Triaromatic compounds, compositions containing them and their use

 

(57) Abstract:

The invention relates to new triaromatic compounds of General formula I, characterized in paragraph 1 of the claims. The compound of formula I possess antagonistic activity to retinoic acid receptors and can be used for the preparation of pharmaceutical compositions intended for use in human medicine or animal in particular when used for dermatological, rheumatic, respiratory, cardiovascular and ophthalmological diseases, and in cosmetic compositions suitable for the hygiene of the body or hair care. 3 S. and 9 C.p. f-crystals, 2 ill., table 2.

The invention relates to triaromatic compounds as new and useful industrial products. It relates also to the use of these compounds in pharmaceutical compositions intended for use in human medicine and animal, or in cosmetic compositions.

Compounds according to the invention have significant activity in the areas of differentiation and proliferation of cells and may find particular application for topical and systemic treatment of dermatological diseases, tie the lergicheskie component and benign or malignant dermal or epidermal of proliteracy. These compounds can also be used to treat degeneration of connective tissue, to fight against photoinductive or age-related skin aging and for the treatment of impaired wound healing (scarring). They also find application in the field of ophthalmology, in particular for the treatment of corporate.

Compounds according to the invention can also be used in cosmetic compositions for the care of the body and for hair care.

Compounds according to the invention can be represented by the following General formula (I):

< / BR>
where R1means (ii) -CH2OH, (iii) -O-R4, (iv) -CO-R5where R4and R5have the meanings stated below;

Ar1selected among the radicals of the following formulae (a) to(d):

< / BR>
where R6has the following value;

X-Y means connecting link, selected from the following formulas (e) to (m), which can be attached to the phenyl ring from left to right or Vice versa:

< / BR>
where R7, R8and R9have the meanings stated below;

Ar2selected among the radicals of the following formulae (j)-(l):

< / BR>
and Ar2located in the ortho - or meta-position relative to the link X-Y, and R10and R11
R4means a hydrogen atom, lower alkyl;

R5means (a) a hydrogen atom;

(C) a radical of the formula:

< / BR>
where R' and R" have the meanings stated below; and (d) radical OR13where R13has the following value;

R6means a hydrogen atom, a linear alkyl with 1-20 carbon atoms, a hydroxyl radical; a radical OR14or the radical-OCOR14where R14has the following value; or the residue of polyether,

R7and R8represent a hydrogen atom, lower alkyl;

R9means a hydrogen atom;

R10and R11identical or different, denote a hydrogen atom, a linear alkyl with 1-20 carbon atoms, a halogen atom; hydroxyl, alkoxyl, the remainder of the polyether, CF3alkenyl or the radical -(CH2)n-R15where n and R15have the meanings stated below;

R' and R", identical or different, denote a hydrogen atom, lower alkyl, unsubstituted or substituted by a hydroxy-group phenyl, or both radicals together form a heterocycle;

R13means a hydrogen atom,

R14means a lower alkyl radical;

R15means hydroxyl;

.

Thus, the invention relates also to the salts of compounds of formula (I), when R1means carboxyl. When the compounds according to the invention are in the form of salts by the addition of acid, it is a pharmaceutically or cosmetically acceptable salts obtained by attaching an inorganic or organic acid, in particular hydrochloric, sulfuric, acetic, citric, fumaric, succinic (with formation of incomplete salts), maleic and almond acid. When the compounds according to the invention are in the form of salts by the addition of base, it is preferably of the salts of alkali or alkaline earth metal or zinc salts or organic amine.

According to the present invention from a linear or branched alkyl radical with 1-20 carbon atoms, preferably can be called methyl, ethyl, isopropyl, butyl, tert-butyl, hexyl, octyl, nonyl, 2-ethylhexyl and dodecyl. These radicals preferably contain 1 to 12 carbon atoms. When the alkyl radical is a lower one, it usually contains 1-6 carbon atoms. As the lower alkyl radical can be called methyl, ethyl, propyl, isopropyl, tert-butyl, hexyl.

From lineinyi, hexadecyl and octadecyl.

From branched alkyl radicals with 1-20 carbon atoms especially can be called 2-methylbutyl, 2-methylpentyl, 1-etylhexyl, 3-methylheptan.

Under alkenyl understand radical, a linear or branched radical with 2 to 20 carbon atoms, comprising one or more double bonds.

From alkenyl preferred radicals is a radical with 2 to 5 carbon atoms, comprising one or more unsaturated double bonds, such as more preferably allyl.

Under monohydroxyethyl or polyhydroxyalkane radical need to understand the radical with 1-6 carbon atoms, containing 1-5 hydroxyl groups.

From monohydroxyethyl radicals is preferred radical is preferably 1 or 3 carbon atoms, especially hydroxymethyl, 2-hydroxyethyl, 2 - or 3-hydroxypropyl.

From polyhydroxyalkane preferred radicals is a radical of 3-6 carbon atoms from 2 to 5 hydroxyl groups, such as 2,3-dihydroxypropyl, 2,3,4-trihydroxybutane, 2,3,4,5-tetrahydroxyphenyl or residue of pentaerythritol.

Under the heterocycle preferably understand piperidinyl, morpholinyl, pirroni carbon or polyhydroxyalkane radical, such as the above.

Under the polyether radical see radical, preferably containing 2 to 6 carbon atoms, especially methoxyethoxy, ethoxyethoxy, methoxyethoxy-methoxy group, methoxyethoxymethyl, methoxyethoxymethyl and methoxyphenylacetate.

From CNS radicals is preferred CNS radical with 1-12 carbon atoms, such as especially a methoxy group, ethoxypropan, profilaxia, isopropylacetate, hexyloxy, heptyloxy, aktionsgruppe and nonassignable.

When the radicals R2, R3, R6, R10, R11mean halogen atom, it preferably represents a fluorine atom, bromine or chlorine.

Of the compounds of the above formula (I) included in the scope of the present invention particularly include the following:

4-[4-(biphenyl-2-yl)but-3-EN-1-inyl]benzoic acid;

4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-1-inyl]benzoic acid;

4-[3-(4'-methylbiphenyl-2-yl)acrylamido]benzoic acid;

4-[3-(4'-methylbiphenyl-2-yl)-(E)-tioacridine]benzoic acid;

4-[3-(4'-methylbiphenyl-2-yl)acryloyloxy]benzoic acid;

4-[4-(4'-methylbiphenyl-2-yl)b(4'-methylbiphenyl-2-yl)propenyloxy]benzoic acid;

4-[4-(4'-methylbiphenyl-2-yl)-(E)/(Z)-buta-1-ene-3-inyl]benzoic acid;

4-[4-(4'-methylbiphenyl-2-yl)buta-1,3-dienyl]benzoic acid;

4-[4-(3-fluoro-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4,4'-dimethylbiphenyl-2-yl)but-3-EN-1-inyl]benzoic acid;

4-[4-(5,4'-dimethylbiphenyl-2-yl)but-3-EN-1-inyl]benzoic acid;

4-[4-(6,4'-dimethylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4-hydroxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(5-hydroxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(6-hydroxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(4'-methylbiphenyl-2-yl)Penta-3-EN-(E)-1-inyl]benzoic acid;

4-[3-(4'-methylbiphenyl-2-yl)propylamino]benzoic acid;

4-[3-(4'-methylbiphenyl-2-yl)propertyelement]benzoic acid;

4-[4-(3'-methylbiphenyl-2-yl)but-3-EN-1-inyl]benzoic acid;

4-[4-(2'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-chlorobiphenyl-2-yl)but-3-EN-1-inyl]benzoic acid;

4-[4-(3'-chlorobiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-forbiden-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-propylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-vinylite the slot;

4-[4-(3'-methoxyethoxymethyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(2-thiophene-3-ylphenyl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(2-thiophene-2-ylphenyl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-hydroxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-propoxyphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(3'-hydroxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(3'-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(3'-propoxyphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methyl-4-hydroxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methyl-4-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(4'-methyl-4-propoxymethyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methyl-5-hydroxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methyl-5-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(4'-methyl-5-propoxymethyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methyl-6-hydroxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methyl-6-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(4'-tryptomine acid;

4-{4-[4'-(2-hydroxyethyl)biphenyl-2-yl]but-3-EN-(E)-1-inyl}benzoic acid;

4-[4-(3'-methylbiphenyl-3-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(2-pyridin-4-ylphenyl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(2-pyridin-3-ylphenyl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(3-methoxyethoxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(3-hydroxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(3-methoxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(4'-ethoxymethylene-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

methyl ester of 4-[4-(4'-ethoxymethylene-2-yl)but-3-EN-(E)-1 - inyl]benzoic acid;

2-methyl-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

2-hydroxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

6-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]pyridine-3-carboxylic acid;

5-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]pyridine-2-carboxylic acid;

5-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] thiophene-3-carboxylic acid;

3 methoxyethoxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

3-hydroxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

3-methoxy-4-[4-(4'-met;

4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzaldehyde;

4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]phenol;

4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzamide;

N-ethyl-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzamide;

{ 4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] phenyl}-morpholine - 4-ylmethanone;

N-(4-hydroxyphenyl)-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzamide;

5-[4-(4'-methylbiphenyl-2-yl)buta-1,3-dienyl]thiophene-3-carboxylic acid.

According to the present invention, the most preferred compounds of formula (I) are such that adhere to at least one and preferably all of the following conditions: R1means the radical-CO-R5; Ar1means radicals of formulae (a) and (b); X-Y means of communication of formula (e), (f), (h); Ar2means a radical of the formula (j). Preferred compounds correspond to the formula (I) in which R1means the radical-CO-OR13where R13means a hydrogen atom or a linear or branched alkyl radical with 1-20 carbon atoms, such as indicated above.

The object of the present invention are methods for producing compounds of formula (I), in particular according to Fig. 1 and 2 reaction schemes.

Thus, the compounds of formula I (b) can be obtained (Fig. 1) by reaction Horner-Emmons between the aldehyde derivative (6) and phosphonate derivatives (11). Derivative (6) can be obtained by restoring the nitrile derivative (5) with diisobutylaluminium. Derivative (5) is obtained by reaction, Horner-Emmons between the aldehyde derivative (3) and citizen.metropolitan in the presence of a base such as potassium hydroxide.

Thus, the compounds of formula I(c) can be obtained (Fig. 1) by outside, and in the presence of tertiary amine (e.g. triethylamine or pyridine), an activated form of a derivative of cinnamic acid (7), for example, carboxylic acid, with an aniline derivative of the formula (12). Derivatives of cinnamic acid (7) can be obtained by reaction type reaction Knoevenagel of the aldehyde derivative (3) by introducing them into interaction with malonic acid or diethylmalonate.

Thus, the compounds of formula I(d) can be obtained (Fig. 2) by the reaction of a combination of diacetylene derivatives (15) with the halogenated (preferably iodirovannoye) derivative (8) in a solvent such as dimethylformamide, in the presence of PPh3, CuJ and K2CO3. Derivative (15) is obtained by reaction of Korah-Maurus Fuchs of aldehydes (14), which in turn is obtained from acetylene derivative (12) by introducing into the interaction of acetylene derivative (12) with butyllithium, followed by reaction with dimethylformamide.

Thus, the compounds of formula I(f) can be obtained (Fig. 2) by entering into interaction in an anhydrous medium, in an organic solvent, preferably in tetrahydrofuran, in the presence of tertiary amine (e.g. triethylamine or pyridi the formulas (12). Derivative (13) can be obtained by litvinovna acetylene derivative (12) with utility, followed by reaction with carbon dioxide.

When R1means the radical-COOH, connections get:

any protecting R1protective group, alkyl, allyl, benzyl or tert-Putilkovo type;

moreover, the transition to a free form can be done as follows:

in the case of alkyl protective group, with sodium hydroxide or lithium hydroxide in an alcohol solvent such as methanol, or tetrahydrofuran;

in the case of allyl protective group, by using a catalyst, such as certain transition metal complexes, in the presence of a secondary amine, such as morpholine;

- in the case of the benzyl protective group, by dibenzylamine in the presence of hydrogen using a catalyst such as palladium-on-coal;

in case the protective group is tert-Putilkovo type, using trimethylsilane;

or from the corresponding phenol by turning it into triflate derived, then carbonylation in the presence of a catalyst based on palladium.

When R1means alcohol function of the compound is of atalla, such as sodium borohydride in an alcohol solvent (e.g. methanol);

- derived from acids by restoring using sociallyengaged.

When R1means aldehyde function compounds can be obtained from the alcohol derivative by oxidation in the presence of oxide of manganese, pyridineboronic or reagent Swarna.

When R1means amide function compounds can be obtained from the corresponding carboxylic derivatives by reaction with aliphatic, aromatic, heterocyclic amines, or through a carboxylic acid or in the presence of dicyclohexylcarbodiimide or carbonyldiimidazole.

The thus obtained products of General formula (I) can serve as initial products to obtain other compounds of formula (I) according to the invention. These compounds get the classical methods of synthesis used in chemistry, such as the methods described in "Advanced Organic Chemistry", J. March, John Willey and Sons, 1985.

For example, you can perform functional modification group, R1as indicated below:

carboxylic acid ---> esters;

ester ---> carboxylic acid;
slot ---> alcohol;

alcohol ---> aldehyde;

amide ---> Amin.

Compounds according to the invention show activity in the test cell differentiation (F9) embryonic teratocarcinoma mice (Cancer Research, 43, of 5,268 (1983)) and/or in the test of inhibition of interdiscursivity after induction with terephthalic acid in the case of mice (Cancer Research, 38, 793-801 (1978)). These tests show the activity of these compounds, respectively, in the areas of differentiation and proliferation of cells. In the test cell differentiation (F9) can be estimated agonistic activity as antagonistic activity to retinoic acid receptors. In fact, the antagonist is inactive, when he is alone in this test, however, partially or completely inhibits the effect of the agonist-retinoid on the morphology and allocation plasminogen activator. These compounds, therefore, also are active in the test, which consists in the identification of molecules antagonists RARs and described in the application for French patent N 95-07302 filed June 19, 1995 by the applicant. This test includes the following stages: (i) to an area of skin of a mammal locally cause a sufficient number of molecules of agonist RARs, (ii) the system or tapicerki (i), enter the molecule, which may have antagonistic activity of RARs, and (iii) assess the response to the thus treated area of skin of a mammal. Thus, the response to topical introduction to the ear of the mammal molecule-agonist RARs, which is expressed in this thickening of the ear, can be suppressed by introducing topical or systemic by molecule-antagonist RARs.

The object of the present invention are also compounds of the above formula (I) as a drug.

Compounds according to the invention is particularly suitable in the following areas of treatment:

1) for treating dermatological diseases associated with disorders of keratinization-induced differentiation and proliferation, in particular for the treatment of ordinary, youth, polymorphic and pink acne, nodules and nodular acne, senile acne, secondary acne such as solar acne, medication or occupational acne;

2) for treating other types of disorders of keratinization, such as ichthyosis, idiotphone condition, disease Daria, Palmar-plantar keratoderma, leukoplakia and leukoplasia status, skin iscertainly with inflammatory and/or immunoallergic component, and especially all forms of psoriasis, which may be cutaneous, mucosal or ungual, and also psoriatic arthritis, or cutaneous atopy, such as eczema, or respiratory atopy or gingival hypertension; the connection can also be used in certain inflammatory diseases without disorders of keratinization;

4) for the treatment of all benign or malignant dermal or epidermal of proliteracy viral or non-viral origin, such as ordinary simple warts, flat warts, or resembling a wart dysplasia of the epidermis, oral or flowering papillomatosis, and proliferate, which can be caused by ultraviolet radiation, especially in the case of basal cell and Spino-cellular epithelium;

5) for treating other dermatological disorders such as bubble dermatoses and collagen;

6) to treat certain eye disorders, especially corporate;

7) to restore or against photoinductive age or aging, or for reducing pigmentations and actinic keratoses, or any pathologies associated with chronological or actinic aging;

8) for predotvraschenii corticosteroids, or any other form of cutaneous atrophy;

9) to prevent or treat disorders of scarring or for the prevention or healing of the bands on the skin when it is stretched;

10) to fight against disorders of the sebaceous function, such as acne affected Hyperborea or simple seborrhoea;

11) for the treatment or prevention of cancerous or precalcination conditions, more preferably promyelocytic leukemia;

12) for the treatment of inflammatory diseases such as arthritis;

13) for the treatment of any disease of viral origin at the level of the skin, such as sarcoma Galoshes, or General disease;

14) for the prevention or treatment of alopecia;

15) for the treatment of dermatological or General diseases with an immunological component;

16) for the treatment of diseases of the cardiovascular system such as arteriosclerosis, hypertension, non-insulin-dependent diabetes as well as obesity;

17) for the treatment of skin disorders due to long time under the influence of ultraviolet radiation.

In the above-mentioned therapeutic areas compounds according to the invention preferably can be used in combination with other compounds,Tami against free radicals, with a - hydroxy or a - keto acid or their derivatives, or even with blockers of ion channels. Under vitamin D or derivatives of them understand, for example, derivatives of vitamin D2or D3and in particular 1,25-dihydroxyvitamin D3. Under tools against free radicals see, for example, a - tocopherol, disputations, original or some agents education chelated ORGANOMETALLIC compound. Under - hydroxy - or - keto acid or their derivatives see, for example, lactic, malic, citric, glycolic, almond, wine, glycerol or ascorbic acid or their salts, amides or esters. Finally, under the blockers of ion channels see, for example, Minoxidil-(2,4-diamino-6-piperidinedione-3-oxide) and its derivatives.

The object of the present invention are also pharmaceutical compositions containing at least one compound of the above formula (I), one of its optical or geometric isomers or one of its salts.

Therefore, an object of the present invention is a new pharmaceutical composition, intended in particular for the treatment of the above diseases and characterized in that it contains, in FA is ina least one compound of formula (I), one of its optical or geometric isomers or one of its salts in an effective amount. Compounds according to the invention can enter the intestinal, parenteral, local or ocular.

For the introduction intestinal, medicines can be in the form of tablets, gelatin capsules with the medicine, pills, syrups, suspensions, solutions, powders, granules, emulsions, microspheres or nanospheres or lipid or polymeric vesicles, allowing controlled release. For administration parenterally, the composition can be in the form of solutions or suspensions for perfusion or for injection.

Compounds according to the invention is usually administered in a daily dose from about 0.01 mg/kg to 100 mg/kg of body weight, and is 1-3 reception.

For topical injection, the pharmaceutical compositions based on compounds according to the invention are, in particular, for the treatment of skin and mucous membranes and then they can be in the form of ointments, creams, jelly, lipstick, powders, absorbency tampons, solutions, gels, sprays, lotions or suspensions. They can also be in the form of microspheres or nanospheres or lipid or polymeric vesicles or polymeric patches and guide the top, can be either in anhydrous form or in aqueous form, depending on clinical indications.

For the introduction of the eyepiece, the compositions according to the invention are mainly eye drops.

These compositions for local or ocular use contain at least one compound of the above formula (I) or one of its optical or geometric isomers or one of its salts, preferably in a concentration of 0.001-5 wt.%, in the calculation of the total mass of the composition.

The compounds of formula (I) according to the invention also find application in cosmetics, in particular for hygiene of the body and for hair care especially for the treatment of skin with a tendency towards acne, for faster hair growth, prevent hair loss, to combat oily type of skin or hair, for protection against the harmful effects of the sun or for the treatment of physiologically dry skin, to prevent and/or combat photoinduced or age-related skin aging.

In the field of cosmetics, the compounds according to the invention, in addition, preferably can be used in combination with other compounds with activity is dikalov, - hydroxy - or - keto acid or their derivatives, or blockers of ion channels, and all of these different products represent the products listed above.

Therefore, the present invention relates also to a cosmetic composition, characterized in that it contains, in a cosmetically acceptable and suitable for topical administration carrier, at least one compound of the above formula (I) or one of its optical or geometric isomers or one of its salts in an effective amount, with this cosmetic composition may in particular be in the form of a cream, a milk, a lotion, a gel, microspheres or nanospheres or lipid or polymeric vesicles, a soap or shampoo.

The concentration of the compounds of formula (I) in the cosmetic compositions according to the invention is preferably 0.001 to 3 wt.%, in the calculation of the totality of the composition.

The medicinal and cosmetic compositions according to the invention, can also contain inert or pharmacodynamically or cosmetically active additives or combinations of these additives, and in particular, the following: wetting; depigmenting agents, such as hydroquinone, azelaic cisol with a molecular weight of 400, thiomorpholine and its derivatives, or urea; protivoseborainey or protivougrevoe additives, such as S-carboxymethylcysteine, S-benzylcyanide, their salts and their derivatives, or benzoyl peroxide; antibiotics as erythromycin and its esters, neomycin, clindamycin and its esters, tetracyclines; antifungal agents such as ketoconazole or 4,5-polymethylene-3-isothiazolinones; conducive to hair growth agents, as Minoxidil (2,4-diamino-6-piperidinedione-3-oxide) and its derivatives, diazoxide (7-chloro-3-methyl-1,2,4-benzothiadiazine-1,1-dioxide) and phenytoin (5,4-di-phenylimidazoline-2,4-dione); non-steroidal anti-inflammatory drugs type; carotenoids and especially - carotene; anti-psoriatic agents such as anthralin and its derivatives; and, finally, eicosa-5,8,11,14-tetralogia acid and eicosa-5,8,11 - TRINOVA acid, their esters and amides.

Compositions according to the invention can also include improving the taste substances, preservatives such as esters of p-hydroxybenzoic acid, stabilizers, humidity regulators, pH regulators-values, osmotic pressure modifiers, emulsifiers, UV-a and UV-B filters, antioxidants, such as tocopherol, butylhydroxyanisole or buteratte, some examples of active compounds of the formula (I) according to the invention, and various concrete compositions based on these compounds.

A. Examples of compounds

Example 1: 4-(4-biphenyl-2-yl-but-3-EN-(E)-1-inyl)benzoic acid

(a) Ethyl ester of 4-trimethylsilylmethylamine acid

In a three-neck flask in a stream of nitrogen injected 21,50 g (100.0 mmol) of methyl ester of 4-bromobenzoyl acid, 300 ml of triethylamine and the mixture of 200 mg of palladium acetate with 400 mg of triphenylphosphine. Then add 20,00 g (204 mmol) of trimethylsilylacetamide, heated gradually to 90oC for one hour and kept at this temperature for five hours. The reaction medium is cooled, the salt is filtered off and the filtrate is evaporated. The residue is treated with 200 ml of 5% hydrochloric acid and 400 ml of diethyl ether. The ether phase is decanted, washed with water, dried over magnesium sulfate, and evaporated. The resulting residue is purified by chromatography on a column of silica, elwira dichloromethane. After evaporation of the solvents get 23,00 g (100%) of target compound as a colourless oil.

1H-NMR-spectrum (deuterochloroform), M. L.: 0,36 (s, 9H); of 1.20 (t, 3H, J= 7,1 Hz); 4,19 (K, 2H, J=7,1 Hz); 7.6 for the t 45,90 g (197 mmol) of ethyl ester of 4-trimethylsilylmethylamine acid, 300 ml of methanol and add 500 mg of potassium carbonate. Stirred at room temperature for twelve hours and the reaction medium is evaporated to dryness. The resulting residue is purified by chromatography on a column of silica, elwira dichloromethane. After evaporation of the solvent receive 32,00 g (100%) of target compound in the form of a solid of light yellow color with so square 86-88oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,23 (s, 1H); to 3.92 (s, 3H); at 7.55 (d, 2H, J=8,3 Hz); 7,99 (d, 2H, J=8,2 Hz).

(C) Biphenyl-2-carboxaldehyde

In a three-neck flask in a stream of nitrogen injected 11,43 g (49 mmol) of 2-bromobiphenyl and 50 ml of tetrahydrofuran. At a temperature of -78oC was added dropwise to 21.6 ml (54 mmol) of a 2.5 M solution of n-utility in hexane and stirred for hours at the same temperature. Then added dropwise to 4.17 ml (53,9 mmol) of dimethylformamide and leave the temperature to rise to room. The reaction medium is acidified using 1N. hydrochloric acid, extracted with diethyl ether, the organic phase is decanted, dried over magnesium sulfate, and evaporated. The resulting residue is purified by chromatography on a column of silica, elwira with a mixture of 60% hexane and 40% dichloromethane. Obtain 6.50 g (73%) C(m, 7H); a 7.62 (DD, 1H, J=7,5/1,4 Hz); 8,03 (DD, 1H, J=7,7/1.2 Hz).

(g) 2-((Z)/(E)-2-Iodine)biphenyl -

In a three-neck flask in a stream of argon, is injected 11,90 g (97 mmol) chloride chromium (II) and 195 ml of anhydrous tetrahydrofuran. Cooled to a temperature of 0oC and maintaining this temperature was added dropwise a solution of 3.54 g (to 19.4 mmol) biphenyl-2-carboxaldehyde, 15,30 g (38,8 mmol) of iodoform in 97 ml of anhydrous tetrahydrofuran. Stirred for three hours at a temperature of 0oC, the reaction medium is poured into water, extracted with diethyl ether, the organic phase is decanted, dried over magnesium sulfate, and evaporated. The resulting residue is purified by chromatography on a column of silica, elwira heptane. Get 4,70 g (79%) of target compound in the form of a slightly yellowish oil in the form of a mixture of 70% (E)-isomer and 30% (Z)-isomer (determined by NMR).

1H-NMR-spectrum (deuterochloroform) [(E)-isomer], in memorial plaques: 6,74 (d, 1H, J= 14,8 Hz); 7,25-7,49 (m, 10H).

(d) Methyl ester of 4-(4-biphenyl-2-yl-but-3-EN-(E)-1-inyl)benzoic acid

Into the flask is injected sequentially 4,22 g (to 13.8 mmol) of 2-(2-iodine)biphenyl, of 2.21 g (to 13.8 mmol) of methyl ester 4-ethylbenzoyl acid, 131 mg CuJ, 362 mg (1.38 mmol)

triphenylphosphine, 2.86 g (20,7 mmol) of potassium carbonate vylivayut in water, extracted with ethyl acetate, the organic phase is decanted, dried over magnesium sulfate, and evaporated. The resulting residue is purified by chromatography on a column of silica, elwira with a mixture of 70% heptane and 30% dichloromethane. After evaporation of the solvents to obtain 2.25 g (48%) of target compound in the form of a white powder with so pl. 97 - 100oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,91 (s, 3H); 6,35 (d, 1H, J=16.2 Hz); to 7.09 (d, 1H, J=16.2 Hz); 7,30 - 7,49 (m, 10H); 7,63-to 7.68 (m, 1H); of 7.97 (DD, 2H, J=6,7/1,7 Hz).

(e) 4-(4-Biphenyl-2-yl-but-3-EN-(E)-1-inyl)benzoic acid

Into the flask enter 1,99 g (5.9 mmol) obtained in example 1 (d) of ester, 40 ml of methanol and 40 ml of tetrahydrofuran. Add to 11.8 ml (59 mmol) of 5h. the sodium hydroxide solution in methanol and refluxed for one hour. Is evaporated to dryness, the residue is treated with a mixture of diethyl ether with 4h. hydrochloric acid, the organic phase is decanted, dried over magnesium sulfate and evaporated. The obtained residue proscout in a mixture of 20% diethyl ether and 80% heptane, filtered off, dried. Obtain 1.70 g (90%) of 4-(4-biphenyl-2-yl-but-3-EN-(E)- 1-inyl)benzoic acid as white powder with so pl. 228 - 229oC.

1H-NMR-spectrum (date-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

(a) 4-Methylphenylamine acid

In a three-neck flask in a stream of nitrogen injected 17.1 g (0.1 mol) of 4-bromthymol and 70 ml of tetrahydrofuran. At a temperature of -78oC was added dropwise 48 ml (120 mmol) of a 2.5 M solution of n-utility in hexane and stirred for hours at the same temperature. Then added dropwise 34,6 ml (150 mmol) of triisopropylsilyl, leave the temperature to rise to room temperature and stirred for 16 hours. Slowly add 450 ml of 1N., hydrochloric acid and stirred for one hour at room temperature. The reaction medium is extracted with dichloromethane, the organic phase is decanted, dried over magnesium sulfate and evaporated. Get 11,10 g (61%) of target compound in the form of a pulverized solid white with so pl. 250-252oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42(s, 3H); 7,29(d, 2H, J= 7,6 Hz); 8,10(d, 2H, J 7.9 Hz).

(b) 2-Bromo-4'-methylbiphenyl

In a three-neck flask enter 5.34 g (39,3 mmol) of 4-methyl-phenylboric acid, 10.0 g (35,3 mmol) 1-bromo-2-iodine-benzene, 100 ml of toluene and 42 ml of a 2M aqueous solution of potassium carbonate. Reaction medium Tegaserod by ozonation of argon and type of 1.23 g (1.06 mmol) tetranitroaniline-(O) and heated at a temperature of 90o

1H-NMR-spectrum (deuterochloroform), M. D.: is 2.40 (s, 3H); 7,13 and 7.36(m, 7H); to 7.64(d, 1H, J=7.9 Hz).

(in) 4'-Methylbiphenyl-2-carboxaldehyde

Similarly to the method of example 1(C), based on 5,90 g (of 23.9 mmol) of 4'-methyl-2-bromobiphenyl get to 3.92 g (84%) of target compound as a colourless oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43 (s, 3H); 7,28(s, 4H); 7,42-to 7.50(m, 2H); to 7.61(DD, 1H, J=7,5/1,4 Hz); 8,02(DD, 1H, J=7,6/1.2 Hz); 9,99(s, 1H).

(g) 2-((E)-2-Iodine)-4'-methylbiphenyl

Similarly to the method of example 1(g), according to 3.92 g (20.0 mmol) of 4'-methylbiphenyl-2-carboxaldehyde get to 4.98 g (78%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42 (s, 3H); 6.73 x(d, 1H, J= 14,8 Hz); 7,22-7,74(m, 10H).

(d) Methyl ester of 4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1 - inyl]benzoic acid

Similarly to the method of example 1 (d), by the interaction of 4.12 g (12.9 mmol) of 2-(2-iodine)-4'-methylbiphenyl with of 2.06 g (12.9 mmol) of methyl ester 4-ethynylbenzene acid, get the Mr spectrum (deuterochloroform), in M. D.: 2,43(s, 3H); 3,91(s, 3H); 6,34(d, 1H, J= 16.2 Hz); 7,11(d, 1H, J=16.2 Hz); 7,26-7,37(m, 7H); 7,47(d, 2H, J=8,4 Hz); 7,63-7,66(m, 1H); of 7.97 (d, 2H, J=8,4 Hz).

(e) 4-[4-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e), based on a 1.46 g (4.14 mmol) obtained in example 2 (d) complex methyl ester, get 1,31 g(93%) 4-[4-(4'-methylbiphenyl-2-yl)-but-3-EN-(E)-1-inyl] benzoic acid in the form of a solid white color with so pl. 241-242oC.

1H-NMR-spectrum (deuterochloroform), M. D.: a 2.36(s, 3H); of 6.29(d, 1H, J= 16.2 Hz); 7,02(d, 1H, J=16.2 Hz); 7,15-7,31 (m, 7H); 7,39 (d, 2H, J=8,4 Hz); EUR 7.57-to 7.61 (m, 1H); to $ 7.91(d, 2H, J=8,4 Hz).

Example 3: 4-[3-(4'-Methylbiphenyl-2-yl)acrylamido]benzoic acid

(a) Ethyl ester of 3-(4'-methylbiphenyl-2-yl)-(E)-acrylic acid

In a three-neck flask in a stream of nitrogen injected 20,75 g (92.0 mmol) of ethyl ether diethylphosphonate acid and 40 ml of tetrahydrofuran. Cooled to a temperature of 0oC, add small portions of 3.45 g (115,0 mmol) of 80% sodium hydride and the reaction medium is stirred for 15 minutes at a temperature of 0oC. was added dropwise a solution of 15.00 g (to 76.4 mmol) obtained in example 2 (C) of the aldehyde in 40 ml of tetrahydrofuran. The reaction medium is stirred for 10 minutes at room temperature, podci is up to neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by chromatography on a column of silica, elwira with a mixture of 50% ethyl acetate and 50% heptane. After evaporation of the solvents get 19,40 g (95%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D. : of 1.29(t, 3H, J=7,1 Hz); is 2.41(s, 3H); 4,21(K, 2H, J 7.2 Hz); to 6.39(d, 1H, J=15,9 Hz); 7.18 in-7,26(m, 4H); 7,32 was 7.45(m, 3H); to 7.67 - 7,71(m, 1H); of 7.75(d, 1H, J=16.0 Hz).

(b) 3-(4'-Methylbiphenyl-2-yl)-(E)-acrylic acid

In a three-neck flask in a stream of nitrogen injected 19,00 g (71,0 mmol) obtained in example 3(a) of ester, 70 ml 10h. an aqueous solution of sodium hydroxide and 150 ml of tetrahydrofuran. The reaction medium is heated for four hours at a temperature of 67oC, cooled, acidified to pH 1 using 2n. hydrochloric acid and extracted with ethyl acetate. The organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. Get 16,92 g (99%) of target compound in the form of "fluffy" crystalline solid white with so pl. 214-216oC.

1H-NMR-spectrum (deuterochloroform), M. D.: is 2.41 (s, 3H); 6,38(d, 1H, J= 16.0 Hz); 7.18 in-7,26(m, 4H); 7,32 was 7.45(m, 3H); 7 is the notes

In a three-neck flask in a stream of nitrogen injected 17,50 g (73.4 mmol) obtained in example 3(b) acid and 350 ml of dichloromethane. Added dropwise 14.9 ml (74.9 mmol) of dicyclohexylamine and the resulting solution is stirred for one hour at room temperature. The reaction medium is evaporated to dryness, the obtained crystals proscout in diethyl ether, filtered and dried in a drying Cabinet. Get 29.67 per g (96%) of white powder.

20,00 g (47,6 mmol) of This salt are dissolved in 400 ml of dichloromethane. Was added dropwise and 3.8 ml (52,0 mmol) of thionyl chloride and the resulting solution is stirred for one hour at room temperature. The reaction medium is filtered and the filtrate is evaporated to dryness. The resulting residue is dissolved in 200 ml of tetrahydrofuran, and the thus obtained solution was added dropwise to a solution of 7.20 g (47,6 mmol) of methyl ester of 4-aminobenzoic acid and 7,24 ml (52,0 mmol) of triethylamine in 150 ml of tetrahydrofuran. The reaction medium is stirred for one hour and 15 minutes at room temperature, acidified to pH 1 using 2n. hydrochloric acid and extracted with diethyl ether. The organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. Recip is 0% heptane. After evaporation of the solvents get 6,00 g (33%) of target compound in a solid pink color with so pl. 207oC.

1H-NMR-spectrum (deuterochloroform), M. D.: of 2.38 (s, 3H); 3,88 (s, 3H); 6,70(d, 1H, J=15,5 Hz); 7.18 in-7,25(m, 4H); 7,31-7,44 (m, 3H); to 7.68(d, 1H, J= 8.0 Hz); for 7.78(d, 2H, J=8,8 Hz); 7,80(d, 1H, J=15.7 Hz); of 7.97(d, 2H, J=8,8 Hz); 9,48(s, 1H).

(g) 4-[3-(4'-Methylbiphenyl-2-yl)-(E)-acrylamido]benzoic acid

In a flask with a volume of 250 ml and in a stream of nitrogen injected 2,10 g (5.6 mmol) obtained in example 3(g) connection and 100 ml of tetrahydrofuran. Quickly poured 5.6 ml (56.0 mmol) 10h. an aqueous solution of sodium hydroxide and reaction medium for 6 hours, refluxed, and then to stand for 16 hours at room temperature. The reaction medium is cooled, acidified to pH 1 using 2n. hydrochloric acid and extracted with diethyl ether. The organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. Get 1,82 g(90%) 4-[3-(4'-methylbiphenyl-2-yl)-(E)- acrylamido] benzoic acid in the form of a crystalline powder of white colour with so pl. 265oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,39(s, 3H); is 6.78(d, 1H, J= 15.6 Hz); 7.18 in-7,25(m, 4H); 7,32-7,44(m, 3H)thiocresol-amino] benzoic acid

(a) Methyl ester of 4-[3-(4'-methylbiphenyl-2-yl)-(E)-tioacridine] benzoic acid

In a flask with a volume of 250 ml in a stream of nitrogen injected 2.50 g (6.7 mmol) obtained in example 3(g) compounds of 1.36 g (3,36 mmol) of the reagent Lawesson and 60 ml of toluene. The reaction medium is refluxed for one hour, cooled and evaporated to dryness. The obtained residue proscout in a mixture of 50% dichloromethane and 50% heptane, filtered and dried. Obtain 1.92 g (73%) of target compound in powder form bright orange color with so pl. 183oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42 (s, 3H); 3,91(s, 3H); 7,17-7,26(m, 5H); 7,37-7,49(m, 3H); 7,71(d, 1H, J=7.2 Hz); 7,95-of 8.04 (m, 6H); to 11.28 (s, 1H).

(b) 4-[3-(4'-Methylbiphenyl-2-yl)-(E)-tioacridine]benzina acid

Similarly to the method of example 1(e) on the basis of 1.50 g (3.9 mmol) obtained in example 4 (a) connections, earn 1.25 g(86%) 4-[3-(4'-methylbiphenyl-2-yl)-tioacridine] (E)- benzoic acid in the form of a powder orange with so pl. 220oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: 2,39(s, 3H); 7.23 percent-7,33(m, 4H); 7,39-7,42(m, 2H); of 7.48-7,51(m, 2H); 7,80-7,83 (m, 1H); 7,88(d, 1H, J= 15.1 Hz); 8,00(d, 2H, J=8.5 Hz); 8,12(m, 2H); 11,91(s, 1H); 12,99(s, 1H).

Example 5: 4-[3-(4'-Methylbiphenyl-2-yl)acryloyloxy]-benzoin the reception of 1 litre in a stream of nitrogen injected of 9.30 g (22,0 mmol) obtained in the first part of example 3(C) salts dicyclohexylamine and 100 ml of dichloromethane. Added dropwise 1.77m (24,0 mmol) of thionyl chloride and the resulting solution was stirred for fifteen hours at room temperature. The reaction medium is filtered and the filtrate is evaporated to dryness. The residue is dissolved in 200 ml of tetrahydrofuran, and the thus obtained solution was added dropwise to a solution of 7.20 g (47,6 mmol) allyl ether of 4-hydroxybenzoic acid and to 3.34 ml (24,0 mmol) of triethylamine in 130 ml of tetrahydrofuran. The reaction medium is stirred for 24 hours at room temperature, acidified to pH 1 using 2n. hydrochloric acid and extracted with diethyl ether. The organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by chromatography on a column of silica, elwira mixture of 15% ethyl acetate and 85% heptane. After evaporation of the solvents gain of 4.95 g (55%) of target compound in the form of a white powder with so pl. 68oC.

1H-NMR-spectrum(deuterochloroform), M. D.: is 2.41 (s, 3H); 4,81-4,84 (m, 2H); from 5.29(DD, 1H, J-10,4/1.3 Hz); 5,41(DD, 1H, J=17,2/1.5 Hz); 5,96-6,12 (m, 1H); 6,59(d, 1H, J=15,9 Hz); 7,21 - 7,28(m, 6H); 7,39-7,51(m, 3H); to 7.77(d, 1H, J=7.2 Hz); of 7.95(d, 1H, J=15,9 Hz); 8,10(d, 2H, J=8.7 Hz).

(b) 4-[3-(4'-Methylbiphenyl-2-yl)-(E)-acryloylmorpholine and add in small portions 170 mg (5,65 mmol) of 80% sodium hydride. The reaction mixture was stirred at room temperature for 20 minutes, then transferred to an addition funnel. This solution is added slowly to a mixture of 2.00 g (5.0 mmol) obtained in example 3(a) connections, 290 mg tetranitropentaerithrite-(O) and 75 ml of tetrahydrofuran. The reaction medium is stirred for 20 minutes at room temperature, acidified to pH 1 using 2n. hydrochloric acid and extracted with diethyl ether. The organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. After powdering in a minimal amount of ethyl acetate to obtain 1.50 g(83%) 4-[3-(4'-methylbiphenyl-2-yl)- (E)-acryloyloxy]-benzoic acid in the form of flakes of a light beige color with so pl. 234-236oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: is 2.37(s, 3H); 6.90 to(d, 1H, J=15,9 Hz); 7.23 percent-7,33(m, 6H); 7,39 - to 7.59(m, 3H); to 7.77(d, 1H, J= 15,9 Hz); 7,99-8,07(m, 3H); to 13.09(s, 1H).

Example 6: 4-[4-(4'-Methylbiphenyl-2-yl)buta-1(E), 3(Z)-dienyl] benzoic acid

(a) (Z)/(E)-3-(4'-Methylbiphenyl-2-yl)Acrylonitrile

In a flask with a volume of 250 ml in a stream of nitrogen introduced to 5.40 g (30,5 mmol) citizen.metropolitan and 20 ml of tetrahydrofuran. The resulting solution was cooled to a temperature of 0oC, Uchenie 10 minutes at a temperature of 0oC, and then was added dropwise a solution of 5.00 g (25,0 mmol) obtained in example 2 (C) of the aldehyde in 20 ml of tetrahydrofuran. The reaction medium is stirred for 15 minutes at room temperature, acidified to pH 1 using 2n., hydrochloric acid and extracted with diethyl ether. The organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by chromatography on a column of silica, elwira mixture of 2% ethyl acetate and 98% heptane. After evaporation of the solvents to obtain 1.40 g (25%) of (Z)-isomer in the form of slightly yellow crystals with so pl. 80-82oC and 2,87 g (52%) of (E)-isomer as white crystals with so pl. 95-97oC.

1H-NMR-spectrum (deuterochloroform), M. D. [(E)-isomer]: 2,43 (s, 3H); of 5.83(d, 1H, J= 16,7 Hz); 7,16(d, 2H, J=8.1 Hz); 7,27(d, 2H, J=7,1 Hz); 7,35 is 7.50(m, 4H); to 7.59(d, 1H, J=7,6 Hz).

1H-NMR-spectrum (deuterochloroform), M. D. [(Z)-isomer]: to 2.41 (s, 3H); 5,41(d, 1H, J= 12.0 Hz); for 7.12(d, 1H, J=12.1 Hz); 7,07-7,26(m, 4H); 7,37-7,52(m, 3H); to 8.14(d, 1H, J and 6.7 Hz).

(b) 3-(4'-Methylbiphenyl-2-yl)propen-(E)/(Z)-al

In a three-neck flask with a volume of 100 ml in a stream of nitrogen injected 1.35 g (6.1 mmol) obtained in example 6 (a) (Z)-isomer and 15 ml of toluene. The resulting solution is OLE. The reaction medium is stirred for one hour at a temperature of -78oC, hydrolyzing with a saturated solution of sodium tartrate, potassium and filtered. The organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by chromatography on a column of silica, elwira mixture of 5% ethyl acetate and 95% heptane. After evaporation of the solvents gain of 1.00 g (74%) of target compound containing 16% (E)-isomer.

1H-NMR-spectrum (deuterochloroform), M. D. [(Z)-isomer]: to 2.41(s, 3H); x 6.15(DD, 1H, J= 11,5/8,2 Hz); 7,20-7,26(m, 4H); of 7.36-of 7.60(m, 5H); of 10.05(d, 1H, J=8,2 Hz).

(b) Ethyl ester of 4-[4-(4'-methylbiphenyl-2-yl)buta-1(E),3(Z)- dienyl]benzoni acid

In a three-neck flask with a volume of 100 ml in a stream of nitrogen injected 2,01 g (6.7 mmol) of the ethyl ester of 4-(diethylphosphonate)benzoic acid and 10 ml of tetrahydrofuran. Add small portions 270 mg (9.0 mmol) of 80% sodium hydride and the reaction medium is stirred for 10 minutes at room temperature. Was added dropwise a solution of 1.00 g (4.5 mmol) obtained in example 6(b) of the aldehyde in 15 ml of tetrahydrofuran. The reaction medium is stirred for 20 minutes at room te minutes. The reaction medium is acidified to pH 1 using 2n., hydrochloric acid and extracted with diethyl ether. The organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by chromatography on a column of silica, elwira a mixture of 1% ethyl acetate and 99% heptane. After evaporation of the solvents to obtain 440 mg (26%) of target compound as a colourless oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 1.39(t, 3H, J=7,1 Hz); 2,39 (s, 3H); 4,37 (K, 2H, J=7,1 Hz); 6,34 - 6,46(m, 2H); 6,70(d, 1H, J=15.6 Hz); then 7.20(d, 2H, J=8.0 Hz); 7,29(d, 2H, J=8.1 Hz); 7,35 - 7,51(m, 7H); 7,98(d, 2H, J=8,4 Hz).

(g) 4-[4-(4'-Methylbiphenyl-2-yl)buta-1(E),3(Z)-dienyl]benzoic acid

Similarly to the method of example 1 (e) on the basis of 440 mg (1.2 mmol) obtained in example 6 (C) connection receive 370 mg(90%) 4-[4-(4'-methylbiphenyl-2-yl)buta-1(E),3(Z)-dienyl]benzoic acid in the form of powder light yellow color with so pl. 180-182oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: 2,32 (s, 3H); 6,33-of 6.49 (m, 2H); 6,85(d, 1H, J=15.6 Hz); 7,20-7,27 (m, 4H); 7,32-7,49(m, 5H); 7,53(d, 2H, J=8,3 Hz); 7,89(d, 2H, J=8,3 Hz).

Example 7: 4-[4-(4'-Methylbiphenyl-2-yl)buta-1(E), 3(E)- dienyl]benzoic acid

(a) to (E)-3-(4'-Methylbiphenyl-2-yea, obtain 420 mg of the target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,44 (s, 3H); 6,69(DD, 1H, J=15,9/7,8 Hz); 7,20-7,29(m, 4H); 7,37 - 7,52(m, 3H); 7,56(d, 1H, J=15,9 Hz); 7,73(d, 1H, J=7.8 Hz); of 9.55(d, 1H, J=7,8 Hz).

(b) Ethyl ester of 4-[4-(4'-methylbiphenyl-2-yl)buta-1(E),3(E)-dienyl] benzoic acid

Similarly to the method of example 6(C), by reacting 700 mg (3,15 mmol) obtained in example 7 (a) (E)-isomer and of 1.32 g (4.4 mmol) of the ethyl ester of 4-(diethylphosphonate) benzoic acid, receive 860 mg (74%) of target compound in the form of a yellow powder with so pl. 136oC.

1H-NMR-spectrum (deuterochloroform), M. D.: of 1.39(t, 3H, J=7,1 Hz); 2, 44 (s, 3H); 4, 37 (K, 2H, J=7,1 Hz); 6, 62-6, 79 (m, 2H); 6.87 in-6,97(m, 2H); 7,26-7,35(m, 7H); the 7.43(d, 2H, J and 8.3 Hz); 7,71(d, 1H, J=6.0 Hz); of 7.97(d, 2H, J=8,3 Hz).

() 4-[4-(4'-Methylbiphenyl-2-yl)buta-1(E),3(E)-dienyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 860 mg (2.3 mmol) obtained in example 7(b) connections, receive 500 mg(64%) 4-[4- (4'-methylbiphenyl-2-yl)buta-1(E), 3(E)-dienyl]benzoic acid in the form of a yellow powder with so pl. 244-246oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: is 2.37(s, 3H); 6,69-to 6.80(m, 2H);? 7.04 baby mortality-7,41(m, 9H); to 7.59(d, 2H, J=8,4 Hz); 7,80(d, 1H, J=6.9 Hz); 7,86(d, 2H, J=8,3 Hz).

Example 8: 4-[3-(4'-Malbu volume of 100 ml in a stream of nitrogen injected 5.35 g (to 20.4 mmol) of triphenylphosphine, to 3.38 g (10.2 mmol) of tetrabromide carbon and 30 ml of dichloromethane. The solution is stirred for five minutes at room temperature, then added dropwise a solution of 1.00 g (5.1 mmol) obtained in example 2 (C) of the aldehyde in 10 ml of dichloromethane. The reaction medium is stirred for two hours at room temperature, add a dilute solution of potassium carbonate to bring the pH to 9-10 and extracted with dichloromethane. The organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by chromatography on a column of silica, elwira a mixture of 3% ethyl acetate and 97% heptane. After evaporation of the solvents get to 1.60 g (88%) of target compound as a colourless oil.

1H-NMR-spectrum (deuterochloroform), M. D.: is 2.41 (s, 3H); 7,21-of 7.23(m, 5H); 7,31-the 7.43(m, 3H); 7,65-of 7.69(m, 1H).

(b) 2-Ethinyl-4'-methylbiphenyl

In a three-neck flask of 500 ml in a stream of nitrogen injected 20,00 g (56,8 mmol) obtained in example 8 (a) connection and 150 ml of tetrahydrofuran. The resulting solution was cooled to -78oC and added dropwise 48 ml (119.0 mmol) of a 2.5 n solution of n-utility in hexane, maintaining the temperature below -68oC. Reactionto to bring the pH to 1. The product is extracted with diethyl ether, the organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by chromatography on a column of silica, elwira heptane. After evaporation of the solvent receive 9,05 g (81%) of target compound as a colourless oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,39(s, 3H); 3,03(s, 1H); 7,20-7,29(m, 3H); 7,31-7,41(m, 2H); of 7.48(d, 2H, J=8.1 Hz); of 7.60(d, 1H, J=7.5 Hz).

(C) Methyl ether (4'-methylbiphenyl-2-yl)propionic acid

In a three-neck flask with a volume of 250 ml and in a stream of nitrogen introduced to 5.00 g (25.5 mmol) of the compound obtained in example 8(b), and 60 ml of tetrahydrofuran. The resulting solution was cooled to -78oC and added dropwise to 11.2 ml (for 29.3 mmol) of a 2.5 n solution of n-utility in hexane, maintaining the temperature below -70oC. the Reaction medium is stirred for 15 minutes at a temperature of -78oC, and then was added dropwise a solution of 2.26 ml (for 29.3 mmol) methylcarbamate in 10 ml of tetrahydrofuran. Stirred for fifteen hours at a temperature of -78oC and quickly add 2n. hydrochloric acid to bring the pH to 1. The product is extracted with diethyl ether, organic evaporated. The resulting residue is purified by chromatography on a column of silica, elwira heptane. After evaporation of the solvent receive 5,97 g (93%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: is 2.41 (s, 3H); of 3.77(s, 3H); 7,25 was 7.36(m, 3H); 7,41-7,53(m, 4H); to 7.68(DD, 1H, J=7,7/1.0 Hz).

(g) (4'-Methylbiphenyl-2-yl)propionic acid

In a flask of 250 ml is injected of 5.83 g (23,3 mmol) obtained in example 8(C) compound, 10 ml of tetrahydrofuran, 5 ml of methanol and 11.6 ml (116,5 mmol) 10h. an aqueous solution of sodium hydroxide. The reaction medium is stirred for one and a half hours at room temperature, and then quickly add 2n. hydrochloric acid to bring the pH to 1. The product is extracted with diethyl ether, the organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The obtained residue proscout in heptane, filtered and dried. Get 5.35 g (97%) of target compound in the form of a powder beige with so pl. 114oC.

1H-NMR-spectrum (deuterochloroform), M. D.: is 2.37 (s, 3H); 7,29(d, 2H, J= 7.9 Hz); 7,42-to 7.50(m, 4H); to 7.59(d, 1H, J=7,1 Hz); 7,72(d, 1H, J=7.4 Hz); 13,68 (s, 1H).

(d) Allyl ester 4-[3-(4'-methylbiphenyl-2 in example 8 (g) connection, 1.45 g (8.0 mmol) of dicyclohexylamine, 20 ml dichloromethane and added dropwise of 0.58 ml (8.0 mmol) of thionyl chloride. The reaction medium is stirred for 5 minutes at room tempera ture, then the precipitate is filtered off, washed with dichloromethane, the filtrate is evaporated to dryness and the residue is treated with 15 ml of tetrahydrofuran. The thus obtained solution was added dropwise to a mixture of 1.35 g (7.6 mmol) allyl ether of 4-hydroxybenzoic acid, 1,17 ml (8.4 mmol) of triethylamine and 20 ml of tetrahydrofuran. After stirring for four hours quickly add 2n. hydrochloric acid to bring the pH to 1. The product is extracted with diethyl ether, the organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by chromatography on a column of silica, elwira mixture of 99% heptane and 1% ethyl acetate. After evaporation of the solvents to obtain 1.50 g (50%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42(s, 3H); 4,81-4,84(m, 2H); and 5.30(DD, 1H, J=10,4/1.3 Hz); 5,41(DD, 1H, J=17.2 in/1,4 Hz); 5,96-6,11(m, 1H); 7,21-7,40(m, 5H); 7,45-rate of 7.54(m, 4H); 7,73(DD, 1H, J=7,7/1.0 Hz); 8,10(d, 2H, J=11.2 Hz).

(e) 4-[3-(4'-Methylbiphenyl-2-yl)dimalanta, 3 ml of tetrahydrofuran and small portions 128 ml (4,27 mmol) of 80% sodium hydride. The reaction mixture is stirred for 15 minutes at room temperature, then the resulting solution was added dropwise to a mixture of 1.50 g (of 3.78 mmol) obtained in example 8(d) connections, 218 mg (0,19 mmol) tetranitropentaerithrite-(O) and 10 ml of tetrahydrofuran. The reaction medium is stirred for 30 minutes at room temperature, acidified to pH 1 using 2n., hydrochloric acid and extracted with diethyl ether. The organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The obtained residue chromatographic on a column of silica, elwira with a mixture of 70% heptane and 30% of ethyl acetate. After evaporation of the solvents receive 200 mg(15%) 4-[3-(4'- methylbiphenyl-2-yl)propenyloxy]benzoic acid in the form of a powder beige with so pl. 178oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: is 2.37 (s, 3H); 7,31(d, 2H, J=8.0 Hz); 7,38(d, 2H, J=8.7 Hz); 7,47-7,56(m, 4H); 7,65-7,71(m, 1H); of 7.82(d, 1H, J=7,7 Hz); 8,01(d, 1H, J=8.7 Hz); 13,14(s, 1H).

Example 9: 4-[4-(4'-Methylbiphenyl-2-yl)-(E)/(Z)-buta-1-ene-3-inyl] benzoic acid

(a) (4'-Methylbiphenyl-2-yl)propenal

In a three-neck Eana. The resulting solution was cooled to -78oC and added dropwise to 8.6 ml (21.5 mmol) of a 2.5 M solution of n-utility in hexane, maintaining the temperature below -65oC. the Reaction medium is stirred for 20 minutes at a temperature of -78oC, and then added dropwise and 2.26 ml (for 29.3 mmol) of N,N-dimethylformamide. Stirred for two hours at a temperature of -78oC, leave to stand for increasing tempera tours to -30oC and quickly add 2n. hydrochloric acid for maintaining the pH value to 1. The product is extracted with diethyl ether, the organic phase is alkalinized by adding 10h. the sodium hydroxide solution and extracted with ethyl acetate. The combined organic phases are washed with water to neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by chromatography on a column of silica, elwira with a mixture of 95% heptane and 5% ethyl acetate. After evaporation of the solvents get the 3.65 g (83%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42 (s, 3H); 7,27(d, 1H, J= 8,2 Hz); 7,32-7,56(m, 6H); of 7.70(DD, 1H, J=7,7/1.2 Hz); 9.28 are(s, 1H).

(b) Ethyl ester of 4-[4-(4'-methylbiphenyl-2-yl)but-1-EN-(E)/ (Z)-3-inyl] benzoic acid

Oppo is mole) of ethyl ester of 4-(diethylphosphonate) benzoic acid, get 2,12 g (80%) of target compound in the form of a yellow oil containing 78% (E)-isomer and 22% (Z)-isomer.

1H-NMR-spectrum (deuterochloroform), M. D. [(E)-isomer]: of 1.41 (t, 3H, J= 7.0 Hz); 2,43 (s, 3H); 4,37 (K, 2H, J=7.0 Hz); 6,38(d, 1H, J=16.2 Hz); 6,86(d, 1H, J=16.2 Hz); 7,20 to 7.62(m, 10H); to 7.99(d, 2H, J=8,4 Hz).

1H-NMR-spectrum (deuterochloroform), M. D. [(Z)-isomer]: of 1.40 (t, 3H, J= 7.0 Hz); of 2.38 (s, 3H); 4,36 (K, 2H, J=7.0 Hz); 5,96(d, 1H, J=12.0 Hz); 6,60(d, 1H, J= 12.0 Hz); 7,20 to 7.62(m, 8H); to 7.68(d, 2H, J=8,4 Hz); 7,83(d, 2H, J=8,4 Hz).

() 4-[4-(4'-Methylbiphenyl-2-yl)(E)/(Z)-buta-1-ene-3-inyl]-benzoic acid

Similarly to the method of example 1(e) on the basis of 2.00 g (5.4 mmol) obtained in example 9(b) product and after heating for an hour and a half, get a yellow powder, identified as a mixture of (Z)- and (E)-isomers. This mixture is separated by chromatography on a column of silica, elwira gradient solvent, moving from pure heptane to a mixture of 50% heptane and 50% ethyl acetate. After evaporation of the solvents gain of 1.03 g(55%) 4-[4-(4'-methylbiphenyl-2-yl)-(E)-but-1-EN-3-inyl]benzoic acid with so pl. 225oC and 0.30 g(16%) 4-[4-(4'-methylbiphenyl-2 - yl)-(2)-buta-1-ene-3-inyl] benzoic acid with so pl. 177-179oC.

1H-NMR-spectrum (hexacyanometallate), M. D. [(E)-isomer]: of 2.38 (s, 3H
H-NMR-spectrum (hexacyanometallate), M. D. [(Z)-isomer]: of 2.34 (s, 3H); 6,11(d, 1H, J=12.0 Hz); 6,79(d, 1H, J=12.1 Hz); of 7.25(d, 2H, J= 7.9 Hz); 7,40-7,53 (m, 5H); to 7.64-to 7.95(m, 5H).

Example 10: 4-[4-(4'-Methylbiphenyl-2-yl)buta-1,3-dienyl]-benzoic acid

(a) 2-Bromanil-4'-methylbiphenyl

In a flask with a volume of 250 ml in a stream of nitrogen injected 1.45 g (7,39 mmol) obtained in example 8(b) compounds of 7.35 g (22,2 mmol) tetrabromide carbon and 50 ml of dichloromethane. The resulting solution was cooled to a temperature of 0oC, then add 17,44 g to 66.5 mmol) of triphenylphosphine and stirred for four hours at room temperature. Add silicon dioxide, is evaporated to dryness and the product purified by chromatography on a column of silica, elwira heptane. After evaporation of the solvents receive 750 mg (37%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: is 2.41 (s, 3H); 7.23 percent-to 7.32 (m, 3H); 7,35-7,42 (m, 2H); of 7.48(d, 2H, J=8.1 Hz); 7,56(d, 1H, J=7.5 Hz).

(b) Methyl ester of 4-[4-(4'-methylbiphenyl-2-yl)buta-1,3-dienyl] benzoic acid

In a three-neck flask with a volume of 50 ml in a stream of nitrogen injected 128 mg (of 1.84 mmol) hydroxylaminopurine, 45 mg (0.46 mmol) of the chloride of monovalent copper (CuCl), 1 ml (15 mmol) of ethylamine, 20 ml of methanol and 128 μl of water. Prov.mperature 45oC for one hour under vigorous stirring. After this was added dropwise a solution of 750 mg) obtained in example 10 (a) compounds in 10 ml of methanol. The reaction medium is stirred for 24 hours at a temperature of 30oC, cooled and quickly add 2n. hydrochloric acid to bring the pH to 1. The product is extracted with diethyl ether, the organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is treated with diethyl ether, add silica and evaporated to dryness. The product was then purified by chromatography on a column of silica, elwira heptane. After evaporation of the solvent to obtain 380 mg (47%) of target compound in the form of a powder beige with so pl. 100-102oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42 (s, 3H); to 3.92(s, 3H); 7,26-7,34(m, 2H); 7,39-7,47(m, 2H); 7,50-7,58(m, 5H); 7,66(d, 1H, J=7.4 Hz); 7,99(d, 2H, J=8.5 Hz).

() 4-[4-(4'-Methylbiphenyl-2-yl)buta-1,3-dienyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 340 mg (0.97 mmol) obtained in example 10(b) receive 300 mg(93%) 4-[4-(4' -methylbiphenyl-2-yl)buta-1,3-dienyl] -benzoic acid as white powder with so pl. 217-219o=7.4 Hz); of 8.00(d, 2H, J=8,4 Hz).

Example 11: 4-[4-(3-Fluoro-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

(a) Methyl ester of 2-fluoro-6-iodobenzoyl acid

In a flask with a volume of 100 ml and in a stream of nitrogen introduced to 5.00 g (18,8 mmol) 2-fluoro-6-iodobenzoyl acid and 30 ml of dimethylformamide. Cooled to a temperature of 0oC and add in small portions 62 mg (20,7 mmol) of 80% sodium hydride. The reaction medium is stirred for one hour at room temperature, then added dropwise to 1.76 ml (28,2 mmol) under the conditions. The reaction medium is stirred for one hour at room temperature, then add water and diethyl ether. The product is extracted with diethyl ether, the organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by chromatography on a column of silica, elwira with a mixture of 50% heptane and 50% dichloromethane. After evaporation of the solvents get to 5.08 g (97%) of target compound in the form of a colourless liquid.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,98 (s, 3H); 7,09-7,16(m, 2H); to 7.61-to 7.68(m, 1H).

(b) Methyl ester of 3-fluoro-4'-methylbiphenyl-2-carboxylic acid

Similarly to the method of example is islote, obtained in example 11(a), (629 mg (0.54 mmol) tetranitroaniline-(O) and 23.6 ml of aqueous 2M potassium carbonate solution, get to 4.14 g (93%) of target compound in the form of a white powder with so pl. 62-65oC.

1H-NMR-spectrum (deuterochloroform), M. D.: of 2.38 (s, 3H); 3,70(s, 3H); 7,05-7,28(m, 6H); 7,38-7,47(m, 1H).

(C) (3-Fluoro-4'-methylbiphenyl-2-yl)methanol

Similarly to the method of example 6(b), based on 3,34 g (13.7 mmol) obtained in example 11(b) fluorine-containing ether complex, get 2,95 g (100%) of target compound in the form of a white powder with so pl. 76-78oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 1,82 (dt, 1H, J=6,3/1.3 Hz); is 2.41(s, 3H); with 4.65 (DD, 2H, J=6,3/1,7 Hz);? 7.04 baby mortality for 7.12(m, 2H); 7.23 percent - 7,37(m, 5H).

(g) 3-Fluoro-4'-methylbiphenyl-2-carboxaldehyde

In the flask 500 ml mix of 2.16 g (10.9 mmol) obtained in example 11(C) fluorine-containing alcohol, 17,39 g of manganese oxide and 150 ml of dichloromethane. The reaction medium is stirred for 20 hours at room temperature, then filtered manganese oxide and dichloromethane is evaporated. The resulting residue is purified by chromatography on a column of silica, elwira with a mixture of 30% heptane and 70% dichloromethane. After evaporation of the solvents to obtain 1.47 g (69%) target 9(m, 5H); 7,52-to 7.61(m, 2H); 9,94(s, 1H).

(d) 2-((E)-2-Iodine)-3-fluoro-4'-methylbiphenyl

Similarly to the method of example 1(g), on the basis of 1.47 g (6.26 mmol) obtained in example 11(d) 3-fluoro-4'-methyl-biphenyl-2-carboxaldehyde, obtain 770 mg (36%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42 (s, 3H); to 6.95(d, 1H, J= 15.1 Hz); 7,01-7,17(m, 2H); 7,21-7,31(m, 7H).

(e) Methyl ester of 4-[4-(3-fluoro-4'-methylbiphenyl-2-yl)but-3-EN-(E)- 1-inyl]benzoic acid

Into the flask consistently give 770 mg (2.28 mmol) of 2-((E)-2-iodine)- 3-fluoro-4'-methylbiphenyl and 50 ml of piperidine. Was added dropwise a solution of 548 mg (3.4 mmol) of methyl ester 4-ethynylbenzene acid in 50 ml of piperidine. Add 132 mg (0.11 mmol) tetranitroaniline-(O) and the reaction medium is stirred for 16 hours at room temperature. The reaction medium is poured into water, extracted with ethyl acetate, the organic phase is decanted, dried over magnesium sulfate and evaporated. The resulting residue is purified by chromatography on a column of silica, elwira with a mixture of 90% heptane and 10% ethyl acetate. After evaporation of the solvents to obtain 490 mg (58%) of target compound in the form of a crystalline solid beige color with so pl. 92

(W) 4-[4-(3-Fluoro-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1(e) on the basis of 490 mg (1.3 mmol) obtained in example 11(e) complex methyl ester, receive 450 mg(95%) 4-[4-(3-fluoro-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid in the form of a crystalline solid beige color with so pl. 202oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,43 (s, 3H); of 6.52(d, 1H, J=16.6 Hz); 6,83(d, 1H, J=16.6 Hz); 7,05-7,13(m, 2H); 7,21-7,31(m, 5H); 7,46(d, 2H, J=8,3 Hz); 7,98(d, 2H, J=8,3 Hz).

Example 12: 4-[4-(4,4'-Dimethylbiphenyl-2-yl)but-3-EN-1-inyl]benzoic acid

(a) Methyl ester of 2-hydroxy-5-methylbenzoic acid

In flask 1 litre dissolve 20,60 g (135,4 mmol) 2-hydroxy-5-methylbenzoic acid in 670 ml of methanol. Was added dropwise to 6.7 ml of sulfuric acid and the reaction medium is refluxed for 48 hours. After cooling, the methanol is evaporated, then add ice and extracted with diethyl ether. The organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by chrom is g (93%) of target compound in the form of a colourless liquid.

1H-NMR-spectrum (deuterochloroform), M. D.: of 2.28 (s, 3H); 3,93(s, 3H); to 6.88(d, 1H, J=8.5 Hz); 7,26(DD, 1H, J=8,5/a 2.2 Hz); a 7.62(d, 1H, J=1.8 Hz).

(b) Methyl ester of 5-methyl-2-triftoratsetilatsetonom acid

In a flask of 500 ml in a stream of nitrogen injected 13,48 g (81,13 mmol) methyl ester of 2-hydroxy-5-methylbenzoic acid obtained in example 12 (a), are 22.42 g (162,3 mmol) of potassium carbonate and 135 ml of dimethylformamide. Cooled to a temperature of 0oC and added dropwise a solution of 22.0 g of 4-nitrodriverreadspool in 80 ml of dimethylformamide. The reaction medium is stirred for 2.5 hours at room temperature, then add water and diethyl ether. The product is extracted with diethyl ether, the organic phase is washed with water until neutral pH, dried over magnesium sulfate and filtered. After evaporation of the solvent receive 23,89 g (99%) target compound as a colorless liquid.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43 (s, 3H); of 3.96(s, 3H); 7.18 in(d, 1H, J=8,4 Hz); 7,41(DD, 1H, J=8,4/a 2.3 Hz); 7,89(d, 1H, J=2.1 Hz).

(C) Methyl ester of 4,4'-dimethylbiphenyl-2-carboxylic acid

In a three-neck flask enter 12,37 g (91,0 mmol) 4-methylphenylimino acid, 22,61 g (to 75.8 mmol) obtained in example 12(b) of the triflate, irout by ozonation of argon, add 2,63 g of 2.27 mmol) tetranitroaniline-(O) and heated at a temperature of 90oC for 5 hours. The reaction medium is poured into water, extracted with diethyl ether, the organic phase is decanted, dried over magnesium sulfate and evaporated. The resulting residue is purified by chromatography on a column of silica, elwira with a mixture of 20% dichloromethane and 80% heptane. After evaporation of the solvents get 18,26 g (96%) of target compound as a colourless oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,39(s, 3H); to 2.41(s, 3H); the 3.65(s, 3H); 7,19-7,34(m, 6H); to 7.61(s, 1H).

(g) (4,4'-Dimethylbiphenyl-2-yl) methanol

In a three-neck flask with a volume of 1 liter injected 160 ml of diethyl ether and of 2.81 g (74,1 mmol) sociallyengaged. The reaction medium is cooled to a temperature of 0oC, and then was added dropwise a solution of 17,81 g (74,1 mmol) obtained in example 12 (b) of ester in 160 ml of diethyl ether. The reaction medium is stirred for two hours at a temperature of 0oC add 1.40 g of sociallyengaged and stirred for two hours at room temperature. The medium is cooled to a temperature of 0oC, and then was added dropwise a saturated solution of sodium chloride, filtered through celite, tobeytailor pH, dried over magnesium sulfate, filtered and the solvent is evaporated. Get 15,48 g (98%) target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 1,59(t, 1H, J=5,9 Hz); 2,39 (s, 3H); 2.40 a (s, 3H); 4,59(d, 2H, J=5.8 Hz); 7,13-7,27(m, 6H); to 7.35(s, 1H).

(d) 4,4'-Dimethylbiphenyl-2-carboxaldehyde

Similarly to the method of example 11(d), on the basis of 14,80 g (69,7 mmol) obtained in example 12 (g) of alcohol, get 14,27 g (97%) of target compound in the form of a white powder with so pl. 61-67oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43 (s, 3H); of 2.45(s, 3H); 7.18 in-7,26(m, 4H); 7,33(d, 1H, J=7.8 Hz); 7,44(DD, 1H, J=7,9/1,6 Hz); 7,82(c, 1H); becomes 9.97(c, 1H).

(e) 2-((E)-2-Iodine)-4,4'-dimethylbiphenyl

Similarly to the method of example 1(g), on the basis of the data obtained in example 12(d) 4,4'-dimethylbiphenyl-2-carboxaldehyde get 4,47 g (93%) of target compound as an orange oil.

1H-NMR-spectrum (deuterochloroform), M. D.: is 2.40(s, 3H); 2,43(s, 3H); 6,72(d, 1H, J=14,7 Hz); 7.18 in-7,32(m, 8H).

(g) Methyl ester of 4-[4-(4,4'-dimethylbiphenyl-2-yl)but-3-EN- (E)-1-inyl] benzoic acid

Similarly to the method of example 1 (d), by the interaction of 4.00 g (12,0 mmol) obtained in example 12 (e) 2-((E)-2-iodine)- 4,4'-dimethylbiphenyl with 1,74 g (10.9 mmol) of methyl ester 4-Atin/P>1H-NMR-spectrum (deuterochloroform), M. D.: is 2.41(s, 3H); to 2.42(s, 3H); 3,91(s, 3H); 6,34(d, 1H, J=16.2 Hz); to 7.09(d, 1H, J=16.2 Hz); 7,13 - 7,26(m, 6H); 7,45(s, 1H); 7,47(d, 2H, J=8,3 Hz); of 7.97 (d, 2H, J=8,4 Hz).

(C) 4-[4-(4,4'-Dimethylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]- benzoic acid

Similarly to the method of example 1(e) on the basis of 360 g (1.0 mmol) obtained in example 12 (g) of complex methyl ester, 240 mg get(74%) 4-[4-(4,4'-dimethylbiphenyl-2-yl)-but-3-EN-(E)-1-inyl] benzoic acid in the form of powder light yellow color with so pl. 217oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: of 2.25(s, 6H); 6,50(d, 1H, J=16.2 Hz); 6,83(d, 1H, J=16,3 Hz); 7,05-to 7.18 (m, 6H); 7,42(d, 2H, J=8,3 Hz); at 7.55 (s, 1H); 7,79(d, 2H, J=8,32 Hz).

Example 13: 4-[4-(5,4'-Dimethylbiphenyl-2-yl)but-3-EN-1-inyl] benzoic acid

(a) Methyl ester of 2-hydroxy-4-methylbenzoic acid

Similarly to the method of example 12 (a), on the basis of 30,43 g (200.0 mmol) of 2-hydroxy-4-methylbenzoic acid, get, after boiling under reflux for 72 hours, 29,49 g (89%) of target compound in the form of a colourless liquid, which slowly crystallizes. So pl. 20-25oC.

1H-NMR-spectrum (deuterochloroform), M. D.: of 2.34 (s, 3H); to 3.92(s, 3H); 6,69(d, 1H, J=8,2 Hz); 6,79(s, 1H); of 7.70(d, 1H, J=8,1 Hz).

(b) Methyl ester of 4-methyl-2-Trifonova in example 13 (a) methyl ester of 2-hydroxy-4-methylbenzoic acid, get 13,0 g (73%) of target compound in the form of a colourless liquid.

1H-NMR-spectrum (deuterochloroform), M. D.: a 2.45(s, 3H); of 3.95 (s, 3H); to 7.09 (s, 1H); 7,27(DD, 1H, J=7,9/2,9 Hz); 7,98(d, 1H, J=8.0 Hz).

(C) Methyl ether 5,4'-dimethylbiphenyl-2-carboxylic acid

Similarly to the method of example 12 (b), on the basis of 7,11 g (52,3 mmol) 4-methylphenylimino acid and 13.0 g (43,6 mmol) obtained in example 13(b) of the triflate, get 10,15 g (97%) of target compound in the form of white crystals with so square 86-88oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,39 (s, 3H); 2.40 a(s, 3H); the 3.65(s, 3H); 7,16-7,24(m, 6H); 7,74(d, 1H, J=7,7 Hz).

(g) (5,4'-Dimethylbiphenyl-2-yl)methanol

Similarly to the method of example 12 (d), based on 10,08 g (42.0 mmol) obtained in example 13(g) of ester, get 8,21 g (92%) of target compound in the form of white crystals with so pl. 71-73oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 1,66(t, 1H, J=5,9 Hz); is 2.37 (s, 3H); 2,39 (s, 3H); 4,56(d, 2H, J=5,9 Hz); to 7.09(s, 1H); 7,15-7,27(m, 5H); 7,39(d, 1H, J=7,8 Hz).

(d) 5,4'-Dimethylbiphenyl-2-carboxaldehyde

Similarly to the method of example 11(d), based on 8,17 g (a 38.5 mmol) obtained in example 13(g) alcohol, get a 7.62 g (94%) of target compound as a pale yellow oil.

1H-NMR spectra the Nile)-5,4'-dimethylbiphenyl

Similarly to the method of example 1(g), on the basis of 3.00 g (of 14.3 mmol) obtained in example 13(d) 5,4'-dimethyl-biphenyl-2-carboxaldehyde receive of 3.69 g (77%) of target compound as an orange oil, which was directly used in the next stage.

(g) Methyl ester of 4-[4-(5,4'-dimethylbiphenyl-2-yl)but-3-EN- (E)-1-inyl] benzoic acid

Similarly to the method of example 1 (d), by the interaction of 3.69 g (11.0 mmol) obtained in example 13(e) 2-((E)-2-iodine)-5,4'- dimethylbiphenyl with 1,60 g (10.0 mmol) of methyl ester of 4 - ethynylbenzene acid, receive and 1.00 g (27%) of target compound in the form of a white powder with so pl. 123-125oC.

1H-NMR-spectrum (deuterochloroform), M. D.: is 2.40(s, 3H); of 2.44(s, 3H); to 3.92(s, 3H); 6.30-in(d, 1H, J 16.2 Hz); 7,10(d, 1H, J=16,3 Hz); 7,13 - 7,26(m, 6H); 7,47 (d, 2H, J=8.5 Hz); to 7.61(m, 1H); of 7.97 (d, 2H, J=8,4 Hz).

(C) 4-[4-(5,4'-Dimethylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e), based on a 1.00 g (2.7 mmol) obtained in example 13 (f) complex methyl ester, obtain 920 mg(97%) 4-[4-(5,4'-dimethylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid in the form of a yellow powder with so pl. 269-271oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: 2,14 (s, 3H); 2,17 (s, 3H); 6,37(d, 1H, J=16.2 Hz); 6.73 x(d, 1H, J=16,3 Hz); 6,-(6,4'-Dimethylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

(a) Methyl ester of 2-hydroxy-3-methylbenzoic acid

Similarly to the method of example 12 (a), on the basis of 30,43 g (200.0 mmol) of 2-hydroxy-3-methylbenzoic acid, get, after boiling under reflux for 6 days, 27,71 g (83%) of target compound in the form of a colourless liquid.

1H-NMR-spectrum (deuterochloroform), M. D.: of 2.34 (s, 3H); to 3.92(s, 3H); 6,69(DD, 1H, J= 8,2/1,1 Hz); 6,79(s, 1H); of 7.70(d, 1H, J=8,1 Hz); 10,70(s, 1H).

(b) Methyl ester of 3-methyl-2-triftoratsetilatsetonom acid

Similarly to the method of example 12(b), according to 13.29 g a (80.0 mmol) obtained in example 14 (a) methyl ester of 2-hydroxy-3-methylbenzoic acid, receive of 11.69 g (49%) of target compound in the form of a colourless liquid.

1H-NMR-spectrum (deuterochloroform), M. L.: 2,43 (s, 3H); of 3.94(s, 3H); 7,34(t, 1H, J= 7,7 Hz); of 7.48(DD, 1H, J=7,7/1.2 Hz); 7,81(DD, 1H, J=7,7/1,8 Hz).

(C) Methyl ether 6,4'-dimethylbiphenyl-2-carboxylic acid

Similarly to the method of example 12 (C), according to 6.39 g (47,0 mmol) 4-methylphenylimino acid and of 11.69 g (39,2 mmol) obtained in example 14(b) of the triflate, get at 8.60 g (91%) of target compound as a colourless oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,10(s, 3H); 2.40 a(s, 3H); of 3.57 (s, 3H);? 7.04 baby mortality(d, 2H, J=7.8 Hz); then 7.20(d, 2H, J=7.8 for the logical method of example 12 (d), on the basis of at 8.60 g (35.8 mmol) obtained in example 14(C) of ester, get to 7.59 g (100%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 1,47(ush.s, 1H); 2,04 (s, 3H); to 2.41 (s, 3H); 4,37(d, 2H, J=3.8 Hz); 7,06(d, 2H, J=7.9 Hz); 7, 19-7, 36 (m, 7H).

(d) 6,4'-Dimethylbiphenyl-2-carboxaldehyde

Similarly to the method of example 11 (d), according to 7.59 g (35,75 mmol) obtained in example 14(g) alcohol, get to 7.09 g (94%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,14 (s, 3H); 2,52 (s, 3H); for 7.12 (d, 2H, J= 8.0 Hz); 7,26 (d, 2H, J=7.8 Hz); 7,37 (t, 1H, J=7,6 Hz); of 7.48(DD, 1H, J-7,4/0.5 Hz); to 7.84 (d, 1H, J=7,7 Hz); 9,71 (s, 1H).

(e) 2-((E)-2-Iodine)sphere-6,4'-dimethylbiphenyl

Similarly to the method of example 1(g), on the basis of 3.00 g (of 14.3 mmol) obtained in example 14(d) 6,4'-dimethylbiphenyl-2-carboxaldehyde, get a 3.06 g (64%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,11 (s, 3H); 2,39 (s, 3H); 6,60(d, 1H, J= 14,8 Hz); 6,99-7,05 (m, 3H); 7.24 to 7,35(m, 4H); 7,52-to 7.59(m, 1H).

(g) Methyl ester of 4-[4-(6,4'-dimethylbiphenyl-2-yl)but-3-EN-(E) -1-inyl] benzoic acid

Similarly to the method of example 1 (d), by the interaction of 3.06 g (9.2 mmol) obtained in example 14(e) 2-((E)-2-iodine)sphere-6,4'-dimethylbiphenyl from 2.20 s yellow with so pl. 67oC.

1H-NMR-spectrum (deuterochloroform), M. D.: of 2.06 (s, 3H); of 2.44 (s, 3H); to 3.92(s, 3H); of 6.25(d, 1H, J=16.2 Hz); 6,79(d, 1H, J=16,3 Hz); 7,05 (d, 2H, J= 8.0 Hz); 7.23 percent-7,26 (m, 4H); 7, 44 (d, 2H, J=8,3 Hz); 7,51-EUR 7.57 (m, 1H); 7, 95 (d, 2H, J=8,4 Hz).

(C) 4-[4-(6,4'-Dimethylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 700 mg (1.9 mmol) obtained in example 14 (g) complex methyl ester, obtain 580 mg(86%) 4-[4-(6,4'-dimethylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid in the form of yellow crystals with so pl. 238oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: of 2.06(s, 3H); of 2.44(s, 3H); of 6.25(d, 1H, J=16.2 Hz); 6,79(d, 1H, J= 16,3 Hz); 7,05(d, 2H, J=7.9 Hz); 7.24 to 7,28(m, 4H); was 7.45(d, 2H, J and 8.3 Hz); 7,49-7,52(m, 1H); to 7.99(d, 2H, J=8,3 Hz).

Example 15: 4-[4-(4-Hydroxy-4'-methylbiphenyl-2-yl)but-3-EN- (E)-1-inyl] benzoic acid

(a) 2-Hydroxy-5-methoxysalicylaldehyde

In a three-neck flask enter 15,00 g (108,6 mmol) of 2,5-dihydroxybenzaldehyde and 180 ml of dichloromethane. The resulting solution was cooled to a temperature of 0oC, was added dropwise to 20.8 ml diisopropylethylamine and stirred at 0oC for 15 minutes. Then added dropwise at 9.0 ml (119.0 mmol) METHYLCHLOROSILANE simple ether and the reaction medium is stirred enjoyed ether, extracted with diethyl ether, the organic phase is decanted, dried over magnesium sulfate and evaporated. The resulting residue is purified by chromatography on a column of silica, elwira with a mixture of 10% diethyl ether and 90% heptane. After evaporation of the solvents to obtain 4.42 g (22%) of target compound in a solid white color with so pl. 36-41oC.

1H-NMR-spectrum (deuterochloroform), M. D.: a 3.50(s, 3H); further 5.15(s, 2H); 6,91-to 6.95(m, 1H); 7,22-7,27(m, 2H); 9,85(d, 1H, J-0.35 Hz); of 10.72 (s, 1H).

(b) 2-Formyl-4-ethoxymethylenemalonic

Similarly to the method of example 12(b), based on 3,70 g (20.3 mmol) obtained in example 15 (a) 2-hydroxy-5 - methoxysalicylaldehyde, obtain 2.65 g (41%) of target compound in the form of a colourless liquid, which is directly used in the next stage.

(in) 4 Methoxyethoxy-4'-methylbiphenyl-2-carboxaldehyde

Similarly to the method of example 12 (C), according to 1.37 g (10.1 mmol) of 4-methylphenylimino acid and 2.65 g (8.4 mmol) obtained in example 15(b) of the triflate, obtain 1.92 g (89%) of target compound in the form of a powder beige with so pl. 58-63oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42 (s, 3H); 3,51(s, 3H); of 5.26(s, 2H); 7,21-7,25(m, 4H); 7,30(DD, 1H, J=8,5/a 2.6 Hz); 7,38(d, 1 is the method of example 1(g), on the basis of 1.92 g (7.5 mmol) obtained in example 15(b) 4-methoxyethoxy-4'-methylbiphenyl-2 - carboxaldehyde receive a 2.00 g (70%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: is 2.41(s, 3H); 3,51(s, 3H); 5,22(s, 2H); 6.75 in(d, 1H, J=14,8 Hz); 6,98-7,29(m, 7H); to 7.35(d, 1H, J is 14.8 Hz).

(d) Methyl ester of 4-[4-(4-Methoxyethoxy-4'-methylbiphenyl-2-yl) but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1 (d), by reacting a 2.00 g (5.3 mmol) obtained in example 15(g), 2-((E)-2-iodine)-4 - methoxyethoxy-4'-methylbiphenyl with 766 mg (4.8 mmol) of methyl ester 4-ethynylbenzene acid, obtain 880 mg (44%) of target compound in the form of powder light yellow color with so pl. 89-91oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42 (s, 3H); of 3.53(s, 3H); 3,91(s, 3H); of 5.24(s, 2H); 6,34(d, 1H, J=16.2 Hz); 7,05-to 7.09(m, 1H); 7,07(d, 1H, J= 16.1 Hz); 7,19-7,27(m, 5H); to 7.32(d, 1H, J=2.4 Hz); 7,47(d, 2H, J=8,4 Hz); of 7.97(d, 2H, J=8,4 Hz).

(e) 4-[4-(4-Methoxyethoxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1 - inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 170 mg (0.41 mmol) obtained in example 15(d) complex methyl ester, 110 mg get(69%) 4-[4-(4- methoxyethoxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid in the form of a yellow powder with so .d: to 2.42 (s, 3H); 3.43 points (s, 3H); further 5.15 (s, 2H); 6,27(d, 1H, J= 16.2 Hz); to 6.95(d, 1H, J=16.2 Hz); 6,97(DD, 1H, J=8,7/2,4 Hz); 7,10-7,19(m, 5H); 7,22(d, 1H, J=2.4 Hz); 7,37(d, 2H, J=8,3 Hz); 7,88(d, 2H, J=8,3 Hz).

Example 16: 4-[4-(5-Hydroxy-4'-methylbiphenyl-2-yl)but-3-EN- (E)-1-inyl] benzoic acid

(a) 2-Hydroxy-4-methoxysalicylaldehyde

Similarly to the method of example 15(a), on the basis of 20,00 g (144,8 mmol) of 2,4-dihydroxybenzaldehyde get 21,05 g (80%) of target compound in a solid white color with so pl. 58-64oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,49(s, 3H); 5,23(s, 2H); 6,60 of 6.68(m, 2H); 7,46(d, 1H, J=8.6 Hz); 9,74(s, 1H); 11,38(s, 1H).

(b) 2-Formyl-5-ethoxymethylenemalonic

Analogously to example 12(b), according to 6.67 g (36.6 mmol) obtained in example 16(a) 2-hydroxy-4-methoxy-methoxybenzaldehyde get 8,03 g (70%) of target compound in the form of a colourless liquid.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,51(s, 3H); at 5.27(s, 2H); 7,05(d, 1H, J= 2.2 Hz); 7.18 in(DD, 1H, J=8,8/2,1 Hz); 7,94(d, 1H, J=8.7 Hz); 10,14 (s, 1H).

(C) 5-Methoxyethoxy-4'-methylbiphenyl-2-carboxaldehyde

Analogously to example 12 (b), according to 4.17 g (30.7 mmol) of 4-methylphenylimino acid and 8,03 g (25.6 mmol) obtained in example 16(b) of the triflate, get to 6.19 g (95%) of target compound as colorless m is,7/2,4 Hz); 7,26-7,28 (m, 4H); 8,01(d, 1H, J=8.7 Hz); 9,86(d, 1H, J=0.5 Hz).

(g) 2-((E)-2-Iodine)-5-methoxyethoxy-4'-methylbiphenyl

Analogously to example 1(g), on the basis of 6.20 g (or 24.2 mmol) obtained in example 16 (C) 5-methoxyethoxy-4'-methylbiphenyl-2 - carboxaldehyde, get the ceiling of 5.60 g (60%) of target compound in the form of a red oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 2.34 (s, 3H); to 3.41(s, 3H); 5,12(s, 2H); 6,51(d, 1H, J=14,8 Hz); 6.87 in-7,01(m, 2H); 7,12-to 7.18(m, 5H); of 7.23(d, 1H, J=14,9 Hz).

(d) Methyl ester of 4-[4-(5-methoxyethoxy-4'-methylbiphenyl-2-yl) but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1 (d), by reacting the ceiling of 5.60 g (14.7 mmol) obtained in example 16(g), 2-((E)-2-iodine)-5 - methoxyethoxy-4'-methylbiphenyl with 2.14 g (a 13.4 mmol) of methyl ester 4-ethynylbenzene acid, gain of 2.51 g (45%) of target compound in the form of a powder beige with so pl. 96-98oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43(s, 3H); to 3.49(s, 3H); 3,91(s, 3H); 5,22(s, 2H); 6,24(d, 1H, J=16.2 Hz); 6,98-7,07 (m, 3H); 7,26(s, 4H); 7,46(d, 2H, J=8,4 Hz); of 7.60 (d, 1H, J=8.6 Hz); of 7.96 (d, 2H, J=8,5 Hz).

(e) 4-[4-(5-Methoxyethoxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1 - inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 500 mg (1.2 mmol) obtained in example 16 (d) complex methyl ester, the floor is with so pl. 235oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: of 2.38(s, 3H); 3.40 in(s, 3H); at 5.27(s, 2H); of 6.52(d, 1H, J=16.2 Hz); 6.90 to(d, 1H, J=16.1 Hz); 6,92(d, 1H, J= 2.6 Hz); 7,07(DD, 1H, J=8,7/2,4 Hz); 7.23 percent(d, 2H, J=8.0 Hz); 7,31(d, 2H, J=8.0 Hz); 7,53(d, 2H, J and 8.3 Hz); 7,80(d, 1H, J=8,8 Hz); to $ 7.91(d, 2H, J=8,3 Hz); 13,13(ush.s, 1H).

Example 17: 4-[4-(6-Hydroxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

(a) 2 Formyl-6-methoxybenzenesulfonyl

Similarly to the method of example 12(b), on the basis of 1.40 g (9.2 mmol) of 2-hydroxy-3-methoxybenzaldehyde, obtain 1.70 g (65%) of target compound as an orange oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 3.97 (s, 3H); to 7.32(DD, 1H, J=7,8/1,7 Hz); 7,44-of 7.55(m, 2H); of 10.25(s, 1H).

(b) 6-Methoxy-4'-methylbiphenyl-2-carboxaldehyde

Similarly to the method of example 12 (C), based on 6,34 g (to 46.7 mmol) 4-methylphenylimino acid 11.00 g (of 38.7 mmol) obtained in example 17(a) of the triflate, gain of 7.75 g (88%) of target compound in the form of white crystals with so pl. 63-65oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42(s, 3H); 3,79(s, 3H); 7,16-of 7.23(m, 1H); 7,21(d, 2H, J=8.0 Hz); 7,27(d, 2H, J=8.1 Hz); the 7.43 (t, 1H, J=7.9 Hz); to 7.61(DD, 1H, J=7,9/1,1 Hz); 9,74(s, 1H).

(b) 6-Hydroxy-4-methylbiphenyl-2-carboxaldehyde

Into the flask is injected 950 mg (4.2 mmol) obtained the amide. The reaction medium is heated at 150oC for two hours, poured into a mixture of 1H. hydrochloric acid in diethyl ether and extracted with diethyl ether. The organic phase is decanted, dried over magnesium sulfate and evaporated. The resulting residue is purified by powdering in a mixture of 10% diethyl ether and 90% heptane. After drying in a vacuum drying Cabinet get 550 mg (61%) of target compound in the form of a powder orange with so pl. 170-171oC.

1H-NMR-spectrum (deuterochloroform), M. D.: a 2.45 (s, 3H); 5,14(ush.s, 1H); 7,22-7,27 (m, 3H); 7,35-the 7.43(m, 3H); of 7.60(DD, 1H, J=7,7/1.2 Hz); 9,74(s, 1H).

(g) 6 Methoxyethoxy-4'-methylbiphenyl-2-carboxaldehyde

Similarly to the method of example 15 (a), on the basis of 4.35 g of 20.5 mmol) obtained in example 17 (b) 6-hydroxy-4'-methylbiphenyl-2 - carboxaldehyde, receive or 4.31 g (82%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43 (s, 3H); at 3.35(s, 3H); 5,09(s, 2H); 7,22(d, 2H, J=8,3 Hz); 7,27(d, 2H, J=8,2 Hz); 7,38 was 7.45(m, 2H); to 7.64-7,71(m, 1H); 9,74(s, 1H).

(d) 2-((E)-2-Iodine)-6-methoxyethoxy-4'-methylbiphenyl

Similarly to the method of example 1(g), based on 4,30 g (16,8 mmol) obtained in example 17 (d) 6 methoxyethoxy-4'- methylbiphenyl-2-carboxaldehyde get 3,74 g (58%) Celes, 3H); 5,03(c, 2H); to 6.67(d, 1H, J=14,8 Hz); 7,09-7,41(m, 8H)

(e) Methyl ester of 4-[4-(6-methoxyethoxy-4'-methylbiphenyl-2-yl) but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1 (d), by reacting 3,74 g (9.8 mmol) obtained in example 17 (d) 2-((E)-iodine)-6 - methoxyethoxy-4'-methylbiphenyl with 1.89 g (to 11.8 mmol) of methyl ester 4-ethynylbenzene acid, receive 900 mg (22%) of target compound in the form of powder light orange color with so pl. 98 - 100oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43(c, 3H); of 3.32(s, 3H); 3,91(s, 3H); 5,04(s, 2H); 6,28(d, 1H, J=16.2 Hz); 6,83 (d, 1H, J=16.2 Hz); to 7.15 (d, 2H, J= 8.0 Hz); 7,16 (d, 1H, J=8,3 Hz); 7,27 (d, 2H, J=8,3 Hz); to 7.32 and 7.36 (m, 2H); was 7.45(d, 2H, J=8,3 Hz); of 7.96(d, 2H, J=8,2 Hz).

(W) 4-[4-(6-Methoxyethoxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)- 1-inyl] benzoic acid

Similarly to the method of example 1(e), starting from 200 mg (0.48 mmol) obtained in example 17 (e) complex methyl ester, get 165 mg(87%) 4-[4-(6-methoxyethoxy-4'-methylbiphenyl-2-yl)but - 3-EN-(E)-1-inyl] benzoic acid as white powder with so pl. 185-187oC.

1H - NMR-spectrum (hexacyanometallate), M. D.: of 2.38(s, 3H); 3,20(s, 3H); 5,07(s, 2H); to 6.58(d, 1H, J=16,3 Hz); of 6.68 (d, 1H, J of 16.3 Hz); 7,10 (d, 1H, J= 7.9 Hz); 7.18 in (d, 1H, J=8,1 Hz); 7,28(d, 2H, J=7.9 Hz); to 7.35(t, 1H, J-8.0 Hz); 7,52(d, 1H, J=8.0 Hz); 7,53(d, 2H, J=8,3 Hz); of 7.90 a) 1-(4'-Methylbiphenyl-2-yl)alanon

Similarly to the method of example 2(b), on the basis of 15,00 g (75,0 mmol) of 2-bromoacetophenone and 13.3 g (98,0 mmol) obtained in example 2 (a) 4-methylphenylimino acid, receive 15,10 g of target compound as a yellow oil.

H-NMR-spectrum (deuterochloroform), M. D.: 2,02(s, 3H); to 2.41(s, 3H); from 7.24(s, 4H); 7,37-7,56(m, 4H).

(b) 3-(4'-Methylbiphenyl-2-yl)but-2-EN-(E)-nitrile

Similarly to the method of example 6 (a), based on 13,00 g (61,8 mmol) obtained in example 18(a) ketone, 16,40 g (93,0 mmol) citizen.metropolitan and 3.15 g (105,0 mmol) of 80% sodium hydride and 160 ml of tetrahydrofuran, get 14,40 g (100%) of target compound in the raw state in the form of a brown oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 1.97(d, 3H, J=1.0 Hz); 2.40 a (s, 3H); to 5.35(d, 1H, J=1.1 Hz); 7,16-7,46 (m, 8H).

(b) 3-(4'-Methylbiphenyl-2-yl)but-2-EN-(E)-al

Similarly to the method of example 6(b), on the basis of 14.4 g (of 61.7 mmol) obtained in example 18(b) nitrile, get 16,00 g (75% of net connection) of the target product in the raw state in the form of a yellow oil containing about 25% of the original product.

1H-NMR-spectrum (deuterochloroform), M. D. : 2,04(d, 3H, J=1.2 Hz); 2,39(s, 3H); 6,16(DD, 1H, J=8,1/1.3 Hz); 7,17 was 7.45(m, 8H); 10,01(d, 1H, J= 8,1 Hz).

(g) 2-(4,4-Dibromo-1-methylbuta-1-(E)-3-dianilide, 48,80 g (of 186.0 mmol) of triphenylphosphine, 30,87 g (br93.1 mmol) tetrabromide carbon and 300 ml of dichloromethane, get 16,70 g (91%) of target compound as a yellow oil, which slowly crystallizes.

1H-NMR-spectrum (deuterochloroform), M. D. : of 1.62(d, 3H, J=1.3 Hz); 2,39(s, 3H); 6,18(DD, 1H, J=10,7/1,4 Hz); 6.75 in(d, 1H, J=13,7 Hz); 7,12-7,37(m, 8H).

(d) 4'-Methyl-2-(1-methylbut-1-EN-(E)-3-inyl)biphenyl -

Similarly to the method of example 8(b), on the basis of 5,00 g (12.7 mmol) obtained in example 18 (d) dibromononane connection and 10.7 ml of 2.5 n solution of n-utility in hexane, to obtain 3.25 g (100%) of target compound as an orange oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 1.80(s, 3H); 2,39(s, 3H); 3,18 (d, 1H, J=2.3 Hz); 5,56-to 5.57 (m, 1H); 7,10-7,38(m, 8H).

(e) Methyl ester of 4-[4-(4'-methylbiphenyl-2-yl)Penta-3-EN- (E)-1-inyl] benzoic acid

Into the flask is injected sequentially 3.00 g (13,0 mmol) obtained in example 18(e) connection, 3,40 g (13,0 mmol) of methyl ester 4-iodobenzoyl acid and 40 ml of triethylamine. Reaction medium Tegaserod by passing nitrogen for 20 minutes, then add 250 mg of iodide monovalent copper and 360 mg of bis(triphenylphosphine) palladium-11-chloride. Stirred at room temperature for three hours, the reaction medium howled niroot, dried over magnesium sulfate and evaporated. The resulting residue is purified by chromatography on a column of silica, elwira with a mixture of 90% ethyl acetate and 10% heptane. After evaporation of the solvents get 2,43 g (50%) of target compound as an orange oil.

1H-NMR-spectrum (deuterochloroform), M. D.: a 1.88(d, 3H, J=1.0 Hz); of 2.38 (s, 3H); to 3.92 (s, 3H); of 5.82(d, 1H, J=1.1 Hz); 7,14-7,40(m, 8H); 7,49(d, 2H, J=8,4 Hz); 7,99(d, 2H, J=8,4 Hz).

(W) 4-[4-(4'-Methylbiphenyl-2-yl)Penta-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e), based on 2,40 g (6.5 mmol) obtained in example 18(e) connection receive 1.20 g(52%) 4-[4-(4'-methylbiphenyl-2-yl)Penta-3-EN-(E)-1-inyl] benzoic acid in the form of a powder beige with so pl. 261-265oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: a 1.88(s, 3H); of 2.34(s, 3H); of 5.82(d, 1H, J=1.0 Hz); 7,25-the 7.43(m, 8H); 7,56(d, 2H, J=8,3 Hz); to 7.93(d, 2H, J=8,3 Hz).

Example 19: 4-[3-(4'-Methylbiphenyl-2-yl)propylamino]benzoic acid

(a) Allyl ester 4-[3-(4'-methylbiphenyl-2-yl)propylamino] benzoic acid

Similarly to the method of example 8 (e), based on 3,30 g (14.0 mmol) obtained in example 8 (g) connection and 1.98 g (11.0 mmol) allyl ether of 4-aminobenzoic acid, receive 900 mg (20%) of target compound in VI,2 Hz); of 5.39(DD, 1H, J=17,2/1.5 Hz); 5,95-6,10(m, 1H); 7,25-7,33(m, 3H); 7,39 to 7.62(m, 6H); 7,73(s, 1H); 8,00(d, 2H, J=8.6 Hz).

(b) 4-[3-(4'-Methylbiphenyl-2-yl)propylamino]benzoic acid

Similarly to the method of example 3(g), starting from 500 mg (1.3 mmol) obtained in example 19(a) compound 350 mg get(77%) 4-[3-(4'-methylbiphenyl-2-yl)propylamino] benzoic acid in the form of a powder beige with so pl. 184-188oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: is 2.37(s, 3H); 7,30(d, 2H, J=7.9 Hz); 7,45-to 7.64(m, 5H); 7,71-7,79(m, 3H); a 7.92(d, 2H, J=8.6 Hz); 11,06 (s, 1H); 12,83(ush. s, 1H).

Example 20: 4-[3-(4'-Methylbiphenyl-2-yl)propertyelement]benzoic acid

(a) Allyl ester 4-[3-(4'-methylbiphenyl-2-yl)propertyelement] benzoic acid

Similarly to the method of example 4 (a), on the basis of 310 mg (0.8 mmol) obtained in example 19(a) connection receive 160 mg (50%) of target compound in the form of a red oil.

1H-NMR-spectrum (deuterochloroform), M. D.: is 2.40(s, 3H); 4,82(d, 2H, J= 5.6 Hz); from 5.29(d, 1H, J=10.4 Hz); 5,42(DD, 1H, J=17,2/1.5 Hz); 5,99-6,10(m, 1H); 6,60(s, 1H); for 7.12(d, 2H, J=8.5 Hz); 7,19-7,26(m, 4H); 7,42-7,44(m, 2H); 7,49 - EUR 7.57(m, 2H); 8,08(d, 2H, J=8.5 Hz).

(b) 4-[3-(4'- Methylbiphenyl-2-yl)propertyelement]benzoic acid

Similarly to the method of example 1(e) on the basis of 100 mg (0.24 mmol) obtained in example 20(a) toedialog color with so pl. 170oC (decomposition).

1H - NMR-spectrum (hexacyanometallate), M. D.: a 2.36(s, 3H); 7,14(s, 1H); 7,28(ush.s, 6H); 7,46-to 7.68(m, 4H); 8,00(d, 2H, J=8,2 Hz).

Example 21: 4-[4-(3'-Methylbiphenyl-2-yl)but-3-EN-1-inyl]benzoic acid

(a) 3'-Methylbiphenyl-2-carboxaldehyde

In a three-neck flask enter of 3.85 g (28,0 mmol) 3-methylbenzeneboronic acid, 3.50 g (of 18.9 mmol) of 2-bromobenzaldehyde, to 18.9 ml (37.8 mmol) of a 2M aqueous solution of potassium carbonate and 75 ml of dimethoxyethane. The mixture Tegaserod at room temperature by ozonation of argon for one hour, then add 1,09 g (0.95 mmol) tetranitroaniline-(O) and refluxed for two hours and forty minutes. Cool, the reaction medium is poured into water, extracted with ethyl acetate, the organic phase is decanted, dried over magnesium sulfate and evaporated. The resulting residue is purified by chromatography on a column of silica, elwira mixture of 5% ethyl acetate and 95% heptane. After evaporation of the solvents get 3,70 g (100%) of target compound in the form of oil is pale yellow in color.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43 (s, 3H); 7,17-7,20(m, 1H); 7.24 to 7,27(m, 1H); to 7.35(d, 1H, J=7,7 Hz); 7,39-to 7.67 (m, 3H); a 7.62(DD, 1H, J=7,4/1.5 Hz); 8,02(DD, 1H, J=7,6/1,4 Hz); 9,99 ol) obtained in example 21(a) 3'-methylbiphenyl-2-carboxaldehyde, get 2,10 g (89%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 2.34 (s, 3H); of 6.65(d, 1H, J= 14,8 Hz); 6,91-7,38 (m, 9H).

(C) Methyl ester of 4-[4-(3'-methylbiphenyl-2-yl)but-3-EN-(E)- 1-inyl]benzoic acid

Similarly to the method of example 1 (d), by the interaction of 2.10 g (6,55 mmol) of 2-(2-iodine)-3'-methylbiphenyl obtained in example 21(b) of 1.05 g (6,55 mmol) of methyl ester 4-ethynylbenzene acid, obtain 520 mg (22%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43(s, 3H); 3,91(s, 3H); 6,35(d, 1H, J=16.2 Hz); to 7.09(d, 1H, J=16,3 Hz); 7,17-7,38 (m, 7H); 7,47 (d, 2H, J=8,4 Hz); of 7.64-to 7.68 (m, 1H); of 7.97 (d, 2H, J=8,4 Hz).

(g) 4-[4-(3'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 520 mg (about 1.47 mmol) obtained in example 21(b) complex methyl ester, obtain 370 mg(74%) 4-[4-(3'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid in the form of a powder beige with so pl. 211oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,43(s, 3H); 6,36(d, 1H, J=16.2 Hz); 7,07(d, 1H, J=16,3 Hz); 7,12-of 7.23(m, 3H); 7.29 trend-of 7.48(m, 4H); 7,46(d, 2H, J=8,3 Hz); 7,65-of 7.69(m, 1H); 7,98(d, 2H, J=8,3 Hz).

Example 22: 4-[4-(2'-Methylbiphenyl-2-yl)but-3-EN-(Ejada from 3,86 g (28.4 mmol) of 2-methylbenzeneboronic acid and 3.50 g (of 18.9 mmol) of 2-bromobenzaldehyde, get 2.50 g (67%) of target compound in the form of a slightly yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,10(s, 3H); 7,17-7,38(m, 5H); 7,47-7,53(m, 1H); 7,63(DD, 1H, J=7,5/1,5 Hz); 8,03(DD, 1H, J=7,7/1.3 Hz); 9,75(d, 1H, J=0.6 Hz).

(b) 2-((E)-2-Iodine)-2'-methylbiphenyl

Similarly to the method of example 1(g), on the basis of 2.00 g (10.2 mmol) obtained in example 22(a) 2'-methylbiphenyl-2-carboxaldehyde get 3,26 g (100%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,04 (s, 3H); 6,70(d, 1H, J= 14,8 Hz); 7,10(d, 1H, J=14,8 Hz); 7,09-7,49(m, 8H).

(C) Methyl ester of 4-[4-(2'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1 (d), by reacting 3,26 g (10.2 mmol) obtained in example 22(b) 2-(2-iodine-vinyl)-2'-methylbiphenyl with 1.63 g (10.2 mmol) of methyl ester 4-ethynylbenzene acid, obtain 360 mg (10%) of target compound as an orange oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,07 (s, 3H); 3,91 (s, 3H); 6,32(d, 1H, J= 16,3 Hz); 6,77(d, 1H, J=16,3 Hz); 7,13-EUR 7.57(m, 7H); was 7.45(d, 2H, J=8,4 Hz); 7,66-of 7.70(m, 1H); to 7.95(d, 2H, J=8.5 Hz).

(g) 4-[4-(2'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 360 mg (1,02 mmol) obtained in example 22 (C) complex m is Oska with so pl. 250oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,07 (s, 3H); 6,33(d, 1H, J=16,3 Hz); 6.75 in(d, 1H, J=16,3 Hz); 7,12-7,19(m, 2H); 7,27 - 7,46(m, 5H); 7,44(d, 2H, J=8,3 Hz); to 7.67-7,71 (m, 1H); of 7.96(d, 2H, J=8,3 Hz).

Example 23: 4-[4-(4'-Chlorobiphenyl-2-yl)but-3-EN-1-inyl]benzoic acid

(a) 4'-Chlorobiphenyl-2-carboxaldehyde

Similarly to the method of example 21 (a), on the basis of 5,00 g (31.9 per mmol) 4-chlorobenzamido acid and 3.94 g (of 21.3 mmol) of 2 - bromobenzaldehyde receive and 4.40 g (95%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D. : to 7.32(d, 2H, J=8.5 Hz); 7,42-of 7.55 (m, 2H); was 7.45(d, 2H, J= 8.5 Hz); to 7.64(DD, 1H, J=7,5/1,5 Hz); 8,03(DD, 1H, J=7,7/1.3 Hz); becomes 9.97(s, 1H).

(b) 2-((E)-2-Iodine)-4'-chlorobiphenyl

Similarly to the method of example 1(g), on the basis of 2.50 g (11.5 mmol) obtained in example 23 (a) 4'-chlorobiphenyl-2-carboxaldehyde get 2,40 g (61%) of target compound as an orange oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 6,76(d, 1H, J=14,8 Hz); 7.24 to 7,47 (m, 9H).

(C) Methyl ester of 4-[4-(4'-chlorobiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1 (d), by the interaction of 2.40 g (7.0 mmol) obtained in example 23(b) 2-((E)-(2-iodine)-4'- chlorobiphenyl with 1,03 g (6.4 mmol) is of Elo-yellow with so pl. 135oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,91 (s, 3H); 6,35 (d, 1H, J= 16.2 Hz); 7,01 (d, 1H, J=16.2 Hz); 7,26 was 7.45(m, 7H); 7,49(d, 2H, J=8,4 Hz); 7,63-to 7.67(m,1H); 7, 97 (d, 2H, J=8,4 Hz).

(g) 4-[4-(4'-Chlorobiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 0.97 g (26,01 mmol) obtained in example 23 (b) complex methyl ester, get 880 mg(94%) 4-[4-(4'-chlorobiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid in the form of a solid of light yellow color with so pl. 273oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D. : x 6.15(d, 1H, J=16.2 Hz); 6,76(d, 1H, J=16.2 Hz); 7,05-to 7.18(m, 7H); 7,21(d, 2H, J=8,2 Hz); 7,43-7,46(m, 1H); 7,73(d, 2H, J=8,3 Hz).

Example 24: 4-[4-(3'-Chlorobiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

(a) 3'-Chlorobiphenyl-2-carboxaldehyde

Similarly to the method of example 21(a), on the basis of 5,00 g (31.9 per mmol) 3-chlorobenzamido acid and 3.94 g (of 21.3 mmol) of 2-bromobenzaldehyde get 4,39 g (95%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 7.23 percent - 7,27 (m, 1H); 7,37 was 7.45(m, 4H); 7,50-7,56(m, 1H); to 7.64(DD, 1H, J=7,5/1,5 Hz); 8,04(DD, 1H, J= 7,7/1,4 Hz); 9,98(d, 1H, J=0.6 Hz).

(b) 2-((E)-2-Iodine)-3'-chlorobiphenyl

Similarly to the method of example 1(g), based on the 2.5 is in the form of a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D. : 6,77(d, 1H, J=14,9 Hz); 7,19-7,47(m, 9H).

(C) Methyl ester of 4-[4-(3'-chlorobiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1 (d), by the interaction of 1.85 g (5.4 mmol) obtained in example 24(b) 2-((E)-(2-iodine)-3'-chlorobiphenyl with 791 mg (4.9 mmol) of methyl ester 4-ethanbentley acid, receive 900 mg (49%) of target compound in the form of a powder beige color with a similar 120 - 125oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,91 (s, 3H); 6,36 (d, 1H, J= 16.2 Hz); 7,01 (d, 1H, J=16.2 Hz); 7,20-7,30 (m, 2H); 7,35-7,42 (m, 5H); of 7.48 (d, 2H, J=8,4 Hz); of 7.64-to 7.68 (m, 1H); of 7.97 (d, 2H, J=8.5 Hz).

(g) 4-[4-(3'-Chlorobiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 900 mg (24,1 mmol) obtained in example 24(C) complex methyl ester, receive 800 mg(92%) 4-[4-(3'-chlorobiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid in the form of a solid of light yellow color with so pl. 212oC.

1H-NMR-spectrum (deuterochloroform + drops hexacyanometallate), M. D. : 6,38 (d, 1H, J=16.2 Hz); 6,99 (d, 1H, J=16.2 Hz); 7,22-7,51 (m, 7H); of 7.48 (d, 2H, J=8,3 Hz); 7,66-of 7.70 (m, 1H); of 7.97 (d, 2H, J=8,3 Hz).

Example 25: 4-[4-(4'-Forbiden-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

(a) 4'-Forbefore of 3.84 g (20,7 mmol) of 2-bromobenzaldehyde, obtain 4.09 g (98%) target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D. : 7,15(d, 2H, J=8.7 Hz); 7,17-rate of 7.54 (m, 4H); 7,63(DD, 1H, J=7,5/1,5 Hz); 8,02(DD, 1H, J=7,7/1.3 Hz); becomes 9.97(d, 1H, J=0.6 Hz).

(b) 2-((E)-2-Iodine)-4'-forbiden

Similarly to the method of example 1(g), on the basis of 2.50 g (12.4 mmol) obtained in example 25 (a) 4'-forbiden-2-carboxaldehyde get 2,69 g (66%) of target compound as an orange oil, which was directly used in the next stage.

(C) Methyl ester of 4-[4-(4'-forbiden-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1 (d), by reacting 2,69 g (8.3 mmol) obtained in example 25(b) 2-((E)-(2-iodine)-4'- forbefore with 1.20 g (7.5 mmol) of methyl ester of 4-ethynylbenzene acid, obtain 1.20 g (45%) of target compound in the form of a yellow powder with so pl. 113oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,91(s, 3H); 6,35(d, 1H, J= 16.2 Hz); 7,02(d, 1H, J= 16.2 Hz); 7,11-7,19(m, 2H); 7,25-7,40(m, 5H); of 7.48(d, 2H, J=8,4 Hz); a 7.62 to 7.68 (m, 1H); of 7.97 (d, 2H, J=8,4 Hz).

(g) 4-[4-(4'-Forbiden-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 1.20 g (33,7 mmol) obtained in example 25 (b) complex methyl ester, obtain 1.12 g(97%) 4-[4-(4'-forbiden-2-the

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D. : 6,36(d, 1H, J=16.2 Hz); 7,01(d, 1H, J=16.2 Hz); 7,12-7,19(m, 2H); 7,27-7,40(m, 5H); 7,47(d, 2H, J=8,4 Hz); of 7.64-to 7.68(m, 1H); to 7.99(d, 2H, J=8,4 Hz).

Example 26: 4-[4-(4'-Propylbiphenyl-2-yl)but-3-EN-(E)-1 - inyl]benzoic acid

(a) 4'-Propylbiphenyl-2-carboxaldehyde

Similarly to the method of example 21(a), based on 3,40 g (20,7 mmol) 4-propylbenzamide acid and of 2.56 g (to 13.8 mmol) of 2-bromobenzaldehyde get 2,07 g (67%) of target compound in the form of a slightly yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 0,99 (t, 3H, J=7.4 Hz); to 1.70(m, 2H, J= 7.4 Hz); of 2.66 (t, 2H, J 7.4 Hz); 7,29-to 7.32(m, 4H); 7,44-7,66(m, 2H); to 7.61(DD, 1H, J=7,5/1,5 Hz); 8,01(DD, 1H, J=6,5/1.3 Hz); 9,99 (s, 1H).

(b) 2-((E)-2-Iodine)-4'-propylbiphenyl

Similarly to the method of example 1(g), according to 2.06 g (9.1 mmol) obtained in example 26 (a) 4'-propylbiphenyl-2-carboxaldehyde, obtain 2.14 g (67%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: a 1.00 (t, 3H, J=7.5 Hz); 1.69 in(m, 2H, J= 7,6 Hz); to 2.65 (t, 2H, J=7,3 Hz); 6.73 x(d, 1H, J=14,8 Hz); 7,21-of 7.48(m, 9H).

(C) Methyl ester of 4-[4-(4'-propylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1 (d), by reacting 2.14 g (6.1 mmol) obtained in Prime (32%) of target compound as a colourless oil.

1H-NMR-spectrum (deuterochloroform), M. D.: a 1.01 (t, 3H, J=7.2 Hz); 1,72(m, 2H, J=7.4 Hz); of 2.66 (t, 2H, J=7.5 Hz); 3,91(s, 3H); 6,36(d, 1H, J= 16.2 Hz); for 7.12(d, 1H, J= 16.2 Hz); 7,26-7,31(m, 4H); 7,33-7,38(m, 3H); of 7.48(d, 2H, J=8,4 Hz); of 7.64-to 7.67 (m, 1H); of 7.97 (d, 2H, J=8,4 Hz).

(g) 4-[4-(4'-Propylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 760 mg (2.0 mmol) obtained in example 26(C) complex methyl ester, get a 670 mg(91%) 4-[4-(4'-propylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid in the form of a greenish powder with so pl. 198oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: a 1.00 (t, 3H, J=7,3 Hz); 1,64-to 1.79(m, 2H); to 2.66(t, 2H, J=7.4 Hz); 6,36(d, 1H, J= 16.2 Hz); 7,11(d, 1H, J=16.2 Hz); 7,27-7,38(m, 7H); 7,47(d, 2H, J=8,4 Hz); of 7.64-to 7.68 (m, 1H); 7,98 (d, 2H, J=8,4 Hz).

Example 27: 4-[4-(4'-Vinylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

(a) 4'-Vinylbiphenyl-2-carboxaldehyde

Similarly to the method of example 21(a), on the basis of 5,00 g (33.8 mmol) of 4-vinylbenzoate acid and 4.17 g (to 22.5 mmol) of 2-bromobenzaldehyde get to 4.33 g (92%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 5,24(d, 1H, J=10,9 Hz); of 5.75(DD, 1H, J=18,2/0.6 Hz); 6,69(DD, 1H, J=17,6/10,9 Hz); 7,26(d, 2H, J=8,2 Hz); 7,31-7,58(m, 2H); 7,42(d, 2H, J=8,2 Hz); 7,53(DD, 1H, J=7,5/1,4 Hz); 7,94(DD, 1H, J=2.50 g (12,0 mmol) obtained in example 27 (a) 4'-vinylbiphenyl-2-carboxaldehyde, gain of 2.08 g (52%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: and 5.30(d, 1H, J=10,9 Hz); of 5.82(d, 1H, J= 17.6 Hz); 6,69-6,83 (m, 1H); 6.75 in(d, 1H, J=14,7 Hz); 7.24 to to 7.50(m, 9H).

(C) Methyl ester of 4-[4-(4'-vinylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1 (d), by the interaction of 2.08 g (6.3 mmol) obtained in example 27(b) 2-((E)-(2-iodine)-4'- vinylbiphenyl with 912 mg (5.9 mmol) of methyl ester 4-ethynylbenzene acid, receive 960 mg (45%) of target compound in the form of powder light yellow color with so pl. 136oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,91(s, 3H); 5,31(d, 1H, J= 11,0 Hz); of 5.83(d, 1H, J and 17.2 Hz); 6,35(d, 1H, J=16.2 Hz); 6,79(DD, 1H, J= 17,6/10,9 Hz); to 7.09(d, 1H, J=16.2 Hz); 7,31-7,39(m, 5H); 7,46-7,52(m, 4H); of 7.64-to 7.68(m, 1H); of 7.97(d, 2H, J=8,4 Hz).

(g)4-[4-(4'-Vinylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1(e) on the basis of 960 mg (26,3 mmol)obtained in example 27(b)complex methyl ester, obtain 910 mg(98%)4-[4-(4'-vinylbiphenyl-2-yl)but-3-EN-(E)- 1-inyl]benzoic acid in a solid yellow color with so pl. 254-257oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 4,67(d, 1H, J=10,9 Hz); 5,20(d, 1H, J=17.6 Hz); 5,77(d, 1H, J=

Example 28: 4-[4-(4'-Methoxyethoxymethyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

(a) 4-Methoxyethoxymethyl

In a three-neck flask enter 48,84 g (of 282.3 mmol) of 4-bromophenol, 150 ml of tetrahydrofuran and 150 ml of dimethylformamide. The resulting solution was cooled to 0oC, add small portions 11,74 g (366,9 mmol) of 75% sodium hydride and stirred at a temperature of 0oC for one hour. Added dropwise 25,0 ml (310.5 to mmol) METHYLCHLOROSILANE simple ether and the reaction medium is stirred for two hours at room temperature. The reaction medium is poured into a mixture of 1H. hydrochloric acid with ethyl acetate, extracted with ethyl acetate, the organic phase is decanted, dried over magnesium sulfate. After evaporation of the solvents get 63,85 g (100%) of target compound in the form of a beige oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 3.46 (s, 3H); 5,14 (s, 2H); 6,92(d, 2H, J=9.0 Hz); EUR 7.57(d, 2H, J=9.0 Hz).

(b) 4-Methoxymethamphetamine acid

Similarly to the method of example 2 (a), on the basis of expenses 63.81 g (293,0 mmol) obtained in example 28 (a) 4-methoxy-methoxypropanol get 35,42 g (80%)of target compound in the form of a white powder with so pl. 122oC.

1H-NMR-spectrum (deuterochloroform), /BR> Similarly to the method of example 21(a), based on 14,00 g (9.3 mmol) obtained in example 28(b) 4-methoxymethamphetamine acid and to 11.56 g (6.2 mmol)of 2-bromobenzaldehyde get 13,10 g (87%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,51(s, 3H); of 5.24 (s, 2H); 7,14(d, 2H, J=8.7 Hz); 7,30(d, 2H, J=8.7 Hz); 7,40-7,49(m, 2H); of 7.60(DD, 1H, J=7,5/1,5 Hz); 8,00(DD, 1H, J=7,6/1,1 Hz); 10,00(d, 1H, J=0.6 Hz).

(g) 2-((E)-2-Iodine)-4'-methoxyethoxymethyl

Similarly to the method of example 1(g), based on 13,10 g (54,0 mmol) obtained in example 28(C) 4'-methoxy-methoxybiphenyl-2 - carboxaldehyde get the 5.51 g (28%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 3.54 (s, 3H); of 5.24 (s, 2H); 6.73 x(d, 1H, J=14,8 Hz);? 7.04 baby mortality for 7.12 (m, 3H); 7,22-7,44 (m, 6H).

(d) Methyl ester of 4-[4-(4'-methoxyethoxymethyl-2-yl)but-3 - EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1 (d), by reacting the 5.51 g (15.1 mmol)obtained in example 28 (g), 2-(2-iodine)- 4'-methoxyethoxymethyl with 2,19 g (13.7 mmol) of methyl ester 4-ethynylbenzene acid, receive of 3.42 g (63%) of target compound in the form of a yellow powder with so pl. 76-80oHC.

1H-NMR-spectrum (deuterochloroform), M. D.: of 3.54 (s, 3H); 3,91 (s, 3H); of 5.24 (s, 2H); 6,34 (but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1 (e) on the basis of 850 mg (2,13 mmol) obtained in example 28 (e) complex methyl ester, obtain 490 mg(60%) 4-[4-(4'-methoxyethoxymethyl-2-yl)but-3-EN-(E)- 1-inyl]benzoic acid as a yellow powder with so pl. 209-213oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 3,30 (s, 3H); free 5.01 (s, 2H); 6,13(d, 1H, J=16.2 Hz); 6,85(d, 1H, J= 16.0 Hz); 6.89 in(d, 2H, J=8,4 Hz);? 7.04 baby mortality(d, 2H, J=8.6 Hz); 7,08-7,13(m, 3H); to 7.25(d, 2H, J=8,2 Hz); 7,26-7,28(m, 1H); 7,41-the 7.43(m, 1H); 7,74(d, 2H, J=8,2 Hz).

Example 2 9: 4-[4-(3'-Methoxyethoxymethyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

(a) 3-Methoxyethoxymethyl

Similarly to the method of example 28(a), on the basis of 48,84 g (of 282.3 mmol) 3-bromophenol and 25,00 g (310.5 to mmol) METHYLCHLOROSILANE simple ester, get 65,00 g (100%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 3.48 (s, 3H); further 5.15(s, 2H); 6,92-7,00(m, 2H); 7,10-to 7.18(m, 4H); 7.18 in - 7,22(m, 2H).

(b) 3-Methoxymethamphetamine acid

Similarly to the method of example 2 (a), based on 65,00 g (299,4 mmol) obtained in example 29 (a) 3-methoxyethoxymethyl get 30.20mm g (67%) of target compound in the form of a powder beige with so pl. 45oC.

1H-NMR-spectrum (tataroglu the
Similarly to the method of example 21 (a), on the basis of 15,00 g (100.0 mmol) obtained in example 29(b) 3-methoxyethoxy-basavaraj acid and 12.33 g (66,6 mmol) of 2-bromobenzaldehyde get 7,60 g (31%) of target compound as a colourless oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,51(s, 3H); 5,22(s, 2H); 7,01(d, 1H, J=7.5 Hz); 7,07-7,14 (m, 2H); of 7.36(d, 1H, J=7.8 Hz); 7,41-7,53 (m, 2H); a 7.62(DD, 1H, J=7,5/1,5 Hz); 8,02(DD, 1H, J=7,7/1.2 Hz); of 10.01(s, 1H).

(g) 2-((E)-2-Iodine)-3'-methoxyethoxymethyl

Similarly to the method of example 1(g), based on 7,60 g (of 31.4 mmol)obtained in example 29(b) 3'-methoxy-methoxybiphenyl-2 - carboxaldehyde get 4,25 g (37%) of target compound as a brown oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,51(s, 3H); 5,22(s, 2H); 6.73 x(d, 1H, J=14,8 Hz); 6,95-7,07(m, 3H); 7,30 - the 7.43(m, 5H).

(d) Methyl ester of 4-[4-(3'-methoxyethoxymethyl-2-yl)but-3-EN- (E)-1-inyl]benzoic acid

Similarly to the method of example 11 (e), by the interaction of 6.96 g (17.5 mmol) obtained in example 29 (g), 2-((E)-2-iodine)-3'- methoxyethoxymethyl with 5,59 g (34,9 mmol)of methyl ester 4-ethynylbenzene acid, receive 1.84 g (25%) of target compound in the form of powder light yellow color with so pl. 102oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,50 shall ethoxymethyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1(e) on the basis of 450 mg (1.2 mmol) obtained in example 29(e) complex methyl ester, get 420 mg(93%) 4-[4-(3'-methoxyethoxymethyl-2-yl)but-3-EN- (E)-1-inyl] benzoic acid in the form of a powder beige with so pl. 213oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: a 3.50 (s, 3H); 5,23 (s, 2H); 6,36(d, 1H, J=16.2 Hz); 6,98-was 7.08(m, 3H); to 7.09(d, 1H, J=16,3 Hz); 7,34-7,42(m, 4H); 7,46(d, 2H, J=8,3 Hz); the 7.65 to 7.68 (m, 1H); 7,98(d, 2H, J=8,3 Hz).

Example 30: 4-[4-(2-thiophene-3-ylphenyl)but-3-EN-(E)-1-inyl] -benzoic acid

(a) 2-Thiophene-3-ivansanchez

Similarly to the method of example 21 (a), on the basis of 5,15 g (40,2 mmol) 3-tiotemporal acid and 4,96 g (26.8 mmol) of 2-bromobenzaldehyde get 4,08 g (81%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 7,18-7,20 (m, 1H); 7,28-7,30(m, 1H); 7,44 is 7.50(m, 3H); of 7.60(DD, 1H, J=7,0/1.5 Hz); 8,00(DD, 1H, J= 6,9/1,6 Hz); 10,11 (s, 1H).

(b) 2-((E)-2-Iodine)-2-thiophene-3-albenza

Similarly to the method of example 1(g), on the basis of 2.50 g (13.3 mmol) obtained in example 30 (a) 2-thiophene-3-yl-benzaldehyde, get to 2.74 g (66%) of target compound as an orange oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 6,74(d, 1H, J=14,8 Hz); 7,14-7,44 (m, 7H); 7,50(d, 1H, J=14,8 Zdice of example 1 (d), by interacting 2,74 g (8,8 mmol) obtained in example 30(b) 2-(2-iodine-vinyl)-2-thiophene-3-albenzae with 1,41 g (8,8 mmol) of methyl ester 4-ethynylbenzene acid, obtain 950 mg (31%) of target compound in the form of a powder beige with so pl. 89-91oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,91(s, 3H); 6,33(d, 1H, J= 16.2 Hz); 7,17 and 7.36(m, 7H); 7,49(d, 2H, J=8,3 Hz); 7, 61-7, 63 (m, 1H); 7, 97 (d, 2H, J=8,3 Hz).

(g) 4-[4-(2-Thiophene-3-ylphenyl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 950 mg (2.8 mmol) obtained in example 30 (b) complex methyl ester, get 880 mg(96%) 4-[4-(2-thiophene-3-yl-phenyl)but-3-EN-(E)-1 - inyl]benzoic acid as a yellow powder with so pl. 218oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D. : 6,38(d, 1H, J=16.2 Hz); 6,99(d, 1H, J=16.2 Hz); 7,22-7,51(m, 6H); of 7.48(d, 2H, J=8,3 Hz); 7,66-of 7.70 (m, 1H); of 7.97(d, 2H, J=8,3 Hz).

Example 31: 4-[4-(2-Thiophene-2-ylphenyl)but-3-EN-(E)-1-inyl]benzoic acid

(a) 2-Thiophene-2-ivansanchez

Similarly to the method of example 21(a), based on 4,19 g (to 32.7 mmol) 2-tiotemporal acid and 4.04 g (to 21.8 mmol) of 2-bromobenzaldehyde, gain of 3.85 g (89%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D. who yl)-2-thiophene-2-albenza

Similarly to the method of example 1(g), on the basis of 2.50 g (13.3 mmol) obtained in example 31 (a) 2-thiophene-2-yl-benzaldehyde, get 3,17 g (76%) of target compound in the form of oil chestnut color, which is directly used in the next stage.

(C) Methyl ester of 4-[4-(2-Thiophene-2-ylphenyl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1 (d), by reacting 3,17 g (10.2 mmol) obtained in example 31(b) 2-(2-iodine)-2-thiophene-2 - albenzae with 1.63 g (10.2 mmol)of methyl ester 4-ethynylbenzene acid, obtain 555 mg (16%) of target compound in a solid yellow color with so pl. 100oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,91 (s, 3H); 6,35(d, 1H, J 15.2 Hz); 7,07(d, 1H, J=1.2 Hz); 7,08 - 7,14 (m, 1H); 7,30-7,46(m, 5H); 7,50(d, 2H, J=8,3 Hz); to 7.61-7,63(m, 1H); 7,98(d, 2H, J=8,3 Hz).

(g) 4-[4-(2-Thiophene-2-ylphenyl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 550 mg (1.6 mmol) obtained in example 31 (b) complex methyl ester, obtain 530 mg(100%) 4-[4-(2-Thiophene-2-ylphenyl)but-3-EN-(E)-1-inyl]benzoic acid as a yellow powder with so pl. 221oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D. : 6,37(d, 1H, J=16.2 Hz); 7,11(s, 1H, J=16.2 Hz); 7,08-7,17(m, 1H); 7,34 is] benzoic acid

(a) Methyl ester of 4-[4-(4'-hydroxybiphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

In a three-neck flask with a volume of 100 ml in a stream of nitrogen injected 1,95 g (4.9 mmol) obtained in example 28(e) compound, 20 ml of methanol and 20 ml of tetrahydrofuran. Added dropwise 2,62 ml (48,9 mmol) of concentrated sulfuric acid in solution in 20 ml of methanol. The reaction medium is stirred for 15 hours at room temperature, then add water, extracted with diethyl ether, the organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by chromatography on a column of silica, elwira heptane, and then with a mixture of 20% ethyl acetate and 80% heptane. After evaporation of the solvents to obtain 1.50 g (86%) of target compound in the form of a powder beige with so pl. 130oC.

1H-NMR-spectrum (deuterochloroform), M. D.: to 3.92(s, 3H); 4,96 (s, 1H); 6,34(d, 1H, J= 16.2 Hz); 6,93(d, 2H, J=8.6 Hz); to 7.09(d, 1H, J=16,3 Hz); from 7.24(d, 2H, J= 8.6 Hz); 7,26-7,37(m, 3H); of 7.48(d, 2H, J=8,4 Hz); a 7.62-7,66 (m, 1H); 7,98(d, 2H, J=8,3 Hz).

(b) 4-[4-(4'-Hydroxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 660 mg (1.9 mmol) obtained in example 32 (a) slo is orosco beige with so pl. 235oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 6,27(d, 1H, J=16.2 Hz); 6,83(d, 2H, J=8.5 Hz); 7,00(d, 1H, J= 16,3 Hz); 7,07(d, 2H, J=8.5 Hz); 7.18 in-7,26(m, 3H); 7,39(d, 2H, J=8,3 Hz); 7,54-7,58(m, 1H); 7,88(d, 2H, J=8,3 Hz); 9,10 (s, 1H).

Example 33: 4-[4-(4'-Methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

(a) Methyl ester of 4-[4-(4'-methoxybiphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

In a three-neck flask with a volume of 100 ml and in a stream of nitrogen, is injected 420 mg (1.2 mmol) obtained in example 32 (a) compound, 20 ml of dimethylformamide and 20 ml of tetrahydrofuran. Cool and add in small portions 49 mg (1.5 mmol) of 75% in oil of sodium hydride. The reaction medium is stirred for 40 minutes at room temperature, then added dropwise a solution of 81 μl (1.3 mmol) under the conditions in 5 ml of dimethylformamide. The reaction medium is stirred for three hours at room temperature, then add water, extracted with diethyl ether, the organic phase is washed with water, dried over magnesium sulfate, filtered and the solvents evaporated. Obtain 470 mg (100%) of target compound in the form of a yellow powder with so pl. 190oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,88 (s, 3H); 3,91(s, 3H); 6,35(d, 1H, J is).

(b) 4-[4-(4'-Methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1 (e) on the basis of 430 mg (1.2 mmol) obtained in example 33 (a) complex methyl ester, obtain 390 mg(94%) 4-[4-(4'-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid as a yellow powder with so pl. 253oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 3,88 (s, 3H); 6,35(d, 1H, J=16.2 Hz); 7,00(d, 2H, J=8.7 Hz); was 7.08(d, 1H, J= 16.2 Hz); 7,28(d, 2H, J=8,8 Hz); 7,32-7,40(m, 3H); 7,47(d, 2H, J=8,3 Hz); 7,63-to 7.67 (m, 1H); 7,98(d, 2H, J=8,3 Hz).

Example 34: 4-[4-(4'-Propoxyphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

(a) Methyl ester of 4-[4-(4'-propoxyphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

Similarly to the method of example 33 (a), on the basis of 420 mg (1.2 mmol) obtained in example 32 (a)connection and 127 μl (1.3 mmol) of n-propyliodide get 460 mg (98%) of target compound in the form of a powder beige with so pl. 110-113oC.

1H-NMR-spectrum (deuterochloroform), memorial plaques with 1.07 (t, 3H, J=7.5 Hz); 1.85 to (K, 2H, J=7.2 Hz); 3,91 (s, 3H); 3,99 (t, 2H, J=6.5 Hz); 6,34(d, 1H, J=16.2 Hz); 6,92-7,00 (m, 3H); 7,11(d, 1H, J=16.2 Hz); 7,29-7,35(m, 4H); of 7.48(d, 2H, J=8,3 Hz); 7,62-of 7.69 (m, 1H); of 7.97(d, 2H, J=8,4 Hz).

(b) 4-[4-(4'-Propoxyphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similar methods(90%) 4-[4-(4'-propoxyphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid as a yellow powder with so pl. 235oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), memorial plaques with 1.07 (t, 3H, J=7.4 Hz); of 1.85(m, 2H, J=7.0 Hz); 3,99 (t, 2H, J=6.5 Hz); 6,35(d, 1H, J=16.2 Hz); 6,99(d, 2H, J=8.7 Hz); to 7.09(d, 1H, J=16.2 Hz); 7,27(d, 2H, J=8.6 Hz); 7,32-7,38(m, 3H); 7,47(d, 2H, J=8,3 Hz); 7,63 - 7,66(m, 1H); 7,98(d, 2H, J=8,3 Hz).

Example 35: 4-[4-(3'-Hydroxybiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

(a) Methyl ester of 4-[4-(3'-hydroxybiphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

Similarly to the method of example 32 (a), on the basis of 1.39 g (3.5 mmol) obtained in example 32 (a) complex methyl ester, get 1,17 g (95%) of target compound in the form of a powder beige with so pl. 120-125oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,91 (s, 3H); 5,02(s, 1H); 6,35(d, 1H, J= 16.2 Hz); 6,82-6,93(m, 3H); 7,10(d, 1H, J=16.2 Hz); 7,30-7,39(m, 4H); of 7.48(d, 2H, J=8.5 Hz); of 7.64-to 7.67 (m, 1H); of 7.97(d, 2H, J=8,5 Hz).

(b) 4-[4-(3'-Hydroxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]-benzoic acid

Similarly to the method of example 1(e) on the basis of 450 mg (1.3 mmol) obtained in example 35 (a)complex methyl ester, get 420 mg(97%) 4-[4-(3'-hydroxybiphenyl-2-yl)but-3-EN- (E)-1-inyl]benzoic acid as a white powder with so pl. 219oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate) 36: 4-[4-(3'- Methoxybiphenyl-2-yl)but-3-EN-(E)-1 - inyl]benzoic acid

(a) Methyl ester of 4-[4-(3'-methoxybiphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

Similarly to the method of example 33 (a), on the basis of 360 mg (1.0 mmol) obtained in example 35(a) connection and 70 μl (1.1 mmol) under the conditions that obtain 370 mg (100%) of target compound in the form of a white powder with so pl. 105oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,85(s, 3H); 3,91 (s, 3H); 6,35(d, 1H, J= 16.2 Hz); 6.89 in-of 6.96 (m, 3H); 7,10(d, 1H, J=16.2 Hz); 7,34-7,39(m, 4H); of 7.48(d, 2H, J=8,4 Hz); a 7.62 to 7.64 (m, 1H); of 7.97(d, 2H, J=8,4 Hz).

(b) 4-[4-(3'-Methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1 (e) on the basis of 370 mg (1.0 mmol) obtained in example 36(a)complex methyl ester, obtain 330 mg(92%)4-[4-(3'-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid in the form of a powder beige with so pl. 214oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 3,85 (s, 3H); 6,35(d, 1H, J=16.2 Hz); 6,88-6,97 (m, 3H); was 7.08(d, 1H, J=16.2 Hz); 7,30-7,40(m, 4H); 7,47(d, 2H, J=8,3 Hz); the 7.65 to 7.68 (m, 1H); 7,98(d, 2H, J=8,2 Hz).

Example 37: 4-[4-(3'-Propoxyphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

(a) Methyl ester of 4-[4-(3'-propoxyphenyl-2-yl)but-3 - EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 33 (a), on the basis of 360 mg (1.0 mmole in the form of a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 1,82 (K, 2H, J=7,1 Hz); 3,91 (s, 3H); of 3.97 (t, 3H, J=6.6 Hz); 6,34(d, 1H, J=16.2 Hz); 6.87 in-to 6.95(m, 3H); 7,11(d, 1H, J=16.2 Hz); 7,31-7,39 (m, 4H); of 7.48(d, 2H, J=8,4 Hz); of 7.64-to 7.67 (m, 1H); of 7.97(d, 2H, J=8,4 Hz).

(b) 4-[4-(3'-Propoxyphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 400 mg (1.0 mmol) obtained in example 37(a) complex methyl ester, obtain 330 mg(86%) 4-[4-(3'-propoxyphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid as a pale yellow powder with so pl. 177oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: of 1.03 (t, 3H, J=7.4 Hz); to 1.83(m, 2H, J=7,1 Hz); of 3.97 (t, 2H, J=6.6 Hz); 6,35(d, 1H, J=16.2 Hz); 6.89 in-to 6.95(m, 3H); 7,10(d, 1H, J=16.2 Hz); 7,30-7,38(m, 4H); 7,47(d, 2H, J=8,2 Hz); of 7.64-to 7.67 (m, 1H); to 7.99(d, 2H, J= 8,3 Hz).

Example 38: 4-[4-(4'-Methyl-4-hydroxybiphenyl-2-yl)but-3 - EN-(E)-1-inyl] benzoic acid

(a) Methyl ester of 4-[4-(4'-methyl-4-hydroxybiphenyl-2-yl)-but - 3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 32 (a), from 700 mg (1.7 mmol) obtained in example 15(d) complex methyl ester, obtain 630 mg (100%) of target compound in the form of a yellow powder with so pl. 205oC.

1H-NMR-spectrum (deuterochloroform), M. D.: is 2.41(s, 3H); 3,91 (s, 3H); 6.30-in(d, 1H, J= 16.1 Hz); 6.89 in(DD, 1H, J-(E)-1-inyl] benzoic acid

Similarly to the method of example 1 (e) on the basis of 270 mg (0.7 mmol) obtained in example 38 (a) complex methyl ester, obtain 210 mg(85%) 4-[4-(4'-methyl-4-hydroxybiphenyl-2-yl)but-3-EN-(E) -1-inyl]benzoic acid as a yellow powder with so pl. 285oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D. : 2,32 (s, 3H); 6,24(d, 1H, J=16.2 Hz); 6,77(DD, 1H, J= 8,3/a 2.2 Hz); 6,91(d, 1H, J= 16.2 Hz); 7,01-7,05(m, 2H); to 7.09(d, 2H, J=8.1 Hz); 7,16(d, 2H, J=8.0 Hz); 7,39(d, 2H, J=8,3 Hz); 7,86(d, 2H, J=8,3 Hz); 9,29(ush.s, 1H).

Example 39: 4-[4-(4'-Methyl-4-methoxybiphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

(a) Methyl ester of 4-[4-(4'-methyl-4-methoxybiphenyl-2-yl)-but-3 - EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 33 (a), on the basis of 180 mg (0.49 mmol) obtained in example 38(a) connection and 79 mg (0,56 mmol) under the conditions that obtain 140 mg (75%) of target compound in the form of a yellow powder with so pl. 111oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42(s, 3H); 3,88 (s, 3H); 3,91 (s, 3H); 6,34(d, 1H, J=16.2 Hz); 6,94(DD, 1H, J=8,5/a 2.6 Hz); was 7.08(d, 1H, J=16.2 Hz); to 7.15(d, 1H, J=2.6 Hz); 7,19-7,26 (m, 5H); 7,47(d, 2H, J=8,3 Hz); of 7.97(d, 2H, J=8,3 Hz).

(b) 4-[4-(4'-Methyl-4-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1(e) on the basis of 140 mg (from 0.37 mmol) obtained is]benzoic acid as a yellow powder with so pl. 225oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,37(c, 3H); 3,85(c, 3H); 6,72(d, 1H, J=16.2 Hz); to 6.95(d, 1H, J= 16,3 Hz); 7,01(DD, 1H, J=8,5/a 2.3 Hz); 7,16-7,30 (m, 5H); 7,38(d, 1H, J=2.3 Hz); at 7.55(d, 2H, J=8,2 Hz); a 7.92(d, 2H, J=8,2 Hz); 13,14(ush.s, 1H).

Example 40: 4-[4-(4'-Methyl-4-propoxymethyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

(a) Methyl ester of 4-[4-(4'-methyl-4-propoxymethyl-2-yl)-but-3 - EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 33 (a), on the basis of 180 mg (0.49 mmol) obtained in example 38 (a) connection and 95 mg (0,56 mmol) n - propyliodide, obtain 131 mg (65%) of target compound in the form of a yellow powder with so pl. 87oC.

1H-NMR-spectrum (deuterochloroform), memorial plaques with 1.07 (t, 3H, J=7.5 Hz); of 1.85(m, 2H, J=7.2 Hz); to 2.42 (s, 3H); 3,91 (s, 3H); 3,99 (t, 2H, J=6.6 Hz); 6,33(d, 1H, J=16.2 Hz); 6,93(DD, 1H, J=8,5/a 2.6 Hz); was 7.08(d, 1H, J=16.2 Hz); to 7.15(d, 1H, J=2.5 Hz); 7,19-7,25(m, 5H); 7,47(d, 2H, J=8,3 Hz); of 7.97(d, 2H, J=8,3 Hz).

(b) 4-[4-(4'-Methyl-4-propoxymethyl-2-yl)but-3-EN-(E)- 1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 131 mg (0.32 mmol) obtained in example 40 (a) complex methyl ester, 126 mg get(100%) 4-[4-(4'-methyl-4-propoxymethyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid as a yellow powder with so pl. 181oC.

1H-J=8,4/2,5 Hz); 7,10(d, 1H, J=16.2 Hz); 7,16(d, 1H, J= 2.4 Hz); 7,20-7,27(m, 5H); 7,50(d, 2H, J=8,3 Hz); 8,04(d, 2H, J=8,3 Hz).

Example 41: 4-[4-(4'-Methyl-5-hydroxybiphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

(a) Methyl ester of 4-[4-(4'-methyl-5-hydroxybiphenyl-2-yl)-but-3 - EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 32 (a), on the basis of 2.00 g (4.8 mmol) obtained in example 16(d) complex methyl ester, gain of 1.57 g (88%) of target compound in the form of a yellow powder with so pl. 166oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,42(s, 3H); 3,91(s, 3H); 6,18(d, 1H, J=16.2 Hz); to 6.80(d, 1H, J=2.5 Hz); 6,86(d, 1H, J=8.6 Hz); 7,02(d, 1H, J=16.2 Hz); 7.24 to (s, 4H); was 7.45(d, 2H, J=8,4 Hz); 7,53(d, 1H, J=8.6 Hz); of 7.95(d, 2H, J=8,4 Hz); 8,99(s, 1H).

(b) 4-[4-(4'-Methyl-5-hydroxybiphenyl-2-yl)but-3-EN-(E)- 1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 700 mg (1.9 mmol) obtained in example 41(a) complex methyl ester, receive 500 mg(75%) 4-[4-(4'-methyl-5-hydroxybiphenyl-2-yl)but-3-EN- (E)-1-inyl] benzoic acid as a yellow powder with so pl. 230-232oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: of 2.38 (s, 3H); 6.42 per(d, 1H, J=16.2 Hz); to 6.67(d, 1H, J=2.4 Hz); 6,83(DD, 1H, J=8,6/2,4 Hz); 6.87 in(d, 1H, J=2.4 Hz); 7,19(d, 2H, J=8.0 Hz); 7,30(d, 2H, J=7.9 Hz); 7,52 l-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

(a) Methyl ester of 4-[4-(4'-methyl-5-methoxybiphenyl-2-yl)- but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 33 (a), on the basis of 400 mg (1.1 mmol) obtained in example 41(a) connection and 185 mg (1.3 mmol) under the conditions that obtain 420 mg (100%) of target compound in the form of a yellow powder with so pl. 130oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43(s, 3H); of 3.84(s, 3H); 3,91(s, 3H); from 6.22(d, 1H, J=16.2 Hz); PC 6.82(d, 1H, J=2.7 Hz); 6,91(DD, 1H, J= 8,7/2.7 Hz); 7.03 is(d, 1H, J=16.2 Hz); 7,26(s, 4H); 7,46(d, 2H, J=8,4 Hz); of 7.60(d, 1H, J=8.7 Hz); of 7.96(d, 2H, J=8,4 Hz).

(b) 4-[4-(4'-Methyl-5-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1 (e) on the basis of 420 mg (1.1 mmol) obtained in example 42(a) complex methyl ester, receive 300 mg(74%) 4-[4-(4'-methyl-5-methoxybiphenyl-2-yl)but-3-EN- (E)-1-inyl]benzoic acid as a yellow powder with so pl. 258-260oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: of 2.38(s, 3H); is 3.82(s, 3H); 6,50(d, 1H, J=16.2 Hz); PC 6.82(d, 1H, J=2.5 Hz); 6.90 to(d, 1H, J= 16,3 Hz); 6,99(DD, 1H, J=8,8/2,4 Hz); 7.23 percent(d, 2H, J=8.0 Hz); 7,31(d, 2H, J= 7.9 Hz); 7,53(d, 2H, J=8,2 Hz); 7,81(d, 1H, J=8,8 Hz); to $ 7.91(d, 2H,J=8,2 Hz); 13,12(ush.s, 1H).

Example 43: 4-[4-(4'-Methyl-5-propoxymethyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

(a) Methyl ester of 4-[4-(4'-methyl-5-propoxymethyl-2-yl)-but-3 - aimere 41(a) connection and 194 mg (1.1 mmol) of n - propyliodide, obtain 410 mg (100%) of target compound in the form of yellow crystals with so pl. 107oC.

1H-NMR-spectrum (deuterochloroform), M. D.: the 1.04 (t, 3H, J=7.5 Hz); is 1.82(m, 2H, J= 7.2 Hz); 2,43 (s, 3H); 3,91 (s, 3H); 3.96 points(t, 2H, J=6.6 Hz); 6,21(d, 1H, J=16.2 Hz); PC 6.82(d, 1H, J=2.6 Hz); 6.90 to(DD, 1H, J=8,6/2,6 Hz); 7,03(d, 1H, J=16.2 Hz); of 7.25 (s, 3H); was 7.45(d, 2H, J=8,4 Hz); to 7.59(d, 1H, J= 8.7 Hz); of 7.96 (d, 2H, J=9.4 Hz); 8,02-with 8.05 (m, 1H).

(b) 4-[4-(4'-Methyl-5-propoxymethyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1(e) on the basis of 400 mg (0.97 mmol) obtained in example 43 (a) complex methyl ester, get 270 mg(71%) 4-[4-(4'-methyl-5-propoxymethyl - 2-yl)but-3-EN-(E)-1-inyl]benzoic acid as a yellow powder with so pl. 255-257oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: and 0.98 (t, 3H, J= 7.4 Hz); at 1.73(m, 2H, J=7,1 Hz); of 2.38 (s, 3H); 3,99 (t, 2H, J=6.5 Hz); of 6.49 (d, 1H, J= 16.2 Hz); to 6.80 (d, 1H, J=2.5 Hz); 6.90 to (d, 1H, J=16,3 Hz); 6,98(DD, 1H, J=8,7/a 2.3 Hz); 7.23 percent (d, 2H, J=8.0 Hz); 7,31 (d, 2H, J=8.0 Hz); 7,52 (d, 2H, J=8,2 Hz); 7,79(d, 1H, J=8,8 Hz); to $ 7.91(d, 2H, J=8,3 Hz).

Example 44: 4-[4-(4'-Methyl-6-hydroxybiphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

(a) Methyl ester of 4-[4-(4'-methyl-6-hydroxybiphenyl-2-yl)-but-3 - EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 32 (a), from 700 mg (1.7 mmol) obtained in example 17(e) methyl complex is 1
H-NMR-spectrum (deuterochloroform), M. D.: the 2.46(s, 3H); 3,91(s, 3H); to 4.92(s, 1H); of 6.29(d, 1H, J=16.2 Hz); 6,77(d, 1H, J=16.2 Hz); 6,95-6,99 (m, 1H); then 7.20 (d, 2H, J= 8.0 Hz); 7,25 - 7,27(m, 2H); of 7.36(d, 2H, J 7.8 Hz); was 7.45(d, 2H, J=8,4 Hz); of 7.96 (d, 2H, J=8,4 Hz).

(b) 4-[4-(4'-Methyl-6-hydroxybiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1(e) on the basis of 350 mg (0.95 mmol) obtained in example 44 (a) complex methyl ester, receive 300 mg(90%) 4-[4-(4'-methyl-6-hydroxybiphenyl-2-yl)but - 3-EN-(E)-1-inyl]benzoic acid in the form of a powder beige with so pl. 234-236oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: is 2.37(s, 3H); 6,51(d, 1H, J= 16,3 Hz); of 6.71(d, 1H, J=16,3 Hz); 6,92(d, 2H, J=7.8 Hz); was 7.08(d, 1H, J=7.8 Hz); 7,16-7,31(m, 4H); 7,52(d, 2H, J=8,2 Hz); of 7.90(d, 2H, J=8,2 Hz); 9,41(ush.s, 1H).

Example 45: 4-[4-(4'-Methyl-6-methoxybiphenyl-2-yl)but-3-EN-(E)- 1-inyl] benzoic acid

(a) Methyl ester of 4-[4-(4'-methyl-6-methoxybiphenyl-2-yl)-but - 3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 33 (a), on the basis of 270 mg (0.73 mmol) obtained in example 44 (a) compound and 50 μl (0.80 mmol) under the conditions that obtain 270 mg (98%) of target compound in the form of a powder beige Art. square 116-118oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43(s, 3H); 3,74(s, 3H); 3,91(s, 3H); of 6.29(d, 1H, J=16.2 Hz); at 6.84(d, 1H, J=16.2 Hz); the Nile-2-yl)but-3-EN-(E) -1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 270 mg (to 0.72 mmol) obtained in example 45(a) complex methyl ester, 240 mg get(92%) 4-[4-(4'-methyl-6-methoxybiphenyl-2-yl) but-3-EN-(E)-1-inyl]benzoic acid as a beige flakes with so pl. 235-236oC.

1H-NMR-spectrum (hexanitrodiphenylamine), M. D.: is 2.37 (s, 3H); 3,66 (s, 3H); to 6.57(d, 1H, J=16,3 Hz); to 6.67(d, 1H, J=16,3 Hz);? 7.04 baby mortality-to 7.09(m, 3H); to 7.25(d, 2H, J= 7,7 Hz); 7,33 - 7,47(m, 2H); 7,52(d, 2H, J=8,3 Hz); 7,89(d, 2H, J=8,3 Hz); 13,12(ush.s, 1H).

Example 46: 4-[4-(4'-Triptorelin-2-yl)but-3-EN-(E)-1 - inyl]benzoic acid

(a) 4'-Triptorelin-2-carboxaldehyde

Similarly to the method of example 21(a), based on 1,43 g (7.5 mmol) of 4-triftorperasin acid and 928 mg (5.0 mmol) of 2-bromobenzaldehyde, obtain 1.13 g (60%) of target compound in the form of a slightly yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D. : the 7.43(d, 1H, J=7.5 Hz); 7,51(d, 2H, J= 7.8 Hz); EUR 7.57(d, 1H, J=7,6. Hz); to 7.67(d, 1H, J=7.5 Hz); 7,74(d, 2H, J=8,3 Hz); of 8.06(d, 1H, J=7,7 Hz); 9, 96 (s, 1H).

(b) 2-((E)-2-Iodine)-4'-triptorelin

Similarly to the method of example 1(g), on the basis of 1.13 g (4.5 mmol) obtained in example 46(a) 4'-triptorelin-2-carboxaldehyde, obtain 520 mg (31%) of target compound as a yellow oil.

1H-NMR-spectrum (de is normativity-2-yl)but-3-EN- (E)-1-inyl]benzoic acid

Similarly to the method of example 11 (e), by reacting 520 mg (1.4 mmol) obtained in example 46(b) 2-((E)-(2-iodine)-4'- triptoreline with 245 mg (1.5 mmol)of methyl ester of 4 - ethynylbenzene acid, receive 200 mg (35%) of target compound in the form of a yellow powder with so pl. 119oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,91 (s, 3H); 6,38(d, 1H, J= 16.2 Hz); 6,98(d, 1H, J= 16.2 Hz); 7,28 - to 7.50(m, 7H); 7,66-of 7.70 (m, 1H); 7,72(d, 2H, J=8,4 Hz); of 7.97(d, 2H, J=8,2 Hz).

(g) 4-[4-(4'-Triptorelin-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1(e), starting from 200 mg (0.49 mmol) obtained in example 46(b) complex methyl ester, receive 150 mg(77%) 4-[4-(4'-triptorelin-2-yl)but-3-EN-(E)-1-inyl] benzoic acid as a yellow powder with so pl. 270oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D. : of 6.31(d, 1H, J=16.2 Hz); to 6.88(d, 1H, J=16.2 Hz); 7,20-7,24(m, 1H); 7,31 - 7,46(m, 6H); to 7.59 to 7.62 (m, 1H); to 7.64(d, 2H, J=8,3 Hz); 7,88(d, 2H, J=8,2 Hz).

Example 47: 4-[4-(4'-Hydroxymethyluracil-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

(a) 4-Ethoxymethyleneamino

In a three-neck flask enter 8.00 g (42.8 mmol) of 4-bromo-benzyl alcohol, 1,02 g tetrabutylammonium and 200 ml of toluene. Received ratem add 200 ml of water 10h. the sodium hydroxide solution. The reaction medium is stirred for two hours at a temperature of 0oC, then poured into a mixture of 1H. hydrochloric acid in diethyl ether and extracted with diethyl ether. The organic phase is decanted and dried over magnesium sulfate. After evaporation of the solvents get 10,48 g (100%) of target compound in the form of oil beige.

1H-NMR-spectrum (deuterochloroform), M. D.: of 1.23 (t, 3H, J=7.0 Hz); 3,64 (K, 2H, J= 7,1 Hz); 4,55 (s, 2H); 4.75 V (s, 2H); 7.23 percent(d, 2H, J=8,3 Hz); 7,47(d, 2H, J=8,3 Hz).

(b) 4-Ethoxymethyleneamino acid

Similarly to the method of example 2 (a), on the basis of of 10.58 g (43.2 mmol) obtained in example 47(a) 4-ethoxyethoxy-methylpropanol receive 9.00 g (99%) target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 1.26(t, 3H, J=7.0 Hz); 3,69 (K, 2H, J= 7,1 Hz); 4,71 (s, 2H); to 4.81 (s, 2H); 7,49(d, 2H, J=7,7 Hz); by 8.22(d, 2H, J=7,7 Hz).

(in) 4'-Ethoxymethylene-2-carboxaldehyde

Similarly to the method of example 21 (a), on the basis of 9.00 g (42.8 mmol) of 4-ethoxymethylenemalonic acid obtained in example 47(b), and 5,33 g (28.8 mmol) of 2-bromo-benzaldehyde, get 6,04 g (77%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterono is,4/1,4 Hz); 8,03(DD, 1H, J-7,7/1.2 Hz); 9,99 (s, 1H).

(g) 2-((E)-2-Iodine)-4'-ethoxyresorufin

Similarly to the method of example 1(g), on the basis of 3.50 g (12.9 mmol) of 4'-ethoxymethylene-2-carboxaldehyde obtained in example 47(b) gain of 1.97 g (39%) of target compound as an orange oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 1.29 (t, 3H, J=7.0 Hz); 3,69 (K, 2H, J= 7.0 Hz); of 4.67 (s, 2H); a 4.83 (s, 2H); 6.75 in(d, 1H, J=14,8 Hz); 7,28-7,49(m, 9H).

(d) Methyl ester of 4-[4-(4'-ethoxymethylene-2-yl)but-3 - EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 11 (e), by the interaction of 1.97 g (5.0 mmol) of 2-((E)-(2-iodine)-4'-ethoxy-methoxypyridine obtained in example 47 (g), 1.20 g (7.5 mmol) of methyl ester of 4-ethynylbenzene acid, receive 537 mg (25%) of target compound in the form of powder light yellow color with so pl. 60oC.

1H-NMR-spectrum (deuterochloroform), M. D.: of 1.27(t, 3H, J=7,1 Hz); 3,70 (K, 2H, J and 7.1 Hz); 3,91 (s, 3H); and 4.68 (s, 2H); 4,84(s, 2H); 6,35(d, 1H, J= 16.2 Hz); was 7.08(d, 1H, J=16.2 Hz); 7.29 trend is 7.50 (m, 7H); of 7.48(d, 2H, J=8,3 Hz); of 7.64-to 7.68 (m, 1H); of 7.97(d, 2H, J=8,4 Hz).

(e) Methyl ester of 4-[4-(4'-hydroxymethyluracil-2-yl)but-3-EN- (E)-1-inyl]benzoic acid

Similarly to the method of example 32 (a), on the basis of 387 mg (of 0.91 mmol) obtained in example 47(e) complex"ptx2">

1H-NMR-spectrum (deuterochloroform), M. D.: 1,79(ush.s, 1H); 3,91 (s, 3H); rate 4.79 (s, 2H); 6,36(d, 1H, J=16.2 Hz); 7,07(d, 1H, J=16.2 Hz); 7,32 (m, 5H); 7,45-7,49 (m, 2H); 7,47(d, 2H, J=8,4 Hz); a 7.62 to 7.68 (m, 1H); of 7.97(d, 2H, J=8,4 Hz).

(W) 4-[4-(4'-Hydroxymethyluracil-2-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1 (e) on the basis of 310 mg (0.84 mmol) obtained in example 47(e) complex methyl ester, receive 250 mg(84%) 4-[4-(4'-hydroxymethyluracil-2-yl)but-3-EN-(E)-1-inyl] benzoic acid in the form of a powder beige with so pl. 227oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 4,69 (s, 2H); 6,33(d, 1H, J=16.2 Hz); 7.03 is(d, 1H, J=16,3 Hz); 7,27 was 7.36(m, 5H); 7,42-

7,46(m, 2H); 7,44(d, 2H, J=8,3 Hz); 7,62-7,66(m, 1H); 7,94(d, 2H, J=8,3 Hz).

Example 48: 4-{4-[4'-(2-Hydroxyethyl)biphenyl-2-yl]but-3-EN-(E)-1 - inyl} benzoic acid

(a) 2-(4-Bromophenyl)ethanol

In a three-neck flask with a volume of 2 l in a stream of nitrogen injected 15,00 g (81,9 mmol) of 4-rostirolla and 300 ml of tetrahydrofuran. Cooled to a temperature of 0oC, was added dropwise 482 ml (245,8 mmol) 9-borabicyclo[3.3.1]nonane (0.5 M solution in tetrahydrofuran), keeping the temperature below 5oC. the Reaction medium is stirred for four hours at room temperature, then cooled to 0oC, pricap is a, maintaining the temperature below 10oC. the Reaction medium is stirred for four hours at room temperature, then add water, 1N., hydrochloric acid, extracted with diethyl ether, the organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by chromatography on a column of silica, elwira with a mixture of 30% ethyl acetate and 70% heptane. After evaporation of the solvents get 12,92 g (78%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 1,54 (s, 1H); of 2.81(t, 2H, J 6.5 Hz); a 3.83(t, 2H, J=6.4 Hz); 7,10(d, 2H, J=8,32 Hz); the 7.43(d, 2H, J=8,3 Hz).

(b) 4-Ethoxymethyleneamino

Similarly to the method of example 47 (a), on the basis of 12,92 g (64,3 mmol) obtained in example 48 (a) 2-(4-bromophenyl)-ethanol, receive 16,65 g (100%) of target compound as a yellow oil.

91H-NMR-spectrum (deuterochloroform), M. D.: 1,17 (t, 3H, J=7.0 Hz); 2,84 (t, 2H, J=6,7 Hz); 3,50 (K, 2H, J=7,1 Hz); 3,74 (t, 2H, J=6,7 Hz); with 4.64 (s, 2H); 7,10(d, 2H, J=8,2 Hz); 7,40(d, 2H, J=8,2 Hz).

(in) 4-Ethoxymethyleneamino acid

Similarly to the method of example 2 (a), on the basis of 17,31 g (66,8 mmol) obtained in example 48(b) 4-atoxin the range (deuterochloroform), in M. D.: 1,19 (t, 3H, J=7.0 Hz); 2,99 (t, 2H, J=6,7 Hz); 3,54 (K, 2H, J=7,1 Hz); a-3.84 (t, 2H, J=6.9 Hz); 4,70 (s, 2H); 7,38(d, 2H, J=7.9 Hz); 8,16(d, 2H, J=7,8 Hz).

(g) 4'-Ethoxymethylene-2-carboxaldehyde

Similarly to the method of example 21(a), based on 14,00 g (67,0 mmol) 4-ethoxymethyleneamino acid obtained in example 48(C), and 8,30 g (44,8 mmol) of 2-bromo-benzaldehyde, get 11,68 g (93%) of target compound as an orange oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 1.18 (t, 3H, J=7,1 Hz); 2,98 (t, 2H, J= 6.8 Hz); 3,54 (K, 2H, J=7,1 Hz); a-3.84(t, 2H, J=6.9 Hz); 4,70(s, 2H); 7.29 trend-7,37(m, 4H); 7,44(d, 1H, J= 7.5 Hz); 7,49(d, 1H, J=7,6 Hz); to 7.61(DD, 1H, J=7,4/1,4 Hz); 8,02(DD, 1H, J=7,7/1.3 Hz); 9,98(s, 1H).

(d) 2-((E)-2-Iodine)-4'-ethoxyresorufin

Similarly to the method of example 1(g), on the basis of 3.50 g (12.6 mmol) of 4'-ethoxymethylene-2-carboxaldehyde obtained in example 48 (d) receive 2,07 g (40%) of target compound as a pale yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 1,19 (t, 3H, J=7,1 Hz); of 2.97 (t, 2H, J=6.8 Hz); 3,54 (K, 2H, J=7,1 Hz); of 3.85 (t, 2H, J=6.8 Hz); 4,71 (s, 2H); 6.73 x (d, 1H, J=14,8 Hz); 7.23 percent-7,49(m, 9H).

(e) Methyl ester of 4-[4-(4'-ethoxymethylene-2-yl)-but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 11(e), by reacting 2,07 g (5.1 mmol) of 2-((E)-(2-iodine)-4 the slots, get 1,02 g (46%) of target compound in the form of powder light yellow color with so pl. 68oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 1,19 (t, 3H, J=7,1 Hz); 2,98 (t, 2H, J= 6.9 Hz); 3,54 (K, 2H, J=7,1 Hz); 3,86(t, 2H, J=6.9 Hz); 3,91(s, 3H); 4,71(s, 2H); 6,35(d, 1H, J=16.2 Hz); to 7.09(d, 1H, J=16.2 Hz); 7,30-7,38 (m, 7H); of 7.48(d, 2H, J=8,3 Hz); of 7.64-to 7.67(m, 1H); of 7.97(d, 2H, J=8,3 Hz).

(g) Methyl ester 4-{4-[4'-(2-hydroxyethyl)biphenyl-2-yl]-but-3 - EN-(E)-1-inyl}benzoic acid

Similarly to the method of example 32 (a), on the basis of 670 mg (1.5 mmol) obtained in example 48(e) complex methyl ester, get 540 mg (93%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 1,47 (t, 1H, J=5,9 Hz); 2,96(t, 2H, J=6.5 Hz); 3,91 (s, 3H); 3.95 to (K, 2H, J=6.4 Hz); 6,36(d, 1H, J= 16.2 Hz); 7,10(d, 1H, J=16.2 Hz); 7,32 - 7,39(m, 7H); of 7.48(d, 2H, J=8,4 Hz); of 7.64-to 7.68(m, 1H); of 7.97(d, 2H, J=8,4 Hz).

(C) 4-{4-[4'-(2-Hydroxyethyl)biphenyl-2-yl]but-3-EN-(E)-1-inyl} benzoic acid

Similarly to the method of example 1(e) on the basis of 540 mg (1.4 mmol) obtained in example 48 (W) complex methyl ester, obtain 470 mg(90%) 4-{ 4-[4'-(2-hydroxyethyl)biphenyl-2-yl] but-3-EN-(E)-1-inyl} benzoic acid in the form of a powder beige with so pl. 205oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,84 (t,-7,60(m, 1H); 7,88(d, 2H, J=8,2 Hz).

Example 49: 4-[4-(3'-Methylbiphenyl-3-yl)but-3-EN-(E)-1-inyl]benzoic acid

(a) 3-Methylphenylamine acid

Similarly to the method of example 2 (a), on the basis of 9,07 g (53,0 mmol) 3-methylpropanol get 7,12 g (99%) of target compound in a solid white color with so pl. below 30oC.

1H-NMR-spectrum (deuterochloroform), M. D.: the 2.46(s, 3H); 7,28-of 7.55(m, 2H); of 7.90-of 8.06(m, 2H).

(b) 3'-Methylbiphenyl-2-carboxaldehyde

Similarly to the method of example 21 (a), on the basis of 7,12 g (52,4 mmol) 3-methylphenylamine acid and 6,46 g (34,9 mmol) 3-bromobenzaldehyde get 6,56 g (90%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,44 (s, 3H); of 7.23(t, 1H, J= 7.2 Hz); 7,33-7,44(m, 3H); of 7.60(t, 1H, J=7,6 Hz); 7,83-7,87(m, 2H); 8,09-8,10(m, 1H); to 10.09(c, 1H).

(a) 2-((E)-2-Iodine)-3'-methylbiphenyl

Similarly to the method of example 1(g), based on 3,34 g (17,0 mmol) obtained in example 49(b) 3'-methylbiphenyl-3-carboxaldehyde get 5,47 g (100%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42 (s, 3H); 6.90 to(d, 1H, J= 14,9 Hz); 7,16-7,52(m, 8H); 7,51(d, 1H, J=14,9 Hz).

(d) Methyl ester of 4-[4-(3'-methylbiphenyl-3-yl)but-3-EN-(E)-1-inyl] benzoic acid

Analogically 49(b), with the 2.46 g (15,4 mmol) of methyl ester 4-ethynylbenzene acid, get to 3.09 g (57%) of target compound in the form of a yellow powder with so pl. 98-100oC.

H-NMR-spectrum (deuterochloroform), M. D.: 2,43(s, 3H); to 3.92(s, 3H); 6,46(d, 1H, J= 16.2 Hz); to 7.15(d, 1H, J=16.2 Hz); 7.18 in-7,21(m, 1H); 7,31 was 7.45(m, 5H); 7,51-of 7.55(m, 1H); 7,53 (d, 2H, J=8.5 Hz); a 7.62 (s, 1H); of 8.00 (d, 2H, J=8,4 Hz).

(d) 4-[4-(3'-Methylbiphenyl-3-yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of a 1.25 g (mmol) obtained in example 49(g) complex methyl ester, get 1,15 g(96%) 4-[4-(3'-methylbiphenyl-3-yl)-but-3-EN-(E)-1-inyl] benzoic acid in the form of powder light yellow color with so pl. 224-228oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: of 2.26(s, 3H); 6,69(d, 1H, J=16,3 Hz); 7,05-7,38(m, 3H); 7,41 - 7,49(m, 5H); 7,47(d, 2H, J= 8,4 Hz); 7,74(s, 1H); 7,83 (d, 2H, J=8,3 Hz); 13,00(ush.s, 1H).

Example 50: 4-[4-(2-Pyridine-4-ylphenyl)but-3-EN-(E)-1-inyl] benzoic acid

(a) 2 Pyridine-4-yl-benzaldehyde

Similarly to the method of example 21 (a), on the basis of 2.50 g (of 16.7 mmol) of 2-formylbenzeneboronic acid and 2.16 g (11.1 mmol) of 4-broneeringukoodid receive 1.98 g (97%) of target compound in the form of a white powder with so pl. 59oC.

1H-NMR-spectrum (deuterochloroform), M. D. : 7,33(d, 2H, J=6.0 Hz); the 7.43(DD, 1H, J=8,4/0,9 who yl]pyridine

Similarly to the method of example 1(g), on the basis of 1.98 g (10,8 mmol) obtained in example 50 (a) 2-pyridin-4-yl-benzaldehyde, obtain 490 mg (15%) of target compound in the form of oil is green in color.

1H-NMR-spectrum (deuterochloroform), M. D.: at 6.84(d, 1H, J=14,8 Hz); 7,28-7,51(m, 7H); 8,69(d, 2H, J=5,5 Hz).

(C) Methyl ester of 4-[4-(2-pyridin-4-ylphenyl)but-3-EN-(E)-1 - inyl]benzoic acid

Similarly to the method of example 11(e), by reacting 490 mg (1.6 mmol) obtained in example 50(b) 4-[2-((E)-2-iodine)phenyl] pyridine with 380 mg (2.4 mmol) of methyl ester 4-ethynylbenzene acid, receive 200 mg (37%) of target compound in the form of a powder orange with so pl. 120oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,91 (s, 3H); 6,38(d, 1H, J= 16.1 Hz); 6,99(d, 1H, J= 16.1 Hz); 7,29 - to 7.32(m, 3H); 7,39-7,44 (m, 2H); 7,49(d, 2H, J= 8,3 Hz); to 7.67 - of 7.70(m, 1H); 7,98 (l, 2H, J=8,3 Hz); to 8.70(d, 2H, J=5,2 Hz).

(g) 4-[4-(2-Pyridin-4-ylphenyl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1(e) on the basis of 200 mg (0.6 mmol) obtained in example 50 (C) complex methyl ester, get 190 mg(99%) 4-[4-(2-pyridine-4-ylphenyl)but-3-EN-(E)-1-inyl] benzoic acid as white powder with so pl. 169-177oC.

1H-NMR-spectrum (metadatareader), M. D.: 6,70(d, 1H, J=16,fenil)but-3-EN-(E)-1-inyl]- benzoic acid

(a) 2 Pyridine-3-yl-benzaldehyde

Similarly to the method of example 21(a), on the basis of 2.50 g (of 16.7 mmol) of 2-formylbenzeneboronic acid and 1.76 g (11.1 mmol) of 3-bromopyridine, obtain 1.48 g (73%) of target compound in the form of a yellow powder with so pl. 54oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 7,4 0-7,45 (m, 2H); 7,58 (t, 1H, J= 7.5 Hz); of 7.69(DD, 1H, J=7,4/1.5 Hz); 7,72(DD, 1H, J=7,9/2,0 Hz); 8,07(DD, 1H, J=7,8/1.3 Hz); 8,67-8,72(m, 2H); 9,99(s, 1H).

(b) 3-[2-((E)-2-Iodine)phenyl]pyridine

Similarly to the method of example 1(g), on the basis of 1.48 g (8.1 mmol) obtained in example 51 (a) 2-pyridin-3-yl-benzaldehyde, receive 600 mg (24%)of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: PC 6.82(d, 1H, J=14,8 Hz); 7,26-7,30(m, 2H); 7,34-7,42(m, 3H); 7,50-7,53(m, 1H); 7,63-to 7.67(m, 1H); 8,61-8,65(m, 2H).

(C) Methyl ester of 4-[4-(2-pyridin-3-ylphenyl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 11(e), by reacting 600 mg (2.0 mmol) obtained in example 51(b) 3-[2-((E)-2-iodine) phenyl] pyridine with 469 mg (2.9 mmol) of methyl ester 4 - ethynylbenzene acid, receive 550 mg (83%) of target compound in the form of a yellow powder with so pl. 85oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,91 (s, 3H); 6,38(d, 1H, J= 16.1 Hz); 7,00(d, 1H, J= 16.2 Hz); 7,30 - to 7.50(m, 6H); 7BR>
Into the flask inject 550 mg (1.6 mmol) obtained in example 51 (C) complex methyl ester, 10 ml of methanol and 10 ml of tetrahydrofuran. Add 1.6 ml (16.0 mmol) 10h. the sodium hydroxide solution in methanol and refluxed for one hour. Is evaporated to dryness, add ethyl acetate, acidified to pH 5 with citric acid, the precipitate filtered off, washed with water, dried in a vacuum drying Cabinet. Obtain 290 mg of 4-[4-(2-pyridin-3-ylphenyl)but-3-EN- (E)-1-inyl]benzoic acid in the form of a solid beige color with so square 264oC.

1H-NMR-spectrum (metadatareader), M. D.; of 6.68(d, 1H, J=16.1 Hz); 7.23 percent-7,34 (m, 4H); 7,38-7,44 (m, 2H); 7,58-of 7.70(m, 1H); to 7.61(d, 2H, J=8,3 Hz); 7,82-a 7.85 (m, 1H); at 8.36(d, 2H, J=8,2 Hz); 8,72 - a total of 8.74(m, 1H); 8,84(d, 1H, J=2.0 Hz).

Example 52: 4-[4-(3-Methoxyethoxy-4 methylbiphenyl-2-yl)but-3-EN- (E)-1-inyl]benzoic acid

(a) 2-Formyl-3-methoxybenzenesulfonyl

Similarly to the method of example 12(b), based on 11,00 g (72,3 mmol) 2-hydroxy-6-methoxybenzaldehyde get 15,00 g (73%) of target compound in the form of a powder beige with so pl. 65-67oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,98 (s, 3H); 6.90 to (d, 1H, J=8,3 Hz); 7,07(d, 1H, J=8.6 Hz); of 7.60 (t, 1H, J=8.5 Hz); 10,46(c, 1H).

(b) 3-Methoxy-4'-mativity and 14,50 g (51,0 mmol) obtained in example 52(a) triflate, get 10,80 g (94%) of target compound in the form of crystals pale yellow with so pl. 89-91oC.

1H-NMR-spectrum (deuterochloroform), M. D.: is 2.40 (s, 3H); of 3.95(s, 3H); 6,98(t, 2H, J=7,3 Hz); 7,22(s, 4H); 7,51(t, 1H, J=7,7 Hz); 10,07 (s, 1H).

(b) 3-Hydroxy-4'-methylbiphenyl-2-carboxaldehyde

Similarly to the technique of example 17 (b), on the basis of 10,00 g (a 44.2 mmol) of 3-methoxy-4'-methylbiphenyl-2-carboxaldehyde obtained in example 52(b), receive 7,00 g (75%) of target compound in the form of orange powder with so pl. 52 - 53oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42 (s, 3H); 6.87 in(DD, 1H, J= 7,7/0,8 Hz); 6,97(d, 1H, J=8.5 Hz); 7,26(s, 4H); 7,51(t, 1H, J and 7.6 Hz); 9,85(s, 1H).

(g) 3-Methoxyethoxy-4'-methylbiphenyl-2-carboxaldehyde

Similarly to the method of example 28 (a), based on 7,00 g (33.0 mmol) obtained in example 52 (b) of phenol and 3,18 g (40.0 mmol)m yellowmaterial simple ester, get to 7.95 g (94%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: is 2.40(s, 3H); of 3.54 (s, 3H); 5,31(s, 2H); 7,02(d, 1H, J=7,6 Hz); 7.18 in - 7,26(m, 5H); 7,49(t, 1H, J=7.8 Hz); 10,11(s, 1H).

(d) 2-((E)-2-Iodine)-3-methoxyethoxy-4'-methylbiphenyl

Similarly to the method of example 1(g), according to 7.95 g (31,0 mmol) obtained in example 52 (g) 3-methoxyethoxy-4'-metalbite the spectrum (deuterochloroform), in M. D.: is 2.41 (s, 3H); 3,51(s, 3H); 5.25 in(s, 2H); 6.87 in(d, 1H, J= 14,8 Hz); 6,93(DD, 1H, J=7,5/1.2 Hz); 7,10-to 7.35(m, 5H); 9,84(s, 1H).

(e) Methyl ester of 4-[4-(3-methoxyethoxy-4 methylbiphenyl-2 - yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1 (d), by the interaction of 1.30 g (3.4 mmol) of 2-((E)-2-iodine)-3-methoxyethoxy-4'-methylbiphenyl obtained in example 52 (e), 650 mg (4.1 mmol) of methyl ester 4-ethynylbenzene acid, receive 750 mg (53%) of target compound as a yellow powder corresponding to a mixture of Z/E-isomers.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42 (s, 3H); of 3.54(s, 3H); 3,91(s, 3H); and 5.30(s, 2H); to 6.57(d, 1H, J=16.5 Hz); of 7.48 (d, 1H, J=16.2 Hz); 7.18 in-7,26(m, 7H); 7,46(d, 2H, J=8,3 Hz); of 7.96 (d, 2H, J=8,4 Hz).

(W) 4-[4-(3-Methoxyethoxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

Similarly to the method of example 1 (e), starting from 200 mg (0.48 mmol) obtained in example 52 (e) complex methyl ester, obtain 152 mg(80%) 4-[4-(3-methoxyethoxy-4'-methylbiphenyl-2-yl)but - 3-EN-(E)-1-inyl] benzoic acid as a yellow powder with so pl. 160-162oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: is 2.37(s, 3H); 3,44(s, 3H); are 5.36(s, 2H); to 6.57(d, 1H, J=16.5 Hz); 6.89 in (d, 1H, J=16,3 Hz); 6,91 (d, 1H, J=7.8 Hz); 7.18 in and 7.36(m, 6H); 7,53(d, 2H, J=8,2 Hz); of 7.90(d, 2H, J=8,3 Hz); 13,08(ush.s, 1H).

Example methylbiphenyl-2-yl)-but-3-EN- (E)-1-inyl]benzoic acid

Similarly to the method of example 32 (a), on the basis of 500 mg (1.2 mmol) obtained in example 52(e) complex methyl ester, obtain 350 mg (80%) of target compound in the form of a powder beige color formed by the mixture of (Z)- and (E)-isomers.

1H-NMR-spectrum (deuterochloroform), M. D. [(E)-isomer]: to 2.42(s, 3H); 3,91(s, 3H); 5,38(s, 1H); 6,53(d, 1H, J=16.6 Hz); 6,88-to 6.95(m, 3H); 7,20-7,26(m, 5H); 7,47(d, 2H, J=8,3 Hz); of 7.97(d, 2H, J=8,4 Hz).

(b) 4-[4-(3-Hydroxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1(e) on the basis of 320 mg (0.87 mmol) of a mixture of methyl esters obtained in example 53 (a), 250 mg get(80%) 4-[4-(3-hydroxy-4'-methylbiphenyl-2-yl)but-3-EN- (E)-1-inyl]benzoic acid as a yellow powder with so pl. 221-223oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: is 2.37(s, 3H); 6,70(d, 1H, J= 8,3 Hz); 6.75 in(d, 1H, J=16.6 Hz); 6.87 in(d, 1H, J=16.4 Hz); 6,93(d, 1H, J=7.8 Hz); 7,16(d, 1H, J=7,6 Hz); 7.18 in(d, 2H, J=8.0 Hz); 7,28(d, 2H, J=8.0 Hz); 7,51(d, 2H, J=8,3 Hz); 7,89(d, 2H, J=8,3 Hz); accounted for 10.39(s, 1H).

Example 54: 4-[4-(3-Methoxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

(a) 2-((E)-2-Iodine)-3-methoxy-4'- methylbiphenyl

Similarly to the method of example 1(g), based on 4,43 g (a 19.6 mmol) obtained in example 52(b) connection receive 3,61 g (53%) of target compound is 7,41(m, 6H).

(b) Methyl ester of 4-[4-(3-methoxy-4 methylbiphenyl-2-yl)but-3-EN- (E)-1-inyl]benzoic acid

Similarly to the method of example 1 (d), by reacting 3,61 g (10.3 mmol) obtained in example 54 (a)connection from 1.80 g (11.3 mmol)of methyl ester 4-ethynylbenzene acid, receive 900 mg (23%) of target compound in the form of a yellow powder with so pl. 124-126oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42(s, 3H); 3,91 (s, 3H); 3,93 (s, 3H); 6.90 to (d, 1H, J=7.4 Hz); 6,93 (d, 1H, J=7,1 Hz); 7,00 (d, 1H, J= 16.5 Hz); 7.24 to 7,30 (m, 5H); was 7.45 (d, 2H, J=8,4 Hz); of 7.95 (d, 2H, J=8,4 Hz).

(C) 4-[4-(3-Methoxy-4'-methylbiphenyl-2-yl)but-3-EN-(E) -1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 900 mg (2.3 mmol) obtained in example 54(b) complex methyl ester, get 700 mg(82%) 4-[4-(3-methoxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid in the form of powder light yellow color with so pl. 200-202oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: of 2.51 (s, 3H); is 4.03 (s, 3H); of 6.71(d, 1H, J=16.5 Hz); 7,07 (d, 1H, J=16.4 Hz); 6,98(d, 1H, J=7,6 Hz); 7.03 is(d, 1H, J=7.9 Hz); 7,32-7,40 (m, 5H); 7,53(d, 2H, J=8,3 Hz); with 8.05(d, 2H, J=8,3 Hz).

Example 55: 4-[4-(4'-Ethoxymethylene-2-yl)but-3-EN-(E)- 1-inyl] benzoic acid

Analogously to example 1(e), based on ethylbiphenyl-2-yl)but-3-EN- (E)-1-inyl]benzoic acid in the form of a powder beige with so pl. 183oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: of 1.27 (t, 3H, J=7,1 Hz); 3,70 (K, 2H, J=7,1 Hz); and 4.68 (s, 2H); a 4.83 (s, 2H); 6,36 (d, 1H, J=16.2 Hz); 7,07 (d, 1H, J=16.2 Hz); 7,29-7,47 (m, 7H); 7,47 (d, 2H, J=8,3 Hz); the 7.65 to 7.68 (m, 1H); to 7.99 (d, 2H, J=8,3 Hz).

Example 56: Methyl ester of 4-[4-(4'-ethoxyethoxy-biphenyl-2 - yl)but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1(e) on the basis of 350 mg (0,79 mmol) obtained in example 48(e) complex methyl ester, get 320 mg(94%) 4-[4-(4'-ethoxymethylene-2-yl)but-3-EN-(E)-1-inyl] benzoic acid in the form of a powder beige with so pl. 135oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 1,19 (t, 3H, J=7,1 Hz); 2,99(t, 2H, J=6.8 Hz); 3,55 (K, 2H, J= 7,1 Hz); a 3.87 (t, 2H, J=6.8 Hz); 4.72 in(c, 2H); 6,36(d, 1H, J=16.2 Hz); 7,11(d, 1H, J= 16.2 Hz); 7,25-7,38(m, 7H); 7,50(d, 2H, J=8,2 Hz); of 7.64-to 7.68(m, 1H); 8,04(d, 2H, J=8,2 Hz).

Example 57: 2-Methyl-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

(a) Methyl ester of 4-trimethylsilylethynyl-2-methylbenzoic acid

Similarly to the method of example 1(a), on the basis of 4,00 g (18.4 mmol) of methyl ester of 4-bromo-2-methylbenzoic acid, receive of 3.54 g (100%) of target compound as a yellow oil.

1H-NMR is R 4-ethinyl-2-methylbenzoic acid

In a three-neck flask of 500 ml mix 3,29 g (17.6 mmol) obtained in example 57 (a) compounds with 50 ml of tetrahydrofuran and added dropwise to 19.3 ml (or 19.3 mmol) of 1.0 M solution of tetrabutylammonium in tetrahydrofuran. Stirred for one hour at room temperature, the reaction medium is poured into water, extracted with diethyl ether, the organic phase is decanted, dried over magnesium sulfate and evaporated. Obtain 1.20 g (59%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 2.58 (s, 3H); 3,18(s, 1H); to 3.89(s, 3H); 7,34-7,42(m, 2H); 7,87 (d, 1H, J=7.9 Hz).

(C) Methyl ester of 2-methyl-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)- 1-inyl]benzoic acid

Similarly to the method of example 1 (d), by the interaction of 1.20 g (10.4 mmol) obtained in example 57(b) connection from 3.67 g (11,4 mmol) obtained in example 2 (g) connection receive 900 mg (23%) of target compound in the form of a white powder with so pl. 105oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43(s, 3H); 2.57 m (s, 3H); 3,88 (s, 3H); 6,34 (d, 1H, J=16.2 Hz); to 7.09 (d, 1H, J=16.2 Hz); 7,26-7,38 (m, 9H); 7,63-to 7.67 (m, 1H); 7,86 (d, 1H, J=8.0 Hz).

(g) 2-Methyl-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1 (e), based on ITIL-2-yl)but-3-EN-(E)-1-inyl] benzoic acid as white powder with so pl. 187oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,43(s, 3H); at 2.59(s, 3H); 6,34 (d, 1H, J=16.2 Hz); was 7.08 (d, 1H, J= 16.2 Hz); 7,26-7,37 (m, 6H); 7,34 (d, 2H, J=7.9 Hz); 7,63-to 7.67 (m, 1H); to $ 7.91 (d, 2H, J=7,8 Hz).

Example 58: 2-Hydroxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

(a) Methyl ester of 4-trimethylsilylethynyl-2-hydroxybenzoic acid

Similarly to the method of example 1(a), on the basis of 4,00 g (14.4 mmol) of methyl ester 4-iodine-2-hydroxybenzoic acid, receive of 3.07 g (86%) of target compound as an orange oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 0,06(s, 9H); of 3.75(s, 3H); 6,76 (DD, 1H, J=8,2/1.5 Hz); 6.87 in (d, 1H, J=1.4 Hz); 7,56 (d, 1H, J=8,2 Hz); 10,53 (s, 1H).

(b) Methyl ester of 4-ethinyl-2-hydroxybenzoic acid

Similarly to the method of example 57(b), on the basis of of 3.07 g (12.4 mmol) obtained in example 58 (a) connection receive 2,48 g (100%) of target compound in the form of a powder beige with so pl. 62oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,21(s, 1H); of 3.96(s, 3H); 6,98 (DD, 1H, J=8,2/1.5 Hz); 7,10 (d, 1H, J=1.3 Hz); for 7.78 (d, 1H, J=8,2 Hz); of 10.76(s, 1H).

(C) Methyl ester of 2-hydroxy-4-[4-(4'-methylbiphenyl-2-yl)-but-3 - EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1 (d), the d 2 (g) connection, obtain 1.24 g (26%) of target compound in the form of a yellow powder with so pl. 96oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43(s, 3H); of 3.94 (s, 3H); 6,33 (d, 1H, J= 16.2 Hz); 6,92 (DD, 1H, J=8,2/1.5 Hz); 7.03 is (d, 1H, J=1.3 Hz); 7,11 (d, 1H, J=16.2 Hz); 7,22-7,29(m, 4H); 7,31-7,38(m, 3H); 7,63-7,66(m, 1H); of 7.75 (d, 1H, J=8,2 Hz); a 10.74 (s, 1H).

(g), 2-Hydroxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1(e) on the basis of 1.24 g (3.4 mmol) obtained in example 58(C) complex methyl ester, obtain 910 mg (76%) of 2-Hydroxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN- (E)-1-inyl]benzoic acid as a yellow powder with so pl. 211oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,43 (s, 3H); 6,34 (d, 1H, J=16.2 Hz); 6.90 to (DD, 1H, J= 8,2/1.5 Hz); 6,98 (d, 1H, J=1.3 Hz); to 7.09 (d, 1H, J=16,3 Hz); 7,22-7,38(m, 7H); 7,63-to 7.67(m, 1H); 7,79 (d, 1H, J=8.1 Hz); 11,29(ush.s, 1H).

Example 59: 6-[4-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]- pyridine-3-carboxylic acid

(a) Ethyl ester of 6-trimethylsilylethynyl-3-carboxylic acid

Similarly to the method of example 1(a), on the basis of 4,00 g (14.4 mmol) of the ethyl ester of 6-iodopyridine-3-carboxylic acid, receive 3,29 g (92%) of target compound in the form of a powder beige with so pl. 55oC.

1H-NMR-SP is J=2.1 Hz).

(b) Methyl ester of 6-ethynylpyridine-3-carboxylic acid

Similarly to the method of example 57(b), based on 3,29 g (13.3 mmol) obtained in example 59(a) connections, gain of 1.00 g (43%) of target compound in the form of flakes beige with so pl. 35oC.

1H-NMR-spectrum (deuterochloroform), M. D.: of 1.42 (t, 3H, J=7,1 Hz); of 3.33(s, 1H); 4,42 (K, 2H, J=7.2 Hz); 7,56 (d, 1H, J=8,1 Hz); of 8.28 (DD, 1H, J=8,1/2,1 Hz); 9,18 (d, 1H, J=2.0 Hz).

(C) Methyl ester of 6-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1 - inyl]pyridine-3-carboxylic acid

Similarly to the method of example 1 (d), by reacting 920 mg (5.3 mmol) obtained in example 59(b) connection with 1.86 g (5.8 mmol) obtained in example 2 (g) connection, get 680 mg (35%) of target compound in the form of a powder beige with so pl. 75-80oC.

1H-NMR-spectrum (deuterochloroform), M. D.: of 1.41 (t, 3H, J=7,1 Hz); 2,43 (s, 3H); to 4.41 (K, 2H, J=7,1 Hz); 6,35 (d, 1H, J=16.2 Hz); 7,19-7,26(m, 5H); 7,34-7,39(m, 3H); 7,47 (d, 1H, J=8,2 Hz); of 7.64-to 7.68 (m, 1H); 8,23 (DD, 1H, J=8,2/2,1 Hz); to 9.15 (d, 1H, J=1.6 Hz).

(g) 6-[4-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]pyridine-3 - carboxylic acid

Similarly to the method of example 1(e) on the basis of 680 mg (1.9 mmol) obtained in example 60 (C) complex methyl ester, obtain 530 mg(84%)6-[4-(4'-methylbiphenyl-2-yl)-but-3-EN-(E)- 1-inyl] pyridine-3-carbon is hexacyanometallate), in M. D.: of 2.25 (s, 3H); 6,18(d, 1H, J=16.2 Hz); 6,99-7,21(m, 7H); of 7.48-7,51(m, 1H); of 8.06 (DD, 1H, J=8,1/2,0 Hz); 8,96 (d, 1H, J=1.3 Hz).

Example 60: 5-[4-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]- pyridine-2-carboxylic acid

(a) Methyl ester of 6-trimethylsilylethynyl-2-carboxylic acid

Similarly to the method of example 1(a), based on 7,00 g (to 26.6 mmol)of methyl ester of 6-iodopyridine-2-carboxylic acid, receive 4,25 g (68%) of target compound in the form of orange powder with so pl. 45oC.

1H-NMR-spectrum (deuterochloroform), M. D.: of 0.28 (s, 9H); 4,01(s, 3H); 7,87 (DD, 1H, J=8,1/2,0 Hz); 8,08 (d, 1H, J=8,1 Hz); 8,77 (d, 1H, J=1.3 Hz).

(b) Methyl ester of 6-ethynylpyridine-2-carboxylic acid

Similarly, Metalica of example 57(b), on the basis of 2.25 g (9.6 mmol) obtained in example 60(a) connection receive 380 mg (24%) of target compound in the form of a yellow powder with so pl. 40-45oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3.40 in(s, 1H); was 4.02(s, 3H); to 7.93 (DD, 1H, J=8,1/2,0 Hz); to 8.12(d, 1H, J=8,1 Hz); 8,83 (d, 1H, J=1.9 Hz).

(C) Methyl ester 5-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)- 1-inyl]pyridine-2-carboxylic acid

Similarly to the method of example 1(d), by the interaction obtained in example 60(b) connection with 568 mg (1.8 mmol) obtained in example 2(g) connections, receive 130 mg (23%) cereform), in M. D.: 2,44(s, 3H); 4,01(s, 3H); 6,35 (d, 1H, J=16,3 Hz); 7,17 (d, 1H, J=16.2 Hz); 7,26-7,38(m, 6H); 7,62 to 7.75(m, 2H); to 7.84 (DD, 1H, J=8,2/1.2 Hz); 8,08 (d, 1H, J=8,1 Hz); is 8.75 (d, 1H, J=1.2 Hz).

(g) 5-[4-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] pyridine-2-carboxylic acid

Similarly to the method of example 1(e) on the basis of 130 mg (from 0.37 mmol) obtained in example 60 (C) complex methyl ester, receive 90 mg(72%)5-[4-(4'- methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] pyridine-2-carboxylic acid in the form of a powder beige with so pl. 190oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,44 (s, 3H); 6,36 (d, 1H, J=16.2 Hz); 7,19(d, 1H, J=16,3 Hz); 7,22-7,40(m, 7H); the 7.65 to 7.68(m, 1H); 7,92 (DD, 1H, J=8,1/1,8 Hz); 8,16 (d, 1H, J=8,1 Hz); 8, 63 (s, 1H).

Example 61: 5-[4-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]- thiophene-3-carboxylic acid

(a) Methyl ester thiophene-3-carboxylic acid

In a three-neck flask with a volume of 2 l and in a stream of nitrogen injected 19,85 g (154,9 mmol) thiophene-2-carboxylic acid and 700 ml of methanol, was added dropwise 7 ml of concentrated sulfuric acid and refluxed for 16 hours. Cool, methanol is evaporated, water is added, extracted with diethyl ether, the organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered SUP>H-NMR-spectrum (deuterochloroform), M. D.: a 3.87 (s, 3H); 7,30 (DD, 1H, J=3,1/5,0 Hz); 7,53 (DD, 1H, J=1,1/5,1 Hz); 8,10 (DD, 1H, J=1,1/3,0 Hz).

(b) Methyl ester of 5-bromothiophene-3-carboxylic acid

In a three-neck flask with a volume of 2 l in a stream of nitrogen injected 24,74 g (174,0 mmol) obtained in example 61 (a) connection and 410 ml of dichloromethane. Cooled to a temperature of 10oC and add in small portions 51,04 g (382,8 mmol) of aluminium chloride. The medium is then heated to a temperature of 35oC and added dropwise 30,60 g of bromine in the form of a solution in 30 ml of dichloromethane. Reached boiling under reflux is continued for one hour, then the reaction medium is cooled and poured into a mixture of water with diethyl ether. The product is extracted with diethyl ether, the organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The resulting residue is purified by column chromatography on silica, elwira with a mixture of 20% dichloromethane and 80% heptane. After evaporation of the solvents get 27,42 g (71%) of target compound in the form of crystals pale yellow with so pl. below the 40oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,86 (s, 3H); 7,47 (d, 1H, J=1.5 Hz); 7,99 (d, 1H, J=1.4 Hz).

(stepping down from 27,42 g (124,0 mmol) obtained in example 61(b) connection get 16,70 g (66%) of target compound as an orange oil.

1H-NMR-spectrum (deuterochloroform), M. D.: a 0.25(s, 9H); 3,85(s, 3H); of 7.60 (d, 1H, J=1.2 Hz); of 7.96 (d, 1H, J=1.2 Hz).

(d) Methyl ester of 5-idenitifed-3-carboxylic acid

Similarly to the method of example 57(b), on the basis of 16,70 g (8.5 mmol) obtained in example 61 (C) connections, get to 3.67 g (27%) of target compound in the form of a yellow powder with so pl. 42-45oC.

1H-NMR-spectrum (deuterochloroform), M. D.: on 3.36(s, 1H); a 3.87 (s, 3H); the 7.65 (d, 1H, J=1.2 Hz); 8,00 (d, 1H, J=1.2 Hz).

(d) Methyl ester 5-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1 - inyl]thiophene-3-carboxylic acid

Similarly to the method of example 1 (d), by the interaction of 1.00 g (6.0 mmol) obtained in example 61(g) connection with a 2.12 g (6.0 mmol) obtained in example 2 (g) connection receive 1.50 g (69%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43(s, 3H); 3,85(s, 3H); 6,32 (d, 1H, J=16.2 Hz); 7,07 (d, 1H, J=16.2 Hz); 7.24 to 7,29(m, 4H); 7,32-7,41(m, 3H); at 7.55 (d, 1H, J=1.2 Hz); 7,62-the 7.65 (m, 1H); of 7.97 (d, 1H, J=1.2 Hz).

(e) 5-[4-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] thiophene-3 - carboxylic acid

Similarly to the method of example 1(e) on the basis of 1.50 g (4.2 mmol) obtained in example 61 (e) complex methyl ester, the floor is and so pl. 156oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,43 (s, 3H); 6,32 (d, 1H, J=16.2 Hz); was 7.08(d, 1H, J=16,3 Hz); 7,25 was 7.36(m, 6H); EUR 7.57(s, 1H); to 7.61-7,66 (m, 1H); of 8.09(s, 1H).

Example 62: 3 Methoxyethoxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN- (E)-1-inyl]benzoic acid

(a) 3-Hydroxy-4-identia acid

In a three-neck flask with a volume of 1 l in a stream of nitrogen injected 25,00 g (180,00 mmol) of 3-hydroxybenzoic acid, 7.20 g (180,0 mmol) of sodium hydroxide in the form of tablets, 27,13 g (180,0 mmol) of sodium iodide and 500 ml of methanol. Cooled to 0oC and added dropwise within one hour fifteen minutes 374,30 g (180,0 mmol) of an aqueous solution of sodium hypochlorite. The reaction medium is stirred for two hours at 0oC, then add the sodium thiosulfate solution, acidified to pH 5, extracted with diethyl ether, the organic phase is washed to neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. Get 43,80 g (92%) of target compound in the form of a powder beige with so pl. 198oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: 7,13(DD, 1H, J= 8,1/1,9 Hz); the 7.43(d, 1H, J=1.8 Hz); 7,80(d, 1H, J=8,1 Hz); 10,69(ush.s, 1H); 12,98(ush.s, 1H).

(b) Methyl ester of 3-hydroxy-4-the(a) acid, get 43,54 g (94%) of methyl ester of 3-hydroxy-4-iodobenzoyl acid in the form of a powder beige with so pl. 153oC.

1H-NMR-spectrum (deuterochloroform), M. D.: the 3.89(s, 3H); to 7.25(DD, 1H, J= 8,2/1,9 Hz); 7,58(d, 1H, J=1.9 Hz); to 7.77(d, 1H, J=8,2 Hz); 8,79(ush.s, 1H).

(C) Methyl ester of 3-methoxyethoxy-4-iodobenzoyl acid

Similarly to the method of example 28(a), on the basis of 20,00 g (71,9 mmol) of methyl ester of 3-hydroxy-4-iodobenzoyl acid and 6.0 ml (79,1 mmol) METHYLCHLOROSILANE simple ester, get 12,38 g (53%) of target compound as a yellow oil.

1H-NMR-spectrum (deuterochloroform), M. D.: to 3.52(s, 3H); 3,91(s, 3H); and 5.30(s, 2H); 7,41(DD, 1H, J=8,2/1,8 Hz); 7,66(d, 1H, J=1.8 Hz); 7,86(d, 1H, J=8,2 Hz).

(d) Methyl ester of 4-trimethylsilylethynyl-3-methoxy-methoxybenzoic acid

Similarly to the method of example 1(a), on the basis of 12,38 g (38.4 mmol) obtained in example 62 (b)connection receive 11,73 g (100%) of target compound as an orange oil.

1H-NMR-spectrum (deuterochloroform), M. D.: of 0.08(s, 9H); at 3.35(s, 3H); 3,71(s, 3H); 5,10(s, 2H); 7,30 (d, 1H, J=8.0 Hz); 7,44 (DD, 1H, J=8,0/1.5 Hz); 7,53 (d, 1H, J=1.4 Hz).

(d) Methyl ester of 4-ethinyl-3-methoxyethoxymethyl acid

Similarly, Metalica of example 57(b), on the basis of 11,73 g (40,1 mmol) obtained Spectr (deuterochloroform), in M. D.: 3,43 (s, 1H); of 3.53 (s, 3H); to 3.92 (s, 3H); 5,32 (s, 2H); 7,52 (d, 1H, J=8.0 Hz); 7,66 (DD, 1H, J=8,0/1.3 Hz); for 7.78 (d, 1H, J=1.3 Hz).

(e) Methyl ester 3-methoxyethoxy-4-[4-(4'-methylbiphenyl-2-yl) but-3-EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 1 (d), by interacting with 3.89 g (17,7 mmol) obtained in example 62 (e) connection to 6.22 g (to 19.4 mmol) obtained in example 2 (g) connections, gain of 3.46 g (47%) of target compound in powder form with so pl. 64oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42 (s, 3H); 3,50(s, 3H); 3,90(s, 3H); 5,28(s, 2H); 6,40(d, 1H, J=16.2 Hz); 7,11(d, 1H, J=16.2 Hz); 7,20-7,30 (m, 3H); 7,32-7,37 (m, 4H); was 7.45(d, 1H, J=8.0 Hz); a 7.62-of 7.65(m, 2H); 7,74 (s, 1H).

(W) 3-Methoxyethoxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid

Similarly to the method of example 1(e), based on a 1.00 g (2.4 mmol) obtained in example 62(e) complex methyl ester, get 540 mg (56%) 3 methoxyethoxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1 - inyl] benzoic acid in the form of a powder beige with so pl. 185oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,43 (s, 3H); to 3.49 (s, 3H); at 5.27(s, 2H); 6,40(d, 1H, J=16.2 Hz); to 7.09(d, 1H, J= 16.2 Hz); 7,25-7,37(m, 8H); the 7.43(d, 1H, J=8.0 Hz); 7,63-7,66(m, 2H); of 7.75 (s, 1H).

Example 63: 3-Hydroxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-e is Noah acid

Similarly to the method of example 32 (a), on the basis of the 2.46 g (6.0 mmol) obtained in example 62(e) of ester, gain of 1.81 g (82%) of target compound in the form of a powder beige with so pl. 111oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43(s, 3H); 3,90(s, 3H); 6,37(d, 1H, J= 16.2 Hz); 7,13(d, 1H, J=16.2 Hz); 7,25-7,29(m, 4H); 7,34-7,39(m, 4H); at 7.55(DD, 1H, J=8,0/1.5 Hz); to 7.59(d, 1H, J=1.5 Hz); 7,63-to 7.67 (m, 1H).

(b) 3-Hydroxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1 (e) on the basis of 900 mg (2.4 mmol) obtained in example 63 (a) complex methyl ester, obtain 130 mg (15%) 3-hydroxy-4-[4-(4'-methyl-biphenyl-2-yl) but-3-EN-(E)-1-inyl]benzoic acid as a yellow powder with so pl. 101oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,47 (s, 3H); 6,69 (s, 1H); 6,97(d, 1H, J=16.1 Hz); 7,26-7,49(m, 7H); 7,56(d, 1H, J=8,2 Hz); 7,60-7,74 (m, 2H); of 7.97(d, 1H, J=9.4 Hz); 8,15 (s, 1H).

Example 64: 3-Methoxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN- (E)-1-inyl] benzoic acid

(a) Methyl ester of 3-methoxy-4-[4-(4'-methylbiphenyl-2-yl)-but-3 - EN-(E)-1-inyl]benzoic acid

Similarly to the method of example 33 (a), on the basis of 910 mg (2.5 mmol) obtained in example 63(e) compounds and 170 μl (2.7 mmol) under the conditions that obtain 870 mg (92%) target 3H); to 3.92(s, 3H); 6,40(d, 1H, J=16.2 Hz); to 7.09(d, 1H, J=16.2 Hz); 7,32-7,37 (m, 5H); 7,44(d, 2H, J=8.0 Hz); 7,53 (s, 1H); 7,58(DD, 1H, J=8,2/1.2 Hz); 7,62-7,72(m, 1H).

(b) 3-Methoxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid

Similarly to the method of example 1 (e) on the basis of 870 mg (2.3 mmol) obtained in example 64 (a) complex methyl ester, receive 500 mg (60%)of 3-methoxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid in the form of a powder beige with so pl. 217oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,43 (s, 3H); to 3.92 (s, 3H); 6,40(d, 1H, J=16.2 Hz); 7,10(d, 1H, J=16.2 Hz); 7,25-7,37(m, 9H); the 7.43(d, 1H, J=7.9 Hz); 7,56-the 7.65(m, 3H).

Example 65: {4-[4-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]phenyl} methanol

Similarly to the method of example 12(d), based on a 1.00 g (2.8 mmol) obtained in example 2 (d) of ester receive 900 mg(98%) {4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] phenyl} methanol as white crystals with so pl. 118-120oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 1,67 (t, 1H, J=5,9 Hz); 2,43 (3H); and 4.68(d, 2H, J=5.7 Hz); 6,34(d, 1H, J=16.2 Hz); 7,06(d, 1H, J=16.2 Hz); 7,26 and 7.36 (m, 9H); 7,42(d, 2H, J=8,2 Hz); 7,62-7,66(m, 1H).

Example 66: 4-[4-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzaldehyde

Similarly to the method of example 11 (d), based on 500 g (1.5 IMO is in the form of a yellow powder with so pl. 85oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,44(s, 3H); 6,36(t, 1H, J= 16.2 Hz); 7,13(d, 1H, J=16.2 Hz); 7,26-7,30(m, 4H); 7,34(d, 1H, J=4,1 Hz); to 7.35(d, 1H, J=1.7 Hz); 7,38(d, 2H, J=4,1 Hz); 7,56(d, 2H, J=8,2 Hz); of 7.64-to 7.68 (m, 1H); of 7.82(d, 2H, J=8,2 Hz); 9,99 (s, 1H).

Example 67: 4-[4-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]phenol

(a) 4-Trimethylsilylethynyl

Similarly to the method of example 1(a), on the basis of 8.00 g (38.4 mmol) of 4-itfinal receive 7.50 g (100%) of target compound as a brown oil.

1H-NMR-spectrum (deuterochloroform), M. D.: a 0.23(s, 9H); to 6.75 (d, 2H, J= 8,8 Hz); of 7.36 (d, 2H, J=8.7 Hz).

(b) 4-Ethinyl phenyl

In a three-neck flask in a stream of nitrogen injected 500 mg (2.6 mmol) obtained in example 67 (a) connection, 500 mg (8.6 mmol) of potassium fluoride, 500 mg (3.3 mmol) of cesium fluoride, 300 ml of methanol and 30 ml of tetrahydrofuran. The reaction medium is stirred for 16 hours at room temperature, then the solvent is evaporated and the resulting residue purified by passing through a layer of silicon dioxide, elwira with a mixture of 80% heptane and 20% dichloromethane. After evaporation of the solvents to obtain 280 mg (90%) of target compound as a brown oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 3,16 (s, 1H); 6,55 (d, 2H, J=8.6 Hz); to 7.09 (d, 2H, J=8.6 Hz); 9,67 (s, 1H) who interacted 200 mg (1.7 mmol) obtained in example 67(b)connection with 420 mg (1.3 mmol) obtained in example 2(g) connection, receive 60 mg(15%) 4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] phenol in the form of a powder brown color with so pl. 80-82oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42(s, 3H); to 5.03 (s, 1H); 6,32 (d, 1H, J= 16.2 Hz); 6,76 (d, 2H, J=8.7 Hz); 7,01(d, 1H, J=16.2 Hz); 7,25 was 7.36(m, 9H); to 7.61-7,63(m, 1H).

Example 68: 4-[4-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzamide

(and) 4-[4-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoyl chloride

In a three-neck flask in a stream of nitrogen, is injected 450 mg (1.3 mmol) obtained in example 2(e) acid and 20 ml of dichloromethane. Added dropwise 279 μl (1.4 mmol) of dicyclohexylamine and the resulting solution was stirred for 10 minutes at room temperature. Added dropwise 101 μl (1.4 mmol) of thionyl chloride and the resulting solution was stirred for 15 minutes at room temperature. The reaction medium is evaporated to dryness, treated the residue with diethyl ether, filtered and the filtrate is evaporated to dryness. The resulting residue is directly used in the next stage.

(b) 4-[4-(4'-Methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzamide

Obtained in the previous stage, the acid chloride of the acid dissolved in 10 ml of tetrahydrofuran, and the thus obtained solution was added dropwise to a solution prepared from 87 μl (1.5 mmol)of aqueous 32% Rastas at room temperature, poured into water and extracted with diethyl ether. The organic phase is washed with water until neutral pH, dried over magnesium sulfate, filtered and the solvents evaporated. The obtained residue proscout in a mixture of 90% heptane and 10% diethyl ether, filtered and dried. Get 380 mg(84%) 4-[4-(4'- methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzamide as a pale yellow powder with so pl. 195-197oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D. : 2,43 (s, 3H); 5,98(ush.s, 1H); 6,35(d, 1H, J=16.2 Hz); 7,10(d, 1H, J=16.2 Hz); 7,26-7,29(m, 4H); to 7.32(d, 1H, J=4, 2 Hz); 7,34(d, 1H, J 1.1 Hz); 7,37(d, 1H, J=4,8 Hz); of 7.48(d, 2H, J=8,4 Hz); 7,63-to 7.67 (m, 1H); for 7.78(d, 2H, J=8,4 Hz).

Example 69: N-Ethyl-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzamide

Similarly to the method of example 68 (b), on the basis of 498 mg (1.4 mmol) obtained in example 68 (a) the carboxylic acid and 3 ml (4.1 mmol)of aqueous 70% solution of ethylamine, receive 400 mg (80%) N-ethyl-4-[4-(4'-methylbiphenyl-2 - yl)but-3-EN-(E)-1-inyl]benzamide in the form of a white powder with so pl. 133-135oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: of 1.12 (t, 3H, J=7,1 Hz); of 2.38(s, 3H); 3,28(K, 2H, J=6.9 Hz); only 6.64(d, 1H, J= 16.2 Hz); of 6.96(d, 1H, J=16,3 Hz); 7,22(d, 2H, J=8.0 Hz); 7,31(d, 2H, J=7.8 Hz); 7,29-enyl-2-yl)but-3-EN-(E)-1-inyl]phenyl} morpholine-4-ylmethanol

Similarly to the method of example 68(b), on the basis of 498 mg (1.4 mmol) obtained in example 68 (a) the carboxylic acid and 3 ml (to 34.4 mmol)of the research, obtain 510 mg(92%) {4-[4-(4'-methylbiphenyl-2-yl)but - 3-EN-(E)-1-inyl]-phenyl}morpholine-4-ylmethanone in the form of a meringue orange with so pl. 50oC.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,43 (s, 3H); 3,30-3,90(ush. m, 8H); 6,34(d, 1H, J=16.2 Hz); to 7.09(d, 1H, J=16.2 Hz); 7,26-7,29(m, 4H); 7,33 and 7.36(m, 5H); 7,46(d, 2H, J=8,3 Hz); 7,63-to 7.67 (m, 1H).

Example 71: N-(4-Hydroxyphenyl)-4-[4-(4'-methylbiphenyl-2-yl)-but-3 - EN-(E)-1-inyl]benzamide

Similarly to the method of example 68 (b), on the basis of 380 mg (1.1 mmol) obtained in example 68 (a) the carboxylic acid and 138 mg (1.2 mmol) of 4-aminophenol, obtain 340 mg (70%) of N-(4-hydroxyphenyl)-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)- 1-inyl] benzamide in the form of a fine white powder with so pl. 253-255oC.

1H-NMR-spectrum (deuterochloroform + 2 drops of hexacyanometallate), M. D.: 2,35 (s, 3H); 6,28(d, 1H, J=16.2 Hz); 6.73 x(d, 2H, J=8,8 Hz); 7,00(d, 1H, J= 16.2 Hz); 7,14-7,30(m, 6H); 7,41(d, 2H, J=8.5 Hz); 7,44(d, 2H, J= 9.1 Hz); 7,56-of 7.60 (m, 1H); 7,83(d, 2H, J=8,3 Hz); 8,67 (s, 1H); 9,31(c, 1H).

Example 72: 5-[4-(4'-Methylbiphenyl-2-yl)buta-1,3-dienyl]thiophene-3 - carboxylic acid

(a) Methyl ester 5-[4-(4'-methylbiphenyl-2-yl)buta-1,3-dienyl] thiophene-3-carboxylic acid
with 950 mg (3.5 mmol) obtained in example 10(a) product get 650 mg (63%) of target compound as an orange oil.

1H-NMR-spectrum (deuterochloroform), M. D.: 2,42(s, 3H); 3,86(s, 3H); 7,27(d, 2H, J=8.1 Hz); 7,29-7,33(m, 1H); 7,38 - the 7.43 (m, 1H); 7,40(d, 1H, J= 1.4 Hz); 7,50(d, 2H, J=8.1 Hz); 7,62 - 7,66 (m, 1H); the 7.65(d, 1H, J=1.2 Hz); 8,00(d, 1H, J=1.2 Hz).

(b) 5-[4-(4'-Methylbiphenyl-2-yl)buta-1,3-dienyl]thiophene-3-carboxylic acid

Similarly to the method of example 1 (e) on the basis of 650 mg (1.8 mmol) obtained in example 72(a) complex methyl ester, obtain 570 mg(93%)5-[4-(4'-methylbiphenyl-2-yl)-buta-1,3-dienyl]thiophene-3-carboxylic acid in the form of a powder beige with so pl. 160-165oC.

1H-NMR-spectrum (hexacyanometallate), M. D.: of 2.38(s, 3H); 7,30(d, 2H, J=8.0 Hz); 7,40-to 7.59(m, 5H); 7,72 to 7.75(m, 1H); of 7.75(d, 1H, J=1.2 Hz); of 8.37(d, 1H, J=1.2 Hz); to 13.09(ush.s, 1H).

B. Examples of formulations

1) For oral use:

(a) Prepare the following composition in the form of tablets weighing 0.8 g:

Connection example 1 - 0,005 grams

Pre gelatinizing starch - 0,265 g

Microcrystalline cellulose - 0,300 g

Lactose - 0,200 g

Magnesium stearate - 0,030 g

For acne treatment adult appoint 1-3 tablets a day for 3-6 months depending on the severity of treatable cases.

(b) Prepare susp is in 0,500 g

70% Sorbitol - 0,500 g

The sodium saccharinate - 0,010 g

Methyl parahydroxybenzoate - 0,040 g

Flavor is Enough

Purified water To total amount 5 ml

For acne treatment adults appoint 1 ampoule daily for three months depending on the severity of treatable cases.

(C) Prepare the following composition intended for packaging in gelatin capsules:

Connection example 1 - 0.025 g

Corn starch - to 0.060 g

Lactose - Up to the total number 0,300 g

Used gelatin capsule consists of gelatin, titanium dioxide and preservative.

For the treatment of psoriasis adults appoint 1 gelatin capsule with medication daily for 30 days.

2) To apply locally:

(a) Prepare a cream-type water-in-oil non-ionic type the following composition:

Connection example 1 - 0,100 g

The mixture forming the emulsion of lanolin alcohols, waxes and refined oils produced in the sale of the company BDF called "Eucerine anhydre" - 39,900 g

Methyl parahydroxybenzoate - 0.075 g

Sodium propyl parahydroxybenzoate - 0.075 g

Sterile demineralized water Up to the total number of

This cream n is R>
Connection example 2 - 0,050 g

Erythromycin (base) - 4,000 grams

Equivalent - 0,050 g

Hydroxypropylcellulose, issued for the sale by the company Hercules under the name "KLUCEL HF" - 2,000 g

Ethanol (95o) - To a total of 100,000 g

This gel is to be applied to the affected skin skin or skin with acne 1-3 times a day for 6-12 weeks depending on the severity of treatable cases.

(C) Prepare protivoseborainey lotion by mixing the following ingredients:

The compound of example 5 - 0,030 g

Propylene glycol - 5,000 g

Equivalent - 0,100 g

Ethanol (95o) - To a total of 100,000 g

This lotion is applied twice daily to the affected seborrhea of the scalp and state significant improvement during the period of 2-6 weeks.

(g) Preparing a cosmetic composition against the harmful effects of the sun by mixing the following ingredients:

The compound of example 8 - 1,000 grams

Benzylideneamino - 4,000 grams

Triglycerides of fatty acids - 31,000 g

Glycerylmonostearate - 6,000 g

Stearic acid - 2,000 g

Cetyl alcohol - 1,200 g

Lanolin - 4,000 grams

Preservatives - 0,300 g

Propylene glycol - 2,000 the
This composition is applied daily, it helps to fight against photoinductive aging.

(d) Prepare the cream of type oil-in-water nonionic type the following composition:

Connection 10 - 0,500 g

Vitamin D3at 0.020 g

Cetyl alcohol - 4,000 grams

Glycerylmonostearate - 2,500 grams

Stearate PEG-50 - 2,500 grams

Oil Shea butter - 9,200 g

Propylene glycol - 2,000 g

Methyl parahydroxybenzoate - 0.075 g

Sodium propyl parahydroxybenzoate - 0.075 g

Sterile demineralized water To a total of 100,000 g

This cream is applied to psoriatic skin 1-2 times a day for 30 days.

(e) Prepare the gel for local application by mixing the following ingredients:

The compound of example 9 - 0,050 g

Ethanol - 43,000 g

- Tocopherol - 0,050 g

Carboxyvinyl the polymer produced in the sale by the company "Goodrich" under the name "Carbopol 941" - 0,500 g

Triethanolamine in aqueous 20 wt.%-aqueous solution - 3,800

Water - 9,300 g

The propylene glycol To the total number of 100,000 g

This gel acne treatment is applied 1-3 times a day for 6-12 weeks depending on the severity of treatable cases.

(g) Prepare a lotion against hair loss and accelerate hair growth by with the title "Minoxidil" - 1,00 g

Propylene glycol - 20,00 g

Ethanol - 34,92 g

Polyethylene glycol (molecular weight=400) - 40,00 g

Butylhydroxyanisole - 0.01 g

Equivalent - 0.02 g

Water - To the total number of 100.00 g

This lotion is applied 2 times a day for three months on the scalp, subject largely to the loss of hair.

(C) Prepare protivougrevoe cream by mixing the following ingredients:

The compound of example 18 - 0,050 g

Retinoic acid - 0,010 g

A mixture of glycerol stearates and polyethylene glycol (75 mol) produced in the sale by the company "GATTEFOSSE" called "Gelot 64" - 15,000 g

Stone fruit oil, polyoxyethylenated 6 moles of ethylene oxide produced in the sale by the company "GATTEFOSSE" under the name "Labrafil M2130 CS - 8,000 g

Perhydrosqualene - 10,000 g

Preservatives - Sufficient

Polyethylene glycol (molecular weight=400) - 8,000 g

The disodium salt of ethylenediaminetetraacetic acid - 0,050 g

Purified water To total amount 100,000 g

This cream is applied on the affected skin skin or covered with acne problems skin rash 1-3 times a day for 6-12 weeks.

(I) Prepare the cream of type oil-in-water stood next/BR> The polyoxyethylene stearate (40 moles of ethylene oxide), issued for the sale by the company "ATLAS" under the name "Myrj 52" - 4,000 grams

Sorbitanoleat, polyoxyethylenated 20 moles of ethylene oxide produced in the sale of the company "ATLAS" under the name "Tween" - 1,800 g

A mixture of mono - and distearate glycerin produced in the sale by the company "GATTEFOSSE" under the name "Geleol" - 4,200 g

Propylene glycol - 10,000 g

Butylhydroxyanisole - 0,010 g

Equivalent - 0,020 g

Cetostearyl alcohol - 6,200 g

Preservatives - Sufficient

Perhydrosqualene - 18,000 g

A mixture of glycerides of Caprylic and capric acids, sold under the name "Miglyol 812" by the company "DYNAMIT NOBEL" - 4,000 grams

Triethanolamine (99 wt.%) - 2,500 grams

Water To a total of 100,000 g

This cream is applied 2 times a day to the affected skin skin within 30 days.

(K) Prepare the following cream of type oil-in-water:

Lactic acid - 5,000 g

The compound of example 56 - 0,020 g

The polyoxyethylene stearate (40 moles of ethylene oxide), issued for the sale by the company "ATLAS" under the name "Myrj 52" - 4,000 grams

Sorbitanoleat, polyoxyethylenated 20 moles of ethylene oxide produced in the sale of the company "ATLAS" called "Twee 20" - 1,800 g

A mixture of mol - 10,000 g

Butylhydroxyanisole - 0,010 g

Equivalent - 0,020 g

Cetostearyl alcohol - 6,200 g

Preservatives - Sufficient

Perhydrosqualene - 18,000 g

A mixture of triglycerides of Caprylic and capric acids produced in the sale of the company "DYNAMIT NOBEL" called "Migliol 812", - 4,000 grams

Water To a total of 100,000 g

This cream is applied 1 time per day, it helps in the fight against photoinductive or chronological aging of the skin.

Century Examples test

Example 1

The results of the test to identify molecules antagonists RARs, similar to the test described in the application for French patent N 95-07302 filed June 19, 1995 by the applicant.

Used test is a test on the mouse ear oedema induced by topical application of 2-(5,6,7,8-Tetra-hydro-5,5,8,8-tetramethyl-2 - naphthyl)-6-benzo[b] thiophencarboxylic acid (CD270) in an amount of 0.01 wt.% on the volume.

According to this model, topical application of compounds CD270 ear provokes inflammation, which is characterized by thickening of the ear of a mouse. The response can be prevented by topical dose (expressed in wt.% volume) of compound X.

The results are presented in tab what disiniame - antagonists RARs.

Example 2

The results of the test cell differentiation (F9) embryonic teratocarcinoma mouse to identify molecules antagonists RARs described in Cancer Research, 43, of 5,268 (1983).

In the test used, the connection is considered as the RAR antagonist, if it reduces the activity of the agonist (4-[(5,5,8,8-tetramethyl - 5,6,7,8-tetrahydronaphthalen-2-ylamino)-methyl] benzoic acid, referred to as connection CD2043) in relation to morphology and allocation plasminogen activator cell F9. In this test, the compounds have at a concentration of 10-6M and CD2043 experience at a concentration of 10-8M

The results are presented in table. 2.

The results of this table show that the compounds of examples 1, 2, 11, 12, 14-18, 28, 42-45 and 52 are compounds antagonists RARs.

1. Triaromatic compounds of General formula I

< / BR>
where R1means (ii) -CH2OH, (iii) -O-R4, (iv) -CO-R5where R4and R5have the meanings stated below;

Ar1selected among the radicals of the following formulae (a) to (d):

< / BR>
where R6has the following value;

X-Y means connecting link, selected from the following residues of formula (e) - (m), which can be attached to the phenyl to which
Ar2selected among the radicals of the following formulae (j) - (l):

< / BR>
and Ar2is ortho - or metaprogram with respect to the relationship X-Y, and R10and R11have the meanings stated below;

R2and R3identical or different, denote a hydrogen atom, a linear or branched alkyl radical with 1 to 20 carbon atoms, a halogen atom; hydroxyl, alkoxyl, the remainder of the polyether;

R4means a hydrogen atom, lower alkyl;

R5means (a) a hydrogen atom; (b) a radical of the formula

< / BR>
where R' and R" have the meanings stated below; and (r) radical OR13where R13has the following value;

R6means a hydrogen atom, a linear alkyl with 1 to 20 carbon atoms, a hydroxyl; a radical OR14or the radical-OCOR14where R14has the following value; or the residue of polyether,

R7and R8means a hydrogen atom, lower alkyl;

R9means a hydrogen atom;

R10and R11identical or different, denote a hydrogen atom, a linear alkyl with 1 to 20 carbon atoms, a halogen atom; hydroxyl, alkoxyl, the remainder of the polyether, CF3alkenyl or -(CH2)n-R15where n and R15have yiewsley hydroxy-group phenyl, or both radicals together form a heterocycle;

R13means a hydrogen atom;

R14means a lower alkyl radical;

R15means hydroxyl;

n = 1 or 2;

and optical and geometrical isomers of the above compounds of the formula I or their salts.

2. Connection on p. 1, characterized in that they represent a salt of an alkaline or alkaline earth metal, zinc, organic amine, an inorganic or organic acid.

3. Connection on p. 1, characterized in that they are chosen from the group of the following compounds:

4-[4-(biphenyl-2-yl)but-3-EN-1-inyl]benzoic acid;

4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-1-inyl]benzoic acid;

4-[3-(4'-methylbiphenyl-2-yl)acrylamido]benzoic acid;

4-[3-(4'-methylbiphenyl-2-yl)-(E)-tioacridine]benzoic acid;

4-[3-(4'-methylbiphenyl-2-yl)acryloyloxy]benzoic acid;

4-[4-(4'-methylbiphenyl-2-yl)buta-1(E),3(Z)-dienyl]benzoic acid;

4-[4-(4'-methylbiphenyl-2-yl)buta-1(E),3(E)-dienyl]benzoic acid;

4-[3-(4'-methylbiphenyl-2-yl)propenyloxy]benzoic acid;

4-[4-(4'-methylbiphenyl-2-yl)-(E)/(Z)-buta-1-ene-3-inyl]benzoic acid;

4-[4-(4'-methylbiphenyl-2-yl)buta-1,3-dienyl]benzoic acid;

4-[4-(5,4'-dimethylbiphenyl-2-yl)but-3-EN-1-inyl]benzoic acid;

4-[4-(6,4'-dimethylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4-hydroxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(5-hydroxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(6-hydroxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methylbiphenyl-2-yl)Penta-3-EN-(E)-1-inyl]benzoic acid;

4-[3-(4'-methylbiphenyl-2-yl)propylamino]benzoic acid;

4-[3-(4'-methylbiphenyl-2-yl)propertyelement]benzoic acid;

4-[4-(3'-methylbiphenyl-2-yl)but-3-EN-1-inyl]benzoic acid;

4-[4-(2'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-chlorobiphenyl-2-yl)but-3-EN-1-inyl]benzoic acid;

4-[4-(3'-chlorobiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-forbiden-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-propylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-vinylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methoxyethoxymethyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(3'-methoxyethoxymethyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(2-thiophene-3-ylphenyl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(2-tikota;

4-[4-(4'-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-propoxyphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(3'-hydroxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(3'-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(3'-propoxyphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methyl-4-hydroxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methyl-4-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(4'-methyl-4-propoxymethyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methyl-5-hydroxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methyl-5-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(4'-methyl-5-propoxymethyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methyl-6-hydroxybiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(4'-methyl-6-methoxybiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(4'-triptorelin-2-yl)but-3-EN-(E)-1-inyl] -benzoic acid;

4-[4-(4'-hydroxymethyluracil-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-(4-[4'-(2-hydroxyethyl)biphenyl-2-yl]but-3-EN-(E)-1-inyl)benzoic acid;

4-[4-(3'-methylbiphenyl-3-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(3-methoxyethoxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(3-hydroxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

4-[4-(3-methoxy-4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

4-[4-(4'-ethoxymethylene-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

methyl ester of 4-[4-(4'-ethoxymethylene-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

2-methyl-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

2-hydroxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

6-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]pyridine-3-carboxylic acid;

5-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]pyridine-2-carboxylic acid;

5-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] thiophene-3-carboxylic acid;

3 methoxyethoxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

3-hydroxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzoic acid;

3-methoxy-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl] benzoic acid;

(4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]phenyl)-methanol;

4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]benzaldehyde;

4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl]phenol;

4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-1-inyl-inyl] phenyl)-morpholine-4-ylmethanone;

N-(4-hydroxyphenyl)-4-[4-(4'-methylbiphenyl-2-yl)but-3-EN-(E)-2-inyl] benzamide;

5-[4-(4'-methylbiphenyl-2-yl)buta-1,3-dienyl]thiophene-3-carboxylic acid.

4. Connection on p. 1, characterized in that they have at least one of the following groups: R1means-CO-R5, Ar1means a radical of formula (a) and (b); X-Y means connecting link formula (e), (f), (h); Ar2means a radical of the formula (j).

5. Compounds according to any one of paragraphs.1 to 4, characterized in that R1represents-CO-OR13where R13means a hydrogen atom.

6. Compounds according to any one of paragraphs.1 to 5, which has antagonistic activity to retinoic acid receptors.

7. Connection PP.1 - 6 of pharmaceutical compositions having an antagonistic activity to the receptor retinoic acid used for the treatment of dermatological diseases associated with disorders of keratinization-induced differentiation and proliferation, for the treatment of ordinary, youth, polymorphic and pink acne, nodules and nodular acne, senile acne, secondary acne such as solar acne, medication or occupational acne; treatment of other types of disorders of keratinization, h is aplasia and leukoplasia state, cutaneous or mucosal (oral) lichen; for treating other dermatological diseases associated with disorders of keratinization with inflammatory and/or immunoallergic component, and in particular all forms of psoriasis, which may be cutaneous, mucosal or ungual, and psoriatic arthritis, or cutaneous atopy, such as eczema, or respiratory atopy or gingival hypertension; the connection can also be used in certain inflammatory diseases without disorders of keratinization; for the treatment of all benign or malignant dermal or epidermal of proliteracy viral or non-viral origin, such as an ordinary simple warts, flat warts, or resembling a wart dysplasia of the epidermis, oral or flowering papillomatosis, and proliferate, which can be caused by ultraviolet radiation, in particular, in the case of basal cell and speckletone of epithelium; for treating other dermatological disorders such as bubble dermatoses and collagen; to treat certain eye disorders, especially corporate; to restore or against photoinductive or senile aging machinecheck aging; to prevent or cure the characteristic features of epidermal and/or dermal atrophy caused by local or systemic corticosteroids, or any other form of cutaneous atrophy; to prevent or treat disorders of scarring or for the prevention or healing of the bands on the skin when it is stretched; to fight against disorders of the sebaceous function, such as acne affected Hyperborea or simple seborrhoea; for treating or preventing carcinomatosa or predication-matanah conditions, more preferably promyelocytic leukaemia; for the treatment of inflammatory diseases such as arthritis; for the treatment of any disease of viral origin at the level of skin or systemic diseases; for the prevention or treatment of alopecia; for the treatment of dermatological or General diseases with an immunological component; for the treatment of diseases of the cardiovascular system such as arteriosclerosis, hypertension, non-insulin-dependent diabetes as well as obesity; for the treatment of skin disorders due to long time under the influence of ultraviolet radiation.

8. Pharmaceutical composition having antagonistic activity to the receptor retinova the pharmaceutically acceptable carrier, at least one of the compounds according to any one of paragraphs.1 to 5 in an effective amount.

9. The composition according to p. 8, characterized in that the amount of the compound according to any one of paragraphs.1 - 5 0.001 - 5 wt.%, calculated on the whole composition.

10. Cosmetic composition having antagonistic activity to retinoic acid receptors containing compound and a cosmetically acceptable carrier, characterized in that it comprises in a cosmetically acceptable medium, at least one of the compounds according to any one of paragraphs.1 to 5 in an effective amount.

11. The composition according to p. 10, characterized in that the amount of the compound according to any one of paragraphs.1 - 5 0.001 - 3 wt.%, calculated on the whole composition.

12. Cosmetic composition according to any one of paragraphs.10 or 11 in the form suitable for body hygiene, or for hair care.

 

Same patents:

The invention relates to new derivatives of pyrrolidinone possessing biological activity, in particular derivatives of 1H-3-aryl-pyrrolidin-2,4-dione

The invention relates to compounds of the following formula 1, which inhibit the enzyme glycinamide ribonucleotide the formyl transferase (GARFT)

The invention relates to equipment for carrying out the catalytic oxidation of gas-vapor mixtures in stationary conditions, preferably for the production of nicotinic acid, which finds application in the pharmaceutical industry, fine organic synthesis, agriculture

The invention relates to equipment for carrying out the catalytic oxidation of gas-vapor mixtures in stationary conditions, preferably for the production of nicotinic acid, which finds application in the pharmaceutical industry, fine organic synthesis, agriculture

The invention relates to 5,6-disubstituted-3 - pyridylmethylamine compounds of the formula I

< / BR>
where Z is hydrogen, halogen;

Z1represents hydrogen, halogen, cyano and nitro;

X represents Cl, Br, J, or R3SO3;

R3represents C1-C4-alkyl or phenyl, are not necessarily substituted with one to three C1-C4-alkoxygroup, C1-C4- alkyl groups, nitro groups: cyano groups or halogen atoms;

Y and Y1each independently represents OR4, NR4R5or, if they are taken together, YY1represent-O-, -S - or;

R4and R5are each independently hydrogen, C1-C4-alkyl, does not necessarily substituted C1-C4- alkoxygroup, or phenyl, does not necessarily substituted with one to three C1-C4-alkyl groups, C1-C4- alkoxygroup or halogen atoms; or phenyl, does not necessarily substituted with one to three C1-C4-alkyl groups, C1-C4- alkoxygroup atoms or halogen;

R6represents hydrogen or C1- C4- alkyl;

Q is

The invention relates to a new bi-aromatic compounds acetylenes with a group of adamantyl formula (I), with activity in relation to differentiation and cell proliferation

The invention relates to medicine, in particular to therapy, and is intended for the treatment and prevention of atherosclerosis

The invention relates to substituted azetidinone General formula I listed in the description
The invention relates to physiologically active compounds and relates amidoalkylation and method of production thereof

The invention relates to a new compound is a sodium salt of 6-nitro-3H-gynazole-4-yl-3-acetic acid of formula (I), which is antioxidant and anti-ischemic activity and may find application in medicine
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