UA82642C2 - Use of metal complexes containing perfluoroalkyl, as contrast agents in mr imaging for the representation of plaque, tumors and necroses - Google Patents

Abstract

The invention relates to the use of metal complexes containing perfluoroalkyl, comprising a critical micelle formation concentration < 10mol/l, a hydrodynamic micelle dynameter of (2 Rh) > 1nm and a proton relaxivity in plasma (R) > 10 l/mmol-s, as contrast agents in MR imaging for the representation of plaque, lymph node, infarcted and necrotic tissue and for independent representation of necrotic tissue and tumoural tissue.

Description

This invention relates to the use of perfluoroalkyl-containing metal complexes, which are characterized by a critical micelle formation concentration of less than 10 Zmol/l, a hydrodynamic diameter of micelles (22) of more than 1 nm, and a relaxation of protons in plasma (B) of more than 10 l/mmol-s, as contrast agents in magnetic resonance (MR) ) tomography for visualization of plaques, lymph nodes, infarcted and necrotic tissue, as well as for independent visualization of necrotic tissue and tumor tissue. When creating the invention, it was established that perfluoroalkyl-containing metal complexes, which have the above properties, are most suitable for independent visualization of plaques, tumors and necrosis with the help of MR tomography and at the same time allow to cover the field of tomography, which plays an important role in the diagnosis of heart attacks and necrosis.

Arteriosclerosis is a painful change in arteries, which is of the most important importance and is the most common, accompanied by compaction and thickening of their walls, loss of elasticity of their walls and stenosis. Arteriosclerosis is the most common cause of death in Western industrialized countries. Changes in the vessel walls result in the deposition of lipids, the growth of connective tissue and unevenly distributed calcinosis, leading to the instability of the vessel walls, their narrowing, and the deposition of clots. Such a disease is caused by various exogenous and endogenous factors, respectively diseases, for example, hypertension, hyperlipidemia, hyperfibrinogenemia, diabetes, toxins, nicotine, antigen-antibody complexes, inflammatory processes, hypoxia, mental stress, age and problems in family relationships. Under the influence of all such factors, the integrity of the inner lining of blood vessels is disturbed, the control over the growth of smooth muscle cells of the vessel walls is disturbed, and the process of decomposition of the components of aged cells is also disturbed. Actually, arteriosclerosis cannot be treated in principle, and therefore all medical efforts are mainly reduced to the prevention of this disease by reducing the risk factors for its occurrence, for example, by using means that lower the level of lipids in the blood.

Currently, clinical practice mainly uses angiography to diagnose arteriosclerosis, which is a kind of "gold standard" in this field. However, all methods based on the measurement of the degree of reduction of the lumen of the vessel are limited to the diagnosis of that early stage of the development of the disease, which is characterized by thickening of the vessel wall with a normal lumen (see Siadom 5., 7agip5 S.K.,

Otsapiyaknpoud ashegozsiegov5i5, Siipisa! Oiadpovi5 oi Aipegossiegosii. Otsapiyaeyme Meipoaz oi EmaIchakop, under the editorship.

Vopam.a., pe! M/., Siadom 5., Spapaieg A.V., Sotpy 9.R., ed. Zrhipdeg Megiad, Mem Mogk 1983, p. 11-

Z5|Y. Another method that allows for diagnostic purposes to assess the state of the vessel wall and its lumen is intravascular or percutaneous ultrasound.

Tomography, based on the method of nuclear magnetic resonance (NMR-tomography or MRI), is a modern, non-invasive radiological method that allows to visualize physiological and pathophysiological structures with an exceptionally high spatial and temporal resolution. The use of special contrast agents capable of selectively accumulating in certain tissues and organs during such tomography significantly increases its value as a method of diagnostic research. It is obvious that compositions based on contrast agents capable of selectively accumulating in atherosclerotic plaques would make it possible to determine at an earlier point in time the location of the focus of the disease and the degree of its development and thereby provide the possibility of targeted treatment and prevention of this or that disease, and therefore the search for suitable contrast agents have been used for this purpose for a long time.

So, for example, in |patent 05 4577636) it was proposed to use hematoporphyrin derivatives as contrast agents for the detection of atherosclerotic plaques. Scintigraphy, radiography, fluorescence-based methods, and NMR spectrometry for paramagnetic metalloporphyrins are named as research methods in the specified patent. As paramagnetic ions in the specified publication, Sai, Сg, Со,

Mee, Ad and Em. The disadvantage of all these compounds is that porphyrins are deposited in the skin and change its color, this effect can persist for several weeks. In addition, such compounds cause photosensitization. In addition, if these compounds remain in the environment for a long time, there is a danger of "losing" the metal by metalloporphyrin.

In the Statement of the UMO 95/09856)| described metalloporphyrins (deuteroporphyrins) intended for the diagnosis and therapy of plaques. MRI is mentioned as a diagnostic method in this publication. However, porphyrins belonging to this type also change skin color.

In the Statement of the UMO 95/09013| described conjugates of polypeptides and metal complexes that bind specifically. According to the specified application, these compounds should also bind to plaques and thereby provide the possibility of their diagnosis and therapy. Scintigraphy, computed tomography and MRI are mentioned as diagnostic methods in this publication. In this application, experimentally confirmed data are given only for scintigraphy, while no data are available for MRI.

In (patent 5 5807536) labeled phycocyanins are described for use as contrast agents for plaque visualization. Radiography, computed tomography, scintigraphy, single-photon emission computed tomography (SPECT) and MRI are mentioned as diagnostic methods in this publication.

Experimentally confirmed data are given in the specified patent only for scintigraphy.

Numerous contrast agents for visualization of infarctions and necrosis are known from the literature. Attempts to increase the efficiency of localization, i.e. determining the location, infarcts and necrosis due to the use of contrast agents in non-invasive methods such as scintigraphy or NMR-tomography, began quite a long time ago. At the same time, a large number of published works are devoted to experimental studies on the use of porphyrins for visualization of necrosis. However, the results obtained in such studies are contradictory. So, in particular, in Irobot UMpkKeitap and

Novels, published in Maishige, 200 (1967), p. 903|, refers to the selective accumulation of manganese-5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TFPS) in the necrotic area of the tumor.

In contrast to this, in the work of ISuop et al. (Madp. Ke5. Med. 4 (1987), p. 24)| it is about the effect observed by these authors that manganese-TFPS is essentially distributed throughout the body, namely, it accumulates in the kidneys, liver, tumor and only slightly in muscle tissues. Of particular interest is the fact that the concentration of this substance in the tumor reaches a maximum only on the 4th day after administration, and then only after increasing the dose from 0.12 mmol/kg to 0.2 mmol/kg. Therefore, the authors also conclude about the non-specific accumulation of TFPS in the tumor tissue. In the work (Voskpigv5i et al., published in Asia Meigospig. 60 (1994, supplement), p. 347|), it is again referred to the selective binding of Mp-

TFPS with tumor cells.

In turn, based on the results of research conducted by Rovieg et al. (U. Mysi. Mei. 26 (1985), p. 756)Y), it was established that /""Chp-5,10,15,20-tetrakis(4-M-methylpyridinium)uporphyrin (TMPIP) accumulates not in the necrotic area, and in the living marginal layers surrounding it. Based on this, it would be possible to draw an obvious conclusion about the presence of interaction between porphyrin and tissue, which, however, does not necessarily correspond to reality.

In the work (Mi et al., published in Sigstiayop, vol. 90, Me4, part 2, p. 1468, Abstract Me2512 (1994)), it was reported about the possibility of visualization of infarcted areas with the help of manganese-tetraphenylporphyrin (Mp-TFP) and gadolinium-mesoporphyrin (c5a-MP). According to (UMO application 95/31219) both of these substances were used to visualize infarcts and necrosis. In this application, the authors of which are

Magspa! and Mi, it is said (see example 3) that when using the compound 5a-MP, the metal content in the infarcted kidney was at the same level as in the non-infarcted organ, while the metal content in the infarcted tissue was in the myocardium (see example 1 ) was nine times higher than its content in non-infarcted tissue. What is unexpected is the fact that in MRI the ratio between the intensity of the signal formed by the infarcted tissue and the intensity of the signal formed by the healthy tissue was in both cases at a relatively high level and was 2.10 and 2.19, respectively. Other metalloporphyrins are described in (application OE 19835082 (in the name of 5spegipd AS).

Porphyrins tend to accumulate in the skin, which leads to its photosensitization. Such sensitization can persist for several days, and sometimes for several weeks. This is an undesirable side effect that occurs when porphyrins are used in some diagnostics. In addition, porphyrins have only an exceptionally low therapeutic index, since, for example, in the case of Mp-

TFPS its effect is revealed only when it is used in a dose of 0.2 mmol/kg, while its lethal dose of LDvho is already 0.5 mmol/kg.

Other contrast substances, which are not derivatives of the porphyrin framework and are intended for visualization of necrosis and infarcts, are described in applications OE 19744003 (in the name of 5spegipd AS), OE 19744004 (in the name of Zspegip

Ab) and UMO 99/17809 (in the name of ERICH)).

Thus, in particular, in (application OE 19744003) oligomeric compounds are described, which consist of a nucleus with which from 1 to 3 metal complexes are connected.

Lipophilic metal complexes for visualization of necrosis and infarctions are described in Izayavka OE 19744004. These compounds include metal complexes of polyaminopolycarboxylic acids, polyaminopolyphosphonic acids, porphyrins, texaphyrins, sapphirins, and peptides.

In the UMO application 99/17809| described the use of DTPK (diethylenetriaminepentaacetic acid) derivatives for visualization of necrosis. The most significant compound is the gadolinium complex of phosphodiester hydroxymethyl-DTPK (M5-325).

The use of perfluoroalkyl-containing metal complexes as contrast agents in MR tomography is also known. Thus, in particular, the application of UMO 97/26017 (in the name of Zspegipu) and MO 99/01161 (in the name of Zspegipod) describes the use of perfluoroalkyl-containing metal complexes as contrast agents in lymphography.

The application M/O 99/011611 also refers to the suitability of these compounds for visualization of the intravascular cavity (contrast substances for visualization of blood pools).

The literature also describes the use of contrast agents for individual visualization of tumors and necrosis using MR tomography.

Thus, in particular, compounds intended for the diagnosis and therapy of tumors are described in the EP application 417870 AT|

The compounds described in this application are chelate complexes of the M2bE2 and Mz5 types with radioisotopes. Scintigraphy is mentioned as a diagnostic method in this application.

Scintigraphy is also used as a diagnostic method in |application OE 19646762). This publication describes chelated metal complexes used as radiosensitizers for the therapy of hypoxia-induced tumors and for the diagnosis of hypoxia-induced conditions and necrosis. In the descriptive part of this application, NMR diagnostics, X-ray diagnostics and radionuclide diagnostics are mentioned as diagnostic methods.

In application OE 19824653) porphyrins are described as substances that have an affinity for necrosis and are intended for tumor therapy. This application states, in particular, that these compounds accumulate in necrotic and hypoxic areas of tumors. Such compounds can be used for diagnostic purposes in the form of their metal derivatives with paramagnetic ions, respectively radioisotopes.

Common to both of these applications - (OE 19646762 and OE 19824653) - is the fact that they do not provide for the possibility of visualization of necrosis regardless of the visualization of tumors (or vice versa), but only the visualization of necrosis as a part of the tumor is possible.

The basis of this invention was the task of offering contrast agents suitable for MR-tomography, which would allow not only to visualize plaques, lymph nodes, infarcted and necrotic tissue, but also to visualize necrosis regardless of the visualization of tumors (or vice versa).

When creating the invention, it was unexpectedly established that perfluoroalkyl-containing metal complexes, which are characterized by a critical concentration of micelle formation of less than 10 Zmol/l, a hydrodynamic diameter of micelles (22) of more than 1 nm, and a relaxation of protons in plasma (2) of more than 10 l/mmol-s, are highly suitable for use as contrast agents in MR tomography for visualization of plaques. In addition, such compounds can also be used for visualization of lymph nodes, infarcted and necrotic tissue, as well as for independent visualization of necrotic and tumor tissue.

Perfluoroalkyl-containing metal complexes suitable for use in accordance with the invention mean amphiphilic compounds, the molecule of which has a perfluoroalkyl side chain as a non-polar fragment, which is not necessarily connected to the entire molecule by a lipophilic linker. The polar fragment of the compounds proposed in the invention is formed by one or several metal complexes and optionally other polar groups.

In aqueous systems, similar amphiphilic molecules exhibit properties characteristic of traditional surfactants (such as, for example, sodium dodecyl sulfate, DSN). So, for example, these molecules reduce the surface tension of water. With the help of tensiometry, it is possible to determine the so-called critical concentration of micelle formation (CCM, in mol/l). For this purpose, the surface tension is determined depending on the concentration of the analyzed substance. KCM can be calculated on the basis of the change characteristics of the obtained surface tension function (c). The critical concentration of micelle formation in the compounds proposed in the invention should be less than 10 mol/l, preferably less than 10 mol/l.

The amphiphilic compounds proposed in the invention are associated in solution and are presented in the form of aggregates.

The size (2CP) of such aggregates (having, for example, the shape of micelles, rods, wafers, etc.) can be determined using photon correlation spectroscopy (PCO).

Accordingly, the second criterion is the hydrodynamic diameter of micelles 2, which should be greater than 1Tnm. According to the invention, those perfluoroalkyl-containing metal complexes whose value of 2Kp is equal to or exceeds Znm, most preferably exceeds 4nm, are more preferred.

The method of determining CCM, as well as photon-correlation spectroscopy are described in (N.-0. O5plieg, "Step2Paspeppa KopPoiidspetie", ed. MN, Uuetpeit, Mem Mogk, Vazei, Satbgiade, ToKkuo, 1994).

The third criterion is the relaxation of protons in plasma (E") at 402C and a field strength of 0.47 tesla. Relaxability, which is expressed in |l/mmol-s|, is a quantitative measure that characterizes the decrease in the relaxation time Ti of protons. For the application envisaged by the invention such relaxation should be extremely high and should be more than 1Ol/mmol-s, preferably more than 1Zl/mmol-s, most preferably more than 15l/mmol-s.

The relaxivity B (l/mmol-s) of the contrast agents proposed in the invention for MR-tomography was determined using the Mipisres R 20 device of the Vgykeg company. The measurement was carried out at 40"C and a field strength of 0.47 tesla. For each Ti-sequence: 1802- TI-907, "inversion-recovery" mode, measurements were carried out at 8 points. Bovine plasma supplied by Kgaereg was used as a medium for measurements. The concentration of the contrast agent in the analyzed mixtures was from 0.30 to 1.16 mmol/l.

In one of the variants of implementation of this invention, compounds of the general formula I according to paragraphs 8-11 of the claims are preferred for use. At the same time, we are talking about known compounds described in the application

MO 97/26017). The method of obtaining such compounds is also described in this application. Unexpectedly, it was found that these compounds are also suitable for use as contrast agents in MRI to visualize plaques.

It is most preferable to use compounds that are metal complexes I-IM,

MEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEE (see also Table 1).

In another embodiment of the present invention, compounds of the general formula Ia according to paragraphs 12-21 are preferable for use. These compounds are known and described in (application M/O 99/01161). However, the possibility of using such compounds as contrast agents in MRI for visualization of plaques has not been described in the literature so far. Among these compounds, it is especially preferable to use the KHIM metal complex (see Table 1).

According to another preferred embodiment of the invention, it is possible to use macrocyclic perfluoroalkyl compounds of the general formula II

A av), k-M AK" in which

K is a complexing agent or a metal complex of the general formula IB n - Z cho: o

M --iu soy Fi; o sook' (ПБ) where

IN! means a hydrogen atom or the equivalent of a metal ion with sequence number 23-29, 42-46 or 58-70,

B2 and EZ mean a hydrogen atom, a C-Stalkyl group, a benzyl group, a phenyl group, -СНг2ОН or -СНе-

OsSnZi 02 is a residue of I", while I! and 02 independently of each other can have identical or different values,

AND! represents a hydrogen atom, a linear or branched C-C 2 -C 2 alkyl group, which is optionally interrupted by 1-15 oxygen atoms and/or optionally substituted by 1-10 hydroxy groups, 1-2 COOH groups, a phenyl group, a benzyl group and/or 1-5 -ONZ-groups, where KU means a hydrogen atom or Si-

Steel balance, or -1 1-81",

Eat! is a linear or branched C1i-Czoalkylene group, which is optionally interrupted by 1-10 oxygen atoms, 1-5 -MH-CO groups, 1-5 -CO-MH groups, optionally substituted COOH group by a phenylene group , 1-3 sulfur atoms, 1-2 -M(B')-5Og-groups and/or 1-2 -502-M(B')-groups, where B' has the specified for A! value or means МНСО-group, СОМН-group, -М(В')-5О2-group or -502-М(В!)-group and/or optionally substituted by the residue Р", and

BP is a linear or branched perfluorinated alkyl residue of the formula СПЕгпЕ, where n denotes the odd number of ZO, and

E means the terminal atom of fluorine, chlorine, bromine, iodine or hydrogen, while optionally present acid groups can under certain conditions be presented in the form of salts of organic and/or inorganic bases or amino acids or amino acid amides.

Since the compounds proposed in the invention are intended for use in NMR diagnostics, the metal ion of the signal-generating group must be paramagnetic. Such ions primarily include divalent and trivalent ions of elements with ordinal numbers 23-29, 42-46, and 58-70. As an example of ions suitable for use for the specified purposes, we can mention the ions of chromium), iron(I), cobalt(I), nickelium, copper(I!), praseodymium), neodymium(II), samarium!) and ytterbium(I ). Given their high magnetic moment, the most preferred ions are gadolinium, terbium, dysprosium, holmium, erbium, zinc, and manganese.

Predominant ions are manganese(s), iron(s), iron(s), praseodymium), neodymium), samarium), gadolinium) and ytterbium), primarily dysprosium|).

Alkyl groups, indicated as values for B, VU, Be, can have a straight or branched chain. Examples of such groups include methyl, ethyl, propyl, isopropyl, n-butyl, 1-methylpropyl, 2-methylpropyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl and 1,2-dimethylpropyl.

Preferred values of P, BZ and 2: are hydrogen and C-Alalkyl groups, and most preferred are hydrogen and a methyl group.

Benzyl and phenyl group, indicated as values for P, A! and B' can be substituted in the phenyl ring. In this case, the ООН group is considered as a substitute.

If in the compound of the formula IB there are simultaneously residues I! and 02, then each of these residues Г! and 02 may have a value different from that of the other residue.

C 1 -C 2 -alkylene groups indicated as values for 0 2 may be straight chain or branched. Examples of such groups include methylene, ethylene, propylene, isopropylene, n-butylene, 1-methylpropylene, 2-methylpropylene, n-pentylene, 1-methylbutylene, 2-methylbutylene, 3-methylbutylene and 1,2-dimethylpropylene.

Preferred values for |, when it is an alkylene, are C1-Sioalkylene groups, most preferably C1-Szalkylene groups.

Ci-Szoalkyl groups indicated as values for A" can have a straight or branched chain. Examples of such groups include methyl, ethyl, propyl, isopropyl, n-butyl, 1-methylpropyl, 2-methylpropyl, n-pentyl, 1 -methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl and n-hexyl.

In addition, the C1-C2 alkyl groups indicated as values for A" may be interrupted by 1-15 oxygen atoms and/or may be substituted by 1-10 hydroxy groups, 1-5 alkoxy groups, or 1-2 COOH groups, and accordingly may be, for example, С2На-0О-СН3, С3Не-О-СН3, С2На-О-(С2На-О-С2НА-ОН, С2На-О- (Сгна-О)-С2На-ОСН:, where 1-0-13 . (OnNeCHON, Sgnasn(OnHsNeOHn, (SNeg)zCOOH, where 51-15, SgNa-O-(С2Ни-О0О)-СНСООН, where

I1-0-13, C2Na-O-(C2Na-O)-C2Na-SpEgoE, where 1-0-13, p-4-20, and E means a fluorine, hydrogen, chlorine, bromine or iodine atom.

Preferred values of A" are hydrogen, C1-Csoalkyl, CgNa-O-CH3, C3He-O-CH3, C2Na-O-(C2Na-O)"-C2Na-

OH, С2На-О-(С2На-О0)х-С2На-ОСН3, where х-0-5, С»НаОН, СзНеОНН, СНа|ИСН(ОНуЛУСН»ОН, where in 1-6, снНИСТТОНСН(ОНСНеОН, (СнНГУСООН) , where m/-1-10, С2На-О-(С2На-0)-СНоСООН, where x-0-5, С»На-О-(С2На-

O)x-C2Na-SpvEpE, where x-0-5, n-4-15, and E means a fluorine atom.

If there are two residues 1.!-B" in the compound of the general formula Ir, then they can have different, independent values.

As an example of the value of the remainder of Г! the following can be named, while c; means a bond with a nitrogen atom, a

B means a bond with the B residue: o-(CHg)5-B, where 5::1-15, c0-СНа-СНо-(0О-СН2а-СНе-у-В, where х1-6, о- СНо-(0-СНе-

СНе-)уу-В, where у-1-6, 0-СНо-МН-СО-р, о-СНа-СНо-МН-502-рД, о0-СНа-МН-СО-СнНо-М(СНгСООН) -502-B, o-CHg-MH-

СО-Сно-М(С2Нв)-502-DV,.. «-СНа-МН-СО-СНа-М(СтоНГи)-502-8,.. o-СНа-МН-СО-СНо-М(СеНиз) -502-rD,.. o-СНо-МН-

CO-(CHg)1o-M(C2Hb)-502-D,. o-СНа-МН-СО-СНг-М(-СНе-SeviН)-502-рД,. о-СНа-МН-СО-СНа-М(-СНа-СНа-ОН)ЗО»-р, о-СН»АМНОСО-(СНг)1о-5-СНаСНег-р,. o0-SNaMnNSOoSNI-O-SnNeSNe-r,. o0-СН».-СНаМНСОСНоИ-О-СнНаСНг-р,. Н-СНе- (Сн»АСнН»-0у-(СнгззМНнСО-СНг-О-СНаС Не-Д, where у-1-6, о-СНаМНОСО(СНг)1о-О-СНеаСнНе-р, о-

СнНгснНгМНоСо(СНг)1о-О-СНеаСнНЕ-р,. o-СНа-СвНа-О-СН»СН»-Д, while the phenylene group is attached in position 1,4 or 1,3, o-СН»-ОО-СНо-С(СН»-ОСНаСНег-СвЕ13)2- СН»-ОСНо-СНе-В,. o-СНоАМНСОоСНа.НгСОМ-

SnNa.SNaMNSOsSNaM(С2Н5) ЗО» Svig17-В,. o-СНао-СНаМНСОСНгМ(С2Нвъ)-502-рД,. a-CHg-O-CHno-CH(OsStoHg1i)-CHg-O-

SneSNeo-B,. "-(СНаМНСО)И-СНгО-СнНеСНе-В,. "-(СНаМНОСО)з-СНг2О-СНаСНег-р,. o-CH»-OoCn(CHgOH)2-CHg-O-

Is --o-( Renault Mch ,

Snsne-r, dream with "-SNaMNSOSNoM(SeN)-502-B,. 0-МНСО-СНо-СнНе-В,. o-MNSO-

Sn»-O-SneSNe-r,. o-МН-СО-В, o-МН-СО-СНо-МЩ(СНг.СООН)-505-8,.. о-МН-СО-СНо-М(Се2Н5х)-502-8,.. о- MH-CO-

SNo-M(StoNgi)-505-8,. o-MH-CO-SNeg-M(SeNiz)-502-8,. o-MH-CO-(CHg)1o-M(Cg2H)-502-8,. o-MH-CO-СНо-МЩ(-СНе-

SeH5z)-502-rD,. o-МН-СО-СНо-М(-СНг-СНг-ОН)ЗО»-в8,. о-МН-СО-СНе-в, о-СНг-О-СвНа-О-СНо-СНе-В, о-СНо2-SeviNa-

O-СНо-СнНе-р,. o-M(C2Hg)-505-8,. o-M(SviNg)-502-B,. o-M(StoH2gya)-502-8,. o-M(SvNiz)-502-rD,. o-M(C2NaOH)-502-p, o-M(SNaCOOH)-502-B, a-M(SNeSviN)-502-B, o-M-ISN(CHnOH)gI-502-pD, o-M -|Sn(SngonSsnOnusSNgOH)|-505- r.

In particular, the following residues are preferred: "-СНа2-0О-СНаСНе-р, о-СНа-СНа-(ОО-СНа-СНег-)у-В, where у-1-6, о-СНе-(О-

СНо-СНег-)у-В, where у-1-6, 0-СНо-СНо-МН-505-8, o-СНаМнНСОСН»-О-СНегСНег-ДВ, а-СНо-СНаЙАНСОСНоИ-О-СНоСНе-

B. 0 o-СНа-(СНа-СнНг-ОУ-(СНг)зМННСО-СНг-О-СНаСНо-Д, where у-1-6, о-СНаМНСО(СНг)уо-О-СНаСН»-Д, о /at-

СНа.СН.МНоСо(СНг)тюо-О-СНаСНег-рВ,. o-СНg-О-СНо-СН(ОСтоНГи)-СНо-О-СНоСНе-р,. o0-CHg-O-SvNa-O-СНо-СНе-рД,

o-СНа-СвН4-0О-СНо-СНе-р.

According to the invention, the most preferred residues /" are indicated in the following examples of compounds.

The values of 02 include the above residues as values of И! and are indicated as the preferred and most preferred residues, as well as those given above for the meaning of "alkylene" and under certain conditions are indicated as the preferred and most preferred residues, provided that a nitrogen atom should not be present in the a-position, but in the final position ( D-positions) the 50"- or CO-group should not be present.

Preferable values of the B' residue are hydrogen, linear or branched C1i-Sioalkyl residues, which are optionally interrupted by 1-5 oxygen atoms and/or optionally substituted by 1-5 hydroxy groups, 1-2 COOH- groups, optionally substituted by COOH -group, a phenyl group, a benzyl group and/or 1-5 -"ОВ5- groups, where KZ is a hydrogen atom or a C-C alkyl residue.

Preferable values of the BK" residue are linear or branched perfluorinated alkyl residues of the formula SpoEgeE, in which n means numbers from 4 to 15, and E represents the terminal fluorine atom.

The compounds of the general formula Ir proposed in the invention

E kove

A (B), in which K is a complexing agent or a metal complex of the general formula Ir p v z r:

M

C 1 juice (Pb) can be obtained by the methods discussed below.

Method A

The carboxylic acid of the formula Pr already contains an equivalent of the metal ion B. o and in the current Zh

A pish SIGN --I o ron sne "el o X val o u so" My (Sh) (am a

It is not necessary to use an activated ip with a carboxylic acid of the formula NAME, in which B! is the equivalent of a metal ion, is subjected to interaction under the conditions of a coupling reaction with an amine of the formula IMp to obtain an amide of the formula IB.

This method of obtaining metal complexes of amides of carboxylic acids is known from (CE 19652386).

The mixture used in the coupling reaction consists of a metal complex of carboxylic acid IB, in which, under certain conditions, carboxy- and/or hydroxy groups are presented in a protected form, and at least one substance that promotes dissolution, in an amount of up to 5, preferably from 0, 5 to 2, molar equivalents in terms of the metal complex of the carboxylic acid, or can be obtained at a previous reaction stage and isolated (for example, by evaporation, freeze-drying or spray drying or an aqueous solution of the components mixed with water, or by precipitation from a similar solution with organic solvent) and then subjected to interaction in DMSO with a dehydrating reagent (drying agent) and optionally with an auxiliary coupling agent, or it is possible to obtain ip zish optionally by adding to the suspension of a metal complex of a carboxylic acid in DMSO a contributing substance(s) -yut) dissolution, dehydrating reagent and optionally auxiliary coupling agent.

The reaction solution obtained by one of these methods is kept for its preliminary treatment (acid activation) for 1-24 hours, preferably 3-12 hours, at a temperature from 0 to 50"C, preferably at room temperature.

After that, an amine of the general formula IMr is added to the reaction solution

VAH

M Kk

A (m in which the residues P, 17, VE and A! have the above values, which are used without a solvent or in a dissolved form, for example in dimethyl sulfoxide, alcohols such as methanol, ethanol, isopropanol or their mixtures, formamide, dimethylformamide, water or mixtures of the specified solvents, preferably in dimethyl sulfoxide, in water or in solvents mixed with water. Then, for the formation of the amide, the reaction solution obtained in this way is kept for the coupling reaction at a temperature from 0 to 707C, preferably from 30 to 60"C, for 1- 48 hours, mostly 8-24 hours.

In some cases, as was established, the amine is preferably used in the reaction in the form of its salt, for example, in the form of hydrobromide or hydrochloride. A base such as triethylamine, diisopropylethylamine, M-methylmorpholine, pyridine, tripropylamine, tributylamine, lithium hydroxide, lithium carbonate, sodium hydroxide or sodium carbonate is added to liberate the amine.

After that, the protective groups that are still present under certain conditions split off.

The reaction product is isolated by known methods, preferably by precipitation with organic solvents, preferably acetone, 2-butanone, diethyl ether, acetic acid ethyl ether, methyl tert-butyl ether, isopropanol or their mixtures. Further purification can be carried out, for example, by chromatography, crystallization or ultrafiltration.

Alkali metal salts, alkaline earth metal salts, trialkylammonium salts, tetraalkylammonium salts, ureas, M-hydroxyimides, hydroxyaryltriazoles, substituted phenols and salts of heterocyclic amines are suitable for use as solubilizers. At the same time, specific examples include lithium chloride, lithium bromide, lithium iodide, sodium bromide, sodium iodide, lithium methanesulfonate, sodium methanesulfonate, lithium p-toluenesulfonate, sodium p-toluenesulfonate, potassium bromide, potassium iodide, sodium chloride, magnesium bromide, magnesium chloride, magnesium iodide, tetraethylammonium p-toluenesulfonate, tetramethylammonium p-toluenesulfonate, pyridinium p-toluenesulfonate, triethylammonium p-toluenesulfonate, 2-morpholinoethylsulfonic acid, 4-nitrophenol, 33,5-dinitrophenol, 2,4-dichlorophenol, M-hydroxysuccinimide , M-hydroxyphthalimide, urea, tetramethylurea, M-methylpyrrolidone, formamide, as well as cyclic ureas, while among the above, the first five are predominant.

All known to specialists can be used as dehydrating reagents. At the same time, examples of carbodiimides and onium reagents, such as dicyclohexylcarbodiimide (DCCD), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydroxychloride (EDU,), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOF) and hexafluorophosphate О -(benzotriazol-1-yl)-1,1,9,3-tetramethyluronium (GBTU), mainly DCKD.

Below, as an example, literary sources are presented in which acceptable methods are described: - activation of carboxylic acids: (overview information in Noirep-UUeu!, Meijpodep aeg Ogdapizsnep

Spetiye, volume ХМ/2, ed. zeogd Tpiete Megiad Zishndat, 1974 (and U. Spet. Kezeagsp (5) 1996, p. 302)|; - activation by carbodiimides:| KE. Zspuueg and N. Karreieg, Ne|im. 46 (1963), pp. 15501; - (E. Uuipzoeny et al., V. 100 (1967), p. 17 31; - activation by carbodiimides/hydroxysuccinimide':| U. At. Spet. os. 86 (1964), p. 1839, and also 3.

Oh Spent 53 (1988), p. 3583, Zupipevziv 453 (1972)|; anhydride method, 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline: (V. VePeats et al., U. At. Spet. bos, 90 (1986), p. 1651, N. Kyp? et al., Ipi. 9. Reri. Rgoi. Ke5., 26 (1985), p. 493, and U.K. Mopdpp, At. 5obs. 73 (1951), p. 3547|; - imidazolid method: |IV.R. Bisip, K.V. Mepiey, O.S. Tovieop, At. 5os. 91 (1969), p. 26911; - methods with acid chlorides, thionyl chloride' (| Ne/m., 42 (1959), p. 16531 - oxalyl chloride: U. Ogd. Spet., 29 (1964), p. 8431I.

All agents known to experts are suitable for use as auxiliary splicing agents (Noshirep-Umeu!, Me(podep deg ogdapizspep Spetiv, t KhM/2, ed. Sbeogd Tpiyete Mepad, zhishidap, 1974) are suitable for use as auxiliary coupling agents. 4-nitrophenol, M-hydroxysuccinimide, 1-hydroxybenzotriazole, 1-hydroxy-7-azabenzotriazole, 3,5-dinitrophenol, and pentafluorophenol Among these compounds, 4-nitrophenol and M-hydroxysuccinimide are preferred, and the first of these agents is most preferred.

Protective groups are removed by known methods, for example, by hydrolysis, hydrogenolysis, alkaline saponification of complex esters with alkali in a water-alcohol solution at a temperature from 0 to 50"C, acid saponification with mineral acids or - in the case, for example, of complex tert-butyl ethers - by with the help of trifluoroacetic acid |Rgoyesiime Sgopyr5 ip Ogdapis Zupipevi5, 2nd ed., T.MU. sgeepe and R.O.M.

Uucci5, vid-vo Wopp Umieu api Zop5, Ips. Mem/ Mogk, 1991), and in the case of simple benzyl ethers - with the help of hydrogen in the presence of palladium on charcoal.

The method of obtaining the starting material, that is, the compounds of the formula Pr p

CO

M. der» sb Cl

Moya (ШШ), known from (OE 19652386).

Amines of the general formula IMr

From boms,

A and am) are commercially available products (RIpohospet, AVSK) or they can be obtained by the following method from compounds of the general formula Mr by interaction with an amine of the general formula MIr and subsequent reduction of compounds of the general formula MIIr:

about in KhG. ru How Ж --щ puttya She and She where

A A A

(UV) "(MIB) (MIV) (MV) where

VE, AT, I and Z have the above values,

And" has the values indicated for the /" group, which still lacks the c-СНе group, and

Az means hydrogen or metal group.

The acid of the formula Mr before its interaction with the amine of the formula MIB is activated according to the methods already discussed above for the activation of the carboxylic acid of the formula PIB and described in the literature. If Ke means a metal group, then aminolysis is carried out.

Compounds of the general formula Mo are commercially available products (RIpogospet, AVSE) or they are obtained by the method described in (CE 19603033.

Compounds of the formula MIB are commercially available products (RIpohospet, AVSK) or they can be obtained by the method described in INoirep-UmMeuY, MeiShodep deg ogdapizspep Spetje, t.XI/2, section "BiskeoyMegripaipdep", ed-vo seogd Tpiete Mepad, zishndag, 1957, p. 680; U.E. Kisktap and T. Aikip5, At.

Spent 5os, 96 (1974), p. 2268; R. Spam? and A.O. zZpe!tu, u. Ogd. Spet., 54 (1989), p. 29901|.

Compounds of the general formula IMB are obtained according to a known method (Neim. Spit. Asia, 77 (1994), p. 23) by reduction of compounds of the general formula MII, for example, with diborane or lithium aluminum hydride and subsequent cleavage of protective groups.

Method B

The starting material is a carboxylic acid of the formula Х, where В! means hydrogen, which does not yet contain an equivalent of a VE metal ion." Carboxyl groups are protected by known methods to obtain a compound of the formula Schu, where EZ is any acceptable protecting group, and EZ is its predecessor. slo o sb zhi o sleep still sho (Shu)

As carboxy-protecting groups can be considered, for example, linear or branched C-alkyl, aryl and aralkyl groups, for example methyl, ethyl, propyl, butyl, phenyl, benzyl, diphenylmethyl, triphenylmethyl, bis(p-nitrophenyl)methyl, as well as trialkylsilyl groups.

A tert-butyl group is preferred.

Ore vo vv ovo Zm ne KA u obi 9 I -B5 sbin o, 9 A sya M om (shu) amB) ah)

The interaction of the protected carboxylic acid of the formula Pu with the amine of the formula IMB and removal of the protective groups is carried out according to the method described for method A, and at the next stage, the obtained carboxylic acid of the formula Ih is additionally subjected to interaction with at least one metal oxide or one salt of the required metal with the serial number, as described , for example, in (OE 19525924).

If the metal complex obtained by method A or method B still contains free COOH groups, then these groups can also be presented in the form of salts of physiologically acceptable inorganic or organic bases.

Free carboxy groups that may still be present in this case are neutralized with inorganic bases (such as hydroxides, carbonates or bicarbonates), such as sodium, potassium, lithium, magnesium or calcium, and/or organic bases, in particular primary, secondary and tertiary amines, such as for example, such as ethanolamine, morpholine, glucamine, M-methyl- and M,M-dimethylglucamine, as well as basic amino acids such as, for example, lysine, arginine and ornithine, amides or primarily neutral or acidic amino acids.

The most preferred for the application envisaged by the invention are metal complexes M, MII, MIP,

ХХ and X (see table 1).

These compounds of the general formula IB when used as contrast agents in MRI are particularly suitable for imaging plaques.

According to another preferred embodiment of the invention, it is possible to use perfluoroalkyl-containing complexes with sugar residues of the general formula Is

Fp-0-(2-K you (Is),

SU-Yu ri in which

E means a mono- or oligosaccharide residue attached through the 1-OH- or 1-5H-position,

BP means a perfluorinated, straight or branched carbon chain of the formula -SpEgtE, where E represents the terminal atom of fluorine, chlorine, bromine, iodine or hydrogen, and n means the numbers 4-30,

K means a metal complex of the general formula IIc o

KM de o moomori koos shcha o svo (Pe), in which

IN! represents a hydrogen atom or the equivalent of a metal ion with serial number 23-29, 42-46 or 58-70, provided that at least two radicals EE! mean metal ion equivalents,

B2 and EZ independently of each other are hydrogen, C-Stalkyl, benzyl, phenyl, -CHnOH or -CHnOSH3 and

Mu represents -СвНа-О-СНег-о-, -(СН2г)1-5-о-, phenylene group, -СН-А-МНСО-СН»-СН(СНаСООН)-СеНа-о-, -Sen -(ОСНегСНг)о-М(СНаСООН)-СНг2-о- or optionally interrupted by one or more oxygen atoms, 1-3 -МНОСО-groups, 1-3 -СОМН-groups and/or substituted by 1-3 - "СНг)о5СООН-groups Si-Sigalkylene or С7-С12-СвНа-О-group, while o means the place of attachment to -СО-, or the general formula Ps y

A. I os, 9 soov (Sho), in which

IN! has the above values,

B" means hydrogen or the metal ion equivalent indicated for KE! and

And means -СеН4а-О-СНе-о-, where со means the place of attachment to -СО-, or the general formula of IMS 7

M v'oos r

B and seov (Mo), in which EC! and 2? have the values indicated above, or the general formula of MSA or MeV duty

There is -so0og kos M ml vov

SO OV (us), kiteoov o s -sbov

M di toov! - 600 (MeV), in which VE! has the values indicated above, or the general formula Mis braids di bo voo0--sh - oo Сl),

in which

IN! has the above values, or the general formula MIS pos o poos-t shk kOo0ob-k, M

Ooos-- (UPo), in which

IN! has the above values, and

And means -СеН4а-О-СНег-о-, where o means the place of attachment to -СО-, or the general formula MIS soog se, kos" zh SODU km y shchi (С soov (UShe), in which VE! has the above value, while the free acid groups optionally present in the K residue may optionally be represented in the form of salts of organic and/or inorganic bases or amino acids or in the form of amino acid amides,

Сб in the event that K denotes a Po-Ms metal complex is at least a three-fold functionalized residue selected from the following residues a)-1): (a)

H ve M--(СН СО у

МН и in 2 (5)

N u k-so-0- (SN R

MN and that U (s) s (SU, vych M--y i Ya ssonn-K Mu i

her

In - (in in t

AND

SO shekh lo

Man

Vlyan--M Mech nn N ;

F mn-so-8--(breakfast

Arli (ii 77 I

K- M-so It's clear

WHAT and

Ge

(in)

B i i

And MAV SN Sn odeneyaV

Y MA Son chndrchniaih

ХА чнесосеннурчнохВ

МН и в ях (в) and AV , azny

KAM Yin g yi yi u yi

R. U

(0; i and it n che; venu -som Me

MN. p;

At 5 o'clock

F osaknshchN-NOM - SO --eey u

IS

R n b in the case that K means a metal complex MIS, is at least a three-fold functionalized residue selected from residues K) and 1): (3) rem Snartnosoto iy 7 ?

FO vyso sny Sny sotu g

In this, a means the place of attachment of C to complex K, p means the place of attachment of СО to residue У, and y means the place of attachment of C to residue 2,

M means -CHe-, 5-(CHg)1-5CO-B8, 6-CH»-CHOH-CO-p or 5-CH(ISHON-CHhOp)-CHOH-CHOH-CO-p, where 5 means the place of attachment to the KE sugar residue, and p means the site of attachment to the 0 residue, 2 means the group ря 7-М-М-30-5е у-СОоСНо-М(С2Н5)-502-е, у-СОоСНг-О-(СНг)2 -502-is,

o (o) y-- so. Y.M kore or у-МНонНгСНг»-О-СНеСнНе-в, where у means the place of attachment of 72 to the residue b, and е means the place of attachment of 7 to the perfluorinated residue P".

And, t! independently of each other mean the integers 1 or 2 and p' means the integers from 1 to 4.

Since the compounds proposed in the invention are intended for use in NMR diagnostics, the metal ion of the signal-generating group must be paramagnetic. Such ions primarily include divalent and trivalent ions of elements with ordinal numbers 23-29, 42-46, and 58-70. As an example of ions suitable for use for the specified purposes, we can mention ions of chromium), iron (Ii), cobaltium (Ii), nickelium (Ii), copper (Ii), praseodymium (I!), neodymium (I!), samarium!) and ytterbium (I!). Given their high magnetic moment, the most preferred ions are gadolinium(i!!), terbium(I!), dysprosium(I!), holmium(i!), erbium(i!), iron!) and manganese).

The predominant ions are manganese), iron(II), iron(!I), praseodymium(I), neodymium(I!), samarium!, gadolinium(I), and ytterbium(I!), primarily dysprosium!).

Available under certain conditions in VE! acidic hydrogen atoms, that is, atoms that are not replaced by a central ion, may optionally be completely or partially replaced by cations of inorganic and/or organic bases or amino acids or amino acid amides.

Examples of acceptable inorganic cations include lithium ion, potassium ion, calcium ion, and primarily sodium ion. Acceptable cations of organic bases are, in particular, those of primary, secondary or tertiary amines, such as, for example, ethanolamine, diethanolamine, morpholine, glucamine, M,M-dimethylglucamine and especially M-methylglucamine. Examples of acceptable amino acid cations include cations of lysine, arginine, and ornithine, as well as amides of other acidic or neutral amino acids.

The most preferred compounds of the general formula I include compounds that contain the macrocycle K of the general formula I.

The residue I in the metal complex K preferably means -СНо- or СеН4а-О-СНо-о, where о is the site of attachment to -СО-.

Alkyl groups in the macrocycle of the general formula I, indicated as the values of P: and C, can have a straight or branched chain. At the same time, methyl, ethyl, propyl, isopropyl, n-butyl, 1-methylpropyl, 2-methylpropyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl can be cited as examples.

Preferably R: and EZ independently of each other are hydrogen or C-Slalkyl.

In one of the particularly preferred variants of P? stands for methyl and RZ stands for hydrogen.

Indicated as the value of PE: or EZ is a benzyl group or a phenyl group in the macrocycle K of the general formula

Ps can also be substituted in the ring.

The EK residue in the general formula Is means a mono- or oligosaccharide residue or a thiosugar residue attached through the 1-OH- or 1-5H-position, and in this case, according to the invention, we can also be talking about deoxysugars, which instead of one or more OH groups contain an H atom. In one of the preferred embodiments of the invention, K means a monosaccharide residue with 5 or 6 C atoms, preferably glucose, mannose, galactose, ribose, arabinose or xylose or their deoxysugars, such as, for example, 6-deoxygalactose (fucose) or b-deoxymannose (rhamnose), or their thiosugars, with glucose, mannose and galactose being the most preferred.

Among the compounds of the general formula II proposed in the invention, compounds in which BP stands for -CaERgpii are more preferred. At the same time, n mainly means numbers from 4 to 15. The most preferred residues are -СаР», -

Св1з, -СвиР17, -С12Е2в and -С14Его, as well as the remains of the compounds considered in the examples.

The at least three-fold functionalized residue c in the general formula I, which is a "skeleton", in one of the preferred embodiments of the invention means a lysine residue (a) or (B).

U and 7 represent the linker specified for the general formula I, while independently of each other, 7 preferably means the group 7-m. AM-502-E, and U preferably means the group 56-СН»СО-р.

The method of obtaining perfluoroalkyl-containing complexes of metals with sugar residues of the general formula Is (Yup-0-(2-di (c), (U-Yuri) in which K means one of the metal complexes of the general formulas IIs-MiIs, and C represents one of the groups of formulas a)-i), while M, 2, B, ЕР, т!, р!, and I! have the above values, consists in the fact that the carboxylic acid of the general formula ИИ is

Se, p2 ve i

M-- vbost, S. rya ton i-sook' (Pp), in which V? means the equivalent of a metal ion with serial number 23-29, 42-46 or 58-70 or a carboxy protecting group, and B2, BZ and 0 have the values indicated above, or a carboxylic acid of the general formula Pi uyu h; lesson i- ZON veoos KU soov? (FI, in which VU, V? and I! have the above values, or a carboxylic acid of the general formula IMi in

Se, ve he voosti --i

ZX o sov (MU in which C and 2? have the above values, or a carboxylic acid of the general formula Mi or mii -s0o -ssov

With mosboya and boov voost, the language and language of Moso,

ОО (му, -СООР (ми, where P? has the above values, or a carboxylic acid of the general formula мии посы у бо-он оос-7 М-ВО (mu in which E? has the above values, or a carboxylic acid of the general formula Words in which VZ and I! have the values indicated above are not necessarily subjected in an activated form according to a known method of interaction under the conditions of a coupling reaction with an amine of the general formula IXc

H-0-(2-B (Xo),

Se in which C means one of the groups of the formulas a) -Y), a and E, B", M, 7, t! and p' have the values indicated above, and then, if necessary, the protective groups present under certain conditions are cleaved to obtain as a result of a metal complex of the general formula Is or, if BEZ represents a protective group, after cleavage of such protective groups, at the next stage, they are subjected to interaction according to a known method with at least one metal oxide or metal salt with serial number 23-29, 42-46 or 58-70 , after which, if necessary, acidic hydrogen atoms present under certain conditions are replaced by cations of inorganic and/or organic bases, amino acids or amino acid amides.

The method of obtaining the compounds of the general formula Is proposed in the invention, in which K means a metal complex of the general formula Mis, and b represents a group of the formula K) or 1), consists in the fact that the amine of the general formula MIP is soov se, --Н vvoost і sі shk v r, on (" sov (U) in which VZ means the equivalent of a metal ion with ordinal number 23-29, 42-46 or 58-70 or a carboxy-protecting group, subjected to a known method of interaction under the conditions of a coupling reaction with an optionally activated by a carboxylic acid of the general formula Xx nOo-0-(2-B) (Xe), 53 in which C means a group of the formula K) or I), and B, B", U, 7, t! and p' have the values indicated above, and then, if necessary, the protective groups present under certain conditions are cleaved with the result of obtaining a metal complex of the general formula I or, if BEZ is a protective group, after cleaving such protective groups at the next stage, they are subjected to interaction according to a known technique with at least one metal oxide or metal salt with sequence number 23-29, 42-46 or 58-70, after which, if necessary, the acidic hydrogen atoms present under certain conditions are replaced by cations of inorganic and/or organic bases, amino acids or amino acid amides.

The carboxylic acids of the general formulas PI-Miii used in the reactions described above are either known compounds, or they are obtained by the methods described in the examples. So, in particular, the method of obtaining carboxylic acids of the general formula II is known from (OE 19652386). The method of obtaining carboxylic acids of the general formula IMi is described in (OE 19728954).

M3-(2,6-dioxomorpholinoethyl)-Me-(ethoxycarbonylmethyl)-3,6-diazaprobic acid, which is described in EP 2630591, is the precursor of compounds of the general formula MCA.

Compounds of the general formula MeV are derivatives of the isomeric diethylenetriaminepentaacetic acid (DTPA), which is attached through the acetic acid, which is located near the central M atom. This DTPC is described in (OE 19507819 and OE 19508058).

Compounds of the general formula Miss are derivatives of M-(carboxymethyl)-M-(2-(2,6-dioxo-4-morpholinyl)ethyl|glycine, the method of preparation of which is described in U. At. O.I. Spet. 5os, 59 ( 2) (1982), pp. 104-107).

Compounds of the general formula Mis are derivatives of 1-(4-carboxymethoxybenzyl)ethylenediaminetetraacetic acid, which is described in (patent O5 46224201.

The perbenzylated sugar acids used as starting materials can be obtained similarly to the method described in (SoskpoiYa in Apdem/. Spet., 110, Mo24 (1998), p. 3634 et seq.). So, for example, 1-0-acetic acid is obtained from of perbenzylglucose in two steps, namely, via trichloroacetimidate and interaction with ethyl hydroxyacetic acid, catalyzed by BEz in THF followed by saponification with Maon in MeonltHf.

In one of the preferred options, the perbenzylated sugar acids used as starting substances can also be obtained by dissolving the perbenzylated 1-OH-sugar in an organic solvent immiscible with water, followed by interaction with an alkylating agent of the general formula His

My-I-C00-59 (ХИс) where My is a nucleophobe, GI. means -(CHn)y1-5)-, «-«CH.-CHON-, -CH(ISNON-CHnOH)-CHON-CHON-, and 59 represents a protective group, in the presence of a base and optionally an interphase catalyst.

The alkylating agent of the general formula His can contain as a nucleophobe, for example, -СІ, -Вг, -), -ОТ5, -ОМ5, -О502Сез, -О502С4Ее or -050»СвР17. A protective group means an acid-protecting group commonly used for similar purposes. Such protective groups are well known to those skilled in the art (see, for example, Rgoiesiime

Sgotsrz ip Ogdapis Zupipeze5, T.M. sgeepe and R.O.M. Ears5, 2nd ed., ed. Chopp UMieu 8 5op5 Ips., Mem MogKk 1991).

The interaction discussed above can be carried out at a temperature from 0 to 50°C, preferably from 0°C to room temperature. The duration of the reaction is from 10 minutes to 24 hours, preferably from 20 minutes to 12 hours.

The basis is added either in solid form, preferably in the form of finely divided powder, or in the form of a 10-7095, preferably 30-5095 aqueous solution. The predominant bases are Mahon and KOH.

As an organic solvent immiscible with water, in the alkylation method proposed in the invention, for example, toluene, benzene, C3-benzene, hexane, cyclohexane, diethyl ether, tetrahydrofuran, dichloromethane, MTB or their mixtures can be used.

As interphase catalysts in the method proposed in the invention, quaternary ammonium or phosphonium salts, which are known for their use for this purpose, or crown ethers, such as (15I-crown-5 or (18|-crown-6) are preferred when this salt of a quaternary ammonium base with four identical or different hydrocarbon groups in the cation selected from methyl, ethyl, propyl, isopropyl, butyl and isobutyl The hydrocarbon groups in the cation must be large enough to ensure good solubility of the alkylating agent in the organic solvent. According to the invention, it is most preferable to use M(butyl)y-Cg, M(butyl)4"-NOZO"g, as well as M(methyl)a"-Cg.

Among the compounds of the general formula Is, it is most preferable to use according to the invention the metal complex XU presented in Table 1 (example 1).

According to another preferred embodiment of the invention, it is proposed to use perfluoroalkyl-containing complexes with polar residues of the general formula

VU means a perfluorinated, straight or branched carbon chain of the formula -CoEgpE, where E is a terminal atom of fluorine, chlorine, bromine, iodine or hydrogen, and t means the numbers 4-30,

K means a metal complex of the general formula u

M kash sh- os - o

We are about soov (PF, in which

IN! means a hydrogen atom or the equivalent of a metal ion with sequence number 23-29, 42-46 or 58-70, provided that at least two radicals E! mean metal ion equivalents,

B2 and C independently of each other mean hydrogen, C1i-Stalkyl, benzyl, phenyl, -"CH2OH or -CHgOSH3 and

Mu means -СеН4и-О-СН»-(0-, -(СН2е)1-5-5-, phenylene group, -СН-АМНСО-СН»А-СН(СНгСООН)-СвНа-о-, -

SenA-(ОСНСН?г)о-1-М(СНаСООН)-СНг-о- or optionally interrupted by one or more oxygen atoms, 1-3 -МНОСО-groups, 1-3 -СОМН-groups and/or substituted 1-3 -"СНг)о5СООН-groups Si-Sigalkylene or С7-С12-СвНа-О-group, where со means the place of attachment to -СО-, or the general formula Sha o ra о о о о о о о о о о о о о о о о SHO, in which

IN! has the above values,

IN? means hydrogen or specified for B! equivalent of a metal ion and

AND! means -СеНа-О-СНе-о-, where o means the place of attachment to -СО-, or the general formula ma

M or r: - Quality noOos M

Are we about? juice (IF), in which B! and 2? have the above values, or the general formula MaA or mav mu

There is -soov shschoOos7 in doe mov o with -soov

Fa de VE! has the above values, or the general formula MY

КооОсС- and и-С0-m

M M

Vieo0S-7 ZhZ-soov (Ua), where V! has the above values or the general formula Ma

VooS-9

Oo0-t7 ul shen voob-kh SUIF), in which

IN! has the above values, and

And means -СеНа-О-СНе-о-, where o means the place of attachment to -СО-, while the free acid groups optionally present in the K residue may optionally be represented in the form of salts of organic and/or inorganic bases or amino acids or in the form of amino acid amides, C means at least a three-fold functionalized residue selected from the following residues a)-i): (a) ac --(СНдг ССО nt т

MN

In 2 (5)

N t meso-s-(sndgu R

MN

N

(Z ii ue, zhenan | fah y v ( m shi (d « ; dilii Menu 2 my

U. | Sha

H

IN

(9th so: A lo

VyayaA- HM Ken

M i (V n n ze M (SHO (SN manifest

M SHY Yi and her M

I and I in E:

R i (c)

TA i M CHA shi also V V Y (c) 7 pochenakirnsotiy:

We

AND

(0) In pit SON du SNO pit , it has where c means the site of attachment of b to the complex K, Dr means the site of attachment of C to residue K, and y means the site of attachment of c to residue 7, 2 means the group 7-хх яМ-5ОЕ y-С(О)СнНГО(СНег) 2-e, where y means the place of attachment of 72 to the residue b, and 5 means the place of attachment of 7 to the perfluorinated residue B".

K is a polar residue selected from K complexes of the general formulas Ia-MIa, and in this case E! means a hydrogen atom or the equivalent of a metal ion with serial number 20, 23-29, 42-46 or 58-70, and the residues В, ВУ, ВУ, Ш and Ш! have the above values, or is a folic acid residue or a carbon chain with 2-30 C atoms attached through -СО-, 502- or a direct bond to the C residue,

which is straight or branched, saturated or unsaturated and which is optionally interrupted by 1-10 oxygen atoms, 1-5 -МНОСО-groups, 1-5 -СОМН-groups, 1-2 sulfur atoms, 1-5 -МН-groups or 1-2 phenylene groups, which may optionally be replaced by 1-2 OH-groups, 1-2 MNeo-groups, 1-2 -

COOH-groups or 1-2 -5О3Н-groups, or optionally substituted with 1-8 OH-groups, 1-5 -COOH-groups, 1-2 5ОзН-groups, 1-5 MNeo-groups, 1-5 Si -Slalcoxygroups, i

IP, t", p" independently of each other mean integers 1 or 2.

Since the compounds proposed in the invention are intended for use in NMR diagnostics, the metal ion of the signal-generating group must be paramagnetic. Such ions primarily include divalent and trivalent ions of elements with ordinal numbers 23-29, 42-46, and 58-70. As an example of ions suitable for use for the specified purposes, we can mention ions of chromium), iron (Ii), cobaltium (Ii), nickelium (Ii), nickelium (Ii), praseodymium (I!), neodymium (I!), samarium (I!) and ytterbium (I!) . Given their high magnetic moment, the most preferred ions are gadolinium(i!!), terbium(I!), dysprosium(I!), holmium(i!), erbium(i!), iron!) and manganese).

The predominant ions are manganese), iron(s), iron(1!), praseodymium(I!), neodymiumI!), samarium!), gadolinium(I) and ytterbium(I!), primarily dysprosium!).

Available under certain conditions in VE! acidic hydrogen atoms, that is, atoms that are not replaced by a central ion, may optionally be completely or partially replaced by cations of inorganic and/or organic bases or amino acids or amino acid amides.

Examples of acceptable inorganic cations include lithium ion, potassium ion, calcium ion, and primarily sodium ion. Acceptable cations of organic bases are, in particular, those of primary, secondary or tertiary amines, such as, for example, ethanolamine, diethanolamine, morpholine, glucamine, M,M-dimethylglucamine and especially M-methylglucamine. Examples of acceptable amino acid cations include cations of lysine, arginine, and ornithine, as well as amides of other acidic or neutral amino acids.

The most preferred compounds of the general formula (4) include compounds containing the macrocycle K of the general formula Pa, Sha, Mav or MPa.

The residue I in the metal complex K preferably means -СНо- or СеН4а-О-СНо-о, where о is the site of attachment to -СО-.

Alkyl groups in the macrocycle of the general formula are indicated as P: and EZ values and can have a straight or branched chain. At the same time, methyl, ethyl, propyl, isopropyl, n-butyl, 1-methylpropyl, 2-methylpropyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl can be cited as examples.

Preferably R: and EZ independently of each other are hydrogen or C-Slalkyl.

In one of the particularly preferred variants of P? stands for methyl and RZ stands for hydrogen.

Indicated as the PE value? or EZ is a benzyl group or a phenyl group in the macrocycle K of the general formula

Pa can also be substituted in the ring.

The polar residue K in the general formula Id in one of the preferred variants is a complex K, which preferably, in addition to the Caz-- or Mp2-complex, can also be a Ca"-complex. The most preferred as polar residues E are complexes K of the general formulas Pa, Sha, MaA and MIIide.Like B!, they particularly preferably contain the equivalent of a metal ion with sequence number 20, 25, 39 or 64.

According to another preferred variant, the polar residue K has the following values: -

Fs(OosSnN.nNnZOozZN, -FS(O)SnNgoSnangosSnNgspon, -C(O)SnNgoSnN.nogoN, -C(O)SNgoSnNsSn(OneSNeon, - c(osSNngchn-sS(OSnNgOOnN, -C(00SnNnOnesNnonN, -C(O0) CHgOSnNOOH, -BUDSNaCHCOOH, -C(0)-SeHz- (m-COOH)", -FKO)SnHgoO(CHg)2-SvHz-(m-COOH)", -F(O)CHgO-SvNa-m-5OzH , - c(o)Sngchne(osSNnaMnoS()SngSsnNoOon, -C(O0)SnNgoSsnNsSnNgosSnsSOOn, -K(O)SngoSsnsn(OHn)SNngo- cSnsnoon, -K(O)SnNgoSsnN.n(OnSNngosSNnI-CH(OH)-CH »OH, -С(0)СН»БозЗН, -Ф(0О0)СНСНСООН, шЮ(- с(ФсСНнонеСНноНонеНон, -С(О)СНго(СНг)гО|ia-СН3, -С(О)СНГО((СНг )гОЙ5-Н, -"Ф(О)СНгОСН(СНОН)", - (ОСНО Ссн(СНгоСНСООоН)», -6(0)-СеНз-(m-ОСнНСООН)», -bo-snho-(СнНгго(СНгг6о) - (СнНгго(СНггОснН;», mainly -С(О)СНгО|(СНг)291-СН»).

In another preferred embodiment, the polar residue E is a folic acid residue.

Among the compounds of the general formula II proposed in the invention, compounds in which B" means -CoEgpy. n preferably means numbers from 4 to 15. The most preferred residues are -СаР9, -СеРи13, -СвР17, -С12Е25 and -Сч4Его.

At least three-fold functionalized residue Cb in the general formula Id, which is a "skeleton", in one of the preferred embodiments of the invention means a lysine residue (a) or (B). 27 means indicated for the general formula and the linker, while the preferred group

U-m UM-505E

The method of obtaining perfluoroalkyl-containing metal complexes with polar residues of the general formula is (Yup-a-(2-8 (9), (Yura in which K, b, B, 2, BP, I, t! and p" have the above values, consists in the fact that the carboxylic acid of the general formula IIK is defined as:

M v'bost c. ra ot ton (g so? (Pyu, in which E? is the equivalent of a metal ion with ordinal number 23-29, 42-46 or 58-70 or a carboxy protecting group, and 22, BZ and 0 have the above values, or a carboxylic acid of the general formula SHK roya

Ship

A-; is he up to 9 soov? (Shu, in which 7, Vo and /! have the above values, or a carboxylic acid of the general formula IMC soov 2 iy on voos7 S. rya

And soov (Uk), in which R? and 2? have the values indicated above, or a carboxylic acid of the general formula MK or Mt -i-so-0 --soov

There is mossoove "A m. soov -f 14 Ya--M vbost ; 5 noos7 o;

M losoov M moto toov: -SOOR (uyu, -bOOB? (ut), where RE? has the values indicated above, or a carboxylic acid of the general formula MIK olive С y-so-оН voos-7 -с0О (lyu, in which E ? has the above values, or a carboxylic acid of the general formula MIK

Voos- her v'Fos-7 to on os sht voos SUP), in which VZ ii Sh! have the above values, optionally in an activated form they are subjected according to a known method of interaction under the conditions of a coupling reaction with an amine of the general formula Ua

H-o-(2B (UShe), (p in which С, Р, 72, ВР, т! and р" have the above values, and then, if necessary, the protective groups present under certain conditions are cleaved off, resulting in a metal complex of general Id formula or, if

VAZ is a protective group, after cleavage of the specified protective groups, at the next stage, they are subjected to interaction according to a known method with at least one metal oxide or metal salt with serial number 23-29, 42-46 or 58-70, after which, if necessary, they are present under certain conditions acidic hydrogen atoms are replaced by cations of inorganic and/or organic bases, amino acids or amino acid amides.

The carboxylic acids of general formulas IK-MIIK used in the reactions described above are either known compounds, or they are obtained by the methods described in the examples. So, in particular, the method of obtaining carboxylic acids of the general formula IC is known from |(OE 19652386). The method of obtaining carboxylic acids of the general formula of IMC is described in (CE 19728954).

The precursor of the compounds of the general formula UVA is M3-(2,6-dioxomorpholinoethyl)-Mb-(ethoxycarbonylmethyl)-3,6-diazaprobic acid, which is described in (EP 2630591.

Compounds of the general formula Mav are derivatives of isomeric diethylenetriaminepentaacetic acid (DTPA), which is attached via an acetic acid near the central M atom. This DTPC is described in (OE 19507819 and OE 19508058).

Compounds of the general formula are derivatives of M-(carboxymethyl)-M-(2-(2,6-dioxo-4-morpholinyl)ethyl|glycine, the method of preparation of which is described in U. At. O.I. Spet. 5os, 59 ( 2) (1982), pp. 104-107).

Compounds of the general formula My are derivatives of 1-(4-carboxymethoxybenzyl)ethylenediaminetetraacetic acid, which is described in patent O5 46224201.

Among the compounds of the general formula II, it is most preferable to use according to the invention the metal complex HMI, presented below a in Table 1.

In another preferred embodiment of the invention, it is possible to use galena compositions containing paramagnetic and diamagnetic perfluoroalkyl-containing substances. Such paramagnetic perfluoroalkyl-containing substances are preferably used in the form of a solution in an aqueous solvent.

As paramagnetic perfluoroalkyl-containing compounds in such compositions, all the above-mentioned metal complexes of the general formulas I, Ia, IB, Is and/or Id can be used according to the invention.

Diamagnetic perfluoroalkyl-containing substances are compounds of the general formula ХХ: вВР-И12-в2 (ХХ) in which ER means a linear or branched perfluoroalkyl residue with 4-30 carbon atoms, 12 means a linker, and В? means a hydrophilic group. Linker 7? is a direct bond, a -5Og group or a straight or branched carbon chain containing up to 20 carbon atoms and which may be substituted by one or more groups -OH, -SOS", -5Oz and/or optionally contains one or several - о-, -5-, -СО-, -СОМН-, -МНОСО-, -СОМВАЗ-, -МАЗСО-, -502-, -РОг-, -МН-, -МАЗ-groups, an aryl ring or piperazine, while VZ means a C-C0 alkyl residue, which in turn may contain one or more O-atoms and/or may be substituted by -SOO-- or 5Oz-groups.

Hydrophilic group B2 is a mono- or disaccharide, one or more adjacent -СОО-- or -5053- groups, dicarboxylic acid, isophthalic acid, picolinic acid, benzenesulfonic acid, tetrahydropyrandicarboxylic acid, 2,6-pyridinedicarboxylic acid, quaternary ammonium ion, aminopolycarboxylic acid, aminodipolyethyleneglycolsulfonic acid, aminopolyethyleneglycol group, 5O2-(CHg)2-OH group, polyhydroxyalkyl chain with at least two hydroxyl groups, or one or more polyethylene glycol chains with at least two glycol links, while the polyethylene glycol links end with the -OH or -ОНз group . Similar substances are already partly known, and partly have been re-synthesized to obtain the compositions proposed in the invention. Known perfluoroalkyl-containing substances and their production are described in the following publications:

IU Ov. Viezv, doshgpa! Ogyd Tagdeiipod, 1994, vol. 2, pp. 455-468;

U.V. Mimei and others, Yeig. U. Med. Speth, 1991, vol. 26, pp. 953-960;

M.-R. Kgaiy and others, Apdem. Speth, 1994, vol. 106, Me10, p. 1146-1148;

M. Hapieg and others. Techgapedgop I etsegv5, 1995, vol. 36, Me14, p. 2491-2492;

ER. Siyoa, etc. Sagropuagasee Kezeagsp, 1994, vol. 261, pp. 37-55;

Z. Aspiyeti and others. doigpai oi Ritsogipe Spetivigu, 1995, vol. 70, pp. 19-26;

I. Siagu and others. Tezgapeagop, 1995, vol. 51, Mo47, pp. 13073-13088;

E. 520Pi and others. doigpai oi Рitsogipe Spetizighu, 1989, vol. 42, pp. 59-68;

N. My and others, Zyrgatoiesshag Spetivigu, 1994, vol. 3, pp. 175-180;

E. Shshiyegi and others, Apdem/. Spent 1994, vol. 106, Mo. 14, pp. 1583-1585;

M.-R. Kgaiy and others, Eig. U. Med. Speth, 1991, vol. 26, pp. 545-550;

U. Ogeipeg and others. doigpai oi Рitsogipe Spetivigu, 1992, vol. 56, p. 285-293;

A. Miiyiv and others. Sagropuagaie Kezeagsi, 1992, vol. 229, pp. 323-336;

U. Kiezv and others. Sopoiaz apa Zygpasez A, 1994, vol. 84, pp. 33-48; b. Matpy et al., U. Med. Speth, 1996, vol. 39, pp. 4483-4488;

M. Sigkma and others, dFoshipai oi Riogipe Spitivigu, 1997, vol. 83, pp. 151-158;

A. Osha Atapeioshiai and others. doshigpai oi Ritsogipe Spetivigu, 1997, vol. 84, p. 149-153;

U. Spep and others, Ipogd. Speth, 1996, vol. 35, pp. 1590-161;

I. Siagu and others. Teigapeagop I ebegv5, 1995, vol. 36, Me4, p. 539-542;

M.M. Spaaroipi and others. doigpai oi RIsogipe Spetizighu, 1990, vol. 46, pp. 307-315;

A. Miiiv and others. Mem/ U. Speth, 1991, vol. 15, pp. 337-344;

M.-R. Kgaiy and others. Memo U. Speth, 1990, vol. 14, p. 869-875;

U.-V. Mimei and others. Mem/ U. Speth, 1994, vol. 18, pp. 8961-869;

S. zapiaegna and others. Memo U. Speth, 1991, vol. 15, p. 685-692;

S. Zapiaega and others. Memo U. Speth, 1992, vol. 16, pp. 399-404;

A. Miiiv and others. Mem/ U. Speth, 1992, vol. 16, p. 771-773;

E. 52bpui and others. dUoishpai oi Ripogipe Spetivigu, 1991, vol. 55, p. 85-92;

S. Bapiae!Ia and others, Apdem/. Speth, 1991, vol. 103, Me5, p. 584-586;

M.-R. Kgai and others, Apdem/. Speth, 1993, vol. 105, Me5, p. 783-785;

ER 0548096 VI).

The preparation of new perfluoroalkyl-containing substances is similar to the preparation of the above-mentioned compounds known from the literature and is described in the examples. At the same time, we are talking about substances of the general formula XXI

WOW! (XXI) in which

B means a linear or branched perfluoroalkyl residue with 4-30 carbon atoms, and

X' means a residue selected from the group of the following residues (while n means a number from 1 to 10): on y go) no y aa ps 9)

ON

«nosti vou s he) o V... c) he o

M a y y (in) on o N she no 9) on on o no (in; washing

To o shi ra yun y 8) but and o

N o5 "neo pi on efito

ОН and it ele to ОН (osv) on o

ON Jon no o shk sho re o i (c)

I | WITH

KO, teach cha o c) o. SHE

SHY Jews

Cats in shi teki tia on

IF, sho 8-X iv) sell him and t o oho

Moss,

ON

9-00 we 000 -so5

Her -b00 syayi fe y pa va drink her di? pok b roo: "vo: shi n o ZO Z ry they money for pete shi CHI HE he zapy rev com don teshchi sh u t- no he sob - pt Otut stran o bo o or A uov

N

HE he oh no pound dos" i

Ak rani AI, - -- - so

Preferred diamagnetic perfluoroalkyl-containing substances are those that contain a monosaccharide as the hydrophilic group of the WU.

Particularly preferred diamagnetic perfluoroalkyl-containing compounds contain a perfluoroalkyl residue E: with 6-12 carbon atoms, a linker I2, which is a -"5O2-group or a straight or branched carbon chain, the number of carbon atoms in which is up to 20 and which, in turn, contains one or several -О-, -СО-, -СОМН-, -

МНеоО-, -СОМВ-, -МАСО-, -5О2-groups or piperazine, where KE has the above values, and monosaccharide as a hydrophilic group B".

Other acceptable diamagnetic perfluoroalkyl-containing compounds are conjugates of cyclodextrin and perfluoroalkyl-containing compounds. Such conjugates consist of co-, p- or y-cyclodextrin and compounds of the general formula XXIII

A1-13-VE (XXII) in which A! means a molecule of adamantane, biphenyl or anthracene, IZ means a linker, and B" means a linear or branched perfluoroalkyl residue with 4-30 carbon atoms. The IZ linker is a straight hydrocarbon chain with 1-20 carbon atoms, which can be interrupted by one or by several oxygen atoms, one or several CO-, 505-, СОМН-, МНСО-, СОМВА-, МАСО-, МН-, MA- groups or piperazine, while K is a C-Szalkyl residue.

In particular, the following compounds are preferred:

sk shi and o ak shi

Or 6) ? nn

M. ZO. new building 5,847 sq. m and 6) Fr.

M

WITH

ЗО» Sv ryttya what and o o ; D in i

Moscow State University "N o g

Railway m

M your 9)

And about

OO o Ko on vyk

N

The ratio in the mixture between paramagnetic and diamagnetic perfluoroalkyl-containing compounds in the galena compositions proposed in the invention is from 5:95 to 95:5. It is more preferable that the ratio in the mixture between both substances is from 40:60 to 60:40. Both of these substances are used in millimolar concentrations. At the same time, their concentration ranges from 0.5 to 1000 mmol/l of solvent. It is preferable to use water as a solvent. The concentration of the metal or metals in the compositions ranges from 50 to 250 mmol/l.

Preferred mixtures of paramagnetic and diamagnetic perfluoroalkyl-containing compounds, in which the length of the perfluoroalkyl chains is from b to 12 carbon atoms. More preferred mixtures in which both paramagnetic and diamagnetic perfluoroalkyl-containing compounds have a perfluoroalkyl chain with 8 carbon atoms.

The technology for obtaining galena compositions is that paramagnetic perfluoroalkyl-containing compounds (component A) and diamagnetic perfluoroalkyl-containing substances (component B) are mixed with each other in such a way that the mole fraction of one of the components A or B is from 0.05 to 0.95, and dissolve in a solvent suitable for this purpose. It is most preferable to use water as a solvent.

Additives usually used in galenic forms are then added to this solution in excess, such as, for example, buffer solutions and the Ca salt of the complexing agent. Next, the solution is intensively stirred at a temperature from 10 to 100"C. Alternatively, the solution can be subjected to ultrasound treatment at a temperature from 10 to 100"C. According to another option, the solution can be treated with microwave radiation.

To substances that are not soluble in water as individual components, it is preferable to add a hydrotropic solubilizer, such as an alcohol (for example, methanol or ethanol), or another solvent that is miscible with water, and then slowly drive it away. Such distillation can be carried out in a vacuum. After that, the residue is dissolved in water and the obtained solution is filtered. It is also possible to dissolve each of the components separately in the appropriate solvent, and then combine the resulting solutions and subject them to further processing according to the method described above. It was found that it is expedient to first prepare a relatively highly concentrated solution (more than 100 mmol) of the metal complex (component A), and then add components B to this solution in its pure form, and then, according to the method described above, mix the resulting solution or treat it with ultrasound, respectively, with microwave radiation .

Summarizing all of the above, it should be noted that the criteria provided for by this invention are satisfied by the gadolinium I-HMI complexes presented below in Table 1, which are the most preferable for the use of compounds proposed in the invention. Physical characteristics of these metal complexes

I-XMI are listed in Table 2.

It should also be noted that the paramagnetic compounds proposed in the invention of the general formulas |, Pa, IB, Is and

IA, as well as the compositions proposed in the invention, which contain paramagnetic and diamagnetic perfluoroalkyl-containing substances, are most suitable for use as contrast agents in MR tomography for visualization of plaques, tumors and necrosis.

Table G Nabiyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyy

Mmeishleni KolMekSy iKsmpneyu Plyuzhuettrne networks horror 00000000 and DUTY, prokona 33 N i and upokvny komtslekh MM walls of hearing Hall of pride N: yuerbutouvyutvyasuykaoni hi neramny S iipektych 7» N

NICK AND DREAMS,

NV TK ZI MIN I, prikoda di N : prrekhtsnkviykh kommeleh GII tidnekov- 4 -kano i kdd Tk N : 1 yam DZZ NE N : I gpezutadekeftoruettaleuy rve arksimetva it V» N

Ed KVK 00

PE ZHI, friend of Mykh; N and IKushkhtsienno coma BUT led kev I In February and

N iperoktorakvya nepeurkhyanY liliy trsikuuhvuyusimsuvh N yin - "about Oetrnvnykadieyany"

Pe ha YAMI, shturakh B N: igadodive vva komeldeka NM children ia oka ivan N

N rdera orlauva su vAfOYA t Z Tur kalik omen I TV- N

Her nn rnikh

NU Miryvladov, Dena pezhe 1: pal ltuzhki punishes NV for Ya kam prav DK N: 1545 pas uraksnaravya M NNI NNI. I

N Tora pkoyutortryudecia hm tezranzaknahalidevst, E: "and SO, prokhlaa N

N Niadokhiityunnih mosses Z0-EI idrokeyui ke» N and NEDNONAN UVP EN M yaurfzhtarinranetsyani MT. N

NU Sheokylva U. dnekYa yuudk: N

And TEa. t trukikanoo umo TD Z-vai i-okoogekohts-ya iy. N

N izhvkyutakh NAME ZMK I ZU pevtyaoko eko MM N

N IPPEIVINANAN NN - Z -vvokasrfkhortridecnya from at.

I oplnlchn KVNVKANNKIKM TAZH MNN ZhK ptn

Kovnaskk, NOZHUVNE KAK, JAKA...

NEVI Ntrmyazah Zk, dyaniy "tako E and PA prin button VM NM Z divi lk Kk ZI N : INAU NIDE NA KAN. N i Zk ikh hi vilk kV di AT pera oko keKah, N

NK ChirnazA Ob, this disaster E

I REA zuyikoikrvk close KO. ТZ -azn From Ohestehova i. N i kis Z V, Nestet rah dz V uh N

N pok fan miya MO uodkayuhamikivy, N

NKU Z iaklaliya, dhnvy above: N i Er uteuvik cream PO uzd y codec k V y" N i iklamy X netokok M ND NANNYA NN NO. i and pokeziper trusy vad TO m tera cyk no dykayu, and hi : OZ IMMNI yaryachah YAZ : pudcVeny koma NEGA ksi i am Z he Tu va N i peda aa i av va Taka va N ! пееййкогафтвр ная мк I стр клика сети Ne N yn DVK ooo

WHAT? an example of KNOWLEDGE; N : igzaolivisvyuy domlayeke PZ isooviv and azanyaoksa of Eeavaniya. N i ireraprautvlsua wn prim l I tora khrksya Uk i

PP with NN, sx GUMY? example 38: ! ! irzdrdiyuzyy vima PMG of izrrak in the Czech Republic"! Nperacrtvasuzafsnkh mu okt I also teach trkiklum tu iti IMC, example I: E

I N Balko 1 Lens m karkyukenavtayumini MUR ukolu diayayi i THUYA Dogryokohtttikh lyne Otrik pnia my lekny Se i and ikomizeks BEIJING NIANY LNZ okehper fluor id A KA KTK VAK KIN. MKK son

ХХ Mrnklyad LIK, LoBUMY you N and Tsile asuvkdon i i era in V i

Novo karivrenatoyuevya and JSC, PO totriak ky kl vuekano M. : : Nero we dream of ZM seie e i PODANA r ia o s NI

IV Tireyuty 240, dyan pishche:

H 1-14 wigs in fev Kklerzavyiaakya ZAM A I:

N Huka chicken U I I spider ok ektsi WE. She

Kosi KEKV Z JAK JAK NYA, KE KOZH un

The table "on Physico-chemical properties of compounds that can be deduced to disappear." predetavasnnh in haihyami i

NU N 10537 KOM M N

MDONNNNYN and OO EH THEY ARE NOT MONO EH NNY.

NO : iaYahii ZX 273 i

KON NK and but men their men

Prumizka:

House of Housing Ronachak criticizes the concentration of Mibezou Vorona:

ZK honors the tydrokhunyamichy diimete of Mycenae; 1-year relaxation.

Examples of implementation of the invention

Example 1 a) M-(2-methoxy)ethylamide of 2H,2H.4H,4H,5H,5H-3-oxaperfluorotridecanoic acid

To 30 g (57.45 mmol) of 2H.2H.4H.AN,5H,5H-3-oxaperfluorotridecanoic acid in 300 ml of dichloromethane, add 8.90 g (/Omole) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane, and at 0"C it is added dropwise to a solution of 4.51 g (bOmoles) of 2-methoxyethylamine and 6.07g (bOmoles) of triethylamine in 200 ml of dichloromethane. The mixture is stirred for hours at 0"C, and then for two hours at room temperature. Then add ZbOml

of aqueous hydrochloric acid and mix thoroughly for 15 minutes. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 20:1).

Yield: 30.28g (9195 from theory) of a colorless solid.

Elemental analysis: solution: C 31.10 H 2.44 M 2.42 E 55.76 found: C 30.87 H 2.58 M 2.35 E 55.51 b) M-(2-methoxyethyl) -M-(1Н,1Н,2нН 24 НАН,5Н,ЗН-3-oxa)perfluorotridecylamine

Zog (51.79 mmol) of the compound indicated in the title of Example 1a is dissolved in 300 ml of tetrahydrofuran and 10 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran) is added. Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C and 200ml of methanol is added dropwise, after which it is evaporated to dryness under vacuum. The residue is dissolved in a mixture of 100ml of ethanol with 500ml of 1095 aqueous hydrochloric acid and stirred at 40"C for 8 hours. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 300 ml of 5965 aqueous caustic sodium and extracted three times with dichloromethane in portions of 300 ml. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 20:1).

Yield: 26.93 g (9295 from theory) of a colorless solid.

Elemental analysis (in terms of anhydrous substance): solution: С 31.87 Н2.85 М 2.48 РЕ 57.14 found: С 31.69 Н 3.10 М 2.27 Е 56.88 c) 1 ,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-(M-(2-methoxyethyl)-M-

ИН 2гН2 нн НН, Н-З-oxa)perfluorotridecylamide)-1,4,7,10-tetraazacyclododecane, gadolinium complex (metal complex X) 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|- 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 1.35 g (31.7 bmmol) of lithium chloride are dissolved in 100 ml of dimethyl sulfoxide at 60 °C. Then they are cooled to 15 °C and 8.98 g ( 15.88 mmol) of the compound indicated in the title of example 16. The mixture is stirred for 10 minutes, and then 7.42 g (ZOmmol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline are added. After that, stir for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 15.14 g (8195 from theory) of colorless amorphous powder.

Water content: 5.790.

Elemental analysis (in terms of anhydrous substance): solution: С 34.70 Н 3.77 М 7.14 Е 27.44 Са 13.36 found.: С 34.51 Н 3.94 М 7.02 Е 27 ,25 Sa 13,18

Example 2 a) M-(2,3-dihydroxypropyl)amide of 2H,2H.4H,4H,5H,5H-3-oxaperfluorotridecanoic acid

To Zog (57.45 mmol) of 2H,2H.4H.4H,5H,5H-3-oxaperfluorotridecanoic acid in ZOO0 ml of dichloromethane, add 8.90 g (/Omol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"C is added dropwise to a solution of 5.47 g (bOmoles) of 2,3-dihydroxypropylamine and 6.07g (bOmoles) of triethylamine in 200 ml of dichloromethane. The mixture is stirred for 1 hour at 0"C, and then for two hours at room temperature. Next, add 30 ml of 595% aqueous hydrochloric acid and mix thoroughly for 15 minutes.

The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/ethanol in a ratio of 15:1).

Yield: 29.70 g (8795 from theory) of a colorless solid.

Elemental analysis: solution: C 30.32 H 2.20 M 2.36 E 54.35 detected: C 30.12 H 2.41 M 2.18 E 54.15 b) M-(2,3- dihydroxypropyl)-M-(1H, 1H,2H,2H,4H,4H,5H,5H-3-oxaperfluorotridecyl)amine

Zog (48.8 mmol) of the compound indicated in the title of example 2a is dissolved in 300 ml of tetrahydrofuran and 50 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran) is added. Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C and 300ml of methanol is added dropwise and then evaporated to dryness under vacuum. The residue is dissolved in a mixture of 200ml of ethanol and 500ml of 1095% aqueous hydrochloric acid and stirred at 60"C for 8 hours. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 30 ml of 5965 aqueous caustic sodium and extracted three times with dichloromethane in portions of 30 ml. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum and the residue is chromatographed on silica gel (eluent: dichloromethane/methanol in a ratio of 15:1).

Yield: 24.07 g (8595 from theory) of a colorless solid.

Elemental analysis: solution: С 31.05 Н 2.61 М 2.41 ЕЕ 55.66 detected: С 31.91 Н2.78 М 2.33 Е 55.47 c) 1,4,7-tris( carboxylatomethyl)-10-((3-aza-4-oxohexan-5-yl)-acid-M-(2,3-dihydroxypropyl)-M- nin 2gH2 nn H,5H,ZH-3-oxa)perfluorotridecyl)amide |-1,4,7,10-tetraazacyclododecane, gadolinium complex (metal complex M) 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1, 4,7-triacetic acid and 1.35 g (31.7 mmol) of lithium chloride are dissolved at 60"C in 100 ml of dimethylsulfoxide. Then it is cooled to 15"7C and 9.21 g (15.88 mmol) of the compound indicated in the title of example 26 is added. The mixture is stirred for 10 minutes and then 7.42 g (ZOmmol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline are added. After that, stir for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered off, dissolved in a mixture of a small amount of ethanol/water and chromatographed on silica gel EP-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 16.09 g (8595 from theory) of colorless amorphous powder.

Water content: 6.395.

Elemental analysis (in terms of anhydrous substance): solution: C 3426 H 3.64 M 7.05 27.10 Ca 13.19 found: C 34.12 3.834 6.91 E 26.88 (for 12.93

Example C a) M-(5-hydroxy-3-oxapentyl)amide of 2H,2H,4H,4H,5nH,5H-3-oxaperfluorotridecanoic acid

To Zog (57.45 mmol) of 2H,2H.4H.4H,5H,5H-3-oxaperfluorotridecanoic acid in ZOO0 ml of dichloromethane, add 8.90 g (/Omol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"C it is added dropwise to a solution of 6.25 g (bOmoles) of 5-hydroxy-3-oxapentylamine and 6.07g (bOmoles) of triethylamine in 200 ml of dichloromethane. The mixture is stirred for 2 hours at 0"C. and then for 2 hours at room temperature. Next, add 30 ml of 595% aqueous hydrochloric acid and mix thoroughly for 15 minutes.

The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 15:1).

Yield: 32.20 g (9295 from theory) of a colorless solid.

Elemental analysis: solution: C 31.54 H 2.65 M 2.30 E 53.01 found: C 31.61 H 2.84 M 2.14 E 52.85 b) M-(5-hydroxy- 3-oxapentyl)-M-(1Н1Н,2Н,2На4НаН,5Н,5ЗН-З-oxaperfluorotridecyl)amine

Zog (49.24 mmol) of the compound specified in the title of Example 3 is dissolved in 300 ml of tetrahydrofuran and 10 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran) is added. Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness under vacuum. The residue is dissolved in a mixture of 100ml of ethanol and 50ml of 1095 aqueous hydrochloric acid and stirred for 10 hours at 50"C. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 300 ml of 5965 aqueous caustic sodium and extracted three times with dichloromethane in portions of 300 ml. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 20:1).

Yield: 26.09g (8995 from theory) of a colorless solid.

Elemental analysis: solution: C 32.28 H 3.05 M 2.35 E 54.25 found: C 3212 H 3.21 M 2.18 E 54.09 c) 1,4,7-tris(carboxylatomethyl )-10-((3-aza-4-oxohexan-5-yl)-acid-IM-(5-hydroxy-3-oxapentyl)-M-nin 2гН 2 NN НН, Н-З-oxa)perfluorotridecyl)amide |-1,4,7,10-tetraazacyclododecane, gadolinium complex (Miya metal complex) 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1, 4,7-triacetic acid and 1.35g (31.7bmmol) of lithium chloride are dissolved in 100ml of dimethylsulfoxide at 60"C. Then, it is cooled to 15"7C and 9.45g (15.88mmol) of the compound indicated in the title of example 3b is added. The mixture is stirred for 10 minutes and then 7.42 g (ZOmmol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline are added. After that, stir for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 16.10 g (8495 from theory) of colorless amorphous powder.

Water content: 5.790.

Elemental analysis (in terms of anhydrous substance): solution: С 34.83 Н 3.84 М 6.96 РЕ 26.76 Са 13.03 found.: С 34.65 Н 3.96 М 6.84 Е 26 ,62 Sa 12,91

Example 4 a) M-(2-hydroxyethyl)amide of 2H,2H,4H,4H,5H,5H-3-oxaperfluorotridecanoic acid

To Zog (57.45 mmol) of 2H,2H.4H.4H,5H,5H-3-oxaperfluorotridecanoic acid in ZOO0 ml of dichloromethane, add 8.90 g (/Omol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"C is added dropwise to a solution of 3.66 g (bOmole) of 2-aminoethanol and 6.07g (bOmole) of triethylamine in 200 ml of dichloromethane. The mixture is stirred for hours at 0"C, and then for bh at room temperature. Then add ZOOml

of aqueous hydrochloric acid and mix thoroughly for 15 minutes. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 20:1).

Yield: 28.90g (8995 from theory).

Elemental analysis: solution: C 29.75 H 2.14 M 2.48 E 57.14 found: C 29.61 H 2.29 M 2.37 E 57.01 b) M-(2-hydroxyethyl) -M-(1NH,2H,2H,4NaH,5H,5ZH-3-oxaperfluorotridecyl)amine 28 g (49.54 mmol) of the compound indicated in the title of example 4a is dissolved in 30 ml of tetrahydrofuran and 1 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran) is added. Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness under vacuum. The residue is dissolved in a mixture of 300ml of ethanol and 500ml of 1095 aqueous hydrochloric acid and stirred for 10 hours at 50"C. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 300 ml of 5965 aqueous caustic sodium and extracted three times with dichloromethane in portions of 300 ml. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 15:1).

Yield: 25.12 g (9295 from theory) of a colorless solid.

Elemental analysis (in terms of anhydrous substance): solution: C 30.50 H 2.56 M 2.54 E 58.59 found: C 30.32 H 2.71 M 2.48 E 58.43 c) 1,4,7-tris(carboxylatomethyl)-10-|(3-aza-4-oxohexan-5-yl)-acid-M-(2-hydroxyethyl)-M-

ИНиНн 22 ННЯ Н,5Н,5Н-З-oxa)perfluorotridecyl)aminoamide!|-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-"carboxymethylcarbamoyl)ethyl-1, 4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 1.35 g (31.7 bmmol) of lithium chloride are dissolved in 100 ml of dimethyl sulfoxide at 60"C. Then they are cooled to 15"C and 8.75 g (15, 88mmol) of the compound indicated in the title of example 46. The mixture is stirred for 10 minutes and then 7.42g (ZOmmol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline are added. After that, stir for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 16.81 g (9195 from theory) of colorless amorphous powder.

Water content: 7.295.

Elemental analysis (in terms of anhydrous substance): solution: C 34.08 H 3.64 M 7.23 BE 27.77 (a 13.52 found.: C 33.91 H 3.82 M 7.14 E 27.58 Sa 13.41

Example 5 a) Amide of 2H,2H.AN.4H,5H,5H-3-oxaperfluorotridecanoic acid

To Zog (57.45 mmol) of 2H,2H.4H.4H,5H,5H-3-oxaperfluorotridecanoic acid in ZOO0 ml of dichloromethane, add 8.90 g (/Omol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 200 ml of dichloromethane. Then the solution at 0"C is bubbled with gaseous ammonia for about 2 hours. After that, the mixture is stirred for 4 hours at 0"C, and then for 2 hours at room temperature. Next, add ZOOml of 595% aqueous hydrochloric acid and mix thoroughly for 15 minutes. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a 20:1 ratio).

Yield: 27.85 g (9395 from theory).

Elemental analysis: solution: C 27.66 H 1.55 M 2.69 E 61.97 found: C 27.49 H 1.72 M 2.54 E 61.81 6) 1nNiNn 2 2naNNYN,5N,ZnN -Z-oxaperfluorotridecylamine, hydrochloride 27g (51.8mmol) of the compound indicated in the title of example 5a is dissolved in 300ml tetrahydrofuran and 10M borane dimethylsulfide (in tetrahydrofuran) is added. Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness under vacuum. The residue is dissolved in a mixture of 400ml of ethanol and 100ml of 1095 aqueous hydrochloric acid and stirred for 8 hours at 60"C. The mixture is evaporated to dryness in vacuo and the residue is recrystallized from a small amount of ethanol/diethyl ether.

Yield: 26.75 g (9595 from theory) of a colorless, crystalline solid.

Elemental analysis:

solution. C 2.51 H2.04 M 2.58 E 59.41 SI 6.52 found: C 26.37 H 2.21 M 2.46 E 59.25 SI 6.38 c) MA NN Нн2гН 3,6,9,12,15-pentaoxahexadecanoic acid

To 26.5 g (48.74 mmol) of the compound indicated in the title of example 56 and 14.8 g (146.2 mmol) of triethylamine, dissolved in 30 ml of dichloromethane, at 0"C, 14.24 g (5 b0 mmol) of chloride 3,6,9,12 are added ,15-pentaoxahexadecanoic acid and stir for 10 minutes at 0"С. Next, add 300 ml of 595% aqueous hydrochloric acid and mix thoroughly for 30 minutes. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 20:1).

Yield: 32.03g (8795 from theory) of colorless oil.

Elemental analysis: solution: C 36.57 H 4.00 M 1.85 E 42.75 found: C 36.46 H 4.12 M 1.76 E 42.53 g) M-(3.6, 9,12,15-pentaoxahexadecyl)-M-(1H1n,2n,2NanH,a4nH-3-oxaperfluorotridecyl)amine

3g (41.03mmol) of the compound indicated in the title of example 5c is dissolved in 300ml of tetrahydrofuran and 25ml of 10M borane dimethyl sulfide (in tetrahydrofuran) is added. Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness in a vacuum. The residue is dissolved in a mixture of 300ml of ethanol and 50ml of 1095 aqueous hydrochloric acid and stirred for 8 hours at 40"C. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 300 ml of 5965 aqueous caustic sodium and extracted three times with dichloromethane in portions of 300 ml. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 15:1).

Output: 27.68g (9195 from theory).

Elemental analysis: solution: C 37.26 H 4.35 M 1.89 E 43.56 detected: C 37.11 H 4.51 M 1.73 E 43.41 d) 1,4,7-tris (carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-(M-(3,6,9,12,15-pentaoxahexadecyl)-M-(1H1H,2H,2nNanNaH,5H, ЗН-3-oxa)perfluorotridecylamide)-1,4,7,10-tetraazacyclododecane, gadolinium complex (MII metal complex) 10 g (15.88 mmol) gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7 . in the title of example 5g. The mixture is stirred for 10 minutes and then 7.42 g (ZOmole) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline is added. After that, it is stirred for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 18.05 g (8495 from theory) of colorless amorphous powder.

Water content: 6.295.

Elemental analysis (in terms of anhydrous substance): solution: С 37.28 Н 4.47 М 6.21 ЕР 23.87 (а 11.62 found.: С 37.11 Н 4.61 М 6.03 Е 23.64 Sa 11.42

Example 6 a) 1,4,7-tris(carboxylatomethyl)-10-((3-aza-4-oxohexan-5-yl)-acid-M-(12-amino-3,6,9-trioxadodecyl)amide |-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-"carboxymethylcarbamoyl)ethyl-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, 1.35 g (31.7 bmmol) of lithium chloride and 3.6 bg (31.7 bmmol) of M-hydroxysuccinimide are dissolved in 100 ml of dimethylsulfoxide at 60"C. Then it is cooled to 157C and 3.51 g (17 mmol) of M,M'-dicyclohexylcarbodimide are added and stir for 5 hours at 1570. To separate the urea, filter the solution. 14.66 bg (bOmol) of 1,12-diamino-3,6,9-trioxadodecane and 2.02 g (20 mmol) of triethylamine are added to the filtrate and stirred for 12 hours at room temperature.

The solution is poured into a mixture of 1500 ml of diethyl ether and 5 x 0 ml of n-butanol and stirred for 30 minutes.

The precipitated solid is filtered off and chromatographed on KR-18 silica gel (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 12.66 g (6995 from theory) of colorless amorphous powder.

Water content: 3.595.

Elemental analysis (in terms of anhydrous substance): solution: C 30.16 H 4.54 M 8.49 ER 27.96 Ca 13.61 found: C 30.02 H 4.68 M 8.35 E 27 .81 Са 13.45 b) 1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-(M-(3,6,9,16-tetraoxa -13-aza-14-oxo-С19-Sovheptadecafluoro)hexacosylamide)-1,4,7,10-tetraazacyclododecane, gadolinium complex (metal complex IX) 11.3 g (21.64 mmol) 2Н,2Н,4Н,4Н,5Н ,5H-3-oxaperfluorotridecanoic acid, 0.85 g (20 mmol) of lithium chloride and 4.95 g (43 mmol) of M-hydroxysuccinimide are dissolved at 25"C in 150 ml of dimethylsulfoxide. Then, cool to 15"C, add 6.19g (ZOmmol) of M ,M'-dicyclohexylcarbodiimide and are stirred continuously

Bhd at 15"C. Filter the solution to separate the urea. 12.5g (10.82mmol) of the compound indicated in the title of example ba and 3.29g (32.47mmol) of triethylamine are added to the filtrate and stirred for 12h at room temperature. The solution pour into a mixture of 1300 ml of diethyl ether and 100 ml of acetone and stir for 30 minutes.

Yield: 13.01g (9095 from theory).

Water content: 6.790.

Elemental analysis (in terms of anhydrous substance): solution: C 36.86 H 4.30 M 7.34 E 24.17 (a 11.77 found.: C 36.68 H 4.41 M 7.25 E 24.03 Sa 11.55

Example 7 1,4,7-tris(carboxylatomethyl)-10-|((3-aza-4-oxohexan-5-yl)-acid-M-(1н1н,2Нн,2наНаН5Н,5Н-3-oxaperfluorotridecyl)amide| -1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid , 1.35g (31.7bmmol) of lithium chloride and 3.6bg (31.7bmmol) of M-hydroxysuccinimide at 60"C are dissolved in 100 ml of dimethylsulfoxide. Then it is cooled to 1570 and 3.51g (17mmol) of M,M'-dicyclohexylcarbodimide are added and stirred for 5 hours at 1570. To separate the urea, the solution is filtered. 8.63 g (15.88 mmol) of the compound indicated in the title of Example 56 and 5.06 g (50 mmol) of triethylamine are added to the filtrate and stirred for 12 hours at room temperature. The solution is drained into a mixture of 1500 ml of diethyl ether and 100 ml of acetone and stir for

REFERENCE The precipitated solid is filtered off and chromatographed on KR-18 silica gel (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 13.86 g (7895 from theory) of colorless amorphous powder.

Water content: 9.395.

Elemental analysis (in terms of anhydrous substance): solution: C 33.28 H 3.42 M 7.51 E 28.87 (a 14.05 found.: C 33.12 H 3.61 M 7.37 E 28.69 Sa 13.89

Example 8 a) M-(2,3,4,5,6-pentahydroxy)hexylamide of 2H,2H.4H,4H,5H,5H-3-oxaperfluorotridecanoic acid

To Zog (57.45 mmol) of 2H,2H.4H,4H,5H,5H-3-oxaperfluorotridecanoic acid in ZOO0 ml of dichloromethane, add 8.90 g (/Omole) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"C is added dropwise to a solution of 10.87 g (bOmoles) of glucamine and 6.07g (bOmoles) of triethylamine in a mixture of 150 ml of dichloromethane and 150 dioxane. The mixture is stirred for 10 hours at 0"C, and then for 8 hours at room temperature. Next, add 400 ml of 595% aqueous hydrochloric acid and mix thoroughly for 15 minutes. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/methanol in a ratio of 5:1).

Yield: 30.71g (7895 from theory).

Elemental analysis: solution: C 31.55 H 2.94 M 2.04 E 47.13 found: C 31.44 H 3.09 M 1.97 E 47.01 b) M-(2.3, 4,5,6-pentahydroxyhexyl)-M-1H.1H,2H.2nNa4H4H,5H,5H-3-oxaperfluorotridecylamine

Zog (43.77 mmol) of the compound indicated in the title of example va is dissolved in 300 ml of tetrahydrofuran and 50 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran) is added. Then, for 48 hours, it is boiled under reflux. After that, it is cooled to 0"C, 500ml of methanol is added dropwise and then evaporated to dryness under vacuum. The residue is dissolved in a mixture of 500ml of ethanol and 100ml of 1095 aqueous hydrochloric acid and stirred for 15 hours at 60"C. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 400 ml

Aqueous caustic sodium and extract five times with chloroform in portions of 400 ml. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/methanol in a ratio of 3:1).

Yield: 19.69 g (6795 from theory) of a colorless solid.

Elemental analysis: solution: C 32.20 H 3.30 M 2.09 E 48.11 found: C 32.05 H 3.43 M 1.97 E 47.93 c) 1,4,7-tris (carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-|Im-(2,3,5,6-pentahydroxy)hexyl-m-n Н2Н2гННН,5Н,ЗН-З-oxaperfluorotridecylamide )-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid acid and 1.35 g (31.7 mmol) of lithium chloride are dissolved in 100 ml of dimethylsulfoxide at 60"C. Then it is cooled to 15"7C and 15.88 g (15.88 mmol) of the compound specified in the title of example 86 is added. The mixture is stirred for 10 minutes and then add 7.42 g (ZOmol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline. After that, stir for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 16.10 g (7995 from theory) of colorless amorphous powder.

Water content: 6.395.

Elemental analysis (in terms of anhydrous substance): solution: C 36.64 H 3.93 M 6.55 E 25.17 Ca 12.26 found: C 34.49 H 4.13 M 6.48 E 25 ,03 Sa 12.11

Example 9 a) M-(2,2-dimethyl-5-hydroxy-1,3-dioxepane-b-ylamide | 2H,2H.4H4Hn,5nH,5H-3-oxaperfluorotridecanoic acid

To Zog (57.45 mmol) of 2H,2H.4H.4H,5H,5H-3-oxaperfluorotridecanoic acid in ZOO0 ml of dichloromethane, add 8.90 g (/Omol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"C it is added dropwise to a solution of 9.67 g (bOmoles) of 5-amino-2,2-dimethyl-1,3-dioxepan-b-ol and 6.07 g (bOmoles) of triethylamine in 200 ml of dichloromethane. The mixture is stirred for 1 hour at 0"C, and then for 5 hours at room temperature. Next, add 30 ml of water and mix thoroughly for 15 minutes. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel

(eluent: dichloromethane/acetone in a ratio of 15:1).

Output: 27.62g (8595 from theory).

Elemental analysis: solution: C 34.30 H 3.03 M 2.11 E 48.54 found: C 34.15 H 3.19 M 2.04 E 48.37 b) M-(1-hydroxymethyl- 2,3Z-dihydroxypropyl)-M-(1H1H,2H,2H,4H,aH,5ZnH,5H-3-oxaperfluorotridecyl)amine 27 g (40.58 mmol) of the compound indicated in the title of Example 3 is dissolved in 30 ml of tetrahydrofuran and 26 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran). Then, for 20 hours, it is boiled under reflux. After that, it is cooled to 0"C, 300ml of methanol is added dropwise and then evaporated to dryness under vacuum. The residue is dissolved in a mixture of 300ml of ethanol and 100ml of 1095 aqueous hydrochloric acid and stirred at 60"C for 2 hours. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 400 ml of 5965 aqueous caustic sodium and extracted five times with chloroform in portions of 2500 ml. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/methanol in a 6:1 ratio).

Yield: 20.09g (8195 from theory) of a colorless solid.

Elemental analysis: solution: C 31.44 H 2.97 M 2.29 E 52.83 found: C 31.26 H 3.11 M 2.18 P 52.67 c) 1,4,7-tris (carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-(M-(1-hydroxymethyl-2,3-dihydroxypropyl)-M-(1 НН 2Н2НаНнЯН,5Н,ЗН-З- oxaperfluorotridecylamide)-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1,4,7- of triacetic acid and 1.35 g (31.7 mmol) of lithium chloride are dissolved in 100 ml of dimethyl sulfoxide at 60 "C. Then it is cooled to 157 and 9.71 g (15.88 mmol) of the compound indicated in the title of example 96 is added. The mixture is stirred for 10 minutes and then add 7.42 g (ZOmol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline, and then stir for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 13.40 g (6995 from theory) of colorless amorphous powder.

Water content: 9.195.

Elemental analysis (in terms of anhydrous substance): solution: C 34.37 H 3.79 M 6.87 E 24.41 Ca 12.86 found: C 34.18 H 3.95 M 6.71 E 24 ,25 Sa 12, 70

Example 10 a) M-(2-benzyloxycarbonylamino)ethyliamide of perfluorooctylsulfonic acid 40g (173.4mmol) of 1-benzyloxycarbonylamino-2-aminoethane hydrochloride, 87.1g (173.4mmol) of perfluorooctylsulfofluoride and 35.42g (350mmol) of triethylamine are heated to 80" C and kept at this temperature for 1 hour, then cooled to room temperature and directly applied to a silica gel column for chromatographic purification (eluent: dichloromethane/acetone in a ratio of 20:71).

Yield: 42.22 g (3695 from theory) of a colorless solid.

Elemental analysis: solution: C 31.97 NI1.94 M 4.14 P 47.75 5 4.74 found: C 31.83 H 2.11 M 4.03 E 47.63 5 4.63 b) M-(2-amino)ethylamide of perfluorooctylsulfonic acid

Zog (44.3 mmol) of the compound indicated in the title of example 10a is dissolved in 300 ml of methanol, 5 g of palladium catalyst (1095 Pa/C) is added and hydrogenated overnight at room temperature. After that, the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 24.05 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 22.15 H 1.30 M 5.17 E 59.57 found: C 22.04 H 1.41 M 5.05 E 59.62 c) 1,4,7-tris (carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-M-((2-perfluorooctylsulfonylamino)ethylamide)-1,4,7,10-tetraazacyclododecane, gadolinium complex 10g (15.88mmol ) gadolinium complex of 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, 1.35g (31.7bmmol) of lithium chloride and 3.6bg (31, 7bmmol) of M-hydroxysuccinimide at 60"C is dissolved in 100ml of dimethylsulfoxide. Then it is cooled to 157C, 3.51g (17mmol) of M,M'-dicyclohexylcarbodiimide are added and stirred for 5 hours at 1570C. To separate the urea, the solution is filtered. To the filtrate add 8, 61 g (15.88 mmol) of the compound indicated in the title of Example 106 and 2.02 g (20 mmol) of triethylamine were stirred for 12 h at room temperature. The solution was poured into a mixture of 1500 ml of diethyl ether and 100 ml of acetone and stirred for

REFERENCE The precipitated solid is filtered off and chromatographed on KR-18 silica gel (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 15.76 g (8695 from theory) of colorless amorphous powder.

Water content: 6.595.

Elemental analysis (in terms of anhydrous substance): solution: C 30.19 N 3.06 M 8.50 ER 27.99 (a 13.63 5 2.78 detected: C 30.03 N 3.18 M 8.41 E 27.81 Sa 13.50 5 2.61

Example 11 a) M-(2-benzyloxycarboxyaminoethyl)amide of 2H,2H,4H,4H,5H,5H-3-oxaperfluorotridecanoic acid

To Zog (57.45 mmol) of 2H,2H.4H.4H,5H,5H-3-oxaperfluorotridecanoic acid in ZOO0 ml of dichloromethane, add 8.90 g (/Omol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"C it is added dropwise to a solution of 13.84 g (bOmoles) of 1-benzyloxycarbonylamine-2-aminoethane hydrochloride and 12.14 g (120 mmoles) of triethylamine in 200 ml of dichloromethane. The mixture is stirred for hours at 0"C , and then for 5 hours at room temperature. Next, add ZOOml of 595% aqueous hydrochloric acid and mix thoroughly for 15 minutes. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum.

The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 20:1).

Yield: 33.30 g (8395 from theory) of a colorless solid.

Elemental analysis: solution: C 37.84 H 2.74 M 4.01 PE 46.25 found: C 37.67 H 2.89 M 3.88 E 46.11 b) M-(2-amino) ethyl amide of 2H,2H.4H,4H,5H,5H-3-oxaperfluorotridecanoic acid

Zog (42.96 mmol) of the compound indicated in the title of example 11a is dissolved in 500 ml of methanol, 5 g of a palladium catalyst (1095 Pa/cС) is added and hydrogenated overnight at room temperature. After that, the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 24.24 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 29.80 H 2.32 M 4.96 E 57.24 detected: C 29.67 H 2.41 M 4.88 E 57.15 c) 1,4,7-tris (carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl-acid-M-I|IZ-aza-6-oxa-4-oxo-(Co-

Sivheptadecafluoro)hexadecylamide)-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1,4, 7-triacetic acid, 1.35g (31.7bmmol) of lithium chloride and 3.6bg (31.7bmmol) of M-hydroxysuccinimide are dissolved in 100 ml of dimethylsulfoxide at 60"C. Then it is cooled to 157C, 3.51g (17mmol) of M are added. M'-dicyclohexylcarbodiimide and stirred for 5 hours at 1570. To separate urea, the solution was filtered. 8.96 g (15.88 mmol) of the compound indicated in the title of Example 116 and 2.02 g (20 mmol) of triethylamine were added to the filtrate and stirred for 12 hours at room temperature. temperature. The solution is poured into a mixture of 1500 ml of diethyl ether and 100 ml of acetone and stirred for

REFERENCE The precipitated solid is filtered off and chromatographed on KR-18 silica gel (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 15.31 g (8295 from theory) of colorless amorphous powder.

Water content: 6.395.

Elemental analysis (in terms of anhydrous substance): solution: С 33.71 Н 3.51 М 8.34 Е 27.46 Са 13, 37 found.: С 33.61 Н 3.63 М 8.17 Е 27 ,31 (and 13, 20

Example 12 a) M-K2-hydroxy)ethylamide of 2H,2H,4H,4H,5nH,5H-3-oxaperfluoroundecanoic acid

To 24.25 g (57.45 mmol) of 2H,2H.4H,4H,5H,5H-3-oxaperfluorotridecanoic acid in 300 ml of dichloromethane, add 8.90 g (/mol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"C it is added dropwise to a solution of 3.6b6g (bOmoles) of ethanolamine and 6.07g (bOmoles) of triethylamine in 200 ml of dichloromethane. The mixture is stirred for 2h at 0"C, and then for 2h at room temperature. Then add ZOOml

of aqueous hydrochloric acid and mix thoroughly for 15 minutes. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 20:1).

Yield: 24.86 g (9395 from theory) of a colorless solid.

Elemental analysis: solution: C 30.98 H 2.60 M 3.01 E 53.09 found: C 30.71 H 2.81 M 2.87 E 52.82 b) M-(2-hydroxyethyl) -M-1H.1H,2H,2nNaH4H,5H,ZH-3-oxaperfluoroundecyl)amine 24 g (51.59 mmol) of the compound indicated in the title of example 12a is dissolved in 30 ml of tetrahydrofuran and 1 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran) is added. Next, it is boiled under reflux for 12 hours. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness under vacuum. The residue is dissolved in a mixture of 300ml of ethanol and 50ml of 1095 aqueous hydrochloric acid and stirred for 8 hours at 40"C. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 300 ml of 5965 aqueous caustic sodium and extracted three times with dichloromethane in portions of 30 ml. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 20:1).

Yield: 20.95 g (9095 from theory) of a colorless solid.

Elemental analysis: solution: С 31.94 НЗ3.13 М 3.10 Е 54.73 detected: С 31.71 Н 3.31 М 3.01 Е 54.58 c) 1,4,7-tris( carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-M-((2-hydroxy)ethyl-M- (ni Hn,2n2nYANnYanH,ZnH,5H-3-oxa)perfluoroundecyliamide)- 1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 1.35 g (31.7 mmol) of lithium chloride is dissolved in 100 ml of dimethylsulfoxide at 60"C. Then it is cooled to 157 and 8.98 g (15.88 mmol) of the compound indicated in the title of example 126 is added. The mixture is stirred for 10 minutes and then 7, 42 g (ZOmole) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline.After that, it is stirred for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 14.01 g (8395 from theory) of colorless amorphous powder.

Elemental analysis: solution: C 35.03 H 3.98 M 7.91 E 23.24 Ca 14.79 found: C 34.85 H 4.19 M 7.75 E 23.05 Ca 14.58

Example 13 a) M-(3,6,9,12-tetraoxatridecyl)amide of 2H.2H,4H,4H,5nH,5H-3-oxaperfluoroundecanoic acid

To 24.25 g (57.45 mmol) of 2H.2H.4H.4H,5nH,5H-3-oxaperfluoroundecanoic acid in 300 ml of dichloromethane, add 8.90 g (/Omol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"С it is added dropwise to a solution of 12.44 g (bOmoles) of 3,6,9,12-tetraoxatridecylamine and 6.07 g (bOmoles) of triethylamine in 200 ml of dichloromethane. The mixture is stirred for 2 hours at 0" C, and then for a few hours at room temperature. Next, add 30 ml of 595% aqueous hydrochloric acid and mix thoroughly for 15 minutes.

The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 15:1).

Yield: 31.61 g (9095 from theory) of a colorless solid.

Elemental analysis: solution: C 37.33 H 4.29 M 2.29 E 40.40 found: C 37.15H441 212 E 40.18 b) m-(3,6,9,12-tetraoxatridecyl)- M-(1H1H,2H,2H,4H,4H,5H,ZH-Z-oxaperfluoroundecyl)amine

31g (50.7mmol) of the compound specified in the title of example 1Z3a is dissolved in 300ml of tetrahydrofuran and 32ml of 10M borane dimethyl sulfide (in tetrahydrofuran) is added. Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness under vacuum. The residue is dissolved in a mixture of 300ml of ethanol and 50ml of 1095 aqueous hydrochloric acid and stirred for 8 hours at 40"C. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 300 ml of 5965 aqueous caustic sodium and extracted three times with dichloromethane in portions of 30 ml. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 20:1).

Yield: 28.17 g (9395 from theory) of a colorless solid.

Elemental analysis (in terms of anhydrous substance): solution: C 38.20 H 4.72 M 2.34 E 41.34 found: C 38.05 H 4.83 M 2.40 E 41.50 c) 1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-M-|(3,6,9,12-tetraoxa)tridecyl-m-n H2H2nNaNH, 5H,ZN-Z-oxa)perfluoroundecyliamide-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-"carboxymethylcarbamoyl)ethyl-1,4,7,10-tetraazacyclododecane-1 ,4,7-triacetic acid and 1.35g (31.7bmmol) of lithium chloride are dissolved in 100ml of dimethylsulfoxide at 60"C. Then it is cooled to 157 and 9.49g (15.88mmol) of the compound specified in the title of example 136 is added. The mixture stirred for 10 min, and then 7.42 g (ZOmole) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline was added, followed by stirring for 12 h at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 16.13g (8495 from theory).

Elemental analysis: solution: C 37.75 H 4.67 M 6.95 E 20.43 (for 13.01 found: C 37.91 H 4.81 M 6.83 E 20.60 Ca 13.15

Example 14 a) tert-Butyl ether of 2-M-1 НН,2нН,2НаНаН,5Н,ЗН-3-oxaperfluorotridecyl)aminoacetic acid

To 32.0 g (58.65 mmol) of the compound indicated in the title of Example 56 and 24.89 g (1 in 80 mmol) of potassium carbonate in 30 Oml of acetonitrile at 50 "C, 6.523 g (40 mmol) of tert-butyl bromoacetic acid is added dropwise and stirred for Agree at this temperature. Next, add ZOO ml of dichloromethane, the precipitated salts are filtered off and the filtrate is evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in the ratio 20:1).

Yield: 28.11 g (5795 from theory) of a colorless solid.

Elemental analysis: solution: C 34.80 H 3.24 M 2.25 E 51.98 found: C 34.98 H 3.31 M 2.20 E 52.16 b) 1,4,7-tris (carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-M-tert-butyloxycarbonylmethyl)-M-(1HT H,2H2nH,4H4H,5H,5H-3-oxa)perfluorotridecylamide) -1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 1.35 g (31.7 mmol) of lithium chloride at 60"C are dissolved in 100 ml of dimethyl sulfoxide. Then it is cooled to 157 and 9.87 g (15.88 mmol) of the compound specified in the title of example 14a is added. The mixture is stirred for 10 minutes and then 7 .42 g (ZOmmol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline.After that, it is stirred for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 16.64g (8595 from theory).

Elemental analysis: solution: C 36.04 H 3.92 M 6.82 E 26.19 (a 12.72 found.: C 35.92 H 3.83 M 6.91 E 26.29 (a 12, 84 c) 1,4,7-tris-(carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-Mm-(carboxymethyl)-M-

ИН 2гН2 нн НН, Н-З-oxa)perfluorotridecylamide)-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (8.11 mmol) of the compound indicated in the title of example 14b is dissolved in 5 bml of trifluoroacetic acid and stirred for 5 hours at room temperature. The mixture is evaporated to dryness under vacuum and the residue is chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

After evaporation of fractions containing the product, the residue is dissolved in water and the pH value is set to 7.2 with the help of 595 aqueous caustic sodium. The solution is filtered and the filtrate is lyophilized.

Yield: 10.48g (9195 from theory).

Elemental analysis (in terms of anhydrous substance): solution: С 33.06 Н 3.28 М 7.01 Е 26.94 Са 13.12 Ма 1.92 found.: С 33.19 Н 3.40 М 7 ,20 E 27.14 Sa 13.25 Ma 2.00

Example 15 a) M-(2-hydroxyethyl)amide of 2H,2H,4H,4H,5H,5H-3-oxaperfluorotridecanoic acid

To 32 g (56.61 mmol) of the compound indicated in the title of example 4a, add 2.96 g (74 mmol) of sodium hydride (from 6095 sodium hydride in paraffin oil) in ZOO ml of tetrahydrofuran and stir for 2 hours at room temperature in a nitrogen atmosphere. Next, 7.67 g (74 mmol) of bromoacetic acid tert-butyl ether, dissolved in 20 ml of tetrahydrofuran, is added dropwise and stirred for 5 hours at 5070.

Next, add 500 ml of methanol and evaporate to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 20:1).

Yield: 23.46g (6195 from theory).

Elemental analysis: solution: C 35.36 H 3.26 M 2.06 E 47.54 found: C 35.52 H 3.40 M 2.17 E 47.40 b) MAYA NN 2n, 2 nan, NN, nH-3-oxaperfluorotridecyl)-IM-(4-tert-butyloxycarbonyl-3-oxa)butylamine 35.0 g (51.52 mmol) of the compound indicated in the title of example 15a is dissolved in 30 ml of tetrahydrofuran and 1 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran). Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness in a vacuum. The residue is dissolved in a mixture of 300ml of ethanol and 500ml of 1095 aqueous hydrochloric acid and stirred for 8 hours at 40"C. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 300 Oml of 5965 aqueous caustic sodium and extracted three times with dichloromethane in portions of 30 Oml. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 20:1).

Yield: 31.88g (9395 from theory).

Elemental analysis: solution: C 36.10 H 3.64 M 2.11 E 48.54 found: C 35.90 H 3.75 M 2.20 E 48.71 c) 1,4,7-tris (carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-M-|(4-tert-butyloxycarbonyl-3-oxa)butyl)-M-( NT H.hn.2hn.a4HnYAN ,5H,5H-3-oxa)perfluorotridecylamide)-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10 - tetraazacyclododecane-1,4,7-triacetic acid and 1.35g (31.7bmmol) of lithium chloride are dissolved in 100ml of dimethylsulfoxide at 60"C. Then, cool to 15"C and add 10.57g (15.88mmol) of the specified compound in the title of example 156. The mixture is stirred for 10 minutes and then 7.42 g (ZOmmol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline are added. After that, stir for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 16.63g (8295 from theory).

Elemental analysis: solution: C 36.68 H 4.10 M 6.58 E 25.29 (at 12.31 found: C 36.81 H 4.20 M 6.41 E 25.40 Ca 12.19 d) 1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-|m-(4-carboxy-3-oxa)butyl)-M- (ni Нн,2н2нЯНяЯНН,Зн,ЗН-3-oxa)perfluorotridecylamide)-1,4,7,10-tetraazacyclododecane, gadolinium complex 12 g (94 mol) of the compound indicated in the title of example 15c is dissolved in 50 ml of trifluoroacetic acid and stirred at room temperature for 5 hours temperature The mixture is evaporated to dryness under vacuum and the residue is chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

After evaporation of fractions containing the product, the residue is dissolved in water and the pH value is set to 7.2 with the help of 595 aqueous caustic sodium. The solution is filtered and the filtrate is lyophilized.

Yield: 11.41g (9295 from theory).

Water content: 5.895.

Elemental analysis (in terms of anhydrous substance): solution: С 33.82 Н 3.49 М 6.76 РЕ 25.98 (а 12.65 Ма 1.85 detect.: С 33.95 Н 3.60 М 6.88 E 26.15 Sa 12.49 Ma 1.93

Example 16 a) M-2H2nNanNYAN,5H,ZnH-3-oxalerfluorotridecyl)amide of 2H,2H.4H,4H,5H,5H-3-oxaperfluorotridecanoic acid

To 30 g (57.45 mmol) of 2H,2H.4H.AN,5H,5H-3-oxaperfluorotridecanoic acid in 30 ml of dichloromethane, add 8.90 g (/Omol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"C it is added dropwise to a solution of 32.62 g (bOmoles) of the compound specified in the title of example 56 and 6.07g (bOmoles) of triethylamine in 200 ml of dichloromethane. The mixture is stirred for hours at 0"C , and then for two hours at room temperature. Next, add 30 ml of 595% aqueous hydrochloric acid and mix thoroughly for 15 minutes.

The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 15:1).

Yield: 52.87g (9195 from theory).

Elemental analysis: solution: C 28.50 H 1.49 M 1.38 E 63.87 found: C 28.65 H 1.61 M 1.50 E 64.01 b) M-bis(t NT H .2n2nH NN, 5H-3-oxa)perfluorotridecylamine 52 g (51.42 mmol) of the compound indicated in the title of example 16ba is dissolved in 500 ml of tetrahydrofuran and 1 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran) is added. Next, it is boiled under reflux for 16 hours. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness under vacuum. The residue is dissolved in a mixture of 4A00ml of ethanol and 7Oml of 1095 aqueous hydrochloric acid and stirred for 8 hours at 4070.

The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 400 ml of 5956 aqueous caustic sodium and extracted three times with dichloromethane in portions of 400 ml each. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 20:1).

Yield: 47.18 g (9295 from theory) of a colorless solid.

Elemental analysis: solution: C 28.90 H 1.72 M 1.40 P 64.77 found: C 30.03 H 1.81 M 1.55 E 65.00 c) 1,4,7-tris (carboxylatomethyl)-10-((3-aza-4-oxohexan-5-yl)-acid-M-bis(! Н1Н,2нН,2наНн4Н5Нн,5Н-

3-oxaperfluorotridecyl)amide (|-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1 ,4,7-triacetic acid and 1.35g (31.7bmmol) of lithium chloride are dissolved in 100ml of dimethylsulfoxide at 60"C. Next, it is cooled to 15"C and 15.84g (15.88mmol) of the compound indicated in the title of example 166 is added. The mixture is stirred for 10 minutes and then 7.42 g (ZOmmol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline are added. After that, stir for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 20.95g (8295 from theory).

Elemental analysis: solution: C 32.10 H 2.82 M 5.22 E 40.14 Ca 9.77 found: C 29.87 H 2.91 M 5.09 E 40.28 Ca 9.98

Example 17 a) M-hydroxy-3-oxapentyl)amide of 2H,2H,4H,4H,5H,5H-3-oxaperfluorotridecanoic acid

To 32 g (52.52 mmol) of the compound indicated in the title of Example 3a, add 2.80 g (7/Omol) of sodium hydride (from 6B095 sodium hydride in paraffin oil) in 30 Oml of tetrahydrofuran and stir for 2 hours at room temperature in a nitrogen atmosphere . Then 9.68 g (/mol) of bromoacetic acid tert-butyl ether is added dropwise to 20 ml of tetrahydrofuran and stirred for 5 hours at 50"C. Then 50 ml of methanol is added and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/2- propanol in a ratio of 20:1).

Yield: 19.31g (5995 from theory).

Elemental analysis: solution: C 32.76 H 2.91 M 2.25 E 51.82 detected: C 32.98 H 2.99 M 2.36 E 51.98 b) M-(3,6- dioxaheptyl)-M-(1 Н.Н 2Н2Н4Н4Н,5Н,ЗН-3-oxaperfluorotridecyl)amine 32 g (51.34 mmol) of the compound indicated in the title of example 17a is dissolved in 30 ml of tetrahydrofuran and 1 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran) is added. Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness in a vacuum. The residue is dissolved in a mixture of 300ml of ethanol and 500ml of 1095 aqueous hydrochloric acid and stirred for 8 hours at 40"C. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 300 Oml of 5965 aqueous caustic sodium and extracted three times with dichloromethane in 300 Oml portions. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 20:1).

Yield: 28.47g (9195 from theory).

Elemental analysis: solution: C 33.51 H 3.31 M 2.30 E 53.01 detected: C 33.63 H 3.41 M 2.21 E 52.87 c) 1,4,7-tris (carboxylatomethyl)-10-((3-aza-4-oxohexan-5-yl)-acid-M-(3,6-dioxa)heptyl-M- iNiHn2gH 2 НЯ Н,5Н,ЗН-З-oxaperfluorotridecyl)amide !|-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1,4,7 -triacetic acid and 1.35 g (31.7 mmol) of lithium chloride are dissolved in 100 ml of dimethylsulfoxide at 60 °C. Then it is cooled to 15 °C and 9.68 g (15.898 mmol) of the compound indicated in the title of example 176 is added. The mixture is stirred for 10 minutes and then add 7.42 g (ZOmole) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline. After that, stir for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Output: 16.09g (83905 from theory).

Elemental analysis: solution: C 35.41 H 3.96 M 6.88 E 26.45 Ca 12.88 found: C 35.57 H 4.11 M 6.72 E 26.58 Ca 12.97

Example 18 a) M-(hexyl)amide of 2H,2H.4H.4H,5H,5H-3-oxaperfluorotridecanoic acid

To Zog (57.45 mmol) of 2H,2H.4H.4H,5H,5H-3-oxaperfluorotridecanoic acid in ZOO0 ml of dichloromethane, add 8.90 g (/Omol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"С it is added dropwise to a solution of 6.07g (bOmoles) of n-hexylamine and 6.07g (bOmoles) of triethylamine in 200ml of dichloromethane. The mixture is stirred for 10 hours at 0"С, and then for 2 hours at room temperature. Then add ZOOml

of aqueous hydrochloric acid and mix thoroughly for 15 minutes. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 20:1).

Yield: 30.95g (8995 from theory).

Elemental analysis: solution: C 35.72 H 3.33 M 2.31 E 53.35 found: C 35.60 H 3.45 M 2.43 E 53.63 b) M-(hexyl)-M -(1 NN 2hnH2nNaH,YAN,ZN,ZN-Z-oxaperfluorotridecyl)amine Z1g (51.21 mmol) of the compound specified in the title of example 178a is dissolved in 300 ml of tetrahydrofuran and 1 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran) is added. Next, it is boiled under reflux for 16 hours.

After that, it is cooled to 0"C, 200 ml of methanol is added dropwise and then evaporated to dryness in a vacuum.

The residue is dissolved in a mixture of 100 ml of ethanol and 5 ml of 1095 aqueous hydrochloric acid and stirred for 8 hours at 40°C. The mixture is evaporated to dryness under vacuum, the residue is dissolved in 100 ml of 595 aqueous caustic sodium and extracted three times with dichloromethane in portions of 30 ml. Organic phases dried over magnesium sulfate, evaporated to dryness in a vacuum and the residue chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 20:1).

Output: 28.16g (9395 from theory).

Elemental analysis: solution: C 36.56 H 3.75 M 2.37 E 54.62 found: C 36.40 H 3.82 M 2.27 E 54.81 c) 1,4,7-tris (carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-|M-(hexyl)-M-ny n,2n2nYANnyanH,Zn,ZnH-Z-oxaperfluorotridecylamide)-1,4,7 ,10-tetraazacyclododecane, gadolinium complex 10g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 1.35g (31 .7bmmol) of lithium chloride at 60"С is dissolved in 100ml of dimethyl sulfoxide. Then it is cooled to 157С and 10.98g (15.88mmol) of the compound indicated in the title of example 186 is added. The mixture is stirred for 10 minutes and then 7.42g (ZOmmol) 2 is added -ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline.After that, it is stirred for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 16.29g (8495 from theory).

Elemental analysis: solution: C 36.94 H 4.19 M 6.99 P 26.85 (a 13.07 found: C 37.18 H 4.31 M 7.18 E 26.67 Ca 13.19

Example 19 a) M-(10-tert-butyloxycarbonyl)decylamide of 2H,2H,4H4H,5H,5H-3-oxaperfluorotridecanoic acid

To 30 g (57.45 mmol) of 2H,2H.4H.AN,5H,5H-3-oxaperfluorotridecanoic acid in 300 ml of dichloromethane, add 8.90 g (/Omole) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"С it is added dropwise to a solution of 15.45 g (bOmoles) of tert-butyl ether of 11-aminoundecanoic acid and 6.07g (bOmoles) of triethylamine in 200 ml of dichloromethane. The mixture is stirred for hours at 0"С , and then for two hours at room temperature. Next, add ZOOml of 595% aqueous hydrochloric acid and mix thoroughly for 15 minutes. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum.

The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 20:1).

Yield: 42.04g (9295 from theory).

Elemental analysis: solution: C 42.58 H 4.76 M 1.84 E 42.41 detected: C 42.74 H 4.90 M 1.73 E 42.61 b) M-(10-tert- butyloxycarbonyldecyl)-M-(1H,1n,2n,2n,aH,4H,5H,5H-3-oxaperfluorotridecyl)amine

39 g (51.21 mmol) of the compound indicated in the title of example 19a is dissolved in 30 ml of tetrahydrofuran and 1 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran) is added. Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness in a vacuum. The residue is dissolved in a mixture of 400ml of ethanol and 7Oml of 1095 aqueous hydrochloric acid and stirred for 8 hours at 40"C. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 350 ml of 5965 aqueous caustic sodium and extracted three times with dichloromethane in portions of 400 ml each. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 20:1).

Output: 34.84g (9195 from theory).

Elemental analysis: solution: C 43.38 H 5.12 M 1.87 E 43.20 detected: C 43.22 H 5.23 M 1.96 E 43.33 c) 1,4,7-tris (carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-(M-(10-tert-butyloxycarbonyldecyl-M-(1H1H,2H,2nNa4H4H,5H,3H-3-oxaperfluorotridecylamide)- 1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-"carboxymethylcarbamoyl)ethyl-1,4,7,10-

tetraazacyclododecane-1,4,7-triacetic acid and 1.35 g (31.7 mmol) of lithium chloride are dissolved in 100 ml of dimethylsulfoxide at 60 "C. Then it is cooled to 15 "C and 11.87 g (15.88 mmol) of the compound indicated in title of example 196. The mixture is stirred for 10 minutes and then 7.42 g (ZOmmol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline are added. After that, stir for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Output: 17.92g (8395 from theory).

Elemental analysis: solution: С 40.65 Н 4.89 М 6.18 РЕ 23.76 (а 11.57 found.: С 40.81 Н 4.99 М 6.32 Е 23.94 Са 11.73 d) 1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)u-acid-(M-(10-carboxy)decyl-m-

НН 2гН2 NN НН, Н-З-oxa)perfluorotridecylamide)-1,4,7,10-tetraazacyclododecane, gadolinium complex, sodium salt 12g (8.83mmol) of the compound indicated in the title of example 19c is dissolved in 50ml of trifluoroacetic acid and during Stir for 5 hours at room temperature. The mixture is evaporated to dryness under vacuum and the residue is chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

After evaporation of fractions containing the product, the residue is dissolved in water and the pH value is set to 7.2 with the help of 595 aqueous caustic sodium. The solution is filtered and the filtrate is lyophilized.

Yield: 12.48g (9295 from theory).

Water content: 6.295.

Elemental analysis (in terms of anhydrous substance): solution: C 38.07 N 4.34 M 6.34 РЕ 24.37 (30 11.87 Ma 1.73 detect.: C 37.89 N 4.44 M 6.22 E 24.51 Sa 12.01 Ma 1.80

Example 20 a) 15-benzyl-3,6,9,12,15-pentaoxahexadecyl acid m-n Н2хН2хНАНЯНА,5Н,5Н-З-oxa)perfluorotrvdecyl)amide

To 19.67 g (57.45 mmol) of 15-benzyl-3,6,9,12,15-pentaoxahexadecyl acid in 250 ml of dichloromethane, add 8.90 g (/Omol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"C it is added dropwise to a solution of 32.62 g (bomoles) of 1H.1H,2H2NaNaH,5H,5ZnH-3-oxaperfluorotridecylamine hydrochloride and 6.07 g (bomoles) of triethylamine in 200 ml of dichloromethane. The mixture is stirred. for hours at 0"C, and then for two hours at room temperature. Next, add 300 ml of 595% aqueous hydrochloric acid and mix thoroughly for 15 minutes. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 20:1).

Yield: 44.91 g (9495 from theory) of a colorless solid.

Elemental analysis: solution: C 41.89 H 4.12 M 1.68 E 38.84 found: C 42.02 H 4.25 M 1.83 E 39.07 b) M-15-benzyl-3 ,6,9,12,15-pentaoxahexadecyl)-M-(1H1H,2n2HnaH4H,5Hn,5H-3-oxa)superfluorotridecyl)amine 43 g (51.72 mmol) of the compound indicated in the title of example 20a is dissolved in 400 ml of tetrahydrofuran and added Add 10M borane dimethyl sulfide (in tetrahydrofuran). Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness under vacuum. The residue is dissolved in a mixture of 400ml of ethanol and 5Oml of 1095 aqueous hydrochloric acid and stirred for 8 hours at 40"C. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 350 ml of 5965 aqueous caustic sodium and extracted three times with dichloromethane in portions of 400 ml each. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 20:1).

Yield: 39.32g (9395 from theory).

Elemental analysis: solution: C 42.60 H 4.12 M 1.68 E 38.84 detected: C 42.45 H 4.23 M 1.57 E 38.99 c) 1,4,7-tris (carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-(M-(15-benzyl-3,6,9,12,15-peotaoxa)hexadecyl-M-(1H1 НН 2НаНаН5Н ,ZN-3-oxa)tridecylamide)-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane -1,4,7-triacetic acid and 1.35g (31.7bmmol) of lithium chloride are dissolved in 100ml of dimethylsulfoxide at 60"C. Then, it is cooled to 15"C and 12.98g (15.88mmol) of the compound specified in the title is added of example 206. The mixture is stirred for 10 minutes and then 7.42 g (ZOmole) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline is added. After that, stir for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 18.84g (8395 from theory).

Elemental analysis: solution: C 40.34 H 4.51 M 5.88 E 22.60 (a 11.00 found: C 40.50 H 4.62 M 5.76 E 22.73 Ca 11.16 d) 1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-(M-(14-hydroxy-3,6,9,12-tetraoxa)tetradecyl -M-(1Н 1224 НЯН,ЗН,5Н-3-oxa)perfluorotridecylamide)-1,4,7,10-tetraazacyclododecane, gadolinium complex 12 g (8.40 mmol) of the compound indicated in the title of example 20c is dissolved in 150 ml of methanol, add 1.0 g of palladium catalyst (1095 Pa/C) and hydrogenate overnight at room temperature. After that, the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 10.13g (9595 from theory).

Elemental analysis: solution: C 38.80 H 4.61 M 1.10 P 25.45 Ca 12.39 found: C 38.87 H 4.73 M 1.20 E 25.58 (for 12.50

Example 21 a) 2-M-trifluoroacetyl-6-M-benzyloxycarbonyl-1-lysine 100.0 g (356.7 mmol) of 6-M-benzyloxycarbonyl-1-lysine is dissolved in a mixture of 1000 ml of trifluoroacetic acid ethyl ether and 500 ml of ethanol and during Stir for 24 hours at room temperature. After that, it is evaporated to dryness and the residue is crystallized from the action of isopropyl ether.

Yield: 128.9 g (9695 from theory) of colorless crystalline powder.

Melting point: 98.570.

Elemental analysis: solution: C 51.07 H 5.09 M 7.44 E 15.14 found: C 51.25 H 5.18 M 7.58 E 15.03 b) (1-(4-perfluorooctylsulfonyl )piperazinamide 2-M-trifluoroacetyl-6-M-benzyloxycarbonyl-y-lysine

To 125.0 g (332.0 mmol) of the compound indicated in the title of example 21a and 188.7 g (332.0 mmol) of 1-perfluorooctylsulfonylpiperazine (obtained according to OE 19603033) in 750 00 ml of tetrahydrofuran at 0"С, 164.2 g (0.664 mmol ) EEDH (2-ethoxy-1,2-dihydroquinoline-1-carboxylic acid ethyl ester) and stirred overnight at room temperature, then evaporated to dryness in vacuo and chromatographed on silica gel (eluent: dichloromethane/methanol 20:1) .

Yield: 286.0 g (9395 from theory) of a colorless solid.

Melting point: 9276.

Elemental analysis: solution: C 36.30 H 2.83 M 6.05 E 41.01 5 3.46 found: C 36.18 H 2.94 M 5.98 E 40.87 5 3.40 ) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-benzyloxycarbonyl-y-lysine

A solution of 280.0 g (302.2 mol) of the compound indicated in the title of example 216 in 2000 ml of ethanol at 0"C is bubbled with gaseous ammonia for one hour. Then the mixture is stirred for 4 hours at 0"C.

After that, it is evaporated to dryness and the residue is separated from the water by stirring. The solid substance is filtered off and dried in a vacuum at 507C.

Yield: 243.5 g (9795 from theory) of amorphous solid.

Elemental analysis: solution: C 37.60 H 3.28 M 6.75 E 38.89 5 3.86 found: C 37.55 H 3.33 M 6.68 E 38.78 5 3.81 g ) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-benzyloxycarbonyl-2-M-|1-O-y-0-carbonylmethyl(2,3,4,6-tetra-O-benzylmannopyranose|- lysine

To a solution of 100.0 g (120.4 mol) of the compound indicated in the title of example 21c, 721 g (120 4 mol) of 1-O-o-0-carboxymethyl-2,3,4,6-tetra-O-benzylmannopyranose and 13, 41.27 g (200.0 mmol) of M,M-dicyclohexylcarbodiimide is added to 86 g (120.4 mol) of M-hydroxysuccinimide in 500 ml of dimethylformamide at 0 "C. The mixture is stirred for 2 hours at 0 "C, and then overnight at room temperature. The precipitated urea is filtered off, the filtrate is evaporated to dryness under vacuum and chromatographed on silica gel (eluent: dichloromethane/ethanol in a ratio of 20:1).

Yield: 136.1 g (8795 from theory) of viscous oil.

Elemental analysis: solution: C 57.32 H 4.89 M 4.31 E 24.86 52.47 found: C 57.38 H 5.07 M 4.22 E 24.78 5 2.39 d) 1-K4-perfluorooctylsulfonyl)piperazine|amide 2-M-(1-O-0-O-carbonylmethylmannopyranose|-I-lysine) 130.0 g (100.0 mmol) of the compound indicated in the title of example 21 g are dissolved in 2000 ml of ethanol and added 10.0 g of palladium catalyst (1095 Pa/C). After that, hydrogenation is carried out for 12 hours at room temperature. The catalyst is then filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 91.7 g (quantitative) of a colorless solid.

Elemental analysis: solution: С 34.07 НЗ.63 М 6.11 5 3.50 Е 35.24 found.: С 33.91 НЗ.72 М 6.04 5 3.40 Е 35.31 Е) ( 1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-M-(pentanoyl-3-aza-4-oxo) -5-methyl-5-yl)|-2-M-(1-O-y-0-carbonylmethylmannopyranose|-I-lysine, ba-complex (metal complex XM) 50.0g (54.55mmol) of the specified compound in the header of example 21d, 6.28 g (54.55 mmol) of M-hydroxysuccinimide, 4.62 g (109.0 mol) of lithium chloride and 34.35 g (54.55 mol) of Ca-complex 1,4,7-tris(carboxylatomethyl) -10-(carboxy-3-aza-4-oxo-5-methylpent-5-yl)-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 400 ml of dimethyl sulfoxide. Then, at 10"C, 16.88 g ( 81.8mol) of M,M-dicyclohexylcarbodiimide and then stirred overnight at room temperature.

The solution is poured into 300 ml of acetone and stirred for 10 minutes. The precipitated solid is filtered and then purified by chromatography (KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 75.9 g (91.095 from theory) of a colorless solid.

Water content: 8.695.

Elemental analysis (in terms of anhydrous substance): solution: С 35.34 Н4.09 М 8.24 52.10 EE 21.12 Са 10.28 detected: С 35.28 Н4.15 М 8.19 52 ,15 PE 21.03 (and 10.14

Example 22 a) (1-(4-perfluorooctylsulfonyl)piperazineamide 6-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-

Tetraazacyclododecane-10-M-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|-2-M-(1-O-y-0-carbonylmethylmannopyranose|-I-lysine, Са-complex 50.0 g (54.55 mmol) of the compound indicated in the title of example 21d, 6.28 g (54.55 mmol) of M-hydroxysuccinimide, 4.62 g (109.00 mol) of lithium chloride and 34.35 g (54.55 mol) of Ca-complex 1,4,7-tris(carboxylatomethyl)-10-(carboxy-3-aza-4-oxo-5-methylpent-5-yl)-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 400 ml of dimethyl sulfoxide. Next, 16.88 g (81.8 mmol) of M,M-dicyclohexylcarbodiimide are added at 10"C and then stirred overnight at room temperature.

The solution is poured into 300 ml of acetone and stirred for 10 minutes. The precipitated solid is filtered and then purified by chromatography (KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 76.Og (92.095 from theory) of a colorless solid.

Water content: 6.88905.

Elemental analysis (in terms of anhydrous substance): solution: С 34.90 Н 3.93 М 8.32 522.12 Е 21.33 Са 10.38 found.: С 34.81 Н4.02 М 8.27 5 2.09 E 21.22 Sa 10.19

Example 23 a) Methyl ether of 2-I4-(3-oxaethylpropionate)|phenylacetic acid

233.8 g (1400.0 mmol) of 2-bromoacetic acid ethyl ether are added to 200.0 g (1204.0 mmol) of 4-hydroxyphenylacetic acid methyl ether and 212.0 g (2000.00 mmol) of sodium carbonate in 2000 ml of acetone and boiled for 5 hours with a return cooler. The solid substance is filtered off and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: n-hexane/ethyl ether of bulk acid in a ratio of 15:1).

Yield: 288.5 g (95.0905 from theory) of colorless oil.

Elemental analysis: solution: C 61.90 H 6.39 found: C 61.75 H 6.51 b) Methyl ether of 2-I4-(3-oxaethylpropionate)|phenyl-2-bromoacetic acid

201.0 g (1130.00 mmol) of M-bromosuccinimide and 100.00 mg of dibenzoyl peroxide are added to 285.0 g (1130.00 mmol) of the compound indicated in the title of example 23a, dissolved in 2000 ml of carbon tetrachloride, and refluxed for 8 hours. Then it is cooled in an ice bath, the precipitated succinimide is filtered off and the filtrate is evaporated to dryness under vacuum. The residue is purified on silica gel (eluent: n-hexane/acetone in a ratio of 15:1).

Yield: 359.2 g (96.0905 from theory) of colorless viscous oil.

Elemental analysis: solution: C 47.28 H 4.57 V 24.16 found: C 47.19 H 4.71 V 24.05 c) Methyl ether 2-I4-(3-oxaethylpropionate)|phenyl-2 -|1-(1,4,7,10-tetraazacyclododecan-1-yl|acetic acid

To 603.0 g (3500.0 mmol) of 1,4,7,10-tetraazacyclododecane in 100 ml of chloroform was added 350.0 g (1057.0 mmol) of the compound indicated in the title of Example 236 and stirred overnight at room temperature. Next, it is extracted three times with water in portions of 300 Oml, the organic phase is dried over magnesium sulfate and evaporated to dryness in a vacuum. The residue without additional purification is used in the next reaction (example 23G).

Output: 448,Og (quantitative) of viscous oil.

Elemental analysis: soln.: C 59.70 H 8.11 M 13.26 found.: C 59.58 H 8.20 M 13.18 g) 2-I4-(3-oxapropionic acid)|phenyl-2- (1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-10-yl|acetic acid 445.0 g (1053.0 mmol) of the compound specified in the title of example 23c and 496.0 g (5270 , ommol) of chloroacetic acid are dissolved in 4000 ml of water. The pH value is set to 10 with the help of 30956 aqueous caustic sodium and stirred for 8 hours at 70"C. After that, the pH value of the reaction solution is set to 13 by mixing with 30956 aqueous caustic sodium and reflux for 30 minutes. Then the solution is cooled in an ice bath and the pH value is set to 1 by adding concentrated hydrochloric acid. After that, it is evaporated to dryness under vacuum. The residue is dissolved in 4000 ml of methanol and stirred at room temperature for an hour. Common salt, which precipitated, filtered, the filtrate was evaporated to dryness and the residue was purified on C KR-18 (eluent: a gradient of water/ethanol/ acetonitrile).

Yield: 403.Og (69.0905 from theory) of a colorless solid.

Water content: 10.295.

Elemental analysis (in terms of anhydrous substance): soln.: 251.98 6.18 M 10.10 found: C 51.80 H 6.31 M 10.01 d) 2-(4-(3-oxapropionic acid) )|phenyl-2-|1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-10-yl|acetic acid, sa-complex

130.7g (360.65mmol) of gadolinium oxide is added to 400g (721.3mmol) of the compound indicated in the title of example 23g in 2000ml of water and stirred for 5 hours at 80°C. The solution is filtered and the filtrate is lyophilized.

Yield: 511g (quantitative) of amorphous solid.

Water content: 11.095.

Elemental analysis (in terms of anhydrous substance): solution: С 40.67 Н 4.41 М 7.98 Са 22.19 found.: С 40.51 Н 4.52 М 8.03 Са 22.05 e) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6--(2-I4-(3-oxapropionyl)phenyl|-2-|1,4,7-

tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-10-yl|acetic acid)|-2-M-(1-O-o-0-carbonylmethylmannopyranose)-I-lysine, α-complex, sodium salt 50.0 g (54.55 mmol) of the compound indicated in the title of the example guide, 6.28 g (54.55 mmol) of M-hydroxysuccinimide, 4.62 g (109.00 mmol) of lithium chloride and 38.6 g (54.55 mmol) of the compound, indicated in the title of example 2Zd, dissolve under moderate heating in 4А00 ml of dimethyl sulfoxide. Next, at 10"C, 16.88 g (81.8 mmol) of M,M-dicyclohexylcarbodiimide are added and then stirred overnight at room temperature. The solution is poured into 300 ml of acetone and stirred for 10 min. The precipitated solid is filtered and then purified chromatography (KR-18, eluent: water/ethanol/acetonitrile gradient). The obtained product is dissolved in a small amount of water and the pH value of the solution is set to 7.4 using aqueous caustic sodium. After that, the solution containing the product is lyophilized.

Yield: 79.1 g (8995 from theory) of a colorless solid.

Water content: 10.3905.

Elemental analysis (in terms of anhydrous substance): solution: С 36.86 Н 3.77 М 6.88 5 1.97 Е 19.82 Са 9.65 found.: С 36.75 Н 3.84 М 6 .80 5 2.03 E 19.75 Са 9.57

Example 24 a) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(11,4,7-tris(tert-butyloxycarbonylmethyl)-10-carboxymethyl-1,4,7,10-tetraazacyclododecane-10-carbonylmethyl) |-2-M-(1-O-y-0-carbonylmethylmannopyranose)-I-lysine 15.0 g (26.19 mmol) 1,4,7-tris(tert-butyloxycarbonylmethyl)-10-carboxymethyl-1,4, 7,10-tetraazacyclododecane, 24.0 g (26.19 mmol) of the compound indicated in the title of example 21e, and 3.01 g (26.19 mmol) of M-hydroxysuccinimide are dissolved in 150 ml of dimethylformamide and at 0"C, 8.25 g (40, mol) of M,M-dicyclohexylcarbodiimide.The mixture was stirred overnight at room temperature.

The precipitated urea is filtered off and the filtrate is evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/methanol in a ratio of 20:1).

Yield: 35.45 g (92.0905 from theory) of a colorless solid.

Elemental analysis: solution: C 44.08 H 5.69 M 7.62 E 21.95 52.18 found: C 44.01 H 5.81 M 7.53 E 21.87 5 2.03 b) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-carbonylmethyl|-2-M-(1-O -c-O-carbonylmethylmannopyranose|-I-lysine, va-complex 30.00 g (20.39 mmol) of the compound indicated in the title of example 24a is dissolved in 50 ml of chloroform and 3000 ml of trifluoroacetic acid is added. The mixture is stirred for 1 min at room temperature.

After that, it is evaporated to dryness in a vacuum and the residue is dissolved in 30 ml of water. Next, add 3.69 g (10.19 mmol) of gadolinium oxide and stir for 5 hours at 80"C. The solution is evaporated to dryness under vacuum and purified on silica gel (KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 11.0 g (37.095 from theory) of a colorless and amorphous solid.

Water content: 11.3905.

Elemental analysis (in terms of anhydrous substance): solution: С 34.62 Н 3.87 М7.69 Е 22.16 5 2.20 Са 10.97 found.: С 34.57 Н 3.95 М7.60 E 22.05 52.13 (and 10.90

Example 25 a) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-I3,6,9-tris(carboxymethyl)-3,6,9-triazanone dicarboxylic acid-1-carboxy-11-oyl|-2- M-(1-O-0-O-carbonylmethylmannopyranose|-I-lysine).

12.10 g (30.0 mmol) of 3-M-(2,6-dioxomorpholinoethyl)-6-M is added to 24.0 g (26.19 mmol) of the compound indicated in the title of Example 2, dissolved in a mixture of 100 0 ml of dimethylformamide and 30 ml of pyridine - (ethoxycarbonylmethyl)-3,b6-diazaprobic acid and stir for 1 hour at 50°C. After that, evaporate to dryness in a vacuum. The residue is dissolved in 200 ml of water and the pH value of the resulting solution is set to 13 by adding 2095 aqueous caustic sodium. The mixture is stirred for 8 hours at 22"C and a pH value of 13. Next, the pH value of the solution is set to 7.2 by adding concentrated hydrochloric acid and then evaporated to dryness under vacuum. The residue is chromatographed on KR-18 silica gel (eluent: water/ethanol/acetonitrile gradient).

Yield: 17.26 g (51.0905 from theory) of a colorless solid.

Water content: 9.395.

Elemental analysis (in terms of anhydrous substance): solution: C 37.19 H 4.21 M 7.59 E 25.00 5 2.48 found: C 37.10 H 4.30 M 7.48 E 25 .07 5 2.42 b) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-I3,6,9-tris(carboxylatomethyl)-3,6,9-triazanone dicarboxylic acid-1-carboxy-11-oyl |-2-M-11-O-co-O-carbonylmethylmannopyranose|-I-lysine, cCa-complex, sodium salt

1.40 g (3.87 mmol) of gadolinium oxide is added to 10.0 g (7.74 mmol) of the compound specified in the title of example 25a in 1000 ml of water and stirred for 2 hours at 70 "C. After that, the solution is filtered.

The pH value of the filtrate is set to 7.4 using 2N. caustic sodium and lyophilized.

Yield: 11.36 g (quantitative) of amorphous solid.

Water content: 10.595.

Elemental analysis (in terms of anhydrous substance): solution: C 32.72 N 3.43 M 6.68 5 2.18 (a 10.71 Ma 1.57 E 22.00 det.: C 32.65 N 3.51 M 6.71 5 2.08 (for 10.61 Ma 1.68 E 21.87

Example 26 a) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-benzyloxycarbonyl-2-M-|1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-( pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|-I -

lysine, Cd-complex of 50.0g (60.20mmol) of the compound indicated in the title of example 21c, 6.93g (6020mmol) of M-hydroxysuccinimide, 5.09g (120.0mmol) of lithium chloride and 37.91g (60.200mmol) sa-complex 1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl) is dissolved under moderate heating in 400 ml of dimethyl sulfoxide. Next, at 10"C, 20.63 g (100.00 mmol) of M,M-dicyclohexylcarbodiimide are added and then stirred overnight at room temperature.

The solution is poured into 300 ml of acetone and stirred for 10 minutes. The precipitated solid is filtered off and then purified by chromatography (silica gel KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 75.53g (87.090 from theory) of a colorless solid.

Water content: 10.1905.

Elemental analysis (in terms of anhydrous substance): solution: С 37.48 Н 3.84 М 8.74 52.22 Е 22.39 Са 10.90 found.: С 37.39 Н 4.02 М 8, 70 522.16 E 22.29 Са 10.75 b) (1-(4-perfluorooctylsulfonyl)piperazine|amide 2-M-(11,4,7-tris(carboxylatomethyl)-1,4,7,10- tetraazacyclododecane -10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|-I -lysine, Ca-complex 70.0 g (48.53 mmol) of the compound indicated in the title of example 21 g are dissolved in a mixture with 500 ml of water and 100 ml of ethanol, mixed with 5.0 g of palladium catalyst (1095 Ra/C) and hydrogenated at room temperature in a hydrogen atmosphere (Tatm) until hydrogen absorption stops. After separation of the catalyst by vacuum filtration, it is thoroughly washed with ethanol (twice in 75ml portions) and concentrated to dryness under vacuum.In this way, the title compound is obtained in the form of a highly viscous and colorless oil.

Yield: 63.5g (quantitative).

Water content: 9.895.

Elemental analysis (in terms of anhydrous substance): solution: С 37.48 Н 3.84 М 8.74 52.22 Е 22.39 Са 10.90 found.: С 37.39 Н 4.03 М 8, 65 5 2.20 E 22.31 Са 10.78 c) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(1-O-c-O-carbonylmetal-2,3,4,6-tetra -O- benzylmannopyranose)-2-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4oxo-5-methyl-5-yl) )|-I -lysine, Ca-complex of 50.0 g (38.22 mmol) of the compound indicated in the title of example 266, 4.40 g (38.22 mmol) of M-hydroxysuccinimide, 3.39 g (80.00 mmol) of lithium chloride and 22 .88 g (38.22 mmol) of 11-O-y-O-carboxymethyl-2,3,4,6-tetra-O-benzyl-mannopyranose is dissolved under moderate heating (30-40"C) in 4000 ml of dimethylsulfoxide. Then at 10 10.32 g (50.0 mmol) of M,M-dicyclohexylcarbodiimide are added to C and then stirred overnight at room temperature. After that, the solution is poured into 300 ml of acetone and stirred for 100 min. The precipitated solid is filtered and then purified by chromatography (silica l KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 64.25 g (89.0905 from theory) of a colorless solid.

Water content: 10.995.

Elemental analysis (in terms of anhydrous substance): solution: С 46.42 Н4.54 M 6.67 51.70 B 17.10 Са 8.33 detected: С 46.36 Н 4.71 М 6.60 5 1.61 E 17.19 Са 8.21 g) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(1-O-y-O-carbonylmethyl-2,3,4,6-tetra- O-benzylmannopyranose)-2-M-(1,4,7-tris(carboxylatomethyl)-1,4,8,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5- il)|-I -lysine, a complex of 60,Og (31,77 mmol) of the compound indicated in the title of example 26c, is dissolved in 500 ml of ethanol and mixed with 6b,Og of a palladium catalyst (10,956 Ra/C). After that hydrogenate at room temperature under a hydrogen atmosphere (Tatm) until hydrogen absorption ceases.After that, the catalyst is removed by vacuum filtration, washed thoroughly with ethanol (two portions of 150 ml) and concentrated to dryness under vacuum.

Yield: 48.55 g (quantitative) of a colorless solid.

Water content: 3.995.

Elemental analysis (in terms of anhydrous substance): solution: С 35.37 Н4.02 М 8.25 52.10 Р 21.13 Са 10.29 detected: С 35.28 Н 4.13 М 8.17 5 2.03 E 21.05 sa 10.20

Example 27 a) 1,7-bis(benzyloxycarbonyl)-4-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-1,4,7,10-tetraazacyclododecane

Up to 5000 g (113.5 mmol) of 1,7-bis(benzyloxycarbonyl)-1,4,7,10-tetraazacyclododecane and 66.42 g (113.5 mmol) of 2-(M-ethyl-M-perfluorooctylsulfonyl)aminoacetic acid (obtained according to from OE 19603033) in 300 ml of tetrahydrofuran at 0"C, add 49.46 g (200.0 mmol) of EEDH (ethyl ether of 2-ethoxy-1,2-dihydroquinoline-1-carboxylic acid) and stir overnight at room temperature. After that, dry evaporated in vacuo and chromatographed on silica gel (eluent: dichloromethane/methanol in a ratio of 20:1).

Yield: 65.2 g (57905 from theory) of a colorless solid.

Elemental analysis: solution: C 42.91 H 3.80 M 6.95 E 32.05 5 3.18 found: C 42.85 H 3.90 M 6.87 E 31.98 5 3.15 b ) 1,7-bis(benzyloxy)-4-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-10-11-O-os-O-carbonylmethyl-2,3,4,6-tetra- O-benzylmannopyranose!|-1,4,7,10-tetraazacyclododecane

To 60.0 g (59.53 mmol) of the compound specified in the title of example 27a, and 35.64 g (59.53 mmol) of 1-O-o-0-carboxymethyl-2,3,4,6-tetra-O-benzylmannopyranose, (obtained according to OE 19728954) in 10 ml of tetrahydrofuran at 0"C, add 24.73 g (100 mmol) of EEDH (ethyl ether of 2-ethoxy-1,2-dihydroquinoline-1-carboxylic acid) and stir overnight at room temperature. evaporated to dryness under vacuum and chromatographed on silica gel (eluent: dichloromethane/methanol in a ratio of 20:1).

Yield: 76.6 g (81.095 from theory) of a colorless solid.

Elemental analysis: solution: C 5444 4.70 M 4.41 P 20.33 52.02 found: C 54.37 H 4.81 M 4.35 E 20.27 5 1.96 c) 1-( 2-(m-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-7-(1-0-5-YOO-carbonylmethylmannopyranose)-1,4,7,10-tetraazacyclododecane 70 g (44.07 mmol) of the compound specified in the title of the example 276, dissolve in 800 ml of ethanol and add 8 g of palladium catalyst (1095 Pa/C). After that, hydrogenate at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 42.3 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 35.04 H 3.99 M 7.30 E 33.65 5 3.34 found: C 35.15 H 4.13 M 7.13 E 33.48 5 3.26 g ) o01,7-6is(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)- 4-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|)acetyl-10-(1-O-c0-O-carbonylmethylmannopyranose)-1,4,7,10-tetraazacyclododecane, α-complex 20g (20, 84 mmol) of the compound indicated in the title of example 27b, 5.09 g (120 mmol) of lithium chloride and 37.78 gH (bommol) of the Ca-complex 1,4,7-tris(carboxylatomethyl)-10-(pentanoyl-3-aza-4- oxo-5-methyl-5-yl)-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 4A00 ml of dimethylsulfoxide. Then, at 1070, 29.67 g (120 mmol) of EEDH are added and then stirred overnight at room temperature. The solution is drained in 30000 ml of acetone and stir for 17 h. The precipitated solid is filtered off and then purified by chromatography (silica gel KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 13.2 g (29.095 from theory) of a colorless solid.

Water content: 11.895.

Elemental analysis (in terms of anhydrous substance): solution: С 36.31 Н 4.34 М 9.62 5 1.47 Е 14.79 Са 14.41 detect.: С 36.24 Н 4.27 М 9 .58 5 1.51 E 14.85 Са 14.25

Example 28 a) 1,7-bis(benzyloxycarbonyl)-4-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-10-(pentanoyl-3-aza-4-oxo-5-methyl-5- yl-I1,4,7-tris(carboxylatomethyl)-α-complex-1,4,7,10-tetraazacyclododecane-10-yl|- 1,4,7,10-tetraazacyclododecane 50.0 g (49.6 mmol) of compounds , indicated in the title of example 27a, 5.71 g (4961 mmol) of M-hydroxysuccinimide, 4.24 g (100 mmol) of lithium chloride and 31.24 g (496 mmol) of the α-complex 1,4,7-tris(carboxylatomethyl)-10-( pentanoyl-3-azaoxo-5-methyl-5-yl)-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 3500 ml of dimethyl sulfoxide. Then, at 10"C, 15.47 g (75 mmol) of M,M-dicyclohexylcarbodiimide are added and then stirred overnight at room temperature.

The solution is poured into 2000 ml of acetone and stirred for 10 minutes. The precipitated solid is filtered off and then purified by chromatography (silica gel KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 65.1 g (81.095 from theory) of a colorless solid.

Water content: 7.995.

Elemental analysis (in terms of anhydrous substance): solution: С 40.79 Н4.11 М 8.65 5 1.98 Е 19.94 Са 9.72 detected: С 40.71 Н 4.20 М 8, 58 5 2.03 E 19.87 Са 9.68 b) 1-(2-(m-ethyl-M-perfluorooctylsulfonyl)amino|Iacetyl-7-(pentanoyl-3-aza-4-oxo-5-methyl- 5-yl)-10-

1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane, z-complexi)-1,4,7,10-tetraazacyclododecane 60.0 g (37.05 mmol) of the compound indicated in the title of example 28a , dissolve in bOOml of ethanol and add 6b.0g of palladium catalyst (10956 Pa/C). After that, they are hydrogenated at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 50.06 g (quantitative) of a colorless solid.

Water content: 3.995.

Elemental analysis (in terms of anhydrous substance): solution: C 34.67 N 4.03 M 10.37 52.37 E 23.90 (a 11.64 found: C 34.58 N 4.15 M 10 .28 5 2.30 E 23.84 Са 11.57 c) 1-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-4,10-bis!1-O-c-O-carbonylmethyl- 2,3,4 b-tetra-

O-benzylmannopyranose|-7-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10 -cy|-sa-complex)-1,4,7,10-tetraazacyclododecane 40.0 g (29.60 mmol) of the compound indicated in the title of example 286, 2.54 g (60, mol) of lithium chloride and 44.9 g (75 .0 mmol) /1-O-c-O-carboxymethyl-2,3,4,6-tetra-O-benzylmannopyranose is dissolved under moderate heating in Zbbml of dimethylsulfoxide. Next, at 107"C, 24.73 g (100.00 mmol) of EEDH are added and then stirred overnight at room temperature. The solution is poured into 300 mL of acetone and stirred for 10 min. The precipitated solid is filtered and then purified by chromatography (silica gel KR -18, eluent: water/ethanol/acetonitrile gradient).

Yield: 31.98 g (43.0905 from theory) of a colorless solid.

Water content: 3.595.

Elemental analysis (in terms of anhydrous substance): solution: С 53.06 Н 5.05 М 5.57 5 1.28 Е 12.85 Са 6.26 found.: С 52.95 Н 5.19 М 5 .48 5 1.23 E 12.77 Са 6.14 g) 1-2-(mM-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-4,10-bis(1-O-c-O-carbonylmethyl-2 ,3,4,6-tetra-O-benzylmannopyranose|-7-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)-(1,4,7-tris(carboxylatomethyl)-1, 4,7,10-tetraazacyclododecane-10-yl|-sa-complex)-1,4,7,10-tetraazacyclododecane 30.0 g (11.94 mmol) of the compound indicated in the title of example 28b is dissolved in a mixture with 30 ml of ethanol and

ZOml of water and add 4.0 g of palladium catalyst (1095 Pa/C). After that, it is hydrogenated at room temperature, the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 21.39 g (quantitative) of a colorless solid.

Water content: 3.495.

Elemental analysis (in terms of anhydrous substance): solution: С 36.87 Н 4.39 М 7.82 5 1.79 Е 18.03 Са 8.78 found.: С 36.80 Н 4.50 М 7 .85 5 1.68 E 17.91 Са 8.70

Example 29 a) (1 1-(4-perfluorooctylsulfonyl)piperazine|iamide /6-M-I(3,6-bis(carboxymethyl)octane-1,8-dicarboxylic acid-1-carboxy-8-oyl|-2 -M-(1-O-0-O-carboxymethylmannopyranose) lysine

To 27.5 g (30.0 mmol) of the compound indicated in the title of example 2, dissolved in a mixture of 30 ml of dimethylformamide and 100 ml of pyridine, add 25.62 g (100.00 mmol) of ethylenediamine-M,M, M" M'-tetraacetic acid dianhydride and stir for 5 hours at 50"C. After that, it is evaporated to dryness under vacuum.

The residue is dissolved in ZbOml of water, the pH value is set to 10 by adding 2095 aqueous caustic sodium, then the pH value of the alkaline solution containing the product is set to 3 by adding concentrated hydrochloric acid and evaporated to dryness under vacuum. The residue is chromatographed on KR-18 silica gel (eluent: water/ethanol/acetonitrile gradient).

Yield: 18.22 g (51.0905 from theory) of a colorless solid.

Water content: 7.995.

Elemental analysis (in terms of anhydrous substance): solution: C 36.91 H 3.98 M 7.06 ER 27.12 5 2.69 found: C 36.23 H 4.07 M 6.98 E 27 .05 5 2.62 b) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-I3,6-bis(carboxylatomethyl)octane-1,8-dicarboxylic acid-1-carboxylato-8-oyl|-2-M -(1-0O-y-O-carboxymethylmannopyranose)-I-lysine, MP complex, sodium salt 10 g (8.397 mmol) of the compound indicated in the title of example 29a is dissolved in 200 ml of water. Then 965 mg (8.397 mmol) of manganese carbonate is added (II) It is stirred for 1 hour at 60°C. Then the pH value of the solution is set to 7.4 with the help of 595 aqueous caustic sodium, filtered and then lyophilized.

Yield: 10.52 g (99.0905 from theory) of a colorless solid.

Water content: 7.895.

Elemental analysis (in terms of anhydrous substance): solution: C 34.16 H 3.50 M 6.64 5 2.53 E 25.52 Mp 4.34 Ma 1.82 detection: C 34.06 H 3 .61 M 6.58 5 2.47 E 25.47 Mp 4.30 Ma 1.97

Example 30 a) 1,2,3,4,6-penta-O-acetyl-x,p-YOO-mannopyranose

Similarly to the method described in the literature (MH. UMoytot and A. Tpotrzop, "Meshyoa" ip Sagopnuagaie

Spetivigu" (under the editorship of K.G. M/pizNeg, M.S. MMoitot and 9U.M. VemiPeg), ed. )), as a result of the interaction of 150 g (832.5 mmol) of o,p-Y-mannopyranose with a mixture of 1500 ml of absolute pyridine and 1500 ml of acetic anhydride, after processing, 315 g (96.7905) of the above-mentioned compound in the form of a crude product in the form of "viscous and colorless oil. The ratio between both c- and d-anomers in the title compound obtained in this way is 4:1 according to

IN-NMR spectroscopic analysis. To carry out the following reactions, the compound indicated above in the title may not be separated into separate c, p-anomers.

Elemental analysis: soln.: C 49.21 H 5.68 detected: C 49.12 H 5.78 b) 1-O-o-0-(5-ethoxycarbonyl)pentyl-2,3,4,6- tetra-O-acetylmannopyranose

Analogously to the method described in the literature for the synthesis of arylglycopyranosides (U. Sopospie and 5.A. Iumu, "Meshoa5 ip Sagropudgaee Spetivigu" (ed. K.G. M/pizNTseg, M.S. MMoigot and U.M. Vemieg), Asadetis species

Rgez5, Memu MogkK, vol. II, 90, p. 345-347 (1963) |, as a result of the interaction of 156.2 g (4А00 mmol) of the compound indicated in the title of example 21a in the form of a mixture of ос,р-anomers with β7/ml (400 mmol ) of ethyl ether of 6-hydroxyhexanoic acid and 60.8 ml (520 mmol) of stannous chloride (IM) in 1,2-dichloroethane in a total amount of bOOml after purification by column chromatography (eluent: hexane/ethyl acetic acid in a ratio of 2:11) obtain 100 .05 g (51905 from the theory) of the compound indicated above in the title in the form of a colorless and viscous oil. The data of H-NMR spectroscopic analysis of the compound indicated in the title obtained in this way indicate that this compound is only a pure c-anomer.

Elemental analysis: solution: C 52.94 H 6.77 found: C 52.80 H 6.78 c) 1-O-o-0-(5-carboxy)pentyl-2,3,4,6- tetra-O-benzylmannopyranose

A mixed suspension of 141.0 g (289 mmol) of the compound indicated in the title of example 306 in 200 ml of dioxane at room temperature and with simultaneous intensive stirring is mixed in portions with highly dispersed powdered potassium hydroxide in a total amount of 238.5 g (4.2 bmol). To increase its miscibility, the reaction mixture is mixed with another 200 ml of dioxane, the resulting suspension is then heated to the boiling point and at this temperature for two hours it is mixed dropwise with benzyl bromide in a total amount of 372 ml (3.128 mol). After conducting the reaction for 4 hours at 110"C, and then for 12 hours at room temperature, the reaction mixture for its processing is slowly poured into a mixture of water and ice in a total amount of 2.5 liters, and the aqueous phase is then completely extracted with diethyl ether.

After washing the ether phase obtained in this way and its subsequent drying over sodium sulfate, the salt is separated by vacuum filtration and the diethyl ether is removed under vacuum. After that, the excess benzyl bromide is quantitatively distilled off from the reaction mixture in a vacuum created by an oil pump at an oil bath temperature of 1807°C. The resinous-oily residue obtained in this way is purified on silica gel using ethyl acetic acid/hexane (in a ratio of 1:10) as an eluent.

Yield: 172.2 g (91.095 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 75.68 H 7.16 found: C 75.79 H 7.04 g) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-benzyloxycarbonyl-2-M-|/ 1-O-x-0-(5-carbonyl)pentyl-2,3,4,6-tetra-O-benzylmannopyranose|-I-lysine 100.0 g (134.0 mmol) of the carboxylic acid obtained in Example 30 and 32, 4 g (281.4 mmol) of M-hydroxysuccinimide is dissolved in 500 ml of dimethylformamide, at 0"С it is mixed in portions with M,M'-dicyclohexylcarbodiimide in a total amount of 58.0 g (281.4 mmol) and then stirred for 2 hours at this temperature. To the solution obtained in this way of the activated complex ether, a solution of 111.3 g (134.0 mmol) of the compound specified in the title of Example 2 in 300 ml of dimethylformamide, cooled to 0 °C, is added dropwise and stirred for 2 hours at 0 °C, and then for 12 hours at room temperature. To process dicyclohexylurea, which has precipitated, is filtered and then the solvent is distilled off to obtain a dry residue. The residue obtained in this way is then chromatographed on silica gel ( eluent: dichloromethane/(ethanol in a ratio of 20:11, chromatography is carried out using a solvent gradient, continuously increasing the fraction of ethanol).

Yield: 132.5 g (67.4905 from theory) of the title compound in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 54.02 H 4.88 M 3.82 E 22.01 522.19 found: C 53.87 H 4.85 M 4.02 E 22.55 5 2.06 d) (1-(4-perfluorooctylsulfonyl)piperazinamide 2-M-(11-O-o-0O-(5-carbonyl)pentylmannopyranose|-I-lysine) 120.0 g (81.77 mmol) of the compound obtained in example 3g is dissolved in 800 ml of ethanol , mixed with 4.5 g of Perlman's catalyst (2090 Ra/C) and hydrogenated at room temperature in a hydrogen atmosphere (Tatm) until hydrogen absorption stops (approximately within dhours). After that, the catalyst is removed by vacuum filtration, then thoroughly washed with ethanol (about 200 ml) and concentrated to dryness in vacuo to give the title compound as a highly viscous and colorless oil.

Yield: 78.5g (98.790 from theory).

Elemental analysis: solution: C 37.04 H 4.25 M 5.76 E 33.20 5 3.30 found: C 36.96 H 4.85 M 5.41 E 34.13 5 3.22 e ) /(1-(4-perfluorooctylsulfonyl)piperazine|iamide - 2-М-11-О-с-0-(5-carbonyl)pentylmannopyranose|-6-М-

I1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-ylpentanoyl)-1,4,7,10-tetraazacyclododecane|-I - lysine, Сd-complex 99 .8 g (158.4 mmol, 2.2 molar equivalents in terms of the amount of the used amine component from example ZOd) (described in the application OE 19728954 С1) in example З31p of the Ca-complex 10-(4-carboxy-1-methyl-2- oxo-3-azabutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 6.7 g of anhydrous lithium chloride (158.4 mmol) at 40"C are dissolved with stirring in 800 ml of absolute dimethyl sulfoxide. Next at this temperature, a total amount of 18.2 g (158.4 mmol) and 70.0 g (71.96 mmol) of the compound indicated in the title of Example 3, dissolved in 250 ml of absolute dimethyl sulfoxide, are mixed with M-hydroxysuccinimide. After cooling to room temperature, the reaction solution is mixed with 32 .7 g (158.4 mmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature. Then the resulting suspension was mixed with a sufficient amount of acetone to after precipitation of the compound indicated above in the title, the precipitate is separated by vacuum filtration, dried, dissolved in water, dicyclohexylurea, which has not dissolved, is filtered, and the filtrate is passed through an ultrafiltration membrane of AMISOM for its desalination and purification from low molecular weight components

UM-3 (limit permeability: 3000Da) Retentate (substance that did not pass through the filtration membrane) is finally lyophilized.

Yield: 93.Og (81.695 from theory) in the form of a colorless lyophilizate.

NgO content (when using Karl Fischer's reagent): 9.5390.

Elemental analysis (in terms of anhydrous substance): solution: С 37.15 Н 4.39 М 7.96 РЕ 20.38 52.02 Za 9.92 found.: С 36.92 Н 4.50 М 7, 68 E 19.77 51.91 Sa 10.08

Example 31 a) (1-(4-perfluorooctylsulfonyl)piperazinamide /-2-M-(1-O-c-0-(5-carbonyl)pentylmannopyranose|-6-M-(2-

I4-(3-oxapropionyl)phenyl/|-2-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-yl|acetic acid)-I-lysine, c-complex , sodium salt

A stirred suspension of 5.0 g (9.0 mmol) of the compound indicated in the title of example 23d in 15 ml of absolute dimethyl sulfoxide at 70"C is mixed with 0.68 g (15.9 mmol) of lithium chloride. After 30 minutes of stirring at 70"C, a clear reaction the solution is mixed in portions with 3 M hydroxysuccinimide in a total amount of 1.83 g (15.9 mmol) and the reaction mixture is kept for another hour at this temperature. After cooling to 0"C, it is mixed with 4.52 g (23.85 mmol) of dicyclohexylcarbodiimide and the reaction solution is stirred for another hour at 0"C, and then for 12 hours at 22"C. The reaction solution of the M-hydroxysuccinimidoether of the compound specified in of the title of example 2Zd, at 22"C, is mixed dropwise with a solution of 4.0 g (4.12 mmol) of the compound specified in the title of example ZOd in 15 ml of absolute dimethyl sulfoxide and stirred for another 12 hours at room temperature. For processing, the reaction solution at 227С is added dropwise to 900 ml of acetone, while the compound indicated in the title precipitates as a colorless precipitate. This precipitate is separated by vacuum filtration, dissolved in 200 ml of distilled water, and then the pH value of this solution is set to exactly 7.2 with the help of 1-molar caustic sodium. The aqueous solution obtained in this way, which contains the product, is subjected to ultrafiltration three times through an ultrafiltration membrane UMZ3 (AMISOM?, limit permeability: 3000Da) for desalination and for the separation of low-molecular components. The resulting retentate is finally lyophilized.

Yield: 6.33 g (92.49 from theory, based on the amount of the amine component used) in the form of a colorless lyophilizate with a water content of 7.38905.

Elemental analysis (in terms of anhydrous substance): solution: С 38.48 Н 4.13 М 6.65 Е 19.16 5 1.90 Са 9.33 Ма 1.36 detect.: С 39.52 Н 4 ,12 M 6.67 E 19.70 5 1.89 Sa 9.30 Ma 1.41

Example 32 a) M-(Z-oxa-1HT Н.Н 2, НН, 5Н,ЗН-perfluorotridecyl)amide of 3,5-bisbenzyloxycarbonylaminobenzoic acid 20 g (47.5 mmol) of 3,5-bisbenzyloxycarbonylaminobenzoic acid synthesis according to the method described in ZKiYipisk Nagmeu I, dopp5op Rashi 0O., Agizioi Ratsi A., Moiti5 UCheapetse K., Goma57 Kgiziipe 0. and others, 9.

Mea. Spet., 40, 7, (1997), pp. 1149-1164|, as well as 4.78 g (47.5 mmol) of triethylamine are dissolved in a solvent mixture consisting of 125 ml of dry tetrahydrofuran and 125 ml of dry dioxane. After cooling to -15"C, a solution of 6.56g (48mmol) of isobutyl ether of chloroformic acid in 30ml of dry tetrahydrofuran is slowly added dropwise while stirring, while the internal temperature should be maintained below -10"C. After carrying out the reaction for 15 minutes at -157C, a solution of 58.6 g (47.5 mmol) of 1-amino-1H,1H,2H,2H.4nH,4H,5H,5H-3Z-oxoperfluorotridecane and 4.78g is added dropwise at -2070 (47.5 mmol) of triethylamine in 1000 ml of dry tetrahydrofuran. After conducting the reaction for one hour at -157C, and then for two hours at room temperature, the reaction solution is concentrated to dryness in a vacuum. The obtained residue is dissolved in ZOO ml of ethyl acetic acid and washed twice with a saturated solution of sodium bicarbonate in portions of 200 ml and once with water in portions

ZOOml. After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the ethyl acetic acid is distilled off under vacuum. The resulting oily residue is purified on silica gel using dichloromethane/hexane/2-propanol (in a ratio of 10; 5:1) as an eluent.

Yield: 36.2 g (82.595 from theory) of the title compound as a colorless oil.

Elemental analysis: dissolved: C 46.82 H 3.27 M 4.55 E 34.97 detected: C 47.21 H 3.31 M 4.61 E 34.48 b) M-(Z-oxa- 1H1H,2H,2H4H YAN,ZH,5H-perfluorotridecyl)amide of 3,5-diaminobenzoic acid 30.0 g (32.4 mmol) of the amide obtained in example 32a is dissolved in ZOO ml of ethanol and mixed with 1.2 g of Perlman's catalyst (2095 Ra /WITH). After that, it is hydrogenated at room temperature in a hydrogen atmosphere (1 atm) until hydrogen absorption stops. After that, the catalyst is removed by vacuum filtration, thoroughly washed with ethanol (approximately Zb0Oml) and concentrated to dryness under vacuum. In this way, the compound specified in the title is obtained in the form of a highly viscous yellowish oil.

Yield: 20.12 g (94.89 from theory).

Elemental analysis: solution: C 36.66 H 2.77 Mb, 41 E 49.28 detected: C 36.07 H 2.87 Mb, 23 E 49.43 c) M-(Z-oxa-IN1H, 2H,2NaNYAN,5H,5H-perfluorotridecyl)amide /- 3-M-(1-O-0-O-carbonylmethyl-2,3,4,6-tetra-O-benzylmannopyranose)-5-aminobenzoic acid 10.95g (18.3 bmmol) of 1-carboxymethyloxy-2,3,4,6-tetra-O-benzyl-o-Y-mannopyranoside (obtained according to the patent ЮОЕ 19728954 С1| is dissolved in 150 ml of dimethylformamide and mixed with M-hydroxysuccinimide in a total amount of 2 .09g (18.3mmol). Then cool to 0"C and add 3.78g (18.3mmol) of dicyclohexylcarbodiimide. After that, stir for an hour at room temperature, and then for 4h at room temperature. Then cool to 0"C and for A solution of 24.0g (36.6bmmol, 2 molar equivalents based on the amount of carboxylic acid used) of the diamino compound obtained in Example 326 in 350ml of dimethylformamide is slowly added dropwise. Then it is stirred for another hour at 0"C, and then overnight at room temperature. temperature the mixture is evaporated to dryness in a vacuum and the residue is dissolved in ZOO ml of ethyl acetic acid. The precipitated urea is filtered and the filtrate is washed twice with a 5906 aqueous solution of soda in portions of 100O0ml. The organic phase is dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: n-hexane/isopropanol in a ratio of 13:1). In this way, 16.8 g (74.39 from theory, in terms of the amount of carboxylic acid used) of the title compound are obtained in the form of a colorless oil. By increasing the polarity of the eluent by changing the ratio between n-hexane and isopropanol to 5:11, a total of 10.15 g of the unreacted diamino compound from example 32b is recovered in the following chromatographic fractions, which can be used again in the reaction according to the method discussed above.

Elemental analysis: solution: C 54.42 H 4.40 M 3.40 P 26.13 found: C 54.32 H 4.49 M 3.48 E 25.94 g) M-(3-oxa- 1Н1 НН 2Н,2Н,аНаН,5Н,ЗН-perfluorotridecyl)amide of 3-M-(1-O-o-0-carbonylmethylmannopyranose)-5-aminobenzoic acid

Analogously to the method of synthesis of the compound indicated in the title of example 326, as a result of hydrogenolysis

12.0 g (9.70 mmol) of the compound indicated in the title of example 32c, using 0.5 g of Perlman's catalyst (2095 Ra/cС) in a mixture of ethanol and water (in a ratio of 9:1), after processing, 8.08 g ( 96.795 from theory) of the above title compound as a viscous yellow oil.

Elemental analysis: solution: C 37.64 H 3.28 M 4.88 E 37.49 found: C 37.32 H 3.17 M 4.97 E 37.55 d) Mm-(3-oxa- иН.1 НН 2Н,2Н,аН,ЯН,5Н,ЗН-perfluorotridecyl)amide 3-M-(1-O-o-0-carbonylmethylmannopyranose)-5-M-(2-(4-(3-oxapropionyl) phenyl|-2-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-yl|acetic acid) benzoic acid, sa-complex, sodium salt 13.6g (19.2mmol , 2.2 molar equivalents in terms of the amount of the used amine component from example 32d) of the Ca-complex described in example 23d and 0.81g of anhydrous lithium chloride (19.2mmol) at 40"C are dissolved with stirring in 100ml of absolute dimethylsulfoxide and at this temperature is mixed with M-hydroxysuccinimide in a total amount of 2.2 g (19.2 mmol) and with 7.5 g (8.7 mmol) of the compound indicated in the title of example 32 g, dissolved in 5 x 0 ml of absolute dimethyl sulfoxide. After cooling to room temperature, the reaction solution is mixed with 3, 96 mg (19.2 mmol) of M,M'-dicyclohexylcarbodiimide and stir for 12 hours at room temperature. The resulting suspension is then mixed with a sufficient amount of acetone to completely precipitate the compound indicated above in the title, the precipitate is separated by vacuum filtration, dried, dissolved in water, dicyclohexylurea, which has not dissolved, is filtered, and the filtrate is passed through an AMISOM ultrafiltration membrane for desalting and purification from low molecular weight components ?In UM-3 (limit permeability: 3000Da) the retentate is finally lyophilized.

Yield: 11.51 g (84.5905 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 6.77905.

Elemental analysis (in terms of anhydrous substance): solution: C 40.05 N 3.94 M 6.29 P 20.71 (a 10.08 Ma 1.47) found: C 39.98 N 4.00 M 6.31 EE 20.73 Sa 10.11 Ma 1.42

Example 33 a) 3,5-bis(benzyloxycarbonylamino)-1-(M-(1-(4-perfluorooctylsulfonyl)piperazine) benzamide 10 g (23.75 mmol) of 3,5-bisbenzyloxycarbonylaminobenzoic acid | synthesis according to the method described in ZKiiYipisk Nagmueu I., hoppsop Ratsi 0., Ag Rashtsi A., Moitiz deapece K., I oma57 Kgizipe O. and others, 9.

May Spet., 40, 7 (1997), pp. 1149-1164), as well as 2.39 g (23.75 mmol) of triethylamine are dissolved in a solvent mixture consisting of 1 ml of dry tetrahydrofuran and 7 ml of dry dioxane. After cooling to -157"C, a solution of 3.28g (24mmol) isobutyl ether of chloroformic acid in 20ml of dry tetrahydrofuran is slowly added dropwise while stirring, while the internal temperature does not exceed -10"C. After carrying out the reaction for 15 minutes at -15"C, a solution of 23.0g (23.75mmol) of perfluorooctylsulfonylpiperazine and 2.39g (23.75mmol) of triethylamine in 5Oml of dry tetrahydrofuran is added dropwise at -20"C. After carrying out the reaction for one hour at -15"C, and then for two hours at room temperature, the reaction solution is concentrated to dryness in a vacuum. The resulting residue is dissolved in 200 ml of ethyl acetic acid and washed twice with a saturated solution of sodium bicarbonate in portions of 100 ml and once with water in a portion of 30 ml After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the ethyl ether of acetic acid is distilled off under vacuum.

The obtained oily residue is purified on silica gel using dichloromethane/hexane/2-propanol (in a ratio of 15:5:1) as an eluent.

Yield: 18.35 g (79.6905 from theory) of the title compound as a colorless oil.

Elemental analysis: solution: C 43.31 H2.80 M 5.77 E 33.27 5 3.30 found: C 43.21 H 2.75 M 5.61 E 33.38 5 3.22 b) 3,5-diamino-1-1M-(11-(4-perfluorooctylsulfonyl)piperazine)benzamide 9.70 g (10.00 mmol) of the amide obtained in Example 33 are dissolved in 100 ml of ethanol and mixed with 0.4 g of Perlman's catalyst (2095 Ra/S). After that, it is hydrogenated at room temperature in a hydrogen atmosphere (1 atm) until hydrogen absorption stops. After that, the catalyst is removed by vacuum filtration, thoroughly washed with ethanol (approximately 150 ml) and concentrated to dryness under vacuum. In this way, the compound specified in the title is obtained in the form of a highly viscous yellowish oil.

Yield: 6.9g (98.295 from theory).

Elemental analysis: solution: C 32.49 H 2.15 M 7.98 E 45.98 5 4.56 found: C 32.56 H 2.17 M 8.09 E 45.63 5 4.61 ). M-(1-(4-perfluorooctylsulfonyl)piperazinamide. 5-amino-3-M-(1-O-c-O-carbonylmethyl-2,3,4,6-tetra-O-benzylmannopyranose)benzoic acid 5.48g (915 mmol) of 1-carboxymethyloxy-2,3,4,-tetra-O-benzyl-c-ХО-mannopyranoside (obtained according to the method described in patent OE 19728954 С1| is dissolved in 100 ml of dimethylformamide and mixed with M-hydroxysuccinimide in a total amount of 1 .04g (9.15mmol). Next, cool to 0" and add 1.89g (9.15mmol) of dicyclohexylcarbodiimide. After that, stir for an hour at RT, and then for 4h at room temperature. After re-cooling to 0"C for 2h a solution of 12.85 g (18.30 mmol, 2 molar equivalents based on the amount of carboxylic acid used) of the diamino compound described in example 336 in 250 ml of dimethylformamide is slowly added dropwise.

After that, it is stirred for another hour at 0"C, and then overnight at room temperature.

The mixture is evaporated to dryness in a vacuum and the residue is dissolved in 100 ml of ethyl acetic acid.

The precipitated urea is filtered and the filtrate is washed twice with a 596% aqueous solution of soda in portions of 100 ml. The organic phase is dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: n-hexane/isopropanol in a ratio of 13:1). In this way, 8.14 g are obtained (69.4905 from the theory, in terms of the amount of carboxylic acid used)

of the title compound in the form of a colorless oil. By increasing the polarity of the eluent by changing the ratio between its components (n-hexane and isopropanol) to 6:1 in the chromatography process, a total of 4.36 g of unreacted diamino compound from example 336, which can be used again in the reaction, is recovered in the following chromatographic fractions according to the method discussed above.

Elemental analysis: solution: C 51.49 84.01 M 4.37 RE 25.17 52.50 found: C 51.60 H 4.19 M 4.28 E 25.14 5 2.44 g) M -(1-(4-perfluorooctylsulfonyl)piperazine|amide of 5-amino-3-M-(1-O-c-0-carbonylmethylmannopyranose)benzoic acid

Similarly to the method described for the synthesis of the compound specified in the title of example 336, as a result of hydrogenolysis of 6.4 g (5.00 mmol) of the compound specified in the title of example 33v using 0.3 g of a catalyst

Perlman (2095 Ra/C) in a mixture of ethanol and water (in a ratio of 8:1), after processing, 4.43 g (96.295 from the theory) of the above title compound are obtained in the form of a viscous yellow oil.

Elemental analysis: solution: C 35.15 H 2.95 M 6.07 E 35.01 5 3.48 found: C 35.32 H 3.02 M 5.89 E 35.05 5 3.58 d ). M-P1-(4-perfluorooctylsulfonyl)piperazinamide. 3-M-(1-0O-c0-O-carbonylmethylmannopyranose)-5-M-(1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-ylpentanoyl) )-1,4,7,10-tetraazacyclododecane|benzoic acid, Ca-complex 5.54 g (8.9 mmol, 2.2 molar equivalents in terms of the amount of the used amine component from example C33g) |described in the application OE 19728954 С1| in example Z31p of the ba-complex of 10-(4-carboxy-1-methyl-2-oxo-3-azabutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 0.37 gM of anhydrous chloride lithium (83.mmol) at 40"C is dissolved with stirring in bOml of absolute dimethylsulfoxide and at this temperature is mixed with M-hydroxysuccinimide in a total amount of 1.01g (8.8mmol) and with 3.7g (4.0mmol) indicated in the title of the example 33g of the compound dissolved in 4A0ml of absolute dimethylsulfoxide.After cooling to room temperature, the reaction solution was mixed with 1.82g (in dmmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature.

The resulting suspension is then mixed with a sufficient amount of acetone until the compound specified above in the title is completely precipitated, the precipitate is separated by vacuum filtration, dried, dissolved in water, the undissolved dicyclohexylurea is filtered off, and the filtrate is passed through an AMISOM ultrafiltration membrane for desalting and purification from low molecular weight components UM-3 (limit permeability: 3000Da) The retentate is finally lyophilized.

Yield: 5.36 g (87.495 from theory) in the form of a colorless lyophilizate.

NgO content (when using Karl Fischer's reagent): 6.77905.

Elemental analysis (in terms of anhydrous substance): solution: C 36.01 N 3.61 M 8.22 E 21.05 sa 10.25 5 2.09 found: C 35.87 N 3.70 M 8 ,22 E 20.91 Sa 10.18 52.16

Example 34 a) Diamide 1,4,7-triazaheptane-1,7-bis(2-M-trifluoroacetyl-6-M-benzyloxycarbonyl-y-lysine) 100 g (107.9 mmol) of the carboxylic acid obtained in example 21a and 26, 1 g (226.59 mmol) of M-hydroxysuccinimide is dissolved in 500 ml of dimethylformamide, at 0"С it is mixed in portions with M,M'-dicyclohexylcarbodiimide in a total amount of 46.7 g (226.59 mmol) and then stirred for 2 hours at this temperature. Until obtained in this way to the solution of the activated complex ether, a solution of 5.57 g (53.95 mmol) of diethylenetriamine cooled to 0"C in bOml of dimethylformamide is added dropwise and stirred for 2 hours at 0"C, and then for 12 hours at room temperature. To process the precipitated dicyclohexylurea , filtered off, and then the solvent was distilled off until a dry residue was obtained. The residue obtained in this way was then chromatographed on silica gel (eluent: dichloromethane/ethanol in a ratio of 15:1; chromatography was carried out using a "solvent gradient, continuously increasing to ethanol).

Yield: 26.0 g (58.895 from theory, calculated on the amount of the amine component used) of the title compound in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 52.74 H 5.78 M 11.96 E 13.90 found: C 52.66 H 5.89 M 11.88 E 14.02 b) 1,7-bis(2 -M-trifluoroacetyl-6-M-benzyloxycarbonyl-i-lysine)diamide-4-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-1,4,7-triazaheptane

16.18 g (27.0 mmol) of 2-(M-ethyl-M- perfluorooctylsulfonyl)aminoacetic acid (obtained according to OE 19603033), dissolved in 50 ml of tetrahydrofuran. After that, a total of 18.0 g (36.6 bmmol) of EEDH (2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline) is added in portions at 0"C |, left to stir overnight at room temperature and then concentrated in vacuo. The resulting oil was chromatographed on silica gel (eluent: n-hexane/isopropanol in a ratio of 15:1). In this way, 24.74 g (72.495 from theory, calculated as amount of secondary amine used) of the title compound as a colorless oil.

Elemental analysis: solution: C 42.01 H 3.96 E 31.19 M 8.00 52.29 found: C 41.92 H 4.07 E 31.22 M 7.87 5 2.34 c) 1,7-bis(6-M-benzyloxycarbonyl-1!-lysine)diamide-4-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-1,4,7-triazaheptane 22.0g (15, 7 mmol) of the compound obtained in example 346 is dissolved in 100 ml of ethanol and at 07C this solution is bubbled with gaseous ammonia for 40 minutes. After that, it is stirred for 4 hours at room temperature, and then for 3 hours at room temperature and concentrated to dryness in a vacuum at a bath temperature of 40"C.

The obtained oily residue is purified on silica gel using dichloromethane/hexane/2-propanol (in a ratio of 20:10:1) as an eluent.

Yield: 12.92 g (98.495 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 44.22 H 4.64 M 9.38 5 2.68 E 27.03 found: C 44.31 H 4.72 M 9.30 5 2.74 E 26.99 g ) 0 1,7-bis|(b6-M-benzyloxycarbonyl-2-M-(1-0-х-ХО-carbonylmethyl-2,3,4,6-tetra-O-benzylmannopyranose)-I - lysine|diamide -4-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-1,4,7-triazaheptane 5.47 g (9.15 mmol) 1-carboxymethyloxy-2,3,4,6-tetra-O- benzyl-o0-YOO-mannopyranoside (obtained according to the method described in patent OE 19728954 С1| is dissolved in 30 ml of dimethylformamide and mixed with M-hydroxysuccinimide in a total amount of 1.05 g (9.15 mmol). Then it is cooled to 0"C and 1, 9 g (9.15 mmol) of dicyclohexylcarbodiimide. After that, it is stirred for an hour at RT, and then for 4 hours at room temperature. Then it is cooled to 0"C and over the course of 5 hours, a solution of 7.65 g (9.15 mmol) obtained in example 34c is slowly added dropwise amino compounds in 5X0 ml of dimethylformamide. After that, it is stirred for an hour at 0"C, and then overnight at room temperature. The mixture is evaporated in a vacuum to dryness and the residue is dissolved in 100 ml of ethyl acetic acid. The precipitated urea is filtered and the filtrate is washed twice with a 5956 aqueous solution of soda in portions of 5 Oml. The organic phase is dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: n-hexane/isopropanol in the ratio 20:11). In this way, 17.01 g (78.990 from theory, in terms of the amount of carboxylic acid used) of the title compound are obtained as a colorless oil.

Elemental analysis: solution: C 59.13 H 5.43 M 4.76 E 13.71 5 1.36 found: C 59.22 H 5.39 M 4.85 E 13.70 5 1.40 d ) 1,7-bis(2-M-(1-O-o-O-carbonylmethylmannopyranose)-I -lysine|diamide-4-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-1,4 ,7-triazaheptane 15.0 g (6.3 bmmol) of 34 g of the amide obtained in the example is dissolved in 150 ml of ethanol and mixed with 0.5 g of Perlman's catalyst (2095 Ra/C). After that, it is hydrogenated at room temperature in a hydrogen atmosphere (1 atm) until hydrogen absorption ceases. The catalyst is then removed by vacuum filtration, washed thoroughly with ethanol (about 100 mL), and concentrated to dryness in vacuo to give the title compound as a highly viscous, yellowish oil.

Yield: 8.54g (97.2905 from theory).

Elemental analysis: solution: C 39.13 H 5.04 M 8.11 P 23.38 5 2.32 found: C 39.07 H 4.98 M 8.18 E 23.40 5 2.30 e ) 1,7-bisI2-M-(1-0O-50-O0-carbonylmethylmannopyranose)-6-M-|1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5- methyl-5-ylpentanoyl)-1,4,7,10-tetraazacyclododecane|-I-lysine|diamide-4-(2-(M-ethyl-1M-perfluorooctylsulfonyl)amino|acetyl-1,4,7-triazaheptane, digadolinium complex

A mixed suspension of 5.7 g (9.0 mmol) (described in the application OE 19728954 С1 | in example З1p of the 10-(4-carboxy-1-methyl-2-oxo-3-azabutyl)-1,4,7 10-tetraazacyclododecane-1,4,7-triacetic acid is mixed with 0.68 g (15.9 mmol) of lithium chloride in 75 ml of absolute dimethyl sulfoxide at 70"C.

After stirring for 330 minutes at 70"C, the clear reaction solution is mixed in portions with M-hydroxysuccinimide in a total amount of 1.83g (15.9mmol) and the reaction mixture is kept for another 1h at this temperature. After cooling to 0"C, it is mixed with 4.52g (23.85 mmol) of dicyclohexylcarbodiimide and the reaction solution are stirred for another 1 hour at 02С, and then for 12 hours at 2296. The reaction solution of M-hydroxysuccinimidoether of the α-complex 10-(4-carboxy-1-methyl-2-oxo-

3-azabutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid at 22"C is mixed dropwise with a solution of 2.84 g (2.0 mmol) of the compound indicated in the title of example 34d in 15 ml of absolute dimethyl sulfoxide and then stirred for 12 hours at room temperature. For processing, the reaction solution is added dropwise at 22"C to 500 ml of acetone, while the compound indicated in the title precipitates as a colorless precipitate. This sediment is separated by vacuum filtration, dissolved in 200 ml of distilled water and subjected to ultrafiltration three times through an ultrafiltration membrane UM3 (AMISOM?, limit permeability: 3000Da) for desalination and separation of low molecular weight components.

The resulting retentate is finally lyophilized.

Yield: 4.80 g (89.69 from theory, based on the amount of the amine component used) in the form of a colorless lyophilizate with a water content of 8.9895.

Elemental analysis (in terms of anhydrous substance): solution: С 38.28 Н 4.84 М 9.68 Е 12.40 51.23 Са 12.07 found.: С 38.20 Н 4.91 М 9, 77 E 12.45 51.19 Sa 12.10

Example 35 a) 1,7-bis(benzyloxycarbonyl)-4-(3-oxapentane-1,5-dicarboxylic acid-1-oyl-5-|1-(4-perfluorooctylsulfonyl)piperazinamide)-1,4,7,10 -tetraazacyclododecane

16.56 g (24 4 mmol) of the compound specified in the title of example C5d, dissolved in 150 ml of tetrahydrofuran. After that, a total of 18.0 g (36.6 mmol) of EEDH (2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline) is added in portions at 09 C, and left overnight at at room temperature for stirring and then concentrated in vacuo. The resulting oil is chromatographed on silica gel (eluent: n-hexane/isopropanol in a ratio of 12:1). In this way, 17.22 g (64.395 of theory based on the amount of secondary amine used) of monoamide are obtained, and 3.8 g (8.895 from theory) of diamide as a by-product.The title compound was isolated as a colorless oil.

Elemental analysis: solution: C 43.41 H 3.92 E 29.18 M 7.59 5 2.60 found: C 43.52 H 4.07 E 29.24 M 7.67 52.55 b) 1,7-bis(benzyloxycarbonyl)-4-(3-oxapentane-1,5-dicarboxylic acid-1-oyl-5-11-(4-perfluorooctylsulfonyl)piperazinamide)-10-1-0O-o-0-( 5-carbonyl)pentyl-2,3,4,6-tetra-O-benzylmannopyranose!|-1,4,7,10-tetraazacyclododecane 10.0 g (13.4 mmol) of the carboxylic acid obtained in Example 3v and 3.24 g ( 28.1 mmol) of M-hydroxysuccinimide is dissolved in 100 ml of dimethylformamide, mixed with M,M'-dicyclohexylcarbodiimide in a total amount of 5.8 g (28.1 mmol) in portions at 0"C, and then stirred for 2 hours at this temperature. The activated solution obtained in this way is ether is added dropwise to a solution of 14.83 g (13.4 mmol) of the compound indicated in the title of example C5a in 100 ml of dimethylformamide, cooled to 0 "C, and stirred for 2 hours at 0 "C, and then for 12 hours at room temperature. To process dicyclohexylurea, which precipitated, filtered and then distilled water agent to obtain a dry residue. The residue obtained in this way is then chromatographed on silica gel (eluent: dichloromethane/ethyl acetic acid in a ratio of 20:1; chromatography is performed using a solvent gradient, continuously increasing the proportion of ethyl acetic acid).

Yield: 18.3 g (78.295 from theory) of the title compound in the form of a colorless and highly viscous oil.

Elemental analysis: dis. 3-oxapentane-1,5-dicarboxylic acid-1-oyl-5-| 1-(4-perfluorooctylsulfonyl)piperazinamide)-7-|1-

O-o-0-(5-carbonyl)pentylmannopyranose|-1,4,7,10-tetraazacyclododecane 17.0 g (9.75 mmol) obtained in example 346, the compounds are dissolved in 150 ml of ethanol, mixed with 1.0 g of Perlman's catalyst ( 2090 Pa/C) and hydrogenated at room temperature in a hydrogen atmosphere (1 atm) until hydrogen absorption stops. After that, the catalyst is removed by vacuum filtration, thoroughly washed with ethanol (two portions of 75 ml) and concentrated to dryness in a vacuum. In this way, the compound specified in the title is obtained in the form of a highly viscous and colorless oil.

Yield: 10.76g (99.095 from theory).

Elemental analysis: solution: C 38.78 H 4.61 M 7.54 E 8.97 5 2.88 found: C 38.86 H 4.65 M 7.41 E 29.02 52.92 g) o01,7-6is(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)-4 -(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-2-oxaacetyl|i-10-I(1-O-c-0-carbonylpentylmannopyranose|-1,4,7,10-tetraazacyclododecane, sa- complex 24.86 g (39.46 mmol, 4.4 molar equivalents in terms of the amount of the used amine component from example 35) (described in the application OE 19728954 С1 | in example З1p of the ba-complex 10-(4-carboxy-1-methyl- 2-oxo-3-azabutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 1.67 g of anhydrous lithium chloride (39.4 mmol) at 40"C are dissolved with stirring in 200 ml of absolute dimethyl sulfoxide and at this temperature is mixed with M-hydroxysuccinimide in a total amount of 4.53g (39.4bmmol) and with 10.0g (8.p97mmol) of the compound indicated in the title of example 34c, dissolved in 100ml of absolute dimethylsulfoxide. cooling to room temperature, the reaction solution is mixed with 8.14 g (39.46 mmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature. The resulting suspension is then mixed with a sufficient amount of acetone to completely precipitate the compound indicated above in the title, the precipitate is filtered off by vacuum filtration, dried, dissolved in water, dicyclohexylurea that has not dissolved is filtered off, and the filtrate is passed through an ultrafiltration membrane for desalting and for purification from low molecular weight components AMISOM UM-3 (limit permeability: 3000Da) The retentate is finally lyophilized.

Yield: 16.37 g (79.3905 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 7.6590.

Elemental analysis (in terms of anhydrous substance): solution: С 38.01 Н 4.61 М 9.58 Е 13.81 51.37 Са 13.45 found.: С 37.92 Н 4.55 М 9, 58 E 13.77 51.31 Са 13.48 d) Mono|1-(4-perfluorooctylsulfonyl)piperazinamide of 3-oxapentane-1,5-dicarboxylic acid 25 g (44, Ommol) of 1-perfluorooctylsulfonylpiperazine are dissolved in 150 ml of tetrahydrofuran, mixed at at room temperature with diglycolic acid anhydride in a total amount of 5.1 g (44.00 mmol) and the reaction solution obtained in this way is refluxed for 12 hours. After cooling to room temperature, it is concentrated to dryness and the resulting oily residue is purified on silica gel using dichloromethane/2-propanol (16:1) as eluent.

Yield: 27.94 g (92.895 from theory) of the above title compound in the form of a colorless and viscous oil.

Elemental analysis: cal. C 58.52Н427М1.9852.26 Е 2.80 found: С 58.42 Н 4.41 М1.80 52.28 Е 23.02

Example 36 a) 1,7-bis(benzyloxycarbonyl)-4-(3-oxapentane-1,5-dicarboxylic acid-1-oyl-5-|1-(4-perfluorooctylsulfonyl)piperazinamide)x-(10-11-O -y-O-carbonylpentyl-2,3,4,6-tetra-O-benzylglucopyranose|-1,4,7,10-tetraazacyclododecane)

In 750 ml of dry tetrahydrofuran, dissolve 68.5 g (91.79 mmol) of 1-carboxymethyloxy-2,3,4,6-tetra-O-benzyl-o-YOO-mannopyranoside (obtained according to the method described in patent OE 19728954 С1| and then add 9.25g (91.79mmol) of triethylamine. After cooling the reaction solution to a temperature in the range from -15 to -20"7C, at this temperature and while stirring, slowly add a solution of 12.64g (92.5mmol) of chloroformic acid isobutyl ether in 150 ml of dry tetrahydrofuran, while the rate of dropwise addition should be such that the internal temperature does not exceed -107C. After conducting the reaction for 15 minutes at -157C, a solution of 101.6g (91.79mmol) specified in of the title of example C5a of the compound and 9.25 g (91.79 mmol) of triethylamine in 500 ml of dry tetrahydrofuran. After carrying out the reaction for one hour at -15"C, and then for two hours at room temperature, the reaction solution is concentrated to dryness under vacuum. The resulting residue is dissolved in 450 ml of ethyl ether of acetic acid and washed twice with a saturated solution of sodium bicarbonate in portions of 30 ml and once with water in a portion of 400 ml. After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the ethyl acetic acid is distilled off under vacuum.

The obtained oily residue is purified on silica gel using dichloromethane/hexane/2-propanol (in a ratio of 10:20:1) as an eluent.

Yield: 130.6 g (81.695 from theory) of the above title compound in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 55.11 H 5.03 M 4.82 E 18.52 51.84 found: C 55.20 H 5.09 M 4.91 E 18.48 5 1.80 b) 1-(3-oxapentane-1,5-dicarboxylic acid-1-oyl-5-(1-(4-perfluorooctylsulfonyl)piperazinamide)-7-|1-

О-о-0-(5-carbonyl)pentylmannopyranose|-1,4,7,10-tetraazacyclododecane 110.0 g (63.08 mmol) of the compound obtained in example Zba is dissolved in 1000 ml of ethanol, mixed with 5.0 g of Perlman's catalyst ( 2095th Pa/sС) and hydrogenate until quantitative absorption of hydrogen. After that, the catalyst is removed by vacuum filtration, then washed with ethanol and concentrated to dryness under vacuum. In this way, the compound specified in the title is obtained in the form of a viscous and colorless oil.

Yield: 92.61g (99.5905 from theory).

Elemental analysis: solution: C 52.10 H 512 M 5.70 B 21.89 52.17 found: C 52.20 H 5.09 M 5.71 B 21.87 52.20 c) 1.7 -bis(1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-ylpentanoyl)-4-(3-oxapentane-1,5-dicarboxylic acid-1- yl-5-(1-(4-perfluorooctylsulfonyl)piperazinamide)-10-(11-O-o-0-(5-carbonyl)pentylmannopyranose!|-1,4,7,10-tetraazacyclododecane, digadolinium complex 55 .4 g (88.0 mmol, 4.4 molar equivalents in terms of the amount of the used diamine component from example 3Z3g) (described in the application OE 19728954 С1 | in example Z31p of the ba-complex 10-(4-carboxy-1-methyl-2- oxo-3-azabutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 3.7 g of anhydrous lithium chloride (88.0 mmol) at 40"С are dissolved with stirring in 500 ml of absolute dimethyl sulfoxide and at at this temperature, it is mixed with M-hydroxysuccinimide in a total amount of 10.1 g (88.0 mmol) and with 29.5 g (20.0 mmol) of the compound indicated in the title of example 36b, dissolved in 200 ml of absolute dimethyl sul of epoxide. After cooling to room temperature, the reaction solution is mixed with 18.2 g (88.0 mmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature. The obtained suspension is then mixed with a sufficient amount of acetone to completely precipitate the above-mentioned compound, the precipitate is separated by vacuum filtration, dried, dissolved in water, dicyclohexylurea, which has not dissolved, is filtered off, and the filtrate is passed through an ultrafiltration membrane for desalting and purification from low molecular weight components AMISOM UM-3 (limit permeability: 3000Da) The retentate is finally lyophilized.

Yield: 35.96 g (76.9905 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 5.9890.

Elemental analysis (in terms of anhydrous substance): solution: С 38.01 Н 4.61 М 8.22 EE 13.81 Са 13.45 51.37 found l.: С 37.87 Н 4.70 М 8 ,22 E 13.90 Sa 13.48 5 1.36

Example 37 a) 5-(ethoxycarbonyl)pentyl-2,3,4,6-tetra-O-acetyl-o-ХО-mannopyranoside

Analogously to the method described in the literature for the synthesis of arylglycopyranosides (U, Sopspie and S.A. Imu, "Meshpoad5 ip Sagropuagaee Spetivigu (edited by K.G. M/pisTseg, M.S. Muoitot and U.M. VemiSeg ), Asadetis species

Rhev55, Mem/mMogkK, vol. II, 90, p. 345-347 (1963))| as a result of the interaction of 156.2 g (400 mmol) of O-mannose pentaacetate in the form of a mixture of o, p-anomers (the ratio between c and dD is 4:1) (synthesis of 1,2,3,4,6-penta-O-acetyl -o,D-YUO-mannopyranoses, see M. I. Muoygot and A. Tpotrzop, "Meshpoavz ip Sagropuagate Spetivigu" (ed.

A.G. M/piszeg, M.S. UMoytot and 9U.M. VemiSheg), ed. Asadetis Rgez5, Mem/ Mogk, vol. II, 53, p. 211-215 (1963)| with 6b7ml (400 mmol) of ethyl ether of b-hydroxyhexanoic acid and 60.8 ml (520 mmol) of tin(IM) chloride in 1,2-dichloroethane in a total amount of bOOml after purification by column chromatography (eluent: hexane/ethyl acetic acid in a ratio of 2:1 ) yield 100.05 g (5195 from theory) of the above-mentioned compound in the form of a colorless and viscous oil. The data of "H-NMR-spectroscopic analysis of the compound indicated in the title obtained in this way indicate that this compound is only a pure o-anomer.

Elemental analysis: solution: C 52.94 H 6.77 detected: C 52.80 H 6.78 b) 5-(carboxy)pentyl-2,3,4,6-tetra-O-benzyl-o- UO-mannopyranoside

A mixed suspension of 141.0 g (289 mmol) of the compound specified in the title of example 37a in 200 ml of dioxane at room temperature and simultaneous intensive stirring is mixed in portions with highly dispersed powdered potassium hydroxide in a total amount of 238.5 g (4.2 bmol). To increase its miscibility, the reaction mixture is mixed with another 200 ml of dioxane, and the suspension obtained as a result is then heated to the boiling point and at this temperature for two hours it is mixed dropwise with benzyl bromide in a total amount of 372 ml (3.128 moles). After carrying out the reaction for 4 hours at

110"C, and then for 12 hours at room temperature, the reaction mixture for processing is slowly poured into a mixture of water and ice in a total amount of 2.5 l, and the aqueous phase is then completely extracted with diethyl ether. After washing the ether phase obtained in this way and its subsequent drying over sulfate the sodium salt is separated by vacuum filtration and the diethyl ether is distilled off in a vacuum. After that, the excess benzyl bromide is quantitatively distilled off from the reaction mixture in a vacuum created by an oil pump at an oil bath temperature of 1807"C. The resinous-oily residue obtained in this way is purified on silica gel using ethyl acetic acid/hexane (in a ratio of 1:10) as an eluent.

Yield: 172.2 g (91.095 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 75.68 H 7.16 found: C 75.79 H 7.04 c) 5-Kcarboxy)pentyl-2,3,4,6-tetra-O-benzyl-o-Y -mannopyranoside|-M-hydroxysuccinimidoester 60.0 g (91.5 mmol) of the compound indicated in the title of example 376 is dissolved in 750 ml of dimethylformamide and mixed with M-hydroxysuccinimide in a total amount of 10.4 g (91.5 mmol). Then it is cooled to 0"C and 18.9 g (91.5 mmol) of dicyclohexylcarbodiimide is added. After that, it is stirred for one hour at 0"C, and then for 4 hours at room temperature. The solvent is distilled off in a vacuum, the resulting residue is mixed with 100 ml of ethyl acetic acid and cooled to 0"C. The precipitated urea is filtered off and the resulting filtrate is concentrated to dryness in a vacuum. The resinous-oily residue obtained in this way is purified on silica gel using ethyl ether acetic acid/hexane (in a ratio of 1:20) as an eluent.

Yield: 61.23g (89.095 from theory) of the above title compound in the form of a colorless and viscous oil.

Elemental analysis: solution: C 70.29 N 6.57 M 1.86 found: C 70.39 N 5.64 M 1.91 g) Methyl ether 2,6-bis(6-Me-2-Ma -|1-O-c-ХО-carbrnylpentyl-(2,3,4,6-tetra-O-benzyl)mannopyranose|-I - lysine)

To a cooled to 0"C solution of 4.26 g (18.30 mmol, 0.5 molar equivalents in terms of the amount of carboxylic acid used) dihydrochloride methyl ether of I-lysine (supplied by Vaspet) and 4.05 g (40.26 bmmol) of triethylamine in 100 ml of dimethylformamide, a solution of 27.51 g (36.bmmol) of the compound specified in the title of example 37c in 150 ml of dimethylformamide is added dropwise. After this addition is completed, it is stirred for another hour at 0"C, and then overnight at room temperature. The mixture is evaporated to dryness under vacuum and the residue is dissolved in ZOO ml of ethyl acetic acid. The precipitated urea is filtered off and the filtrate is washed twice with a 595% aqueous soda solution in portions of 100 ml. The organic phase is dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: n-hexane/isopropanol in a ratio of 25:1).

In this way, 39.56 g (75.490 from theory) of the title compound are obtained in the form of a colorless oil.

Elemental analysis: solution: C 72.88 H 7.31 M 1.95 found: C 72.90 H 7.29 M 2.02 d) 2,6-bisIb-Me-2-Ma-(11- O-c-0-6-carbonylpentyl-(2,3,4,6-tetra-O-benzyl)mannopyranozai||-I -lysine

30.0 g (20.92 mmol) of 37 g of the compound obtained in the example are dissolved in 150 ml of ethanol. Next, add a solution of 4 g (100 mol) of sodium hydroxide in 10 ml of distilled water and stir for 1 hour at 50°C. According to the chromatogram of thin-layer chromatography, the saponification is quantitative. and the organic phase is extracted twice with a dilute aqueous solution of citric acid in portions of 10 Oml. After drying over sodium sulfate, it is filtered and concentrated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: n-hexane/isopropanol in the ratio 13:1). In this way, 25 is obtained, 56g (88.595 from theory) of the title compound as a colorless oil.

Elemental analysis: solution: C 72.88 H 7.31 M 1.95 detected: C 72.78 H 7.33 M 1.96 e) M-hydroxysuccinimidoether 2.,6-bis|b-Me-2 -Me-|1-O-o-0-6-carbonylpentyl-(2,3,4,6-tetra-O-benzyl)mannopyranose|-I-lysine 14.0 g (9.15 mmol) of the compound indicated in the title of example C7d, dissolve in 100 ml of dimethylformamide and mix with M-hydroxysuccinimide in a total amount of 1.04 g (915 mmol). Next, it is cooled to 0"C and 1.89 g (9.15 mmol) of dicyclohexylcarbodiimide is added. After that, it is stirred for one hour at 0"C, and then for 4 hours at room temperature. Next, the solvent is distilled off in a vacuum, the resulting residue is mixed with 100 ml of ethyl acetic acid and cooled to 0"C. The precipitated urea is filtered off and the resulting filtrate is concentrated to dryness in a vacuum. The resinous-oily residue obtained in this way is purified on silica gel using ethyl of acetic acid ether/i-hexane (in a ratio of 1:20) as an eluent.

Yield: 12.94 g (92.495 from theory) of the above title compound in the form of a colorless and viscous oil.

Elemental analysis: solution: C 71.40 H 7.05 M 2.74 found: C 71.39 H 7.14 M 2.81 w 1,7-(1,4,7-triazaheptane)diamide 2, 6-M,M'-6bis1-O-c-0-(6-carbonyl)pentyl-2,3,4,6-tetra-O-benzylmannopyranose|-I-lysine

To a solution of 0.47 g (4.57 mmol) of diethylenetriamine in 25 ml of dimethylformamide cooled to 0 °C, a solution of 14.0 g (9.15 mmol; 2 molar equivalents based on the amount of amine used) of the compound specified in the title of example 37e in 100 ml is slowly added dropwise After this addition is completed, the mixture is stirred for one hour at 0"C, and then overnight at room temperature. The mixture is evaporated to dryness in a vacuum and the residue is dissolved in 200 ml of ethyl acetic acid. The precipitated urea is filtered and the filtrate is washed twice with a 595% aqueous solution of soda in portions of 5O0ml. The organic phase is dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: n-hexane/isopropanol in a ratio of 25:1).

In this way, 9.53 g (71.495 from theory) of the title compound are obtained in the form of a colorless oil.

Elemental analysis: soln.: C 72.79 H 7.42 M 3.36 detected: C 72.90 H 7.39 M 3.32 3) Methyl ether 2-M-(2-(M-ethyl-M) -perfluorooctylsulfonyl)amino|acetyl-6-M-(benzyloxycarbonyl)-I - lysine 20.8g (35.bmmol) 2-(M-ethyl-M-perfluorooctylsulfonyl)aminoacetic acid, as well as 3.bOg (35.bmmol) triethylamine is dissolved in 200 ml of dimethylformamide and 4.09 g (35 bmol) of M-hydroxysuccinimide is added.

Next, it is cooled to 0"C and 7.34 g (35.6 mmol) of dicyclohexylcarbodiimide is added. After that, it is stirred for one hour at 0"C, and then for 4 hours at room temperature. It is then cooled to 0"C and a solution of 11.77 g (35.6 mmol) of 6-M-benzyloxycarbonyl-I-lysine methyl ether hydrochloride and 4.0 g (40.0 mmol) of triethylamine in 100 ml of dimethylformamide is added dropwise over 7 hours. The mixture is stirred for hours at 0"C and then overnight at room temperature. The mixture is evaporated to dryness in a vacuum and the residue is dissolved in 100 ml of ethyl acetic acid. The precipitated urea is filtered and the filtrate is washed twice with a 5906 aqueous solution of soda in portions of 100 ml.

The organic phase is dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: n-hexane/oethyl acetic acid in a ratio of 20:11). In this way, 27.43 g (88.0905 from theory) of colorless oil are obtained.

Elemental analysis: solution: C 38.41 H 3.45 M 4.80 E 36.89 5 3.66 found l.: C 38.45 H 3.38 M 4.88 E 37.02 5 3.71 i) 2-Ma-C2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl)-6-M-(benzyloxycarbonyl)-I-lysine

25.0 g (28.55 mmol) of the compound obtained in example 373 is dissolved in 150 ml of ethanol. Next, add a solution of 4g (100, 00mmol) of sodium hydroxide in 1Oml of distilled water and stir for 1 hour at 5070. According to the chromatogram of thin-layer chromatography, saponification is quantitative. After that, it is concentrated to dryness in a vacuum, the obtained residue is dissolved in 300 ml of ethyl acetic acid, and the organic phase is extracted twice with a dilute aqueous solution of citric acid in portions of 10 ml. After drying over sodium sulfate, it is filtered and concentrated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: n-hexane/isopropanol in a ratio of 10:1). In this way, 22.73 g (92495 from theory) of the title compound are obtained in the form of a colorless oil.

Elemental analysis: solution: C 37.64 H 3.28 M 4.88 E 37.49 5 3.72 found: C 37.65 H 3.38 M 4.88 E 37.52 5 3.73 1,4,7-triazaheptane-4-(2-M-(2-(m-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-6b-M- benzyloxycarbonyl)-I -lysinamide-1,7-bis2,6- M,M'-bis(1-O-x-0-(5-carbonyl)pentyl-2,3,4,6-tetra-O-benzylmannopyranose!|-I-lysindiamide) 15.33g (17.8mmol) of the compound indicated in the title of example 37i, as well as 1.80 g (17.8 mmol) of triethylamine are dissolved in 250 ml of dry tetrahydrofuran. After cooling the reaction solution to a temperature in the range from -15 to -207 C at this temperature, solution 4 is slowly added dropwise while stirring. 92g (35.6bmmol) isobutyl ether of chloroformic acid in 50ml of dry tetrahydrofuran, while the rate of dropwise addition should be such that the internal temperature does not exceed -1070. After conducting the reaction for 15 minutes at -157C, slowly add the solution dropwise at -20"C 52.0 g (17.8 mmol) of the compound indicated in the title of example 37g and 1.80 g (17, C mmol) of triethylamine in ZOOml of dry tetrahydrofuran. After carrying out the reaction for one hour at -15"7C, and then for two hours at room temperature, the reaction solution is concentrated to dryness in a vacuum. The resulting residue is dissolved in 50 ml of ethyl acetic acid and washed twice with a saturated solution of sodium bicarbonate in portions of 200 ml and once with water in portions of 200 ml After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and ethyl acetic acid is distilled off under vacuum.

Yield: 54.6 g (81.695 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 65.09 H 6.45 M 3.72 E 8.58 5 0.85 found: C 65.13 H 4.41 M 3.69 E 8.5250.90 l) 1 ,4,7-triazaheptane-4-(2-M-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl)-I -lysinamide-1,7-bis(2,6-M,M'- bis(1-O-c-0-(5-carbonyl)pentylmannopyranose|-I-lysindiamide) 50.0 g (13.28 mmol) of the compound obtained in example 37k is dissolved in 500 ml of ethanol, mixed with 4.0 g of Perlman's catalyst (2090- ny Ra/C) and hydrogenated at room temperature in a hydrogen atmosphere (1 atm) until hydrogen absorption stops. After that, the catalyst is removed by vacuum filtration, thoroughly washed with ethanol (approximately 400 ml) and concentrated to dryness under vacuum. In this way, the indicated in the title compound in the form of a highly viscous and colorless oil.

Yield: 26.85 g (93.0905 from theory).

Elemental analysis:

dist.: C 45.85 H 6.35 M 6.44 R 14.86 51.47 found.: C 45.76 H 6.35 M 6.41 E 14.92 5 1.39 m) 1.4 ... -oxo-5-methyl-5-ylpentanoyl)-1,4,7,10-tetraazacyclododecane)-I - lysinamide-1,7-bis(2,6-M,M'-bis/!1-O-s -0-(5-carbonyl)pentylmannopyranose |-I -lysindiamide), gadolinium complex 5.54 g (8.9 mmol, 2.2 molar equivalents in terms of the amount of the used amine component from example 37l) (described in application OE 19728954 C1 | in example 31p of the complex of 10-(4-carboxy-1-methyl-2-oxo-3-azabutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 0.37 g of anhydrous chloride lithium (83, mmol) at 40"С is dissolved with stirring in bOml of absolute dimethyl sulfoxide and at this temperature is mixed with M-hydroxysuccinimide in a total amount of 1.01 g (8.8 mmol) and with 1.84 g (4.0 mmol) of the example indicated in the title 37 liters of the compound dissolved in 40 ml of absolute dimethyl sulfoxide. After cooling to room temperature, the reaction solution was mixed with 1.82 g (in 8 dmmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature.

The obtained suspension is then mixed with a sufficient amount of acetone until the compound specified above in the title is completely precipitated, the precipitate is separated by vacuum filtration, dried, dissolved in water, the undissolved dicyclohexylurea is also filtered, and the filtrate for desalting and for purification from low molecular weight components is passed through an ultrafiltration AMISOM membrane? UM-3 (limit permeability: Z000Da). Finally, the retentate is lyophilized.

Yield: 8.77 g (78.795 from theory) in the form of a colorless lyophilizate.

NgO content (when using Karl Fischer's reagent): 4.4390.

Elemental analysis (in terms of anhydrous substance): solution: С 43.98 Н 5.97 М 7.54 Е 11.59 (а 5.64 51.15 found.: С 43.97 Н 6.02 М 7 .62 E 11.61 Sa 10.18 51.15

Example 38 a) Methyl ether of 2-Ma-6-Me-bis!1-O-5-O-carbonylnylmethyl-2,3,4,6-tetra-O-benzylmannopyranose|-I - lysine! 10.95 g. (18.30 mmol) of 1-carboxymethyloxy-2,3,4,6-tetra-O-benzyl-o-Y-mannopyranoside (obtained according to the method described in the patent OE 19728954 C1) is dissolved in 150 ml of dimethylformamide and mixed with M-hydroxysuccinimide with a total amount of 2.09 g (18.3 mmol). Next, cool to 0"C and add 3.78 g (18.3 mmol) of dicyclohexylcarbodiimide. After that, stir for an hour at room temperature, and then for 4 hours at room temperature. Then cool to 0" C and within an hour a solution of 2.13 g (9.15 mmol, 0.5 molar equivalents based on the amount of carboxylic acid used) of dihydrochloride of methyl ether I-lysine (supplied by Vaspet) and 2.02 g (20.13 mmol) is added dropwise of triethylamine in 7 bml of dimethylformamide. After this addition is completed, it is stirred for an hour at 0"C, and then overnight at room temperature. The mixture is evaporated to dryness under vacuum, and the residue is dissolved in 3bOml of ethyl acetic acid. The precipitated urea is filtered off and filtrate twice p ruminate with a 595% aqueous solution of soda in portions of 100 ml. The organic phase is dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: n-hexane/isopropanol in the ratio 25:11). In this way, 10.05 g (82.395 from theory) of the title compound are obtained in the form of a colorless oil.

Elemental analysis: solution: C 71.94 H 6.79 M 2.10 found: C 71.90 H 6.79 M 2.09 b) 2-Ma-6-Me-bisy1-O-c-O -carbonylmethyl-2,3,4,6-tetra-O-benzylmannopyranose|-I -lysine

Similarly to the method described in example 37d for the synthesis of the compound indicated in its title, as a result of saponification of 15 g (11.23 mmol) of the methyl ether of the compound indicated in the title of example Zv8a, 13.89 g (93.695 from theory) of the compound indicated above in the title are obtained in in the form of colorless and viscous oil.

Elemental analysis: solution: C 71.80 H 6.71 M 2.12 detected: C 71.84 H 6.69 M 2.15 c) M-hydroxysuccinimidoether 2-Ma-6-Me-bis(1- O-c-O-carbonylmethyl-2,3,4,6-tetra-O-benzylmannopyranose|-I-lysine 12.09 g (9.15 mmol) of the compound indicated in the title of example 38b is dissolved in 100 ml of dimethylformamide and mixed with M -hydroxysuccinimide in a total amount of 1.04g (9.15mmol). Next, cool to 0"C and add 1.89g (9.15mmol) of dicyclohexylcarbodiimide. After that, stir for an hour at 0"C and then for 4h at room temperature. Next, the solvent distilled off in a vacuum, the obtained residue is mixed with 100 ml of ethyl acetic acid and cooled to 070.

The precipitated urea is filtered off and the resulting filtrate is concentrated to dryness under vacuum.

The resinous-oily residue obtained in this way is purified on silica gel using ethyl acetic acid/n-hexane (in a ratio of 1:20) as an eluent.

Yield: 12.24 g (94.495 from theory) of the compound indicated above in the title in the form of a colorless and viscous oil.

Elemental analysis: solution: C 70.27 N 6.47 M 2.96 found: C 70.31 N 6.44 M 3.01 g) 0 (1-(4-perfluorooctylsulfonyl)piperazinamide / 6-M- benzyloxycarbonyl-2-M-C2,6-M,M'-bis(1-0O-x-0-carbonylmethyl-2,3,4,6-tetra-O-benzylmannopyranose)|-I -lysyl/)-I -lysine 19.0g (13.4mmol) of the M-hydroxysuccinimidoester carboxylic acid obtained in Example 3 is dissolved in 75ml of dimethylformamide and mixed dropwise at 0"C with a solution of 11.13g (13.4mmol) of the example indicated in the title, cooled to 0"C 21 in compounds in 50.0 ml of dimethylformamide. The resulting reaction solution is stirred for another 2 hours at 0"C, and then for 12 hours at room temperature. To process the dicyclohexylurea that precipitated, it is filtered and then the solvent is distilled off in a vacuum to obtain a dry residue. The residue obtained in this way is chromatographed on silica gel (eluent : dichloromethane/ethanol in a ratio of 28:11, while the chromatography is carried out using a solvent gradient, continuously increasing in the chromatography process the share of its polar component used in the eluent (in this case, ethanol)).

Yield: 25.28 g (88.4905 from theory) of the title compound in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 59, 10 H 5.34 M 3.94 E 15.13 5 1.50 found: C 59, 18 H 5.35 M 4.02 E 15.15 5 1.56 d ) (1-(4-perfluorooctylsulfonyl)piperazine|amide 2-M-Х2.,6-М,М'-bis(1-О-с-0-carbonylmethylmannopyranose)|-I-lysyl-Y-lysine 20.0g (9.37 mmol) of the compound obtained in Example C8g is dissolved in 200 ml of ethanol, mixed with 1.5 g of Perlman's catalyst (2090 Pa/C) and hydrogenated at room temperature in a hydrogen atmosphere (Tatm) until hydrogen absorption stops. this catalyst is removed by vacuum filtration, thoroughly washed with ethanol (two portions of approximately 100 ml each) and concentrated to dryness under vacuum.

In this way, the compound specified in the title is obtained in the form of a highly viscous and colorless oil.

Yield: 11.62g (97.0905 from theory).

Elemental analysis: solution: C 38.50 H 4.65 M 6.57 E 25.25 5 2.51 found: C 38.46 H 4.65 M 6.51 E 25.23 52.52 e) 1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-(1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-ylpentanoyl)-1,4,7, 10-tetraazacyclododecane)-2-M-C2,6-M,M'-bis(1-O-o-0O-carbonylmethylmannopyranose)|-I -lysyl)-I -lysine, Sd-complex 9.98g (15, 84 mmol, 2.2 molar equivalents in terms of the amount of the used amine component from example C8d) (described in the application OE 19728954 C1) in example C31n of the Ca-complex 10-(4-carboxy-1-methyl-2-oxo-3-azabutyl )-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 067 g of anhydrous lithium chloride (15.84 mmol) at 40"С are dissolved with stirring in 100 ml of absolute dimethyl sulfoxide and at this temperature are mixed with M-hydroxysuccinimide with a total amount of 1.82 g (15.84 mmol) and from 9.19 g (7.19 mmol) of the compound specified in the title of Example 3, dissolved in 50 ml of absolute dimethyl sulfoxide. After cooling to room temperature temperature, the reaction solution is mixed with 3.27 g (15.84 mmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature. The resulting suspension is then mixed with a sufficient amount of acetone to completely precipitate the above-mentioned compound, the precipitate is separated by vacuum filtration, dried, dissolved in water, dicyclohexylurea, which has not dissolved, and the filtrate are filtered for desalting and for simultaneous purification from those that may still be present in it low-molecular components are subjected to ultrafiltration through an ultrafiltration membrane AMISOM UM-3 (limit permeability: З000Da)

Finally, the retentate is lyophilized.

Yield: 11.85 g (87295 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 5.5490.

Elemental analysis (in terms of anhydrous substance): solution: С 38.12 Н 4.64 М 8.15 РЕ 20.38 51.70 Са 8.532 found.: С 38.16 Н 4.59 М 8.18 Е 20.37 5 1.68 Ca 8.28

Example 39 a) 1,7-bis(benzyloxycarbonyl)-4-(3-oxa-2n 2H,4H,4H,5H,5H-perfluorotridecanoyl)-1,4,7,10-tetraazacyclododecane

12.74 g (24 .4 mmol) of the compound indicated in the title of Example 30, dissolved in 150 ml of tetrahydrofuran. After that, at 0"C, a total of 18.0 g (36.bmmol) of EEDX (2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline) is added in portions, leaving overnight to stir at room temperature and then concentrated in vacuo. The resulting oil was chromatographed on silica gel (eluent: i-hexane/isopropanol in a ratio of 16:1). This gave 15.89 g (69.095 from theory, based on the amount of secondary used amine) of the monoamide, and 3.8 g (8.890 from theory) of the diamide as a by-product.The title compound was isolated as a colorless oil.

Elemental analysis: solution: C 45.77 H 3.95 E 34.19 M 5.93 found: C 45.72 H 4.01 E 34.22 M 5.88 b) 1,7-bis(benzyloxycarbonyl)- 4-(3-oxa-2H,2H,4H.4H,5nH,5H-perfluorotridecanoyl)- 10-(11-5-х-0-(2-carbonyl)ethyl-2,3,4,6-tetra- O-acetylmannopyranose!|-1,4,7,10-tetraazacyclododecane 7.09 g (13.4 mmol) of M-hydroxysuccinimidoether 3-(2,3,4,6-tetra-O-acetyl-1-thio-c-0 - mannopyranosyl)propionic acid (obtained according to the method described in U. Naepbhieg and others,

Viosopidaie Spet. 4, 85 (1993); Spiromu5Ku 5. and Gee U.S., zupipeviv oi 1-(Shio-aIdosidez, Sagropuagaye Nezeagsi 31(1973), p. 339-346| dissolve in 100 ml of dimethylformamide and at 0"C dropwise mix with pre-cooled to 0" With a solution of 12.65 g (13.4 mmol) of the compound indicated in the title of example 39a in 100 ml of dimethylformamide. The mixture is stirred for 2 hours at 0"C, and then for 12 hours at room temperature. For processing, the solvent is distilled off in a vacuum until a dry residue is obtained, which then chromatographed on silica gel (eluent: dichloromethane/ethyl acetic acid in a ratio of 20:11; chromatography is carried out using a solvent gradient, continuously increasing the proportion of ethyl acetic acid).

Yield: 16.23 g (88.9905 from theory) of the title compound in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 46.70 H 4.36 M 4.11 P 23.69 5 2.35 found: C 46.66 H 4.35 M 4.12 E 23.65 5 2.30 in ) 1-(3-oxa-2nH 2nH4H.4H,5H,5H-perfluorotridecanoyl)-7-(1-5-c-0-(2-carbonyl)ethyl-2,3,4,6-tetra-O- acetylmannopyranose!|-1,4,7,10-tetraazacyclododecane 15.0 g (11.0 mmol) of the compound obtained in example 396 is dissolved in 150 ml of ethanol, mixed with 1.0 g of Perlman's catalyst (2090 Pa/C) and hydrogenated at room temperature temperature in a hydrogen atmosphere (1 atm) until hydrogen absorption stops. After that, the catalyst is removed by vacuum filtration, thoroughly washed with ethanol (two portions of 75 ml) and concentrated to dryness under vacuum. In this way, the title compound is obtained in the form of a highly viscous and colorless oil.

Yield: 11.56 g (96.095 from theory).

Elemental analysis: solution: C 40.59 H 4.33 M 5.12 E 29.50 5 2.93 found: C 40.63 H 4.35 M 5.11 E 29.52 52.92 g) 1-(3-oxa-2H,2H,4H,4H,5H,5H-perfluorotridecanoyl)-7-|1-5-х-0-(2-carbonyl)ethylmannopyranose|- 1,4,7,10-tetraazacyclododecane 10.0 g (91 mmol) of the compound indicated in the title of example 39c is suspended in 100 ml of absolute methanol and mixed with a catalytic amount of sodium methanolate at 5°C. /methanol in a ratio of 4:1) already indicate a quantitative transformation. For processing, the clear reaction solution is neutralized by mixing with the cation exchange resin Atregiye IC 120 (H"- form), the ionite is removed by vacuum filtration, after which it is washed with methanol and the methanol filtrate obtained in this way distilled in a vacuum until a dry residue is obtained. The resulting oily residue is purified by column chromatography on silica gel (eluent: dichloromethane/n-hexane/ethyl acetic acid in a ratio of 15:20:11; chromatography is performed using a solvent gradient, continuously increasing the proportion of ethyl acetic acid). The data of "H-NMR-spectroscopic analysis of the compound specified in the title allow on the basis of the value of the interaction constants

At 1250.9Hz, we can draw an unambiguous conclusion about the presence of the o-configuration in the anomeric center of O-mannopyranose. Such a c-configuration is the only configuration present in the center of anomerism, i.e., the amount of possible formed anomer of the compound indicated in the title with the p-configuration is therefore below the detection threshold during "H-NMR spectroscopic analysis. Accordingly, the compound indicated above in the title is obtained only in the form of a pure a-configuration anomer.

Yield: 8.28 g (98.095 from theory) of the title compound in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 37.59 H 4.24 M 6.05 E 34.85 5 3.46 found: C 37.57 H 4.28 M 6.02 E 34.85 5 3.44 d ) /1-(Z-oxa-2H,2H,4H.4H,5H,5H-perfluorotridecanoyl)-7-|1-5-х-0-(2-carbonyl)ethylmannopyranose|-4.,10- bis1, 4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-ylpentanoyl)|-1,4,7,10-tetraazacyclododecane, digadolinium complex 2.A8g (3.p94mmol , 4.4 molar equivalents in terms of the amount of the used diamine component from example 39d) | described in the application OE 19728954 С1| in example Z31n of the Ca complex of 10-(4-carboxy-1-methyl-2-oxo-3-azabutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 167 mg of anhydrous lithium chloride ( 3.p94mmol) at 40"С are dissolved with stirring in 40ml of absolute dimethylsulfoxide and at this temperature are mixed with M-hydroxysuccinimide in a total amount of 453mg (3.p94mmol) and from 980mg (0.895mmol) of the compound specified in the title of example 39g, dissolved in 10ml of absolute of dimethyl sulfoxide. After cooling to room temperature, the reaction solution is mixed with 814 mg (3.946 mmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature. The resulting suspension is then mixed with a sufficient amount of acetone until the above title compound is completely precipitated, the precipitate is separated under vacuum - by filtration, dry, dissolve in water, filter off dicyclohexylurea, which has not dissolved, and pass the filtrate through an ultrafiltration membrane for desalination and purification from low molecular weight components brane AMISOM UM-3 (limit permeability: 3000Da) The retentate is finally lyophilized.

Yield: 1.32 g (69.195 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 7.6590.

Elemental analysis (in terms of anhydrous substance): solution: С 37.43 Н4.45М9.12 РЕ 15.02 51.49 Са 14.63 found.: С 37.42 Н 4.50 М 9.18 Е 15 ... -1-decanol (supplied by Giapsavieg) is dissolved in 250 ml of absolute toluene and mixed with a catalytic amount (approximately 0.75 g) of tetra-n-butylammonium hydrosulfate at room temperature. After that, a total of 7.55 g (134, b6mmol, 2.5 equivalents based on the amount of the alcohol component used) of highly dispersed powdered potassium hydroxide, and then 15.73g (80./mmol, 1.5 equivalents based on the amount of the alcohol component used) of tert-butyl bromoacetic acid ether and mixed for another 2 hours at 0"C. The reaction solution obtained in this way is stirred for 12 hours at room temperature and then mixed with ethyl acetate for processing of acid in a total amount of 500 ml and with 250 ml of water. The organic phase is separated and washed twice with water.

After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the solvent is distilled off under vacuum. The obtained oily residue is purified on silica gel using ethyl acetic acid/hexane (1:10 ratio) as an eluent.

Yield: 26.3 g (84.695 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 33.23 H 2.61 E 55.85 found: C 33.29 H 2.61 E 55.90 g) 3-oxa-2H,2H.4H,4H,5H,5H -perfluorotridecanecarboxylic acid 20.0 g (34.58 mmol) of the compound indicated in the title of example 39e is suspended at room temperature with stirring in 200 ml of a mixture consisting of methanol and 0.5 molar caustic sodium in a ratio of 21, and then heated to 60 "C. After conducting the reaction for 12 hours at 60"C, the transparent reaction mixture for its processing is neutralized by mixing with the cation exchange resin Atregiye IV 120 (H"-form), the ionite is removed by vacuum filtration, and the resulting methanol-water filtrate is distilled in a vacuum to obtaining a dry residue The resulting amorphous oily residue is purified on silica gel using ethyl acetate/n-hexane (in a ratio of 1:3) as an eluent.

Yield: 16.0 g (88.695 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 27.60 H 1.35 E 61.85 found: C 27.58 H 1.36 E 61.90

Example 40 a) Methyl ether of 6-benzyloxycarbonyl-2-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-y-lysine

To 8.0 g (24.4 mmol) of methyl ether hydrochloride of ve-carbonyloxybenzyl-i-lysine (supplied by the Vaspet company), dissolved in a mixture of 150 ml of tetrahydrofuran, 15 ml of chloroform and 2.62 g (26, Ommol) of triethylamine, at 0"C in 16.18 g (27.0 mmol) of 2-(M-ethyl-M-perfluorooctylsulfonyl)aminoacetic acid (obtained according to OE 19603033), dissolved in 50 ml of tetrahydrofuran, is added dropwise to a nitrogen atmosphere. After that, at 0"C, a total of 18 ,0g (36b,bmmol) of EEDH (2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline) and left overnight for stirring at room temperature. After that, it was concentrated in vacuo and the resulting oil was chromatographed on silica gel (eluent: m-hexane/ zopropanol in a ratio of 15:1).In this way, 17.0 g (79.695 of theory, based on the amount of primary amine used) of the title compound are obtained as a colorless oil.

Elemental analysis: solution: C 38.41 H 3.45 E 36.89 M 4.80 5 3.66 found: C 38.42 H 3.47 E 36.92 M 4.87 5 3.64 b ) Methyl ether of 2-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-y-lysine 15.0 g (20.23 mmol) of the compound obtained in example 40a is dissolved in 200 ml of ethanol, mixed with 800 mg of Perlman's catalyst (2090- ny Pa on activated carbon) and hydrogenate until the calculated amount of hydrogen is absorbed. After that, the catalyst is removed by vacuum filtration, washed thoroughly with ethanol, and concentrated to dryness under vacuum. In this way, the title compound is obtained in the form of a colorless oil.

Output: 14.68g (97.995 from theory)

Elemental analysis: solution: C 32.40 H 3.26 E 43.56 M 5.67 5 4.532 found: C 32.42 H 3.27 E 43.60 M 5.67 5 4.34 c) Methyl 6-(1-O-5-O-carbonylmethyl-2,3,4,6-tetra-O-benzylmannopyranose)-2-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-y-lysine ester

In 500 ml of dry tetrahydrofuran, dissolve 21.31 g (35.mmol) of 1-carboxymethyloxy-2,3,4,6-tetra-O-benzyl-o-YOO-mannopyranoside (obtained according to the method described in patent OE 19728954 STI, as well as Z,bog (35.6 mmol) of triethylamine. After cooling the reaction solution to a temperature in the range from -15 to -20"C, at this temperature, a solution of 4.92 g (35.b mmol) of isobutyl ether of chloroformic acid in 75 ml is slowly added dropwise while stirring of dry tetrahydrofuran, while the rate of dropwise addition should be such that the internal temperature does not exceed -107C. After conducting the reaction for 15 minutes at -157C, a solution of 26.39g (35.6bmmol) indicated in the title of the example is slowly added dropwise at -20"C 406 compounds and 3.60 g (35.6 mmol) of triethylamine in 100 ml of dry tetrahydrofuran. After carrying out the reaction for one hour at -15"С, and then for two hours at room temperature, the reaction solution is concentrated to dryness in a vacuum. The resulting residue is dissolved in 250 ml of Et of acetic acid silt ether and washed twice with a saturated solution of sodium bicarbonate in portions of 100 ml and once with water in a portion of 200 ml. After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the ethyl acetic acid is distilled off under vacuum.

The obtained oily residue is purified on silica gel using ethyl acetic acid/n-hexane (in a ratio of 1:10) as an eluent.

Yield: 38.12 g (81.095 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 49.92 H 3.92 M 2.53 E 29.18 5 2.90 found: C 49.99 Ni, 11 M 2.69 E 29.22 5 3.01 g) 6-(1-O-o-O-carbonylmethyl-2,3,4,6-tetra-O-benzylmannopyranose)-2-I(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-y-lysine Dissolve 27.65 g (20.92 mmol) of the compound obtained in Example 40c in 250 ml of methanol. Next, add a solution of 4.0 g (100.00 mmol) of sodium hydroxide in 10 ml of distilled water and stir for hours at 50°C. Control of the course of the reaction by thin-layer chromatography indicates the already quantitative saponification of methyl ether. After that, the mixture is concentrated to dryness in a vacuum, the resulting residue is dissolved in

Zb0Oml of acetic acid ethyl ether and the organic phase are extracted twice with a dilute aqueous solution of citric acid in portions of 100 ml. After drying over sodium sulfate, it is filtered and concentrated to dryness in a vacuum. The obtained residue is chromatographed on silica gel (eluent: "- hexane/chloroform/isopropanol in the ratio 15:10:11). In this way, 24.31 g (88.995 from theory) of the title compound are obtained in the form of a colorless and viscous oil.

Elemental analysis: solution: C 51.46 H 4.70 M 3.21 P 24.71 52.45 found: C 51.49 H 4.71 M 3.19 E 24.72 5 2.41 d) 6-(1-O-o-O-carbonylmethylmannopyranose)-2-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-y-lysine 20.0 g (15.30 mmol) of the compound specified in the title of the example 40 g , dissolved in a mixture of 250 ml of 2-propanol and 25 ml of water and mixed with 1.0 g of palladium catalyst (1095 Pa on activated carbon).

After that, it is hydrogenated for 12 hours at room temperature and one atmosphere of hydrogen pressure. Next, the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum. The residue is dissolved in 200 ml of methanol and the reaction product is precipitated by mixing with diethyl ether in a total amount of 80 ml. After separation of the solid obtained in this way by vacuum filtration, it is dried in a vacuum at 5070.

Yield: 14.32 g (99.095 from theory) of amorphous solid.

Elemental analysis: solution: C 35.56 H 3.84 M 4.44 5 3.39 E 34.15 found: C 35.58 H 3.81 M 4.45 5 3.40 E 34.17 e ). M-(2-hydroxyprop-Z-yl-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-ylIdamide 6-(1-O-o-O-carbonylmethylmannopyranose)- 2-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-!-lysine, -sa- complex 7.48 g (7.9 mmol) of the compound indicated in the title of example 40d, at 40"С, are dissolved in 50 ml of dimethyl sulfoxide and add 1.00g (8.7O0mol) of M-hydroxysuccinimide. Next, cool to 20"C and add 1.795g (8.7mmol) of dicyclohexylcarbodiimide. After that, stir for an hour at 207C, and then for 4 hours at 40"C. at this temperature, a solution of 4.53 g (7.9 mmol) of the gadolinium complex 10-(2-hydroxy-33-aminopropyl)-4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecanine is added dropwise for 10 minutes (for preparation, see UMO 97/02051| in 20 ml of dimethyl sulfoxide. The mixture is stirred for an hour at 40"C, and then overnight at room temperature. The suspension obtained in this way is then mixed with a sufficient amount of acetone until complete precipitation of the above-mentioned trapping of the compound, the sediment is separated by vacuum filtration, dried, dissolved in water, the dicyclohexylurea that has not dissolved is filtered off, and the filtrate for desalination and for cleaning from low molecular weight components is passed through an ultrafiltration membrane AMISOM UM-3 (limit permeability: 3000Da) The retentate is finally lyophilized .

Yield: 9.71 g (81.795 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 3.97905.

Elemental analysis (in terms of anhydrous substance): solution: С 35.16 Н 4.16 М 7.45 Е 21.48 Са 10.46 52.13 found.: С 35.17 Н 4.20 М 7, 42 E 21.49 Са 10.48 5 2.09

Example 41 a) Methyl ether 6-M-(11-O-c-0-(5-carbonyl)pentyl-2,3,4,6-tetra-O-benzylmannopyranose|-2H-(2-(M-ethyl) -

M-perfluorooctylsulfonyl)amino|acetyl-y-lysine 5.23 g (8.0 mmol) of 5-(carboxy)pentyl-2,3,4,6-tetra-O-benzyl-o-O-mannopyranoside described in Example 3, 1.3 g (8.0 mmol) of 1-hydroxybenzotriazole and 2.6 g (8.0 mmol) of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU; Rebros Gitie company, Great Britain) ) is dissolved in 75 ml of DMF and stirred for 15 minutes. This solution is then mixed with 5.1 bml (ZOmmol) of M-ethyldiisopropylamine and 5.93 g (8.0 mmol) of the amine described in example 406 and stirred for 1.5 days at room temperature. For processing, the solvent is distilled off in a vacuum to obtain a dry residue, which is then chromatographed on silica gel (eluent: dichloromethane/ethyl acetic acid in a ratio of 30:11; chromatography is carried out using a solvent gradient, continuously increasing the proportion of ethyl acetic acid).

Yield: 9.70 g (88.095 from theory) of the title compound in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 52.29 H 4.97 M 3.05 E 23.43 5 2.33 found: C 52.33 H 4.95 M 3.12 E 23.50 5 2.30 b ) 6-M-(1-O-c-0-(5-carbonyl)pentyl-2,3,4,b-tetra-O-benzylmannopyranose|-2M-(2-(M-ethyl-M-perfluorooctylsulfonyl) amino|acetyl-y-lysine 9.0 g (12.40 mmol) of the compound obtained in example 41a is dissolved in 150 ml of methanol. Next, a solution of 2.48 g (62.0 mmol) of sodium hydroxide in 15 ml of distilled water is added and stirred for 1 h at 50 "С Control of the course of the reaction by thin-layer chromatography already indicates quantitative saponification of the methyl ether after the end of the above-mentioned reaction time. Then the mixture is concentrated to dryness in a vacuum, the resulting residue is dissolved in 300 ml of ethyl acetic acid, and the organic phase is extracted twice with a dilute aqueous solution of citric acid in portions of 1700 ml After drying over sodium sulfate, it is filtered and concentrated to dryness under vacuum. The resulting residue is chromatographed on silica gel (eluent: n-hexane/chloroform/isopropanol in the ratio 25:10:11). m by obtaining 15.88 g (93.995 from theory) of the title compound in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 51.95 H 4.88 M 3.08 E 23.67 5 2.35 found: C 51.99 H 4.91 M 3.09 E 23.70 5 2.33 ) 6-M-(1-O-2-0-(5-carbonyl)pentylmannopyranose|-2M-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-y-lysine

13.0 g (9.52 mmol) of the compound specified in the title of example 41b is dissolved in a mixture of 150 ml of 2-propanol and 25 ml of water and 1.0 g of palladium catalyst (10956 Ra on activated carbon) is added.

After that, it is hydrogenated for 12 hours at a hydrogen pressure of 1 atmosphere and room temperature. After that, the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum. The obtained residue is chromatographed on silica gel (eluent: n-hexane/chloroform/isopropanol in the ratio 15:10:11). In this way, 9.09 g (95.195 from theory) of the title compound are obtained in the form of a colorless and highly viscous oil.

Elemental analysis: solution: С3710Н422М4.9 Е 32.18 5 3.10 found: С 37.09 Н 4.21 М 4.19 ЕР 32.20 5 3.13 g) M-(2-hydroxyprop-3 -yl-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-yl)amide 6-M-(1-O-o-0-(5-carbonyl)pentylmannopyranose) -2M-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-i-lysine, cSyd-complex 7.93 g (7.9 mmol) of the compound indicated in the title of example 41c, dissolved at 40"С in 75 ml of dimethyl sulfoxide and mixed with 1.00 g (8.70 mol) of M-hydroxysuccinimide. Next, cool to room temperature and add a total of 1.795 g (8.7 mmol) of dicyclohexylcarbodiimide. After that, stir for an hour at 20"C, and then for 4 hours at 40" C. A solution of 4.53 g (7.9 mmol) of gadolinium complex 10-(2-hydroxy-33-aminopropyl)-4 is added dropwise to this solution of the activated ester of the compound specified in the title of example 41c, then at 40"C for 10 minutes . lfoxide. The mixture is stirred for one hour at 40°C, and then overnight at room temperature. The suspension obtained in this way is then mixed with a sufficient amount of acetone/2-propanol mixture (in a ratio of 2:1) until complete precipitation of the above title compound, the precipitate is separated by vacuum filtration, then washed with ethyl acetic acid, dried, dissolved in water, dicyclohexylurea, which did not dissolve, filtered, and the filtrate for desalting and for cleaning from low molecular weight components is passed through an ultrafiltration membrane AMISOM UM-3 (permeability limit: z00oDa) Retentate finally lyophilized.

Yield: 9.71 g (78.895 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 6.6595.

Elemental analysis (in terms of anhydrous substance): solution: C 36.97 N 4.52 M 7.19 RE 20.71 sa 10.08 5 2.06 detected: C 37.02 N 4.50 M 7 ,22 E 20.69 Са 10.08 5 2.09

Example 42 a) (1-(4-perfluorooctylsulfonyl)piperazineamide 6-M-14-(2,3-bis(M,M-bis(tert-butyloxycarbonylmethyl)amino)propylIfenyl)-3-oxapropionyl-2-M -(1-0-O-carbonylmethylmannopyranose)-I - lysine 5.25 g (7.72 mmol) of tetra-tert-butyl ether "Tuy-EDTK-carboxylic acid" and 781 mg (7.72 mmol) of triethylamine are dissolved in 50 ml of methylene chloride . Next, a solution of 1.16 g (8.5 mmol) of isobutyl ether of chloroformic acid in 1.0 ml of methyl chloride is added dropwise for 5 minutes at -157C and stirred for another 20 minutes at -157C. After that, the solution is cooled to -25C, added dropwise for 330 minutes a solution of 7.07 g (7.72 mmol) of the compound specified in the title of Example 3 and 2.12 g (21.0 mmol) of triethylamine in 7 Oml of tetrahydrofuran and then stirred for 30 minutes at -15"C, and then overnight at room temperature. For processing the solvent is distilled off under vacuum and the resulting oily residue is dissolved in 250 ml of chloroform. The chloroform phase is extracted twice with a 1095% aqueous ammonium chloride solution portions of 100 ml, the organic phase is dried over magnesium sulfate and evaporated to dryness under vacuum.

The residue is chromatographed on silica gel (eluent: methylene chloride/ethanol in a ratio of 20:1).

Yield: 9.6Og (79.095 from theory) of colorless and highly viscous oil.

Elemental analysis: solution: C 46.39 H 5.55 M 5.32 E 20.45 5 2.03 found: C 46.42 H 5.51 M 5.29 E 20.49 5 2.09 b ) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-14-I(2,3-bis(M, M-bis(carboxymethyl)amino)propyl|phenyl-Z-oxapropionyl-2-M-(1 -c-XO-carbonylmethylmannopyranose)-I-lysine 9.0 g (5.70 mmol) of the compound obtained in example 42a is dissolved in 150 ml of methanol. Next, a solution of 4.0 g (100.00 mmol) of sodium hydroxide in 25 ml of distilled water is added and stirred for 2 hours at 6070.

Control of the course of the reaction by thin-layer chromatography indicates already quantitative saponification of tetra-tert-butyl ether after the end of the above-mentioned reaction time. After that, the mixture is concentrated to dryness in a vacuum, the resulting residue is dissolved under warm conditions in 5X0 ml of dimethylsulfoxide and then mixed with a sufficient amount of a mixture of acetone and ethyl acetic acid (in a ratio of 1:1) until the compound specified above in the title is completely precipitated, after which the obtained the precipitate is separated by vacuum filtration, thoroughly washed with ethyl acetic acid, dried, dissolved in water, the pH value of the solution containing the product is set to 3.5 with the help of 1-molar hydrochloric acid, the possibly present insoluble components and the filtrate are filtered for desalination and for purification from low-molecular-weight components is passed through an ultrafiltration membrane AMISOM? UM-3 (limit permeability: Z000Da). Finally, the retentate is lyophilized.

Yield: 6.76 g (87.695 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 3.30905.

Elemental analysis (in terms of anhydrous substance): solution: С 39.89 Н4.09 М 6.20 Р 23 84 52.37 found.: С 39.92 Н 4.15 М 6.22 Е 23.92 5 2.29 c) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-14-I(2,3-bis(M, M-bis(carboxylatomethyl)amino)propylIfenyl)-3-oxapropionyl-2-M -(1-х-ХО-carbonylmethylmannopyranose)-I - lysine, Mp-complex, disodium salt

3.0 g (2.22 mmol) of the compound indicated in the title of example 426 is dissolved at boiling temperature in 150 ml of a mixture of water and ethanol (in a ratio of 3:1) and mixed with 0.25 g (2.22 mmol) of carbonate in portions at 80"C (manganese). After that, the reaction solution obtained in this way is refluxed for 5 hours. After cooling to room temperature, the mixture of solvents is completely distilled off in a vacuum, and the obtained residue is dissolved in a mixture of 200 ml of distilled water and n-butanol (in a ratio of 1:1) . Further, with intensive stirring, the pH value is set to 7.2 by mixing with 1N caustic sodium. After complete distillation of n-butanol in a vacuum, the remaining aqueous phase is passed through an ultrafiltration membrane of AMISOM UM-3 for desalting and for purification from low molecular weight components ( ultimate permeability: 3000Da).The retentate is finally lyophilized.

Yield: 3.19 g (99.095 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 5.08905.

Elemental analysis (in terms of anhydrous substance): solution: С 37.23 Н 3.54 Е 22.25 Mp 3.78 М 5.79 Ma 3.17 5 2.21 detect.: С 37 .30 Н 3 ,49 E 22.29 Mp 3.81 M 5.76 Ma 3.19 52.18

Example 43 a) (1-(4-perfluorooctylsulfonyl)piperazine|monoamide of 3-benzyloxycarbonylaminoglutaric acid

A mixed solution of 25.0 g (94.96 mmol) of 3-M-(benzyloxycarbonyl)glutaric anhydride (synthesis according to Naiapaka Mipoga, Matatoyo mmi-ispi, Miya Na)ite, Izpitagi Tozpiuase, TEG EAH; Temapeagop I ek, EM, 22, 39 (1981), pp. 3883-3886| in 150 ml of absolute tetrahydrofuran, while stirring, dropwise mix with a solution of 53.97 g (95.0 mmol) of 1-perfluorooctylsulfonylpiperazine in 150 ml of tetrahydrofuran, and the reaction solution obtained in this way is refluxed for 12 hours. After cooling to room temperature, it is concentrated to dryness and the resulting oily residue is purified on silica gel using dichloromethane/2-propanol (20:1) as eluent.

Yield: 75.80 g (96.095 from theory) of the compound indicated above in the title in the form of a colorless and viscous oil.

Elemental analysis: solution: C 36.11 H 2.67 M 5.05 5 3.86 E 38.84 found: C 36.12 H 2.61 M 5.08 53.88 E 38.82 b) (1-(4-perfluorooctylsulfonyl)piperazine|monoamide of 3-aminoglutaric acid) 31.50 g (37.88 mmol) of the compound obtained according to example 43b is dissolved in 30 ml of ethanol, mixed with 2.5 g of Perlman's catalyst (2090 Pa/cС) and hydrogenated until quantitative absorption of hydrogen at a hydrogen pressure of 1 atmosphere. After that, the catalyst is removed by vacuum filtration, washed with ethanol and concentrated to dryness under vacuum. In this way, the title compound is obtained as a pale yellow viscous oil.

Yield: 25.22g (95.590 from theory).

Elemental analysis: solution: C 29.28 H 2.31 M 6.03 5 4.06 E 46.31 found: C 29.32 H 2.29 M 6.08 5 4.08 E 46.28 ) (1-(4-perfluorooctylsulfonyl)piperazine|3-M-(1-o-O-carbonylmethyl-2,3,4,6-tetra-O-benzylmannopyranose)glutaric acid monoamide 21.52g (18.96mmol) 1 -carboxymethyloxy-2,3,4,6-tetra-O-benzyl-o0-ХО-mannopyranoside (obtained according to the method described in patent OE 19728954 C1) is dissolved at room temperature in 100 ml of absolute dimethylformamide and at 0"C is mixed with 2 .56 g (22.2 mmol) of M-hydroxysuccinimide, and then with 4.55 g (22.2 mmol) of dicyclohexylcarbodiimide. After carrying out the reaction for two minutes at 0"C and for hours at 22"C, the undissolved dicyclohexylurea is filtered off and the resulting by a clear solution of the activated ether of the compound indicated above in the title at 0"C, 13.22 g (18.96 mmol) of the compound from Example 436 in 100 ml of dimethylformamide is slowly added dropwise to the mixed solution. After the reaction has been carried out for 12 hours at room temperature, the solvent distilled off in a vacuum and the obtained residue is dissolved in ZOO ml of ethyl acetic acid, after which the urea is filtered off and the organic filtrate is washed twice with a saturated solution of sodium bicarbonate in portions of 100 ml, once with 100 ml of 1095 aqueous solution of citric acid and once with 200 ml of water. After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the ethyl acetic acid is distilled off under vacuum. The obtained oily residue is purified on silica gel using ethyl acetic acid/-hexane (in a ratio of 1:15) as an eluent.

Yield: 21.39 g (88.395 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 49.81 4.10 M 3.29 P 25.27 52.51 found: C 49.89 H 4.11 M 3.32 E 25.22 5 2.51 g) 1 -(4-perfluorooctylsulfonyl)piperazine|monoamide of 3-N-(1-5-O-carbonylmethylmannopyranose)glutaric acid 19.55 g (15.30 mmol) of the compound specified in the title of example 43c is dissolved in a mixture of 250 ml of 2-propanol and 25 ml of water and mixed with 1.5 g of palladium catalyst (1095 Pa on activated carbon).

After that, it is hydrogenated for 12 hours at room temperature and one atmosphere of hydrogen pressure. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum. The residue is dissolved in 200 ml of methanol and the reaction product is precipitated by mixing with diethyl ether in a total amount of 80 ml. After separation of the solid substance obtained in this way by vacuum filtration, it is dried in a vacuum at 40"C.

Yield: 17.49 g (97.5905 from theory) of amorphous solid.

Elemental analysis: solution: C 32.73 H 3.08 M 4.58 5 3.49 E 35.20 found: C 32.68 H 3.15 M 4.55 5 3.50 E 35.17 d ) 3-M-(1-0-O-carbonylmethylmannopyranose)glutaric acid-|1-(4-perfluorooctylsulfonyl)piperazine|iamide-5-M-(2-hydroxyprop-Z-yl-|1,4,7-tris( carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-yl|)amide, a complex of 14.43 g (15.84 mmol) of the compound indicated in the title of example 43 g, and 0.67 g of anhydrous lithium chloride (15, 84 mmol) at 40"C is dissolved with stirring in 100 ml of absolute dimethyl sulfoxide and at this temperature is mixed with M-hydroxysuccinimide in a total amount of 1.82 g (15.84 mmol) and with a solution of 9.08 g (15.864 mmol) of gadolinium complex 10-(2-hydroxy -33-aminopropyl)-4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane (for the preparation see UMO 97/02051| in 5 Oml of dimethylsulfoxide. After cooling to room temperature, the reaction solution is mixed with 3 ,27 g (15.84 mmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature. the suspension is then mixed with a sufficient amount of acetone until the compound specified above in the title is completely precipitated, the precipitate is separated by vacuum filtration, dried, dissolved in water, dicyclohexylurea, which has not dissolved, and the filtrate are filtered for desalting and for simultaneous purification from possible low molecular weight substances still present in it components are subjected to ultrafiltration through an ultrafiltration membrane

AMISOM? UM-3 (limit permeability: 3000Da) The retentate is finally lyophilized.

Yield: 18.71 g (80.2905 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 4.87905.

Elemental analysis (in terms of anhydrous substance): solution: С 34.24 Н 3.83 М7.61 Е 21.92 5 2.18 Са 10.67 found.: С 34.26 Н 3.79 М7.58 E 21.87 52.18 Са 10.68

Example 44 a) 1,7-bis(benzyloxycarbonyl)-4-(3-oxapentane-1,5-dicarboxylic acid-1-oyl-5-11-(4-perfluorooctylsulfonyl)piperazinamide)-10-(2,6- M,M'-bis(1-O-x-O-carbonylmethyl-2,3,4,6-tetra-O-benzylmannopyranose)|-I-lysyl-1,4,7,10-tetraazacyclododecane

To a solution of 27.0 g (24.4 mmol) of the secondary amine obtained in example C5a in a mixture of 150 ml of tetrahydrofuran and 15 ml of chloroform at 0"C in a nitrogen atmosphere, add 33.04 g (25.0 mmol) of the compound indicated in the title of example C8c, dissolved in 250 ml tetrahydrofuran. After that, a total of 18.0 g (36.6 mmol) of EEDH (2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline) is added in portions at 0"C and left overnight for stirring at room temperature. Then the mixture is concentrated to dryness in vacuum and the resulting oil is chromatographed on silica gel (eluent: i-hexane/isopropanol in a ratio of 25:1) to give 45.87 g (78.095 from theory based on the amount of secondary amine used) of the title compound as a colorless oil.

Elemental analysis: solution: C 59.30 H 5.39 E 13.40 M 4.65 5 1.33 found: C 59.32 H 5.37 E 13.37 M 4.70 5 1.34 b ) 1-(3-oxapentane-1,5-dicarboxylic acid-1-oyl-5-(1-(4-perfluorooctylsulfonyl)piperazine|amide)-7-

I(2,6-M,M'-bis(1-O-c-O-carbonylmethylmannopyranose)|-I -lysyl-1,4,7,10-tetraazacyclododecane 241 g (10.00 mmol) obtained in example 44a and specified in its title, the compounds are dissolved in 250 ml of ethanol and mixed with 1.4 g of Perlman's catalyst (2095 Ra/C). After that, hydrogenation is carried out until the quantitative absorption of hydrogen, after which the catalyst is removed by vacuum filtration, thoroughly washed with ethanol and concentrated to dryness under vacuum. The product is obtained in the form of a highly viscous yellow oil.

Yield: 12.80g (90.195 from theory).

Elemental analysis: solution: C 39.72 H 4.89 E 22.73 M 7.88 52.26 found: C 39.72 H 4.87 E 22.77 M 7.90 5 2.24 c) 1-(3-oxapentane-1,5-dicarboxylic acid-1-oyl-5-(1-(4-perfluorooctylsulfonyl)piperazine|amide)-7-(2,6-M,M'-bis(1-O -c-O-carbonylmethylmannopyranose)|-I -lysyl-4,10-bis(1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-ylpentanoyl)| -1,4,7,10-tetraazacyclododecane, digadolinium complex 5.54 g (8.9 mmol, 2.2 molar equivalents in terms of the amount of the used amine component from example 446) (described in the application OE 19728954 C1 | in example 31p sa- complex of 10-(4-carboxy-1-methyl-2-oxo-3-azabutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 0.37 g (8.2 mmol) of anhydrous chloride lithium at 40"C is dissolved with stirring in bOml of absolute dimethyl sulfoxide and at this temperature is mixed with M-hydroxysuccinimide in a total amount of 1.01 g (8.8 mmol) and with 5.68 g (4.0 mmol) of the compound indicated in the title of example 446, dissolved in 40 ml of absolute smoke tylsulfoxide. After cooling to room temperature, the reaction solution was mixed with 1.82 g (in 8 dmmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature.

The obtained suspension is then mixed with a sufficient amount of acetone to completely precipitate the above-mentioned compound, the precipitate is separated by vacuum filtration, dried, dissolved in water, dicyclohexylurea, which has not dissolved, is filtered off, and the filtrate is passed through an ultrafiltration membrane for desalting and purification from low molecular weight components AMISOM UM-3 (limit permeability: 3000Da) The retentate is finally lyophilized.

Yield: 8.52 g (80.690 from theory; in terms of the amount of diamine component used) in the form of a colorless lyophilizate.

NgO content (when using Karl Fischer's reagent): 6.09905.

Elemental analysis (in terms of anhydrous substance): solution: С 38.61 Н 4.76 М 9.53 Р 12.21 са 11.89 51.12 found.: С 38.57 Н 4.82 М 9, 52 E 12.21 Sa 11.93 51.15

Example 45 a) 1,7-bis(benzyloxycarbonyl)-4-(3-oxapentane-1,5-dicarboxylic acid-1-oyl-5-|1-(4-perfluorooctylsulfonyl)piperazinamide)-10-42.6-M ,M'-bis(1-O-os-0-(5-carbonyl)pentyl-2,3,4,6-tetra-O-benzylmannopyranose))-I -lysyl-1,4,7,10-tetraazacyclododecane

To a solution of 27.0 g (24.4 mmol) of the secondary amine obtained in example C5a in a mixture of 150 ml of tetrahydrofuran and 15 ml of chloroform at 0"C in a nitrogen atmosphere, add 35.80 g (25.0 mmol) of the compound indicated in the title of example C7d, dissolved in 250 ml tetrahydrofuran. After that, a total of 18.0 g (36.6 mmol) of EEDH (2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline) is added in portions at 0"C and left overnight for stirring at room temperature. Then the mixture is concentrated to dryness in vacuum, and the resulting oil is chromatographed on silica gel (eluent: n-hexane/isopropanol in a ratio of 20:1) to give 49.48 g (80.495 from theory based on the amount of secondary amine used) of the title compound as a colorless oil.

Elemental analysis: solution: C 60.47 H 5.79 E 12.80 M 4.44 51.27 found: C 60.52 H 5.77 E 12.77 M 4.50 5 1.30 b) 1-(3-oxapentane-1,5-dicarboxylic acid-1-oyl-5-(1-(4-perfluorooctylsulfonyl)piperazine|amide)-7-

I(2,6-M,M'-bis(1-O-os-0-(5-carbonyl)pentylmannopyranose)|-I -lysyl-1,4,7,10-tetraazacyclododecane 25.2 g (10.00 mmol ) obtained in example 45a and the compound indicated in its title is dissolved in 250 ml of ethanol and mixed with 1.8 g of Perlman's catalyst (2095 Ra/C). After that, hydrogenation is carried out until the quantitative absorption of hydrogen, after which the catalyst is removed by vacuum filtration, thoroughly washed ethanol and concentrated to dryness under vacuum.The product is obtained as a highly viscous yellow oil.

Yield: 14.11g (92.5905 from theory).

Elemental analysis: solution: C 49.60 H 7.20 g 21.17 M 7.34 52.10 found: C 49.62 H 7.17 E 21.20 M 7.30 5 2.14 c) 1-(3-oxapentane-1,5-dicarboxylic acid-1-oyl-5-(1-(4-perfluorooxalsulfonyl)piperazine|amide)-7-

I(2,6-M,M'-bis(1-O-os-0-(5-carbonyl)upentylmannopyranose)|-I -lysyl-4,10-bis(1,4,7-tris(carboxylatomethyl) -10-(3-aza-4-oxo-5-methyl-5-ylpentanoyl)|-1,4,7,10-tetraazacyclododecane, digadolinium complex 5.54 g (8.9 mmol, 2.2 molar equivalents in terms of the amount of the used amine component from example 456) (described in the application OE 19728954 C1 | in example C31p of the Ca-complex 10-(4-carboxy-1-methyl-2-oxo-3-azabutyl)-1,4,7,10- tetraazacyclododecane-1,4,7-triacetic acid and 0.37 g (8.2 mmol) of anhydrous lithium chloride at 40"С are dissolved with stirring in boOml of absolute dimethyl sulfoxide and at this temperature are mixed with M-hydroxysuccinimide in a total amount of 1.01 g (8, 8 mmol) and from 6.10 g (4.0 mmol) of the compound specified in the title of Example 456, dissolved in 40 ml of absolute dimethyl sulfoxide. After cooling to room temperature, the reaction solution is mixed with 1.82 g (v8.d mmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature.

The obtained suspension is then mixed with a sufficient amount of acetone to completely precipitate the above-mentioned compound, the precipitate is separated by vacuum filtration, dried, dissolved in water, dicyclohexylurea, which has not dissolved, is filtered off, and the filtrate is passed through an ultrafiltration membrane for desalting and purification from low molecular weight components AMISOM UM-3 (limit permeability: 3000Da) The retentate is finally lyophilized.

Yield: 9.26 g (84.090 from theory; calculated on the amount of diamine component used) in the form of a colorless lyophilizate.

NgO content (when using Karl Fischer's reagent): 5.89965.

Elemental analysis (in terms of anhydrous substance): solution: С 40.52 5.16 М 9.15 РЕ 11.72 (а 11.41 51.16 found.: С 40.57 Н 5.20 М 9, 12 E 11.69 Sa 11.43 51.18

Example 46 a) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-tert-butyloxycarbonyl-2-M-benzyloxycarbonyl-y - lysine 19.02 g (50.00 mmol) o-M-(benzyloxycarbonyl)-y- M'-(tert-butyloxycarbonyl)-I-lysine (supplied by Vaspet) is dissolved in 150 ml of absolute tetrahydrofuran. Then, at 0"C, 8.31 g (50.0 mmol) of carbonyldiimidazole and 5.03 g (50.0 mmol) of triethylamine are added dropwise , dissolved in 75 ml of dry tetrahydrofuran, and stirred for 100 minutes at this temperature. Then, at 0"C, a solution of 48.42 g (50.0 mmol) of perfluorooctylsulfonylpiperazine and 5.03 g (50.00 mmol) of triethylamine in 250 ml of dry tetrahydrofuran is added dropwise. After stirring tetrahydrofuran is distilled off in vacuo overnight and the resulting oil is chromatographed on silica gel (eluent: n-hexane/isopropanol in a 15:1 ratio).

In this way, 49.48 g (80.495 from theory, calculated on the amount of secondary amine used) of the title compound in the form of a colorless oil are obtained.

Elemental analysis (in terms of anhydrous substance): solution: C 40.01 H 3.79 M 6.02 E 34.70 5 3.45 found: C 40.07 H 3.82 M 6.02 E 34 .67 5 3.48 b) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-tert-butyloxycarbonyl-I-lysine 30.0 g (32.2 mmol) of the compound specified in the title of example 4ba is dissolved in 30 ml of isopropanol and mixed with 1.5 g of Perlman's catalyst (palladium hydroxide 2095 on carbon). After that, hydrogenation is carried out for 1 hour at room temperature, while control of the course of the reaction by thin-layer chromatography already indicates quantitative hydrogenolytic cleavage of the benzyloxycarbonyl protecting group after the end of the above reaction time. Then the catalyst filtered off and the filtrate was concentrated to dryness in vacuo. The resulting residue was chromatographed on silica gel (eluent: n-hexane/isopropanol in a ratio of 25:1). In this way, 25.13 g (98.095 from theory) of the title compound were obtained as a colorless oil.

Elemental analysis: solution: C 34.68 H 3.67 E 40.55 M 7.03 5 4.03 found: C 34.72 H 3.70 E 40.60 M 7.01 5 3.98 in ) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-tert-butyloxycarbonyl-2-IM-|1-5--0-(2-carbonyl)ethyl-2,3,4,6-tetra-O -acetylmannopyranose|-I-lysine 15.53 g (35.60 mmol) 3-(2,3,4,6-tetra-O-acetyl-1-thio-2-Y-mannopyranosyl)propionic acid

(obtained according to 9. Naepwieg et al., Viosopidasge Spet. 4 (1993), p. 85; SpiromuzKu 5. and Gee U.S., bBupiipeviv og 1-(Pio-aidozide5, Sagropuagase Kezeagsp 31 (1973), p. 339-346|, as well as 3.60g (35.6O0mmol) of triethylamine are dissolved in 30Oml of dry tetrahydrofuran. After cooling the reaction solution to a temperature in the range from -15 to -207C at this temperature, slowly add a solution of 4.92g ( 35.600 mmol) of isobutyl ether of chloroformic acid in 75 ml of dry tetrahydrofuran, while the rate of dropwise addition should be such that the internal temperature does not exceed -10"C. After conducting the reaction for 15 minutes at -157C, slowly add solution 28 dropwise at 20"C .35 g (35.60 mmol) of the compound specified in the title of Example 426 and 3.60 g (35.60 mmol) of triethylamine in 200 ml of dry tetrahydrofuran. After carrying out the reaction for one hour at -15"7C, and then for two hours at room temperature, the reaction solution was dried concentrate in vacuo E. The obtained residue is dissolved in 250 ml of ethyl acetic acid and washed twice with a saturated solution of sodium bicarbonate in portions of 100 ml and once with water in a portion of 200 ml. After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the ethyl acetic acid is distilled off under vacuum. The obtained oily residue is chromatographed on silica gel using ethyl acetic acid/n-hexane (1:25 ratio) as an eluent.

Yield: 34.21 g (79.195 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 39.54 4.23 M 4.61 P 26.58 5 5.28 found: C 39.49 H 4.21 M 4.59 RE 26.52 5 5.31 g) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-tert-butyloxycarbonyl-2-M-(11-5--0-(2-carbonyl)ethylmannopyranose|-I-lysine 29.93 g (24.64 mmol) the compound indicated in the title of example 46bv is suspended in 400 ml of absolute methanol and mixed with a catalytic amount of sodium methanolate at 5"C. After the reaction has been carried out for 10 hours at room temperature, control over the course of the reaction by thin-layer chromatography (eluent: chloroform/methanol in a ratio of 9:1 ) indicates an already quantitative transformation. For processing, the clear reaction solution is neutralized by mixing with the cation exchange resin Atrbegije? IV 120 (H"- form), the ionite is removed by vacuum filtration, and the methanol filtrate obtained in this way is distilled off in a vacuum until a dry residue is obtained. The resulting amorphous residue purified by chromatography on silica gel using 2-propanol/ethyl acetic acid/n-hex well (in the ratio 1:1:15) as an eluent.

Yield: 23.42 g (90.8905 from theory) of colorless viscous oil.

Elemental analysis: solution: C 36.72 H 4.14 M 5.35 E 30.85 56.13 found: C 36.69 H 4.11 M 5.35 E 30.82 5 6.11 d) (1-(4-perfluorooctylsulfonyl)piperazine|amide 2-M-(11-5-х5-0-(2-carbonyl)ethylmannopyranose|-I-lysine) 20.93 g (20.0 mmol) of the compound indicated in the title of example 46bg at 0"C is dissolved with intensive stirring in a mixture of Xb0ml of trifluoroacetic acid and 100ml of dichloromethane and stirred for 10 minutes at this temperature. After that, the mixture is evaporated to dryness in a vacuum and the residue is dissolved in 150ml of water.

The pH value of this aqueous solution, which contains the product, is set to 9.5 by adding dropwise 2-molar aqueous caustic sodium. Next, the aqueous solution containing the product is subjected to ultrafiltration through the AMISOM UM-3 ultrafiltration membrane (permeability limit: 3000Da) for desalination and for simultaneous purification from low molecular weight components that may still be present in it.

Finally, the retentate is lyophilized.

Yield: 17.79 g (94.2905 from theory) of free amine in the form of a colorless lyophilizate.

NgO content (when using Karl Fischer's reagent): 3.09905.

Elemental analysis (in terms of anhydrous substance): solution: С 34.26 Н 3.73 М 5.92 Е 34.12 56.77 found.: С 34.26 Н 3.79 М 5.88 Е 34, 07 5 6.80 e) P-(4-perfluorooctylsulfonyl)piperazine|amide -2-M-11-5-:-0-(2-carbonyl)ethylmannopyranose|-6-M-(1,4,7- tris (carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-ylpentanoyl)-1,4,7,10-tetraazacyclododecani|-I -lysine, gadolinium complex 5.54g (8.9mmol, 2 ,2 molar equivalents in terms of the amount of the used amine component from example 4bd) (described in the application OE 19728954 С1| in example З1p of the sa-complex 10-(4-carboxy-1-methyl-2-oxo-3-azabutyl)-1 ,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 0.37 g of anhydrous lithium chloride (83, mmol) at 40"С are dissolved with stirring in bOml of absolute dimethylsulfoxide and at this temperature are mixed with M-hydroxysuccinimide in total in the amount of 1.01 g (8.8 mmol) and from 3.78 g (4.0 mmol) of the compound indicated in the title of example 4bd, dissolved in 40 ml of absolute dimethyl sulfoxide. After cooling brought to room temperature, the reaction solution was mixed with 1.82 g (in 8 dmmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature.

The resulting suspension is then mixed with a sufficient amount of acetone to completely precipitate the above-mentioned compound, the precipitate is separated by vacuum filtration, dissolved in water, the undissolved dicyclohexylurea is filtered off, and the filtrate is passed through an ultrafiltration membrane of AMISOM UM for desalting and purification from low molecular weight components -3 (limit permeability: 3000 Da) The retentate is finally lyophilized.

Yield: 5.17 g (83.095 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 4.43905.

Elemental analysis (in terms of anhydrous substance): solution: C 35.45 N 4.07 M 8.09 E20.72 (for 10.09 5 4.11 detect.: C 35.50 N 4.01 M 8 ,12 E 20.68 Са 10.13 5 4.14

Example 47 a) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-benzyloxycarbonyl-2-M-(1-0-pD-O-carbonylmethyl-

2,3,4,6-tetra-O-benzylglucopyranose)-I-lysine 8.02 g (13.4 mmol) of the compound indicated in the title (described in the application OE 19728954 C1 | example 46ba (1-carboxymethyloxy-2,3, 4,6-tetra-O-benzyl-d-YUO-glucopyranoside and 3.24 g (28.14 mmol) of M-hydroxysuccinimide are dissolved in 100 ml of dimethylformamide and mixed with M,M'-dicyclohexylcarbodiimide in a total amount of 5.80 g in portions at 0"C (28.14 mmol). Then it is stirred for 10 minutes at this temperature. To the solution of the activated ester obtained in this way, a solution of 11.13 g (13.44 mmol) of the compound indicated in the title of example 21c, dissolved in 50 ml of dimethylformamide, cooled to 0"C, is added dropwise , and stirred for 2 hours at 0"C, and then for 12 hours at room temperature. To process the dicyclohexylurea that has precipitated, filter and then distill off the solvent to obtain a dry residue. The residue obtained in this way is then chromatographed on silica gel (eluent: dichloromethane/ ethanol in a ratio of 20:1, chromatograph is carried out using a solvent gradient, continuously increasing the proportion of ethanol).

Yield: 12.67 g (67.095 from theory) of the title compound in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 52.77 H 4.50 M 3.97 RE 22.89 52.27 found: C 52.75 H 4.61 M 3.98 E 22.94 5 2.26 b) (1-(4-perfluorooctylsulfonyl)piperazinamide 2-M-(1-0-8-YOO-carbonylmethylglucopyranose)-I-lysine 11.52 g (8.17 mmol) of the compound obtained in example 47a is dissolved in 100 ml of ethanol, mixed with 0, 5 g of Perlman catalyst (2090 Ra/C) and hydrogenated at room temperature in a hydrogen atmosphere (1 atm) until hydrogen absorption stops. After that, the catalyst is removed by vacuum filtration, thoroughly washed with ethanol (three portions of approximately 40 ml) and dried concentrate in a vacuum.

In this way, the compound specified in the title is obtained in the form of a highly viscous and colorless oil.

Yield: 7.36 bg (98.495 from theory).

Elemental analysis: solution: C 34.07 H 3.63 M 6.11 E 35.24 5 3.50 found: C 34.11 H 3.59 M 6.08 E 35.23 5 3.52 ). (1-(4-perfluorooctylsulfonyl)piperazine|Iiamide 2-M-(1-0-8-O-carbonylmethylglucopyranose)-6-M-(1,4,7- tris(carboxylatomethyl)-10-(aza-4- oxo-5-methyl-5-ylpentanoyl)-1,4,7,10-tetraazacyclododecane|-I-lysine, cSid complex 9.98 g (15.84 mmol, 2.2 molar equivalents in terms of the amount of the used amine component with of example 476) |described in the application OE 19728954 C1| in example 31p of the sa-complex 10-(4-carboxy-1-methyl-2-oxo-3-azabutyl)-1,4,7,10-tetraazacyclododecane-1,4 ,7-triacetic acid and 067 g (15.84 mmol) of anhydrous lithium chloride at 40"С are dissolved with stirring in 30 ml of absolute dimethyl sulfoxide and at this temperature are mixed with M-hydroxysuccinimide in a total amount of 1.82 g (15.84 mmol) and with 7.25 g (7.19 mmol) of the compound specified in the title of Example 476, dissolved in 30 ml of absolute dimethyl sulfoxide. After cooling to room temperature, the reaction solution was mixed with 3.27 g (15.84 mmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature temperature The resulting suspension is then mixed with a sufficient amount of acetone to completely precipitate the above-mentioned compound, the precipitate is separated by vacuum filtration, dissolved in water, the undissolved dicyclohexylurea is filtered, and the filtrate for desalting and for purification from low-molecular components is passed through an ultrafiltration membrane of AMISOM UM -3 (limit permeability: 3000 Da) The retentate is finally lyophilized.

Yield: 9.11 g (83.095 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 4.02965.

Elemental analysis (in terms of anhydrous substance): solution: С 35.37 Н4.02 М 8.25 Е 21.13 52.10 Са 10.29 detected: С 35.42 Н 4.07 М 8.18 E 21.09 52.06 Ca 10.34

Example 48 a) (1-(4-perfluorooctylsulfonyl)piperazinamide 2-M-trifluoroacetyl-y-lysine 10.0 g (11.4 b6 mmol) of the compound obtained in example 216 is dissolved in 100 ml of ethanol, mixed with 1.0 g of Perlman's catalyst (2095- ny Ra/cС) and hydrogenated until quantitative absorption of hydrogen. After that, the catalyst is removed by vacuum filtration, washed with ethanol, and concentrated to dryness under vacuum. In this way, the title compound is obtained as a viscous and colorless oil.

Yield: 8.85g (97.590 from theory).

Elemental analysis: solution: C 30.91 H 2.54 M 7.07 E 47.95 5 4.05 found: C 30.36 H 2.50 M 7.11 E 47.99 5 4.00 b ) (1-(4-perfluorooctylsulfonyl)piperazinamide 2-M-trifluoroacetyl-6b-M-(1-O-o-0-(5-carbonyl)pentyl-2,3,4,6-tetra-O-benzylmannopyranose| -I -lysine

To a solution of 29.0 g (36 bmmol) of the compound specified in the title of example 48a and 4.05 g (40.2 bmmol) of triethylamine in 100 ml of dimethylformamide, cooled to 0"C, a solution of 27.51 g (36 bmmol) specified in the title is added dropwise of the compound of example 37c in 150 ml of dimethylformamide. Upon completion of this addition, the mixture is stirred for an hour at 0"C and then overnight at room temperature. The mixture is evaporated to dryness under vacuum and the residue is dissolved in ZOO ml of ethyl acetic acid. The undissolved components are filtered and the filtrate is washed twice with a 595% aqueous solution of soda in portions of 1000 ml. The organic phase is dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: n-hexane/isopropanol in a ratio of 25:1). In this way, 42.05 g (80.495 from theory) of the title compound are obtained in the form of a colorless oil.

Elemental analysis: solution: C 50.42 H 4.51 M 7.96 P 26.59 52.24 found: C 50.38 H 4.50 M 7.91 E 26.62 5 2.20 c) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(1-O-c-0-(5-carbonyl)pentyl-2,3,4,6-tetra-O-benzylmannopyranose|-I-lysine 20 0.0 g (14 Ommol) of the compound obtained in Example 486 is dissolved in 150 ml of ethanol. Then a solution of 2.8 g (70 Ommol) of sodium hydroxide in 25 ml of distilled water is added and stirred for 0.5 h at 5070.

According to the chromatogram of thin-layer chromatography, quantitative cleavage of the protective group occurs by this point in time. Then the mixture is concentrated to dryness in a vacuum and traces of water are removed by repeated co-distillation with ethanol. The residue is chromatographed on silica gel (eluent: n-hexane/isopropanol in a ratio of 20:1). In this way, 16.66 bg (89.390 from theory) of the title compound are obtained as a colorless oil.

Elemental analysis: solution: С 52.254.91 М 4.20 РЕ 24.22 5 2.41 found.: С 52.30 Н4.90 4 18 Е 24.22 5 2.38 g) (1-(4- perfluorooctylsulfonyl)piperazinamide 6-M-(11-O-c-0-(5-carbonyl)pentylmannopyranose|-I-lysine 15.0 g (11.25 mmol) of the compound obtained in example 48c is dissolved in 150 ml of a mixture of ethanol and water in a ratio of 10 :1 and mixed with 1.0 g of Perlman's catalyst (2095 Pa/C). After that, it is hydrogenated until the quantitative absorption of hydrogen at room temperature and at a hydrogen pressure of one atmosphere. After that, the catalyst is removed by vacuum filtration, and the residue is washed with a mixture of ethanol and water (in a ratio of 10:11) and concentrated to dryness in vacuo to give the title compound as a viscous and colorless oil.

Yield: 10.77g (98.4905 from theory).

Elemental analysis: solution: C 37.04 H 4.25 M 5.76 E 33.20 5 3.30 found: C 37.06 H 4.20 M 5.81 E 33.19 5 3.30 d ) /(1-(«4-perfluorooctylsulfonyl)piperazine|iamide 6-M-(1-O--0-(5-carbonyl)upentylmannopyranose|-2-IM-Y 1,4,7-tris(carboxylatomethyl)- 10-(3-aza-4-oxo-5-methyl-b5-ylpentanoyl)-1,4,7,10-tetraazacyclododecani|-lysine, Sd-complex 5.54g (8.9mmol, 2.2 molar equivalents in terms of the amount of the used amine component from example 48g) | described in the application OE 19728954 C1 | in example З31p of the ba-complex 10-(4-carboxy-1-methyl-2-oxo-3-azabutyl)-1,4, 7,10-tetraazacyclododecane-1,4,7-triacetic acid and 0.37 g (8.2 mmol) of anhydrous lithium chloride at 40"С are dissolved with stirring in bOml of absolute dimethyl sulfoxide and at this temperature are mixed with M-hydroxysuccinimide in a total amount of 1, 01 g (8.8 mmol) and from 3.89 g (4.0 mmol) of the compound indicated in the title of Example 48 g, dissolved in 60 ml of absolute dimethyl sulfoxide. After cooling to room temperature, the reaction the second solution is mixed with 1.82 g (in 8 dmmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature.

The obtained suspension is then mixed with a sufficient amount of acetone until the above-mentioned compound is completely precipitated, the precipitate is separated by vacuum filtration, dissolved in water, the undissolved dicyclohexylurea is filtered off, and the filtrate is passed through an ultrafiltration membrane AMISOM? UM-3 (limit permeability: 3000Da) The retentate is finally lyophilized.

Yield: 4.81 g (75.995 from theory) in the form of a colorless lyophilizate.

NgO content (when using Karl Fischer's reagent): 8.98965.

Elemental analysis (in terms of anhydrous substance): solution: С 37.15 Н 4.39 М 7.96 Р 20.38 са 9.92 52.02 found.: С 37.27 Н 4.40 М 8, 02 E 20.31 Са 10.00 5 1.98

Example 49 a) 1,7-bis(benzyloxycarbonyl)-4-(1-0-D-O-carbonylmethyl-2,3,4,6-tetra-O-benzylgalactopyranose)-10-(3-oxapentane-1, 5-dicarboxylic acid-1-oyl-5-(1-(4-perfluorooctylsulfonyl)piperazinamide)-1,4,7,10-tetraazacyclododecane

To a solution of 27.0 g (24.4 mmol) of the secondary amine obtained in example C5a in a mixture of 150 ml of tetrahydrofuran and 15 ml of chloroform at 0"C in a nitrogen atmosphere, add 35.80 g (25.0 mmol) of the compound indicated in the title of example C7d, dissolved in 250 ml tetrahydrofuran. After that, a total of 18.0 g (36.6 mmol) of EEDH (2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline) is added in portions at 0"C and left overnight for stirring at room temperature. Then it is concentrated to dryness in a vacuum and the resulting oil was chromatographed on silica gel (eluent: n-hexane/isopropanol in a ratio of 20:1) to give 32.11 g (78.095 of theory, based on the amount of secondary amine used) of the title compound as a colorless oil.

Elemental analysis: solution: C 54.09 H 4.72 E 19.14 M 4.98 51.90 found: C 54.12 H 4.77 E 19.17 M 5.03 5 1.90 b) /1-(1-0-8-O-carbonylmethylgalactopyranose)-7-(3-oxapentane-1,5-dicarboxylic acid-1-oyl-5-(1-(4-perfluorooctylsulfonyl)piperazinamide)-1,4, 7,10-tetraazacyclododecane 30.0 g (17.77 mmol) obtained in example 49a and the compound indicated in its title is dissolved in 250 ml of ethanol and mixed with 3.0 g of Perlman's catalyst (20956 Ra/C). After that, hydrogenation is carried out until quantitative absorption hydrogen, after which the catalyst is removed by vacuum filtration, washed thoroughly with ethanol, and concentrated to dryness in vacuo to give the product as a highly viscous yellow oil.

Yield: 17.89g (95.1905 from theory).

Elemental analysis: solution: C 36.30 H 4.09 E 30.50 M 7.94 5 3.03 found: C 36.26 H 4.12 E 30.46 M 7.90 5 3.04 in ) 1-11-0-pD-O-carbonylmethylgalactopyranose)-7-(3-oxapentane-1,5-dicarboxylic acid-1-oyl-5-|1-(4-perfluorooctylsulfonyl)piperazinamide)-4,10-bis1 ,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-

B5-ylpentanoyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraazacyclododecane, digadolinium complex

5.54 g (8.9 mmol, 4.4 molar equivalents in terms of the amount of the used amine component from example 496) (described in the application OE 19728954 С1 | in example 31p of the 10-(4-carboxy-1-methyl-2 -oxo-3-azabutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 0.37 g (8.dmol) of anhydrous lithium chloride at 40"С are dissolved with stirring in bOml of absolute dimethyl sulfoxide and at this temperature, it is mixed with M-hydroxysuccinimide in a total amount of 1.01 g (8.0 mmol) and with 2.11 g (2.00 mmol) of the compound indicated in the title of Example 496, dissolved in 25 ml of absolute dimethyl sulfoxide. After cooling to room temperature, the reaction solution is mixed with 1.82 g (in 8, dmmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature.

The obtained suspension is then mixed with a sufficient amount of acetone to completely precipitate the above-mentioned compound, the precipitate is separated by vacuum filtration, dried, dissolved in water, dicyclohexylurea, which has not dissolved, is filtered off, and the filtrate is passed through an ultrafiltration membrane for desalting and purification from low molecular weight components AMISOM UM-3 (limiting permeability; З000Da) The retentate is lyophilized at the end.

Yield: 3.29 g (72.2905 from theory; calculated on the amount of the amine component used) in the form of a colorless lyophilizate.

NgO content (when using Karl Fischer's reagent): 5.99905.

Elemental analysis (in terms of anhydrous substance): solution: С 36.84 Н 4.37 М 9.82 Е 14.15 Са 19.63 5 1.40 found.: С 36.87 Н 4.40 М 9 .82 E 14.09 Sa 19.59 5 1.38

Example 50 a) 3-(1-O-c-0-2,3,4,6-tetra-O-benzylmannopyranose)-2-M-benzyloxycarbonyl-I-serine methyl ester

In 500 ml of dry acetonitrile, dissolve 21.42 g (39.61 mmol) of 2,3,4,6-tetra-O-benzyl-o-O-mannopyranose (obtained according to R. Kopd et al., U. Sagropuyg. Spet., 16, 6 (1997), pp. 877-890. After cooling the reaction solution to 5"C at this temperature, a solution of 13.23 g (59.52 mmol) of trimethylsilyl ether of trifluoromethanesulfonic acid in 30 ml of acetonitrile is slowly added dropwise while stirring. and then a solution of 20.06 g (79.21 mmol) of M-benzyloxycarbonyl-I-serine methyl ether (supplied by

Vaspet) in 500 ml of acetonitrile, while the rate of dropwise addition should be such that the internal temperature does not exceed 10"C. After the reaction has been carried out for 15 hours at room temperature, the reaction solution is concentrated to dryness in a vacuum. The resulting residue is dissolved in 250 ml of ethyl acetic acid and twice washed with a saturated solution of sodium bicarbonate in portions of 100 ml and once with water in a portion of 200 ml. After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and ethyl acetic acid is distilled off in a vacuum. The resulting oily residue is purified on silica gel using ethyl acetic acid/ hexane (in a ratio of 1:5) as an eluent.

Yield: 23.60 g (76.8905 from theory) of the above title compound as a colorless oil.

Elemental analysis: solution: C 71.21 H 6.37 M 1.81 detected: C 71.19 H 6.41 M 1.79 b) 3-(1-O-o-0-2.3, 4,6-tetra-O-benzylmannopyranose)-2-M-benzyloxycarbonyl-I-serine 10.0 g (12.90 mmol) of the compound obtained in example 50a is dissolved in a mixture of 20 ml of methanol, 20 ml of water and 5 ml of tetrahydrofuran. Next, at room temperature, add 0.47 g (19.35 mmol) of lithium hydroxide dissolved in 25 ml of distilled water, and then stir for 2 hours at 60 "C. Control of the course of the reaction by thin-layer chromatography (eluent: methylene chloride/methanol in a 10:1 ratio) indicates the already quantitative saponification of the methyl ether from example 50a after the end of the above reaction time. For processing, the solution containing the product is concentrated to dryness in a vacuum and the obtained residue is dissolved in 250 ml of ethyl acetic acid under warm conditions (approximately 60 "C). After that, the ethyl acetate phase obtained in this way is washed twice with 15956 aqueous hydrochloric acid in portions of 5 Oml and once with distilled water in a portion of 17O0 Oml. The organic phase is dried over magnesium sulfate, filtered and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: n-hexane/ethyl acetic acid in a ratio of 5:11). In this way, 8.40 g (85.795 from theory) of the title compound are obtained as a colorless oil.

Elemental analysis: solution: C 70.94 H 6.22 M 1.84 found: C 70.97 H 6.30 M 1.78 c). (1-(4-perfluorooctylsulfonyl)piperazinamide 3-(1-O--0-2,3,4,6-tetra-O-benzylmannopyranose)-2-M-benzyloxycarbonyl-II-serine

To 13.86 g (24.40 mmol) of 1-perfluorooctylsulfonylpiperazine (obtained according to OE 19603033), dissolved in a mixture of 150 ml of tetrahydrofuran and 15 ml of chloroform, at 0"C in a nitrogen atmosphere, 20.57 g (27.0 mmol) obtained according to to example 506 of carboxylic acid dissolved in 500 ml of tetrahydrofuran. After that, a total of 18.0 g (36.6 b00 mmol) of EEDH (2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline) are added in portions at 0"C and left overnight for stirring at room temperature. For processing, the reaction solution is concentrated in vacuo and the resulting extremely viscous oil is chromatographed on silica gel using a mixture of n-hexane/isopropanol (in a ratio of 15:1) as an eluent. In this way, 17.0 g (79.695 from theory , in terms of the amount of primary amine used) of the title compound in the form of a colorless viscous oil.

Elemental analysis: solution: С 51.53 Н423 М 3.15 Е 25.65 5 2.41 detected: С 51.48 Н4.27 М 3.10 РЕ 25.71 5 2.35 g) (1- (4-perfluorooctylsulfonyl)piperazinamide 3-(1-O-c-O-mannopyranose)-I-serine 15.0 g (11.41 mmol) of the compound obtained according to example 50c is dissolved in 200 ml of ethanol and mixed with 1.5 g of Perlman's catalyst ( 20956 Pa/C). After that, the reaction solution is hydrogenated at room temperature in a hydrogen atmosphere (1 atm) until hydrogen absorption stops (approximately within an hour). For processing, the catalyst is removed by vacuum filtration, thoroughly washed with ethanol (two portions of approximately 1O00ml each) and the ethanol filtrate containing the product are concentrated to dryness under vacuum.This way, the title compound is obtained as a highly viscous and colorless oil.

Yield: 8.79g (94.095 from theory).

Elemental analysis: solution: C 30.78 H 3.20 M 5.13 E 39.41 5 3.91 found: C 30.87 H 3.14 M 5.19 E 39.50 5 3.88 d ) (1-(4-perfluorooctylsulfonyl)piperazinamide 3-(1-0O-c-O-mannopyranose)-2-M-(11,4,7-tris(carboxylatomethyl)-10-(3-aza-4 -oxo-5-methyl-5-ylpentanoyl)-1,4,7,10-tetraazacyclododecani|-I - serine, sa-complex

A mixed suspension of 5.7 g (9.0 bmmol, corresponds to 1.5 molar equivalents in terms of the amount of the compound used, indicated in the title of the example 50 g (primary amine)) (described in the application OE 19728954 С1 | in the example of the ЗІІ Са-complex 10-( 4-carboxy-1-methyl-2-oxo-3-azabutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid in 75 ml of absolute dimethyl sulfoxide at 70"C is mixed with 0.68 g (15 .9 mmol) of lithium chloride. After stirring for 30 minutes at 707C, the clear reaction solution is mixed with M-hydroxysuccinimide in a total amount of 1.83 g (15.9 mmol) in portions, and the reaction mixture is kept for another 1 hour at 70"C. After cooling to 10"C is mixed with 4.52 g (23.85 mmol) of dicyclohexylcarbodiimide and the reaction solution is stirred for another hour at room temperature, and then for 12 hours at 22"C. The solution of M-hydroxysuccinimidoether of Ca-complex 10-(4-carboxy-1-methyl) obtained in this way -2-oxo-3-azabutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, then dropwise is treated at 22"C with a solution of 4.94 g (6.03 mmol) of 50 g of the compound specified in the title of the example in 15 ml of absolute dimethyl sulfoxide and then stirred for another 12 hours at room temperature. For processing, the reaction solution at 22"C is slowly added dropwise to a mixture of solvents consisting of 250ml of acetone and 250ml of 2-propanol, while the compound indicated in the title completely precipitates within 12 hours at 10"C in the form of a light yellow oil . The supernatant eluent is carefully decanted and the oily product is dissolved in 200 ml of distilled water, while this product completely goes into solution with the formation of an aqueous solution of the compound indicated above in the title, which has a light yellow color. Next, this aqueous solution, which contains the product, is first filtered through a membrane filter, and then, for desalination and to separate low-molecular components, it is subjected to ultrafiltration three times through an ultrafiltration membrane UM3 (AMISOM?, limit permeability: З000Da). The resulting retentate is finally lyophilized.

Yield: 8.63g (80.290 from theory, calculated on the amount of the compound used, indicated in the title of example 50g) in the form of a colorless lyophilizate with a water content of 7.65905.

Elemental analysis (in terms of anhydrous substance): solution: C 33.57 N 3.80 M 7.83 E 22.57 (a 10.99 5 2.24 found.: C 33.57 N 3.76 M 7.82 E 22.63 (for 11.06 5 2.18

Example 51 a). (1-(4-perfluorooctylsulfonyl)piperazine|iamide 6-M-benzyloxycarbonyl-2-M-(O-D-Y-galactopyranosyl-(1-4)-gluconosyl|-I-lysine

A solution of 13.3 g (37.2 mmol) is added dropwise to a mixed solution of 4.98 g (b.0 mmol) of the compound indicated in the title of example 21c in 40 ml of absolute dimethyl sulfoxide at room temperature

O-8-O-galactopyranosyl-(1-5)-O-glucono-1,5-lactone (lactobionolactone; production according to (a) UMIatzv T.u.,

Riezza5 M.K., soyavieip I9U., Sagropuag. Kev. 67, SI. (1978); (b) Korauavzpi K., Zityoto N, Ipa U., Roiut. in. 17 (1985), p. 567; (c) Nigoti Kpapo, Kaiziko 5opaa and Auako Kozaka, Viosopivdaste Spet. 6 (1995), pp. 131-134) in 40 ml of absolute dimethyl sulfoxide. The reaction solution obtained in this way is then stirred for 14 hours at 40"C. For processing, this solution is mixed at room temperature with 500 ml of absolute 2-propanol, the resulting colorless precipitate is separated by vacuum filtration using frit 04 and then thoroughly washed with absolute 2-propanol in the total amount 250 ml. The solid substance obtained in this way is further dissolved in ZbOO ml of distilled water and subjected to ultrafiltration three times through an ultrafiltration membrane UM3 (AMISOM?, limit permeability: 3000Da).

Such triple ultrafiltration allows for the separation of excess lactobionolactone from the target product, as well as possible low molecular weight components. Finally, the sediment on the ultrafiltration membrane is completely dissolved in 300 ml of distilled water and lyophilized.

Yield: 6.51 g (92.795 from theory) in the form of a colorless lyophilisate.

Water content: 10.03905.

Elemental analysis (in terms of anhydrous substance): solution: С 38.98 Н 4.05 М 4.79 Р 27.58 52.74 found.: С 39.04 Н 4.09 М 4.82 Е 27, 61 5 2.71 b) (1-(4-perfluorooctylsulfonyl)piperazine-iamide 2-M-(O-D-YUO-galactopyranosyl-(1--54)-gluconosyl)-lysine 5.0g (4, 27 mmol) of the compound obtained in Example 51a is dissolved in 100 ml of ethanol, mixed with 0.5 g of Perlman's catalyst (2095 Pa/C) and hydrogenated until quantitative absorption of hydrogen at a hydrogen pressure of 1 atmosphere. After that, the catalyst is removed by vacuum filtration, then washed with ethanol and concentrated to dryness in vacuo to give the title compound as a colorless and viscous oil.

Yield: 4.36g (98.595 from theory).

Elemental analysis: solution: C 34.76 H 3.99 M 5.40 E 31.51 5 3.09 found: C 34.78 H 4.04 M 5.34 E 31.51 5 3.15 ) (1-(4-perfluorooctylsulfonyl)piperazinylamide /2-M-(O-pD-O-galactopyranosyl-(1-»4)-gluconosyl|-6-M-

I1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-ylpentanoyl)-1,4,7,10-tetraazacyclododecani|-I - lysine, Сd-complex 5 .54 g (8.6 mmol, 2.2 molar equivalents in terms of the amount of the used amine component from example 516) (described in the application OE 19728954 С1| in example 31p of the sa-complex 10-(4-carboxy-1-methyl-2- oxo-3-azabutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 0.37 g (8.2 mmol) of anhydrous lithium chloride at 40"С are dissolved with stirring in bOml of absolute dimethyl sulfoxide and at at this temperature is mixed with M-hydroxysuccinimide in a total amount of 1.01 g (8.8 mmol) and with 3.85 g (4.0 mmol) of the compound indicated in the title of Example 516, dissolved in bbml of absolute dimethyl sulfoxide. After cooling to room temperature, the reaction solution is mixed with 1 ,82 g (in 8, dmmol) of M,M'-dicyclohexylcarbodiimide and stirred for 12 hours at room temperature.

The resulting suspension is then mixed with a sufficient amount of acetone/2-propanol (in a 1:1 ratio) to completely precipitate the above title compound and the precipitate is separated by vacuum filtration. The precipitate obtained in this way is then dissolved in 300 ml of water and dicyclohexylurea, which has not dissolved, is filtered off. The filtrate is subjected to ultrafiltration three times through an ultrafiltration membrane AMISOM UM-

With (limit permeability: 3000Da). Such three-fold ultrafiltration allows to separate the excess sa-complex from the target product, as well as possible low-molecular components. Finally, the sediment on the ultrafiltration membrane is completely dissolved in 500 ml of distilled water and lyophilized.

Yield: 4.64 g (70.495 from theory) in the form of a colorless lyophilizate.

NgO content (when using Karl Fischer's reagent): 10.08905.

Elemental analysis (in terms of anhydrous substance): solution: С 35.70 Н4.22 М 7.65 BE 1.59 (а 9.54 5 1.95 found.: С 35.77 Н 4.17 М 7 ,71 E 19,61 Sa 9,60 5 1,99

Example 52 a) 2-M-trifluoroacetyl-6-M-benzyloxycarbonyllysine 100g (356.7 mmol) of 6-M-benzyloxycarbonyllysine is dissolved in a mixture of 1000ml trifluoroacetic acid ethyl ether and 500ml ethanol and stirred at room temperature for 24 hours. After that, it is evaporated to dryness and the residue is crystallized from diisopropyl ether.

Yield: 128.9 g (9695 from theory) of colorless crystalline powder.

Elemental analysis: soln.: C 51.07 H 5.09 E 15.14 M 7.44 found.: C 51.25 H 5.18 E 15.03 M 7.58 b) (1-(4-perfluorooctylsulfonyl ) piperazinamide of 2-M-trifluoroacetyl-6-M-benzyloxycarbonyllysine

164.2 g (0.664 mmol) of EEDH (ethyl ether of 2-ethoxy-1,2-dihydroquinoline-1-carboxylic acid) and stirred overnight at room temperature, then evaporated to dryness in vacuo and chromatographed on silica gel (eluent: dichloromethane/methanol 20:1).

Yield: 286g (9395 from theory) of a colorless solid.

Elemental analysis: solution: C 36.30 H 2.83 E 41.01 M 6.05 5 3.46 found: C 36.18 H 2.94 E 40.87 M 5.98 5 3.40 in ) (1-(4-perfluorooctylsulfonyl)piperazine|6-M-benzyloxycarbonyllysine amide

A solution of 280 g (302.2 mmol) of the compound indicated in the title of example 526 in 2000 ml of ethanol at 0"C is bubbled for one hour with gaseous ammonia. Then the mixture is stirred for 4 hours at 0"C. After that, it is evaporated to dryness and the residue is separated from the water by stirring. The solid was filtered off and dried in vacuo (5075).

Yield: 243.5 g (9795 from theory) of amorphous solid.

Elemental analysis: solution: C 37.60 H 3.28 E 38.89 M 6.75 5 3.86 found: C 37.15 H 3.33 E 38.78 M 6.68 5 3.81 g ) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-benzyloxycarbonyl-2-M-(3,6,9,12,15-pentaoxahexadecanoyl)lysine

To 50 g (60.20 mmol) of the compound indicated in the title of example 528 and 7.10 g (/Omol) of triethylamine in

A solution of 19.93 g (70 mmol) of 3,6,9,12,15-pentaoxahexadecanoic acid chloride (obtained according to Gierid5 App. Spec. (6), (1980), p. 852-) is added dropwise to 35 ml of dichloromethane at 0"C. 862| in 5 Oml of dichloromethane and stirred for 1 hour at 0"C. Next, 200 ml of 595% aqueous hydrochloric acid was added and stirred for 5 minutes at room temperature. The organic phase was separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue was chromatographed on silica gel ( eluent: dichloromethane/acetone in a ratio of 15:1)

Yield: 53.7 g (9390 from theory) of colorless viscous oil.

Elemental analysis: solution: C 33.83 H 4.94 E 3.34 M 5.84 5 33.69 found: C 33.75 H 5.05 E 3.29 M 5.78 5 33.75 d ) (1-(4-perfluorooctylsulfonyl)piperazinamide 2-H-(3,6,9,12,15-pentaoxahexadecanoyl)lysine 50 g (52.15 mmol) of the compound indicated in the title of example 52 g is dissolved in 500 ml of ethanol and BG of palladium is added of catalyst (1096 Pa/C). After this, hydrogenation is carried out at room temperature. The catalyst is then filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 43.0 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 27.68 H 5.01 E 39.17 M 6.79 5 3.89 found: C 27.60 H 5.13 E 39.09 M 6.68 5 3.81 e ) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-

Tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|-2-M-(3,6,9,12,15-pentaoxahexadecanoyl)lysine, per-complex 20g (24 .25 mmol) of the compound indicated in the title of example 52d, 2.79 g (24.25 mmol) of M-hydroxysuccinimide, 2.12 g (5 mmol) of lithium chloride and 15.27 g (24.25 mmol) of C4-complex 1,4,7-tris (carboxylatomethyl)-10-|(3-aza-4-oxo-5-methyl-5-yl)upentanoic acid|-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 200 ml of dimethylsulfoxide. Next, at 107"C, 8.25 g (40 mmol) of /M,M-dicyclohexylcarbodiimide is added and then stirred overnight at room temperature. The solution is poured into

Add 0.000 ml of acetone and stir for 10 minutes. The precipitated solid is filtered off and then purified by chromatography (silica gel KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 28.21 g (8195 from theory) of a colorless solid.

Water content: 11.095.

Elemental analysis (in terms of anhydrous substance): solution: С 31.78 Н 4.84 Е 22.49 М 8.78 52.23 Са 10.95 found.: С 31.74 Н 4.98 Е 22, 39 M 8.69 52.15 Sa 10.87

Example 53 a) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-I3,9-bis(tert-butyloxycarbonylmethyl)-3,6,9-triazaundecane-1,11-dicarboxylic acid-bis(tert-butyl ether)-6-carbonylmethyl|/|-2-M-(3,6,9,12,15- pentaoxahexadecanoyl)lysine

To a solution of 20 g (24.08 mmol) of the compound indicated in the title of example 52d, 14.88 g (24.0 v8 mmol) of bis(tert-butyl ether) 3,9-bis(tert-butyloxycarbonylmethyl-3,6,9-triazaundecane-1 ,11-dicarboxylic acid and 2.17 g (24.08 mmol) of M-hydroxysuccinimide in 150 ml of dimethylformamide at 0"С add 8.25 g (40 mmol)

M,M-dicyclohexylcarbodiimide. The mixture is stirred for 10 minutes at 0"C, and then overnight at room temperature. The precipitated urea is filtered off, the filtrate is evaporated to dryness under vacuum and chromatographed on silica gel (eluent: dichloromethane/ethanol in a ratio of 20:1).

Yield: 31.61 g (9195 from theory) of viscous oil.

Elemental analysis: solution: C 40.80 H 6.71 P 22.39 M 6.80 52.22 found: C 40.72 H 6.82 E 22.30 M 6.75 5 2.14 b) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-(b-carbonylmethyl-3,9-bis(carboxylatomethyl)-3,6,9-triazaundecanedicarboxylic acid-1-carboxy-11-carboxylato|-2-M-( 3,6,9,12,15- pentaoxahexadecanoyl)lysine, sa-complex, sodium salt

30 g (20.8 mmol) of the compound specified in the title of example 53a is dissolved in 300 ml of trifluoroacetic acid and stirred at room temperature for 5 hours. After that, it is evaporated to dryness, the residue is dissolved in 30 ml of water and the pH value is set to 2.5 using 1095 aqueous Mahon. Next, 3.77 g (10.4 mmol) of gadolinium oxides are added and stirred for 1 h at 60 °C. After that, the mixture is allowed to cool to room temperature and the pH value is adjusted to 7.4 with caustic sodium.

Then it is evaporated to dryness and the residue is purified on silica gel KR-18 (eluent: water/acetonitrile gradient).

Yield: 19.18 g (6795 from theory) of a colorless amorphous solid.

Water content 9.895.

Elemental analysis (in terms of anhydrous substance): solution: C 28.80 N 4.25 E 23.47 M 7.12 52.33 (Ca 11.48 Ma 1.67 detected: C 28.67 N 4 ,34 E 23.38 M 7.03 522.27 Sa 11.37 Ma 1.74

Example 54 a) Lysine 1-(4-perfluorooctylsulfonylpiperazinamide) 20 g (24.0 v8 mmol) of the compound indicated in the title of example 52 c is dissolved in 30 ml of ethanol and 4 g of a palladium catalyst (1096 Pa/C) is added. After that, it is hydrogenated at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 16.77 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 31.04 H 3.04 P 46.38 M 8.04 5 4.60 found: C 30.97 H 3.15 E 46.91 M 7.98 5 4.51 b ) (1-(4-perfluorooctylsulfonylpiperazinamide /2,6-M,M'-bis(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza- 4-oxo-5-methyl-5-yl)|lysine, sa-complex (metal complex

HMI) 10 g (14, Zbmmol) of the compound indicated in the title of example 54a, 3.34 g (29 mmol) of M-hydroxysuccinimide, 2.54 g (mmol) of lithium chloride and 18.26 g (29 mmol) of the cCa-complex 1,4,7- tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-yl)-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 200 ml of dimethyl sulfoxide. Then, at 107"C, 12.38 g (bOmoles) of M5M-dicyclohexylcarbodiimide are added and then stirred overnight at room temperature. The solution is poured into 3000 ml of acetone and stirred for 100 min. The precipitated solid is filtered and then purified by chromatography (silica gel KR -18, eluent: water/ethanol/acetonitrile gradient).

Yield: 19.02 g (6995 from theory) of a colorless solid.

Water content: 11.3905.

Elemental analysis (in terms of anhydrous substance): solution: С 35.03 Н4.04 Р 16.82 М 10.21 51.67 Са 16.38 found.: С 34.96 Н 4.13 Е 16.74 M 10.16 51.61 Sa 16.33

Example 55 a) Methyl ether of 2-I4-(3-oxaethylpropionate)|phenylacetic acid

To 200 g (1.204 mol) of 4-hydroxyphenylacetic acid methyl ether and 212 g (2 mol) of sodium carbonate in 2000 ml of acetone, add 233.8 g (1.4 mol) of 2-bromoacetic acid ethyl ether and boil under reflux for 5 hours. The solid substance is filtered off and evaporated to dryness under vacuum.

The residue is chromatographed on silica gel (eluent: m-hexane/ethyl acetic acid in the ratio

Yield: 288.5 g (9595 from theory) of colorless oil.

Elemental analysis: solution: C 61.90 H 6.39 found: C 61.75 H 6.51 b) Methyl ether of 2-I4-(3-oxaethylpropionate)|phenyl-2-bromoacetic acid

201 g (1.13 mol) of M-bromosuccinimide and 100 mg of dibenzyl peroxide are added to 285 g (1.1 mol) of the compound indicated in the title of example 55a, dissolved in 2000 ml of carbon tetrachloride, and refluxed for 2 hours. Then it is cooled in an ice bath, the precipitated succinimide is filtered off and the filtrate is evaporated to dryness under vacuum. The residue is purified on silica gel (eluent: n-hexane/acetone in a ratio of 15:1).

Yield: 359.2 g (9695 from theory) of colorless, viscous oil.

Elemental analysis: solution: C 47.28 H 4.57 V 24.16 found: C 47.19 H 4.71 V 24.05 c) Methyl ether 2-I4-(3-oxaethylpropionate)|phenyl-2 -|1-(1,4,7,10-tetraazacyclododecan-7-yl|acetic acid

To 6ozZg (3.5mol) of 1,4,7,10-tetraazacyclododecane in bbbOOml of chloroform, add 350g (1.057mol) of the compound indicated in the title of example 556, and stir overnight at room temperature. Next, 3000 ml of water is extracted three times, the organic phase is dried over magnesium sulfate and evaporated to dryness under vacuum.

The residue without additional purification is used in the next reaction (example 55Hg).

Yield: 448g (quantitative) of viscous oil.

Elemental analysis: solution: C 59.70 H 8.11 M 13.26 found: C 59.58 H 8.20 M 13.18 g) 0 2-I4-(3-oxapropionic acid)|phenyl-2- (1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-10-yl|acetic acid 445 g (1.053 mol) of the compound indicated in the title of example 55c and 496 g (5.27 mol) of chloroacetic acid dissolve in 4000 ml of water. Then the pH value is set to 10 with the help of 3095 aqueous caustic sodium. Next, the mixture is heated to 70"C and the pH value is maintained at the level of 10 by adding 3090 aqueous caustic sodium. The mixture is stirred for 8 hours at 70"C . After that, the pH value is set to 13 and refluxed for 30 minutes. Then the solution is cooled in an ice bath and the pH value is set to 1 by adding concentrated hydrochloric acid. After that, it is evaporated to dryness in a vacuum. The residue is dissolved in 4000 ml of methanol and stirred for hours at room temperature. The common salt that has precipitated is filtered off, the filtrate is evaporated to dryness and the residue on silica gel KR-18 (eluent: water/ethanol/acetonitrile gradient).

Yield: 403g (69905 from theory) of a colorless solid.

Water content: 10.295.

Elemental analysis (in terms of anhydrous substance): solution: 251.98 86.18 M 10.10 found: C 51.80 H 6.31 M 10.01 d) /2-I4-(3-oxapropionic acid) |phenyl-2-(1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-10-yl|acetic acid, sa-complex

130.7g (360.65mmol) of gadolinium oxide is added to 400g (721.3mmol) of the compound indicated in the title of example 55g in 2000ml of water and stirred for 5 hours at 80°C. The solution is filtered and the filtrate is lyophilized.

Yield: 511g (quantitative) of amorphous solid.

Water content: 11.095.

Elemental analysis (in terms of anhydrous substance): solution: С 40.67 Н 4.41 Са 22.19 М 7.98 detected: С 40.51 Н 4.52 Са 22.05 М 8.03 e) (4-perfluorooctylsulfonyl)piperazine|amide 2,6-M,M'-bis(2-(4-(3-oxapropionyl)phenyl|-2-|1,4,7-tris(carboxylatomethyl)-1,4, 7,10-tetraazacyclododecan-10-yl|acetic acid|lysine, digadolinium complex, disodium salt 10g (14, Zbmmol) of the compound indicated in the title of example 54a, 3.45g (ZOmole) of M-hydroxysuccinimide, 2.54g (bmmol) of lithium chloride and 21.26 g (30 mmol) of the compound indicated in the title of example 55d are dissolved under moderate heating in 250 ml of dimethylsulfoxide. Then, at 107"C, 16.51 g (8 mmol) of M,M-dicyclohexylcarbodiimide are added and then stirred overnight at room temperature The solution is poured into 2000 ml of acetone and stirred for 10 min. The solid substance that has precipitated is filtered off and then purified by chromatography (silica gel KR-18, eluent: water/ethanol/acetonitrile gradient). This substance is dissolved in a small amount of of water, the pH value is set to 7.4 with caustic sodium and lyophilized.

Yield: 21.02 g (6995 from theory) of a colorless solid.

Water content: 11.295.

Elemental analysis (in terms of anhydrous substance): solution: C 37.36 N 3.66 E 15.22 (a 14.82 M 7.92 Ma 2.17 5 1.51 detect.: C 37.28 N 3.74 E 15.14 Ca 14.75 M 8.03 Ma 2.23 5 1.46

Example 56 a) (1-(4-perfluorooctylsulfonyl)piperazine|amide 2,6-M,M'-bisIb-carbonylmethyl-3,9-bis(tert-butyloxycarbonylmethyl)-3,6,9-triazaundecane-1,11 -dicarboxylic acid-bis(tert-butyl ether)|lysine

To a solution of 10 g (14.3 mmol) of the compound specified in the title of example 54a, 18.53 g (3 mmol) of bis(tert-butyl ether) 3,9-bis(tert-butyloxycarbonylmethyl)-6-carboxymethyl-3,6,9- of triazaundecane-1,11-dicarboxylic acid and 3.45 g (30 moles) of M-hydroxysuccinimide in 150 ml of dimethylformamide at 0"C, add 10.32 g (5 mmoles) of M,M-dicyclohexylcarbodiimide. The mixture is stirred for 2 hours at room temperature, and then overnight at room temperature.The precipitated urea is filtered off, the filtrate is evaporated to dryness under vacuum and chromatographed on silica gel (eluent: dichloromethane/ethanol in a ratio of 20:1).

Yield: 19.60 g (7295 from theory) of viscous oil.

Elemental analysis: solution: C 49.41 H 6.75 E 17.03 M 7.39 51.69 found: C 49.35 H 6.82 E 16.92 M 7.32 51.62 b) 2 ,6-M,M-bisIb-carbonylmethyl-3,9-bis(carboxylatomethyl)-3,6,9-triazaundecanedicarboxylic acid-1-carboxy-11-carboxylatolysine-|1-(4-perfluorooctylsulfonyl)piperazinamide, complex , sodium salt) 15 g (7.9 mol) of the compound specified in the title of example 5ba is dissolved in 530 ml of chloroform and 200 ml of trifluoroacetic acid is added. The mixture is stirred for 10 minutes at room temperature. After that, it is evaporated to dryness in a vacuum and the residue is dissolved in 150 ml of water. Next, 2.87 g (7.91 mmol) of gadolinium oxide are added and stirred for 5 hours at 80"C. Then the mixture is allowed to cool to room temperature and the pH value is set to 7.4 using 2N caustic sodium. The solution is evaporated to dryness under vacuum and purified on KR-18 (eluent: water/ethanol/acetonitrile gradient).

Yield: 8.11 g (57905 from theory) of a colorless amorphous solid.

Water content: 9.695.

Elemental analysis (in terms of anhydrous substance): solution: С 30.70 Н 3.08 Са 17.48 М 7.78 Ма 2.56 5 1.78 found.: С 30.58 Н 3.19 Са 17 .42 M 7.71 Ma 2.68 51.72

Example 57 a) (1-(4-perfluorooctylsulfonyl)piperazine|iamide /6-M-benzyloxycarbonyl-2-M-(b-carboxymethyl-3,9-bis(tert-butyloxycarbonylmethyl)-3,6,9-triazaundecane- 1,11-dicarboxylic acid-bis(tert-butyl ether) of lysine

To a solution of 20 g (24.0 mmol) of the compound indicated in the title of example 52c, 14.88 g (24.08 mmol) of bis(tert-butyl ether) 3,9-bis(tert-butyloxycarbonylmethyl)-6-carboxymethyl-3,6, 9-triazaundecane-1,11-dicarboxylic acid and 2.88 g (25 mmol) of M-hydroxysuccinimide in 100 ml of dimethylformamide at 0"С add 8.25 g (40 mol) of M,M-dicyclohexylcarbodiimide. The mixture is stirred for 2 hours at RT, and then overnight at room temperature.The precipitated urea is filtered off, the filtrate is evaporated to dryness in vacuo and chromatographed on silica gel (eluent: dichloromethane/ethanol 20:1).

Yield: 27.21 g (7995 from theory) of viscous oil.

Elemental analysis: solution: C 47.03 H 5.64 E 22.58 M 6.85 5 2.24 found: C 46.94 H 5.58 E 22.65 M 6.84 5 2.31 b ) (1-(4-perfluorooctylsulfonyl)piperazineamide 2-M-(carbonylmethyl-3,9-bis(tert-butyloxycarbonylmethyl)-3,6,9-triazaundecane-1,11-dicarboxylic acid-bis(tert-butyl ether )|lysine 25 g (17.48 mmol) of the compound indicated in the title of example 57a is dissolved in 350 ml of ethanol and 5 g of a palladium catalyst (1096 Pa/C) is added. After that, it is hydrogenated at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness in vacuum

Yield: 22.66 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 44.48 H 5.75 E 24.92 M 7.56 5 2.47 found: C 44.59 H 5.81 E 25.03 M 7.46 522.52 c) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo- 5-methyl-5-yl)|-2-M-Ib-carbonylmethyl-3,9-bis(tert-butyloxycarbonylmethyl)-3,6,9-triazaundecane-1,11-dicarboxylic acid-bis(tert-butyl ether )|lysine, sodium complex of 20 g (15.4 mmol) of the compound indicated in the title of example 576, 1.78 g (15.4 mmol) of M-hydroxysuccinimide, 1.48 g (35 mmol) of lithium chloride and 9.72 g (15.4 mmol) sa complex of 1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-ylopentanoic acid-1,4,7,10-tetraazacyclododecane) is dissolved under moderate heating in 150 ml of dimethyl sulfoxide . Next, at 107"C, 5.16 g (25 mmol) of /M,M-dicyclohexylcarbodiimide is added and then stirred overnight at room temperature. The solution is poured into 2500 ml of acetone and stirred for 10 minutes. The solid substance that has precipitated is filtered off and then purified by chromatography (silica gel KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 22.94 g (7895 from theory) of a colorless solid.

Water content: 7.995.

Elemental analysis (in terms of anhydrous substance): solution: С 42.22 Н 5.29 Е 16.95 са 8.25 М 8.82 5 1.68 found.: С 42.15 Н 5.41 Е 16 .87 Са 8.13 M 8.70 5 1.60 g) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10 - tetraazacyclododecane-10-(3-aza-4-oxo-5-methyl-5-ylpentanoyl)|-2-M-(b-carbonylmethyl-3,9-bis(carboxylatomethyl)-3,6,9-triazaundecane- dicarboxylic acid-carboxy-11-carboxylato-2|lysine, digadolinium complex, sodium salt 20 g (10.49 mmol) of the compound indicated in the title of example 57c is dissolved in 200 ml of trifluoroacetic acid. The mixture is stirred for 2 min at room temperature. Then it is evaporated to dryness in vacuum and the residue is dissolved in 150 ml of water. Then 1.90 g (5.25 mmol) of gadolinium oxide is added and stirred for 5 hours at 80"C. The mixture is allowed to cool to room temperature and the pH value is set to 7.4 with caustic sodium. The solution is dried evaporated in a vacuum and purified on silica gel KR-18 (eluent: a gradient of water/ethanol/ acetonitrile).

Yield: 11.89 g (6195 from theory) of a colorless amorphous solid.

Water content: 10.295.

Elemental analysis (in terms of anhydrous substance): solution: С 32.97 Н 3.47 Е 17.39 (а 16.93 М 9.05 Ма 1.24 51.73 detect.: С 32.90 Н 3 .53 E 17.31 Ca 16.87 M 8.92 Ma 1.33 5 1.67

Example 58 a) tert-Butyl ether of 5,6-bis(benzyloxy)-3-oxahexanoic acid 100 g (376.2 mmol) of 1,2-di-O-benzylglycerol (obtained according to Spec. RPuz. Giria 5, 43(2) (1987), pp. 113-127| and 5g of tetrabutylammonium hydrosulfate are dissolved in a mixture of 400ml of toluene and 200ml of 5095 aqueous caustic sodium. Then, at 0"C for 30 minutes, 7a8g (400 mmol) of tert-butyl 2-bromoacetate is added dropwise acid and then stirred for 1 h at 0"C. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: M-hexane/acetone in a ratio of 20:1).

Yield: 133.4 g (9495 from theory) of colorless oil.

Elemental analysis: solution: С 71.48 Н 7.82 detected: С 71.61 Н 7.92 b) 5,6-bis(benzyloxy)-3-oxahexanoic acid 130 g (336.4 mmol) of the compound specified in of the title of example 5b8a, is dissolved in 200 ml of dichloromethane and at 0"C, 100 ml of trifluoroacetic acid is added. The mixture is stirred for 4 hours at room temperature and then evaporated to dryness. The residue is crystallized from pentane/diethyl ether.

Yield: 102.2 g (9295 from theory) of a waxy solid.

Elemental analysis: solution: C 69.07 H 6.71 found: C 69.19 H 6.82 c) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-benzyloxycarbonyl-2-M-|1 ,4,7- tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|lysine, cSid-complex 50g (60 , 20 mmol) of the compound indicated in the title of example 52c, 6.93 g (60.20 mmol) of M-hydroxysuccinimide, 5.09 g (120 mmol) of lithium chloride and 37.91 g (60.20 mmol) of Sba-complex 1,4,7-tris (carboxylatomethyl)-1,4,7,10-tetraazacyclo to decan-10-(pentanoyl-3-aza-4-oxo-5-methyl-b5-yl) is dissolved under moderate heating in 400 ml of dimethylsulfoxide. Then, at 10"C, add 20.63 g (100 mmol) of /M,M- dicyclohexylcarbodiimide and then stirred overnight at room temperature. The solution was poured into

Add 0.000 ml of acetone and stir for 10 minutes. The precipitated solid is filtered off and then purified by chromatography (silica gel KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 75.53 g (8795 from theory) of a colorless solid.

Water content: 10.1905.

Elemental analysis (in terms of anhydrous substance): solution: С 37.48 Н 3.84 Е 22.39 (а 10.90 М 8.74 52.22 found.: С 37.39 Н 4.02 Е 22 ,29 tsa 10.75 M 8.70 52.22 g) (1-(4-perfluorooctylsulfonyl)piperazinamide 2-M-(11,4,7-tris(carboxylatomethyl)-1,4,7,10- tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5methyl-5-yl|lysine, Ca-complex) 70g (48.53mmol) of the compound specified in the title of example 58c is dissolved in a mixture of 500ml of water and 100l of ethanol and add 5 g of palladium catalyst (1095 Pa/C). After that, hydrogenate at room temperature. The catalyst is then filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 63.5 g (quantitative) of a colorless solid.

Water content: 9.895.

Elemental analysis (in terms of anhydrous substance): solution: С 37.48 Н 3.84 Е 22.39 (а 10.90 М 8.74 52.22 found.: С 37.39 Н 4.03 Е 22 ,31 Са 10.78 M 8.65 5 2.20 d) (1-(4-perfluorooctylsulfonyl)piperazine|iamide /6-M-I|5,6-bis(benzyloxy)-3-oxahexanoyl|-2- M-(1,4,7-tris(carboxylatomethyl)-1,4,710-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|lysine, cSid-complex 10g (7 .64 mmol) of the compound indicated in the title of example 58g, 3.30 g (10 mmol) of the compound indicated in the title of example 586, 0.85 g (20 mmol) of lithium chloride and 1.15 g (1LO mmol) of M-hydroxysuccinimide are dissolved under moderate heating in 150 ml of dimethyl sulfoxide . Next, at 10"C, 3.10 g (15 mmol) of M,M'-dicyclohexylcarbodiimide are added and stirred for 8 hours at room temperature. The reaction solution is poured into 2000 ml of acetone and the precipitate that has precipitated is isolated. The compound indicated in the title is purified on silica gel KR-18 (eluent: water/ethanol/acetonitrile gradient).

Yield: 11.14 g (9095 from theory) of a colorless amorphous solid.

Water content: 4.395.

Elemental analysis (in terms of anhydrous substance): solution: С 41.51 Н 4.29 ГЭ 19.93 М 7.78 (а 9.70 5 1.98 found.: С 41.45 Н 4.38 Е 19.84 M 7.70 Са 9.58 5 1.90 e) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(5,6,-dihydroxy-3-oxahexanoyl)-2-M-( 1,4,7-tricarboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|lysine, cSid complex 10g (6.17mmol ) of the compound indicated in the title of example 58d is dissolved in 200 ml of ethanol and 3 g of palladium catalyst (1096 Pa/C) is added. After that, they are hydrogenated at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 8.89 g (quantitative) of a colorless solid.

Water content: 3.195.

Elemental analysis (in terms of anhydrous substance): solution: C 35.03 N 3.99 E 22.42 (a 10.92 M 8.75 5 2.23 det.: C 34.95 N 4.12 E 22.30 Sa 10.78 M 8.71 52.18

Example 59 a) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-benzyloxycarbonyl-2-M-I5,6-bis(benzyloxy)-3-oxahexanoyl|lysine

To a solution of 20 g (24.08 mmol) of the compound indicated in the title of example 52c, 9.91 g (30 mmol) of the compound indicated in the title of example 586, and 3.45 g (30 mmol) of M-hydroxysuccinimide in 100 ml of dimethylformamide at 0"C is added 9 28 g (45 mmol) of M,M-dicyclohexylcarbodiimide. The mixture was stirred for 2 hours at 0"C and then overnight at room temperature. The precipitated urea is filtered off, the filtrate is evaporated to dryness under vacuum and chromatographed on silica gel (eluent: dichloromethane/ethanol in a ratio of 20:71).

Yield: 24.50 g (8995 from theory) of viscous oil.

Elemental analysis: solution: C 47.29 H4.14 E 28.26 M 4.90 5 2.81 found: C 47.14 H4.26 E 28.17 M 4.91 52.69 b) (1 -(4-perfluorooctylsulfonyl)piperazinamide 2-M-(5,6-dihydroxy-3-oxahexanoyl)lysine 20 g (17.5 mmol) of the compound indicated in the title of example 59a is dissolved in 30 ml of ethanol and 5 g of palladium catalyst (1096 Ra/C).After that, hydrogenate at room temperature.The catalyst is then filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 17.65 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 44053410 R 32.02 M 5.55 5 3.18 found: C 43.96 H 4.21 E 31.94 M 5.48 5 3.24 c) (1-(4 -perfluorooctylsulfonyl)piperazinamide 6-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5 -yl)|lysine, (x34-complex of 15g (14.87mmol) of the compound indicated in the title of example 596, 1.73g (15mmol) of M-hydroxysuccinimide, 1.27g (ZOmmol) of lithium chloride and 9.48g (15mmol) of -complex of 1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-yl)pentanoic acid-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 100 ml of dimethylsulfoxide. Next, at 107C, 5.16 g (25 mol) of M,M-dicyclohexylcarbodiimide are added and then stirred overnight at room temperature. The solution is poured into 1500 ml of acetone and stirred for 100 min. The precipitated solid is filtered and then purified by chromatography ( silica gel KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 19.28 g (8095 from theory) of a colorless solid.

Water content: 10.3905.

Elemental analysis (in terms of anhydrous substance): solution: С 41.51 Н 4.29 Р 19.93 Са 9.70 М 7.78 5 1.98 found.: С 41.37 Н 4.40 Е 19 .88 Са 9.58 M 7.67 5 1.85

Example 60 a) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-benzyloxycarbonyl-2-M-|(2,6-M,M'-bis(benzyloxycarbonyl)lysyl|lysine 20g (24.0 dmmol) of compounds , indicated in the title of example 52b, and 2.53 g (25 mmol) of triethylamine are dissolved in 200 ml of tetrahydrofuran (THF) and 14.46 g (27 mmol) of di-M,M'-paranitrophenol ether of 2-lysine are added. The mixture is stirred for 5 hours at 50" C. After that, it is evaporated to dryness under vacuum and the residue is chromatographed on silica gel (eluent: dichloromethane/methanol in a ratio of 20:1).

Yield: 28.07g (9595 from theory) of a colorless solid.

Elemental analysis: solution: C 46.99 H 4.19 E 26.32 M 6.85 5 2.61 found: C 47.08 H 4.32 E 26.21 M 6.75 5 2.54 b ) (1-(4-perfluorooctylsulfonyl)piperazinamide 2-M-(lysyl)lysine, trihydrobromide

To 25 g (20.37 mmol) of the compound indicated in the title of example bba, add 100 ml of hydrobromic acid in glacial acetic acid (4895) and stir for 2 hours at 40 °C. Then cool to 0 °C, add 1500 ml of diethyl ether dropwise and the precipitated solid is filtered off.

After drying in a vacuum (60"C), 21.52 g (9995 from theory) of a clear yellow crystalline solid are obtained.

Elemental analysis: solution: C 27.01 N 3.40 Vg 22.46 RE 30.26 M 7.87 5 3.00 found: C 26.92 N 3.53 Vi 22.15 E 30.14 M 7.69 5 2.87 c) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl -3-aza-4-oxo-5-methyl-5-yl)|-2-M-(2,6-M,M'-bis(1,4,7-tris(carboxylatomethyl)-1,4, 7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl/|lysyl lysine, trigadolinium complex 31.49 g (5 mol) of the Si-complex 1,4,7-tris(carboxylatomethyl )-10-(3-aza-4-oxo-5-methyl)-5- yl . Next, at 10"C, 16.51 g (8 mmoles) of M,M-dicyclohexylcarbodiimide are added and stirred for 5 hours at 10 "C. To this mixture, 10 g (9.37 mmol) of the compound specified in the title of example 606 and 3.03 g ( ZOmmoles) of triethylamine and stir for 12 hours at 60"C. Then the mixture is allowed to cool to room temperature emperature and after that it is poured into 300 ml of acetone. The deposited precipitate is filtered off and purified on silica gel KR-18 (eluent: water/ethanol/acetonitrile gradient).

Yield: 16.7 g (6790 from theory) of a colorless solid.

Water content: 7.995.

Elemental analysis (calculated per anhydrous substance): solution: С 36.58 Н 4.43 Р 12.14 (а 17.74 М 11.06 5 1.14 found.: С 36.47 Н 4.54 Е 12.03 Sa 17.65 M 10.95 51.21

Example 61 a) 1,7-bis(benzyloxycarbonyl)-4-(3,6,9,12,15-pentaoxahexadecanoyl)-1,4,7,10-tetraazacyclododecane

To 18.13 g (68.1 mmol) of 3,6,9,12,15-pentaoxahexadecanoic acid and 30 g (68.1 mmol) of 1,7-di-2-cyclene (obtained according to 7. Komas5 and A.O. Zpeigtu, U. Spec. 5os. Spec. Sottyp., 2 (1995), p. 185), 24.73 g (100 mmol) of EEDH (ethyl ether of 2-ethoxy-1,2-dihydroquinoline) are added to 3 ml of tetrahydrofuran at 0"C -1- carboxylic acid) and stirred overnight at room temperature, then evaporated to dryness in vacuo and chromatographed on silica gel (eluent: dichloromethane/methanol 20:1).

Yield: 19.13 g (4295 from theory) of a colorless solid.

Elemental analysis: solution: C 61.03 H 7.61 M 8.13 found: C 60.92 H 7.75 M 8.04 b) 1,7-bis(benzyloxycarbonyl)-4-(3,6 ,9,12,15-pentaoxahexadecanoyl)-10-(2H,2H,4H,5H,5H-3-oxaperfluorotridecanoyl)-1,4,7,10-tetraazacycle odo decane

To 18 g (26.9 mmol) of the compound specified in the title of example b, and 14.05 g (26.91 mmol) of 2Н,2ННАННЙАН,5НН,5Н-3-oxaperfluorotridecanoic acid (obtained according to OE 19603033), in 12.36 g (500 mmol) of EEDH (ethyl ether of 2-ethoxy-1,2-dihydroquinoline-1-carboxylic acid) is added to 30 ml of tetrahydrofuran at 0"C and stirred overnight at room temperature. After that, it is evaporated to dryness in a vacuum and chromatographed on silica gel (eluent: dichloromethane/methanol in a ratio of 20:1).

Yield: 21.51 g (6795 from theory) of a colorless solid.

Elemental analysis: solution: C 47.32 H4.82 E 27.07 M 4.70 found: C 47.26 H 5.01 E 26.94 M 4.59 c) 1-(3,6,9 ... , dissolve in 200 ml of ethanol and add 2.5 g of palladium catalyst (1095 Pa/C). After that, they are hydrogenated at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 15.5 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 40.27 N 4.90 ER 34.93 M 6.06 detected: C 40.15 N 4.99 E 34.87 M 5.94 g) o01.7-bis(1 ,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|-4-(3,6, 9,12,15-pentaoxahexadecanoyl)-10-(2H,2H,4H,4H,5H,5H-3-oxaperfluorotridecanoyl)-1,4,7,10-tetraazacyclododecane, sa-complex 15g (16.22mmol) of compounds, indicated in the title of example b1c, 4.60 g (40 mmol) of M-hydroxysuccinimide, 3.39 g (VO mmol) of lithium chloride and 25.19 g (4 A0 mmol) of the 1,4,7-tris(carboxylatomethyl)-10-(3- of aza-4-oxo-5-methyl-5-yl)pentanoic acid is dissolved under moderate heating in 300 ml of dimethylsulfoxide.

Next, at 10"C, 24.73 g (100 mmol) of EEDH is added and then stirred overnight at room temperature. The solution is poured into 300 ml of acetone and stirred for 10 min. The solid substance that has precipitated is filtered and then purified by chromatography (silica gel KR-18 , eluent: water/ethanol/acetonitrile gradient).

Yield: 19.86 g (5795 from theory) of a colorless solid.

Water content: 11.3905.

Elemental analysis (in terms of anhydrous substance): solution: С 38.58 Н 4.74 Е 15.04 Са 14.64 М 9.13 found.: С 38.47 Н 4.91 Е 14.95 Са 14 .57 M 9.04

Example 62 a) 1-K4-perfluorooctylsulfonyl)piperazinamide of 3,5-dinitrobenzoic acid

To 20 g (35.2 mmol) of perfluorooctylsulfonylpiperazine and 8.1 g (dOmol) of triethylamine, dissolved in 200 ml of dichloromethane, a solution of 8.76 g (38 mmol) of 3,5-dinitrobenzoyl chloride in 55 ml of dichloromethane is added dropwise at 0"C and stirred for 1 hour at 0 "WITH. Next, add 200 ml of 595% aqueous hydrochloric acid and stir for 5 minutes at room temperature. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 15:1).

Yield: 24.96 g (9395 from theory) of a colorless solid.

Elemental analysis: solution: C 29.35 H 1.45 E 42.37 M 7.35 54.21 found: C 29.28 H 1.61 E 42.15 M 7.25 54.15 b) ( 1-(4-perfluorooctylsulfonyl)piperazinamide of 3,5-diaminobenzoic acid 20 g (26.23 mmol) of the compound indicated in the title of example 62a is dissolved in 400 ml of ethanol and BG of palladium catalyst (1096 Pa/C) is added. After that, it is hydrogenated at The catalyst is then filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 18.43 g (quantitative) of a cream-colored solid.

Elemental analysis: solution: C 32.49 H 2.15 E 45.98 M 7.98 5 4.57 found: C 32.29 H 2.35 E 45.69 M 7.81 5 4.40 in ) (1-(4-perfluorooctshisulfonyl)piperazinamide /3,5-M,M'-bis(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3- aza-4-oxo-5-methyl-5-yl)|benzoic acid, a complex of 10 g (14.24 mmol) of the compound indicated in the title of example 626, 3.45 g (ZO mmol) of M-hydroxysuccinimide, 2.54 g (60 mols) of lithium chloride and 18.89 g (ZOmols) of the sa-complex 1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-yl)pentanoic acid are dissolved under moderate heating in 200 ml of dimethyl sulfoxide.

Next, at 107C, 10.32 g (5 mol) of M,M-dicyclohexylcarbodiimide are added and then stirred overnight at room temperature. The solution is poured into 2000 ml of acetone and stirred for 10 minutes. The precipitated solid is filtered off and then purified by chromatography (silica gel KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 19.74 g (7295 from theory) of a colorless solid.

Water content: 11.895.

Elemental analysis (calculated per anhydrous substance): solution: С 35.55 Н 3.72 Е 16.77 Са 16.33 М 10.18 5 1.67 found.: С 35.48 Н 3.84 Е 16 .58 Sa 16.24 M 10.07 5 1.58

Example 63 a) tert-Butyl ether of 3-oxa-2H,2H,4H.4H,5H,5H-perfluorotridecanecarboxylic acid 25.0 g (53.8 mmol) 1H,1H,2H,2H-perfluoro-1-decanol (supplied by the company And apsavieg| is dissolved in 250 ml of absolute toluene and mixed at room temperature with a catalytic amount (approximately 0.75 g) of tetra-n-butylammonium hydrosulfate. Then, at 0"C, a total of 7.55 g (134.6 mmol, 2.5 equivalents in calculated on the amount of the alcohol component used) of highly dispersed powdered potassium hydroxide, and then 15.73 g (80.7 mmol, 1.5 equivalents on the amount of the alcohol component used) of tert-butyl bromoacetic acid ether and left for 2 hours for stirring at 0"С . The reaction solution obtained in this way is then stirred for 12 hours at room temperature and for processing it is mixed with ethyl acetic acid in a total amount of 500 ml and 250 ml of water. The organic phase is separated and washed twice with water. After drying the organic phase over salt fathom sodium salt is separated by vacuum filtration and the solvent is distilled off in a vacuum. The obtained oily residue is purified on silica gel using ethyl acetic acid/hexane (1:10 ratio) as an eluent.

Yield: 26.3 g (84.695 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 33.23 H 2.61 E 55.85 found: C 33.29 H 2.61 E 55.90 b) 3-oxa-2H,2H4H,4H,5H,5H-perfluorotridecanecarbon acid 20.0 g (34.58 mmol) of the compound indicated in the title of example bZa, with stirring, is suspended at room temperature in 200 ml of a mixture consisting of methanol and 0.5 molar caustic sodium in a ratio of 21, and then heated to 60"С After carrying out the reaction for 12 hours at 60"C, the clear reaction mixture for processing is neutralized by mixing with Atregiye cation exchange resin? IV 120 (H--form), ionite is removed by vacuum filtration, and the methanol-water filtrate obtained in this way is distilled in a vacuum until a dry residue is obtained. The obtained amorphous-oily residue is purified on silica gel using ethyl acetic acid/n-hexane (in a ratio of 1:3) as an eluent.

Yield: 16.0 g (88.695 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 27.60 H 1.35 E 61.85 found: C 27.58 H 1.36 E 61.90 c) 1,7-bis(11,4,7-tris(carboxylatomethyl )-10-(3-aza-4-oxo-5-methyl-5-ylpentanoyl)|-1,4,7,10-tetraazacyclododecane)diethylenetriamine, digadolinium complex 2.A8g (3.94 mmol, 2.05 molar equivalents in terms of the amount of diethylenetriamine used) (described in the application OE 19728954 C1 | in example 31p of the Ca-complex 10-(4-carboxy-1-methyl-2-oxo-3-azabutyl)-1,4,7,10-tetraazacyclododecane -1,4,7-triacetic acid and 167 mg of anhydrous lithium chloride (3.94 mmol) at 40"C are dissolved with stirring in 40 ml of absolute dimethyl sulfoxide and at this temperature are mixed with M-hydroxysuccinimide in a total amount of 453 mg (3.94 mmol). After cooling. to room temperature, the reaction solution obtained in this way is mixed with 814 mg (3.946 mmol) of NM'-dicyclohexylcarbodiimide and stirred for 2 hours at room temperature. The resulting suspension of activated ether is then mixed with 198.3 mg (1.92 mmol) of di of ethylene triamine, dissolved in zml of absolute dimethylsulfoxide, and stirred for 12 hours at room temperature. For processing, the reaction mixture is mixed with a sufficient amount of acetone until the compound specified above in the title is completely precipitated, the precipitate is separated by vacuum filtration, dried, dissolved in water, the undissolved dicyclohexylurea is filtered off, and the filtrate for desalting and for purification from low molecular weight components is passed through an ultrafiltration AMISOM membrane

In M-3 (limit permeability Z000Da), the retentate is finally lyophilized.

Yield: 1.85 g (72.795 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 3.89965.

Elemental analysis (in terms of anhydrous substance): solution: С 38.03 Н 5.24 М 13.73 Са 23.71 detected: С 37.98 Н 5.20 М 13.69 Са 23.78 g) 1,7-bis(11,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-ylpentanoyl)|-1,4,7,10-tetraazacyclododecane)-4 -(3-oxa-2Н.2Н,4Н,4Н,5Н,5Н-perfluorotridecanoyl)diethylenetriamine, digadolinium complex

1.27 g (2.44 mmol) of the compound indicated in the title of example 636 is added dropwise to a solution of 3.23 g (2.44 mmol) of the compound specified in the title of example bZv, in a mixture of 30 mL of dimethyl sulfoxide and 3 mL of tetrahydrofuran at 50"C in a nitrogen atmosphere , dissolved in a mixture of 15 ml of tetrahydrofuran and 15 ml of dimethyl sulfoxide. After that, a total of 1.80 g (3.6 mmol) of EEDH (2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline) is added in portions at 0"C and left overnight for stirring at room temperature. The resulting reaction solution is then mixed with a sufficient amount of acetone until the above title compound is completely precipitated, the precipitate is separated by vacuum filtration, dried, dissolved in water, the undissolved components are filtered off, and the filtrate is subjected to ultrafiltration through an AMISOM ultrafiltration membrane UM-3 (limit permeability: 3000Da), which ensures complete desalination of the compound indicated in the title and at the same time its purification from low molecular weight components.

Finally, the retentate is lyophilized.

Yield: 3.54 g (79.495 from theory) in the form of a colorless lyophilisate.

NgO content (when using Karl Fischer's reagent): 5.87905.

Elemental analysis (in terms of anhydrous substance): solution: С 35.43 Н 4.07 M 9.95 Р 17.64 (а 17.18 found.: С 35.42 Н 4.01 М 9.89 Е 17,67 Sa 17,18

Example 64 a) 2-M-trifluoroacetyl-6-M-benzyloxycarbonyl-1-lysine 100.0 g (356.7 mmol) of 6-M-benzyloxycarbonyl-1-lysine is dissolved in a mixture of 1000 ml of trifluoroacetic acid ethyl ether and 500 ml of ethanol and during Stir for 24 hours at room temperature. After that, it is evaporated to dryness and the residue is crystallized from the action of isopropyl ether.

Yield: 128.9 g (9695 from theory) of colorless crystalline powder.

Melting point: 98.570.

Elemental analysis: solution: C 51.07 H 5.09 M 7.44 P 15.14 found: C 51.25 H 5.18 M 7.58 E 15.03 b) (1-(4-perfluorooctylsulfonyl )piperazinamide 2-M-trifluoroacetyl-6-M-benzyloxycarbonyl-y-lysine

To 125.0 g (332.0 mmol) of the compound indicated in the title of example 52a and 188.7 g (332.00 mmol) of 1-perfluorooctylsulfonylpiperazine (obtained according to OE 19603033) in 75000 ml of tetrahydrofuran at 0"C, add 164.2 g (0.664 mmol ) EEDH (2-ethoxy-1,2-dihydroquinoline-1-carboxylic acid ethyl ester) and stirred overnight at room temperature, then evaporated to dryness in vacuo and chromatographed on silica gel (eluent: dichloromethane/methanol 20:1) .

Yield: 286.0 g (9395 from theory) of a colorless solid.

Melting point: 9276.

Elemental analysis: solution: C 36.30 H 2.83 M 6.05 E 41.01 5 3.46 found: C 36.18 H 2.94 M 5.98 E 40.87 5 3.40 ) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-benzyloxycarbonyl-y-lysine

A solution of 280.0 g (302.2 mol) of the compound indicated in the title of example 526 in 2000 ml of ethanol at 0"C is bubbled for one hour with gaseous ammonia. After that, the mixture is stirred for 4 hours at 07C.

Next, it is evaporated to dryness and the residue is separated from the water by stirring. The solid substance is filtered off and dried in a vacuum at 507C.

Yield: 243.5 g (97.0905 from theory) of amorphous solid.

Elemental analysis: solution: C 37.60 H 3.28 M 6.75 E 38.89 5 3.86 found: C 37.55 H 3.33 M 6.68 E 38.78 5 3.81 g ) (1-(4-perfluorooctylsulfonyl)piperazinamide I-lysine 200.0g (240.mmol) of the compound obtained in example b4c is dissolved in 1000ml of ethanol, mixed with 5.0g of Perlman's catalyst (2090 Pa/C) and hydrogenated at room temperature temperature in a hydrogen atmosphere (1 atm) until hydrogen absorption stops.After that, the catalyst is removed by vacuum filtration, washed thoroughly with ethanol (three portions of approximately 100 ml each) and concentrated to dryness under vacuum.

In this way, the compound indicated in the title is obtained in the form of a highly viscous yellow oil.

Yield: 162.5 g (96.995 from theory).

Elemental analysis: solution: C 31.04 H 3.04 M 8.05 E 46.38 5 4.60 found: C 31.11 H 3.09 M 8.08 E 46.33 5 4.62 d ) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-2 M-bis(4-(2,3-bis(M,M-bis(tert-butyloxycarbonylmethyl)amino)propylIfenyl)-3-oxa-propionyl-! -lysine 5.25 g (7.72 mmol) of 4-(2,3-bis-(M, M-bis(tert-butyloxycarbonylmethyl)amino)propyl|phenyl)-3-oxapropionic acid and 781.0 mg (7.72 mmol) triethylamine is dissolved in 50 ml of methylene chloride. Then, at -1570, a solution of 1.16 g (8.5 mmol) of isobutyl ether of chloroformic acid in 100 ml of methyl chloride is added dropwise for 5 minutes and stirred for another 20 minutes at -157C. Then the solution is cooled to -25"C, for ZOkhv is added dropwise to a solution of 2.68 g (3.8 mmol) of the B4Ag compound indicated in the title of the example and 2.12 g (21.0 mmol) of triethylamine in 700 ml of tetrahydrofuran, after which it is stirred for

ЗОхв at -15"С, and then overnight at room temperature. For processing, the solvent is distilled off in a vacuum and the obtained oily residue is dissolved in 250 ml of chloroform. The chloroform phase is extracted twice with a 1096 aqueous solution of ammonium chloride in portions of 100 ml each, the organic phase is dried over sulfate magnesium and evaporated to dryness in vacuo.The residue is chromatographed on silica gel (eluent: methylene chloride/ethanol in a ratio of 20:1).

Yield: 5.37 g (68.895 from theory) of colorless and highly viscous oil.

Elemental analysis: solution: C 52.27 H 6.43 M 5.54 P 15.97 51.59 found: C 52.22 H 6.51 M 5.49 E 15.99 5 1.63 e) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-2M-bisi4-I(2,3-bis(M,M-bis(carboxylatomethyl)amino)propylIfenyl)-Z-oxapropionyl-!-lysine, octasodium salt 5 .0g (2.47mmol) of the compound indicated in the title of example b4d is dissolved in bOml of absolute dichloromethane. After that, the resulting solution at 0"C is mixed dropwise with trifluoroacetic acid in a total amount of 75ml. After the reaction has been carried out for 12 hours at room temperature, the mixture is concentrated to dryness in vacuum. The resulting residue is mixed with 100 ml of water and distilled again under vacuum until a dry residue is obtained. The residue obtained in this way is dissolved in 200 ml of distilled water and the aqueous solution of the compound indicated above in the title, which contains the product, is extracted twice with diethyl ether in boml portions. General the volume of the obtained aqueous solution, which contains the product, is brought up to 30 Oml by mixing with water, filtered Are the undissolved components and the filtrate subjected to ultrafiltration through an AMISOM ultrafiltration membrane? UM-3 (limit permeability: З000Da), which ensures complete desalination of the compound indicated in the title and at the same time its purification from low molecular weight components. The total volume of the retentate is brought up to 200 ml by mixing with water, and then the pH value of this solution is set to 10.0 with the help of 1595 caustic sodium. The alkaline aqueous solution containing the product is finally lyophilized.

In this way, 4.0 g (92.895 from the theory) of the title compound in the form of an octasodium salt in the form of an amorphous lyophilizate are obtained.

Water content: 5.37905.

Elemental analysis (in terms of anhydrous substance): solution: C 38.46 H 3.28 M 6.41 E 18.47 51.83 Ma 10.52 found: C 38.42 H 3.31 M 6, 39 E 18.51 5 1.87 Ma 10.38 g (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-2 M-bisi4-I(2,3-bis(M, M-bis(carboxymethyl)amino) propyl|phenyl)-Z-oxapropionyl-Y-lysine, dimanganese complex, tetrasodium salt 1.94 g (1.11 mmol) of the compound indicated in the title of example 6b4e is dissolved in 100 ml of distilled water and the pH value of the resulting solution is set to 4.0 by mixing with 1-molar aqueous hydrochloric acid. Then, at 80"C, it is mixed with 0.25 g (2.22 mmol) of manganese carbonate in portions. The reaction solution obtained in this way is then refluxed for 5 hours. After cooling to room temperature, the pH value of the aqueous solution, which contains the product, is set with intensive stirring at 7.2 by mixing with 1N caustic sodium and for desalting and for cleaning from low molecular weight components is passed through an ultrafiltration into the AMISOM UM-3 membrane (permeability limit: З000Da). Finally, the retentate is lyophilized.

Yield: 1.80 g (92.095 from theory) of the title compound in the form of a colorless lyophilizate.

NgO content (when using Karl Fischer's reagent): 7.28905.

Elemental analysis (in terms of anhydrous substance): solution: C 38.07 N 3.25 E 18.28 Mp 6.22 M 6.34 Ma 5.20 5 1.81 detection: C 38.01 N 3 ,29 E 18.29 Mp 6.21 M 6.36 Ma 5.28 5 1.78

Example 65 a) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(benzyloxycarbonyl)-2-M-|(M-pteroyl)-Y-glutaminyl|lysine 20g (45.31mmol) of folic acid is dissolved in 300ml of dimethyl sulfoxide and 9.49 g (4 mmol) of M,M-dicyclohexylcarbodiimide are added at 107 C. The mixture is stirred overnight at room temperature.

Next, 29.1 g (35 mmol) of the compound indicated in the title of example 52c and 20 ml of pyridine are added to this mixture and stirred for 1 hour at 50°C. Then it is cooled to room temperature and a mixture of 1500 ml of diethyl ether and 1500 ml of acetone is added. The precipitate that precipitated, filtered and purified on silica gel KR-18 (eluent: water/ethanol/tetrahydrofuran gradient).

Yield: 21.59g (3895 from theory) of a yellow solid.

Water content: 2.195.

Elemental analysis (in terms of anhydrous substance): solution: C 43.10 H 3.54 E 25.76 M 11.29 5 2.56 found: C 43.02 H 3.62 E 25.68 M 11 .21 52.48 b) (1-(4-perfluorooctylsulfonyl)piperazinamide 2-M-|(M-pterothyl)-I -glutaminyl|lysine

To 20 g (15.95 mmol) of the compound indicated in the title of example b5a, add 200 ml of hydrobromic acid in glacial acetic acid (48905) and stir for 2 hours at 40°C. Then cool to 0°C, add 2000 ml of diethyl ether dropwise. and the precipitated solid is filtered off.

After drying in a vacuum (60"C), 18.96 g (9995 from theory) of a yellow crystalline solid are obtained.

Elemental analysis: solution: C 37.01 H 3.27 Vi 6.65 E 26.90 M 12.83 5 2.67 found: C 36.91 H 3.42 Vg 6.31 E 29.75 M 12.72 5 2.56 c) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl -3-aza-4-oxo-5-methyl-5-yl|-2-M-(M-pteroyl)-I-glutaminyl|lysine, -sa- complex 0.92g (3Vmmols) of M-hydroxysuccinimide, 0, 68 g (16 mol) of lithium chloride and 5.04 g (35 mmol) of 1,4,7-tris(carboxylatomethyl)-10-(3-aza-4-oxo-5-methyl-5-yl)-1 sa-complex, 4,7-10-tetraazacyclododecane is dissolved under moderate heating in 0 ml of dimethylsulfoxide. Then, at 10"C, 2.06 mg (1 mol) of M,M-dicyclohexylcarbodiimide is added and then stirred for hours at room temperature. To this reaction solution, 5 g (4 .16 mmol) of the compound indicated in the title of Example 656 and 10 ml of pyridine.

The mixture is stirred overnight at room temperature. Then the solution is poured into 1000 ml of acetone and stirred for 1 hour. The precipitated solid is filtered and then purified by chromatography (silica gel KR-18, eluent: water/ethanol/acetonitrile gradient). The product is dissolved in a small amount of water, the pH value is set to 7.4 with caustic sodium and lyophilized.

Yield: 3.87 g (5395 from theory) of a yellow solid.

Water content: 5.895.

Elemental analysis (in terms of anhydrous substance): solution: С 38.36 Н 3.74 Е 18.42 Са 8.97 М 12.78 Ма 1.31 5 1.83 detect.: С 38.28 Н 3 .85 E 18.33 Ca 8.85 M 12.69 Ma 1.42 51.75

Example 66 a) M-(2,3-dihydroxypropyl)amide of 2H,2H.4H,4H,5H,5H-3-oxa)perfluorotridecanoic acid

To Zog (57.45 mmol) of 2H,2H.4H.4H,5H,5H-3-oxaperfluorotridecanoic acid in ZOO0 ml of dichloromethane, add 8.90 g (/Omol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"C it is added dropwise to a solution of 5.47 g (bOmoles) of 2,3-dihydroxypropylamine and 6.07g (bOmoles) of triethylamine in 200 ml of dichloromethane. The mixture is stirred for 1 hour at 0"C, and then for two hours at room temperature. Next, add 30 ml of 595% aqueous hydrochloric acid and mix thoroughly for 15 minutes.

The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/ethanol in a ratio of 15:1).

Yield: 29.70 g (8795 from theory) of a colorless solid.

Elemental analysis: solution: C 30.32 H 2.20 M 2.36 E 54.35 found: C 30.12 H 2.41 M 2.18 E 54.15 b) m-(2,3- diphydroxypropyl)-M-(1H1H,2H.2H4NH,5H,5H-Z-oxaperfluorotridecyl)amine

Zog (48.8 mmol) of the compound indicated in the title of example bba is dissolved in 300 ml of tetrahydrofuran and 50 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran) is added. Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C, 3000ml of methanol is added dropwise and then evaporated to dryness under vacuum. The residue is dissolved in a mixture of 300ml of ethanol and 50ml of 1095 aqueous hydrochloric acid and stirred for 8 hours at 60"C. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 300 ml of 5965 aqueous caustic sodium and extracted three times with dichloromethane in portions of 30 ml. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum and the residue is chromatographed on silica gel (eluent: dichloromethane/methanol in a ratio of 15:1).

Yield: 24.07 g (8595 from theory) of a colorless solid.

Elemental analysis: solution: C 31.05 H 2.61 M 2.41 P 55.66 found: C 31.91 H 2.78 M 2.33 E 55.47 c) 1,4,7-tris (carboxylatomethyl)-10-((3-aza-4-oxohexan-5-yl)-acid-M-(2,3-dihydroxypropyl)-M- nin 2gH2 nn H,5H,ZH-3-oxa)perfluorotridecyl) amide|-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1,4,7- of triacetic acid and 1.35 g (31.7 mmol) of lithium chloride are dissolved in 100 ml of dimethyl sulfoxide at 60 °C. Then it is cooled to 15 °C and 9.21 g (15.88 mmol) of the compound indicated in the title of example 666 is added. The mixture is stirred for 10 minutes and then add 7.42 g (ZOmole) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline. After that, stir for 12 hours at room temperature.

The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The deposited precipitate is filtered off, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 16.09 g (8595 from theory) of colorless amorphous powder.

Water content: 6.395.

Elemental analysis (in terms of anhydrous substance): solution: С 34.26 Н 3.64 М 7.05 РЕ 27.10 са 13.19 found.: С 34.12 Н 3.83 М 6.91 Е 26 ,88 Sa 12,93

Example 67 1,4,7-tris(carboxylatomethyl)-10-|((3-aza-4-oxohexan-5-yl)-acid-M-(1н1н,2Нн,2на4Н4Н5Н,5Н-3-oxaperfluorotridecyl)amide| -1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid , 1.35 g (31.7 bmmol) of lithium chloride and 3.66 bg (31.7 bmmol) of M-hydroxysuccinimide are dissolved at 60"C in 100 ml of dimethyl sulfoxide. Then it is cooled to 157C, and 3.51 g (17 mmol) of M,M'-dicyclohexylcarbodimide are added and stirred for 5 hours at 1570. To separate the urea, the solution is filtered. 8.63 g (15.88 mmol) of the compound indicated in the title of Example 686 and 5.06 g (500 mmol) of triethylamine are added to the filtrate and stirred for 12 hours at room temperature. The solution is drained into a mixture of 1500 ml of diethyl ether and 100 ml of acetone and stir for

REFERENCE The precipitated solid is filtered off and chromatographed on KR-18 silica gel (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 13.86 g (7895 from theory) of colorless amorphous powder.

Water content: 9.395.

Elemental analysis (in terms of anhydrous substance): solution: C 33.28 H 3.42 M 7.51 E 28.87 (a 14.05 found.: C 33.12 H 3.61 M 7.37 E 28.69 Sa 13.89

Example 68 a) Amide of 2H,2H.4H.4H,5H,5H-3-oxaperfluorotridecanoic acid

To Zog (57.45 mmol) of 2H,2H.4H4H,5nH,5H-3-oxaperfluorotridecanoic acid in ZOO0 ml of dichloromethane, add 8.90 g (/Omol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 200 ml of dichloromethane. Then the solution at 0"C is bubbled with gaseous ammonia for about 2 hours. After that, the mixture is stirred for 4 hours at room temperature, and then for 2 hours at room temperature. Next, 10 ml of 595% aqueous hydrochloric acid is added and thoroughly mixed for 15 minutes. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a 20:1 ratio).

Yield: 27.85g (9395 from theory).

Elemental analysis: solution: С 27.66 Н 1.55 М 2.69 Е 61.97 found.: С 27.49 Н 1.72 М 2.54 Е 61.81 -Z-oxaperfluorotridecylamine, hydrochloride 27g (51.8mmol) of the compound indicated in the title of example bva is dissolved in 300ml tetrahydrofuran and 10M borane dimethylsulfide (in tetrahydrofuran) is added. Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness under vacuum. The residue is dissolved in a mixture of 400ml of ethanol and 100ml of 1095 aqueous hydrochloric acid and stirred for 8 hours at 60"C. The mixture is evaporated to dryness in vacuo and the residue is recrystallized from a small amount of ethanol/diethyl ether.

Yield: 26.75 g (9595 from theory) of a colorless crystalline solid.

Elemental analysis: resolved: C 26.51 H 2.04 M 2.58 E 59.41 SI 6.52 detected: C 26.37 H 2.21 M 2.46 E 59.25 SI 6.38 ) MAN 2gH,2NNYAN,5H,5H-3-oxa)perfluorotridecyl)amide of 3,6,9,12,15-pentaoxahexadecanoic acid

To 26.5 g (48.74 mmol) of the compound indicated in the title of example 686 and 14 8 g (146 2 mmol) of triethylamine, dissolved in 30 ml of dichloromethane, at 0"C, 14.24 g (5 b0 mmol) of chloride 3,6,9,12 are added ,15-pentaoxahexadecanoic acid and stir for 10 minutes at 0"C. Next, add 300ml of 595% aqueous hydrochloric acid and mix thoroughly for 300 minutes. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 20:1).

Yield: 32.03g (8795 from theory) of colorless oil.

Elemental analysis: solution: C 36.57 H 4.00 M 1.85 E 42.75 found: C 36.46 H 4.12 M 1.76 E 42.53 g) M-(3.6, 9,12,15-pentaoxahexadecyl)-M-(1H1Hn,2nH,2nNanNa4nH-3-oxa)perfluorotridecyl)amide

31 g (41.03 mmol) of the compound indicated in the title of example b8c is dissolved in 300 ml of tetrahydrofuran and 25 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran) is added. Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness in a vacuum. The residue is dissolved in a mixture of ZOOml of ethanol and 5O0ml of 1095 aqueous hydrochloric acid and stirred for 8 hours at 40"C. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 300 ml of 5965 aqueous caustic sodium and extracted three times with dichloromethane in portions of 30 ml. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 15:1).

Output: 27.68g (9195 from theory).

Elemental analysis: solution: C 37.26 H 4.35 M 1.89 E 43.56 detected: C 37.11 H 4.51 M 1.73 E 43.41 d) 1,4,7-tris (carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid-(M-(3,6,9,12,15-pentaoxahexadecyl)-M-(1H1H,2H,2nNanNaH,5H, ZH-3-oxa)perfluorotridecylamide)-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-"carboxymethylcarbamoyl)ethyl-1,4,7,10-tetraazacyclododecane-1, 4,7-triacetic acid and 1.35g (31.7bmmol) of lithium chloride are dissolved in 100ml of dimethylsulfoxide at 60"C. Next, it is cooled to 157C and 11.77g (15.88mmol) of the compound indicated in the title of the example is added. The mixture is stirred for 10 minutes and then add 7.42 g (ZOmol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline. The mixture is stirred for 12 hours at room temperature. The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature temperature alum and water and chromatographed on KR-18 silica gel (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 18.05 g (8495 from theory) of colorless amorphous powder.

Water content: 6.295.

Elemental analysis (in terms of anhydrous substance): solution: С 37.28 Н 4.47 М 6.21 ЕР 23.87 (а 11.62 found.: С 37.11 Н 4.61 М 6.03 Е 23.64 Sa 11.42

Example 69 a) M-(5-hydroxy-3-oxapentyl)amide of 2H,2H,4H,4H,5nH,5H-3-oxaperfluorotridecanoic acid

To Zog (57.45 mmol) of 2H,2H.4H.4H,5H,5H-3-oxaperfluorotridecanoic acid in ZOO0 ml of dichloromethane, add 8.90 g (/Omol) of oxalyl chloride and stir for 12 hours at room temperature. The mixture is evaporated to dryness under vacuum. The residue is dissolved in 100 ml of dichloromethane and at 0"C it is added dropwise to a solution of 6.25 g (bOmoles) of 5-hydroxy-3-oxapentylamine and 6.07g (bOmoles) of triethylamine in 200 ml of dichloromethane. The mixture is stirred for 2 hours at 0"C. and then for 2 hours at room temperature. Next, add 30 ml of 595% aqueous hydrochloric acid and mix thoroughly for 15 minutes.

The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 15:1).

Yield: 32.20 g (9295 from theory) of a colorless solid.

Elemental analysis: solution: С 31.54 Н 2.65 М 2.30 Е 53.01 detect.: С 31.61 Н 2.84 М 2.14 РЕ 52.85 b) M-(5-hydroxy- 3-oxapentyl)-M-(1H1H,2H,2NaNaH,5H,5ZH-Z-oxaperfluorotridecyl)amine

Zog (49.24 mmol) of the compound specified in the title of example bZa is dissolved in 300 ml of tetrahydrofuran and 10 ml of 10 M borane dimethyl sulfide (in tetrahydrofuran) is added. Then, for 16 hours, it is boiled under reflux. After that, it is cooled to 0"C, 200ml of methanol is added dropwise and then evaporated to dryness in a vacuum. The residue is dissolved in a mixture of 300ml of ethanol and 50ml of 1095 aqueous hydrochloric acid and stirred for 10 hours at 50"C. The mixture is evaporated to dryness in a vacuum, the residue is dissolved in 300 ml of 5905 aqueous caustic sodium and extracted three times with dichloromethane in portions of 300 ml. The organic phases are dried over magnesium sulfate, evaporated to dryness under vacuum, and the residue is chromatographed on silica gel (eluent: dichloromethane/2-propanol in a ratio of 20:1).

Yield: 26.09g (8995 from theory) of a colorless solid.

Elemental analysis: solution: C 32.28 H 3.05 M 2.35 E 54.25 found: C 32.12 H 3.21 M 2.18 E 54.09 c) 1,4,7-tris (carboxylatomethyl)-10-((3-aza-4-oxohexan-5-yl)-acid-M-(5-hydroxy-3-oxa-pentyl)-M-

ИНиНн 22 ННЯ Н,5Н,5Н-З-oxa)perfluorotridecyl)amide|-1,4,7,10-tetraazacyclododecane, gadolinium complex 10 g (15.88 mmol) of gadolinium complex 10-P1-(carboxymethylcarbamoyl)ethyl)|- 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid and 1.35 g (31.7 mmol) of lithium chloride are dissolved in 100 ml of dimethyl sulfoxide at 60"C. Then they are cooled to 157 and 9.45 g (15, 88mmol) of the compound indicated in the title of example 696. The mixture is stirred for 10 min and then 7.42g (ZOmmol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline is added. The mixture is stirred for 12h at room temperature. The solution is poured into a mixture of 200 ml of acetone and 1300 ml of diethyl ether and stirred for 2 hours at room temperature. The precipitate that fell out was filtered, dissolved in a mixture of a small amount of ethanol and water and chromatographed on silica gel KR-18 (eluent: tetrahydrofuran/acetonitrile/water gradient).

Yield: 16.10 g (8495 from theory) of colorless amorphous powder.

Water content: 5.790.

Elemental analysis (in terms of anhydrous substance): solution: С 34.83 Н 3.84 М 6.96 Е 26.76 Са 13.03 found.: С 34.65 Н 3.96 М 6.84 Е 26 .62 and 12.91

Example 70 a) 1,2,3,4,6-penta-O-acetyl-x,p-YOO-mannopyranose

Similarly to the method described in the literature (M.S. UMoyot and A. Tpotrzop, "Meipoaz ip Sagropuagaie

Spetivigu" (under the editorship of EH. Mupiztseg, M.I. Muoitot and 9U.M. VemiPeg), ed. Asadetis Rge55, Mem/ Mo, vol. II, 53, p. 211-215 (1963) | as a result interaction of 150 g (832.5 mmol) of ",p-Y-mannopyranose with a mixture of 1500 ml of absolute pyridine and 1500 ml of acetic anhydride after processing yields 315 g (96.7905) of the above-mentioned compound in the form of a crude product in the form of a viscous and colorless oil The ratio between both c- and D-anomers in the title compound obtained in this way is 4:11 according to the data

IN-NMR spectroscopic analysis. To carry out the following reactions, the compound indicated above in the title may not be separated into separate o,p-anomers.

Elemental analysis: solution: C 49.21 H 5.68 detected: C 49.12 H 5.78 b) Ethyl ether 6-(1-O-o-(2,3,4,6-tetra-O) -acetyl-O-mannopyranosyl)|hexanoic acid

Analogous to the method described in the literature for the synthesis of arylglycopyranosides (U. Soposopie and O.A. Imu, "Meshoa5 ip Sagropudgaee Spetivigu" (ed. K.G. M/pizNTseg, M.S. MMoigot and U.M. Vemieg), Asadetis species

Rgez5, Mem/ Hogk, vol. II, 90, p. 345-347 (1963))| as a result of the interaction of 156.2g (400mmol) of Example 70a indicated in the title in the form of a mixture of p,p-anomers with b/7ml (400mmol) of ethyl ether of b-hydroxyhexanoic acid and 60.8ml (520mmol) of tin(U) chloride in 1, 2-dichloroethane in a total amount of bOOml after purification by column chromatography (eluent: hexane/ethyl acetic acid in a ratio of 271) yield 100.05 g (5195 from theory) of the compound indicated above in the title in the form of a colorless and viscous oil. The data of H-NMR spectroscopic analysis of the title compound obtained in this way indicate that this title compound is only a pure c-anomer.

Elemental analysis: solution: C 52.94 H 6.77 found: C 52.80 H 6.78 c) 6-1-O-o-(2,3,4,6-tetra-O-benzyl- O-mannopyranosyl)hexanoic acid

A mixed suspension of 141.0 g (289 mmol) of the compound indicated in the title of Example 70b in 200 ml of dioxane is mixed in portions at room temperature and simultaneously with intensive stirring with a total amount of 238.5 g (4.2 mmol) of powdered potassium hydroxide. To increase its miscibility, the reaction mixture is mixed with another 200 ml of dioxane, the resulting suspension is then heated to boiling point and at this temperature for two hours it is mixed dropwise with benzyl bromide in a total amount of 372 ml (3.128 mol). After carrying out the reaction for 4 hours at 110"C, and then for 12 hours at room temperature, the reaction mixture for processing is slowly poured into a mixture of water and ice in a total amount of 2.5 liters, and the aqueous phase is then completely extracted with diethyl ether. After washing the ether phase obtained in this way and after its subsequent drying over sodium sulfate, the salt is separated by vacuum filtration and the diethyl ether is distilled off in a vacuum. After that, the excess benzyl bromide is quantitatively distilled off from the reaction mixture in a vacuum created by an oil pump at an oil bath temperature of 1807"C. The resinous-oily residue obtained in this way is purified on silica gel using ethyl acetic acid/hexane (in a ratio of 1:10) as an eluent.

Yield: 172.2 g (91.095 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 75.68 N 7.16 found: C 75.79 N 7.04 g) M-(3-oxa-1H.TN.2H.2NaH,YAN5H,ZH-perfluorotridecyl)amide 6 -11-O-o-(2,3,4,6-tetra-O-benzyl-O-mannopyranosyl)hexanoic acid 100 g (134 mmol) of the acid described in example 70c, as well as 13.5 g (134 mmol) of triethylamine are dissolved in 1200 ml dry tetrahydrofuran. After cooling to -157"С, a solution of 18.45 g (135 mmol) of isobutyl ether of chloroformic acid in 200 ml of dry tetrahydrofuran is slowly added dropwise with stirring, while the internal temperature should not exceed -107С. After conducting the reaction for 15 minutes at -157С dropwise with At -20"C, add a solution of 165.5 g (134 mmol) of 1-amino-1Nu1H2H in 2H-perfluorodecane and 13.5 g (134 mmol) of triethylamine in 250 ml of dry tetrahydrofuran. After carrying out the reaction for one hour at -15"C, and then for two hours at room temperature, the reaction solution is concentrated to dryness in a vacuum. The resulting residue is dissolved in 300 ml of ethyl acetic acid and washed twice with 400 ml of saturated sodium bicarbonate solution in portions of 40000 ml and once with water 500 ml. After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the ethyl acetic acid is distilled off under vacuum. The resulting oily residue is purified on silica gel using dichloromethane/hexane/2-propanol (10:5:1 ratio) as eluent.

Yield: 143.8g (86.995 from theory).

Elemental analysis: solution: С 57.38 Н4.98 M 1.13 Р 26.15 detected: С 57.30 Н 5.44 М 1.01 РЕ 26.25 d) M-(3З-oxa-1Н1Н2Н) .2 NN aH,ZH,ZH-perfluorotridecyl)amide 6-I1-O-0-YUO-mannopyranosyl)hexanoic acid 40.0 g (32.3 dmmol) of the compound indicated in the title of example 70 g are dissolved in 750 ml of 2-propanol and mixed with 2.0 g of palladium catalyst (1095 Pa/C). Then the reaction solution is hydrogenated for 12 hours at 22"C and a hydrogen pressure of 1 atmosphere. After that, the catalyst is filtered off and the filtrate is concentrated to dryness. The resulting residue is dissolved in 30ml of dimethylsulfoxide and from the solution obtained in this way, which contains the product, mixed with diethyl ether in a total amount of 100Oml and after separation of the precipitated solid substance, 21.52 g (88.0905 from theory) of the above-mentioned compound in the form of a colorless crystalline powder with a melting point of 88.57C (with decomposition) are obtained by vacuum filtration.

Elemental analysis: solution: C 36.01 H 5.92 M 1.75 E 40.34 detected: C 36.07 H 6.08 M 1.76 E 40.66 e) Preparation of a composition containing a metal complex | and M-(3-oxa-1H1H NN Hn,aH,5Hn,n-perfluorotridecyl)amide of 6-|11-O-y-YUO-mannopyranosyl)hexanoic acid

To 35 ml of a solution of metal complex I (280 mmol/l) in a 0.4595 aqueous solution of table salt (pH 7.4, 0.25 mg/l SamazdDtPA) add 3.17 g (4.2 mmol) of the compound specified in the title of example 7Od , and the volume is brought up to 98 ml with the help of a 0.995% aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 100 mmol/l).

Example 71 a) 1-O-a-0-((1-perfluorooctylsulfonylpiperazine-4-carbonyl)pentyl-51-2,3,4,6-tetra-O-benzylmannopyranose

In 800 ml of a mixture of tetrahydrofuran and acetonitrile (in a ratio of 7:3), dissolve 74.59 g (100 mmol) of the acid described in Example 7, as well as 10.11 g (100 mmol) of triethylamine. After that, at room temperature, a solution of 58.0 g (102.00 mmol) of 1-perfluorooctylsulfonylpiperazine in tetrahydrofuran, 10.11 g (100 mmol) of triethylamine and 16.84 g (110 mmol) of 1-hydroxybenzotriazole is mixed dropwise with 500 ml of solution.

The reaction solution obtained in this way is mixed at -57C with a solution of 22.7 g (110 mmol) of dicyclohexylcarbodiimide in 100O0 ml of tetrahydrofuran and then stirred at -57C for the next two hours. After the reaction solution is thawed, it is stirred at room temperature for another 12 hours, the precipitated dicyclohexylurea is filtered off, and the resulting filtrate is concentrated to dryness under vacuum. The obtained residue is dissolved in b0O0ml of ethyl acetic acid and washed twice with a saturated solution of sodium bicarbonate in portions of ZbOml and twice with water in portions of

ZOOml. After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the ethyl acetic acid is distilled off under vacuum. The obtained oily residue is purified on silica gel using dichloromethane/acetone/2-propanol (in a ratio of 16:2:1) as an eluent

Yield: 113.01 g (79.895 from theory) of colorless and viscous oil.

Elemental analysis: solution: C 58.52 4.27 M 1.98 52.26 E 22.80 found: C 58.42 H 4.41 M 1.80 5 2.28 E 23.02 b) 1 -O-c-0-(1-perfluorooctylsulfonylpiperazine-4-carbonyl)pentyl-5|-mannopyranose 50g (35.30mmol) of the compound indicated in the title of example 71a is dissolved in a mixture of 5x00ml of 2-propanol and 50ml of water and 2g is added palladium catalyst (10,956 Pa on activated carbon). After that, hydrogenate for 12 hours at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum. The residue is dissolved in 200 ml of methanol and the reaction product is precipitated by mixing with diethyl ether in a total amount of 80 ml. After separation of the solid obtained in this way by vacuum filtration, it is dried in a vacuum at 5070.

Yield: 29.51 g (9995 from theory) of amorphous solid.

Elemental analysis: solution: C 34.13 H 3.46 M 3.32 5 3.80 E 38.23 found: C 34.28 H 3.81 M 3.25 5 3.80 E 38.01 ) Preparation of a composition containing a metal complex of HER and 1-O-o-0-|(/1-perfluorooctylsulfonylpiperazine-4-carbonyl)pentyl-5|mannopyranose

9.92 g (11.75 mmol) of the compound indicated in the title of example 716 is added to 47 ml of a solution of metal complex II (250 mmol/l) in a 0.4595 aqueous solution of sodium chloride, and heated in a microwave oven for 10 minutes. The solution is cooled to room temperature, filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 250 mmol/l.)

Example 72 a) 2-acetamido-2-deoxy-1,3,4,6-(tetra-O-benzyl)-o,p-SO-glucopyranose

A total of 24.0 g (108.5 mmol) of 2-

acetamido-2-deoxy-o,3-Y-glucopyranose, dissolved in 500 ml of absolute dimethylsulfoxide. After that, it is left to stir at room temperature for 120 minutes, and then 159.5 g (1.26 mol) of benzyl chloride is added dropwise. The reaction solution obtained in this way is then stirred for another 12 hours at room temperature. For processing, the reaction solution is slowly poured into 1.5 l of a mixture of water and ice and then almost completely extracted with diethyl ether. The combined diethyl ether phases are then washed twice with a saturated solution of sodium hydrogen carbonate in portions of 10 ml and twice with water in portions of 80 ml. After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the solvent is distilled off under vacuum. The obtained oily residue is purified on silica gel using ethyl acetic acid/hexane (in a ratio of 1:5) as an eluent.

Yield: 48.68 g (73.695 from theory) of the above title compound in the form of a viscous and colorless oil.

Elemental analysis: solution: C 70.92 H 6.45 M 6.89 found: C 71.43 H 6.44 M 7.02 b) 1-O-benzyl-3,4,6-tri-O -benzyl-2-amino-2-deoxy-o,D-SO-glucopyranose 30.0 g (49.2 mmol) of the compound indicated in the title of example 72a is suspended in a mixture of 750 ml of methanol and 215 ml of water and mixed dropwise at room temperature with a 0.112-molar aqueous solution of perchloric acid in a total amount of 440 ml (49.2 mmol). Upon completion of this addition, the reaction solution is stirred for another 10 min at room temperature, and the resulting homogeneous reaction solution is then concentrated to dryness under vacuum. The resulting oily residue is crystallized by mixing it with a mixture of hexane and dichloromethane, taken in equal proportions. The crystalline reaction product is separated by vacuum filtration, washed with hexane and dried in a vacuum at room temperature.

Yield: 27.08 g (8695 from theory) of the above title compound in the form of its perchlorate, which is a colorless crystalline compound.

Melting point: 180.5-181.570.

Elemental analysis: solution: C 63.68 H 5.98 M 2.19 SI 5.54 found: C 63.43 H 6.04 M 2.02 SI 5.71 c) 1,3,4,6 -tetra-O-benzyl-2-deoxy-2-(acetyl-(2-amino-M-ethyl-M-perfluorooctylsulfonyl)amino|-1-o;, p-

O-glucopyranose 20.8 g (35.6 bmmol) of 2-|N-ethyl-M-perfluorooctylsulfonyl)aminoacetic acid and 3.b0g (35.bmmol) of triethylamine are dissolved in 350 ml of dry tetrahydrofuran. After cooling the reaction solution to a temperature in the range from -15 to -207C, at this temperature, a solution of 4.92g (35.bmmol) isobutyl ether of chloroformic acid in 75ml of dry tetrahydrofuran is slowly added dropwise while stirring, while the rate of dropwise addition should be such that so that the internal temperature does not exceed -10"C. After conducting the reaction for 15 minutes at -157"C dropwise at -207C, a solution of 22.78g (35.bmmol) perchlorate of the compound specified in the title of Example 726 and 3.60g (35. 6 mmol) of triethylamine in 100 ml of dry tetrahydrofuran. After conducting the reaction for one hour at -157C, and then for two hours at room temperature, the reaction solution is concentrated to dryness in a vacuum. The obtained residue is dissolved in 250 ml of ethyl acetic acid and washed twice with a saturated solution of sodium bicarbonate in portions of 100 ml and once with water in a portion of 200 ml. After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the ethyl acetic acid is distilled off under vacuum. The obtained oily residue is purified on silica gel using ethyl acetate/hexane (1:5 ratio) as an eluent.

Yield: 33.3 g (84.695 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 49.92 H 3.92 M 2.53 E 29.18 5 2.90 found: C 49.99 H 4.11 M 2.69 E 29.22 5 3.01 g ) 2-deoxy-2-(acetyl-(2-amino-M-ethyl-M-perfluorooctylsulfonyl)amino|-1-x,8-O-glucopyranose 20.0 g (18.0 bmmol) of the compound indicated in the title of example 72c , dissolved in 250 ml of 2-propanol and mixed with 1.5 g of palladium catalyst (1095 Pa/C). The reaction solution was hydrogenated for 12 hours at 2276 and a hydrogen pressure of 1 atmosphere. After that, the catalyst was filtered off and the filtrate was concentrated to dryness.

The obtained residue is dissolved in 300 ml of dimethyl sulfoxide and from the solution obtained in this way, which contains the product, by mixing with 750 ml of a mixture of diethyl ether and ethyl acetic acid, taken in equal proportions, and after separating the precipitated solid substance, by vacuum filtration, 12 .65 g (93.895 from the theory) of the compound indicated above in the title in the form of a colorless crystalline powder.

This above title compound is represented as a mixture of o/p anomers, while the ratio between both possible anomers is approximately 1:1.2 according to H-NMR spectroscopic analysis. Accordingly, the title compound is a mixture o/p-anomers with practically the same ratio between them.

Melting point: 132.5-13370.

Elemental analysis: solution: C 28.97 H 2.57 M 3.75 E 43.27 5 4.30 found: C 29.09 H 2.56 M 3.84 E 43.36 5 4.42 d ) Preparation of a composition containing a metal complex of KHM and 2-deoxy-2-I(acetyl-(2-amino-M-ethyl-M-perfluorooctylsulfonyl)amino|-1-o,8-O-glucopyranose

A solution of 4.90 g (6.57 mmol) of the compound indicated in the title of example 3g in 200 ml is added to 51 ml of a solution of the metal complex KHIM (30 mmol/l) in a 0.4595% solution of sodium chloride (pH 7 4; 0.25 mg/l SamazATPA) of ethanol and stir for 2 hours at 50"C. Next, the solution is concentrated to dryness in a vacuum, and the volume of the residue is brought to 153 ml by adding distilled water. The mixture is stirred for 1 hour at 40"C and filtered through a filter with a pore size of 0.2 μm. The filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 100 mmol/l.)

Example 73 a) 1,2,3,4,6-penta-O-acetyl-o-O-glucopyranose

Analogously to the method described for the synthesis of the compound indicated in the title of example 70a, as a result of the reaction of 100 g (555.0 mmol) of o-O-glucopyranose with a mixture of 1000 ml of absolute pyridine and 1000 ml of acetic anhydride after processing and recrystallization from 95956 aqueous ethanol, 190 is obtained .6 g (88.095) of the compound indicated above in the title in the form of a colorless crystalline compound. In the compound indicated in the title obtained in this way, the ratio between both possible c- and D-anomers is, according to "H-NMR spectroscopic analysis, approximately 98:2. Accordingly, the compound indicated in the title is presented only as an anomer with the o-configuration.

Melting point: 110.576.

Elemental analysis: soln.: C 49.21 H 5.68 detected: C 49.24 H 5.68 b) 5-(ethoxycarbonyl)pentyl-2,3,4,6-tetra-O-acetyl-o- UO-glucopyranoside

Similarly to the method described for the synthesis of the compound indicated in the title of example 706, as a result of the reaction of 130.0 g (332.8 mmol) of the compound indicated in the title of example 4a with 55.8 ml (332.8 mmol) of ethyl ether of 6-hydroxyhexanoic acid and 50 .6 ml (520 mmol) of stannous chloride (IM) in 500 ml of 1,2-dichloroethane after purification by column chromatography (eluent: hexane/ethyl acetic acid in a ratio of 271) yield 101.85 g (62.495 from theory) of the above title compound in in the form of colorless and viscous oil. The data of the "H-NMR spectroscopic analysis of the compound specified in the title, based on the value of the interaction constants уU12-8.8Hz, make it possible to draw an unequivocal conclusion about the presence of the p-configuration in the anomeric center, which, in addition, is the only configuration present in the anomeric center. According to this compound indicated above in the title can be obtained only in the form of an anomer with p-configuration.

Elemental analysis: solution: C 52.94 H 6.77 detected: C 52.77 H 6.70 c) 5-(carboxy)pentyl-2,3,4,6-tetra-O-benzyl-o- UO-glucopyranoside

A mixed suspension of 100.0 g (204.96 mmol) of the compound indicated in the title of example 736 in 150 ml of dioxane at room temperature and simultaneous intensive stirring is mixed in portions with a total amount of 169.14 g (3.02 mol) of highly dispersed potassium hydroxide powder. To increase its miscibility, the reaction mixture is mixed with another 150 ml of dioxane, the suspension obtained as a result is then heated to the boiling point and at this temperature for two hours it is mixed dropwise with benzyl bromide in a total amount of 264 ml (2.21 d8 mol). After carrying out the reaction for 4 hours at 110"C, and then for 12 hours at room temperature, the reaction mixture for processing is slowly poured into a mixture of water and ice in a total amount of 2.0 l, and the aqueous phase is then completely extracted with diethyl ether. After washing the ether phase obtained in this way and after drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the diethyl ether is distilled off in a vacuum. After that, the excess benzyl bromide is quantitatively distilled off from the reaction mixture in a vacuum created by an oil pump at an oil bath temperature of 1807C. The oily residue obtained in this way is purified on silica gel using ethyl acetic acid/hexane (1:10 ratio) as an eluent.

Yield: 128.8 g (84.395 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 75.68 H 7.16 found: C 75.66 H 7.23 g) 2,3,4,6-tetra-O-benzyl1-O-D-O-I|b -hexanoic acid-M-(3Z-oxa-1H 1H,2H2 NN H,5H,H- perfluorotridecyl)amide | Iglucopyranose 68.5 g (91.79 mmol) of the acid described in example 7C, as well as 9.25 g (91.79 mmol ) triethylamine is dissolved in 825 ml of dry tetrahydrofuran. After cooling the reaction solution to a temperature in the range from -15 to -20"C, at this temperature, a solution of 12.6b4g (92.5mmol) of isobutyl ether of chloroformic acid in 150ml of dry tetrahydrofuran is slowly added dropwise while stirring, while the rate of dropwise addition should be such that the internal temperature does not exceed -1070. After conducting the reaction for 15 minutes at -157C, a solution of 46.40 g (91.79 mmol) of 1H/1H,2H,2H-heptadecafluoro-1-(2 -aminoethoxy)udecane and 9.25 g (91.79 mmol) of triethylamine in 200 ml of dry tetrahydrofuran. After conducting the reaction for one hour at -15"C, and then for two hours at room temperature, the reaction solution is concentrated to dryness in a vacuum.

The obtained residue is dissolved in 250 ml of ethyl acetic acid and washed twice with a saturated solution of sodium bicarbonate in portions of 30 ml and once with water in a portion of 400 ml. After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the ethyl acetic acid is distilled off under vacuum. The resulting oily residue is chromatographed on silica gel using dichloromethane/hexane/2-propanol (in a ratio of 10:5:1) as an eluent.

Yield: 104.7 g (92.495 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 57.38 H4.98 M 1.13 P 26.15 found: C 57.27 H 5.09 M 1.11 E 26.08 d) 1-0-8-0- Ib-hexanoic acid-M-(3-oxa-1H 1 22 N NN 5H-perfluorotridecyl)amide|glucopyranose 40.0 g (32.3 dmmol) of the compound specified in the title of example 73g is dissolved in 750 ml of 2-propanol and mixed with 2 .0 g of palladium catalyst (1095 Pa/C). The reaction solution is hydrogenated for 12 hours at

22"C and a hydrogen pressure of 1 atmosphere. Then the catalyst is filtered off and the filtrate is concentrated to dryness.

The obtained residue is dissolved in 300 ml of dimethyl sulfoxide and from the solution obtained in this way, which contains the product, by mixing with diethyl ether in a total amount of 1000 ml and the subsequent separation of the solid substance that has precipitated, by vacuum filtration, 22.05 g (90.295 from the theory) are obtained indicated in of the title compound in the form of a colorless crystalline powder with a melting point of 122-1247C (with decomposition).

Elemental analysis: soln.: C 36.01 H 5.92 M 1.75 E 40.34 detected: C 36.07 H 6.08 M 1.76 E 40.66 e) Preparation of the composition containing specified in title of example 12 in (application MO 99/011611 compound (1,4,7-tris(1,4,7-tris(M-carboxylatomethyl)-10-(M-1-methyl-3-aza-2,5- dioxopentane-1,5-diyl|-1,4.7,10-tetraazacyclododecane, ba-complex)-10-(I2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-1,4,7,10- tetraazacyclododecane) and 1-0-8-0-|6b-hexanoic acid-M-(3-oxa-1Н 1 2Н,2наН НН, Н- perfluorotridecyl)amide|Iglucopyranose

To 37 ml of a solution of 1,4,7-tris1,4,7-tris(M-carboxylatomethyl)-10-(M-1-methyl-3-aza-2,5-dioxopentane-1,5-dioxyyl|-1, 4,7,10-tetraazacyclododecane, α-complex)-10-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-1,4,7,10-tetraazacyclododecane (30 mmol/l) in 0.4595- in an aqueous solution of table salt (pH 7.4; 0.25 mg/l

SamazdtpA) add 20.29 g (25.9 mmol) of the compound indicated in the title of example 7Zd, and the volume is brought up to 111 ml with the help of a 0.995% aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 100O0mmol/l.)

Example 74 a) 1-0-(1Н1Н,2Н 2Н-perfluorodecyl)-(2,3,4,6-tetra-O-acetyl)-c-ХО-mannopyranose

By the interaction of 50 g (128.09 mmol) of the compound indicated in the title of example 70a, which is used as a mixture of ",p-anomers in a ratio of 4:1, with a solution of 75.84 g (128.1 mmol) of 1-hydroxy-1H, 1H, 2H,2H-perfluorodecane in 150 ml of 1,2-dichloroethane, as well as with stannous chloride (IM) in a total amount of 19.47 g (166.53 mmol) similarly to the method described for the synthesis of the compounds indicated in the titles of examples 16 and 46, after processing and Purification by column chromatography (eluent: hexane/ethyl acetic acid in a ratio of 2:11) afforded 74.2 g (63.490 from theory) of the above title compound as a viscous colorless oil. The data of the "H-NMR spectroscopic analysis of the compound specified in the title, based on the value of the U12-1.3Hz interaction constants, make it possible to draw an unequivocal conclusion about the presence of an α-configuration in the anomeric center, which, in addition, is the only configuration present in the anomeric center, and therefore the compound mentioned above in the title can be obtained only in the form of a pure a-configuration anomer.

Elemental analysis: solution: C 44.65 H 2.53 E 35.32 found: C 44.77 H 2.61 E 35.09 b) 1-9-1H1H 2H,2H-perfluorodecyl)-o-O -mannopyranose 25 g (27.33 mmol) of the compound indicated in the title of example 74a is suspended in 400 ml of absolute methanol and mixed with a catalytic amount of sodium methanolate at 5"C. After the reaction has been carried out for 10 hours at room temperature, data on the control of the course of the reaction by thin-layer chromatography (eluent : chloroform/methanol in a ratio of 9:1) already indicates a quantitative conversion. For processing, the clear reaction solution is neutralized by mixing with the cation exchange resin Atrbegije IV 120 (H--form), the ionite is removed by vacuum filtration, and the methanol filtrate obtained in this way is distilled off in a vacuum until a dry residue is obtained.

The resulting crystalline residue is purified by double recrystallization from ethanol. The data of "H-NMR-spectroscopic analysis of the compound specified in the title allow on the basis of the value of the interaction constants

U12-1.0Hz to draw an unambiguous conclusion about the presence of an o-configuration in the anomeric center. Such a c-configuration is the only configuration present in the center of anomerism, i.e. the amount of possibly formed anomer of the compound with the D-configuration indicated in the title is below the detection threshold during "H-NMR-spectroscopic analysis. Accordingly, the compound indicated above in the title is obtained only in the form pure anomer with o-configuration.

Yield: 16.2 g (94.695 from theory) of a colorless crystalline solid.

Melting point: 172-1747C (with decomposition).

Elemental analysis: solution: С 30.69 Н 2.41 Е 51.57 detect.: С 30.57 Н 2.48 Е 51.65 c) Preparation of the composition containing metal complex II and 1-0-(1Н) ,1H,2H,2H-perfluorodecyl)-o-O-mannopyranose

To 50 ml of a solution of metal complex II (150 mmol/l) in a 0.4595 sodium chloride solution (pH 74; 0.25 mg/l SamMmazDtPA), add a solution of 2.01 g (3.21 mmol) of the compound specified in the title of example 746 in 200 ml of ethanol and stir for 2 hours at 50"C. Then the solution is concentrated to dryness in a vacuum and the volume of the residue is brought to 75ml by adding distilled water. The mixture is stirred for 1 hour at 40"C and filtered through a filter with a pore size of 0.2 μm. The filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 100 mmol/l.)

Example 75 a) 1-0O-(1H1H.2H 2H-perfluorododecyl)-2,3,4,6-tetra-O-acetyl-o-Y-mannopyranose

The interaction of 35 g (89.6 mmol) of the compound indicated in the title of example 7b0a, which is used as a mixture of o, p-anomers in a 4:1 ratio between them, with a solution of 50.60 g (89.7 mmol) of 1-hydroxy-1H1 НН н -

of perfluorododecane in 100 ml of 1,2-dichloroethane, as well as with stannous chloride (IM) in a total amount of 13.63 g (16.6 mmol) similarly to the method described for the synthesis of the compounds indicated in the titles of examples 16, 46 and 56, and after processing and purification column chromatography (eluent: hexane/ethyl acetic acid in a ratio of 2:11) yielded 62.49 g (68.7905 from theory) of the above title compound in the form of a viscous colorless oil. The data of the "H-NMR spectroscopic analysis of the compound specified in the title, based on the value of the interaction constants 12-21.4Hz, allow us to draw an unambiguous conclusion about the presence of the o-configuration in the anomeric center, which, in addition, is the only configuration present in the anomeric center, and therefore the compound indicated above in the title can be obtained only in the form of a pure anomer with a co-configuration.

Elemental analysis: solution: C 42.62 H 2.28 E 39.32 found: C 42.55 H 2.38 E 39.40 b). 1-0-(1H1H,2H 2H-perfluorododecyl)-c-Y-mannopyranose 25 g (24.64 mmol) of the compound indicated in the title of example 75a is suspended in 400 ml of absolute methanol and mixed with a catalytic amount of sodium methanolate at 5"C. conducting the reaction for 10 hours at room temperature, the data of monitoring the course of the reaction by thin-layer chromatography (eluent: chloroform/methanol in the ratio 9:1) indicate a quantitative conversion. For processing, the clear reaction solution is neutralized by mixing with the cation exchange resin Atregpye I 120 (H'-form ), the ionite is removed by vacuum filtration, and the methanol filtrate obtained in this way is distilled off in a vacuum until a dry residue is obtained. The obtained crystalline residue is purified by double recrystallization from a mixture of 2-propanol and ethanol (in a 1:1 ratio). The data of "H-NMR spectroscopic analysis of the compounds indicated in the title allow, based on the value of the interaction constants U12-:0.9Hz, to draw an unambiguous conclusion about the presence of the α-configuration in ano measurement center. Such an o-configuration is the only configuration present in the center of anomerism, i.e., the amount of possibly formed anomer of the compound with the p-configuration indicated in the title is below the detection threshold during "H-NMR spectroscopic analysis. Accordingly, the compound indicated above in the title is obtained only in the form pure anomer with o-configuration.

Yield: 16.96 g (90.895 from theory) of a colorless crystalline solid.

Melting point: 187-1887C (with decomposition).

Elemental analysis: solution: С 29.77 Н 2.08 Е 54.93 detected: С 29.70 Н 2.28 Е 54.83 c) Preparation of a composition containing a metal complex of MI and 1-0-(1Н /1H,2H,2H-perfluorododecyl)-o-

O-mannopyranose

1.70 g (2.34 mmol) of the compound indicated in the title of example 756 is added to 52 ml of a solution of the MI metal complex (18 mmol/l) in a 0.4595 aqueous solution of sodium chloride, and heated in a microwave oven for 10 minutes. The solution is cooled to room temperature, filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 180 mmol/l.)

Example 76 a) 2,3,4,6-tetra-O-acetyl)-1-O-o-0-|3,6,9-trioxa(C12-Cyaheptadecafluoro)nonadecyl|mannopyranose

By the interaction of 20 g (51.23 mmol) of the compound specified in the title of example 70a, which is used as a mixture of o, p-anomers in a ratio of 4:1 between them, with a solution of 30.54 g (51.23 mmol) of 1-hydroxy-tris- (NH 2hn2n-O)-1H1H,2H 2 H-perfluorodecane in 100 ml of 1,2-dichloroethane, as well as with stannous chloride (ImM) in a total amount of 5.98 g (51.233 mmol) similarly to the method described for the synthesis of the examples indicated in the headings 16, 46 and 56 compounds, after processing and purification by column chromatography (eluent: hexane/ethyl acetic acid in a ratio of 1:11) yield 34.22 g (72.190 from theory) of the above-mentioned compound in the form of a viscous colorless oil. The data of the "H-NMR spectroscopic analysis of the compound specified in the title, based on the value of the interaction constants 9U12-1.1Hz, make it possible to draw an unequivocal conclusion about the presence of an α-configuration in the anomeric center, which, in addition, is the only configuration present in the anomeric center, and therefore the above title compound can be obtained only as a pure anomer with the o-configuration.

Elemental analysis: solution: C 38.89 H 3.81 E 34.86 found: C 39.02 H 3.77 E 34.90 b). 1-O-o-0-I3,6,9-trioxa(C1i2-Cia-heptadecafluoro)nonadecyl|mannopyranose 20 g (21.58 mmol) of the compound indicated in the title of example 7ba is suspended in 350 ml of absolute methanol and mixed with catalytic amount of sodium methanolate. After carrying out the reaction for 10 minutes at room temperature, data on the control of the course of the reaction by thin-layer chromatography (eluent: chloroform/methanol in a ratio of 6:1) indicate a quantitative conversion. For processing, the clear reaction solution is neutralized by mixing it with Atreguier cation exchange resin!" 120 (H"-form), the ionite is removed by vacuum filtration, and the methanol filtrate obtained in this way is distilled off in a vacuum until a dry residue is obtained. The obtained crystalline residue is purified by double recrystallization from a mixture of ethyl acetic acid with 2-propanol and ethanol (in a ratio of 1: 0.5:1). The data of "H-NMR spectroscopic analysis of the compound specified in the title allow, on the basis of the value of the interaction constants

U12-1.0Hz to draw an unambiguous conclusion about the presence of an o-configuration in the anomeric center. Such a-configuration is the only configuration present in the center of anomerism, i.e., the amount of possibly formed anomer of the compound with the D-configuration indicated in the title is below the detection threshold during "H-NMR-spectroscopic analysis. Accordingly, the compound indicated above in the title is obtained only in the form pure anomer with o-configuration.

Yield: 15.20 g (92.9905 from theory) of a colorless crystalline solid.

Melting point: 141760.

Elemental analysis:

solution: C 34.84 H 3.59 E 42.58 detected: C 34.72 H 3.66 E 42.67 c) Preparation of the composition containing the compound indicated in the title of example 68 and 1-O-5- 0-I3,6,9-trioxa(C12-Sizaheptadecafluoro)nonadecyl|mannopyranose

3.71 g (4.89 mmol) of the compound specified in the title of example 766, and the volume is brought to 114 ml with the help of a 0.995 aqueous solution of table salt.

Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 100 mmol/l.)

Example 77 a) 2,3,4,6-tetra-O-acetyl-1-c-0-(3-thiopropionic acid-Mm-(3-oxa-yH1 НН 2н,аНаН5НН-perfluorotridecyl)amide|mannopyranose

25.0 g (57.28 mmol) of 3-(tetra-O-acetyl-o-O-mannopyranosylmercapto)propionic acid is dissolved in 5 bOml of dry tetrahydrofuran (preparation according to Roprirot Miigee M., Vidiapesi Korep G.,

Corrip5 Chate5 S, Juoerreg T.M/., Zpep T.U., U. Med. Spet., 24, 12 (1981), pp. 1388-1395I|, as well as 5.77 g (57.28 mmol) of triethylamine. After cooling the reaction solution to a temperature in the range from -15 to -20"C, at this temperature, a solution of 7.82 g (57.28 mmol) of isobutyl ether of chloroformic acid in 100 ml of dry tetrahydrofuran is slowly added dropwise with stirring, while the rate of dropwise addition should be such that the internal temperature does not exceed -107C. After conducting the reaction for 15 minutes at -157C, a solution of 29.05g (57.28mmol) is slowly added dropwise at -20C. 1H.1H,2H,2H-heptadecafluoro-1-(2-aminoethoxy)decane and 5.77 g (57.28 mmol) of triethylamine in 200 ml of dry tetrahydrofuran. After conducting the reaction for one hour at -157C, and then for two hours at room temperature, the reaction solution is concentrated to dryness in a vacuum. The obtained residue is dissolved in 250 ml of ethyl acetic acid and washed twice with a saturated solution of sodium bicarbonate in portions of 200 ml and once with water in a portion of ZbOml. After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the ethyl acetic acid is distilled off under vacuum. The resulting oily residue is purified on silica gel using dichloromethane/hexane/2-propanol (8:5:1 ratio) as eluent.

Yield: 44.90 g (84.795 from theory) of the compound indicated above in the title in the form of a colorless and highly viscous oil.

Elemental analysis: solution: C 37.63 H 3.48 M 1.51 5 3.46 E 34.89 found: C 37.77 H 3.37 M 1.61 5 3.57 E 35.21 b ) 1-o--0-IZ-thiopropionic acid-M-(3-oxa-1Н 1Н,2Н,2НН,Н,5Н,5Н- perfluorotridecyl)amide|mannopyranose

30g (32.41mmol) of the compound indicated in the title of example 77a is suspended in 400ml of absolute methanol and mixed with a catalytic amount of sodium methanolate at 5"С. After the reaction has been carried out for 10 hours at room temperature, data on the control of the course of the reaction by thin-layer chromatography (eluent: chloroform /methanol in a ratio of 9:1) already indicate a quantitative transformation. For processing, the clear reaction solution is neutralized by mixing it with the cation exchange resin Atregije IC 120 (H"- form), the ionite is removed by vacuum filtration, and the methanol filtrate obtained in this way is distilled off in a vacuum to obtain of dry residue. The resulting crystalline residue is purified by recrystallization from a mixture of ethyl acetic acid and methanol (in a ratio of 0.5:1). The data of "H-NMR-spectroscopic analysis of the compound specified in the title allow on the basis of the value of the interaction constants

At 12-1.1Hz, we can draw an unambiguous conclusion about the presence of an o-configuration in the anomeric center. Such a-configuration is the only configuration present in the center of anomerism, i.e., the amount of possibly formed anomer of the compound with the D-configuration indicated in the title is below the detection threshold during "H-NMR-spectroscopic analysis. Accordingly, the compound indicated above in the title is obtained only in the form pure anomer with o-configuration.

Yield: 23.76 g (96.8905 from theory) of a colorless crystalline solid.

Melting point: 113-114.576.

Elemental analysis: solution: C 33.30 H 3.19 M 1.85 54.23 E 42.64 found: C 33.21 H 3.26 M 1.96 5 4.08 E 42.77 c) Preparation of the composition containing the compound indicated in the title of example 66 and 1-0-0-IZ-thiopropionic acid-M-(3-oxa-1!H1H.2H,2 НН, Н,5Н,ЗН-perfluorotridecyl)amide|mannopyranose

A solution of 27.41 g (36.19 mmol) of the compound indicated in the title of the example is added to 47 ml of a solution of compound 66 (33 mmol/l) in a 0.4595% sodium chloride solution (pH 7.4; 0.25 mg/l CaMmazDtTpPA) 776 compounds in 200 ml of ethanol and stirred for 2 hours at 50 "C. Then the solution was concentrated to dryness in a vacuum and the volume of the residue was brought to 155 ml by adding distilled water. The mixture was stirred for 10 minutes at 40 "C and filtered through a filter with a pore size of 0.2 μm . The filtrate is packaged in vials.

The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 100 mmol/l.)

Example 78 a) 2,3,4,6-tetra-O-acetyl-1-p-0-I|3,6,9-trioxa(St12-

Cyoheptadecafluoro)nonadecyl|glucopyranosyluronic acid 20.2 g (50.65 mmol) methyl (1-bromo-2,3,4-tri-O-acetyl-o-O-glucopyranoside)uronate (production according to

Reigeg, Norre-5euiegv 2. Rpuzioi. Spet., 314 (1949), pp. 234, 237, as well as Soebrei, Vabregv, 9. Vioi. Spet., 111 (1935), pp. 347, 350, and VoPeprask and others, U. Ateg. Spent Boss, 77 (1955), p. 3310, 3313) and 60.64g

(101.7 mmol) of 3,6,9-trioxa(C12-Sysheptadecafluoro)nonadecan-i1-ol is dissolved in 250 ml of anhydrous acetonitrile and mixed with 13.0 g of freshly precipitated silver oxide at room temperature. After conducting the reaction for 12 hours at room temperature, undissolved silver salts are filtered off, after which the salts are thoroughly washed with dichloromethane and the filtrate obtained in this way is distilled off in a vacuum until a dry residue is obtained. The resulting residue is purified by column chromatography (eluent: hexane/ethyl acetic acid in a ratio of 3:1).

Yield: 22.99 g (53.395 from theory) of the above title compound in the form of a colorless, highly viscous oil.

Elemental analysis: solution: C 41.05 H 3.92 E 38.06 found: C 41.20 H 3.76 E 38.22 b) 1-0-8-0-I3,6,9-trioxa (C12-Siaheptadecafluoro)nonadecyl|glucopyranosyluronic acid 10.0 g (11.78 mmol) of the compound indicated in the title of example 78a is suspended at room temperature with stirring in 200 ml of a mixture consisting of methanol and 0.5-molar caustic sodium in a ratio of 2 :1. After conducting the reaction for 12 hours at room temperature, the transparent reaction mixture for its processing is neutralized by mixing it with the cation exchange resin Atrbegije IV 120 (H"-form), the ionite is removed by vacuum filtration, and the methanol-water filtrate obtained in this way is distilled off in a vacuum until a dry residue is obtained. The resulting crystalline residue is purified by recrystallization from a mixture of ethyl acetic acid with methanol (in a ratio of 0.25:1). The data of "H-NMR spectroscopic analysis of the compound indicated in the title allow us to draw an unequivocal conclusion about the presence of p -configurations in the anomeric center. Such a p-configuration is the only configuration present in the center of anomerism, i.e., the amount of possibly formed anomer of the compound with the c-configuration indicated in the title is below the detection threshold during "H-NMR-spectroscopic analysis. Accordingly, the compound indicated above in the title is obtained only in the form of pure anomer with p-configuration.

Melting point: 78.570.

Elemental analysis: solution: С 34.21 Н 3.26 Е 41.81 detected: С 34.38 Н 3.26 Е 41.90 c) Preparation of a composition containing a metal complex !/ and 1-0-8- 0-I3,6,9-trioxa (Si12-

Sioheptadecafluoro)nonadecyl|glucopyranosyluronic acid

19.18 g (24.63 mmol) of the compound specified in the title of example 786 is added to 1 ml of a solution of metal complex I (280 mmol/l) in a 0.4595 aqueous solution of table salt (pH 7.4; 0.25 mg/l CaMmazDtPA) , and the volume is brought up to 53.2 ml using a 0.995 strength aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 200 mmol/l.)

Example 79 a) 6-(2-oxa-y NT H,ZN.ZnH AN, 4H-perfluorodecyl)-01,02,05,0y-diisopropylidene-o-O-galactopyranose

A total of 12.15 g (46.6 mmol) is added dropwise to a mixed suspension of 2.01 g (70.00 mmol) of sodium hydride (8090 in mineral oil) in 25 ml of dimethylformamide at room temperature

OO7,05,0-diisopropylidene-o-galactopyranose (production according to I emepe, Meueg, u. Vioi. Spet., 64 (1925), p. 473, and also MeoSgeai, tii, u. Spet. Zos. 1939, pp. 387, 389 and Rgepdepregd, Nihop, Spec. Veg., 56 (1923), pp. 2119, 21221, dissolved in 200 ml of absolute dimethylformamide. After that, it is left for another 120 minutes to stir at room temperature and then slowly added dropwise to a total of 30.09g (48, Ommol) of 1-bromo-1H.1H 2H,2H-perfluorododecane, dissolved in 150 ml of absolute dimethylformamide. Then the reaction solution obtained in this way is stirred for the next 12 hours at room temperature. For processing, the reaction solution is slowly poured into 1 liter a mixture of water and ice, after which it is almost completely extracted with diethyl ether. The combined organic phases are then washed twice with a saturated solution of sodium bicarbonate in portions of 200 ml and twice with water in portions of 200 ml. After drying the organic phase over sodium sulfate, the salt is separated by vacuum filtration and the solution nick is driven off in a vacuum. The obtained oily residue is purified on silica gel using ethyl acetic acid/hexane (1:10 ratio) as an eluent.

Yield: 29.8 g (79.395 from theory) of the above title compound as a viscous colorless oil.

Elemental analysis: solution: C 35.75 H 2.87 E 49.47 found: C 35.64 H 2.98 E 49.54 b) 6-(2-oxa-TIN 1 H,ZN.ZN αH,4H-perfluorodecyl)-o-O-galactopyranose 20 g (24.8 mmol) of the compound specified in the title of example 79a is mixed with 30 ml of a 195% aqueous solution of sulfuric acid and stirred for 1 h at 80 °C. After cooling to room temperature are neutralized by mixing with an aqueous solution of barium hydroxide, after which the precipitated barium sulfate is filtered off and the clear aqueous solution that contains the product obtained in this way is lyophilized. the presence of both possible configurations in the anomeric center, while the ratio between c/D-configurations present in the anomeric center is, according to the "H-NMR-spectroscopic analysis, 1:1.4 (osr).

Accordingly, the compound indicated above in the title is isolated only in the form of a mixture of "- and D-anomers with a ratio between them of 1:1.4, that is, the obtained compound is not separated into separate anomers.

Yield: 15.28 g (98.4905 from theory) of the above title compound in the form of a colorless lyophilizate.

Elemental analysis (in terms of anhydrous substance): solution: С 35.75 Н 2.87 Е 49.47 found.: С 35.64 Н 2.98 Е 49.54 c) Preparation of the composition containing indicated in the title example 67 compound and 6-(2-oxa-1H/1H,

ZN.ZN.aNaH-perfluorodecyl)-o-O-galactopyranose

A solution of 1.68 g (2.69 mmol) of the compound indicated in the title of example 67 (250 mmol/l) in a 0.4595 solution of sodium chloride (pH 7.4; 0.25 mg/l SamazDtPA) is added to 4 ml of a solution of compound 67 indicated in the title of the example 796 compounds in 200 ml of ethanol and stir for 2 hours at 50"C. Then the solution is concentrated to dryness in a vacuum and the volume of the residue is brought to 107.5 ml by adding distilled water. The mixture is stirred for 1 hour at 40"C and filtered through a filter with a pore size of 0 , 2 μm. The filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 100 mmol/l.)

Example 80 a) 1-O-5-0-(1-perfluorooctylsulfonylpiperazine-4-carbonyl)umethyl|mannopyranose

Zog (52.8 mmol) of 1-perfluorooctylsulfonylpiperazine (production described in OE 19603033) and 31.73 g (5 mmol) of 2,3,4,6-tetra-O-benzyl-0-Y-carboxymethylmannopyranose (production described in OE 19728954) are dissolved in 30 Oml of tetrahydrofuran. Next, 24.73 g (100 mmol) of EEDH (ethyl ether of 1,2-dihydro-2-ethoxyquinoline-1-carboxylic acid) is added at 0"C and stirred for 2 hours at room temperature, and then for 2 hours at room temperature. Then the solution is evaporated to dryness in a vacuum and the residue is purified by flash chromatography on silica gel (eluent: hexane/ethyl acetic acid in a ratio of 10:1).

The fractions containing the product are evaporated to dryness, the residue is dissolved in a mixture of 200 ml of methanol and 150 ml of dichloromethane and hydrogenated over palladium on charcoal (2 g of 10956 Ra/sС) for 8 hours. After that, the hydrogenation catalyst is filtered off and the filtrate is evaporated to dryness. The residue is recrystallized from acetone/diethyl ether.

Yield: 30.39g (7395 from theory) of waxy colorless solid.

Elemental analysis: solution: C 30.47 H 2.68 E 40.96 M 3.55 5 4.07 found: C 30.61 H 2.75 E 41 TO M 3.46 5412 b) Obtaining the composition, containing metal complex I and 1-0-a-0-((1-perfluorooctylsulfonylpiperazine-4-carbonyl)methyl|mannopyranose

4.71 g (5.97 mmol) of the compound specified in the title of example 80a is added to 32 ml of a solution of metal complex I (280 mmol/l) in a 0.4595% aqueous solution of table salt (pH 7.4; 0.25 mg/l SamazdtPA) , and the volume is brought up to 55 ml with the help of a 0.995% aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 200 mmol/l.)

Example 81 a) 3-oxa-2H.2H,4H,4H,5H,5ZH-perfluorotridecanoic acid, sodium salt 20g (38,3mmol) of 3-oxa-2H,2H,4H.4H,5H,5H-perfluorotridecanoic acid | preparation described in OE 19603033) is dissolved in 300 ml of ethanol and 7.7 ml of 5N is added. aqueous caustic sodium. After that, it is evaporated to dryness and the residue is dried in a vacuum oven (hours, 60"7C).

Yield: 20.85 g (quantitative) of colorless crystalline powder.

Elemental analysis: solution: C 26.49 H 1.11 ER 59.35 Ma 4.22 found: C 26.60 H 1.19 E 59.47 Ma 4.30 b) Preparation of a composition containing a metal complex And the sodium salt of З-oxa-2Н,2НН,4НН4НН,5НН,5НН- perfluorotridecanoic acid

2.09 g (3.84 mmol) of the compound specified in the title of example 814 is added to 32 ml of a solution of metal complex I (280 mmol/l) in a 0.4595 aqueous solution of table salt (pH 7.4; 0.25 mg/l SamazdtPA) , and the volume is brought up to 9 Oml with the help of a 0.995 aqueous solution of common salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 100O0mmol/l.) c) Preparation of a composition containing metal complex I and sodium salt 3-oxa-2Н,2Н,4нН4Нн,5Нн,5Н- perfluorotridecanoic acid

1.00 g (1.84 mmol) of the compound specified in the title of example 814 is added to 32 ml of a solution of metal complex I (280 mmol/l) in a 0.4595 aqueous solution of table salt (pH 7.4; 0.25 mg/l SamazdtPA) , and the volume is brought up to 9 Oml with the help of a 0.995 aqueous solution of common salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 100O0mmol/l.) d) Preparation of a composition containing metal complex I and sodium salt 3-oxa-2Н,2НН,4ННА4НН,5НН,5Н- perfluorotridecanoic acid

To 32 ml of a solution of metal complex I (280 mmol/l) in a 0.4595 aqueous solution of common salt (pH 7.4; 0.25 mg/l SamazDtTPA) add 0.54 g (1.0 mmol) of the compound specified in the title of example 81a , and the volume is brought up to 9 Oml with the help of a 0.995 aqueous solution of common salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 100O0mmol/l.)

Example 82 a) 1-perfluorooctylsulfonyl-4-(3,6,9,12,15-pentaoxahexadecanoyl)piperazine 20 g (3522 mmol) of perfluorooctylsulfonyl piperazine (see example 30a) is dissolved in 30 ml of dichloromethane and 5.06 g (500 mmol) of triethylamine is added. Then it is cooled to 0"C, after which 14.24 g (50 mmol) of 3,6,9,12,15-pentaoxahexanoic acid chloride is added dropwise for 20 minutes and stirred for 2 hours at 0"C. Next, add 400 ml of 595% aqueous hydrochloric acid and mix thoroughly. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum.

The residue is chromatographed on silica gel (eluent: dichloromethane/methanol in a ratio of 15:1).

Yield: 26.44 (9295 from theory) of a waxy solid.

Elemental analysis: solution: C 33.83 H 3.58 M 3.43 E 39.55 5 3.93 found: C 33.96 H 3.66 M 3.50 E 39.67 5 3.82 b ) Preparation of a composition containing metal complex I and 1-perfluorooctylsulfonyl-4-(3,6,9,12,15-pentaoxahexadecanoyl)piperazine

4.61 g (5.64 mmol) of the compound indicated in the title of example 82a is added to 47 ml of a solution of metal complex I (280 mmol/l) in a 0.4595 aqueous solution of table salt (pH 7.4; 0.25 mg/l SamazdtPA) , and the volume is adjusted to bbml using a 0.995% aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 200 mmol/l.)

Example 83 a) Ester of TIN.1H,2H 2H-perfluorodecyl-i-toluenesulfonic acid 20g (43.1mmol) of 1H.1H,2H,2H-perfluorodecanol is dissolved in 200ml of pyridine and at 0"C portions add 9.53g (50mmol) of p-toluenesulfonic acid chloride. The mixture is stirred for 5 hours at room temperature. Then the solution is poured into 1000 ml of a mixture of water and ice and stirred for 10 minutes. The precipitate is filtered, washed with a large amount of water and then recrystallized from acetone.

Yield: 22.04 g (9795 from theory) of a colorless crystalline solid.

Elemental analysis: solution: С 22.78 НО0.76 Е 61.26 5 6.08 detected: С 22.89 Н 0.70 Е 61.39 5 6.15 9,12,15-pentaoxapentacosan-1-ol 20g (37.94mmol) of the compound indicated in the title of example 83Za, 35.74g (150mmol) pentaethylene glycol and 1T1g of crown ether 18-crown-b6 are dissolved in 300ml of tetrahydrofuran and 10 1 g (18 Ommol) of highly dispersed powdered potassium hydroxide. The mixture is stirred for 17 hours at room temperature. After that, the solid substance is filtered off and the filtrate is concentrated to dryness under vacuum.

The residue is chromatographed on silica gel (eluent: dichloromethane/methanol in a ratio of 15:1).

Yield: 5.45 g (2190 from theory) of colorless viscous oil.

Elemental analysis: solution: C 35.10 H 3.68 E 47.19 detection: C 35.22 H 3.77 E 47.10 c) Preparation of the composition containing the compound indicated in the title of example 69 and C-Soheptadecaftor - 3,6,9,12,15-pentaoxapentacosan-1-ol

44.98 g (65.72 mmol) of the compound indicated in the title of example 836 is added to 5 ml of a solution of the compound indicated in the title of example 69 (3100 mmol/l) in a 0.45956% aqueous solution of sodium chloride, and heated in a microwave oven for 10 minutes. The solution is cooled to room temperature, filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 3100 mmol/l.)

Example 84 a) M,M-bis(8-hydroxy-3,6,-dioxaoctylperfluorooctylsulfonic acid amide) 15 g (29.23 mmol) of perfluorooctyl sulfonic acid amide and 22.16 g (87.7 ml) of 9-(tetrahydropyran-2-yl)- 3,6,9-trioxanonyl chloride is dissolved in 200 ml of acetonitrile. Next, 41.46 g (300 mmol) of potassium carbonate and 1 g (b mmol) of potassium iodide are added and refluxed for 10 hours. The solid substance is filtered off and the filtrate is evaporated to dryness under vacuum. The residue dissolve in 400 ml of ethanol and add

ZOml of 1095 aqueous hydrochloric acid. The mixture is stirred for 2 hours at room temperature. Next, the pH value is set to 7 with caustic sodium and the solution is concentrated under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/methanol in a ratio of 10:1).

Yield: 11.38 g (5195 from theory) of colorless viscous oil.

Elemental analysis: solution: C 31.46 H 3.43 M 1.83 ER 42.30 54.20 found: C 31.59 H 3.50 M 1.90 E 42.46 5 4.08 b) Obtaining a composition containing a metal complex and! and M,M-bis(8-hydroxy-3,6,-dioxaoctyl)perfluorooctylsulfonic acid amide

To 37 ml of a solution of metal complex I (280 mmol/l) in a 0.4595 aqueous solution of table salt (pH 7.4; 0.25 mg/l CaMmazdtpA) add 7.91 g (10.3 bmmol) of the compound indicated in the title of example 84a , and the volume is brought up to 104 ml with the help of a 0.9956 aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 100O0mmol/l.)

Example 85 a) Amide M,M-bis(tert-butyloxycarbonylmethyl/uperfluorooctylsulfonic acid) 20g (38.97mmol) of perfluorooctylsulfonic acid amide and 20.73g (150mmol) of potassium carbonate are suspended in 200ml of acetone and 17.56g (9O0mmol) of tert- butyl ether of bromoacetic acid.

Then boil under reflux for 10 minutes. The solid is filtered off and the filtrate is evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: n-hexane/ethyl acetic acid in a ratio of 10:1).

Yield: 23.53g (8395 from theory) of a colorless waxy solid.

Elemental analysis: solution: C 33.02 H 3.05 E 44.40 M 1.93 5 4.41 found: C 33.19 H 3.11 E 44.30 M 1.99 54.32 b) M,M-bis(carboxymethyl)ulperfluorooctylsulfonic acid amide, disodium salt of 23g (31.62mmol) of the compound indicated in the title of example 85a are dissolved in 100ml of trifluoroacetic acid and stirred at room temperature for 5 hours. The mixture is evaporated to dryness under vacuum and the residue is recrystallized from acetone. The crystals are separated by vacuum filtration and dried under vacuum at 5076.

Yield: 17.7 g (9190 from theory) of colorless crystalline powder. 17g (27.63mmol) of diacid obtained in this way is dissolved in a mixture of 1t100ml of water and 300ml of ethanol and 92ml of Zn is added. aqueous caustic sodium. The mixture was stirred for 20 min at room temperature and then evaporated to dryness under vacuum. The residue is dried in a vacuum (60"C, 8 hours).

Yield: 18.2 g of colorless crystalline powder.

Elemental analysis: solution: C21.87 HO,61 M 2.12 E 49.00 5 4.86 Ma 6.98 found: C 22.00 H 0.70 M 2.20 E 49.17 5 4, 93 Ma 7.10 c) Preparation of a composition containing a metal complex | ii monosodium salt of amide

Non-bis(carboxymethyl)/perfluorooctylsulfonic acid

2.89 g (4.39 mmol) of the compound indicated in the title of example 856 is added to 41 ml of a solution of metal complex II (250 mmol/l) in a 0.4595% aqueous solution of table salt (pH 7.4; 0.25 mg/l CaMmazdtpPA) , and the volume is brought up to 52 ml with the help of a 0.995% aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 200 mmol/l.)

Example 86 a) Monoester 1Н.1Н,2Н,2Н-perfluorododecylsulphuric acid, sodium salt 10 g (17.7 mmol) of 1Н,1Н,2Н,2Н-perfluorododecanol is dissolved in 100 ml of chloroform and at 0"С, 2.82 g (17.73 mmol) are added ) of a complex of sulfur trioxide and pyridine. The mixture is stirred for an hour at 0"C and then evaporated to dryness under vacuum. The residue is dissolved in 300 ml of ethanol and mixed with 17.8 ml of other aqueous caustic sodium. The solution is evaporated to dryness and the residue is dried in a vacuum (60"C, 2 hours).

Yield: 11.81g (quantitative).

Elemental analysis: solution: C 21.64 H 0.61 E 59.89 Ma 3.45 5 4.81 found: C 21.70 H 0.72 E 60.00 Ma 3.57 5 4.92 b ) Preparation of a composition containing a metal complex of mi and the sodium salt of the monoester ИНМ1Н,2Ннагн-perfluorododecylsulphuric acid

4.90 g (7.35 mmol) of the compound indicated in the title of example 8ba is added to 1 ml of a solution of the MI metal complex (290 mmol/l) in a 0.4596% aqueous solution of sodium chloride, and heated in a microwave oven for 10 minutes. The solution is cooled to room temperature, filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 290 mmol/l.)

Example 87 a) 2H,2H,4H.4H,5H,5H-3-oxaperfluoropentadecanoic acid, sodium salt 10 g (16.07 mmol) of 2H,2H.4H.4H,5nH,5H-3-oxaperfluoropentadecanoic acid is dissolved in 300 ml of ethanol and mix with 16.1 ml of 1n. aqueous caustic sodium. The solution is evaporated to dryness and the residue is dried in a vacuum (60"C, 2 hours).

Yield: 10.35 g (quantitative) of colorless amorphous powder.

Elemental analysis: solution: C 26.10 H 0.94 E 61.94 Ma 3.57 found: C 26.22 H 1.00 E 62.05 Ma 3.66 b) Preparation of the composition containing the indicated of the title of example 66, the compound and the sodium salt of 2nH,2nNa4NYAH,5H,5H-3-oxaperfluoropentadecanoic acid

A solution of 3.36 g (5.21 mmol) of the compound indicated in the title of the example is added to 45 ml of a solution of the compound 66 indicated in the title of the example (270 mmol/l) in a 0.4595 sodium chloride solution (pH 7.4; 0.25 mg/l CaMmazDtPA) 87a compounds in 200 ml of ethanol and stirred for 2 hours at 50 "C. Then the solution was concentrated to dryness in a vacuum and the volume of the residue was brought to 122 ml by adding distilled water. The mixture was stirred for 10 minutes at 40 "C and filtered through a filter with a pore size of 0.2 μm . The filtrate is packaged in vials.

The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 100 mmol/l.)

Example 88 a) М- ННЯ Н НН, Н-З-oxaperfluorotridecyl)monoamide of ethylenediamine-M,M-tetraacetic acid

10.14 g (20 mmol) of 1H.1H,2H,2nNa4nNaH,5nH,ZH-3-oxaperfluorotridecylamine is added in portions to 30g (117.1mmol) of EDTC bishydride suspended in 200ml of dimethylformamide and 500ml of pyridine at 50"C and stirred for 2 hours at 507 C. Next, add 100 ml of water, stir for 1 hour at 50 "C and evaporate the residue to dryness. Next, the residue is dissolved in a small amount of water and the pH value is set to 4 using glacial acetic acid. The undissolved precipitate is filtered off and chromatographed on KR-18 (eluent: acetonitrile/water gradient).

Yield: 9.58 g (6195 from theory) of a colorless solid.

Water content: 8905.

Elemental analysis: solution: C 33.64 H 3.59 M 5.35 E 41.12 found: C 33.51 H 3.69 M 5.44 E 41.24 b) MA nNiH2gH nn Н,ЗН, 5H-3-oxaperfluorotridecyl) monoamide of ethylenediamine-M,M-tetraacetic acid, calcium salt, sodium salt 9.0 g (11.4 b6 mmol) of the compound specified in the title of example C8a is suspended in ZOO ml of water and 11.4 ml of Mn are added. aqueous caustic sodium. After that, 1.15 g (11.46 mmol) of calcium carbonate is added and stirred for 5 hours at 50"C. The solution is filtered and the filtrate is lyophilized.

Yield: 9.7 g (10095 from theory) of a colorless amorphous solid.

Water content: 7.595.

Elemental analysis: solution: C 31.25 H 2.98 M 4.97 E 38.20 Ma 2.72 Ca 4.74 found: C 31.40 H 3.09 M 5.10 E 38.07 Ma 2.81 Са 4.82 c) Preparation of a composition containing a metal complex | and calcium salt and sodium salt of M-nin 2гН 2 нн Н,5Н,ЗН-З-oxaperfluorotridecyl)monoamide of ethylenediamine-M,M-tetraacetic acid

2.54 g (3.01 mmol) of the compound specified in the title of example 886 is added to 4 ml of a solution of metal complex I (280 mmol/l) in a 0.45956 aqueous solution of table salt (pH 7.4; 0.25 mg/l SamazdtPA) , and the volume is brought up to 121 ml with the help of a 0.996 aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 100O0mmol/l.)

Example 89 a) Simple IN.1H,2H 2H-perfluorodecyl(2,2-dimethyl-5-hydroxy-1,3-dioxepan-b-yl) ether

Zog (64.64 mmol) of 1H.1H,2H,2H-perfluorodecanol is dissolved in 200 ml of tetrahydrofuran and 1.68 g (/Omol) of sodium hydride is added at 0"C. The mixture is stirred for 2 hours at room temperature, and then for 4 hours at 60" WITH. Next, the solution is placed in a metal autoclave, after which 9.31 g (64.64 mmol) of 2,2-dimethyl-1,3,6-trioxabicyclo!y5.1.F|octane is added and then kept for 10 hours at 15070.

After that, the reaction solution is poured into a mixture of water and ice and extracted twice with diethyl ether.

The combined organic phases are evaporated to dryness and the residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 10:1)

Yield: 16.12 g (4195 from theory) of a colorless solid.

Elemental analysis: solution: С 33.57 Н 2.82 Е 53.10 detected: С 33.69 Н 2.90 Е 53.35 b) Simple 1Н,1Н,2Н,2Н-perfluorodecyl (1-hydroxymethyl- 2,3-dihydroxypropyl) ether 15 g (24.66 mmol) of the compound specified in the title of example 89a is dissolved in 300 ml of ethanol and added

ZOml of 1095 aqueous hydrochloric acid. Then boil for 5 hours under reflux. The pH is then adjusted to 7 with caustic sodium, after which it is concentrated to dryness and the residue is chromatographed on KR-18 (eluent: acetonitrile/water gradient).

Yield: 12.75 g (9195 from theory) of a colorless solid.

Water content: 4.595.

Elemental analysis: solution: С 29.59 Н 2.31 Е 56.84 detected: С 29.48 Н 2.37 Е 56.99 c) Preparation of the composition containing indicated in the title of example 12 y (MO 99/ 011611 compound (1,4,7-tris(1,4,7-tris(M-carboxylatomethyl)-10-(M-1-methyl-3-aza-2,5-dioxopentane-1,5-diyl|- 1,4,7,10-tetraazacyclododecane, ba-complex)-10-(I2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-1,4,7,10-tetraazacyclododecane) and simple 1H.1H,2H ,2H-perfluorodecyl (1-hydroxymethyl-2,3-dihydroxypropyl) ether

To 37 ml of a solution of 1,4,7-tris1,4,7-tris(M-carboxylatomethyl)-10-(M-1-methyl-3-aza-2,5-dioxopentane-1,5-diyl|-1, 4,7,10-tetraazacyclododecane, c-complex)-10-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|Iacetyl-1,4,7,10-tetraazacyclododecane (30 mmol/l) in 0.4595- in an aqueous solution of table salt (pH 7.4; 0.25 mg/l

SayazdtpA) add 9.46 g (16.65 mmol) of the compound indicated in the title of example 896, and the volume is brought up to 111 ml with the help of a 0.995 aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 100O0mmol/l.)

Example 90 a) Simple 1H.1H,2H,2H-perfluorodecyl/1,2-bis(2,2-dimethyl-1,3-dioxolan-4-yl)-2-hydroxyethyl ether

Zog (64.64 mmol) of 1H.1H,2H,2H-perfluorodecanol is dissolved in 200 ml of tetrahydrofuran and 1.68 g (/Omol) of sodium hydride is added at 0"C. The mixture is stirred for 2 hours at room temperature, and then for 4 hours at 60" WITH. Next, the solution is placed in a metal autoclave, after which 15.78 g (64.64 mmol) of 1,2-bis-(2,2-dimethyl-1,3-dioxolan-4-yl)uoxirane is added and then kept for 10 hours at 15070. After that, the reaction solution is poured into a mixture of water and ice and extracted twice with diethyl ether. The combined organic phases are evaporated to dryness and the residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 10:1)

Yield: 14.2 g (3195 from theory) of a colorless solid.

Elemental analysis: solution: C 37.30 H 3.56 E 45.59 detect.: C 37.48 H 3.66 E 45.71 b) Simple 1H.1H,2H,2H-perfluorodecyl1,2-bis( 1,2-dihydroxyethyl)-2-hydroxyethyl ether 14 g (19.7 mmol) of the compound indicated in the title of example 9ba is dissolved in 3000 ml of ethanol and added

ZOml of 1095 aqueous hydrochloric acid. Then boil for 5 hours under reflux. The pH is then adjusted to 7 with caustic sodium, after which it is concentrated to dryness and the residue is chromatographed on KR-18 (eluent: acetonitrile/water gradient).

Yield: 10.55 g (8595 from theory) of a colorless solid.

Water content: 3.295.

Elemental analysis: solution: С 30.59 Н 2.73 Е 51.41 detected: С 30.73 Н 2.81 Е 51.58 c) Obtaining a composition containing metal complex II and simple 1Н, 1Н, 2Н ,2H-perfluorodecyl/1,2-bis(1,2-dihydroxyethyl)-2-hydroxyethyl| ether

Up to 41 ml of solution of metal complex I! (30 mmol/l) in a 0.4595 aqueous solution of table salt (pH 7.4; 0.25 mg/l SamMmazdtpA) add 11.98 g (19.07 mmol) of the compound indicated in the title of example 906, and the volume according to with the help of a 0.995% aqueous solution of table salt, it is brought up to b4ml. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 200 mmol/l.)

Example 91 a) MM-bis((8-sulfuric acid-monoester, sodium salt)-3,6-dioxaoctylamide of perfluorooctylsulfonic acid 13.54 g (17.733 mmol) of the compound indicated in the title of example 84a is dissolved in 300 ml of chloroform and at 0"C, add 2.82g (17.733mmol) of a complex of sulfur trioxide with pyridine. The mixture is stirred for an hour at 0"C and then evaporated to dryness under vacuum. The residue is dissolved in 300ml of ethanol and mixed with 17 ml of aqueous caustic sodium. The solution is evaporated to dryness and the residue is dried in a vacuum (60"C, 2 hours).

Yield: 17.15g (quantitative).

Elemental analysis: solution: C 24.83 H 2.50 E 33.83 M 1.45 5 9.94 Ma 4.75 found: C 24.96 H 2.62 E 33.97 M 1.53 5 10.05 Ma 4.86 b) Preparation of a composition containing a metal complex | and M,M-bis((8-sulfuric acid-monoester, sodium salt)-3,6-dioxaoctylamide of perfluorooctylsulfonic acid

142.29 g (147.0 bmmol) of the compound indicated in the title of example 91a is added to 43 ml of a solution of metal complex I (35 mmol/l) in a 0.4595% aqueous solution of table salt (pH 7.4; 0.25 mg/l CaMmazDtTPA) , and its volume is brought up to 164 ml with the help of a 0.995% aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 1000 mmol/l.)

Example 92 a) Diethyl ether of 2-(2H,2H.ZH.ZH,5,5H,vHn,vHn-1,4-dioxaperfluorotetradec-1-yl)succinic acid

30 g (590 mmol) of 1H1H2Hn2NANYAN,5H,5H-Z-oxaperfluorotridecanol is dissolved in 300 ml of tetrahydrofuran and 1.68 g (7/Omol) of sodium hydride is added at 0 °C. Then it is stirred for an hour at 0 °C, and then for 5 hours at 40 °C. C. Then, 20.25 g (800 mmol) of diethyl ether of 2-bromosuccinic acid is added dropwise to this solution heated to 40"C over 10 minutes, after which it is stirred for 12 hours at this temperature. Next, add 500 ml of a mixture of water and ice and extract twice with ZbOml of diethyl ether. The combined organic phases are evaporated to dryness under vacuum and the residue is chromatographed on silica gel (eluent: n-hexane/ethanol in a ratio of 201).

Yield: 12.05g (3095 from theory).

Elemental analysis: solution: С 35.31 НЗ, 11 РЕ 47.47 detected: С 35.19 Н 3.20 Е 47.59 b) 2-(-2Н,2НЗН.ЗН,5Н,5Нн,вНн, vHn-1,4-dioxaperfluorotetradec-1-yl)succinic acid, disodium salt

To 11.5 g (16.90 mmol) of the compound indicated in the title of example 92a, dissolved in 300 ml of methanol, add 500 ml of Zn. aqueous caustic sodium and boil under reflux for 8 hours. After that, it is evaporated to dryness and the residue is dissolved in 30 ml of water. Next, the aqueous phases are extracted twice with 300 ml of diethyl ether. After that, the aqueous phases are acidified with concentrated hydrochloric acid to pH 1 and extracted twice

ZbOml of chloroform. The combined chloroform phases are dried over magnesium sulfate and evaporated to dryness.

The residue is dissolved in 300 ml of water and the pH value is set to 7.4 with the help of 595 aqueous caustic sodium. Finally, lyophilize.

Yield: 10.50 g (9395 from theory) of a colorless amorphous solid.

Water content: 5.790.

Elemental analysis: solution: C 28.76 H 1.66 E 48.33 Ma 6.88 found: C 28.88 H 1.71 E 48.25 Ma 6.95 c) Preparation of a composition containing a metal complex | and the monosodium salt of 2-(2нН2НЗНЗнН,Зн вн, вН-1,4-dioxaperfluorotetradec-1-yl)succinic acid

1.14 g (1.71 mmol) of the compound indicated in the title of example 926 is added to 57 ml of a solution of metal complex II (ZOO mmol/l) in a 0.4595 aqueous solution of table salt (pH 7.4; 0.25 mg/l CaMmazdtPpA) , and the volume is brought up to 154 ml with the help of a 0.995% aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 1000 mmol/l.)

Example 93 a) M-(succin-2-yl)amide of 2H,2H.4H,4H,5H,5H-3-oxaperfluorotridecanoic acid

To 20g (38.30mmol) of 2H,2H,4H.4H,5H,5ZnH-3-oxaperfluorotridecanoic acid and 9.21g (8Omol) of M-hydroxysuccinimide, dissolved in 150ml of dimethylformamide, add 16.51g (8Omol) at 0"C. M,M'-dicyclohexylcarbodiimide and stirred for 30 minutes at this temperature. To the solution of the activated ester obtained in this way, add a cooled to 0"C solution of 5.10 g (38.30 mmol) of I-aspartic acid in 3000 ml of a 595% aqueous solution of sodium carbonate and stir for 2 hours at

OS Next, the precipitated dicyclohexylurea is poured into a 50-ml mixture of water and ice, filtered, and the pH value is adjusted to 1 using concentrated hydrochloric acid. After that, 300ml of chloroform is extracted three times. The combined organic phases are concentrated to dryness and the residue is chromatographed on KR-18 (eluent: acetonitrile/water gradient). The diacid obtained in this way is dissolved in 400 ml of water and the pH value is set to 7.4 with the help of 1N. aqueous caustic sodium. After that, it is filtered and the filtrate is lyophilized.

Water content: 6.395.

Yield: 21.13 g (8195 from theory) of colorless amorphous powder.

Elemental analysis: solution: C 28.21 H 1.48 M 2.06 RE 47.41 Ma 6.75 found: C 28.30 H 1.53 M 2.11 E 47.53 Ma 6.83 b ) Preparation of a composition containing a metal complex of KHM and M-(succin-2-yl)amide 2Н,2Н4Н4Н,5Нн,5Н-

Z-oxaperfluorotridecanoic acid

422 mg (0.62 mmol) of the compound indicated in the title of example 93a is added to 337 ml of a solution of the KIM metal complex (300 mmol/l) in a 0.4595 aqueous solution of common salt (pH 7.4; 0.25 mg/l SamMmazDtTPpA) and the volume is brought up to 111 ml with the help of a 0.995% aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 100 mmol/l.)

Example 94

Preparation of the composition containing the compound indicated in the title of example 67 and the sodium salt of perfluorooctanesulfonic acid

A solution of 1.34 g (269 mmol) of the sodium salt of perfluorooctanesulfonic acid in 200 ml of ethanol is added to 4 ml of a solution of the compound 67 (250 mmol/l) indicated in the title of example 67 in a 0.4595 sodium chloride solution (pH 7.4; 025 mg/l SamMazDTPA) and stir for 2 hours at 50"C. Next, the solution is concentrated to dryness in a vacuum and the volume of the residue is brought up to 108 ml by adding distilled water. The mixture is stirred for 1 hour at 40"C and filtered through a filter with a pore size of 0.2 μm. The filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 100 mmol/l.)

Example 95

Preparation of the composition containing the compound indicated in the title of example 68 and the sodium salt of perfluorodecanesulfonic acid

3.03g (5.0bmmol) of the sodium salt of perfluorodecanesulfonic acid is added to 49ml of the solution of compound 68 indicated in the title of the example (31Omole/l) in a 0.4595 aqueous solution of sodium chloride and heated in a microwave oven for 10 minutes. The solution is cooled to room temperature, filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 3100 mmol/l.)

Example 96 a) Simple (IN1H.2H.2H-perfluorodecyl)-5-(1,3-dicarboxy, disodium salt)phenyl ether

To 20 g (80.62 mmol) of the trisodium salt of 5-hydroxyphthalic acid in 300 ml of dimethylformamide, 42.5 g (80.62 mmol) of the compound indicated in the title of example 14a is added and stirred for 10 hours at 60 "С. After that, it is poured into 1500 ml of a mixture of water with with ice and the pH value is set to 1 with the help of concentrated hydrochloric acid. Next, extract three times with ZbOml of chloroform. The combined organic phases are evaporated and the residue is chromatographed on KR-18 (eluent: acetonitrile/water gradient). The diacid purified in this way is dissolved in 400 ml of water and the pH value is adjusted to 7.4 with 1N aqueous caustic soda.Finally, it is filtered and the filtrate is lyophilized.

Yield: 20.05 g (3795 from theory) of a colorless amorphous solid.

Water content: 5.095.

Elemental analysis: solution: C 32.16 H 1.05 E 48.05 Ma 6.84 detected: C 32.30 H 1.15 E 48.20 Ma 6.95 b) Obtaining a composition containing the indicated in title of example 12 in MO 99/01161) compound (1,4,7-tris(1,4,7-tris(M-carboxylatomethyl)-10-(M-1-methyl-3-aza-2,5-dioxopentane -1,5-diyl|-1,4,7,10-tetraazacyclododecane, ba-complex)-10-(I2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-1,4,7,10- tetraazacyclododecane ) and simple (NH 2H2H-perfluorodecyl)-5-(1,3-dicarboxy, disodium salt)uphenyl ether

Up to 51 ml of a solution of 1,4,7-tris/1,4,7-tris(M-carboxylatomethyl)-10-(M-1-methyl-3-aza-2,5-dioxopentane-1,5-diyl|- 1,4,7,10-tetraazacyclododecane, c-complex)-10-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|Iacetyl- 1,4,7,10-tetraazacyclododecane (3000 mmol/l) in 6.86 g (10.2 mmol) of the compound specified in the title of example 9ba is added to a 0.45956% aqueous solution of table salt (pH 7.4; 0.25mg/l CaMmazdDtpA) and the volume using a 0.996% aqueous solution table salt is brought to 153 ml. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0 ,2μm and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 1000 mmol/l.)

Example 97

Preparation of a composition containing a metal complex of KHM and sodium salt of 3-oxa-2H2H4H4Hn,5Hn,5H-perfluorotridecanoic acid

434 mg (0.55 mmol) of the compound specified in the title of example 80a is added to 4 ml of a solution of the KHIM metal complex (320 mmol/l) in a 0.4596 aqueous solution of table salt (pH 7.4; 0.25 mg/l SamazDtPpA) and the volume is brought up to 12.8 ml with the help of a 0.9956 aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials. The solution obtained in this way can be used directly for conducting biological experiments. (The concentration is 100 mmol/l.)

Example 98 a) tert-Butyl ether of (adamant-1-yl)-3-oxapropionic acid

To 15.22g (100mmol) of 1-adamantanol in ZOOml of 5095 aqueous caustic potash and 200ml of toluene at 0"C, add 29.26g (150mmol) of muret-butyl bromoacetic acid and stir intensively for 2 hours. After that, pour into 1500ml of water and extracted twice with 300 ml of diethyl ether. The combined organic phases were dried over magnesium sulfate and evaporated to dryness in vacuo. The residue was chromatographed on silica gel (eluent: n-hexane/diethyl ether in the ratio 20:1).

Yield: 21.58 g (8195 from theory) of viscous colorless oil.

Elemental analysis: solution: C 72.14 H 9.84 found: C 72.26 H 9.95 b) (Adamant-1-yl)-3-oxapropionic acid 20 g (75 mmol) of the compound indicated in the title of example 98a at 0"С, it is dissolved in 200 ml of trifluoroacetic acid and stirred at room temperature for 8 hours. After that, it is evaporated to dryness and the residue is recrystallized from diisopropyl ether.

Yield: 14.68 g (9395 from theory) of a colorless substance in the form of scales or flakes.

Elemental analysis: solution: C 68.55 H 8.63 found: C 68.41 H 8.74 c) 1-(perfluorooctylsulfonyl)-4-((adamant-1-yl)oxapropionyl|Ipiperazine 14g (66, mmol) of the compound indicated in the title of Example 986 and 37.50 g (66, mmol) of 1-perfluorooctylsulfonylpiperazine are dissolved in

32.15 g (13 mol) of 1,2-dihydro-2-ethoxyquinoline-1-carboxylic acid ethyl ether (EEDH) is added to 32.15 g (13 mol) of tetrahydrofuran and at 0"C. The mixture is stirred for 5 hours at room temperature. Then the solution is evaporated to dryness in a vacuum and the residue chromatographed on silica gel (eluent: dichloromethane/diethyl ether in a ratio of 301).

Yield: 43.05 g (8595 from theory) of a colorless solid.

Elemental analysis: solution: C 37.90 H 3.91 M 3.68 5 4.22 EE 42.47 found: C 38.04 H 3.42 M 3.49 54.11 E 42.30 g) A composition containing 0.5 parts of the metal complex I and 0.5 parts of the inclusion compound in the form of p-cyclodextrin hydrate and 1-(perfluorooctylsulfonyl)-4-Cadamant-1-yl)oxapropionyl|piperazine

To 32 ml of a solution of metal complex I (280 mmol/l) in a 0.4595 aqueous solution of table salt (pH 7.4; 0.25 mg/l SamazDtTPA) add 6.81 g (8.96 mmol) of the compound indicated in the title of example 98c and 10.33 g (8.96 mmol) of D-cyclodextrin monohydrate and the volume is brought up to 9 ml with the help of a 0.995% aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials

The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 100 mmol/l.)

Example 99 a) M-(1-adamantyl)amide of 3-oxa-2H,2H,4H,4H,5H,5H-perfluorotridecanoic acid

Up to 15.12g (10b0mmol) of 1-aminoadamantane, 52.21 (10mmol) /Z-oxa-2H.2nH,4nNaH,5Hn,5H-

of perfluorotridecanoic acid and 11.51 g (100 mmol) of M-hydroxysuccinimide, dissolved in 30 ml of tetrahydrofuran, add 30.95 g (150 mmol) of M,M-dicyclohexylcarbodiimide at 0 °C. The mixture is stirred for 2 hours at 0 °C, and then for 2 hours at room temperature temperature The precipitated urea is filtered off, the filtrate is evaporated to dryness and the residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 30:1).

Yield: 54.4 g (8390 from theory) of a waxy solid.

Elemental analysis: solution: C 40.32 H 3.38 M 2.14 ER 49.28 found: C 40.47 H 3.49 M 2.03 E 49.09 b) Composition containing 0.6 parts of metal complex II and 0.4 parts of the inclusion compound in the form of p-cyclodextrin hydrate and M-(1-adamantyl)amide of 3-oxa-2H,2H,.4H4H,5H,5ZH-perfluorotridecanoic acid

To 41 ml of a solution of metal complex II (250 mmol/l) in a 0.4595 aqueous solution of common salt (pH 7.4; 0.25 mg/l SaMazdDtPpA) add 4.48 g (6b, 83 mmol) of the compound specified in the title of example 989a , and 7.87 g (6.83 mmol) of D-cyclodextrin monohydrate, and the volume is brought up to 103 ml with the help of a 0.995% aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials

The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 100 mmol/l.)

Example 100 a) M-(adamantyl)amide of 2-(M-(ethyl)-M-(perfluorooctylsulfonyl)amino|acetic acid

To 15.12 g (100 mmol) of 1-aminoadamantane, 58.52 g (100 mmol) of M-(ethyl)-M-(perfluorooctylsulfonyl)aminoacetic acid and 11.51 g (100 mmol) of M-hydroxysuccinimide, dissolved in 300 ml of tetrahydrofuran, at 0" 30.95 g (150 mmol) of M,M-dicyclohexylcarbodiimide are added to C. The mixture is stirred for 2 hours at 0"C, and then for 2 hours at room temperature. The precipitated urea is filtered off, the filtrate is evaporated to dryness and the residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 30:1).

Yield: 55.65 g (7995 from theory) of amorphous solid.

Elemental analysis: solution: C 37.51 H 3.29 E 45.85 M 1.99 54.55 found: C 37.64 H 3.41 E 45.99 M 2.12 5 4.43 b) A composition containing 0.6 parts of metal complex I and 0.4 parts of the inclusion compound in the form of p-cyclodextrin hydrate and M-(1-adamantyl)amide 2-|M-(ethyl)-M-(perfluorooctylsulfonyl)amino|acetate acid

To 32 ml of a solution of metal complex I (280 mmol/l) in a 0.4595 aqueous solution of common salt (pH 7.4; 0.25 mg/l CaMmazDtpPA) add 4.20 g (5.97 mmol) of the compound indicated in the title of the example 10ba, and 6b, 88g (5.p97mmol) of D-cyclodextrin monohydrate, and the volume is brought up to 9O0ml with the help of a 0.995% aqueous solution of table salt. Then it is kept for 2 hours at 60"C, exposing the mixture to ultrasound. The solution is cooled to room temperature and the pH value is set to 7.4 with the help of aqueous 2N caustic sodium. After that, it is filtered through a filter with a pore size of 0.2 μm, and the filtrate is packaged in vials

The solution obtained in this way can be used directly for conducting biological experiments. (Sa concentration is 100 mmol/l.)

Example 101 a) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-benzyloxycarbonyl-2-M-(3,6,9,12-tetraoxatridecanoyl)lysine

A solution of 16.85 g (/Omol) of hydrogen chloride 3,6,9 of 12-tetraoxatridecanoic acid in 50 ml of dichloromethane and stirred for 10 minutes at 0"C. Next, add 200 ml of 595% aqueous hydrochloric acid and stir for 5 minutes at room temperature.

The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 15:1)

Yield: 30.94 g (9295 from theory) of colorless, viscous oil.

Elemental analysis: solution: C 40.63 H4419 E 31.21 M 5.41 53.10 found: C 40.75 H 4.08 E 31.29 M 5.58 5 53.25 b) (1- (4-perfluorooctylsulfonyl)piperazinamide 2-M-(3,6,9,12-tetraoxatridecanoyl)lysine 53.96 g (52.15 mmol) of the compound indicated in the title of example 101a is dissolved in 500 ml of ethanol and BG of palladium catalyst (1095- ny Pa/cС). After that hydrogenation is done at room temperature. The catalyst is then filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 43.0 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 36.01 H 4.14 RE 35.86 M 6.22 5 3.56 found: C 36.20 H 4.23 E 35.99 M 6.38 5 3.71 ) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo -5-methyl-5-yl)|-2-M-(3,6,9,12-tetraoxatridecanoyl)lysine, cSid complex 21.84 (24.25 mmol) of the compound specified in the title of example 1016, 2.79 g (24.25 mmol) of M-hydroxysuccinimide, 2.12 g (50 mmol) of lithium chloride and 15.27 g (24.25 mmol) of Ca-complex 1,4,7-tris(carboxylatomethyl)-10-((3-aza-4- Oxo-5-methyl-5-ylopentanoic acid!|-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 200 ml of dimethylsulfoxide. Next, 8.25 g (40 mmol) of M,M-dicyclohexylcarbodiimide are added at 107 and then stirred overnight at room temperature. The solution is poured into 300 Oml of acetone and stirred for 10 min. The precipitated solid is filtered and then purified by chromatography (silica gel KR-18, eluent: water/ethanol/acetone gradient nitrile).

Yield: 28.21 g (8195 from theory) of a colorless solid.

Water content: 11.095.

Elemental analysis (in terms of anhydrous substance): solution: С 36.53 Н 4.33 Е 21.36 М 8.34 52.12 Са 10.40 found.: С 36.64 Н 4.48 Е 21, 39 M 8.29 52.15 Sa 10.57

Example 102 a) (1-(4-perfluorooctylsulfonyl)piperazinamide /6-M-benzyloxycarbonyl-2-M-(propyl-3-sulfonic acid)lysine

To 50 g (60.20 mmol) of the compound indicated in the title of example 52c and 7.10 g (/Omol) of triethylamine, dissolved in 250 ml of dry tetrahydrofuran, at 507"C, a solution of 7.33 g (60 mol) of propansulphtone in 50 ml of tetrahydrofuran is added dropwise. and stir for a few minutes at 60"C. Next, add 200 ml of 595% aqueous hydrochloric acid and stir for 5 minutes at room temperature. The organic phase is separated, dried over magnesium sulfate and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 15:1).

Yield: 45.16 g (7995 from theory) of colorless viscous oil.

Elemental analysis: solution: C 36.56 H 3.49 E 33.90 M 5.88 5 6.73 found: C 36.72 H 3.35 E 33.79 M 5.78 56.75 b) (1-(4-perfluorooctylsulfonyl)piperazinamide 2-M-(propyl-3-sulfonic acid)lysine 49.68 g (52.15 mmol) of the compound indicated in the title of example 102a are dissolved in 500 ml of ethanol and 10 g of palladium catalyst (1095- ny Pa/cС). After that hydrogenation is done at room temperature. The catalyst is then filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 42.69 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 30.81 H 3.32 E 39.46 M 6.84 5 7.83 found: C 30.64 H 4.1 E 39.29 M 6.68 5 7.89 ) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo -5-methyl-5-yl)|-2-M-(propyl-3-sulfonic acid) lysine, cSide complex 19.85g (24.25mmol) of the compound indicated in the title of example 1026, 2.79 (24.25mmol ) of M-hydroxysuccinimide, 2.12 g (50 mmol) of lithium chloride and 15.27 g (24.25 mmol) of the 1,4,7-tris(carboxylatomethyl)-10-((3-aza-4-oxo-5- methyl-5-ylopentanoic acid!|-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 200 ml of dimethylsulfoxide.Then, at 107, 8.25 g (40 mmol) of M,M-dicyclohexylcarbodiimide are added and then stirred overnight at room temperature. The solution is poured into 300 Oml of acetone and stirred for 10 min. The precipitated solid is filtered off and then purified by chromatography (silica gel KR-18, eluent: water/ethanol/acetonite gradient snout).

Yield: 28.13 g (8195 from theory) of a colorless solid.

Water content: 11.095.

Elemental analysis (in terms of anhydrous substance) solution: С 33.27 Н 3.70 Е 22.36 М 8.73 5 4.44 Са 10.89 found.: С 32.41 Н 3.88 Е 22, 49 M 8.69 5 4.35 Sa 10.97

Example 103 a) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-benzyloxycarbonyl-2-M,M-bis(propyl-3-sulfonic acid)lysine

To 50 g (60.20 mmol) of the compound indicated in the title of example 52c and 12.14 g (120 mmol) of triethylamine, dissolved in 250 ml of dry tetrahydrofuran, at 507C, a solution of 14.65 g (120 mmol) of 1,3-propansulphtone in 100 ml of tetrahydrofuran is added dropwise. and stir for 10 minutes at 60"C. Then add 400 ml of 595% aqueous hydrochloric acid, stir for 5 minutes at room temperature, mix with sodium chloride, separate the organic phase, dry it over magnesium sulfate and evaporate to dryness in a vacuum. The residue is chromatographed on silica gel (eluent: dichloromethane/acetone in a ratio of 15:1).

Yield: 52.24 g (8195 from theory) of colorless viscous oil.

Elemental analysis: solution: C 35.76 H 3.66 E 30.05 M 5.21 5 8.95 found: C 35.75 H 3.55 E 30.19 M 5.08 5 9.04 b ) (1-(4-perfluorooctylsulfonyl)piperazinamide 2-M,M-bis(propyl-3-sulfonic acid)lysine 53.74 g (52.15 mmol) of the compound indicated in the title of example 10Z3a is dissolved in 500 ml of ethanol and BG of palladium is added of catalyst (1095 Pa/sC). After this, hydrogenation is carried out at room temperature. The catalyst is then filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 49.06 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 30.64 H 3.54 E 34.33 M 5.96 5 10.23 found: C 30.69 H 3.71 E 34.19 M 6.08 5 10.38 in ) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclodo decan-10-(pentanoyl-3-aza-4- oxo-5-methyl-5-yl)|-2-M,M-bis(propyl-3-sulfonic acid)lysine, ca4-complex, disodium salt 38.76 g (24.25 mmol) of the compound indicated in the title of example 1036 . aza-4-oxo-5-methyl-5-ylopentanoic acid!|-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 200 ml of dimethylsulfoxide. Then, at 107, 8.25 g (40 mmol) of M,M-dicyclohexylcarbodiimide are added and then stirred overnight at room temperature. The solution was poured into 300 Oml of acetone and stirred for 10 min. The precipitated solid was filtered off and then purified by chromatography (silica gel KR-18, eluent: grade ent of water/ethanol/acetonitrile).

Yield: 31.63 g (8195 from theory) of a colorless solid.

Water content: 11.095.

Elemental analysis (in terms of anhydrous substance): solution: С 32.07 Н 3.57 Е 20.06 М 7.83 5 5.97 Са 9.76 Ма 2.86 detect.: С 31.94 Н 3 ,48 E 20.19 M 7.69 5 5.85 Sa 9.87 Ma 2.99

Example 104 a) 5-benzyl ether of M-trifluoroacetyl-i-glutamic acid 100 g (421.5 mmol) of 5-benzyl ether of I-glutamic acid is dissolved in a mixture of 1000 ml of ethyl trifluoroacetic acid and 500 ml of ethanol and stirred for 24 hours at room temperature.

After that, it is evaporated to dryness and the residue is crystallized from diisopropyl ether.

Yield: 140.47 g (9695 from theory) of colorless crystalline powder.

Elemental analysis: solution: C 50.46 4.23 HE 17.10 M 4.20 found: C 51.35 H 4.18 E 17.03 M 4.28 b) M-bis(2-hydroxyethyl) Amide of 2-M-trifluoroacetyl-1-glutamic acid 5-benzyl ether

To a solution of 24.9 g (24.08 mmol) of the compound indicated in the title of example 104a, 2.53 g (24.08 mmol) of diethanolamine, and 2.77 g (24.08 mmol) of M-hydroxysuccinimide in 150 ml of dimethylformamide at 0"С, 8.25 g is added (40 mmol). of M,M-dicyclohexylcarbodiimide. The mixture was stirred for 1 h at RT and then overnight at room temperature. The precipitated urea was filtered off, the filtrate was evaporated to dryness in vacuo and chromatographed on silica gel (eluent: dichloromethane/ethanol in ratio 20:1).

Yield: 9.11 g (9095 from theory) of viscous oil.

Elemental analysis: solution: C 51.43 H 5.51 E 13.56 M 6.66 found: C 51.22 H 5.41 E 13.40 M 6.75 v) M-bis(2-hydroxyethyl) )umonoamide of M-trifluoroacetyl-II-glutamic acid 21.92 g (52.15 mmol) of the compound specified in the title of example 1046 is dissolved in 500 ml of ethanol and 3 g of palladium catalyst (IOb-ny Ra/C) is added. After that, they are hydrogenated at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 43.0 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 40.01 H 5.19 PE 17.26 M 8.48 found: C 39.84 H 5.13 E 17.09 M 8.68 g) Trifluoroacetyl-ii -glutamic acid- M-bis(2-hydroxyethyl)amide-5-|1-(4-perfluorooctylsulfonyl)piperazinamide

To 10.96 g (33.2 mmol) of the compound specified in the title of example 104a and 18.87 g (33.2 mmol) of 1-perfluorooctylsulfonylpiperazine (obtained according to OE 19603033 in vOml of tetrahydrofuran at 0"C, add 16.42 g (66b.4 mmol ) EEDH (2-ethoxy-1,2-dihydroquinoline-1-carboxylic acid ethyl ester) and stirred overnight at room temperature, then evaporated to dryness in vacuo and chromatographed on silica gel (eluent: dichloromethane/methanol 20:1) .

Yield: 30.93 g (9395 from theory) of a colorless solid.

Elemental analysis: solution: C 39.61 H 2.89 E 35.66 M 6.19 5 3.54 found: C 39.68 H 2.74 E 35.81 M 6.13 5 3.40 d ) I-glutamic acid-M-bis(2-hydroxyethyl)amide-5-|1-(4-perfluorooctylsulfonyl)piperazine|amide

A solution of 30.24 g (30.22 mmol) of Example 1046 indicated in the title in 200 ml of ethanol at 0"C is bubbled with gaseous ammonia for one hour. The mixture is then stirred for 4 hours at 0"C. After that, it is evaporated to dryness and the residue is separated from the water by stirring. The solid was filtered off and dried in vacuo (5070).

Yield: 26.55 g (9795 from theory) of amorphous solid.

Elemental analysis: solution: C 41.12 H 2.89 E 35.66 M 6.19 5 3.54 found: C 41.15 H 2.83 E 35.78 M 6.28 5 3.71 e ) M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|-I - glutamic acid-M-bis(2-hydroxyethyl)amide-5-11-(4-perfluorooctylsulfonyl)piperazinamide, cSide complex 211.96g (24.25mmol) of the compound indicated in the title of example 104d, 2.79g (24.25mmol ) of M-hydroxysuccinimide, 2.12 g (50 mmol) of lithium chloride and 15.27 g (24.25 mmol) of the 1,4,7-tris(carboxylatomethyl)-10-((3-aza-4-oxo-5- methyl-5-ylopentanoic acid!|-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 200 ml of dimethylsulfoxide.Then, at 107, 8.25 g (40 mmol) of M,M-dicyclohexylcarbodiimide are added and then stirred overnight at room temperature. The solution is poured into 300 ml of acetone and stirred for 10 min. The precipitated solid is filtered off and then purified by chromatography (silica gel KR-18, eluent: water/ethanol gradient lu/acetonitrile).

Yield: 27.43 g (8195 from theory) of a colorless solid.

Water content: 11.095.

Elemental analysis (in terms of anhydrous substance): solution: С 34.41 Н 3.83 Е 23.13 М 9.03 5 2.30 Са 11.26 found.: С 34.34 Н 3.98 Е 23 ,29 M 9.19 52.15 Sa 11.07

Example 105 a) M-dimethylbis(1,1-dihydroxymethyl)amide of 5-benzyl ether of M-trifluoroacetyl-i-glutamic acid

To a solution of 8.03 g (24.08 mmol) of the compound indicated in the title of example 104a, 3.98 g (24.08 mmol) of dimethylbis(1,1-dihydroxymethyl)amine and 2.1 g (24.08 mmol) of M-hydroxysuccinimide in 150 ml of dimethylformamide at 0"C, add 8.25 g (40 mmol) of M,M-dicyclohexylcarbodiimide. The mixture is stirred for hours at 0"C, and then overnight at room temperature. The precipitated urea is filtered off, the filtrate is evaporated to dryness under vacuum and chromatographed on silica gel (eluent: dichloromethane/ethanol in a ratio of 20:1).

Yield: 110.53 g (9195 from theory) of viscous oil.

Elemental analysis: solution: C 50.00 H 5.66 E 11.86 M 7.18 found: C 50.17 H 5.82 E 11.80 M 7.15 b) (1-(4-perfluorooctylsulfonyl )piperazinamide of 5-benzyl ether of M-trifluoroacetyl-1-glutamic acid 25.05 g (52.15 mmol) of the compound indicated in the title of example 105a is dissolved in 500 ml of ethanol and BG of palladium catalyst (1095 Pa/cC) is added. hydrogenated at room temperature.The catalyst is then filtered off and the filtrate is evaporated to dryness in vacuo.

Yield: 20.36 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 40.00 N 5.42 ER 14.60 M 7.18 detected: C 40.10 N 5.53 E 14.69 M 7.28 c) M-trifluoroacetyl-i-glutamine acid-M-dimethylbis(1,1-dihydroxymethyl)amide-5-|1-(4-perfluorooctylsulfonyl)piperazine|amide

To 12.96 g (33.2 mmol) of the compound indicated in the title of example 1056, and 18.87 g (33.2 mmol) of 1-perfluorooctylsulfonylpiperazine (obtained according to OE 19603033 in 800 ml of tetrahydrofuran at 0"C, add 16.42 g (66 b.4 mmol ) EEDH (2-ethoxy-1,2-dihydroquinoline-1-carboxylic acid ethyl ester) and stirred overnight at room temperature, then evaporated to dryness in vacuo and chromatographed on silica gel (eluent: dichloromethane/methanol 20:1) .

Yield: 28.42 g (9195 from theory) of a colorless solid.

Elemental analysis: solution: C 31.93 H 3.00 E 40.40 M 5.96 5 3.41 found: C 32.08 H 2.94 E 40.57 M 5.88 5 3.31 g ) 1-glutamic acid-M-Idimethylbis(1,1-dihydroxymethyl)|amide-5-|1-(4-perfluorooctylsulfonyl)piperazine|amide

A solution of 28.41 g (30.2 mmol) of the compound indicated in the title of example 1058 in 200 ml of ethanol at 0" is bubbled with gaseous ammonia for one hour. The mixture is then stirred for 4 hours at 0"C. After that, it is evaporated to dryness and the residue is separated from the water by stirring. The solid was filtered off and dried in vacuo (5075).

Yield: 24.74 g (9795 from theory) of amorphous solid.

Elemental analysis: solution: C 32.71 H 3.46 E 38.24 M 6.63 5 3.80 found: C 32.75 H 3.33 E 38.38 M 6.68 5 3.81 d ) 2-M-(11,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|- I-glutamic acid-M-Idimethylbis(1,1-dihydroxymethyl)amide 1|-5-|1-(4-perfluorooctylsulfonyl)piperazine|Iamide, Ca-complex 20.48g (24.25mmMmol) of the compound indicated in the title of the example 105g , 2.79 (24.25 mmol) M-hydroxysuccinimide, 2.12 g (50 mmol) lithium chloride and 15.27 g (24.25 mmol) Ca-complex 1,4,7-tris(carboxylatomethyl)-10-((3- aza-4-oxo-5-methyl-5-ylopentanoic acid!|-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 200 ml of dimethylsulfoxide. Then, at 107, 8.25 g (40 mmol) of M,M-dicyclohexylcarbodiimide are added and then stir overnight at room temperature. The solution is poured into 300 ml of acetone and stirred for 10 min. The precipitated solid is filtered off and then purified by chromatography (silica gel KR-18, eluent: g water/ethanol/acetonitrile adient).

Yield: 29.05 g (8395 from theory) of a colorless solid.

Water content: 11.095.

Elemental analysis (in terms of anhydrous substance): solution: С 34.12 Н 3.91 Е 22.38 М 8.73 52.22 At 10.90 detect.: С 34.24 Н 3.98 Е 22, 39 M 8.69 52.15 Sa 10.87

Example 106 a) (1-(4-perfluorooctylsulfonyl)piperazinamide of 5-benzyl ester of M-trifluoromethylacetylchi-glutamic acid

To 11.06g (33.2mmol) of the compound indicated in the title of example 104a and 18.87g (33.2mmol) of 1-perfluorooctylsulfonylpiperazine (obtained according to OEE 19603033 in vOml of tetrahydrofuran at 0"С add 16.42g (66b.4mmol ) EEDH (2-ethoxy-1,2-dihydroquinoline-1-carboxylic acid ethyl ester) and stirred overnight at room temperature, then evaporated to dryness in vacuo and chromatographed on silica gel (eluent: dichloromethane/methanol 20:1) .

Yield: 27.28 g (9395 from theory) of a colorless solid.

Elemental analysis: solution: C 35.35 H 2.40 RE 43.01 M 4.76 5 3.63 found: C 35.48 H 2.51 E 42.87 M 4.73 5 3.50 b ) 5-11-(4-perfluorooctylsulfonyl)piperazinamide M-trifluoroanethyl-1-glutamic acid 21.92 g (52.15 mmol) of the compound specified in the title of example 10ba is dissolved in 500 ml of ethanol and 3g of palladium catalyst (1095 Ra/ cS). After that, they are hydrogenated at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 41.37 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 28.76 H 1.91 E 47.89 M 5.30 5 4.04 found: C 28.84 H 2.03 E 47.79 M 5.28 5 4.19 in ) M-trifluoroacetyl-i -glutamic acid-M-bis(2-hydroxyethyl)amide-5-|1-(4-perfluorooctylsulfonyl)piperazine|amide

To a solution of 24.9 g (24.08 mmol) of the compound indicated in the title of example 10ba, 2.53 g (24.08 mmol) of diethanolamine and 2.77 g (24.0 in 8 mmol) of M-hydroxysuccinimide in 150 ml of dimethylformamide at 0"С, 8.25 g is added (40 mmol). of M,M-dicyclohexylcarbodiimide. The mixture was stirred for 1 h at RT and then overnight at room temperature. The precipitated urea was filtered off, the filtrate was evaporated to dryness in vacuo and chromatographed on silica gel (eluent: dichloromethane/ethanol in ratio 20:1).

Yield: 9.11 g (9095 from theory) of viscous oil.

Elemental analysis: solution: C 31.37 H 2.75 E 43.15 M 6.36 5 3.64 found: C 31.22 H 2.61 E 43.30 M 6.25 5 3.81 g ) --glutamic acid-M-bis(2-hydroxyethyl)amide-5-(1-(4-perfluorooctylsulfonyl)piperazine|amide

A solution of 26.61 g (30.22 mmol) of the compound specified in the title of example 10bv in 200 ml of ethanol at 0"C is bubbled with gaseous ammonia for one hour. The mixture is then stirred for 4 hours at 0"C. After that, it is evaporated to dryness and the residue is separated from the water by stirring. The solid was filtered off and dried in vacuo (5075).

Yield: 23.93 g (9795 from theory) of amorphous solid.

Elemental analysis: solution: C 30.89 H 3.09 E 39.56 M 6.86 5 3.93 found: C 30.75 H 3.13 E 39.78 M 6.75 5 3.81 d ) M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|-I - glutamic acid-M-bis(2-hydroxyethyl)amide-5-11-(4-perfluorooctylsulfonyl)piperazinamide, cSid complex 16.43g (24.25mmol) of the compound indicated in the title of example 10bg, 2.79 (2425mmol) M - hydroxysuccinimide, 2.12 g (50 mmol) of lithium chloride and 15.27 g (24.25 mmol) of 1,4,7-tris(carboxylatomethyl)-10-((3-aza-4-oxo-5-methyl- 5-ilopentanoic acid!|-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 200 ml of dimethylsulfoxide. Then, at 107, 8.25 g (40 mmol) of M,M-dicyclohexylcarbodiimide are added and then stirred overnight at room temperature. The solution is drained in 300 Oml of acetone and stir for 10 min. The precipitated solid is filtered off and then purified by chromatography (silica gel KR-18, eluent: a gradient of water/ethanol/ acetonitrile).

Yield: 28.10 g (8395 from theory) of a colorless solid.

Water content: 11.095.

Elemental analysis (in terms of anhydrous substance) solution: С 34.41 Н 3.83 Е 23.13 М 9.03 5 2.30 Са 11.26 found.: С 34.44 Н 4.98 Е 23, 19 M 8.89 5 2.15 Sa 11.17

Example 107 a) (1-(4-perfluorooctylsulfonyl)piperazinamide of 5-benzyl ether of M-trifluoroacetylglutamic acid

To 11.06g (33.2mmol) of the compound specified in the title of example 104a and 18.87g (33.2mmol) of 1-perfluorooctylsulfonylpiperazine (obtained according to OE 19603033 in 8Oml of tetrahydrofuran at 07) add 16.42g (66b.4mmol) of EEDH (2-ethoxy-1,2-dihydroquinoline-1-carboxylic acid ethyl ether) and stirred overnight at room temperature, then evaporated to dryness in vacuo and chromatographed on silica gel (eluent: dichloromethane/methanol 20:1).

Yield: 27.28 g (9395 from theory) of a colorless solid.

Elemental analysis: solution: C 35.35 H 2.40 RE 43.01 M 4.76 5 3.63 found: C 35.48 H 2.54 E 42.87 M 4.73 5 3.40 b ) 5-11-(4-perfluorooctylsulfonyl)piperazinamide of M-trifluoroacetyl-i-glutamic acid 21.92 g (52.15 mmol) of the compound specified in the title of example 107a is dissolved in 500 ml of ethanol and 3 g of palladium catalyst (1095 Ra/ cS). After that, they are hydrogenated at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 41.37 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 28.76 H 1.91 E 47.89 M 5.30 5 4.04 found: C 28.84 H 1.81 E 47.79 M 5.28 54.16

Example 108 a) (1-(4-perfluorooctylsulfonyl)piperazine|amide of 6-M-benzyloxycarbonyl-2-M-(2,3,4,5-pentahydroxyhexanoyl)-I-lysine

A solution of 21.45 g (120.4 mol) of 5-gluconolactone in 50 ml of tetrahydrofuran is added dropwise to a solution of 100.0 g (120.4 mol) of the compound indicated in the title of example 21c in 500 ml of dry tetrahydrofuran at 50"C. The mixture is stirred for 10 minutes at 60"C, and then overnight at room temperature. After that, it is evaporated to dryness under vacuum and the residue is chromatographed on silica gel (eluent: dichloromethane/ethanol in a ratio of 20:1).

Yield: 98.37 g (8295 from theory) of viscous oil.

Elemental analysis: solution: C 38.10 H 3.70 E 32.02 M 5.55 5 3.18 found: C 38.22 H 3.79 E 32.02 M 5.42 5 3.29 b ) 1-(4-perfluorooctylsulfonyl)piperazinamide 2-M-(2,3,4,5-pentahydroxyhexanoyl)-I-lysine 100.9 g (100.00 mmol) of the compound indicated in the title of example 108a is dissolved in 2000 ml of ethanol and added 10.0 g of palladium catalyst (1095th RoMS). After that, hydrogenate for 12 hours at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 87.46 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 32.96 H 3.57 M 6.41 5 3.67 E 36.93 found: C 32.91 H 3.72 M 6.34 5 3.50 E 36.78 ) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(1,4,7-tris(carboxylatomethyl)|-1,4,7,10- tetraazacyclododecane-10-M-(pentanoyl-3-aza- 4-oxo-5-methyl-5-yl)|-2-M-(11-O-o-0-carbonylmethylmannopyranose|-I-lysine, Ca-complex 50.0g (54.55mmol) of the compound indicated in the title of example 21e, 6.28 g (54.55 mmol) of M-hydroxysuccinimide, 4.62 g (109, Omol) of lithium chloride and 34.35 g (54.55 mol) of the α-complex 1,4,7-tris(carboxylatomethyl)-10- (carboxy-3-aza-4-oxo-5-methylpent-5-yl)-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 400 ml of dimethyl sulfoxide. Then, at 10"C, 16.88 g (81.8 mol ) of M,M-dicyclohexylcarbodiimide and then stirred overnight at room temperature.

The solution is poured into 300 ml of acetone and stirred for 10 minutes. The precipitated solid is filtered and then purified by chromatography (KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 75.9 g (91.095 from theory) of a colorless solid.

Water content: 8.695.

Elemental analysis (in terms of anhydrous substance): solution: С 35.34 Н4.09 М 8.24 52.10 EE 21.12 Са 10.28 detected: С 35.28 Н 4.15 М 8.19 5 2.15 E 21.03 Са 10.14

Example 109 a) (1-(4-perfluorooctylsulfonyl)piperazine|amide of 6-M-benzyloxycarbonyl-2-M-(2,3,4,5-pentahydroxyhexanoyl)-I-lysine

To a solution of 100.0 g (120.4 mmol) of the compound indicated in the title of example 21c and 12.18 g (120.4 mmol) of triethylamine in 500 ml of dry tetrahydrofuran at 50 "C, a solution of 21.45 g (120 4 mol) of 5-gluconolactone is added dropwise in 50 ml of tetrahydrofuran. The mixture is stirred for several hours at 60"C, and then overnight at room temperature. After that, add 400 ml of 595 aqueous hydrochloric acid, stir for 5 minutes at room temperature, mix with sodium chloride, separate the organic phase, dry it over magnesium sulfate, evaporate to dryness in a vacuum, and chromatograph the residue on silica gel (eluent: dichloromethane/ethanol in the ratio 20:1).

Yield: 100.97 g (8295 from theory) of viscous oil.

Elemental analysis: solution: C 37.58 H 3.45 E 31.58 M 5.48 5 3.14 found: C 37.72 H 3.59 E 31.72 M 5.42 5 3.29 b ) 1-(4-perfluorooctylsulfonyl)piperazinamide 2-M-(2,3,4,5-pentahydroxyhexanoyl)-I-lysine 100.9 g (100.00 mmol) of the compound indicated in the title of example 108a is dissolved in 2000 ml of ethanol and added 10.0 g of palladium catalyst (1095 Ra/C). After that, hydrogenate for 12 hours at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 87.46 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 32.96 H 3.57 M 6.41 5 3.67 E 36.93 found: C 32.91 H 3.72 M 6.34 5 3.50 E 36.78 ) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(1,4,7-tris(carboxylatomethyl)|-1,4,7,10- tetraazacyclododecane-10-M-(pentanoyl-3-aza- 4-oxo-5-methyl-5-yl)|-2-M-(11-O-o-0-carbonylmethylmannopyranose|-I-lysine, Ca-complex 50.0g (54.55mmol) of the compound indicated in the title of example 21d, 6.28 g (54.55 mmol) of M-hydroxysuccinimide, 4.62 g (109, Omol) of lithium chloride and 34.35 g (54.55 mol) of Ca-complex 1,4,7-tris(carboxylatomethyl)-10- (carboxy-3-aza-4-oxo-5-methylpent-5-yl)-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 400 ml of dimethyl sulfoxide. Then, at 107"C, 16.88 g (81, 8 moles) of M,M-dicyclohexylcarbodiimide and then stirred overnight at room temperature.

The solution is poured into 300 ml of acetone and stirred for 10 minutes. The precipitated solid is filtered and then purified by chromatography (KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 75.9 g (91.095 from theory) of a colorless solid.

Water content: 8.695.

Elemental analysis (in terms of anhydrous substance): solution: С 35.34 Н4.09 М 8.24 52.10 EE 21.12 Са 10.28 detected: С 35.28 Н 4.15 М 8.19 5 2.15 E 21.03 Са 10.14

Example 110 a) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-benzyloxycarbonyl-2-M-11-O-c-ХО-carbonylmethyl-(2,3,4,6-tetra-O-benzylglucopyranose)|- And -lysine

To a solution of 100.0 g (120 4 mol) of the compound indicated in the title of example 21c, 72.1 g (120.4 mol) of 1-O-o-O-carboxymethyl-2,3,4,6-tetra-O-benzylglucopyranose and 13 41.27 g (200.00 mmol) of M5M-dicyclohexylcarbodiimide is added to 500 ml of dimethylformamide at 0°C. the precipitate is filtered off, the filtrate is evaporated to dryness under vacuum and chromatographed on silica gel (eluent: dichloromethane/ethanol in a ratio of 20:1).

Yield: 136.1 g (8795 from theory) of viscous oil.

Elemental analysis: solution: C 57.32 H 4.89 M 4.31 E 24.86 52.47 found: C 57.48 H 5.04 M 4.20 E 24.69 5 2.38 b) 1-(4-perfluorooctylsulfonyl)piperazinamide 2-M-(1-O-x-O-carbonylmethylglucopyranose|-I-lysine) 130.0 g (100.00 mmol) of the compound indicated in the title of example 110a is dissolved in 2000 ml of ethanol and 10 .0 g of palladium catalyst (1095 Pa/C). After that, it is hydrogenated for 12 hours at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 91.7 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 34.07 H 3.63 M 6.11 5 3.50 E 35.24 found: C 33.92 H 3.71 M 6.02 5 3.42 E 35.33 ) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(1,4,7-tris(carboxylatomethyl)|-1,4,7,10- tetraazacyclododecane-10-M-(pentanoyl-3-aza- 4-oxo-5-methyl-5-yl)|-2-M-(11-O-o-0-carbonylmethylglucopyranose!|-I-lysine, a complex of 50.0 g (54.55 mmol) of the compound specified in of the title of example 1106, 6.28 g (54.55 mmol) of M-hydroxysuccinimide, 4.62 g (109, Omol) of lithium chloride and 34.35 g (54.55 mol) of α-complex 1,4,7-tris(carboxylatomethyl)-10 -(carboxy-3-aza-4-oxo-5-methylpent-5-yl)-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 400 ml of dimethyl sulfoxide. Then, at 10"C, 16.88 g (81, 8 moles) of M,M-dicyclohexylcarbodiimide and then stirred overnight at room temperature.

The solution is poured into 300 ml of acetone and stirred for 10 minutes. The precipitated solid is filtered and then purified by chromatography (KR-18, eluent: di/ethanol/acetonitrile gradient).

Yield: 75.9 g (91.095 from theory) of a colorless solid.

Water content: 8.695.

Elemental analysis (in terms of anhydrous substance): solution: С 35.34 Н4.09 М 8.24 52.10 EE 21.12 Са 10.28 detected: С 35.26 Н 4.18 М 8.14 5 2.158 RE 21.01 Са 10.13

Example 111 a) (1-(4-perfluorooctylsulfonyl)piperazinamide 6-M-benzyloxycarbonyl-2-M-11-O-c-ХО-carbonylmethyl-(2,3,4,6-tetra-O-benzylgalactopyranose)|- And -lysine

To a solution of 50.0 g (60.2 mol) of the compound indicated in the title of example 21c, 36.05 g (60.2 mmol) of 1-O-o-O-carboxymethyl-2,3,4,6-tetra-O-benzylgalactopyranose and 20.64 g (100.0 mmol) of M,M-dicyclohexylcarbodiimide is added to 6.93 g (60.2 mmol) of M-hydroxysuccinamide in 500 ml of dimethyl formamide at 0 "C. The mixture is stirred for 2 hours at 0 "C, and then overnight at room temperature . The precipitated urea is filtered off, the filtrate is evaporated to dryness under vacuum and chromatographed on silica gel (eluent: dichloromethane/ethanol in a ratio of 20:1).

Yield: 68.1 g (8795 from theory) of viscous oil.

Elemental analysis: solution: C 57.32 H 4.89 M 4.31 E 24.86 52.47 found: C 57.47 H 5.05 M 4.19 E 24.72 5 2.29 b) 1-(4-perfluorooctylsulfonyl)piperazinamide 2-M-(1-O-x-O-carbonylmethylgalactopyranose|-I-lysine) 65.0 g (50.00 mmol) of the compound indicated in the title of example 111a are dissolved in 1000 ml of ethanol and 5 .0 g of palladium catalyst (1095 Pa/sC). After that, hydrogenation is carried out for 12 hours at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 45.85 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 34.07 H 3.63 M 6.11 5 3.50 E 35.24 found: C 33.93 H 3.74 M 6.01 5 3.39 E 35.05 ) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(1,4,7-tris(carboxylatomethyl)|-1,4,7,10- tetraazacyclododecane-10-M-(pentanoyl-3-aza- 4-oxo-5-methyl-5-yl)|-2-M-(11-O-o-0-carbonylmethylgalactopyranose|-I-lysine, complex of 50.0 g (54.55 mmol) of the compound indicated in the title of example 1116, 6.28 g (54.55 mmol) of M-hydroxysuccinimide, 4.62 g (109, mol) of lithium chloride and 34.35 g (54.55 mol) of Ca-complex 1,4,7-tris(carboxylatomethyl)-10- (carboxy-3-aza-4-oxo-5-methylpent-5-yl)-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 400 ml of dimethyl sulfoxide. Then, at 10"C, 16.88 g (81, 8 mol) of NN-dicyclohexylcarbodiimide and then stirred overnight at room temperature.

The solution is poured into 300 ml of acetone and stirred for 10 minutes. The precipitated solid is filtered and then purified by chromatography (KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 37.95 g (91.0905 from theory) of a colorless solid.

Water content: 8.695.

Elemental analysis (in terms of anhydrous substance): solution: С 35.34 Н4.09 М 8.24 52.10 EE 21.12 Са 10.28 detected: С 35.22 Н4.17 М 8.18 52 ,19 E 20.91 Sa 10.12

Example 112 a) Monobenzyl ether of M-trifluoroacetyl-1-glutamic acid 100 g (421.5 mmol) of monobenzyl ether of I-glutamic acid is dissolved in a mixture of 1000 ml of ethyl trifluoroacetic acid and 500 ml of ethanol and stirred at room temperature for 24 hours. After that, it is evaporated to dryness and the residue is crystallized from diisopropyl ether.

Yield: 140.47 g (9695 from theory) of colorless crystalline powder.

Elemental analysis: solution: C 50.46 4.23 HE 17.10 M 4.20 found: C 51.35 H 4.18 E 17.03 M 4.28 b) 5-M-(methyl)- M-(2,3,4,5,6-pentahydroxyhexyl)uamide of 2-M-trifluoroacetyl-y-glutamic acid monobenzyl ether

To a solution of 24.9 g (24.08 mmol) of the compound indicated in the title of example 112a, 2x g (24.08 mmol) of M-

of methylglucamine and 2.77g (24.08mmol) of M-hydroxysuccinimide in 150ml of dimethylformamide at 0"C, add 8.25g (40mmol) of M,M-dicyclohexylcarbodiimide. The mixture is stirred for hours at room temperature, and then overnight at room temperature. Urea , which has precipitated, is filtered off, the filtrate is evaporated to dryness under vacuum and chromatographed on silica gel (eluent: dichloromethane/ethanol in a ratio of 20:1).

Yield: 109.40 g (8995 from theory) of viscous oil.

Elemental analysis: solution: C 51.43 H 5.51 E 13.56 M 6.66 found: C 51.22 H 5.41 E 13.40 M 6.75 c) M-(methyl)-M -(2,3,4,5,6-pentahydroxyhexyl)amide M-trifluoroacetyl-1-glutamic acid 21.9xx g (52.15 mmol) of the compound indicated in the title of example 1126 is dissolved in 500 ml of ethanol and 3 g of palladium catalyst ( 1095th Ra/sS). After that, they are hydrogenated at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 43.0 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 40.01 H 5.19 E 17.26 M 8.48 found: C 39.84 H 5.13 E 17.09 M 8.68 g) Trifluoroacetyl-i-glutamic acid- 5-M-(methyl)-M-(2,3,4,5,6-pentahydroxyhexyl)amide-|1-(4-perfluorooctylsulfonyl)piperazinamidepiperazine|amide

16.42 g (66b, 66b, 4mmol) of EEDH (2-ethoxy-1,2-dihydroquinoline-1-carboxylic acid ethyl ester) and stirred overnight at room temperature, then evaporated to dryness in vacuo and chromatographed on silica gel (eluent: dichloromethane/methanol 20:1 ).

Yield: 28.67 g (9295 from theory) of a colorless solid.

Elemental analysis: solution: C 39.61 H 2.89 E 35.66 M 6.19 5 3.54 found: C 39.68 H 2.74 E 35.81 M 6.13 5 3.40 d ) N-glutamic acid-5-M-(methyl)-H-(2,3,4,5,6-pentahydroxyhexyl)amide-|1-(4-perfluorooctylsulfonyl)piperazine|amide

A solution of 28.36 g (30.22 mmol) of the compound indicated in the title of example 112g in 200 ml of ethanol at 0"C is bubbled with gaseous ammonia for one hour. The mixture is then stirred for 4 hours at 0"C. After that, it is evaporated to dryness and the residue is separated from the water by stirring. The solid was filtered off and dried in vacuo (5075).

Yield: 24.19 g (9595 from theory) of amorphous solid.

Elemental analysis: solution: C 41.12 H 2.89 E 35.66 M 6.19 5 3.54 found: C 41.15 H 2.83 E 35.78 M 6.28 5 3.71 e ) M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|-I - glutamic acid-5-M-(methyl)-M-(2,3,4,5,6-pentahydroxyhexyl)amide-5-H11-(4-perfluorooctylsulfonyl)piperazine|amide, per-complex 20.43g (24, 25mmMmol) of the compound indicated in the title of example 112d, 2.79g (24.25mmol) of M-hydroxysuccinimide, 2.12g (50mmol) of lithium chloride and 15.27g (24.25mmol) of the cCa-complex 1,4,7-tris( carboxylatomethyl)-10-((3-aza-4-oxo-5-methyl-5-ylopentanoic acid!|-1,4,7,10-tetraazacyclododecane) is dissolved under moderate heating in 200 ml of dimethyl sulfoxide. Then, at 107, 8.2 g (40 mmol) of M,M-dicyclohexylcarbodiimide and then stirred overnight at room temperature. The solution was poured into 300 mL of acetone and stirred for 10 min. The precipitated solid was filtered off and then purified by chromatography (silica gel KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 28.45 g (7995 from theory) of a colorless solid.

Water content: 11.095.

Elemental analysis (in terms of anhydrous substance): solution: С 34.41 Н 3.83 Е 23.13 М 9.03 5 2.30 Са 11.26 found.: С 34.34 Н 3.98 Е 23 ,29 M 9.19 52.15 Sa 11.07

Example 113 a) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-benzyloxycarbonyl-2-M-|/1-O-y-0-carbonylmethyl(2,3,4-tri-O-benzylglucuronic acid- benzyl ether)|-I -lysine

To a solution of 100.0 g (120.4 mol) of the compound indicated in the title of example 21c, 73.77 g (120.4 mol) of benzyl ether of 1-O-c-Y-carboxymethyl-2,3,4-tri-O-benzylglucuronic acid and 13.86 g (120.4 mol) of M-hydroxysuccinimide in 500 ml of dimethylformamide at 0"C, add 41.27 g (200, mol) of M,M-dicyclohexylcarbodiimide. The mixture is stirred for hours at 0"C, and then overnight at room temperature . The precipitated urea is filtered off, the filtrate is evaporated to dryness under vacuum and chromatographed on silica gel (eluent: dichloromethane/ethanol in a ratio of 20:1).

Yield: 147.58 g (8695 from theory) of viscous oil.

Elemental analysis: solution: C 52.25 H 4.31 M 3.93 E 22.66 5 2.45 found l.: C 52.38 H 4.17 M 4.12 E 22.78 5 2.39 b) 1-(4-perfluorooctylsulfonyl)piperazine|iamide 2-M-11-O-x-ХО-carbonylmethylglucuronic acid|-1 - lysine 142.52 g (100, Ommol) of the compound indicated in the title of example 113a, dissolve in 2000 ml of ethanol and add 10.0 g of palladium catalyst (1095 Pa/C). After that, hydrogenate for 12 hours at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 93.06 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 33.56 H 3.36 M 6.02 5 3.45 E 34.71 found: C 33.31 H 3.42 M 6.04 5 3.40 E 35.51 ) (1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(1,4,7-tris(carboxylatomethyl)|-1,4,7,10- tetraazacyclodo decan-10-M-(pentanoyl-3-aza -4-oxo-5-methyl-5-yl)|-2-M-1-O-c-0-carbonylmethylglucuronic acid|-I-lysine, α-complex, sodium salt 50.76g (54.55mmol) of the compound , indicated in the title of example 1136, 6.28 g (54.55 mmol) of M-hydroxysuccinimide, 4.62 g (109, Omol) of lithium chloride and 34.35 g (54.55 mol) of the α-complex 1,4,7-tris(carboxylatomethyl )-10-(carboxy-3-aza-4-oxo-5-methylpent-5-yl)-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 400 ml of dimethyl sulfoxide. Then, at 10"C, 16.88 g (81.8mol) of M,M-dicyclohexylcarbodiimide and then stirred overnight at room temperature.

The solution is poured into 300 ml of acetone and stirred for 10 minutes. The precipitated solid is filtered and then purified by chromatography (KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 75.14.9 g (88.095 from theory) of a colorless solid.

Water content: 8.695.

Elemental analysis (in terms of anhydrous substance): solution: C 34.53 N 3.80 M 8.05 Ma 1.47 52.05 E 20.63 at 10.05 detection: C 34.38 N 3, 95 M 8.19 Ma 1.63 5 2.15 E 20.83 Ca 10.14

Example 114 a) 6-M-benzyloxycarbonyl-2-(2-(M-ethyl-M-perfluorooctylsulfonyl|amino|acetyl-y-lysine)

To a solution of 31.82 g (113.5 mmol) of 6-M-benzyloxycarbonyl-y-lysine and 66.42 g (113.5 mmol) of 2-(M-ethyl-M-perfluorooctylsulfonyl)aminoacetic acid (obtained according to OE 19603033) in ZoOml of tetrahydrofuran at 0"C, 49.46 g (200.0 mmol) of EEDH (ethyl ether of 2-ethoxy-1,2-dihydroquinoline-1-carboxylic acid) is added and stirred overnight at room temperature. After that, it is evaporated to dryness in a vacuum and chromatographed on silica gel (eluent: dichloromethane/methanol in a ratio of 20:1).

Yield: 55.79 g (5895 from theory) of a colorless solid.

Elemental analysis: solution: C 36.85 H 3.09 M 4.96 E 38.11 5 3.78 found: C 36.85 H 3.19 M 4.87 E 38.28 5 3.95 b ) M-methyl-H-(2,3,4,5,6-pentahydroxyhexyl)amide 6-M-benzyloxycarbonyl-2-M-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-1-lysine

To a solution of 51.02 g (60.2 mol) of the compound indicated in the title of example 114a, 11.75 g (60.2 mol) of M-methylglucamine and 6.93 g (60.2 mol) of M-hydroxysuccinimide in 250 ml of dimethylformamide at 0"С, 20 .64 g (100.00 mmol). M-dicyclohexylcarbodiimide. The mixture was stirred for 2 h at RT and then overnight at room temperature. The precipitated urea was filtered off, the filtrate was evaporated to dryness under vacuum and chromatographed on silica gel (eluent: dichloromethane/ ethanol in a ratio of 20:1).

Yield: 53.05 g (8695 from theory) of viscous oil.

Elemental analysis: solution: C 38.68 H 4.03 M 5.47 E 31.52 5 3.13 found: C 38.49 H 4.17 M 5.32 E 31.70 5 3.29 ) M-methyl-H-(2,3,4,5,6-pentahydroxyhexyl)amide 2-M-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-y-lysine 102.48g (100, ommol) of the compound indicated in the title of example 1146 is dissolved in 2000 ml of ethanol and 10.0 g of palladium catalyst (1095 Pa/C) is added. After that, it is hydrogenated for 12 hours at room temperature. Then the catalyst is filtered off and the filtrate is evaporated to dryness under vacuum.

Yield: 89.06 g (quantitative) of a colorless solid.

Elemental analysis: solution: C 33.72 H 3.96 M 6.29 5 3.60 E 36.26 found: C 33.91 H 3.82 M 6.14 5 3.47 E 36.31 g ) M-methyl-ich-(2,3,4,5,6-pentahydroxyhexyl)amide 6-M-(1,4,7-tris(carboxylatomethyl)|-1,4,7,10-tetraazacyclododecane-10- M-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|-2-M-(2-(M-ethyl-M-perfluorooctylsulfonyl)amino|acetyl-y-lysine, α-complex 48.58 g (54.55 mmol) of the compound indicated in the title of example 114c, 628 g (54.55 mmol) of M-hydroxysuccinimide, 4.62 g (109, mol) of lithium chloride and 34.35 g (54.55 mol) of Ca-complex 1, 4,7-tris(carboxylatomethyl)-10-(carboxy-3-aza-4-oxo-5-methylpent-5-yl)-1,4,7,10-tetraazacyclododecane is dissolved under moderate heating in 400 ml of dimethylsulfoxide. 16.88 g (81.8 mol) of M,M-dicyclohexylcarbodiimide are added at 10"C and then stirred overnight at room temperature.

The solution is poured into 300 ml of acetone and stirred for 10 minutes. The precipitated solid is filtered and then purified by chromatography (KR-18, eluent: water/ethanol/acetonitrile gradient).

Yield: 73.27g (89.4905 from theory) of a colorless solid.

Water content: 8.695.

Elemental analysis (in terms of anhydrous substance): solution: С 35.18 Н423М4.23 52.13 Е 21.50 Са 10.47 found l.: С 35.28 Н 4.15М 4.19 52.18 Е 21.33 Sa 10.61

Example 115: Visualization of atherosclerotic plaques using MRI after intravenous administration of the metal complexes proposed in the invention

In rabbits with genetically induced arteriosclerosis (Watanabe rabbits) after 5-6 hours, as well as after 24 hours and 48 hours after intravenous (iv) administration of the compounds proposed in the invention with a concentration of 25 μmol/kg of body weight on Ti-suspended images obtained on based on the gradient echo (TE 11.1ms, TE 4.Zms, angle of rotation of spins a 15), a significant increase in the intensity of the signal formed by atherosclerotic plaques was observed. In contrast, the contrast agent did not accumulate at all or accumulated only slightly in the walls of healthy vessels, for which therefore no or only a slight increase in signal intensity was recorded on T1i-weighted images. Thanks to the pronounced contrast between the plaque, which forms an intense signal, and the wall of a healthy vessel, which forms a weak signal, it was possible to diagnose atherosclerotic changes in the vessel wall.

Figure 1 shows images of the aorta obtained by MR tomography before administration, as well as 24 hours and 48 hours after intravenous administration of the metal complex XM to Watanabe rabbits (with genetically induced arteriosclerosis) at the rate of 25 μmol (i per kg of body weight. On Ti-dependent images obtained on the basis of gradient echo (1.5T; TC: 11.1ms, TE: 4.3ms; MA: 2; matrix: 213x256; layer thickness: 1.0mm) show a significant increase in the intensity of the signal formed by atherosclerotic plaque The location of the plaques, primarily in the arch of the aorta, as well as in the places of branching vessels, was confirmed by staining with Sudan-II.

Example 116: Visualization of atherosclerotic plaques by MRI after intravenous administration of the XM metal complex to Watanabe rabbits, as well as correlation with the postmortem image obtained by Sudan-PI staining

Fig. 2 shows MR-tomography images of the aorta before administration, as well as 35 min, 20 min and 24 h after intravenous administration of gadolinium metal complex XM to Watanabe rabbits (with genetically induced arteriosclerosis) at the rate of 1 µmol of Ca per kg of body weight. On Ti-suspended images obtained on the basis of gradient echo (MRCapde; 1.5T; TE: 11.1ms, TE: 4.Zms; MA: 2; matrix: 213x256; layer thickness: 1.0mm), a significant increase in intensity is visible signal formed by atherosclerotic plaque. The location of the plaques, primarily in the arch of the aorta, as well as in the places of branching vessels, was confirmed by Sudan-1 staining. After that, the drug placed in agar was examined again, obtaining its MR image based on the Ti-dependent gradient echo sequence (MRCapde; 1.5T; TC 11.1ms, TE 4.3ms, spin angle a 157; MA: 2; matrix : 213x256), as well as spin echo sequences (1.5T; TE: 400ms, TE: 15ms; MA: 16; matrix: 256x256) (postmortem images).

At the same time, an exceptionally high correlation was found between the results obtained for sections of the aorta in which, after the introduction of the metal complex, a significant increase in the intensity of the signal generated by them was observed, and the results obtained when plaques were stained with a histological dye, which indicates the accumulation of the compounds proposed in the invention in atherosclerotic plaques .

Example 117: Visualization of a heart attack (MRI) after intravenous administration of the metal complex XM to rats

Fig. 3 shows images of the heart obtained by MR tomography (immediate and postmortem) 24 hours after intravenous administration to rats with an induced acute myocardial infarction of the XM metal complex at the rate of 100 micromoles per kg of body weight. On Ti-suspended images obtained on the basis of spin echo (1.5T; TE: 400ms, TE: bms; MA: 4; matrix: 128x128; layer thickness: 2.5mm), a significant increase in signal intensity is visible in the infarcted area. Successful induction of acute myocardial infarction was confirmed by MV staining.

Example 1.18: Visualization of a heart attack (MRI) after intravenous administration of a metal complex to rats

Figure 4 shows images of the heart obtained by MR tomography (immediate and postmortem) 24 hours after intravenous administration of the metal complex to rats with induced acute myocardial infarction | at the rate of 100 micromoles of SA per kg of body weight. On Ti-suspended images obtained on the basis of spin echo (1.5T; TE: 400ms, TE: bms; MA: 4; matrix: 128x128; layer thickness: 2.5mm), a significant increase in signal intensity is visible in the infarcted area. Successful induction of acute myocardial infarction was confirmed by MV staining.

Example 119: Visualization of lymph nodes (MRI) after intravenous administration of a metal complex of XM to rabbits with tumor cells UH2

Figure 5 shows images of iliac lymph nodes obtained by MR tomography, registered before the injection of the contrast agent, as well as at various time points during the 24-hour period after intravenous administration to rabbits with intramuscularly (im) implanted tumor cells

MUH2 of the metal complex XM at the rate of 200 micromoles of sa per kg of body weight. On T1i-suspended images obtained on the basis of gradient echo (1.5T; sequence: MRKapde; TC 11.1ms, TE 4.Zms, and 15), a significant increase in signal intensity, which is formed by healthy tissues of lymph nodes, is visible. Those areas within the lymph node, in which the signal intensity did not increase, were diagnosed as metastases, which was confirmed histologically (staining of lymph node sections with H/E).

However, at later moments of time after the introduction of the contrast agent (after 24 hours), a reverse change in signal intensity was unexpectedly detected. In other words, in the healthy tissue of the lymph nodes, the intensity of the signal generated by them decreased, while in the metastasis, on the contrary, a significant increase in the intensity of the signal generated by them was observed.

It should be noted the unexpected fact that immediately after the introduction of the contrast agent, a clear increase in the intensity of the signal formed by the primary tumor (primarily in its periphery) was observed. At later times (24 hours after injection), the signal intensity gradually increased in the direction of the center of the tumor.

Example 120: Visualization of tumors (MRI) after intravenous administration of a metal complex to rabbits with tumor cells UH2

Figure 6 shows images of the iliac lymph node and the primary tumor (intramuscularly implanted tumor cells UH2) obtained during MR tomography, registered before the injection of the contrast agent, as well as after the injection and 20 hours after the intravenous injection of the metal complex Is at the rate of 100 μmol to rabbits sa per kg of body weight. On Ti-suspended images obtained on the basis of gradient echo (1.5 T; sequence: MRKapde; TE 11.1ms, TE 4.Zms, and 15"), a significant increase in signal intensity, which is formed by healthy tissues of the lymph node, can be seen. In more at an early time point after administration (about 10 h after administration), a clear increase in signal intensity was observed, which is formed by the primary tumor (primarily in its periphery). At a later time point (after 20 hours after administration), the signal intensity gradually increased towards the center of the tumor.

Of particular note is the increase in signal intensity, which is formed by a pathological structure (probably a secondary tumor or necrosis) on the contralateral side, which became noticeable only on the image obtained at a later time point ("late increase in intensity").

Metal complex Kh

Example 121: Visualization of a heart attack (MRI) after intravenous injection of a contrast agent in rats

Fig. 7 shows MR tomography images of the heart (immediate and postmortem) two hours after intravenous administration to rats with acute induced myocardial infarction of a polar sa-chelate with a perfluorinated side chain (metal complex X) at the rate of 100 μmol sa per kg of body weight . On T-suspended, ECG-initiated images obtained on the basis of spin echo (1.5T; TC (effective): 400ms, TE: 12ms; MA: 4; matrix: 128x128; layer thickness: 2.5mm), a significant increase is visible signal intensity in the infarcted area. Successful induction of acute myocardial infarction was confirmed by staining with the help of MW.

Example 122: Distribution of a contrast agent in organs (including accumulation in lymph nodes) after its intravenous administration to rats

After intravenous administration to rats of a polar chelate with a perfluorinated side chain (metal complex X) at the rate of 100 micromoles of total gadolinium per kg of body weight, 24 hours after administration, the metal content was determined in various organs, as well as in lymph nodes (data for which are grouped in the form of data for mesenteric and peripheral lymph nodes) (the table shows average values, n-g). in μmol/l kidney dose. | 150 | 065 ( stomach. | 49 2 | 08

Re teoniniiy LOWER NS muscle gland | 77717000 lymph nodes lymph nodes "

Total | (R | 3858

Example 123: Visualization of lymph nodes (MRI) after intravenous injection of a contrast agent in rats

As an example, Fig. 8 shows MR-tomography images of popliteal lymph nodes registered before the injection of contrast material, as well as at different time points during a 60-minute time period after intravenous administration of metal complex X to rats at the rate of 100 μmol of ba per kg of body weight . On T1-suspended images obtained on the basis of gradient echo (1.5T; sequence:

MRKapde; TE 11.1ms, TE 4.Zms, and 15), a significant increase in the signal intensity in the healthy tissue of the lymph node is visible, which is observed already after a short time interval after the injection. So, in particular, the signal intensity 15 minutes after the introduction was 263905 from the initial level, and after 2 minutes after the introduction it was 25495 from the initial level.

Example 124: Visualization of lymph nodes (MRI) after intravenous administration of a contrast agent to rabbits with UH2 tumor cells

As an example, Fig. 9 shows images of iliac lymph nodes obtained by MR tomography, recorded before the injection of the contrast agent, as well as at different time points during the 60-minute time period after intravenous administration to rabbits with intramuscularly implanted tumor cells UH2 of metal complex X at the rate of 200 micromoles of SA per kg of body weight. On T1-suspended images obtained on the basis of gradient echo (1.5T; sequence: MRKapde; TE 11.1ms,

TE 4, Zms, and 15), a significant increase in signal intensity is visible in the healthy tissue of the lymph node.

The intensity of the signal, which is formed by the healthy tissue of the lymph node, 15 minutes after the injection was 38295 from the initial level, and after 2 minutes after the injection it was 41995 from the initial level. Those areas within the lymph node, in which the signal intensity did not increase, were diagnosed as metastases, which was confirmed histologically (staining of lymph node sections with H/E). The ratio between the intensity of the signal generated by the healthy tissue of the lymph node and the intensity of the signal generated by the metastasis was 3.0 15 min after injection and 3.4 2 min after injection.

It should be noted the unexpected fact that immediately after the injection of the contrast agent, a clear increase in the signal intensity was observed, which is formed not only by the lymph node, but also by the primary tumor (primarily in its periphery) (15 minutes after the injection, the signal intensity was 27795 from the initial level) . At later time points (within 24 hours after the injection), the signal intensity gradually increased towards the center of the tumor (24 hours after the injection, the signal intensity was 21795 from the initial level).

Metal complex M

Example 125: Visualization of a heart attack (MRI) after intravenous injection of a contrast agent in rats

Fig. 10 shows images of the heart obtained during MR tomography (immediate and postmortem) 24 hours after intravenous administration to rats with acute induced myocardial infarction of polar sa-chelate with a perfluorinated side chain (metal complex M) at the rate of 100 μmol sa per kg of body weight . On

Ti-suspended, ECG-initiated images obtained on the basis of spin echo (1.5T; TE (effective): 400ms, TE: 12ms; MA: 4; matrix: 128x128; layer thickness: 2.5mm) show a significant increase in intensity signal in the infarcted area. Successful induction of acute myocardial infarction was confirmed by staining with the help of MW.

Example 126: Distribution of a contrast agent in organs (including accumulation in lymph nodes) after its intravenous administration to rats

After intravenous administration to rats of a polar chelate with a perfluorinated side chain (metal complex M) at the rate of 200 micromoles of total gadolinium per kg of body weight, 24 hours after administration, the metal content was determined in various organs, as well as in lymph nodes (the data for which are grouped in the form of data for mesenteric and peripheral lymph nodes) (the table shows average values, n-g). and

Organ μmOols/L of kidney dose. | 436 | 177 stomach. | --:/((B 28 2 ЮЩЦЦ| 008 pancreatic muscle | 9 2 юЮЩЩЩ(| 002 lymph nodes lymph nodes

Total | -(|P | 4843

Example 127: Visualization of lymph nodes (MRI) after intravenous injection of a contrast agent in rats

As an example, Fig. 11 shows MR-tomography images of popliteal lymph nodes registered before the injection of the contrast agent, as well as at different time points during the 6-minute period of time after intravenous administration of metal complex M to rats at the rate of 200 μmol sa per kg of body weight . On T1-suspended images obtained on the basis of gradient echo (1.5T; sequence:

MRKapde; TE 11.1ms, TE 4.Zms, and 15), a significant increase in the signal intensity in the healthy tissue of the lymph node is visible, which is observed already after a short time interval after the injection. So, in particular, the signal intensity 15 minutes after the introduction was 14795 from the initial level, and 2 minutes after the introduction it was 23095 from the initial level.

Example 128: Visualization of lymph nodes (MRI) after intravenous administration of a contrast agent to rabbits with UH2 tumor cells

As an example, Fig. 12 shows images of iliac lymph nodes obtained during MR tomography, recorded before the injection of contrast material, as well as at different time points during the 600-minute period after intravenous administration to rabbits with intramuscularly implanted tumor cells UH2 of the metal complex M at the rate of 200 micromoles of SA per kg of body weight. On T1-suspended images obtained on the basis of gradient echo (1.5T; sequence: MRKapde; TE 11.1ms,

TE 4, Zms, and 15), a significant increase in signal intensity is visible in the healthy tissue of the lymph node.

The intensity of the signal, which is formed by the healthy tissue of the lymph node, 15 minutes after the injection was 24695 from the initial level, and after 20 minutes after the injection it was 28295 from the initial level. Those areas within the lymph node in which the signal intensity did not increase were diagnosed as metastases, which was confirmed histologically (staining of lymph node sections with H/E). The ratio between the intensity of the signal generated by the healthy tissue of the lymph node and the intensity of the signal generated by the metastasis was 2.5 15 min after injection and 1.7 2 min after injection.

It should be noted the unexpected fact that immediately after the injection of the contrast agent, a clear increase in the signal intensity was observed, which is formed not only by the lymph node, but also by the primary tumor (primarily in its periphery) (15 minutes after the injection, the signal intensity was 35095 from the initial level) . At later time points (within 24 hours after the injection), the signal intensity gradually increased towards the center of the tumor (24 hours after the injection, the signal intensity was 10695 of the initial level).

KHIM metal complex

Example 129: Visualization of a heart attack (MRI) after intravenous administration of a contrast agent to rats

Fig. 13 shows images of the heart obtained by MR tomography (immediate and postmortem) after Zhod after intravenous administration to rats with an acute induced myocardial infarction of polar Ca-chelate with a perfluorinated side chain (metal complex KM) at the rate of 100 micromoles of Ca per kg of body weight .

On Ti-suspended, ECG-initiated images obtained on the basis of spin echo (1.5T; TC (effective): 400ms, TE: 12ms; MA: 4; matrix: 128x128; layer thickness: 2.5mm), a significant increase is visible signal intensity in the infarcted area. Successful induction of acute myocardial infarction was confirmed by staining with the help of MW.

Example 130: Distribution of the contrast agent in organs (including accumulation in the tumor and lymph nodes) after its intravenous administration to rats with prostate cancer

After intravenous administration to rats (copulatory inbreeding, 12 days before conducting the experiments, prostate cancer cells of the bippipd K3327 MAT-IC line) were intramuscularly implanted with a polar Sba-chelate with a perfluorinated side chain (metal complex KHIM) at the rate of 200 μmol of total gadolinium per kg of body weight 10 minutes, an hour and 24 hours after administration (p.v.) the metal content was determined in various organs, in the tumor, as well as in lymph nodes (data for which are grouped in the form of data for mesenteric and peripheral lymph nodes) (in the table the average values and mean square deviation are indicated, n--3).

N KO... KVU UM on AKTAM,

N z zhen ii zamen khamenky ryn IZHKOMI I mezh ROUZ i yu bK o :Ozhimkm MAM : FC

Ptoschuetov th N MI oromaeme 10 N Bonya RLMIZHH : SAHM AYU Y hlme ro olneh N m tok. N m s: sp»Mme ioMmizKh N ши ше ши и

Mol Koka r still sova oi je s blk t Oiyum

Pelovnchaiye 0005 0 ж 0 жо 0 ХЖе on 0 Зм

PMuediememufeuhm 1 MMMZH Ro zhyuMa oh To blaMuM o AND FOR i VEMM

Мимухеецтуюемня: РОЗМ РО НЖЕМО из 1 ОлеДХt о: ПЛЕЩ ОСУМОМЮ

Mykh szuyurokhkes: OSHEMYKH OYI Ooshkeal' eat N MK I OMIKAM: slekeme Й pre RO ЖТНХ roatmjo her и7M5 ro BIL both

KEKV dele dor V she PV

Tiryumizkhai: I saw a thorny fly

EK ma zhyutyai yah klgya zitsdi thzduakhy; y) didzesch dya Zrkhavia curves, ssyulka komn misyutsya i retsei orgechimuu

UeUtTSUKa acted in the way of TyHNYMV,

Example 131: Imaging of lymph nodes (MRI) after intravenous injection of contrast material in guinea pigs

Figure 14 shows, as an example, images of iliac and inguinal lymph nodes obtained by MR tomography, registered before the administration of the contrast agent, as well as at various time points during the 24-hour period after intravenous administration to sea urchins with stimulated lymph nodes (adjuvant Freund) of the KIM metal complex at the rate of 200 micromoles of sa per kg of body weight. On Ti-suspended images obtained on the basis of gradient echo (2.0T;

TA 10ms, TE 5ms, and 40), a significant increase in signal intensity is visible in healthy tissue of lymph nodes, which is observed already after a short time interval after the injection. So, in particular, the signal intensity through bOhv after the introduction was 12795 from the initial level.

Example 132: Visualization of lymph nodes (MRI) after intravenous administration of a contrast agent to rabbits with UH2 tumor cells

As an example, Fig. 15 shows images of iliac lymph nodes obtained during MR tomography, recorded before the injection of contrast material, as well as at different time points during a 23-hour time period after intravenous administration to rabbits with intramuscularly implanted tumor cells УХ2 of the metal complex of ХМ at the rate of 200 micromoles of SA per kg of body weight. On T1-suspended images obtained on the basis of gradient echo (1.5T; sequence: МРЕapde; TE 11.1ms,

TE 4, Zms, and 15), a significant increase in signal intensity is visible in the healthy tissue of the lymph node.

The intensity of the signal, which is formed by the healthy tissue of the lymph node, 10 minutes after the injection was 29795 from the initial level, and after 20 minutes after the injection it was 26995 from the initial level. Those areas within the lymph node in which the signal intensity did not increase were diagnosed as metastases, which was confirmed histologically (staining of lymph node sections with H/E). The ratio between the intensity of the signal formed by the healthy tissue of the lymph node and the intensity of the signal formed by the metastasis was 5.1 10 min after injection and 1.9 2 min after injection.

It should be noted the unexpected fact that immediately after the injection of the contrast agent, a clear increase in the signal intensity was observed, which is formed not only by the lymph nodes, but also by the primary tumor (primarily in its periphery) (15 minutes after the injection, the signal intensity was 59495 from the initial level) . At later time points (within 24 hours after the injection), the signal intensity gradually increased towards the center of the tumor (120 minutes after the injection, the signal intensity was 162595 from the initial level).

Her metal complex

Example 133: Visualization of a heart attack (MRI) after intravenous injection of a contrast agent in rats

Fig. 16 shows images of the heart obtained by MR tomography (immediate and postmortem) 22 hours after intravenous administration to rats with acute induced myocardial infarction of polar Ca-chelate with a perfluorinated side chain (metal complex II) at the rate of 100 μmol of Ca per kg of body weight . On

Ti-suspended, ECG-initiated images obtained on the basis of spin echo (1.5T; TC (effective): 400ms, TE: 12ms; MA: 4; matrix: 128x128; layer thickness: 2.5mm) show a significant increase in intensity signal in the infarcted area. Successful induction of acute myocardial infarction was confirmed by staining with the help of MW.

Example 134: Distribution of a contrast agent in organs (including accumulation in lymph nodes) after its intravenous administration to rats

After intravenous administration to rats of a polar chelate with a perfluorinated side chain (metal complex II) at the rate of 200 μmol of total gadolinium per kg of body weight, 24 hours after administration, the metal content was determined in various organs, as well as in lymph nodes (the data for which are grouped in the form of data for mesenteric and peripheral lymph nodes) (the table shows average values, n-g). and

Organ mmol/L kidney dose. | 489.7 | .1.97.YushЩЦЦ2 stomach. | 165 | 057 (pancreatic lung. | 338 | 096 lymph nodes lymph nodes "

Total | (6 | 7320 2

Example 135: Visualization of lymph nodes (MRI) after intravenous injection of a contrast agent in rats

As an example, Fig. 17 shows images of iliac lymph nodes obtained during MR tomography, registered before the injection of contrast material, as well as at different time points during a 60-minute time period after intravenous administration of metal complex III to rats at the rate of 200 μmol sa per kg of body weight . On T/suspended images obtained on the basis of gradient echo (1.5T; sequence:

MRKapde; TE 11.1ms, TE 4.Zms, and 15), a significant increase in the signal intensity in the healthy tissue of the lymph node is visible, which is observed already after a short time interval after the injection. So, in particular, the signal intensity 15 minutes after the introduction was 320905 from the initial level, and 2 minutes after the introduction it was 40195 from the initial level.

Example 136: Visualization of lymph nodes (MRI) after intravenous administration of a contrast agent to rabbits with UH2 tumor cells

As an example, Fig. 18 shows images of iliac lymph nodes obtained by MR tomography, registered before the injection of contrast material, as well as at different time points during the 600-minute period after intravenous administration to rabbits with intramuscularly implanted tumor cells UH2 of the metal complex Ii at the rate of 200 micromoles per kg of body weight. On T1-suspended images obtained on the basis of gradient echo (1.5T; sequence: MRKapde; TE 11.1ms,

TE 4, Zms, and 15), a significant increase in signal intensity is visible in the healthy tissue of the lymph node.

The intensity of the signal, which is formed by the healthy tissue of the lymph node, 15 minutes after the injection was 19595 of the initial level, and 20 minutes after the injection it was 23395 of the initial level. Those areas within the lymph node in which the signal intensity did not increase were diagnosed as metastases, which was confirmed histologically (staining of lymph node sections with H/E). The ratio between the intensity of the signal formed by the healthy tissue of the lymph node and the intensity of the signal formed by the metastasis was 1.9 15 min after injection and 1.8 2 min after injection.

It should be noted the unexpected fact that immediately after the injection of the contrast agent, a clear increase in the signal intensity was observed, which is formed not only by the lymph node, but also by the primary tumor (primarily in its periphery) (15 minutes after the injection, the signal intensity was 23295 from the initial level) .

Fig. 1. N . . - Farcing

Baseline state 24 hours after injection After 1 hour after administration of sudanomya poison still A. with E n m H 7 th

V i Ya E i Kh same v Ko v tsk v Y she iy z 5 . x yap y 5 B 7 psa "NISHNANNY U is

Metal complex KhU; 25 μmol/kg IV; 30-13 kapde, TAITE 113 me, a 15 "(Watanabe rabbits; A: vorta; NOT heart; arrows: branching vessels;

MeE-projection; histology after staining with Sudan-J)

Fig. and J

Жерва ЗБ халуюлі Жера в квв лсля 28 h later

Initial state of input guidance | introduction. i Sk she SHY; в и "и и и ши I "a I SHE: 4e и vyTO I Z NE OO i . still hey, :

Metal complene Hu 10 vkmolivlk av; 301 MRKapde, TELE TET yaku a 15 (rabbits Watanabe, U perme, A zorta, arrows uterosclerotic plaques)

On the basis of the sequence It is based on the spitting echo Painting by the ship" MEASURE: zadesposliDOVNOS to Ko o. x Z Me s» m j EOM tk ke u 5 8 B a u . z shk: "o v 7 ! oh x x Z EE. V. x. v: g. Z W M y sht g,

GO ZE: :

Metal complex KHU. 10 μmolivkg vv: 3021 -MeKapde,

TALE LAZ me, e 15 " (Watanabe rabbits; preparation of aorta 24 h after administration; histology after staining with Sudan-yi; postmortem MR image of the abrata, located vtra

Fig. WITH

After 24 hours after administration, After 25 hours after driving, After 24 hours after driving, with mms, vksivlna postmortem, yaksalno And postmortem, korsnarno nych ki sha k 7

Metal complex ХУ: 100 μmol/kg vv 11-56, TRUTE 4005 me (arrow: myocardial infarction)

Fig. 4

24 hours after administration, 24 hours after eating, 74 hours after injection; we are her; ayuvially postmortem, axially postmortem; hobonzrno still gu and She she and in t Va

From the Goat 1st book and voy x KE. wow

Metal complexes: 100 μmol/kg body weight. ZE, PUTE 4006 mo (arrow: myocardial infarction)

Fig. 5

In a minute after In 30 minutes after After BO-.he song After: 74 hours after

The initial state of the introduction of the introduction of the introduction entered she shi et -ya : de lot v: she eh SHOSH o you se zh Ж, y che v she

Metal complex XM: 200 μmol/kg av: 30-11-MRKapde, TVITE 11.1/4 3 me, 15 (shooting metastasis; Her: tumor)

ШЙ In 30 min In bo ha In 24 h

Baseline after administration after administration. after entering ! it's a pit I | pe NISHKYA where E her Sh

She and her

Metal complex KhU; 200 mimolivkg of air; TV/TE TIL mo, x 157: primary tumor

Fig, 6

Initial state Through Bosch after driving After 20 hours, the song of the introduction and Until the wounds as for all I nina НН ши ОН | m WE: And. | po i still M y g I sho s t STILL

Metal complex I: 100 μmol/kg d.v.; 30-T1-MRKapde, TELE 11/43 mo, I 157 (arrow with stained end: pymosal nodule, 1: tumor; bar with unstained end: late increase in signal intensity)

Fig. 7 and o. d After B h of the input field

In b hours after administration; 6 hours after administration; the eyes are knowingly gone, they are posthumous, they are posthumous, they are radically enlightened | - ke Zh, MT

I | se ozh zho iv i rn "Ko zov: I in M 5:

I I ro VV her rah Kak. SE o same Zh in DK I and del "ah More | still r at Ko : B shk. E ! still nene y After V h after introduction, Cut,

After about an hour, the application of dyeing of the MVT was carried out

Metal complex X: 100 micromoles; ZE, TAL'E-400/12 Mo (arrow; myocardial infarction)

Fig. 8

And Merez 15 min. After 80 min

The initial state of the introduction song after the introduction of lm yar: romete i pe ov i den pek Memny tk, Kyryk, i Veshta ia: aa en nya s nat ee nn V v Ka CHA ta I sh i

Metal complex x: ТО0y micromolivykg v.v.; 30-T11-MRAapde, TELE 13 (arrow: popliteal lymph node)

Fig. 9 -

I 15 ha after Merez'80 min after

The initial state of the input of the input Dyeing N/E ho U Pavrnenyanya ze as M M o sho Vij I RYA shoi How about wild her V Z shi S sho "y sce. y SHEU zho | your shi y zi I schi meh - E and Kt sot Х Х Still OK oddet В й І 7 To ryaishishe ko я гЯ I и She zah Х y r For your mouth

Metal complex X: 200 μmol/v.v., CJSC - MyKapde, TEUTE TINA, Z me, n 15 (arrows: M: metastases; T: tumor)

Fig. 10"

24 hours after administration, 24 hours after administration; postmortem, axial postmortem, coronary "4 sy Y i E K. i ok x kozh V salt veins I I | I I ka E a i

24 hours after administration, 24 hours after administration, section, ex myo section, staining of MVT "Metal complex m; 100 mumol/ke IV ZE, TEUTE 40012 mo. (arrow: myocardial infarction)

Fig. 11 and 15 min. After 3 min

The initial state of the construction of the introduction: l NI kro a she sha. I respect you: sis sis sis OS 3 is not in VN

Metal complex NOT 200 μmolivkg of water; ZV-T3-MRAEaid, TAUTE

MLK Z me, at 15 strip: popliteal pimphatic node)

Fig. 12 J

15 ha after Through BO he song

The initial state of the input input Dyeing IDEA movement Yang Ya | IN.

Eh r. cache: . kN: i U Va v she ie nn Shu i Shche kt | t jo gen Beoshh i vk Kk - a pekan y vne o, SHHI x y

E t " Uk , Z y g: oz Z : Dt rey : Eh. Che zv i ko Ko hid;

I and | Ж Ж Ж I A g ne y rya y

Metal homplex of m: 200 mumolivikg вv; ZO-T MR apde, TA/TE T.Z mo, at 15 (arrows: M: metastases; t: tumor)

Fig, 713 and three hours after the introduction, three hours after the introduction, post-smartly, three hours after the introduction, ip mimo, axially, postmortem, coronary still can. with you from her and ! she and he: their what with Y Z

BizhZ VZN ih where I pkt Z zhazhyuzheayu o y - y o SVB in Z K- ia Y y / more» shchi I schu | o, sharez With tod after injection, Through Z'od after injection, section, ex MU section, staining of MVT

Metal Complex of Chemical Industry; 100 μmol/kg IV; ZE, TRTE 40012 me. (arrow: myocardial infarction)

is

Fig. 14

Initial state After 80 minutes after the introduction, after the introduction of the drug, it is not: INN Esh schi I sho zh: she ee po an she I dt. wa t ryn shen y shi ore oh hu yo z TE ah v te eh E ele y y ka shik kZ Ka soya v no ka ME Ya ee s zhvtai. wai shko y y ony haka oSHY y y BO ny nn V Ж Ж дов шко

In o NNYA i Y Kk ok also and . N ; sho ss Shk Ya Shu UPNSHY i dae sk

Metal complex ХУ: 200 μmol/kg v.ao Yaazy oiirnavze, TELTE 157543 mo, a 407 (strip; iliac and inguinal lymph nodes)

Fig. On the 15th of the third century, through Zaha Cherva, I am at the same time. after the assignment of field management | tslnyavedenyu ZEO bvObovation NOT 1 sho her shk gai pe WH U al gak i r J sov y VO M MNE ku Ka ki. In o ve i ro MY ; . 2 of them Be of 3 3 B still schu A s zach I ; Z Ouki y Sche Sche ey t y; E Ko ZHE sh Ж и g MA ТЕ ня я х B y "y

Lya she be o 00 B, with a ; и ме а А kuki ех. Ж You she BO pu u i and her voi m da shk ND ee But, OSHNYE YANNYE en VA A

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SHE metal compeno zh; 200 mimoplivike vv; MeNYapde, .

TALE ON ms; 157; VO sections, dots With tumors! m cells of the UC (streliyuzh metastva I

Fig. 16

After 22 hours of introduction, the worm after 22 hours of induction, after 22 hours of erection. with yo, vksial posthumously, akoially posthumously; coronary

And set with live I S I | Even B. v. And Veyaki: y vk tih Ba z I kozh zai ne Ba her eh kt sih SCHI i no SE U boss CY i -

What and p Z and Sho i

22 h after After 22 tod song introduction, cut; oh Mo input, slice,

And painting: NO

Metal complex: 100 μmol/kg IV: ZE, TV/TE 40012. me (arrow: myocardial infarction)

Phoebe -

And E. Exit SHY "Through'5 yah" | Chervo Bo-hv: g. w sty ЧОпсле introduction Ш ssslevnodenny ВЙ ше ши a s ZU NN s V Vozhe s y s ke M y Ь Be: з шж окис КК ВА ву tv ! o NN tk / eh : : ov i v y ee kim VO ! i sk y Kri : su . z. ev lya y y - y y ; b: y U y y "ah tod that not in Я. 7 her OK she she: in the Metal Hostess me 200 memolivl V well, li skh y ZT MAN ande TEITE LIT NYA mere ate what else

Kozu E fsnikha: popliteal phimphatic node) | WITH

Fig. 18 I

Between the 15th and after Through the 15th and after I

Initial state input input Dyeing NO. iy "Z Z | ih y ! t | 5 and a syh z KI "y V r e i z. v Y I B. s v k what S Ya rya Y Kf v She ee is io g; them

E " boho m h a z i and some: oh V still "and Y ,

MK. in sy shi uch i, x I i ! braid

Metapazy hkompex NO: 200 μmol/kg intravenously. ZO T1-MRKavde, TAITE 111.3 Mo, p 18? (arrows: M: metastases; T: tumor)

Claims (1)

1. The use of perfluoroalkyl-containing gadolinium complexes, which are characterized by a critical micelle formation concentration of less than 107 mol/l, a hydrodynamic micelle diameter (2VI) of more than 1 nm, and a proton relaxivity in plasma (VC) of more than 10 l/mmol-s, as a contrast agent in magnetic resonance imaging tomography (MRI) for visualization of atherosclerotic plaques. 2. Application according to point I, which differs in that the indicated metal complexes are also used as a contrast agent in MRI for visualization of lymph nodes. 3. Application according to claim 1 or 2, which differs in that the indicated metal complexes are also used as a contrast agent in MRI for visualization of infarcted 1 necrotic tissue. 4. Application according to any of claims 1-3, which differs in that the indicated metal complexes are also used as a contrast agent in MRI for independent visualization of necrosis and tumors. 5. Application according to point I, which differs in that metal complexes are used, which are characterized by a micelle formation concentration of less than 107 mol/l. 6. Application according to claim 1, which differs in that metal complexes are used, which are characterized by a hydrodynamic diameter of micelles equal to or greater than 3 nm, preferably greater than 4 nm. 7. The application according to claim 1, which differs in that metal complexes are used, which are characterized by the relaxation of protons in plasma more than 13 l/mmol-s, preferably more than 15 l/mmol-s. 8. Application according to any of claims 1-7, which is characterized by the fact that compounds of the general formula I are used as perfluoroalkyl-containing metal complexes: VAK, () in which B" means a perfluorinated, straight or branched carbon chain of the formula -SuEE, where E represents the terminal atom of fluorine, chlorine, bromine, iodine or hydrogen, and n means the numbers from 4 to 30, I means a direct bond, a methylene group, -MHSO-group, a group Da - (CHO) AMNeOSHno (sna -word - where p means the numbers from 0 to 10, while i independently means the numbers 0 or 1, 1 K" represents a hydrogen atom, a methyl group, -СНо-ОН-group, -СН»А-СО3»Н-group or Oo-Ciz-chain, which is optionally interrupted by 1-3 oxygen atoms, 1-2 "CO-groups or an optionally substituted aryl group and/or substituted by 1-4 hydroxyl groups, 1-2 C-Slalkoxy groups, 1-2 carboxyl groups, the group -503H-, or means a straight, branched, saturated or unsaturated C2-C2 carbon chain, which optionally contains from I to 10 oxygen atoms, from I to 3 -MK "-groups, from 1 to 2 sulfur atoms, piperazine, -"СОМК"-group, -МК"СО-group, -502-group, -МК"-СО3-group, from 1 to 2 -СО-groups, group -СО-М-Т-М(К")-502-КЕ or from I to 2 optionally substituted aryl groups 1/or interrupted by the specified groups 1/or optionally substituted by 1-3 -OK" groups, 1- 2 oxo groups, 1-2 -MNA-SOK"-groups, 1-2-SOMNK"-groups, 1-2 -"СНо)р-СО»Н-groups, 1-2 groups -"(СНо)р- (О)2-СНоСНОо-В, where В», КЕ, р and д have the above values, and T is a C2-SiO chain, which is optionally interrupted by 1-2 oxygen atoms or 1-2 -CHNSO groups , 1 K means a complexing agent or a metal complex or their salts with organic 1/or inorganic bases or amino acids or amino acid amides, namely, it means a complexing agent or a complex of the general formula P ry /bsn s-m so m M sov ne 7 Ka Ov m' owl owls; and in which KU, В В have values independent of each other, and Е: has the values specified for KE? value or means -"SNo)tp-I -B, where t means 0, I or 2, and I. and KE" have the above values, B in each case independently means a hydrogen atom or the equivalent of a metal ion with serial number 22-29, 42-46 or 58-70, 1 B means the group -OV! or the group snisnIATI-VE sx -кк ши - М М-50, 1-8 o or -0-0- , where ВК! И, В" and В" have the above values, or a complexing agent or a complex of the general formula Ш Я-С60,8! s vo M buya lllAA-SN,SNU Y M o ! m bo! x-sbo,8B! 7.0) in which VU B! have the values indicated above, and B? has the values indicated for BK" or a complexing agent or a complex of the general formula IM I - C06,18! ос о00/-х и M ! m bo! Mch V! ah) in which B! has the above values, or a complexing agent or a complex of the general formula U bo I x--60.8V! post sn sh-k A - 608! M u and M osov! shk (U) in which VE! has the values indicated above, and o 1 d mean the numbers 0 or 1, while the sum of o4-i1, or the complex generator or the complex of the general formula MI pos U bov! y vch U 1 Sov 7 MU in which B has the values indicated above, or a complexing agent or a complex of the general formula UP toast in beans! that with x / sov SO,V! d; SMIE) in which V! and B have the above values, or a complexing agent or a complex of the general formula МШ pPoschi zbo! What an owl! ? tt (U) in which VU V! have the above values, and E? has the above values for B, or a complex generator or a complex of the general formula IX o - shchi u bozh 0) he M M sho 1 i i .) in which Vi B! have the values indicated above, or a complexing agent or a complex of the general formula X of the battle on M M shin sov! 0) in which Vi V! have the above values, or a complexing agent or a complex of the general formula ХИ ВО, н тыЮХх бо М М З ( (mn-СН. (СН) СОМ Ск sov! where 8О2- ; ОО) in which VU, rii d have the above values, and E? has the values indicated above for VC: either a complexing agent or a complex of the general formula ЧП о -М М - М ра 2 И х--60.8! M. so u Y, YAU-26b-M 000 M-80,-I-VE M s "oso ? ; (HP) in which I, Viii B! have the above values, or a complexing agent or a complex of the general formula ХШ m А - because V! I sov! Mo -690--M. M--80,- I! ts A - 600.8! x sov! So,. (HP) zo 1 .- in which K. has the above values -СН, - СН.СН, - -(СН.дУ - -3-15,0- СН.О - СН.СН, - -СнН,-(0-СН,-сСН,.-), - . " and 97 "Application according to" paragraph c Which differs in that the compounds of the General shaft НН од о-СН,-МН-СО-СН, - М(СН.СООН)-50, - D, Formulas are used; p) which She; means b- СН.МН- СО - СН, - М(С,Н.)- 50, - В, а-СсН,-МнН-СО - СН, - М(СоН.;)-50, -В,а - СН, - МН- СО - СН, - M(С,Н.з) -50, - В, а-СН,-МН-СО-(СН,) - M(С.Н.)-50, - В,а-СН, -МН-сО-СН, - Х(-СН, - СН.) -50, -Д, а-СН,-МнН-сО-сНн, - M(-СН, - СН, - ОН)5О, - В,а- CH, - МНСО - (CH); -5- СН.СН, - В, а-СН,МНСОСН, -0-СН,СН, - В, а.- СН, МНСО(СН,) 0 - СН. СН, - D, а-СН,-С,Н,-О-СН,СН, -В,а- СН, -О- СН, -С(СН, -ОСН.СН, -С,Е.); - СН, - ОСН, - СН, - D, « - СН» - ЧМНСОСТСНСОМ- СССНоМНСОСТМ (Сон )5О»сСви 7 сн - СМНСОСНМ(Сонв) - ЗО» - В, о - sno -0- sno - СНО, оНаз ) - sno -0- Ssnsn, - Vo - (snNMnoSO, - sno - Ssnsn, - r. o - (snNMnsSOz - sno - snsn, - Dos - sn, - osn non) - sn, -0- snsn, - р в--СН ФЩСОСв (3 o fny-хНгО-ed, -SIVnie-HСО- CH, -0- CH. CH, - P, a-МН-СО -В,а- Mne - CH, - MISN.СООН )-50, -В,а- МН-СО -СН.М(С.Н.) -50, -В, а-МнНСО-сН, -М(СнНН,) EfONB, а - МН- СО -СН, - M(С.Н.з)-50, -В,а- МН-СО -(СН,)- M(С.Н.з) -50, -В, а-Мн-СОо-сн,-Мм (-СН, -С,Н.)-50,-В,а0- МН-СО -СН, - M(-СН, - СН, -ОН)5О, - В, а-МнН-СОо-СсН,- В,а-СН,-0-сС,нН,-О-сСН, - СН, -Б, о -Сн -СеН -0 - СН» - СН - DF, о- M(СаНв) - BO» - Do; - MSHSvNv) - 5O» - D,x- M(StoNai) -5O» - p, o - M(SeNi z) - ZO» - V os - MC2NAON) - ZO» - V os - MmSNHSOOH) - ZO » - Vo. - М(СНЬSeНБв) - ЗО» - r. ос -М-|СН(СНоОН)»1- 505 - В, - М- |ISNISSNSONISN(СНОН)) - 80» - В, where x means the place of attachment to the complexing agent or metal complex K, and P means the site of attachment to the fluorine-substituted residue. 10. Application according to claim 8 or 9, which differs in that compounds of the formula I are used, in which n in the formula -CoEvE means numbers from 4 to 15 1/or E in this formula means a fluorine atom. 11. Application according to any of claims 8-10, which differs in that the following compounds are used: - gadolinium complex 10-PI-methyl-2-oxo-3-aza-5-oxo-14-perfluorooctylsulfonylpiperazin-1-yl | pentyl |-1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane, - gadolinium complex 10-(2-tihydroxy-4-aza-5-oxo-7-oxa-10,10, 11,11,12,12,13,13,14,14,15,15,16,16,17,17-heptadecaftorheptadecyl |-1,4,7- tris(carboxymethyl)-1,4,7,10- tetraazacyclododecane, - gadolinium complex 10-|2-hydroxy-4-aza-5,9-dioxo-9-I4-perfluorooctylpiperazin-1-yl|nonyl|-1,4,7-tris(carboxymethyl)-1,4, 7,10-tetraazacyclododecane, - gadolinium complex 10-|2-hydroxy-4-aza-5-oxo-7-aza-7-(perfluorooctylsulfonyl)nonyl |- 1,4,7-tris(carboxymethyl)-1,4 . carboxymethyl)-1,4,7,10-tetraazacyclododecane, - gadolinium complex 10-(2-tihydroxy-4-aza-5-oxo-7-oxa-10,10,11,11,12,12,13,13 - gadolinium complex 10-(2-hydroxy-4-aza-5-oxo-11-aza-11- (perfluorooctyls sulfonyl)tridecyl|-1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane, - gadolinium complex 10-(2-hydroxy-4-aza-5-oxo-7-aza-7- (perfluorooctylsulfonyl)-8-phenyloctyl|-1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane. 12. Application according to any 3 claims 1-7, which is characterized by the fact that as perfluoroalkyl-containing metal complexes compounds of the general formula Ia А-В", (Ia) in which A is a fragment of a molecule containing 2-6 metal complexes are used , which are directly or through a linker attached to the nitrogen atom of the cyclic skeleton chain, 1 ER is a perfluorinated straight or branched carbon chain of the formula -Co»E, where E means the terminal atom of fluorine, chlorine, bromine, iodine or hydrogen, and n means numbers from 4 to 30, while the indicated fragment of molecule A has the following structure: or a metal complex or their salts with organic 1/or inorganic bases or amino acids or amino acid amides, X means a direct bond with a perfluoroalkyl group, a phenylene group or a C-Cisaalkylene chain, optionally containing 1-15 oxygen atoms, 1- 5 sulfur atoms, 1-10 carbonyl groups, 1-10 (ME)-groups, 1-2 M ВЯ5О"-groups, 1-10 СОМ -groups, 1 piperidine group, 1-3 5Оо-groups, 1-2 phenylene groups or optionally substituted by 1-3 B" residues, while VI is a hydrogen atom, phenyl, benzyl or C-Sisalkyl group, which optionally contains 1-2 MHSO groups, 1-2 CO groups, 1-5 oxygen atoms and is optionally substituted with 1-5 hydroxy groups, 1-5 methoxy groups, 1-3 carboxy groups , 1-3 residues B", M means a direct connection or a chain of the general formula Tsa or Sha ne iv) B sh - sna (sno (Pa) IF) vB-m-sn.-0-M o Y OO (snu bo o 270-5 K- ia st b ii Н H (Sha where KU represents a hydrogen atom, a phenyl group, a benzyl group or a C;-C alkyl group, which is optionally substituted by a carboxy-, methoxy- or hydroxy group, MU is a direct link, a group of polyglycol ether containing up to 5 glycol units, or a fragment of a molecule of the general formula IMa -CH(BZ)-, Ua) in which ВЕ: means a C-Slcarboxylic acid, a phenyl group, a benzene group or -"CH »)1-5-MH-K-group, o means a bond with the nitrogen atom of the chain-rock and, B means connection with a complexing agent or a metal complex K, K and t mean natural numbers from 0 to 10 1 1 means 0 or 1, 1 P is a CO or 5O2 group. 13. Application according to claim 12, which differs in that compounds of the general formula a are used, in which 4 means the number 1. 14. Application according to claim 12, which differs in that compounds of the general formula Ia are used, in which the X molecule fragment is an alkylene chain containing 1-10 СНоСН»оО groups or 1-5 СОСНоМН groups, or is further direct connection or one of the following structures: uU-sn-0-(SNU,- 5, To u-sn.-M-50,--5, "tbnavtm o sn, -30,7 5, son" n Sleep u-sn.-M-80,--5, -7- p u sN-M-50,- 5, u-(Snuv o (Sn u, SeN.: u-sn.-M-50,- 5, in a dream TM vo, -, with Zion, where 7 means joining I, and Z means joining B". 15. Application according to claim 12, which differs in that compounds of the general formula Ia are used, in which M is a fragment of a molecule having one of the following structures: iv) o petenyatv "-b-СНАМН-- В, сно.сооН iv) iv) is -30-СН-АМН-В "ж (З0-СН-МН-Р, Сну сн(сН.), iv) ? a dream nn « bosН-МН.v is -0-СНАСН-МН-В « -0-СНА СН- МН. R, (CH); - MNAK 16. Application according to claim 12, which differs in that compounds of the general formula Ia are used, in which K is a complex of the general formula Ma, Mia, Upa or Usha and soov: where 0 M Also A - M dova v'cOS or What about y soov: 5 ve I M still A 4 vieOS chu on prasch ra 7 de Sov M Ho --- y Sho soov M soon ; (Upa) iv) play rutu M M M pos ch sh I soove soon; (MPa) where B in each case independently means a hydrogen atom or the equivalent of a metal ion with serial number 23-29, 42-46 or 58-70, BO means a hydrogen atom, a linear or branched C-Slaalkyl residue, a phenyl residue or a benzyl residue, B/ means a hydrogen atom, a methyl or ethyl group, which is optionally substituted by a hydroxy or carboxy group, O means a linear, branched, saturated or unsaturated C - Sooalkylene group, which optionally contains 1-5 imino groups, 1-3 phenylene groups, 1-3 phenylenoxy groups, 1-3 phenyleneimino groups, 1-5 amide groups, 1-2 hydrazide groups, 1-5 carbonyl groups, 1- 5 ethyleneoxy groups, I urea group, 1 thiourea group, 1-2 carboxyalkylimino groups, 1-2 ester groups, 1-10 oxygen atoms, 1-5 sulfur atoms and/or 1-5 nitrogen atoms and/or optionally substituted 1 -5 hydroxy groups, 1-2 mercapto groups, 1-5 oxo groups, 1-5 thiooxo groups, 1-3 carboxy groups, 1-5 carboxyalkyl groups, 1-5 ester groups, 1/or 1-3 amino groups, while optionally present phenylene groups can be replaced by 1-2 carboxyl groups, 1-2 sulfonic groups or 1-2 hydroxy groups amy, 1 T means group 99-B-MNOSO-R or group "MNOBZ-R, where P means the place of joining TO U. 17. Application according to claim 16, which differs in that it is specified as the value for I Si- The sosalkylene chain contains the groups -СН»МНСО-, -МНСОСНоО-, -МНСОСНоОСценА-, - М(SNСОН)О-, -СПОСН»о- . 18. Application according to claim 16, which differs in that O means -Сно--СТСН»о-, -СНСНСН»-, -СеНа-, -СеНио-, -СНоСеНя-, -СПМНСОСНСН(СН»СОН)-СеНа- , -"SNOMNSOSNoOSNO- or -SNOMNSOSN"oseNa group. 19. Application according to claim 12, which differs in that compounds of the general formula Ia are used, in which K has one of the following structures: sho sh I soov Ssoovy (ooo oso M Ya tboov: y M bUbo--- sh What it. r y ovo yus chi sh shi i, M y o bot o oioivy dsoo Bo --- /Z-2M M MO A voos /1 ЧО и он N ost 20. Application according to any of claims 12-19, which is characterized by the fact that compounds of the general formula Ia are used, in which the perfluoroalkyl chain B" is -CeRiz, -Cv8Ei7, -Ci0b»1 or -C1i2E5. 21. Application according to any of claims 12-20, which differs in that the gadolinium complex 1,4,7-tris/ 1,4,7-tris(M-(carboxylatomethyl)-10-|M-1- methyl-3,b-diaza-2,5,8-trioxooctane-1,8-diyl |)-1,4,7,10-tetraazacyclododecane, Sd-complex Y-10-|M- 2H.2NANN,ZN,ZN-Z-oxaperfluorotridecanoyl |-1,4,7,10-tetraazacyclododecane. 22. Application according to any of claims 1-7, which differs in that as perfluoroalkyl-containing metal complexes compounds of the general formula IB A com am in which K is a complexing agent or a metal complex of the general formula or iv) -. oso (PV) where B means a hydrogen atom or the equivalent of a metal ion with a serial number of 23-29, 42-46 or 58-70, VE and VZ mean a hydrogen atom, a C-Alalkyl group, a benzyl group, a phenyl group, - СОН or - ЧНО-ОСН», 1 I is a residue of I, while I and Y can independently have identical or different values, and A is a hydrogen atom, a linear or branched C-Szoalkyl group, which is optionally interrupted 1-15 by oxygen atoms and/or optionally substituted by 1-10 hydroxy groups, 1-2 COOH groups, a phenyl group, a benzyl group and/or 1-5 -OKR- groups, where VE means a hydrogen atom or a C-Stalkyl residue, or - 17-B7, I// represents a linear or branched C-Szdalkylene group, which is optionally interrupted by 1-10 oxygen atoms, 1-5 -MH-CO groups, 1-5 -CO-MH groups, necessarily substituted by a carboxyl phenylene group, 1-3 sulfur atoms, 1-2. -M(B)-5O2-groups and/or 1-2 -502-M(B')-groups, where B! has specified for A! value or means МНСО-group, СОМН-group, М(В)-502-group or -505-М(В!)-group and/or optionally substituted by a Ви residue B. is a linear or branched perfluorinated alkyl residue of the formula CaEooe, where n means numbers from 4 to 30, and E means the terminal atom of fluorine, chlorine, bromine, iodine or hydrogen, while optionally present acid groups may optionally be presented in the form of salts of organic 1/or inorganic bases or amino acids or in the form of amides of amino acids. 23. Application according to claim 22, which differs in that compounds of the general formula IB are used, in which VU, B and B? independently of each other mean hydrogen or a C-S alkyl group. 24. The application according to claim 22, which differs in that compounds of the general formula IB are used, in which A means hydrogen, a C-Sialkyl residue, a SoNA-O-CH»z residue, a CzHe-O-CHz residue, a residue. CoNai-0O-(C2Na-0)-C2NA-OH, residue. SoNai-O-(SoNa-O)-SoNa- OSN", residue SoNAaOH, residue CzNeOH, residue SANeOH, residue C5NiOOH, residue SeNi2OH, residue C7/Ni0OH, residue CH(OH)CH»OOH, residue CH(IONI)CH(OH)SESON, residue CH»U|(CH (ОН))шШСН»OH, residue SNСНХОН)СН(ООН)СНоОН, / residue СНАСН(ОН)СН»ОН, residue (СН»О»СООН, residue SoNi-0О-(С2НА-О)-СНоСООН or residue SoНА -О-(СоНа-О)АСоНа-СаовЕ, where means integers from 1 to 15, и means integers from 0 to 13, и! means integers from 1 to 10, n means integers from 4 to 20, 1 E means an atom of hydrogen, fluorine, chlorine, bromine or iodine, and their branched isomers are used, if possible. 25. The application according to claim 22, which differs in that compounds of the general formula IB are used, in which A means hydrogen, Ci-Sioalkyl, SoNA-O-CH3, C3He-O-CH3, SoNa-O-(C2Na-O-SoNA -OH, / SoNi-O-(C2Na-0).-SoNA-OSNiI, SoBON, sSzHneOnH, CHnPISNONSNON, CsSNISCHOHN)CH(OH)SiOOH, (SNASOOH, SoNA-O-(SHA-0O)O-CHNOOH or SoNa4 -О-(СоНа- ОХ-СоНа-СаЕЕ, where x means integers from 0 to 5, y means integers from 1 to 10, х means integers from 1 to 10, п means integers from 4 to 15.1 E means a fluorine atom, and their branched isomers are also used, if possible. о - (СНАЗО- Vastoguvanja-3yu ns, -yane" does not differ anywhere against the general formulas, umshchievB. ovnachae" Mn sosno - СНХСООН) - 50" - В, с - Сн - МН-А СО- СН - M(СоНВ) - 80" - В.о; - СН - МН- СО -- СН - M(СоНой) - ЗО» - В, o.- СН» -МН-А СО- SNХ - M(SeNiz) - 5О» - V, - СНХ - МН-- СО --(СНХ)zo - MЩ(СНХ) - BO» - V, o -Sna -МН-СО- СН -М-СНХ - СеНв) - 5О» - V.o; - СН - МН--СО- СН» - Х-СН - СН - ОН)ВО» - В, с -Сн -МНСО-(СНе)о -8- СНоСНє - Д,о;- STМНСОСІ - О- СНІСН - р, с -Сн - СТМНСОС -О- СнеСН - В, о; - СН» - (СН - СН - 0); - (СН»)зЗМНСО- Сн -0- СС» - р, с - STМНОДСН зо -О- СНСН» - Vo; - СННСНМНОО(СНХ)zo - 0 - СНХСНХ - р, с - СНХ - СвН; -0-SNoSNH - B, o.-Sn -0 СН - С(СН -ОСНСНСН - Сея)» - СН» - ОС - В kon KD VOVK VR IV KO kon ab 1, о - Сн - СНМНСОСНИМСНв) - 5О» - D, o. - СН» - О- СН» - СНОС:оН»ои)- СН» -0-СНСН, - р, is - (СННМНСО) - СННО - ССНН - В, - (СННМНСОз - СННО - ССНН -- ВД, ос - СН» - ОСНС(СНоОН)» - СНо - О- СНСН» - r, j o o sn.-o shk ! s - СННЕМНСОСНМ(СНоН) - 5О» - V.o: - МНСО- СН - СН - В .o; - МНСО- СН -О- СННСН - В, and -МНАСО- to - MOV sn -М(СТСООН)- 805 - В.о - МН- СО-- СН» - МЩ(СоН)- 805 - В , is -MH- СО-СН - M(СзоН»и) - 5О» - В.о; - МН-- СО- СНи - M(СеНиз) - ЗО» - Б, - МН--СО-(СНе о - -M(СоН)- 80" - В,«- МН-- СО - Сн - Ш-СН - SeНв)- 80" - В, o -MH-CO- CH -M(CH" - CH" - OH)BO" - b, o. - МН- СО- СН - Fo. - СНо -0- Сен, -0- СН, -СНо - р, о -СН - Сен; -0- СН - СН - Ко - МЩЩС»оН)- ЗО» - Ко. - MOSbNv)- 5O" - To - MS oNaz) - 505 - r, o -M(SeNiz)- 50" - VD, o. - SHS2NAON) - BO" - DF, Fr. - С NoСООН) - 505 - D, Fr. - ЧО NoSeNbv) - 50" - p, o - MA ISN(SNYON)"1- 50" - V or oh - M-- |(ISNISNSONISNONUSNYON) - 80" -- p, where 5 means integers from I to 15 ,4 y means whole numbers from 1 to 6. sn 25 Date loading. si kr is different from piMnIO, they apply the formulas of the general formula Ib, in which I. means u u o -СН-СнН-МН-БО» - D,o.- СНМНСОСН, -О -СНоСН» - L,o.- СН». - СНОМНСОСН -0- No - p, o -СНе -(Сно -СнНН - 0), - (СН;)izМНнСО- Сн -0-СнНСН» - p, o.- СНМНОО(СН)о - 0 - SNСНО - В.о - СНЯСНоМНО DSН» )zo - 0 - СНХСН» - В, о -СН -0-СН»-СНОС:оН»и)- СНо -0- СНХСН - В, - СНь -О-СеНИО - СНь - СН» - В or о -СНо- Sen; -0-СНХ - СН» - В, where у means integers from | until 6 28. The application according to claim 22, which differs in that compounds of the general formula IB are used, in which B" means a linear or branched perfluorinated alkyl residue of the formula СлЕовЕ, where n means numbers from 4 to 15, and E represents a terminal fluorine atom. 29. Application according to any of claims 22-28, which differs in that the following compounds are used: -14,7-tris(carboxylatomethyl)-10-(3-aza-4-oxohexan-5-yl)-acid- M-(2,3-dihydroxypropyl)-M-(1H.IN.2H.2H.aNN,ZH,5H-Z-oxa)perfluorotridecyl)amide-1,4,7,10-tetraazacyclododecane, gadolinium complex, -14 ,7-tris(carboxylatomethyl)-10-1(3-aza-4-oxohexan-5-yl)-acid-M-(3,6,9,12,15-pentaoxahexadecyl)-(1H.1H.2H. 2Н.аН.Н,5Н,5Н-3-oxa)perfluorotridecyl |amide )-1,4,7,10-tetraazacyclododecane, gadolinium complex, -14,7-tris(carboxylatomethyl)-10-1(3-aza- 4-oxohexane-5-1l)-acid-M-5-hydroxy-3-oxapentyl)-M-(1H,1H.2H.2NaNaH,5H,ZN-3-oxa)perfluorotridecyl|amide /-1,4, 7,10-tetraazacyclododecane, gadolinium complex, -14,7-tris(carboxylatomethyl)-10-1(3-aza-4-oxohexan-5-yl)-acid-|M-3,6,9,15-tetraoxa - 12-aza-15-oxo(C17-Sovheptadecafluoro)hexacosyl |amide | -1,4,7,10-tetraazacyclododecane, gadolinium complex, -1,4,7-tris(carboxylatomethyl)-10-|(3-aza-4-oxohexane-5-1l)-acid-M-(2- methoxyethyl)-M- (НИН.2Н.2ННН,ЗН,5Н-З-oxa)perfluorotridecyl|amide)-1,4,7,10-tetraazacyclododecane, gadolinium complex. 30. Application according to any 3 claims 1-7, which is characterized by the fact that as perfluoroalkyl-containing metal complexes, compounds with sugar residues of the general formula Isshi zt (M-Ar1, ac) are used, in which H means attached through 1-OH- or The I-5H position is a mono- or oligosaccharide residue, B means a perfluorinated, straight or branched carbon chain of the formula - CoEoE, where E is a terminal atom of fluorine, chlorine, bromine, iodine or hydrogen, and n means the numbers 4-30, K means metal complex of the general formula Ps g Ssoov! che More vag iy o om x v UM M y i v'OOS M iv) -. ozone (Pe) in which B! represents a hydrogen atom or the equivalent of a metal ion with serial number 23-29, 42-46 or 58-70, provided that at least two radicals B! mean the equivalents of metal ions, B? and B independently of each other mean hydrogen, C-C7 alkyl, benzyl, phenyl, - СНоОН or -СОСН,», 1 ОС represents 7СеНа 79 СНх 75 -(СНо) and in 595 a phenylene group, -сн, - МНСО- СНх - СнСНсСООН) - SenА -В?2-,- Sen, - (ОСНСН»)o. 4 - МСНХСООН) - CHН БВ?хОо-, or optionally interrupted by one or several oxygen atoms, 1-3 - МНСО-groups, 1-3 - СОМН-groups and/or substituted 1-3 -"СНо)о5" СООН-groups Si-Sigalkylenov or С7-С12-СеНы-О-group, while 9 means the place of attachment to -СО-, or the general formula Shs and СОов! s What a dream about ZM M r M ХХ play С щ С Сов! , (Sho), in which VE! has the above values, ВЕ means hydrogen or the metal ion equivalent indicated for B., and I means 76Na 7О-СН-о where в means the place of attachment to -СО-, or the general formula ИМс лосо че шк вд: / ЯКЖА-- -Я M M Y Vpsos and SHI M -. osov (IMs) in which V/i VE? have the values indicated above, or the general formula UsA or UsV M ЖКЖбом ЧИ m sov! ra M in F0)o; M -«-bo0ov r And sooo! Mo and Moosov! KA -M we-b m boov! р 1 in which B has the above values, or of the general formula MIs poos-- / у ц ЮЯМ-бОм М '0s - M ' in which B has the above values, or of the general formula У Ps iv) В'ООС А M в 'e0S -- Shk V'OOS M post (UP) in which KE! has the above values, and IL -6Н, -0-сн, -- Ф : means where 9 means the place of joining to -СО-, or the general formula MShes and soov! that ЮУКЖЖ- M M M OO she M on Son! (Sho) in which B has the values indicated above, while the free acid groups optionally present in the K residue may optionally be represented in the form of salts of organic and/or inorganic bases or amino acids or in the form of amino acid amides, (E) in therefore, if K means metal complexes of the formulas Ce-MOPCs, represents at least a three-fold functionalized residue selected from the following residues (a)-(1): (a) . o she - «sno, -59 - 560--my7U MN B 5 (B) N ui-so -6-(sn tvyi o 5 (s) ! M M shk - (d V Y what o M- - M M --yami y - V z (is) 7 Y so seams (0 mmN-s -sn-- (SNU); MN Um o and other sh ! mmn -А-С -- сн--(СН.) МН Ум с чн In with (in) В И" and -с0--сн--(СНА;--МНАМ in m-с0-- СН (Сн; МН о Г in Мн-со--сн--(сно)/ МН m r МН В 5 ( n) sn s M-s60 that - (sn M-ii o me - 2)4 be! Ф , Ф ях У--МН-АСНА-СО--m u r 1 С in the case that K means a metal complex of the formula MShes, is at least a three-fold functionalized residue selected from residues (I) 1 (1): ( 0ю В m-смн-(сн; novo about T 7 5 (0) about m-bosn, сН-СНУ bo m in ТВ 5 while x means the place of attachment of C to complex K, 7 means the place of attachment of C to of residue Y, and 7 means the place of attachment of C to residue 7, U means (СТ) есО-в-сі -снОонН- СО- or 5- СНСНОН- СНОН) - СНОН- СНОН- СО- Б, where 5 means the place of attachment to the sugar residue КВ. and 7 means the place of attachment to the residue b, 7 means the group y-M M-50; 5 у-СОСНУ-МозНь)- 80» -e, у-сОост -0-(СНХ»)» - 5О5 -е, iv) iv) Zh х ув о007--к M. 80578 ! or у-МНССНЙ -О- СНоСНЙ - is, where 7 means the place of joining 7; to the CO residue, and is means the place of joining / to the perfluorinated residue B", I, t! independently of each other mean integers 1 or 2, 1p' means integers, numbers from 1 to 4. 31. Application according to claim 30, which differs in that compounds of the general formula I are used, in which K means a monosaccharide residue with 5-6 C atoms or its deoxy compound, preferably glucose, mannose or galactose. 32. Application according to claim 30, which differs in that it uses compounds of the general formula I, in which В and ВЕ? independently of each other mean hydrogen or C-Slalkyl and/or E in the formula -CoEopE; means a fluorine atom. 33. Application according to claim 30, which differs in that compounds of the general formula I are used, in which C represents a lysine residue (a) or (b). 34. The application according to claim 30, which differs in that compounds of the general formula I are used, in which 7 means the group y-mM M-50.5 where 7 means the place of attachment of 7 to the residue 0, and is means the place of attachment of 7 ; to the perfluorinated residue B, and/or Y means the group 5-CHCO-B where 6 means the place of attachment to the sugar residue B, and P means the place of attachment to the residue b. 35. The application according to claim 30, which differs in that compounds of the general formula I are used, in which M in the metal complex K means -СНо- or -Сб56Н4-О0- СН» - о, which denotes the place of joining to -СО-. 36. Application according to claim 30, which differs in that the gadolinium complex |1-(4-perfluorooctylsulfonyl)piperazine|amide 6-M-(1,4,7-tris(carboxylatomethyl)-1,4,7,10- tetraazacyclododecane-10-M-(pentanoyl-3-aza-4-oxo-5-methyl-5-1l)|-2-M-(1-0-e-0-carbonylmethylmannopyranose|-I-lysine). 37. Application according to any 3 claims 1-7, which differs in that as perfluoroalkyl-containing metal complexes compounds with polar residues of the general formula Id also Y TA (Роreg ад in which B" means a perfluorinated, straight or branched carbon chain of the formula - CoEE, where E represents the terminal atom of fluorine, chlorine, bromine, iodine or hydrogen, and n means numbers 4-30, K means a metal complex of the general formula ЦЯ и соов! (t In g her IF) koi, YM and zu os Chi What about M in which B! means a hydrogen atom or the equivalent of a metal ion with serial number 23-29, 42-46 or 58-70, provided that at least two radicals of B! mean equivalents of metal ions, B? and B independently of each other mean hydrogen, C-C7 alkyl, benzyl, phenyl, - СНоОН or -СОСН,», 1 -СвНу -О енфчаве-,-(СН); 5 -о-, phenylene group pu - CH» - МНСО- СН - СНСНСНОН) - SeНу - о-, -СвН, - (ОСННСН)д. 1 - MSНОСОН) - СН» - в - or optionally interrupted by one or several oxygen atoms, 1 -3 - МНСО-groups, 1-3 - СОМН-groups and/or substituted 1-3 -"СНо)о5"СООН-groups of Si-Sigalkylene or C7-С12-SeNy-O-group, where 2? means the place of attachment to -СО-, or the general formula ШО и соов! С Ше соОпт о /-k dra Ah В'оОС С щ и SOов! , (Ш a) in which BE has the above values, BE means hydrogen or the metal ion equivalent indicated for B., and IL means "Sen. -O- SN" oh where? means the place of joining to -СО-, or the general formula IM y y Soov cho ШЭ wag K- -lM te v'sos S What about M .osov Ua in which V/i VE? have the values specified above, or the general formula of UdDA or UaV M KZh-bom CHI M osoov' M r pOos M -«Zh-bo0ov ko A -soov! -M o s soosov! KA -M we-b m boov! "-soov! (av) in which KE! has the above values or the general formula MY poOos- / x MU M Vie0S--- m ! in which KE! has the values indicated above, or the general formula UtsaYA IF) V'OS--, M vieoS --- three Vo, M post (UP) in which VE! has the above values, and (L means 76х470-СН Со where Ф means the place of attachment to -СО-, while the free acid groups optionally present in the residue К can optionally be represented in the form of salts of organic and/or inorganic bases or amino acids or in the form of amides of amino acids, C means at least a three-fold functionalized residue selected from the following residues (a)-(1): (a) in « M (CH; -6 -60-m in ІТ В 5 (B) H in the bridge In Her (oh (c) o scho r m-YAOM M -A-- khy uy A Sho 2 (a) r so MA - -I1M M muy i sh B 2 (e) y (F;6) r She M o ( n n o y -(sn;), on -s60 Shchi (sn,), ЧУ r МН 1 7 V , (c) Mn o, u r , (c) 7-60 without on -60--m In her o 2 0) in; -Oo emus on -0-mo iy o where x means the place of attachment of C to complex K, B means the place of attachment of C to the residue B. and 7 means the place of attachment of C to the residue 7, 7, means the group у-МХ M -50, 5 ko уУ-Фб(О)СНОо(СНХ)" in where 7 means the place of attachment 7 ; to the ОС residue, and 5 means the attachment site of 7, to the perfluorinated residue Б", БЕ is a polar residue selected from complexes К of the general formulas Pa-UpPa, and in this case K means a hydrogen atom or the equivalent of a metal ion with serial number 20, 23-29, 42-46 or 58-70, and the residues B", KU, B", 0 and TL have the above values, or is a folic acid residue or attached through -СО-, 5025- or a direct bond to the residue (C carbon chain with 2-30 C-atoms, which is straight or branched, saturated or unsaturated and which is optionally interrupted by 1-10 oxygen atoms, 1-5 --UNCO-groups, 1-5 -СОМН- groups, 1-2 sulfur atoms, 1-5 -MH groups or 1-2 phenylene groups, which may optionally be replaced by 1-2 OH groups, 1-2 МНОо groups, 1-2 -СООН groups or 1-2 -5О3Н-groups, or optionally substituted with 1-8 OH- groups, 1-5 -СООН-groups, 1-2 5ОзН-groups, 1-5 МНо-groups, 1-5 Si-Slalkoxy groups, i, t, p" independently of each other mean integers 1 or 2. 38. Application according to claim 37, which differs in that compounds of the general formula Id are used, in which K means a metal complex of the general formula PO, Sha, Uav or UPa. 39. The application according to claim 37, which differs in that compounds of the general formula Id are used, in which the polar residue K has the values indicated for the complex K, preferably means the complex K of the general formula Pa, Sha, МЯА or УП. 40. Application according to claim 37, which differs in that compounds of the general formula Id are used, in which the polar residue K has the following values: . -(m-СООН)», -С(О)СНо»О-SeNai-l-5ОЗН, -СсООСТМНСоОсНтМнеоОхснНостсСОон, -КО)СНОСТСНОСТсСООН, -«0ustOosTSsNn(OnНСНn:IO-STСНооН, -«О)СОСТСН(ОНСТОСНо- - СН(ОН)-СОН, -(О)СНоБОЗН, -СОХСТСТСООН, -ЯЧО)СН(ОН)СН(ОН)СНОН-С(О)СНОО | (СНо)20115-СНиАС(О)СН»ОЙ (СНО | 9-Н, -ФКО)СТОСН(СТОН)», -Ч(0)СТОСН(ИСН»ООСТСООН)», -С(О)-СеНз- - cm-0ОСТСООН)», -СО-СН:О-«СНОХ О(СНИ2БОо--(СНО о О(СНО2ОСН,»), mainly -СХОХХСН»О КГ (СН»)2О|-СН. 41. Application according to claim 37, which differs in that compounds of the general formula Id are used, in which the polar residue K. is a residue of folic acid. 42. Application according to claim 37, which differs in that compounds of the general formula Id are used, in which C is a lysine residue (a) or (B). 43. The application according to claim 37, which differs in that compounds of the general formula Id are used, in which |) in the metal complex K represents the group -СНо- or -С6Н.-О- СН - о, where ? means the place of attachment to -СО-. 44. Application according to any of claims 37-43, which is characterized by the fact that the gadolinium complex |1-(4-perfluorooctylsulfonylpiperazine|amide /2,6-M,M'-bis(1,4,7-tris) is used carboxylatomethyl)-1,4,7,10-tetraazacyclododecane-10-(pentanoyl-3-aza-4-oxo-5-methyl-5-yl)|lysine. 45. Application according to any of claims 1-7, which differs in that as perfluoroalkyl-containing metal complexes galena compositions are used, which contain paramagnetic perfluoroalkyl-containing metal complexes of the general formulas I, Ia, IB, Is 1/or Id 1 diamagnetic perfluoroalkyl-containing substances, preferably in the form of a solution in an aqueous solvent. 46. Application according to claim 45, which differs in that how are diamagnetic perfluoroalkyl-containing substances of the general formula ХХ ВЕИ2-В used? (XX) in which B means a linear or branched perfluoroalkyl residue with 4-30 carbon atoms, and? means a linker and B" means a hydrophilic group. 47. Application according to claim 46, which is characterized by the fact that the linker "I" is a direct bond, a -5O2 group or a straight or branched carbon chain containing up to 20 carbon atoms and which can be replaced by one or more -OH groups , -СОО-, -503 and/or optionally contains one or more -О-, -5-, -СО-, -СОМН-, -МНСОО-, -СОМЕ--, - МЕСО-, -505-, -РОз-, -МН-, -ME-groups, an aryl ring or piperazine, while ВЕ" means a C-Alalkyl residue, which in turn may contain one or more O-atoms 1/or may be substituted by -СОО- or 5Oz-groups. 48. Application according to claim 46, which differs in that the hydrophilic group B" is a mono- or disaccharide, one or more adjacent -СОО- or -5О3-groups, dicarboxylic acid, isophthalic acid, picolinic acid, benzenesulfonic acid, tetrahydropyrandicarboxylic acid . , while the polyethylene glycol links end with the -ОН or -ОСН group." 49. Application according to claim 45, which differs in that, as diamagnetic perfluoroalkyl-containing substances, conjugates of P or y - (ichlodextrin and compounds of the general formula XX A?RIA-VI, (XXI) in which A" means a molecule of adamantane, biphenyl are used or anthracene, I means a linker, and B means a linear or branched perfluoroalkyl residue with 4-30 carbon atoms, while the I7 linker is a straight hydrocarbon chain with 1-20 carbon atoms, which can be interrupted by one or more oxygen atoms, one or several CO-, 505-, SOMN-, MNSO-, SOME"-, MK CO-, MH-, MW O-groups or piperazine, while VZ is a C-C alkyl residue. 50. Application according to claim 45, which differs in that as diamagnetic perfluoroalkyl-containing substances such general formula XXI VAH! (XXI) in which B means a linear or branched perfluoroalkyl residue with 4-30 carbon atoms, and X! means a residue selected from the group of the following residues (while n means a number from 1 to 10): on on no o eto ; ot dit iv) ; he (and he nn no IF) rek Kene i pa o 2 he no o eto, NM t d-vy Pi o 2 he ON no |v) no om a Ge) IF) pa i Zv do on H no (in M sh sho flisu it no o on on no (o no child o - ---- Y TI on o on Hu no (v) m? no t h mor o o on on o fo dity tt N o o no |v) inf) oto he he in po no OH (St) o 2 B vv vyu. c) 6) ry Ya zo-Yar- en o 2 s 85--kh I 79 on c) ----v--M I o o ho, on c) in voi ---85--kКХМ І M -с600 c) Со: о т Sagsha и и и соо Со: что 50 я Z priya no on on rim ОН no no on СО: vyv Ge) (0:00 СО: 9:00 a.m. Sat