Imidazole derivatives having inhibitory activity against farnesyltransferase, the retrieval method, intermediate compounds, pharmaceutical composition

 

(57) Abstract:

The invention relates to new imidazole derivative of General formula (1), where n1is an integer from 1 to 3, a represents hydrogen, linear or branched C1-C10-alkyl, which may be optionally substituted C3-C7-cycloalkyl or lower alkoxy, or a radical selected from the group shown in the formula of the invention, Y represents a radical selected from the group described in the claims, or to his new pharmaceutically acceptable salts. The compounds possess inhibitory activity against farnesyltransferase. Also disclosed is a method of obtaining these compounds, intermediate compounds and pharmaceutical composition on the basis of new derivatives of imidazole. The invention can be used in medicine for the prevention and treatment of cancer. 5 C. and 7 C.p. f-crystals, 7 PL.

The technical field

The present invention relates to new imidazole derivative represented by the following formula (1), which has inhibitory activity against farnesyltransferase

< / BR>
where A, n1and Y are defined as indicated below,

or its farmace the treatment of compounds of formula (1), to intermediate products, which are used for obtaining the compounds of formula (1), as well as to pharmaceutical compositions comprising a compound of formula (1) as an active ingredient.

Prior art

Ras mammalian proteins act as molecular switches in the processes of transmission of a signal associated with cell growth and differentiation. Protooncogene the ras family consists of three members of the family, N-, K - and H-ras, which represent 4 types largely homologous proteins; namely, N-, N-ras proteins, including 189 residues, and two isomorphic K-ras 4A and K-Ras 4A protein, consisting of 188 and 189 residues, respectively. The chemical aspect of the switching mechanism associated with cyclic transitions between protein inactive ("off") limit state guanozintrifosfata (GDP) and active ("on") the limiting state for GTP-independent (GTP) (Bourne, H. R.; Sanders, D. A.; McCormick, F.; Nature, 1991, 349, 117). Biochemical and structural studies have shown that point mutations 12, 13 and 61 residues located adjacent to the phosphoryl plot GTP, leading to reduced activity of the GTP-independent, which is associated with the development of many types of cancer in humans, in particular cancer PAGEL is synthesized as a cytoplasmic precursor, which after a series of posttranslational modifications of completely localized on the cytoplasmic side of the plasma membrane (Gibbs, L. B., Cell, 1991, 65, 1). As a result of this series of biochemical modifications due to changes in electric charge or spatial patterns that increase the hydrophobicity of the molecules, facilitated the accession of the Ras protein to the cell membrane. The first and necessary stage of this series is to attach varnishlog fragment to the cysteine residue of the C-terminal SAH motif (C, cysteine; A, usually aliphatic residue; X, any amino acid) in the reaction catalyzed by farnesyltransferase (FTase). This modification is essential for Ras function, as evidenced by the inability of Ras mutants that have lost the ability farnesiana C-terminal cysteine, be localized in the plasma and to transform mammalian cells in culture (Hancock, J. R. ; Magee, A. I.; Childs, J. E.; Marshall, C. J., Cell, 1989, 57, 1167). Subsequent post-translational modification, cleavage AAH residues, methylation of carboxyl fertilising cysteine and the introduction of Palmitoyl in cvetinovic fragments located in the upstream position relative to SAH motif in the N - and K-Ras proteins, not the two who-ras 4B, different from the H - and N-ras, contains instead of cysteine required for the introduction of Palmitoyl, numerous enriched lysine sites, called poliennali domain that facilitates binding fertilising ras protein with anionic lipid layer of cell membrane. Thus, assume that the inhibitors transferase FTase, which catalyzes the necessary modification, are anticancer drugs in the case of tumors, due to the transformation associated with the Ras oncogenes (Buses J. E. et al., Chemistry & Biology, 1995, 2, 787). A number of recently identified inhibitors transferase FTase has a strong and specific ability to block Ras-farnesiana, signal transmission and transformation in transformed cells and lines of tumor cells both in vitro and in animal models (Kohl, N. E. et al., Proc.Natl. Acad.Sci. USA, 1994, 91, 9141; Kohl, N. E. et al., Nature Medicine, 1995, 1, 792).

However, most of the inhibitors belong to SHAH-motif to mimic Ras substrate and which peptide in nature or contain sulfhydryl group (U.S. patent 5141851; Kohl, N. E. et al., Science, 1993, 260, 1934; application PCT/US95/12224, Graham et al., Sebti, S. M. et al., J. Biol. Chem. , 1995, 270, 26802; James, G. L. et al., Science, 1993, 260, 1937; Bishop, W. R. et al., J. Biol.Chem., 1995, 270, 30611). Recently ase (Poulter, C. D. et al., J. Am.Chem. Soc., 1996, 118, 8761). Chemical basis of molecular design of inhibitors associated with the reaction mechanism. Namely, the migration of the phenyl group by the enzyme is an electrophilic substitution and reaction transition state required charge (+).

However, these previously described inhibitors have limited activity and selectivity against oncogenic actions of Ras proteins, particularly protein K-ras 4B, which, as it was discovered, is the most typical cancer in humans. Thus, new inhibitors with the ability to effectively inhibit the activity of K-ras.

With regard to restenosis and proliferative vascular diseases, it is shown that the inhibition of cellular ras prevents the proliferation of smooth muscle in vivo after vascular damage (Indolfi C. et al., Nature Med., 1995 1(6), 541-545). This message definitely confirms the role of inhibitors farnesyltransferase in these diseases, demonstrating the inhibition of the accumulation and proliferation of vascular smooth muscle.

The invention

The present invention is the result of the research on the development of compounds having the structure of the matrix is found, what imidazole derivatives, which are the subject of the present invention, can strongly inhibit the activity of the enzyme.

Thus, the purpose of the present invention is to provide imidazole derivatives of the formula (1), which inhibit the activity of FTase, the method of obtaining such derivatives and intermediate compounds that can be effectively used to obtain the compounds of formula (1).

Another objective of the present invention is to provide a pharmaceutical composition comprising a compound of formula (1) as an active ingredient.

The best way of carrying out the invention

The first aim of the present invention are imidazole derivatives of the formula (1), which inhibit the activity farnesyltransferase

[Formula 1]

< / BR>
where n1is an integer from 1 to 4

And represents hydrogen; a linear or branched C1-C10-alkyl, which may be optionally substituted C3-C7-cycloalkyl or lower alkoxy; or a radical selected from the following group:

< / BR>
< / BR>
< / BR>
where R1and R1' independently of one another represent sober, benzyloxy, or lower alkyl which may be optionally substituted C3-C6-cycloalkyl,

R2represents hydrogen or lower alkyl or is a group-E-F where E denotes-CH2-, -C(O)- or-S(O)2and F represents hydrogen, lower alkyl which may be optionally substituted, phenoxy or biphenyl; lower alkoxy which may be optionally substituted by aryl; phenyl; benzyl; benzyloxy; or amino which may be optionally substituted lower alkyl, benzyl or5-C6-cycloalkyl,

R3represents hydrogen, lower alkyl or phenyl,

R4 represents a radical selected from the following group:

< / BR>
< / BR>
< / BR>
where n2and n3independently denote 0, 1, 2, 3, or 4

R5and R9independently represent hydrogen, lower alkyl, lower alkoxy, phenoxy, phenyl, hydroxy or halogen,

R6and R8independently represent hydrogen, lower alkyl, lower alkoxy, phenoxy, phenyl, piano, hydroxy or halogen,

R7represents hydrogen; lower alkyl which may be optionally substituted C3-C6cycloalkyl; lower alkoxy; hydrox the t are hydrogen, lower alkyl or lower alkoxy,

Y represents a radical selected from the following group:

< / BR>
< / BR>
< / BR>
where X represents O or S,

Represents a hydrogen or lower alkyl which may be optionally substituted hydroxy, mercapto, lower alkoxy, lower alkylthio or aryl,

With represents hydrogen or lower alkyl which may be substituted by aryl; or represents a radical selected from the following group:

< / BR>
< / BR>
< / BR>
< / BR>
< / BR>
< / BR>
where R11and R12independently represent hydrogen, lower alkyl, lower alkoxy, halogen, cyano, hydroxycarbonyl, aminocarbonyl, aminothiazolyl, hydroxy, phenyl or phenoxy,

R13and R14independently represent hydrogen, lower alkyl, aryl or a group

< / BR>
where X is defined as above, n4is an integer from 2 to 4, and R15represents lower alkyl,

D represents an amino acid residue or a residue of the lower Olkiluoto ether amino acids; or represents a radical selected from the following group:

< / BR>
< / BR>
< / BR>
< / BR>
< / BR>
< / BR>
< / BR>
where R10defined in this way, as mentioned above,
20or N-R20(where R20represents hydrogen, lower alkyl or hydroxy),

n5means an integer from 1 to 3,

R16and R17independently represent hydrogen; aryl; lower alkyl which may be optionally substituted by aryl or Canarian, or group

< / BR>
where n4, Q, R10defined as above,

R18and R19independently represent hydrogen; halogen; hydroxy; cyano; lower alkyl, lower alkoxy, alkoxyalkyl, alkylthio; hydroxycarbonyl; aminocarbonyl; aminothiophenol; alkylsulfonyl; alkylthiols; alkylthiols; aryl; or hydroxy, thio, sulfonyl or lower alkyl, substituted aryl,

G is a radical selected from the following group:

< / BR>
< / BR>
where R11and R12defined as above,

I represents a lower alkoxy or a radical selected from the following group:

< / BR>
where R16, R17and Z are defined as above, L represents a radical selected from the following group:

< / BR>
where Z and Q are defined as above, provided that

(1) the value of n2is other than 0, when R3represents hydrogen, and

In particular, the connection which is the subject of the present invention, has a structure quite different from the structures of known inhibitors farnesyltransferase and, in addition, never contains tially fragment.

When the definition of the substituents of the compounds of formula (1), the term "lower alkyl" means a linear or branched alkyl containing from 1 to 4 carbon atoms, including methyl, ethyl, isopropyl, isobutyl and tert-butyl.

Since the compound of the formula (1), which is the subject of the present invention, depending on the nature of the substituents can contain asymmetric carbon atom, it may be in the form of the R or S isomer, racemate, or a mixture thereof. Thus, this connection also includes all of these stereoisomers and mixtures thereof.

In addition, the compound of formula (1), which is the subject of the present invention may form pharmaceutically acceptable salts. Such salts include non-toxic salts of the addition products of acids containing pharmaceutically acceptable anion, for example inorganic salts such as chloromethane acid, sulfuric acid, nitric acid, phosphoric acid, bromoadenosine acid, citric acid, acetic acid, trichloroacetic acid, triperoxonane acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, aspartic acid, etc., salts of sulfonic acids, such as methanesulfonate acid, benzolsulfonat acid, p-toluensulfonate, naphthalenesulfonate and so on; salt - addition products of base, for example a salt of pyridine or ammonia; and salts with metals such as the alkali metal salt or a salt of alkaline-earth metal, such as lithium salt. In addition, the present invention includes a solvate of the compound of formula (1), such as alcoholate or hydrates. They can be obtained by conventional methods of carrying out the reaction.

Among the compounds of formula (1), which is the subject of the present invention, preferred compounds include compounds in which:

n1is an integer from 1 to 3,

And represents hydrogen; a linear or branched C1-C10-alkyl, which may be optionally substituted C3-C7-cycloalkyl or lower alkoxy; or a radical selected from the following group:

< / BR>
< / BR>
< / BR>
where R1and R1' staticerror, lower alkoxy, phenoxy, phenyl, benzyloxy or lower alkyl which may be optionally substituted C3-C6-cycloalkyl,

R2represents hydrogen or lower alkyl, or represents-E-F where E represents-CH2-, -C(O)- or-S(O)2-, and F represents hydrogen; lower alkyl which may be optionally substituted, phenoxy or biphenyl; lower alkoxy which may be optionally substituted by aryl; phenyl; benzyl; benzyloxy; or amino which may be optionally substituted lower alkyl, benzyl or5-C6-cycloalkyl,

R3represents hydrogen or lower alkyl,

R4represents a radical selected from the following group:

< / BR>
< / BR>
< / BR>
where n2and n3independently of one another denote 0, 1, 2, 3, or 4

R5, R6, R8and R9independently from each other represent hydrogen, lower alkyl, lower alkoxy, hydroxy or halogen,

R7represents hydrogen; lower alkyl which may be optionally substituted C3-C6-cycloalkyl; lower alkoxy; hydroxy; C3-C6-cycloalkyl; or halogen,

R10the submitted the
< / BR>
< / BR>
where X represents O or S,

Represents a hydrogen or lower alkyl which may be optionally substituted lower alkoxy or aryl,

With represents hydrogen or lower alkyl which may be optionally substituted by aryl, or represents a radical selected from the following group:

< / BR>
< / BR>
< / BR>
< / BR>
< / BR>
< / BR>
where R11and R12independently represent hydrogen, lower alkyl, lower alkoxy, halogen, cyano, aminocarbonyl, phenyl or phenoxy,

R13and R14independently represent hydrogen, lower alkyl, aryl or a group

< / BR>
where X is defined as above, n4equal to 2 and R15represents lower alkyl,

D represents an amino acid residue or lower alkilany ether amino acid residue; or represents a radical selected from the following group:

< / BR>
< / BR>
< / BR>
< / BR>
< / BR>
< / BR>
< / BR>
where R10defined as above,

Q represents O, S, S=O or SO2,

Z represents O, S, S=O, SO2or C=O, or represents CH-R20or N-R20(where R20represents hydrogen, lower alkyl or hydroxy),

n5; the Rila; lower alkyl which may be optionally substituted by aryl or Canarian, or

< / BR>
where n4, Q and R10defined as above,

R18and R19independently represent hydrogen; halogen; hydroxy; cyano; lower alkyl, lower alkoxy, alkoxyalkyl, alkylthio; hydroxycarbonyl; aminocarbonyl; aminothiophenol; alkylsulfonyl; alkylthiols; alkylthiols; aryl; or hydroxy, thio, sulfonyl or lower alkyl, substituted aryl,

G is a radical selected from the following group:

< / BR>
< / BR>
where R11and R12defined as above,

I represents a lower alkoxy or a radical selected from the following group:

< / BR>
where R16, R17and Z are defined as above,

L represents a radical selected from the following group:

< / BR>
where Z and Q are defined as above, provided that

(1) the value of n2different from 0, when R3represents hydrogen; and

(2) Y is other than

< / BR>
when But a

< / BR>
The most preferred such compounds in which Y is represented by formula

< / BR>
and represented by the formula

< / BR>
ugogo the aim of the present invention is a method for imidazole derivative of the above formula (1).

According to the present invention imidazole derivative of formula (1) can be obtained by a method characterized in that:

(a) compound represented by the formula (2), interacts in the environment of a solvent in the presence of a base with a compound represented by the formula (3), then trailing group in the thus obtained product is removed in the presence of triperoxonane acid (TFA) to obtain the compound represented by formula (1A) (see reaction scheme 1 in the end of the description); or

(b) compound represented by the formula (4), interacts in the environment of a solvent in the presence of a base with a compound represented by the formula (3), to obtain compounds represented by a formula (1b) ) (see reaction scheme 2 below); or

(c) compound represented by the formula (5), interacts in the environment of a solvent in the presence of a base with a compound represented by the formula (3), trityloxy group in the thus obtained product is removed in the presence of triperoxonane acid to obtain compounds represented by a formula (6) and then carry out a hydrogenation reaction to obtain a compound represented by the formula (1C) (see reaction scheme 3 in the end of the description); or

(d) the connection is), which then reacts with the compound represented by the formula (9), in the presence of a combining agent to obtain compounds represented by formula (1d) (see reaction scheme 4 below); or

(e) a carbonyl group in the compound represented by the formula (1E), turns into a thiocarbonyl group in the presence of sulfureuse agent to obtain the compound represented by the formula (1f) (see reaction scheme 5 below); or

(f) a compound represented by formula (1g), interacts in the environment of the solvent with a compound represented by the formula (10), with compounds represented by formula (1h) (see reaction scheme 6 below); or

(g) a compound represented by the formula (11), cyclized in an inert solvent with the formation of compounds represented by formula (1i) (see reaction scheme 7 in the end of the description); or

(h) an amide group in the compound represented by the formula (11), in turn thioamide group in a compound represented by the formula (12), which then cyclist in an inert solvent to obtain the compound represented by the formula (1j) (see reaction scheme 8 at the end of the description); or

(i) a compound represented by the formula the formula (lj) (see the reaction scheme 9 at the end of the description); or

(j) a compound represented by the formula (13), interacts in the environment of the solvent with a compound represented by the formula (I) to obtain the compound represented by the formula (1k) (see reaction scheme 10 at the end of the description); or

(k) a compound represented by the formula (1l), hydrolized in the presence of a base, and thus obtained product interacts in the environment of a solvent in the presence of combining the agent with a compound represented by the formula (15), with the formation of compounds represented (1m) (see reaction scheme 11 in the end of the description); or

(l) a compound represented by the formula (16), interacts in the environment of a solvent in the presence of a base with a compound represented by the formula (17), with the formation of compounds represented by formula (1n) (see reaction scheme 12 in the end of the description); or

(m) compound represented by the formula (18), interacts in the environment of a solvent in the presence of a base with a compound represented by the formula (17), and after removing the protective group to obtain the compound represented by formula (1B), which then combine with the compound represented by the formula (19), with the formation of compounds represented by formula (1P) (who, and F are defined as above,

I' represents a lower alkoxygroup,

I is identical to I, except that in the list of values I" is not the lowest alkoxygroup,

T represents a hydroxy or tsepliaeva the reaction of (a leaving group, preferably halogen,

Tg is trityl,

Cbz is benzyloxycarbonyl and has this value throughout this description.

In addition, the compounds that are the subject of the present invention can be easily obtained by any means, representing a combination of different synthetic methods known from the prior art, and such a combined technique can be easily implemented by specialist secondary qualifications in this area. Methods (a)-(m) will be explained in more detail below.

In the methods (a)-(e) to obtain compounds that are the subject of the present invention may be used any inert solvents which do not adversely impact on the course of the reaction, preferably one or more solvents selected from the group comprising dimethylformamide, dimethylacetamide, ethanol, water, dichlorethane, chloroform, tetragenic from the group including sodium hydride, potassium hydroxide, potassium carbonate, tert-piperonyl potassium, sodium amide, bis(trimethylsilyl)amide and sodium bis (trimethylsilyl)amide and potassium, more preferably sodium hydride or potassium hydroxide. As a combining agent used in the interaction of the compounds of formula (8) with the compound of the formula (9), can be used a mixture of 1-hydroxybenzotriazole (NOVT) with one or more substances selected from the group comprising carbodiimide, such as dicyclohexylcarbodiimide (DCC), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), 1,11-dicarbonitriles (CDI) and others, as well as inorganic dehydrating agents such as silicon tetrachloride. Among these the most preferred mixture of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and hydrate of 1-hydroxybenzotriazole.

As sulfurous agent to obtain compounds of formula (1f) of the compounds of formula (1E) can be used 2,4-bis(phenylthio)-1,3-dithia-2,4-diphosphate-2,4-disulfid, the reagent Laussane (Lawesson) and R4S10. It is most preferable to use 2,4-bis(phenylthio)-1,3-dithia-2,4-diphosphate-2,4-disulfide.

The compound of formula (1g), which is used as ohodnocovanie protective benzyloxycarbonyloxy group in position 1 piperidinol balance. The reaction of removing the protective group can be performed under standard conditions, preferably using Pd(OH)2/C or Pd/C in an alcohol solvent in a hydrogen atmosphere. Thus obtained compound of the formula (1g) is combined with the compound of the formula (10) in the inert solvent may, as indicated above, optionally in the presence of a tertiary amine as a base to form compounds of formula (1h). Alternatively, the compound of formula (1g) can interact in the presence of a combining agent, as indicated in the description of method (d), with a derivative of carboxylic acid (T=OH) with the formation of the compounds of formula (1h) in the form of an amide.

When carrying out reactions of cyclization (g) and (h) to obtain the compound (1i) and (1j) can be used any inert solvents, preferably one or more selected from the group comprising tetrahydrofuran and ethanol. As sulfurous agent used for the conversion of the amide group in thioamino in the way (h), can be used 2, 4-bis(phenylthio)-1,3-dithia-2, 4-diphosphate-2, 4-disulfide, reagent Laussane and R4S10the most preferred reagent Laussane.

In the implementation methods (i) 14b) you can use one or more solvents, selected ethanol and isopropyl alcohol. In the process (k) according to which the compound of the formula (11) is subjected to hydrolysis and then the interaction with the compound of the formula (15) with the formation of the compounds of formula (1m), can also be used a conventional Foundation, such as, for example, one or more bases selected from the group comprising lithium hydroxide, sodium hydroxide and potassium hydroxide, preferably lithium hydroxide. As a combining agent you can use the agents specified in the description of the method (d).

When implementing methods (l) and (m) may be used any inert solvents, preferably one or more selected from dimethylformamide and dimethylacetamide, and the base can be used one or more compounds selected from the group including sodium hydride, sodium amide, bis(trimethylsilyl)amide and sodium bis(trimethylsilyl)amide and potassium. In the implementation of method (m) the reaction of removing the protective group can be carried out in a standard reaction conditions for the removal of the protective group, preferably in the presence of Pd(OH)2/C or Pd/C in an atmosphere of hydrogen. Further, the combining agent, ispolzuy the same combining agent, as in method (d).

The compound of the formula (3) used as a key intermediate in the implementation of the methods (a)-(C) to obtain the compounds of formula (1) according to the present invention, is itself a new connection. Thus, one of the purposes of the present invention is a compound of the formula (3). As shown in the schemes of reactions 14-16 (see end of description), the compound of formula (3) can be obtained using the method, characterized in that the compound represented by the formula (20), interacts in the environment of a solvent in the presence of combining the agent with a compound represented by the formula (21); a compound of formula (20) interacts in the environment of a solvent in the presence of dimethylformamide (DMF) with thionyl chloride with the formation of compounds represented by formula (20A), and then the thus obtained compound (20A) interacts in the environment of the solvent with the compound of the formula (21); or the compound represented by formula (3A), is oxidized in the environment of the solvent with the formation of compounds represented by formula (3b).

In the schemes of reactions 14, 15 and 16, C and D are defined as above,

Qarepresents S or S=O.

In predstavlenie used any inert solvents, preferably one or more selected from the group comprising dimethylformamide, dimethylacetamide, dichloromethane, tetrahydrofuran and 1,2-dichloroethane. As a blending agent in accordance with reaction scheme 14 can be used a mixture of 1-hydroxybenzotriazole with one or more substances selected from the group comprising carbodiimide, such as dicyclohexylcarbodiimide (DCC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and the other From among these the most preferred mixture of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and hydrate of 1-hydroxybenzotriazole. In sposobu accordance with reaction scheme 15 dimethylformamide is used in catalytic quantities. As oxidant in sposobu accordance with reaction scheme 16 preferably using an excess of metallocarboranes acid. In addition, combining agent, oxidant, solvent, catalyst, etc. may be appropriately selected from among other than the above compounds, if this will be necessary reaction. Reaction conditions, including the number of reagents, reaction temperature, reaction time, etc. can be easily selected by a person skilled in the art depending on the specific promezhutochnogo product to obtain the compounds of formula (1d) according to the method (d), also is a new compound similar to the compound of formula (3), another

the aim of the present invention is an intermediate compound of formula (8). It can be obtained by hydrolysis of compounds of formula (7).

On the other hand, the source compounds used according to the above methods, can be obtained in accordance with the methods described in reaction schemes 17-29 (see the end of the description).

First, the compound of the formula (2) can be obtained by introducing protective groups and halogenation, as shown in reaction scheme 17 (see the end of the description).

The compound of the formula (4) in which a represents a 4-cyanobenzyl, can be synthesized by introducing a protective group, acetylation, combinations, removing the protective group and halogenation, as shown in reaction scheme 18 (see end of description). More often, the compound of formula (4) obtained by method, according to which the connection to the amino group interacts with dihydroxyacetone with the formation of mercapto-imidazole derivative, which is then desulfurized and halogenous, as shown in reaction scheme 19 (see end of description). Detail conditions for such reactions) is my reaction 19, where a represents 1-(benzyloxycarbonyl) piperidine-4-ylmethyl, can be obtained from 4-aminomethylpyridine by introducing a protective group, benzyloxycarbonylamino and subsequent removal of the protective group, as shown in reaction scheme 20 (see end of description).

The reaction scheme 20 CbzCl denotes benzylchloride and this Convention is used throughout this description.

The compound of the formula (5) can be synthesized by the esterification, the introduction of a protective group, recovery and halogenation, as shown in the reaction scheme 21 (see the end of the description).

The reaction scheme 21 DIBAL means diisobutylaluminium.

Thus, figure 21 connection with the alcohol group, synthesized to obtain the target compound is a chloride, can be recovered in the usual way and then introduced into reaction with thionyl chloride to obtain the compounds of formula (2), where n1is a 3.

The compound of formula (20), used as starting material at the intermediate compounds of formula (3) can be obtained, for example, according to the method shown in the reaction scheme 22, and as the initial break of the 1-naphthyl, can be easily synthesized according to reaction schemes 23 and 24 (see end of description).

The compound of the formula (11) used as starting product in the process (g) can be obtained by a combination of hydrochloride glycinate derived from salt - hydrochloride 4-imidazolinone acid as shown in reaction scheme 25 (see the end of the description). As a combining agent can be used combining the agents specified in the description of the method (d). Meanwhile, the compound of formula (13) used in the implementation of method (i) can be obtained in accordance with methods described in reaction scheme 26 (see end of description), according to which the chloride derivative, obtained in accordance with the method indicated in the reaction scheme 19, is used as starting compound.

Compound (14a) and (14b) used to implement the methods (i) and (j), can be obtained in accordance with reaction schemes 27 and 28 (see end of description), respectively. The compound of formula 14a can be synthesized by interaction of the aldehyde derivative with methyldichlorosilane in the presence of tert-butoxide potassium. The compound of formula (14b), where I refers to the I', may be the Ktsia thus obtained product with sulfurylchloride.

Finally, the reagent of formula (17) used to implement the methods (l) and (m), where G is a 1-naphthyl and L represents N-methyl-N-(2-methoxyethyl)amino, can be obtained from 1-naphthaldehyde according to the reaction scheme 29 (see the end of the description). Other compounds of formula (17) with different substituents can also be obtained in accordance with reaction scheme 29.

The compound of formula (1) obtained in accordance with the above methods, shows inhibitory activity against farnesyltransferase and therefore can be effectively used as anti-cancer tool. Thus, the present invention also provides pharmaceutical compositions comprising as active ingredient new compound of the formula (1), as defined above, or its pharmaceutically acceptable salt or isomer in combination with a pharmaceutically acceptable carrier. In particular, the compound of formula (1) can very effectively be used to treat cancer, stenosis, atherosclerosis and infectious diseases caused by hepatitis Delta and similar viruses.

In cases where the connection which is the subject of the present invention, in the day. The total daily dose may be entered at one time or divided into several doses. However, the specific dose for a patient may vary depending on the specific compound, the patient's weight, sex, hygiene, diet, time and route of administration, rate of excretion, the ratio of components in the drug, the severity of the disease, etc.

The connection which is the subject of the present invention, can be introduced in the form of preparations for parenteral or oral administration. Preparations for parenteral reference, for example a sterile aqueous or oily suspensions for parenteral administration the compounds can be prepared according to known methods using suitable dispersing agent, a wetting agent and a suspending agent. Solvents that can be used to prepare drugs for parenteral administration include water, liquid ringer and NaCl solution, and the solvent or suspendida environment may be convenient to use sterile fixing oil. For these purposes may be used any inert retainer oil, including mono - and SS="ptx2">

As solid dosage forms for oral administration can be used in capsules, tablets, pills, powders and granules, preferably, the use of capsules and tablets. In the case of tablets and drops them desirable to produce intersolubility coating. Solid formulation can be prepared by mixing the active compounds of the formula (1), which is the subject of the present invention, at least one carrier selected from the group including inert diluents such as sucrose, lactose, starch, etc., lubricating agents such as magnesium stearate dispersing agent and a binding agent.

The present invention will be explained in more detail in the following examples. However, it should be noted that the examples are only for purposes of illustrating the present invention and do not limit the scope of the claimed invention. The following preparatory examples also illustrates in greater detail the receipt of the initial compounds for the synthesis of compounds of formula (1).

PREPARATION EXAMPLE 1: Synthesis of 1-(3,4-methylenedioxybenzyl) -5-chloromethyl-1H-imidazole hydrochloride

1-1) 1-(3,4-Methylenedioxybenzyl)-5-hydroxymethyl-1H-imidazol

Use the t dimer of dihydroxyacetone and piperacillin. of 1.37 g (10 mmol) of piperacillin, 1.08 g (5.5 mmol) of the dimer of dihydroxyacetone, and 1.15 g (11 mmol) of thiocyanide potassium is introduced into 10 ml of isopropyl alcohol and then add 2 ml of acetic acid and reactio in the mixture is carried out at room temperature for 48 hours. The reaction mixture was filtered and the remaining solid is washed with 5 ml of isopropyl alcohol (x2) and 5 ml of water (x2). The filtered solid is placed in 12.5 ml of 10% aqueous solution of nitric acid and the resulting solution was cooled to 0oC. Then, to the reaction solution parts add 10 mg of sodium nitrite and conduct the reaction mixture at room temperature for 1 hour. The resulting aqueous solution was washed with 10 ml of ethyl acetate, alkalinized and then recrystallized, gain of 1.16 g (yield 50%) specified in the title compound.

1H-NMR (Dl3) : of 4.45 (s, 2H), 5,13 (s, 2H), 5,97 (s, 2H), 6,70 (m, 2H), 6,78 (d, 1H), 6,95 (s, 1H), 7,45 (s, 1H).

FAB mass spectrometry with ionization by fast atom bombardment): 233 (M+N), C12H12N2O3.

1-2) 1-(3,4-Methylenedioxybenzyl)-5-chloromethyl-1H-imidazole hydrochloride

233 mg (1 mmol) of the compound obtained according to preparation example 1-1), dissolved in 3 ml of PI is within 2 hours the solvent is distilled off under reduced pressure and remove the remaining hydrochloride with obtaining specified in the title compound, yield 95%. The resulting product is used in subsequent reactions without further purification.

PREPARATORY EXAMPLE 2: Synthesis of 1-(naphthalene-1-yl-methyl) -5-chloromethyl-1H-imidazole hydrochloride

2-1) 1-(Naphthalene-1-ylmethyl)-5-hydroxymethyl-1H-imidazol

Specified in the title compound is obtained in yield 65%, using the same method as in preparation example 1-1) except that as the starting compounds used dimer of dihydroxyacetone and (naphthalene-1-ylmethyl)-amine.

1H-NMR (Dl3) : of 4.44 (s, 2H), 5,42 (s, 2H), 6,78 (d, 1H), 6,85 (s, 1H), 7,25 (m, 1H), 7,35 (s, 1H), 7,43 (m, 2H), 7,65 (d, 1H), 7,68 (d, 1H), 8,02 (d, 1H).

FAB 239 (M+N), C15H14N2O.

2-2) 1-(Naphthalene-1-ylmethyl)-5-chloromethyl-1H-imidazole hydrochloride

Specified in the title compound are obtained from the output 90%, according to the same method as in preparation example 1-2), using the compound obtained according to preparation example 2-1). Thus obtained product is used in subsequent reactions without further purification.

PREPARATORY EXAMPLE 3: Synthesis of 1-((R)--methylbenzyl) -5-chloromethyl-1H-imidazole hydrochloride

3-1) 1-((R)--Methylbenzyl)-5-hydroxymethyl-1H-imidazol

Specified Em exception as source compounds used dimer of dihydroxyacetone and (R)-(+) - methylbenzylamine.

1H-NMR (CDCl3) : of 1.73 (d, 3H), 4,28 (s, 1H), 4,43 (d, 1H), ceiling of 5.60 (m, 1H), 6.75 in (s, 1H),? 7.04 baby mortality (d, 2H), 7.23 percent (m, 3H), 7,42 (s, 1H).

FAB 203 (M+N), C12H14N2O.

3-2) 1-((R)--Methylbenzyl)-5-chloromethyl-1H-imidazole hydrochloride

Specified in the title compound are obtained from the output 90%, according to the same method as in preparation example 1-2), using the compound obtained according to preparation example 3-1). Thus obtained product is used in subsequent reactions without further purification.

PREPARATORY EXAMPLE 4: Synthesis of 1-((3)--methylbenzyl) -5-chloromethyl-1H-imidazole hydrochloride

4-1) 1-((S)--Methylbenzyl)-5-hydroxymethyl-1H-imidazol

Specified in the title compound are obtained from the output 55%, using the same method as in preparation example 1-1), except that as the starting compounds used dimer of dihydroxyacetone and (S)-(+) - methylbenzylamine.

1H-NMR(Dl3) : of 1.73 (d, 3H), 4,28 (s, 1H), 4,43 (d, 1H), ceiling of 5.60 (m, 1H), 6.75 in (s, 1H),? 7.04 baby mortality (d, 2H), 7.23 percent (m, 3H), 7,42 (s, 1H).

FAB 203 (M+N), C12H14N2O.

4-2) 1-((S)--Methylbenzyl)-5-chloro the ICA, as in preparation example 1-2), using the compound obtained according to preparation example 4-1). Thus obtained product is used in subsequent reactions without further purification.

PREPARATORY EXAMPLE 5: Synthesis of 1-phenethyl-5-chloromethyl-1H-imidazole hydrochloride

5-1) 1-Phenethyl-5-hydroxymethyl-1H-imidazol

Specified in the title compound is obtained in yield 70%, using the same method as in preparation example 1-1), except that as the starting compounds used dimer of dihydroxyacetone and phenetylamine.

1H-NMR (Dl3) : is 3.08 (t, 2H), 4,27 (t, 2H), 4,47 (s, 2H), 6.89 in (s, 1H), 7,05 (d, 2H), 7,26 (m, 3H), 7,44 (s, 1H).

FAB 203 (M+N), C12H14N2O.

5-2) 1-Phenethyl-5-chloromethyl-1H-imidazole hydrochloride

Specified in the title compound are obtained from the output 90%, according to the same method as in preparation example 1-2), using the compound obtained according to preparation example 5-1). Thus obtained product is used in subsequent reactions without further purification.

PREPARATORY EXAMPLE 6: Synthesis of 3-[N-(2-methoxyethyl)-N-methyl]-carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrol

6-1) Ethyl epino added to the resulting solution of 30.4 g (0.2 mol) of 1,8-diazabicyclo[5.4.0]undec-7-ene-(1,5-5) (DBU). To this solution is slowly added 15.6 g (0.10 mol) of 1-naphthaldehyde dissolved in 20 ml of tetrahydrofuran, and stirred the mixture for 8 hours. The organic solvent is distilled off under reduced pressure. The resulting residue is dissolved in ethyl acetate, washed twice with water, dried over magnesium sulfate, concentrated and then subjected to column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 95/5 V/V), receiving of 20.3 g (0,090 mol, yield 90%) specified in the title compound.

1H-NMR (CDCl3) : of 1.33 (t, 3H), 4,10 (kV, 2H), 6.75 in (kV, 1H), 7,50 (m, 3H), 7,73 (d, 1H), a 7.85 (m, 2H), 8,10 (d, 1H), 8,21 (d, 1H).

FAB 227 (M+H).

6-2) 3-(Etoxycarbonyl)-4-(naphthalene-1-yl)-1H-pyrrol

4.3 g (of 18.9 mmol) of ethyl ester of 3-(naphthalene-1-yl)-acrylic acid obtained according to preparation example 6-1), and 3,68 g (of 18.9 mmol) toiletrieschoice dissolved in 100 ml of tetrahydrofuran. To the resulting solution was added slowly to 2.55 g (22.7 mmol) of tert-butoxide potassium, dissolved in 100 ml of tetrahydrofuran, and the resulting mixture heated under reflux for 30 minutes. To the reaction solution to terminate the reaction, add 100 ml of water and the solvent is distilled off under reduced pressure. The reaction of restoe. The solvent is distilled off under reduced pressure, and after column chromatography of the resulting residue on silica gel (eluent: ethyl acetate/n-hexane = 1/3, V/V) gain of 3.85 g (14.5 mol, yield 77%) specified in the title compound.

1H-NMR (CDCl3) : of 1.27 (t, 3H), 4,07 (kV, 2H), 6,76 (s, 1H), 7,28-7,47 (m, 5H), to 7.59 (s, 1H), 7,82 (m, 2H), 9,99 (s, 1H).

FAB 266 (M+H).

6-3) 3-(Hydroxycarbonyl)-4-(naphthalene-1-yl)-1H-pyrrol

2.64 g (10 mmol) of the compound obtained according to preparation example 6-2), dissolved in 50 ml of 50% ethanol and added dropwise to the obtained solution of 2.24 g (40 mmol) of potassium hydroxide. The reaction mixture is heated under reflux for 7 hours, cooled to room temperature, adjusted pH to 4-5, extracted with ethyl acetate and dried over sodium sulfate. The solvent is distilled off under reduced pressure and get 1,90 g (8.1 mol, yield 81%) specified in the title compounds. Thus obtained product is used in subsequent reactions without further purification.

1H-NMR (CDCl3) : 6,60 (s, 1H), 7,32-7,49 (m, 5H), 7,54 (s, 1H), to 7.84 (m, 2H), 9,92 (s, 1H).

FAB 238 (M+H).

6-4) 3-[N- (2-Methoxyethyl)-N-methyl]carbarnoyl-4-(naphthalene-1-yl)-1H-Pirro

234 mg (1 mmol) of the compound obtained to sawaru 230 mg (1.2 mmol) of EDC, 101 mg (1 mmol) of triethylamine and 162 mg (1.2 mmol) NOWT. The resulting mixture was stirred at 0oC for 5 minutes. To the reaction solution was added 124 mg (1 mmol) of the hydrochloride of N-(2-methoxyethyl)-N-methylamine and then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure, and then to the residue add 10 ml of a saturated solution of sodium carbonate. Thus obtained solution is extracted with 20 ml ethyl acetate, washed with 10 ml of 1 N. aqueous solution chloroethanol acid, washed with an aqueous solution of sodium chloride and water, dried over sodium sulfate and after evaporation obtain 246 mg (0,79 mmol, yield 79%) specified in the title compound.

1H-NMR (CDCl3) : 2,46 (s, 2H), 2,80 is 3.40 (m, 8H), 3,40 (s, 1H), 6,80 (s, 1H), 7,00 (s, 1H), 7,42 (m, 4H), 7,73 (d, 1H), 7,81 (d, 1H), 8,17 (d, 1H), 10,66 (s, 1H).

FAB 309 (M+H).

PREPARATORY EXAMPLE 7: Synthesis of 3-(morpholine-4-yl)-carbonyl-4- (naphthalene-1-yl) -1H-pyrrol

234 mg (1 mmol) of the compound obtained according to preparation example 6-3), dissolved in 2 ml of dimethylformamide and then added to the resulting solution of 230 mg (1.2 mmol) of EDC and 162 mg (1.2 mmol) NOWT. The resulting mixture was stirred at 0oC for 5 minutes. To the PE the 5 hours. The solvent is distilled off under reduced pressure, and then to the residue add 10 ml of saturated potassium carbonate solution. Thus obtained solution is extracted with ethyl acetate, washed with 10 ml of 1 N. aqueous solution chloroethanol acid, washed with an aqueous solution of sodium chloride and water, dried over sodium sulfate and after evaporation obtain 243 mg (0.8 mmol, yield 80%) specified in the title compound.

1H-NMR (CDCl3) : 2,13-3,52 (Shir, 8H), is 6.54 (s, 1H), 7,31-7,51 (m, 5H), 7,53 (s, 1H), 7,81 (m, 2H), to 9.93 (s, 1H).

FAB 307 (M+H).

PREPARATORY EXAMPLE 8: Synthesis of 3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrol

Specified in the title compound is obtained in a yield of 75%, using the same method as in preparation example 6-4), with the exception that they use the compound obtained according to preparation example 6-3), and 4-methylpiperazin.

1H-NMR (CDCl3) : 1,15 (W, 2H), 1,87 (W, 2N), with 1.92 (s, 3H), 2,96 (W, 2H), 3,41 (W, 2H), 6,83 (s, 1H), to 7.09 (s, 1H), was 7.36-7,42 (m, 4H), 7,73 (d, 1H), of 7.75 (d, 1H), 8,10 (d, 1H), 10,52 (s, 1H).

FAB (M+H): 320.

PREPARATION EXAMPLE 9: Synthesis of 3-{N-[2-(N,N-dimethylamino) ethyl] -N-methyl}carbarnoyl-4- (naphthalene-1-yl) -1H-pyrrol

Specified in the title of the that is used as a compound obtained according to preparation example 6-3), and N,N,N'-trimethylethylenediamine.

1H-NMR (CDCl3) : 1,89 (Shir, 3H), 2,18 (Shir, 4H), 2,44 (W, 2H), 2,75 (s, 1H), 2,98 (W, 1H), 3,36 (W, 2N), at 6.84 (s, 1H), 7,07 (c, 1H), 7,38-the 7.43 (m, 4H), 7,74 (d, 1H), 7,83 (d, 1H), 8,13 (W, 1H), 10,14 (W, 1H).

FAB (M+H): 322.

PREPARATORY EXAMPLE 10: Synthesis of 4-(naphthalene-1-yl)-3-(thiomorpholine-4-yl) carbonyl-1H-pyrrol

234 mg (1 mmol) of the compound obtained according to preparation example 6-3), dissolved in 2 ml of dimethylformamide and then added to the resulting solution of 230 mg (1.2 mmol) of EDC and 162 mg (1.2 mmol) NOWT. The resulting mixture was stirred at 0oC for 5 minutes. To the reaction solution was added 87 mg (1 mmol) thiomorpholine and then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure, and then to the residue add 10 ml of saturated potassium carbonate solution. Thus obtained solution is extracted with ethyl acetate, washed with 10 ml of 1 N. aqueous solution chloroethanol acid, washed with a saturated solution of sodium chloride and water, dried over sodium sulfate and after evaporation obtain 258 mg (0.8 mmol, yield 80%) specified in the title compound.

1H-I IS, N), 10,69 (s, 1H).

FAB 323 (M+H).

PREPARATORY EXAMPLE 11: Synthesis of 3-(1,1-diocletianopolis-4-yl) -carbonyl-4-(naphthalene-1-yl)-1H-pyrrol

323 mg (1 mmol) of the compound obtained according to preparation example 10, dissolved in 5 ml of dichloromethane and then added to the resulting solution of 430 mg (1.5 mmol) of 60% 3-chloroperbenzoic acid (MSRA), after which the mixture was stirred at room temperature for 1 hour. To remove excess 3-chloroperbenzoic acid to the mixture add 3 ml of 10% solution of thiosulfate sodium and the resulting mixture was stirred at room temperature for 30 minutes. After adding 10 ml of saturated potassium carbonate solution to the thus obtained product mixture is extracted with dichloromethane, washed with saturated sodium chloride solution and water, dried over sodium sulfate and after evaporation obtain 264 mg (0.75 mmol, 75% yield) specified in the title compound.

1H-NMR (Dl3) : 1,50-2,30 (Shir, 4H), 3,65 (Shir, 4H), 6,92 (s, 1H), 7,20 (s, 1H), 7,32-rate of 7.54 (m, 4H), 7,81 (d, 1H), 7,88 (d, 1H), 8,12 (d, 1H), 10,69 (s, 1H).

FAB 355 (M+H).

PREPARATION EXAMPLE 12: Synthesis of 3-[N-(2-methylthioethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrol

234 mg (1 mmol) of the compound, polushina a solution of 230 mg (1.2 mmol) of EDC, 101 mg (1 mmol) of triethylamine and 162 mg (1.2 mmol) NOWT. The resulting mixture was stirred at 0oC for 5 minutes. To the reaction solution was added 140 mg (1 mmol) N-(2-methylthioethyl)-N-methylamine hydrochloride and then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure, and then to the residue add 10 ml of saturated potassium carbonate solution. Thus obtained solution is extracted with 20 ml ethyl acetate, washed with 10 ml of 1 N. aqueous solution chloroethanol acid, washed with an aqueous solution of sodium chloride and water, dried over sodium sulfate and after evaporation obtain 243 mg (0.75 mmol, 75% yield) specified in the title compound.

1H-NMR (CDCl3) : to 1.98 (s, 3H), 2.13 and (W, 2H), 2,46 (W, 2H), 2,65 (W, 1H), 2.95 and (W, 1H), 3,29 (W, 1N), for 6.81 (s, 1H), 7,02 (s, 1H), 7,43 (m, 4H), 7,72 (d, 1H), 7,82 (d, 1H), 8,18 (d, 1H), 10,65 (s, 1H).

FAB 325 (M+H).

PREPARATION EXAMPLE 13: Synthesis of 3-hydroxycarbonyl-5-methyl-4- (naphthalene-1-yl) -1H-pyrrol

13-1) 3-Etoxycarbonyl-5-methyl-4- (naphthalene-1-yl)-1H-pyrrol

4.3 g (of 18.9 mmol) of ethyl ester of 3-(naphthalene-1-yl)-acrylic acid obtained according to preparation example 6-1), and 3.95 g (of 18.9 mmol) methylethylidene described in: A the t of 2.55 g (22.7 mmol) of tert-butoxide potassium, dissolved in 100 ml of tetrahydrofuran, and the resulting mixture is then heated under reflux for 30 minutes. To the reaction solution to terminate the reaction, add 100 ml of water and the solvent is distilled off under reduced pressure. The residue is extracted with diethyl ether, washed with a saturated solution of sodium chloride and dried over magnesium sulfate. The solvent is distilled off under reduced pressure, and the residue is subjected to column chromatography on silica gel using as eluent a solvent mixture of ethyl acetate/n-hexane (1/3, V/V) to give 3.50 g (12.5 mol, yield 66%) specified in the title compound.

FAB 280 (M+H).

13-2) 3-Hydroxycarbonyl-5-methyl-4-(naphthalene-1-yl)-1H-pyrrol

2,80 g (10 mmol) of the compound obtained according to preparation example 13-1), dissolved in 50 ml of 50% ethanol and then added to the resulting solution of 2.24 g (40 mmol) of potassium hydroxide and the resulting mixture heated under reflux for 7 hours. The reaction mixture is cooled to room temperature, adjusted pH to 4-5, extracted with ethyl acetate and dried over sodium sulfate. The solvent is distilled off under reduced pressure and get 2,02 g (8.1 mol, yield 81%) specified in sahlawi the Il-4-(naphthalene-1-yl)-1H-pyrrol

248 mg (1 mmol) of the compound obtained according to preparation example 13-2), dissolved in 2 ml of dimethylformamide and then added to the resulting solution of 230 mg (1.2 mmol) of EDC and 162 mg (1.2 mmol) NOWT. The resulting mixture was stirred at 0oC for 5 minutes. To the reaction solution was added 87 mg (1 mmol) of the research and then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure, and then to the residue add 10 ml of saturated potassium carbonate solution. Thus obtained solution is extracted with ethyl acetate, washed with 10 ml of 1 N. aqueous solution chloroethanol acid, washed with a saturated solution of sodium chloride and water, dried over sodium sulfate and after evaporation obtain 224 mg (0.7 mmol, yield 70%) specified in the title compound.

1H-NMR (Dl3) : 2,12 (s, 3H), 2,80-3,40 (Shir, 8H), 7,01 (s, 1H), 7,30-to 7.50 (m, 4H), 7,75-to 7.95 (m, 3H), or 10.60 (W, 1H).

FAB 321 (M+H).

EXAMPLE 1: Synthesis of 3-N-(2-methoxyethyl) -N-methyl]carbarnoyl-1-[1-(3,4-methylenedioxybenzyl) -1H-imidazol-5-ylmethyl]-4-(naphthalene-1-yl)-1H-pyrrole (1)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then add Uchenie 5 minutes. To this mixture is added 50 mg (2.2 mmol) of the compound obtained according to preparation example 1, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure, and then to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and then subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 78 mg (yield 75%) specified in the title compound.

1H-NMR (Dl3) : 2,40 (m, 2H), 2,72 (m, 1H), 2.91 in (s, 3H), to 3.09 (m, 2H), 3,32 (W, 1H), 4.09 to (W, 1H), 4,89 (s, 2H), 4.95 points (s, 2H), of 5.89 (s, 2H), 6,45 (s, 1H), 6,62 (d, 1H), 6,63 (s, 1H), 6,70 (d, 1H), 7,0 (s, 1H), 7,16 (s, 1H), 7,31 (m, 1H), 7,41 (m, 3H), 7,66 (s, 1H), 7,73 (d, 1H), 7,81 (d, 1H), 8,03 (d, 1H).

FAB (M+H) 523,31H30N4O2.

EXAMPLE 2: Synthesis of 1-[1-(3,4-methylenedioxybenzyl)-1H-imidazol-5-ylmethyl] -3- (morpholine-4-yl) carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (2)

62 mg (0.2 mmol) of the compound obtained according to preparation example 7, dissolved in 2 ml of dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is remediat at room temperature for 3 hours. The solvent is distilled off under reduced pressure, and then to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and then subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 70 mg (yield 67%) specified in the title compound.

1H-NMR (CDCl3) : 2,36 (W, 2H), 3,06 (Shir, 4H), 3.33 and (W, 2H), 5,23 (s, 2H), 5,33 (s, 2H), 5,96 (s, 2H), 6,65 (s, 1H), 6,70-6,85 (m, 3H), 7,18 is 7.50 (m, 7H), 7,79 (d, 1H), 7,81 (d, 1H), 7,94 (d, 1H).

FAB (M+H) 521, C31H28N4O4.

EXAMPLE 3: Synthesis of 1-[1-(3,4-methylenedioxybenzyl) -1H-imidazol-5-ylmethyl] -3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl) -1H-pyrrole (3)

64 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 50 mg (2.2 mmol) of the compound obtained according to preparation example 1, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml wosaam after column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, about/about) obtain 73 mg (yield 67%) specified in the title compound.

1H-NMR (Dl3) / : to 2.18 (s, 3H), 2,30-2,50 (Shir, 4H), 3,10-3,30 (Shir, 4H), to 4.98 (s, 2H), of 5.05 (s, 2H), 5,95 (s, 2H), 6,44 (s, 1H), 6,53 (d, 1H), 6,70 (d, 1H), 6.73 x (d, 1H), 7,14 (d, 1H), 7,20-7,40 (m, 3H), 7,50 (m, 3H), 7,81 (d, 1H), 7,83 (d, 1H), 7,88 (d, 1H).

FAB (M+H) 534,32H31N5O3.

EXAMPLE 4: Synthesis of 3-{N-[2-(N,N-dimethylamino) ethyl]-N-methyl}carbarnoyl-1-[1- (3,4-methylenedioxybenzyl)-1H-imidazol-5-ylmethyl] -4-(naphthalene-1-yl)-1H-pyrrole (4)

64 mg (0.2 mmol) of the compound obtained according to preparation example 9, was dissolved in 2 ml of dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 50 mg (2.2 mmol) of the compound obtained according to preparation example 1, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure, and then to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 78 mg (yield 71%) N2,50-3,00 (width, 1H), 3,29 (W, 2N), to 4.87 (s, 2H), 4.95 points (s, 2H), of 5.89 (s, 2H), 6,45 (s, 1H), 6,50 (d, 1H), 6,63 (d, 1H), 6,72 (d, 1H), 7,00 (s, 1H), 7,18 (s, 1H), 7,31 (W, 1H), 7,35-7,47 (m, 3H), 7,54 (s, 1H), 7,73 (d, 1H), 7,81 (d, 1H), 8,01 (W, 1H).

FAB (M+H) 536,32H33H5O3.

EXAMPLE 5: Synthesis of 3- [N- (2-methoxyethyl) -N-methyl] -carbarnoyl-4-(naphthalene-1-yl) -1-[1-naphthalene-1-ylmethyl)1H-imidazole-5-ylmethyl] -1H-pyrrole (5)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 58 mg (2.2 mmol) of the compound obtained according to preparation example 2, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and then subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 79 mg (75% yield) specified in the title compound.

1H-NMR (Dl3) : 2,37 (W, 2H), 2,72 (W, 1H), 2,99 (Shir, 3H), 3.00 and (W, 2N), and 3.31 (,81 (d, 2H), 7,87 (d, 1H), 8,00 (d, 1H).

FAB (M+H) 529,32H34H4O2.

EXAMPLE 6: Synthesis of 3-(morpholine-4-yl) carbonyl-4-(naphthalene-1-yl) -1-[1-(naphthalene-l-ylmethyl) -1H-imidazol-5-ylmethyl] -1H-pyrrole (6)

62 mg (0.2 mmol) of the compound obtained according to preparation example 7, dissolved in 2 ml of dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 58 mg (2.2 mmol) of the compound obtained according to preparation example 2, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 76 mg (yield 72%) specified in the title compound.

1H-NMR (CDCl3) : 2,38 (W, 2H), 3,06 (Shir, 4H), 3,30 (W, 2H), 4,99 (s, 2H), 5,42 (s, 2H), return of 6.58 (d, 1H), 6,80 (d, 1H), 7,00 (s, 1H), 7,17 (d, 1H), 7,25 (s, 1H), 7,26-rate of 7.54 (m, 6N), of 7.69 (d, 1H), 7,71-7,81 (m, 3H), the 7.85 (d, 1H), to $ 7.91 (d, 1H).

FAB (M+H) 527, C34H30N4O2.


62 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 58 mg (2.2 mmol) of the compound obtained according to preparation example 2, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 75 mg (yield 69%) specified in the title compound.

1H-NMR (CDCl3) : 1,07 (W, 2H), 1.77 in (d, 2N), of 1.85 (s, 3H), 2,84 (W, 2H), 3.27 to (W, 2H), 4,99 (s, 2H), 5,42 (s, 2H), return of 6.58 (d, 1H), 6,80 (d, 1H), 7,01 (d, 1H), 7,16 (d, 1H), 7,25 (c, 1H), 7,31-of 7.60 (m, 6N), to 7.68 (d, 1H), 7,69-7,83 (m, 3H), a 7.85 (d, 1H), 7,94 (d, 1H).

FAB (M+H) 540,33H33N5O.

EXAMPLE 8: Synthesis of 3-[N-(2-methoxyethyl)-N-methyl] -carbarnoyl-1-[1- ((R)--methylbenzyl) -1H-imidazol-5-ylmethyl]-4-(naphthalene-1-yl)-1H-pyrrole (8)

62 mg (0.2 mmol) of the compound obtained according to prepare,4 mg (0.66 mmol) of sodium hydride (60%), then the mixture is stirred for 5 minutes. To this mixture is added 50 mg (2.2 mmol) of the compound obtained according to preparation example 3, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 70 mg (71% yield) specified in the title compound.

1H-NMR (Dl3) : of 1.78 (d, 3H), 2,28 (s, 1H), 2.40 a (W, 2H), 3,02 (Shir, 3H), 3,09 (W, 2H), 3,32 (W, 2H), 4,71 (d, 2H), 4.92 in (d, 2H), 5,12 (kV, 1H), 6,59 (d, 1H), 7,00 (m, 3H), 7,18 (s, 1H), 7,20-7,39 (m, 4H), 7,40 to 7.62 (m, 3H), 7,74 (m, 2H), 7,82 (d, 1H),

of 8.04(d, 1H).

FAB (M+H) 493, C31H32N4O2.

EXAMPLE 9: Synthesis of 1-[1-((R)--methylbenzyl) -1H-imidazol-5-ylmethyl]-3-(morpholine-4-yl)-carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (9)

62 mg (0.2 mmol) of the compound obtained according podgotovitelnoe example 7, dissolved in 2 ml of dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is remediat at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 71 mg (yield 72%) specified in the title compound.

1H-NMR (Dl3) : is 1.81 (d, 3H), 2,28 (W, 2H), 3,06 (Shir, 4H), 3,29 (W, 2N) and 4.65 (d, 1H), 4,96 (d, 1H), 5,14 (kV, 1H), 6,62 (d, 1H), 7,01 (d, 2H),? 7.04 baby mortality (s, 1H), 7,20 (s, 1H), 7.23 percent and 7.36 (m, 5H), 7,39-to 7.50 (m, 3H), 7,76 (s, 1H), 7,78 (d, 1H), to 7.84 (d, 1H), 8,00 (d, 1H).

FAB (M+H) 491, C31H30N4O2.

EXAMPLE 10: Synthesis of 1-[1-((R)--methylbenzyl) -1H-imidazol-5-ylmethyl-3-(4-methylpiperazin-1-yl)-carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (10)

64 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 50 mg (2.2 mmol) of the compound obtained according to preparation example 3, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to OSM sodium, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 73 mg (yield 73%) specified in the title compound.

1H-NMR (CDCl3) : 1,09 (W, 2H), 1.77 in (d, 3H) and 1.83 (s, 3H), 1,70-1,90 (W, 2H), 2,90 (W, 2N), and 3.31 (W, 2N), to 4.73 (d, 1H), 4.92 in (d, 1H), 5,14 (kV, 1H), 6,60 (d, 1H), 7,01 (m, 3H), 7,17 (s, 1H), 7,20-7,35 (m, 4H), was 7.45 (m, 3H), 7,73 (m, 2H), 7,80 (d, 1H), 8,00 (d, 1H).

FAB (M+H) 504,32H33N5O.

EXAMPLE 11: Synthesis of 3-[N-(2-methoxyethyl)-N-methyl] -carbarnoyl-1- [1-((S)--methylbenzyl) -1H-imidazol-5-ylmethyl] -4-(naphthalene-1-yl)-1H-pyrrole (11)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 50 mg (2.2 mmol) of the compound obtained according to preparation example 4, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on CSS="ptx2">

1H-NMR (Dl3) : of 1.78 (d, 3H), 2,28 (s, 1H), 2.40 a (W, 2H), 3,02 (Shir, 3H), 3,09 (W, 2H), 3,32 (W, 2H), 4.72 in (d, 2N), is 4.93 (d, 2H), 5,12 (kV, 1H), 6,59 (d, 1H), 7,00 (m, 3H), 7,18 (s, 1H), 7,20-7,39 (m, 4H), 7,40 to 7.62 (m, 3H), 7,74 (m, 2H), 7,82 (d, 1H), 8,04 (d, 1H).

FAB (M+H) 493, C31H32N4O2.

EXAMPLE 12: Synthesis of 1-[1-((S)--methylbenzyl) -1H-imidazol-5-ylmethyl]-3-(morpholine-4-yl) carbonyl-4-(naphthalene-1-yl) -1H-pyrrole (12)

62 mg (0.2 mmol) of the compound obtained according to preparation example 7, dissolved in 2 ml of dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 50 mg (2.2 mmol) of the compound obtained according to preparation example 4, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 73 mg (yield 73%) specified in the title compound.

1H-NMR (CDCl3) : is 1.81 (d, 3H), 2,28 (W, 2H), 3,06 (Shir, 4H), 3 1H), to 7.84 (d, 1H), 8,00 (d, 1H).

FAB (M+H) 491, C31H30N4O2.

EXAMPLE 13: Synthesis of 1-[1-((S)--methylbenzyl) -1H-imidazol-5-ylmethyl]-3-(4-methylpiperazin-1-yl) carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (13)

64 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 50 mg (2.2 mmol) of the compound obtained according to preparation example 4, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 75 mg (75% yield) specified in the title compound.

1H-NMR (Dl3) : 1,09 (W, 2H), 1.77 in (d, 3H) and 1.83 (s, 3H), 1,70-1,90 (W, 2H), 2,90 (W, 2N), and 3.31 (W, 2H), 4,74 (d, 1H), is 4.93 (d, 1H), 5,14 (kV, 1H), 6,60 (d, 1H), 7,01 (m, 3H), 7,17 (s, 1H), 7,20-7,35 (m, 4H), was 7.45 (m, 3H), 7,73 (m, 2H), 7,80 (d, 1H), 8,00 (d, 1H).

FAB (M+H) 504, C32H33 is idazole-5-ylmethyl]-1H - pyrrole (14)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 50 mg (2.2 mmol) of the compound obtained according to preparation example 5, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure, and then to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 77 mg (yield 78%) specified in the title compound.

1H-NMR (Dl3) : 2,38 (W, 2H), 2,70 (m, 1H), 2,80 (t, 2H), 2,90 (m, 3H), 3.00 and (W, 2N), and 3.31 (W, 1H), 3,41 (W, 1N), a 4.03 (t, 2H), of 4.77 (s, 2H), 6,66 (d, 1H), 6,97 (d, 1H), 7,06 (d, 1H), 7,22 (m, 3H), 7,30-of 7.60 (m, 5H), of 7.75 (d, 1H), 7,80 (d, 1H), 8,04 (d, 1H).

FAB (M+H) 493, C31H32N4O2.

EXAMPLE 15: Synthesis of 3-(morpholine-4-yl) carbonyl-4-(naphthalene-1-yl) -1-[1-(phenethyl) -1H-imidazol-5-ylmethyl] -1H-pyrrole (15)

62 mg (0.2 mmol) of the compound obtained according to preparation, it is From 26.4 mg (0.66 mmol) of sodium hydride (60%), then the mixture is stirred for 5 minutes. To this mixture is added 50 mg (2.2 mmol) of the compound obtained according to preparation example 5, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 79 mg (yield 80%) specified in the title compound.

1H-NMR (CDCl3) : 2,28 (W, 2N), of 2.81 (t, 2H), 2,83 (Shir, 4H), 3,21 (W, 2H), 4,07 (t, 2H), 4,78 (s, 2H), of 6.68 (d, 1H), 6,99 (d, 1H), 7,10 (d, 2H), 7,10 (d, 2H), 7.23 percent (m, 3H), 7,30 (d, 1H), 7,50 (m, 3H), to 7.67 (s, 1H), to 7.77 (d, 1H), 7,82 (d, 1H), 8,00 (d, 1H).

FAB (M+H) 491,31H30N4O2.

EXAMPLE 16: Synthesis of 3- (4-methylpiperazin-1-yl) carbonyl-4-(naphthalene-1-yl) -1-[1-(phenethyl)-1H-imidazol-5-ylmethyl]-1H-pyrrole (16)

62 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture dobavlaut at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 75 mg (75% yield) specified in the title compound.

1H-NMR (CDCl3) : 1,06 (W, 2H), 1,90-2,00 (W, 2N), is 2.05 (s, 3H), 2,80 (t, 2H), 3,37 (Shir, 4H), Android 4.04 (t, 2H), of 4.77 (s, 2H), 6,69 (d, 1H), 6,99 (m, 2H), to 7.09 (d, 2H), 7,20-7,56 (m, 8H), 7,78 (d, 1H), 7,83 (d, 1H), of 8.00 (d, 1H).

FAB (M+H) 504, C32H33N5O.

PREPARATION EXAMPLE 15: Synthesis of 1-(2-methoxy)-phenethyl - 5-chloromethyl-1H-imidazole hydrochloride

15-1) 1-(2-Methoxy)phenethyl-5-hydroxymethyl-1H-imidazol

Specified in the title compound is obtained in yield 65%, using the same method as in preparation example 1-1), except that as the starting compounds used dimer of dihydroxyacetone and 2-methoxyphenethylamine.

1H-NMR (Dl3) : 3,03 (t, 2H in), 3.75 (s, 3H), of 4.16 (t, 2H), 4,47 (s, 2H), and 4.75 (s, 1H), 6,74 (s, 1H), 's 6.75 to 7.00 (m, 3H), 7,13-7,30 (m, 1H).

FAB 233 (M+H)13H16N2O2(M).

15-2) 1-(2-Methoxy)phenethyl-5-chloromethyl-1H-imidazole hydrochloride

The uke is 1-2), using the compound obtained according to preparation example 15-1). The resulting product is used in subsequent reactions without further purification.

PREPARATION EXAMPLE 16: Synthesis of 1-(4-methoxy)-phenethyl-5-chloromethyl-1H-imidazole hydrochloride

16-1) 1-(4-Methoxy)phenethyl-5-hydroxymethyl-1H-imidazol

Specified in the title compound is obtained in yield of 60%, using the same method as in preparation example 1-1), except that as the starting compounds used dimer of dihydroxyacetone and 4-methoxyphenethylamine.

1H-NMR (Dl3) : only 2.91 (t, 2H), 3,68 (s, 3H), 4.09 to (t, 2H), 4,36 (s, 2H), 6,70 (d, 2H), 6,77 (s, 1H), 6.87 in (d, 2H), 7,13 (s, 1H).

FAB 233 (M+H)13H16N2O2(M).

16-2) 1-(4-Methoxy)phenethyl-5-chloromethyl-1H-imidazole hydrochloride

Specified in the title compound is obtained in yield 89% according to the same method as in preparation example 1-2), using the compound obtained according to preparation example 16-1). The resulting product is used in subsequent reactions without further purification.

PREPARATION EXAMPLE 17: Synthesis of 1-(2-fluoro)phenethyl-5-chloromethyl-1H-imidazole hydrochloride

17-1) 1-(2-Fluoro)phenethyl-5-hydroc is in preparation example 1-1), except that as starting compounds used dimer of dihydroxyacetone and 2-fortunetelling.

1H-NMR (Dl3) : of 3.12 (t, 2H), 3,50 (W, 1H), 4,23 (t, 2H), to 4.52 (s, 2H), PC 6.82 (s, 1H), 7,02 (m, 3H), 7,20 (m, 2H).

FAB 221 (M+N), C12H13N2OF (M).

17-2) 1-(2-Fluoro)phenethyl-5-chloromethyl-1H-imidazole hydrochloride

Specified in the title compound is obtained in yield 89%, according to the same method as in preparation example 1-2), using the compound obtained according to preparation example 17-1). The resulting product is used in subsequent reactions without further purification.

PREPARATION EXAMPLE 18: Synthesis of 1-(2-chloro)phenethyl-5-chloromethyl-1H-imidazole hydrochloride

18-1) 1-(2-Chloro)phenethyl - 5-hydroxymethyl-1H-imidazol

Specified in the title compound is obtained in 71% yield using the same method as in preparation example 1-1), except that as the starting compounds used dimer of dihydroxyacetone and 2-chlorophenethylamine.

1H-NMR (CDCl3) : of 3.13 (t, 2H), 3,34 (W, 1H), 4,18 (t, 2H), 4,42 (s, 2H), 6,79 (s, 1H), 6,94 (d, 1H), 7.03 is-7,20 (m, 3H), 7,29 (d, 1H).

FAB 237 (M+N), C12H13N2OCl (M).

18-2) 1-(2-Chloro)phenethyl-5-hamadiche, as in preparation example 1-2), using the compound obtained according to preparation example 18-1). The resulting product is used in subsequent reactions without further purification.

PREPARATION EXAMPLE 19: Synthesis of 1-(3-chloro)phenethyl-5-chloromethyl-1H-imidazole hydrochloride

19-1) 1-(3-Chloro)phenethyl-5-hydroxymethyl-1H-imidazol

Specified in the title compound is obtained in yield 72%, using the same method as in preparation example 1-1), except that as the starting compounds used dimer of dihydroxyacetone and 3-chlorophenethylamine.

1H-NMR (Dl3) : 2,95 (t, 2H), 3,90 (W, 1H), 4,10 (t, 2H), 4,37 (s, 2H), 6,74 (s, 1H), 6,85 (m, 1H), 6,98 (s, 1H), 7,10 (m, 3H).

FAB 237 (M+N), C12H13N2OCl (M).

19-2) 1-(3-Chloro)phenethyl-5-chloromethyl-1H-imidazole hydrochloride

Specified in the title compound is obtained in yield of 91% according to the same method as in preparation example 1-2), using the compound obtained according to preparation example 19-1). The resulting product is used in subsequent reactions without further purification.

PREPARATION EXAMPLE 20: Synthesis of 1-(3-phenyl)propyl-5-chloromethyl-1H-imidazole hydrochloride

20-1) 1-(3-Feng technique as in preparation example 1-1), except that as the starting compounds used dimer of dihydroxyacetone and 3-phenylpropylamine.

1H-NMR (CDCl3) : 2,11 (m, 2H), 2,61 (t, 2H), 3,98 (t, 2H), 4,25 (W, 1H), 4.53-in (s, 1H), 6,76 (s, 1H), 7,10-of 7.60 (m, 6N).

FAB 217 (M+N), C13H16N2O (M).

20-2) 1-(3-Phenyl)propyl-5-chloromethyl-1H-imidazole hydrochloride

Specified in the title compound is obtained in yield of 91% according to the same method as in preparation example 1-2), using the compound obtained according to preparation example 20-1). The resulting product is used in subsequent reactions without further purification.

PREPARATION EXAMPLE 21: Synthesis of 1-(naphthalene-2-yl)methyl-5-chloromethyl-1H-imidazole hydrochloride

21-1) 1-(Naphthalene-2-yl)methyl-5-hydroxymethyl-1H-imidazol

Specified in the title compound are obtained from the output 58%, using the same method as in preparation example 1-1), with the exception that as the starting compounds used dimer of dihydroxyacetone and (naphthalene-2-yl) methylamine.

1H-NMR (CDCl3) : 4,36 (s, 2H), 5,28 (s, 2H), 6.89 in (s, 1H), 7,17(d, 1H), 7,35(m, 2H), 7,41 (s, 1H), 7,50 (s, 1H), 7,65 (m, 1H), 7, 69 (m, 2H).

FAB 239 (M+N), C15H14

PREPARATION EXAMPLE 22: Synthesis of 1-[2-naphthalene-1-yl)ethyl]- 5-chloromethyl-1H-imidazole hydrochloride

22-1) 1-[2-Naphthalene-1-yl)ethyl] -5-hydroxymethyl-1H-imidazol

Specified in the title compound are obtained from the output 58%, using the same method as in preparation example 1-1), except that as the starting compounds used dimer of dihydroxyacetone and (naphthalene-1-yl) ethylamine.

1H-NMR (Dl3) : 3,44 (t, 2H), 4,23 (t, 2H), to 4.38 (s, 2H), 6,79 (s, 1H), 7,07 (d, 1H), 7,17 (s, 1H), 7,24 (t, 1H), 7,32-of 7.48 (m, 2H), a 7.62 (d, 1H), 7,74 (d, 1H), 7,92 (d, 1H).

FAB 253 (M+N), C16H16N2O (M).

22-2) 1-[2-(Naphthalene-1-yl)ethyl] -5-chloromethyl-1H-imidazole hydrochloride

Specified in the title compound is obtained in yield of 87% according to the same method as in preparation example 1-2), using the compound obtained according to preparation example 22-1). The resulting product is used in subsequent reactions without further purification.

PREPARATION EXAMPLE 23: Synthesis of 1-(4-bromo)phenethyl-5-x is Abijah connection receive with the release of 72%, using the same method as in preparation example 1-1), except that as the starting compounds used dimer of dihydroxyacetone and 4-bromophenethylamine.

1H-NMR (Dl3) : to 2.94 (t, 2H), 3,76 (W, 1H), 4,11 (t, 2H), 4,37 (s, 2H), 6,74 (s, 1H), 6,85 (d, 2H), at 6.84 (d, 2H), 7,12 (s, 1H), 7,29 (d, 2H).

FAB 281 (M+N), C12H13N2OBr (M).

23-2) 1-(4-Bromo)phenethyl-5-chloromethyl-1H-imidazole hydrochloride

Specified in the title compound is obtained in yield of 91% according to the same method as in preparation example 1-2), using the compound obtained according to preparation example 23-1). The resulting product is used in subsequent reactions without further purification.

PREPARATION EXAMPLE 24: Synthesis of 1-(4-fluoro)phenethyl-5-chloromethyl-1H-imidazole hydrochloride

24-1) 1-(4-Fluoro)phenethyl-5-hydroxymethyl-1H-imidazol

Specified in the title compound is obtained in yield 72%, using the same method as in preparation example 1-1), except that as the starting compounds used dimer of dihydroxyacetone and 4-fortunetelling.

1H-NMR (Dl3) : to 2.99 (t, 2H), 3,76 (W, 1H), 4,15 (t, 2H), of 4.45 (s, 2H), 6,80-7,20 (m, 5H), 7,26 (s, 1H).

FAB 221 (M+N), C12

PREPARATION EXAMPLE 25: Synthesis of 1-(4-methyl)phenethyl-5-chloromethyl-1H-imidazole hydrochloride

25-1) 1-(4-Methyl)phenethyl-5-hydroxymethyl-1H-imidazol

Specified in the title compound is obtained in yield 72%, using the same method as in preparation example 1-1), except that as the starting compounds used dimer of dihydroxyacetone and 4-methylphenethylamine.

1H-NMR (Dl3) : to 3.02 (t, 2H), 2,99 (t, 2H), 3,76 (W, 1H), 4,19 (t, 2H), 4,47 (s, 2H), 6,83 (s, 1H), 6,94 (d, 2H), 7,06 (d, 2H), 7,28 (s, 1H).

FAB 217 (M+N), C13H16N2O (M).

25-2) 1-(4-Methyl)phenethyl-5-chloromethyl-1H-imidazole hydrochloride

Specified in the title compound is obtained in yield of 91% according to the same method as in preparation example 1-2), using the compound obtained according to preparation example 25-1). The resulting product is used in subsequent reactions without further purification.

PREPARATION EXAMPLE 26: Synthesis of 1-(4-chloro)phenethyl-5-chloromethyl-1H-imidazole hydrochloride
3%, using the same method as in preparation example 1-1), except that as the starting compounds used dimer of dihydroxyacetone and 4-chlorophenethylamine.

1H-NMR (CDCl3) : 3.04 from (t, 2H), 4,18 (t, 2H), 4,48 (s, 2H), 6,79 (s, 1H), of 6.96 (d, 2H), 7,20-7,40 (m, 3H).

FAB 237 (M+N), C12H13N2OCl (M).

26-2) 1-(4-Chloro)phenethyl-5-chloromethyl-1H-imidazole hydrochloride

Specified in the title compound is obtained in yield of 91% according to the same method as in preparation example 1-2), using the compound obtained according to preparation example 26-1). The resulting product is used in subsequent reactions without further purification.

PREPARATION EXAMPLE 27: Synthesis of 1-[2-(naphthalene-2-yl)ethyl] -5-chloromethyl-1H-imidazole hydrochloride

27-1) 1-2-(Naphthalene-2-yl) ethyl]-5-hydroxymethyl-1H-imidazol

Specified in the title compound are obtained from the output 58%, using the same method as in preparation example 1-1), except that as the starting compounds used dimer of dihydroxyacetone and 2-(naphthalene-2-yl)-ethylamine.

1H-NMR (Dl3) : up 3.22 (t, 2H), 4,28 (t, 2H), 4,48 (s, 2H), at 6.84 (s, 1H), 7,19 (d, 1H), 7,24 (d, 2H), 7,44 (m, 2H), 7,52 (s, 1H), 7,76 (m, 3H).

FAB 253 (
Specified in the title compound is obtained in yield 88% according to the same method as in preparation example 1-2), using the compound obtained according to preparation example 27-1). The resulting product is used in subsequent reactions without further purification.

EXAMPLE 17: Synthesis of 3- [N- (2-methoxyethyl) -N-methyl] -carbarnoyl-1-[1-(2-methoxy) phenethyl-1H-imidazol-5-yl] -methyl-4-(naphthalene-1-yl) 1H-pyrrole (17)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then added to the resulting solution at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 63 mg (2.2 mmol) of the compound obtained according to preparation example 15, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure, and then to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 78 mg (yield 75%) specified in the title compound.

1

FAB 523 (M+N), C32H34N4O3(M).

EXAMPLE 18: Synthesis of 1-[1-(2-methoxy)phenethyl-1H-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)- 1H-pyrrole (18)

62 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then to the obtained product is added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 63 mg (2.2 mmol) of the compound obtained according to preparation example 15, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure, and then to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 75 mg (yield 70%) specified in the title compound.

1H-NMR (Dl3) : 1,09 (W, 2H), 1.70 to 2,10 (W+s, 5H), 2,85 (t, 2H), 2,99 (W, 2H), 3,40 (W, 2H), 3,76 (s, 3H), Android 4.04 (t, 2H), around 4.85 (s, 2H), 6,69 (d, 1H), 6,80-6,92 (m, 3H),? 7.04 baby mortality (s, 1H)SUB>O2(M).

EXAMPLE 19: Synthesis of 3- [N- (2-methoxyethyl) -N-methyl] -carbarnoyl-1-[1-(4-methoxy)phenethyl-1H-imidazol-5-yl]-methyl-4-(naphthalene-1 - yl)-1H-pyrrole (19)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then to the obtained product is added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 63 mg (2.2 mmol) of the compound obtained according to preparation example 16, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure, and then to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 83 mg (yield 80%) specified in the title compound.

1H-NMR (CDCl3) : 2,38 (W, 2N), of 2.72 (t, 2H), 2,85 is 3.15 (m, 7H), 3,31 (W, 1H), and 3.72 (s, 3H), of 3.97 (t, 2H), 4,78 (s, 2H), 6,69 (d, 1H), 6,77 (d, 2H), 6,85 (d, 2H), 7,03 (s, 1H), 7,06 (s, 1H), 7.24 to to 7.50 (m, 5H), 7,73 (d, 1H), 7,82 (d, 1H), with 8.05 (d, 1H).

FAB 523 (M+H)32H34N4O3(M).

EXAMPLE 20: Synthesis of 1-[1-the g (0.2 mmol) of the compound, obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then to the obtained product is added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 63 mg (2.2 mmol) of the compound obtained according to preparation example 16, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 83 mg (yield 78%) specified in the title compound.

1H-NMR (CDCl3) : 1,05 (W, 2H), 1.70 to 2,10 (W+s, 4H), 2,24 (W, 1H), rating of 2.72 (t, 2H), 2,89 (W, 2H), 3,30 (W, 1H), of 3.73 (s, 3H), 3,98 (t, 2H), 4,79 (s, 2H), 6,69 (d, 1H), 6,76 (d, 2H), 6,86 (d, 2H), was 7.08 (m, 2H), 7,30-to 7.50 (m, 5H), 7,74 (d, 1H), 7,80 (d, 1H), 8,00 (d, 1H).

FAB 534 (M+N), C33H35N5O2(M).

EXAMPLE 21: Synthesis of 1-[1-(2-fluoro) phenethyl-1H-imidazol-5-yl]methyl-3-[N-(2-methoxyethyl) -N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (21)

62 mg (0.2 mmol) of the compound obtained according to preparation p is then the mixture is stirred for 5 minutes. To this mixture is added 61 mg (2.2 mmol) of the compound obtained according to preparation example 17, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 78 mg (yield 77%) specified in the title compound.

1H-NMR (CDCl3) : 2,38 (W, 2H), 2,70 (W, 1H), of 2.81 (t, 2H), 2,90-to 3.38 (m, 7H), is 4.03 (t, 2H), 4,91 (s, 2H), of 6.71 (d, 2H), 6,92 (m, 1H), 6,95 for 7.12 (m, 4H), 7,19 (m, 1H), 7,30-the 7.65 (m, 4H), 7,73 (d, 1H), 7,80 (d, 1H), with 8.05 (d, 1H).

FAB 511 (M+N), C31H31N4O2F (M).

EXAMPLE 22: Synthesis of 1-[1-(2-fluoro)phenethyl - 1H-imidazol-5-yl]methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (22)

62 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 61 mg (2.2 mmol) of the compound obtained according to preparation example 17, hinnon pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 78 mg (yield 75%) specified in the title compound.

1H-NMR (Dl3) : 1,04 (W, 2H), 1.70 to 2,10 (W+s, 5H), of 2.81 (m, 2H), 3,90 (W, 2H), 3,32 (W, 2N), of 4.05 (t, 2H), is 4.93 (s, 2H), 6,72 (d, 1H), 6.90 to (t, 1H), 6,95-7,05 (m, 2H), 7,10 (d, 2H), 7,20 (m, 1H), 7,25 is 7.50 (m, 4H), of 7.75 (d, 1H), 7,82 (d, 2H), 8,00 (d, 1H).

FAB 522 (M+N), C32H32N5OF (M).

EXAMPLE 23: Synthesis of 1-[1-(2-chloro)phenethyl-1H-imidazol-5-yl]methyl-3-[N-(2-methoxyethyl) -N-methyl] -carbarnoyl-4-(naphthalene-1-yl) -1H-pyrrole (23)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 64 mg (2.2 mmol) of the compound obtained according to preparation example 18, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous self the about/about), receiving 75 mg (71% yield) specified in the title compound.

1H-NMR (CDCl3) : 2,39 (W, 2H), 2,71 (W, 1H), 2,90-to 3.38 (m, N), 4,06 (t, 2H), to 4.87 (s, 2H), of 6.71 (s, 1H), 6.87 in (m, 1H), 7,00-7,20 (m, 4H), 7,30-of 7.60 (m, 6N), 7,73 (d, 1H), 7,89 (d, 1H), of 8.06 (d, 1H).

FAB 527 (M+N), C31H31N4O2Cl (M).

EXAMPLE 24: Synthesis of 1-[1-(2-chloro)phenethyl-1H-imidazol-5-yl]mechtel-3-[4-methylpiperazin-1-yl] -carbonyl-4-(naphthalene-1-yl) -1H-pyrrole (24)

62 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 64 mg (2.2 mmol) of the compound obtained according to preparation example 18, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 84 mg (yield 78%) specified in the title compound.

1H-NMR (CDCl3) : 1,04 (W, 1H), 1.70 to 2,10 (W+C, 5 7,81 (d, 1H), 8,01 (d, 1H).

FAB 538 (M+N), C32H32N5OCl (M).

EXAMPLE 25: Synthesis of 1- [1- (3-chloro) phenethyl-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl) -N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (25)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 64 mg (2.2 mmol) of the compound obtained according to preparation example 19, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 80 mg (yield 76%) specified in the title compound.

1H-NMR (Dl3) : 2,37 (W, 2H), 2,71 (m, 3H), 2,90-3,20 (m, 6N), 3,30 (W, 1H), 3,99 (t, 2H), a 4.86 (s, 2H), 6,69 (d, 1H), for 6.81 (d, 1H), 7,00 (s, 1H), 7,05-7,20 (m, 5H), 7,30-to 7.50 (m, 4H), 7,74 (d, 1H), 7,81 (d, 1H), of 8.04 (d, 1H).

FAB 527 (M+N), C31H31N4O2Cl (M).

EXAMPLE 26: Synthesis of 1-[2 mmol) of the compound, obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then added at 0oC 26,4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 64 mg (2.2 mmol) of the compound obtained according to preparation example 19, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 85 mg (yield 79%) specified in the title compound.

1H-NMR (Dl3) : 1,05 (W, 2H), 1.70 to 2,10 (W+s, 5H), 2,69 (t, 2H), 2,90 (W, 2H), 3,32 (W, 2H), 3,98 (t, 2H), to 4.87 (s, 2H), 6,70 (d, 1H), 6,79 (d, 1H), 6,98 (s, 1H), 7,05-7,21 (m, 3H), 7,30-to 7.50 (m, 6N), 7,74 (d, 1H), of 7.82 (d, 1H), to 7.99 (d, 1H).

FAB 538 (M+H)32H32N5Ol (M).

EXAMPLE 27: Synthesis of 3-[N-(2-methoxyethyl)-N-methyl]-carbarnoyl - 4-(naphthalene-1-yl)-1-[1-(3-phenyl) propyl-1H-imidazol-5-yl]methyl-1H-pyrrole (27)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and GT. To this mixture is added 62 mg (2.2 mmol) of the compound obtained according to preparation example 20, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 76 mg (75% yield) specified in the title compound.

1H-NMR (Dl3) : at 1.91 (m, 2H), 2,24 (t, 2H), 2,56 (m, 5H), 2,90-of 3.07 (m, 4H), 3,18 (W, 1N), a 4.03 (t, 2H), 5,12 (s, 2H), to 6.57 (s, 1H), 6.90 to-7,20 (m, 8H), 7,21-7,52 (m, 3H), 7,66 (d, 1H), 7,72 (d, 1H), 7,89 (d, 1H), 8,06 (W, 1H).

FAB 507 (M+H)32H34N4O2(M).

EXAMPLE 28: Synthesis of 3-[4-methylpiperazin-1-yl]carbonyl-4-(naphthalene-1-yl)-1-[1-(3-phenyl)propyl-1H-imidazol-5-yl]methyl-1H-pyrrole (28)

62 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 62 mg (2.2 mmol) of the compound obtained according to preparation example 20, hinnon pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 77 mg (yield 74%) specified in the title compound.

1H-NMR (Dl3) : 1,01 (W, 2H), 2,80 for 2.01 (+width+m, 6N), 2,30 (W, 1H), to 2.55 (t, 2H), 2,86 (W, 2H), 3,30 (W, 2N), with 3.79 (t, 2H), 5,00 (s, 2H), return of 6.58 (s, 1H), 7,00-7,20 (m, 8H), was 7.36 (m, 1H), 7,41 (m, 2H), 7,50 (s, 1H), 7,74 (d, 1H), 7,80 (d, 1H), 8,00 (d, 1H).

FAB 518 (M+N), C33H35N5O (M).

EXAMPLE 29: Synthesis of 3-[N-(2-methoxyethyl) -N-methyl] -carbarnoyl-4-(naphthalene-1-yl) -1-[1-(naphthalene-2-yl)methyl-1H-imidazol-5-yl]methyl-1H-pyrrole (29)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 65 mg (2.2 mmol) of the compound obtained according to preparation example 21, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. The mixture is then extracted twice with 10 ml dilatata, dried over anhydrous is l = 95/5, about/about) to give 85 mg (yield 80%) specified in the title compound.

1H-NMR (CDCl3) : 2,36 (W, 2H), 2,72 (W, 1H), 2,98 (Shir, 3H), 3,02 (W, 2N), and 3.31 (W, 1H), of 3.73 (W, 1H), 5,10 (s, 2H), vs. 5.47 (s, 2H), return of 6.58 (s, 1H), 7,03 (s, 1H), was 7.08 (d, 1H), 7,15 (d, 1H), 7,21 (s, 1H), 7,34-7,53 (m, 7H), 7,60 (s, 1H), 7,70-7,83 (m, 4H), of 7.97 (d, 1H).

FAB 529 (M+H)34H30N4O2(M).

EXAMPLE 30: Synthesis of 3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1-[1-(naphthalene-2-yl) methyl-1H-imidazol-5-yl]methyl-1H-pyrrole (30)

62 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 65 mg (2.2 mmol) of the compound obtained according to preparation example 21, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 74 mg (yield 69%) specified in the title compound.

FAB 540 (M+H)33H33N5O (M).

EXAMPLE 31: Synthesis of 3- [N- (2-methoxyethyl) -N-methyl] -carbarnoyl-4-(naphthalene-1 - yl)-1-{1-[2-(naphthalene-1-yl) -ethyl]-1H-imidazol-5-yl}methyl-1H-pyrrole (31)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 68 mg (2.2 mmol) of the compound obtained according to preparation example 22, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure, and then to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silicagel (eluent:

dichloromethane/methanol = 95/5, V/V) to give 77 mg (71% yield) specified in the title compound.

1H-NMR (Dl3) : 2,34 (W, 2H), 2,68 (W, 1H), 2,80-3,20 (m, 5H), 3,23 (t, 2H), 3,29 (W, 2N), of 4.12 (t, 2H), of 4.45 (s, 2H), to 6.43 (d, 1H), at 6.84 (d, 1H), 6,97 (m, 2H), 7,21-7,52 (m, 10H), 7,72 (d, 1H), 7,78-a 7.85 (m, 2H), 8,01 (d, 1H).

1H-NMR (Dl3) : 1,01 (W, 2H), 1.70 to 2.00 in (W+s, 5H), 2,89 (W, 2N), with 3.27 (t, 2H), 3,40 (W, 2N), of 4.16 (t, 2H), 4,50 (s, 2H), 6,45 (d, 1H), 6.90 to (d, 1H), 6,97 (d, 1H), 6,99 (s, 1H), 7,25-of 7.55 (m, 8H), 7,73-to 7.95 (m, 5H), of 8.00 (d, 1H).

FAB 554 (M+N), C36H35N5O (M).

EXAMPLE 33: Synthesis of 1-[1-(4-bromo)phenethyl-1H-imidazol-5-yl]methyl-3-[N-(2-methoxyethyl) -N-methyl]carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (33)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of d is up for 5 minutes. To this mixture is added 74 mg (2.2 mmol) of the compound obtained according to preparation example 23, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 88 mg (yield 77%) specified in the title compound.

1H-NMR (CDCl3) : 2,38 (Shir, 3H), to 2.67 (t, 2H), 2,90 is 3.23 (m, 7H), 3,30 (W, 1H), of 3.97 (t, 2H), 4,88 (s, 1H), 6,69 (d, 1H), PC 6.82 (d, 2H), was 7.08 (d, 2H), 7,27-7,53 (m, 7H), 7,73 (d, 1H), 7,80 (d, 1H), 8,02 (d, 1H).

FAB 571 (M+N), C31H31N4O2Br (M).

EXAMPLE 34: Synthesis of 1-[1-(4-bromo)phenethyl-1H - imidazol-5-yl]methyl-3-[4-methylpiperazin-1-yl]carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (34)

62 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 74 mg (2.2 mmol) of the compound obtained according to preparation example 23, and poluchenii and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 82 mg (yield 70%) specified in the title compound.

1H-NMR (Dl3) : 1,04 (W, 2H), 1,80-2,00 (W+s, 4H), 2,48 (W, 1H), 2,66 (t, 2H), 2,90 (W, 2N), and 3.31 (W, 1H), 2,96 (t, 2H), 4,88 (s, 2H), 6,70 (s, 1H), PC 6.82 (d, 2H), 7,10 (d, 2H), 7,25-of 7.60 (m, 7H), of 7.75 (d, 1H), of 7.82 (d, 1H), 8,01 (d, 1H).

FAB 582 (M+H)32H32N5OBr (M).

EXAMPLE 35: Synthesis of 1-[1-(4-fluoro)phenethyl-1H-imidazol-5-yl]methyl-3-[N-(2-methoxyethyl)-N-methyl]carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (35)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 60 mg (2.2 mmol) of the compound obtained according to preparation example 24, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sulfate matlacha 77 mg (yield 76%) specified in the title compound.

1H-NMR (Dl3) : 2,34(Shir, 3H), 2,70(t, 2H), 2,90-3,20 (W, 6N), 3,30(W, 1H), 3.96 points(t, 2H), a 4.86(s, 1H), of 6.68(d, 1H), 6.90 to(m, 4H), 7,05(s, 1H), to 7.09(s, 1H), 7,25-7,52(m, 5H), 7,73(d, 1H), with 8.05(d, 1H).

FAB 511 (M+N), C31H31N4O2F (M).

EXAMPLE 36: Synthesis of 1- [1- (4-fluoro) phenethyl-1H-imidazol-5-yl]methyl-3- [4-methylpiperazin-1-yl]carbonyl-4- (naphthalene-1-yl)-1H-pyrrole (36)

62 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 60 mg (2.2 mmol) of the compound obtained according to preparation example 24, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 78 mg (yield 75%) specified in the title compound.

1H-NMR (CDCl3) : 1,05 (W, 2H), 1.70 to 2.00 in (W+s, 4H), 2,25 (W, 1H), 2,70 (t, 2H), 2,90 (W, 2H), 3,30 (W, 2H), 3,88 (t, 2H), to 4.87 (s, 2H), 6,6 N5OF (M).

EXAMPLE 37: Synthesis of 3-[N-(2-methoxyethyl)-N-methyl]-carbarnoyl-1- [1-(4-methyl) phenethyl-1H-imidazol-5-yl]methyl-4-(naphthalene-1-yl)-1H-pyrrole (37)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 60 mg (2.2 mmol) of the compound obtained according to preparation example 25, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 78 mg (yield 80%) specified in the title compound.

1H-NMR (CDCl3) : 2,02 (W, 1H), 2,28 (s, 3H), 2,38 (W, 2H), 2,70 (W, 1H), 2,75 (t, 2H), 2.95 and-3,20 (m, 5H), 3,31 (W, 1H), 3,99 (t, 2H), of 4.77 (s, 2H), to 6.67 (s, 1H), 6,85 (d, 2H), 7,06 (m, 4H), 7,25 is 7.50 (m, 5H), 7,74 (d, 1H), 7,81 (d, 1H), 8,07 (d, 1H).

FAB 507 (M+N), C32H34N4O2(M).

EXAMPLE 38: Synthesis of 1- [1- (4-methyl) phenethyl-1H-imidazol-5-yl]methylase preparatory example 8, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 60 mg (2.2 mmol) of the compound obtained according to preparation example 25, and the resulting mixture was stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 81 mg (yield 78%) specified in the title compound.

1H-NMR (CDCl3) : 1,07 (W, 1H), 1.70 to 2,10 (W+C, 6N), of 2.28 (s, 3H), of 2.75 (t, 2H), 2,90 (W, 2H), 3.33 and (W, 2H), 4.00 points (t, 2H), 4,78 (s, 2H), 6,72 (s, 1H), 6,86 (m, 2H),? 7.04 baby mortality-of 7.23 (m, 4H), 7,25-of 7.60 (m, 5H), of 7.75 (d, 1H), of 7.82 (d, 1H), 8,01 (d, 1H).

FAB 518 (M+H)33H35N5O (M).

EXAMPLE 39: Synthesis of 1- [1- (4-chloro) phenethyl-1H-imidazol-5-yl]methyl-3-[N-(2-methoxyethyl) -N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (39)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) getidbyusername according to preparation example 26, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 74 mg (yield 70%) specified in the title compound.

1H-NMR (CDCl3) : 2,38 (W, 2H), 2,70 (t, 2H), 2,90-3,20 (m, 7H), 3,30 (W, 1H), of 3.97 (t, 2H), 4,88 (s, 2H), 6,69 (d, 1H), to 6.88 (d, 2H),? 7.04 baby mortality (s, 1H), to 7.09 (s, 1H), 7,19 (d, 1H), 7.24 to to 7.50 (m, 5H), of 7.75 (d, 1H), 7,81 (d, 1H), 8,02 (d, 1H).

FAB 527 (M+N), C31H31N4O2Cl (M).

EXAMPLE 40: Synthesis of 1-[1-(4-chloro)phenethyl-1H-imidazol-5-yl]methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (40)

62 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 64 mg (2.2 mmol) of the compound obtained according to preparation example 26, and the resulting mixture was stirred at room temperature for 2 hours. The solvent of Otho is, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 84 mg (yield 78%) specified in the title compound.

1H-NMR (Dl3) : 1,08 (W, 2H), 1,80 (W, 2N), of 1.95 (s, 3H), by 2.73 (t, 2H), 2,93 (W, 2H), 3,35 (W, 2H), 4.00 points (t, 2H), 4,90 (s, 2H), of 6.71 (d, 1H), 6,91 (d, 2H), 7,13-of 7.60 (m, N), 7,78 (d, 1H), 7,82 (d, 1H), 8,01 (d, 1H).

FAB 538 (M+N), C32H32N5OCl (M).

EXAMPLE 41: Synthesis of 3-[N-(2-methoxyethyl)-N-methyl] -carbarnoyl-4-(naphthalene-1-yl)-1-{ 1-[2-(naphthalene - 2-yl)-ethyl]-1H-imidazol-5-yl}methyl-1H-pyrrole (41)

62 mg (0.2 mmol) of the compound obtained according to preparation example 6, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 67 mg (2.2 mmol) of the compound obtained according to preparation example 27, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on CSS="ptx2">

1H-NMR (Dl3) / : 2,96 (W, 1H), 2,39 (W, 2H), 2,71 (W, 1H), 2,80 is 3.15 (m, 7H), 3,32 (W, 1H), 4,10 (t, 2H), 4,78 (s, 1H), 6,66 (s, 1H), to 7.09 (m, 3H), 7,42 (m, 8H), 7,63 (m, 1H), to 7.75 (m, 3H), of 7.82 (d, 1H), of 8.06 (d, 1H).

FAB 543 (M+H)35H34N4O2(M).

EXAMPLE 42: Synthesis of 3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1-{1-[2-(naphthalene-2-yl) ethyl]-1H-imidazol-5-yl}methyl-1H-pyrrole (42)

62 mg (0.2 mmol) of the compound obtained according to preparation example 8, dissolved in 2 ml of dimethylformamide and then added at 0oFrom 26.4 mg (0.66 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture is added 67 mg (2.2 mmol) of the compound obtained according to preparation example 27, and the resulting mixture was stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and to the residue add 3 ml of water. Then the mixture is twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 82 mg (yield 74%) specified in the title compound.

1H-NMR (CDCl3) : 1,05 (W, 2H), 1.70 to 2,00 (+Shir, 4H), 2,34 (W, 1H), 2,90 (t, 2H), 3,01 (W, 2H), 3,32 (width, 236
H35N5O (M).

EXAMPLE 43: Synthesis of 1-[1-(4-hydroxy) phenethyl-1H-imidazol-5-yl]methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (43)

53 mg (0.1 mmol) of the compound obtained according to example 20 is dissolved in 1 ml of dichloromethane and then added 75 mg (0.3 mmol) tribromide boron (VVG3), after which the mixture is stirred for 3 hours. To terminate the reaction, to the mixture was added 1 ml of methanol and the solvent is distilled off under reduced pressure. After column chromatography of the resulting residue on silica gel (eluent: dichloromethane/methanol = 20/80, V/V) to obtain 26 mg (yield 50%) specified in the title compound.

1H-NMR (Dl3) : 1,20 (W, 2H), 1,80-2,05 (W+s, 4H), to 2.65 (t, 2H), 3.00 and-3,60 (Shir, 5H), 3,98 (t, 2H), 4,88 (s, 2H), 6,72 (m, 5H), to 7.09 (s, 1H), 7,14 (d, 1H), 7.23 percent (s, 1H), 7,27 (s, 1H), 7,33 (d, 1H), 7,40-7,53 (m, 3H), to 7.77 (d, 1H), 7,82 (d, 1H), to 7.93 (d, 1H).

FAB 520 (M+N), C32H33O2N5(M).

PREPARATION EXAMPLE 28: Synthesis of 4-chloromethyl-1-trityl-1H-imidazole hydrochloride

28-1) 4-Hydroxy-1-trityl-1H-imidazol

3,99 g (29.6 mmol) hydroxymethylimidazole hydrochloride dissolved in a mixture of 30 ml of dimethylformamide and 10 ml of triethylamine, then slowly add solution a 9.35 g (of 33.5 mmol) triphenylmethylchloride product. This solid product is recrystallized from dioxane to obtain 8,82 g (yield 87%) specified in the title compound.

So pl. 227-229oWITH

28-2) 4-Chloromethyl-1-trityl-1H-imidazole hydrochloride

1.50 g (to 4.41 mmol) of the compound obtained according to preparation example 28-1), dissolved in 50 ml of chloroform and then added slowly at 0oFrom 0.94 ml (13,2 mmol) of thionyl chloride, whereupon the mixture is stirred at room temperature for 2 hours. The organic solvent is distilled off under reduced pressure and obtain 1.66 g (4.20 mmol, yield 95%) specified in the title compound, which was used in further reactions without additional purification.

PREPARATION EXAMPLE 29: Synthesis of 4-(5-chloromethyl-1H-imidazole-1-ylmethyl)benzonitrile hydrochloride

29-1) 4-Acetoxymethyl-1 trityl-1H-imidazol

To 100 ml of pyridine added to 5.00 g (14.7 mmol) of the compound obtained according to preparation example 28-1), and 1.65 g (16.2 mmol) of acetic anhydride, the mixture is stirred at room temperature for 24 hours. Of the reaction solution is distilled off under reduced pressure pyridine and then the obtained residue is dissolved in 200 ml ethyl acetate and washed with 100 ml of an aqueous solution of sodium chloride. About the military balance (eluent: dichloromethane/methanol = 20/1, about/about) get 5,22 mg (13.7 mmol, yield 93%) specified in the title compound.

1H-NMR (Dl3) : a 2.01 (s, 3H), of 4.95 (s, 2H), to 6.88 (s, 1H), 7,08 (s, 5H), 7,27 (s, 10H), was 7.45 (s, 1H).

29-2) 4 -(4-Acetoxymethyl-1 trityl-1H-imidazol-3-ylmethyl)benzonitrile bromide

to 5.00 g (of 13.1 mmol) of the compound obtained according to preparation example 29-1), dissolved in 20 ml of dichloromethane and then add 2,82 ml (14.4 mmol) of 4-cyanobenzaldehyde, after which the mixture was stirred at room temperature for 60 hours. The organic solvent is removed by distillation under reduced pressure and after column chromatography obtained residue (eluent: dichloromethane/methanol = 5/1, V/V) receive 5.31g (9,17 mmol, yield 70%) specified in the title compound.

1H-NMR (CDCl3+CD3OD) : 1,95 (s, 3H), of 4.95 (s, 2H), of 5.45 (s, 2H), 7,11-7,40 (m, N), the 7.65 (d, 2H), 8,21 (s, 1H).

29-3) 4-(5-Acetoxymethyl-1H-imidazol-1-ylmethyl)benzonitrile

9,10 g (15.7 mmol) of the compound obtained according to preparation example 29-2), dissolved in 500 ml of dichloromethane and then slowly at 0oTo add the 6.06 ml (to 78.7 mmol) triperoxonane acid and 12.5 ml (to 78.7 mmol) of triethylsilane, after which the mixture was stirred at room temperature for 1 hour. Annum aqueous solution TO a2CO3and extracted with 300 ml of ethyl acetate. The organic solvent is removed by distillation under reduced pressure and after column chromatography of the resulting residue using ethyl acetate as eluent gain of 3.60 g (14.1 mmol; yield 90%) specified in the title compound.

1H-NMR (CDCl3) : 1,90 (s, 3H), equal to 4.97 (s, 2H), 5.25 in (s, 2H), 7,14 (d, 2H), 7,21 (d, 1H), to 7.67 (s, 1H), of 7.75 (d, 2H).

29-4) 4-(5-Hydroxymethyl-1H - imidazol-1-ylmethyl)benzonitrile

4,20 g (16.5 mmol) of the compound obtained according to preparation example 29-3), dissolved in 200 ml of methanol and then add 4,50 g (32,9 mmol) TO a2CO3, after which the mixture was stirred at room temperature for 20 minutes. The organic solvent is removed by distillation under reduced pressure at room temperature. The resulting residue is then extracted with 300 ml of ethyl acetate and after column chromatography obtained residue (eluent: dichloromethane/methanol = 10/1, V/V) receive 3,19 g (15.0 mmol, yield 91%) specified in the title compound.

1H-NMR (CDCl3+CD3OD) : to 4.28 (s, 2H), by 5.18 (s, 2H), at 6.84 (s, 1H), 7,12 (d, 2H), 7,42 (s, 1H), 7,55 (d, 2H).

29-5) 4-5-Chloromethyl-1H-imidazole-1-ylmethyl)benzonitrile hydrochloride

3.00 g (14,1 Molina added at 0oWith 5,02 ml (70.5 mmol) of thionyl chloride, whereupon the mixture is stirred at room temperature for 2 hours. The organic solvent is removed by distillation under reduced pressure and obtain 3.50 g (of 13.1 mmol, yield 93%) specified in the title compounds. The resulting product is used in further reactions without additional purification.

PREPARATION EXAMPLE 30: Synthesis of 4-(3-chloro-1-propenyl) -1-trityl-1H-imidazole

30-1) Methyl-3-(1H-imidazol-4-yl)acrylate

500 mg (3.62 mmol) of 3-(1H-imidazol-4-yl)acrylic acid is added to 20 ml of methanolic solution of Hcl and stirred the mixture at room temperature for 10 hours. The solvent is removed by distillation under reduced pressure and to the residue is added 30 ml of dichloromethane. The resulting mixture was sequentially washed with a saturated solution Panso3, an aqueous solution of sodium chloride and water. The organic layer is dried over anhydrous magnesium sulfate and after evaporation obtain 510 mg (3.35 mmol, yield 93%) specified in the title compounds. This connection is used in further reactions without additional purification.

30-2) Methyl-3-(1-trityl-1H-imidazol-4-ml)acrylate

350 mg (2,30 mmol) of the compound obtained according to preparation primal) of triethylamine. After 2 hours the reaction mixture was added 100 ml of ice water to obtain a solid substance. The obtained solid is filtered off, washed with diethyl ether and hexane, then dried to obtain 810 mg (2.05 mmol, yield 87%) specified in the title compound.

1H-NMR (Dl3) : of 3.75 (s, 3H), 6.35mm (d, 1H), 7,05 is 7.50 (m, N).

30-3) 1-(1-Trityl-1H-imidazol-4-yl)propen-3-ol

800 mg (2.03 mmol) of the compound obtained according to preparation example 30-2), add 20 ml of anhydrous dichloromethane. After cooling the mixture to -78oWith her type of 6.1 ml (1 M solution in hexane) diisobutylaluminium hydride. The temperature is slowly increased to room and then to the mixture to terminate the reaction, add 2 ml of water. Add 3 ml of 1 n NaOH solution and then 2 ml of water, after which the mixture is filtered through celite. The organic layer of the filtrate is separated and combined with dichlormethane extract the aqueous layer. The mixture is dried over anhydrous magnesium sulfate. The organic solvent is removed by distillation under reduced pressure and after column chromatography of the resulting residue on silica gel (eluent: dichloromethane/methanol = 20/1, V/V) receive 671 mg (1,83 mmol, yield 90%) specified in S4) 4-(3-Chlorophenyl)-1-trityl-1H-imidazol

650 mg (1.77 mmol) of the compound obtained according to preparation example 30-3), add 10 ml of chloroform. Then add at 0oWith 135 ml (1.9 mmol) of thionyl chloride and stirred the mixture at room temperature for 2 hours. The organic solvent is removed by distillation under reduced pressure and the resulting residue is dissolved in 10 ml of ethyl acetate. The solution was washed with saturated aqueous NaHCO3, the organic solvent is distilled off under reduced pressure and receive 647 mg (1,68 mmol, yield 95%) specified in the title compound.

1H-NMR (Dl3) : 4,22 (d, 2H), 6,40-6,55 (m, 2H), for 6.81 (s, 1H), 7,10-to 7.50 (m, N).

PREPARATION EXAMPLE 31: Synthesis of 5-chloromethyl-1-Mei hydrochloride

31-1) 5-Hydroxymethyl-1-Mei

Specified in the title compound are obtained from the output 32% in accordance with the methodology described in: J. M. Dener, L-H Zhang, H. Rapoport, J. Org.Chem., 1993, 58, 1159, using as starting compounds dihydroxyacetone and methylamine hydrochloride.

1H-NMR (CDCl3) : to 3.67 (s, 3H), 4,58 (s, 2H), lower than the 5.37 (W, 1H), 6,76 (s, 1H), 7,32 (s, 1H).

31-2) 5-Chloromethyl-1-metilimidazola hydrochloride

Specified in the title compound is obtained in yield of 95% according to the same medicamenta, obtained in preparatory example 31-1).

PREPARATION EXAMPLE 32: Synthesis of 1-(4-bromobenzyl)-5-chloromethyl-1H-imidazole hydrochloride

32-1) 1-(4-Bromobenzyl)-5-hydroxymethyl-1H-imidazol

Specified in the title compound is obtained in yield of 50% in accordance with the methodology described in: J. M. Dener, L-H Zhang, H. Rapoport, J. Org.Chem., 1993, 58, 1159, using as starting compounds dimer of dihydroxyacetone hydrochloride and 4-bromobenzylamine.

1H-NMR (CDCl3+CD3OD) : to 4.46(s, 2H), 5,26 (s, 2H), 7,00 (s, 1H), 7,07(d, 2H), 7,50(d, 2H), 7,65(s, 1H).

32-2) 1-(4-Bromobenzyl)-5-chloromethyl-1H-imidazole hydrochloride

Specified in the title compound are obtained from the output 96% according to the same method as in preparation example 28-2), with the exception that as the starting compound using the compound obtained in preparatory example 32-1). Thus obtained product is used in further reactions without additional purification.

PREPARATION EXAMPLE 33: Synthesis of 5-chloromethyl-1-isobutyramide hydrochloride

33-1) 5-Hydroxymethyl-1-isobutylamides

Specified in the title compound is obtained in yield of 45% according to the same method as in preparation example 31-1), using 3
) : 0,90 (d, 6N), to 1.76 (m, 1H), 3,62 (d, 2H), 4,24 (W, 1H), 4,60 (s, 2H), 6,85 (s, 1H), 7,45 (s, 1H).

FAB (M+H): 155.

33-2) 5-Chloromethyl-1-isobutyramide hydrochloride

Specified in the title compound is obtained in yield of 95% according to the same method as in preparation example 28-2), with the exception that as the starting compound using the compound obtained in preparatory example 33-1).

PREPARATION EXAMPLE 34: Synthesis of 5-chloromethyl-1-cyclohexylethylamine hydrochloride

34-1) 5-Hydroxymethyl-1-cyclohexylmaleimide

Specified in the title compound is obtained in yield of 45% according to the same method as in preparation example 31-1), using as starting compounds dihydroxyacetone and hydrochloride cyclohexylethylamine.

1H-NMR (CDCl3) : 0,94 (m, 2H), 1,16 (m, 3H), 1,50-1,70 (m, 6N), the 3.65 (d, 2H), 4,24 (cm, 1H), 4,60 (s, 2H), 6,85 (s, 1H), 7,45 (s, 1H).

FAB (M+H): 195.

34-2) 5-Chloromethyl-1-cyclohexylethylamine hydrochloride

Specified in the title compound is obtained in yield of 95% according to the same method as in preparation example 28-2), with the exception that as the starting compound using the compound obtained in preparation when proximity-1-Intimidator

Specified in the title compound is obtained in yield of 50% according to the same method as in preparation example 31-1), using as starting compounds dihydroxyacetone and hydrochloride pentylamine.

1H-NMR (Dl3) : of 0.90 (t, 3H), 1,08 (W, 2N), of 1.30 (m, 4H), of 1.45 (m, 2H), to 3.64 (t, 2H), 4,24 (W, 1H), 4,60 (s, 2H), at 6.84 (s, 1H), 7,44 (s, 1H).

FAB (M+H): 169.

35-2) 5-Chloromethyl-1-intimidate hydrochloride

Specified in the title compound are obtained from the output 90% according to the same method as in preparation example 28-2), with the exception that as the starting compound using the compound obtained in preparatory example 35-1).

PREPARATION EXAMPLE 36: Synthesis of 5-chloromethyl-1-octylimidazolium hydrochloride

36-1) 5-Hydroxymethyl-1-octylimidazolium

Specified in the title compound are obtained from the output 52% according to the same method as in preparation example 31-1), using as starting compounds dihydroxyacetone and hydrochloride octylamine.

1H-NMR (CDCl3) : to 0.88 (t, 3H), 1.18 to (W, 2H), 1,30 (Shir, 10H), of 1.42 (m, 2H), to 3.67 (t, 2H), 4,23 (W, 1H), 4,60 (s, 2H), at 6.84 (s, 1H), 7,44 (s, 1H).

FAB (M+H): 211.

36-2) 5-Chloromethyl-1-octylimidazolium hydrochloride

The decree is), with the exception that as the starting compound using the compound obtained in preparatory example 36-1).

PREPARATION EXAMPLE 37: Synthesis of 5-chloromethyl-1-deliminator hydrochloride

37-1) 5-Hydroxymethyl-1-deliminator

Specified in the title compound are obtained from the output 52% according to the same method as in podgotovitelnyy example 31-1), using as starting compounds dihydroxyacetone and decylamine hydrochloride.

1H-NMR (Dl3) : to 0.88(t, 3H), 1.04 million(Shir, 2H), 1,30(Shir, 14N), of 1.42(m, 2H), 3,68(t, 2H), 4,23(W, 1H), 4,60(s, 2H), at 6.84(s, 1H), 7,44 (s, 1H).

FAB (M+H): 239.

37-2) 5-Chloromethyl-1-deliminator hydrochloride

Specified in the title compound is obtained in yield 93% according to the same method as in preparation example 28-2), with the exception that as the starting compound using the compound obtained in preparatory example 37-1).

PREPARATION EXAMPLE 38: Synthesis of 5-chloromethyl-1-(3-methyl)butylimidazole hydrochloride

38-1) 5-Hydroxymethyl-1-(3-methyl)butylimidazole

Specified in the title compound are obtained from the output 52% according to the same method as in preparation example 31-1), using as the source from which of 1.65 (m, 1H), to 3.67 (t, 2H), 4,23 (W, 1H), 4,60 (s, 2H), at 6.84 (s, 1H), 7,44 (s, 1H).

FAB (M+H): 169.

38-2) 5-Chloromethyl-1-(3-methyl)butylimidazole hydrochloride

Specified in the title compound is obtained in yield 93% according to the same method as in preparation example 28-2), with the exception that as the starting compound using the compound obtained in preparatory example 38-1).

PREPARATION EXAMPLE 39: Synthesis of 5-chloromethyl-1-(2-methoxy)ethylimidazole hydrochloride

39-1) 5-Hydroxymethyl-1-(2-methoxy)ethylimidazole

Specified in the title compound is obtained in yield of 60% according to the same method as in preparation example 31-1), using as starting compounds dihydroxyacetone hydrochloride and 2-methoxyethylamine.

1H-NMR (CDCl3) : to 3.38 (s, 3H), 3.42 points (t, 2H), the 3.65 (t, 2H), 4,23 (W, 1H), 4,60 (s, 2H), at 6.84 (s, 1H), 7,44 (s, 1H).

FAB (M+H): 157.

39-2) 5-Chloromethyl-1-(2-methoxy)ethylimidazole hydrochloride

Specified in the title compound is obtained in yield 93% according to the same method as in preparation example 28-2), with the exception that as the starting compound using the compound obtained in preparatory example 39-1).

PREPARATORY eliminator

Specified in the title compound are obtained from the output 61% according to the same method as in preparation example 31-1), using as starting compounds dihydroxyacetone hydrochloride and 3-methoxypropylamine.

1H-NMR (CDCl3) : 1,72 (m, 2H), 3,32 (s, 3H), 3.46 in (t, 2H), 3,63 (t, 2H), 4,23 (W, 1H), 4,60 (s, 2H), at 6.84 (s, 1H), 7,44 (s, 1H).

FAB (M+H): 171.

40-2) 5-Chloromethyl-1-(3-methoxy)propylimidazol hydrochloride

Specified in the title compound are obtained from the output 90% according to the same method as in preparation example 28-2), with the exception that as the starting compound using the compound obtained in preparatory example 40-1).

PREPARATION EXAMPLE 41: Synthesis of 5-chloromethyl-1- (3-ethoxy)propylimidazol hydrochloride

41-1) 5-Hydroxymethyl-1-(3-ethoxy) propylimidazol

Specified in the title compound are obtained from the output 61% according to the same method as in preparation example 31-1), using as starting compounds dihydroxyacetone hydrochloride and 3-ethoxypropylamine.

1H-NMR (Dl3) : of 1.20 (t, 3H), 1,72 (m, 2H), 3,50 (s, 4H), 3,63 (t, 2H), 4,23 (W, 1H), 4,60 (s, 2H), at 6.84 (s, 1H), 7,44 (s, 1H).

FAB (M +H): 185.

41-2) 5-Chloromethyl-1-(3-ethoxy)propyl what about in preparatory example 28-2), with the exception that as the starting compound using the compound obtained in preparatory example 41-1).

PREPARATION EXAMPLE 42: Synthesis of 5-chloromethyl-1- (3-isopropoxy)propylimidazol hydrochloride

42-1) 5-Hydroxymethyl-1-(3-isopropoxy)propylimidazol

Specified in the title compound are obtained from the output 61% according to the same method as in preparation example 31-1), using as starting compounds dihydroxyacetone hydrochloride and 3-isopropoxypropylamine.

1H-NMR (CDCl3) : 1,15 (d, 6N), 1,71 (m, 2H), 3,45-3,55 (m, 3H), 3,63 (t, 2H), 4,23 (W, 1H), 4,60 (s, 2H), at 6.84 (s, 1H), 7,44 (s, 1H).

FAB (M+H): 199.

42-2) 5-Chloromethyl-1-(3-isopropoxy)propylimidazol hydrochloride

Specified in the title compound are obtained from the output 90% according to the same method as in preparation example 28-2), with the exception that as the starting compound using the compound obtained in preparatory example 42-1.

EXAMPLE 44: Synthesis of 1-(1H-imidazol-4-yl) methyl-4-(naphthalene-1-yl)-3- (thiophene-2-yl) carbonyl-1H-pyrrole (44)

44-1) 3-(Naphthalene-1-yl)-1-(thiophene-2-yl)-prop-2-EN-1-he

3.12 g (20 mmol) 1-naphthaldehyde and 2.52 g (20 mmol) of 2-acetylthiophene dissolved in 20 ml of methanol and temperature for 8 hours and then the thus obtained solid product is filtered off and dried. The pH value of the filtrate is adjusted to 4-6 with 1 n solution chloroethanol acid, and then extracted filtrate with ethyl acetate. The organic solvent is distilled off under reduced pressure and the residue is subjected to column chromatography (eluent: hexane/ethyl acetate = 4/1, V/V), getting to 4.23 g (16 mmol, yield 80%) specified in the title compound, together with the filtered solid.

1H-NMR (CDCl3) : 7,13-7,31 (m, 2H), 7,55-of 7.70 (m, 3H), of 7.70 (d, 1H), 7,85-of 7.90 (m, 4H), of 8.28 (d, 1H), to 8.70 (d, 1H).

44-2) of 4- (Naphthalene-1-yl)-3-(thiophene-2-yl)carbonyl-1H-pyrrol

2.64 g (9,99 mmol) of the compound obtained according to example 44-1), and 2.35 g (12,0 mmol) toiletrieschoice dissolved in 30 ml of tetrahydrofuran. Then slowly add 1.35 g (12,0 mmol) of tert-butoxide potassium and the resulting mixture heated under reflux for 30 minutes. The solvent is distilled off under reduced pressure and then added to the obtained residue, 15 ml of water and 20 ml of ethyl acetate. The mixture was mixed thoroughly by shaking and filtered to isolate a target of the solid residue. The obtained solid residue is extracted with diethyl ether and after drying gain of 1.97 g (6,48 mmol, yield 65%) specified in the title compound.

Naphthalene-1-yl) -3-(thiophene-2-yl)carbonyl-1-(1 - trityl-1H-imidazol-4-ylmethyl-1H-pyrrol

200 mg (0,99 mmol) of the compound obtained according to example 44-2), dissolved in 5 ml of dimethylformamide and then added at 0oWith 95 mg (4.0 mmol) of sodium hydride (50%), after which the mixture is stirred for 5 minutes. To the reaction solution was added 391 mg (0,99 mmol) of the compound obtained according to preparation example 28-2), and stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and the resulting residue extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, evaporated and subjected to column chromatography (eluent: hexane/ethyl acetate = 1/3, V/V) to give 205 mg (0.33 mmol, yield 33%) specified in the title compound.

1H-NMR (CDCl3) : 5,02 (s, 2H), 6.75 in (s, 1H), 6,79 (s, 1H), 6,86 (t, 1H), 7,10-7,52 (m, N), 7,71 (d, 1H), 7,78 (d, 1H), 7,89 (d, 1H).

44-4) 1-(1H-Imidazol-4-yl)methyl-4- (naphthalene-1-yl)-3-(thiophene-2-yl)carbonyl-1H-pyrrol

190 mg (0,304 mmol) of the compound obtained according to example 44-3), dissolved in a mixture of solvents triperoxonane acid/dichloromethane (0.5 ml/0.5 ml) and the resulting solution was stirred at room temperature for 2 hours. The organic solvent is distilled off under reduced pressure. The residue is dissolved in 10 ml of e is tion, evaporated and subjected to column chromatography (eluent: ethyl acetate) to give 103 mg (0,269 mmol, yield 88%) specified in the title compound.

1H-NMR (CDCl3) : 4,87 (c, 2H), 6,55 (s, 1H), 6,72 (s, 1H), to 6.88 (t, 1H), 7,11-7,34 (m, 7H), 7,50-to 7.67 (m, 3H), 7,83 (d, 1H).

FAB MS: 384 (M+1).

EXAMPLES 45-72:

Connection characteristics are listed in tables 2-1 and 2-3 are in accordance with techniques which are analogous to the methods described in example 44.

EXAMPLE 73: Synthesis of 1-[1-(4-cyanobenzyl) -1H-imidazol-5-yl] methyl-4-(naphthalene-1-yl)-3-(thiophene-2-yl)carbonyl-1H-pyrrole (73)

80 mg (0.3 mmol) of the compound obtained according to preparation example 29-5), and 90 mg (0.3 mmol) of the compound obtained according to example 44-2), dissolved in 2 ml of dimethylformamide and then added 36 mg of sodium hydride (60%), after which the mixture is stirred for 2 hours. The solvent is distilled off under reduced pressure and the residue is subjected to column chromatography (eluent: dichloromethane/methanol = 10/1, V/V) to give 83 mg (0,17 mmol, yield 56%) specified in the title compound.

1H-NMR (CDCl3) : 5,02 (s, 2H), 5,08 (s, 1H), 6.73 x (s, 1H), 6,85 (s, 1H), 7,03 (t, 1H), 7,32 was 7.45 (m, 11N), 7,63 (s, 1H), of 7.75 (d, 1H), 7,82 (d, 1H), 8,02 (d, 1H).

FAB MS: 499 (M+1).

WHEN is the quiet similar to the method shown in example 73.

EXAMPLE 78: Synthesis of 3-(4-perbenzoic)-1-(1-methyl-1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (78)

Specified in the title compound is obtained in 75% yield according to the same method as in example 44-3), except using 3-(4-perbenzoic)-4-(naphthalene-1-yl)-1H-pyrrole and the compound obtained in preparatory example 31-2).

1H-NMR (Dl3) : of 3.42 (s, 3H), free 5.01 (s, 2H), 6.73 x (m, 3H), 7,11 (s, 1H), 7.24 to EUR 7.57 (m, 8H), to 7.67 to 7.75 (m, 2H).

FAB MS (M+1): 410.

EXAMPLE 79: Synthesis of 1-(1-methyl-1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(4-phenoxybenzoyl)-1H-pyrrole (79)

Specified in the title compound is obtained in yield 70% according to the same method as in example 44-3), except using 4-(naphthalene-1-yl)-3-(4-phenoxybenzoyl) -1H-pyrrole and the compound obtained in preparatory example 31-2).

1H-NMR (Dl3) : to 3.52 (s, 3H), 5,12 (s, 2H), 6,63 (d, 2H), 6,76 (d, 1H), 6,85 (d, 2H), 7,12 (t, 1H), 7,20 (s, 1H), 7,28-7,40 (m, 7H), 7,51 (d, 2H), 7,68 (d, 2H), 7,74 (d, 1H), 7,83 (d, 1H).

FAB MS (M+1): 484.

EXAMPLE 80: Synthesis of (S)-1-(1H-imidazol-4-yl)methyl-3-[N-(1-methoxycarbonyl-3-methylthio)propyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (80)

80-1) Ethyl 3-(naphthalene-1-yl)acrylate

of 22.4 g (0.10 mol) triethylphosphate nomu solution slowly added 15.6 g (0.10 mol) of 1-naphthaldehyde, dissolved in 20 ml of tetrahydrofuran, and the resulting mixture is stirred for 8 hours. The organic solvent is distilled off under reduced pressure. The residue is dissolved in ethyl acetate, washed twice with water, dried over anhydrous magnesium sulfate, evaporated and subjected to column chromatography (eluent: hexane/ethyl acetate = 95/5, V/V), receiving of 20.3 g (0,090 mol, yield 90%) specified in the title compound.

1H-NMR (Dl3) : of 1.42 (t, 3H), 4,30 (kV, 2H), 6,50 (d, 1H), 7,40-of 7.60 (m, 3H), 7,73 (d, 1H), 7,82 (m, 2H), to 8.20 (d, 1H), and 8.50 (d, 1H).

80-2) 3-Etoxycarbonyl-4-(naphthalene-1-yl)-1H-pyrrol

500 mg (1,89 mmol) ethyl-3-(naphthalene-1-yl)acrylate obtained according to example 80-1), and 368 mg (1,89 mmol) toiletrieschoice dissolved in 10 ml of tetrahydrofuran. Then slowly add 255 mg of 2.27 mmol) of tert-butoxide potassium, dissolved in tetrahydrofuran (10 ml) and the resulting mixture is heated under reflux for 30 minutes. To the reaction solution to terminate the reaction, add 10 ml of water and the solvent is distilled off under reduced pressure. The resulting residue is extracted with diethyl ether, washed with aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The solvent is removed by distillation is about/about) obtain 385 mg (1,45 mmol, yield 77%) specified in the title compound.

1H-NMR (Dl3) : 0,86 (t, 3H), was 4.02 (q, 2H), for 6.81 (s, 1H), of 7.48-to 7.61 (m, 5H), of 7.90-of 7.97 (m, 3H), of 8.92 (s, 1H).

80-3) 3-Etoxycarbonyl-1-(1H-imidazol-4-yl) methyl-4-(naphthalene-1-yl)-1H-pyrrol

Specified in the title compound are obtained from the output 39%, using techniques that are described in the examples 44-3 and 44-4), of the compounds obtained according to example 80-2) and preparatory example 28-2).

1H-NMR (CDCl3) : a 1.11 (t, 3H), 4,20 (kV, 2H), of 5.05 (s, 2H), 6,78 (s, 1H), 6.89 in (s, 1H), 7,38-7,49 (m, 6N), the 7.85-of 7.97 (m, 3H).

80-4) 3-Hydroxycarbonyl-1-(1H-imidazol-4-yl) methyl-4-(naphthalene-1-yl)-1H-pyrrol

220 mg (0.64 mmol) of the compound obtained according to example 80-3), dissolved in 5 ml of 50% ethanol. Then added dropwise 216 mg (3.8 mmol) of potassium hydroxide and the resulting mixture heated under reflux for 7 hours. The reaction solution is cooled to room temperature, adjusted the pH to 4-5, extracted with ethyl acetate and dried over anhydrous sodium sulfate. The solvent is removed by distillation under reduced pressure to obtain 162 mg (0.51 mmol, yield 80%) specified in the title compounds. The compound obtained is used in the further reactions without additional purification.

1H-NMR (CDCl3) : to 1.21 (m, 1H), 1.55V (m, 3H), of 1.80 (s, 3H), 3,42 (s, 3H), 4,43 (m, 1H), of 5.05 (s, 2H), ceiling of 5.60 (d, 1H), of 6.71 (s, 1H), 6,95 (s, 1H), 7,21 was 7.45 (m, 7H), 7,75-7,87 (m, 3H).

FAB MS: 463 (M+1).

EXAMPLE 81: Synthesis of (S)-3-[N-(1-hydroxycarbonyl-3-methylthio) propyl]carbarnoyl-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (81)

70 mg (0.15 mmol) of the compound obtained according to example 80-5), dissolved in 2 ml of a mixture of restoril stirred at room temperature for 4 hours. The solvent is removed under reduced pressure and obtain 68 mg (0.15 mmol, yield of 99.7%) lithium salts specified in the title compound.

1H-NMR (CD3OD+CDCl3) : 1,25 (m, 1H), 1,49 (m, 3H), of 1.85 (s, 3H), to 4.41 (m, 1H), 5,11 (s, 2H), to 5.58 (d, 1H), 6, 70 (s, 1H), 6.89 in (s, 1H), 7,15-7,38 (m, 7H), 7,76-7,81 (m, 3H).

FAB MS: 449 (M+1).

EXAMPLES 82-98:

Connection characteristics are listed in tables 4-1 and 4-2 are in accordance with techniques which are analogous to the methods described in example 80.

EXAMPLE 99: Synthesis of 1-(1-methyl-1H-imidazol-5-yl)methyl-3-(morpholine-4-yl) carbonyl-4- (naphthalene-1-yl) -1H-pyrrole (99)

In the compound obtained according to example 85, enter trailing protective group according to the same method, which is described in preparatory example 28-1), after which get mentioned in the title compound with a yield of 55%, using the method described in preparation examples 29-2 and 29-3), and using methyliodide.

1H-NMR (CDCl3) : 2,80 is-3.45 (m, 8H), to 3.58 (s, 3H), 5,19 (s, 2H), 6.75 in (d, 1H), 7,18 (d, 1H), 7,21 (s, 1H), 7,35 (d, 1H), 7,40-to 7.50 (m, 3H), 7,72 (d, 1H), 8,03 (d, 1H).

FAB MS: 401 (M+1).

EXAMPLE 100: Synthesis of (S)-1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl]methyl-3- [N- (1-methoxycarbonyl-3-methylthio) -propyl] carbarnoyl-4-(naphthalene-1-yl)
Specified in the title compound is obtained in a yield of 75% of the compounds obtained according to example 80-2) and preparatory example 29-5), consistently applying the methods described in example 73 example 80-4).

1H-NMR (CDCl3+CD3OD) : 5,02 (s, 2H), 5,10 (s, 2H), 6,76 (s, 1H), 7,07 (m, 2H), 7,25-of 7.82 (m, N).

100-2) (S) -1- [1- (4-Cyanobenzyl) -1H-imidazol-5-yl]methyl-3-[N-(1-methoxycarbonyl-3-methylthio)propyl]-carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrol

Specified in the title compound are obtained from the output 35% according to the same method described in example 80-5), with the exception that they use the compound obtained according to example 100-1).

1H-NMR (Dl3) : of 1.85 (s, 3H), 2,04 (m, 1H), 2,13 (m, 1H), 2,42 (t, 2H), 3,61 (s, 3H), of 4.83 (m, 1H), 5,02 (s, 2H), 5,11(s, 2H), 6,63 (s, 1H), 7,01 (d, 2H), 7,13 (d, 1H), 7,22-the 7.43 (m, 7H), 7,65-a 7.92 (m, 4H).

FAB MS: 578 (M+1).

EXAMPLE 101: the Synthesis of (S)-1-[1-(4-cyanobenzyl) -1H-imidazol-5-yl]methyl-3- [N- (1-hydroxycarbonyl-3-methylthio) -propyl]carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (101)

Lithium salt specified in the title compounds are obtained from the output 96% according to the method similar to that described in example 81, from the compound obtained according to example 100-2).

1H-NMR (CDCl3+CD3OD4).

FAB MS: 564 (M+1).

EXAMPLES 102-103:

Connection characteristics are listed in table 5 are in accordance with techniques which are analogous to the methods described in examples 100 and 101.

EXAMPLES 104-105:

Connection characteristics are shown in table 6 are in accordance with techniques which are analogous to the methods described in example 101.

EXAMPLE 106: Synthesis of 1- [2- (1H-imidazol-1-yl)ethyl] -3-(morpholine-4-yl) -carbonyl-4- (naphthalene-1-yl) -1H-pyrrole (106)

106-1) 2-(1H-Imidazol-1-yl)ethyl-p-toilet

0.24 g (2,41 mmol) of 2-(1H-imidazol-1-yl)ethanol and 0.55 g (2,88 mmol) taillored dissolved in 20 ml of dichloromethane and then added slowly at 0oWith 0.67 ml of triethylamine, after which the mixture was stirred at room temperature for 4 hours. The organic solvent is distilled off under reduced pressure. The resulting residue is dissolved in 10 ml of ethyl acetate, washed sequentially 1 N. solution chloroethanol acid, saturated sodium bicarbonate solution and aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and then evaporated. After column chromatography of the resulting residue (eluent: dichloromethane/methanol = 20/1, V/V) gain of 0.30 g (1.13 mmol is N), of 6.99 (s, 1H), 7,29 (d, 2H), 7,45 (s, 1H), to 7.64 (d, 2H).

106-2) 3-Hydroxycarbonyl-4-(naphthalene-1-yl)-1H-pyrrol

Specified in the title compound is obtained in yields of 80% hydrolysis of the compound obtained according to example 80-2), according to the same method described in example 80-4).

1H-NMR (CDCl3+CD3OD) : for 7.12 (m, 3H), 7,20-7,31 (m, 3H), 7,50 (d, 1H), 7,68 (d, 1H), 7,76 (d, 1H).

106-3) 3-(Morpholine-4-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrol

Specified in the title compound is obtained in yield of 99% according to the same method described in example 80-5), from the compound obtained according to example 106-2), and the research.

1H-NMR (CDCl3) : 2,68-3,62 (Shir.s, 8H), to 6.88 (s, 1H), 7,20 (s, 1H), 7,30 to 7.62 (m, 4H), 7,78 (d, 1H), a 7.85 (d, 1H), 8,08 (d, 1H), 10,34 (s, 1H).

106-4) 1-[2-(1H-Imidazol-1-yl)ethyl] -3-(morpholine-4-yl)-carbonyl-4-(naphthalene-1-yl)-1H-pyrrol

Specified in the title compound poluchauyut in 51% yield by the interaction of the compound obtained according to example 106-1), with the compound obtained according to example 106-3), in accordance with the same method described in example 44-3).

1H-NMR (CDCl3) : 2,20-3,72 (Shir.with, N), 7,20 (s, 1H), 7,40-of 7.55 (m, 8H), of 7.82 (d, 1H), 7,88 (d, 1H), with 8.05 (d, 1H).

FAB MS: 401 (M+1).

EXAMPLE 107: Synthesis of (S)-1-[3-(1H-the 3-Etoxycarbonyl-4-(naphthalene-1-yl)-1-[3-(1-trityl-1H-imidazol-4-yl)allyl]-1H-pyrrol

Specified in the title compound is obtained in yield of 85% by the interaction of the compound obtained according to example 80-2), and the compound obtained according to preparation example 30-4), using the same technique described in example 44-3).

1H-NMR (Dl3) : of 0.82 (t, 3H), of 3.95 (q, 2H), 4, 67 (s, 2H), 6,23 (d, 1H), 6,47 (m, 1H), 6,63 (s, 1H), 7,02 (s, 1H), 7,25-7,81 (m, 24N).

107-2) 3-Etoxycarbonyl-4-(naphthalene-1-yl)-1-[3-(1-trityl-1H-imidazol-4-yl)propyl]-1H-pyrrol

300 mg (0.49 mmol) of the compound obtained according to example 107-1), dissolved in 2 ml of methanol, add a catalytic amount of Pd/C and the resulting mixture was stirred for 1 hour in a hydrogen atmosphere. The mixture is filtered to remove catalyst and the solvent is distilled off under reduced pressure. After column chromatography of the residue (eluent: dichloromethane/methanol = 98/2, V/V) obtain 246 mg (0.40 mmol, yield 82%) specified in the title compound.

1H-NMR (Dl3) : to 0.92 (t, 3H), 2,22 (m, 2H), by 2.73 (t, 2H), 4,01 (m, 4H), 6,70 (s, 1H), PC 6.82 (s, 1H), 7,32-7,73 (m, N), to $ 7.91 (m, 3H).

107-3) (S)-1-[3-(1H-imidazol-4-yl) propyl]-3-[N-(1-methoxycarbonyl-3-methylthio)propyl]carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrol

The compound obtained according to example 107-2), process in sootv. Then, the thus obtained product interacts with the methyl ester of (L)-methionine in accordance with the same method as described in example 80-5), with the formation specified in the title compound with a yield of 29%.

1H-NMR (Dl3) : of 1.65(m, 2H), 1,90 (s, 3H), 2,12 (m, 2H), 2,31 (m, 2H), by 2.73 (m, 2H), 3,54 (s, 3H), was 4.02 (m, 2H), 4,56 (m, 1H), 5,77 (d, 1H), 6,72 (s, 1H), 6.90 to (s, 1H), 7,42-to 7.67 (m, 7H), 7,82 shed 8.01 (m, 5H).

FAB MS: 491 (M+1).

EXAMPLE 108: Synthesis of (S)-3-[N-(1-hydroxycarbonyl-3-methylthio) propyl]carbarnoyl-1-[3-(1H-imidazol-4-yl) -propyl]-4-(naphthalene-1-yl)-1H-pyrrole (108)

Specified in the title compound is obtained in yield of 95% according to the method similar to those shown in example 81, except that the use of the compound obtained according to example 107-3).

1H-NMR (Dl3) : of 1.57 (m, 2H), of 1.88 (s, 3H), of 2.08 (m, 2H), to 2.29 (m, 2H), 2,77 (m, 2H), 4,12 (m, 2H), 4,49 (m, 1H), 5,69 (d, 1H), 6,77 (s, 1H), 6,92 (s, 1H), 7,34-7,58 (m, 7H), 7,80-7,89 (m, 5H).

FAB MS: 477 (M+1).

EXAMPLE 109: Synthesis of 1-[3-(1H-imidazol-4-yl)propyl] -3-(morpholine-4-yl)carbonyl-4- (naphthalene-1-yl) -1H-pyrrole (109)

Specified in the title compound is obtained in yield of 42% according to the method similar to those shown in example 107-3), except that the use of morpholine and connection, polucen the 4 (s, 3H), of 3.96 (m, 2H), 6,74 (d, 1H), 6,76 (s, 1H), 7,07 (s, 1H), 7,33 (t, 1H), was 7.36-to 7.50 (m, 4H), 7,76 (d, 1H), to 7.84 (d, 1H), 8,08 (d, 1H).

FAB MS: 415 (M+1).

EXAMPLE 110: Synthesis of 1-[1-(4-cyanobenzyl) -1H-imidazol-5-yl]methyl-3- [N- (2-methoxyethyl) -N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (110)

110-1) 3-N-(2-Methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrol

100 mg (0.42 mmol) of the compound obtained according to example 106-2), and 38 mg (0.4 mmol) of N-(2-methoxyethyl)-N-methylamine interact according to the method similar to that used in example 80-5), with the formation of 110 mg (0.35 mmol, yield 85%) specified in the title compound.

1H-NMR (CDCl3) : of 2.21 (s, 3H), 2,64 (Shir.s, 1H), 2,75 (Shir. s, 1H), to 3.02 (s, 3H), 3,13 (Shir.s, 3H), 3,32 (Shir.s, 1H), 6,72 (s, 1H), 7,05 (m, 2H), 7,21 (m, 2H), 7,54 (m, 1H), 7,78 (m, 2H), of 8.04 (d, 1H), 8,78 (Shir.s, 1H).

110-2) 1-[1-(4-Cyanobenzyl)-1H-imidazol-5-yl] methyl-3- [N-(2-methoxyethyl)-N-methyl]carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrol

98 mg (0.32 mmol) of the compound obtained according to example 110-1), and 85 mg (0.32 mmol) of the compound obtained according to preparation example 29-5), interact according to the method similar to that used in example 44-3), with the formation of 115 mg (0.23 mmol, yield 72%) specified in the title compound.

1H-NMR (Dl3) : to 2.41 (s, 3H), 2,75 (8 (d, 1H), of 8.06 (d, 1H).

FAB MS: 504 (M+1).

EXAMPLE 111: Synthesis of 1-[1-(4-bromobenzyl)-1H-imidazol-5-yl]methyl-3- [N- (2-methoxyethyl) -N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (111)

105 mg (0.29 mmol) of the compound obtained according to example 110-1), and 78 mg (0.29 mmol) of the compound obtained according to preparation example 32-2) interact according to the method similar to that used in example 44-3), with the formation of 121 mg (0.21 mmol, 75% yield) specified in the title compound.

1H-NMR (Dl3) : is 2.37 (s, 3H), 2,72 (Shir.s, 2H), 3.04 from (s, 3H), 3.15 in (Shir. s, 1H), 3,31 (Shir.s, 1H), 4.95 points (s, 2H), 5,10 (s, 2H), to 6.67 (s, 1H), 7,11 (s, 1H), 7.23 percent-of 7.65 (m, 10H), 7,81 (d, 1H), 7,89 (d, 1H), 8,02 (d, 1H).

FAB MS: 557 (M+1).

EXAMPLE 112: Synthesis of 1-[1-(4-bromobenzyl)-1H-imidazol-5-yl] methyl-3-(morpholine-4-yl)carbonyl-4- (naphthalene-1-yl)-1H-pyrrole (112)

100 mg (0.33 mmol) of the compound obtained according to example 106-3), and 105 mg (0.33 mmol) of the compound obtained according to preparation example 32-2) interact according to the method similar to that used in example 44-3), with the formation of 130 mg (0.23 mmol, 71% yield) specified in the title compound.

1H-NMR (Dl3) : 2,04 (Shir.s, 2H), 2,25 (Shir.s, 1H), 3,03 (Shir.s, 5H), is 4.93 (s, 2H), 5,07 (s, 2H), 6,62 (s, 1H), 7,10 (m, 3H), 7,29 (m, 2H), 7,41 (m, 3H), 7.6 for the azole-5-yl] methyl-3-(morpholine-4-yl) thiocarbonyl-4-(naphthalene-1-yl)-1H-pyrrole (113)

20 mg (0.04 mmol) of the compound obtained according to example 104, and 18 mg of 2,4-bis(phenylthio)-1, 3-dithia-2,4-diphosphate-2,4-disulfide dissolved in 1 ml of tetrahydrofuran and the resulting mixture was stirred at room temperature for 3 hours. To the reaction solution was added 2 ml of saturated solution of sodium bicarbonate. The resulting mixture was extracted with ethyl acetate and dried over anhydrous sodium sulfate. The organic solvent is distilled off under reduced pressure and the residue is subjected to column chromatography (eluent: dichloromethane/methanol = 9/1, V/V) to give 9 mg (0,017 mmol, yield 43%) specified in the title compound.

1H-NMR (Dl3) : 1,88 (Shir.s, 2H), 2,64 (Shir.C, 6N), a 4.86 (s, 2H), free 5.01 (s, 2H), to 6.67 (s, 1H), 7,14 (m, 3H), 7,26-7,58 (m, 8H), 7,81 (m, 2H), 8,03 (d, 1H).

FAB MS: 518 (M+1).

EXAMPLE 114: Synthesis of 3- [N- (2-methoxyethyl) -N-methyl] -carbarnoyl-1-(1-methyl-1H-imidazol-5-yl) methyl-4-(naphthalene-1-yl)-1H-pyrrole (114)

114-1) of 4- (Naphthalene-1-yl)-1H-pyrrole-3-carboxylic acid

2.64 g (10 mmol) of the compound obtained according to example 80-2), dissolved in 50 ml of 50% ethanol and added 2.24 g (40 mmol) of potassium hydroxide. The reaction mixture is heated under reflux for 7 hours, cooled to room temperature, bring Mat under reduced pressure and gain of 1.62 g (8.1 mmol, yield 81%) specified in the title compounds. Thus obtained product is used in further reactions without additional purification.

1H-NMR (CDCl3) : 6,60 (s, 1H), 7,32-7,49 (m, 5H), 7,54 (s, 1H), to 7.84 (m, 2H), 9,92 (s, 1H).

FAB (M+H): 236.

114-2) 3-[N-(2-Methoxyethyl) -N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrol

234 mg (1 mmol) of the compound obtained according to example 114-1), dissolved in 2 ml of dimethylformamide and then added 230 mg (1.2 mmol) of EDC, 101 mg (1 mmol) of triethylamine and 162 mg (1.2 mmol) NOWT. The resulting mixture was stirred at 0oC for 5 minutes. To the reaction solution was added 124 mg (1 mmol) of the hydrochloride of N-(2-methoxyethyl)-N-methylamine, and then stirred at room temperature for 5 hours. The solvent is removed by distillation under reduced pressure, and then to the obtained residue, add 10 ml saturated potassium carbonate solution. The resulting solution was extracted with 20 ml ethyl acetate, washed with 10 ml of 1 N. aqueous solution chloroethanol acid, washed with an aqueous solution of sodium chloride and water, dried over anhydrous sodium sulfate and evaporated, getting 246 mg (0.8 mmol) specified in the title compound.

1H-NMR (Dl3) : 2,46 (s, 2H), 2,80 is 3.40 (m, 7H), 3,40 (the Il-1H-imidazol-5-yl)methyl-3- [N-(2-methoxyethyl)N-methyl] carbarnoyl-4- (naphthalene-1-yl)-1H-pyrrol

618 mg (2.0 mmol) of the compound obtained according to example 114-2), dissolved in 10 ml of dimethylformamide and then added at 0oWith 264 mg (6.6 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture 367 mg (2.2 mmol) of the hydrochloride of 5-chloromethyl-1-methylimidazole and thus obtained mixture was stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then this mixture is twice extracted with 20 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V), getting 644 mg (yield 80%) specified in the title compound.

1H-NMR (Dl3) : 2,42 (s, 2H), 2,71 (m, 1H), 3,10 (Shir.C, 6N), 3,30 (Shir. s, 1H), 3,50 (s, 3H), 5,09 (s, 2H), 6,70 (d, 1H), 7,05 (s, 1H), 7,15 (s, 1H), 7,30-7,49 (m, 4H), 7,72 (d, 1H), to 7.84 (d, 2H), 8,08 (d, 1H).

FAB (M+H): 403.

EXAMPLE 115: Synthesis of 1- (1-isobutyl-1H-imidazol-5-yl) -methyl-3- [N- (2-methoxyethyl) -N-methyl] carbarnoyl-4-(naphthalene-1-yl) -1H-pyrrole (115)

618 mg (2.0 mmol) of the compound obtained according to example 114-2), dissolved in 10 ml of dimethylformamide, add at 0oWith 264 mg (6.6 mmol) of sodium hydride (60%), then cm is sustained fashion to example 33-2), and thus obtained mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 20 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 667 mg (75% yield) specified in the title compound.

1H-NMR (CDCl3) : 0,90 (d, 6N), a 1.75 (m, 1H), 2,41 (Shir.s, 2H), 2,72 (Shir.s, 1H), 3,01 (Shir.C, 6N), 3,32 (Shir.s, 1H), 3,62 (d, 2H), 5,13 (s, 2H), 6,72 (s, 1H), to 7.09 (s, 1H), 7,19 (s, 1H), 7,30-7,49 (m, 4H), 7,78 (d, 1H), to 7.84 (d, 2H), 8,08 (d, 1H).

FAB (M+H): 445.

EXAMPLE 116: Synthesis of 1-(1-cyclohexylmethyl-1H-imidazol-5-yl)methyl-3-[N-(2-methoxyethyl) -N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (116)

618 mg (2.0 mmol) of the compound obtained according to example 114-2), dissolved in 10 ml of dimethylformamide, add at 0oWith 264 mg (6.6 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture 647 mg (2.2 mmol) of the compound obtained according to preparation example 34-2), and thus obtained mixture was stirred at room temperature for 5 hours. Solvent organette, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V), getting 726 mg (75% yield) specified in the title compound.

1H-NMR (CDCl3) / : 0.87 (m, 2H), 1,12 (m, 3H), 1,30 (Shir.s, 1H), of 1.40 and 1.80 (m, 5H), 2,41 (Shir.s, 2H), 2,72 (Shir.s, 1H), 3,01 (Shir.C, 6N), 3,32 (Shir. s, 1H), 3,63 (d, 2H), 5,09 (s, 2H), 6,72 (s, 1H), to 7.09 (s, 1H), 7,19 (s, 1H), 7,25 (s, 1H), 7,30-7,49 (m, 3H), 7,78 (d, 1H), 7,83 (d, 2H), 8,08 (d, 1H).

FAB (M+H): 485.

EXAMPLE 117: Synthesis of 3-[N-(2-methoxyethyl)-N-methyl]-carbarnoyl-4- (naphthalene-1-yl) -1-(1-pentyl-1H-imidazol-5-yl)methyl-1H-pyrrole (117)

618 mg (2.0 mmol) of the compound obtained according to example 114-2), dissolved in 10 ml of dimethylformamide, add at 0oWith 264 mg (6.6 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture 429 mg (2.2 mmol) of the compound obtained according to preparation example 35-2), and obtained the mixture is then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. The resulting mixture was twice extracted with 20 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel1H-NMR (CDCl3) : of 0.90 (t, 3H), 1,08 (Shir.s, 2H), 1,30 (m, 2H), 1,45 (m, 2H), 2,41 (Shir.s, 2H), 2,72 (Shir.s, 1H), 3,01 (Shir.C, 6N), 3,32 (Shir.s, 1H), 3,63 (t, 2H), 5,09 (s, 2H), 6,72 (s, 1H), to 7.09 (s, 1H), 7,19 (s, 1H), 7,25 (s, 1H), 7,30-7,49 (m, 3H), 7,78 (d, 1H), 7,83 (d, 2H), 8,08 (d, 1H).

FAB (M+H): 459.

EXAMPLE 118: Synthesis of 3-[N-(2-methoxyethyl) -N-methyl] -carbarnoyl-4-(naphthalene-1-yl) -1-(1-octyl-1H-imidazol-5-yl)methyl-1H-pyrrole (118)

618 mg (2.0 mmol) of the compound obtained according to example 114-2), dissolved in 10 ml of dimethylformamide, add at 0oWith 264 mg (6.6 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture 508 mg (2.2 mmol) of the compound obtained according to preparation example 36-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 20 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 760 mg (yield 76%) specified in the title compound.

1H-NMR (Dl3) : of 0.87 (t, 3H), 1,17 (Shir.s, 2H), 1,30 (Shir s, 10H), of 1.44 (m, 2H), 2,41 (Shir.s, 2H), 2,72 (Shir.s, 1H), 3,01 (Shir.C, 6N), 3,32

FAB (M+H): 501.

EXAMPLE 119: Synthesis of 1-(1-decyl-1H-imidazol-5-yl) methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (119)

618 mg (2.0 mmol) of the compound obtained according to example 114-2), dissolved in 10 ml of dimethylformamide, add at 0oWith 264 mg (6.6 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture 567 mg (2.2 mmol) of the compound obtained according to preparation example 37-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 20 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 667 mg (75% yield) specified in the title compound.

1H-NMR (Dl3) : of 0.87 (t, 3H), 1,17 (Shir.s, 2H), 1,30 (Shir, 14N), the 1.44 (m, 2H), 2,41 (Shir.s, 2H), 2,72 (Shir.s, 1H), 3,01 (Shir.C, 6N), 3,32 (Shir.s, 1H), 3,62 (t, 2H), 5,0 (s, 2H), 6,72 (s, 1H), to 7.09 (s, 1H), 7,19 (s, 1H), 7,25 (s, 1H), 7,30-7,49 (m, 3H), 7,78 (d, 1H), 7,83 (d, 2H), 8,08 (d, 1H).

FAB (M+H): 529.

EXAMPLE 120: Synthesis of 3-[N-(2-methoxyethyl)-N-methyl] -carbarnoyl-1-[1-(3-methylbutyl)-1H-imidazol-varaut in 10 ml of dimethylformamide, add at 0oWith 264 mg (6.6 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture 429 mg (2.2 mmol) of the compound obtained according to preparation example 38-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 20 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 667 mg (75% yield) specified in the title compound.

1H-NMR (Dl3) : of 0.91 (d, 6N), 1,31 (kV, 2H), 1,67 (m, 1H), 2,41 (Shir. s, 2H), 2,72 (Shir.s, 1H), 3,01 (Shir.C, 6N), 3,32 (wide s, 1H), 3,62 (t, 2H), 5,09 (s, 2H), 6,72 (s, 1H), to 7.09 (s, 1H), 7,19 (s, 1H), 7,25 (s, 1H), 7,30-7,49 (m, 3H), 7,78 (d, 1H), 7,83 (d, 2H), 8,08 (d, 1H).

FAB (M+H): 459.

EXAMPLE 121: Synthesis of 1- [1- (2-methoxyethyl) -1H-imidazol-5-yl]methyl-3-[N-(2-methoxyethyl)-N-methyl]carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (121)

618 mg (2.0 mmol) of the compound obtained according to example 114-2), dissolved in 10 ml of dimethylformamide, add at 0oWith 264 mg (6.6 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To mesh then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 20 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 667 mg (75% yield) specified in the title compound.

1H-NMR (Dl3) : 2,41 (Shir.s, 2H), 2,72 (Shir.s, 1H), 3,01 (Shir.C, 6N), 3,32 (Shir. s, 1H), 3,37(s, 3H), of 3.45 (t, 2H), 3,63 (t, 2H), 5,09 (s, 2H), 6,72 (s, 1H), to 7.09 (s, 1H), 7,19 (s, 1H), 7,25 (s, 1H), 7,30-7,49 (m, 3H), 7,78 (d, 1H), 7,83 (d, 2H), 8,08 (d, 1H).

FAB (M+H): 447.

EXAMPLE 122: Synthesis of 3-[N-(2-methoxyethyl)-N-methyl] -carbarnoyl-1-[1-(3-methoxypropyl) -1H-imidazol-5-yl]-methyl-4-(naphthalene-1-yl) -1H-pyrrole (122)

618 mg (2.0 mmol) of the compound obtained according to example 114-2), dissolved in 10 ml of dimethylformamide was added when 0oWith 264 mg (6.6 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture 459 mg (2.2 mmol) of the compound obtained according to preparation example 40-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resultant mixture of double-extras is adopted on silica gel (eluent: dichloromethane/methanol=90/10, about/about), getting 683 mg (yield 70%) specified in the title compound.

1H-NMR (Dl3) : 1,71 (m, 2H), 2,41 (Shir.s, 2H), 2,72 (wide s, 1H), 3,01 (Shir. C, 6N), and 3.31 (s, 3H), 3,32 (Shir.s, 1H), 3,48 (t, 2H), 3,63 (t, 2H), 5,09 (s, 2H), 6,72 (s, 1H), to 7.09 (s, 1H), 7,19 (s, 1H), 7,25 (s, 1H), 7,30-7,49 (m, 3H), 7,78 (d, 1H), 7,83 (d, 2H), 8,08 (d, 1H).

FAB (M+H): 461.

EXAMPLE 123: Synthesis of 1-[1-(3-ethoxypropan)-1H-imidazol-5-yl]methyl-3- [N- (2-methoxyethyl) -N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (123)

618 mg (2.0 mmol) of the compound obtained according to example 114-2), dissolved in 10 ml of dimethylformamide, add at 0aboutC 264 mg (6.6 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture 459 mg (2.2 mmol) of the compound obtained according to preparation example 41-2), and thus obtained mixture was stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. The resulting mixture was twice extracted with 20 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 712 mg (71% yield) specified in the title compound.

1H-NMR (Dl3) : 1,20 (t (c, 1H), 7,25 (c, 1H), 7,30-7,49 (m, 3H), 7,78 (d, 1H), 7,83 (d, 2H), 8,08 (d, 1H).

FAB (M+H): 475.

EXAMPLE 124: Synthesis of 1-[1-(3-isopropoxyphenyl)-1H-imidazol-5-yl]methyl-3- [N- (2-methoxyethyl) -N-methyl] -carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (124)

618 mg (2.0 mmol) of the compound obtained according to example 114-2), dissolved in 10 ml of dimethylformamide, add at 0oWith 264 mg (6.6 mmol) of sodium hydride (60%), after which the mixture is stirred for 5 minutes. To this mixture 459 mg (2.2 mmol) of the compound obtained according to preparation example 42-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 20 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V), getting 751 mg (yield 73%) specified in the title compound.

1H-NMR (Dl3) : of 1.16 (d, 6N), to 1.70 (m, 2H), 2,41 (Shir.s, 2H), 2,72 (Shir.s, 1H), 3,01 (Shir.C, 6N), 3,32 (Shir.s, 1H), 3,45-3,55 (m, 3H), 3,63 (t, 2H), 5,09 (s, 2H), 6,72 (s, 1H), to 7.09 (s, 1H), 7,19 (s, 1H), 7,25 (s, 1H), 7,30-7,49 (m, 3H), 7,78 (d, 1H), 7,83 (d, 2H), 8,08 (d, 1H).

FAB (M+H): 489.

EXAMPLE 125: Synthesis of 1-[1-(4-br is piperazin-1-yl]carbonyl-4-(naphthalene-1-yl)-1H-pyrrol

Specified in the title compound are obtained from the output 90% according to the method similar to those shown in example 80-5), from the compound obtained according to example 106-2), and methylpiperazine.

1H-NMR (Dl3) : 1,15 (W, 2H), 1,87 (W, 2N), with 1.92 (s, 3H), 2,96 (W, 2H), 3,41 (W, 2H), 6,83 (s, 1H), to 7.09 (s, 1H), was 7.36-7,42 (m, 4H), 7,73 (d, 1H), of 7.75 (d, 1H), 8,10 (d, 1H), 10,52 (s, 1H).

FAB (M+H): 320.

125-2) 1-[1-(4-Bromobenzyl)-1H-imidazol - 5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrol

64 mg (0.2 mmol) of the compound obtained according to example 125-1), dissolved in 2 ml of dimethylformamide, add at 0oWith 26 mg (0.66 mmol) of sodium hydride, and then the mixture is stirred for 5 minutes. To the mixture is added 66 mg (0.22 mmol) of the compound obtained according to preparation example 32-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 91 mg (yield 80%) specified in the title compound,55 (C, 1H), 6,79 (d, 2H), 6,97 (s, 1H), 7,16 (s, 1H), was 7.36 (d, 1H), was 7.36-7,39 (m, 5H), to 7.50 (s, 1H), 7,71 (d, 1H), 7,79 (d, 1H), to 7.93 (d, 1H).

FAB (M+H): 568.

EXAMPLE 126: Synthesis of 1-[1-(4-Chlorobenzyl) -1H-imidazol-5-yl]methyl-3-[4-methylpiperazin-1-yl] carbonyl-4- (naphthalene-1-yl)-1H-pyrrole (126)

64 mg (0.2 mmol) of the compound obtained according to example 125-1), dissolved in 2 ml of dimethylformamide, add at 0oWith 26 mg (0.66 mmol) of sodium hydride, and then the mixture is stirred for 5 minutes. To the mixture is added 55 mg (0.22 mmol) of the hydrochloride of 1-(4-Chlorobenzyl)-5-chloromethylthiazole obtained according to the method similar to that described in preparation example 32, and thus obtained mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. The resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 77 mg (yield 57%) specified in the title compound.

1H-NMR (Dl3) : 1,15 (Shir, 3H), 1.77 in (W, 2N), of 1.86 (s, 3H), 2,82 (W, 2H), 3,28 (W, 2N), to 4.92 (s, 2H), 4.95 points (s, 2H), 6,60 (s, 1H), 6,91 (d, 2H), 6,01 (s, 1H), 7,22 (s, 1H), 7,26 and 7.36 (m, 3H), of 7.36-of 7.48-imidazol-5-yl]methyl-3-[N-(2-methoxyethyl)-N-methyl]carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (127)

62 mg (0.2 mmol) of the compound obtained according to example 114-2), dissolved in 2 ml of dimethylformamide, add at 0oWith 26 mg (0.66 mmol) of sodium hydride, and then the mixture is stirred for 5 minutes. To the mixture of 51 mg (0.22 mmol) of the hydrochloride of 1-(4-terbisil)-5-chloromethylthiazole obtained according to the method similar to that described in preparation example 32, and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 77 mg (yield 80%) specified in the title compound.

1H-NMR (Dl3) : 2,12 (Shir, 3H), 2,72 (W, 1H), 3,00-3,20 (m, 5H), 3,32 (s, 1H), 3,98 (s, 2H), equal to 4.97 (s, 2H), only 6.64 (s, 1H), 6,95-7,10 (m, 5H), 7,21 (s, 1H), 7,33 (m, 1H), 7,40-7,51 (m, 3H), 7,66 (s, 1H), 7,74 (d, 1H), 7,81 (d, 1H), 8,08 (d, 1H).

FAB (M+H): 497.

EXAMPLE 128: Synthesis 1-1-(4-terbisil)-1H-imidazol-5-yl]methyl-3- [4-methylcobalamin-1-yl] carbonyl-4- (naphthalene-1-yl)-1H-pyrrole (128)

64 mg (0.2 mmol) of the compound obtained according to example 125-1), the solution is ut for 5 minutes. To the mixture of 51 mg (0.22 mmol) of the hydrochloride of 1-(4-terbisil)-5-chloromethylthiazole obtained according to the method similar to that described in preparation example 32, and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column of chromatogra-Sofia on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 79 mg (yield 80%) specified in the title compound.

1H-NMR (Dl3) : 1,15 (W, 2H), 1.77 in (W, 2N), of 1.86 (s, 3H), 2,82 (W, 2H), 3,28 (W, 2N), to 4.92 (s, 2H), equal to 4.97 (s, 2H), 6,60 (s, 1H), 6,93 (d, 2H), 6,01 (s, 1H), 7,22 (s, 1H), 7,25 was 7.36 (m, 3H), of 7.36-7,47 (m, 2H), EUR 7.57 (s, 1H), 7,78 (d, 1H), 7,82 (d, 1H), to 7.93 (d, 1H).

FAB (M+H): 508.

PREPARATION EXAMPLE 43: Synthesis of 5-chloromethyl-1-(4-methoxybenzyl)imidazole hydrochloride

43-1) 5-Hydroxymethyl-1-(4-methoxybenzyl)imidazol

Specified in the title compound is obtained in 30% yield using the same method as in preparation example 31-1), using as starting compounds dihydroxyacetone hydrochloride and 4-methoxybenzylamine.

1

43-2) 5-Chloromethyl-1-(4-methoxybenzyl)imidazole hydrochloride

Specified in the title compound is obtained in yield of 95% according to the same method as in preparation example 28-2), with the exception that as the starting compound using the compound obtained in preparatory example 43-1).

PREPARATION EXAMPLE 44: Synthesis of 5-chloromethyl-1-(3-Chlorobenzyl)imidazole hydrochloride

44-1) 5-Hydroxymethyl-1-(3-Chlorobenzyl)imidazol

Specified in the title compound is obtained in yield of 60% according to the same method as in preparation example 31-1), using as starting compounds dihydroxyacetone hydrochloride and 3-chlorobenzylamino.

1H-NMR (Dl3+CD3OD) : 3,81 (s, 3H), 4,47 (s, 2H), 5.25 in (s, 2H), 6,99 (s, 1H), 7,05 (m, 1H), 7,14 (s, 1H), 7,30 (m, 2H), to 7.61 (s, 1H).

FAB (M+H): 239,5.

44-2) 5-Chloromethyl-1-(3-Chlorobenzyl)imidazole hydrochloride

Specified in the title compound is obtained in yield of 92% according to the same method as in preparation example 28-2), with the exception that as the starting compound using the compound obtained in preparatory example 44-1).

PREPARATION EXAMPLE 45: Synthesis of 5-chloromethyl-1-(2-Chlorobenzyl)imidazole hydrochlo the m 60% according to the same method, as in preparatory example 31-1), using as starting compounds dihydroxyacetone hydrochloride and 2-chlorobenzylamino.

1H-NMR (Dl3) : 3,24 (s, 2H), of 4.44 (s, 2H), 5,26 (s, 2H), 6,78 (d, 1H), 6.90 to (s, 1H), 7,15 (m, 1H), 7,21 (m, 1H), 7,34 (d, 1H), 7,38 (s, 1H).

FAB (M+H): 239,5.

45-2) 5-Chloromethyl-1-(2-chlorbenzyl)imidazole hydrochloride

Specified in the title compound is obtained in yield of 92% according to the same method as in preparation example 28-2), with the exception that as the starting compound using the compound obtained in preparatory example 45-1).

PREPARATION EXAMPLE 46: Synthesis of 5-chloromethyl-1-(2-terbisil)imidazole hydrochloride

46-1) 5-Hydroxymethyl-1-(2-terbisil)imidazol

Specified in the title compound is obtained in 71% yield according to the same method as in preparation example 31-1), using as starting compounds dihydroxyacetone hydrochloride and 2-forbindelsen.

1H-NMR (Dl3) : of 3.25 (s, 2H), of 4.45 (s, 2H), 5,27 (s, 2H), 6,79 (d, 1H), 7,17 (m, 1H), 7,26 (m, 1H), 7,35 (d, 1H), 7,38 (s, 1H).

FAB (M+H): 223.

46-2) 5-Chloromethyl-1-(2-terbisil)imidazole hydrochloride

Specified in the title compound is obtained in yield 93% according to elswout connection, obtained in preparatory example 46-1).

PREPARATION EXAMPLE 47: Synthesis of 5-chloromethyl-1-(4-methylbenzyl)imidazole hydrochloride

47-1) 5-Hydroxymethyl-1-(4-methylbenzyl)imidazol

Specified in the title compound is obtained in yield of 65% according to the same method as in preparation example 31-1), using as starting compounds dihydroxyacetone hydrochloride and 4-methylbenzylamine.

1H-NMR (Dl3) : 2,32 (s, 3H), 4,50 (s, 2H), 5,19 (s, 2H), 6,95 (s, 1H), 7,05 (d, 2H), 7,15 (d, 2H), to 7.59 (s, 1H).

FAB (M+H): 219.

47-2) of 5-Chloromethyl-1-(4-methylbenzyl)imidazole hydrochloride

Specified in the title compound is obtained in yield of 91% according to the same method as in preparation example 28-2), with the exception that as the starting compound using the compound obtained in preparatory example 47-1).

PREPARATION EXAMPLE 48: Synthesis of 5-chloromethyl-1-(3-methylbenzyl)imidazole hydrochloride

48-1) 5-Hydroxymethyl-1-(3-methylbenzyl)imidazol

Specified in the title compound is obtained in yield of 60% according to the same method as in preparation example 31-1), using as starting compounds dihydroxyacetone hydrochloride and 3-methylbenzylamine.

FAB (M+H): 219.

48-2) 5-Chloromethyl-1-(3-methylbenzyl)imidazole hydrochloride

Specified in the title compound is obtained in yield of 92% according to the same method as in preparation example 28-2, with the exception that as the starting compound using the compound obtained in preparatory example 48-1).

EXAMPLE 129: Synthesis of 1-[1-(4-methoxybenzyl)-1H-imidazol-5-yl] methyl-3- [N- (2-methoxyethyl) -N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (129)

62 mg (0.2 mmol) of the compound obtained according to example 114-2), dissolved in 2 ml of dimethylformamide, add at 0oWith 26 mg (0.66 mmol) of sodium hydride, and then the mixture is stirred for 5 minutes. To the mixture of 60 mg (0.22 mmol) of the compound obtained according to preparation example 43-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 77 mg (yield 76%) specified in the title compound.

FAB (M+H): 509, C31H32N4ABOUT3.

EXAMPLE 130: Synthesis of 1-[1-(4-methoxybenzyl)-1H-imidazol-5-yl]methyl-3- (4-methylpiperazin-1-yl) carbonyl-4-(naphthalene-1-yl) -1H-pyrrole (130)

64 mg (0.2 mmol) of the compound obtained according to example 125-1), dissolved in 2 ml of dimethylformamide, add at 0oWith 26 mg (0.66 mmol) of sodium hydride, and then the mixture is stirred for 5 minutes. To the mixture of 60 mg (0.22 mmol) of the compound obtained according to preparation example 43-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 79 mg (yield 80%) specified in the title compound.

1H-NMR (Dl3) : 1,06 (W, 2H), 1,72 (m, 2H), equal to 1.82 (s, 3H), 2,86(W, 2H), 3,28 (W, 2N in), 3.75 (s, 3H), 4,91 (s, 2H), is 4.93 (s, 2H), 6,63 (d, 1H), PC 6.82 (d, 2H), 6.90 to-7,07 (m, 3H), of 7.23 (s, 1H), 7,33 (m, 1H), 7,44 (m, 2N), to 7.61 (s, 1H), of 7.75 (d, 1H), 7,82 (d, 1H), 8,08 (d, 1H).
64 mg (0.2 mmol) of the compound obtained according to example 125-1), dissolved in 2 ml of dimethylformamide, add at 0oWith 26 mg (0.66 mmol) of sodium hydride, and then the mixture is stirred for 5 minutes. To the mixture is added 61 mg (0.22 mmol) of the compound obtained according to preparation example 44-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 75 mg (71% yield) specified in the title compound.

1H-NMR (Dl3) : 1,02 (W, 2H), 1,78 (W, 2N), of 1.87 (s, 3H), 2,84 (W, 2H), 3,30 (W, 2H), only 6.64 (m, 2H), 7,01 (s, 1H), 7,10-7,30 (m, 4H), 7,31-7,47 (m, 4H), 7,53 (s, 1H), 7,73 (d, 1H), 7,81 (d, 1H), of 7.96 (d, 1H).

FAB (M+H): 524, C31H30N5Cl.

EXAMPLE 132: Synthesis of 1-[1-(3-Chlorobenzyl)-1H-imidazol-5-yl] methyl-3- [N- (2-methoxyethyl) -N-methyl]carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (132)

62 mg (0.2 mmol) of the compound obtained according to example 114-2), dissolved in 2 ml of dimethylformamide, add at 0oWith caedite, obtained according to preparation example 44-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 80 mg (yield 78%) specified in the title compound.

1H-NMR (Dl3) : 2,39 (W, 2H), 2,71 (m, 1H), 3,02 (Shir, 4H), 3,09 (W, 1H), 3,32 (W, 1H), 4.09 to (W, 1H), equal to 4.97 (s, 2H), 5,04 (s, 2H), only 6.64 (d, 1H), 6.90 to (m, 1H), 7,02 (d, 2H), 7,20-7,40 (m, 4H), 7,40-of 7.60 (m, 3H), 7,74 (d, 1H), 7,76 (d, 1H), a 7.85 (s, 1H), 8,04 (d, 1H).

FAB (M+H): 513, C30H29N4ABOUT2Cl.

EXAMPLE 133: Synthesis of 1-[1-(2-Chlorobenzyl)-1H-imidazol-5-yl]methyl-3-(4-methylpiperazin-1-yl) carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (133)

64 mg (0.2 mmol) of the compound obtained according to example 125-1), dissolved in 2 ml of dimethylformamide, add at 0oWith 26 mg (0.66 mmol) of sodium hydride, and then the mixture is stirred for 5 minutes. To the mixture is added 61 mg (0.22 mmol) of the compound obtained according to preparation example 45-2), and the resulting mixture is then displaced the add 10 ml of water. Then the resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 80 mg (yield 76%) specified in the title compound.

1H-NMR (Dl3) : 1,06 (W, 2H), 1,80 (W, 2N), of 1.86 (s, 3H), 2,84 (W, 2H), 3,30 (W, 2N), to 4.98 (s, 2H), 5,11 (s, 2H), 6,63 (m, 2H), 7,01 (s, 1H), 7,12-7,30 (m, 4H), 7,32-7,46 (m, 4H), 7,53 (s, 1H), 7,73 (d, 1H), 7,81 (d, 1H), of 7.97 (d, 1H).

FAB (M+H): 524, C31H30N5OCl.

EXAMPLE 134: Synthesis of 1-[1-(2-Chlorobenzyl)-1H-imidazol-5-yl]methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (134)

62 mg (0.2 mmol) of the compound obtained according to example 114-2), dissolved in 2 ml of dimethylformamide, add at 0oWith 26 mg (0.66 mmol) of sodium hydride, and then the mixture is stirred for 5 minutes. To the mixture is added 61 mg (0.22 mmol) of the compound obtained according to preparation example 45-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, the UPA is mg (75% yield) specified in the title compound.

1H-NMR (Dl3) : 2,37 (W, 2N), of 2.72 (m, 1H), 3,01 (Shir, 4H), 3,10 (W, 1H), 3,32 (W, 1H), 4,18 (W, 1H), 5,04 (s, 2H), 5,17 (s, 2H), of 6.65 (d, 1H), 6,76 (1, 2N),? 7.04 baby mortality (d, 1H), 7,13-7,35 (m, 4H), of 7.36-to 7.50 (m, 4H), 7,71 (s, 1H), of 7.75 (d, 1H), 7,82 (d, 1H), 8,01 (d, 1H).

FAB (M+H): 513, C30H29N4ABOUT3Cl.

EXAMPLE 135: Synthesis of 1-[1-(2-terbisil)-1H-imidazol-5-yl]methyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (135)

64 mg (0.2 mmol) of the compound obtained according to example 125-1), dissolved in 2 ml of dimethylformamide, add at 0oWith 26 mg (0.66 mmol) of sodium hydride, and then the mixture is stirred for 5 minutes. To the mixture of 51 mg (0.22 mmol) of the compound obtained according to preparation example 46-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol= 90/10, V/V) to give 79 mg (yield 77%) specified in the title compound.

1H-NMR (Dl3) : 1,06 (W, 2H), 1,80 (W, 2N), of 1.86 (s, 3H), 2,93 (W, 2H), 3,35 (W, 2H), 5,03 (, 31H30N5OF.

EXAMPLE 136: Synthesis of 1-[1-(4-methylbenzyl)-1H-imidazol-5-yl]methyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (136)

64 mg (0.2 mmol) of the compound obtained according to example 125-1), dissolved in 2 ml of dimethylformamide, add at 0oWith 26 mg (0.66 mmol) of sodium hydride, and then the mixture is stirred for 5 minutes. To the mixture is added 57 mg (0.22 mmol) of the compound obtained according to preparation example 47-2), and thus obtained mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 81 mg (yield 80%) specified in the title compound.

1H-NMR (Dl3) : 1,09 (W, 2N) and 1.83 (W, 2N), of 1.86 (s, 3H), 2,24 (s, 3H), 2,93 (W, 2H), 3,30 (W, 2N), a 4.86 (s, 2H), 4,91 (s, 2H), 6,59 (d, 1H), 6.87 in (m, 2H), 7,01 (s, 1H), 7,07 (d, 2H), 7,15 (s, 1H), 7,25 (m, 1H), to 7.50 (m, 3H), 7,53 (s, 1H), 7,73 (d, 1H), 7,78 (d, 1H), of 7.97 (d, 1H).

FAB (M+H): 504, C32H33N5O.

EXAMPLE 137: Synthesis of 1-[1-(4-mailbee, obtained according to example 106-3), dissolved in 2 ml of dimethylformamide, add at 0oWith 26 mg (0.66 mmol) of sodium hydride, and then the mixture is stirred for 5 minutes. To the mixture is added 57 mg (0.22 mmol) of the compound obtained according to preparation example 47-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 80 mg (yield 81%) specified in the title compound.

1H-NMR (Dl3) : to 2.29 (s, 3H), 2,30-3,60 (Shir, 8H), 4,94 (s, 1H), 4,99 (s, 2H), is 6.61 (d, 1H), 6,91 (d, 1H), 7,07 (d, 1H), 7,12 (d, 2H), 7,21 (s, 1H), 7,32 (d, 1H), 7,35 is 7.50 (m, 4H), 7,71 (s, 1H), to 7.77 (d, 1H), to 7.84 (d, 1H), 7,98 (d, 1H).

FAB (M+H): 491,31H30N4O2.

EXAMPLE 138: Synthesis of 1-[1-(3-methylbenzyl)-1H-imidazol-5-yl]methyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl) -1H-pyrrole (138)

64 mg (0.2 mmol) of the compound obtained according to example 125-1), dissolved in 2 ml of dimethylformamide, add at 0oWith 26 mg (0.66 mmol) GIOChannel according to preparatory example 48-2), and the resulting mixture was then stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. Then the resulting mixture was twice extracted with 10 ml ethyl acetate, dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 74 mg (yield 73%) specified in the title compound.

1H-NMR (Dl3) : 1,06 (W, 2H), 1,80 (W, 2N), of 1.84 (s, 3H), 2.91 in (W, 2H), 3.27 to (W, 2N), a 4.86 (s, 2H), 4,89 (s, 2H), to 6.57 (d, 1H), of 6.71 (d, 1H), 6,77 (s, 1H), 6,97 (s, 1H), 7,01 (d, 1H), 7,15 (m, 2H), 7,25 (d, 1H), 7,37 (m, 3H), 7,51 (s, 1H), of 7.70 (d, 1H), 7,72 (d, 1H), 7,98 (d, 1H).

FAB (M+H): 504, C32H33N5O.

PREPARATION EXAMPLE 49: Synthesis of 3-(naphthalene-1-yl) carbonyl-1H-pyrrol

49-1) Methyl (N-methyl-1-naphthalene hydroxamate)

3,44 g (20 mmol) of 1-naphthoic acid was dissolved in 20 ml of dimethylformamide and then added 4.6 g (24 mmol) of EDC, 2,02 g (20 mmol) of triethylamine or 3.24 g (24 mmol) NOWT. The resulting mixture was stirred at 0oC for 5 minutes. To the reaction solution was added 1.85 g (20 mmol) of the hydrochloride of N, O-dimethylhydroxylamine, followed by stirring at room temperature for 5 hours sennoga potassium carbonate solution. The resulting solution was extracted with ethyl acetate. Then the organic layer is washed successively 1 N. aqueous solution chlorobutanol acid, aqueous solution of sodium chloride and water, dried over anhydrous sodium sulfate and after evaporation receive 3.04 from g (1.50 mmol) specified in the title compound.

1H-NMR (Dl3) : to 2.42 (s, 3H), 3,24 (s, 3H), 7,47 (m, 4H), to 7.67 (d, 1H), 7,74 (m, 2H).

FAB 216 (M+H).

49-2) 1-(Naphthalene-1-yl)-prop-2-EN-1-he

2,03 g (9.4 mmol) of the compound obtained according to preparation example 49-1), dissolved in 20 ml of anhydrous tetrahydrofuran and then at 0oSlowly add 20 ml of 1 n solution of vinylmania in tetrahydrofuran. The mixture is stirred at room temperature for 30 minutes and add to it 20 ml of 1 N. chloroethanol acid, then the resulting solution is extracted with 50 ml ethyl acetate. The organic layer is dried over anhydrous magnesium sulfate, then the solvent is distilled off under reduced pressure and obtain 1.63 g (9 mmol, yield 96%) specified in the title compound.

1H-NMR (Dl3) : 6,92 (m, 1H), 7,51 (m, 4H), 7,74 (d, 1H), a 7.85 (m, 2H), 7,98 (d, 1H), 8,31 (d, 1H).

49-3) 3-(Naphthalene-1-yl)carbonyl-1H-pyrrol

901 mg (5 mmol) set in 10 ml of tetrahydrofuran. Then slowly add 555 mg (5/5 mmol) of tert-butoxide potassium, dissolved in 10 ml of tetrahydrofuran, and the mixture was stirred for 30 minutes. To the reaction solution to terminate the reaction, add 10 ml of water and the solvent is distilled off under reduced pressure. To the residue is added 20 ml of water and the resulting mixture extracted with ethyl acetate, washed with aqueous solution of sodium chloride and then dried over anhydrous magnesium sulfate. The solvent is removed by distillation under reduced pressure and after column chromatography of the resulting residue on silica gel (eluent: ethyl acetate/hexane = 1/3, V/V) receive 884 mg (4 mmol, yield 80%) specified in the title compound.

1H-NMR (Dl3) : to 6.57 (s, 1H), 6,66 (s, 1H), 6,79 (s, 1H), was 7.36 (m, 3H), of 7.48 (d, 1H), to 7.77 (d, 1H), 7,82 (d, 1H), 8,04 (d, 1H), to 9.91 (s, 1H).

PREPARATORY EXAMPLE 50: Synthesis of 4-(naphthalene-1-yl)-carbonyl-3-[N-(2-methoxyethyl)-N-methylcarbamoyl]-1H-pyrrol

50-1) 4-(Naphthalene-1-yl)-4-oxo-2-butenova acid

5,88 g (60 mmol) of dry maleic acid dissolved in 100 ml of anhydrous tetrahydrofuran and the resulting mixture is cooled to -78oC. to 4.14 g (20 mmol) of 1-bromonaphthalene dissolved in 100 ml of anhydrous tetrahydrofuran and at -78oTo add to 13.8 ml of 1.6 but through a cannula to a previously prepared solution of dry maleic acid. The resulting mixture was stirred for 10 minutes, after which water is added to terminate the reaction. The solvent is distilled off under reduced pressure and the obtained residue acidified with 1 N. aqueous solution chloroethanol acid and extracted with ethyl acetate. The organic layer is washed with water and an aqueous solution of sodium chloride, then dried over anhydrous magnesium sulfate, evaporated under reduced pressure and subjected to column chromatography (eluent: ethyl acetate/hexane = 2/1, V/V) to give 1.35 g (6.0 mmol, 30% yield) specified in the title compound.

1H-NMR (Dl3) : for 6.81 (d, 1H), 7,52-the 7.65 (m, 3H), a 7.85 (d, 1H), 7,89 (d, 1H), 7,92 (d, 1H), of 8.06 (d, 1H), 8,56 (d, 1H).

50-2) N-(2-Methoxyethyl)-M-methyl-4-(naphthalene-1-yl)-4-oxo-2-butenoate

1.3 g (5.9 mmol) of the compound obtained according to preparation example 50-1), dissolved in 10 ml of dimethylformamide and then at 0oWith added 1.7 g (8.9 mmol) of EDC and 1.2 g (8.9 mmol) NOWT. The resulting mixture was stirred for 5 minutes. To the reaction solution was added 530 mg (5.9 mmol) of N-(2-methoxyethyl) -N-methylamine and 1.2 ml (8.9 mmol) of triethylamine, after which the resulting mixture was stirred at room temperature for 2 hours. The solvent is removed by distillation at reduced is. The organic layer was washed with aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate evaporated under reduced pressure. After column chromatographie the obtained residue (eluent: ethyl acetate/hexane = 1/1 V/V) to obtain 1.4 g (4.7 mmol, yield 80%) specified in the title compound.

1H-NMR (Dl3) : 3,05 (s, 3H), of 3.32 (s, 3H), of 3.54 (m, 2H), 3,65 (m, 2H), 7,40-7,58 (m, 4H), 1,71 (t, 1H), 7,89 (m, 2H), 8,03 (d, 1H), 8,54 (d, 1H).

50-3) 3-[N-(2-Methoxyethyl)-N-methyl)carbarnoyl-4-(naphthalene-1-yl)carbonyl-1H-pyrrol

1.4 g (4.7 mmol) of the compound obtained according to preparation example 50-2), and 1.0 g (5.1 mmol) of toiletrieschoice dissolved in 20 ml of tetrahydrofuran. Then add 790 g (7.0 mmol) of tert-butoxide potassium and the resulting mixture was stirred at room temperature for 3 hours. To the reaction solution to terminate the reaction, add 2 ml of water and the solvent is distilled off under reduced pressure. The residue is extracted with ethyl acetate, washed with aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The solvent is removed by distillation under reduced pressure and the residue is subjected to column chromatography (eluent: ethyl acetate/hexane = 2/3, V/V) to give 1.2 g (3.6 mmol, yield 76%) indicated 1H), 6,63 (m, 1H), 7,21-7,40 (m, 4H), 7,74 (m, 2H), 8,00 (m, 1H), 11,4 (W, 1H).

EXAMPLE 139: Synthesis of 1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl] methyl-3-(naphthalene-1-yl)carbonyl-1H-pyrrole (139)

Specified in the title compound are obtained from the output 35% according to the same method as in example 1, except using the compound obtained according to preparation example 29-5), and the compound obtained according to preparation example 49-3).

1H-NMR (Dl3) : a 4.86 (s, 2H), 4.95 points (s, 2H), of 6.52 (s, 1H), is 6.61 (s, 1H), 6.89 in (m, 3H), 7,20 (s, 1H), 7,49 (m, 6N), of 7.75 (s, 1H), 7,87 (d, 1H), 7,95 (d, 1H), 8,11 (d, 1H).

FAB: 417 (M+1).

EXAMPLE 140: Synthesis of 1-[1-(4-bromobenzyl) -1H-imidazol-5-yl] methyl-3-(naphthalene-1-yl)carbonyl-1H-pyrrole (140)

Specified in the title compound is obtained in yield of 20% according to the same method as example 1, except using the compound obtained according to preparation example 32-2), and the compound obtained according to preparation example 49-3).

1H-NMR (Dl3) : 4,84 (s, 2H), 4.92 in (s, 2H), is 6.54 (s, 1H), to 6.67 (s, 1H), 6,78 (d, 2H), 6,93 (s, 1H), 7,22 (s, 1H), 7,38 (d, 2H), 7,50 (m, 3H), 7,58 (d, 1H), 7,89 (d, 1H), 7,95 (d, 1H), 8,13 (d, 1H), 8,16 (s, 1H).

FAB: 470 (M+1).

EXAMPLE 141: Synthesis of 1-[1-(4-bromobenzyl)-1H-imidazol-5-yl]methyl-3-[N-(2-what ucaut exit 81% according to the same method, as in example 1, except using the compound obtained according to preparation example 32-2), and the compound obtained according to preparation example 50-3).

1H-NMR (Dl3) : to 2.94 (s, 3H), of 3.25 (s, 3H), 3,42 (m, 2H), 3,48 (m, 2H), 4.72 in (s, 2H), 4,78 (s, 2H), 6, 64 (m, 4H), 7,28-of 7.48 (m, 8H), 7,81 (m, 2H), 8,14 (m, 1H).

FAB: 585 (M+1).

PREPARATION EXAMPLE 51: Synthesis of ethyl-(1-naphtol-glycinate) hydrochloride

51-1) Ethyl-N-(diphenylmethylene)glycinate

In accordance with the methodology described in: M. J. O'donnell, R. L. Polt, J. Org. Chem. , 47, 2663, 1982, the hydrochloride of the ethyl ester of glycine and diphenylacetylene react with the formation of the compound indicated in the title, with a yield of 90%.

1H-NMR (Dl3) : of 1.20 (t, 3H), of 4.12 (m, 4H), 7,10-7,40 (m, 8H), to 7.59 (d, 2H).

51-2) of Ethyl 1-afterprint hydrochloride

In accordance with the method described in J. Singh, et al., Tetrahedron Lett., 34(2), 211, 1993, 1-aftercare and the compound obtained according to preparation example 51-1), react with the formation of the compound indicated in the title, with a yield of 48%.

1H-NMR (DMSO-d6) : 1,78 (s, 3H), of 3.65 (q, 1H), 3.95 to to 4.15 (m, 2H), 6,33 (s, 1H), 7,58-a 7.85 (m, 3H), of 8.15 (d, 1H), 8,31 (d, 1H), scored 8.38 (d, 2H), 8,42 (d, 2H).

PREPARATORY EXAMPLE 52: Synthesis of 2-[1-(4-harbe the following compound is obtained in yield of 50% in accordance with the methodology described in: J. M. Dener, L.-H. Zhang, H. Rapoport, J.Org Chem., 1993, 58, 1159, using as starting compounds dimer of dihydroxyacetone hydrochloride and 4-chlorobenzylamino.

1H-NMR (Dl3+CD3OD) : 4,50 (s, 2H), 5,20 (s, 2H), 6,94 (s, 1H), 7,06 (d, 2H), 7,32 (d, 2H), 7,46 (s, 1H).

52-2) 1-(4-Chlorobenzene)-5-chloromethyl-1H-imidazole hydrochloride

3.00 g (13.5 mmol) of the compound obtained according to preparation example 52-1), dissolved in 40 ml of chloroform and then slowly at 0oTo add 2,88 ml (40,5 mmol) of thionyl chloride and the resulting mixture was stirred at room temperature for 2 hours. The organic solvent is removed by distillation under reduced pressure to get to 3.64 g (of 13.1 mmol, yield 97%) specified in the title compounds. The connection used in further reactions without additional purification.

52-3) [1-(4-Chlorobenzyl)-1H-imidazol-5-yl]acetonitrile

1.2 g (4.3 mmol) of the compound obtained according to preparation example 52-2), dissolved in 10 ml of dimethyl sulfoxide and then add 1.3 g (26 mmol) of sodium cyanide. The mixture is stirred at room temperature for 6 hours. Then add 30 ml of water and the resulting mixture extracted with ethyl acetate (20 ml x 3). The organic layer is dried over basw is the connection used in further reactions without additional purification.

1H-NMR (Dl3) : 3,70 (s, 2H), 5,12 (s, 2H), to 6.88 (s, 1H), 7,34 (d, 2H), a 7.62 (d, 2H), 7,71 (s, 1H).

52-4) 2-[1-(4-Chlorobenzyl) -1H-imidazol-5-yl]thioacetamide

150 mg (0.64 mmol) of the compound obtained according to preparation example 52-3), dissolved in a solvent mixture consisting of 1 ml of pyridine and 0.3 ml of triethylamine, and then saturated with gaseous hydrogen sulfide, barbotine it through the solution for 30 minutes. The reaction solution was stirred at room temperature for 12 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. The resulting mixture was extracted with 10 ml ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 20/1, V/V) to give 110 mg (0.41 mmol, yield 64%) specified in the title compound.

1H-NMR (Dl3+CD3OD) : 3,21 (s, 2H), of 5.05 (s, 2H), 6,76 (s, 1H), 7,24 (d, 2H), to 7.61 (d, 2H), to 7.67 (s, 1H).

FAB: 266 (M+1).

PREPARATION EXAMPLE 53: Synthesis of 2-{1-[1-(benzyl-oxycarbonyl) piperidine-4-yl]methyl-1H-imidazol-5-yl}-thioacetamide

53-1) 4-Aminomethyl-1-(benzyloxycarbonyl)piperidine

of 22.2 g (0.2 mol) of 4-aminomethylpyridine dissolved in 250 ml to hours a trap Dean-stark removal of water and then cooled to 0oC. While mixing, slowly add to 34.2 g (0.2 mol) of benzylchloride. The mixture is stirred at room temperature for 3 hours and add 220 ml of 1 N. aqueous KHSO4. The resulting mixture is extracted with 3 times 200 ml of diethyl ether and the aqueous layer was alkalinized 1 N. aqueous sodium hydroxide solution. An aqueous solution saturated with sodium chloride. The aqueous layer was extracted three times with 100 ml of dichloromethane, dried over anhydrous magnesium sulfate and after distillation under reduced pressure to obtain 38 g (yield 91%, molecular weight 248) specified in the title compound.

1H-NMR (Dl3) : 1,11 (s, 2H), 1,49 (s, 3H), 1.70 to (d, 2H), 2.57 m (d, 2H), 2,78 (s, 2H), 4,20 (s, 2H), 5,12 (s, 2H), 7,34-to 7.35 (m, 5H).

53-2) 1-[1-(Benzyloxycarbonyl)piperidine-4-yl] methyl-5-hydroxymethyl-2-mercapto-1H-imidazol

24.8 g (0.1 mol) of the compound obtained according to preparation example 53-1), and 6.0 g (0.1 mol) of acetic acid are dissolved in 50 ml of n-butanol, then add a solution of 12.6 g (0.13 mol) of potassium thiocyanate, 15.2 g (0.1 mol) of 1,3-dimer of dihydroxyacetone and 10.0 g (to 0.17 mol) of acetic acid in 50 ml of n-butanol, the resulting mixture was stirred at room temperature. After 48 hours the solvent is removed by distillation under reduced divinely dried over anhydrous magnesium sulfate and after evaporation obtain 27 g (75 mmol, a 75% yield) specified in the title compound.

1H-NMR (Dl3) : 1,22 (d, 2H), 1.57 in (d, 2H), 2,30 (s, 1H), 2,72 (s, 2H), 3.96 points (s, 2H), 4,15 (d, 2H), 4,46 (s, 2H), 5,10 (s, 2H), 6,62 (s, 1H), 7,26-7,37 (m, 5H).

53-3) 1-[1-(Benzyloxycarbonyl)piperidine-4-yl] methyl-5-hydroxymethyl-1H-imidazol

18,05 g (50 mmol) of the compound obtained according to preparation example 53-2), is added to a mixture of 100 ml of 10% nitric acid and 10 ml of ethyl acetate, the reaction mixture is cooled with ice water, and then stirred at room temperature for 3 hours. The mixture is alkalinized using 4 N. aqueous sodium hydroxide solution and extracted twice with 100 ml of ethyl acetate. Extracted organic solution is dried over magnesium sulfate and after distillation under reduced pressure to obtain 12.3 g (38 mmol, 75% yield) specified in the title compound.

1H-NMR (Dl3) : of 1.16 (d, 2H), and 1.56 (d, 2H), 1,98 (s, 1H), 2,70 (s, 2H), 3,88 (d, 2H), 4,18 (s, 2H), 4,49 (s, 1H), 4,56 (s, 3H), 5,10 (s, 2H), PC 6.82 (s, 1H), 7,27-7,40 (m, 6N).

53-4) 1-[1-(Benzyloxycarbonyl)piperidine-4-yl] methyl-5-chloromethyl-1H-imidazole hydrochloride

to 9.9 g (30 mol) of the compound obtained according to preparation example 53-3), dissolved in 50 ml of chloroform and added slowly at 0oWith 7.1 g (60 mmol) of tionally, getting to 9.9 g (yield 95%, molecular weight to 347.5) salt - hydrochloride specified in the title compounds. This connection is used in further reactions without additional purification.

53-5) [1-[1-(Benzyloxycarbonyl)piperidine-4-yl] methyl-1H-imidazol-5-yl} acetonitrile

Specified in the title compound are obtained from the output 39% in accordance with methods similar to those used in preparatory example 52-3), using the compound obtained according to preparation example 53-4).

1H-NMR (Dl3) : 1,19(W, 2H), 1,60(W, 2H), 1,90 (m, 1H), 2,72 (W, 2H), 3,71 (s, 2H), 3,81 (d, 2H), 4,22 (W, 2H), 5,11 (s, 2H), 7,03 (s, 1H), 7.29 trend was 7.36 (m, 5H), 7,51 (s, 1H).

53-6) 2-{ 1-[1-(Benzyloxycarbonyl)piperidine-4-yl] methyl-1H-imidazol-5-yl}thioacetamide

Specified in the title compound is obtained in yield 74% in accordance with methods similar to those used in preparatory example 52-4), using the compound obtained according to preparation example 53-5).

1H-NMR (Dl3) : 1,21 (W, 2N), and 1.63 (W, 2N), of 1.87 (m, 1H), 2,71 (W, 2N), and 3.31 (s, 2H), 3,84 (d, 2H), 4,25 (W, 2H), 5,12 (s, 2H), 7,10 (s, 1H), 7,33-7,41 (m, 5H), a 7.62 (s, 1H).

FAB: 373 (M+1).

PREPARATION EXAMPLE 54: Synthesis of methyl 3-chloro-3- (naphthalene-1-yl)-2-oxopropionate

7,80 g is dobavlaut 6,15 g (of 54.8 mmol) of tert-butoxide potassium. The resulting mixture was stirred at room temperature for 24 hours and then to terminate the reaction, add 50 ml of water. The solvent is distilled off under reduced pressure and the residue extracted with ethyl acetate. The organic layer is dried over magnesium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 90/10, V/V) to give 2.5 g (9,52 mmol, yield 19%) specified in the title compound.

1H-NMR (Dl3) : of 3.78 (s, 3H), 6,92 (s, 1H), 7,45-7,73 (m, 4H), to 7.95 (m, 2H), 8,12 (d, 1H).

PREPARATION EXAMPLE 55: Synthesis of methyl 2-chloro-3-(naphthalene-1-yl)-3-oxopropionate

55-1) Methyl-3-(naphthalene-1-yl)-3-oxopropionate

10.2 g (59,9 mmol) 1-acetonaphthone and 4.8 g (60% in mineral oil, 120 mmol) of sodium hydride is added to 100 ml of dimethylcarbonate and the mixture is heated under reflux for 24 hours. The solvent is distilled off under reduced pressure, to the residue was added 100 ml of 1 n HCl solution and the resulting mixture is extracted with 100 ml of ethyl acetate. The organic layer was washed with water (100 ml x 3), dried over anhydrous magnesium sulfate and evaporated. After column chromatography of the resulting residue on silica gel (eluent: n-hexane/ethyl acetate = 90/10, V/V) to give 10.0 g (43,8 is 8 (m, 3H), 7,82-8,08 (m, 3H), 8,77 (d, 1H).

55-2) Methyl-2-chloro-3-(naphthalene-1-yl)-3-oxopropionate

4,56 g (20.0 mmol) of the compound obtained according to preparation example 55-1), dissolved in 50 ml of 1,2-dichloroethane and added slowly at 0oWith 2.70 g (20.0 mmol) of sulfurylchloride. The mixture is stirred at room temperature for 3 hours. The solvent is removed by distillation under reduced pressure to get 4,70 g (to 17.9 mmol, yield 89%) specified in the title compound.

1H-NMR (Dl3) : of 3.75 (s, 3H), of 5.82 (s, 2H), 7,50-7,72 (m, 3H), a 7.85-of 8.15 (m, 3H), 8,65 (d, 1H).

EXAMPLE 142: Synthesis of 4-etoxycarbonyl-2- (1H-imidazol-5-yl-methyl)-5-(naphthalene-1-yl)oxazole (142)

142-1) Ethyl-2-[(1H-imidazol-5-yl)acetylamino])-3-(naphthalene-1-yl)oxopropionate

293 mg (0,997 mmol) of the compound obtained according to preparation example 51-2), 162 mg (0,996 mmol) of the hydrochloride of 4-imidazolinone acid 135 mg (0,999 mmol) NOWT and 191 mg (0,996 mmol) of EDC are added to 10 ml of dimethylformamide and then slowly added with stirring 202 mg (1,99 mmol) of triethylamine. The mixture is stirred at room temperature for 5 hours, after which the solvent is removed by distillation under reduced pressure. To the obtained residue, add 30 ml of ethyl acetate, then p is including magnesium, evaporated and subjected to the obtained residue column chromatography on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to give 200 mg (0,547 mmol, yield 55%) specified in the title compound.

1H-NMR (Dl3) : to 0.92 (t, 3H), 3,70 (s, 2H), 3,98-to 4.15 (m, 2H), of 6.20 (d, 1H), 6,92 (s, 1H), 7,55 (m, 4H), of 7.65 (s, 1H), 7,89 (d, 1H), of 8.06 (d, 1H), 8,12 (W, 1H), 8,21 (d, 1H), 8,45 (d, 1H).

142-2) 4-Etoxycarbonyl-2-(1H-imidazol-5-yl-methyl)-5-(naphthalene-1-yl)oxazol

100 mg (0.27 mmol) of the compound obtained according to example 142-1), dissolved in 5 ml of THF and then heated under reflux for 6 hours. The solvent is removed by distillation under reduced pressure and after column chromatography of the resulting residue on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to obtain 40 mg (0.12 mmol, yield 44%) specified in the title compound.

1H-NMR (Dl3) : and 0.98 (t, 3H), of 4.13 (q, 2H), 4,27 (s, 2H), 6,92 (s, 1H), 7,45-7,58 (m, 4H), of 7.65 to 7.75 (m, 2H), 7,89 (d, 1H), of 7.97 (d, 1H).

FAB: 348 (M+1).

EXAMPLE 143: Synthesis of 2-(1H-imidazol-5-ylmethyl)-4- (morpholine-4-yl)carbonyl-5-(naphthalene-1-yl)oxazole (143)

31 mg (0.09 mmol) of the compound obtained according to example 142-2), dissolved in a solvent mixture of tetrahydrofuran/methanol/water (0.6 ml/0.3 ml/1 ml) and added 6 mg (0.1 is m the solvent is distilled off under reduced pressure. The pH value of the obtained residue was adjusted to 6 using 0.1 G. of an aqueous solution chloroethanol acid, and then extracted with ethyl-acetate. The organic layer is dried over anhydrous magnesium sulfate and evaporated. The concentrate was dissolved in 1 ml of dimethylformamide, at 0oWith added 18 mg (0.13 mmol) NOWT and 26 mg (0.13 mmol) of EDC and the mixture is stirred for 10 minutes. Add 9 μl (0.09 mmol) of the research and 18 μl (0.13 mmol) of triethylamine, after which the mixture was stirred at room temperature for 2 hours. The reaction solution is treated in accordance with the method similar to that shown in example 142-1) to give 14 mg (0.04 mmol, yield 45%) specified in the title compound.

1H-NMR (Dl3) : 2,97 (W, 2H), 3,24 (W, 2H), 3.43 points (lat, 2H), 3,57 (W, 2H), 4,27 (s, 2H), 6,95 (s, 1H), 7,52-to 7.67 (m, 6N), 7,81-to 7.95 (m, 3H).

FAB: 389 (M+1).

EXAMPLE 144: Synthesis of 4-etoxycarbonyl-2- (1H-imidazol-5-ylmethyl)-5-(naphthalene-1-yl)thiazole (144)

105 mg (0,287 mmol) of the compound obtained according to example 142-1), and 116 mg (0,287 mmol) of the reagent Laussane dissolved in 10 ml of tetrahydrofuran and heat the mixture under reflux for 6 hours. The solvent is removed

by distillation under reduced pressure, to the residue add the organic layer is dried over anhydrous magnesium sulfate, evaporated and after column chromatography of the resulting residue on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) to obtain 26 mg (0,075 mmol, yield 26%) of the compounds according to example 142-2) and 24 mg (of 0.066 mmol, yield 23%) specified in the title compound.

1H-NMR (Dl3) : 0,63 (t, 3H), 3,92 (kV, 2H), 4,42 (s, 2H), 6,97 (s, 1H), 7,405 to 7.75 (m, 6N), the 7.85-to 7.95 (m, 2H).

FAB: 364 (M+1).

EXAMPLE 145: Synthesis of 2-[1-(4-Chlorobenzyl)-1H-imidazol-5-ylmethyl] -4-methoxycarbonyl-5- (naphthalene-1-yl) thiazole (145)

130 mg (0.49 mmol) of the compound obtained according to preparation example 52-4), and 129 mg (0.49 mmol) of the compound obtained according to preparation example 54, dissolved in 5 ml of ethanol and heat the mixture under reflux for 5 hours. The solvent is removed by distillation under reduced pressure and after column chromatography of the resulting residue on silica gel (eluent: dichloromethane/methanol = 40/1, V/V) to obtain 45 mg (0,095 mmol, yield 19%) specified in the title compound.

1H-NMR (Dl3) : 3,50 (s, 3H), 4.26 deaths (s, 2H), 5,11 (s, 2H), 6,92 (d, 2H), 7,07 (s, 1H), 7,21-the 7.43 (m, 7H), 7,53 (s, 1H), 7,83 (m, 2H).

FAB: 474 (M+1).

EXAMPLE 146: Synthesis 2-1-(4-Chlorobenzyl)-1H-imidazol-5-ylmethyl] -4-(morpholine-4-yl)carbonyl-5-(naphthalene-1-yl)-TIA is yodice in example 143, using the compound obtained according to example 145.

1H-NMR (Dl3) / : 2,63 (W, 2H), 3,02 (W, 2H), 3,24 (W, 2H), 3,42 (W, 2H), 4.26 deaths (2N), to 5.21 (s, 2H), 7,02 (m,2H), 7,18 (s, 1H), 7,31 (m, 2H), 7,43-of 7.60 (m, 5H), 7,78-of 7.96 (m, 3H).

FAB: 529 (M+1).

EXAMPLE 147: Synthesis of 2-[1-(4-Chlorobenzyl)-1H-imidazol-5-ylmethyl] -4-[N-(2-methoxy) ethyl-N-methylcarbamoyl] -5-(naphthalene-1-yl)thiazole (147)

Specified in the title compound are obtained from the output 41% in accordance with methods similar to those used in example 143, using the compound obtained according to example 145, with the exception that instead of the research using N-(2-methoxyethyl)methylamine.

1H-NMR (Dl3) : 2,68 (Shir, 3H), 2,89-3,39 (m, 7H), 4,22 (s, 2H), 5,17 (s, 2H), 7,01 (m, 2H), 7,15 (s, 1H), 7,33 (m, 2H), 7,40-to 7.61 (m, 5H), 7,71-of 7.82 (m, 3H).

FAB: 531 (M+1).

EXAMPLE 148: Synthesis of 2-[1-(4-Chlorobenzyl)-1H-imidazol-5-ylmethyl] -5-methoxycarbonyl-4- (naphthalene-1-yl) thiazole (148)

250 mg (0.95 mmol) of the compound obtained according to preparation example 52-4), and 249 mg (0.95 mmol) of the compound obtained according to preparation example 55-2), dissolved in 10 ml of ethanol and heat the mixture under reflux for 24 hours. The solvent is removed by distillation under reduced pressure and after colonic who mmol, yield 40%) specified in the title compound.

1H-NMR (Dl3) : of 3.53 (s, 3H), 4,22 (s, 2H), 5,12 (s, 2H), 6,91 (m, 2H), 7,11 (s, 1H), 7,21-rate of 7.54 (m, 7H), 7,83 (m, 3H).

FAB: 474 (M+1).

EXAMPLE 149: Synthesis of 2-[1-(4-Chlorobenzyl)-1H-imidazol-5-ylmethyl] -5-(morpholine-4-yl)carbonyl-4-(naphthalene-1-yl)-thiazole (149)

Specified in the title compound are obtained from the output 39% in accordance with methods similar to those used in example 143, using the compound obtained according to example 148.

1H-NMR (Dl3) : 2,38 (W, 2H), 2,82 (W, 2H), 3,21 (W, 2H), 3,42 (W, 2H), 4,27 (s, 2H), total of 5.21 (s, 2H), 6,98 (m, 2H), 7,25 (m, 3H), 7,50-to 7.61 (m, 5H), 7,89-to 7.99 (m, 3H).

FAB: 529 (M+1).

EXAMPLE 150: Synthesis of 2-{1-[1-(benzyloxycarbonyl)-piperidine-4-ylmethyl] -1H-imidazol-5-ylmethyl}-5-methoxy-carbonyl-4-(naphthalene-1-yl) -thiazole (150)

124 mg (0.33 mmol) of the compound obtained according to preparation example 53-6) and 87 mg (0.33 mmol) of the compound obtained according to preparation example 55-2), dissolved in 10 ml of ethanol and heat the mixture under reflux for 20 hours. The solvent is removed by distillation under reduced pressure and after column chromatography of the resulting residue on silica gel (eluent: dichloromethane/methanol = 95/5, V/V) obtain 95 mg (0H), 2,50 (W, 2H), 3,62 (s, 3H), 3,81 (d, 2H), 4,19 (W, 2N), to 4.41 (s, 2H), 5,14 (d, 2H), 7,16 (s, 1H), 7,27-to 7.61 (m, 10H), 7,78 (s, 1H), to $ 7.91 (d, 1H), of 7.96 (d, 1H).

FAB: 595 (M+1).

EXAMPLE 151: Synthesis of 2 -{1-[1-(benzyloxycarbonyl)piperidine-4-ylmethyl] -1H-imidazol-5-ylmethyl} -5- [N- (2-methoxy) -ethyl-N-methylcarbamoyl] -4-(naphthalene-1-yl)thiazole (151)

Specified in the title compound are obtained from the output 36% in accordance with methods similar to those used in example 143, using the compound obtained according to example 150, with the exception that instead of the research using N-(2-methoxyethyl)methylamine.

1H-NMR (Dl3) : 2,68 (Shir, 3H), 2,89-3,39 (m, 7H), 4,22 (s, 2H), 5,17 (s, 2H), 7,01 (m, 2H), 7,15 (s, 1H), 7,33 (m, 2H), 7,40-to 7.61 (m, 5H), 7,71-of 7.82 (m, 3H).

FAB: 638 (M+1).

PREPARATION EXAMPLE 56: Synthesis of benzyl ester 4-(5-chloromethyl-1H-imidazole-5-ylmethyl) -piperidine-1-carboxylic acid

56-1) Benzyl ether of 4-aminomethylpyridine-1-carboxylic acid

of 22.2 g (0.2 mol) of 4-aminomethylpyridine dissolved in 250 ml of toluene, then added to 21.2 g (0.2 mol) of benzaldehyde. The mixture is heated with reflux condenser and a trap Dean-stark for 3 hours, cooled to 0oAnd then added under stirring to 34.2 g (0.2 mol) of benzylchloride. After stirring twice extracted with 200 ml diethyl ether and then the aqueous layer was alkalinized with sodium hydroxide. An aqueous solution saturated with sodium chloride and extracted three times with 100 ml dichloromethane. The organic solution is dried over magnesium sulfate and after distillation under reduced pressure to obtain 38 g (yield 91%, molecular weight 248) specified in the title compound.

1H-NMR (Dl3) : 1,11 (s, 2H), 1,49 (s, 3H), 1.70 to (d, 2H), 2.57 m (d, 2H), 2,78 (s, 2H), 4,20 (s, 2H), 5,12 (s, 2H), 7,34-to 7.35 (m, 5H).

FAB (M+H): 249.

56-2) Benzyl ester 4-(5-hydroxymethyl-2-mercapto-1H-imidazol-1-ylmethyl)piperidine-1-carboxylic acid

24.8 g (0.1 mol) of the compound obtained according to preparation example 56-1), and 6.0 g (0.1 mol) of acetic acid are dissolved in 50 ml of n-butanol and the resulting solution was added to a solution obtained by dissolution of 12.6 g (0.13 mol) of potassium thiocyanate, 15.2 g (0.1 mol) of 1,3-dimer of dihydroxyacetone and 10.0 g (to 0.17 mol) of acetic acid in 50 ml of n-butanol. The resulting mixture is stirred for 48 hours. The solvent is removed by distillation under reduced pressure, add 200 ml of ethyl acetate and the resulting mixture was washed three times with 100 ml of water. The organic layer is dried over magnesium sulfate and after removal of the solvent under reduced pressure to obtain 27 g (75 mmol, 75% yield, molecular weight 361) specified in the title soybeans is (s, 2H), 6,62 (s, 1H), 7,26-7,37 (m, 5H).

FAB (M+H): 362.

56-3) Benzyl ester 4-(5-hydroxymethyl-1H-imidazol-1-ylmethyl)piperidine-1-carboxylic acid

18,05 g (50 mmol) of the compound obtained according to preparation example 56-2) add to the mixture 100 ml of nitric acid (10%) and 10 ml of ethyl acetate. The mixture was incubated for 5 minutes in ice-cold water and stirred at room temperature for 3 hours. The mixture is alkalinized 4 N. aqueous sodium hydroxide solution and then twice extracted with 100 ml of ethyl acetate. The organic layer is dried over magnesium sulfate and after distillation under reduced pressure to obtain 12.3 g (38 mmol, 75% yield, molecular weight of 329) specified in the title compound.

1H-NMR (Dl3) : of 1.16 (d, 2H), and 1.56 (d, 2H), 1,98 (s, 1H), 2,70 (s, 2H), 3,88 (d, 2H), 4,18 (s, 2H), 4,49 (s, 1H), 4,56 (s, 3H), 5,10 (s, 2H), PC 6.82 (s, 1H), 7,27-7,40 (m, 5H).

FAB (M+H): 330.

56-4) Benzyl ester 4-(5-chloromethyl-1H-imidazol-1-yl-methyl)piperidine-1-carboxylic acid

to 9.9 g (30 mmol) of the compound obtained according to preparation example 56-3), dissolved in 50 ml of chloroform and added slowly at 0oWith 7.1 g (60 mmol) of thionyl chloride. The mixture is stirred for 2 hours, the solvent is removed by distillation AI connection.

1H-NMR (Dl3) : of 1.12 (d, 2H), 1,53 (d, 2H), 2, 65 (s, 2H), 3,82 (d, 2H), 4,22 (s, 2H), 4,42 (s, 1H), 4,49 (s, 3H), 5,12 (s, 2H), 6,60 (s, 1H), 7,30-7,41 (m, 5H).

FAB (M+H): 349.

PREPARATION EXAMPLE 57: Synthesis of 1-(4-Chlorobenzyl)-5-chloromethyl-1H-imidazole hydrochloride

57-1) 1-(4-Chlorobenzyl)-5-hydroxymethyl-1H-imidazol

Specified in the title compound is obtained in yield of 50% in accordance with the methodology described in: J. M. Dener, L.-H. Zhang, H. Rapoport, J. Org.Chem., 1993, 58, 1159, using as starting compounds dimer of dihydroxyacetone hydrochloride and 4-chlorobenzylamino.

1H-NMR (Dl3+CD3OD) : to 4.46 (s, 2H), 5,26 (s, 2H), 7,00 (s, 1H), 7,07 (d, 2H), 7,50 (d, 2H), 7,65 (s, 1H).

57-2) 1-(4-Chlorobenzyl)-5-chloromethyl-1H-imidazole hydrochloride

Specified in the title compound are obtained from the output 96% in accordance with methods similar to those used in example 56-4), with the exception that as the starting compound using the compound obtained according to preparation example 57-1). This connection is used in further reactions without additional purification.

PREPARATION EXAMPLE 58: Synthesis of 4-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-3-(naphthalene-1-yl)-1H-pyrazole

58-1) N-Tert-butyl-N-naphthalene-1-ylmethylene)hydrazine

5.0 g (o the mixture interacts with 1 ml of acetic acid at room temperature for 24 hours. After removal of the solvent by distillation under reduced pressure to the residue is added 20 ml of ethyl acetate. The mixture was washed with a saturated solution of sodium bicarbonate. Then the separated organic layer is dried over anhydrous magnesium sulfate and removal of solvent is distilled under reduced pressure, obtaining 6.3 g (28 mmol, yield 86%) specified in the title compound.

1H-NMR (Dl3) : 1,70 (s, N), of 7.23 (s, 1H), 7,32 (m, 1H), 7,42 (m, 2H), 7,80 (d, 1H), of 7.90 (d, 2H), at 8.60 (d, 1H), to 9.91 (s, 1H), 12,1 (W, 1H).

FAB (M+H): 227.

58-2) Ethyl ester of 1-(tert-butyl)-3-(naphthalene-1-yl)-1H-pyrazole-4-carboxylic acid

6.3 g (28 mmol) of the compound obtained according to preparation example 58-1), and of 2.44 g (30,8 mmol) ethylpropyl dissolved in a solvent consisting of a mixture of 27 ml of acetic acid and 32 ml of acetonitrile, and the resulting mixture interacts on the air for 3 days. The solvent is removed and after column chromatography of the resulting residue on silica gel (eluent: ethyl acetate/n-hexane = 9/1, V/V) receive 6,76 g (21 mmol, 75% yield) specified in the title compound.

1H-NMR (Dl3) : to 0.80 (t, 3H), of 1.65 (s, N), 3,98 (kV, 2H), 7,38 (m, 2H), of 7.48 (m, 1H), 7,55 (m, 1H), 7,74 (m, 1H), a 7.85 (m, 2H), 8,21 (s, 1H), 11,31 (W, 1H).

1H-NMR (Dl3) : to 0.80 (t, 3H), 3,98 (kV, 2H), 7,35-of 7.60 (m, 5H), of 7.90 (m, 2H), 7,94 (s, 1H).

FAB (M+H): 267.

58-4) 3-(Naphthalene-1-yl)-1H-pyrazole-4-carboxylic acid

1.1 g (4.1 mmol) of the compound obtained according to preparation example 58-3), and 2.1 g (12.4 mmol) of potassium hydroxide dissolved in 50 ml of solvent consisting of a mixture of methanol and water (1:1, V/V). The mixture interacts with heating under reflux for 12 hours. The solvent is removed by distillation under reduced pressure. The obtained residue acidified with 1 N. aqueous solution chloroethanol acid, extracted with 50 ml ataut 910 mg (3,8. mmol, yield 92%) specified in the title compound.

1H-NMR (CD3OD+CDl3) : 7,30 (m, 3H), 7,56 (d, 1H), 7,80-to 7.95 (m, 3H), 8,07 (s, 1H).

FAB (M +H): 239.

58-5) 4-N-(2-Methoxyethyl)-N-methyl] carbarnoyl-3-(naphthalene-1-yl)-1H-pyrazole

238 mg (1 mmol) of the compound obtained according to preparation example 58-4), dissolved in 10 ml of dimethylformamide and added 230 mg (1.2 mmol) of EDC, 101 mg (1 mmol) of triethylamine and 162 mg (1.2 mmol) NOUT (1-hydroxybenzotriazole), after which the mixture was stirred at 0oC for 5 minutes. To the mixture is added 124 mg (1 mmol) of the hydrochloride of N-(2-methoxyethyl)-N-methylamine and stirred at room temperature for 5 hours. The solvent is removed by distillation under reduced pressure, to the obtained residue, add 10 ml of a saturated aqueous solution of potassium carbonate. The mixture is extracted with 20 ml ethyl acetate, washed with 10 ml of 1 N. aqueous solution chloroethanol acid, saturated sodium chloride solution and water, dried over anhydrous sodium sulfate and after evaporation obtain 247 mg (0.8 mmol, yield 80%) specified in the title compound.

1H-NMR (Dl3) : 2,40 (s, 2H), 2,81 (s, 1H), 2,84 (s, 1H), 2,96 (s, 1H), to 3.02 (s, 4H), 3.15 in (s, 1.5 H) to 3.34 (s, 1.5 H), 7.24 to 7,52 (m, 4H), to 7.59 (s, 1H), to 7.77 (m, 2H), to 7.93 (d, 1 ሺ-1H-pyrazole

238 mg (1 mmol) of the compound obtained according to preparation example 58-4), dissolved in 10 ml of dimethylformamide, then add 230 mg (1.2 mmol) of EDC and 162 mg (1.2 mmol) NOUT and the mixture was stirred at 0oC for 5 minutes. To the resulting mixture are added 87 mg (1 mmol) of the research and stirred at room temperature for 5 hours. The solvent is removed under reduced pressure, to the obtained residue, add 10 ml of a saturated aqueous solution of potassium carbonate. The mixture is extracted with 20 ml ethyl acetate, washed with 10 ml of 1 n solution chloroethanol acid, then washed with saturated aqueous sodium chloride and water, dried over anhydrous sodium sulfate and after evaporation receive 240 mg (0.8 mmol, yield 80%) specified in the title compound.

1H-NMR (Dl3) : 2,5 (W, 2H), 2.95 and (W, 2H), 3.15 in (W, 2H), 3,40 (W, 2N), to 7.50 (m, 4H), to 7.95 (m, 4H), 9,73 (W, 1H).

FAB (M+H): 308.

EXAMPLE 152: Synthesis of 1-[1-(1-benzyloxycarbonylamino-4-ylmethyl) -1H-imidazol-5-ylmethyl] -4-[N-(2-methoxyethyl) -N-methyl] carbarnoyl-3- (naphthalene-1-yl) -1H-pyrazole (152)

616 mg (2.0 mmol) of the compound obtained according to preparation example 56-4), dissolved in 10 ml of dimethylformamide, add at 0oWith 264 mg (6.6 m the organisations, obtained according to preparation example 58-5), and the resulting mixture was stirred at room temperature for 5 hours. The solvent is removed by distillation under reduced pressure and the obtained residue add 10 ml of water. The mixture is then extracted twice with 20 ml of ethyl acetate, dried over magnesium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 930 mg (75% yield) specified in the title compound.

1H-NMR (Dl3) : 1,11 (m, 2H), 1,37 (W, 1H), 1,50 (W, 2H), 2,35 (W, 1H), 2,55 (W, 2H), 2,71 (W, 1H), 2,90-is 3.21 (m, 7H), 3,35 (W, 1H), 3,90 (W, 2H), 3,98 (d, 1H), 4,50 (d, 1H), 5,02 (s, 2H), 5,10 (s, 2H), 7,21-7,40 (m, 6N), 7,41-of 7.60 (m, 4H), of 7.70 (s, 1H), 7,80 (s, 1H), 7,95 (m, 2H), 8,13 (d, 1H).

FAB (M+H) 621.

EXAMPLE 153: Synthesis of 1-[1-(1-ethoxycarbonylpyrimidine-4-ylmethyl)-1H-imidazol-5-ylmethyl] -4-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-3-(naphthalene-1-yl)-1H-pyrazole (153)

153-1) 1-[1-(piperidine-4-ylmethyl)-1H-imidazol-5-yl-methyl] -4-[N- (2-methoxyethyl)-N-methyl]carbarnoyl-3-(naphthalene-1-yl)-1H-pyrazole

227 mg (0.36 mmol) of the compound obtained according to example 152, dissolved in methanol, add 20 mg of palladium hydroxide on coal and the mixture interacts with the hydrogen pressure is 1 ATM, the raffia of the filtrate on silica gel (eluent: aqueous ammonia/methanol = 15/85, about/about) obtain 128 mg (0.26 mmol, yield 74%) specified in the title compound.

1H-NMR (Dl3) : 1,08 (s, 2H), 1,53 (m, 4H), 2,33 (s, 2H), 2,64 (Shir, 4H), 3,20 (m, 6N), and 3.31 (s, 1H), 3,75 (d, 2H), 4,13 (m, 2H), 5,10 (s, 2H), of 6.71 (s, 1H), 7,11 (s, 1H), 7,30 (m, N), 7,74 (d, 1H), 7,81 (d, 1H), of 7.90 (s, 1H), of 8.06 (d, 1H).

FAB (M+H): 486.

153-2) 1-[1-(1-Ethoxycarbonylpyrimidine-4-ylmethyl) -1H-imidazol-5-ylmethyl]-4-[N-(2-methoxyethyl) -N-methyl]-carbarnoyl-3-(naphthalene-1-yl)-1H-pyrazole

30 mg (62 μmol) of the compound obtained according to example 153-1), add 2 ml of dichloromethane, using a syringe add to 5.4 mg (6,9 mmol) methylcarbamate and stirred the mixture for 2 hours. The solvent is removed under reduced pressure and after column chromatography of the resulting residue on silica gel (eluent: dichloromethane/methanol = 80/20, V/V) gain of 27.8 mg (5.3 mmol, yield 85%) specified in the title compound.

1H-NMR (Dl3) : 1,11 (W, 2H), 1,33 (W, 1H), 1,53 (W, 2H), 2,39 (s, 2H), 2,70 (Shir, 4H), 2,90-3,20 (W, 6N), 3,32(s, 1H), 3,62 (s, 3H), of 3.78 (d, 2H), 4.16 the (m, 2H), 5,16 (s, 2H), 6,74 (s, 1H), 7,10 (s, 1H), 7,21-to 7.50 (m, 14N), 7,76 (d, 1H), to 7.84 (d, 1H), to $ 7.91 (s, 1H), 8,07 (d, 1H).

FAB (M+H): 545.

EXAMPLE 154: Synthesis of 1-[1-(4-bromobenzyl)-1H-imidazol-5-ylmethyl]-4-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-3-(naphthalene-1-yl)-1H-pyrazole (154)

example 152, except, that is used as a compound obtained according to preparation example 32-2), and the compound obtained according to preparation example 58-5).

1H-NMR (Dl3) : 2,41 (s, 2H), 2,82 (s, 1H), 2,85 (s, 1H), 2,98 (s, 1H), 3.04 from (s, 4H), 3,17 (s, 1.5 H) to 3.36 (s, 1.5 H), of 5.11 (s, 2H), total of 5.21 (s, 2H), 6,95 (d, 2H), 7,25 (d, 2H), 7,35-of 7.60 (m, 5H), to 7.64 (s, 1H), 7,72 (s, 1H), 7,81 (m, 2H), 8,11 (d, 1H).

FAB (M+H): 558.

EXAMPLE 155: Synthesis of 1-[1-(4-Chlorobenzyl)-1H-imidazol-5-ylmethyl]-4-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-3-(naphthalene-1-yl)-1H-pyrazole (155)

Specified in the title compound is obtained in yield of 81% in accordance with methods similar to those used in example 152, except that used as a compound obtained according to preparation example 57-2), and the compound obtained according to preparation example 58-5).

1H-NMR (Dl3) : 2,41 (s, 2H), 2,82 (s, 1H), 2,85 (s, 1H), 2,98 (s, 1H), 3.04 from (s, 4H), 3,17 (s, 1.5 H) to 3.36 (s, 1.5 H), 5,20 (s, 2H), 5.25 in (s, 2H), 6,97 (d, 2H), 7,26 (d, 2H), 7,35-7,46 (m, 5H), 7,47 (s, 1H), 7,58 (s, 1H), 7,88 (m, 2H), 8,11 (d, 1H).

FAB (M+H): 514.

EXAMPLE 156: Synthesis of 1-[1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl] -4-[N-(2-methoxyethyl) -N-methyl] carbarnoyl-3-(naphthalene-1-yl) -1H-pyrazole (156)

Specified in the title compound are obtained from the output 81% according the according to preparatory example 29-5), and the compound obtained according to preparation example 58-5).

1H-NMR (Dl3) : 2,41 (s, 2H), 2,82 (s, 1H), 2,85 (s, 1H), 2,98 (s, 1H), 3.04 from (s, 4H), 3,17 (s, 1.5 H) to 3.36 (s, 1.5 H), 5,20 (s, 2H), 5,31 (s, 2H), 6,99 (d, 2H), 7,26 (d, 2H), 7,35-7,46 (m, 5H), of 7.48 (s, 1H), EUR 7.57 (s, 1H), 7,89 (m, 2H), 8,12 (d, 1H).

FAB (M+H): 505.

EXAMPLE 157: Synthesis of 1-[1-methyl-1H-imidazol-5-ylmethyl] -4-[N-(2-methoxyethyl)-N-methyl]carbarnoyl-3-(naphthalene-1-yl)-1H-pyrazole (157)

Specified in the title compound is obtained in yield of 81% in accordance with methods similar to those used in example 152, except that the use of the hydrochloride of 1-methyl-5-chloromethyl-1H-imidazole and the compound obtained according to preparation example 58-5).

1H-NMR (Dl3) : 2,42 (W, 2H), 2,71 (W, 1H), 3,10 (Shir, 5H), 3,30 (W, 1H), 3,50 (s, 3H), of 5.17 (s, 2H), 6,69 (s, 1H), to 7.09 (s, 1H), 7,41 (m, N), 7,74 (d, 1H), 7,83 (d, 1H), 7,89 (s, 1H), with 8.05 (d, 1H).

FAB (M+H): 404.

EXAMPLE 158: Synthesis of 1-[1-(1-benzyloxycarbonylamino-4-ylmethyl) -1H-imidazol-5-ylmethyl] -4-(morpholine-4-yl)carbonyl-3- (naphthalene-1-yl)-1H-pyrazole (158)

612 mg (2.0 mmol) of the compound obtained according to preparation example 59, dissolved in 10 ml of dimethylformamide and then added at 0oWith 264 mg (6.6 mmol) of sodium hydride (60%), after which the mixture is displaced is a specific example 56-4), and the resulting mixture was stirred at room temperature for 5 hours. The solvent is distilled off under reduced pressure and to the residue add 10 ml of water. The resulting mixture was twice extracted with 20 ml ethyl acetate, dried over magnesium sulfate, evaporated and subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 90/10, V/V) to give 930 mg (75% yield) specified in the title compound.

1H-NMR (Dl3) : 1,11 (W, 2H), 1,37 (W, 1H), 1,50 (W, 2H), 1,62 (W, 1H), 2,35 (W, 1H), 2,55 (W, 2H), 2,71 (W, 1H), 3,14 (W, 2H), 3,35 (W, 2H), 3,90 (W, 2N), is 4.15 (m, 4H), 5,02 (s, 2H), 5,10 (s, 2H), 7,21-7,40 (m, 6N), 7,41-of 7.60 (m, 4H), 7,76 (d, 1H), of 7.70 (s,1H), 7,80 (s, 1H), 7,95 (m, 2H), 8,13 (d, 1H).

FAB (M+H): 619.

EXAMPLE 159: Synthesis of 1-[1-(1-ethoxycarbonylpyrimidine-4 - ylmethyl)-1H-imidazol-5-ylmethyl] -4-(morpholine-4-yl)-carbonyl-3-(naphthalene-1-yl) -1H-pyrazole (159)

159-1) 1-[1-(piperidine-4-ylmethyl)-1H-imidazol-5-yl - methyl]-4-(morpholine-4-yl) carbonyl-3-(naphthalene-1-yl)-1H-pyrazole

227 mg (0.36 mmol) of the compound obtained according to example 158, dissolved in methanol, add 20 mg of palladium hydroxide angle and the resulting mixture interacts with the hydrogen pressure is 1 ATM for 2 hours. After completion of the reaction the mixture is filtered and removed solvent. the 85, about/about) receive 120 mg (0.26 mmol, yield 74%) specified in the title compound.

1H-NMR (Dl3) : of 1.06 (m, 2H), USD 1.43 (m, 3H), 1,36 (Shir, 5H), 2,41-3,79 (Shir, 13H), of 3.78 (d, 2H), with 5.22 (s, 2H), to 6.88 (s, 1H), 7,12 (d, 2H), 7,26 (m, 1H), 7,35 (m, 3H), 7,63 (s, 1H), of 7.75 (d, 1H), 7,80 (d, 1H), to 7.93 (d, 1H).

FAB (M+H): 484.

159-2) 1-[1-(1-Ethoxycarbonylpyrimidine-4-ylmethyl)-1H - imidazol-5-ylmethyl]-4-(morpholine-4-yl) -carbonyl-3-(naphthalene-1-yl)-1H-pyrazole

30 mg (62 μmol) of the compound obtained according to example 159-1), dissolved in 2 ml of dichloromethane, and then with a syringe type of 5.4 mg (6,9 mmol) methylcarbamate, after which the mixture is stirred for 2 hours. The solvent is distilled off under reduced pressure and the resulting residue is subjected to column chromatography on silica gel (eluent: dichloromethane/methanol = 80/20, V/V), receiving of 27.8 mg (5.3 mmol, yield 85%) specified in the title compound.

1H-NMR (Dl3) : 1,05 (W, 2H), 1,32 (W, 1H), 1,53 (W, 2H), 2,31-of 2.72 (m, 5H), 3,03-to 3.33 (m, 7H), 3,62 (s, 3H), 3,66 (m, 2H), 4,13 (W, 2H), 5,12 (s, 2H), of 6.71 (s, 1H), 7,03 (s, 1H), 7,14 (s, 1H), 7.24 to the 7.43 (m, 5H), 7,74 (d, 1H), 7,82 (d, 1H), 8,10 (d, 1H).

FAB (M+H): 543.

EXAMPLE 160: Synthesis of 1-[1-(4-bromobenzyl) -1H-imidazol-5-ylmethyl] -4-(morpholine-4-yl) carbonyl-3-(naphthalene-1-yl)-1H-pyrazole (160)

Specified in the title of a connection is the exception, using the compound obtained according to preparation example 32-2), and the compound obtained according to preparation example 59.

1H-NMR (Dl3) : 2,35 (W, 2H), 2,80 (W, 2H), 3.15 in (W, 2H), 3,35 (W, 2N), from 5.29 (s, 2H), 5,31 (s, 2H), 7,00 (d, 2H), 7,20-7,35 (m, 3H), 7,40-of 7.60 (m, 4H), 7,72 (s, 1H), 7,80 (s, 1H), of 7.90 (m, 2H), 8,01 (d, 1H).

FAB (M+H): 556.

EXAMPLE 161: Synthesis of 1-[1-(4-Chlorobenzyl)-1H-imidazol-5-ylmethyl] -4-(morpholine-4-yl)carbonyl-3-(naphthalene-1-yl)-1H-pyrazole (161)

Specified in the title compound is obtained in yield of 81% in accordance with the same method as in example 152, except that used as a compound obtained according to preparation example 57-2), and the compound obtained according to preparation example 59.

1H-NMR (Dl3) : 2,35 (W, 2H), 2,80 (W, 2H), 3.15 in (W, 2N), and 3.31 (s, 2H), 3,35 (W, 2N), from 5.29 (s, 2H), 7,00 (d, 2H), 7,20-7,35 (m, 3H), 7,40-of 7.60 (m, 4H), 7,72 (s, 1H), 7,80 (s, 1H), of 7.90 (m, 2H), 8,01 (d, 1H).

FAB (M+H): 512.

EXAMPLE 162: Synthesis of 1-[1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl] -4-(morpholine-4-yl)carbonyl-3-(naphthalene-1-yl)-1H-pyrazole (162)

Specified in the title compound is obtained in yield of 81% in accordance with the same method as in example 152, except that use the connection, receiving the CLASS="ptx2">

1H-NMR (Dl3) : 2,35 (W, 2H), 2,80 (W, 2H), 3.15 in (W, 2H), 3,35 (W, 2H), 5,28 (s, 2H), of 5.34 (s, 2H), 7,03 (d, 2H), 7,20-7,35 (m, 3H), 7,40-of 7.60 (m, 4H), 7,72 (s, 1H), 7,80 (s, 1H), of 7.90 (m, 2H), 8,01 (d, 1H).

FAB (M+H): 503.

EXAMPLE 163: Synthesis of 1-(1-Michel-1H-imidazol-5-ylmethyl) -4-(morpholine-4-yl)carbonyl-3-(naphthalene-1-yl)-1H-pyrazole (163)

Specified in the title compound is obtained in yield of 81% in accordance with the same method as in example 152, except that the use of the hydrochloride of 1-methyl-5-chloromethyl-1H-imidazole and the compound obtained according to preparation example 59.

1H-NMR (Dl3) : 2,35 (W, 2H), 2,80 (W, 2H), 3.15 in (W, 2H), 3,35 (W, 2H), 3,62 (s, 3H), from 5.29 (s, 2H), 7,20-7,35 (m, 3H), 7,40-of 7.60 (m, 2H), 7,72 (s, 1H), 7,80 (s, 1H), of 7.90 (m, 2H), 8,01 (d, 1H).

FAB (M+H): 402.

EXPERIMENTAL EXAMPLE 1: a Study of inhibitory activity towards Ras farnesyltransferase in vitro

For research use Ras farnesyltransferase obtained by the method of genetic recombination in accordance with the improved method Pompliano (Pompliano et al., Biochemistry, 1992, 31, 3800), and substrate protein Ras (Ras-CVLS), described in patent application Korea 97-14409, which is used after purification by a known method (see Chung et al., Biochimica et Biophysica Acta, 1992, 278, ethylpiperazin-N'-2-econsultancy acid), containing 25 mm potassium chloride, 25 mm magnesium chloride, 10 mm DTT (dithiothreitol) and 50 μm zinc chloride. Use 1.5 μm substrate protein Ras, and 0.15 μm tritium-farnesylpyrophosphate and 4.5 nm farnesyltransferase.

More specifically, in the first stage farnesyltransferase added to the above buffer solution, carry out the reaction for 30 minutes at 37oSince, then stop the reaction by adding 1 ml of ethanol solution containing 1 M model HC1. The resulting precipitate adsorbs onto GF/B filter using to bind to the filter harvester hopper (Hopper FH 225V), washed with ethanol and then measure the radioactivity of the dried filter using the-counter LKB. The titer of the enzyme is determined at unsaturated condition of the substrate, when the substrate concentration of the protein Ras and concentration farnesyltransferase there is a quantitative relationship. The connection which is the subject of the present invention, dissolved in dimethyl sulfoxide (DMSO), added to the reaction solution in an amount of less than 5% of the total amount of the reaction solution, and then measure the activity of the enzyme. The activity of the enzyme present in a ratio in percent of the number farne the frame with the substrate protein Ras in the absence of the tested compound. The value of the IC50for the studied compounds is defined as the concentration at which inhibited 50% of enzyme activity.

To assess the selectivity of inhibition of enzyme activity under the action of compounds that are the subject of the present invention, the measured activity of inhibiting geranylgeranyltransferase. Geranylgeranyltransferase was isolated from bovine brain according to a modified method Scraper (Schaber et al., J. Biol.Chem., 1990, 265, 14701) and conducted research with the use of geranylgeranylpyrophosphate and Ras-CVIL and using the same experimental procedures as in the case farnesyltransferase.

The test results presented in table 7.

EXPERIMENTAL EXAMPLE 2: a Study of inhibitory activity towards Ras farnesyltransferase in vivo

This study used the Rat2 cell line, which expresses a protein C-Harvey-Ras with transforming activity, and Rat2 cell line which is transformed fused protein H-Ras with politnonym site lysine at the C-end of K-Ras. The experiment was performed using a modified method of Declue (Declue, J. E. et al., Cancer Research, 1991, 51, 712). The next experiment will be a description of the etu for growing cells and cells were grown for 48 hours at 37oC in the incubator for cells, and once achieved cell density of 50% or more, the cells were treated with the investigational compound. The connection according to the present invention used in the form of a solution in dimethyl sulfoxide. As in the control and study group used a solution of dimethyl sulfoxide 1% concentration. 4 hours after treatment with investigational compound was added methionine, radiolabelled [35S] , the rate of 150 µci per 1 ml of medium, and after 20 hours of cultivation, the cells were washed with physiological saline solution. Cells were literally, using 1 ml of cold buffer solution for cell lysis (50 mm buffer solution of sodium Sodi HEPES containing 5 mm magnesium chloride, 1 mm DTT, 1% NP 40, 1 mm add, 1 mm PMSF (phenylmethanesulfonyl), 2 μm leupeptin, 2 μm pepstatin and 2 μm antipain), and the supernatant, which was lysed cells received high-speed centrifugation at 12000g x 5 minutes. To obtain quantitative characteristics of the reaction thus measured and brought to standard conditions the quantity of radioactive isotope in the supernatant, after which was added monoclonal antibodies Y1 the 4oC. To the solution was added a suspension of protein a (associated with goat antibodies against mouse immunoglobulin) - agarose and reaction was performed for 1 hour at 4oWith, then deleted the nonspecific related product, immunoprecipitate washed with buffer solution (50 ml Tris chloride buffer solution containing 50 ml of sodium chloride, 0.5% of deoxycholate sodium, 0,5% NP and 0.1% SDS (sodium dodecyl sulphate)). Sediments were added to the buffer solution for electrophoresis and boiled, and then electrophoresis was performed using a 13.5% SDS-polyacrylamide gel. After electrophoresis the gel was fixed and dried. Then the gel was exposed to x-ray film showed and printed. According to the results of the experiment evaluated the intensity of protein bands associated with Farnesina Ras protein or without farnesyl Ras protein, and determined the concentration of the investigated compounds inhibitory to 50% binding farnesyl designated as CIC50taken for the activity of inhibiting Ras-farnesyltransferase in vivo. The results are given in table 7.

1. A derivative of imidazole, represented by the following formula (1):

< / BR>
where n1is an integer from 1 to 3;

And is the UB>3-C7-cycloalkyl or lower alkoxy; or a radical selected from the following group:

< / BR>
< / BR>
< / BR>
where R1and R'1independently represent hydrogen, halogen, cyano, lower alkoxy;

R2represents hydrogen or lower alkyl, or is a group-E-F where E denotes-C(O) -, and F represents a lower alkoxy that may be optionally substituted by phenyl; benzyloxy;

R3represents hydrogen or lower alkyl;

R4represents a radical selected from the following group:

< / BR>
< / BR>
< / BR>
where n2and n3independently denote 0, 1, 2, 3 or 4;

R5and R9independently represent hydrogen, lower alkoxy or halogen;

R6and R8independently represent hydrogen, lower alkyl or halogen;

R7represents hydrogen; lower alkyl which may be optionally substituted C3-C6-cycloalkyl; lower alkoxy; hydroxy; C3-C6-cycloalkyl or halogen;

R10represents hydrogen, lower alkyl or lower alkoxy,

Y represents a radical selected from the following group:

< / BR>
< / BR>
< / BR>
where X represents slalom;

With represents hydrogen or represents a radical selected from the following group:

< / BR>
< / BR>
where R11and R12independently represent hydrogen;

D represents an amino acid residue or a residue of the lower Olkiluoto ether, amino, or represents a radical selected from the following group:

< / BR>
< / BR>
< / BR>
< / BR>
where R10defined as above;

Q represents O or S;

Z represents O, S, S= O, SO2C= O or represents N-R20(where R20represents hydrogen, lower alkyl or hydroxy);

n5= 1 or 2;

R16and R17independently from each other represent hydrogen or lower alkyl which may be optionally substituted by phenyl or cyanophenyl;

R18represents hydrogen or halogen;

R19represents hydrogen, halogen, lower alkoxy, alkoxyalkyl, alkylthio, alkylthiols;

G represents the radical

< / BR>
where R11and R12defined as above;

I represents a lower alkoxy, or represents a radical selected from the following group:

< / BR>
where R16and R17defined as above;

Z as mentioned above,

provided that

(1) the value of n2different from 0, when R3represents hydrogen, and

(2) Y is other than

< / BR>
when But a

< / BR>
or its pharmaceutically acceptable salt.

2 Connection on p. 1, where n1and Y are defined as indicated in paragraph 1; and

And represents hydrogen; a linear or branched C1-C10-alkyl, which may be optionally substituted C3-C7-cycloalkyl or lower alkoxy; or a radical selected from the following group:

< / BR>
< / BR>
< / BR>
where R1, R'1, R2and R3determined as specified in paragraph 1;

R4represents a radical selected from the following group:

< / BR>
< / BR>
< / BR>
where n2n3, R5, R6, R7, R8and R9determined as specified in paragraph 1;

R10represents hydrogen, methyl or methoxy.

3. Connection on p. 1, in which Y represents a

< / BR>
and is a

< / BR>
4. Connection on p. 1, selected from the group comprising the following compounds:

3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-1-[1-(3,4-methylenedioxybenzyl)-1H-imidazol-5-ylmethyl] -4-(naphthalene-1-yl)-1H-pyrrole (1),

1-[1-(atlanticcity)-1H-imidazol-5-ylmethyl] -3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (3),

3-{ N-[2-(N, N-dimethylamino)ethyl] -N-methyl} carbarnoyl-1-[1-(3,4-methylenedioxybenzyl)-1H-imidazol-5-ylmethyl] -4-(naphthalene-1-yl)-1H-pyrrole (4),

3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1-[1-naphthalene-1-ylmethyl)-1H-imidazol-5-ylmethyl] -1H-pyrrole (5),

3-(morpholine-4-yl)carbonyl-4-(naphthalene-1-yl)-1-[1-(naphthalene-1-ylmethyl)-1H-imidazol-5-ylmethyl] -1H-pyrrole (6),

3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl)-1-[1-(naphthalene-1-ylmethyl)-1H-imidazol-5-ylmethyl] -1H-pyrrole (7),

3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-1-[1-((R)--methylbenzyl)-1H-imidazol-5-ylmethyl] -4-(naphthalene-1-yl)-1H-pyrrole (8)

1-[1-((R)--methylbenzyl)-1H-imidazol-5-ylmethyl] -3-(morpholine-4-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (9),

1-[1-((R)--methylbenzyl)-1H-imidazol-5-ylmethyl] -3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (10),

3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-1-[1-((S)--methylbenzyl)-1H-imidazol-5-ylmethyl] -4-(naphthalene-1-yl)-1H-pyrrole (11),

1-[1-((S)--methylbenzyl)-1H-imidazol-5-ylmethyl] -3-(morpholine-4-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (12),

1-[1-((S)--methylbenzyl)-1H-imidazol-5-ylmethyl] -3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (13),

3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1-[1-(phenethyl)-1H-imidazol-5-ylmethyl] -1H-pyrrole (14),

3-(morpholine-4-yl)ka is Talin-1-yl)-1-[1-(phenethyl)-1H-imidazol-5-ylmethyl] -1H-pyrrole (16),

3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-1-[1-(2-methoxy)-phenethyl-1H-imidazol-5-yl] methyl-4-(naphthalene-1-yl)-1H-pyrrole (17),

1-[1-(2-methoxy)phenethyl-1H-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (18),

3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-1-[1-(4-methoxy)-phenethyl-1H-imidazol-5-yl] methyl-4-(naphthalene-1-yl)-1H-pyrrole (19),

1-[1-(4-methoxy)phenethyl-1H-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (20),

1-[1-(2-fluoro)phenethyl-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (21),

1-[1-(2-fluoro)phenethyl-1H-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (22),

1-[1-(2-chloro)phenethyl-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (23),

1-[1-(2-chloro)phenethyl-1H-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (24),

1-[1-(3-chloro)phenethyl-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (25),

1-[1-(3-chloro)phenethyl-1H[-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (26),

3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1-[1-(3-phenyl)propyl-1H-imidazol-5-yl] methyl-1H-pyrrole (27),

3-[4-methylethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1-[1-(naphthalene-2-yl)methyl-1H-imidazol-5-yl] methyl-1H-pyrrole (29),

3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1-[1-(naphthalene-2-yl)methyl-1H-imidazol-5-yl] methyl-1H-pyrrole (30),

3-N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1-{ 1-[2-(naphthalene-1-yl)ethyl] -1H-imidazol-5-yl} methyl-1H-pyrrole (31),

3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1-{ 1-[2-(naphthalene-1-yl)ethyl] -1H-imidazol-5-yl} methyl-1H-pyrrole (32),

1-[1-(4-bromo)phenethyl-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (33),

1-[1-(4-bromo)phenethyl-1H-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (34),

1-[1-(4-fluoro)phenethyl-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (35),

1-[1-(4-fluoro)phenethyl-1H-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (36),

3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-1-[1-(4-methyl)-phenethyl-1H-imidazol-5-yl] methyl-4-(naphthalene-1-yl)-1H-pyrrole (37),

1-[1-(4-methyl)phenethyl-1H-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (38),

1-[1-(4-chloro)phenethyl-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (39),

1-[1-(4-chloro)phenethyl-1H-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (40),

3-[N-(2-m 3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1-{ 1-[2-(naphthalene-2-yl)ethyl] -1H-imidazol-5-yl} methyl-1H-pyrrole (42),

1-[1-(4-hydroxy)phenethyl-1H-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (43),

1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(thiophene-2-yl)carbonyl-1H-pyrrole (44),

1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(thiophene-3-yl)carbonyl-1H-pyrrole (45),

3-benzoyl-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (46),

3-(2-bromobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (47),

3-(3-bromobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (48),

3-(4-bromobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (49),

1-(1H-imidazol-4-yl)methyl-3-(2-methylbenzoyl)-4-(naphthalene-1-yl)-1H-pyrrole (50),

1-(1H-imidazol-4-yl)methyl-3-(3-methylbenzoyl)-4-(naphthalene-1-yl)-1H-pyrrole (51),

1-(1H-imidazol-4-yl)methyl-3-(4-methylbenzoyl)-4-(naphthalene-1-yl)-1H-pyrrole (52),

1-(1H-imidazol-4-yl)methyl-3-(3-methoxybenzoyl)-4-(naphthalene-1-yl)-1H-pyrrole (53),

1-(1H-imidazol-4-yl)methyl-3-(4-methoxybenzoyl)-4-(naphthalene-1-yl)-1H-pyrrole (54),

3-(2-chlorobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (55),

3-(4-chlorobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (56),

3-(2,4-dichlorobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (57),

3-(4-perbenzoic)-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-permeate-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (60),

1-(1H-imidazol-4-yl)methyl-3-(4-methylthiotetrazole)-4-(naphthalene-1-yl)-1H-pyrrole (61)

1-(1H-imidazol-4-yl)methyl-3-[4-(2-methylthioethyl)benzoyl] -4-(naphthalene-1-yl)-1H-pyrrole (62),

1-(1H-imidazol-4-yl)methyl-3-[4-(2-methylthiouracil)benzoyl] -4-(naphthalene-1-yl)-1H-pyrrole (63),

1-(1H-imidazol-4-yl)methyl-3-(3-methylthiotetrazole)-4-(naphthalene-1-yl)-1H-pyrrole (64),

1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(3-phenylbenzyl)-1H-pyrrole (65),

1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(4-phenylbenzyl)-1H-pyrrole (66),

1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(4-phenoxybenzoyl)-1H-pyrrole (67),

3-(4-benzylbutyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (68),

1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(naphthalene-1-yl)carbonyl-1H-pyrrole (69),

1-(1H-imidazol-4-yl)methyl-3-(4-methylbenzoyl)-4-(N-methylindol-3-yl)-1H-pyrrole (70),

5-n-butyl-3-(2,4-dichlorobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (71),

5-benzyl-3-(2,4-dichlorobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (72),

1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl] methyl-4-(naphthalene-1-yl)-3-(thiophene-2-yl)carbonyl-1H-pyrrole (73),

1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl] methyl-4-(naphthalene-1-yl)-3-(thiophene-3-yl)carbonyl-1H-pyrrole (74),

3-benzoyl-1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl] methyl-4-(naphthas

3-(4-bromobenzoyl)-1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl] -methyl-4-(naphthalene-1-yl)-1H-pyrrole (77),

3-(4-perbenzoic)-1-(1-methyl-1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (78),

1-(1-methyl-1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(4-phenoxybenzoyl)-1H-pyrrole (79),

(S)-1-(1H-imidazol-4-yl)methyl-3-[N-(1-methoxycarbonyl-3-methylthio)propyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (80),

(S)-3-[N - (1-hydroxycarbonyl-3-methylthio)propyl] carbarnoyl-1-(1H-imidazol-4-yl)-methyl-4-(naphthalene-1-yl)-1H-pyrrole (81),

1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(N-phenylcarbamoyl)-1H-pyrrole (82),

3-(N-benzylcarbamoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (83),

1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(piperidine-1-yl)carbonyl-1H-pyrrole (84),

1-(1H-imidazol-4-yl)methyl-3-(morpholine-4-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (85),

1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(thiomorpholine-4-yl)carbonyl-1H-pyrrole (86),

1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(S, S-diocletianopolis-4-yl)carbonyl-1H-pyrrole (87),

1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(piperazine-1-yl)carbonyl-1H-pyrrole (88),

1-(1H-imidazol-4-yl)methyl-3-(4-methylpiperazin-1-yl)-4-(naphthalene-1-yl)-1H-pyrrole (89),

1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-3-(thiazolidin-3-yl)carbonyl-1H-pyrrole (90),
3-N-(2-hydroxyethyl)carbarnoyl-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (93),

3-[N-(2-hydroxyethyl)-N-methyl] carbarnoyl-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (94),

1-(1H-imidazol-4-yl)methyl-3-[N-(2-methoxyethyl)-N-methyl] -carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (95),

1-(1H-imidazol-4-yl)methyl-3-(morpholine-4-yl)carbonyl-4-(quinoline-4-yl)-1H-pyrrole (96),

4-(1,2-dehydrogenation-5-yl)-1-(1H-imidazol-4-yl)methyl-3-(morpholine-4-yl)carbonyl-1H-pyrrole (97),

3-N-(4-cyanobenzyl)carbarnoyl-1-(1H-imidazol-4-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (98),

1-(1-methyl-1H-imidazol-5-yl)methyl-3-(morpholine-4-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (99),

(S)-1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl] methyl-3-[N-(1-methoxycarbonyl-3-methylthio)propyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (100),

(S)-1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl] methyl-3-[N-(1-hydroxycarbonyl-3-methylthio)propyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (101),

(S)-1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl] methyl-3-[N-(1-methoxycarbonyl-3-methyl)butyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (102),

(S)-1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl] methyl-3-[N-(1-hydroxycarbonyl-3-methyl)butyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (103),

1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl] methyl-3-(morpholine-4-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (104),<>1-[2-(1H-imidazol-1-yl)ethyl] -3-(morpholine-4-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (106),

(S)-1-[3-(1H-imidazol-4-yl)propyl] -3-[N-(1-methoxycarbonyl-3-methylthio)propyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (107),

(S)-3-[N-(1-hydroxycarbonyl-3-methylthio)propyl] carbarnoyl-1-[3-(1H-imidazol-4-yl)propyl] -4-(naphthalene-1-yl)-1H-pyrrole (108),

1-[3-(1H-imidazol-4-yl)propyl] -3-(morpholine-4-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (109),

1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (110),

1-[1-(4-bromobenzyl)-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (111),

1-[1-(4-bromobenzyl)-1H-imidazol-5-yl] methyl-3-(morpholine-4-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (112),

1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl] methyl-3-(morpholine-4-yl)thiocarbonyl-4-(naphthalene-1-yl)-1H-pyrrole (113),

3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-1-(1-methyl-1H-imidazol-5-yl)methyl-4-(naphthalene-1-yl)-1H-pyrrole (114),

1-(1-isobutyl-1H-imidazol-5-yl)methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (115),

1-(1-cyclohexylmethyl-1H-imidazol-5-yl)methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (116),

3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1-(1-pentyl-1H-imidazol-5-yl)methyl-1H-p

1-(1-decyl-1H-imidazol-5-yl)methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (119),

3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-1-[1-(3-methylbutyl)-1H-imidazol-5-yl] methyl-4-(naphthalene-1-yl)-1H-pyrrole (120),

1-[1-(2-methoxyethyl)-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (121),

3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-1-[1-(3-methoxypropyl)-1H-imidazol-5-yl] -methyl-4-(naphthalene-1-yl)-1H-pyrrole (122),

1-[1-(3-ethoxypropan)-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (123),

1-[1-(3-isopropoxyphenyl)-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (124),

1-[1-(4-bromobenzyl)-1H-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (125),

1-[1-(4-Chlorobenzyl)-1H-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (126),

1-[1-(4-terbisil)-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (127),

1-[1-(4-terbisil)-1H-imidazol-5-yl] methyl-3-[4-methylpiperazin-1-yl] carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (128),

1-[1-(4-methoxybenzyl)-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (129),

1-[1-(4-methoxy [(b)-1H-imidazol-5-yl] methyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (131),

1-[1-(3-Chlorobenzyl)-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (132),

1-[1-(2-Chlorobenzyl)-1H-imidazol-5-yl] methyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (133),

1-[1-(2-Chlorobenzyl)-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)-1H-pyrrole (134),

1-[1-(2-terbisil)-1H-imidazol-5-yl] methyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (135),

1-[1-(4-methylbenzyl)-1H-imidazol-5-yl] methyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (136),

1-[1-(4-methylbenzyl)-1H-imidazol-5-yl] methyl-3-(morpholine-4-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (137),

1-[1-(3-methylbenzyl)-1H-imidazol-5-yl] methyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalene-1-yl)-1H-pyrrole (138),

1-[1-(4-cyanobenzyl)-1H-imidazol-5-yl] methyl-3-(naphthalene-1-yl)carbonyl-1H-pyrrole (139),

1-[1-(4-bromobenzyl)-1H-imidazol-5-yl] methyl-3-(naphthalene-1-yl)carbonyl-1H-pyrrole (140),

1-[1-(4-bromobenzyl)-1H-imidazol-5-yl] methyl-3-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-4-(naphthalene-1-yl)carbonyl-1H-pyrrole (141),

4-etoxycarbonyl-2-(1H-imidazol-5-ylmethyl)-5-(naphthalene-1-yl)oxazol (142),

2-(1H-imidazol-5-ylmethyl)-4-(morpholine-4-yl)carbonyl-5-(naphthalene-1-yl)oxazol (143),

4-etoxycarbonyl-2-(1H-imidazol-5-Eliason (145),

2-[1-(4-Chlorobenzyl)-1H-imidazol-5-ylmethyl] -4-(morpholine-4-yl)carbonyl-5-(naphthalene-1-yl)thiazole (146),

2-[1-(4-Chlorobenzyl)-1H-imidazol-5-ylmethyl] -4-[N-(2-methoxy)ethyl-N-methylcarbamoyl] -5-(naphthalene-1-yl)thiazole (147),

2-[1-(4-Chlorobenzyl)-1H-imidazol-5-ylmethyl] -5-methoxycarbonyl-4-(naphthalene-1-yl)thiazole (148),

2-[1-(4-Chlorobenzyl)-1H-imidazol-5-ylmethyl] -5-(morpholine-4-yl)carbonyl-4-(naphthalene-1-yl)thiazole (149),

2-{ 1-[1-(benzyloxycarbonyl)piperidine-4-ylmethyl] -1H-imidazole-5-ylmethyl} -5-methoxycarbonyl-4-(naphthalene-1-yl)thiazole (150),

2-{ 1-[1-(benzyloxycarbonyl)piperidine-4-ylmethyl] -1H-imidazole-5-ylmethyl} -5-[N-(2-methoxy)ethyl-N-methylcarbamoyl] -4-(naphthalene-1-yl)thiazole (151),

1-[1-(1-benzyloxycarbonylamino-4-ylmethyl)-1H-imidazol-5-ylmethyl] -4-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-3-(naphthalene-1-yl)-1H-pyrazole (152),

1-[1-(1-benzyloxycarbonylamino-4-ylmethyl)-1H-imidazol-5-ylmethyl] -4-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-3-(naphthalene-1-yl)-1H-pyrazole (153),

1-[1-(4-bromobenzyl)-1H-imidazol-5-ylmethyl] -4-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-3-(naphthalene-1-yl)-1H-pyrazole (154),

1-[1-(4-Chlorobenzyl)-1H-imidazol-5-ylmethyl] -4-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-3-(naphthalene-1-yl)-1H-pyrazole (155),

1-[1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl] -4-[N-(2-methoxyethyl)-N-methyl] carbarnoyl-3 is n-1-yl)-1H-pyrazole (157),

1-[1-(1-benzyloxycarbonylamino-4-ylmethyl)-1H-imidazol-5-ylmethyl] -4-(morpholine-4-yl)carbonyl-3-(naphthalene-1-yl)-1H-pyrazole (158),

1-[1-(1-ethoxycarbonylpyrimidine-4-ylmethyl)-1H-imidazol-5-ylmethyl] -4-(morpholine-4-yl)carbonyl-3-(naphthalene-1-yl)-1H-pyrazole (159),

1-[1-(4-bromobenzyl)-1H-imidazol-5-ylmethyl] -4-(morpholine-4-yl)carbonyl-3-(naphthalene-1-yl)-1H-pyrazole (160),

1-[1-(4-Chlorobenzyl)-1H-imidazol-5-ylmethyl] -4-(morpholine-4-yl)carbonyl-3-(naphthalene-1-yl)-1H-pyrazole (161),

1-[1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl] -4-(morpholine-4-yl)carbonyl-3-(naphthalene-1-yl)-1H-pyrazole (162),

1-(1-methyl-1H-imidazol-5-ylmethyl)-4-(morpholine-4-yl)carbonyl-3-(naphthalene-1-yl)-1H-pyrazole (163).

5. The method of obtaining the derivative of imidazole of the formula (1) under item 1, characterized in that the compound represented by the following formula (4):

< / BR>
where n1and As determined as specified in paragraph 1,

interacts in the environment of a solvent in the presence of a base with a compound represented by the following formula (3):

< / BR>
where b, C, D and X are defined as described in paragraph 1;

to obtain compounds represented by the following formula (1b):

< / BR>
where n1, A, b, C, D and X are defined as described in paragraph 1.

6. The connection represented by the following form is

7. The compound represented by the following formula (8):

< / BR>
where W, a, b and C are defined as specified in paragraph 1.

8. Pharmaceutical composition having inhibitory activity against farnesyltransferase containing a therapeutically effective amount of active ingredient in combination with pharmaceutically acceptable carrier, characterized in that as the active ingredient in this composition contains a compound of formula (1) under item 1 or a pharmaceutically acceptable salt of this compound or its isomer.

9. The pharmaceutical composition according to p. 8, suitable for the prevention and treatment of cancer.

10. The pharmaceutical composition under item 8 for the prevention and treatment of restenosis.

11. The pharmaceutical composition under item 8 for the prevention and treatment of atherosclerosis.

12. The pharmaceutical composition under item 8 for the prevention and treatment of infectious diseases caused by hepatitis Delta and related viruses.

Priority points:

28.11.1997 on PP. 1-12;

31.03.1998 on PP. 1-12 (clarification of claims);

23.06.1998 on PP. 1-12 (clarification of claims);

26.06.1998 on PP. 1-12 (clarification of claims);

03.08.1998 on PP. 1-12 (specification concerning

 

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< / BR>
in which the substituents have the following meaning: L, M means hydrogen, C1-C4alkyl, chlorine, Z denotes hydrogen, C1-C4alkyl, C3-C8alkenyl, C3-C5quinil, phenyl, Q means the radical CO-J; J means connected to position 4 of the benzene ring 5-hydroxypyrazoles ring of formula II

< / BR>
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