0.169 g, 3.12 mmol) in methanol (65 ml) was stirred at room temperature for 6 hours. Then, the base was neutralized by the addition of an acid ion exchanger (Amber15!) and the suspension was filtered through Hudo 8 Pyre Ce1®. The filtrate was then concentrated in vacuo and the residual yellow oily substance (3.35 g) was purified by flash chromatography on silica gel (CH ₂ Cl ₂ / MeOH, 19: 1), whereby triol 13 (2.15 g, 88) was obtained %) as a colorless foam: п-NMR (500 MHz, C1) C1 _; ) δ 7.41-7.24 (m, 20H), 4.99 (d, 1 = 3.6 Hz, 1H), 4.95 (d, 1 = 11.2 Hz, 1H), 4.83 (d, 1 = 11.2 Hz, 1H), 4.77 (d, 1 = 11.3 Hz,

1H), 4.69 (d, 1 = 11.3 Hz, 1H), 4.68 (d, 1 = 11.5 Hz,

1H), 4.61 (d, 1 = 11.5 Hz, 1H), 4.53 (s, 2H), 4.34 (d, 1 = 7.0 Hz, 1H), 4.33 (m, 1H), 4.04 (dd, 1 = 3.7, 10.1 Hz, 1H), 4.02 (m, 1H), 3.97 (dd, 1 = 2.9, 10.0 Hz, 1H ), 3.81-3.77 (m, 1H), 3.77 (dd, 1 = 6.0, 9.4 Hz, 1H), 3.70 (dd, 1 = 5.0, 9.6 Hz, 1H), 3.65 (d, 1 = 2.0 Hz, 1H), 3.63-3.54 (m, 4H), 2.95 (br s, 1H), 2.60 (br d , 1 = 2.0 Hz, 2H), 2.07 (m, 1H), 2.01 (m, 1H), 1.69 (m, 2H), 1.45-1.30 (m, 2H) 1.29-1.18 (m, 2H); 1.10 (d, 1 = 6.5 Hz, 3H); MS (EAB, ΤΗ6) 783 (MH), 693 (M-PCH ₂ ).

A mixture of triol 13 (0.515 g, 0.656 mmol) and di-n-butyltin oxide (0.245 g, 0.984 mmol) in anhydrous methanol (15 ml) was heated under reflux in a nitrogen atmosphere for 2 hours. The clear solution was concentrated in vacuo, dissolved in benzene and 3 times concentrated to remove excess methanol. The residues were dried under high vacuum, and then anhydrous C&E was added in an argon atmosphere (dried under high vacuum at 300 ° C, 0.5 g, 3.29 mmol), after which anhydrous 1,2-dimethoxyethane (4.0 ml) and a solution of benzyl-I-3-azido-2-trifluoromethanesulfonyloxy propionate A1 (1.16 g, 3.28 mmol) in anhydrous

1,2-dimethoxyethane (8.0 ml). The reaction mixture was stirred at room temperature for 6 hours, and then a 1M aqueous solution of KH2PO4 (60 ml) was added. The resulting mixture was extracted 3 times with ethyl acetate and the combined organic phases are washed first with aqueous sodium bicarbonate and then sodium chloride solution, dried (№ ₂ 8o _4), filtered and concentrated in vacuo. The oily residue (1.15 g) was purified by flash chromatography on silica gel (the product was first eluted with a toluene / ethyl acetate mixture (4: 1), and then the precursor was eluted with a CH ₂ Cl ₂ / MeOH mixture, 19: 1), resulting in ether 14 (0.488 g, 75%) was obtained as a colorless foam and precursor 13 (0.075 g, 15%). Product 14: Ή-NMR (500 MHz, C1) C1 _; ) δ 7.40-7.22 (m, 25H), 5.25 (d, 1 = 11.7 Hz, 1H), 5.16 (d, 1 = 11.8 Hz, 1H), 4.96 (d, 1 = 10.9 Hz, 1H), 4.95 (d, 1 = 3.1 Hz, 1H), 4.82 (d, 1 = 10.8 Hz, 1H), 4.76 (d , 1 = 11.1 Hz, 1H), 4.72-4.66 (m, 2H), 4.62 (d, 1 = 11.0 Hz, 1H), 4.57 (dd, 1 = 3, 2, 6.0 Hz, 1H), 4.53 (d, 1 = 11.3 Hz, 1H), 4.50 (d, 1 = 11.3 Hz, 1H), 4.39 (q, 1 = 6.2 Hz, 1H), 4.31 (d, 1 = 7.4 Hz, 1H), 4.04 (br.s., 1H), 4.02 (dd, 1 = 3.0, 9 5 Hz, 1H), 3.99 (dd, 1 = 2.4, 9.5 Hz, 1H), 3.82 (ddd, 1 = 1.9, 7.3, 8.9 Hz, 1H) 3.77 (dd, 1 = 6.0, 9.2 Hz, 1H), 3.783.74 (m, 1H), 3.70-3.65 (m, 2H), 3.63 (dd, 1 = 3.0, 12.3 Hz, 1H), 3.58 (ddd, 1 = 4.2, 8.0, 9.5 Hz, 1H), 3.53 (dd, 1 = 6.0, 12 5 Hz, 1H), 3.55-3.51 (m, 1H),

3.44 (dd, 1 = 3.1, 9.0 Hz, 1H), 2.90 (dd, 1 = 1.2, 1.8 Hz, 1 OH), 2.86 (d, 1 = 2 , 0 Hz, 1 OH), 2.09-1.96 (m, 1H), 1.68 (m, 2H), 1.44-1.18 (m, 4H), 1.11 (d, 1 = 6.3 Hz, 3H); MS (EAB, N6) 1010 (M + Na), 984 ^ + N + 2 ^^), 962 (M + 3H-N ₂ ).

P1 / Ba8O ₄ (0.35 g, P1 content: 5%) was added to a solution of azide 14 (0.11 g, 0.111 mmol) in ethyl acetate (12 ml). The contents of the flask were pumped out and purged several times with argon. After purging the flask with hydrogen, the mixture was hydrogenated at atmospheric pressure while stirring vigorously. After 2.5 hours, the hydrogenation was stopped and the suspension was filtered through a cellulose filter (pore size 45 μm), and then the filtrate was concentrated in vacuo. The residue (0.115 g) was purified using flash chromatography on silica gel (eluent: CH ₂ Cl ₂ / MeOn = 19: 1), resulting in not only the desired amine 16 (0.055 g, 51%), but also less polar precursor 14 (0.042 g, 38%). The resulting amine 16 is unstable and can be used directly in subsequent experiments.

¹⁷ B1.3 (1) Preparation of a benzamide intermediate 17.

Diisopropylethylamine (3.5 ml, 0.02 mmol) and benzotriazole-1-yloxytripyrrolidinephosphonium hexafluorophosphate (RuBOP) (0.012 g, 0.0271 mmol) were added at 0 ° C to a solution of β-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). The reaction mixture was stirred for 45 minutes, and then saturated aqueous sodium bicarbonate was added. Then the mixture was extracted 3 times with methylene chloride, and the combined organic phases were washed first with a 1 M aqueous solution of KH ₂ PO ₄ (the pH was adjusted to 1-2 by adding 1 M aqueous HCl) and then with an aqueous solution of NaHCO ₃ , after which SchA ₂ 8O _{4 was} dried), filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluted in a gradient of 35% ethyl acetate / toluene - 40% ethyl acetate / toluene), whereby benzamide 17 (0.0098 g, 68%) was obtained.

(ίί) Release compound 17.

Dioxane (1.5 ml), water (0.7 ml) and glacial acetic acid (0.1 ml) were added to a mixture of P6 (OH) ₂ / C (Reag1tap catalyst, content of P6 = 20%, 0.011 g) and benzyl ether 17 (0.0097 g, 0.0091 mmol). The flask was pumped out and purged several times with argon. Then the flask was purged with hydrogen and the black mixture was hydrogenated at slightly elevated pressure for 14 hours while stirring vigorously. The resulting mixture was filtered through a cellulose filter (pore size 45 μm) and the filtrate was concentrated in vacuo. The residue was dissolved in water and concentrated several times to remove excess acetic acid. Then a solution of the crude product in a small amount of water was passed through an ion-exchange column (1Eo \\ ex 50, form No. +, column diameter 0.9 cm, length 3.5 cm), washing with deionized water. After the filtrate was concentrated in vacuo, the residue (0.007 g) was purified by gel filtration on Vue-6e1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.59 ml / min, detection at 230 nm), and then subjected to reverse phase chromatography (silica gel Megsk KR18, elution in the gradient of 37% MeOH / H ₂ O - 45% MeOH / H ₂ O), as a result, the target molecule B1.3 was obtained (3, 3 mg, 58%) as white solid flakes (after lyophilization). ¹ H-NMR (500 MHz, 1TO) δ 7.74 (d, 1 = 7.5 Hz, 2H), 7.57 (t, 1 = 7.2 Hz, 1H), 7.48 (t, 1 = 7.6 Hz, 2H), 4.92 (d, 1 = 4.0 Hz, 1H), 4.57 (q, 1 = 6.7 Hz,

1H), 4.44 (d, 1 = 7.8 Hz, 1H), 4.17 (dd, 1 = 3.9, 8.1

Hz, 1H), 3.94 (d, 1 = 3.0 Hz, 1H), 3.86 (d, 1 = 3.5 Hz, 1H), 3.84 (t, 1 = 4.0 Hz, 1H), 3.74 (d, 1 = 3.5 Hz, 1H), 3.75-3.65 (m, 4H), 3.60-3.52 (m, 3H), 3.49-3 44 (m, 1H), 3.45 (dd, 1 = 3.5, 9.3 Hz, 1H), 2.03 (m, 2H),

1.64 (br s, 2H), 1.26-1.13 (m, 4H), 1.11 (d, 1 = 6.5 Hz, 3H); MS (RAB, ΤΗ6): 660 (M + No.), 638 (M + H).

Example B4 Obtaining compound No. B 1.4.

(a) Preparation of Amide Intermediate 19. Diisopropylcarbodiimide (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, 0.1 mmol) and 1-hydroxybenzotriazole (0.025 g, 0.185 mmol) in anhydrous THF (1.0 ml). The reaction mixture was stirred for 30 minutes and then concentrated in vacuo. The residue (0.09 g) was purified using flash chromatography on silica gel in two stages (eluent for the first stage of chromatography: methylene chloride / methanol = 39: 1; eluent for the second stage of chromatography: methylene chloride / isopropanol = 39: 1), as a result which gave pure amide 19 (0.031 g, 86%).

(b) Release 19. Dioxane (2.0 ml), water (1.0 ml) and glacial acetic acid (0.5 ml) were added to a mixture of P6 (OH) ₂ / C (Reag1tap catalyst, 20% P6 content, 0.035 g) and benzyl ether 19 (0.031 g, 0.0283 mmol). The flask was pumped out and purged several times with argon. Then the flask was purged with hydrogen and the black mixture was hydrogenated under slightly increased hydrogen pressure for 18 hours with vigorous stirring. The resulting mixture was filtered through a cellulose filter (pore size 45 μm), and the filtrate was concentrated in vacuo. The resulting residue was mixed with toluene (about 2 ml) and concentrated several times to remove excess acetic acid. A solution of the crude product (0.021 g) in a small amount of water was passed through an ion-exchange column (Όο \\ υχ 50, form Να +, column diameter 0.9 cm, length 3.5 cm), washing with deionized water. After the filtrate was concentrated in vacuo, the residue (0.02 g) was purified by reverse phase chromatography on Meскsk YP18 silica gel (column diameter 1.2 cm, length 6 cm, eluent: 60% MeOH / H ₂ O), and then the gel was subjected filtration on Vu-6e1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water, flow rate 0.5 ml / min, detection at 215 nm), whereby the target B1 molecule was obtained .4 (0.014 g, 74%) as colorless solid flakes (after lyophilization). ¹ H-NMR (500 MHz, 1TO) δ 7.32 (m, 2H), 7.24 (m, 3H), 4.93 (d, 1 = 4.1 Hz, 1H), 4.57 (q , 1 = 6.7 Hz, 1H), 4.40 (d, 1 = 8.0 Hz, 1H), 3.9-3.84 (m, 3H), 3.753.66 (m, 5H), 3 63 (dd, 1 = 3.8, 14.0 Hz, 1H), 3.53 (broad dd, 1 = 4.5, 7.5 Hz, 1H), 3.49 (dd, 1 = 7.9 , 9.6 Hz, 1H), 3.50-3.44 (m, 1H), 3.23 (dd, 1 = 7.8, 14.0 Hz, 1H), 3.15 (dd, 1 = 3.2, 9.8 Hz, 1H), 2.88 (br.t., 1 = 7.3 Hz, 2H), 2.59-2.45 (m, 2H), 2.09 (m, 1H), 2.03 (m, 1H), 1.67 (br s, 2H), 1.30-1.15 (m, 4H),

1.13 (d, 1 = 6.6 Hz, 3H); MS (PAB) 666 (M + H), 643 (M + H-Na).

Example B5 Getting connection No. B1.5.

(a) Preparation of Amide Intermediate 21

Diisopropylcarbodiimide (16 ml, 0.103 mmol) was added at room temperature with stirring to a solution of amine 16 (0.026 g, 0.027 mmol), sodium 4-hydroxybutyrate (0.010 g, 0.079 mmol) and 1-hydroxybenzotriazole (0.020 g, 0.148 mmol) a mixture of anhydrous THF (1.0 ml) and DMF (0.2 ml). After 4 hours, another 0.2 ml of DMF (dimethylformamide) was added and the mixture was stirred for 13 hours. After volatiles (including DMF) were distilled off under high vacuum, the residue (0.09 g) was purified by flash chromatography on silica gel (CH ₂ C1 ₂ / MeOH = 29: 1), whereby amide 21 (0.02 g, 71%) was obtained.

(b) Release 21. Dioxane (2.0 ml), water (1.0 ml) and glacial acetic acid (0.5 ml) were added to the mixture P6 (OH) ₂ / C (Reag1tap catalyst, P6 content 20%, 0.04 g) and benzyl ether 21 (0.036 g, 0.034 mmol). The contents of the flask were pumped out and purged several times with argon. Then the flask was purged with hydrogen and the black mixture was hydrogenated under slightly increased hydrogen pressure for 18 hours, while stirring vigorously. The resulting mixture was filtered through a cellulose filter (pore size 45 μm), and the filtrate was concentrated in vacuo. The residue was mixed with toluene (about 2 ml) and concentrated several times to remove excess acetic acid. A solution of the crude product (0.022 g) in a small amount of water was passed through an ion exchange column (Όο \\ υχ 50, form No. +, column diameter 0.9 cm, length 3.5 cm), washing with deionized water. After the filtrate was concentrated in vacuo, the residue (0.02 g) was purified by gel filtration on Vue-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.5 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk YP18, column diameter 1.2 cm, length 6 cm, eluent: MeOH / H ₂ O, 1: 4), whereby the target was obtained B1.5 molecule (0.015 g, 70%) as colorless solid flakes (after lyophilization). ¹ Η NMR (500 MHz, 1TO) δ 4.93 (d, 1 = 3.9 Hz, 1H),

4.59 (q, 1 = 6.7 Hz, 1H), 4.47 (d, 1 = 7.5 Hz, 1H), 4.04 (dd, 1 = 3.8, 7.3 Hz, 1H ), 3.92 (d, 1 = 3.2 Hz, 1H), 3.86 (dd, 1 = 3.4, 10.2 Hz, 1Η), 3.75 (d, 1 = 3.5 Hz , 1H), 3.74-3.65 (m, 4H), 3.62 (dd, 1 = 3.9, 14.0 Hz, 1Η), 3.59-3.51 (m, 2H), 3.55 (t, 1 = 6.3 Hz, 2H), 3.50-3.44 (m, 1H), 3.43 (dd, 1 = 3.5, 9.8 Hz, 1Η), 3 38 (dd, 1 = 7.5, 14.0 Hz, 1Η), 2.27 (t, 1 = 7.4 Hz, 2H), 2.11-2.00 (m, 2H), 1, 77 (n, 1 = 7.1 Hz, 2H), 1.65 (br s, 2H), 1.29-1.13 (m, 4H), 1.15 (d, 1 = 6.8 Hz , 3H), MS (PAB) 643 (M + H-Na), 620 (M + H), 598 (M + 2H-Na).

Example B6 Getting connection No. B1.6.

Dioxane (2.0 ml), water (1.0 ml) and glacial acetic acid (0.5 ml) were added to a mixture of P6 (OH) ₂ / C (Reag1tap catalyst, 20% P6 content, 0.03 g) and azide 14 (0.03 g, 0.03 mmol). The contents of the flask were pumped out and purged several times with argon. After purging the flask with hydrogen, the black mixture was hydrogenated under slightly increased hydrogen pressure for 16 hours, while stirring vigorously. The resulting mixture was filtered through a cellulose filter (pore size 45 μm) and the filtrate was concentrated in vacuo. The residue was purified by gel filtration on Vue-6e1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.5 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk YR18, column diameter 1.2 cm, length 7 cm, eluent: 25% MeOH / H ₂ O), and the target molecule B1.6 (0.011 g, 70%) was obtained as a colorless flocculent solid product (after lyophilization). ¹ H-NMR (500 MHz, O ₂ O) δ 4.93 (d, 1 = 3.9 Hz, 1H), 4.58 (q, 1 = 6.7 Hz, 1Η),

4.48 (d, 1 = 7.9 Hz, 1H), 4.22 (dd, 1 = 3.7, 8.4 Hz, 1H), 3.99 (d, 1 = 3.1 Hz, 1Η), 3.86 (dd, 1 = 3.3, 9.9 Hz, 1Η), 3.75 (d, 1 = 3.3 Hz, 1Η), 3.74-3.65 (m, 4H), 3 , 61-3.55 (m, 2H), 3.50 (dd, 1 = 3.0, 9.3 Hz, 1Η),

3.48 (m, 1H), 3.35 (dd, 1 = 3.7, 12.9 Hz, 1Η), 3.16 (dd, 1 = 8.5, 13.5 Hz, 1Η), 2.10 -2.00 (m, 2H), 1.65 (m, 2H), 1.29-1.15 (m, 4H), 1.14 (d, 1 = 6.5 Hz, 3H); MS (EAB, THS) 510 (M-H).

Example B7 Getting connection No. In 1.7.

Amine B1.6 (0.09 g, 0.176 mmol) was dissolved in anhydrous methanol (1.5 ml) and CH ₂ Cl ₂ (1.8 ml), and then activated 3 A molecular sieves (about 0.2 g) were added. , cinnamaldehyde (24 μl, 0.19 mmol) and acetic acid (9 μl). The yellowish suspension was stirred for 2 minutes, and then No. 1BH ₃ (CH) (0.018 g, 0.286 mmol) was added. After 1.5 hours, the mixture was filtered through a cellulose filter (pore size 45 μm), and the filter was washed with a methanol / methylene chloride mixture (1: 1), and then the filtrate was concentrated in vacuo. The vitreous residue was dissolved in water (5 ml), and the solution was acidified (to a pH of about 1-2) with 1M hydrochloric acid (0.7 ml). The turbid solution was again filtered through a cellulose filter (pore size 45 μm), and then the filtrate was adjusted to pH = 7 by adding a 1 M sodium hydroxide solution (about 1 ml) and concentrated. The residue was purified by gel filtration on Vue-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length 100 cm, eluent: water, flow rate 0.6 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography on silica gel (silica gel Megsk KR18, elution in a gradient of 50% MeOH / H ₂ O - 70% MeOH / H ₂ O), resulting in the desired molecule 1.7 (0.003 g, 27%) as white hard flakes (after lyophilization). ¹ H-NMR (500 MHz, 1CO) δ 7.48 (d, 1 = 8.0 Hz, 2H), 7.41-7.31 (m, 3H),

6.83 (d, 1 = 15.4, 7.0 Hz, 1H), 6.26 (dt, 1 = 15.4, 7.0 Hz, 1H), 4.92 (d, 1 = 3.8 Hz , 1H), 4.56 (q, 1 = 6.3 Hz, 1H), 4.43 (d, 1 = 7.6 Hz, 1H), 4.31 (dd, 1 = 3.5, 8, 2 Hz, 1H), 3.98 (d, 1 = 3.0 Hz, 1H), 3.88-3.81 (m, 2H),

3.84 (d, 1 = 6.0 Hz, 1H), 3.76-3.63 (m, 5H), 3.603.51 (m, 2H), 3.49 (dd, 1 = 3.0, 10, 4 Hz, 1H), 3.49-

3.41 (m, 1H), 3.41 (dd, 1 = 3.5, 13.2 Hz, 1H), 3.26 (dd, 1 = 8.5, 13.2 Hz, 1Η), 2 02 (m, 2H), 1.64 (br s, 2H), 1.27-1.12 (m, 4H), 1.12 (d, 1 = 6.3 Hz, 3H); MS (EAB, THS) 650 (M + N), 628 (M + H).

Example B8 Getting connection No. In 1.8.

A solution of amino acid B1.7 (0.01 g, 0.0159 mmol) in a 1M aqueous solution of No. ₁ HCO ₃ (0.1 ml) was cooled to 0 ° C while stirring vigorously, and then a 1M solution of benzoyl chloride in benzene was added (16 , 0 μl). After 40 minutes, 8.0 μl of benzoyl chloride solution was added, after 130 minutes another 3.0 μl was added, and after

3.5 h for another 1.0 μl. After 4 hours, the reaction mixture was diluted with water and extracted with methylene chloride to remove excess reagent. The aqueous phase was concentrated in vacuo, and the residue was purified by gel filtration on VyuSe1 P2 (particle size 65 μm, column diameter

2.5 cm, length 35 cm, eluent: water; flow rate 0.49 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk KP18, elution in a gradient of 60% MeOH / H2O - 70% MeOH / H2O), resulting in the desired molecule B1 .8 (7.9 mg, 66%) as white solid flakes (after lyophilization). ¹ H-NMR (500 MHz, E ₂ O) δ: mixture (1.4: 1) of rotamers, characteristic signals: 7.52-7.24 (m, 10H, 2xPb), 6.71 (d, 1 = 15.5 Hz, 0.42H, PkSN = CH), 6.42 (dt, 1 = 15.5, 6.1 Hz, 0.42H, PkSN = CH), 6.39 (d, 1 = 15, 5 Hz, 0.58H, PkSN = CH), 6.13 (dt, 1 = 15.5, 5.6 Hz, 0.58H, PkSN = CH), 4.92 (d, 1 = 4.0 Hz , 1H, En-1H), 1.16 (d, 1 = 7.0 Hz, 1.26H, His-6H), 1.11 (d, 1 = 6.8 Hz, 1.74 N, His-6H ); MS (EAB, THS) 776 (M + N), 754 (M + H).

Example B9 Obtaining compounds No. B1.9 and B1.10.

The methylene chloride solution of just distilled benzaldehyde (0.083 g in 1.0 ml of CH ₂ Cl ₂ , 0.1 ml, 0.078 mmol), activated 3 A molecular sieves (0.1 g) and glacial acetic acid (5 μl, 0.087 mmol ) was added to a solution of amino acid B1.6 (0.04 g, 0.078 mmol) in MeOH / CH ₂ Cl ₂ (1: 1, 1.0 ml). The suspension was stirred at room temperature and after 2 minutes No. ₃ (ί.'Ν) (0.008 g, 0.129 mmol) was added. After 2.5 hours, another 15 μl of benzaldehyde solution was added and the mixture was stirred for another 1 hour. The reaction mixture was diluted with water, acidified with diluted acetic acid, filtered through a cellulose filter (pore size 45 μm), and then the filtrate was adjusted to pH = 8- 9 by adding 1M aqueous sodium bicarbonate solution, after which it was concentrated. The residue was purified by gel filtration on B1o-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent; water; flow rate 0.5 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk KR18, elution in a gradient of 35% MeOH / H ₂ O - 60% MeOH / H ₂ O), resulting in monobenzylamine B1.9 (0.020 g, 41%) and dibenzylamine B1.10 (0.005 g, 9%). Monobenzylamine B 1.9: ¹ H-NMR (500 MHz, 1EO) δ 7.45 (s, 5H), 4.93 (d, 1 = 4.0 Hz, 1H), 4.57 (q, 1 = 6, 7 Hz

1H), 4.45 (d, 1 = 7.6 Hz, 1H), 4.33 (dd, 1 = 3.8, 8.8

Hz, 1H), 4.28 (d, 1 = 13.3 Hz, 1H), 4.24 (d, 1 = 13.3 Hz, 1H), 3.99 (d, 1 = 3.1 Hz, 1H), 3.85 (dd, 1 = 3.5, 10.2 Hz, 1H), 3.74-3.65 (m, 5H), 3.59-3.54 (m, 2H),

3.49 (dd, 1 = 3.2, 9.7 Hz, 1H), 3.48-3.44 (m, 1H),

3.42 (dd, 1 = 3.7, 13.2 Hz, 1H), 3.26 (dd, 1 = 8.9, 13.2 Hz, 1H), 2.04 (m, 2H), 1 65 (br s, 2H), 1.28-1.14 (m, 4H), 1.12 (d, 1 = 6.7 Hz, 3H); MS (EAB, THS) 624 (M + No.), 602 (M + H).

Dibenzylamine B1.10: ¹ H-NMR (500 MHz, E ₂ O) δ: 6H α signals with respect to N are very broad at room temperature (d 4.10-3.60, 4H and 3.12-2 67, 2H): δ 7.38 (s, 10H), 4.93 (d, 1 = 4.0 Hz, 1H), 4.60 (q, 1 = 6.6 Hz, 1H), 4, 43 (d, 1 = 8.0 Hz, 1H), 4.23 (dd, 1 = 3.6, 8.5 Hz, 1H), 3.88-3.83 (m, 2H), 3.75 -3.63 (m, 5H), 3.56 (dd, 1 = 8.0, 9.3 Hz, 1H), 3.53-3.44 (m,

2H), 3.32 (dd, 1 = 3.0, 9.5 Hz, 1H), 2.13-1.98 (m,

2H), 1.66 (br s, 2H), 1.31-1.10 (m, 4H), 1.14 (d, 1 = 6.6 Hz, 3H); MS (ELV, THS) 714 (M + N), 692 (M + H).

Example B10 Obtaining compounds No. B1.11 and No. B1.12.

A 1M methylene chloride solution of isobutyraldehyde (0.156 ml), activated 3 A molecular sieves (0.2 g) and glacial acetic acid (10 μl, 0.17 mmol) were added to the solution of amino acid B1.6 (0.08 g, 0.156 mmol) in methanol / methylene chloride (1: 1, 2.0 ml). The resulting suspension was stirred at room temperature and after 1 min NaBH3 (CN) (0.016 g, 0.258 mmol) was added. After 60 min, the reaction mixture was diluted with water and filtered through a cellulose filter (pore size 45 μm), and then the filtrate was adjusted to pH = 8-9 by adding a 1 M aqueous solution of sodium bicarbonate and concentrated. The residue was purified by gel filtration on B1Ce1 P2 (particle size 65 μm, column diameter

2.5 cm, length 35 cm, eluent: water; flow rate 0.5 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk KP18, elution in a gradient of 35% MeOH / H ₂ O - 50% MeOH / H ₂ O) and monoisobutylamine B1 was obtained .11 (0.041 g, 46%) and diisobutylamine B1.12 (0.01 g, 10%). Monoisobutylamine B1.11: ¹ H-NMR (500 MHz, E ₂ O) δ 4.92 (d, 1 = 4.0 Hz, 1H), 4.59 (q, 1 = 6.7 Hz, 1H), 4.47 (d, 1 = 7.6 Hz, 1H), 4.29 (dd, 1 = 4.0, 9.0 Hz, 1H), 3.98 (d, 1 = 3.5 Hz, 1H ), 3.85 (dd, 1 = 3.3, 10.0 Hz, 1H), 3.76-3.65 (m, 5H), 3.56 (dd, 1 = 7.5, 9.3 Hz, 1H), 3.59-3.54 (m, 1H), 3.50 (dd, 1 = 3.0, 9.7 Hz, 1H), 3.50-3.43 (m, 1H) , 3.34 (dd, 1 = 3.9, 13.0 Hz, 1H), 3.20 (dd, 1 = 9.2, 13.2 Hz, 1H), 2.90 (dd, 1 = 7 6, 12.0 Hz, 1H), 2.86 (dd, 1 = 7.3, 12.0 Hz, 1H), 2.111.99 (m, 2H), 1.96 (non, 1 = 6, 9 Hz, 1H), 1.65 (m, 2H), 1.28-1.11 (m, 4H), 1.14 (d, 1 = 6.6 Hz, 3H), 0.94 (d, 1 = 6.6 Hz, 6H); MS (EAB, THS) 590 (M + N), 568 (M + H). Diisobutylamine B1.12: ¹ H-NMR (500 MHz, 1EO) δ 4.92 (d, 1 = 4.1 Hz, 1H), 4.59 (q, 1 = 6.7 Hz, 1H), 4, 46 (d, 1 = 7.1 Hz, 1H), 4.36 (t, 1 = 6.6 Hz, 1H), 4.02 (br s, 1H), 3.85 (dd, 1 = 3 , 3, 10.3 Hz, 1H), 3.76-3.66 (m, 5H), 3.57 (dd, 1 = 4.7,

7.5 Hz, 1H), 3.55-3.50 (m, 2H), 3.49-3.39 (m, 3H), 3.07 (br s, 4H), 2.12 (non , 1 = 6.8 Hz, 2H), 2.121.99 (m, 2H), 1.65 (br s, 2H), 1.28-1.11 (m, 4H),

1.13 (d, 1 = 6.7 Hz, 3H); 0.97 (d, 1 = 6.8 Hz, 12H); MS (EAB, THS) 646 (M + N), 624 (M + H).

Example B11 Getting connection No. B1.13.

A 1M solution of benzoyl chloride in toluene (41 μl) was added at room temperature to a solution of amino acid B1.11 (0.020 g, 0.0339 mmol) in a 1M aqueous solution of MAHCO ^ (100 μl). The resulting mixture was stirred vigorously and after 1 h, an additional amount of benzoyl chloride (41 μl of a 1M solution) was added. After completion of the reaction, the volatiles were removed in high vacuum and the residue was purified by gel filtration on B1-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.5 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk KR18, eluent: 45% methanol / water), after which they were lyophilized and benzamide B1.13 was obtained as a flocculent powder (0.014 g, 59%). ¹ H-NMR (500 MHz, E ₂ O), mixture of rotamers (1: 1): δ 7.50-7.37 (m, 5H), 4.93 (d, 1 = 4.0 Hz, 0, 5H), 4.92 (d, 1 = 4.0 Hz, 0.5 N), 4.60 (q, 1 = 6.4 Hz, 1H), 4.48 (d, 1 = 8.0 Hz , 0.5H), 4.37 (d, 1 = 8.0 Hz, 0.5H), 4.32 (dd, 1 = 4.5, 8.0 Hz, 0.5H), 4.02 ( dd, 1 = 4.3, 8.7 Hz, 0.5H), 3.94 (d, 1 = 3.2 Hz, 0.5H), 3.89-3.61 (m, 7H), 3 82-3.61 (m, 7H), 3.60-3.52 (m, 1.5H), 3.51-

3.43 (m, 2.5H), 3.25 (dd, 1 = 7.9, 14.2 Hz, 0.5H), 3.20 (dd, 1 = 7.9, 14.2 Hz, 0.5H), 3.17-3.10 (m, 1H),

2.16-1.97 (m, 2.5H), 1.86 (nonet, 1 = 6.9 Hz, 0.5H),

1.65 (br s, 2H), 1.29-1.14 (m, 4H), 1.17 (d, 1 = 6.4 Hz, 1.5H), 1.11 (d, 1 = 6.6 Hz, 1.5H), 0.95 (d, 1 = 6.5 Hz, 1.5H), 0.92 (d, 1 = 6.6 Hz, 1.5H), 0.65 ( d, 1 = 6.4 Hz, 1.5H); 0.65 (d, 1 = 6.5 Hz, 1.5H); MS (ΕΑΒ, TH6) 715 (M + N), 694 (M + H).

Example B12 Getting connection No. B1.14.

SOOYa

ΝΟ,

B1.14

A 1 M solution of para-nitrobenzenesulfonyl chloride in toluene (43 μl) was added with vigorous stirring to a solution of amino acid B1.6 (0.02 g, 0.039 mmol) in a 1 M aqueous solution of NaHCO ₃ (0.2 ml). The reaction mixture was 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 Vue-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.5 ml / min, detection at 215 nm). Then, 0.025 g of the crude product was purified by two-phase reverse phase chromatography (silica gel Megsk 1P18, eluent for the 1st stage of chromatography: 50% methanol / water, eluent for the 2nd stage of chromatography: 40% methanol / water), after which it was lyophilized and obtained target compound in the form of flocculent powder (0.0105 g, 39%). ¹ H-NMR (400 MHz, 1) ₃ O) δ 8.39 (m, 2H), 8.07 (m, 2H), 4.93 (d, 1 = 4.0 Hz, 1H), 4, 56 (q, 1 = 6.6 Hz, 1H), 4.43 (d, 1 = 7.9 Hz, 1H), 3.96 (dd, 1 = 3.5, 7.1 Hz, 1H), 3.88-3.83 (m, 2H), 3.76-3.64 (m, 5H), 3.54-3.44 (m, 3H), 3.38 (dd, 1 = 3.5 , 13.7 Hz, 1H), 3.33 (dd, 1 = 3.2, 9.6 Hz, 1H), 3.19 (dd, 1 = 7.3, 13.7 Hz, 1H), 2 05 (br t, 1 = 13.4 Hz, 2H), 1.66 (br s, 2H), 1.30-1.12 (m, 4H), 1.14 (d, 1 = 6 6 Hz, 3H); MS (ΡΑΒ, TH6) 719 (M + N), 697 (M + H).

Example B13 Obtaining compound No. B1.15.

1 M solution of p-toluenesulfonyl chloride in toluene (22 μl) at a temperature of 0 ° C and with vigorous stirring was added to a solution of amino acid B1.6 (0.01 g, 0.02 mmol) in 1M aqueous solution No. ₁ HCO ₃ (0.1 ml ) The reaction mixture was stirred at 0 ° C for 90 minutes, after which an additional amount of p-toluenesulfonyl chloride (10 μl of a 1M solution) was added. Then the reaction mixture was warmed to room temperature, stirred for 18 hours and concentrated in vacuo. The residue was dissolved in water and purified by gel filtration on Vue-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.5 ml / min, detection at 215 nm) and then subjected to reverse phase chromatography (silica gel Megsk 1P18, eluent: 45% MeOH / H ₂ O) and lyophilized, whereby the target compound was obtained in the form of a flocculent powder (0.004 g, 30%). ¹ H-NMR (400 MHz, 1) ₃ O) δ 7.69 (d, 1 = 8.2 Hz, 2H), 7.37 (d, 1 = 8.1 Hz, 2H), 4.88 ( d, 1 = 3.9 Hz, 1H), 4.52 (q, 1 = 6.6 Hz, 1H), 4.35 (d, 1 = 7.9 Hz, 1H), 3.85-3, 78 (m, 2H), 3.74 (d, 1 = 2.8 Hz, 1H), 3.71-3.56 (m, 5H), 3.50-3.39 (m, 3H), 3 29 (dd, 1 = 3.4, 13.8 Hz, 1H), 3.10 (dd, 1 = 3.1,

9.6 Hz, 1H), 3.03 (dd, 1 = 8.0, 13.8 Hz, 1H), 2.34 (s, 3H), 2.08-1.93 (m, 2H), 1.61 (br s, 2H), 1.26-1.07 (m, 4H), 1.09 (d, 1 = 6.6 Hz, 3H).

Example B14. Obtaining compound No. 1.16.

B1.16

Pentafluorophenyl trifluoroacetate (4.5 ml, 0.026 mmol) was added at room temperature with stirring to a solution containing the isoserine derivative 16 (0.025 g, 0.026 mmol) and triethylamine (0.7 ml, 0.005 mmol) in DMF (100 ml). After 15 min, another 2.5 ml (0.015 mmol) of pentafluorophenyl trifluoroacetate was added, and after 30 min another 2.8 ml (0.02 mmol) of triethylamine and 4.5 ml (0.026 mmol) of pentafluorophenyl trifluoroacetate were added. After 20 minutes, some pentafluorophenyl trifluoroacetate was again added. The resulting mixture was stirred for 45 minutes, and then 0.2 ml of a saturated aqueous solution of No. ₁ HCO _{3 was} added and the mixture was diluted with water and extracted several times with ethyl acetate. The combined organic phases were dried SchA ₂ 8O 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 give trifluoroacetamide 24 (0.022 g, 83%).

The release of compound 24. Dioxane (1.4 ml), water (0.7 ml) and glacial acetic acid (0.35 ml) were added to a mixture of Pb (OH) ₂ / C (Reag1tap catalyst, 20% Pb content, 0, 02 g) and benzyl ether 24 (0.021 g, 0.021 mmol). The contents of the flask were pumped out and purged several times with argon. After purging with hydrogen, the black mixture was hydrogenated at slightly elevated pressure for 3.5 hours. The reaction mixture was filtered through a cellulose filter (pore size 45 μm) and the filtrate was concentrated in vacuo. A solution of the residue in a small amount of water was passed through an ion-exchange column (1Eo \\ 'ex 50, form Νι +, column diameter 0.9 cm, length 3.5 cm), washing with deionized water. After the filtrate was concentrated in vacuo, the residue was purified by gel filtration on Vue-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.5 ml / min, detection at 215 nm ), and then subjected to reverse phase chromatography (silica gel Megsk KR18, column diameter 1.2 cm, length 7 cm, elution in a gradient of 30% MeOH / H ₂ O - 40% MeOH / H ₂ O), resulting in the target B1.16 molecule (0.0085 g, 68%) as a flocculent, colorless solid (after lyophilization). ¹ H-NMR (500 MHz, O ₂ O) δ 4.93 (d, 1 = 3.9 Hz, 1H), 4.59 (q, 1 = 6.5 Hz, 1H),

4.45 (d, 1 = 8.2 Hz, 1H), 4.08 (dd, 1 = 3.4, 8.2 Hz, 1H), 3.91 (d, 1 = 3.1 Hz, 1H ), 3.86 (dd, 1 = 3.1, 10.0 Hz, 1Η), 3.75 (d, 1 = 3.1 Hz, 1H), 3.72 (dd, 1 = 3.9, 10.0 Hz, 1H), 3.73-3.65 (m, 4H), 3.61-3.50 (m, 3H), 3.50-3.44 (m, 1H), 3.42 (dd, 1 = 3.1, 9.6 Hz, 1Η), 2.10-2.00 (m, 2H), 1.65 (m, 2H), 1.28-1.15 (m, 4H ),

1.14 (d, 1 = 6.5 Hz, 3H); MS (RAV, THS) 652 (M + Na), 630 (M + H), 608 (M + 2H-Na).

Example B15 Obtaining compound No. B1.17.

B1L7 (a) Preparation of amide 26. Diisopropylcarbodiimide (17 ml, 0.11 mmol) was added at room temperature with stirring to a mixture of amine 16 (0.027 g, 0.028 mmol), cyclohexanecarboxylic acid (0.011 g, 0.086 mmol), 1- hydroxybenzotriazole (0.021 g, 0.155 mmol) and anhydrous tetrahydrofuran (0.9 ml). After standing for 20 minutes, anhydrous DMF (0.4 ml) was added and the mixture was stirred for another 1 hour. The reaction mixture was concentrated in vacuo and the remaining DMF was removed under high vacuum. The residue was purified by flash chromatography on silica gel (CH ₂ Cl ₂ / isopropanol = 39: 1), whereby amide 26 (0.024 g, 80%) was obtained.

(b) Release of compound 26. Dioxane (2.0 ml), water (1.0 ml) and glacial acetic acid (0.5 ml) were added to a mixture of Pb (OH) ₂ / C (Reag1tap catalyst, 20% Pb content) 0.03 g) and benzyl ether 26 (0.024 g, 0.022 mmol). The flask was pumped out and then purged several times with argon. After purging with hydrogen, the black mixture was hydrogenated under slightly reduced pressure for 18 hours. The reaction mixture was filtered through a cellulose filter (pore size 45 μm) and the filtrate was concentrated in vacuo. A solution of the residue in a small amount of water was passed through an ion-exchange column (1Eo \\ 'ex 50, form No. +, column diameter 0.9 cm, length 3.5 cm), washing with deionized water. The filtrate was concentrated in vacuo and the residue was purified by gel filtration on B1o-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.5 ml / min, detection at 215 nm ), and then subjected to reverse phase chromatography (silica gel Megsk KR18, column diameter 1.2 cm, length 6 cm, eluent: MeOH / H ₂ O = 3: 2), whereby the target molecule B1.17 (0.008 g , 56%) as a flocculent colorless solid (after lyophilization). ¹ H-NMR (500 MHz, 1HO) δ 4.93 (d, 1 = 4.0 Hz, 1H), 4.60 (q, 1 = 6.7 Hz, 1H), 4.47 (d, 1 = 8.0 Hz, 1H), 4.04 (dd, 1 = 3.8, 7.5 Hz, 1H), 3.92 (d, 1 = 2.8 Hz, 1H), 3.86 (dd , 1 = 3.2, 10.3 Hz, 1Н), 3.75 (d, 1 = 3.3 Hz, 1Н), 3.74-3.64 (m, 4Н), 3.61 (dd, 1 = 3.8, 13.8 Hz, 1H), 3.59-3.52 (m, 2H), 3.50-3.44 (m, 1H), 3.42 (dd, 1 = 3, 3, 9.8 Hz, 1H), 3.35 (dd, 1 = 7.7, 14.0 Hz, 1H), 2.19 (t, 1 = 3.3, 11.5 Hz, 1H), 2.11-2.00 (m, 2H), 1.78-1.57 (m, 7H), 1.34-1.08 (m, 9H), 1.15 (d, 1 = 6.5 Hz, 3H); MS (RAV, THS) 644 (M + H), 622 (M + 2H-No).

Example B16 Preparation of Compound B1.18

A solution of triol 13 (0.129 g, 0.17 mmol) in anhydrous methanol (4.0 ml) and di-n-butyltin oxide (0.064 g, 0.258 mmol) was refluxed under argon for 2 hours. The clear solution was concentrated in vacuo. and the residue was mixed with pentane (2 ml), concentrated again, and then dried under high vacuum for 30 minutes to remove methanol residues. After that, the residue was mixed under argon with anhydrous CgP (0.131 g, 0.86 mmol) and anhydrous 1,2-dimethoxyethane (0.5 ml), and then a solution of benzyl- (K) -4-phenyl-2 was added. trifluoromethanesulfonyloxybutyrate (A2) (0.3 g, 0.861 mmol) in anhydrous 1,2-dimethoxyethane (1.0 ml). The reaction mixture was stirred at room temperature for 75 minutes, and then a 1M aqueous solution of KH ₂ PO _{4 was} added, and the mixture was diluted with water and extracted with ethyl acetate (phase separation was carried out by adding a small amount of aqueous solution of KR). The organic extracts were combined, dried over sodium sulfate, filtered and concentrated in vacuo to give the crude product as an oily substance (39 g). This material was purified by flash chromatography on silica gel (eluent: toluene / ethyl acetate = 5: 1) to give pure ether 30 (0.143 g, 81%). ¹ H-NMR (250 MHz, SESE) δ 7.35-7.05 (m, 30H), 5.13 (d, 1 = 12.1 Hz, 1Η), 5.03 (d, 1 = 12, 1 Hz, 1H), 4.88 (d, 1 = 11.4

Hz, 1H), 4.87 (d, 1 = 2.0 Hz, 1H), 4.78-4.50 (m, 5H),

4.46 (d, 1 = 12.5 Hz, 1H), 4.40 (d, 1 = 12.5 Hz, 1H), 4.33 (q, 1 = 6.5 Hz, 1H), 4, 24 (d, 1 = 7.8 Hz, 1H), 4.09 (dd, 1 = 4.0, 8.5 Hz, 1H), 3.93 (br s, 2H), 3.80-3 38 (m, 7H), 3.26-3.17 (m, 2H), 2.86-2.62 (m, 2H), 2.59 (d, 1 = 2.0 Hz, 1H), 2.29 (br s, 1 OH), 2.11-1.85 (m, 4H), 1.67-1.52 (m, 2H), 1.40-1.06 (m, 4H) 1.03 (d, 1 = 6.5 Hz, 3H).

Benzyl ether 30 (0.14 g, 0.135 mmol) was dissolved in dioxane (4 ml) and water (2 ml), and then glacial acetic acid (1 ml) and 20% Pb (OH) ₂ / C (0.14) were added. d). The air in the reaction vessel was first replaced with argon, and then the contents were evacuated and purged with argon several times, after which the vessel was purged with hydrogen. The black reaction mixture was hydrogenated at slightly elevated hydrogen pressure for 90 minutes, and then filtered through a cellulose filter (pore size 45 μm) while washing with water. After concentrating the filtrate, the residue was dissolved in toluene and concentrated several times to remove residual acetic acid. The crude product (0.095 g) was dissolved in a small amount of water and filtered through a Potech 50 ion exchange column (No. +). The filtrate was dried by freezing, and then the residue (0.085 g) was purified using reverse phase chromatography (silica gel Megsk KR18, eluent: 40% MeOH / H2O), and then by gel filtration on Vu-6e1 P2 (particle size 65 μm, diameter columns 2.5 cm, length 35 cm, eluent: water; flow rate 0.5 ml / min, detection at 215 nm). After lyophilization, the desired compound B1 was obtained. 1 8 as flocculent powder (0.045 g, 55%). ¹ H-NMR (500 MHz, P ₂ O) δ 7.35-7.27 (m, 4H), 7.22 (tt, 1 = 1.5, 7.0 Hz, 1H), 4.93 ( d, 1 = 4.0 Hz, 1H), 4.60 (q, 1 = 6.7 Hz, 1H),

4.47 (d, 1 = 7.8 Hz, 1H), 3.89-3.82 (m, 3H), 3.76 (d, 1 = 3.5 Hz, 1H), 3.74-3 , 63 (m, 4H), 3.59-3.52 (m, 2H), 3.51-3.45 (m, 1H), 3.37 (dd, 1 = 3.5, 9.8 Hz) , 1H), 2.80-2.68 (m, 2H), 2.12-1.99 (m, 3H), 1.98-1.89 (m, 1H), 1.65 (br s , 2H), 1.30-1.13 (m, 4H), 1.15 (d, 1 = 6.6 Hz, 3H); MS (RAB, TH6) 609 (M + Na), 587 (M + H).

Example B 17. Preparation of Compound No. B 1.19.

Aromatic compound B1.18 (0.02 g, 0.033 mmol) was dissolved in water (1.8 ml) and dioxane (1.2 ml), and then glacial acetic acid (0.3 ml) and 5% Kb / A1 were added. ₂ O ₃ (0.04 g). The air in the reaction vessel was replaced with hydrogen by evacuation, and then the vessel was purged several times with hydrogen and the mixture was hydrogenated under slightly elevated hydrogen pressure for 1.5 days, while stirring vigorously. After filtering through a cellulose filter (pore size 45 μm) and washing with water, the filtrate was concentrated, and the residue was dissolved in toluene and concentrated several times to remove residual acetic acid. The crude product was purified by gel filtration on Vue-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.5 ml / min, detection at 215 nm), and then hydrogenated again under similar conditions for 2 days. The reaction mixture was filtered through a cellulose filter (pore size 45 μm) and washed with water, and then the filtrate was concentrated. The residue was dissolved in toluene and concentrated several times. The crude product was purified by gel filtration on Vue-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.5 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk KR18, eluent: 50% MeOH / H ₂ O) and lyophilized, resulting in the obtained target compound 1.19 in the form of a flocculent powder (0.01 g, 50%). ¹ H-NMR (250 MHz, P ₂ O) δ 4.83 (d, 1 = 4.0 Hz, 1H), 4.48 (q, 1 = 6.7 Hz, 1H), 4.35 (d , 1 = 7.8 Hz, 1H), 3.81-3.69 (m, 3H), 3.67-3.53 (m, 5H), 3.49-3.31 (m, 3H), 3.25 (dd, 1 = 3.1, 9.7 Hz, 1H), 2.03-1.87 (m, 2H), 1.72-1.38 (m, 9H), 1.24- 0.97 (m, 10H), 1.04 (d, 1 = 6.6 Hz, 3H), 0.75 (br s, 2H); MS (RAV, TH6) 615 (M + N), 593 (M + H).

Example B18 Obtaining compound No. B1.38.

A solution of p-nitrobenzenesulfonyl chloride in toluene (1 M 150 μl) was added to a solution of amino acid B1.11 (0.0035 g, 0.0617 mmol) in a 1M aqueous solution of No. ₁ HCO ₃ (315 μl). The resulting mixture was stirred vigorously at room temperature, and after another 17 hours another 120 μl of p-nitrobenzenesulfonyl chloride solution was added. The reaction mixture was stirred for another 24 hours and then diluted with water and washed twice with ethyl acetate. The aqueous phase was concentrated in vacuo to a volume of 0.5 ml, and this solution was purified by gel filtration on Vue-6e1 P2 (particle size 65 μm, column diameter 2.5 cm, length 100 cm, eluent: water; flow rate 0.5 ml / min, detection at 215 nm). The crude product (0.06 g) was then purified using 3-stage reverse phase chromatography (silica gel Megsk KP18, eluent: 40% MeOH / H ₂ O) and lyophilized, whereby sulfonamide B1.38 (0.013 g, 27%) was obtained in as a colorless flocculent powder. ¹ H-NMR (400 MHz, 1) ₃ O) δ 8.34 (m, 2H), 8.05 (m, 2H), 4.88 (d, 1 = 4.0 Hz, 1H), 4.53 (q, 1 = 6.5 Hz , 1H), 4.38 (d, 1 = 7.9 Hz,

Table 1

1H). 4.06 (dd, 1 = 3.9. 8.2 Hz, 1H), 3.84-3.79 (m, 2H), 3.70 (d, 1 = 3.0 Hz, 1H). 3.67 (dd, 1 = 3.9. 10.4 Hz, 1H). 3.69-3.58 (m, 3H), 3.57-3.38 (m, 5H), 3.25 (dd, 1 = 3.2. 9.5 Hz, 1H). 3.10 (dd, 1 = 7.7. 14.1 Hz, 1H). 3.05 (dd, 1 = 7.7. 14.1 Hz, 1H). 2.07-1.94 (m, 2H), 1.89 (hep, 1 = 6.7 Hz, 1H). 1.61 (br.s., 2H), 1.25-1.07 (m, 4H), 1.10 (d, 1 = 6.6 Hz, 3H), 0.70 (d, 1 = 6.6 Hz, 3H), 0.63 (d , 1 = 6.6 Hz, 3H).

The following compounds were obtained by the method described in the above examples.

Getting Example No. Compound No. K3 K4 TAV-M8 TH6 B15 B1.20 No. 1 CH2INS (O) C11H23 716 (M + H). 738 (M + No.) B15 B1.21 No. 1 CH ₃ \ HC (O) CH (C.H,) ₃ 728 (M + H). 750 (M + No.) B12 ⁽¹⁾ B1.22 No. 1 СН2 ^ С (О) С2ШСО2№ 656 (M + H). 678 (M + No.) B15 B1.23 No. 1 CH2 ^ C (O) C6 [(1.3.4.5) OH] 4H7 quinic acid amide 708 (M + H). 730 (M + No.) B15 B1.24 No. 1 СН2 ^ С (О) С6Н4-п-8О3№ 740 (M + H). 762 (M + No.) AT 12 B1.25 No. 1 СН2 ^ С (О) С6ШС1 672 (M + H). 695 (M + No.) AT 12 B1.26 No. 1 CH ^ ODSvNTSO ;, 683 (M + H). 705 (M + No.) AT 12 B1.27 No. 1 СН2 ^ С (О) С6 ШОСН3 668 (M + H). 690 (M + No.) AT 12 B1.28 No. 1 CH ^ HC (O) C (5H ₄ (3.4) C1 ₂ 706 (M + H). 728 (M + No.) AT 12 B1.29 No. 1 CH ^ HC (O) C <5H ₄ CH ₃ 652 (M + H). 674 (M + No.) B12 ⁽²⁾ B1.30 No. 1 CH ^ HC ^ 714 (M + H). 736 (M + No.) B12 ⁽³⁾ B1.31 No. 1 CH ^ HC ^ SL ^ 663 (M + H). 685 (M + No.) AT 12 B1.32 No. 1 CH ^ HC (O) C ₁₀ H ₇ 688 (M + H). 710 (M + No.) B12 ⁽⁴⁾ B1.33 No. 1 СН ^ НС (О) С <5Н ₄ СОО№ 704 (M + H). 726 (M + No.) B12 ⁽⁵⁾ B1.34 No. 1 СН ^ НС (О) (СНОН) ₂ СОО№ 688 (M + H). 710 (M + No.) AT 11 B1.35 No. 1 CH ^ ODSeVDSNsEnz 728 (M + H). 750 (M + No.) AT 11 B1.36 No. 1 CH2 ^ C (O) C6H ₃ ] (CH2) 3C6H ₃ 756 (M + H), 778 (M + No.) B15 ⁽⁶⁾ B1.37 No. 1 СН ₂ МН8О ₂ Н ₄ СР ₃ 666 (M + H). 688 (M + No.)

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

⁽²⁾ A solution of pentafluorophenyl biphenyl carboxylate in dioxane was used as a reagent.

⁽³⁾ A solution of pentafluorophenyl-para-cyanobenzoate in dioxane was used as a reagent.

⁽⁴⁾ A solution of methylpentafluorophenyl terephthalate in dioxane was used as a reagent. After completion of the amide formation, a 1M aqueous solution of No. 1OH was added to the reaction mixture, and the mixture was heated at 65 ° C until the hydrolysis of the methyl ester was complete.

⁽⁵⁾ Instead of 1M No. 1 HCO ₃ , 1M No. 1OH was used. A solution of an anhydride of (+) - di-O-acetyl-tartaric acid in dioxane was used as a reagent.

⁽⁶⁾ The amide formation reaction was carried out in CH ₂ Cl ₂ at a temperature of 0 ° C using trifluoromethanesulfonic acid anhydride as a reagent.

Example B19 Getting connection No.

A suspension of compound 13 (0.086 g, 0.11 mmol) and di-n-butyltin oxide (0.05 g, 0.19 mmol) in dry benzene (3.3 ml) was refluxed under argon for 12 hours. The reaction mixture was concentrated in vacuo and dried in high vacuum for 1 h. To the mixture in an argon atmosphere was added CBP (dried in high vacuum at 300 ° C for several hours, 0.042 g, 0.274 mmol), followed by anhydrous 1,2-dimethoxyethane (0.6 ml) and a solution triflate A3 (0.25 g, 0.66 mmol) in anhydrous 1,2-dimethoxyethane (0.4 ml). The reaction mixture was heated to 35–40 ° C and stirred at this temperature for 5 h. After adding a solution of 15% KE in a 1M aqueous solution of KH ₂ PO ₄ (30 ml), the mixture was extracted 3 times with methylene chloride, and the combined organic phases were dried Scha ₂ 8O ₄ ), filtered and concentrated in vacuo. The oily residue (0.16 g) was purified by silica gel column chromatography (toluene / ethyl acetate gradient elution, 80:20 - 75:25, and then CH ₂ Cl ₂ / MeOH, 19: 1) to give ether 31 (0.049) g, 44%) as a colorless foam and precursor 13 (0.035 g, 40%).

B1.39

Dioxane (2.0 ml), water (1.0 ml) and glacial acetic acid (0.5 ml) were added to a mixture of Pb (OH) ₂ / C (Reag1tap catalyst, 20% Pb content, 0.028 g) and benzyl ether 31 (0.048 g, 0.047 mmol). The flask was pumped out and purged several times with argon. After purging with hydrogen, the black reaction mixture was hydrogenated under slightly reduced hydrogen pressure at room temperature for 17 hours, and then filtered through a cellulose filter (pore size 45 μm). The filtrate was concentrated in vacuo and the residue was dissolved in water and concentrated several times again to remove excess acetic acid. A solution of the residue in water was passed through an EO \\ ex 50 ion-exchange column (Form No. +, column diameter 0.9 cm, length 3.5 cm), washing with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on B1o-6e1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.45 ml / min, detection at 230 nm) and then subjected to reverse phase chromatography (silica gel Megsk KR18, eluent: water / methanol, 7: 3), and the target molecule B1.39 (0.014 g, 51%) was obtained in the form of white solid flakes (after lyophilization). ¹ H-NMR (400 MHz, E2O) δ 4.83 (d, 1 = 4.0 Hz, 1H), 4.49 (q, 1 = 6.6 Hz, 1Η), 4.33 (d, 1 = 7.7 Hz, 1H), 3.74 (d, 1 = 3.1 Hz, 1Η), 3.22 (dd, 1 = 2.6 Hz, 9.5 Hz, 1H); ¹³ C-NMR (100.6 MHz, E2O) 181.5 (C _h ), 100.2 (CH), 95.7 (CH); MS (EAB, TH6) 609 (M + N), 587 (M + H).

Example B20 Preparation of Compound B1.40

The reaction of alcohol 13 with triflate A4 was carried out by the method described in example B19 (obtaining compound 31).

Hydrogenation of benzyl ether with subsequent purification was carried out by the method described in example B19 (preparation of compound B1.39): ¹ H-NMR (400 MHz, E ₂ O) δ 4.88 (d, 1 = 4.1 Hz, 1H), 4.53 (q, 1 = 6.7 Hz, 1H), 4.39 (d, 1 = 7.7 Hz, 1H), 3.29 (dd, 1 = 2.9, 9.8 Hz, 1H ), 1.10 (d, 1 = 6.8 Hz, 3H), 0.89 (d, 1 = 6.8 Hz, 3H), 0.82 (d, 1 = 6.8 Hz, 3H).

Example B21 Preparation of Compound B1.41

Hydroxypiperidine (6.0 g, 34.6 mmol; obtained from E (-) - lyxose, as described for 1SykAa and 1a8a8a (1aSakaaaa, 1aaaaaaaaaaaa, TeDakebgopae11ea8b 36: 4585-4586 (1995 )) and triethylamine (18.1 ml, 130 mmol) were dissolved in dry tetrahydrofuran (100 ml) and the solution was cooled to -10 ° C under argon atmosphere. Allyl chloroformate (3.87 ml, 36 4 mmol), resulting in a white suspension.The reaction mixture was stirred for another 1 h at -10 ° C, then a 1M aqueous solution of KH ₂ PO ₄ (150 ml) was added and the mixture was extracted 3 times with methylene chloride. The venous organic phases were dried with SchA ₂ 8O ₄ ) and concentrated in vacuum, resulting in a yellow oily substance (9 g). This material was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1: 1) to obtain 34 allyl carbamate (7.66 g, 86%). Λ Οθζ / 'O A.

_n I d_ovp

ΒζΟ

4A molecular sieves (dried under high vacuum at 300 ° C, 15 g) were added to a solution of the acceptor 34 (7.66 g, 29.8 mmol) in dry CH ₂ Cl ₂ (150 ml) in an argon atmosphere, and the suspension was stirred at room temperature for 1 h. At the same time, in a second round-bottom flask in an argon atmosphere, a suspension containing EMT8T (15.4 g,

59.6 mmol) and 4A molecular sieves (15 g) in anhydrous methylene chloride (150 ml), and then this suspension was stirred for 1 h. A mixture of EMT8T was added in 4 portions to the acceptor solution over 1 h, and the resulting mixture was stirred for 1 h. The reaction mixture was filtered through WellDo 8irg Ce1®, washing thoroughly with methylene chloride. The filtrate was extracted with shaking with a 10% aqueous NaHCO3 solution, and the aqueous phase was extracted 3 times with methylene chloride, and the combined organic phases were dried (No. ₂ 8 O ₄ ). filtered and concentrated in vacuo. The remaining yellow oily substance (36 g) was purified by silica gel column chromatography (eluted with hexane / ethyl acetate, 3: 1-3: 2). resulting in glycoside 35 (13.1. 54%).

Acetonide 35 (13.1 g, 15.94 mmol) was dissolved in dioxane (140 ml) and a 50% aqueous solution of trifluoroacetic acid (250 ml) was added at room temperature. After 2 hours, the reaction mixture was concentrated in high vacuum and the residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 2: 1). resulting in

mmol) and 4A molecular sieves (dried under high vacuum at 300 ° C, 22 g) were dried under high vacuum for 30 min, and then dry CH2C12 (62 ml) and dimethylformamide (36 ml) were added in an argon atmosphere. The resulting gray suspension was stirred at room temperature for 30 minutes. At the same time, in a second round-bottom flask in an argon atmosphere, a solution of ethyl-2,3,4-tri-O-benzyl1-thio-L-fucopyranoside (7.48 g, 15.62 mmol, prepared as described by Lopp (Lopp, .. Cnobo, Kek. 139: 105-113 (1985)) in dry CH ₂ Cl ₂ (49 ml), and then a solution of bromine (2.85 g of Br _2. 17.84 mmol) in SCHC1 ₂ (25 ml) was added at 0 ° C. The red solution was stirred at 0 ° C for 30 min and excess bromine was removed by adding a few drops of cyclohexene.The resulting solution was added with a needle to the acceptor solution, and the reaction mixture was stirred at room temperature . D for 40 hours The reaction mixture was filtered through CIPC 8ireg Se1® and thoroughly washed with methylene chloride filtrate was washed with 10% aqueous Ν;.. · ιΗί.Ό _3, the aqueous phase was re-extracted thrice SSCHS1 ₂ and the combined organic phases were dried (Ha ₂ 8O ₄ ), filtered and concentrated in vacuo.The residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 35:65). and after elution, the desired product 37 (7.85 g, 44%) was obtained.

A solution of ester 37 (2.4 g, 2.0 mmol) and sodium methoxide (0.11 g, 2.0 mmol) in methanol (48 ml) was stirred at room temperature for 8 hours. The clear, colorless solution was neutralized by the addition of a strongly acidic ion exchanger (Amber1181 15). and then filtered through CuPO 8ireg Ce1®, and concentrated in vacuo. The oily residue was purified by silica gel column chromatography (eluted with a gradient of CH ₂ Cl ₂ / methanol, 98: 2 - 95: 5) to obtain triol 38 (1.72 g, 97%).

A suspension of compound 38 (1.0 g, 1.13 mmol) and di-n-butyltin oxide (0.49 g, 1.98 mmol) in anhydrous benzene (33 ml) was refluxed under argon for 5 h. The reaction mixture was concentrated in vacuo and dried under high vacuum for 1 h. CKE was added to the mixture under argon atmosphere (dried under high vacuum at 300 ° C for several hours, 0.43 g, 2.82 mmol), and then anhydrous 1,2 dimethoxyethane (7.4 ml) and a solution were added benzyl-I-3-phenyl-2-trifluoromethanesulfonyloxypropionate (2.6 g, 6.77 mmol) in anhydrous 1.2 dimethoxyethane (4.9 ml). The reaction mixture was heated to 35-40 ° C and stirred at this temperature for 3 hours. After adding 15% KE in a 1M aqueous solution of KH ₂ PO ₄ (100 ml), the mixture was extracted 3 times with methylene chloride, and the combined organic phases were dried (No. 8O ₄ ). filtered and concentrated in vacuo. The oily residue (3.2 g) was purified by silica gel column chromatography (eluent: toluene / ethyl acetate = 70:30) to give ether 39 (0.98 g, 78%) as a colorless foam.

B1.41

Dioxane (3.5 ml), water (1.7 ml) and glacial acetic acid (0.25 ml) were added to a mixture of Pb (OH) ₂ / C (Reag1tap catalyst. 20% content of Pb. 0.035 g) and benzyl ether 39 (0.038 g, 0.034 mmol). The contents of the flask were pumped out and purged several times with argon. After purging with hydrogen, the black reaction mixture was hydrogenated at slightly elevated hydrogen pressure at room temperature for 24 hours, and then filtered through a cellulose filter (pore size 45 μm). The filtrate was concentrated in vacuo and the residue was dissolved in water, and then concentrated several times again to remove excess acetic acid. A solution of this residue in water was passed through an обменο \\ υχ 50 ion-exchange column (Form No. +, column diameter 0.9 cm, length 3.5 cm), rinsing with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on ΒίοСе1 Р2 (particle size 65 μm, column diameter

2.5 cm, length 35 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk KP18, elution in a gradient of water / methanol, 65: 35-55: 45), and the target molecule B1.41 was obtained (0.014 g, 59%) as white solid flakes (after lyophilization). ¹ H-NMR (500 MHz, 1EO. + 50 ° C) δ 7.58-7.53 (m, 4H), 7.51-7.46 (m, 1H), 5.22 (d, 1 = 4.0 Hz, 1H), 4.57 (d, 1 = 7.6 Hz, 1H), 4.56 (q, 1 = 6.4 Hz, 1H), 4.33 (dd, 1 = 4, 2, 8.6 Hz, 1H), 4.30 (dt, 1 = 6.3, 3.2 Hz, 1Η), 3.66 (dd, 1 = 8.0, 9.4 Hz, 1H), 3.59 (dd, 1 = 3.0, 13.8 Hz, 1H), 3.33 (dd, 1 = 4.2, 14.0 Hz, 1H), 3.13 (dd, 1 = 9, 0, 14.0 Hz, 1H), 1.82 (sextet, 1 = 6.9 Hz, 2H), 1.36 (d, 1 = 6.4 Hz, 3H), 1.10 (t, 1 = 7.5 Hz, 3H); MS (RAB, ΝΒΑ) 720 (M + N), 698 (M + H).

Example B22 Preparation of Compound B1.42

A suspension of compound 38 (0.65 g, 0.73 mmol) and di-n-butyltin oxide (0.32 g, 1.28 mmol) in anhydrous benzene (22 ml) was refluxed under argon for 16 hours The reaction mixture was concentrated in vacuo and dried under high vacuum for 1 h. CgP was added to the mixture in argon atmosphere (dried under high vacuum at 300 ° C for several hours, 0.28 g, 1.83 mmol), and then dry 1,2-dimethoxyethane (4.0 ml) and a solution of A5 triflate (1.74 g, 4.4 mmol) in dry 1,2-dimethoxyethane (2.7 ml) were added. The reaction mixture was heated to a temperature of 35-40 ° C and stirred at this temperature for 3 hours. After adding a solution of 15% KP in a 1M solution of KH ₂ PO ₄ (100 ml), the mixture was extracted 3 times with methylene chloride, and the combined organic phases were dried Scha ₂ 8O ₄ ), filtered and concentrated in vacuo. 2.6 g of the oily residue was purified by silica gel column chromatography (first eluting with toluene / ethyl acetate = 3: 1 and then CH ₂ Cl ₂ / methanol = 19: 1), whereby ether 40 (0.33 g, 40%) as a colorless foam with a partial precursor content of 38 (0.167 g, 26%).

⁴⁰ V1.42

Dioxane (1.2 ml), water (0.6 ml) and glacial acetic acid (0.3 ml) were added to a mixture of P6 (OH) ₂ / C (Reag1tap catalyst, 20% P6 content, 0.025 g) and benzyl ether 40 (0.036 g, 0.032 mmol). The contents of the flask were pumped out and purged several times with argon. After purging with hydrogen, the black reaction mixture was hydrogenated at slightly elevated hydrogen pressure at room temperature for 8 hours, and then filtered through a cellulose filter (pore size 45 μm). The filtrate was concentrated in vacuo and the residue was dissolved in water, and then concentrated several times again to remove excess acetic acid. A solution of this residue in water was passed through an Eo \\ 'ex 50 ion-exchange column (form Ν +, column diameter 0.9 cm, length 3.5 cm), washing with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on ΒίοСе1 Р2 (particle size 65 μm, column diameter

2.5 cm, length 35 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk KR18, eluent: water / methanol = 1: 1), whereby the target molecule B1.42 (0.009 g , 41%) as white solid flakes (after lyophilization). ¹ H-NMR (400 MHz, 1EO) δ 5.09 (d, 1 = 3.7 Hz, 1H), 4.584.46 (m, 2H), 3.94 (d, 1 = 2.2 Hz, 1Η ), 3.58 (t, 1 = 8.4 Hz, 1H), 3.43 (dd, 1 = 1.8, 9.5 Hz, 1H), 1.83 (d, 1 = 12.2 Hz) , 1Η), 1.23 (d, 1 = 6.7 Hz, 3H), 0.95 (t, 1 = 7.6 Hz, 3H); ¹³ C-NMR (100.6 MHz, P ₂ O): 183.0 (C), 101.6 (CH), 98.0 (CH); MS (RAB, ΤΗ6) 704 (M + H).

Example B23 Preparation of Compound B1.43

Morpholine (1.1 ml) and P6 (PPB ₃ ) ₄ (0.071 g, 0.062 mmol) were added to a solution of allyl carbamate 39 (0.695 ml, 0.618 mmol) in tetrahydrofuran (8.5 ml). After exactly 15 minutes, the solution was concentrated and the residue was dried under high vacuum for 1 hour. The residue was purified by silica gel column chromatography (eluent: CH ₂ Cl ₂ / methanol = 98: 2 containing 0.3% concentrated aqueous ammonia) as a result of which first a less polar allylamine 46 (0.24 g, 36%) was obtained, and then a more polar piperidine 41 (0.39 g, 60%) was obtained.

42

Pyridine (5 μl, 0.06 mmol) and acetic anhydride (1.6 μl, 0.04 mmol) were added in an argon atmosphere to a solution of piperidine derivative 41 (0.035 g, 0.0336 mmol) in anhydrous CH ₂ Cl ₂ (0 , 6 ml) at 0 ° C. The resulting solution was stirred for 45 min at 0 ° C, and then washed with 5% aqueous solution No. ₁ HCO ₃₁ . and the aqueous phase was extracted 3 times with methylene chloride. The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The residue (0.05 g) was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 4: 1) to obtain acetyl piperidine 42 (0.033 g, 91%) as a colorless foam.

B1.43

Dioxane (1.4 ml), water (0.7 ml) and glacial acetic acid (0.35 ml) were added to a mixture of Pb (OH) ₂ / C (Reag1tap catalyst, 20% Pb content, 0.03 g) and benzyl ether 42 (0.04 g, 0.037 mmol). The contents of the flask were pumped out and purged several times with argon. After purging with hydrogen, the black reaction mixture was hydrogenated at slightly elevated hydrogen pressure at room temperature for 48 hours, and then filtered through a cellulose filter (pore size 45 μm). The filtrate was concentrated in vacuo and the residue was dissolved in water, and then concentrated several times again to remove excess acetic acid. A solution of this residue in water was passed through an обменο \\ υχ 50 ion-exchange column (Να + form, column diameter 0.9 cm, length 3.5 cm), washing with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on NaOe1 P2 (particle size 65 μm, column diameter

2.5 cm, length 35 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk KP18, elution in a gradient of methanol / water, 2: 3 - 1: 1 - 3: 2), and received the target B 1.43 molecule (0.014 g, 64%) in the form of white solid flakes (after lyophilization). 'H-NMR (400 MHz, Ό ₂ Ο) δ 7.22-7.06 (m, 5H), 4.86 (m, 1H), 1.95 (s, 3H), 0.98 (d, 1 = 6.7 Hz, 3H). MS (RAV, TNO) 654 (M + H), 632 (M + 2H-No).

Example B24 Preparation of Compound B 1.44.

Compound 43 was prepared from piperidine 41 (0.02 g, 0.019 mmol) and benzoyl chloride (2.5 μl, 0.021 mmol) in a similar manner to that described for acetyl piperidine 42 (Example B23). The yield was 0.02 g (90%).

⁴³ B1.44

The target compound B1.44 was obtained by hydrogenation of benzyl ether 43 (0.042 g, 0.0367 mmol), followed by purification, similarly to the method for the acetyl derivative B1.43. After lyophilization, the desired product was obtained in the form of white solid flakes. Yield: 0.015 g (57%). MS (PAB, THO) 716 (M + H), 694 (Μ + 2Η-Να).

Example B25 Preparation of Compound B 1.45.

The target compound B1.45 was obtained by the method described in example 23 (preparation of compound B1.43) from the piperidine derivative 41: ίί-NMR (400 MHz, Ό ₂ Ο) δ 7.28-7.13 (m, 5H) 4.95 (m, 1H), 4.37-4.23 (m, 2H), 3.56 (s, 3H), 3.04 (m, 1H), 2.84 (m, 1H), 2.26 (t, 1 = 7.6 Hz, 2H), 1.08 (d, 1 = 7.4 Hz, 3H); MS (PAB, TNO) 810 (M + H).

Example B26 Preparation of Compound B 1.46.

Pyridine (4 μl, 0.05 mmol) and cyclohexanecarbonyl chloride (7.2 μl, 0.05 mmol) were added at 0 ° C to a solution of piperidine derivative 41 (0.04 g, 0.038 mmol) in dry CH ₂ Cl ₂ (0 7 ml). After 20 minutes, the reaction mixture was washed with a 10% aqueous NaHCO3 solution and the aqueous phase was again extracted three times with methylene chloride. The combined organic phases were dried (Ν; · ι ₃ 8Ο ₃ ). 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%).

B1.46

Dioxane (1.1 ml), water (0.55 ml) and glacial acetic acid (0.27 ml) were added to a mixture of P6 (OH) ₂ / C (Reag1tap catalyst, 20% P6 content, 0.05 g) and benzyl ether 45 (0.029 g, 0.025 mmol). The contents of the flask were pumped out and purged several times with argon. After purging with hydrogen, the black reaction mixture was hydrogenated under slightly elevated hydrogen pressure at room temperature for 24 hours. Then 5% H11 / C (0.02 g) was added to hydrogenate the aromatic ring, and the hydrogenation reaction was continued for 24 hours. The reaction mixture was filtered through a cellulose filter (pore size 45 μm), and then the filtrate was concentrated in vacuo and the residue was dissolved in water, and again concentrated several times to remove excess acetic acid. A solution of the residue in water was passed through an обменο \\ υχ 50 ion-exchange column (Form No. +, column diameter 0.9 cm, length 3.5 cm), washing with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on Vue-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 45 ml / min, detection at 215 nm) and then subjected to reverse phase chromatography (silica gel Megsk YR18, eluent: methanol / water = 60:40), and the target molecule B1.46 (0.012 g, 64%) was obtained as white solid flakes (after lyophilization). ¹ H-NMR (400 MHz, I ₂ O) δ 5.04 (m, 1H), 4.48 (m, 1H), 4.45-4.32 (m, 1H), 2.72 (m, 1H), 1.17 (d, 1 = 5.8 Hz, 3H); MS (PAB, ΤΗ6) 728 (M + H), 706 (M + 2H-Na).

Example B27 Preparation of Compound B 1.47.

Dioxane (1.4 ml), water (0.7 ml) and glacial acetic acid (0.35 ml) were added to a mixture of P6 (OH) ₂ / C (Reag1tap catalyst, 20% P6 content, 0.03 g) and benzyl ether 46 (0.042 g, 0.039 mmol). The contents of the flask were pumped out and purged several times with argon. After purging with hydrogen, the black reaction mixture was hydrogenated at slightly elevated hydrogen pressure at room temperature for 16 hours, and then filtered through a cellulose filter (pore size 45 μm). The filtrate was concentrated in vacuo and the residue was dissolved in water, and then concentrated several times again to remove excess acetic acid.

The crude product (0.014 g) was purified by gel filtration on Vue-6e1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk YP18, eluent: methanol / water = 1: 3), and the target molecule B1.47 (0.009 g, 36%) was obtained as white solid flakes (after lyophilization). ¹ H-NMR (400 MHz, I ₂ O) δ 7.10-7.02 (m, 4H), 7.01-6.94 (m, 1H), 4.80 (br s, 1Η), 4.10 (d, 1 = 7.0 Hz, 1H), 3.84 (dd, 1 = 4.7, 8.5 Hz, 1Η), 3.20 (t, 1 = 8.7 Hz, 1Η), 2.97 (dd, 1 = 3.3, 9.7 Hz, 1Η), 2.83 (dd, 1 = 4.7, 13.1 Hz, 1Η), 2.63 (dd, 1 = 8.5, 13.1 Hz, 1Η), 0.87 (d, 1 = 7.0 Hz, 3H), 0.63 (t, 1 = 7.3 Hz, 3H); MS (RAB, ΤΗ6) 654 (M + No.), 632 (M + H).

Example B28 Preparation of Compound B 1.48.

47

Triethylamine (7 μl, 0.05 mmol) and nbutanesulfonyl chloride (3.7 μl, 0.029 mmol) were added at 0 ° C to a solution of piperidine 41 (0.025 g, 0.024 mmol) in methylene chloride (0.3 ml). After 45 min, the reaction mixture was washed with a 10% aqueous solution of ΝιНСО ₃ and the aqueous phase was again extracted 3 times with methylene chloride. The combined organic phases were dried (No. 8O ₄ ). filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 60:40) to give sulfonamide 47 (0.022 g, 79%).

B1.48

Dioxane (1.0 ml), water (0.5 ml) and glacial acetic acid (0.25 ml) were added to a mixture of P6 (OH) ₂ / C (Reag1tap catalyst, 20% P6 content, 0.013 g) and benzyl ether 47 (0.027 g, 0.023 mmol). The contents of the flask were pumped out and purged several times with argon. After purging with hydrogen, the black reaction mixture was hydrogenated at slightly elevated hydrogen pressure at room temperature for 24 hours, and then filtered through a cellulose filter (pore size 45 μm). After concentrating the filtrate in vacuo, the residue was dissolved in water, and then concentrated several times again to remove excess acetic acid. A solution of the residue in water was passed through an обменο \\ υχ 50 ion-exchange column (form Νι +, column diameter 0.9 cm, length 3.5 cm), washing with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on Vu

Ce1 P2 (particle size 65 μm, column diameter 0.9 cm, length 3.5 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm), and by reverse phase chromatography (silica gel Megg KP18, elution in a methanol / water gradient, 35:55 - 45:55), whereby the target molecule B1.48 (0.011 g, 65%) was obtained in the form of white solid flakes (after lyophilization). ¹ H-NMR (400 MHz, O ₂ O) δ 7.51-7.35 (m, 5H), 5.15 (d, 1 = 3.4 Hz, 1H), 4.54 (q, 1 = 6.2 Hz, 1H), 4.51 (d, 1 = 8.0 Hz, 1H), 4.03 (dd, 1 = 2.8, 10.4 Hz, 1H), 3.59 (t, 1 = 8.9 Hz, 1H), 3.23 (dd, 1 = 4.8, 13.4 Hz, 1H), 3.05 (dd, 1 = 8.6, 13.4 Hz, 1H), 1.84 (pent, 1 = 7.6 Hz, 2H), 1.54 (sextet, 1 = 7.3 Hz, 2H), 1.27 (d, 1 = 6.6 Hz, 3H), 1, 02 (t, 1 = 7.5 Hz, 3H); MS (EAB, THS) 732 (M + H).

Example B29 Preparation of Compound B1.49

The target compound B1.49 was obtained by the method described in example B28 (preparation of compound B1.48) using piperidine derivative 41 and p-toluenesulfonyl chloride as the starting compound. ¹ NNMR (400 MHz, 1GO) δ 7.56 (d, 1 = 7.2 Hz, 2H), 7.33 (d, 1 = 7.2 Hz, 2H), 7.28-7.11 (m 5H), 4.81 (d, 1 = 3.4 Hz, 1H), 4.22 (d, 1 = 7.9 Hz, 1H), 3.75 (d, 1 = 2.4 Hz, 1H ), 3.65 (dd, 1 = 2.4, 10.2 Hz, 1H), 3.41 (t, 1 = 5.7 Hz, 1H), 3.32 (t, 1 = 8.7 Hz) , 1H), 3.13 (dd, 1 = 2.5, 9.3 Hz, 1H), 3.00 (dd, 1 = 4.0, 13.6 Hz, 1H), 2.81 (dd, 1 = 8.9, 13.6 Hz, 1H), 2.67 (br s, 1H), 2.29 (s, 3H), 0.95 (d, 1 = 7.1 Hz, 3H); MS (EAB, THS) 788 (M + N), 766 (M + H).

Example B30 Obtaining connection B1.50.

4 ₇ V1.50

Dioxane (1.5 ml), water (0.75 ml) and glacial acetic acid (0.38 ml) were added to the Pd (OH) ₂ / C mixture (Reag1tap catalyst, 20% Pb content, 0.02 g) and benzyl ether 47 (0.041 g, 0.035 mmol). The contents of the flask were pumped out and purged several times with argon. The flask was then purged with hydrogen and the black reaction mixture was hydrogenated at slightly elevated hydrogen pressure at room temperature for 16 hours. To hydrogenate the aromatic ring, 5% K / C (0.025 g) was added and hydrogenation was continued for 16 hours. The reaction mixture was then filtered through a cellulose filter (pore size 45 μm) and the filtrate was concentrated in vacuo, and then the residue was dissolved in water and concentrated several times again to remove excess acetic acid. A solution of the residue in water was passed through an Eo ^ ex 50 ion-exchange column (Form No. +, column diameter 0.9 cm, length 3.5 cm), rinsing with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on a CuCl2 P2 (particle size 65 μm, column diameter

2.5 cm, length 35 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk KP18, elution in a gradient of methanol / water, 40:60 - 50:50), resulting in the target molecule B 1.50 (0.021 g, 82%) as white solid flakes (after lyophilization). ¹ H-NMR (400 MHz, O ₂ O) δ 4.97 (d, 1 = 3.7 Hz, 1H), 4.41 (d, 1 = 7.7 Hz, 1H), 4.36 (q , 1 = 6.7 Hz, 1H), 3.81 (d, 1 = 2.6 Hz, 1H), 3.76 (dd, 1 = 2.4, 7.3 Hz, 1H), 3.55 (dd, 1 = 4.4, 7.2 Hz, 1H), 3.30 (dd, 1 = 2.7, 9.7 Hz, 1H), 1.34 (sextet, 1 = 7.4 Hz, 2H), 1.10 (d, 1 = 6.7 Hz, 3H), 0.81 (t, 1 = 7.5 Hz, 3H); MS (EAB, THS) 738 (M + H), 716 (M + 2H #).

Example B 31. Preparation of compound B1.51.

49

Morpholine (0.37 ml) and Py (PP ₃ ) ₄ (0.025 g, 0.021 mmol) were added to a solution of allyl carbamate 40 (0.24 g, 0.212 mmol) in tetrahydrofuran (2.9 ml). After exactly 15 minutes, the solution was concentrated and the residue was dried for 1 hour under high vacuum. The residue (0.38 g) was purified by silica gel column chromatography (eluent: CH ₂ Cl ₂ / methanol, 19: 1, containing 0.3% concentrated aqueous ammonia), resulting in the piperidine derivative 49 (0, 17 g, 76%).

Phenyl isocyanate (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 methylene chloride (0.6 ml) . After 90 minutes, the reaction mixture was washed with a 1M aqueous solution of KH ₂ PO ₄ , and the aqueous phase was extracted 3 times with methylene chloride. The combined organic phases were dried (No. 8O ₄ ). filtered and concentrated in vacuo. The crude product (0.047 g) was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 58:42), whereby a urea derivative of 50 (0.035 g, 78%) was obtained.

B1.51

Dioxane (1, s ml), water (0.65 ml) and glacial acetic acid (0, s s ml) were added to a mixture of Pb (OH) ₂ / C (Reag1tap catalyst, 20% Pb content, 0.018 g) and benzyl ether 50 (0,0z6 g, 0,01 mmol). The contents of the flask were pumped out and purged several times with argon. After purging with hydrogen, the black reaction mixture was hydrogenated at slightly elevated hydrogen pressure at room temperature for 16 hours, and then filtered through a cellulose filter (pore size 45 μm). After concentrating the filtrate in vacuo, the residue was dissolved in water and concentrated several times to remove excess acetic acid. A solution of the residue in water was passed through an Eo \\ 'ex 50 ion-exchange column (form Ν; · ι +, column diameter 0.9 cm, length h, 5 cm), washing with deionized water. The clear filtrate was concentrated in vacuo and purified by gel filtration on Vue-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length s5 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm ), and then subjected to reverse phase chromatography (silica gel Megsk BP18, eluent: methanol / water, 1: 1), and the target molecule B 1.51 (0.018 g, 80%) was obtained as white solid flakes (after lyophilization). ¹ H-NMR (400 MHz, O ₂ O) δ 7.14 (t, 1 = 7.9 Hz, 2H), 7.02 (d, 1 = 8.2 Hz, 2H), 6.95 (t ,

1 = 7.7 Hz, 1H), 4.87 (d, 1 = 4.0 Hz, 1H), 4, z0 (d,

1 = 7.4 Hz, 1H), 4.2z (q, 1 = 6.6 Hz, 1H), s, 66 (d,

1 = 2.8 Hz, 1H), h, 42 (dd, 1 = 4.4, 7.7 Hz, 1H), h, 16 (dd, 1 = 2.6, 9.5 Hz, 1H), 1.00 (d, 1 = 6.6 Hz, 3H); MS (RAV, THS) 7s7 (M + H), 715 (M + 2H-No).

Example B32 Preparation of Compound B1.52

B1.52

The piperidine derivative 49 by the method described in example B28 (preparation of compound B1.48), using phenylmethanesulfonyl chloride as the reagent, was converted to the target compound B 1.52: ¹ H-NMR (400 MHz, IX)) δ 7.50 (m, 5H) , 5.02 (d, 1 = 3.5 Hz, 1H), 4.61 (d, 1 = 13.7 Hz, 1H), 4.54 (d, 1 = 13.7 Hz, 1H), 4 , s2 (d, 1 = 8.0 Hz, 1H), s, 62 (t, 1 = 6.0 Hz, 1H), s, 52 (dd, 1 = 7.7, 8.4 Hz, 1H) , s, s6 (dd, 1 = s, 2, 9.6 Hz, 1H), s, 22 (brd, 1 = 12.6 Hz, 1H), 1.17 (d, 1 = 6, 5 Hz, 3H); MS (RAV, THS) 772 (M + H), 750 (M + 2HΝ).

Example View Preparation of Compound B1.53

B1.53

Dioxane (s, 7 ml), water (1.8 ml) and glacial acetic acid (0.9 ml) were added to the mixture Pb (OH) ₂ / C (Reag1tap catalyst, 20% Pb content, 0.05 g) and benzyl ether 49 (0.09 g, 0.086 mmol). The contents of the flask were pumped out and purged several times with argon. After purging with hydrogen, the black reaction mixture was hydrogenated at slightly elevated hydrogen pressure at room temperature for 48 hours, and then filtered through a cellulose filter (pore size 45 μm). After concentrating the filtrate in vacuo, the residue was dissolved in water and concentrated several times to remove excess acetic acid. 0.044 g of the crude product was purified by gel filtration on Vue-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length s5 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography on silica gel (Megsk BP18, elution in a gradient of methanol / water, s0: 70-50: 50), whereby the target molecule B1.53 (0.04 g, 78%) was obtained as white solid flakes (after lyophilization). ¹ H-NMR (400 MHz, IX)) δ 5.04 (d, 1 = 4.2 Hz, 1H), 4.4 s (d, 1 = 7.6 Hz, 1H), 4.27 (m, 2H), 4.20 (q, 1 = 6.5 Hz, 1H), 4.02 (dd, 1 = 2.6, 6.6 Hz, 1H), h, 51 (dd, 1 = 7.8 9.5 Hz, 1H); 1.12 (d, 1 = 6.2 Hz, 3H); MS (RAV, TNS) 618 (M + No.), 596 (M + H).

Example B34 Preparation of Compound B1.54

B1.53 B1.54

1M solution of 2- (1-naphthyl) ethanesulfonyl chloride in toluene (46 .mu.l) was added at room temperature to a solution of the piperidine derivative V1.5z (0.025 g, 0.042 mmol) in 1 M aqueous solution _of №1NSO (0.22 ml). The resulting mixture was stirred vigorously for 22 hours, and then concentrated in vacuo and dried under high vacuum for 15 minutes. The crude product was purified by gel filtration on Vue-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length s5 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography on silica gel (Megsk BP18, eluent: methanol / water, 7: 3), whereby the target molecule B1.54 (0.011 g, 3%) was obtained in the form of white solid flakes (after lyophilization). ¹ H-NMR (400 MHz, E ₂ O) δ 7.72 (d, 1 = 8.8 Hz, 1H), 7.54 (d, 1 = 8.8 Hz, 1H),

7.44 (d, 1 = 8.6 Hz, 1H), 7.28 (t, 1 = 7.2 Hz, 1H), 7.22 (t, 1 = 7.2 Hz, 1H), 7, 14 (t, 1 = 7.2 Hz, 1H), 7.08 (d, 1 = 8.7 Hz, 1H), 4.91 (d, 1 = 4.1 Hz, 1H), 4.20 ( d, 1 = 7.0 Hz, 1H), 3.99 (br s, 1H), 3.90 (br s, 1H), 1.09 (d, 1 = 6.3 Hz, 3H); MS (EAB, ΤΗ6) 858 (M + No.), 836 (M + H).

Example B35 Preparation of Compound B1.55

A 0.5 M solution of acetic anhydride in toluene in small portions (50-100 μl) at room temperature was added to a solution of piperidine derivative B 1.53 (0.035 g, 0.059 mmol) in a 1M aqueous solution of No. ₁ HCO ₃ (0.5 ml) until until the entire precursor was used up, as indicated by thin layer chromatography (TLC plates with silica gel, mobile phase: n-butanol / water / acetone / glacial acetic acid / IN ₄ OH = 70:60: 50: 18: 1,5) . After about 1 hour, the reaction was completed and the mixture was concentrated in vacuo and dried under high vacuum for 15 minutes. The crude product was purified by gel filtration on B1o-6e1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography on silica gel (Megsk KR18, eluent: methanol / water, 3: 7), whereby the target molecule B 1.55 (0.026 g, 67%) was obtained in the form of white solid flakes (after lyophilization). Ή-NMR (400 MHz, B ₂ O) δ 5.01 (d, 1 = 4.2 Hz, 0.5H), 4.99 (d, 1 = 4.2 Hz, 0.5H), 4, 44 (d, 1 = 7.3 Hz, 1H), 4.32 (q, 1 = 6.6 Hz, 0.5H), 3.14 (dd, 1 = 8.0, 12.9 Hz, 0 , 5H), 2.10 (s, 1.5H), 2.08 (s, 1.5H), 1.13 (d, 1 = 6.6 Hz, 3H).

Example B36. Preparation of Compound B1.56

B1.53 B1.56, 5M solution of anhydride (+) - di-O-acetyl tartaric acid in 1,4-dioxane in small portions (50-100 μl) at room temperature was added to a solution of piperidine derivative B 1.53 (0.03 g, 0.05 mmol) in a 1 M aqueous solution of sodium hydroxide (0.15 ml) until the entire precursor was consumed, as indicated by thin layer chromatography (TLC plates with silica gel, mobile phase: n-butanol / water / acetone / glacial acetic acid / IN ₄ OH, 70:60:50: 18: 1,5). The mixture was maintained in an alkaline state by periodically adding 1M solution No. OH. After about 2 hours, the starting product was consumed, after which another 0.13 ml of a 1 M sodium hydroxide solution was added, and then the mixture was heated to 40 ° C to hydrolyze the ether groups. After 1 h, the mixture was concentrated in vacuo and dried under high vacuum for 15 min. The crude product was purified by gel filtration on Vue-6e1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk KR18, eluent: methanol / water, 1: 9), and the target molecule B1.56 (0.020 g, 52%) was obtained as a flocculent white solid (after lyophilization). MS (EAB, ΤΗ6) 794 (M + N), 772 (M + H), 750 (M + 2H-Ia).

Example B37 Preparation of Compound B1.57

B1.53 B1.57

Ν, Ν-Diisopropylcarbodiimide (11.7 μl, 0.075 mmol) was added at 0 ° C to a solution of shikimic acid (0.013 g, 0.075 mmol) and 1hydroxybenzotriazole (0.01 g, 0.075 mmol) in anhydrous Ν, Ν-dimethylformamide (0 , 37 ml), and then the mixture was stirred for 30 minutes. The resulting mixture was warmed to room temperature and piperidine derivative B1.5 (0.015 g, 0.025 mmol) was added. After 3 hours, a 10% aqueous solution of No. ₁ HCO ₃ (0.15 ml) was added and the reaction mixture was stirred for another 20 minutes, and then concentrated in high vacuum. The residue was dissolved in water, filtered through a cellulose filter (pore size 45 μm), and passed through an Oo \ geh 50 ion-exchange column (Form No. 1 +, column diameter 2.5 cm, length 3.5 cm), washing with deionized water . The filtrate was concentrated in vacuo and purified by gel filtration on Vue-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm ), and then subjected to reverse phase chromatography (silica gel Megsk KP18, eluent: methanol / water, 1: 9), whereby the target molecule B1.57 (0.007 g, 33%) was obtained in the form of white solid flakes (after lyophilization) . Ή-NMR (400 MHz, 1EO) δ 5.8 (br s, 1H), 4.94 (m, 1H), 2.55 (m, 1H), 2.10 (m, 1H), 1, 07 (d, 1 = 6.0 Hz, 3H). MS (EAB, ΤΗ6) 796 (M + N), 774 (M + H).

Example B38 Preparation of Compound B1.58

Ν, Ν-Dimethylaminopyridine (1.03 g, 8.44 mmol) and p-nitrobenzene-sulfonyl chloride (1.65 g, 7.44 mmol) were added at room temperature to an alcohol solution 37 (6.11 g, 5.1 mmol) in CH ₂ Cl ₂ (35 ml). After 52 hours, the reaction mixture was washed with a 10% aqueous CaHCO3 solution, and the aqueous phase was extracted 3 times with CH ₂ Cl ₂ . The combined organic phases were dried (Ma ^ Od), filtered and concentrated in vacuo. The crude product (10 g) was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 35:65), whereby nosylate 52 (6.58 g, 93%) was obtained.

A solution of nosylate 52 (7.78 g, 5.62 mmol) and anhydrous ΤίΝ ₃ (0.99 g, 20.21 mmol) in anhydrous Ν, Ν-dimethylformamide (50 ml) was heated to 50-60 ° C in argon atmosphere . After 16 hours, the solvent was removed under high vacuum, and the residue was dissolved in CH ₂ Cl ₂ and washed with a 10% aqueous NaHCO ₃ solution. The aqueous phase was extracted three times with CH ₂ Cl ₂ , and the combined organic phases were dried (SchA ₂ 8O ₄ ), filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 30:70) to obtain the desired azide 53 (4.22 g, 61%) and then 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) was stirred at room temperature for 2.5 hours The pH of the reaction mixture was made neutral by the addition of a strongly acidic ion exchanger (Abb2H3! 15, form H +), after which the suspension was filtered and the filtrate was concentrated in vacuo. The crude product (4.5 g) was purified by silica gel column chromatography (eluent: CH ₂ Cl ₂ / methanol = 19: 1) to obtain triol 54 (2.89 g, 92%).

A suspension of compound 54 (2.89 g, 3.17 mmol) and di-n-butyltin oxide (1.56 g, 6.27 mmol) in anhydrous benzene (95 ml) was refluxed under argon for 16 hours The reaction mixture was concentrated in vacuo and dried under high vacuum for 1 h. To this mixture was added CzP (dried under high vacuum at 300 ° C for several hours; 1.2 g, 7.9 mmol), and then anhydrous 1,2 dimethoxyethane (80 ml) and a solution of A5 triflate (6.3 g, 15.97 mmol) in anhydrous 1,2 dimethoxyethane (50 ml) were added. The reaction mixture was heated to 35-40 ° C and stirred at this temperature for 3 hours. Then, the mixture was washed with a solution of 15% KE in a 1M aqueous solution of KH ₂ PO ₄ (150 ml), and the aqueous phase was extracted three times with CH2C12. The combined organic phases were dried (Na ₂ 8Ο _4), filtered and concentrated in vacuo. The oily residue (10.9 g) was purified by silica gel column chromatography (first eluting with toluene / ethyl acetate (4: 1) and then with CH2C12 / methanol (19: 1) to give the precursor), whereby ether 55 (1 , 94 g, 53%) as a colorless foam, and some precursor (1.1 g, 26%).

Morpholine (215 μl) and Pb (PPy ₃ ) ₄ (0.015 g, 0.013 mmol) were added under argon to a solution of allyl carbamate 55 (0.15 g, 0.13 mmol) in tetrahydrofuran (1.7 ml). After exactly 15 minutes, the solution was concentrated, and the residue was dried under high vacuum for 1 hour. The crude product was purified on a narrow column of silica gel (eluent: CH ₂ Cl ₂ / methanol = 19: 1 containing 0.3% concentrated aqueous ammonia) and then dried under high vacuum for 1 h. The residue was dissolved in anhydrous CH2C12 (1.7 ml) and the resulting solution was cooled to 0 ° C and triethylamine (43 μl, 0.31 mmol) and n-butanesulfonyl chloride (18 μl) were added. 0.14 mmol). After 15 minutes, the reaction mixture was warmed to room temperature and washed with 10% aqueous NaHCO ₃ solution. The aqueous phase was extracted 3 times with methylene chloride, and the organic phases were combined, dried with SchA ₂ 8O ₄ ), filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 30:70), whereby sulfonamide 56 (0.12 g, 77%) was obtained.

'V1.5V

Dioxane (1.2 ml), water (0.6 ml) and glacial acetic acid (0.25 ml) were added to a mixture of Pb (OH) ₂ / C (Reag1tap catalyst, 20% Pb content, 0.035 g) and benzyl ether 56 (0.027 g, 0.023 mmol). The contents of the flask were pumped out and purged several times with argon. After purging with hydrogen, the black reaction mixture was hydrogenated at slightly elevated hydrogen pressure at room temperature for 12 hours, and then filtered through a cellulose filter (pore size 45 μm). The filtrate was concentrated in vacuo and the residue was dissolved in water and concentrated several times to remove excess acetic acid. The crude intermediate (0.017 g; lyophilized) was dissolved in a 1M aqueous solution of No. ₁ HCO ₃ (0.3 ml) for 5 hours, and then several small portions (30-50 ml) of approximately 1M solution of 3,4-dimethoxybenzoyl chloride in toluene were added. until thin layer chromatography (TLC plates with silica gel; mobile phase: n-butanol / water / acetone / glacial acetic acid / ΝΗ. ₄ OH, 70:60:50: 18: 1,5) indicated complete conversion of the intermediate compound. During the course of the reaction, the pH of the solution was maintained mainly by adding several portions of solid NaHCO ₃ (a total of about 0.025 g). Then the reaction mixture was concentrated in vacuo, and the residue was dissolved in a small amount of water and purified by gel filtration on B1Ce1 P2 (particle size 65 μm, column diameter

2.5 cm, length 35 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk KR18, eluent: methanol / water, 65:35), and the target molecule B1.58 was obtained (0.008 g, 39 %) in the form of white solid flakes (after lyophilization). ¹ H-NMR (400 MHz, O ₂ O) δ 7.41 (brd, 1 = 8.3 Hz, 1H), 7.32 (br s, 1H), 7.04 (d, 1 = 8.3 Hz, 1H), 5.05 (d, 1 = 3.9 Hz, 1H), 4.51 (d, 1 = 7.8 Hz, 1H), 4.14 (q, 1 = 6, 7 Hz, 1H), 4.09 (t, 1 = 4.1 Hz, 1H), 3.82 (s, 6H), 3.33 (dd, 1 = 3.1, 9.6 Hz, 1H) 1.13 (d, 1 = 6.3 Hz, 3H); 0.68 (t, 1 = 7.6 Hz, 3H); MS (RAV, TH6) 923 (M + N), 901 (M + H), 879 (M + 2H-No).

Example B39 Preparation of Compound B1.59

B1.59

Dioxane (5.3 ml), water (2.6 ml) and glacial acetic acid (1.1 ml) were added to a mixture of Pb (OH) ₂ / C (Reag1tap catalyst, 20% Pb content, 0.13 g) and benzyl ether 56 (0.12 g, 0.1 mmol). The contents of the flask were pumped out and purged several times with argon. After purging with hydrogen, the black reaction mixture was hydrogenated at slightly elevated hydrogen pressure at room temperature for 24 hours, and then filtered through a cellulose filter (pore size 45 μm). The filtrate was concentrated in vacuo, and the residue was 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 purified by gel filtration on Vue-6e1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water; flow rate 0.45 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk KR18, eluent: methanol / water = 1: 1), and the target molecule B1.59 (0.052 g, 73%) was obtained as white solid flakes (after lyophilization). ¹ H-NMR (400 MHz, 1HO) δ 5.00 (d, 1 = 3.6 Hz, 1H), 4.41 (d, 1 = 7.7 Hz, 1H), 4.28 (q, 1 = 6.5 Hz, 1H), 3.83 (d, 1 = 3.1 Hz, 1H), 3.79 (dd, 1 = 3.1, 9.7 Hz, 1H), 3.32 (dd , 1 = 3.2, 9.6 Hz, 1H), 1.12 (d, 1 = 6.1 Hz, 3H), 0.83 (t, 1 = 7.9 Hz, 3H); MS (RAV, TH6) 737 (M + +), 713 (M + H).

Example B40 Preparation of Compound B1.60

* _ o o • s <n ₈

B1.59

B1.60

Amine B1.59 (0.027 g, 0.038 mmol) was dissolved in a 1 M aqueous solution of Na 3CO ₃ (0.35 ml) and several small portions (30-50 μl) of approximately 0.5 M solution of benzoyl chloride in toluene were added over 4 hours until until thin layer chromatography (TLC plates with silica gel, mobile phase: n-butanol / water / acetone / glacial acetic acid / NΗ ₄ OH = 70: 60: 50: 18: 1,5) indicated a complete conversion of the compound. During the reaction, the pH of the solution was maintained basic by adding several portions of solid NaHCO ₃ (a total of about 0.01 g). Then the reaction mixture was concentrated in vacuo, and the residue was dissolved in a small amount of water and purified by gel filtration on Vue-Ce1 P2 (particle size 65 μm, column diameter 2.5 cm, length 35 cm, eluent: water: flow rate 0 , 45 ml / min, detection at 215 nm), and then subjected to reverse phase chromatography (silica gel Megsk KP18, eluent: methanol / water = 1: 1), and the target molecule B1.60 (0.027 g, 85%) was obtained in in the form of white solid flakes (after lyophilization). ¹ H-NMR (400 MHz, E ₂ O) δ 7.72 (d, 1 = 8.0 Hz, 2H), 7.52 (t, 1 = 6.9 Hz, 2H), 7.44 (t ,

1 = 7.5 Hz, 2H), 5.05 (d, 1 = 3.8 Hz, 2H), 4.50 (d,

1 = 8.1 Hz, 1H), 4.17 (q, 1 = 6.6 Hz, 1H), 3.92 (broad d, 1 = 10.4 Hz, 1H), 3.85 (d, 1 = 2.8 Hz, 1H), 3.80 (dd, 1 = 3.1, 10.4 Hz, 1H), 3.33 (dd, 1 = 2.8, 9.8 Hz, 1H), 1.12 (d, 1 = 7.1 Hz, 3H); 0.70 (t, 1 = 8.2 Hz, 3H); MS (RAV, TH6) 863 (M + N), 841 (M + H).

Example B41 Preparation of Compound B1.61

B1.59 B1.61

Carbamate B1.61 was obtained from amine B1.59 (0.027 g, 0.038 mmol) by the method described in example B40 (preparation of compound B1.60) using benzyl chloroformate as a reagent. Yield = 0.007 g (21%). ¹ H-NMR (400 MHz, 1XO) δ 7.31 (m, 5H), 5.06 (d, 1 = 12.0 Hz, 1H), 4.97 (d, 1 = 12.0 Hz, 1H ), 4.96 (d, 1 = 4.0 Hz, 1H), 4.42 (d, 1 = 7.7 Hz, 1H), 4.19 (q, 1 = 6.6 Hz, 1H), 3.96 (br s, 1Η), 3.80 (d, 1 = 2.9 Hz, 1H), 3.50 (dd, 1 = 8.2, 9.4 Hz, 1H), 3.29 (dd, 1 = 2.9, 9.7 Hz, 1Η), 3.20 (brd, 1 = 12.2 Hz, 1Η), 1.06 (d, 1 = 6.5 Hz, 3H) 0.77 (t, 1 = 8.0 Hz, 3H); MS (RAV, THS) 871 (M + H), 849 (M + 2H-No).

The following compounds were obtained by the method described in the above examples.

Table 1a

Compound No. K3 Εηα B1.64 Νι C (O) -3.4- (OH) 2-C6H5 B1.65 Νι C (O) CH (C6H5) 2 B1.68 Νι C (O) -3.4- (OSN2C6H5) 2-C6H5 B1.70 Νι C (O) -3,4,5- (OH) 3-C6H5 B1.72 Νι C (Ο) [CΗ (ΟΗ)] 2C (Ο) ΟN- B1.73 Νι C (O) CH3 B1.77 Νι ZYuSSSSchSyuk B1.78 Η Η B1.80 Νι 8 (Ο) 2СΗ2С6Η5 B1.81 Νι C (Ο) NΗС6Η5 B1.82 Νι C (O) C6H _P B1.83 Νι 8 (O) 2 (CH2) 3CH3 B1.84 Νι C (O) O (CH2) 2CH3

Table 1a '

Compound No. K3 Εηα Ksa B1.62 Νι C (O) CH3 NΗС (Ο) С1οΗ7 B1.63 Νι C (O) CH3 NΗС (Ο) ΟСΗ2С6Η5 B1.66 Νι C (O) CH3 NΗС (Ο) СΗ2С6Η5 B1.67 Νι C (O) CH3 NΗС (Ο) СΗ2ΟС6Η5 B1.69 Νι C (O) CH3 ΝΗΟΌ) ΟΗ2ΝΗΟ (O) OSN2S6N5 B1.71 Νι NΗ8 (Ο) 2СΗ2С6Η5 B1.74 Νι 8 (O) 2 (CH2) 3CH3 NΗС (Ο) ΟСΗ2С6Η5 B1.75 Νι 8 (O) 2 (CH2) 3CH3 ΝΗΟ ^ ΙΟΗ, B1.76 Η 8 (O) 2 (CH2) 3CH3 ΝΗ2 B1.79 Νι 8 (O) 2 (CH2) 3CH3 ZhS (O) -3.4 (OCH3) 2S6N3

Table1b

Compound No. K3 Kna B1.85 Νι 8 (O) 2-4-CH3-C6H4 B1.86 Νι 0 (0) (0H2) ₈ 0 (0) 00H B1.87 Νι 8 (Ο) 2 (СΗ2) зСΗз B1.88 N (CH2) 2CH3 B1.89 Νι S (O) S6SCH B1.90 Νι C (O) CH3 B1.91 Νι C (O) O (CH2) 2CH3

C. Analysis of ligand binding to determine 1C ₅₀ using positive control.

E-selectin / person. 1dC chimera [cloned and expressed as described by Kohldeg e! A1., VusNeshMGU 35: 6385-6392 (1996)] were incubated in a Ra1coptomBb ™ microtiter plate (Tablet 1) at a concentration of 200 ng / well in 0.01 M Tris, 0.15 M No. C1, 1 mM CaCl ₂ , pH 7.4 (Tris-Ca ⁺⁺ buffer).

The thus obtained solution for inoculation was distributed into the wells in an amount of 100 μl / well with an E-chimera content of 2 μg / ml. Row 12 was left as a dummy, that is, with only one buffer. Plate 1 was closed and incubated for 2 hours at 37 ° C. After incubation, 100 μl / well of 2% B8A in Tris-Ca ⁺⁺ buffer was added and incubated at room temperature for 1 h. During incubation, the compounds (2-fold serial dilution) were titrated in 1% B8A in Tris-Ca ⁺⁺ s using tablets for microtiter with an i-shaped bottom (tablet 2). The rows were serially bred to row 9. Rows 10, 11, and 12 contained only buffer. The final volume was 60 μl / well, and the first well, with the exception of the positive control, contained 10 mm of Compound A (8Le ^x -Let1eyh), and Compound B was used as a positive control for each plate, and the first well contained 5 mM of these compounds. Conjugate Po1u8e ^and 8A-HPP was preliminarily prepared by incubation of sialyl-Le ^and PAA-biotin (ca! # 01044, ClusoTes11 Co., Koskushe, MO) with streptavidin-NKR (NKR - horseradish peroxidase) in a molar ratio of 2. Then, in all wells, except row 11 in plate 2, 60 μl / well of a concentration of 1 ng / μl po1u8e ^and 8A-NKR conjugate in 1% B8A in Tris-Ca ^{++ was} added. Tablet 1 was washed 4 times with Tris-Ca ⁺⁺ - in an automatic device for washing tablets. After that, 100 μl / well was transferred from tablet 2 to tablet 1, starting with the lowest concentration of the compound. Tablet 2 was discarded. The plate was incubated on a shaker for 2 hours at room temperature. Then, the tablet was washed 4 times with Tris-Ca ⁺⁺ using an automatic device for washing the tablets. After that, 100 μl / well of the substrate [mixture of 3.3 ', 5.5'-hegamegilbenzidine reagent and H ₂ O ₂ in a 1: 1 ratio] was added from the right to left with an 8-channel pipette. The plate was incubated for 2 hours at room temperature. The reaction was terminated by adding 100 μl / well of 1M H ₃ PO ₄ (from right to left) using an 8-channel pipette. The optical density at 450 nm was measured in a plate reader.

Control compound A

Control compound B

Jus was calculated by determining the concentration of the compound necessary for 50% inhibition of the maximum binding of po1u8e ^and NKR conjugate to immobilized β-selectin / person Iβ-ximera. Relative values of 1C _{50 were} determined by calculating the ratio of 1C _{50 of the} internal control compound to 1C _{50 of the} test compound.

In the following tables, IP ₅₀ means:

1C. L (test compound)! C ₅₀ (control compound A).

table 2

Compound No. thirteen Κ4 SHS50 Β1.1 Ha -CH2S6N5 0.35 B1.2 Ha CH2C6H11 0.08 B1.3 Ha -CH2KNS (O) C6H5 1,11 B1.4 Ha -СΗ2NΗС (О) (СΗ2) 2С6Η5 1.85 B1.5 Ha -CH2KNS (O) (CH2) 3OH 1.23 B1.6 N 0.96 B1.7 N -C11.-ΝΊ 1C11 .- ((41) 43.1 G 1.15 B1.8 Ha -CH2VDS (O) С6Н5] СН2 (СН) 2С <Н5 0.90 B1.9 N СН2КНСН2С6Н5 0.61 Β1.10 Ha -CH2XCN2C6H5) 2 0.60 Β1.11 N -CH2CH [CH2CH (CH3) 2] 0.74 Β1.12 N -CH2 ^ CH2CH (CH3) 2] 2 0.32 Β1.13 Ha -CH2 ^ C (O) C6H5] [CH2CH (CH3) 2] 0.21 Β1.14 Ha -CH2KH [8O2 (C6H4 ^ O2] 0.12 Β1.15 Ha -C1ΙΛΊ 18 () 43.11.4Ί G 0.13 Β1.16 Ha -CH2KNS (O) CE3 0.64 Β1.17 Ha -CH2KNS (O) C6H11 1.33 Β1.18 Ha -CH2CH2C6H5 0.14

Β1.19 Ha -CH2CH2S6H11 0.17 B1.20 Ha -CH2XNS (O) C11H23 1.76 B1.21 Ha -СΗ2NΗС (О) СΗ (С6Η5) 2 0.71 B1.22 Ha -CH.-HNS (O) S-H.44) .- Ha 1.05 B1.23 Ha -CH2 CNS (O) C6 [(1,3,4,5) OH] 4H7 0.79 B1.24 Ha -CHA'11C (O) (3.11. | 8O; Ha 0.93 B1.25 Ha -CHA'11C (O) (3.11.4'1 1.29 B1.26 Ha -CH ΛΊ 1C (O) (3.1 (AO. 1.21 B1.27 Ha -CH.-CNS (O) C6H., OCH _; 1.15 B1.28 Ha -CH2XNS (O) C6H4 (3.4) C12 2.04 B1.29 Ha -CHA11C (O) (3.11.4'H .; 1.30 B1.30 Ha -CHA11C (O) (3.11.43.1 N 1.65 B1.31 Ha -СΗ2NΗС (О) С6Η4СN 1,04 B1.32 Ha -CH2KNS (O) С10Н7 1.44 B1.9 Ha -CHA11CH43.1 N 0.61 B1.33 Ha -CHA11C (O) (3.11.44) OH 0.96 B1.34 Ha -SNANCE (O) (CH () H) 44) OH 0.78 B1.35 Ha -CH2ZHS (O) С6Н5] СН2С6Н5 0.44 B1.36 Ha -CH2 ^ C (O) C6H5] (CH2) 3C6H5 0.57 B1.37 Ha -CH2KN8O2SE3 0.26 B1.38 Ha - CH2 ^ CH2CH (CH3)] 8O2C6H4 ^ 2 0.32

Table 2a

Compound No. IS50 Compound No. KK '· .. B1.62 0.949 B1.77 0.618 B1.64 0.287 B1.78 0,304 B1.65 0.862 B1.79 0.196 B1.66 1,112 B1.80 0,203 B1.67 0.564 B1.81 0.216 B1.68 0.696 B1.82 0.195 B1.69 2,661 B1.83 0.176 B1.70 0.199 B1.84 0.169 B1.71 0.414 B1.85 1.28 B1.72 0.186 B1.86 2,733 B1.73 0.249 B1.87 0.520 B1.74 0.134 B1.88 1,257 B1.75 0.102 B1.89 0.696 B1.76 0.451 B1.90 0.569 B1.63 0,087

CLAIM

Claims (19)

CLAIM 1. The compound of formula I in which X represents the residue of a non-glycoside aliphatic 1, 2-diol; Κι represents a group of formula III so.h (W), 12 represents hydrogen, C1-C12 alkyl or C ₆ aryl; 13 represents hydrogen or ME; 14 is C1-C12alkyl, C2-C12alkenyl, C3-C12cycloalkyl, C3-S12tsikloalkenil, S2S11geterotsikloalkil, C2-S11geterotsikloalkenil, C6-C10-aryl, C5-S9geteroaril, C7 S11aralkil, C ₆ -C1 ₀ heteroaralkyl, _C8 or C7 -Stsaralkenil C10 heteroaralkenyl which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH halogen, C (O) OK ₈ 1. OS (O) Kk4. C (O) Kk2. nitro, ΝΗ2. cyano, 8o M _{3 y.} OZO ₃ M _at . W ₂₀ 8O ₃ M _U. C ₁ -C ₁₂ alkyl, C2-C12 alkenyl, C1-C12 alkoxy, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C6-C10 aryloxy, C5-C9-hetero, C5-C9 hetero C7-C11 aralkyl, C7-C11 aralkyloxy, C6-C10 heteroaralkyl, C8-C11 aralkenyl, C ₇ -C ₁₀ heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbohydroamide; To _k1 represents hydrogen, M _U. C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroaralkyl; Ki represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10aryl, C5-C9heteroaryl, C7-C11 aralkyl or C6-C10heteroalkyl; _K2 K and K ₂₀ represent hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C2-S11geterotsikloalkil, C2-C11 heterocycloalkenyl, C6-C10-aryl, C5 -C9 heteroaryl, C ₇ -C ₁₁ aralkyl, C ₆ -C ₁₀ heteroaralkyl, C ₈ C11 aralkenyl or C7-C10 heteroaralkenyl; Y is 1 and M is a monovalent metal or y is 1/2 and M is a divalent metal; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl or heteroaralkenyl, in turn, are unsubstituted, substituted or more substituted or substituted consisting of OH, halogen, C (O) OK _k1 . OS (ОЖ _4. С (О) К _к2 . Nitro, НН _2. Cyano, ЗО ₃ М _у . ОЗО ₃ М _у . НК ₂₀ 8О ₃ М _у , С ₁ -С ₁₂ alkyl, С ₂ -С ₁₂ alkenyl, C1-C12 alkoxy, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₆ -C ₁₀ aryloxy, C5-C9 heteroaryl, C5-C9 heteroaryloxy, 11 C6-C10 heteroaralkyl, C8-C11 aralkenyl, C7-C10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamides, including physiologically acceptable aminocarbonylamide annogo compound. 2. The compound according to claim 1, wherein X is a linear or branched C ₂ -C ₂₀ alkylene, alkenylene, C ₃ -C ₁₂ cycloalkylene, cycloalkenylene, C ₃ -C ₁₁ heterocycloalkylene or heterocycloalkenylene with heteroatoms selected from the group consisting of -O-, -8- and -Ν-. 3. The compound according to claim 1, where X represents the remainder of the 1,2-diol having the formula n 'and in which K ₅ and Kb independently represent hydrogen, C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C _p heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroaralkyl ; either K ₅ and K ₆ . taken together with the CH-CH- group, are C3-C12 cycloalkylene, C3C12 cycloalkenylene, C2-C11 heterocycloalkylene and C3-C11 heterocycloalkenylene with heteroatoms selected from the group consisting of -O-, -8- and -Ν-; where alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkylene, cycloalkenylene, heterocycloalkylene and geterotsikloalkenilen are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OK _k1. OS (O) Kk4. C (O) Kk2. nitro, ΝΗ2. cyano, 8O3MU. O8O ₃ M _at . NK ₂₀ 8Ο ₃ M. _at C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₁ -C ₁₂ alkoxy, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C 11 heterocycloalkyl, C 2 -C 11 heterocycloalkenyl, C 6 -C ₁₀ aryl, C ₆ -C ₁₀ aryloxy, C ₅ -C ₅ -9 C9 heteroaryloxy, C7C _p aralkyl, C ₇ -C ₁₁ aralkyloxy, C ₆ -C ₁₀ heteroaralkyl, C8-C11 aralkenyl, C7-C10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, sulfonamide, carbide sulfide where K _k1 represents hydrogen, MU. C1-C12 alkyl, C2-C12 alkenyl, C3-C12 cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C ₆ -C ₁₀ heteroalkyl; _K4 represents hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C3-C12 cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroalkyl; Kk2 and K20 represent hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkenyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl, C11-C11-Calkyl or C7-C10 heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl or heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1; and M is a monovalent metal; or y = 1/2. and M is a divalent metal. 4. The compound according to claim 3, where K ₅ and K ₆ (a) are unsubstituted or substituted with C ₁ -C ₁₂ alkyl or C ₁ -C ₁₂ alkoxy; (b) together with the group —CH — CH— represent a 5-8 membered carbocycle; (c) together with the group —CH — CH represent a 5–8 membered heterocarbocycle; (g) independently of one another are hydrogen, unsubstituted C ₁ -C ₁₂ alkyl or C ₁ -C 12 alkyl which is substituted with a substituent selected from the group consisting of -C (O) RP _81, -OC (O) K _4, -C ( O) OYa or C (O) OK, primary amino, secondary amino, C3-C12cycloalkyl, C1C ₆ alkoxy, phenyloxy and benzyloxy; unsubstituted C ₃ -C ₁₂ cycloalkyl or C ₃ -C ₁₂ cycloalkyl, which is substituted with a substituent selected from the group consisting of —C (O) OH ₈₁ , —OC (O) K ₄ , —C (O) OH or C (O ) OK, primary amino, secondary amino, C1-C6 alkyl, C1-C6 alkoxy, phenyloxy and benzyloxy; C ₆ -C ₁₀ aryl, which is unsubstituted or substituted by -C (O) OA ₈₁ , -OC (O) K ₄ , -C (O) OAa or C (O) OK, primary amino, secondary amino, C ₁ -C ₆ alkyl or C ₁ C ₆ alkoxy; C ₃ -C ₉ heteroaryl with 1 or 2 heteroatoms selected from the group consisting of oxygen and nitrogen atoms; or C ₇ -C ₁₂ aralkyl, which is unsubstituted or substituted by -C (O) OH ₈₁ , -OC (O) K ₄ , -C (O) OH or C (O) OK, primary amino, secondary amino, C1-C6 alkyl or C1C6 alkoxy; (e) together with the group —CH — CH— represent a 5-12 carbocycle or a 5- or 6-membered heterocarbocycle with a heteroatom selected from the group consisting of oxygen and nitrogen atoms; or (e) together with the group —CH — CH— represent C ₃ -C ₁₂ cycloalkylene, C ₄ -C ₁₂ cycloalkenylene, C ₂ -C ₁₁ heterocycloalkylene or C ₃ -C ₁₁ heterocycloalkenylene with heteroatoms selected from the group consisting of —O -, -8- and -Ν-; where cycloalkylene, cycloalkenylene, heterocycloalkylene and heterocycloalkenylene are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OK ₈₁ , OS (O) K ₄ , C (O) K ₂ , nitro, ΝΗ ₂ , cyano, 8O ₃ M _y , O ₈ O ₃ M _y , MK ₂₀ 8 O ₃ M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C1-C12 alkoxy, C3-C12 cycloalkyl, C3C12 cycloalkenyl, C2-C11 heterocycloalkenyl, C2C11 heterocycloalkyl , C6-C10-aryl, C6-S10ariloksi, C5-S9geteroaril, S9geteroariloksi C5, C7 S11aralkil, S11aralkiloksi C7, C6-S10geteroaralkil, C ₈ -C ₁₁ aralkenyl, C ₇ -C ₁₀ heteroaralkenyl , Primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfongidrazid, carbohydrazide, carbohydroxamic acid and aminokarbonilamid where Κι is hydrogen, M _y, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C ₆ -C ₁₀ heteroalkyl; Представляетι represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroalkyl; and K ₂ and K ₂₀ represent hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C ₅ - C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl, C ₆ -C ₁₀ heteroaralkyl, C8-C11 aralkenyl or C7-C10 heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl or heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1, and M denotes a monovalent metal; or y = 1/2, and M denotes a divalent metal. 5. The compound according to claim 4, where K ₅ and K. taken together with the group —CH — CH— represent C ₃ C ₁₂ cycloalkylene or C ₂ -C ₁₁ heterocycloalkylene, where the heteroatom is a nitrogen atom, where K ₅ and C3, taken together with the group —CHCH—, represent C ₃ -C ₁₂ cycloalkylene or C ₂ C ₁₁ heterocycloalkylene, where the heteroatom is a nitrogen atom, said cycloalkylene and heterocycloalkylene being unsubstituted or substituted by one or more substituents selected from the group consisting of OH, C (O) OX, OC (O) K ₄ , C (O) K2, ΝΚΚ, C1-C12 alkyl, Κ ^ ζΝΗΐρΝ ^) -, -С (О) ^) _Р MKK ₉ , K8 (O) 2 ^^ (К ₉ ) - , KK ^ C (O) ^) _P ^ K ₉ ) -, KOS (O) ^^ (K ₉ ) -, -OC (O) (KH) _| KKK and Ya10-8O2-, where K, K9, K0 and K40 independently represent hydrogen, OH, C1-C12 alkyl, C1-C12 alkenyl, C3-C12 cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl , C2-C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C16 aralkyl, C8-C16 aralkenyl with C2-C6 alkenylene and C6-C10 aryl, C6-C15 heteroaralkyl, C6-C15-heteroaryl alkyl, which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OKb OS (O) K ₄ , C (O) K ₂ , nitro, ΝΗ ₂ , cyano, 8O ₃ M _y , О8О ₃ М _у , НК ₂₀ 8О ₃ М _у , С ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C1-C12 alkoxy, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C6-C10 aryloxy, C5-Cio , S7S11aralkil, C7 S11aralkiloksi, C6-S10geteroaralkil, C8 S11aralkenil, C7 S10geteroaralkenil, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfongidrazid, carbohydrazide, carbohydroxamic acid and aminokarbonilamid, where R ₈₁ is hydrogen, M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocyclo alkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroaryl; K ₄ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C ₆ -C ₁₀ heteroalkyl; K: and K ₂₀ represent hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C3-C12 cycloalkyl, C3-C12 cycloalkyl nyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl, C7, C7 -C10 heteroaralkyl, C8-C11aralkenyl or C7-C10 heteroaralkenyl; and the substituents alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroalkyl, aralkenyl and heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1, and M denotes a monovalent metal; or y = 1/2, and M denotes a divalent metal. 6. The compound of claim 5 where R ₈ and R ₉ independently represent hydrogen, C1C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₆ -C ₁₀ aryl, C ₇ -C ₁₆ aralkyl with 1-6 carbon atoms in the alkylene group and C ₆ -C ₁₀ aryl, C ₈ -C ₁₆ aralkenyl with C ₂ -C ₆ alkenylene and C6-C10 aryl, or di-C6-C10 aryl-C1-C6 alkyl, where K ₈ and K ₉ are unsubstituted or substituted with one or more substituents selected from the group consisting of OH, halogen, COOH, C (O) _y ohm, C ₁ -C ₁₂ alkyl, C _{1 to} C ₆ alkoxy, C ₆ -C ₁₀ aryl, C ₆ -C ₁₀ aryloxy, , 8О ₃ М _у , О8О ₃ М _у , NК ₂₀ 8О ₃ М _у , NО ₂ , amino, primary amino, secondary amino and SI, and K ₂₀ p represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ C10 aryl, C5- C9 heteroaryl, C7-C11 aralkyl, C6-C10 heteroaralkyl, C8-C11 aralkenyl or C7-C10 heteroalkenyl; y = 1, and M denotes a monovalent metal, or y = 1/2, and M denotes a divalent metal. 7. The compound according to claim 5, where K ₁₀ represents C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C ₆ -C ₁₀ aryl, C ₇ C16 aralkyl with 1-6 atoms in the alkylene group and C6-C10 aryl, which are unsubstituted or substituted by one or more substituents selected from the group including OH, halogen, carboxyl, С (О) ОМу, С1С ₁₂ alkyl, С ₁ -С ₆ alkoxy, С ₆ -С ₁₀ aryl, §О ₃ М _у , nitro, amino, primary amino, secondary amino and cyano; or C8-C16 aralkenyl with C2-C6 alkenylene and C6-C10 aryl, or di-C6-C10 aryl C1-C6 alkyl. 8. The compound according to claim 5, where K and K ₆ taken together with the group —CH — CH— represent C ₃ C ₁₂ cycloalkylene or C ₂ -C ₁₁ heterocycloalkylene having nitrogen as the heteroatom; and where cycloalkylene and heterocycloalkylene are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, C (O) OK ₈₁ , OC (OJ ₄ , C (O) K ₈₂ , Ν ^, C ₁ -C ₁₂ alkyl, K ₈ C (OMK ₉ ) -, -C (O) 1MK ₈ K ₉ , K ₈ 8 (O) ^ (K ₉ ) -, ^ OCO ^ KD- and K ₁₀ -8O ₂ -, where K ₉ represents hydrogen and K ₈ represents C ₁ -C ₁₂ alkyl, C ₆ C ₁₀ aryl or C ₇ -C ₁₁ aralkyl which are unsubstituted or substituted by one or more C ₁ -C ₁₂ alkoxy; K ₁₀ represents C ₁ -C ₁₂ alkyl, C ₆ -C ₁₀ aryl or C ₇ -C ₁₁ aralkyl, which are unsubstituted or substituted by one or more C ₁ -C ₁₂ alkyl; K ₈₁ and K ,, ₄ are C ₁ -C ₁₂ alkyl, and K ₈₂ is C ₁ -C ₁₂ cycloalkenyl, C ₃ -C ₁₂ cycloalkyl or C6-C10 aryl, and the substituents are alkyl, cycloalkenyl, cycloalkyl and aryl, in turn, can be unsubstituted or substituted by one or more substituents selected from the group consisting of OH, C (O) OK ₈₁ and OC (OZh ₄ , where K represents M _y or C ₁ -C ₁₂ alkyl, a represents C ₁ C ₁₂ alkyl; y = 1, and M denotes a monovalent metal, or y = 1/2, and M denotes a divalent metal. 9. The compound according to claim 5, where K ₅ and Ky taken together with the group —CH — CH— represent cyclohexylene. 10. The compound according to claim 5, where K5 and K6 taken together with the group —CH — CH— represent piperidylene. 11. The compound of claim 10, where K ₅ and K ₆ taken together with the group —CH — CH— represent piperidylene; where the heteroatom is an unsubstituted or substituted substituent selected from the group consisting of C (O) OK ₈₁ , C (O) K ₂ , C (O) MH8K9, HH2, 8O3My, C1-C12 alkyl, C2-C12 alkenyl, C ₁ -C ₁₂ alkoxy, C ₃ -C ₁₂ cycloalkyl, C ₃ C12 cycloalkenyl, C2-C12 heterocycloalkyl, C2C11 heterocycloalkenyl, C6-C10 aryl, C6-C10 aryloxy, C5-C9 heteroaryl, C5-C9 heteroaryloxy, C7-C11-Cara-Cara -C11 aralkenyl, C7-C10 heteroaralkenyl, primary amino, secondary amino, sulfonyl, sulfonamide, sulfonhydrazide; and where one or more C atoms on the ring are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, OC (O) K5 ₄ , MH ₂ , O8O ₃ M _y , NK ₂₀ 8O ₃ M _y , C ₁ - C ₁₂ alkoxy, C ₆ S10ariloksi, S9geteroariloksi C5, C7 S11aralkiloksi, primary amino, secondary amino, sulfonamide, carbamide, carbamate, sulfongidrazid, carbohydrazide, carbohydroxamic acid and aminokarbonilamid, where R ₈₁ is hydrogen, M _y, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C3-C12cycloalkyl, C2-S11geter otsikloalkil, S6S ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ and alkyl or C ₆ to C ₁₀ heteroaralkyl; K ,, ₄ represents hydrogen, C ₁ C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ C ₁₁ heterocycloalkyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C7-C11 aralkyl or C6-C10 heteroaralkyl; K8 and K ₉ independently represent hydrogen, OH, C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C16 aralkyl, C6-C15 heteroaralkyl, C8C16 aralkenyl -C6 alkenylene and C6-C10 aryl, or di-C ₆ -C ₁₀ aryl-C ₁ -C ₆ alkyl, or K ₈ and K ₉ taken together are tetramethylene, pentamethylene, - (CH2) 2-O- (CH2 ) 2-, - (CH2) 2-8 (CH ₂ ) ₂ - or - (CH ₂ ) ₂ -MH ₇ - (CH ₂ ) ₂ -, and K ₇ represents H, C ₁ -C ₆ alkyl, C ₇ —C ₁₁ aralkyl, C (O) K ₂ , or sulfonyl; K, ₂ and K ₂₀ represent hydrogen, C ₁ C1 ₂ alkyl, C ₂ -C ₂ alkenyl, C ₃ -C ₂ cycloalkyl, C ₃ Cl ₂ cycloalkenyl, C ₂ -C heterocycloalkyl, C ₂ heterocycloalkenyl, C ₆ -C ₁ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl, C ₆ -C _{1 0} heteroaralkyl, C8-C11aralkenyl or C7-C10 heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl and heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1, and M denotes a monovalent metal; or y = 1/2, and M denotes a divalent metal. 12. The compounds of claim 11, wherein K ₅ and K ₆ taken together with the —CH — CH— group are piperidylene; where the heteroatom is an unsubstituted or substituted substituent selected from the group consisting of C (O) OK ₈₁ , C (O) K ₈₂ , C (O) HC. ₈ K ₉ and K ₁₀ -8 O ₂ -, and one or more C atoms on the ring are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, Ν ^, KDOJ -, K8C (O) S (K ₉ ) and КЗОС (О) Ы (К ₉ ) -, where К ₉ represents hydrogen, and К ₈ represents С1-С1 ₂ alkyl, С ₆ -С1 ₀ aryl or С ₇ -С and aralkyl, where alkyl, aryl and aralkyl are unsubstituted or substituted by one or more C1-C1 ₂ alkoxy; K. ₁₀ represents C1-C1 ₂ alkyl, C1-C1 ₀ aryl or C ₇ -C ₁₁ aralkyl, which are unsubstituted or substituted by one or more C ₁ -C ₆ alkyls; K ₈₁ represents C ₁ -C ₁₂ alkyl, and K ₈₂ represents C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ cycloalkenyl, C _{3 12} cycloalkyl or C ₆ -C ₁₀ aryl; and the substituents alkyl, cycloalkenyl, cycloalkyl and aryl, in turn, are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, C (O) K ₈₁ 'and OC (O) K ₈₄ ', where K _8G represents M _y or C ₁ -C ₁₂ alkyl, and K ₈₄ represents C ₁ -C ₁₂ alkyl; y = 1, and M denotes a monovalent metal, or y = 1/2, and M denotes a divalent metal. 13. The compound of claim 1, wherein X is cyclohexylene or piperidylene, which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, Ν11 ₂ , C ₃ H ₇ , -C (O) C6H5, -C (O) (CH2) 8C (O) OCH3, -C (O) [CH (OH)] 2C (O) OHa, C (O) -C6H8 (OH) 3, -C (O) -SbN11, -C (O) OS3H ₇ , -SdaVD, -NH8 (Ο) 2CH2C6H5, ^ С (О) С6 ЩОСН3) 2, -8 (О) 2-С4Н ₉ , -ΝΠ ^ ΝΠ С6Н5, -8 (О) 2-С6Н4СН3, -8 (О) 2СН2С6Н5 and -8 (O) 2 (CH2) C10H7. 14. The compound according to claim 1, where K ₂ represents C1-C6 alkyl. 15. The compound according to claim 1, where K ₁ corresponds to a group of formula III in which K ₃ represents hydrogen or M _y ; and K ₄ represents C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C ₂ C11 heterocycloalkenyl, C6-C10 aryl, C6-C9 heteroaryl, C7-C11 aralkyl, C6- C10 heteroaralkyl, C8C11 aralkenyl or C7-C10 heteroaralkenyl which are unsubstituted or substituted by one or more substituents selected from the group consisting of OH, halogen, C (O) OK ₈₁ , OC (O) K ₈₄ , C (O) K ₈₂ , nitro, Ν4 ₂ , cyano, 8О ₃ М _у , О8О ₃ М _у , НК ₂₀ 8 О ₃ М _у , С ₁ -С ₁₂ alkyl, С2-С12 alkenyl, С1-С12 alkoxy, С3-С12 cycloalkyl, С3-С12 cycloalkenyl, С2-С11 heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₆ C10 aryloxy, C5-C9 heteroaryl, C5-C9 heteroaryloxy, C7-C11 aralkyl, C7-C11 aralkyloxy, C6-C10 heteroaralkyl, C8-C11 aralkenyl, C7-C10 heteroaralkenyl, primary amino, amino , urea, carbamate, sulfonhydrazide, carbhydrazide, carbohydroxamic acid and aminocarbonylamide, where K ₈₁ represents hydrogen, M _y , C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl or C ₆ -C ₁₀ heteroaryl; K ₈₄ represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C ₆ -C ₁₀ aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6C ₁₀ heteroalkyl; K ₈₂ and K ₂₀ represent hydrogen, C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ -C ₁₁ heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl C5-C9 heteroaryl, C7-C11 aralkyl, C6-C10 heteroaralkyl, C8-C11 aralkenyl or C7-C10 heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl or heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1; and M is a monovalent metal; or y = 1/2, and M denotes a divalent metal. 16. The compound according to claim 1, which corresponds to formula 1a in which K ₃ represents hydrogen or M _y ; K ₄ represents C ₁ -C ₁₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₃ -C ₁₂ cycloalkenyl, C ₂ C ₁₁ heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl , C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aral95 Cu aralkyl, C ₆ -C 1 ₀ heteroaralkyl, _C8 or C7-S11aralkenil S10geteroaralkenil which are unsubstituted or substituted one or more times; I ₅ and K ₆ independently represent hydrogen, C 1 -C ₂ alkyl, C ₃ -C ₂ cycloalkyl, C ₂ -C heterocycloalkyl, C ₆ -C ₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -Caralkyl or C ₆ -C ₁₀ heteroaralkyl; or K ₅ and K ₆ taken together with the group —CH — CH represent C ₃ -C _{1 2} cycloalkylene, C ₄ Cl ₂ cycloalkenylene, C ₂ -C ₁₁ heterocycloalkylene and C ₃ -Cetheterocycloalkenylene with heteroatoms selected from the group consisting of - O-, -8- and -Ν-; where alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkylene, cycloalkenylene, heterocycloalkylene and geterotsikloalkenilen are unsubstituted or substituted one or more times, wherein the substituent is selected from the group consisting of OH, halogen, C (O) OK _81, OC (О) К ₈₄ , С (ОЖ ₂ , nitro, ΝΧ, cyano, 8О ₃ М _у , О8О ₃ М _у , КВ ₂₀ 8О ₃ М _у , С1-С1 ₂ alkyl, С ₂ -С1 ₂ alkenyl, С1-С12 alkoxy, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C6-C10 aryloxy, C5C9 heteroaryl, C5-C9 heteroaryloxy, C7-C11 C7 S11aralkiloksi, C6-S10geteroaralkil, C8 S11aralkenil, C7 S10geteroaralkenil, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfongidrazid, carbohydrazide, carbohydroxamic acid and aminokarbonilamid where represents hydrogen, M _y, C1-C1 ₂ alkyl, C ₂ -C ₁₂ alkenyl, C3-C12 cycloalkyl, C2-C11 heterocycloalkyl, C6C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6C1 ₀ heteroalkyl; represents hydrogen, C ₁ Cl ₂ alkyl, C ₂ -C ₂ alkenyl, C ₃ -C ₂ cycloalkyl, C ₂ scheterocycloalkyl, C ₆ -C ₁ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl or C 6 -C ₁₀ heteroaryl; K ₂ and K ₂₀ represent hydrogen, C1-C1 ₂ alkyl, C2-C12 alkenyl, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, C2-C11 heterocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C5-C9 heteroaryl-C8, C8, C8 C11 aralkenyl or C7-C10 heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl and heteroaralkenyl are, in turn, unsubstituted or substituted; y = 1; and M is a monovalent metal; or y = 1/2, and M denotes a divalent metal. 17. The compound according to clause 16, where K ₃ represents H, K or Να; K ₅ and Kb taken together with the group —CH — CH— represent C ₃ -C _{1 2} cycloalkylene, C ₄ -C _{1 2} cycloalkenylene, C ₂ -C ₁₁ heterocycloalkylene and C ₃ -C heterocycloalkylene with heteroatoms selected from the group consisting of -O-, -8- and -Ν-, which are unsubstituted or substituted one or more times; where the substituent is selected from the group consisting of OH, halogen, C (O) OK ₈₁ , OS (O) K ₄ , C (O) K ₂ , nitro, ΝΧ, cyano, 8O ₃ M _y , O8O ₃ M _y , YK ₂₀ 8O ₃ M _y , C ₁ Cl ₂ alkyl, C ₂ -C ₂ alkenyl, C 1 -C ₂ alkoxy, C ₃ -C ₂ cycloalkyl, C ₃ -C ₂ cycloalkenyl, C ₂ -Cetherocycloalkyl, C ₂ -C 11 heterocycloalkenyl, C 6 -C 10 aryl, C6-C10 aryloxy, C5-C9 heteroaryl, C5-C9 heteroaryloxy, C7-C11 aralkyl, C7-C11 aralkyloxy, C6-C10 heteroaralkyl, C8-C11 arakenenyl, C7-C10 heteroaralkenyl, primary amino, aminosulfonamide sulfonhydrazide, carbohydrazide, carbohydroxamic acid aminokarbonilamid where represents hydrogen, M _y, C1-C1 ₂ alkyl, C ₂ -C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C6-C10 heteroaralkyl; K ₂₀ and Κ ,, .- ι represents hydrogen, C ₁ -C ₁₂ alkyl, C ₂ C ₁₂ alkenyl, C ₃ -C ₁₂ cycloalkyl, C ₂ -C ₁₁ heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C ₆ -C ₁₀ heteroalkyl; k, ₂ and K ₂₀ represent hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, C2C ₁₁ heterocycloalkyl, C ₂ -C ₁₁ heterocycloalkenyl, C ₆ -C ₁₀ aryl, C ₅ -C ₉ heteroaryl, C ₇ -C ₁₁ aralkyl, C ₆ -C ₁₀ heteroaralkyl, C ₈ -C ₁₁ aralkenyl or C7-C10 heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl and heteroaralkenyl are, in turn, unsubstituted or substituted; and y = 1; and M is a monovalent metal; or y = 1/2, and M denotes a divalent metal; (a) K ₄ represents the remainder K ₁₂ - (CH ₂ ) _p or cyclohexyl, where p = 1 or 2, and K ₁₂ represents C ₁ -C ₁₀ alkyl, C ₅ -C ₈ cycloalkyl, C ₆ -C ₁₀ aryl, or C8-C12aralkenyl, which are unsubstituted or substituted with C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxyl, P, C1, 0Ν or -MO ₂ ; or K ₁₂ represents an amino group ΝΚ ₈ Κ ₉ , and K. ₈ and K. ₉ represent C ₁ -C ₁₂ alkyl, either unsubstituted or C ^ C ₄ -substituted C ₅ or C ₆ cycloalkyl, C ₆ -C ₁₀ aryl, C ₇ -C ₁₂ aralkyl or C ₈ -C ₁₂ aralkenyl; either K ₁₂ represents the amide group -Y (K ₉ ) C (O) K ₈ -, -Y (K ₉ ) 8 (O) K ₈ -, ^ K, ₉ C (O ^ NK. ₈ - or -ΝΚ ^ ^ ΝΉΚ ^ -, where K ₈ represents C6-C10 aryl which is unsubstituted or substituted by C1-C4 alkyl, C1-C4 alkoxy, P, C1, -ΟΝ or ^ O ₂ , or C ₁ -C ₁₀ alkyl which is unsubstituted or substituted by P or C1, and K ₉ represents H, C ₁ -C ₁₀ alkyl, C ₅ - or C ₆ cycloalkyl, C ₅ - or C ₆ cycloalkyl-C ₁ -C ₆ alkyl, phenyl-C ₁ -C ₆ alkyl or phenyl-C ₂ -C ₆ alkenyl; or (b) K ₄ represents C ₁ -C ₁₂ alkyl, C ₃ C ₁₂ cycloalkyl or C ₇ -C ₁₁ aralkyl, which are unsubstituted or substituted by one or more substituents, selected from the group consisting of OH, halogen, C (O) OK ₈₁ , OS (O) K ₄ , C (O) K ₂ , nitro, ΝΉ ₂ , cyano, 8О ₃ М _у , О8О ₃ М _у , ХК2о8ОзМ _у , C ₁ -C ₁₂ alkyl, C2-C12 alkenyl, C1-C12 alkoxy, C3-C12 cycloalkyl, C ₃ -C1 ₂ cycloalkenyl, C ₂ -Cetherocycloalkyl, C2-C11 heterocycloalkenyl, C6-C10 aryl, C6-C10 aryloxy, C5-C9 heteroaryl-aryl, C7-aryl-7-aryl, 11 S11aralkiloksi, S6S10geteroaralkil, S11aralkenil-C8, C7-S10geteroaralkenil, primary amino, secondary amino, sulfonyl, sulfonamide, carbamide, carbamate, sulfongidrazid, carbohydrazide, carbohydroxamic acid and aminokarbonilamid where represents hydrogen, M _{y, C1-C12} alkyl, C2 -C12 alkenyl, C3-C12 cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 Ralko or C6-S10geteroaralkil; Kk4 represents hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C3-C12 cycloalkyl, C2-C11 heterocycloalkyl, C6-C10 aryl, C5-C9 heteroaryl, C7-C11 aralkyl or C ₆ -C _{£ 0} heteroalkyl; By _k2 and R ₂₀ represent hydrogen, C1-C12alkyl, C2-C12alkenyl, C3-C12 cycloalkyl, C3-S12tsikloalkenil, C2-S11geterotsikloalkil, C2-S11geterotsikloalkenil, C6-C10 aryl, C5-S9geteroaril, C7 S11aralkil, C6-C10 heteroaralkyl C8-C11aralkenyl or C7-C10 heteroaralkenyl; moreover, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, aralkyl, aralkoxy, heteroaralkyl, aralkenyl and heteroaralkenyl are, in turn, unsubstituted or substituted; and y = 1; and M is a monovalent metal; or y = 1/2, and M denotes a divalent metal. 18. The compound according to claim 17, where (ί) K ₄ represents C ₆ H ₁₁ , C ₆ H ₁₁ -CH ₂ , C6H11-CH2CH2-, C6H5-CH2-, C6H5-CH2CH2- or C6H5-CH = CH-CH2 -; (ίί) K ₄ represents С ₆ Нц, С ₆ Нц-СН ₂ -, С6Н11-СН2СН2-, С6Н5-СН2-, С6Н5-СН2СН2-, СН21ЧК ₄₉ -8О2К18-, СН2-№1 ₉ -С (О) К40 -, SNUNS (O) NΗK1 _8, CH ₂ NΗK 1 or ₂ -CH ₂ N (R ₂ 1) _2, where R ₁₈ represents -S6N5, phenyl which is substituted by 13 methyl or methoxy, or -ΝΌ _2, or E, or C1 or C ₁ -C ₄ alkyl which is substituted with E; K40 represents phenyl which is unsubstituted or substituted by 1-3 methyl or methoxy groups, or —O ₂ , or P, or C1; By ₁₉ represents H, _C1-C6 alkyl, phenyl- (CH _{2) 2} -, where ζ = 1-3; phenylCH = CH-CH2, -CH2-CH (CH3) 2 or benzyl; and K21 is —CH ₂ —CK ₂₂ K ₂₃ K ₂₄ , where K ₂₂ and K ₂₃ are methyl, ethyl or phenyl, and K24 is H, ethyl or methyl; or (w) K ₄ represents C ₆ Hc, CH ₂ -C ₆ H ₅ , (CH 2) 2-C ₆ H ₅ , methyl, ethyl or isopropyl, which are unsubstituted or substituted by one or more substituents selected from the group consisting of Ν ^, cyclohexyl, C ₆ -C _{£ 0} aryl, K ₈ C (O ^ (K ₉ ) -, K ₈ 8 (O) ₂ AND (K ₉ ) -, W ₉ .C (OYANK ₈ - and K ₈ K ₉ No. -, where K ₈ , K ₉ , K ₈ and K ₉ independently represent hydrogen, C1-C1 ₂ alkyl, C ₃ -C ₂ cycloalkyl, C ₆ -C ₁₀ aryl or C ₇ -Ci aralkyl, which are unsubstituted or substituted with one or more substituents selected from the group consisting of OH, halogen, C (O) OM _y, nitro, q ano, 8o M _{3 y,} M ₃ O8O _y: 8 o NC _{20 3} M _{y 2} S1S1 alkyl S1S1 ₂ alkoxy and C ₆ -C 1 ₀ aryl, where R ₂₀ is hydrogen, C1-C12alkyl, C2-C12 alkenyl, C3-C12cycloalkyl, C3-S12tsikloalkenil, S2S11geterotsikloalkil, C2-S11geterotsikloalkenil, C6-C10-aryl, C5-S9geteroaril, C7-C11 aralkyl, C ₆ -C 1 ₀ heteroaralkyl -Stsaralkenil C ₈ or C ₇ -C 1 ₀ heteroaralkenyl, y = 1, and M denotes a monovalent metal, or y = 1/2, and M denotes a divalent metal. 19. The compound according to p. 1 6, where K4 represents C ₆ Nc, CH (CH ₃ ) ₂ , CH ₂ -phenyl, (CH ₂ ) ₂ -phenyl, CH2INS (O) -phenyl, C1ΙΛΊ 1C (O) (C11 ₉ ) _; -phenyl CH2INS (O) (CH2) 3OH, CH ^ C (O) CP3, CH2INS (O) С6Н11, СН2 ^ С (О) С _П Н23, CH ₂ ANN (O) CH (C ₆ H ₅ ) ₂ , CH2ZHS (O) K1NS ₆ H5, CH ₂ ANN (O) C ₂ H ₄ CO ₂ Na, CH ₂ ANN (O) C ₆ [(1,3,4,5) OH] ₄ H ₇ , CH ₂ LC (O) C ₆ H ₄ -p-8O ₃ No. CH ₂ ANN (O) C ₆ H ₄ C1, SHCHINZO ^ N / zIO ^ CH ₂ ANN (O) C ₆ H ₄ OCH ₃ , CH ₂ ANN (O) C ₆ H ₄ (3,4) Cl ₂ , CH ₂ ANN (O) C ₆ H ₄ CH ₃ , CH ₂ ANN (O) C ₆ H ₄ C ₆ H ₅ , СН2К1НС (О) С6Н4СН СН2 ^ С (О) С10Н ₇ , CH2K1NS (O) С6Н4СООЖ С11; \ 11С (О) (СНОСОЖ СН2ЖСЩСС = СН-phenyl) [С (О) -phenyl], ОД [СН2СН (СН3) 2] [С (О) phenyl], СН2 ^ С (О ) С6Н ₃ ] СН2С6Н5, [С (О) С6Н5] (СН2) 3С6Н5, (СН2) С6Н11, (СН2) 2С6Н11, СН ₂ : НН ₂ , СН ₂ : ННСН ₂ СН = СН-phenyl, CH ₂ INSN ₂ -phenyl, CHL'CH; CH (CH ₃ ) ₂ , CH ₂ S (CH ₂ -phenyl) ₂ , CH ₂ S [CH ₂ CH (CH ₃ ) ₂ ] ₂ , CH ₂ IN8O ₂ -p-nitrophenyl, CH ^ JO ^ p-tolyl, CH ₂ IN8O ₂ CE ₃ , CH ₂ ANN (O) C ₆ H ₅ or CH ₂ N [8O ₂ p-nitrophenyl] [CH ₂ CH ( CH ₃ ) ₂ ].