Carboxylic acid derivative with condensed rings and pharmaceutical composition based on it

 

(57) Abstract:

The invention relates to carboxylic acid derivative with condensed rings of the General formula (A), and its pharmaceutically acceptable salts, intending to obtain drugs that are effective agonists of the retinoic acid receptors. In the above compound of formula (I) symbol denotes a single or double bond; each of X, Y, Z, P, Q, U, V and W represents-O-, -S - or a group of formula (a), in which Rk(k = 1-8) denotes hydrogen, halogen, possibly substituted lower alkyl, or the like group, and one of R7and R8denotes a group of formula (b), in which a and b independently from each other are possibly substituted aromatic hydrocarbon ring or an unsaturated heterocyclic ring; D represents the possible protected carboxyl group. The technical result - new compounds with agonistic activity against receptors retinova acid. 2 C. and 16.C.p. f-crystals, 2 PL.

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The invention relates to derivatives of carboxylic acids with condensed rings and their pharmaceutically acceptable salts. This invention, in particular, relative to the Directors retinoic acid (RAR), and their pharmaceutically acceptable salts.

Retinoic acid is a substance essential for the growth and life of humans and other mammals. As you know, retinoic acid is a morphogenetic factor in ontogenesis and different effects on the differentiation and proliferation of cells in human adults. For example, it is known that this acid is involved in the processes of keratinization, hair education, the functioning of the sebaceous glands and other functions of the epidermis in metabolism in the bone tone and cartilage connective tissue in the regulation of immune functions of the immune system, differentiation of neurons of the nervous system, in the differentiation and proliferation of blood cells, hematopoietic system, lipid metabolism, mineral metabolism, primary metabolism, and so forth. The physiological action of retinoic acid are different regulatory mechanisms through the family of retinoids receptors located in the nucleus of cells, for example, by regulating the expression of activators of transcription, enzymes, such as collagenase, tissue plasminogen activator or tyrosinekinase, or the regulation of cytokines, such as IL-6.

Currently ustanavli. In particular, deserves the attention of a new method of treating certain types of cancer, such as acute promyelocytic leukemia, which is based on the differentiation of cells under the influence of all-TRANS retinoic acid.

However, the application of retinoic acid causes certain difficulties to which it relates, in particular, induction of P450, which is the hepatic metabolic enzyme, the harmful effects due to the accumulation of this acid in the body and other problems. In this regard, there is a need to conduct research and create new connections, related to retinoids, which can be used instead of retinoic acid as a prophylactic and therapeutic agents for treatment of various diseases.

The present invention is the creation of new connections, related to retinoids, which can be used as preventive and therapeutic agents for the treatment of various diseases.

This object is achieved by the use of derivatives carboxylic acids with condensed rings, which will be described below, and this formed the basis of this invention.

This gives to their pharmaceutically suitable salts:

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{ in which the rings L and M condensed with each other; the symbol denotes a single or double bond; X represents a group-O - or-S-, or a group of the formula:

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(in which R1denotes hydrogen, halogen, possibly substituted lower alkyl, possibly substituted cycloalkyl, possibly substituted aryl, possibly substituted heteroaryl, possibly substituted lower alkoxy, possibly substituted, aryloxy, possibly substituted, heteroaromatic, possibly substituted cycloalkenyl, possibly substituted arylalkyl, possibly substituted heteroaromatic, possibly substituted, cycloalkane, possibly substituted, cycloalkylation, possibly substituted, arylalkylamine, possibly substituted, heteroaromatic, possibly substituted alkenyl or possibly substituted quinil) and x is an integer of 0 or 1;

Y represents a group-O - or-S-, or a group of the formula:

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(in which R2denotes hydrogen, halogen, possibly substituted lower alkyl, possibly substituted cycloalkyl, possibly substituted aryl, possibly substituted heteroaryl, possibly substituted lower alkoxy, possibly substituted, aryloxy, possibly substituted, heteroaromatic, possibly substituted cycloalkenyl, Sogno replaced cycloalkylation, possibly substituted, arylalkylamine, possibly substituted, heteroaromatic, possibly substituted alkenyl or possibly substituted quinil) and y is an integer of 0 or 1;

Z represents the group-O - or-S-, or a group of the formula:

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(in which R3denotes hydrogen, halogen, possibly substituted lower alkyl, possibly substituted cycloalkyl, possibly substituted aryl, possibly substituted heteroaryl, possibly substituted lower alkoxy, possibly substituted, aryloxy, possibly substituted, heteroaromatic, possibly substituted cycloalkenyl, possibly substituted arylalkyl, possibly substituted heteroaromatic, possibly substituted, cycloalkane, possibly substituted, cycloalkylation, possibly substituted, arylalkylamine, possibly substituted, heteroaromatic, possibly substituted alkenyl or possibly substituted quinil) and z is an integer of 0 or 1;

R represents a group-O - or-S-, or a group of the formula:

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(in which R4denotes hydrogen, halogen, possibly substituted lower alkyl, possibly substituted cycloalkyl, possibly substituted aryl, possibly substituted heteroaryl, possibly substituted lower alkoxy, possibly substituted alloc is possibly substituted heteroaromatic, possibly substituted, cycloalkane, possibly substituted, cycloalkylation, possibly substituted, arylalkylamine, possibly substituted, heteroaromatic, possibly substituted alkenyl or possibly substituted quinil) and p is an integer of 0 or 1;

Q denotes a group-O - or-S-, or a group of the formula:

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(in which R5denotes hydrogen, halogen, possibly substituted lower alkyl, possibly substituted cycloalkyl, possibly substituted aryl, possibly substituted heteroaryl, possibly substituted lower alkoxy, possibly substituted, aryloxy, possibly substituted, heteroaromatic, possibly substituted cycloalkenyl, possibly substituted arylalkyl, possibly substituted heteroaromatic, possibly substituted, cycloalkane, possibly substituted, cycloalkylation, possibly substituted, arylalkylamine, possibly substituted, heteroaromatic, possibly substituted alkenyl or possibly substituted quinil) and q is an integer of 0 or 1;

U denotes the group-O - or-S-, or a group of the formula:

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(in which R6denotes hydrogen, halogen, possibly substituted lower alkyl, possibly substituted cycloalkyl, possibly substituted aryl, it is possible to zamestnanosti, possibly substituted cycloalkenyl, possibly substituted arylalkyl, possibly substituted heteroaromatic, possibly substituted, cycloalkane, possibly substituted, cycloalkylation, possibly substituted, arylalkylamine, possibly substituted, heteroaromatic, possibly substituted alkenyl or possibly substituted quinil) and w is an integer of 0 or 1;

V denotes the group-O - or-S-, or a group of the formula:

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[in which R7denotes hydrogen, halogen, possibly substituted lower alkyl, possibly substituted cycloalkyl, possibly substituted aryl, possibly substituted heteroaryl, possibly substituted lower alkoxy, possibly substituted, aryloxy, possibly substituted, heteroaromatic, possibly substituted cycloalkenyl, possibly substituted arylalkyl, possibly substituted heteroaromatic, possibly substituted, cycloalkane, possibly substituted, cycloalkylation, possibly substituted, arylalkylamine, possibly substituted, heteroaromatic, possibly substituted alkenyl, possibly substituted quinil or a group of the formula:

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(in which a and b independently of one another denote a possibly substituted aromatic hydrocarbon ring or possibly samewe is 0 or 1; and

W represents a group-O - or-S-, or a group of the formula:

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[in which R8denotes hydrogen, halogen, possibly substituted lower alkyl, possibly substituted cycloalkyl, possibly substituted aryl, possibly substituted heteroaryl, possibly substituted lower alkoxy, possibly substituted, aryloxy, possibly substituted, heteroaromatic, possibly substituted cycloalkenyl, possibly substituted arylalkyl, possibly substituted heteroaromatic, possibly substituted, cycloalkane, possibly substituted, cycloalkylation, possibly substituted, arylalkylamine, possibly substituted, heteroaromatic, possibly substituted alkenyl, possibly substituted quinil or a group of the formula:

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(in which a and b independently of one another denote a possibly substituted aromatic hydrocarbon ring or possibly substituted unsaturated heterocycle, and D denotes a possibly protected carboxyl)] and w is an integer of 0 or 1;

provided that the symbols in the formula:

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used in the above definitions of X, Y, Z, P, Q, U, V and W, denotes a single or double bond; or two adjacent R1, R2, R3, R4, R5, R6, R7and R8together with ATC, y, z, and p must satisfy the relation: 4x+y+z+p3, and u, v, w and q must satisfy the relation: 4u+v+w+q3, and one of V and W is a group of the formula:

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(in which Rk'belongs to R7or R8), where R7or R8is a group of the formula:

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(in which a and b independently of one another denote a possibly substituted aromatic hydrocarbon ring or possibly substituted unsaturated heterocycle, and D denotes a possibly protected carboxyl), except for compounds of the formula (A), in which the ring L is fully saturated}.

Another object of the present invention are pharmaceutical compositions containing a pharmaceutically effective amount of the above derivatives carboxylic acids with condensed rings, their pharmaceutically acceptable salts or hydrates of the salts and pharmaceutically acceptable excipients.

Another object of the present invention are agonists of the retinoic acid receptors (RAR), which constitute the above-mentioned derivatives of carboxylic acids with condensed ring, their pharmaceutically acceptable salts or hydrates of salts.

The present invention relates also to profilestatus agonists of the retinoic acid receptors.

In addition, an object of the present invention is a method of prevention and treatment of diseases for which there are effective agonists of the retinoic acid receptors, through the introduction of needy subject pharmaceutically effective amount of the above derivatives carboxylic acids with condensed rings, their pharmaceutically acceptable salts or hydrates of the salts, and the use of the above derivatives carboxylic acids with condensed rings, their pharmaceutically acceptable salts or hydrates of the salts to obtain drugs to treat diseases for which there are effective agonists of the retinoic acid receptors.

In the above formula (a), the term "halogen" in the definition of R1, R2, R3, R4, R5, R6, R7and R8means fluorine, chlorine, bromine or iodine.

The term "lower alkyl" in the definition of R1, R2, R3, R4, R5, R6, R7and R8means an alkyl group with a linear or branched chain having 1-6 carbon atoms. Examples of such groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 1,2-di is terbutyl, 2.2-dimethylbutyl, 3,3-dimethylbutyl, 1,1-diethylpropion, 2,2-diethylpropane, 1,2-diethylpropion, 1-ethyl-2-methylpropyl, 1-methyl-2-ethylpropyl and 1,1-diethylether. These alkyl groups can be substituted one to three halogen atoms such as fluorine atoms, chlorine, bromine or iodine. That is, the above-mentioned lower alkyl group with a linear or branched chain also means trifluoromethyl, diplomatic and others.

The term "cycloalkyl" in the definition of R1, R2, R3, R4, R5, R6, R7and R8means a group with 3-8 carbon atoms, and examples of such groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

The term "lower alkoxy" in the definition of R1, R2, R3, R4, R5, R6, R7and R8means CNS group with a linear or branched chain having 1-6 carbon atoms. Examples of such groups are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentyloxy, 1,2-dimethylpropylene, 1,1-dimethylpropylene, 2,2-dimethylpropylene, 2-ethylpropoxy, n-hexyloxy, 1,2-dimethylbutylamino, 2,3-dimethylbutylamino, 1,3-dimethylbutylamino, 1-ethyl-2-methylpropyloxy and 1-methyl-2-ethylpropyl fluorine, chlorine, bromine or iodine. That is, above the lower CNS group also means triptoreline, dibromethane and others.

As mentioned above, R1, R2, R3, R4, R5, R6, R7and R8can indicate possible substituted aryl, and the term "aryl" means phenyl, 1-naphthyl, 2-naphthyl, anthracene or the like.

As mentioned above, each of a and b may denote a possibly substituted aromatic hydrocarbon ring, and the term "aromatic hydrocarbon ring" in this case means a benzene ring, naphthalene ring, anthracene ring or the like.

The term "possibly substituted heteroaryl" in the definition of R1, R2, R3, R4, R5, R6, R7and R8means a group derived from a monocyclic or condensed ring with one to four atoms of sulfur, oxygen or nitrogen. Examples of such groups are thienyl, furyl, benzothiazyl, benzofuranyl, isobenzofuranyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolin, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, indolyl, ethenolysis, hinely, phthalazine, honokalani, nafate possibly substituted heterocycle, the term "heterocycle" in this case means a monocyclic or condensed ring with one to four atoms of sulfur, oxygen and/or nitrogen. Examples of such rings are thiophene ring, furan ring, benzothiophene ring, benzopyrrole ring, isobenzofuran ring, pyrrole ring, imidazole ring, pyrazole nucleus ring, isothiazol ring, isoxazole ring, isoindoline ring, indole ring, isoquinoline ring, quinoline ring, phthalazinone ring, hinoksolinov ring, naphthyridine ring, hintline ring, acridine ring and furazane ring.

As mentioned above, R1, R2, R3, R4, R5, R6, R7and R8can indicate possible substituted arylalkyl, and the term "aryl" in this case has the above-mentioned values. In addition, the term "alkyl" in this case has the values specified above for lower alkyl.

The term "possibly substituted heteroaromatic" in the definition of1, R2, R3, R4, R5, R6, R7and R8means a group obtained by attaching the above-mentioned heteroaryl group to any carbon atom of the specified alkyl group is heteroarylboronic groups are lower alkyl groups with linear or branched chain, such as methyl, ethyl, n-propyl and isopropyl; lower CNS group with a linear or branched chain, such as methoxy, ethoxy, n-propoxy, isopropoxy; halogenated groups such as fluorine, chlorine, bromine and iodine; possibly substituted aryl group, possibly substituted heteroaryl group, possibly substituted arylalkyl group, possibly substituted heteroallyl group; halogen-containing group; hydroxy; hydroxyalkyl groups; alkoxyalkyl group and the like.

As mentioned above, D denotes a possibly protected carboxyl, and examples of protective groups for this carboxyl groups are lower alkyl groups such as methyl, ethyl and tert-butyl; possibly substituted generirovanie lower alkyl groups, such as parametersjpanel, paranitrobenzoic, 3,4-dimethoxybenzyl, diphenylmethyl, trityl and phenethyl; halogenated lower alkyl groups such as 2,2,2-trichloroethyl and 2-Iodate; lower alkanoyloxy lower alkyl groups, such as pivaloyloxymethyl, acetoxymethyl, propionylacetate, butyraldoxime, valerolactone, 1-acetoxyethyl, 2-acetoxyethyl, 1-pivaloyloxymethyl and 2-pivaloyloxymethyl; the highest alkanoyloxy lower alkyl GRU and lower alkyl groups, such as methoxycarbonylmethyl, 1-butoxycarbonyloxyimino and 1-(isopropoxycarbonyl)ethyl; karboksilirovanie lower alkyl groups such as carboxymethyl and 2-carboxyethyl; heteroaryl group such as 3-phthalidyl; possibly substituted benzoyloxy lower alkyl groups, such as 4-glycidoxypropyl; (substituted dioxolene) lower alkyl groups such as (5-methyl-2-oxo-1,3-dioxolan-4-yl)methyl; cycloalkylcarbonyl lower alkanoyloxy lower alkyl groups such as 1-cyclohexanediacetic; cycloalkylcarbonyl lower alkyl group, such as 1-cyclohexyloxycarbonyloxy; and possibly substituted amino group. That is, the term "possibly protected carboxyl" means carboxyl or group that can be cleaved by chemical methods or in vivo with obtaining carboxylic acids.

Examples of pharmaceutically acceptable salts of the present invention are inorganic salts such as hydrochloride, hydrobromide, sulfates and phosphates; organic acid salts such as acetates, maleate, tartratami, methansulfonate, benzosulfimide and toluensulfonate; and salts of amino acids such as aspartate and glutamate.

In the volume of the drop of the present invention can be easily obtained by known methods or more of such ways, used in combination. The following is an example of a method of obtaining.

The method of obtaining 1

The compounds of formula (A) where a is a pyrrole ring, can be obtained as follows (see figure I in the end of the description).

(Stage 1)

At this stage receive allyl alcohol (2) as a result of interaction of the aldehyde (1) with an ORGANOMETALLIC reagent in a known manner.

ORGANOMETALLIC reagents include Grignard reagents, organolithium reagents, tsinkorganicheskih reagents, magyarkanizsa complexes and the like. Although at this stage you can use any inert solvent, the preferred ether solvents, such as simple ether or tetrahydrofuran. The reaction temperature may be in the range from -78oC to the boiling point of the solvent, preferably from about -78oWith up to 20oC.

(Phase 2)

At this stage, allyl alcohol (2) obtained in stage (1), oxidizes in vinylmation (3) in a known manner.

Although oxidation can be accomplished in any known manner, preference is given to using acceptable oxidant. Examples of the developer are activated dioxide m the oxidation can be used any inert organic solvent, preference is given dichlormethane, chloroform or acetone. The reaction temperature may be in the range from about -78oC to the boiling point of the solvent, preferably from about -78oWith up to 20oC.

(Stage 3)

At this stage the result of the interaction of vinylketones (3) obtained in stage (2) and aldehyde (4), obtained in accordance with the method of Stetter and others, described in the journal of Org. Synth. 65, 26, get a diketone of the formula (5).

The best results can be obtained by using as the catalyst salt thiazole. In this case, it is preferable to use a base such as triethylamine, sodium acetate and the like. In addition, when carrying out the above reaction, it is possible to use such a solvent as methanol, ethanol, N, N-dimethylformamide or the like. The reaction temperature preferably ranges from about 60oC to the boiling point of the solvent.

(Stage 4)

At this stage of the diketone (5) obtained in stage (3), turns into a pyrrole of the formula (6) in a known manner.

The target compound (6) can be obtained, for example, as a result of interaction of the diketone (5) with an ammonium salt such as ammonium acetate, exusa acid. The reaction temperature preferably is in the range from 70oC to the boiling point of the solvent.

(Stage 5)

At this stage pyrrole (6) obtained in stage (4), hydrolized in a known manner to obtain the final target compounds of formula (7). The best results can be obtained when using the base, in particular an aqueous solution of lithium hydroxide, sodium hydroxide, potassium hydroxide or the like. Preferred examples of the solvent for the specified hydrolysis are alcohols, such as methanol and ethanol, and ethers, such as tetrahydrofuran. The reaction temperature preferably ranges from about 20oC to the boiling point of the solvent.

Scheme II another method of obtaining diketone (5) used in the implementation of the above method of obtaining 1, see the end of the description.

The method of obtaining 1'

Diketone (5) can also be obtained as a result of interaction of vinylketones (8), obtained as in method 1, with an aldehyde (1) in the presence of such a catalyst as salt thiazole, in accordance with the method of Stetter etc. Best results can be obtained when using a base, such as triethylamine,th alcohols, such as methanol and ethanol, N,N-dimethylformamide and the like. The reaction temperature preferably ranges from about 60oC to the boiling point of the solvent.

Below are examples of pharmacological experiments illustrating the effectiveness of the present invention.

An example of pharmacological experiment 1

Analysis of binding to receptor using fractions nuclear extracts of cells containing the transferred genes in them receptors retinoic acid

- ,- , and --Genes of retinoic acid receptors (RAR) people were moved in kidney cells baby hamster (KSS) obtaining cells constantly expressing-and --proteins RAR. Experimental system for measuring specific binding all-TRANS retinoic acid RAR created by using a fraction of the nuclear extract of cells. The ability of each compound to bind to receptor sites of retinoic acid was determined by measuring the inhibition of specific binding. In addition, comparing the ability of compounds to bind to receptor sites of retinoic acid, was determined by the selectivity of each compound against different RAR.

(1) Experimentname in them genes RAR suspended in 15 ml of solution A (sodium phosphate (pH 7.4): 5 mmol, monothioglycerol: 10 mm, glycerol: 10% (volume ratio), phenylmethylsulfonyl (PMSF): 1 mm, Aprotinin: 10 µg/ml and leupeptin: 25 µg/ml). The resulting suspension is homogenized and centrifuged to remove the resulting supernatant. The precipitate suspended in 15 ml of solution (Tris-Hcl (pH 8.5): 10 mmol, monothioglycerol: 10 mm, glycerol: 10% (volume ratio), phenylmethylsulfonyl: 1 mm, Aprotinin: 10 µg/ml, leupeptin: 25 µg/ml and KCl: 0.4 mol). The resulting suspension was left for one hour to maturation at a temperature of 4oWith and subjected to ultracentrifugation with a speed of 100000 x gradient, at a temperature of 4oC for one hour. The obtained supernatant was stored until use in the form of fraction of nuclear extract in a frozen state at a temperature of -80o(Methods in Enzymology, 189, 248).

b) Analysis of binding to receptors

In each well of 96-hole tablet, made of polypropylene, has introduced 180 μl of the above fraction and 10 µl of the diluted solution of all-TRANS retinoic acid or the test compound and then added 10 μl of 10 nmole3H-all-TRANS-retinoic acid. The tablet was left for 16 hours for vystavna, and centrifuged to remove free 3H-all-TRANS-retinoic acid. Using a scintillation counter was determined by the radioactivity of the obtained supernatant. Specific binding for each RAR was defined as follows: for the nonspecific binding was attended radioactivity detected at 500-fold addition of all-TRANS retinoic acid, the value of which is read from a specific higher radioactivity. The following compounds inhibited binding3H-all-TRANS-retinoic acid, depending on the concentration.

(2) the results of the experiment

The concentration at which binding3H-all-TRANS-retinoic acid for each receptor ingibirovalo 50%, i.e. the IC50 was calculated on the basis of specific binding to retinoic acid receptors. The value of the relative activity is shown in table 1, calculated taking into account the fact that the IC50 value of all-TRANS retinoic acid has been taken equal to 1.

An example of pharmacological experiment 2

Measurement activates the transcription of the activity of retinoic acid receptors

Expressing the vectors RAR person and secretory GE is lnasty, expression which ingibirovany as a result of binding to receptors of the retinoic acid depending on the ligand, temporarily transferred into cells COS-1 (kidney cells of the African green monkey), then the vectors PLAP, which were obtained depending on the ligand and secretively in culture medium, were analyzed chemiluminescent method to determine activates the transcription activity of each connection. In addition, we determined the selectivity of each compound in the receptor retinoic acid, which compared activates the transcription activity of the compounds at different receptors.

(1) Experimental method

60 mm Cup for cultivation were placed 2,5104cells COS-1. After four days in these cells tolerated method lipofectin 4 µg-and-expressing vectors RAR and vectors PLAP. Even after one day the obtained cells were isolated and placed on a 96-well culture plate in a number 2104in each well. Four hours later the cells are transferred to medium containing processed carbon fetal calf serum, and added to a diluted solution of all-TRANS retinoic acid or the test compounds. After 36 casuality nonspecific activity. 15 μl of Each sample was mixed with 60 ál 28 mcmole sodium carbonate buffer (pH 10) was added to 75 μl of substrate Smilight (trade name, product of " Sumitomo Metal Industries, Ltd., the substrate for chemiluminescence). The resulting mixture was subjected to interaction at a temperature of 37oC for 30 minutes, after which determined the intensity of the luminescence. The following compounds were caused transcriptional activity of retinoic acid receptors, depending on the concentration.

(2) the results of the experiment

Transcriptional activity induced by 1 µm all-TRANS retinoic acid, taken as 100% for each compound was calculated concentration at which inhibition was achieved 30% of this activity, i.e. ED30. Table 2 shows the values of the relative activity of the compounds for each receptor, calculated taking into account the fact that the value ED30 all-TRANS retinoic acid has been taken equal to 1.

The examples above pharmacological experiments show that derivatives of carboxylic acids of the formula (A) or their pharmaceutically acceptable salts are agonists of the retinoic acid receptors. Therefore, compounds of the present invention p is her in respect of which there are effective agonists of the retinoic acid receptors, i.e. different abnormal keratinization and skin diseases such as xeroderma, psoriasis, eczematous lesions of joints, acne or leukoplakia; different types of alopecia such as alopecia areata, seborrheic alopecia or alopecia due to cachexia; different osteoporosis and osteogenesis, such as postmenopausal osteoporosis, senile osteoporosis, steroid osteoporosis, idiopathic osteoporosis, diabetes violation of osteogenesis, rheumatoid violation of osteogenesis or renal violation of osteogenesis; diseases of bones and joints, such as ectopic hyperetes, osteoarthritis or periarthritis of the shoulder joint; autoimmune diseases such as chronic rheumatoid arthritis, multiple sclerosis, systemic lupoid erythema, Behcet's disease, mushroom avium, systemic sclerosis, sudden thrombocytopenic purpura, myasthenia gravis, dermatomyositis or nodular arteriosclerosis; different types of leukemia, such as acute promyelocytic leukemia, acute military leukemia or chronic leukemia, transplant rejection in organ transplantation; graft versus Ho is glomerulonephritis; malignant lymphomas, in particular, of mycosis fungoides; squamous cell cancer, particularly squamous cell cancer of the head and neck; solid carcinoma, in particular, bladder cancer, lung cancer, esophageal cancer, head and neck cancer, colon cancer, prostate cancer or pancreatic cancer; inflammatory and allergic diseases such as atopic dermatitis or asthma; immunological failure and intractable infectious diseases such as immunodeficiency, infectious disease caused by a virus cytomegaly due to the weakening of the immune system, fetal infections or opportunistic microorganisms; hyperthyroidism; hypercalcemia; different fibrosis, such as pneumovirus, liver fibrosis or cirrhosis, atherosclerosis and restenosis after surgery to restore blood flow; other benign species hyperplasia, such as endometrial hyperplasia, prostatic hypertrophy, proliferative vitreoretinopathy and dysplasia; diseases associated with metabolism and the transport of lipids, such as hyperlipemia; diabetes; wounds; dry eye syndrome; skin lesions under the influence of sunlight and bolesta non-toxic and completely safe substances, that also makes it very useful.

Compounds of the present invention can be entered needy subjects in different ways. In particular, they can be administered orally as a prophylactic or therapeutic agents in the form of tablets, powders, granules, capsules, syrups and the like, or they can be administered parenterally in the form of suppositories, injections, external preparations or drops.

Although the dose of the compounds largely depends on the nature of the disease, severity of symptoms, the time between the sudden attack and the first introduction, age, sex, sensitivity of the subject and the like, and these compounds can enter the adult subject in an amount of from about 0.03 to 1000 mg, preferably from 0.1 to 500 mg, more preferably from 0.1 to 100 mg per day in multiple doses.

When the compound is administered by injection, the dose is usually from about 1 to 3000 μg/kg, preferably from about 3 to 1000 μg/kg

Compounds of the present invention can be introduced in the form of pharmaceutical preparations, using for this purpose the known fillers.

In particular, the solid pharmaceutical preparation for oral administration is RA, lubricating substances dye modifier drugs, antioxidant and similar substances with a primary drug and molding the resulting mixture of tablets, coated tablets, granules, powders, capsules or the like in accordance with known methods.

Examples of fillers are lactose, corn starch, sucrose, glucose, sorbitol, crystalline cellulose and silicon dioxide.

Examples of binding agents are polyvinyl alcohol, polyvinyl ether, ethylcellulose, methylcellulose, Arabian gum, tragant, gelatin, shellac, hydroxypropylcellulose, hypromellose, calcium citrate, dextrin and pectin. Examples of lubricants are magnesium stearate, talc, polyethylene glycol, silica and hardened vegetable oils.

As the dyes, you can use special pharmaceutical additives. Modifiers drugs include cocoa powder, menthol, aromatic powder, menthol oil, borneol, cinnamon powder and the like. As antioxidants, you can use special pharmaceutical additives, for example, ascorbic acid and-t is the EU ETS.

Injection solutions according to the present invention can be obtained in a known manner, whereby the pH regulator, buffer, suspendisse agent, solvent, stabilizer, tonic, antioxidant and/or preservative is mixed with the main tool, and if necessary, the resulting mixture is dried by freezing. Such injection solution can be administered intravenously, subcutaneously or intramuscularly.

Examples suspendida agents include methylcellulose, Polysorbate 80, hydroxyethylcellulose, Arabian gum, powdered tragant, sodium carboxymethylcellulose and monolaurin of polyoxyethylenesorbitan.

Solubilizers agents are utverjdenie a polyoxyethylene castor oil, Polysorbate 80, nicotinamide, monolaurin of polyoxyethylenesorbitan and the like.

Examples of the stabilizer include sodium sulfite, metasulfite sodium and simple ether. Examples of preservatives are methyl parahydroxybenzoate, metilparagidroksibenzoat, sorbic acid, phenol, cresol and chlorocresol.

Below are examples of facilitating understanding of the present invention, and it should be noted that they do not limit the scope of this somosi spectrometer Varian UNITY 400 (400 MHz).

Examples that illustrate how to obtain the compounds of the present invention, preceded by preparatory examples that describe how to obtain the original compounds. Ways to get some of the compounds of the present invention are discussed in the preparatory examples only for a better understanding of the invention, therefore, there is no need to repeat that they in no way limit the invention.

Legend

1H-NMR - Spectrum1H-NMR; (s) - singlet, (d) - doublet, (t) triplet, (q) Quartet, (quint. ) - quintet (m) - multiplet, (dd) doublet of doublets (ddd) - double doublet of doublets, (dt) - doublet of triplets, (brs) - a broad singlet; constant interaction (denoted by J) are expressed in Hertz.

Preparatory example 1

5,8-Dimethyl-2-naphthaldehyde

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25 g of 5,8-Dimethylethylene dissolved in 200 ml of methanol in a nitrogen atmosphere and the resulting solution at 0oWith add 3.0 g of sodium borohydride. The resulting mixture is stirred at a temperature of 0oC for 30 minutes and add to it in order saturated aqueous solution of ammonium chloride and water. The precipitate is collected by filtration, washed with water and dried to obtain the Astaro at 0oWith added dropwise 25 ml of phosphorus oxychloride. Then the reaction mixture is heated, with stirring, at a temperature of 100oC for 2 hours and allowed to cool to room temperature. To the obtained mixture is added a mixture of ice water and 9 g of sodium acetate and extracted with hexane (200 ml 4). The organic layers are combined, washed with saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The obtained filtrate concentrated with the receipt of 21.3 g of crude aldehyde.

20,9 Specified crude aldehyde was dissolved in 300 ml of dioxane in a nitrogen atmosphere and type of 50.9 g dichlorodicyanoquinone. The resulting mixture was heated under reflux for 1.5 hours and allowed to cool to room temperature, and then injected with 500 ml of toluene to obtain a precipitate. Containing precipitate, the mixture is filtered and the filter cake washed several times with toluene. The filtrate is concentrated and the resulting crude product was then purified by chromatography on columns of silica gel, which gives 10.3 g specified in the title compounds as colorless crystals.

1H-NMR(CDCl3, 400MHz) ;

2.69 (s, 3H), 2.76 (s, 3H), 7.31 (d, 1H, J=7.2 Hz), 7.37 (d, 1H, J= 7.2 Hz), 7.99 (dd, 1H, J=1.6, 8.8 Hz), 8.11 (d, 1H, J=8.4 Hz), 8.51 (d, 1H, J= 1.6 Hz), 10.2 connection receive in the form of oil as well as in preparatory example 1, except that as the starting compound used 5,7-dimethyl-1-tetralone.

1H-NMR(CDCl3, 400MHz) ;

2.50 (s, 3H), 2.68 (s, 3H), 7.32 (s, 1H), 7.62 (s, 1H), 7.91 (dd, 1H, J= 1.6, 8.4 Hz), 8.03 (d, 1H, J=8.4), 8.23 (d, 1H, J=1.6 Hz), 10.14 (s, 1H).

Preparatory example 3

2-Cyan-5,6,7,8-tetramethylnaphthalene

< / BR>
4,6 ml Diisopropylamine dissolved in 30 ml of tetrahydrofuran under nitrogen atmosphere and at a temperature of -20oTo the resulting solution was added dropwise n-utility in hexane. Get diamid lithium (LDA). A solution (10 ml) 3.7 g of dimethylacetal-lamprophyllite in tetrahydrofuran are added dropwise to the LDA at a temperature of -7oC and the resulting mixture was stirred at the same temperature for one hour. Then at a temperature of -78oTo the mixture are added dropwise a solution (10 ml) of 4.7 g of 2,3,4,5-tetramethylbenzidine in tetrahydrofuran and slowly increase the temperature of the reaction mixture to -20oC. the resulting mixture was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate (50 ml 3). The organic layers are combined, washed with saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The obtained filtrate the conc is 8.8 g of benzyl alcohol in the form of butter.

Benzyl alcohol (1.0 g) dissolved in 10 ml of methanol. This solution is added dropwise to 50 ml of a 20% aqueous solution of sulfuric acid, heated under reflux for 10 minutes. The resulting mixture was continued heating under reflux for one hour, after which the reaction ceased. The resulting reaction mixture is allowed to cool to room temperature and extracted with ethyl acetate (50 ml of 2). The organic layers are combined sequentially washed with water, saturated aqueous sodium bicarbonate and saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated to obtain 0.65 g of the specified header connection in the form of crude crystals.

1H-NMR(CDCl3, 400MHz) ;

2.45 (s, 3H), 2.46 (s, 3H), 2.62 (s, 3H), 2.63 (s, 3H), 7.56 (dd, 1H, J= 1.6, 8.8 Hz), 8.09 (d, 1H, J=8.8 Hz), 8.42 (d, 1H, J=1.6 H).

Preparatory example 4

5,6,1,8-Tetramethyl-2-naphthaldehyde

< / BR>
0.8 g of 2-Cyan-5,6,1,8-tetramethylnaphthalene dissolved in 30 ml of tetrahydrofuran under nitrogen atmosphere and the resulting solution at 0oWith add 5.7 ml of 1.0 M solution of hydride diisobutylaluminum in hexane. The resulting mixture was stirred at room temperature for 2.5 hours, poml 2). The organic layers are combined, washed with saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated and the resulting crude product was then purified by chromatography on columns of silica gel, which gives 0,68 g specified in the connection header in the form of butter.

1H-NMR(CDCl3, 400MHz) ;

2.46 (s, 3H), 2.47 (s, 3H), 2.65 (s, 3H), 2.72 (s, 3H), 7.90 (dd, 1H, J= 1.6, 8.8 Hz), 8.14 (d, 1H, J=8.8 Hz), 8.55 (d, 1H, J=1.6 Hz), 10.16 (3, 1H).

Preparatory example 5

2-Cyan-7-methoxynaphthalene

< / BR>
Specified in the title compound is obtained from meta-anisic aldehyde according to the procedure described in preparative example 3.

1H-NMR(CDCl3, 400MHz)

3.94 (s, 3H), 7.15 (d, 1H, J=2.8 Hz), 7.28 (dd, 1H, J=2.4, 9.2 Hz), 7.47 (dd, 1H, J=1.6, 8.4 Hz), 7.78 (d, 1H, J=9.2 Hz), 7.83 (d, 1H, J=8.4 Hz), 8.11 (s, 1H).

Preparatory example 6

7-Cyan-2-methoxy-1-naphthaldehyde

< / BR>
3.7 g of 2-Cyan-7-methoxynaphthalene dissolved in 40 ml of dichloromethane under nitrogen atmosphere and the resulting solution withoWith added dropwise to 6.6 ml of titanium tetrachloride and 4.6 ml dichlorodimethyl ether. The reaction mixture was stirred at room temperature for 30 minutes and again cooled to 0oC. To the resulting mixture, water is added to precritical, saturated aqueous sodium bicarbonate and saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated and the resulting crude crystalline material was washed with ether and dried, giving 3.3 grams specified in the title compounds as colorless crystals.

1H-NMR(CDCL3, 400MHz)

4.10 (S, 3H), 7.48 (d, 1H, J=8.8 Hz), 7.57 (dd, 1H, J=1.2, 8.4 Hz), 7.86 (d, 1H, J=8.4 Hz), 8.11 (d, 1H, J=8.8 Hz), 9.74 (s, 1H), 10.87 (s, 1H).

Preparatory example 7

2-Cyan-7-methoxy-8-methylnaphthalene

< / BR>
1.5 g of 7-Cyan-2-methoxy-1-naphthaldehyde suspended in 100 ml of ethanol in a nitrogen atmosphere and the resulting suspension at 0oWith added 0.14 g sodium borohydride. The reaction mixture was stirred at room temperature for 2 hours and again cooled to 0oC. the Reaction is stopped by adding water and dilute hydrochloric acid, after which the resulting mixture was extracted with ethyl acetate (100 ml of 2). The organic layers are combined sequentially washed with water, saturated aqueous sodium bicarbonate and saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated to obtain 1.5 g of alcohol.

1.5 g of the Alcohol is subjected to vzaimodeistviyam add water. The resulting mixture was extracted with ethyl acetate (100 ml of 2). The organic layers are combined sequentially washed with 2 N. a solution of hydrochloric acid, water, saturated aqueous sodium bicarbonate and saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated to obtain 1.9 g acetoxysilane in the form of a colorless solid.

Then 1,9 g acetoxysilane and 0.4 g of 10% palladium on coal (containing 50% water) are suspended in 200 ml of ethanol, and the resulting suspension for 2 hours and subjected to catalytic hydrogenation under normal pressure and normal temperature. The reaction mixture was filtered through celite and the filtrate concentrated. The resulting crude product was then purified by chromatography on columns of silica gel, giving 1.1 g specified in the title compound as a colourless solid.

1H-NMR(CDCl3, 400MHz) ;

2.55 (s, 3H), 3.97 (s, 3H), 7.40 (d, 1H, J=8.8 Hz), 7.45 (dd, 1H, J=1.6, 8.4 Hz), 7.76 (d, 1H, J=8.8 Hz), 7.84 (d, 1H, J=8.4 Hz), 8.34 (m, 1H).

Preparatory example 8

7-Methoxy-8-methyl-2-naphthaldehyde

< / BR>
Specified in the title compound obtained as a colorless solid according to the procedure described in podgetH-NMR(CDCl3, 400MHz)

2.64 (s, 3H), 3.98 (s, 3H), 7.41 (d, 1H, J=8.8 Hz), 7.78 (d, 1H, J= 9.2 Hz), 7.81 (dd, 1H, J=1.2, 8.4 Hz), 7.87 (d, 1H, J=8.4 Hz), 8.46 (s, 1H), 10.17 (s, 1H).

Preparation example 9

2-Cyan-7-methoxy-8-ethylnaphthalene

< / BR>
2.0 g of 7-Cyan-2-methoxy-1-naphthaldehyde suspended in 60 ml of tetrahydrofuran under nitrogen atmosphere and at a temperature of -78oTo the resulting suspension added dropwise to 4.7 ml of 3.0 M solution bromoethylamine in the air. The resulting mixture is stirred at a temperature of -78oC for 2 hours, then the reaction is stopped by adding a saturated aqueous solution of ammonium chloride. To the resulting mixture are added water and extracted with ethyl acetate (100 ml of 2). The organic layers are combined, washed with saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated to obtain 2.2 g of alcohol.

2.2 g of the Alcohol is subjected to interaction with 10 ml of pyridine and 10 ml of acetic anhydride under nitrogen atmosphere at room temperature for 12 hours, and then add water. The resulting mixture was extracted with ethyl acetate (100 ml of 2). The organic layers are combined sequentially washed with 2 N. a solution of hydrochloric acid, water, saturated aqueous sodium bicarbonate and saturated toxicomania in the form of a colorless solid.

Then 2.2 g of acetoxysilane and 0.4 g of 10% palladium on coal (containing 50% water) are suspended in 200 ml of ethanol, and the resulting suspension for 6.5 hours is subjected to catalytic hydrogenation under normal pressure and normal temperature. The reaction mixture was filtered through celite and the filtrate concentrated. The resulting crude product was then purified by chromatography on columns of silica gel, which gives 0,86 g specified in the title compound as a colourless solid.

1H-NMR(CDCl3, 400MHz) ;

1.23 (t, 3H, J=7.6 Hz), 3.08 (q, 2H, J=7.6 Hz), 3.98 (s, 3H), 7.41 (d, 1H, J= 9.2 Hz), 7.44 (dd, 1H, J=1.6, 8.4 Hz), 7.76 (d, 1H, J=9.2 Hz), 7.84 (d, 1H, J=8.4 Hz), 8.35 (s, 1H).

Preparatory example 10

7-Methoxy-8-ethyl-2-naphthaldehyde

< / BR>
Specified in the title compound obtained as a colorless solid according to the procedure described in preparation example 4, using as the starting material 2-cyan-7-methoxy-8-ethylnaphthalene.

1H-NMR(CDCl3, 400MHz) ;

1.27 (t, 3H, J=7.6 Hz), 3.18 (q, 2H, J=7.6 Hz), 3.98 (s, 3H), 7.41 (d, 1H, J= 8.8 Hz), 7.78 (d, 1H, J=9.2 Hz), 7.80 (dd, 1H, J=1.2, 8.4 Hz), 7.88 (d, 1H, J=8.4 Hz), 8.47 (s, 1H), 10.18 (s, 1H).

Preparatory example 11

2-Cyan-8-methylnaphthalene

< / BR>
of 0.60 g of 2-Cyan-7-methoxy-8-methylnaphthalene dissolved in 10 ml dig the boron in dichloromethane. The resulting mixture was stirred at room temperature for 24 hours and again cooled to 0oC. the Reaction is stopped by adding water, and the resulting mixture extracted with ethyl acetate (50 ml of 2). The organic layers are combined sequentially washed with saturated aqueous sodium bicarbonate and saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated and the resulting crude product was then purified by chromatography on columns of silica gel to obtain 0.95 g of the triflate in the form of a colorless solid.

0,85 g of the Triflate, 35 mg of triphenylphosphine and 12 mg of palladium acetate was dissolved in 20 ml of anhydrous N,N-dimethylformamide under nitrogen atmosphere and the resulting solution was added dropwise in the order of 1.1 ml of triethylamine and 0.21 ml of formic acid. The resulting mixture is heated while stirring at a temperature of 70oC for 6 hours and allowed to cool to room temperature. The reaction is stopped by adding a saturated aqueous solution of ammonium chloride and then water. The resulting mixture was extracted with ethyl acetate (50 ml of 2). The organic layers are combined, washed with saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is one triflate in the form of a colorless solid.

0,85 g of the Triflate, 35 mg of triphenylphosphine and 12 mg of palladium acetate was dissolved in 20 ml of anhydrous N,N-dimethylformamide in a nitrogen atmosphere and add water. The resulting mixture was extracted with ethyl acetate (50 ml of 2). The organic layers are combined, washed with saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated and the resulting crude product was then purified by chromatography on columns of silica gel, which gives 0,42 g specified in the title compound as a colourless solid.

1H-NMR(CDCl3, 400MHz) ;

2.72 (s, 3H), 7.44 (d, 1H, J=6.8 Hz), 7.53 (dd, 1H, J=7.2, 8.0 Hz), 7.62 (dd, 1H, J=1.6, 8.4 Hz), 7.74 (d, 1H, J=8.0 Hz), 7.91 (d, 1H, J=8.4 Hz), 8.40 (s, 1H).

Preparation example 12

8-Methyl-2-naphthaldehyde

< / BR>
Specified in the title compound obtained as a colorless solid according to the procedure described in preparation example 4, using as the starting material 2-cyan-8-methylnaphthalene.

1H-NMR(CDCl3, 400MHz) ;

2.79 (s, 3H), 7.42 (d, 1H, J=7.2 Hz), 7.53 (dd, 1H, J=7.2, 8.0 Hz), 7.76 (d, 1H, J=8.0 Hz), 7.93-7.97 (m, 2H), 8.51 (s, 1H), 10.19 (s, 1H).

Preparation example 13

2-Cyan-8-ethylnaphthalene

< / BR>
Specified in the title compound obtained as oils according to% the naphthalene.

1H-NMR(CDCl3, 400MHz) ;

1.39 (t, 3H, J= 7.6 Hz), 3.12 (q, 2H, J=7.6 Hz), 7.46 (d, 1H, J=7.2 Hz), 7.56 (dd, 1H, J=7.2, 8.0 Hz), 7.60 (dd, 1H, J=1.6, 8.4 Hz), 7.74 (d, 1H, J= 8.0 Hz), 7.92 (d, 1H, J=8.4 Hz), 8.45 (s, 1H).

Preparation example 14

8-Ethyl-2-natalidae

< / BR>
Specified in the header connection receive in accordance with the procedure described in preparation example 4, using as the starting material 2-cyan-8-ethylnaphthalene.

1H-NMR(CDCl3, 400MHz) ;

1.36 (t, 3H, J= 7.2 Hz), 3.14 (q, 2H, J=7.2 Hz), 7.38 (d, 1H, J=6.8 Hz), 7.50 (dd, 1H, J=6.8, 8.4 Hz), 7.70 (d, 1H, J=8.4 Hz), 7.88 (d, 2H, J=1.2 Hz), 8.50 (s, 1H), 10.12 (s, 1H).

Preparation example 15

7'-Cyan-2'-methoxy-1'-acetonaphthone

< / BR>
1.2 ml of Oxalicacid dissolved in 25 ml of dichloromethane in a nitrogen atmosphere and at a temperature of -78oTo the resulting solution was added dropwise a solution (5 ml) and 1.4 ml of dimethyl sulfoxide in dichloromethane. Then at a temperature of -78oTo the above mixture is added dropwise a solution (10 ml) of 1.99 g of the alcohol obtained in accordance with preparation example 1, in dichloromethane. The reaction mixture is stirred for 5 minutes and add to 6.1 ml of triethylamine, and then its temperature was raised to 0oWith and stop the reaction by adding water. The resulting mixture was extracted with ethyl acetate (150 I, and filtered. The filtrate is concentrated and the resulting crude crystalline material was washed with hexane and dried, giving 1.88 g specified in the title compound as a colourless solid.

1H-NMR(CDCl3, 400MHz) ;

2.67 (s, 3H), 4.02 (s, 3H), 7.44 (d, 1H, J=9.2 Hz), 7.49 (dd, 1H, J=2.0, 8.4 Hz), 7.87 (d, 1H, J=8.4 Hz), 7.95 (d, 1H, J=9.2 Hz), 8.22 (m, 1H).

Preparation example 16

2-Cyan-8-Isopropenyl-7-methoxynaphthalene

< / BR>
of 0.62 g of Tert-butoxide potassium suspended in 10 ml of toluene in a nitrogen atmosphere and at room temperature to the resulting suspension type of 2.26 g of iodide trimethylphosphine. The resulting mixture is heated, with stirring, at a temperature of 100oC for one hour to obtain a yellow suspension. To this suspension is added 0.84 g of 7'-cyan-2'-methoxy-1'-acetonaphthone, after which the reaction mixture continued to stir at a temperature of 10oC for 30 minutes, allowed to cool to room temperature, diluted with ethyl acetate and filtered through celite. The filtrate is washed with saturated salt solution, dried over anhydrous magnesium sulfate, filtered and concentrated. The resulting crude product was then purified by chromatography on columns of silica gel, which gives 0,78 g specified in the connection header in the form masla.83 (d, 1H, J=9.2 Hz), 7.84 (d, 1H, J= 8.4 Hz), 8.37 (m, 1H).

Preparation example 17

2-Cyan-8-isopropylnaphthalene

< / BR>
Specified in the title compound obtained as oil according to the procedure described in preparative example 11, using as the starting material 2-cyan-8-Isopropenyl-7-methoxynaphthalene.

1H-NMR(CDCl3, 400MHz) ;

2 2.21 (s, 3H), 5.06 (m, 1H), 5.50 (m, 1H), 7.43 (d, 1H, J=7.2 Hz), 7.59 (t, 1H, J=8.0 Hz), 7.59 (dd, 1H, J=1.6, 8.4 Hz), 7.79 (d, 1H, J=8.0 Hz), 7.91 (d, 1H, J=8.4 Hz), 8.48 (m, 1H).

Preparation example 18

8-Isopropenyl-2-naphthaldehyde

< / BR>
Specified in the title compound obtained as oil according to the procedure described in preparation example 4, using as the starting material 2-cyan-8-isopropylnaphthalene.

1H-NMR(CDCl3, 400MHz) ;

2.25 (s, 3H), 5.10 (m, 1H), 5.51 (m, 1H), 7.43 (dd, 1H, J=1.2, 7.2 Hz), 7.60 (dd, 1H, J=7.2, 8.0 Hz), 7.81 (d, 1H, J=8.0 Hz), 7.94 (m, 2H), 8.58 (m, 1H), 10.15 (m, 1H).

Preparation example 19

2-Cyan-8-isopropylnaphthalene

< / BR>
2-Cyan-8-isopropylnaphthalene (0,23 g) and 10% palladium on coal (containing 50% water) (50 mg) are suspended in 20 ml of ethanol, and the resulting suspension for one hour and subjected to catalytic hydrogenation under normal temperature and normal Dawley the product was then purified by chromatography on columns of silica gel, giving 0.20 g specified in the connection header in the form of butter.

1H-NMR(CDCl3, 400MHz) ;

1.41 (d, 6N, 6.8 Hz), 3.71 (quint., 1H, J=6.8 Hz), 7.53 (d, 1H, J=7.2 Hz), 7.60 (d, 1H, J=8.4 Hz), 7.61 (dd, 1H, J=7.2, 8.4 Hz), 7.74 (d, 1H, J=8.4 Hz), 7.92 (d, 1H, J=8.4 Hz), 8.53 (s, 1H).

Preparation example 20

8-Isopropyl-2-naphthaldehyde

< / BR>
Specified in the title compound obtained as oil according to the procedure described in preparation example 4, using as the starting material 2-cyan-8-isopropylnaphthalene.

1H-NMR(CDCl3, 400MHz) ;

1.44 (d, 6H, J= 6.8 Hz), 3.86 (quint., 1H, J=6.8 Hz), 7.53 (d, 1H, J= 7.2 Hz), 7.61 (dd, 1H, J=7.2, 8.0 Hz), 7.76 (d, 1H, J=8.4 Hz), 7.95 (m, 2H), 8.65 (s, 1H), 10.19 (s, 1H).

Preparation example 21

7-Cyan-2-methoxy-1-naphthol

< / BR>
Specified in the title compound obtained as a colorless solid according to the procedure described in preparation example 3, using as the starting material 3-methoxy-2-methoxy-methoxybenzaldehyde.

1H-NMR(CDCl3, 400MHz) ;

4.03 (s, 3H), 7.39 (d, 1H, J=8.8 Hz), 7.44 (d, 2H, J=8.8 Hz), 7.80 (d, 1H, J=8.8 Hz), 8.55 (m, 1H).

Preparation example 22

2-Cyan-7-methoxy-8-triftoratsetilatsetonom

< / BR>
2.9 g of Naphthol are dissolved in 150 ml of dichloromethane in the atmosphere azo is iformatsionnogo anhydride. The reaction mixture was stirred at 0oC for one hour and stop the reaction by adding water. To the obtained mixture is added 6 n hydrochloric acid and extracted with ethyl acetate (500 ml 2). The organic layers are combined sequentially washed with water, saturated aqueous sodium bicarbonate and saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated and the resulting crude product was then purified by chromatography on columns of silica gel, giving 4.3 g specified in the title compound as a colourless solid.

1H-NMR(cdcl3, 400MHz) ;

4.08 (s, 3H), 7.54 (d, 1H, J=9.2 Hz), 7.58 (dd, 1H, J=1.6, 8.8 Hz), 7.93 (d, 1H, J=8.8 Hz), 7.94 (d, 1H, J=8.8 Hz), 8.30 (s, 1H).

Preparation example 23

2-Cyan-7-methoxy-8-phenylnaphthalene

< / BR>
1.2 g of 2-Cyan-7-methoxy-8-triftoratsetilatsetonom, 0.66 g phenylboronic acid, 0.12 g tetranitroaniline and 1.5 ml of triethylamine are suspended in 20 ml of anhydrous N,N-dimethylformamide in a nitrogen atmosphere. The resulting suspension is heated, with stirring, at a temperature of 100oC for 1.5 hours and allowed to cool to room temperature. To the resulting reaction mixture is added saturated the saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated and the resulting crude product was then purified by chromatography on columns of silica gel, which gives 0.95 g specified in the connection header.

1H-NMR(CDCl3, 400MHz)

3.87 (s, 3H), 7.30-7.33 (m, 2H), 7.43-7.55 (m, 5H), 7.88 (m, 1H), 7.89 (d, 1H, J=8.4 Hz), 7.93 (d, 1H, J=8.8 Hz).

Preparation example 24

2-Cyan-8-phenylnaphthalene

< / BR>
Specified in the title compound obtained as a colorless solid according to the procedure described in preparative example 11, using as the starting material 2-cyan-7-methoxy-8-phenylnaphthalene.

1H-NMR(CDCl3, 400MHz) ;

7.43-7.56 (m, 6H), 7.62 (dd, 1H, J=1.6, 8.4 Hz), 7.69 (dd, 1H, J=7.2, 8.0 Hz), 7.90 (d, 1H, J=8.4 Hz), 7.98 (d, 1H, J=8.4 Hz), 8.29 (m, 1H).

Preparation example 25

8-Phenyl-2-naphthaldehyde

< / BR>
Specified in the title compound obtained as a pale yellow oil according to the procedure described in preparation example 4, using as the starting material 2-cyan-8-phenylnaphthalene.

1H-NMR(CDCl3, 400MHz) ;

7.48-7.57 (m, 6N), 7.69 (dd, 1H, J=7.2, 8.0 Hz), 7.92 (d, 1H, J=8.4 Hz), 7.98 (dd, 1H, J=1.2, 8.4 Hz), 8.00 (d, 1H, J=8.4 Hz), 8.39 (m, 1H), 10.02 (s, 1H).

Preparation example 26

Methyl 4-acelorbovar 1.0 M solution (100 ml) brompheniramine in tetrahydrofuran. The resulting mixture was stirred at the same temperature for 30 minutes, quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate (200 ml of 2). The organic layers are combined, washed with saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated and the resulting crude product was then purified by chromatography on columns of silica gel, which gives 11.6 g of allyl alcohol.

Then 11.6 g of allyl alcohol was dissolved in 600 ml of dichloromethane, add 3 g of molecular sieves (3A) and 27 g of bichromate of pyridinium. The resulting mixture was stirred at room temperature for 4 hours and filtered through celite. The filtrate is concentrated and the resulting crude product was then purified by chromatography on columns of silica gel, giving 5.5 g specified in the title compounds as colorless crystals.

1H-NMR(CDCl3, 400MHz) ;

3.96 (s, 3H), 6.00 (d, 1H, J=10.4 Hz), 6.46 (d, 1H, J=17.2 Hz), 7.14 (dd, 1H, J=10.4, 17.2 Hz), 7.98 (d, 2H, J=8.4 Hz), 8.14 (d, 2H, J=8.4 Hz).

Preparation example 27

4,7-Dimethylbenzofuran-2-carbaldehyde

< / BR>
To a 100 ml solution of 10 g of 2,5-dimethylphenol in N,N-dimethylformamide add to 22.6 g of anhydrous potassium carbonate and 14.8 ml of diethylacetal of bromoacetaldehyde. The resulting mixture of nercury and extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and the solvent is evaporated. The resulting residue is purified by chromatography on columns of silica gel, giving 18 g of a simple ester as a colourless oil.

This ester is dissolved in 100 ml of toluene and added dropwise to 50 g of polyphosphoric acid. The reaction mixture is heated, with stirring, at a temperature of 90oC in nitrogen atmosphere for one hour, allowed to cool to room temperature and poured into a mixture of ice water. The resulting mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and the solvent is evaporated. The resulting residue is purified by chromatography on columns of silica gel, giving 3.5 g of 4,7-dimethylbenzofuran in the form of a yellow oil.

To 50 ml of a solution of 3.5 g of 4,7-dimethylbenzofuran in anhydrous tetrahydrofuran at -35oC in nitrogen atmosphere add to 18.4 ml of n-utility (1,56 M solution in hexane). The reaction mixture is stirred for 15 minutes, then added dropwise 5.6 ml of N,N-dimethylformamide. The resulting mixture was left to warm to room temperature and add ethyl acetate. Organical. The resulting crude crystalline material was washed with n-hexane, giving 2.3 g specified in the title compounds as a pale yellow solid.

1H-NMR(CDCl3, 400MHz) ;

2.53 (s, 6H), 7.02 (d, 1H, J=6.8 Hz), 7.20 (d, 1H, J=6.8 Hz), 7.59 (s, 1H), 9.85 (s, 1H).

Preparation example 28

4,7-Dimethylbenzofuran-2-carbaldehyde

< / BR>
To 200 ml of a solution of 17.4 g of 3,6-dimethylaminobenzaldehyde in N,N-dimethylformamide added 32 g of anhydrous potassium carbonate and 17.8 ml of diethylacetal of bromoacetaldehyde. The resulting mixture was stirred at a temperature of 150oC for 2.5 hours, allowed to cool to room temperature and extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and the solvent is evaporated. The resulting residue is purified by chromatography on columns of silica gel, which gives to 23.4 g of simple ether. This ester is dissolved in 120 ml of acetic acid. The resulting solution was heated under reflux in nitrogen atmosphere for 8 hours, allowed to cool to room temperature and poured into saturated extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate, Yedinaya in the form of a pale yellow solid.

Preparation example 29

5-fluoro-4,7-dimethylbenzofuran-2-carbaldehyde

< / BR>
(A) 5-fluoro-2-methoxy-4-methylbenzaldehyde

< / BR>
10 g of 4-Fluoro-3-methylanisole dissolved in 80 ml of dichloromethane and the resulting solution at 0oGradually add 10 ml of titanium tetrachloride and 7.5 ml dichlorodimethyl ether. The resulting mixture was stirred at the same temperature for 30 minutes. The reaction mixture was poured into a mixture of ice water and add 300 ml of ethyl acetate. The organic phase is washed with saturated salt solution and dried over anhydrous magnesium sulfate.

The desiccant is filtered off and the mixture is evaporated to obtain a solid substance. This solid substance is added n-hexane and the resulting mixture filtered. The filter cake was washed with n-hexane to obtain 5.8 g specified in the title compound as white crystals.

1H-NMR(CDCl3, 400MHz) ;

2.33 (s, 3H), 3.88 (s, 3H), 6.79 (d, 1H, J=5.6 Hz), 7.44 (d, 1H, J= 9.6 Hz), 10.36 (s, 1H).

(B) 4-Fluoro-2,5-dimethylanisole

< / BR>
of 17.5 g of 5-fluoro-2-methoxy-4-methylbenzaldehyde dissolved in 100 ml of methanol to the resulting suspension at 0oWith added 4.7 g of sodium borohydride and stirred the mixture for 30 minutes. To the reaction mixture DML ethyl acetate. The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The desiccant (desiccant) is filtered off and the resulting mixture is evaporated to obtain white crystals. These crystals are dissolved in 50 ml of pyridine and add 19,6 ml of acetic anhydride. The reaction mixture was stirred at room temperature for 4 hours and poured into a chilled dilute hydrochloric acid. Then the resulting mixture was stirred for 30 minutes and add ethyl acetate. The organic layer was separated, washed with water, saturated aqueous sodium bicarbonate and saturated salt solution and dried over anhydrous magnesium sulfate. The desiccant is filtered off and the mixture is evaporated to obtain a solid substance. This solid is dissolved in 100 ml of ethyl acetate and add 3 g of 10% palladium on coal (containing 50% water). The resulting mixture for 3 hours and subjected to catalytic hydrogenation under normal temperature and normal pressure, after which it is filtered through celite. The filtrate is concentrated and the resulting crude product was then purified by chromatography on columns of silica gel, which gives 9.7 g specified in the title compounds as colorless oils.

1H-NMR(
< / BR>
9.7 g of 4-Fluoro-2,5-dimethylanisole dissolved in 100 ml of dichloromethane and, at 0oTo the solution was added 76 ml trichromate boron (1.0 M solution in dichloromethane). The reaction mixture is brought to room temperature, stirred for one hour and poured into a mixture of ice water. To the obtained mixture is added 300 ml of ethyl acetate. The organic layer is successively washed with water, saturated aqueous sodium bicarbonate and dried over magnesium sulfate. The desiccant is filtered off and the mixture evaporated. The resulting crude product was then purified by chromatography on columns of silica gel, giving 8.5 g specified in the title compounds as a pale brown oil.

1H-NMR(CDCl3, 400MHz) ;

2.18 (s, 6H), 4.41 (s, 1H), 6.56 (d, 1H, J=6.8 Hz), 6.76 (d, 1H, J= 10.0 Hz).

(D) 5-fluoro-4,7-dimethylbenzofuran-2-carbaldehyde

< / BR>
Specified in the header connection receive in accordance with the procedure described in preparative example 21, using as the starting material 4-fluoro-2,5-dimethylphenol.

1H-NMR(CDCl3, 400MHz) ;

2.42 (s, 6H), 2.53 (s, 3H), 7.04 (d, 1H, J=10.0 Hz), 7.58 (s, 1H), 9.86 (s, 1H).

Preparation example 30

4,7-Diethyl-5-perbendaharaan-2-carbaldehyde

< / BR>
(A) 3-Ethynyl-4-Floransa
and. The resulting suspension is stirred in a stream of nitrogen at 0oC for 30 minutes, then added dropwise a solution of 10 g of 2-fluoro-5-methoxybenzaldehyde in 20 ml of tetrahydrofuran. The resulting mixture was stirred for further one hour, quenched by adding water and extracted with ethyl acetate. The obtained organic layer is successively washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. The resulting residue is treated by chromatography on columns of silica gel (developer: a mixture of 5% ethyl acetate n-hexane), giving 9,1 g specified in the title compounds as colorless oils.

1H-NMR(CDCl3, 400MHz) ;

3.80 (s, 3H), 5.37 (dd, 1H, J= 1.2, 11.2 Hz), 5.81 (dd, 1H, J=1.2, 17.6 Hz), 6.75 (ddd, 1H, J=3.6, 3.6, 8.8 Hz), 6.84 (dd, 1H, J=11.2, 17.6 Hz), 6.93-6.99 (m, 2H).

(B) 3-Ethyl-4-Floransa

< / BR>
To a solution of 9 g of 3-ethynyl-4-fernicola in 200 ml of ethanol is added 0.9 g of palladium on coal. The resulting mixture is stirred in hydrogen atmosphere overnight and filtered through celite. The filtrate is evaporated and the resulting residue is treated by chromatography on columns of silica gel (developer: a mixture of 50% ethyl acetate n-hexane), giving 7.0 g specified in the title compounds as colorless oils.

H, J=8.8 Hz).

(C) 4-Ethyl-5-fluoro-2-methoxybenzaldehyde

< / BR>
Specified in the title compound obtained as a colorless solid according to the procedure described in example 29(A), using as the starting material 3-ethyl-4-Floransa.

1H-NMR(CDCl3, 400MHz)

1.26 (t, 3H, J=7.6 Hz), 2.70 (q, 2H, J=7.6 Hz), 3.92 (s, 3H), 6.80 (d, 1H, J=5.5 Hz), 7.45 (d, 1H, J=9.3 Hz), 10.36 (d, 1H, J=3.1 Hz).

(D) 2,5-Diethyl-4-Floransa

< / BR>
Specified in the title compound obtained as a colorless oil according to the procedure described in the above stage (a) and (b) using as the starting material 4-ethyl-5-fluoro-2-methoxybenzaldehyde.

1H-NMR(CDCl3, 400MHz)

1.17 (t, 3H, J=7.5 Hz), 1.22 (1, 3H, J=7.5 Hz), 2.57 (q, 2H, J=7.5 Hz), 2.62 (q, 2H, J= 7.5 Hz), 3.80 (s, 3H), 6.63 (d, 1H, J=6.4 Hz), 6.80 (d, 1H, J= 10.4 Hz).

2,5-Diethyl-4-terfenol

< / BR>
Specified in the title compound obtained as a colorless oil according to the procedure described in preparation example 29(C), using as the starting material 2,5-diethyl-4-Floransa.

1H-NMR(CDCl3, 400MHz) ;

1.19 (t, 3H, J=7.6 Hz), 1.21 (t, 3H, J=7.6 Hz), 2.54-2.61 (m, 4H), 4.48 (s, 1H), 6.58 (d, 1H, J=6.6 Hz), 7.78 (d, 1H, J=10.4 Hz).

(E) 4,7-Diethyl-5-perbendaharaan-2-carbaldehyde

< / BR>
Kaipola in as the starting material 3-ethyl-4-Floransa.

1H-NMR(CDCl3, 400MHz) ;

1.28 (t, 3H, J= 7.6 Hz), 1.34 (t, 3H, J=7.6 Hz), 2.87 (dq, 2H, J=1.2, 7.6 Hz), 2.94 (q, 2H, J=7.6 Hz), 7.06 (d, 1H, J=10.8 Hz), 7.60 (s, 1H), 9.86 (s, 1H).

Preparation example 31

5-Chloro-3-fluoro-4,7-dimethylbenzofuran

< / BR>
To 20 ml of a solution of 2 g of 5-chloro-4,7-dimethylbenzofuran in hexane is added dropwise 0.9 ml of bromine, the mixture is stirred for 3 hours and poured into saturated aqueous sodium bicarbonate solution. The reaction mixture was extracted with ethyl acetate, the organic layer was washed with saturated aqueous sodium bicarbonate and saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated to obtain 4 g of 2,4-dibromo-5-chloro-2,4-dihydro-4,7-dimethylbenzofuran in the form of a crude product.

Obtained above dibromide was dissolved in 30 ml of a mixture of benzene acetonitrile (9: 1) and to the resulting solution at 0oWith add 3 g of silver fluoride. The reaction mixture was stirred at room temperature under nitrogen atmosphere for 20 hours and filtered through celite. The filtrate is concentrated and the crude product add water. The resulting mixture was extracted with ethyl acetate, the organic layer washed with water and saturated salt solution, dried over anhydrous sulfate is the form of a crude product.

The above differed dissolved in 12 ml of 1 M solution of tert-butoxide potassium tert-butanol and add 4 g of 18-crown-6. The resulting mixture was stirred in nitrogen atmosphere at room temperature for 12 hours, quenched by adding water and extracted with ethyl acetate. The organic layer is washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated and the resulting crude product was then purified by chromatography on columns of silica gel, giving 1.3 g specified in the title compounds as a pale yellow oil.

1H-NMR(CDCl3, 400MHz) ;

2.41 (s, 3H), 2.57 (s, 3H), 7.12 (s, 1H), 7.58 (d, 1H, J=4.8 Hz).

Preparation example 32

4,7-Differentfor-2-carbaldehyde

< / BR>
(A) Allyl ether of 2,5-differenoe

< / BR>
10 g of 2,5-Differenoe dissolved in 120 ml of dimethylformamide and at room temperature to the resulting solution was added in a specified sequence, 21 g of potassium carbonate and to 8.57 ml allylbromide. The reaction mixture is stirred at a temperature of 80oC for one hour and add water. The resulting mixture was extracted with ethyl acetate, the organic layer was washed with saturated salt solution, dried over anhydrous sulfate MAG is 5% ethyl acetate/n-hexane), that gives 13 g specified in the title compounds as colorless oils.

1H-NMR(CDCl3, 400MHz)

4.58 (d, 2H, J=5.2 Hz), 5.33 (dd, 1H, J=2.4, 8.4 Hz), 5.44 (dd, 1H, d, J= 2.4, 17.2 Hz), 5.98-6.10 (m, 1H), 6.55-6.60 (m, 1H), 6.70 (ddd, 1H, J=3.2, 6.8, 10.0 Hz), 7.01 (ddd, 1H, J=5.2, 8.8, 10.0 Hz).

(A) 2-Allyl-3,6-diferena

< / BR>
13 g of Allyl ether of 2,5-differenoe dissolved in 90 ml of N,N-dimethylaniline. The resulting solution was stirred in a stream of nitrogen at a temperature of 170oC for 5 hours and poured into 10% aqueous solution of hydrogen chloride. The resulting mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. The resulting residue is treated by chromatography on silica gel (developer: a mixture of 7% ethyl acetate/n-hexane), giving 7,8 g specified in the title compounds as colorless oils.

1H-NMR(CDCl3, 400MHz) ;

3.44 (dd, 2H, J= 1.2, 6.0 Hz), 5.05-5.09 (m, 1H), 5.26-5.28 (m, 1H), 5.90-5.99 (m, 1H), 6.56 (dt, 1H, J=4.4, 9.2 Hz), 6.91 (dt, 1H, J=5.2, 9.2 Hz).

(C) 4,7-Debtor-2,3-dihydro-2-hydroxymethylbenzene

< / BR>
7 g of 2-Allyl-3,6-differenoe dissolved in 100 ml of dichloromethane and, at 0oWith the flow of nitrogen to the resulting solution was added 3-chloroperoxybenzoic acid. The reaction mixture parmitano, the organic layer was washed with saturated aqueous sodium bicarbonate and saturated salt solution, dried over anhydrous magnesium sulfate and evaporated/ giving 7.2 g of epoxide in the form of a crude product.

To a solution of 7.2 g of the above resin in a mixture of 30 ml of dimethyl sulfoxide with 10 ml of water at room temperature add the potassium hydroxide. The resulting mixture is stirred for 4 hours and add ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. The resulting residue is treated by chromatography on silica gel (developer: a mixture of 20% ethyl acetate/n-hexane), giving 1.2 g specified in the title compounds as colorless oils.

1H-NMR(CDCl3, 400MHz) ;

3.25 (dd, 1H, J=6.7, 16Hz), 3.33 (dd, 1H, J=8.0, 16.0 Hz), 3.75-3.83 (m, 1H), 3.90-3.97 (m, 1H), 5.04-5.13 (m, 1H), 6.49 (ddd, 1H, J=2.8, 10.0, 11.2 Hz), 6.87 (dt, 1H, J=4.4, 10.0 Hz)

(D) 2-Acetoxymethyl-4,7-debtor-2,3-dihydrobenzofuran

< / BR>
To a solution of 1.2 g of 4,7-debtor-2,3-dihydro-2-hydroxymethylbenzene in 6 ml of pyridine at 0oWith the flow of nitrogen added to 0.73 ml of acetic anhydride. The resulting mixture was stirred at room temperature for 17 hours, then poured into 10% aqueous solution of hydrogen chloride and the ex is m magnesium and evaporated. The resulting residue is treated by chromatography on silica gel (developer: a mixture of 5% ethyl acetate/n-hexane), giving 750 mg specified in the title compounds as colorless oils.

1H-NMR(CDCl3, 400MHz) ;

2.17 (s, 3H), 3.08 (dd, 1H, J= 7.2, 15.6 Hz), 3.39 (dd, 1H, J=10.0, 15.6 Hz), 4.28 (dd, 1H, J=6.4, 12Hz), 4.36 (dd, 1H, J=3.6, 12Hz), 5.13-5.20 (m, 1H), 6.51 (ddd, 1H, J=2.8, 10.0, 10.8 Hz), 6.89 (dt, 1H, J=4.4, 10.0 Hz).

(E) 2-Acetoxymethyl-4,7-differentfor

< / BR>
750 mg of 2-Acetoxymethyl-4,7-debtor-2,3-dihydrobenzofuran dissolved in 15 ml of carbon tetrachloride and at room temperature to the resulting solution was successively added 582 mg of N-bromosuccinimide and 10 mg azodiisobutyronitrile. The reaction mixture is heated under reflux for one hour and filtered through a glass filter. The filtrate is concentrated to obtain oil. To the oil is added ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated.

This bromide is dissolved in 6 ml of tert-butyl alcohol at room temperature in a flow of nitrogen to the resulting solution was added 3.3 ml of a 1.0 M solution of tert-butoxide potassium tert-butyl alcohol. The reaction mixture was stirred at room temperature in accordance with the m magnesium sulfate and evaporated. The resulting residue is treated by chromatography on silica gel (developer: mixture of 10% ethyl acetate/n-hexane), giving 252 mg specified in the title compounds as colorless oils.

1H-NMR(CDCl3, 400MHz) ;

2.14 (s, 3H), 5.20 (s, 2H), 6.84 (dt, 1H, J=3.2, 8.8 Hz), 6.89 (d, 1H, J= 2.4 Hz), 6.98 (ddd, 1H, J=4.0, 8.8 Hz).

(F) 4,7-Debtor-2-hydroxymethylbenzene

< / BR>
252 mg of 2-Acetoxymethyl-4,7-differenzierung dissolved in 5 ml of methanol and, at room temperature to the resulting solution was added 455 mg of potassium carbonate. The reaction mixture was stirred at the same temperature for 2 hours and add ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. The resulting residue is treated by chromatography on silica gel (developer: a mixture of 5% ethyl acetate/n-hexane), giving 161 mg specified in the title compounds as colorless oils.

1H-NMR(CDCl3, 400MHz) ;

4.80 (d, 2H, J= 4.0 Hz), 6.80 (d, 1H, J=2.8 Hz), 6.83 (dt, 1H, J=2.8, 8.4 Hz), 6.95 (ddd, 1H, J=4.0, 8.4, 10.0 Hz).

(G), 4,7-Differentfor-2-carbaldehyde

< / BR>
To a mixture of 0.42 ml of dimethyl sulfoxide and 7 ml of dichloromethane at a temperature of -78oC type of 0.26 ml of oxalicacid and stirred proximetry and stirred for 40 minutes, then add 1.2 ml of triethylamine and allowed to warm to room temperature. The resulting mixture was stirred at room temperature for another 30 minutes, add water and extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and evaporated. The resulting residue is treated by chromatography on silica gel (developer: a mixture of 5% ethyl acetate/n-hexane), giving 169 mg specified in the title compound as a colourless solid.

1H-NMR(CDCl3, 400MHz) ;

6.96 (dt, 1H, J=2.8, 8.8 Hz), 7.21 (ddd, 1H, J=4.0, 8.8, 9.6 Hz), 7.66 (d, 1H, J=2.4 Hz), 9.92 (s, 1H).

Example 1

4-{2-[5-(5,8-Dimethylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
(A) 2-Acryloyl-5,8-dimethylnaphthalene

< / BR>
3.7 g of 5,8-Dimethyl-2-naphthaldehyde dissolved in 80 ml of ether at a temperature of -78oWith and to the resulting solution was added 30 ml of 1.0 M solution brompheniramine in tetrahydrofuran. The temperature of the resulting mixture is slowly increased to -30oC. the Reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate (100 ml of 2). The organic layers are combined, washed with saturated salt solution, dried over anhydrous magnesium sulfate and fil is th product is dissolved in 30 ml of dichloromethane and add 30 g of activated manganese dioxide. The reaction mixture was stirred at room temperature for 40 hours and filtered. through celite. The filtrate is concentrated and the resulting crude product was then purified by chromatography on columns of silica gel, giving 1.8 g specified in the connection header with the release of 1.2 g of starting compound.

1H-NMR(CDCl3, 400MHz) ;

2.68 (s, 3H), 2.74 (s, 3H), 6.00 (dd, 1H, J=1.6, 10.4 Hz), 6.50 (dd, 1H, J=1.6, 17.2 Hz), 7.27-7.39 (m, 3H), 8.06-8.10 (m, 2H), 8.64 (s, 1H).

(C) Methyl 4-[4-(5,8-dimethylnaphthalene-2-yl)-4-oxobutanoic]benzoate

< / BR>
(Method 1)

A mixture of 1.8 g of 2-acryloyl-5,8-dimethylnaphthalene, 1.4 g of methyltrifluoroacetamide, of 0.23 g of sodium acetate, to 0.23 g of the chloride of 3-benzyl-5-(2-hydroxymethyl)-4-methylthiazole and 100 ml of ethanol, heated under reflux for 10 hours. The resulting crystals are collected by filtration, washed with ethanol and dried, giving 1.26 g specified in the title compounds as colorless crystals.

(Method 2)

A mixture consisting of 1.0 g of 5,8-dimethyl-2-naphthaldehyde, 1.2 g of methyl 4-acalolepta, 0.28 g of the chloride of 3-benzyl-5-(2-hydroxymethyl)-4-methylthiazole, 0,88 ml of triethylamine and 20 ml of N,N-dimethylformamide, heated, with stirring, at a temperature of 70oC for 3 hours and allowed to cool to komnatnaya, washed with saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated and the resulting crude crystal was washed with a mixture of n-hexane/ethyl acetate, giving 0,82 g specified in the title compounds as colorless crystals.

1H-NMR(CDCl3, 400MHz) ;

2.68 (s, H), 2.75 (s, 3H), 3.54 (t, 2H, J=6.4 Hz), 3.66 (t, 2H, J=6.4 Hz), 3.96 (s, 3H), 7.28 (d, 1H, J=7.2 Hz), 7.33 (d, 1H, J=7.2 Hz), 8.06-8.18 (m, 6H), 8.75 (d, 1H, J=1.6 Hz).

(C) Methyl 4-{2-[5-(5,8-dimethylnaphthalene-2-yl)pyrrolyl]}benzoate

< / BR>
A mixture consisting of 0.5 g of methyl 4-[4-(5,8-dimethylnaphthalene-2-yl)-4-oxobutanoic] benzoate, 2.0 g of ammonium acetate and 20 ml of methanol is heated under reflux for 5 hours and allowed to cool to room temperature. The obtained yellow crystals are collected by filtration, washed with methanol and dried, giving 0,47 g complex methyl ester as yellow crystals.

1H-NMR(CDCl3, 400MHz) ;

2.67 (s, 3H), 2.73 (s, 3H), 3.93 (s, 3H), 6.76 (m, 2H), 7.18 (d, 1H, J= 7.1 Hz), 7.23 (d, 1H, J=7.1 Hz), 7.63 (d, 2H, J=8.6 Hz), 7.74 (dd, 1H, J=1.6, 9.2 Hz), 8.03-8.09 (m, 4H), 8.84 (s, 1H).

(D) 4-{2-[5-(5,8-Dimethylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
A mixture of 0.68 g of complex methyl ester, 40 ml of ethanol and 4 ml of 5 N. aqueous sodium hydroxide solution, heated to about the of vlaa to her water. To the resulting solution add about 3.5 ml of 6 n hydrochloric acid and 40 ml of water. The resulting crystalline precipitate is collected by filtration, washed with water and dried, giving 0.52 g specified in the title compound as yellow crystals.

1H-NMR(CDCl3, 400MHz) ;

2.59 (s, 3H), 2.69 (s, 3H), 6.81 (m, 2H), 7.16 (d, 1H, J=7.1 Hz), 7.22 (d, 1H, J=7.1 Hz), 7.87-8.00 (m, 6N), 8.36 (s, 1H), 11.6 (s, 1H).

Example 2

4-{2-[5-(5,7-Dimethylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
(A) 2-Acryloyl-5,7-dimethylnaphthalene

< / BR>
Specified in the header of the connection receives the same way as in example 1(A).

1H-NMR(CDCl3, 400MHz) ;

2.50 (s, 3H), 2.68 (s, 3H), 5.97 (dd, 1H, J=1.6, 10.8 Hz), 6.49 (dd, 1H, J= 1.6, 17.2 Hz), 7.29 (s, 1H), 7.32 (dd, 1H, J=10.8, 17.2 Hz), 7.59 (s, 1H), 8.00 (m, 2H), 8.37 (s, 1H)

(C) Methyl 4-[4-(5,7-dimethylnaphthalene-2-yl)-4-oxobutanoic]benzoate

< / BR>
Specified in the header connection receive in accordance with method 1 of example 1(B).

1H-NMR(CDCl3, 400MHz) ;

2.51 (s, 3H), 2.6 (s, 3H), 3.53 (t, 2H, J=6.1 Hz), 3.63 (t, 2H, J=6.1 Hz), 3.96 (s, 3H), 7.30 (s, 1H), 7.61 (s, 1H), 8.01 (d, 1H, J=8.8 Hz), 8.03 (dd, 1H, J= 1.6, 8.8 Hz), 8.12 (d, 2H, J=8.8 Hz), 8.15 (d, 2H, J=8.8 Hz), 8.48 (s, 1H).

(C) Methyl 4-{2-[5-(5,7-dimethylnaphthalene-2-yl)pyrrolyl]}benzoate

< / BR>
Specified in the header of the connection receives the same way as in example 1 (the .67 (dd, 1H, J=1.6, 8.8 Hz), 7.85 (d, 1H, J= 1.6 Hz), 7.97 (d, 1H, J=8.8 Hz), 8.07 (d, 2H, J=8.4 Hz), 8.82 (s, 1H).

(D) 4-{2-[5-(5,7-Dimethylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

2.42 (s, 3H), 2.60 (s, 3H), 6.79 (m, 2H), 7.13 (s, 1H), 7.48 (s, 1H), 7.84-7.94 (m, 6H), 8.21 (s, 1H), 11.5 (s, 1H).

Example 3

4-{2-[5-(5,6,7,8-Tetramethylnaphthalene-2-yl)pyrrolyl])benzoic acid

< / BR>
(A) 2-Acryloyl-3,6,7,8-tetramethylnaphthalene

< / BR>
Specified in the header of the connection receives the same way as in example 1(A).

1H-NMR(CDCl3, 400MHz) ;

2.45 (s, 3H), 2.46 (s, 3H), 2.65 (s, 3H), 2.70 (s, 3H), 5.97 (dd, 1H, J= 2.0, 10.8 Hz), 6.50 (dd, 1H, J=1.6, 17.2 Hz), 7.36 (dd, 1H, J=10.8, 17.2 Hz), 7.98 (dd, 1H, J=1.6, 8.8 Hz), 8.11 (d, 1H, J=8.8 Hz), 8.71 (d, 1H, J=1.6 Hz).

(C) Methyl 4-[4-(5,6,7,8-tetramethylnaphthalene-2-yl)-4-oxobutanoic]benta

< / BR>
Specified in the header connection receive in accordance with method 1 of example 1(B).

1H-NMR(CDCl3, 400MHz) ;

2.45 (s, 6H), 2.64 (s, 3H), 2.71 (s, 3H), 3.52 (t, 2H, J=6.2 Hz), 3.65 (t, 2H, J=6.2 Hz), 3.96 (s, 3H), 7.92-8.20 (m, 6H), 8.80 (s, 1H).

(C) Methyl 4-(2-[5-(5,6,7,8-tetramethylnaphthalene-2-yl)pyrrolyl]}benzoate

< / BR>
Specified in the header of the connection receives the same way as in example 1(C).

1H-NMR(CDCl3, 400MHz) ;

2.44 (s, 3H)), 4-{2-[5-(5,6,7,8- Tetramethylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

2.37 (s, 3H), 2.38 (s, 3H), 2.56 (s, 3H), 2.67 (s, 3H), 6.79 (m, 2H), 7.83 (dd, 1H, J=1.2, 8.8 Hz), 7.89 (d, 2H, J=8.0 Hz), 7.93 (d, 2H, J=8.0 Hz), 8.39 (d, 1H, J=1.2 Hz), 11.6 (s, 1H).

Example 4

4-{2-[5-(7-Methoxy-8-methylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
(A) Methyl 4-[4-(7-methoxy-8-methylnaphthalene-2-yl)-4-oxobutanoic]benzoate

< / BR>
Specified in the header connection receive in accordance with method 2 of example 1(B).

1H-NMR(CDCl3, 400MHz) ;

2.64 (s, 3H), 3.53 (t, 2H, J=6.0 Hz), 3.65 (t, 2H, J=6.0 Hz), 3.96 (s, 3H), 3.98 (s, 3H), 7.38 (d, 1H, J=9.2 Hz), 7.76 (d, 1H, J=9.2 Hz), 7.85 (d, 1H, J= 8.8 Hz), 7.93 (dd, 1H, J=1.6, 8.8 Hz), 8.12 (d, 2H, J=8.8 Hz), 8.15 (d, 2H, J=8.8 Hz), 8.71 (m, 1H).

(C) Methyl 4-{2-[5-(7-methoxy-8-methylnaphthalene-2-yl)pyrrolyl]}benzoate

< / BR>
Specified in the header of the connection receives the same way as in example 1(C).

1H-NMR(CDCl3, 400MHz) ;

2.62 (s, 3H), 3.94 (s, 3H), 3.97 (s, 3H), 6.73-6.78 (m, 2H), 7.24 (d, 1H, J= 8.8 Hz), 7.56 (dd, 1H, J=2.0, 8.4 Hz), 7.63 (d, 2H, J=8.4 Hz), 7.70 (d, 1H, J= 8.8 Hz), 7.81 (d, 1H, J=8.4 Hz), 8.02 (s, 1H), 8.07 (d, 2H, J=8.4 Hz), 8.83 (brs, 1H).

(C) 4-{2-[5-(7-Methoxy-8-methylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

2.56 (s, 3 the P> Example 5

4-{2-[5-(7-Methoxy-8-ethylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
(A) Methyl 4-[4-(7-methoxy-8-ethylnaphthalene-2-yl)-4-oxobutanoic]benzoate

< / BR>
Specified in the header connection receive in accordance with method 2 of example 1(B).

1H-NMR(CDCl3, 400MHz)

1.27 (t, 3H, J= 7.4 Hz), 3.18 (q, 2H, J=7.4 Hz), 3.54 (t, 2H, J=6.1 Hz), 3.64 (t, 2H, J=6.1 Hz), 3.96 (s, 3H), 3.98 (s, 3H), 7.39 (d, 1H, J=9.2 Hz), 7.76 (d, 1H, J=9.2 Hz), 7.85 (d, 1H, J=8.4 Hz), 7.92 (dd, 1H, J=1.6, 8.4 Hz), 8.13 (d, 2H, J=8.4 Hz), 8.16 (d, 2H, J=8.4 Hz), 8.72 (s, 1H).

(C) Methyl 4-{2-[5-(7-methoxy-8-ethylnaphthalene-2-yl)pyrrolyl]}benzoate

< / BR>
1H-NMR(CDCl3, 400MHz) ;

1.29 (t, 3H, J= 7.5 Hz), 3.16 (q, 2H, J=7.5 Hz), 3.94 (s, 3H), 3.97 (s, 3H), 6.73-6.78 (m, 2H), 7.24 (d, 1H, J=8.8 Hz), 7.54 (dd, 1H, J=2.0, 8.4 Hz), 7.63 (d, 2H, J=8.0 Hz), 7.70 (d, 1H, J=8.8 Hz), 7.82 (d, 1H, J=8.4 Hz), 8.04 (s, 1H), 8.07 (d, 2H, J=8.0 Hz), 8.82 (brs, 1H).

(C) 4-(2-[5-(7-Methoxy-8-ethylnaphthalene-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

1.18 (t, 3H, J= 7.6 Hz), 3.14 (q, 2H, J=7.6 Hz), 3.91 (s, 3H), 6.81 (m, 2H), 7.33 (d, 1H, J=8.8 Hz), 7.74 (d, 2H, J=8.8 Hz), 7.83 (d, 1H, J=8.8 Hz), 7.91 (d, 2H, J=8.4 Hz), 7.94 (d, 2H, J=8.4 Hz), 8.28 (s, 1H), 11.6 (s, 1H).

Example 6

4-{2-[5-(8-the Methylnaphthalene-2-yl)pyrrolyl])benzoic acid

< / BR>
(A) Methyl 4-[4-(8-methylnaphthalene-2-yl)-4-oxobutanoic]benzoate

< / BR>
Specified in MHz) ;

2.79 (s, 3H), 3.54 (t, 2H, J=6.4 Hz), 3.66 (t, 2H, J=6.4 Hz), 3.96 (s, 3H), 7.40 (d, 1H, J=8.0 Hz), 7.50 (t, 1H, J=8.0 Hz), 7.74 (d, 1H, J=8.0 Hz), 7.92 (d, 1H, J=8.4 Hz), 8.08 (dd, 1H, J=2.0, 8.4 Hz), 8.12 (d, 2H, J=8.8 Hz), 8.16 (d, 2H, J=8.8 Hz), 8.75 (s, 1H).

(C) Methyl 4-{2-[5-(8-the methylnaphthalene-2-yl)pyrrolyl])benzoate

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(CDCl3, 400MHz) ;

2.76 (s, 3H), 3.94 (s, 3H), 6.74-6.78 (m, 2H), 7.34-7.36 (m, 2H), 7.64 (d, 2H, J= 8.4 Hz), 7.68-7.72 (m, 2H), 7.88 (d, 1H, J=8.4 Hz), 8.06-8.10 (m, 3H), 8.84 (brs, 1H).

() 4-{2-[5-(8-the Methylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

2.73 (s, 3H), 6.83 (d, 2H, J=2.0 Hz), 7.30-7.36 (m, 2H), 7.70 (m, 1H), 7.86-7.96 (m, 6H), 8.37 (s, 1H), 11.6 (s, 1H).

Example 7

4-{2-[5-(8-Ethylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
(A) Methyl 4-[4-(8-ethylnaphthalene-2-yl)-4-oxobutanoic]benzoate

< / BR>
Specified in the header connection receive in accordance with method 2 of example 1(B).

1H-NMR(CDCl3, 400MHz) ;

1.42 (t, 3H, J= 7.5 Hz), 3.20 (q, 2H, J=7.5 Hz), 3.55 (t, 2H, J=6.4 Hz), 3.65 (t, 2H, J=6.4 Hz), 3.96 (s, 3H), 7.42 (d, 1H, J=7.6 Hz), 7.53 (t, 1H, J= 7.6 Hz), 7.74 (d, 1H, J=8.0 Hz), 7.92 (d, 1H, J=8.8 Hz), 8.07 (dd, 1H, J=2.0, 8.8 Hz), 8.13 (d, 2H, J=8.4 Hz), 8.16 (d, 2H, J=8.4 Hz), 8.81 (s, 1H).

(C) Methyl 4-{2-[5-(8-ethylnaphthalene-2-yl)pyrrolyl])benzoate

< / BR>
UK.44 (t, 3H, J=7.5 Hz), 3.18 (q, 2H, J=7.5 Hz), 3.94 (s, 3H), 6.74 (dd, 1H, J=2.8, 3.6 Hz), 6.78 (dd, 1H, J=2.8, 3.6 Hz), 7.36-7.42 (m, 2H), 7.63 (d, 2H, J= 8.4 Hz), 7.67-7.70 (m, 2H), 7.89 (d, 1H, J=8.8 Hz), 8.08 (d, 2H, J= 8.4 Hz), 8.13 (s, 1H), 8.82 (brs, 1H).

(C) 4-{2-[5-(8-Ethylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

1.35 (t, 3H, J=7.5 Hz), 3.18 (q, 2H, J=7.5 Hz), 6.82 (s, 2H), 7.34-7.37 (m, 2H), 7.70 (m, 1H), 7.88-7.96 (m, 6H), 8.41 (s, 1H), 11.6 (s, 1H).

Example 8

4-{2-[5-(8-Isopropylnaphthalene-2-yl)pyrrolyl])benzoic acid

< / BR>
(A) Methyl 4-[4-(8-isopropylnaphthalene-2-yl)-4-oxobutanoic]benzoate

< / BR>
Specified in the header connection receive in accordance with method 2 of example 1(B).

1H-NMR(CDCl3, 400MHz) ;

1.44 (d, 6N, J= 7.0 Hz), 3.54 (t, 2H, J=6.4 Hz), 3.66 (t, 2H, J=6.4 Hz), 3.87 (q, 1H, J=7.0 Hz), 3.96 (s, 3H), 7.50 (d, 1H, J=8.0 Hz), 7.58 (t, 1H, J= 8.0 Hz), 7.73 (d, 1H, J=8.0 Hz), 7.92 (d, 1H, J=8.4 Hz), 8.06 (dd, 1H, J=1.6, 8.8 Hz), 8.12 (d, 2H, J=8.0 Hz), 8.16 (d, 2H, J=8.0 Hz), 8.90 (s, 1H).

(C) Methyl 4-{2-[5-(8-isopropylnaphthalene-2-yl)pyrrolyl]}benzoate

< / BR>
Specified in the header of the connection receives the same way as in example 1(C).

1H-NMR(CDCl3, 400MHz) ;

1.45 (d, 6H, J=7.2 Hz), 3.83 (quint., 1H, J=7.2 Hz), 3.94 (s, 3H), 6.74 (dd, 1H, J=2.4, 4.0 Hz), 6.78 (dd, 1H, J=2.4, 4.0 Hz), 7.41-7.46 (m, 2H), 7.63 (d, 2H, J=8.8 Hz), 7.67-7.70 (m, 2H), 7.89 (d, 1H, J=8.4 Hz), 8.07 (d, 2H, J= 8.8 Hz), 8.21 (s, 1H), 8.82 (brs, 1H).

1H-NMR(DMSO-d6, 400MHz)

1.37 (d, 6H, J=6.8 Hz), 3.96 (quint., 1H, J=6.8 Hz), 6.81 (m, 2H), 7.37-7.44 (m, 2H), 7.69 (d, 1H, J=8.0 Hz), 7.88-7.96 (m, 6H), 6.48 (s, 1H), 11.6 (s, 1H).

Example 9

4-{2-[5-(8-Isopropylnaphthalene-2-yl)pyrrolyl])benzoic acid

< / BR>
(A) Methyl 4-[4-(8-isopropylnaphthalene-2-yl)-4-oxobutanoic]benzoate

< / BR>
Specified in the header connection receive in accordance with method 2 of example 1(B).

1H-NMR(CDCl3, 400MHz) ;

2.25 (s, 3H), 3.52 (t, 2H, J=6.4 Hz), 3.63 (t, 2H, J=6.4 Hz), 3.96 (s, 3H), 5.10 (m, 1H), 5.51 (m, 1H), 7.40 (dd, 1H, J=1.2, 6.8 Hz), 7.56 (t, 1H, J=8.0 Hz), 7.79 (d, 1H, J=8.4 Hz), 7.91 (d, 1H, J=8.4 Hz), 8.06 (dd, 1H, J=2.0, 8.8 Hz), 8.11 (d, 2H, J=8.4 Hz), 8.16 (d, 2H, J=8.4 Hz), 8.82 (s, 1H).

(C) Methyl 4-{2-[5-(8-isopropylnaphthalene-2-yl)pyrrolyl]}benzoate

< / BR>
Specified in the header of the connection receives the same way as in example 1(C).

1H-NMR(CDCl3, 400MHz) ;

2.28 (s, 3H), 3.94 (s, 3H), 5.13 (m, 1H), 5.49 (m, 1H), 6.72 (dd, 1H, J= 2.8, 3.6 Hz), 6.76 (dd, 1H, J=2.4, 3.6 Hz), 7.34 (dd, 1H, J=1.6, 7.2 Hz), 7.41 (dd, 1H, J=7.2, 8.0 Hz), 7.62 (d, 2H, J=8.8 Hz), 7.70 (dd, 1H, J=2.0, 8.8 Hz), 7.74 (d, 1H, J=8.0 Hz), 7.88 (d, 1H, J=8.4 Hz), 8.07 (d, 2H, J=8.8 Hz), 8.14 (s, 1H), 8.79 (brs, 1H).

(C) 4-(2-[5-(8-Isopropylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

2.23 (s, 3H), 5.07 (m, 1H), 5.46 (m, 1H), the Lin-2-yl)pyrrolyl]}benzoic acid

< / BR>
(A) Methyl 4-[4-(8-phenylnaphthalene-2-yl)-4-oxobutanoic]benzoate

< / BR>
Specified in the header connection receive in accordance with method 2 of example 1(B).

1H-NMR(CDCl3, 400MHz)

3.45 (m, 4H), 3.95 (s, 3H), 7.46-7.54 (m, 6N), 7.66 (t, 1H, J=8.0 Hz), 7.90 (d, 1H, J=8.4 Hz), 7.98 (d, 1H, J=8.8 Hz), 8.06-8.10 (m, 3H), 8.13 (d, 2H, J=8.4 Hz), 8.66 (s, 1H).

(C) Methyl 4-(2-[5-(8-phenylnaphthalene-2-yl)pyrrolyl]}benzoate

< / BR>
Specified in the header of the connection receives the same way as in example 1(C).

1H-NMR(CDCl3, 400MHz) ;

3.92 (s, 3H), 6.64 (dd, 1H, J=2.4, 3.6 Hz), 6.71 (dd, 1H, J=2.4, 3.6 Hz), 7.44 (dd, 1H, J=1.6, 7.2 Hz), 7.48-7.56 (m, 8H), 7.72 (dd, 1H, J=1.6, 8.4 Hz), 7.84 (d, 1H, J=8.4 Hz), 7.94 (d, 1H, J=8.4 Hz), 8.00 (s, 1H), 8.03 (d, 2H, J= 8.4 Hz), 8.71 (brs, 1H).

() 4-(2-[5-(8-Phenylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

6.48 (m, 1H), 6.72 (m, 1H), 7.41 (dd, 1H, J=1.2, 6.8 Hz), 7.46-7.58 (m, 6H), 7.78 (d, 2H, J=8.4 Hz), 7.88 (d, 2H, J=8.4 Hz), 7.91 (d, 1H, J=8.4 Hz), 8.00 (dd, 1H, J=1.2, 7.8 Hz), 8.02 (d, 1H, J=7.8 Hz), 8.09 (s, 1H), 11.6 (s, 1H).

Example 11

4-{2-[5-(5,8-Dimethylnaphthalene-2-yl)-1-methylpyrrole]}benzoic acid

< / BR>
(A) Methyl 4-(2-[5-(5,8-dimethylnaphthalene-2-yl)-1-methylpyrrole]}benzoate

< / BR>
240 mg of Methyl 4-{ 2-[5-(5,8-dimethylnaphthalene-2-yl)pyrrolyl] )benzoate was dissolved in 5 ml of N,N-dim is one hour andoWith added dropwise 0.06 ml under the conditions. The resulting mixture was stirred at room temperature for one hour, add saturated aqueous solution of ammonium chloride and extracted with ethyl acetate (30 ml 2). The organic layers are combined, washed with saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated to obtain 300 mg specified in the title compound as crude product.

1H-NMR(CDCl3, 400MHz) ;

2.70 (s, 6H), 3.72 (s, 3H), 3.94 (s, 3H), 6.47 (d, 1H, J=3.6 Hz), 6.49 (d, 1H, J=3.6 Hz), 7.21-7.26 (m, 2H), 7.59 (d, 2H, J=8.0 Hz), 7.66 (dd, 1H, J= 1.6, 8.4 Hz), 8.06-8.12 (m, 4H).

() 4-[2-[5-(5,8-Dimethylnaphthalene-2-yl)-1-methylpyrrole]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

2.62 (s, 3H), 2.66 (s, 3H), 3.71 (s, 3H), 6.48 (m, 2H), 7.24 (d, 1H, J= 6.8 Hz), 7.26 (d, 1H, J=6.8 Hz), 7.68 (d, 2H, J=8.0 Hz), 7.73 (d, 1H, J=7.6 Hz), 7.99 (d, 2H, J=8.0 Hz), 8.07 (m, 2H).

Example 12

4-(2-[5-(5,8-Dimethylnaphthalene-2-yl)-1-isopropylpyrazole] )benzoic acid

< / BR>
(A) Methyl 4-{2-[5-(5,8-dimethylnaphthalene-2-yl)-1-isopropylpyrazole]}benzoate

< / BR>
to 0.23 g of Methyl 4-[4-(5,8-dimethylnaphthalene-2-yl)-4-oxobutanoic] benzoate was dissolved in 4 ml acetic acid at room temperature to poluce hours and allowed to cool to room temperature. To the resulting mixture are added water and extracted with ethyl acetate (30 ml 2). The organic layers are combined sequentially washed with saturated aqueous sodium bicarbonate and saturated salt solution, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated and the resulting crude product was then purified by chromatography on columns of silica gel, giving 95 mg specified in the connection header.

1H-NMR(CDCl3, 400MHz) ;

1.30 (d, 6H, J=7.0 Hz), 2.69 (s, 3H), 2.71 (s, 3H), 3.96 (s, 3H), 4.58 (quint. , 1H, J= 7.0 Hz), 6.29 (s, 2H), 7.23-7.28 (m, 2H), 7.58 (d, 2H, J= 8.2 Hz), 7.65 (dd, 1H, J=1.6, 8.4 Hz), 8.05 (d, 1H, J=8.4 Hz), 8.08-8.11 (m, 3H).

(B) 4-{ 2-[5-(5,8-Dimethylnaphthalene-2-yl)-1-isopropylpyrazole] }benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

1.22 (d, 6N, J=7.0 Hz), 2.63 (s, 6H), 4.50 (quint., 1H, J=7.0 Hz), 6.23 (s, 2H), 7.27 (q, type AB, 2H, J=6.8 Hz), 7.58 (d, 2H, J=8.0 Hz), 7.64 (dd, 1H, J=1.6, 8.8 Hz), 7.99 (m, 3H), 8.06 (d, 1H, J=8.8 Hz), 12.9 (brs, 1H).

Example 13

4-{2-[5-(4,7-Dimethylbenzofuran-2-yl)pyrrolyl])benzoic acid

< / BR>
(A) Methyl 4-[4-(4,7-dimethylbenzofuran-2-yl)-4-oxobutanoic]benzoate

< / BR>
Specified in the header connection receive in accordance with method 2 of example 1(B).

1H-NMR(CDCl3, 400MHz)

ethyl 4-{2-[5-(4,7-dimethylbenzofuran-2-yl)pyrrolyl]}benzoate

< / BR>
Specified in the header of the connection receives the same way as in example 1(C).

1H-NMR(CDCl3, 400MHz) ;

2.48 (s, 3H), 2.55 (s, 3H), 3.93 (s, 3H), 6.72-6.77 (m, 2H), 6.83 (s, 1H), 6.93 (d, 1H, J=6.8 Hz), 6.97 (d, 1H, J=6.8 Hz), 7.63 (d, 2H, J=8.4 Hz), 8.07 (d, 2H, J=8.4 Hz), 9.00 (brs, 1H).

() 4-{2-[5-(4,7-Dimethylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

2.43 (s, 3H), 2.46 (s, 3H), 6.71 (t, 1H, J=2.4 Hz), 6.84 (t, 1H, J= 2.4 Hz), 6.92 (d, 1H, J=7.2 Hz), 6.96 (d, 1H, J=7.2 Hz), 7.23 (s, 1H), 7.89 (d, 2H, J=8.4 Hz), 7.95 (d, 2H, J=8.4 Hz), 11.81 (brs, 1H), 12.85 (brs, 1H).

Example 14

4-{2-[5-(4,7-Dichlorobenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(0).

1H-NMR(DMSO-d6, 400MHz)

6.83 (t, 1H, J= 2.4 Hz), 6.89 (t, 1H, J=2.4 Hz), 7.35 (d, 1H, J=7.2 Hz), 7.38 (d, 1H, J=7.2 Hz), 7.39 (s, 1H), 7.91 (d, 2H, J=8.4 Hz), 7.97 (d, 2H, J= 8.4 Hz), 12.02 (brs, 1H), 12.86 (brs, 1H).

Example 15

4-{2-[5-(7-Chlorobenzophenone-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

6.76 (t, 1H, J= 3.2 Hz), 6.86 (t, 1H, J=3.2 Hz), 7.23 (t, 1H, J=7.6 Hz), 7.29 (s, 1H), 7.33 (dd, 1H, J=0.8, 7.6 Hz), 7.61 (dd, 1H, J=0.8, 7.6 Hz), 7.90 (d, 2H, J=8.4 Hz), 7.95 (d, 2H, J=8.4 Hz), 11.96 (s, 1H), 12.83 (brs, 1H).

Example 16

1H-NMR(DMSO-d6, 400MHz) ;

0.95 (t, 3H, J=7.2 Hz), 1.75 (sext, 2H, J=7.2 Hz), 2.87 (t, 2H, J=7.2 Hz), 6.71 (t, 1H, J=3.2 Hz), 6.84 (t, 1H, J=3.2 Hz), 7.06 (dd, 1H, J=1.2, 7.6 Hz), 7.13 (t, 1H, J=7.6 Hz), 7.17 (s, 1H), 7.44 (dd, 1H, J=1.2, 7.6 Hz), 7.88 (d, 2H, J=8.4 Hz), 7.95 (d, 2H, J=8.4 Hz), 11.82 (s, 1H), 12.80 (brs, 1H).

Example 17

4-{2-[5-(4-Methyl-7-ethylbenzophenone-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

1.29 (t, 3H, J= 7.6 Hz), 2.45 (s, 3H), 2.88 (q, 2H, J=7.6 Hz), 6.70 (m, 1H), 6.83 (m, lH), 6.95 (d, 1H, J=7.2 Hz), 6.98 (d, 1H, J=7.2 Hz), 7.23 (s, 1H) 7.89 (d, 2H, J=8.8 Hz), 7.94 (d, 2H, J=8.8 Hz), 11.80 (s, 1H), at 12.82 (brs, 1H).

Example 18

4-{2-[5-(4-Methyl-7-n-propylbenzene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

0.93 (t, 3H, J=7.6 Hz), 1.73 (sext, 2H, J=7.6 Hz), 2.45 (s, 3H), 2.83 (t, 2H, J= 7.6 Hz), 6.70 (m, 1H), 6.83 (m, 1H), 6.94 (d, 1H, J=7.2 Hz), 6.95 (d, 1H, J= 7.2 Hz), 7.22 (s, 1H), 7.89 (d, 2H, J=8.4 Hz), 7.94 (d, 2H, J=8.4 Hz), 11.81 (s, 1H), 12.83 (brs, 1H).

Example 19

4-{2-[5-(4-Chloro-7-methylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

2.48 (s, 3H), 6.78-6.82 (m, 1H), 6.85-6.88 (m, 1H), 7.09 (d, 1H, J= 7.6 Hz), 7.21 (d, 1H, J=7.6 Hz), 7.29 (s, 1H), 7.90 (d, 2H, J=8.4 Hz), 7>/BR>< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

1.30 (t, 3H, J= 7.5 Hz), 2.90 (q, 2H, J=7.5 Hz), 6.79 (dd, 1H, J=2.4, 3.6 Hz), 6.86 (dd, 1H, J=2.4, 3.6 Hz), 7.11 (d, 1H, J=8.0 Hz), 7.23 (d, 1H, J= 8.0 Hz), 7.29 (s, 1H), 7.89 (d, 2H, J=8.6 Hz), 7.95 (d, 2H, J=8.4 Hz), 11.90 (brs, 1H).

Example 21

4-{2-[5-(4-Chloro-7-n-propylbenzene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

0.94 (t, 3H, J=7.2 Hz), 1.68-1.77 (m, 2H), 2.86 (t, 2H, J=7.2 Hz), 6.77-6.80 (m, 1H), 6.84-6.88 (m, 1H), 7.09 (d, 1H, J=8.4 Hz), 7.22 (d, 1H, J= 8.4 Hz), 7.28 (s, 1H), 7.89 (d, 2H, J=8.8 Hz), 7.95 (d, 2H, J=8.8 Hz), 11.90 (brs, 1H).

Example 22

4-{2-[5-(5-Chloro-7-methylbenzofuran-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(0).

1H-NMR(DMSO-d6, 400MHz) ;

2.48 (s, 3H), 6.74-6.77 (m, 1H), 6.83-6.86 (m, 1H), 7.10-7.13 (m, 1H), 7.17 (s, 1H), 7.52-7.54 (m, 1H), 7.88 (d, 2H, J=8.4 Hz), 7.95 (d, 2H, J= 8.8 Hz), 11.89 (brs, 1H).

Example 23

4-{2-[5-(5-Chloro-7-ethylbenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

1.30 (t, 3H, J= 7.6 Hz), 2.90 (q, 2H, J=7.6 Hz), 6.74 (dd, 1H, J=1.6, 3.6 Hz), 6.84 (dd, 1H, J=1.2, 3.6 Hz), 7.12 (s, 1H), 7.17 (s, 1H), 7.54 (s, 1H), 7.89 (d, 2H, J=8.4 Hz), 7.94 (d,
< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

0.94 (t, 3H, J=7.6 Hz), 1.74 (sext, 2H, J=7.6 Hz), 2.86 (t, 2H, J=7.6 Hz), 6.74 (m, 1H), 6.84 (m, 1H), 7.10 (d, 1H, J=2.4 Hz), 7.18 (s, 1H), 7.54 (d, 1H, J=2.4 Hz), 7.89 (d, 2H, J=8.4 Hz), 7.94 (d, 2H, J=8.4 Hz), 11.91 (s, 1H).

Example 25

4-{2-[5-(5-Fluoro-7-ethylbenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz) ;

1.31 (t, 3H, J= 7.6 Hz), 2.91 (q, 2H, J=7.6 Hz), 6.74 (t, 1H, J=3.6 Hz), 6.84 (t, 1H, J=3.2 Hz), 6.94 (dd, 1H, J=2.0, 10.0 Hz), 7.25 (dd, 1H, J=2.4, 8.8 Hz), 7.29 (s, 1H), 7.94 (brs, 4H), 12.04 (brs, 1H).

Example 26

4-{2-[5-(5-Fluoro-7-n-propylbenzene-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

0.95(t, 3H, J= 7.2 Hz), 1.74(q, 2H, J= 7.2 Hz), 2.86(t, 2H, J=7.2 Hz), 6.73(dd, 1H, J=2.0, 3.6 Hz), 6.84(dd, 1H, J=2.4, 3.6 Hz), 6.93(dd, 1H, J=2.0, 10.4 Hz), 7.22-7.28(m, 2H), 7.90-7.96(brs, 4H), 12.00(s, 1H).

Example 27

4-{2-[5-(4,7-Differentfor-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.82(dd, 1H, J=2.4, 3.6 Hz), 6.86(dd, 1H, J=2.4, 3.6 Hz), 7.08(dd, 1H, J= 3.2, 8.8 Hz), 7.19(dd, 1H, J=3.2, 8.8 Hz), 7.42(d, 1H, J=2.4 Hz), 7.92(d, 2H, J=8.4 Hz), 7.96(d, 2H, J=8.4 Hz), 12.08(s, 1 is passed in the header of the connection will receive the same as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.25(s, 3H), 5.48(s, 1H), 5.93(s, 1H), 6.74(m, 1H), 6.84(m, 1H), 7.23(m, 2H), 7.67(m, 1H), 7.88(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.96(s, 1H), 12.87(brs, 1H).

Example 29

4-{2-[5-(5-Chloro-7-isopropylbenzene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.34(d, 6H, J= 7.2 Hz), 3.44 (quint, 1H, J=7.2 Hz), 6.75(m, 1H), 6.84(m, 1H), 7.12(m, 1H), 7.18(d, 1H, J=0.8 Hz), 7.54(dd, 1H, J=1.2, 2.0 Hz), 7.89(d, 2H, J=8.0 Hz), 7.94(d, 2H, J=8.0 Hz), 11.91(s, 1H), 12.88(brs, 1H).

Example 30

4-{2-[5-(5-Methyl-7-n-propylbenzene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

0.94(t, 3H, J=7.2 Hz), 1.74(sext, 2H, J=7.2 Hz), 2.34(s, 3H), 2.82(t, 2H, J= 7.2 Hz), 6.68(m, 1H), 6.83(m, 1H), 6.88(s, 1H), 7.11(s, 1H), 7.22(s, 1H), 7.88(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.81(s, 1H), 12.86(brs, 1H).

Example 31

4-{ 2-[5-(5-Methyl-7-isopropenylbenzene-2-yl)pyrrolyl] }benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.26(s, 3H), 2.38(s, 3H), 5.40(s, 1H), 5.88(s, 1H), 6.68(m, 1H), 6.83(m, 1H), 7.08(s, 1H), 7.15(s, 1H), 7.36(s, 1H), 7.88(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.84(s, 1H), 12.83(brs, 1H).

Example 32

4-{2-[5-(5-Methyl-7-isopropyl the example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.34(d, 6N, J= 6.8 Hz), 2.35(s, 3H), 3.40(quint, 1H, J=6.8 Hz), 6.68(dd, 1H, J= 2.4, 3.6 Hz), 6.82(dd, 1H, J=2.4, 3.6 Hz), 6.92(s, 1H), 7.10(s, 1H), 7.22(s, 1H), 7.88(d, 2H, J= 8.8 Hz), 7.94(d, 2H, J=8.8 Hz), 11.79(s, 1H), at 12.82(brs, 1H).

Example 33

4-{2-[5-(5-Methyl-7-ethylbenzophenone-2-ID)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.30(t, 3H, J= 7.6 Hz), 2.35(s, 3H), 2.87(q, 2H, J=7.6 Hz), 6.69(m, 1H), 6.83(m, 1H), 6.90(s, 1H), 7.11(s, 1H), 7.22(s, 1H), 7.88(d, 2H, J=7.6 Hz), 7.94(d, 2H, J=7.6 Hz), 11.81(s, 1H), 12.84(brs, 1H).

Example 34

4-{2-[5-(4-Methyl-7-isopropylbenzene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.33(d, 6N, J=6.8 Hz), 2.44(s, 3H), 3.41(quint, 1H, J=6.8 Hz), 6.70(m, 1H), 6.84(m, 1H), 6.95(d, 1H, J= 7.6 Hz), 7.00(d, 1H, J=7.6 Hz), 7.22(s, 1H), 7.88(d, 2H, J=7.6 Hz), 7.94(d, 2H, J=7.6 Hz), 11.80(s, 1H), 12.84(brs, 1H).

Example 35

4-{2-[5-(5-Methoxy-7-ethylbenzophenone-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.30(t, 3H, J= 7.6 Hz), 2.87(q, 1H, J=7.6 Hz), 3.77(s, 3H), 6.69(m, 2H), 6.83(dd, 1H, J=2.4, 3.6 Hz), 6.97(d, 1H, J=2.4 Hz), 7.12(s, 1H), 7.88(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.80(s, 1H), 12.83(brs, 1H).

Example 36

4-(2-[5-(5-Methoxy-7-n-propec in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

0.94(t, 3H, J= 7.2 Hz), 1.74(sext, 2H, J=7.6 Hz), 2.82(t, 2H, J=7.6 Hz), 3.76(s, 3H), 6.66(s, 1H), 6.68(m, 1H), 6.83(m, 1H), 6.98(s, 1H), 7.12(d, 1H, J= 1.6 Hz), 7.88(d, 2H, J= 8.4 Hz), 7.94(d, 2H, J= 8.4 Hz), 11.80(s, 1H), 12.83(brs, 1H).

Example 37

4-{2-[5-(4-Methoxy-7-ethylbenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.28(t, 3H, J= 7.6 Hz), 2.84(q, 2H, J=7.6 Hz), 3.87(s, 3H), 6.68(s, 1H), 6.69(d, 1H, J= 8.0 Hz), 6.82(s, 1H), 7.01(d, 1H, J=8.0 Hz), 7.23(s, 1H), 7.87(d, 2H, J=8.0 Hz), 7.94(d, 2H, J=8.0 Hz), 11.73(s1H), 12.80(brs, 1H).

Example 38

4-{2-[5-(4-Methoxy-7-n-propylbenzene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

0.93(t, 3H, J= 7.6 Hz), 1.70(m, 2H), 2.79(t, 2H, J=7.6 Hz), 3.88(s, 3H), 6.68(m, 2H), 6.82(m, 1H), 6.99(d, 1H, J=8.0 Hz), 7.23(s, 1H), 7.87(d, 2H, J= 8.0 Hz), 7.93(d, 2H, J=8.0 Hz), 11.73(s, 1H), 12.68(brs, 1H).

Example 39

4-(2-[5-(Indeno[4,5-b]furan-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.14(quint, 2H, J= 7.2 Hz), 2.97(t, 2H, J=7.2 Hz), 3.10(t, 2H, J=7.2 Hz), 6.68(m, 1H) 6.82(m, 1H), 7.12(d, 1H, J=7.6 Hz), 7.17(s, 1H), 7.39(d, 1H, J= 7.6 Hz), 7.88(d, 2H, J=7.6 Hz), 7.94(d, 2H, J=7.6 Hz), 11.81(s, 1H), at 12.82(brs, 1H).

Example 40

4-{2-[5-(6,7-Dimethyl who in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.30(s, 3H), 2.42(s, 3H), 6.69-6.72(m, 1H), 6.81-6.84(m, 1H), 7.02(d, 1H, J= 8.4 Hz), 7.11(s, 1H), 7.30(d, 1H, J=8.4 Hz), 7.88(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.78(s, 1H), 12.80(brs, 1H).

Example 41

4-{2-[5-(7-Phenoxybenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

6.56-6.59(m, 1H), 6.79-6.84(m, 2H), 7.07-7.21(m, 4H), 7.25(s, 1H), 7.37-7.44(m, 3H), 7.87(d, 2H, J=8.4 Hz), 7.93(d, 2H, J=8.4 Hz), 11.91(s, 1H), at 12.82(brs, 1H).

Example 42

4-(2-[5-(4-Fluoro-7-chlorbenzene-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.79-6.82(m, 1H), 6.86-6.89 (m, 1H), 7.14(t, 1H, J=8.8 Hz), 7.37(dd, 1H, J= 4.4, 8.4 HZ), 7.38 (s, 1H), 7.90(d, 2H, J=8.4 Hz), 7.96(d, 2H, J=8.4 Hz), 11.97(d, 1H), 12.86(brs, 1H).

Example 43

4-{2-[5-(5-Fluoro-7-chlorobenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.76-6.80(m, 1H), 6.84-6.88(m, 1H), 7.29(s, 1H), 7.34(dd, 1H, J=2.4, 8.4 HZ), 7.51(dd, 1H, J= 2.4, 8.4 Hz), 7.90(d, 2H, J=8.4 Hz), 7.96(d, 2H, J= 8.4 Hz), 12.00(s, 1H), 12.86(brs, 1H).

Example 44

4-{2-[5-(7-Triftormetilfosfinov-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header connection get the 6(d, 1H, J=7.6 Hz), 7.89(d, 2H, J=8.4 Hz), 7.96(d, 2H, J=8.4 HZ), 11.98(s, 1H), 12.83(brs, 1H)

Example 45

4-(2-[5(5,7-Dichlorobenzophenone-2-yl)pyrrole]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.76-6.81(m, 1H), 6.84-6.89(m, 1H), 7.28(s, 1H), 7.46(d, 1H, J=2.0 HZ), 7.76(d, 1H, J=2.0 Hz), 7.89(d, 2H, J=8.4 Hz), 7.95(d, 2H, J=8.4 Hz), 12.00(brs, 1H).

Example 46

4-{2[5-(4,7-Dichloro-3-methylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.56(s, 3H), 6.69-6.73(m, 1H), 6.89-6.93(m, 1H), 7.30(d, 1H, J=8.8 Hz), 7.39(d, 1H, J=8.8 Hz), 7.94(s, 4H), 11.97(brs, 1H), at 12.82(brs, 1H).

Example 47

4-{2-[5-(3,4,7-Trimethylbenzoyl-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.50(s, 3H), 2.53(s, 3H), 2.59(s, 3H), 6.57(brs, 1H), 6.82-6.88(m, 2H), 6.94(d, 1H, J=7.2 Hz), 7.90(s, 4H), 11.70(brs, 1H), 12.30(brs, 1H).

Example 48

4-{2-[5-(7-Isopropylbenzene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

1.36(d, 6H, J= 7.6 Hz), 3.45(quint, 1H, J= 7.6 Hz), 6.70-6.73(m, 1H), 6.83-6.86(m, 1H), 7.09-7.16(m, 2H), 7.17(s, 1H), 7.43(d, 1H, J=7.6 Hz), 7.88(d acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.35(s, 3H), 2.43(s, 3H), 6.65-6.68(m, 1H), 6.81-6.84(m, 1H), 6.87(brs, 1H), 7.16-7.21(m, 2H), 7.88(d, 2H, J=8.4 Hz), 7.93(d, 2H, J=8.4 Hz), 11.82(s, 1H), 12.79(brs, 1H).

Example 50

4-[2-[5-(5,7-Dimethylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.32(s, 3H), 2.45(s, 3H), 6.68-6.71(m, 1H), 6.80-6.83(m, 1H), 6.88(d, 1H, J= 1.2 Hz), 7.10(s, 1H), 7.20(d, 1H, J=1.2 Hz), 7.86(d, 2H, J=8.4 Hz), 7.93(d, 2H, J=8.4 Hz), 11.78(s, 1H), 12.80(brs, 1H).

Example 51

4-{2-[5-(4-Methoxy-7-methylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.41(s, 3H), 3.86(s, 3H), 6.66-6.70(m, 2H), 6.81-6.85(m, 1H), 6.99(d, 1H, J= 7.6 Hz), 7.24(s, 1H), 7.88(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.75(s, 1H), 12.80(brs, 1H).

Example 52

4-{2-[5-(7-Ethoxyresorufin-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.40(t, 3H, J= 7.6 Hz), 4.25(q, 2H, J=7.6 Hz), 6.68-6.71(m, 1H), 6.81-6.84(m, 1H), 6.87(d, 1H, J=7.6 Hz), 7.12(t, 1H, J=7.6 Hz), 7.16-7.19(m, 2H), 7.89(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.87(s, 1H), 12.78(brs, 1H).

Example 53

4-(2-[5-(7-� also, as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.73-6.76(m, 1H), 6.84-6.87(m, 1H), 7.05(d, 1H, J=8.0 Hz), 7.22(d, 1H, J= 8.0 Hz), 7.33(s, 1H), 7.90(d, 2H, J=8.4 Hz), 7.95(d, 2H, J=8.4 Hz), at 11.93(s, 1H), 12.88(brs, 1H).

Example 54

4-{2-[5-(7-Methoxybenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

3.93(s, 3H), 6.68-6.71 m, 1H), 6.81-6.84(m, 1H), 6.88(dd, 1H, J=1.2, 8.0 Hz), 7.14(t, 1H, J= 8.0 Hz), 7.18(s, 1H), 7.19(dd, 1H, J=1.2, 8.0 Hz), 7.89(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.87(s, 1H), 12.84(brs, 1H).

Example 55

4-(2-[5-(7-Ethylbenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

1.30(t, 3H, J= 7.6 Hz), 2.90(q, 2H, J=7.6 Hz), 6.70-6.73(m, 1H), 6.82-6.85(m, 1H), 7.08(dd, 1H, J=0.8, 8.0 Hz), 7.14(t, 1H, J=8.0 Hz), 7.44(dd, 1H, J= 0.8, 8.0 Hz), 7.88(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.82(s, 1H), 12.83(brs, 1H).

Example 56

4-{2-[5-(7-Phenylbenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.68-6.71(m, 1H), 6.83-6.86(m, 1H), 7.28(s, 1H), 7.32(t, 1H, J=7.6 Hz), 7.40-7.48(m, 2H), 7.56(t, 2H, J=7.6 Hz), 7.63(d, 1H, J=7.6 Hz), 7.88(d, 2H, J= 8.4 Hz), 7.92-7.98(m, 4H), 11.90(s, 1H), 12.84(brs, 1H).

Example 57

4-{2-[5-(7-Methylbenzofuran-2-yl)pyrrolyl]}benzoin-NMR(DMSO-d6, 400MHz);

2.52(s, 3H), 6.71-6.74(m, 1H), 6.83-6.86(m, 1H), 7.06(d, 1H, J=7.2 Hz), 7.12(t, 1H, J= 7.2 Hz), 7.18(s, 1H), 7.43(d, 1H, J=7.2 Hz), 7.89(d, 2H, J= 8.4 Hz), 7.95(d, 2H, J=8.4 Hz), 11.83(s, 1H), at 12.82(brs, 1H).

Example 58

4-(2-[5-(4,5-Dimethylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMF(DMSO-d6, 400MHz);

2.34(s, 3H), 2.46(s, 3H), 6.70(dd, 1H, J=2.4, 3.6 Hz), 6.83(dd, 1H, J= 2.4, 3.6 Hz), 7.11(s, 1H), 7.22(s, 1H), 7.87-7.95(m, 4H), 11.80(s, 1H), 12.79(s, 1H).

Example 59

4-{2-[5-(4-Methylbenzofuran-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.51(s, 3H), 6.72-6.73(m, 1H), 6.84-6.85 (m, 1H), 7.06(d, 1H, J=7.2 Hz), 7.12(dd, 1H, J=5.2, 5.2 Hz), 7.10(s, 1H), 7.44(d, 1H, J=7.6 Hz), 7.89(d, 2H, J=8.4 Hz), 7.95(d, 2H, J=8.4 Hz).

Example 60

4-(2-[5-(4-Chlorobenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.78-6.80(m, 1H), 6.86-6.87(m, 1H), 7.24-7.33(m, 3H), 7.57(d, 1H, J= 8.0 Hz), 7.92(d, 2H, J=8.4 Hz), 7.95(d, 2H, J=8.4 Hz), 11.97(s, 1H), 12.87(brs, 1H).

Example 61

4-{2-[5(5-Chlorobenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d

Example 62

4-{2-[5-(4,7-Dimethylbenzofuran-2-yl)furyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.46(s, 6N), 6.97(d, 1H, J=7.6 Hz), 7.04(d, 1H, J=7.6 Hz), 7.11(d, 1H, J= 4.0 Hz), 7.35(d, 1H, J=4.0 Hz), 7.40(s, 1H), 7.95(d, 2H, J=8.4 Hz), 8.01(d, 2H, J=8.4 Hz).

Example 63

4-(2-[5(4,7-Dimethylbenzofuran-2-ID)thienyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.42(s, 6N), 6.96(d, 1H, J=7.2 Hz), 7.02(d, 1H, J=7.2 Hz), 7.38(s, 1H), 7.68(d, 1H, J= 4.0 Hz), 7.76(d, 1H, J=4.0 Hz), 7.85(d, 2H, J=7.6 Hz), 7.98(d, 2H, J=7.6 Hz).

Example 64

4-{2-[5(4,7-Dichlorobenzophenone-2-yl)furyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

7.30(d, 1H, J= 3.6 Hz), 7.38-7.42(m, 2H), 7.47(d, 1H, J=8.0 Hz), 7.52(s, 1H), 7.97-8.03(m, 4H).

Example 65

4-{2-[5-(4,7-Dichlorobenzophenone-2-yl)thienyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

7.39(d, 1H, J=8.0 Hz), 7.45(d, 1H, J=8.0 Hz), 7.55(s, 1H), 7.80(d, 1H, J= 4.4 Hz), 7.84-7.90(m, 3H), 7.98(d, 2H, J=8.4 Hz).

Example 66

5-{ 2-[5-(4,7-Dimethylbenzofuran-2-yl)pyrrolyl] }thiophene-2-carboxylic acid is 6, 400MHz);

2.43(s, 3H), 2.45(s, 3H), 6.62-6.65(m, 1H), 6.66-6.69(m, 1H), 6.92(d, 1H, J= 7.6 Hz), 6.96(d, 1H, J=7.6 Hz), 7.19(s, 1H), 7.45(d, 1H, J=3.6 Hz), 7.67(d, 1H, J=3.6 Hz), 11.96(brs, 1H), 12.97(brs, 1H).

Example 67

4-(2-[5-(2,3,4,7-Tetramethylbenzidin-5-yl)pyrrolyl]) benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.28(s, 3H), 2.35(s, 3H), 2.37(s, 3H), 2.57(s, 3H), 6.16(brs, 1H), 6.75(brs, 1H), 7.06(s, 1H), 7.80(d, 2H, J=8.4 Hz), 7.86(d, 2H, J=8.4 Hz), 11.36(brs, 1H), 12.69(brs, 1H).

Example 68

4-{2-[5-(2,3-Dimethylbenzofuran-5-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.18(s, 3H), 2.35(s, 3H), 6.59(brs, 1H), 6.73(brs, 1H), 7.42(d, 1H, J= 8.2 Hz), 7.61(dd, 1H, J= 2.0, 8.2 Hz), 7.82-7.94(m, 5H), 11.36(brs, 1H), 12.76(brs, 1H).

Example 69

4-(2-[5-(7-Chlorobenzamide-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.65-6.68(t, 1H), 6.80-6.83(m, 1H), 7.38-7.42(m, 2H), 7.76-7.82(m, 1H), 7.80(s, 1H), 7.89(d, 2H, J= 8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.87{s, 1H), at 12.82(brs, 1H).

Example 70

4-{2-[5-(5,7-Dimethylbenzofuran-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

Example 71

4-{2-[5-(7-n-Propylbenzamide-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

0.96(t, 3H, J= 7.2 Hz), 1.75(sext, 2H, J=7.2 Hz), 2.78(t, 2H, J=7.2 Hz), 6.56-6.59(m, 1H), 6.78-6.81(m, 1H), 7.13(d, 1H, J=7.2 Hz), 7.30(t, 1H, J= 7.2 Hz), 7.63(d, 1H, J=7.2 Hz), 7.78(s, 1H), 7.89(d, 2H, J=8.4 Hz), 7.93(d, 2H, J=8.4 Hz), 11.77(s, 1H), 12.78(brs, 1H).

Example 72

4-{2-[5(5-Fluoro-7-methylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

3.32(s, 3H), 6.59-6.62(m, 1H), 6.79-6.82(m, 1H), 7.05(dd, 1H, J=2.4, 9.0 Hz), 7.48(dd, 1H, J= 2.4, 9.0 Hz), 7.77(s, 1H), 7.89(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.85(s, 1H), 12.78(brs, 1H).

Example 73

4-{2-[5-(5-Chloro-7-methylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

3.30(s, 3H), 6.60-6.62(m, 1H), 6.79-6.82(m, 1H), 7.19(d, 1H, J=1.6 Hz), 7.73(d, 1H, J= 1.6 Hz), 7.75(s, 1H), 7.88(d, 2H, J=8.4 Hz), 7.94(d, 2H, J= 8.4 Hz), 11.86(s, 1H), 12.80(brs, 1H).

Example 74

4-{2-[5-(7-Ethylbenzamide-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

Example 75

4-{2-[5-(7-Chloro-4-methylbenzofuran-2-ID)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.56(s, 3H), 6.65-6.67(m, 1H), 6.80-6.83(m, 1H), 7.20(d, 1H, J=7.6 Hz), 7.29(d, 1H, J= 7.6 Hz), 7.89(d, 2H, J=8.4 Hz), 7.93(s, 1H), 7.95(d, 2H, J= 8.4 Hz), 11.83(s, 1H), at 12.82(brs, 1H).

Example 76

4-{2-[5-(7-Isopropylbenzoic-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.33(d, 6H, J=7.6 Hz), 3.10(quint, 1H, J=7.0 Hz),6.56-6.59(m, 1H), 6.78-6.81(m, 1H), 7.20(d, 1H, J= 7.6 Hz), 7.33(t, 1H, J=7.6 Hz), 7.63(d, 1H, J= 7.6 Hz), 7.78(s, 1H), 7.89(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.78(s, 1H), at 12.82(brs, 1H).

Example 77

4-(2-[5-(4,7-Dimethylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.42(s, 3H), 2.54(s, 3H), 6.56-6.59(m, 1H), 6.78-6.81(m, 1H), 7.02(d, 1H, J= 6.8 Hz), 7.08(d, 1H, J= 6.8 Hz), 7.89(s, 1H), 7.90(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.76(s, 1H), 12.83(brs, 1H).

Example 78

4-{2-[5-(4,7-Dichlorobenzamide-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

4-{2-[5-(3,4,7-Trimethylbenzoyl-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

2.40(s, 3H), 2.66(s, 3H), 2.72(s, 3H), 6.38-6.41(m, 1H), 6.79-6.82(m, 1H), 6.94-7.10(m, 2H), 7.78-7.96(m, 4H), 11.65(s, 1H).

Example 80

4-{2-[5-(8-Methoxynaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

3.41(s, 3H), 4.97(s, 2H),6.81(m, 1H), 6.83(m, 1H), 7.40(t, 1H, J=7.6 Hz), 7.50(d, 1H, J=6.8 Hz), 7.81(d, 1H, J=8.0 Hz), 7.90-7.97(m, 6N), 8.34(s, 1H), 11.63(s, 1H), 12.83(brs, 1H)

Example 81

4-{2-[5-(8-Ethoxynaphthalene-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.51(t, 3H, J= 6.8 Hz), 4.26(q, 2H, J=6.8 Hz), 6.73(m, 1H), 6.83(m, 1H), 6.95(d, 1H, J= 7.6 Hz), 7.34(t, 1H, J=8.0 Hz), 7.41(d, 1H, J=8.0 Hz), 7.86(d, 1H, J=8.8 Hz), 7.92-7.95(m, 5H), 8.48(s, 1H), 11.70(s, 1H).

Example 82

4-(2-[5-(8-Isopropoxyaniline-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.43(d, 6N, J= 6.0 Hz), 4.82(quint, 1H, J=6.0 Hz), 6.71(m, 1H), 6.82(m, 1H), 7.33(t, 1H, J= 8.0 Hz), 7.39(d, 1H, J=7.6 Hz), 7.85(d, 1H, J=8.8 Hz), 7.93(m, 5H), 8.44(s, 1H), 11.70(s, 1H).

the get out the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

4.01(s, 3H), 6.76(m, 1H),6.82(m, 1H), 6.97(d, 1H, J=7.6 Hz), 7.36(t, 1H, J= 8.0 Hz), 7.42(d, 1H, J= 8.0 Hz), 7.85(d, 1H, J=8.8 Hz), 7.90-7.96(m, 5H), 8.55(s, 1H), 11.69(s, 1H).

Example 84

4-{2-[5-(8-(2-Furyl)naphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

6.72(dd, 1H, J=2.0,3.6 Hz), 6.75(dd, 1H, J=1.6, 3.2 Hz), 6.83(dd, 1H, J= 2.0, 3.6 Hz), 7.05(d, 1H, J=3.2 Hz), 7.50(t, 1H, J=8.0 Hz), 7.74(dd, 1H, J=1.2, 7.2 Hz), 7.88-7.94(m, 5H), 8.01(s, 2H), at 8.62(s, 1H), 11.70(s, 1H).

Example 85

4-{ 2-[5-(7-Hydroxy-8-isopropylnaphthalene-2-yl)pyrrolyl] } benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.10(s, 3H), 4.89(m, 1H), 5.49(m, 1H), 6.61(dd, 1H, J=2.4, 4.0 Hz), 6.79(dd, 1H, J= 2.4, 3.6 Hz), 7.09(dd, 1H, J=2.0, 8.4 Hz), 7.64(d, 1H, J= 9.2 Hz), 7.71(d, 1H, J=8.8 Hz), 7.89(d, 2H, J=8.4 Hz), 7.92(d, 2H, J=8.4 Hz), 8.01(s, 1H), 9.40(s, 1H), 11.66(s, 1H).

Example 86

4-(2-[5-(8-(1-Methoxyethyl)naphthalene-2-yl)pyrrolyl]benzina acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.50(d, 3H, J= 6.0 Hz), 3.24(s, 3H), 5.32(q, 1H, J=6.4 Hz), 6.82(s, 2H), 7.45(t, 1H, J= 7.6 Hz), 7.53(d, 1H, J=6.8 Hz), 7.78(d, 1H, J=7.6 Hz), 7.89-7.97(m, 6H), 8.41(s, 1H), 11.58(s, 1H).

Example 87

4-(2-[5-(8-(2-Thienyl)aftere 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.62(m, 1H), 6.81(m, 1H), 7.29(m, 1H), 7.45(m, 1H), 7.49(t, 1H, J= 7.6 Hz), 7.57(d, 1H, J=7.2 Hz), 7.73(m, 1H), 7.85-7.94(m, 5H), 8.03(s, 2H), 8.47(s, 1H), 11.66(s, 1H).

Example 88

4-{ 2-[5-(5-Methoxy-8-isopropylnaphthalene-2-yl)pyrrolyl] )benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.20(s, 3H), 3.96(s, 3H), 5.04(s, 1H), 5.42(s, 1H), 6.70(m, 1H), 6.81(m, 1H), 6.87(d, 1H, J=8.0 Hz), 7.24(d, 1H, J=8.0 Hz), 7.88-7.96(m, 5H), 8.19(m, 2H), 11.66(s, 1H).

Example 89

4-{2-[5-(5-Methoxy-8-isopropylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.33(d, 6H, J= 6.8 Hz), 3.85(quint, 1H, J=6.8 Hz), 3.93(s, 3H), 6.82(s, 2H), 6.86(d, 1H, J=8.0 Hz), 7.32(d, 1H, J=8.0 Hz), 7.86-7.96(m, 5H), 8.16(d, 1H, J=8.4 Hz), 8.41(s, 1H), 11.62(s, 1H).

Example 90

4-{2-[5-(5-Methoxy-8-ethylnaphthalene-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header connection get the same as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

1.31(t, 3H, J= 7.2 Hz), 3.09(q, 2H, J=7.2 Hz), 3.93(s, 3H), 6.80-6.84(m, 3H), 7.25(d, 1H, J=8.0 Hz), 7.88-7.96(m, 5H), 8.15(d, 1H, J=8.8 Hz), 8.33(s, 1H).

Example 91

4-[2-[5-(5-Methoxy-8-methylnaphthalene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection get t(m, 5H), 8.13(d, 1H, J=8.8 Hz),8.28(s, 1H), 11.62(s, 1H).

Example 92

4-(2-[5-(7-Chloro-5-methoxybenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

3.80(s, 3H), 6.72-6.75(m, 1H), 6.84-6.86(m, 1H), 6.95(d, 1H, J=2.0 Hz), 7.18(d, 1H, J= 2.4 Hz), 7.22(s, 1H), 7.89(d, 2H, J=8.4 Hz), 7.95(d, 2H, J= 8.4 Hz), 11.94(brs, 1H).

Example 93

4-{2-[5-(7-Chloro-5-methylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.37(s, 3H), 6.71-6.75(m, 1H), 6.83-6.87(m, 1H), 7.17(d, 1H, J=0.4 Hz), 7.21(s, 1H), 7.40(d, 1H, J= 0.4 Hz), 7.89(d, 2H, J=8.4 Hz), 7.95(d, 2H, J= 8.8 Hz), at 11.93(brs, 1H).

Example 94

4-{2-[5-(7-Chloro-5-ethylbenzophenone-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.22(d, 3H, J=7.5 Hz), 2.67(q, 2H, J=7.5 Hz), 6.73(dd, 1H, J=2.4, 3.6 Hz), 6.85(dd, 1H, J=2.8, 3.2 Hz), 7.18-7.19(m, 1H), 7.23(s, 1H), 7.43-7.44(m, 1H), 7.89(d, 2H, J=8.4 Hz), 7.95(d, 2H, J=8.8 Hz), at 11.93(brs, 1H).

Example 95

4-{2-[5-(7-Chloro-4,5-dimethylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.29(s, 3H), 2.36(s, 3H), 6.70-6.74 zofran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.21(t, 3H, J= 7.6 Hz), 6.63(q, 2H, J=7.6 Hz), 6.67-6.72(m, 1H), 6.80-6.85(m, 1H), 6.88-6.93(m, 1H), 7.12(s, 1H), 7.22-7.26(m, 1H), 7.88(d, 2H, J= 8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.80(brs, 1H).

Example 97

4-(2-[5-(7-Chloro-5-isopropenylbenzene-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.16(s, 3H), 5.13-5.14(m, 1H), 5.47-5.48(m, 1H), 6.74-6.78(m, 1H), 6.84-6.88(m, 1H), 7.28(s, 1H), 7.47(d, 1H, J=1.6 Hz), 7.73(d, 1H, J=1.6 Hz), 7.90(d, 2H, J=8.4 Hz), 7.95(d, 2H, J=8.8 Hz), 11.97(brs, 1H).

Example 98

4-{2-[5-(5,7-Dichloro-3-methylbenzofuran-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.35(s, 3H), 6.66-6.70(m, 1H), 6.80-6.84(m, 1H), 7.45-7.49(m, 1H), 7.68-7.72(m, 1H), 7.80-7.90(m, 4H), 11.84(brs, 1H).

Example 99

4[2[5(7-Chloro-4-ethylbenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.28(t, 3H, J= 7.6 Hz), 2.83(q, 2H, J=7.6 Hz), 6.74-6.76(m, 1H), 6.84-6.87(m, 2H), 7.07(d, 1H, J= 8.0 Hz), 7.25(d, 1H, J=8.0 Hz), 7.37(s, 1H), 7.90(d, 2H, J=8.4 Hz), 7.95(d, 2H, J=8.4 Hz), 11.91(brs, 1H).

Example 100

4-(2-[5-(4,5,7-Trimethyl the example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.26(s, 3H), 2.35(s, 3H), 2.43(s, 3H), 6.67-6.71(m, 1H), 6.81-6.85(m, 1H), 6.87(s, 1H), 7.21(s, 1H), 7.88(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.0 Hz), 11.78(brs, 1H).

Example 101

4-{2-[5-(6-Chloro-7-n-propylbenzene-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

0.96(t, 3H, J=7.6 Hz), 1.64-1.76(m, 2H), 2.95-3.03(m, 2H), 6.73-6.76(m, 1H), 6.83-6.87(m, 1H), 7.19(s, 1H), 7.26(d, 1H, J=8.8 Hz), 7.47(d, 1H, J= 8.8 Hz), 7.89(d, 2H, J=8.0 Hz), 7.96(d, 2H, J=8.4 Hz), 11.87(brs, 1H).

Example 102

4-(2-[5-(4-Chloro-7-n-butylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

0.92(t, 3H, J=7.6 Hz), 1.29-1.38(m, 2H), 1.64-1.74(m, 2H), 2.84-2.92(m, 2H), 6.75-6.79(m, 1H), 6.83-6.87(m, 2H), 7.08(d, 1H, J=7.7 Hz), 7.22(d, 1H, J=7.7 Hz), 7.28(s, 1H), 7.88(d, 2H, J=8.8 Hz), 7.96(d, 2H, J=8.8 Hz), 11.90(brs, 1H).

Example 103

4-{ 2-[5-(3,5-Dichloro-4,7-dimethylbenzofuran-2-yl)pyrrolyl] )benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.53(s, 3H), 2.69(s, 3H), 6.93(dd, 1H, J=2.4, 4.0 Hz), 7.01(dd, 1H, J= 2.4, 4.0 Hz), 7.27(s, 1H), 7.95(s, 4H), 11.94(brs, 1H).

Example 104

4-{2-[5-(3-Chloro-4,7-dimethylbenzofuran-2-yl)pyrrolyl])benzoic acid

< / BR>
(A)Methyl 4-{2-[5-(Il] }benzoate was dissolved in 10 ml of N,N-dimethylformamide and the resulting solution was added to 0.13 g of N-chlorosuccinimide. The resulting mixture was stirred at room temperature for 14 hours and add 30 ml of ethyl acetate. The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The desiccant is filtered off and the resulting mixture was concentrated. The resulting crude product was then purified by chromatography on silica gel and the obtained solid is washed with methanol, giving 0.12 g specified in the title compounds as pale yellow crystals.

1H-NMR(CDCl3, 400MHz);

2.50(s, 3H), 2.71(s, 3H), 3.92(s, 3H), 6.77-6.80(m, 1H), 6.91(d, 1H, J= 7.6 Hz), 6.98(d, 1H, J= 7.6 Hz), 7.01-7.04 (m, 1H), 7.63(d, 2H, J=8.4 Hz), 8.08(d, 2H, J=8.4 Hz), 9.23(brs, 1H).

(B) 4-{2-[5-(3-Chloro-4,7-dimethylbenzofuran-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.52(s, 3H), 2.65(s, 3H), 6.90-6.93(m, 1H),6.95-6.99(m, 2H), 7.04-7.08(m, 1H), 7.95(s, 4H), 11.89(brs, 1H).

Example 105

4-{2-[5-(4,7-Diethylbenzene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1 (D).

1H-NMR(DMSO-d6, 400MHz)

1.27(t, 3H, J= 7.6 Hz), 1.30(t, 3H, J= 7.6 Hz), 2.81(q, 2H, J=7.6 Hz), 2.88(q, 2H, J= 7.6 Hz), 6.70(dd, 1H, J= 2.4, 4.0 Hz), 6.83(dd, 1H, J=2.8, 3.6 Hz), 6.96(d, 1H, J=7.6 Hz), 7.01(d, 1H, J=7.6 Hz), 7.27(s, 1H), 7.88(d, 2H, J=8.4 Hz), 7.94(d, >BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.75-6.84(m, 2H), 7.25(s, 1H), 7.33(dd, 1H, J=2.4, 8.8 Hz), 7.60(d, 1H, J=2.4 Hz), 7.85(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 12.00(s, 1H).

Example 107

4-{2-[5-(7-Ethynylbenzoate-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

4.55(s, 1H), 6.73(dd, 1H, J=2.4, 4.0 Hz), 6.85(dd, 1H, J=2.4, 4.0 Hz), 7.23(t, 1H, J=8.0 Hz), 7.26(s, 1H), 7.36(dd, 1H, J=4.2, 8.0 Hz), 7.69(dd, 1H, J=1.2, 8.0 Hz), 7.89(d, 2H, J=8.4 Hz),7.95(d, 2H, J=8.4 Hz), 11.94(brs, 1H).

Example 108

4[2[5(7(2-Methoxyethyl)benzofuran-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

3.14(t, 2H, J=7.2 Hz), 3.27(s, 3H), 3.70(t, 2H, J=7.2 Hz), 6.73(dd, 1H, J= 2.4, 3.6 Hz), 6.84(dd, 1H, J= 2.4, 3.6 Hz), 7.11-7.16(m, 2H), 7.18(s, 1H), 7.46(dd, 1H, J= 2.0, 6.8 Hz), 7.89(d, 2H, J=8.4 Hz), 7.94(d, 2H, J=8.4 Hz), 11.85(s, 1H), 12.83(brs, 1H).

Example 109

4-{2-[5-(5-Fluoro-7-methylbenzofuran-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.43(s, 3H), 6.75(brs, 1H), 6.85(brs, 1H), 6.93(d, 1H, J=10.0 Hz), 7.19(s, 1H), 7.26(d, 1H, J= 6.8 Hz), 7.89(d, 2H, J=8.0 Hz), 7.95(d, 2H, J= 8.0 Hz), 11.90(s, 1H).

Example 110

4 is ucaut as well as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.42(s, 3H), 6.72(brs, 1H), 6.84(brs, 1H), 7.06(t, 1H, J=8.0 Hz), 7.19(s, 1H), 7.44(dd, 1H, J=6.0, 8.0 Hz), 7.88(d, 2H, J=8.0 Hz), 7.94(d, 2H, J=8.0 Hz), 11.85(brs, 1H).

Example 111

4-(2-[5-(7-Bromo-4-perbendaharaan-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.78(dd, 1H, J=2.4, 3.6 Hz), 6.87(dd, 1H, J=2.4, 3.6 Hz), 7.09(t, 1H, J= 9.2 Hz), 7.48(dd, 1H, J= 4.8, 8.4 Hz), 7.49(s, 1H), 7.93(d, 2H, J=8.8 Hz), 7.96(d, 2H, J=8.8 Hz), 12.20(brs, 1H).

Example 112

2-{ 2-[5-(4,7-Dimethylbenzofuran-2-yl)pyrrolyl] } pyridine-5-carboxylic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.44(s, 3H), 2.46(s, 3H), 6.72-6.76(m, 1H), 6.92(d, 1H, J=8.0 Hz), 6.96(d, 1H, J=8.0 Hz), 7.04-7.09(m, 1H), 7.51(s, 1H), 7.93(d, 1H, J=7.6 Hz), 8.20(dd, 1H, J=2.4, 7.6 Hz), 9.02(d, 1H, J=2.4 Hz), 12.26(brs, 1H).

Example 113

4-{2-[5-(4,6,7-Trimethylbenzoyl-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

2.29(s, 3H), 2.38(s, 3H), 2.40(s, 3H), 6.69(brs, 1H), 6.81-6.84(m, 2H), 7.17(s, 1H), 7.86-7.95(m, 4H), 11.76((brs, 1H), at 12.82(brs, 1H).

Example 114

6-(2-[5(4,7-Dimethylbenzofuran-2-ID)pyrrolyl]}-2-naphthoic acid

< / BR>
Specified for 3H), 6.73(brd, 1H, J=3.6 Hz), 6.90(brd, 1H, J= 3.7 Hz), 6.92(d, 1H, J=6.8 Hz), 6.96(d, 1H, J=6.8 Hz), 7.25(s, 1H),7.93(d, 1H, J= 8.4 Hz), 7.97(d, 1H, J=8.4 Hz), 8.01(d, 1H, J=8.4 Hz), 8.10(d, 1H, J=8.8 Hz), 8.35(s, 1H), 5.53(s, 1H), 11.88(brs, 1H).

Example 115

4-{2-[5-(4,7-Dimethylbenzofuran-2-yl)pyrrolyl]}-1-naphthoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMF(DMSO-d6, 400MHz);

2.41(s, 3H), 2.47(s, 3H), 6.58(t, 1H, J=3.0 Hz), 6.81(t, 1H, J=3.0 Hz), 6.93(ABq, 2H, J= 9.0 Hz), 7.18(s, 1H), 7.58-7.70 (m, 2H), 7.72(d, 1H, J= 9.0 Hz),8.17(d, 1H, J=9.0 Hz), 8.40(d, 1H, J=9.0 Hz), 8.77(d, 1H, J=9.0 Hz).

Example 116

2,5-Dimethyl-4-{ 2-[5-(4,7-dimethylbenzofuran-2-yl)pyrrolyl] } benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(d)

1H-NMR(DMSO-d6, 400MHz);

2.41(s, 3H), 2.42(s, 3H),2.47(s, 3H), 2.55(s, 3H), 6.48(dd, 1H, J=2.5, 3.0 Hz), 6.71(dd, 1H, J= 2.5, 3.0 Hz), 6.92(ABq, 2H, J=7.0 Hz), 7.18(s, 1H), 7.46(brs, 1H), 7.75(brs, 1H).

Example 117

5-{2-[5-(4,7-Dimethylbenzofuran-2-yl)pyrrolyl]}2-francebuy acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.43(s, 3H), 2.45(s, 3H), 6.58(d, 1H, J=3.6 Hz), 6.79(d, 1H, J=3.6 Hz), 6.87-6.96(m, 3H), 7.01-7.08(brs, 1H), 7.18(s, 1H).

Example 118

3-{2-[5-(4,7-Dimethylbenzofuran-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header connection receive .5, 3.8 Hz), 6.83(s, 1H), 6.93(d, 1H, J= 7.5 Hz), 6.97(d, 1H, J=7.5 Hz), 7.52(t, 1H, J= 8.0 Hz), 7.83(d, 1H, J=7.5 Hz), 7.96(d, 1H, J=7.5 Hz), 8.28(s, 1H), 9.03(brs, 1H).

Example 119

3-Bromo-4-(2-[5-(the oil[1,2-b]furan-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

6.86(m, 2H), 7.31(s, 1H), 7.51(t, 1H, J=7.6 Hz), 7.65(t, 1H, J=7.8 Hz), 7.75(s, 1H), 7.79(d, 1H, J=8.0 Hz), 7.99(dd, 1H, J=1.2, 8.4 Hz), 8.02(d, 1H, J=8.4 Hz), 8.19(s, 1H), 8.32(d, 1H, J=8.0 Hz), 11.98(brs, 1H).

Example 120

3-Bromo-4-{2-[5-(4,7-dichlorobenzophenone-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.80(d, 1H, J=3.6 Hz), 6.83(d, 1H, J=3.6 Hz), 7.34(dd, 1H, J=1.0, 8.2 Hz), 7.35(s, 1H), 7.37(dd, 1H, J=0.6, 8.6 Hz), 7.70(brd, 1H, J=8.4 Hz), 7.94(brd, 1H, J=8.0 Hz), 8.16(brs, 1H).

Example 121

4-{2[5(3, 4-Dimethylnaphthalene-1-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.54(s, 3H), 2.65(s, 3H), 6.57(dd, 1H, J=2.8, 2.8 Hz), 6.85(dd, 1H, J= 3.2, 3.2 Hz), 7.43 s, 1H), 7.47(dd, 1H, J=7.6, 7.6 Hz), 7.55(dd, 1H, J=7.2, 7.2 Hz), 7.62(d, 1H, J=8.4 Hz), 8.11(d, 4H, J=8.0 Hz), 8.68(brs, 1H).

Example 122

4-{2-[5-(5,8-Dimethylnaphthalene-2-yl)thienyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).<.73(d, 1H, J=3.6 Hz), 7.91(d, 3H, J=8.4 Hz), 8.06(d, 1H, J=8.8 Hz), 8.21(s, 1H).

Example 123

4-{2-[5-(5,8-Dimethylnaphthalene-2-yl)furyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.61(s, 3H), 2.70(s, 3H), 7.24(d, 1H, J=6.8 Hz), 7.27(d, 1H, J=7.2 Hz), 7.33(s, 2H), 7.97(d, 2H, J= 8.4 Hz), 8.01(d, 3H, J=8.4 Hz), 8.07(d, 1H, J= 8.8 Hz), 8.39(s, 1H).

Example 124

4-[2-[5-(8-Ethyl-1-methoxynaphthalene-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(CDCl3, 400MHz);

1.36(t, 3H, J= 7.2 Hz), 3.35(q, 2H, J=7.6 Hz), 3.74(s, 3H), 6.77-6.81(m, 2H), 7.30-7.40(m, 2H), 7.60-7.73 (m, 5H), 8.10-8.20(m, 2H), 10.34(brs, 1H).

Example 125

4-{2-[5-(8-Methyl-1-methoxynaphthalene-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(CDCl3, 400MHz);

2.97(s, 3H), 3.73(s, 3H), 6.76-6.80(m, 2H), 7.28-7.35(m, 2H), 7.61-7.72(m, 5H), 8.14(d, 2H, J=8.4 Hz), 10.33(brs, 1H).

Example 126

4-{2-[5-(5-Acenaphthyl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NR(Dl3, 400MHz);

3.40-3.48(m, 4H), 6.64-6.66(m, 1H), 6.84-6.86(m, 1H), 7.33-7.36(m, 2H), 7.50-7.64(m, 4H), 8.03(d, 1H, J=8.4 Hz), 8.09-8.12(m, 2H), 8.76(brs, 1H).

Example e get as well as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.09(s, 3H), 2.34(s, 3H), 4.95(brs, 2H), 6.45-6.47 (m, 1H), 6.67(d, 1H, J= 7.6 Hz), 6.75-6.77(m, 1H), 6.84(d, 1H, J=7.6 Hz), 7.24(brs, 1H), 7.85-7.94(m, 4H).

Example 128

4-{2-[5-(5-Isopropyl-8-methyl-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(CDCl3, 400MHz);

1.30(d, 6N, J= 6.8 Hz), 3.28(hept., 1H, J=6.8 Hz), 4.99(d, 2H, J=1.2 Hz), 6.39-6.40(m, 1H), 6.71-6.73(m, 1H), 6.81-6.86(m, 2H), 6.99(d, 1H, J=8.0 Hz), 7.64(d, 2H, J=8.4 Hz), 8.13(d, 2H, J=8.4 Hz), 8.70(brs, 1H).

Primer

4-{2-[5-(5-Methyl-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.14(s, 3H), 5.04(brs, 2H), 6.43-6.45(m, 1H), 6.75-6.77(m, 1H), 6.81(t, 1H, J= 7.6 Hz), 6.95(t, 1H, J= 8.0 Hz), 7.09(brs, 1H), 7.86-7.93(m, 4H), 11.39(s, 1H), at 12.82(brs, 1H).

Example 130

4-{2-[5-(5-Ethyl-2H-chromen-3-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.13(t, 3H, J= 7.2 Hz), 2.48-2.55(m, 2H), 5.02(brs, 2H), 6.45(brs, 1H), 6.75-7.09(m, 5H), 7.85-7.93(m, 4H), 11.39(s, 1H), 12.81(s, 1H).

Example 131

4-{2-[5-(5-Methoxy-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the get connection as well, 7.08(dd, 1H, 3=1.2, 7.2 Hz), 7.62(d, 2H, J=7.6 Hz), 8.11(d, 2H, J=8.4 Hz), 8.77(brs, 1H).

Example 132

4-{2-[5-(8-Methoxy-7-methyl-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(CDCl3, 400MHz);

2.16(s, 3H), 3.73(s, 3H), 5.01(brs, 2H), 6.44(m, 1H), 6.70-7.77(m, 3H), 7.07(s, 1H), 7.85-7. 93 (m, 4H), 11.38(brs, 1H), 12.80(brs, 1H).

Example 133

4-{2-[5-(4-Methyl-2H-chromen-6-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(CDCl3, 400MHz);

2.10(d, 3H, J=1.6 Hz), 4.79(q, 2H, J=1.6 Hz), 5.65(m, 1H), 6.51(dd, 1H, J= 2.8, 3.6 Hz), 6.74(dd, 1H, J=2.8, 3.6 Hz), 6.85(d, 1H, J=8.0 Hz), 7.29-7.32(m, 2H), 7.59(d, 2H, J=8.8 Hz), 8.10(d, 2H, J=8.4 Hz), 8.60(brs, 1H).

Example 134

4-(2-[5-(5-Bromo-8-methoxy-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

3.75(s, 3H), 4.97(brs, 2H), 6.53(brs, 1H), 6.79-6.82(m, 2H), 7.14(d, 1H, J=8.8 Hz), 7.22(brs, 1H), 7.91(brs, 4H), 11.65(brs, 1H), 12.83(brs, 1H).

Example 135

4-(2-[5-(8-Methoxy-5-methyl-2H-chromen-3-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(CDCl3, 400MHz)

2.37(s, 3H), 3.88(s, 3H), 5.05(brs, 2H), 6.40(brs, 1H), 6.71-6.72(m, 4H), 7.64 (the and

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(CDCl3, 400MHz);

0.97(t, 3H, J=7.2 Hz), 1.63(tq, 2H, J=7.2, 7.2 Hz), 2.59(t, 2H, J=7.6 Hz), 5.04(s, 2H), 6.36(dd, 1H, J=2.4, 2.4 Hz), 6.62(brs, 1H), 6.86(dd, 1H, J=7.6, 7.6 Hz), 6.94-7.01(m, 2H), 7.61(d, 2H, J= 8.4 Hz), 8.11(d, 2H, J=8.4 Hz), 8.63(brs, 1H).

Example 137

4-{2-[5-(5-Chloro-8-methyl-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(CDCl3, 400MHz);

2.19(s, 3H), 5.05(d, 2H, J=1.2 Hz), 6.41(dd, 1H, J=3.6, 3.6 Hz), 6.71(dd, 1H, J= 3.6, 3.6 Hz), 6.90(brs, 3H), 7.64(d, 2H, J=8.8 Hz), 8.11(d, 1H, J= 8.8 Hz), 8.74(brs, 1H).

Example 138

4-{2-[5-(5,7,8-Trimethyl-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.02(s, 3H), 2.15(s, 3H), 2.31(s, 3H), 4.91(s, 2H), 6.43(brs, 1H), 6.60(s, 1H), 6.75(brs, 1H), 7.23(s, 1H), 7.85-7.93 (m, 4H), 11.35(s, 1H), 12.78(brs, 1H).

Example 139

4-{2-[5(5,7-Dimethyl-2H-chromen-3-yl) pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.19(s, 3H), 2.34(s, 3H), 4.90(s, 2H), 6.43(dd, 1H, J=3.2, 3.2 Hz), 6.49(brs, 1H), 6.60(brs, 1H), 6.75(dd, 1H, J=3.2, 3.2 Hz), 7.23(brs, 1H), 7.86(d, 2H, J=8.4 Hz), 7.93(d, 2H, J=8.8 Hz).

Example 140

4-{2-[5-(7,8-Dimethyl-2H-here 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.07(s, 3H), 2.19(s, 3H), 5.00(s, 2H), 6.41-6.43(m, 1H), 6.72-6.76(m, 2H), 6.84(d, 1H, J=7.6 Hz), 7.06(brs, 1H), 7.86(d, 2H, J=8.4 Hz), 7.91(d, 2H, J=8.8 Hz).

Example 141

4-(2-[5-(6-Methyl-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.22(s, 3H), 4.97(s, 2H), 6.44(dd, 1H, J=2.0, 2.0 Hz), 6.70(d, 1H, J= 7.6 Hz), 6.76(dd, 1H, J=2.0, 2.0 Hz), 6.87-6.89(m, 2H), 7.06(s, 1H), 7.85-7.93(m, 4H), 11.39(s, 1H), 12.79(brs, 1H),

Example 142

4-{2-[5-(5,6-Dimethyl-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

2.10(s, 3H), 2.19(s, 3H), 4.99(s, 2H), 6.44(s, 1H), 6.73(s, 1H), 6.77(brs, 2H), 7.04(s, 1H), 7.86-7.93 (m, 4H), 11.38(s, 1H), 12.78(brs, 1H).

Example 143

4-(2-[5-(6-Chloro-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

5.05(s, 2H), 6.46-6.52(m, 1H), 6.74-6.79(m, 1H), 6.83(d, 1H, J=8.8 Hz), 7.05-7.10(m, 3H), 7.86(d, 2H, J=8.4 Hz), 7.92(d, 2H, J=8.0 Hz), 11.47(s, 1H), 12.80(brs, 1H).

Example 144

4-(2-[5-(7-Chloro-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);<, =8.8 Hz), 11.44(s, 1H), 12.81(brs, 1H).

Example 145

4-{2-[5-(5,6,7-Trimethyl-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1 (D).

1H-NMR(DMSO-d6, 400MHz);

2.08(s, 2H), 2.18(s, 3H), 2.31(s, 3H), 4.83(s, 2H), 6.43(dd, 1H, J=2.8, 2.8H2), 6.53(s, 1H), 6.75(dd, 1H, J= 3.2, 3.2 Hz), 7.86(d, 2H, J=8.4 Hz), 7.93(d, 2H, J=8.0 Hz), 11.36(s, 1H), 12.78(brs, 1H).

Example 146

4-{2-[5-(5,6,8-Trimethyl-2H-chromen-3-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.07(s, 3H), 2.14(s, 3H), 2.26(s, 3H), 4.88(s, 2H), 6.46(dd, 1H, J=2.4, 2.4 Hz), 6.75-6.77(m, 2H),7.33(s, 1H), 7.87(d, 2H, J=8.8 Hz), 7.93(d, 2H, J= 8.4 Hz), 11.39(s, 1H), 12.78(brs, 1H).

Example 147

4-{2-[5-(5-Chloro-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

5.04(brs, 2H), 6.54(dd, 1H, J=2.8, 2.8 Hz), 6.29(dd, 1H, J=2.8, 2.8 Hz), 6.82(d, 1H, J= 8.4 Hz), 7.02-7.10(m, 2H), 7.37(brs, 1H), 7.90-7.95(m, 4H), 11.63(s, 1H), 12.81(brs, 1H).

Example 148

4-{2-[5-(8-Methyl-2H-chromen-3-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(CDCl3, 400MHz);

2.13(brs, 2H), 5.03(brs, 2H), 6.43-6.45(m, 1H), 6.75-6.77(m, 1H), 6.81(dd, 1H,sauna acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

5.17(s, 2H), 6.53(brs, 1H), 6.79(brs, 1H), 7.07(dd, 1H, J=7.6, 7.6 Hz), 7.16(s, 1H), 7.36-7.38(m, 2H), 7.86-7.94(m, 4H), 11.49(s, 1H), 12.80(brs, 1H).

Example 150

4-{2-[5-(3-Fluoro-4,7-dimethylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
(A) Methyl 4-(2-[5-(3-fluoro-4,7-dimethylbenzofuran-2-yl)pyrrolyl]}benzoate

< / BR>
0.20 g of Methyl 4-{ 2-[5-(4,7-dimethylbenzofuran-2-yl)pyrrolyl] }benzoate was dissolved in 5 ml of anhydrous tetrahydrofuran and the resulting solution was added 0.20 g of the triflate, N-fluoro-3,5-dichloropyridine. The resulting mixture was stirred at room temperature for 30 minutes, poured into a cooled saturated aqueous sodium bicarbonate solution and add 50 ml of ethyl acetate. The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The desiccant is filtered off and the filtrate concentrated. The resulting crude product was then purified by chromatography on columns of silica gel, which gives 0.05 g specified in the title compounds as pale yellow crystals.

1H-NMR(CDCl3, 400MHz);

2.48(s, 3H), 2.60(s, 3H), 3.94(s, 3H), 6.75-6.79(m, 2H), 6.92(d, 1H, J= 7.6 Hz), 6.99(d, 1H, J=7.6 Hz), 7.62(d, 2H, J=8.4 Hz), 8.07(d, 2H, J=8.4 Hz), 8.92(brs, 1H).

() 4-(2-[5-(3-F. shall have the same as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.45(s, 3H), 2.53(s, 3H), 6.63-6.66(m, 1H), 6.89-6.92(m, 1H), 6.98(d, 1H, J= 7.2 Hz), 7.06(d, 1H, J=7.2 Hz), 7.93(s, 4H), 11.87(s, 1H), 12.83(brs, 1H).

Example 151

4-(2-[5-(3-Bromo-4,7-dimethylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
(A) Methyl 4-{2-[5-(3-bromo-4,7-dimethylbenzofuran-2-yl)pyrrolyl])benzoate

< / BR>
Specified in the header connection receive in accordance with the method of obtaining 3-chloride except that as the starting material instead of N-chlorosuccinimide using N-bromosuccinimide.

1H-NMR(CDCl3, 400MHz);

2.50(s, 3H), 2.73(s, 3H), 3.93(s, 3H), 6.77-6.80(m, 1H), 6.91(d, 1H, J= 7.6 Hz), 6.98(d, 1H, J= 7.6 Hz), 7.11-7.14(m, 1H), 7.63(d, 2H, J=8.4 Hz), 8.08(d, 2H, J=8.4 Hz), 9.38(brs, 1H).

(B) 4-{ 2-[5-(3-Bromo-4,7-dimethylbenzofuran-2-yl)pyrrolyl] } benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.50(s, 3H), 2.67(s, 3H), 6.88-6.91(m, 1H), 6.96(d, 1H, J=7.2 Hz), 7.03-7.07(m, 2H), 7.92(s, 4H), 11.86(s, 1H), 12.83(brs, 1H).

Example 152

4-{2-[5-(6,7-Dichlorobenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.76-6.79(m, 1H), 6.85-6.88(m, 1H), 7.30(s, 1H), 7.47(d, 1H, J=8.4 Hz), 7.64(d, 1H, J=8.4 Hz is alil])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.37(s, 3H), 2.51(s, 3H), 6.90-6.97(m, 2H), 7.02(brs, 1H), 7.16(brs, 1H), 7.94(s, 4H), 11.91(s, 1H), 12.85(brs, 1H).

Example 154

4-{2-[5-(3-Chloro-7-propylbenzene-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

0.95(t, 3H, J= 7.6 Hz), 1.70-1.82(m, 2H), 2.94(t, 2H, J=7.6 Hz), 6.91-6.94(m, 1H), 6.96-6.99(m, 1H), 7.22(dd, 1H, J=1.2, 7.6 Hz), 7.29(t, 1H, J= 7.6 Hz), 7.38(dd, 1H, J=1.2, 7.6 Hz), 7.93(s, 4H), 11.90(s, 1H), 12.89(brs, 1H)

Example 155

4-(2-[5-(3-the Fluorine-5,7-dimethylbenzofuran-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.35(s, 3H), 2.46(s, 3H), 6.61-6.64 (m, 1H), 6.85-6.88(m, 1H), 7.00(brs, 1H), 7.22(brs, 1H), 7.89(s, 4H), 11.86(s, 1H), 12.83(brs, 1H).

Example 156

4-{2-[5-(5-Fluoro-3,7-dimethylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.33(s, 3H), 2.53(s, 3H), 6.64-6.67(m, 1H), 6.87-6.90(m, 1H), 6.95(dd, 1H, J=2.0, 10.4 Hz), 7.22(dd, 1H, J=2.0, 10.4 Hz), 7.93(s, 4H), 11.73(s, 1H), 12.84(brs, 1H).

Example 157

4-{2-[5-(5-Fluoro-4,7-dimethylbenzofuran-2-yl)pyrrolyl]}benzoic d6, 400MHz);

2.34(s, 3H), 2.46(s, 3H), 6.71-6.74(m, 1H), 6.83-6.86(m, 1H), 6.90(d, 1H, J= 10.8 Hz), 7.26(s, 1H), 7.89(d, 2H, J=8.4 Hz), 7.95(d, 2H, J=8.4 Hz), 11.84(s, 1H), 12.83(brs, 1H).

Example 158

4-{ 2-[5-(5-the Fluorine-3,4,7-trimethylbenzoyl-2-yl)pyrrolyl] }benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.48(s, 6N), 2.50(s, 3H), 6.59-6.62(m, 1H), 6.85-6.88(m, 1H), 6.92(d, 1H, J=10.8 Hz), 7.92(s, 4H), 11.72(s, 1H), 12.80(brs, 1H).

Example 159

4-[2-[5-(3,5-Debtor-4,7-dimethylbenzofuran-2-yl)pyrrolyl] )benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.42(s, 3H), 2.48(s, 3H), 6.65-6.68(m, 1H), 6.89-6.92(m, 1H), 7.03(d, 1H, J=10.8 Hz),7.93(s, 4H), 11.91(s, 1H), 12.85(brs, 1H).

Example 160

4-(2-[5-(3-Chloro-5-fluoro-4,7-dimethylbenzofuran-2-yl)pyrrolyl] )benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

2.48(s, 3H), 2.52(s, 3H), 6.91-6.94(m, 1H), 6.98-7.01(m, 1H), 7.04(d, 1H, J=10.8 Hz), 7.95(s, 4H), 11.92(s, 1H), 12.86(brs, 1H).

Example 161

4-{ 2-[5-(7-Ethoxy-5-fluoro-4-methylbenzofuran-2-yl)pyrrolyl] )benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400M, H), 12.80(brs, 1H).

Example 162

4-{ 2-[5-(7-Ethyl-5-fluoro-4-methylbenzofuran-2-yl)pyrrolyl] )benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.27(t, 3H, J= 7.6 Hz), 2.34(s, 3H), 2.85(q, 2H, J=7.6 Hz), 6.71-6.74(m, 1H), 6.83-6.86(m, 1H), 6.91(d, 1H, J=10.8 Hz), 7.88(d, 2H, J=8.4 Hz), 7.95(d, 2H, J=8.4 Hz), 11.83(s, 1H), 12.86(brs, 1H).

Example 163

4-[2-[5-(7-Ethyl-3,5-debtor-4-methylbenzofuran-2-yl)pyrrolyl] } benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.28(t, 3H, J= 7.6 Hz), 2.43(s, 3H), 2.90(q, 2H, J=7.6 Hz), 6.65-6.68(m, 1H),6.86-6.89(m, 1H), 7.04(d, 1H, J=11.2 Hz), 7.85-7.96(m, 4H), 11.87(s, 1H), 12.85(brs, 1H).

Example 164

4-{2-[5-(7-Chloro-4-fermentative-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.71-6.74(m, 1H), 6.81-6.84(m, 1H), 7.27(t, 1H, J=8.8 Hz), 7.42(dd, 1H, J= 4.4, 8.8 Hz), 7.90(d, 2H, J=8.4 Hz), 7.95(d, 2H, J=8.4 Hz), 11.40(s, 1H), 12.81(brs, 1H).

Example 165

4-{2-[5-(3,5-Dichloro-7-methylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.52(s, 3H), 6.87-6.94 (m, 2H), 7.38(brs, 1H), 7.61(brs, 1H),Naya acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.53(s, 3H), 6.88-6.94(m, 4H), 7.24(dd, 1H, J=2.4, 9.6 Hz), 7.40(dd, 1H, J=2.4, 9.6 Hz), 7.93(s, 4H), 11.80(s, 1H), 12.87(brs, 1H).

Example 167

4-(2-[5-(7-Fluoro-4-triftormetilfosfinov-2-yl)pyrrolyl] } benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.87-6.92(m, 2H), 7.35(dd, 1H, J=10.0, 10.4 Hz), 7.53(brs, 1H), 7.62(dd, 1H, J=3.6, 8.8 Hz), 7.93(d, 2H, J=8.8 Hz), 7.96(d, 2H, J=8.8 Hz).

Example 168

4-{ 2-[5-(3-Chloro-5-fluoro-7-methylbenzofuran-2-yl)pyrrolyl] )benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.57(s, 3H), 6.91-6.94(m, 1H), 6.96-7.02(m, 1H), 7.09(dd, 1H, J=2.7, 11.0 Hz), 7.17(dd, 1H, J=2.3, 8.0 Hz), 7.95(brs, 4H), 12.0(s, 1H).

Example 169

4-{2-[5-(3-Chloro-7-ethyl-5-perbendaharaan-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.30(t, 3H, J= 8.0 Hz), 3.00(q, 2H, J=7.2 Hz), 6.90-6.93(m, 1H), 6.98-7.00(m, 1H), 7.12(dd, 1H, J= 2.9, 10.4 Hz), 7.18(dd, 1H, J=2.4, 8.8 Hz), 7.93(d, 2H, J=8.0 Hz), 7.96(d, 2H, J=8.0 Hz), 11.96(brs, 1H).

Example 170

4-{ 2-[5-(3-Chloro-5-fluoro-7-propylbenzene-2-yl)pyrrolyl] )benzoic Ki is-d6, 400MHz)

0.96(t, 3H, J= 6.8 Hz), 1.72-1.80(m, 2H), 2.96(t, 2H, J=7.2 Hz), 6.90-6.93(m, 1H), 6.98-7.01(m, 1H), 7.10(dd, 1H, J=2.0, 10.4 HZ), 7.18(dd, 1H, J= 2.0, 7.6 Hz), 7.92(d, 2H, J=8.4 Hz), 7.96(d, 2H, J=8.4 Hz), 11.88(brs, 1H).

Example 171

4-{2-[5(3-Chloro-5-fluoro-7-propylbenzene-2-yl)-3-chlorpropyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

0.94(t, 3H, J=7.0 Hz), 1.73-1.80(m, 2H), 2.90-2.98(m, 2H), 7.01(d, 1H, J= 2.8 Hz), 7.13(dd, 1H, J=2.6, 10.4 Hz), 7.22(dd, 1H, J=2.4, 8.0 Hz), 7.88(d, 2H, J=8.4 Hz), 8.05(d, 2H, J=8.4 Hz).

Example 172

4-{ 2-[5-(3-Bromo-5-fluoro-7-methylbenzofuran-2-yl)pyrrolyl] }benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.58(s, 3H), 6.92-6.94(m, 1H), 7.06-7.16(m, 3H), 7.95(brs, 4H), 12.00(s, 1H).

Example 173

4-(2-[5-(7-Ethyl-5-fluoro-3-methylbenzofuran-2-yl)pyrrolyl] } benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.31(t, 3H, J= 7.6 Hz), 2.33(s, 3H), 2.97(q, 2H, J=7.6 Hz), 6.64-6.66(m, 1H), 6.86-6.89(m, 1H), 6.97(dd, 1H, J=2.4, 10.0 Hz), 7.22(dd, 1H, J=2.4, 8.8 Hz), 7.91(d, 2H, J=8.4 Hz), 7.93(d, 2H, J=8.4 Hz), 11.73(s, 1H), at 12.82(brs, 1H).

Example 174

4-{2-[5-(3,5-Debtor-7-ethylbenzophenone-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header is connected to the 71(m, 1H), 6.91(dd, 1H, J=2.4, 3.6 Hz), 7.10(dd, 1H, J=2.4, 10.4 Hz), 7.30(dd, 1H, J=2.4, 8.0 Hz), 7.94(brs, 4H), 11.95(s, 1H), 12.86(brs, 1H).

Example 175

4-{ 2-[5-(4-Ethyl-5-fluoro-7-methylbenzofuran-2-yl)pyrrolyl] }benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.23(t, 3H, J= 7.6 Hz), 2.46(s, 3H), 2.79(q, 4H, J=7.6 Hz), 6.72-6.75(m, 1H), 6.84-6.86(m, 1H), 6.90(d, 1H, J=10.8 Hz), 7.30(s, 1H), 7.89(d, 2H, J= 8.4 Hz), 7.95(d, 2H, J=8.4 Hz), 11.84(brs, 1H).

Example 176

4-{ 2-[5-(4,7-Diethyl-3,5-differentfor-2-yl)pyrrolyl] }benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.23(t, 3H, J= 7.2 Hz), 1.30(t, 3H, J=7.2 Hz), 2.82-2.88(m, 2H), 2.92(q, 2H, J= 7.2 Hz), 6.67-6.70(m, 1H), 6.90-6.92(m, 1H), 7.05(d, 1H, J=11.2 Hz), 7.94(s, 4H), 11.90(brs, 1H).

Example 177

4-{ 2-[5-(3-Bromo-4,7-diethyl-5-perbendaharaan-2-yl)pyrrolyl] } benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

1.22(t, 3H, J= 7.6 Hz), 1.30(t, 3H, J= 7.6 Hz), 2.97(q, 2H, J=7.6 Hz), 3.03-3.10(m, 2H), 6.90-6.92(m, 1H), 7.07(d, 1H, J=11.2 Hz), 7.09-7.12(m, 1H), 7.93(d, 2H, J=8.4 Hz), 7.96(d, 2H, J=8.4 Hz), 11.90(brs, 1H).

Example 178

4-(2-[5-{3,5-Dichloro-7-methylbenzofuran-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection get just what .96(s, 4H), 12.00(s, 1H).

Example 179

4-[2-[5-(3,5-Dichloro-7-ethylbenzophenone-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.33(t, 3H, J=7.7 Hz), 3.00(q, 2H, J=7.7 Hz), 6.94(dd, 1H, J=2.8, 4.0 Hz), 7.01(dd, 1H, J= 2.0, 3.6 Hz), 7.29(d, 1H, J=2.0 Hz), 7.42(d, 1H, J=1.6 Hz), 7.96(s, 4H), 11.99(brs, 1H).

Example 180

4-{ 2-[5-(3-the Fluorine-4,5,7-trimethylbenzoyl-2-yl)pyrrolyl] )benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.26(s, 3H), 2.43(s, 3H), 2.45(s, 3H), 6.61-6.65(m, 1H), 6.88-6.90(m, 1H), 6.97-7.00(m, 1H), 7.93(s, 4H), 11.84(brs, 1H).

Example 181

4-(2-[5-(3-Chlorine-4,5,7-trimethylbenzoyl-2-yl)pyrrolyl] } benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.27(s, 3H), 2.50(s, 3H), 2.57(s, 3H), 6.89-6.92(m, 1H), 6.94-6.97(m, 1H), 6.98-7.00(m, 1H),7.94(s, 4H), 11.85(brs, 1H).

Example 182

4-{ 2-[5-(3-Bromine-4,5,7-trimethylbenzoyl-2-yl)pyrrolyl] }benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

2.27(s, 3H), 2.50(s, 3H), 2.61(s, 3H), 6.88-6.91(m, 1H), 6.98-7.00(m, 1H), 7.04-7.07(m, 1H), 7.94(s, 4H), 11.85(brs, 1H).

Example anie get the same as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.40(s, 3H), 6.72-6.75(m, 1H), 6.83-6.86(m, 1H), 7.04(dd, 1H, J=9.2, 9.6 Hz), 7.29(s, 1H), 7.39(dd, 1H, J= 3.6, 8.4 Hz), 7.90(d, 2H, J=8.4 Hz), 7.95(d, 2H, J=8.4 Hz), at 11.93(brs, 1H)

Example 184

4-{2-[5-(5-Chloro-4,7-dimethylbenzofuran-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

3.24(s, 3H), 3.39(s, 3H), 6.73-6.75(m, 1H), 6.84-6.86(m, 1H), 7.12(s, 1H), 7.27(s, 1H), 7.88-7.90(d, 2H, J=8.8 Hz), 7.94-7.96(d, 2H, J=8.8 Hz), 11.59(brs, 1H).

Example 185

4-{ 2-[5-(5-Chloro-3-fluoro-4,7-dimethylbenzofuran-2-yl)pyrrolyl] } benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.49(s, 3H), 2.54(s, 3H), 6. 68-6. 69 (m, 1H), 6.91-6.92 (m, 1H), 7.26(s, 1H), 7.94(s, 4H), 11.59(brs, 1H).

Example 186

4-{ 2-[5-(3-Bromo-5-chloro-4,7-dimethylbenzofuran-2-yl)pyrrolyl] } benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.53(s, 3H), 2.73(s, 3H), 6.91-6.92(m, 1H), 7.10-7.11(m, 1H), 7.27(s, 1H), 7.95(s, 4H), 11.59(brs, 1H).

Example 187

4-{ 2-[5-(5-Chlorine-3,4,7-trimethylbenzoyl-2-yl)pyrrolyl] }benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

Example 188

4-{2-[5(5-Chloro-4-methylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.48(s, 3H), 6.75-6.76(m, 1H), 6.84-6.86(m, 1H), 7.12(d, 1H, J=1.2 Hz), 7.17(s, 1H), 7.54(d, 1H, J=1.6 Hz), 7.88-7.96(m, 4H), 11.90(s, 1H), 12.80(brs, 1H).

Example 189

4-(2-[5-(7-Chloro-5-fluoro-4-propylbenzoate-2-yl)pyrrolyl] )benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

0.94(t, 3H, J= 7.2 Hz), 1.66(q, 2H, J= 7.2 Hz), 2.78(t, 2H, J=7.2 Hz), 6.74-6.77(m, 1H), 6.82-6.85(m, 1H), 7.29(d, 1H, J=10.0 Hz), 7.41(s, 1H), 7.87(d, 2H, J=8.4 Hz), 7.95(d, 2H, J=8.4 Hz), 11.91(brs, 1H).

Example 190

4-{2-[5-(5-the Fluorine-6-methylbenzofuran-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

2.31(s, 3H), 6.68-6.72(m, 1H), 6.82-6.85(m, 1H), 7.15(s, 1H), 7.40(d, 1H, J= 10.0 Hz), 7.47(d, 1H, J=6.4 Hz), 7.88(d, 2H, J=8.4 Hz), 7.94(d, 2H, J= 8.4 Hz), 11.90(brs, 1H).

Example 191

4-{2-[5-(5,7-Differentfor-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

6.78-6.81(m, 1H), 6.85-6.88(m, 1H), 7.18-7.25(m, 1H), 7.29(d, 1H, J= 3.2 Hz), 7. the roll])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.25(t, 3H, J=7.6 Hz), 2.80-2.88(m, 2H), 6.72-6.75(m, 1H), 6.83-6.86(m, 1H), 7.00-7.06(m, 1H), 7.33(s, 1H), 7.38-7.42(m, 1H), 7.89(d, 2H, J=8.8 Hz), 7.95(d, 2H, J=8.8 Hz), 11.91(brs, 1H).

Example 193

4-{2-[5-{5-Chloro-7-ethyl-3-perbendaharaan-2-yl)pyrrolyl])benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.32(t, 3H, J= 7.6 Hz), 2.69(q, 2H, J=7.6 Hz), 6.69-6.72(m, 1H), 6.90-6.93(m, 1H), 7.26-7.28(m, 1H), 7.54-7.57(m, 1H), 7.90-7.96(m, 4H), 11.95(brs, 1H).

Example 194

4-(2-[5-(5-Chloro-7-methyltetrahydrofuran-2-yl)pyrrolyl] )benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

3.36(s, 3H), 4.74(s, 2H), 4.85(s, 2H), 6.74-6.75(m, 1H), 6.85-6.87(m, 1H), 7.22(s, 1H), 7.25(d, 1H, J=2Hz), 7.69(d, 1H, J=2Hz), 7.88(d, 2H, J= 8.4 Hz), 7.95(d, 2H, J=8.4 Hz), at 11.93(brs, 1H).

Example 195

4-{2-[5-(5-Chloro-7-nicevision-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

6.87-6.88(m, 1H), 6.92-6.93(m, 1H), 7.26(s, 1H), 7.64(s, 1H), 7.89(d, 2H, J=8.4 Hz), 7.92(s, 1H), 8.00(d, 2H, J=8.4 Hz), 12.09(brs, 1H).

Example 196

4-{2-[5-(7-Chloro-4-ethyl-5-forbindelse 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.22(t, 3H, J= 7.2 Hz), 2.81(q, 2H, J=7.2 Hz), 6.76-6.79(m, 1H), 6.86-6.89(m, 1H), 7.30(d, 1H, J= 10.0 Hz), 7.42(s, 1H), 7.90(d, 2H, J=8.4 Hz), 7.96(d, 2H, J=8.4 Hz), 11.96(s, 1H), 12.84(brs, 1H).

Example 197

4-{ 2-[5-(4-Ethyl-5-fluoro-7-propoxybenzene-2-yl)pyrrolyl] )benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz)

1.01(t, 3H, J= 7.2 Hz), 1.20(t, 3H, J=7.2 Hz), 1.80(hex, 2H, J=7.2 Hz), 2.73(q, 2H, J=7.2 Hz), 4.10(t, 2H, J=7.2 Hz),6.69-6.72(m, 1H), 6.77(d, 1H, J= 12.4 Hz), 6.82-6.85(m, 1H), 7.30(s, 1H), 7.88(d, 2H, J=8.4 Hz), 7.94(d, 2H, J= 8.4 Hz), 11.86(s, 1H), at 12.82(brs, 1H).

Example 198

4-(2-[5-(4-Ethyl-5,7-differentfor-2-yl)pyrrolyl]}benzoic acid

< / BR>
Specified in the header of the connection receives the same way as in example 1(D).

1H-NMR(DMSO-d6, 400MHz);

1.23(t, 3H, J=7.6 Hz), 2.77-2.83(m, 2H), 6.78-6.80(m, 1H), 6.85-6.88(m, 1H), 7.18(t, 1H, J= 10.8 Hz), 7.41(d, 1H, J=2.8 Hz), 7.90(d, 2H, J=8.8 Hz), 7.96(d, 2H, J=8.8 Hz), 11.98(brs, 1H).

1. Carboxylic acid derivative with condensed rings, expressed by the formula (A), its pharmaceutically acceptable salts and hydrates of salts

< / BR>
in which the rings L and M condensed with each other;

the symbol denotes a single or double bond;

X is a group of the formula

< / BR>
in which R1is hydrogen, halogen, possibly substituted lower alkyl, vessenny of alkenyl, x = 0 or 1;

Y is a group of the formula

< / BR>
in which R2is hydrogen, halogen, possibly substituted lower alkyl, possibly substituted lower alkoxy, possibly substituted alkenyl, y = 0 or 1;

Z is a group of the formula

< / BR>
in which R3is hydrogen, halogen, possibly substituted lower alkyl; z = 0 or 1;

R is a group-O - or a group of the formula

< / BR>
in which R4is hydrogen, halogen, possibly substituted lower alkyl, possibly substituted phenyl, possibly substituted lower alkoxy, possibly substituted, phenyloxy, possibly substituted alkenyl or possibly substituted quinil, p = 0 or 1;

Q is the group-O - or-S - or a group of the formula

< / BR>
in which R5is hydrogen, possibly substituted lower alkyl, q = 0 or 1;

U is a group of the formula

< / BR>
in which R6is hydrogen or a possibly substituted lower alkyl, u = 0 or 1;

V is a group of the formula

< / BR>
in which R7is hydrogen, possibly substituted lower alkyl or a group of the formula

< / BR>
in which a and b independently of one another denote a possibly substituted benzene or naphthalene ring or possibly substituted pyrrole ring, thiophene ring or furan ring and D denotes a possibly protected carboxyl, v =config lower alkyl, possibly substituted lower alkoxy or a group of the formula

< / BR>
in which a and b independently of one another denote a possibly substituted benzene or naphthalene ring or possibly substituted pyrrole ring, thiophene ring or furan ring, D - possibly protected carboxyl and w = 0 or 1,

provided that the symbols in the formula

< / BR>
used in the above definitions of X, Y, Z, P, Q, U, V and W, denotes a single or double bond;

two adjacent R1, R2, R3, R4, R5, R6, R7and R8together with the carbon atoms to which they are attached, can form cyclopentyl or phenyl;

x, y, z, and p must satisfy the relation 4x+y+z+p3;

u, v, w and q must satisfy the relation 4u+v+w+q3;

one of V and W is a group of the formula

in which Rk'belongs to R7or R8where R7or R8is a group of the formula

< / BR>
in which a and b independently of one another denote a possibly substituted benzene or naphthalene ring or possibly substituted pyrrole ring, thiophene ring or furan ring, D - possibly protected carboxyl, except for compounds of the formula (A), in which the ring L is one who irarenai formulas (Ia) and (Ib), its pharmaceutically acceptable salts or hydrates of the salts

< / BR>
< / BR>
in which R1-R8the same or different is hydrogen, halogen, possibly substituted lower alkyl, possibly substituted phenyl, possibly substituted furyl, thienyl, possibly substituted lower alkoxy, possibly substituted, phenyloxy, possibly substituted alkenyl or possibly substituted quinil or alternatively two adjacent R1, R2, R3, R4, R5, R6, R7and R8together with the carbon atoms to which they are attached, can form cyclopentyl or phenyl;

A and b independently from each other - may be substituted benzene or naphthalene ring or possibly substituted pyrrole ring, thiophene ring or furan ring;

D - may be protected carboxyl.

3. Carboxylic acid derivative with condensed rings under item 1, expressed by the formula (IIA), (IIb), (IId) or (IIE), its pharmaceutically acceptable salts or hydrates of the salts

< / BR>
< / BR>
< / BR>
< / BR>
in which each of R1-R8is hydrogen, halogen, possibly substituted lower alkyl, possibly substituted phenyl, possibly substituted furyl or thienyl, possibly substituted lower alkoxy, perhaps C , R4, R5, R6, R7and R8together with the carbon atoms to which they are attached, can form cyclopentyl, phenyl;

A and b independently from each other - may be substituted benzene or naphthalene ring or possibly substituted pyrrole ring, thiophene ring or furan ring;

D - may be protected carboxyl.

4. Carboxylic acid derivative with condensed rings under item 1, expressed by the formula (IIIa) or (IIId), its pharmaceutically acceptable salts or hydrates of the salts

< / BR>
< / BR>
in which each of R1-R8is hydrogen, halogen, possibly substituted lower alkyl, possibly substituted phenyl, possibly substituted furyl or thienyl, possibly substituted lower alkoxy, possibly substituted, phenyloxy, possibly substituted alkenyl or possibly substituted quinil or alternatively two adjacent1, R2, R3, R4, R5, R6, R7and R8together with the carbon atoms to which they are attached, can form cyclopentyl, phenyl;

A and b independently from each other - may be substituted benzene or naphthalene ring or possibly substituted pyrrole ring, thiophene ring or furan who were on p. 1, expressed by the formula (IVa), (IVd) or (VIe), its pharmaceutically acceptable salts or hydrates of the salts

< / BR>
< / BR>
< / BR>
in which each of R1-R8is hydrogen, halogen, possibly substituted lower alkyl, possibly substituted phenyl, possibly substituted furyl, thienyl, possibly substituted lower alkoxy, possibly substituted, phenyloxy possibly substituted alkenyl or possibly substituted quinil, or alternatively two adjacent1, R2, R3, R4, R5, R6, R7and R8together with the carbon atoms to which they are attached, can form cyclopentyl, phenyl;

A and b independently from each other - may be substituted benzene or naphthalene ring or possibly substituted pyrrole ring, thiophene ring or furan ring;

D - may be protected carboxyl.

6. Carboxylic acid derivative with condensed rings under item 1 or 2, expressed by the formula (Ia) or (Ib), its pharmaceutically acceptable salts or hydrates of the salts

< / BR>
< / BR>
in which each of R1-R8the same or different is hydrogen, halogen, possibly substituted lower alkyl, possibly substituted phenyl, possibly substituted furyl, thienyl, maybe zameshannym or alternatively two adjacent R1, R2, R3, R4, R5, R6, R7and R8together with the carbon atoms to which they are attached, can form cyclopentyl, phenyl;

And possibly substituted pyrrole ring, thiophene ring or furan ring;

In a possibly substituted phenyl group;

D - may be protected carboxyl.

7. Carboxylic acid derivative with condensed rings under item 1 or 3, expressed by the formula (IIA) or (IIb), its pharmaceutically acceptable salts or hydrates of the salts

< / BR>
< / BR>
in which each of R1-R8is hydrogen, halogen, possibly substituted lower alkyl, possibly substituted phenyl, possibly substituted furyl or thienyl, possibly substituted lower alkoxy, possibly substituted, phenyloxy, possibly substituted alkenyl or possibly substituted quinil or alternatively two adjacent1, R2, R3, R4, R5, R6, R7and R8together with the carbon atoms to which they are attached, may form having a heteroatom or a substituted ring;

And possibly substituted pyrrole, thiophene ring or furan ring;

In a possibly substituted phenyl group;

D - it is possible to secure what armoloy (IIIa), its pharmaceutically acceptable salts or hydrates of the salts

< / BR>
in which each of R1-R8is hydrogen, halogen, possibly substituted lower alkyl, possibly substituted phenyl, possibly substituted furyl or thienyl, possibly substituted lower alkoxy, possibly substituted, phenyloxy or alternatively two adjacent R1, R2, R3, R4, R5, R6, R7and R8together with the carbon atoms to which they are attached, can form cyclopentyl, phenyl;

And possibly substituted pyrrole ring, thiophene ring or furan ring;

In a possibly substituted phenyl group;

D - may be protected carboxyl.

9. Carboxylic acid derivative with condensed rings under item 1 or 5, expressed by the formula (IVa), its pharmaceutically acceptable salts or hydrates of the salts

< / BR>
in which R1-R8the same or different is hydrogen, halogen, possibly substituted lower alkyl, possibly substituted phenyl, possibly substituted furyl or thienyl, possibly substituted lower alkoxy, possibly substituted, phenyloxy, possibly substituted alkenyl or possibly substituted quinil or alternatively two adjacent R1, R2, R3brazability cyclopentyl or phenyl;

And possibly substituted pyrrole ring, thiophene ring or furan ring;

In a possibly substituted phenyl group;

D - may be protected carboxyl.

10. Carboxylic acid derivative with condensed rings on PP. 1, 2 or 6, expressed by the formula (Ia) or (Ib), its pharmaceutically acceptable salts or hydrates of the salts

< / BR>
< / BR>
in which R1-R8the same or different is hydrogen, halogen, possibly substituted lower alkyl, possibly substituted phenyl, possibly substituted furyl or thienyl, possibly substituted lower alkoxy, possibly substituted, phenyloxy, possibly substituted alkenyl or possibly substituted quinil or alternatively two adjacent R1, R2, R3, R4, R5, R6, R7, R8together with the carbon atoms to which they are attached, can form cyclopentyl or phenyl;

And possibly substituted pyrrole ring;

In a possibly substituted phenyl group;

D - may be protected carboxyl.

11. Carboxylic acid derivative with condensed rings on PP. 1, 3 or 7, expressed by the formula (IIA) or (IIb), its pharmaceutically acceptable salts or hydrates of the salts

< / BR>
< / BR>
th phenyl, possibly substituted furyl or thienyl, possibly substituted lower alkoxy, possibly substituted, phenyloxy, possibly substituted alkenyl or possibly substituted quinil or alternatively two adjacent1, R2, R3, R4, R5, R6, R7, R8together with the carbon atoms to which they are attached, can form cyclopentyl or phenyl;

And possibly substituted pyrrole ring;

In a possibly substituted phenyl group;

D - may be protected carboxyl.

12. Carboxylic acid derivative with condensed rings on PP. 1, 4, or 8, expressed by the formula (IIIa), its pharmaceutically acceptable salts or hydrates of the salts

< / BR>
in which each of R1-R8is hydrogen, halogen, possibly substituted lower alkyl, possibly substituted phenyl, possibly substituted furyl or thienyl, possibly substituted lower alkoxy, possibly substituted, phenyloxy, possibly substituted alkenyl or possibly substituted quinil or alternatively two adjacent1, R2, R3, R4, R5, R6, R7, R8together with the carbon atoms to which they are attached, can form cyclopentyl or phenyl;

And possibly replaced.

13. Carboxylic acid derivative with condensed rings on PP. 1, 5 or 9, expressed by the formula (IVa), its pharmaceutically acceptable salts or hydrates of the salts

< / BR>
in which R1-R8the same or different is hydrogen, halogen, possibly substituted lower alkyl, possibly substituted phenyl, possibly substituted heteroaryl, possibly substituted lower alkoxy, possibly substituted, phenyloxy, possibly substituted alkenyl or possibly substituted quinil or alternatively two adjacent R1, R2, R3, R4, R5, R6, R7, R8together with the carbon atoms to which they are attached, can form cyclopentyl or phenyl;

And possibly substituted pyrrole ring;

In a possibly substituted phenyl group;

D - may be protected carboxyl.

14. Carboxylic acid derivative under item 1, characterized in that it is a 4-{ 2-[5-(3-fluoro-4,7-dimethyl-benzofuran-2-yl)pyrrolyl] } benzoic acid.

15. Carboxylic acid derivative under item 1, characterized in that it is a 4-{ 2-[5-(7-fluoro-4-Cryptor-methylbenzofuran-2-yl)pyrrolyl] } benzoic acid.

16. Carboxylic acid derivative under item 1, its Pharm/P> 17. Pharmaceutical composition having agonistic activity against receptors of the retinoic acid comprising an effective amount of carboxylic acid derivative with condensed rings under item 1, its pharmaceutically acceptable salts or hydrates of the salts and pharmaceutically acceptable filler.

18. Carboxylic acid derivative with condensed rings under item 1, its pharmaceutically acceptable salts and hydrates of salts to obtain a pharmaceutical composition having agonistic activity against receptors of retinoic acid.

 

Same patents:

The invention relates to the chemistry of heterocyclic sulfur compounds and concerns diabeticheskih derivatives of the formula I, having antidepressant activity, where R= H, Na, Me, CH2=CHCH2CH2Ph or CH3CH2CH2CH2X=CONH2; NH2HCl; NHBoc; CH2NH2or C(OEt)2NH2HCl

The invention relates to derivatives of heterocyclic compounds, as well as agricultural and horticultural fungicides containing these compounds as active ingredients

The invention relates to substituted guanidines thiophenemethylamine acid of the formula I

< / BR>
where mean:

at least one of the substituents R(1), R(2) and R(3)

- Op-(CH2)s-CqF2q+1, R(40)CO - or R(31)SOk-;

p is zero or 1;

s is zero, 1, 2, 3 or 4;

q 1,2, 3,4, 5, 6, 7 or 8;

k is zero, 1 or 2;

R(40) alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms,

cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms or phenyl which is not substituted or is substituted by 1-3 substituents selected from the group consisting of F, Cl, CF, methyl or methoxy;

R(31) alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, or phenyl which is not substituted or is substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl or methoxy;

or

R(31) NR(41)R(42);

R(41)and R(42)

independently from each other hydrogen, alkyl with 1, 2, 3 or 4 C-atoms,

perfluoroalkyl with 1, 2, 3 or 4 C-atoms,

or

R(41)and R(42)

together 4 or 5 methylene groups, of which CH2-group may be replaced by oxygen, S, NH, N-CH3or N-benzyl;

and sootwetstwii-OgaWITHraH2raR(10);

PA zero or 1;

mA zero, 1, 2, 3, 4, 5, 6, 7 or 8;

ga zero or 1;

ha zero, 1, 2, 3 or 4;

R(10) cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms or phenyl, where the phenyl is not substituted or is substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl and methoxy;

R(4) and R(5)

independently from each other hydrogen, F, Cl, Br, I, CN, alkyl with 1, 2, 3, 4, 5, 6,

7 or 8 C-atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms or phenyl which is not substituted or is substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR(14)R(15);

R(14)R(15)

independently from each other H, alkyl with 1, 2, 3 or 4 C-atoms or perfluoroalkyl of 1, 2, 3 or 4 C-atoms

and their pharmaceutically tolerable salts

The invention relates to new derivatives of tamilcanadian with the General formula (I) wherein R' represents 2-thienyl or 3-thienyl radical, R represents ceanorhaditis or a radical of the formula-C(O) - and R2 is optional saturated or unsaturated cyclic hydrocarbon radical or aryl radical

The invention relates to the derivatives of thiophene of the General formula I, in which R1is the formula A1- X1- R3; R2is perhaps the formula A2- X2- R4; ring b is 4-10-membered nitrogen-containing cycloalkyl ring or 5 - or 6-membered nitrogen-containing unsaturated heterocycle; Ar represents an aryl ring or heteroaryl ring; A1, A2and A3may be the same or different and each represents a bond or lower alkylenes group; X1and X2may be the same or different and each represents a bond or a formula-O-, -S-; R3and R4may be the same or different, and each represents a hydrogen atom, cyclic aminogroup or a lower alkyl group, aryl group or aracelio group, or its pharmaceutically acceptable salt

The invention relates to new derivatives of 4-hydroxypiperidine formula I

< / BR>
where X represents-O-, -NH-, -CH2-, -CH=, -SNON - or-CO-; R1-R4independently from each other denote hydrogen, a hydroxy-group, (lower) alkylsulfonyl or acetaminoph; R5-R8independently from each other denote hydrogen, a hydroxy-group, (lower)alkyl, halogen, (lower)alkoxygroup, trifluoromethyl or cryptometrics; a and b may denote a double bond, provided that when a represents a double bond, b is unable to designate a double bond; n = 0-2; m = 1-3; p = 0 or 1, and their pharmaceutically acceptable additive salts

The invention relates to aromatic amedieval derivatives and their salts, which have the ability to strong antikoaguliruyuschee action through reversible inhibition of activated coagulation factor, factor X (hereinafter referred to "FXA"), and which can be administered orally

The invention relates to a method for producing derivatives of 3-(5-methylfur-2-yl)-benzofuran having an antihypertensive, antianginal and antiarrhythmic activities

The invention relates to new derivatives of benzofuran-2-ones of formula 1, where a value of substituents specified in paragraph (1 formulas that can be used as stabilizers for organic polymers susceptible to oxidative, thermal or induced light decay

The invention relates to vasoconstrictor /(benzodioxan, benzofuran and benzopyran)-alkylamino/-alkyl-substituted guanidine formula I, their pharmaceutically acceptable salts, or their stereochemical isomers, where X = O, CH2or a direct bond; R1= H, C1-C4alkyl, R2= H, C1-C6alkyl, C3-C6alkenyl, C3-C6quinil, R3= H, C1-C4alkyl; or R2and R1taken together, may form a bivalent radical of the formula/CH2/m-, where m = 4 or 5; or R1and R2taken together may form a bivalent radical of formula-CH=CH -, or the formula/CH2/n-, where n = 2, 3 or 4; or R3may indicate a relationship when R1and R2taken together form a bivalent radical of formula-CH=CH-CH= -, -CH= CH-N= or-CH=N-CH=; where one or two hydrogen atom substituted by a halogen atom, a C1-C6alkoxygroup, C1-C6the alkyl, CN, NH, mono - or di(C1-C6alkyl) amino group, aminocarbonyl, C1-C6alkylaminocarbonyl, R4-H or C1-C6-alkyl; Alk1denotes a divalent C1-C3-ascandilwy radical, A denotes dwuhvalentny a radical of the formula /, lk2represents C2-C15-alcander or C5-C7-cycloalkenyl, and each "R" represents 0, 1, 2, R7and R8each independently is H, a halogen atom, a C1-C6by alkyl, hydroxyl, C1-C6allyloxycarbonyl, C1-C6alkoxygroup, cyano, amino, C1-C6the alkyl, carboxyla, nitro or amino group, aminocarbonyl, C1-C6alkylcarboxylic or mono - or di-(C1-C6)alkylamino, provided that excluded /2-/ (2,3-dihydro-1,4-benzodioxin-2-yl)-methyl/-amino/-ethyl-guanidine

The invention relates to new derivatives of N-(3-hydroxy-4-piperidinyl) (dihydro-2H-benzopyran or dihydrobenzoic) carboxamide, having valuable pharmaceutical properties, namely activity to stimulate gastrointestinal peristalsis

The invention relates to heteroalicyclic alkanoyl derivatives, which have a biocidal effect, and more particularly to aminoalcohols derived molecules containing heteroalicyclic ring system, to methods of their synthesis, their new intermediates, containing pharmaceutical compositions and to their use as biocidal agents, in particular anticancer agents
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