Imidazole derivatives and pharmaceutically acceptable composition

 

(57) Abstract:

The invention relates to imidazole derivative of General formula I, where n=0 or 1, R1is hydrogen, alkyl, R2is hydrogen or R2and R3form a double bond, R3is hydrogen, alkyl, R4is hydrogen, alkyl, hydroxy-group, alkoxy, R5is hydrogen or alkyl, or R4and R5form a carboxyl group, R6, R7, R8is hydrogen, alkyl, hydroxy-group, alkoxy, hydroxyalkyl, halogen, X-CHR9-(CHR10)m-, m = 0 or 1, R9and R10is hydrogen or alkyl. The compounds of formula I possess a 2-agonistic activity and due to this property can be used as active ingredient in pharmaceutical compositions. 2 C. and 13 C.p. f-crystals, 2 PL.

The invention relates to substituted 4(5)-(1-indanyl and 1-inanimate, and 1-endanimation)imidazoles and 4(5)-[1-(1,2,3,4-tetrahydronaphthyl and 1,2,3,4-tetrahydronaphthalene and 1,2,3,4-tetrahydronaphthalene] imidazoles and their isomers, pharmaceutically acceptable salts and esters. It also applies to their acquisition, use and containing pharmaceutical compositions.

The compounds of this invention have affinity what anistemi. Therefore, they are applicable in the treatment of hypertension, glaucoma, migraines, diarrhoea, ischaemia, addiction to chemical substances (such as tobacco and drugs), and various neurological, musculoskeletal, and mental associated with the cognitive ability of the disorders, and also as a sedative and analgesic agents, nasal protivozastojnye funds and auxiliary funds for anesthesia.

Gregory G. B. et al. describe in J. Org.Chem. (1990), 55, 1479-1483 new stage of synthesis of derivatives of 1-phenyl-alkyl-1-(4-imidazolyl)-1,2,3,4-tetrahydronaphthalene applicable as ones of receptor antagonists angiotensin II.

Imidazole derivatives of this invention are any compounds of formula I

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where n represents 0 or 1;

R1denotes hydrogen or C1-C4-alkyl;

R2denotes hydrogen or R2and R3together form a double bond;

R3denotes hydrogen or C1-C4-alkyl, or R2and R3together form a double bond;

R4denotes hydrogen, C1-C4-alkyl, hydroxy or C1-C4-alkoxy;

R5denotes hydrogen or C1-C4-alkyl, or R4and R and R8the same or different and independently represent hydrogen, C1-C4-alkyl or C2-C4alkenyl,3-C7-cycloalkyl, hydroxy, C1-C4-alkoxy, C1-C4-hydroxyalkyl, thiol,1-C4-alkylthio,1-C4-alkylthiol, halogen, trifluoromethyl, nitro or optionally substituted by an amino group;

X denotes-CHR10-(CHR11)m-;

m denotes 0 or 1

and R9and R10the same or different and represent independently hydrogen or1-C4-alkyl;

or their pharmaceutically acceptable ester or salt.

The terms used here have the following meanings: halogen represents chlorine, bromine or fluorine, preferably chlorine or fluorine. Group C1-C4-alkyl, C1-C4-alkoxy and C2-C4alkenyl, etc. can be groups with a branched or unbranched chain. WITH3-C7-cycloalkyl represents a saturated cyclic hydrocarbon group, preferably having 3-5 carbon atoms. Optionally substituted amino group represents an amino group which is unsubstituted or substituted WITH1-C4-alkyl.

Czardom, hydroxy or C1-C4-alkoxy, such as ethoxy,

R5preferably is hydrogen or R4and R5together with the carbon atom to which they are connected, form a carbonyl group.

R6preferably is hydrogen, C1-C4-alkyl, such as methyl, ethyl, tert-butyl, hydroxy or C1-C4-alkoxy, such as methoxy. For example, R6can be1-C4the alkyl in position 4, 5 or 6, such as 4-methyl, 4-tert-butyl, 5-methyl, 6-methyl, 6-ethyl, 6-tert-butyl, 6-isobutyl, hydroxyl in position 5 or position 7 or1-C4-alkoxy at position 5, 6 or 7, such as 5-, 6 - or 7-methoxy. More preferably R6is hydrogen, 4-stands, 6-stands or 7-methoxy.

R7preferably is hydrogen, C1-C4-alkyl, such as methyl or tert-butyl, hydroxyl group or1-C4-alkoxy, for example methoxy. For example, R7can be1-C4the alkyl in position 5, 6 or 7, such as 5-methyl, 7-methyl, 6-tert-butyl, 7-hydroxy or 7-methoxy. More preferably R7is hydrogen.

R8preferably is hydrogen, hydroxy or CUB>4
-alkoxy at position 6, such as 6-methoxy.

R9preferably is hydrogen or stands.

When n=1 and m=0

R1preferably is hydrogen, stands or ethyl.

R2, R3and R9preferably are hydrogen.

R4and R5preferably are hydrogen or stands.

R6preferably is hydrogen, C1-C4-alkyl, such as methyl or tert-butyl, hydroxy, C1-C4-alkoxy, such as methoxy, or C1-C4-hydroxyalkyl, such as hydroxymethyl or halogen. For example, R6may be C1-C4the alkyl in position 4 or 5, such as 4 - or 5-methyl or 4 - or 5-tert-butyl, 4-, 5-, 6 - or 7-hydroxy, C1-C4-alkoxy at position 5, 6 or 7, such as 5-, 6 - or 7-methoxy; or (C1-C4-hydroxyalkyl in position 5, such as 5-hydroxymethyl. R6may be a halogen at position 5 or 6, such as 5 - or 6-fluoro or 5 - or 6-bromo. More preferably R6is a 4-, 5 - or 6-hydroxyl group.

R7preferably is hydrogen, C1-C4-alkyl, a hydroxyl group, a C1-C4-alkoxy, C1-C4-alkoxy at position 6, such as 6-methoxy, C1-C4-hydroxyalkyl in position 6, such as 6-hydroxymethyl or halogen at position 5, such as 5-bromo.

More preferably R7is hydrogen, 6-tert-bootrom, 6-hydroxy or 6-hydroxymethyl.

R8preferably is hydrogen, C1-C4-alkyl, a hydroxyl group, a C1-C4-alkoxy or halogen, for example, C1-C4the alkyl in position 7, such as 7-methyl or 7-tert-butyl, 6 - or 7-hydroxy or C1-C4-alkoxy at position 6, such as 6-methoxy, or by halogen at position 7, such as 7-bromo.

Particularly preferably R6is a hydroxyl group in position 4 or 6 rings indane and R7and R8are hydrogen, or R6is a hydroxyl group in position 5 of the ring indane and R7is a hydroxyl group, a C1-C4-alkyl or C1-C4-hydroxyalkyl in position 6 rings indana, such as 6-tert-butyl-or 6-hydroxymethyl and R8is hydrogen.

When n=m=1

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R1, R2, R31-C4-alkyl, such as methyl.

R6preferably is in position 5, 6 or 7.

R6preferably is a hydrogen, a hydroxyl group,1-C4-alkoxy, for example methoxy or halogen. For example, R6can be a 5-, 6 - or 7-methoxy, 6 - or 7-hydroxy or halogen at position 6, such as 6-bromo.

R7preferably located in position 7.

R7preferably is hydrogen or C1-C4-alkyl, such as, for example, 7-tert-butyl-7-hydroxy.

R8preferably is in position 8.

R8preferably is hydrogen or halogen, such as 8-bromo.

When n=0 and m=1

R3, R4, R5, R7, R8, R9and R10preferably are hydrogen.

R6preferably is hydrogen or halogen, for example chlorine. R6may be a halogen at position 5, such as, for example, 5-chloro.

This invention includes in its scope all the possible isomers and stereoisomers, in particular Z and E (CIS - and TRANS-isomers, and enantiomers.

The compounds of formula I form acid-adults chlorides, bromides, sulfates, nitrates, phosphates, sulfonates, formate, tartratami, maleate, citrates, benzoate, salicylates, ascorbates. In addition, compounds in which one or more R4-R8represent a hydroxy-group, form esters and salts with alkaline metals and alkaline earth metals. Typical esters include lower alkalemia esters, such as methyl, ethyl and propyl esters.

The compounds of this invention can be obtained using the following methods. (It should be noted that in the formulas below, when the imidazole group is protected, the protective group R' is benzyl or trityl) can be attached to either of the two nitrogen atoms of imidazole ring. In accordance with this the use of 1-benzyl-5-imidazolecarboxaldehyde as the source of the substance leads to a 1,5-substituted derivatives, whereas in the case of use of trityl substitution takes place mainly in the 1,4-positions).

Synthesis of 4(5)-(1-indanyl)imidazoles and related 4(5)-[1-(1,2,3,4-tetrahydronaphthyl)]imidazoles

Method A.

The compounds of formula I, where n=0 and m=0 or 1, can be obtained by acid catalyzed the cyclization of protected or MetaDimension way 4(5)-(1-indanyl)imidazoles can be obtained by cyclization of the compounds of formula II

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where R3-R9have the above meanings and R' is a protective group,

in the presence of acid to form compounds of formula III

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where the substituents have the above values,

and the removal of the protective group R' to obtain compounds of the formula Ia

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Appropriate 4(5)-[1-(1,2,3,4-tetrahydronaphthyl)]imidazoles can be prepared by cyclization of compound (II'

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where R3-R10have the above significance, and R' is a protective group,

in the presence of acid to form compounds of formula III'

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where the substituents have the above values,

and the removal of the protective group R' to obtain compounds of the formula Ia'

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where the substituents have the above values.

The protective group R' may be, for example, benzyl or Triticum. When R' is trition, it can be removed with acid, and when the protective group is benzyl, it can be removed by catalytic hydrogenation. The acid used in the cyclization reaction may be, for example, polyphosphoric acid (PFC) or methansulfonate acid.

The original metering is to obtain , -unsaturated ketones via aldorino condensation, the reaction of imidazolylalkyl with appropriately substituted benzaldehyde in the presence of a base:

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Concomitant recovery of carbonyl and subsequent catalytic hydrogenation to give the saturated alcohols used in the cyclization. Reduction of carbonyl groups can be, for example, using sodium borohydride. If imidazole residue substituted benzyl group, it can also be removed by catalytic hydrogenation.

To implement substitution in position 1 of the ring indane or 1,2,3,4-tetrahydronaphthalene possible to conduct the reaction of the 1,2-addition of the intermediate ketone with a nucleophile prior to hydrogenation. This is conveniently done by the Grignard reaction, which is carried out by adding to the reaction mixture of alkylpolyglucoside, for example bromide, obtained from the alkyl-halide and magnesium:

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Another applicable method for obtaining alcohols required as starting materials in the cyclization, is the use of the Grignard reaction to obtain 4(5)-(1-hydroxyphenylethyl)imidazoles. In this case, 4(5)-imidazolecarboxaldehyde or ketone lead in the interaction with the PE the
Method b.

To obtain a substitution at position 3 group indana you can use the following procedure: obtain an intermediate compound of formula Ib, which is also active compound, in which R4and R5together form a carbonyl group.

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There are various ways to obtain this intermediate compounds.

First, it can be obtained by using acid catalyzed cyclization of 1-aryl-3[4(5)-imidazolyl]-, / -unsaturated-1-propanone:

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, -Unsaturated ketone used as starting material in the above reaction, can be obtained catalyzed by base Alderney condensation of substituted or unsubstituted 4(5)-imidazolecarboxaldehyde and from appropriately substituted phenylalkylamine.

Secondly, it can be obtained by condensation of benzyl-substituted Eurocasinobet acid with an appropriately substituted benzene:

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Benzyl protection is removed by hydrogenation, as described earlier.

Ketone group can then be modified additionally by means of different ways. It can be restored to the corresponding alcohol by borohydride natone also be modified using the Grignard reaction:

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These compounds can then be converted into compounds of formula I, where n= m= 0 and R4is alkyl and R5is hydrogen, catalytic hydrogenation, as described above.

The compounds of formula Ib, in which R4represents alkoxy and R5represents hydrogen, can be obtained from the corresponding alcohol in concentrated hydrochloric acid.

Method C.

The following method of synthesis of 4(5)-(1-indanyl)imidazoles of the formula I is to use litoraneo imidazole in the reaction of aromatic electrophilic substitution with 1-indanone (imidazole, bis-protected according to the method described Kudzma et al., in Synthesis (1991), R. 1021). The protection can be removed by treatment with an acid, which induces the simultaneous loss of water. The double bond restore catalytic hydrogenation, as described above.

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Synthesis of 4(5)-(indan-1-ylmethyl)imidazoles and 4(5)-(indan-1-ylmethylene)imidazoles and related tetrahydronaphtalene derivatives

Method d.

Getting 4(5)-(indan-1-ylmethyl and indan-1-ylmethylene)imidazole and the appropriate tetrahydronaphthalene patterns can be performed using the so-called what is titanium low valence. After condensation can be followed by hydrogenation of the double bond and the simultaneous elimination of the protective group in the imidazole ring.

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The compounds of this invention can be enterline, topically or parenterally. Parenteral use, for example, when connections provide as a sedative or ansioliticos agents in connection with different clinical operations and for analgesia or strengthening of anesthesia.

The compounds of this invention can be prepared separately or together with other active ingredients and/or pharmaceutically acceptable diluent or carrier in the form of pharmaceutical forms with different unit dosages, such as tablets, capsules, solutions, emulsions, and powders, etc. using conventional methods. Used pharmaceutical carriers selected with regard to the intended route of administration. So, solid carriers include lactose, sucrose, gelatin and agar, while liquid carriers typically include water, syrup, peanut butter and olive oil. The amount of the active ingredient varies from 0.01 to 75 wt.% depending on the type of dosage form.

A suitable oral dose for souzrest and gender of the subject to treatment of a subject, subject to the treatment condition and the route of administration. In accordance with this dose for parenteral administration is usually from 0.5 μg/kg to 10 mg/kg / day and the dose for oral administration is from 5 μg/kg to 100 mg/kg for adult males.

This invention also provides a compound of this invention or its ester or salt for use in the method of treatment of a human or animal.

This invention also provides a compound of this invention or its ester or salt for use in the treatment of hypertension, glaucoma, chronic and acute pain, migraine, diarrhea, colds (runny nose), ischemia, addiction to chemical substances, anxiety, particularly preoperative anxiety, and various neurological, musculoskeletal, and mental associated with cognitive ability violations or as auxiliary additives for anesthesia.

The invention also provides use of the compounds of this invention or its ester or salt in the preparation of drugs for the treatment of hypertension, glaucoma, chronic and acute pain, migraine, diarrhea, colds (runny nose), ischemia, addiction to chemical substances, anxiety, osoznatelno ability violations or as auxiliary additives for anesthesia.

In addition, this invention relates to a method for the treatment of hypertension, glaucoma, chronic and acute pain, migraine, diarrhea, colds (runny nose), ischemia, addiction to chemical substances, anxiety, particularly preoperative anxiety, and various neurological, musculoskeletal, and mental associated with the cognitive ability of violations by introducing to a subject in need of such treatment, an effective amount of the compounds of this invention or its pharmaceutically acceptable ester or salt.

The results of the tests.

1. A2-agonist in a rat model of VAS duct of the rat.

A2-agonist was determined with the use of a dedicated, electrically stimulated parts of the prostate drug VAS duct rats (Virtanen et al. Arch. Int. Pharmacodyn et Ther. 297 (1989), pp.190-204). In this model, the A2-agonist could inhibit electrically induced muscle contraction by activation of presynaptic A2-adrenergic receptors and decrease, thus, secretion on the engine side. Known A2-agonist, dexmedetomidine was used as reference substance. The results are shown in table 1, where A2-agonistic effect predstavlennogo inhibition).

Were tested the following connections:

1. The hydrochloride of 4-(4-methylinden-1-yl)-1H-imidazole.

2. Hydrochloride 3-(1H-imidazol-4-ylmethyl)indan-5-ol.

3. Hydrochloride 4-[1-(indan-1-yl)ethyl]-1H-imidazole.

4. Hydrochloride, 8-(1H-imidazol-4-ylmethyl)-5,6,7,8-tetrahydronaphthalen-2-ol.

5. Dexmedetomidine (reference compound).

2. Tests link.

Affinity against2-adrenoreceptor and1-adrenergic receptors was assessed by determining the displacement of 1 nm3H-RX821002 (2) or 0.1 nm3N-prazosin (1from-adrenergic receptors in the membranes of rat neocortex. For this purpose, membranes were incubated with various concentrations of test compounds, lying in the concentration range of five orders of magnitude. Nonspecific binding was defined with 10 μm by phentolamine. The membrane was used for protein concentration 2 mg/ml in a total volume of 250 μl. Buffer for incubation consisted of 50 mm Tris-Hcl, pH of 7.7. After 30 minutes incubation at 25oSince the samples were filtered through a filter made of glass fiber and the filters were washed three times in 4 ml ice buffer for washing, consisting of 10 mm Tris-HCl, pH of 7.7. Then the filters were dried, soaked scintillation smjestaj computer program for nonlinear least squares LIGAND.

Each compound was tested at least in three independent experiments on his affinity for2or1-adrenergic receptors in the neocortex of the rat. The results are shown in table 2.

The following examples illustrate the formation of compounds of the present invention.

EXAMPLE 1. 4-(6-tert-Batiliman-1-yl)-1H-imidazole.

a) 3-(4-tert-Butylphenyl)-1-(1H-imidazol-4-yl)-propan-1-ol.

A solution of 4-tert-butylbenzaldehyde (5.7 g), 1-(3-benzyl-3H-imidazol-4-yl)ethanol (7.0 g) and 48% sodium hydroxide (2.0 ml) in methanol (60 ml) is heated at 60-65oWith over 11 hours. Then the reaction mixture is cooled in a bath of ice. The precipitate is filtered off and the solid intermediate product 1-(3-benzyl-3H-imidazol-4-yl)-3-(4-tert-butylphenyl)-propen-1-he washed with methanol. The output of 10.0 g

The intermediate product is dissolved in a mixture of ethanol (170 ml) and conc. hydrochloric acid (3 ml). The reaction mixture hydronaut at 50-60oWith palladium on coal as a catalyst to stop the consumption of hydrogen. The mixture is filtered and the filtrate is evaporated to dryness. The residue is dissolved in water and alkalinized with sodium hydroxide. The product is then extracted with methylene chloride, washed the e with the use of dry hydrochloric acid. The output of 6.8 g

1H NMR (as HCl-salt, MeOH-d4): of 1.29 (s, 9H), 2.06 to a 2.13 (m, 2H), 2,62-2,78 (m, 2H), 4,77 (t, 1H), 7,13 (m, 2H), 7,30 (m, 2H), 7,40 (s, 1H), 8,79 (s, 1H).

b) 4-(6-Tert-Batiliman-1-yl)-1H-imidazole.

A mixture of 3-(4-tert-butylphenyl)-1-(1H-imidazol-4-yl)propan-1-ol (2.0 g) and methanesulfonic acid (30 ml) is heated at 60oC for 5 minutes. Then the reaction quenched by pouring it into a solution of ice water. The acidic solution is alkalinized with ammonium hydroxide solution and extracted with ethyl acetate. The combined organic layers washed with water, dried with sodium sulfate and evaporated to dryness under reduced pressure. The crude product is purified flash chromatography with elution with a mixture of methylene chloride - methanol. The product is crystallized from ethyl acetate. The output 220 mg.

1H NMR (MeOH-d4): 1,24 (s, N), 2,07-of 2.20 (m, 1H), 2,43-of 2.54 (m, 1H), 2,81-a 3.01 (m, 2H), 4,35 (t, 1H), 6,74 (s, 1H), to 7.09 (s, 1H), 7,14-7,21 (m, 2H), 7,60 (s, 1H).

In the same way received the following connections.

4-(Indan-1-yl)-1H-imidazole.

1H NMR (Dl3): 2,08-2,19 (m, 1H), 2,41 is 2.51 (m, 1H), 2,80-2,95 (m, 2H), 4,37 (t, 1H), 6,65 (s, 1H), 7,07-7,21 (m, 4H), 7,25 (s, 1H).

4-(4-Methylinden-1-yl)-1H-imidazole. So pl. hydrochloride 153-156oC.

1H NMR (as HCl-salt, MeOH-d4): 2,08-of 2.20 (m, 1H), 2,30 (s, MN), 2,58,2,69 (m, 1H), 2,87-3,1/SUP>H NMR (as HCl-salt, MeOH-d4): 2,07-of 2.20 (m, 1H), 2,28 (s, 3H), 2,55,2,66 (m, 1H), 2,89-is 3.08 (m, 2H), 4.53-in (t, 1H), to 6.88 (s, 1H), 7,06 (d, J=7,8 Hz, 1H), 7,19 (d, J=7,8 Hz, 1H), 7,30 (s, 1H), 8,79 (s, 1H).

4-(6-Atienden-1-yl)-1H-imidazole.

1H NMR (as HCl-salt, MeOH-d4): of 1.17 (t, 3H), 2,08-of 2.21 (m, 1H), 2,55-to 2.67 (m, 3H), 2,90-3,10 (m, 2H), 4,56 (t, 1H), 6,91 (s, 1H), was 7.08 (d, J=7,7 Hz, 1H), 7,22 (d, J=7,7 Hz, 1H), 7,32 (s, 1H), cent to 8.85 (s, 1H).

4-(4,5-Dietlinde-1-yl)-1H-imidazole. So pl. hydrochloride 161-164oC.

1H NMR (as HCl-salt, MeOH-d4): 2.06 to to 2.18 (m, 1H), 2,22 (s, 3H), and 2.26 (s, 3H), 2,56 of 2.68 (m, 1H), 2,87-3,11 (m, 2H), 4,55 (t, 1H), 6,78 (d, J=7,6 Hz, 1H), 6,99 (d, J=7,6 Hz, 1H), 7,27 (s, 1H), 8,80 (s, 1H).

4-(5,7-Dietlinde-1-yl)-1H-imidazole.

1H NMR (Dl3): 2,07 (s, 3H), 2,07-2,22 (m, 1H), 2,31 (s, 3H), 2.40 a of $ 2.53 (m, 1H), 2.77-to 2,87 (m, 1H), 2,94 was 3.05 (m, 1H), of 4.44 (m, 1H), 6,55 (s, 1H), 6,80 (s, 1H), 6,94 (s, 1H), 7,53 (s, 1H).

4-(2,4-Dietlinde-1-yl)-1H-imidazole.

1H NMR (Dl3): of 1.23 (d, 3H), of 2.28 (s, 3H), 2,46 is 2.55 (m, 2H), 3,05-and 3.16 (m, 1H), 3,92 (d, 1H), for 6.81-6,83 (m, 2H), 6,95-to 7.09 (m, 2H), 7,56 (s, 1H).

4-(5-Methoxyindol-1-yl)-1H-imidazole. So pl. 180-184oC.

1H NMR (CDCl3+MeOH-d4): 2,09-2,19 (m, 1H), 2,48 at 2.59 (m, 1H), 2,87 are 2.98 (m, 2H), 3,79 (s, 3H), 4,35 (t, 1H), 6,69-of 6.73 (m, 2H), PC 6.82 (d, J=2,0 Hz, 1H), 7,03 (d, J=8,2 Hz, 1H), 7,53 (s, 1H).

4-(7-Methoxyindol-1-yl)-1H-imidazole.

1H NMR (DCl3): 2,20-of 2.50 (m, 2H), 2,83 are 2.98 (m, 2H), 3,82 (s, 3H), 4,50-of 4.54 (m, 1H), 6,66-6,72 (m, 2H), 6,86 (d, J=7,7 Hz, 1H), UB>): 2,09-of 2.20 (m, 1H), 2,52 - to 2.65 (m, 1H), 2,87-3,11 (m, 2H), 3,69 (s, 1H), 3,78 (s, 1H), 4,49-of 4.54 (m, 1H), 6,37 (s, 1H), 6,50 (s, 1H), was 7.08 (s, 1H), 8,73 (s, 1H).

EXAMPLE 2. 4-(1-Methylindol-1-yl)-1H-imidazole.

a) 2-(3-Benzyl-3H-imidazol-4-yl)-4-phenylbutane-2-ol.

1.0 g of magnesium shavings pour 5 ml of dry tetrahydrofuran. To this mixture is added to 7.8 g (2-bromacil)benzene in 30 ml of dry tetrahydrofuran at such speed that is supported by a smooth reaction. The mixture is then heated under reflux for 1 hour. After cooling to room temperature is added dropwise 3.0 g of 1-(3-benzyl-3H-imidazol-4-yl)ethanone in 20 ml of tetrahydrofuran to the Grignard reagent and the reaction mixture heated under reflux for 1 hour. The cooled reaction mixture is poured into cold dilute hydrochloric acid. Treatment of this mixture gives the crude product which is recrystallized from ethyl acetate. Output 3.3V,

1H NMR (as HCl-salt, MeOH-d4): 1,67 (s, 3H), 2,01-of 2.08 (m, 2H), 2,37-2,48 (m, 1H), 2.57 m-a 2.71 (m, 1H), of 5.75 (dd, 2H), 6,97-7,42 (m, 10H), to 7.50 (s, 1H), up 8.75 (s, 1H).

b) 2-(1H-imidazol-4-yl)-4-phenylbutane-2-ol.

3.3 grams of 2-(3-benzyl-3H-imidazol-4-yl)-4-phenylbutane-2-ol are dissolved in 100 ml of ethanol. The reaction solution hydronaut at 50oWith 10% palladium on coal is th recrystallized from ethyl acetate. The output of 2.0,

1H NMR (MeOH-d4): of 1.56 (s, 3H), 2,01 and 2.13 (m, 2H), 2,37-2,47 (m, 1H), 2,53-of 2.64 (m, 1H), of 6.96 (s, 1H), 7,07-7,13 (m, 3H), 7.18 in-of 7.23 (m, 2H), to 7.61 (s, 1H).

C) 4-(1-Methylindol-1-yl)-1H-imidazole.

A mixture of 2-(1H-imidazol-2-yl)-4-phenylbutane-2-ol (0.5 g) and methanesulfonic acid (12 ml) is heated at 100oC for 35 minutes. The cooled reaction mixture was poured into water and alkalinized with sodium hydroxide solution. The product is extracted with ethyl acetate, washed with water, dried with sodium sulfate and evaporated under reduced pressure. The product is converted into its cleaners containing hydrochloride salt in ethyl acetate using dry hydrochloric acid. Yield 387 mg, so pl. 164-171oC.

1H NMR (as HCl-salt, MeOH-d4): 1,67 (s, 3H), 2.21 are of 2.30 (m, 1H), 2.40 a - 2,50 (m, 1H), 2,96-3,11 (m, 2H), 7,06-7,33 (m, 5H), 8,84 (s, 1H).

EXAMPLE 3. 4-(5-Chloro-1,2,3,4-tetrahydronaphthalen-1-yl)-1H-imidazole.

a) 4-(2-Chlorophenyl)-1-(1H-imidazol-4-yl)-butane-1-ol.

3.3 grams magnesium turnings pour 40 ml of dry tetrahydrofuran. To this mixture of 32.0 g of 1-(3-bromopropyl)-2-chlorobenzene (obtained according Baddar, F. G. et al., J. Chem. Soc., 1959, 1027) in 100 ml dry tetrahydrofuran at such speed that is supported by a smooth reaction. When magnesium turnings are reacted, the solution is cooled to couective Grignard reagent and the reaction mixture heated under reflux for 1 hour. The cooled reaction mixture is poured into cold dilute hydrochloric acid. The tetrahydrofuran is distilled off under reduced pressure and the residue is cooled. The obtained residue was filtered and washed with water. The crude product is recrystallized from ethanol. Output 8,0, So pl. cleaners containing hydrochloride salt 152-154oC.

1H NMR (as HCl-salt, MeOH-d4): 1,65 is 1.91 (m, 4H), 2,80 (t, 2H), 4,82, (t, 1H), 7,14-7,35 (m, 4H), 7,40 (s, 1H), 8,83 (s, 1H).

b) 4-(5-Chloro-1,2,3,4-tetrahydronaphthalen-1-yl)-1H-imidazole.

A mixture of the hydrochloride of 4-(2-chlorophenyl)-1-(1H-imidazol-4-yl)butane-1-ol (1.0 g) and methanesulfonic acid (15 ml) is heated at 100oC for 2 hours. The cooled reaction mixture was poured into water and alkalinized with sodium hydroxide solution. The product is extracted with ethyl acetate, washed with water, dried with sodium sulfate and evaporated under reduced pressure. The crude product is recrystallized from ethyl acetate. Yield 0.4 g, so pl. 165 to 169oC.

1H NMR (DCl3): 1,74 of - 1.83 (m, 2H), 1,95-2,15 (m, 2H), 2,70 - only 2.91 (m, 2H), 4,19 (t, 1H), of 6.49 (s, 1H), of 6.96-7,05 (m, 2H), 7,21-7,24 (m, 1H), 7,54 (s, 1H).

EXAMPLE 4. 4-(1,2,3,4-Tetrahydronaphthalen-1-yl)-1H-imidazole.

4-(5-Chloro-1,2,3,4-tetrahydronaphthalen-1-yl)-1H-imidazole (300 mg) is dissolved in ethanol (15 is the RC. The mixture is filtered to remove catalyst and the filtrate is evaporated under reduced pressure. The residue is dissolved in water and alkalinized with sodium hydroxide solution. The product is extracted with methylene chloride, washed with water, dried with sodium sulfate and evaporated under reduced pressure. The crude product is recrystallized from ethyl acetate. Exit 169 mg, so pl. 105-110oC.

1H NMR (Dl3): 1,70-of 1.85 (m, 2H), 2.05 is-2,11 (m, 2H), 2,78-of 2.86 (m, 2H), 4,21 (t, 1H), 6,59 (s, 1H),? 7.04 baby mortality-7,14 (m, 4H), 7,52 (s, 1H).

EXAMPLE 5. 3-(1H-Imidazol-4-yl)-5-isobutylidene-1-ol.

a) 3-(3-Benzyl-3H-imidazol-4-yl)-1-(4-isobutylphenyl)propen-1-he

A solution of 4-isobutylacetophenone (2.0 g), 3-benzyl-3H-imidazole-4-carbaldehyde (2.1 g) and 48% sodium hydroxide (0,65 ml) in methanol (20 ml) is heated at 55-60oC for 6 hours. Then the reaction mixture is cooled in a bath of ice. The precipitate is filtered and washed with methanol. Output of 2.5,

1H NMR (Dl3): of 0.91 (d, 6H), 1.85 to 1,95 (m, 1H), 2,54 (d, 2H), 5,28 (s, 2H), 7,12 - 7,14 (m, 2H), 7.23 percent (d, J=8,2 Hz, 2H), 7,30-7,41 (m, 4H), 7,60-to 7.68 (m, 3H), 7,80 (d, J=8,2 Hz, 2H).

b) 3-(3-Benzyl-3H-imidazol-4-yl)-5-isobutylidene-1-it.

A mixture of 3-(3-benzyl-3H-imidazol-4-yl)-1-(4-isobutylphenyl)propen-1-she (2.4 g) and methanesulfonic acid (40 ml) notimeout flash chromatography with elution with a solution of methylene chloride - of methanol. The output of 0.5 g

1H NMR (Dl3): to 0.89 (d, 6H), 1,81 is 1.91 (m, 1H), 2,34 (dd, J=18,8 Hz, J= 4,0 Hz, 1H), of 2.51 (d, 2H), 2,80 (dd, J=18,8 Hz, J=7,9 Hz, 1H), of 4.44-4,48 (m, 1H), 5,03-5,16 (m, 2H), only 6.64 (s, 1H), 7,05 - was 7.08 (m, 2H), 7,13 (s, 1H), 7,22 (d, J=7,8 Hz, 1H), 7,26-7,39 (m, 3H), EUR 7.57 (s, 1H), 7,68 (d, J=7,8 Hz, 1H).

C) 3-(1H-imidazol-4-yl)-5-isobutylidene-1-ol.

3-(3-Benzyl-3H-imidazol-4-yl)-5-isobutylidene-1-it. dissolved in ethanol (15 ml). The reaction solution hydronaut at 50oWith 10% palladium on coal as a catalyst to stop the consumption of hydrogen. The mixture is filtered to remove catalyst and the filtrate is evaporated under reduced pressure. The crude product contains CIS - and TRANS-isomers. Isomers purified flash chromatography.

1H NMR (cis-isomer, CDCl3): of 0.85 (d, 6H), 1,74-of 1.84 (m, 1H), 2,15-of 2.20 (m, 1H), 2.40 a (d, 2H), 2,69-and 2.79 (m, 1H), 4,33 (d, 1H), 5,16 (d, 1H), 6,91 (s, 1H), 6,93 (s, 1H),7,02(d, J=7,7 Hz,1H), 7,39 (d, J=7,7 Hz, 1H), 7,42 (s, 1H).

1H NMR (trans-isomer, DCl3): of 0.85 (d, 6H), 1,74-of 1.84 (m, 1H), 2,35 is 2.46 (m, 4H), 4,60 (t, 1H), 5,26 (t, 1H), 6,65 (s, 1H), 6,95 (s, 1H),? 7.04 baby mortality (d, J= 7,7 Hz, 1H), 7,33 (d, J=7,7 Hz, 1H), 7,46 (s, 1H).

EXAMPLE 6. 3-(1H-Imidazol-4-yl)-5-methoxy-6,7-dietlinde-1-he

a) 3-(3-Benzyl-3H-imidazol-4-yl)-5-methoxy-6,7-dietlinde-1-it.

A mixture of 2,3-dimethylanisole (2.0 g), 3-(3-benzyl-3H-imidazol-4-yl)acrylic acid (3.4 g) and methanesulfonic acid (60 the t solution of sodium hydroxide. The product is extracted with ethyl acetate, washed with water, dried with sodium sulfate and evaporated under reduced pressure. The crude product is purified flash chromatography with elution with a solution of methylene chloride-methanol. The output of 1.1,

1H NMR (Dl3): to 2.13 (s, 3H), 2,35 (dd, J=18,5 Hz, J=4,1 Hz, 1H), 2,61 (s, 3H), of 2.81 (dd, J=18,5 Hz, J=8,2 Hz, 1H), 3,76 (s, 3H), 4,34-to 4.38 (m, 1H), of 5.05 (s, 2H), of 6.52 (s, 1H), 6,72 (s, 1H), 7,00-7,05 (m, 2H), 7,29 was 7.36 (m, 3H), 7,56 (s, 1H).

b) 3-(1H-imidazol-4-yl)-5-methoxy-6,7-dietlinde-1-it.

3-(3-Benzyl-3H-imidazol-4-yl)-5-methoxy-6,7-dietlinde-1-he (1.1 g) is dissolved in ethanol (90 ml). The reaction solution hydronaut at 50-55oWith 10% palladium on coal as a catalyst for 7 hours. The mixture is filtered to remove catalyst and the filtrate is evaporated under reduced pressure. The product is converted into its cleaners containing hydrochloride salt in ethyl acetate using dry hydrochloric acid. Yield 0.6 g, so pl. 258-261oC.

1H NMR (as HCl-salt, MeOH-d4): of 2.16 (s, 3H), 2,62 (s, 3H), 2,68 (dd, J= 18,7 Hz, J= 4,0 Hz, 1H), 3,18 (dd, J=18,7 Hz, J=8,3 Hz, 1H), a 3.87 (s, 3H), 4,77-to 4.81 (m, 1H), for 6.81 (s, 1H), 7,43 (s, 1H), cent to 8.85 (s, 1H).

Using the same method received the following connection:

3-(1H-imidazol-4-yl)-5-methoxy-4,7-dietlinde-1-it.

1H NMR (Dl3): a 1.96 (s, 3H), 2,6 what-Imidazol-4-yl)-5-methoxy-6,7-dietlinde-1-ol

3-(1H-Imidazol-4-yl)-5-methoxy-6,7-dietlinde-1-he (0,53 g) dissolved in ethanol (30 ml) and add 0.3 g of sodium borohydride. The mixture was stirred at 35-40oWith over 7 hours. Then approximately 20 ml of ethanol is distilled off and add 30 ml of water. The solution is extracted with ethyl acetate. United an ethyl acetate extracts are washed with water, dried with sodium sulfate and evaporated under reduced pressure. The product is a mixture of CIS - and TRANS - isomers (approximately 85: 15). Crystallization of the product from ethyl acetate to give CIS - isomer, so pl. 184-189oC.

1H NMR (cis-isomer, CDCl3): 2,09 - and 2.14 (m, 1H), 2,11 (s, 3H), of 2.38 (s, 3H), 2,69-2,77 (m, 1H), of 3.73 (s, 3H), or 4.31 (d, 1H), 5,26 (d, 1H), 6.48 in (s, 1H), 6.90 to (s, 1H), 7,43 (s, 1H).

EXAMPLE 8. 4-(6-Methoxy-4,5-dietlinde-1-yl)-1H-imidazol

3-(1H-Imidazol-4-yl)-5-methoxy-6,7-dietlinde-1-ol (0.29 grams) dissolved in a mixture of ethanol (30 ml) and concentrated hydrochloric acid (0.2 ml). The solution hydronaut at 50-55oWith 10% palladium on coal as a catalyst to stop the consumption of hydrogen. The mixture is filtered and the filtrate is evaporated to dryness. The residue is crystallized from a mixture of ethyl acetate and ethanol. So pl. 174-177oC.

1H NMR (as HCl-salt, MeOH-d4): 2,05-2,17 (m, 1 H), 2,11 (s, 3H), of 2.21 (s, 3H), 2,54-of 2.66 (m, 1H), 2,82 was 3.05 (m, 2H), 3,71 (s, 3H), 4,55 (t, utilidad-1-yl)-1H-imidazole.

1H NMR (as HCl-salt, MeOH-d4): 0,86 (d, 6H), 1,73 of-1.83 (m, 1H), 2,11-to 2.18 (m, 1H), 2,42 (d, 2H), 2,58-to 2.65 (m, 1H), 2,97-of 3.31 (m, 2H), 4,56 (t, 1H), 6,85 (s, 1H),? 7.04 baby mortality (d, J=7,6 Hz, 1H), 7,22 (d, J=7,6 Hz, 1H), 7,30 (s, 1H), 8,83 (s,1H).

EXAMPLE 9. 3-(1H-Imidazol-4-yl)-6,7-dietlinde-5-ol

Stir a mixture of the hydrochloride of 4-(6-methoxy-4,5-dietlinde-1-yl)-1H-imidazole (0.29 grams) and Hydrobromic acid (15 ml) is heated under reflux for 40 minutes. The cooled reaction mixture was poured into water and alkalinized with ammonium hydroxide solution. The product is extracted with ethyl acetate, washed with water, dried with sodium sulfate and evaporated to dryness. The crude product is purified flash chromatography and crystallized from ethyl acetate. So pl. 198-202oC.

1H NMR (CDCl3+MeOH-d4): 2,02-to 2.13 (m, 1H), 2,13 (s, 3H), of 2.18 (s, 3H), 2,43-of 2.54 (m, 1H), 2.71 to 2,82 (m, 1H), 2,86-2,96 (m, 1H), 4,33 (t, 1H), of 6.49 (s, 1H), 6.75 in (s, 1H), 7,50 (s,1H).

Using the same method were obtained the following compounds.

5-Hydroxy-3-(1H-imidazol-4-yl)-6,7-dietlinde-1-it.

1H NMR (MeOH-d4): 2,12 (s, 3H), 2,58 (s, 3H), to 2.67 (dd, J=18,4 Hz, J=4,1 Hz, 1 H), to 3.02 (dd, J=18,4 Hz, J=8,0 Hz, 1 H), 4,43-4,47 (m, 1 H), 6,59 (s, 1 H), 6.90 to (s, 1H), 7.62mm (s, 1H).

1-(1H-Imidazol-4-yl)indan-5-ol. So pl. 210-220oC.

1H NMR (MeOH-d4): 2,04-2,17 (m, 1H), 2,41-2,52 (m, 1H), 2, the Dan-4-ol. So pl. 142-145oC.

1H NMR (CDCl3+MeOH-d4): 2,13-of 2.26 (m, 1H), 2,49-2,60 (m, 1H), 2,89-is 3.08 (m, 2H), 4,54 (t, 1H), of 6.71-6,76 (m, 3H), 7,06 (t, J=7,6 Hz, 1H), 7,55 (s, 1H).

3-(1H-Imidazol-4-yl)indan-4,6-diol.

1H NMR (MeOH-d4): 2,10-of 2.21 (m, 1H), 2,39 is 2.51 (m, 1H), 2.71 to 2,95 (m, 2H), 4,34-4,39 (m, 1H), 6,10 (d, J=1,9 Hz, 1H), 6,20 (d, J=1,9 Hz, 1H), only 6.64 (s, 1H), to 7.59 (s, 1H).

EXAMPLE 10. 4-(3-Ethoxy-6-methoxy-4,5-dietlinde-1-yl)-1H-imidazole (CIS - isomer)

3-(1H-Imidazol-4-yl)-5-methoxy-6,7-dietlinde-1-ol (CIS - isomer, 0.1 g) dissolved in a mixture of ethanol (20 ml) and conc. hydrochloric acid (2 ml). The solution was stirred at 25oC for 1 hour. Processing of this reaction mixture gives the crude product, which was purified flash chromatography using a mixture of methylene chloride-methanol as eluent.

1H NMR (Dl3): of 1.31 (t, J=7,0 Hz, 3H), 2,12 (s, 3H), 2,20-of 2.25 (m, 1H), 2,32 (s, 3H), of 2.51-2,60 (m, 1H), and 3.72 (q, J=7,0 Hz, 2H), of 3.73 (s, 3H), and 4.40 (d, 1H), 4,96 (d, 1H), of 6.52 (s, 1H), 6,93 (s, 1H), 7,41 (s, 1H).

EXAMPLE 11. 4-(Indan-1-yl)-1H-imidazol

a) 4-(3H-Inden-1-yl)-1H-imidazole.

To a stirred solution of 1-(N,N-dimethylsulphamoyl)-1H-imidazole (1.9 g, obtained according to Chadwick D. J. and Ngochindo R. I., J. Chem. Soc., Perkin Trans., 1984, 481) in dry tetrahydrofuran (90 ml) at -70oC in nitrogen atmosphere is added dropwise a 2.5 M is ane (5 ml) and the mixture allowed to warm to 25oC. After 1.5 hours the mixture is again cooled to -70oC and treated with 2.5 M butyllithium in hexane (5,3 ml). After 30 minutes add 1-indanone (2.1 g) in dry tetrahydrofuran (5 ml) and the mixture allowed to warm to room temperature. Then the reaction mixture was quenched with saturated solution of PA2CO3(2 ml) and the solvent is removed under reduced pressure. The residue is dissolved in methylene chloride and washed with water, dried with sodium sulfate and evaporated to dryness under reduced pressure. Bis-protected intermediate compound is heated under reflux with 2 N. hydrochloric acid (200 ml) for 2 hours. The cooled solution is alkalinized with ammonium hydroxide solution and extracted with methylene chloride. The organic layer was washed with water, dried with sodium sulfate and the solvent is removed under reduced pressure. The crude product is purified flash chromatography using a mixture of methylene chloride-methanol as eluent. The product is transformed into cleaners containing hydrochloride salt in solution of ethyl acetate/ethanol, so pl. 232-240oC.

1H NMR (as HCl-salt, MeOH-d4): 3,66 (d, 2H), 7,07 (t, 1H), 7,31-the 7.43 (m, 2H), to 7.59 (d,1H), 7,68 (d,1H), 8,03 (s,1H), 9,06 (s, 1H).

b) 4-(Indan-1-yl)-1H-imidazole.

The hydrochloride of 4-(3H-inden-1-yl)-1H-imidazole (80 catalyst to stop the consumption of hydrogen. Processing of this reaction mixture gives the crude product, which was purified flash chromatography using a mixture of methylene chloride-methanol as eluent.

1H NMR (DCl3): 2,08-2,19 (m, 1H), 2,41 is 2.51 (m, 1H), 2,80-2,95 (m, 2H), 4,37 (t, 1 H), of 6.65 (s, 1 H), 7,07,7,21 (m, 4H), 7,25 (s, 1 H).

Using the same method received the following connection:

4-(6-methoxyindol-1-yl)-1H-imidazole.

1H NMR (as HCl-salt, MeOH-d4): 2,08-of 2.20 (m, 1H), 2,56-to 2.67 (m, 1H), 2,80-of 2.97 (m, 2H), and 3.72 (s, 3H), 4.53-in (t, 1H), of 6.71 (d, J=1,9 Hz, 1H), 6.75 in (dd, J=8,3 Hz, J=1,9 Hz, 1H), 6,92 (s, 1H), 7,15 (d, J=8,3 Hz, 1H), 8,82 (s, 1H)< / BR>
EXAMPLE 12. 4-(Indan-1-ylmethyl)-1H-imidazol

The titanium tetrachloride (17,2 g) is added dropwise to a stirred suspension of powdered zinc (11.9 g) in tetrahydrofuran (100 ml) under ice cooling in a nitrogen atmosphere. The mixture is heated under reflux for 1 hour. After cooling to room temperature the mixture was added 1-indanone (2.0 g) and 3-benzyl-3H-imidazole-4-carbaldehyde (4,2 g) in tetrahydrofuran (30 ml). The mixture is heated under reflux with stirring for 3 hours. The cooled reaction mixture is alkalinized with dilute sodium hydroxide solution. The suspension is filtered and the filtrate is evaporated to dryness under reduced pressure. The remainder, with the raffia.

The purified intermediate product (0.8 g) dissolved in a mixture of ethanol (30 ml), water (2 ml) and conc. hydrochloric acid (0.5 ml). The reaction mixture hydronaut at 50-60oWith 10% palladium on coal as a catalyst to stop the consumption of hydrogen. The mixture is filtered and the filtrate is evaporated to dryness. The residue is dissolved in water and alkalinized with sodium hydroxide. The product is then extracted with methylene chloride, washed with water, dried with sodium sulfate and evaporated to dryness. The product is converted into its hydrochloride in ethyl acetate using dry hydrochloric acid. Yield 0.5 g, so pl. 182-183oC.

1H NMR (as HCl-salt, MeOH-d4): 1,74-of 1.81 (m, 1H), 2,22-to 2.29 (m, 1H), 2,80-2,95 (m, 3H), 3,17 (dd, J=15,1 Hz, J=5,7 Hz, 1H), 3,48-of 3.53 (m, 1H), 7,12-of 7.23 (m, 4H), 7,26 (s, 1H), 8,79 (s, 1H).

Using the same method were obtained the following compounds.

4-(6-Methoxyindol-1-ylmethyl)-1H-imidazole. So pl. hydrochloride 197-200oC.

1H NMR (as HCl-salt, MeOH-d4): 1,72-of 1.84 (m, 1H), 2,19-2,31 (m, 1H), 2,70-2,89 (m, 3H), and 3.16 (dd, J=14,9 Hz, J=5,5 Hz, 1H), 3,42-3,51 (m, 1H), 3,74 (s, 3H), of 6.68 (d, J=2,2 Hz, 1H), 6,74 (dd, J=8,2 Hz, J=2, 2Hz, 1H), 7,10 (d, J=8,2 Hz, 1H), 7,27 (s, 1H), 8,82 (s, 1H).

4-(5-Methoxyindol-1-ylmethyl)-1H-imidazole. So pl. hydrochloride 204-206oC.

1H NMR (as HCl-salt, MeOH-d4): 1,71 of-1.83 (m, 1H), 2,19-, ,82 (s, 1H).

4-(5,6-Dimethoxyindole-1-ylmethyl)-1H-imidazole. So pl. hydrochloride 193-197oC.

1H NMR (as HCl-salt, MeOH-d4): 1,72-of 1.84 (m, 1H), 2,20 of-2.32 (m, 1H), 2,75-is 2.88 (m, ZN) and 3.15 (dd, J=15,1 Hz, J=5,2 Hz, 1H), 3,41-to 3.50 (m, 1H), of 3.77 (s, 3H), 3,79 (s, 3H), 6.73 x (s, 1H), 6,84 (s, 1H), 7,26 (s, 1H), 8,82 (s, 1H).

4-(6-Methoxy-4,5-dietlinde-1-ylmethyl)-1H-imidazole. So pl. hydrochloride 194-197oC.

1H NMR (as HCl-salt, MeOH-d4): 1,70-of 1.81 (m, 1H), 2,09 (s, 3H), of 2.15 (s, 3H), 2,17-to 2.29 (m, 1H), 2,69-2,89 (m, 3H), 3,14 (dd, J=15,1 Hz, J=5,7 Hz, 1H), 3,42-to 3.50 (m, 1 H), 3,74 (s, 3H), is 6.54 (s, 1 H), 7,24 (s, 1 H), 8,81 (s, 1 H).

4-(6-Methoxy-4,7-dietlinde-1-ylmethyl)-1H-imidazole. So pl. hydrochloride 168-175oC.

1H NMR (as HCl-salt, MeOH-d4): 1,88-of 1.94 (m, 1H), 2,07 (s, 3H), 2,09-to 2.18 (m, 1H), 2,19 (s, 3H), 2,69-2,77 (m, MN), 2,90 (dd, J=and 15.2 Hz, J=4,7 Hz, 1H), 3,51 is 3.57 (m, 1H), of 3.77 (s, 3H), 6,60 (s, 1H), 7,21 (s, 1H), 8,80 (s, 1H).

4-(6-Methoxy-5-methylinden-1-ylmethyl)-1H-imidazole. So pl. hydrochloride 183-186oC.

1H NMR (as HCl-salt, MeOH-d4): 1,71-to 1.82 (m, 1H), 2,13 (s, 3H), 2,18-to 2.29 (m, 1H), 2,70 - 2,89 (m, 3H), and 3.16 (dd, J=to 15.0 Hz, J=5,4 Hz, 1H), 3,42 - to 3.50 (m, 1H), 3,76 (s, 3H), of 6.65 (s,1H), 6,95 (s, 1H), 7,26 (s, 1H), 8,82 (s, 1H).

4-(6-Florinda-1-ylmethyl)-1H-imidazole. So pl. hydrochloride 215-222oC.

1H NMR (as HCl-salt, MeOH-d4): 1,76-of 1.88 (m, 1H), 2,23 to 2.35 (m, 1H), was 2.76 of 2.92 (m, 3H), 3,18 (dd, J=and 15.3 Hz, J=a 5.3 Hz, 1H), 3.46 in of 3.56 (m, 1H), 6,86-6,92 (m, 2H), 7,17-7,20 (m, 1 H), 7,31 (s, 1 H), 8,83 (s HCl-salt, MeOH-d4): 1,76-of 1.88 (m, 1 H), 2,23 to 2.35 (m, 1 H), 2,79 are 2.98 (m, 3H), and 3.16 (dd, J=and 15.3 Hz, J=a 5.3 Hz, 1H), 3.43 points-of 3.53 (m, 1H), 6,83-of 6.96 (m, 2H), 7,08 -7,13 (m, 1 H), 7,29 (s, 1 H), 8,82 (s, 1 H).

4-(4-Methoxyindol-1-ylmethyl)-1H-imidazole. So pl. hydrochloride 202-210oC.

1H NMR (as HCl-salt, MeOH-d4): 1,73-to 1.82 (m, 1H), 2,18-of 2.30 (m, 1H), 2,72-2,89 (m, 3H), 3,14 (dd, J=to 15.0 Hz, J=5,5 Hz, 1H), 3,48 of 3.56 (m, 1H), 3,80 (s, 3H), 6,72-of 6.78 (m, 2H), 7,14 (t, 1H), 7,24 (s, 1H), 8,79 (s, 1H).

4-(6-Methoxy-7-methylinden-1-ylmethyl)-1H-imidazole. So pl. hydrochloride 152-158oC.

1H NMR (as HCl-salt, MeOH-d4): 1,86-of 1.93 (m, 1H), 2,11 (s, 3H), 2,12-of 2.20 (m, 1H), 2,68-2,96 (m, 4H), 3,52-3,59 (m, 1H), 3,79 (s, 3H), of 6.75 (d, J=8,2 Hz, 1H), 6,99 (d, J=8,2 Hz, 1H), 7,22 (s, 1H), 8,79 (s, 1H).

4-(7-Methoxyindol-1-ylmethyl)-1H-imidazole.

1H NMR (as HCl-salt, MeOH-d4): 1,82-1,90 (m, 1H), 2,09-2,19 (m, 1H), 2,72-only 2.91 (m, 3H), 3,14 (dd, J=14,9 Hz, J=4,8 Hz, 1H), 3,59-3,74 (m, 1H), 3,76 (s, 3H), 6,72-to 6.80 (m, 2H), of 6.96 (s, 1H), 7,13 (t, 1H), scored 8.38 (s, 1H).

4-(5,6-Dimethoxy-3,3-dietlinde-1-ylmethyl)-1H-imidazole.

1H NMR (Dl3): of 1.12 (s, 3H), of 1.28 (s, 3H), and 1.63 (dd, J=12,5 Hz, J=8,3 Hz, 1H), 2,09 (dd, J=12,5 Hz, J=7,5 Hz, 1H), 2,72 (dd, J=14,6 Hz, J=9,0 Hz, 1H), and 3.16 (dd, J=14,6 Hz, J=5,5 Hz, 1H), 3,47-to 3.52 (m, 1H), of 3.78 (s, 3H), 3,86 (s, 3H), of 6.61 (s, 1H), 6,66 (s, 1H), PC 6.82 (s, 1H), 7,58 (s, 1H).

4-(5-tert-Batiliman-1-ylmethyl)-1H-imidazole.

1H NMR (Dl3): 1,32 (s, N), 1,71 of-1.83 (m, 1H), 2,19-of 2.30 (m, 1H), 2,73-2,87 (m, 3H), is 3.08 (dd, J=14,7 Hz, J=5,6 Hz, 1H), 3,44 - of 3.53 (m, 1H), for 6.81 (s, 1H), to 7.09 (d, J=7,SS="ptx2">

1H NMR (CDCl3): a 1.11 (s, 3H), of 1.27 (s, 3H), and 1.63 (dd, J=12,5 Hz, J=8,9 Hz, 1H), 2.06 to (dd, J=12,5 Hz, J=7,5 Hz, 1H), 2,72 (dd, J=14,7 Hz, J=9,0 Hz, 1H), 3,19 (dd, J=14,7 Hz, J=5,4 Hz, 1H), 3,47,3,55 (m, 1H), 3,74 (s, 3H), to 6.67 (d, J= 2,2 Hz, 1H), 6,74 (dd, J=8,2 Hz, J=2,2 Hz, 1H), 6,83 (s, 1H), 7,03 (d, J=8,2 Hz, 1H), 7,58 (s, 1H).

EXAMPLE 13. 4-[1-(Indan-1-yl)ethyl]-1H-imidazole.

The procedure of example 12 is repeated, except that instead of 3-benzyl-3H-imidazole-4-carbaldehyde using 1-(3-benzyl-3H-imidazol-4-yl)Etalon. The product contains two diastereoisomer ad and bc (78% ad and 22% bc).

1H NMR (as HCl-salt, MeOH-d4): of 1.23 (d, J=7,1 Hz, -CH3, b diastereomer), to 1.38 (d, J=7,1 Hz, -CH3ad diastereomer), 1,81 of-2.32 (m, 2H), 2,70-2,87 (m, 2H), 3,29-3,39 (m, 1H), 3,47 is 3.57 (m, 1H), 6,98-7,30 (m, 5H), 8,77 (s, 1H, ad diastereomer), 8,84 (s, 1H, bc diastereomer).

Using the same method received the following substituted derivative:

4-[1-(6-methoxyindol-1-yl)-ethyl]-1H-imidazole.

The reaction mixture contains two diastereoisomer ad and b who share flash chromatography with elution with a solution of methylene chloride - methanol.

1H NMR (ad diastereomer as HCl-salt, MeOH-d4): 1.37 (d, J=7,1 Hz, 3H), 1,83-of 1.94 (m, 1H), 2,20-of 2.33 (m, 1H), 2,58-2,77 (m, 2H), 3,30-3,39 (m, 1H), 3.43 points-to 3.49 (m, 1H), 3,74 (s, 3H), 6,63 (d, J=2,4 Hz, 1H), 6.73 x (dd, J=8,2 Hz, J=2,4 Hz, 1H), 7,05 (d, J=8,2 Hz, 1H), 7,13 (s, 1H), total of 8.74 (s, 1H).

1H NMR (b diastereomer as HCl-salt, MeOH-d4): of 1.23 (d, J=7,1 Hz, 3H), 1,90 for 2.01 (m, 1H), H).

EXAMPLE 14. 4-(5-tert-Butyl-6-methoxyindol-1-ylmethyl)-1H-imidazol

Sulfuric acid (0.5 ml) is added to a mixture of the hydrochloride of 4-(6-methoxyindol-1-ylmethyl)-1H-imidazole (50 mg) and tert-butanol (2 ml). The mixture was stirred at 35-40oC for 10 hours. Then the reaction mixture was poured into water and alkalinized with sodium hydroxide. The product is extracted with methylene chloride, washed with water, dried with sodium sulfate and evaporated to dryness. The residue, consisting of crude product is converted into its cleaners containing hydrochloride salt in ethyl acetate. Yield 23 mg, so pl. 174-184oC.

1H NMR (as HCl-salt, MeOH-d4): of 1.33 (s, 9H), 1,71 of-1.83 (m, 1H), 2,19 - 2,31 (m, 1H), 2,73-2,89 (m, 3H), 3.15 in (dd, J=to 15.0 Hz, J=5,1 Hz, 1H), 3,40-to 3.50 (m, 1H), of 3.77 (s, 3H), 6,69 (s, 1 H), 7,11 (s, 1 H), 7,27 (s, 1 H), 8,81 (s, 1 H).

Using the same method are the following compounds.

4-(6-tert-Butyl-5-methoxyindol-1-ylmethyl)-1H-imidazole.

1H NMR (as HCl-salt, MeOH-d4): of 1.30 (s, 9H), 1,73-of 1.84 (m, 1H), 2.21 are of 2.33 (m, 1H), 2,75-to 2.94 (m, 3H), 3,05 (dd, J=14,9 Hz, J=6,3 Hz, 1H), 3,35,3,45 (m, 1H), 3,80 (s, 3H), 6,83 (s, 1H), 6,86 (s, 1H), 7.23 percent (s, 1H), 8,81 (s, 1H).

5,7-Di-tert-butyl-1-(1H-imidazol-4-ylmethyl)-indan-4-ol.

1H NMR (as HCl-salt, MeOH-d4): of 1.39 (s, 9H), of 1.41 (s, 9H), 1,87-of 1.93 (m, 1H), 2,01-to 2.06 (m, 1H), 2,66 is 2.75 (m, 3H), 2,89-2,95 (m, 1H), 3,82-to 3.89 (m, 1H), 7,15 (s, 1H), 7,33 (s, 1H), 8,77 (s, 1H).

< (m, 1H), 2,82-to 3.02 (m, 2H), 4,46 (t, 1H), 6,69 (s, 1H), to 6.88 (s, 1H), 7,25 (s, 1H), 8,79 (s, 1H).

4-(6-tert-Butyl-4-methylinden-1-yl)-1H-imidazole. So pl. hydrochloride 235-242oC.

1H NMR (as HCl-salt, MeOH-d4): a 1.25 (s, 9H), 2,09-2,19 (m, 1H), 2.57 m-to 2.67 (m, 1H), 2,84-of 3.07 (m, 2H), 4,55 (t, 1H), 6,91 (s, 1H), 7,12 (s, 1H), 7,25 (s, 1H), total of 8.74 (s,1H).

5,7-Di-tert-butyl-3-(1H-imidazol-4-yl)indan-4-ol. So pl. hydrochloride 216-222oC.

1H NMR (as HCl-salt, MeOH-d4): of 1.35 (s, 9H), of 1.39 (s, 9H), 2,11-to 2.18 (m, 1H), 2,44-2,52 (m, 1H), 3,06-and 3.16 (m, 2H), 4,59-4,63 (m, 1H), 6,78 (s, 1H), 7.23 percent (s, 1H), up 8.75 (s, 1H).

EXAMPLE 15. 3-(1H-Imidazol-4-ylmethyl)indan-5-ol

Stir a mixture of the hydrochloride of 4-(6-methoxyindol-1-ylmethyl)-1H-imidazole (140 mg) and 48% Hydrobromic acid (7 ml) is heated under reflux for 45 minutes. The cooled reaction mixture was poured into water and alkalinized with ammonium hydroxide solution. The product is extracted with ethyl acetate, washed with water, dried with sodium sulfate and evaporated to dryness. The crude product is converted into its cleaners containing hydrochloride salt in ethyl acetate. So pl. 206-208oC.

1H NMR (as HCl-salt, MeOH-d4): 1,70-of 1.81 (m, 1H), 2,18-to 2.29 (m, 1H), 2,70-is 2.88 (m, 3H), of 3.12 (dd, J=and 15.3 Hz, J=5,8 Hz, 1H), 3,38-of 3.46 (m, 1H), 6,53 (d, J =2,2 Hz, 1H), 6,60 (dd, J=8,1 Hz, J=2,2 Hz, 1H), 7,01 (d, J=8,1 Hz, 1H), 7,27 (s, 1H), 8,81 (s, 1H).

Using the same method LASS="ptx2">

1H NMR (as HCl-salt, MeOH-d4): was 1.69 and 1.80 (m, 1H), 2,17-to 2.29 (m, 1H), 2.71 to 2,89 (m, 3H), 3,11 (dd, J=14,8 Hz, J=5,7 Hz, 1H), 3,35 is - 3.45 (m, 1H), to 6.57 (dd, J= 8,1 Hz, J=2,2 Hz, 1H), only 6.64 (d, J=2,2 Hz, 1H), 6.89 in (d, J=8,1 Hz, 1H), 7,24 (s, 1H), 8,79 (s, 1H).

1-(1H-imidazol-4-ylmethyl)indan-5,6-diol.

1H NMR (as HCl-salt, MeOH-d4): 1,67-of 1.78 (m, 1H), 2,15-of 2.27 (m, 1H), 2,65 - to 2.85 (m, 3H), 3,05 (dd, J=15,1 Hz, J=5,8 Hz, 1H), 3,30 is 3.40 (m, 1H), 6,51 (s, 1H), 6,63 (s, 1H), 7,24 (s, 1H), 8,80 (s, 1H).

6-tert-Butyl-3-(1H-imidazol-4-ylmethyl)-indan-5-ol.

1H NMR (as HCl-salt, MeOH-d4): of 1.35 (s, 9H), 1,69-to 1.79 (m, 1H), 2,18 - of 2.28 (m, 1H), 2,69-of 2.86 (m, 3H), is 3.08 (dd, J=to 15.0 Hz, J=6,0 Hz, 1H), 3,35-of 3.43 (m, 1H), 6,46 (s, 1H),? 7.04 baby mortality (s,1H), 7,26 (s, 1H), 8,81 (s, 1H).

6-tert-Butyl-1-(1H-imidazol-4-ylmethyl)indan-5-ol. So pl. hydrochloride 229-230oC.

1H NMR (as HCl-salt, MeOH-d4): of 1.32 (s, 9H), 1,72-of 1.81 (m, 1H), 2,18-to 2.29 (m, 1H), 2,72-2,87 (m, 3H), 3,03 (dd, J=15,1 Hz, J=6,5 Hz, 1H), 3,32 is 3.40 (m, 1H), 6,59 (s, 1H), 6,79 (s, 1H), 7.23 percent (s, 1H), 8,81 (s, 1H).

3-(1H-Imidazol-4-ylmethyl)-6,7-dietlinde-5-ol. So pl. hydrochloride 229-238oC.

1H NMR (as HCl-salt, MeOH-d4): 1,66-of 1.78 (m, 1 H), of 2.08 (s, 3H), 2.13 and (s, 3H), 2,14 - of 2.26 (m, 1H), 2,66-to 2.85 (m, 3H), 3,06 (dd, J=15,1 Hz, J=5,8 Hz, 1H), 3,35-of 3.43 (m, 1 H), to 6.39 (s, 1 H), 7,22 (s, 1 H), 8,79 (s, 1 H).

3-(1H-Imidazol-4-ylmethyl)-4,7-dietlinde-5-ol.

1H NMR (as HCl-salt, MeOH-d4): 1,85-of 1.93 (m, 1 H) 2,07 (s, 3H), 2,11 (s, 3H), 2,11-of 2.20 (m, 1H), 2,65-2,77 (m, 3H), 2,90 (dd, J=15,1 Hz, J=4,6 Hz, 1H), 3,49 is 3.57 (m, 1H), 6,47/P>1H NMR (base, CDCl3+MeOH-d4): of 1.12 (d, J=7,0 Hz, -CH3ad diastereomer), 1,22 (d, J=7,1 Hz, -CH3, bc diastereomer).

3-(1H-Imidazol-4-ylmethyl)-6-methylindol-5-ol.

1H NMR (as HCl-salt, MeOH-d4): 1,68-to 1.79 (m, 1H), 2,13 (s, 3H), 2,15-of 2.27 (m, 1H), 2,68-of 2.86 (m, 3H), is 3.08 (dd, J=and 15.3 Hz, J=5,8 Hz, 1H), 3,36-of 3.43 (m, 1H), of 6.49 (s, 1H), 6.90 to (s, 1H), 7,25 (s, 1H), 8,81 (s, 1H).

1-(1H-Imidazol-4-ylmethyl)indan-4-ol. So pl. hydrochloride 199-205oC.

1H NMR (MeOH-d4): 1,68-of 1.80 (m, 1H), 2,10-2,22 (m, 1H), 2,60-of 2.86 (m, ZN), of 3.00 (dd, J=14,6 Hz, J=a 5.3 Hz, 1H), 3,38-of 3.48 (m, 1H), 6,56 (d, J=7,8 Hz, 1H), 6,62 (d, J=7,8 Hz, 1H), of 6.71 (s, 1H), 6,94 (t, J=7,8 Hz, 1H), 7,56 (s, 1H).

3-(1H-Imidazol-4-ylmethyl)indan-4-ol.

1H NMR (as HCl-salt, MeOH-d4): 1,78-to 1.87 (m, 1H), 2,12 - 2,22 (m, 1H), 2,78 of 2.92 (m, MN), 3,24 (dd, J=and 15.3 Hz, J=a 5.3 Hz, 1H), 3,59 - the 3.65 (m, 1H), 6,56 (d, J=7,7 Hz, 1H), of 6.68 (d, J=7,7 Hz, 1H), 6,99 (t, J=7,7 Hz, 1H), 7,15 (s, 1H), is 8.75 (s, 1H).

3-(1H-Imidazol-4-ylmethyl)-1,1-dietlinde-5,6-diol.

1H NMR (MeOH-d4): 1,09 (s, 3H), 1,24 (s, 3H), and 1.54 (dd, J=12,4 Hz, J=8,5 Hz, 1H), 1,98 (dd, J=12,4 Hz, J=7,4 Hz, 1H), 2,60 (dd, J=14,5 Hz, J=9,0 Hz, 1H), of 3.07 (dd, J=14,5 Hz, J=5,5 Hz, 1H), 3,36-to 3.41 (m, 1H), 6,54 (s, 2H), 6,79 (s, 1H), 7,65 (s,1H).

3-(1H-Imidazol-4-ylmethyl)-1,1-dietlinde-5-ol.

1H NMR (as HCl-salt, MeOH-d4): to 1.14 (s, 3H), of 1.29 (s, 3H), 1,59 (dd, J= 12,5 Hz, J=8,8 Hz, 1H), 2.06 to (dd, J=12,5 Hz, J=7,5 Hz, 1H), 2,80 (dd, J=15,1 Hz, J=9,3 Hz, 1H), 3.27 to (dd, J=15,1 Hz, J=5,2 Hz, 1H), 3,45 - 3,55 (m, 1H), 6,56 (d, J= 2,0 Hz, 1H), 6,65 (dd, J=8,1 Hz, J=2,0 Hz, naguru of example 12 is repeated, except that instead of 1-indanone using 1-tetralone. So pl. cleaners containing hydrochloride salt 185-188oC.

1H NMR (as HCl-salt, MeOH-d4): 1,59-of 1.93 (m, 4H), 2.70 height is 2.80 (m, 2H), 2,96 (dd, J= 14,8 Hz, J=9,5 Hz, 1H), is 3.08-up 3.22 (m, 2H), 7,08-7,14 (m, 4H), 7,25 (s, 1H), 8,81 (s, 1H).

Using the same method were obtained the following compounds.

4-(5-Methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-1H-imidazole. So pl. hydrochloride 210-218oC.

1H NMR (as HCl-salt, MeOH-d4): 1,58-of 1.64 (m, 1H), 1,71 is 1.86 (m, 3H), 2,50-2,60 (m, 1H), 2,66-to 2.74 (m, 1H), 2,96 (dd, J=14,8 Hz, J=9,5 Hz, 1H), 3,05-3,18 (m, 2H), 3,79 (s, MN), 6.73 x-6,77 (m, 2H), to 7.09 (t, 1H), 7,25 (s, 1H), 8,81 (s, 1H).

4-(6-Methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-1H-imidazole. So pl. hydrochloride 184-191oC.

1H NMR (as HCl-salt, MeOH-d4): 1,58-of 1.88 (m, 4H), 2,70 was 2.76 (m,2H), 2,93 (dd, J= 14,5 Hz, J=9,2 Hz, 1H), 3.04 from - of 3.32 (m, 2H), 3,74 (s, 3H), 6,63 (d, J=2,5 Hz, 1H), 6,69 (dd, 8,4 Hz, J=2,5 Hz, 1H), 7,03 (d, J=8,4 Hz, 1H), 7,24 (s, 1H), 8,81 (s, 1H).

4-(7-Methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-1H-imidazole. So pl. hydrochloride 180-183oC.

1H NMR (as base, Dl3): 1,59-to 1.82 (m, 4H), 2,64 of 2.68 (m, 2H), 2,85 (dd, J= 14,6 Hz, J=9,3 Hz, 1H), 3,01 (dd, J=14,6 Hz, J=4,8 Hz, 1H), 3,12-3,17 (m, 1H), and 3.72 (s, 3H), 6,68-of 6.71 (m, 2H), 6,78 (s, 1H), 6,97-7,00 (m, 1H), 7,56 (s, 1H).

4-(4-Methyl-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-1H-imidazole. The product is a mixture of two isomers ad and isomer), 1,50 is 2.10 (m, 4H), 2,80 totaling 3.04 (m, 2H), of 3.10-3.20 (m, 2H), 7,10-7,26 (m, 5H), 8,83 (s, 1H).

EXAMPLE 17. 4-(7-tert-Butyl-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-1H-imidazol

Sulfuric acid (0.75 ml) is added to a mixture of the hydrochloride of 4-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-1H-imidazole (75 mg) and tert-butanol (3 ml). The mixture was stirred at 35-40oC for 15 hours. The reaction mixture was poured into water and alkalinized with sodium hydroxide. The product is extracted with methylene chloride, washed with water, dried with sodium sulfate and evaporated to dryness. The residue, consisting of crude product is converted into its cleaners containing hydrochloride salt in ethyl acetate. The output 40 mg.

1H NMR (as HCl-salt, MeOH-d4): of 1.28 (s, 9H), 1,65-of 1.95 (m, 4H), 2.70 height is 2.80 (m, 2H), 2,87-3,10 (m, 3H), of 3.78 (s, 3H), 6,63 (s, 1H), 6,79 (s, 1H), 7,22 (s, 1H), 8,81 (s, 1H).

EXAMPLE 18. 5-(1H-Imidazol-4-ylmethyl)-5,6,7,8-tetrahydronaphthalen-2-ol

Stir a mixture of 4-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-1H-imidazole (220 mg) and 48% Hydrobromic acid (11 ml) is heated under reflux for 1 hour. The cooled reaction mixture was poured into water and alkalinized with ammonium hydroxide solution. The product is extracted with ethyl acetate, washed with water, dried with sodium sulfate and evaporated to dryness.tx2">

1H NMR (as HCl-salt, MeOH-d4): 1,54-1,90 (m, 4H), 2,62-of 2.72 (m, 2H), 2,88-3,11 (m, 3H), 6,51 (d, J=2,5 Hz, 1H), 6,56 (dd, J=8,3 Hz, J=2,5 Hz, 1H), 6,94 (d, J=8,3 Hz, 1H), 7.23 percent (s, 1H), 8,81 (s, 1H).

Using the same method received the following connection:

8-(1H-Imidazol-4-ylmethyl)-5,6,7,8-tetrahydronaphthalen-2-ol. So pl. hydrochloride 245-251oC.

1H NMR (as HCl-salt, MeOH-d4): 1,53-1,89 (m, 4H), 2,60-2,70 (m, 2H), 2,90-2,99 (m, 1H), 3,05-of 3.12 (m, 2H), 6,55-6,60 (m, 2H), make 6.90 (d, J=8,0 Hz, 1H), 7,24 (s,1H), 8,80 (s, 1H).

EXAMPLE 19. 6-Bromo-3-(1H-imidazol-4-ylmethyl)indan-5-ol

Bromine (130 mg, 1 EQ.) added dropwise to a stirred suspension of the hydrochloride of 3-(1H-imidazol-4-ylmethyl)-indan-5-ol (130 mg) in acetic acid (6 ml). The mixture was stirred at 20-23oC for 3 hours. Then the reaction mixture was poured into water and alkalinized with ammonium hydroxide solution. The product is extracted with ethyl acetate, washed with water, dried with sodium sulfate and evaporated to dryness. The product was then purified flash chromatography using a mixture of methylene chloride - methanol as eluent and then turn to cleaners containing hydrochloride salt in solution in ethyl acetate-ethanol.

1H NMR (as HCl-salt, MeOH-d4): 1,71 of-1.83 (m, 1H), 2,16-of 2.30 (m, 1H), 2,72-2,89 (m, 3H), 3,10 (dd, J=14,9 Hz, J=5,9 Hz, 1H), 3,36-of 3.46 (m, 1H), 6,65 (s, 1H), 7,29 (s, 2H), 8,81 (s, 1H).

EXAMPLE 20. 1,3-Dibro is my suspension of the hydrochloride of 8-(1H-imidazol-4-ylmethyl)-5,6,7,8-tetrahydronaphthalen-2-ol (150 mg) in acetic acid (5 ml). The mixture was stirred at 20-23oC for 3 hours. Then the reaction mixture was poured into water and alkalinized with ammonium hydroxide solution. The product is extracted with ethyl acetate, washed with water, dried with sodium sulfate and evaporated to dryness. The product was then purified flash chromatography using a mixture of methylene chloride - methanol as eluent and then turn to cleaners containing hydrochloride salt in solution in ethyl acetate - ethanol.

1H NMR (MeOH-d4): 1,51 - of 1.93 (m, 4H), 2,56 is 2.75 (m, 3H), 2,99 (dd, J= 14,8 Hz, J= 3,2 Hz, 1H), 3,30 - to 3.33 (m, 1H), to 6.88 (s, 1H), 7.23 percent (s, 1H), to 7.61 (s, 1H).

Using the same method were obtained the following compounds.

4,6-Dibromo-3-(1H-imidazol-4-ylmethyl)indan-5-ol.

1H NMR (MeOH-d4): 1,95-of 2.16 (m, 2H), 2,58-2,89 (m, 3H), to 3.02 (dd, J=14,6 Hz, J= 3,5 Hz, 1H), 3.45 points-to 3.52 (m, 1H), 6,72 (s, 1H), 7.23 percent (s, 1H), 7.62mm (s, 1H).

5,7-Dibromo-1-(1H-imidazol-4-ylmethyl)indan-4-ol.

1H NMR (as HCl-salt, MeOH-d4): 1,93 is 2.01 (m, 1H), 2,19 is 2.33 (m, 1H), 2,80-of 3.07 (m, 3H), of 3.12 (dd, J=and 15.2 Hz, J=4,9 Hz, 1H), 3,51-3,59 (m, 1H), 7,25 (s, 1H), 7,46 (s, 1H), 8,82 (s, 1H).

EXAMPLE 21. 6-Hydroxymethyl-3-(1H-imidazol-4-ylmethyl)indan-5-ol

a) 1-(1H-Imidazol-4-ylmethyl)-6-methoxyindol-5-carbaldehyde.

Chloride tin(IV) (1.60 g) is added dropwise to a stirred solution dichlorodimethyl ether is their 1 hour before adding a solution of 4-(6-methoxyindol-1-ylmethyl)-1H-imidazole (0,60 g) in methylene chloride (4 ml). The obtained mixture is allowed to warm to ambient temperature with stirring for 4 hours. The mixture is then poured into cold water and alkalinized with ammonium hydroxide solution. The product is extracted with methylene chloride, washed with water, dried with sodium sulfate and evaporated to dryness. The crude product is purified flash chromatography using a mixture of methylene chloride-methanol as eluent.

1H NMR (DCl3): of 1.78-1.90 (m, 1 H), 2.21 are 2,31 (m, 1 H), 2,72-of 2.86 (m, 3H), 3.04 from (dd, J=14,5 Hz, J=6,0 Hz, 1H), 3,50-3,61 (m, 1H), 3,85 (s, 3H), 6.75 in (s, 1H), 6,79 (s,1H), to 7.61 (s,1H), 7,66 (s,1H), the 10.40 (s, 1H).

b) 6-Hydroxy-1-(1H-imidazol-4-ylmethyl)indan-5-carbaldehyde.

a 1.0 M solution of tribromide boron in methylene chloride (2 ml) is added dropwise to a stirred solution of 1-(1H-imidazol-4-ylmethyl)-6-methoxyindol-5-carbaldehyde (144 mg) in methylene chloride (10 ml) at -70oC in nitrogen atmosphere. Once added, the mixture allowed to warm to room temperature and stirred for 3 hours. The mixture is then poured into cold water and alkalinized with ammonium hydroxide solution. The product is extracted with methylene chloride, washed with water, dried with sodium sulfate and evaporated to dryness. The crude product is purified flash chromatography to use the> The NMR (Dl3): 1,76-of 1.88 (m, 1H), 2,20 of-2.32 (m, 1H), 2.71 to only 2.91 (m, 3H), to 3.02 (dd, J= 14,7 Hz, J=5,9 Hz, 1H), 3,44-of 3.54 (m, 1H), 6.73 x (s, 1H), 6,76 (s, 1H), was 7.36 (s, 1H), 7,54 (s, 1H), 9,81 (s, 1H).

C) 6-Hydroxymethyl-3-(1H-imidazol-4-ylmethyl)indan-5-ol.

Sodium borohydride (8 mg) is added to a solution of 6-hydroxy-1-(1H-imidazol-4-ylmethyl)indan-5-carbaldehyde (44 mg) in ethanol (6 ml). The mixture is stirred at room temperature for 1 hour and then poured into water. The product is extracted with ethyl acetate, washed with water, dried with sodium sulfate and evaporated to dryness. The crude product is purified flash chromatography using a mixture of methylene chloride - methanol as eluent and crystallized from ethyl acetate.

1H NMR (Dl3+MeOH-d4): of 1.66-1.77 in (m, 1H), 2,12 - of 2.23 (m, 1H), 2,62-of 2.81 (m, 3H), of 2.93 (dd, J=14,7 Hz, J=5,7 Hz, 1H), 3,30 is 3.40 (m, 1H), and 4.68 (s, 2H), return of 6.58 (s, 1H), 6,70 (s, 1H), 6,97 (s, 1H), 7,49 (s, 1H).

EXAMPLE 22. 6-Hydroxymethyl-1-(1H-imidazol-4-ylmethyl)indan-5-ol

a) 3-(1H-Imidazol-4-ylmethyl)-6-methoxyindol-5-carbaldehyde.

Chloride tin(IV) (800 mg) is added dropwise to a stirred solution dichloromethylsilane ester (343 mg) in methylene chloride (8 ml) with ice cooling in a nitrogen atmosphere. The solution was stirred at 0oC for 1 hour before adding a solution of 4-(5-matossian is a growing medium under stirring for 4 hours. The mixture is then poured into cold water and alkalinized with ammonium hydroxide solution. Treatment of this mixture gives the crude product, which was purified flash chromatography and recrystallized from ethyl acetate.

1H NMR (Dl3): 1,78,1,90 (m, 1 H), 2,22 is 2.33 (m, 1 H), 2,73-2,96 (m, 3H), 3,05 (dd, J=14,6 Hz, J=5,5 Hz, 1H), 3.43 points-of 3.53 (m, 1H), 3,90 (s, 3H), 6,76 (s, 1H), only 6.64 (s, 1H), 7,52 (s, 1H), to 7.61 (s, 1H), accounted for 10.39 (s, 1H).

b) 6-Hydroxy-3-(1H-imidazol-4-ylmethyl)indan-5-carbaldehyde.

a 1.0 M solution of tribromide boron in methylene chloride (3.9 ml) is added dropwise to a stirred solution of 3-(1H-imidazol-4-ylmethyl)-6-methoxyindol-5-carbaldehyde (318 mg) in methylene chloride (15 ml) at -70oC in nitrogen atmosphere. Once added, the mixture allowed to warm to room temperature and stirred for 3 hours. The mixture is then poured into cold water and alkalinized with ammonium hydroxide solution. Treatment of the mixture gives the crude product, which was purified flash chromatography and recrystallized from ethyl acetate.

1H NMR (Dl3): 1,77-1,89 (m, 1H), 2,22-of 2.34 (m, 1H), 2,75-2,90 (m, 3H), 3,01 (dd, J= 14,6 Hz, J=6,2 Hz, 1H), 3,47 of 3.56 (m, 1H), 6,77 (s, 1H), 6,83 (s, 1H), 7,20 (s, 1H), to 7.61 (s, 1H), 9,76 (s, 1H).

C) 6-Hydroxymethyl-1-(1H-imidazol-4-ylmethyl)indan-5-ol.

Sodium borohydride (10 mg) debut at room temperature for 1 hour and then poured into water. Treatment of the mixture gives the crude product, which was purified flash chromatography and recrystallized from ethyl acetate.

1H NMR (MeOH-d4): 1,62-1,72 (m, 1H), 2,08-2,19 (m, 1H), 2,59 was 2.76 (m, 3H), 2,99 (dd, J=14,4 Hz, J=5,2 Hz, 1H), 3,28 - to 3.38 (m, 1H), 4,59 (s, 2H), 6,62 (s, 1H), 6.73 x (s, 1H), 7,01 (s, 1H), 7,58 (s, 1H).

EXAMPLE 23. 3-[1-(1H-Imidazol-4-yl)propyl]indan-5-ol

a) 4-[1-(6-Methoxyindol-1-yl)propyl]-1H-imidazole.

Repeat the procedure of Example 12, except that instead of 3-benzyl-3H-imidazole-4-carbaldehyde using 1-(3-benzyl-3H-imidazol-4-yl)propan-1-he instead of 1-indanone using 6-methoxyindol-1-it. The product is a mixture of two diastereoisomers (1:1).

1H NMR (as HCl-salt, MeOH-d4): 0,86 (t, 3H), of 0.92 (t, 3H), 1,65-of 1.95 (m, 4H), 1,98-of 2.08(m, 2H), 2,15 was 2.25 (m, 2H), 2,50-by 2.73 (m, 4H), 2,96 totaling 3.04 (m, 1H), 3,10-3,18 (m, 1H), 3,35-to 3.50 (m, 2H), 3,69 (s, 3H), of 3.78 (s, 3H), 6,38 (d, J= 2,3 Hz,1H), 6,68-of 6.73 (m, 2H), 6,85 (d, J=2,3 Hz,1H), 7,03 (d, J=8,2 Hz, 1H), 7,06 (d, J=8,2 Hz, 1 H), of 7.23 (s, 1 H), 7,28 (s, 1 H), a total of 8.74 (s, 1 H), cent to 8.85 (s, 1 H).

b) 3-[1-(1H-imidazol-4-yl)propyl]indan-5-ol.

Stir a mixture of 4-[1-(6-methoxyindol-1-yl)propyl]-1H-imidazole (174 mg) and 48% Hydrobromic acid (9 ml) is heated under reflux for 50 minutes. The cooled reaction mixture was poured into water and alkalinized with ammonium hydroxide solution. Product extrasocial flash chromatography using a mixture of methylene chloride - methanol as eluent. The product is a mixture of two diastereoisomers (1:1).

1H NMR (MeOH-d4): of 0.79 (t, 3H), from 0.84 (t, 3H), 1.60 - to and 2.14 (m, 8H), of 2.51 2.63 in (m, 4H), 2,78 - to 2.85 (m, 2H), 3.27 to to 3.38 (m, 2H), of 6.31 (d, J=2,2 Hz, 1H), 6,51-6,55 (m, 2H), 6,59 (s, 1H), only 6.64 (s, 1H), of 6.68 (d, J=2,2 Hz, 1H), 6,89 (d, J=8,5 Hz, 1H), 6,92 (d, J=8,5 Hz, 1 H), 7,52 (s, 1 H), to 7.59 (s, 1 H).

1. A derivative of imidazole, which is a compound of formula I

< / BR>
where n represents 0 or 1;

R1denotes hydrogen or C1-C4-alkyl;

R2denotes hydrogen or R2and R3together form a double bond;

R3denotes hydrogen or C1-C4-alkyl, or R2and R3together form a double bond;

R4denotes hydrogen, C1-C4-alkyl, a hydroxyl group or a C1-C4-alkoxy;

R5denotes hydrogen or C1-C4-alkyl, or R4and R5together with the carbon atom to which they are connected, form a carbonyl group;

R6, R7and R8the same or different and independently represent hydrogen, C1-C4-alkyl or C2-C4alkenyl, hydroxyl group, WITH1-C4-alkoxy, C1-C4-hydroxyalkyl or halogen;

X denotes-CHR9is hydrogen or1-C4-alkyl;

provided that R3-R10cannot simultaneously represent hydrogen when n=0 and m=1;

or their pharmaceutically acceptable ester or salt.

2. Derived under item 1, where m=n=0.

3. Derived under item 1 or 2, where each of R6, R7and R8represents hydrogen.

4. Derived under item 1 or 2, where R6represents a C1-C4-alkyl at position 4 or 6 rings indane and R7and R8represent hydrogen.

5. Derived under item 1 or 2, where R6represents a C1-C4-alkoxy at position 7 of the ring indane and R7and R8represent hydrogen.

6. Derived under item 1, where n=1 and m=0.

7. Derived by p. 6, where R1represents methyl or ethyl.

8. Derived under item 6 or 7, where each of R6, R7and R8represents hydrogen.

9. Derived under item 6 or 7, where R6represents a hydroxyl group at position 4 or 6 rings Indiana, and R7and R8represent hydrogen.

10. Derived under item 6 or 7, where R6represents a hydroxyl group in position 5 of ring inancially in position 6 rings Indiana, and R8represents hydrogen.

11. Derived under item 1, where n=m=1.

12. Derived under item 11, where R5-R8all represent hydrogen.

13. Derived under item 11, where R6represents a hydroxyl group in position 7 of the ring 1,2,3,4-tetrahydronaphthalene and R7and R8represent hydrogen.

14. Pharmaceutically acceptable composition having 2-agonistic activity, containing derivative defined in any of paragraphs.1-13, and a pharmaceutically acceptable carrier.

15. Derivative defined in any of paragraphs.1-13, with2-agonistic activity.

 

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< / BR>
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