Derivatives of indole, method for their preparing and their applying

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to a method for preparing derivatives of indole of the general formula (I):

wherein R1 represents hydroxy-group; R2 represents hydrogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, (C2-C6)-alkoxyalkyl or 4-methoxybenzyl; R3 represents hydrogen atom or (C1-C6)-alkyl; each among R4 and R represents independently hydrogen atom, (C1-C6)-alkyl or (C1-C6)-alkoxy-group; D represents an ordinary bond, (C1-C6)-alkylene, (C2-C6)-alkenylene or (C1-C6)-oxyalkylene; in the group-G-R6 wherein G represents an ordinary bond, (C1-C6)-alkylene; R represents saturated or unsaturated carbocyclic ring (C3-C15) or 4-15-membered heterocyclic ring comprising 1-5 atoms of nitrogen, sulfur and/or oxygen wherein this ring can be substituted. Also, invention describes a method for preparing derivatives of indole and DP-receptor antagonist comprising derivative of the formula (I) as an active component. As far as compounds of the formula (I) bind with DP-receptors and they are antagonists of DP-receptors then they can be useful for prophylaxis and/or treatment of diseases, for example, allergic diseases.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

11 cl, 7 tbl, 353 ex

 

The technical field to which the invention relates.

The present invention relates to the derivatives of indole. More specifically, the present invention relates to an indole derivative represented by the formula (I)

(where all the symbols have the meanings specified below), method of their production and their use.

The level of technology

Prostaglandin D (hereinafter called "PGD") is known as a metabolite in the arachidonic acid cascade, and it is known that it exerts an inhibitory action on bronchostenosis, vasodilation or vasoconstriction and platelet aggregation. It is believed that PGD is produced in the fat cells, and increasing the concentration PGD is determined in patients with systemic mastocytosis (New Eng. J. Med., 303, 1400-1404 (1980)). It is also believed that PGD is associated with neuroactivity, especially sleep and secretion of hormones. In addition, there are reports suggesting its involvement in platelet aggregation, glycogen metabolism, and the regulation of intraocular pressure, etc.

PGD exerts its effect by binding to DP receptor, which receptor. The DP antagonist-receptor associated with it and is an antagonist to the receptor, so that it can inhibit the function of PGD. Accordingly, it is considered that it is useful for prevention and/or treatment of diseases such as allergic diseases, such is AK allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergies, etc.; system mastocytosis; disorders due to systemic activation of mastocytes; anaphylactic shock; bronchostenosis; urticaria; eczema; allergic bronchopulmonary aspergillosis; inflammation of the paranasal sinus; nasal polyps; hypersensitive of angita; eosinophilia; contact dermatitis, diseases accompanied by itch, such as atopic dermatitis, urticaria, allergic conjunctivitis, allergic rhinitis, contact dermatitis, and the like; secondary diseases caused by behavior (scratches, bruises, and the like), such as cataract, retinal detachment, inflammation, infection, sleep disorder, and the like; inflammation; chronic obstructive pulmonary disease, ischemic reperfusion disorders; cardiovascular disorders; pleurisy, acute rheumatoid arthritis; ulcerative colitis; etc. in Addition, it is believed that it is related to sleep and platelet aggregation and are useful in the case of such diseases.

Currently some known antagonists DP receptor, and is considered the most selective BW-A868C represented by the formula (A)

It was also recently published (WO 98/25915, WO 98/25919, WO 97/00853, WO 98/15502 etc) about the antagonists of P-receptor, derived thromboxane.

On the other hand, as a compound similar to the compound of the present invention, known indole represented by the formula (In) (J. Heterocyclic Chem., 19, 1195 (1982))

Description of the invention

The authors of the present invention conducted intensive studies with the aim of finding a compound that specifically binds to DP receptor and shows antagonistic activity, and found that the above purpose can be achieved by using indole derivatives represented by the formula (I), and thus made the present invention.

In other words, the present invention relates to (1) derived indole represented by the formula (I)

where R1represents hydroxy, (C1-6)-alkoxy or NR8R9where R8and R9each independently represents a hydrogen atom, (C1-6)-alkyl or SO2R13where R13represents (C1-6)-alkyl, saturated or unsaturated carbocyclic ring, (C3-15) or a 4-15 membered heterocyclic ring containing 1 to 5 nitrogen atoms, sulfur atoms and/or oxygen atoms;

R2represents a hydrogen atom, (C1-6)-alkyl, (C1-6)-alkoxy, (C2-6)-alkoxyalkyl, halogen atom, amino, trihalomethyl, cyano, hydroxy, benzyl or 4-methoxybenzyl;

R3represents the t of a hydrogen atom, (C1-6)-alkyl, (C1-6)-alkoxy, halogen atom, trihalomethyl, cyano or hydroxy;

R4and R5each independently represents a hydrogen atom, (C1-6)-alkyl, (C1-6)-alkoxy, (C2-6)-alkoxyalkyl, halogen atom, nitro, amino, trihalomethyl, cyano or hydroxy;

D represents a simple bond, (C1-6)-alkylene, (C2-6)-albaniles or (C1-6)-oxyalkylene;

in-G-R6

1) G represents a simple bond, (C1-6)-alkylene, which may be substituted by 1-2 oxygen atoms and/or sulfur atoms, (C2-6)-albaniles that can be. substituted by 1-2 oxygen atoms and/or sulfur atoms, where alkylene and albaniles can be substituted by hydroxy or (C1-4)-alkoxy, -C(O)NH-, -NHC(O)-, -SO2NH-, -NHSO2- or diazo;

R6represents a saturated or unsaturated carbocyclic ring, (C3-15) or a 4-15 membered heterocyclic ring containing 1 to 5 nitrogen atoms, sulfur atoms and/or oxygen atoms, where the ring may be substituted by 1-5 substituents selected from (C1-6)alkyl, (C1-10)alkoxy, (C2-6)-alkoxyalkyl, halogen atom, hydroxy, trihalomethyl, nitro, amino, phenyl, phenoxy, oxo, (C2-6)-acyl, (C1-6)-alkanesulfonyl and cyano;

2) G and R6taken together, represent

(i) (C1-15)alkyl which may be substituted by 1-5 atoms of oxygen and/or sulfur atoms;

(ii) (C2-15)-alkenyl, which may be substituted by 1-5 atoms of oxygen and/or sulfur atoms; the Li

(iii) (C2-15)-quinil, which may be substituted by 1-5 atoms of oxygen and/or sulfur atoms,

where alkyl, alkenyl or quinil can be substituted by 1-12 substituents selected from (C1-6)-alkoxy, halogen atom, hydroxy, cyano, oxo and NR11R12where R11and R12each independently represents a hydrogen atom, (C1-6)-alkyl, (C2-6)-alkenyl, phenyl, benzoyl, naphthyl, phenyl, substituted (C1-6)alkyl, or (C1-6)-alkyl substituted by phenyl or cyano;

n equals the number of 1-3;

m equals the number of 1-3;

i equals the number of 1-4; and

represents a simple bond or double bond,

or its non-toxic salt;

(2) the method of its production;

(3) a pharmaceutical agent containing a specified compound as an active ingredient; and

(4) 2-methylindole-4-acetic acid, which is a new synthetic intermediate connection.

In the formula (I) (C1-6)-alkyl represented by R2, R3, R4, R5, R6, R8, R9, R11, R12or R13includes methyl, ethyl, propyl, butyl, pentyl, hexyl and its isomers.

In the formula (I) (C1-6)-alkoxy represented by R1, R2, R3, R4or R5includes methoxy, ethoxy, propyloxy, bucalossi, pentyloxy, hexyloxy and their isomers.

In the formula (I), (C1-10)alkoxy, presents R6includes met the XI, ethoxy, propyloxy, bucalossi, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy and their isomers.

In the formula (I) (C1-15)alkyl represented by G and R6taken together, includes methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl and their isomers.

In the formula (I) (C1-15)alkyl which may be substituted by 1-5 atoms of oxygen and/or sulfur atoms represented by G and R6taken together, represents the above-mentioned alkyl in which from 1 to 5 carbon atoms substituted atom(s) of oxygen and/or atom(s) of sulfur.

In the formula (I) (C2-15)-alkenyl represented by G and R6taken together, includes vinyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonanal, decanal, undecanal, dodecanal, tridecanal, tetradecanol, pentadecanol and their isomers.

In the formula (I) (C2-15)-alkenyl, which may be substituted by 1-5 atoms of oxygen and/or sulfur atoms represented by G and R6taken together, is above alkenyl, in which 1-5 carbon atoms substituted atom(s) of oxygen and/or atom(s) of sulfur.

In the formula (I) (C2-15)-quinil represented by G and R6taken together, includes ethinyl, PROPYNYL, butynyl, pentenyl, hexenyl, heptenyl, octenyl, nonini, decenyl, undecenyl, dodecenyl, tridecanol, tetradecanol, pentadecanol and them and the Windows.

In the formula (I) (C2-15)-quinil, which may be substituted by 1-5 atoms of oxygen and/or sulfur atoms represented by G and R6taken together, represents the above quinil, in which 1-5 carbon atoms substituted atom(s) of oxygen and/or atom(s) of sulfur.

In the formula (I) (C2-6)-alkoxyalkyl represented by R2, R4, R5or R6includes methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxyphenyl, ethoxymethyl, ethoxyethyl, ethoxypropan, ethoxymethyl, propylacetate, propylacetate, propylacetate, butylacetate, butylacetyl, petrochemical and their isomers.

In the formula (I) (C1-6)-alkylen, is D or G, includes methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene and their isomers.

In the formula (I) (C2-6)-albaniles represented by D includes vinile, propylen, butylen, penttinen, geksanalem and their isomers.

In the formula (I) (C1-6)-oxyalkylene represented by D includes oxymethylene, oksietilenom, oxybutylene, occidentalis, exigencies and their isomers.

In the formula (I) (C1-6)-alkylene, which may be substituted by 1-2 oxygen atoms and/or sulfur, presents G, includes the above (C1-6)-alkylene in which any(s) atom(s) substituted carbon(s) atom(s) of oxygen and/or atom(s) of sulfur.

In the formula (I) (C2-6)-albaniles, which may be substituted by 1-2 atoms of CI is of oxygen and/or sulphur, presents G, includes the above (C2-6)-albaniles in which any(s) saturated(s) atom(s) substituted carbon(s) atom(s) of oxygen and/or atom(s) of sulfur.

In the formula (I) (C2-6)-alkenyl represented by R11or R12includes vinyl, propenyl, butenyl, pentenyl, hexenyl and their isomers.

In the formula (I), the halogen atom represented by R2, R3, R4, R5or R6includes fluorine, chlorine, bromine and iodine.

In the formula (I) trihalomethyl represented by R2, R3, R4, R5or R6includes trifluoromethyl, trichloromethyl, tripometer and triodetic.

In the formula (I), (C1-10)alkoxy, presents R10includes methoxy, ethoxy, propyloxy, bucalossi, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy and their isomers.

In the formula (I) (C2-6)-acyl represented by R6includes acetyl, propionyl, butyryl, valeryl, hexanoyl and their isomers.

In the formula (I) (C1-6)-alkanesulfonyl represented by R6includes methanesulfonyl, econsultancy, propanesulfonyl, butanesulfonyl, pentanesulfonic, hexanesulfonic and their isomers.

In the formula (I) carbocyclic ring (C3-15), presents R6or R13includes monocyclic, bicyclic or tricklecharge unsaturated or saturated carbocyclic ring with the carbon atoms is from 3 to 1.

Examples of monocyclic, bicyclic or triticosecale unsaturated or saturated carbocyclic ring with the carbon atoms is from 3 to 15 are cyclopropane ring, CYCLOBUTANE, cyclopentane, cyclohexane, Cycloheptane, cyclooctane, cyclopentene, cyclohexene, cyclopentadiene, cyclohexadiene, benzene, pentalene, indene, naphthalene, azulene, perhydroanthracene, palikonda, dihydronaphthalene, tetrahydronaphthalene, perhydroanthracene, perhydroanthracene, heptylene, biphenylene, fluorene, phenanthrene, anthracene, dihydroanthracene, tetrahydropyrane, perhydroanthracene, dihydrofluoride, tetrahydrofluorene, perhydrofluorene, norbornane, morphinan, norbornene, Korpinen and the like.

In the formula (I) 4-15 membered heterocyclic ring containing 1 to 5 nitrogen atoms, sulfur atoms and/or oxygen atoms, represented by R6or R13is unsaturated or saturated, and its examples are the cycles having the formula below:

In the formula (I) R1preferably represents hydroxy, (C1-6)-alkyl or NR8R9and preferably hydroxy or (C1-2)alkyl.

In the formula (I) R2preferably represents a hydrogen atom, (C1-6)-alkyl Il is (C1-6)-alkoxyalkyl, and preferably a hydrogen atom, (C1-2)alkyl or (C1-2)-alkoxyalkyl.

In the formula (I) R3preferably represents a hydrogen atom or (C1-6)-alkyl.

In the formula (I) R4preferably represents a hydrogen atom or (C1-6)-alkyl, and preferably a hydrogen atom or (C1-2)alkyl.

In the formula (I) R5preferably represents a hydrogen atom or (C1-6)-alkyl, and preferably a hydrogen atom or (C1-2)alkyl.

In the formula (I), D preferably represents a simple bond or (C1-6)-alkylene, and preferably simple bond or (C1-2)-alkylen.

In the formula (I) G preferably represents (C1-6)-alkylene, which may be substituted by 1 or 2 oxygen atoms, and preferably(C1-2)-alkylene, which may be substituted with one oxygen atom.

In the formula (I) R6preferably represents (C5-10) carbocyclic ring, or a monocyclic or bellicose 5-10-membered heterocyclic ring containing 1-3 nitrogen atom, oxygen and/or sulphur, each of which may be substituted, and preferably a bicyclic 9 - or 10-membered heterocyclic ring containing 1-3 nitrogen atom, oxygen and/or sulfur, which may be substituted.

Also, G and R6taken together preferably represent (C1-10)alkyl which may be substituted by 1 to 4 oxygen atoms and/or sulfur, (C2-10)-Ala the Nile, which may be substituted by 1 to 4 atoms of oxygen and/or sulphur, or (C2-10)-quinil, which may be substituted by 1 to 4 oxygen atoms and/or sulfur.

Unless otherwise indicated, all isomers are included in the present invention. For example, alkyl, alkeline and alkyline group and Allenova group include groups with linear chains and groups with branched chains. In addition, in the present invention included isomers on double bond, cyclic, condensed cyclic (E-, Z-, CIS-, TRANS) isomers, the isomers formed from asymmetric(s) atom(s) C (R-, S-, α-, β-isomers, enantiomers, diastereomers), optically active isomers having optical rotation (D-, L-, d-, l-isomer), polar compounds, which are separated by chromatography (celinopravno connection, polar compound), equilibrium compounds, mixtures thereof at an arbitrary ratio, and a racemic mixture.

Among the compounds of the present invention represented by the formula (I), preferred are the compounds mentioned in the examples, compounds represented by formula (I-A1)

(where R6is a ring, R61is Deputy ring; p is 0 or an integer from 1 to 3; and other symbols have the meanings specified above), formula (I-A2)

(where all the symbols have the meanings specified above), formula (I-A3):

(where all the symbols have the meanings specified above), formula (I-A4):

(where all the symbols have the meanings specified above), formula (I-A5):

(where all the symbols have the meanings specified above), formula (I-A6):

(where all the symbols have the meanings specified above), formula (I-A7):

(where all the symbols have the meanings specified above), formula (I-A8):

(where all the symbols have the meanings specified above), formula (I-A9):

(where all the symbols have the meanings specified above), formula (I-A10):

(where all the symbols have the meanings specified above), formula (I-B1):

(where all the symbols have the meanings specified above), formula (I-B2):

(where all the symbols have the meanings specified above), formula (I-B3):

(where all the symbols have the meanings specified above), formula (I-B4):

(where all the symbols have the meanings specified above), formula (I-B5):

(where all the symbols have the meanings specified above), formula (I-B6):

(where all the symbols have the meanings specified above), formula (I-B7):

(where all the symbols have the meanings specified above), formula (I-B8):

(where all the symbols have the meanings specified above), formula (I-C1):

(where all the symbols have the meanings specified above), formula (I-C2):

(where all the symbols have the meanings specified above), formula (I-C3):

(where all the symbols have the meanings specified above), formula (I-C4);

(where all the symbols have the meanings specified above) of the formula (I-C5):

(where all the symbols have the meanings specified above), formula (I-C6):

(where all the symbols have the meanings specified above), formula (I-C7):

(where all the symbols have the meanings specified above), formula (I-C8):

(where all the symbols have the meanings specified above), formula (I-C9):

(where all the symbols have the meanings specified above), formula (I-C10):

(where all the symbols have the meanings specified above), formula (I-C11):

(where all the symbols have the meanings specified above), formula (I-C12):

(where all the symbols have the meanings specified above), formula (I-C13):

(where all the symbols have the meanings specified above), formula (I-C14):

(where all the symbols have the meanings specified above), formula (I-C15):

(where all the symbols have the meanings specified above), formula (I-D1):

(where all the symbols have the meanings specified above), formula (I-D2):

(where all the symbols have the meanings specified above), formula (I-D3):

(where all the symbols have the meanings specified above), formula (I-D4):

(where all the symbols have the meanings specified above), formula (I-D5):

(where all the symbols have the meanings specified above), formula (I-D6):

(where all the symbols have the meanings specified above), formula (I-D7):

(where all the symbols have the meanings specified above), formula (I-D8):

(where all the symbols have the meanings specified above), formula (I-D9):

(where all the symbols have the meanings specified above), formula (I-E1):

(where all the symbols have the meanings specified above), formula (I-E2):

(where all the symbols have the meanings specified above), formula (I-E3):

(where all the symbols have the meanings specified above), formula (I-E4):

(where all the symbols have the meanings specified above), formula (I-E5):

(where all the symbols have the meanings specified above), formula (I-E6):

(where all the symbols have the meanings specified above), formula (I-E7):

(where all the symbols have the meanings specified above), formula (I-E8):

(where all the symbols have the meanings specified above), formula (I-e):

(where all the symbols have the meanings specified above), formula (I-E10):

(where all the symbols have the meanings specified above), formula (I-E11):

(where all the symbols have the meanings specified above), formula (I-E12):

(where all the symbols have the meanings specified above), formula (I-E13):

(where all the symbols have the meanings specified above), formula (I-E14)

(where all the symbols have the meanings specified above), formula (I-E15 motorway):

(where all the symbols have the meanings specified above), formula (I-e):

(where all the symbols have the meanings specified above), formula (I-E17):

(where all the symbols have the meanings specified above), formula (I-E18):

(where all the symbols have the meanings specified above), formula (I-E19):

(where all the symbols have the meanings specified above), formula (I-E20):

(where all the symbols have the meanings specified above), formula (I-E21):

(where all the symbols have the meanings specified above), formula (I-E22):

(where all the symbols have the meanings specified above), formula (I-E23):

(where all the symbols have the meanings specified above), formula (I-F1):

(where all the symbols have the meanings specified above), formula (I-F2):

(where all the symbols have the meanings specified above), formula (I-F3):

(where all the symbols have the meanings specified above), formula (I-F4):

(where all the symbols have the meanings specified above), formula (I-F5):

(where all the symbols have the meanings specified above), formula (I-F6):

(where all the symbols have the meanings specified above), formula (I-F7):

(where all the symbols have the meanings specified above), formula (I-F8):

(where all the symbols have the meanings specified above), formula (I-F9):

(where all the symbols have the meanings specified above), formula (I-F10):

(where all the symbols have the meanings specified above), formula (I-F11):

(where all the symbols have the meanings specified above), formula (I-F12):

(where all the symbols have the meanings specified above), formula (I-F13):

(where all the symbols have the meanings specified above), formula (I-F14):

(where all the symbols have the meanings specified above), the compounds listed in the table is 1-5, and non-toxic salts of such compounds.

Table 1
-G-R6

Table 2
-G-R6

Table 3
-G-R6

Table 4
-G-R6

Table 5
-G-R6
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Salt

The compound of the present invention represented by the formula (I)can be converted into the corresponding salt by known methods. Salt, preferably, is non-toxic and water-soluble salt. Suitable salts are salts of alkali metals (potassium, sodium and the like), salts of alkaline earth metals, ammonium salt (salt of Tetramethylammonium, tetrabutylammonium, etc.) and pharmaceutically acceptable organic amines (triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenylamine, piperidine, monoethanolamine, diethanolamine, Tris(hydroxymethyl)methylamine, lysine, arginine, N-methyl-D-GL the fireplace and so on).

The compound of the present invention represented by the formula (I)and its salt can be converted into the hydrate by known methods.

Methods for obtaining compounds of the present invention

The compound of the present invention represented by the formula (I)can be obtained in the following ways and methods shown in the examples.

(a) Among the compounds represented by formula (I), the compound wherein R1represents hydroxy, i.e. the compound represented by formula (Ia)

(where all the symbols have the meanings indicated above, can be obtained from compounds represented by formula (IV), using the reaction of removing the protective group

(where R20represents allyl or benzyl group, and other symbols have the meanings specified above).

It is known, for example, that the reaction of removing the protective group of the allyl or benzyl ether complex is carried out in an organic solvent (e.g. methanol, ethanol, tetrahydrofuran, dioxane, ethyl acetate, and the like) at a temperature of from -10 to 90°

1) using tetrakis(triphenylphosphine)palladium and the research or

2) using palladium-on-charcoal, palladium, platinum, spongy Nickel (trade name "Raney Nickel") and the like, in an atmosphere of hydrogen.

(b) Among the compounds, represented by formula (I), the compound wherein R1represents (C1-6)-alkoxy (where all the symbols have the meanings mentioned above), i.e. the compound represented by formula (Ib)

(where R10represents (C1-6)-alkyl, and other symbols have the meanings indicated above, can be obtained by the reaction of esterification of the compound represented by formula (Ia), a compound represented by the formula

(where all the symbols have the meanings specified above), followed, optionally, by the reaction of removing the protective group.

It is known, for example, that the esterification reaction is carried out in an inert organic solvent (tetrahydrofuran, methylene chloride, benzene, acetone, acetonitrile, their mixtures and the like) in the presence or absence of tertiary amine (dimethylaminopyridine, pyridine, triethylamine and the like) using a condensing agent (1,3-dicyclohexylcarbodiimide (DCC), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) and the like) or gelegenheid (oxalicacid, thionyl chloride, phosphorus oxychloride and the like) at 0-50°C.

(C) Among the compounds represented by formula (I), the compound wherein R1is-NR8R9(where all the symbols have the meanings mentioned above), i.e. the compound represented by formula (Ic)

(where all the symbols have the meanings indicated above, can be obtained by amidation reaction of the compound represented by formula (Ia), a compound represented by the formula

(where all the symbols have the meanings specified above), followed, optionally, by the reaction of removing the protective group.

It is known, for example, that the amidation reaction is carried out in an inert organic solvent (tetrahydrofuran, methylene chloride, benzene, acetone, acetonitrile, their mixtures and the like) in the presence or absence of tertiary amine (dimethylaminopyridine, pyridine, triethylamine and the like) using a condensing agent (1,3-dicyclohexylcarbodiimide (DCC), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) and the like) or gelegenheid (oxalicacid, thionyl chloride, phosphorus oxychloride and the like) at 0-50°C.

The compound represented by formula (IV)can be obtained by subjecting the compound represented by formula (V)

(where R21, R31and R41have the same meaning as R2, R3and R4accordingly, and when they represent an amino group or a hydroxyl group protected by a protective group; and other symbols have the meanings specified above), the amidation of the compound represented by formula (VI)

(where R51has the same meaning as R5and when he represents the amino group or a hydroxy-group, it is protected by a protective group; and G1and R61has the same meaning as G and R6accordingly, and when they contain an amino group or a hydroxy-group, such a group protected by a protective group), followed, optionally, by the reaction of removing the protective group. The amidation reaction can be performed as described above.

Compounds represented by formulas (II), (III), (V) and (VI), known in themselves, or they can be obtained by known methods.

Among the compounds represented by formula (Ia), the compound, where D represents alkylene, can be obtained by reduction of compound represented by formula (Ia), or it can be obtained by increasing chain of carbon atoms in alkalinous part.

In each reaction in the present description, the reaction products can be cleaned with conventional methods of purification, for example, by distillation at atmospheric or reduced pressure, high performance liquid chromatography, thin-layer chromatography or column chromatography using silica gel or magnesium silicate, washing, recrystallization or similar methods. Cleaning can be performed after each reaction or after a series of reactions.

Pharmacological properties

Connect the Oia of the present invention, represented by formula (I)effectively communicate with the DP receptor and show antagonistic activity. For example, when laboratory tests such action can confirm the following test for receptor binding using cells expressing prostanoid receptors.

(i) Testing the binding of the receptor using cells expressing prostanoid DP receptors

Cells SNO expressing mouse DP receptor, get under way Hirata et al. (Proc. Natl. Acad. Sci., 11192-11196 (1994)) and used as the membrane of the standard.

The reaction solution (200 μl)containing the obtained membrane standard (30-166 µg) and3H-PGD2, incubated at room temperature for 20 minutes. The reaction is stopped by the buffer, chilled on ice (1 ml), and the associated3H-PGD2grab a glass filter with immediate filtration with suction under reduced pressure and measure the associated radioactivity using a liquid scintillation counter.

The Kd value and the value of Bmax is obtained from the graph of Scatchard (Ann. N.Y. Acad. Sci., 51, 660 (1949)). Nonspecific binding obtained as associated radioactivity in prisutstvie its PGD2excess amount (10 µmol/l). Inhibition of binding3H-PGD2the real connection is th invention is measured, adding3H-PGD2(2.5 nmol/l) and the compound of the present invention in different concentrations. For reactions using the buffers listed below.

Buffer for incubation:

HEPES-NaOH (25 mmol/l, pH 7.4)

Add (1 mmol/l)

MgCl2(5 mmol/l)

MnCl2(10 mmol/l)

Buffer for washing:

Tris-HCl (10 mmol/l, pH 7.5)

NaCl (0.1 mol/l)

Bovine serum albumin (0.01 per cent)

The dissociation constant (Ki) (µmol/l) of each compound is determined using the following equation:

Ki=IC50/(1+([L*]/Kd))

[L*] is the concentration of radioactive ligand. The results are shown in table 6.

Table 6
# exampleKi (µmol/l) DP
1 (3)0,0018
1 (4)0,0043

As can be seen from the above results, it appears that the compound of the present invention strongly inhibits the binding of the DP receptor.

(ii) Analysis on the antagonistic activity to DP using cells expertsyou prostanoid DP receptors

Cells SNO, accressories prostanoid DP receptor, get under way Nishigaki et al. (FEBS lett., 364, 339-341 (1995)), inoculant on 24-well microplate in an amount of 105cells per well, and then cultured for 2 su is OK and is used for the analysis. Each well was washed with 500 μl of MEM (minimum support environment) and 450 μl environment for analysis (MEM containing 1 mmol/l IBMX and 0.1 or 1% BSA) followed by incubation at 37°C for 10 minutes. Then add environment for analysis (50 μl)containing one PGD2or PGD2with the test connection, and start the reaction and after the reaction at 37°C for 10 minutes, the reaction mixture was added 500 μl of chilled on ice trichloroacetic acid (TCA) (10%, wt./about.) to terminate the reaction. The reaction solution was immediately frozen (-80° (C) and melted, and the cells clean off using a scraper and then centrifuged at 13,000 rpm for 3 minutes. The concentration of camp is measured using the test kit of camp using the obtained supernatant. In other words, the buffer set for the analysis of [125I]-cAMP added to 125 μl of the supernatant, receiving a total number of 500 μl, and the resulting mixture was mixed with 1 ml of 0.5 mol/l solution of tri-n-octylamine in chloroform. Trichloroacetic acid (TCA) is extracted in a chloroform layer is removed, the amount of camp in the sample is determined with the use of the water layer as a sample, according to the method described in the test kit [125I]-cAMP.

Also, as for antagonistic activity (IC50) test connection, then the value of the IC50chislet as the degree of inhibition on the basis of the reaction at 100 nm, which is the concentration, showing a submaximal production of camp one PGD2.

Table 7
# exampleNo. of example DP-Antagonistic activity IC50(µm)
1(3)0,12

As can be seen from the above results, it appears that the compound of the present invention has an antagonistic activity against the DP receptor.

Toxicity

The toxicity of the compounds of the present invention represented by the formula (I), very low, so that confirms that the connection is secure enough for use as pharmaceuticals.

Industrial applicability

Application for pharmaceutical

Since the compound of the present invention represented by the formula (I), is associated with the DP receptor and is an antagonist, it is assumed that the compound is useful for preventing and/or treating diseases, for example, allergic diseases such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergies, etc.; system mastocytosis; disorders due to systemic activation of mastocytes; anaphylactic shock; bronchostenosis; urticaria; eczema; al is ergicheskoe bronchopulmonary aspergillosis; inflammation of the paranasal sinus; nasal polyps; hypersensitive of angita; eosinophilia; contact dermatitis, diseases accompanied by itch, such as atopic dermatitis, urticaria, allergic conjunctivitis, allergic rhinitis, contact dermatitis, and the like; secondary diseases caused by behavior (scratches, bruises, and the like), such as cataract, retinal detachment, inflammation, infection, sleep disorder, and the like; inflammation; chronic obstructive pulmonary disease, ischemic reperfusion disorders; cardiovascular disorders; pleurisy, acute rheumatoid arthritis; ulcerative colitis; and so on in Addition, it is believed that the compound has an effect on sleep and platelet aggregation and is useful in the case of related diseases.

Among the compounds of the present invention represented by the formula (I)compound with a weak binding activity with a connection other than the DP receptor, could be used as pharmaceutical agents with less side effects because of the absence of other activity.

The compound of the present invention represented by the formula (I), its non-toxic salt or cyclodextrine connection inclusions are usually administered systemically or topically and orally or parenterally.

Dosage set the Ute depending on age, body weight, symptom, therapeutic effect, the route of administration, duration of treatment, etc. As a rule, adult administered orally from 1 μg to 100 mg one to several times per day or parenteral from 0.1 μg to 10 mg, preferably by intravenous injection) one or several times a day, or continuously injected into a vein 1-24 hours.

Because changes in the doses depend on various circumstances described above, there are cases when you can use a dose of less than or greater than the above interval.

Compounds of the present invention can be introduced in the form of solid compositions, liquid compositions or other compositions for oral administration, injections, liniments, suppositories etc. for parenteral administration.

Solid compositions for oral administration include compressed tablets, pills, capsules, dispersible powders, granules, etc.

Capsules include hard capsules and soft capsules.

In such solid compositions one or more active compounds are mixed with at least one inert diluent such as lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone or metasilicates magnesium.

The composition may also contain other substances other than inert diluents, for example, the R, lubricants such as magnesium stearate, substances that contribute to litter, such as calcipala cellulose, and substances that contribute to the dissolution, such as glutamic acid, aspartic acid, according to conventional methods. On tablets or pills, if necessary, can be applied film of the gastro - or intersolubility substances, such as sugar, gelatin, hydroxypropylcellulose or phthalate of hydroxypropylcellulose, or cause two or more films. In addition, also included capsules of absorbable material such as gelatin.

Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, syrups and elixirs. In such compositions, one or more active compounds are dissolved, suspended or emuleret in commonly used inert diluent (for example, purified water, ethanol). In addition, such liquid compositions may also contain wetting agents or suspendresume substances, emulsifiers, sweeteners, corrigentov, flavorings and preservatives.

Other compositions for oral administration include sprays containing one or more active compounds obtained by known methods. Composition sprays can contain stabilizers, such as sodium hydrosulphate, stabilizers attached to the I isotonicity, isotonic solutions, such as solutions of sodium chloride, sodium citrate or citric acid, other than inert diluents. The method of producing sprays described in U.S. patent 2868691 and 3095355.

Injections for parenteral administration include sterile aqueous or nonaqueous solutions, suspensions and emulsions. Aqueous solutions or suspensions include, for example, distilled water for injection and physiological saline. Non-aqueous solutions or suspensions include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, alcohol such as ethanol, Polysorbate 80 (registered trademark), etc.

Such compositions may also contain additional components, such as preservatives, wetting agents, emulsifiers, dispersing agents, stabilizers, excipients, such as substances that promote dissolution (e.g., glutamic acid, aspartic acid). They can be sterilized by filtering through a filter that traps the bacteria, or by irradiation, or by the introduction of sterilizing agents. They can also be obtained in the form of sterile solid compositions which can be dissolved in sterile water or other sterile diluent for injection immediately before use.

Other compositions for oral administration include liquids for Nar is the author of the application, endemic liniments, ointments, suppositories for rectal administration and pessaries for intravaginal injection containing one or more active compounds, which can be obtained by known methods.

The best way of carrying out the invention

Following reference examples and examples illustrate the present invention but do not limit the present invention.

In the following chemical formulas Tf represents triftormetilfosfinov, Vos is tertbutoxycarbonyl group, TMS is trimethylsilyl group, and Bn represents a benzyl group.

The solvents given in parentheses indicate the solvents for the manifestation or elution, and the ratio of solvents used for chromatographic separation or TLC, is volume.

The solvents given in parentheses in NMR spectra show solvents for the dimension.

Reference example 1

2-Methyl-4-triftormetilfosfinov

A solution of 2-methyl-4-hydroxyindole (10 g) in methylene chloride (100 ml) stirred at 0°C. To the solution add lutidine (10,28 ml) and triftormetilfullerenov anhydride (13,72 ml) and the solution incubated at the same temperature for 1 hour. To the mixture are added water and then extracted with ethyl acetate. The aqueous layer is xtraceroute with ethyl acetate. The combined organic layers are successively washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, obtaining mentioned in the title compound having the following physical data. The connection used in the next reaction without further purification.

TLC: Rf of 0.57 (hexane:ethyl acetate = 7:3).

Reference example 2

1-tert-Butoxycarbonyl-2-methyl-4-triftormetilfosfinov

To a solution of 2-methyl-4-triftormetilfosfinov (1 g, obtained in reference example 1) and di-tert-BUTYLCARBAMATE (1 ml) in acetonitrile (12 ml) add dimethylaminopyridine (catalytic amount) and the mixture is stirred at room temperature overnight. To the reaction mixture are added water and ethyl acetate and then the mixture is separated. The organic layer is successively washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, getting named the title compound (1,38 g)having the following physical data.

TLC: Rf of 0.50 (hexane:ethyl acetate = 1:1).

Reference example 3

1-tert-Butoxycarbonyl-2-methyl-4-(2-trimethylsilylethynyl)indole

To a solution of 1-tert-butoxycarbonyl-2-methyl-4-t is evermetamorphosing (17.9 g, obtained in reference example 2), dichlorobis(triphenylphosphine)palladium (1.6 g), copper iodide (0.88 g) and tetrabutylammonium iodide (3.4 g) in N,N-dimethylformamide (180 ml) add trimethylsilylacetamide (11 ml)and the mixture stirred at 65°C for 2 hours. To the mixture of 0.5 N hydrochloric acid and ethyl acetate, and then the insoluble matter is removed by filtration through celite (trademark). The organic layer is successively washed with water (twice) and saturated aqueous sodium chloride, dried and concentrated under reduced pressure. The residue is purified column chromatographie on silica gel (hexane:ethyl acetate = 10:1), getting named the title compound (15.0 g)having the following physical data.

NMR (CDCl3): δ 8,09-with 8.05 (d, J=8.5 Hz, 1H), 7,32-7,29 (m, 1H), 7,17-was 7.08 (m, 1H), of 6.49 (s, 1H), 2,61 (s, 3H), 0,29 (s, N).

Reference example 4

1-tert-Butoxycarbonyl-2-methylindole-4-acetic acid

A solution of cyclohexane (16.1 ml) in tetrahydrofuran (160 ml) cooled to -10°Since, then, to the mixture is added dropwise balancerationality complex (1m, 80 ml) and the mixture was stirred at 0°C for 1 hour. To the solution was added dropwise a solution of 1-tert-butoxycarbonyl-2-methyl-4-(2-trimethylsilylethynyl)indole (13,1 g, obtained in reference example 3) in tetrahydrofuran (60 ml) and the mixture stirred for 1 h the sa at room temperature. To the reaction solution was sequentially added dropwise 3 N aqueous sodium hydroxide solution (40 ml) and 30% hydrogen peroxide (in water, 45 ml) and the mixture is stirred for 12 hours. The reaction mixture is extracted with water and diethyl ether. The aqueous layer was acidified with hydrochloric acid and then extracted with ethyl acetate. The extract is successively washed with water and saturated aqueous sodium chloride, dried and concentrated under reduced pressure, getting named the title compound (10.4 g, crude).

Reference example 5

2-Methylindole-4-acetic acid

To a mixture of 1-tert-butoxycarbonyl-2-methylindole-4-acetic acid (96,3 g) in methanol (200 ml) - water (100 ml) at room temperature is added dropwise a 5 N aqueous solution of sodium hydroxide (200 ml), the mixture was stirred at 50°C for 3 hours and then stirred at room temperature for 12 hours. The reaction mixture is extracted with a mixture of hexane-ether. The aqueous layer was acidified with hydrochloric acid and then extracted with ethyl acetate. The extract is successively washed with water and saturated aqueous sodium chloride, dried and concentrated under reduced pressure, getting named the title compound (53,9 g, crude).

In addition, this intermediate connection is a new connection is observed not described in the literature.

Reference example 6

Allyl ester 2-methylindole-4-acetic acid

To a solution of 2-methylindole-4-acetic acid (53 g) in N,N-dimethylformamide (500 ml) is added dropwise allylbromide (31 ml) and added anhydrous potassium carbonate (59 g). The mixture was stirred at 50°C for 1 hour. After cooling to room temperature the reaction mixture was poured into a mixture of 2 N hydrochloric acid-ethyl acetate and then extracted with ethyl acetate. The extract is successively washed with water and saturated aqueous sodium chloride, dried and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (hexane-ethyl acetate), obtaining mentioned in the title compound (43,5 g)having the following physical data.

TLC: Rf of 0.50 (hexane:ethyl acetate = 1:2).

NMR (CDCl3): δ 7,92 (USS, 1H), 7,19 (d, J=7,0 Hz, 1H), 7,06 (t, J=1H), of 6.96 (DD, J=7,0, 1.2 Hz, 1H), 6,27 (m, 1H), 5,90 (DDT, J=17.2 in, 10,4, a 5.4 Hz, 1H), 5.25-inch (d, J=and 17.2 Hz, 1H), 5,18 (d, J=10.4 Hz, 1H), 4,59 (m, 2H), 3,88 (s, 2H), 2,43 (s, 3H).

Reference example 7

4-(2-Propylacetate)benzoic acid

To a solution of 4-hydroxybenzoic acid (3.04 from g) and anhydrous potassium carbonate (5,52 g) in N,N-dimethylformamide (20 ml) is added 2-propylacetophenone (2,94 g), the mixture is stirred at room temperature during the night is then stirred at 80° C for 8 hours. To the reaction solution was added water and the mixture is then extracted with ethyl acetate. The organic layer is successively washed with water and saturated aqueous sodium chloride, dried and concentrated under reduced pressure, getting named the title compound (total of 5.21 g, crude).

TLC: Rf of 0.47 (hexane:ethyl acetate = 2:1).

Reference example 8

Allyl ester 1-(4-(2-propylacetate)benzoyl-2-methylindole-4-acetic acid

To a solution of 4-(2-propylacetate)benzoic acid (448 mg, obtained in reference example 7) in toluene (5 ml) is added N,N-dimethylformamide (catalytic amount) and oxacillin (350 μl), the mixture is stirred for 30 minutes at room temperature and then concentrated. A solution of the residue in methylene chloride (2 ml) was added to a solution of allyl ester 2-methylindole-4-acetic acid (230 mg) obtained in reference example 6), sodium hydroxide (200 mg) and tetrabutylammonium chloride (15 mg) in methylene chloride (8 ml)and the mixture stirred for 30 minutes at room temperature. To the reaction solution was added 1 N hydrochloric acid and ethyl acetate. The organic layer is successively washed with water and saturated aqueous sodium chloride, dried and concentrated under reduced pressure. The residue is purified column chromatograph is she on silica gel (n-hexane-ethyl acetate), getting named the title compound (276 mg)having the following physical data.

TLC: Rf to 0.39 (hexane:ethyl acetate = 2:1).

Example 1

1-(4-(2-Propylacetate)benzoyl-2-methylindole-4-acetic acid

To a solution of allyl ester 1-(4-(2-propylacetate) benzoyl-2-methylindole-4-acetic acid (276 mg, obtained in reference example 8) and research (275 μl) in tetrahydrofuran (3 ml) is added tetrakis(triphenylphosphine)palladium (35 mg) and the mixture is stirred for 2 hours at room temperature. To the reaction solution was added a mixture of 1 N hydrochloric acid-ethyl acetate. The organic layer is successively washed with water and saturated aqueous sodium chloride, dried and concentrated under reduced pressure. The residue is dissolved in a mixture of hexane-ethyl acetate (1/2) and then filtered nerastvorimaya substance. To the filtrate add cyclohexylamine (70 mg) and the mixture is stirred for 30 minutes at room temperature. The reaction solution is filtered. To the resulting crystalline substance, add a mixture of 1 N hydrochloric acid-ethyl acetate. The organic layer is successively washed with water and saturated aqueous sodium chloride, dried and concentrated, obtaining mentioned in the header of the compound of the present invention (204 mg)having the following physical data is.

TLC: Rf of 0.20 (ethyl acetate).

NMR (CDCl3): δ 7,71-of 7.69 (m, 2H),? 7.04 baby mortality-6,92 (m, 5H), 6.48 in (s, 1H), 4,23-4,19 (m, 2H), 3,86 (s, 2H), 3,86-3,81 (m, 2H), 3,51 (t, J=7,0 Hz, 2H), 2,44 (s, 3H), 1,65 (TCEs., J=7,0, 7.5 Hz, 2H), were 0.94 (t, J=7.5 Hz, 3H).

Examples 1(1)-1(75)

Each connection having the following physical data, receive by methods analogous series of reactions of reference examples 1, 2, 3, 4, 5, 6, 7 and 8 and example 1. In the examples 1(8), 1(51), 1(67), 1(68) 1(69) hydroxy - or amino group protected and the protective group is removed before the interaction, corresponding to example 1.

Example 1(1)

1-(4-Butoxybenzoyl)-2-methylindole-4-acetic acid

TLC: Rf and 0.46 (chloroform:methanol = 9:1).

NMR (CDCl3): δ of 7.70 (d, J=9.0 Hz, 2H), 7,08-of 6.90 (m, 5H), of 6.49 (s, 1H), of 4.05 (t, J=6.6 Hz, 2H), a 3.87 (s, 2H), of 2.45 (s, 3H), 1,88-of 1.74 (m, 2H), 1,80-1,40 (ush, 1H), 1.60-to a 1.45 (m, 2H), and 1.00 (t, J=7.5 Hz, 3H).

Example 1(2)

1-(4-Propylacetate)-2-methylindole-4-acetic acid

TLC: Rf value of 0.52 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,74-of 7.69 (m, 2H), 7,12-of 6.90 (m, 5H), of 6.49 (s, 1H), 4,01 (t, J=6.6 Hz, 2H), a 3.87 (s, 2H), of 2.45 (s, 3H), of 1.86 (dt, J=7,5, and 6.6 Hz, 2H), with 1.07 (t, J=7.5 Hz, 3H).

Example 1(3)

1-(4-(2-Phenoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.60 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,72-7,66 (m, 2H), 7,38-of 7.23 (m, 5H), 7,07-6,92 (m, 5H), of 6.49 (s, 1H), 4.26 deaths (t, J=6.9 Hz, 2H), 3,86 (s, 2H), 3,14 (t, J=6.9 Hz, 2H), 2,44 (s, 3H).

P is the iMER 1(4)

1-(4-Pentyloxybenzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.64 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,73-7,66 (m, 2H), 7,07-6,92 (m, 5H), of 6.49 (s, 1H), Android 4.04 (t, J=6.6 Hz, 2H), a 3.87 (s, 2H), 2,44 (s, 3H), 1,86 is 1.23 (m, 6N), of 0.95 (t, J=6.9 Hz, 3H).

Example 1(5)

1-(4-Isobutylacetate)-2-methylindole-4-acetic acid

TLC: Rf of 0.34 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,73-to 7.67 (m, 2H), 7,06-6,91 (m, 5H), 6.48 in (s, 1H), 4,07 (t, J=6.6 Hz, 2H), 3,86 (s, 2H), of 2.45 (s, 3H), of 1.84 (m, 1H), 1,72 (m, 2H), and 0.98 (d, J=6,4 Hz, 6N).

Example 1(6)

1-(4-(2-Ethoxyethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 10:1).

NMR (CDCl3): δ of 7.70 (d, J=8.7 Hz, 2H), 7,08-6,92 (m, 5H), of 6.49 (s, 1H), 4,21 (t, J=4,8 Hz, 2H), a 3.87-3,81 (m, 4H), 3,62 (sq, J=7.5 Hz, 2H), of 2.45 (s, 3H), of 1.26 (t, J=7.5 Hz, 3H).

Example 1(7)

1-(4-Benzyloxybenzyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.55 (chloroform:methanol = 10:1).

NMR (CDCl3): δ the 7.65 7,33 (d, J=8,8 Hz, 2H), 7,45 was 7.36 (m, 5H), 7,05-of 6.90 (m, 5H), 6.48 in (s, 1H), 5,14 (s, 2H), 3,85 (s, 2H), 2,43 (d, J=1.0 Hz, 3H).

Example 1(8)

1-(4-(2-(4-Hydroxyphenyl)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.30 (chloroform:methanol = 10:1).

NMR (CDCl3): δ to 7.68 (d, J=8.6 Hz, 2H), 7,14 (d, J=8,2 Hz, 2H), 7,08-6,89 (m, 5H), is 6.78 (d, J=8.0 Hz, 2H), 6.48 in (s, 1H), 4,20 (t, J=7,0 Hz, 2 is), 3,85 (s, 2H), 3,05 (t, J=7,0 Hz, 2H), 2,43 (s, 3H).

Example 1(9)

1-(4-Butoxybenzoyl)indole-4-acetic acid

TLC: Rf 0.25 in (hexane:ethyl acetate = 1:1).

NMR (CDCl3): δ compared to 8.26 (d, J=8,2 Hz, 1H), 7,72-to 7.68 (m, 2H), 7,38-7,16 (m, 3H), 7,00-of 6.96 (m, 2H), 6,65 (d, J=3.6 Hz, 1H), of 4.05 (t, J=6.4 Hz, 2H), a 3.87 (s, 2H), equal to 1.82 (m, 2H), of 1.52 (m, 2H), and 1.00 (t, J=7.2 Hz, 3H).

Example 1(10)

1-(4-(3-Phenylpropyl)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf and 0.61 (chloroform:methanol = 10:1).

NMR (CDCl3): δ to 7.64 (d, J=8.0 Hz, 2H), 7,38-7,16 (m, 7H), 7,08-6,93 (m, 3H), of 6.49 (s, 1H), 3,85 (s, 2H), 2,82-2,60 (m, 4H), 2,42 (s, 3H), of 2.05 (m, 2H).

Example 1(11)

1-(4-(2-(4-Methoxyphenyl)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,72-the 7.65 (m, 2H), 7.23 percent-7,17 (m, 2H), 7,06-6,84 (m, 7H), 6,47 (s, 1H), 4,21 (t, J=7,0 Hz, 2H), 3,85 (s, 2H), 3,80 (s, 3H), is 3.08 (t, J=7,0 Hz, 2H), 2,43 (s, 3H).

Example 1(12)

1-(4-(2-(2-Pyridyl)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.40 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 8,59 (d, J=5,2 Hz, 1H), 7.68 per-to 6.88 (m, 10H), of 6.52 (s, 1H), 4,39 (t, J=6.6 Hz, 2H), 3,86 (s, 2H), and 3.31 (t, J=6.6 Hz, 2H), 2,43 (s, 3H).

Example 1(13)

1-(4-(2-Cyclopropylmethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.37 (ethyl acetate).

NMR (CDCl3): δ 7,73-of 7.69 (m, 2H), 7,08-6,94 (m, 5H) of 6.49 (s, 1H), 4,12 (t, J=6.5 Hz, 2H), a 3.87 (s, 2H), of 2.45 (s, 3H), 1,72 (sq, J=6,5 Hz, 2H), 0,96-0,80 (m, 1H), 0.56 to to 0.47 (m, 2H), of 0.18 to 0.13 (m, 2H).

Example 1(14)

1-(4-(2-Isopropoxyphenoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.35 (ethyl acetate).

NMR (CDCl3): δ 7,72-to 7.67 (m, 2H),? 7.04 baby mortality-of 6.90 (m, 5H), 6.48 in (s, 1H), 4,22-4,17 (m, 2H), 3,86 (s, 2H), 3,84-of 3.80 (m, 2H), 3,78-3,62 (m, 1H), 2,44 (s, 3H), 1,21 (d, J=6.0 Hz, 6N).

Example 1(15)

1-(4-(4-Methoxybenzyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.33 (ethyl acetate).

NMR (CDCl3): δ 7,74-of 7.69 (m, 2H), 7,40-7,35 (m, 2H), 7,08-6,92 (m, 7H), of 6.49 (s, 1H), 5,07 (s, 2H), a 3.87 (s, 2H), 3,83 (s, 3H), of 2.45 (s, 3H).

Example 1(16)

1-(4-(2-Utiltiies)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,71 (d, J=9.0 Hz, 2H), 7,05-6,93 (m, 5H), 6.48 in (s, 1H), 4,22 (t, J=6,8 Hz, 2H), 3,86 (s, 2H), 2.95 points (t, J=6,8 Hz, 2H), 2,67 (sq, J=7,4 Hz, 2H), 2,44 (s, 3H), of 1.31 (t, J=7.4 Hz, 3H).

Example 1(17)

1-(4-(3,3-Dimethylbutane)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.45 (chloroform:methanol = 10:1).

NMR (CDCl3): δ to 7.68 (d, J=8,8 Hz, 2H), 7,08-6,86 (m, 5H), 6,47 (s, 1H), 4.09 to (t, J=7.2 Hz, 2H), 3,83 (s, 2H), 2,43 (s, 3H), of 1.76 (t, J=7.2 Hz, 2H), 1.00 m (s, N).

Example 1(18)

1-(4-Benzyloxybenzyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methane is l = 10:1).

NMR (CDCl3): δ 7,72 (d, J=8,4 Hz, 2H), of 7.48 (d, J=8,4 Hz, 2H), 7,39-7,31 (m, 4H), 7,06-of 6.96 (m, 4H), of 6.50 (s, 1H), of 4.66 (s, 2H), 4,63 (s, 2H), 3,86 (s, 2H), 2,42 (s, 3H).

Example 1(19)

1-(4-(3-Ethoxypropane)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf is 0.22 (ethyl acetate:hexane = 3:1).

NMR (CDCl3): δ of 7.70 (d, J=9.0 Hz, 2H), 7,10-6,86 (m, 5H), of 6.49 (s, 1H), 4,16 (t, J=6.4 Hz, 2H), 3,86 (s, 2H), 3,62 (t, J=6.4 Hz, 2H), 3,51 (sq, J=6,8 Hz, 2H), of 2.45 (s, 3H), of 2.09 (m, 2H), 1,21 (t, J=6,8 Hz, 3H).

Example 1(20)

1-(4-(4-Methylpentylamino)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.43 (ethyl acetate:hexane = 3:1).

NMR (CDCl3): δ of 7.70 (d, J=8.6 Hz, 2H), 7,07-to 6.88 (m, 5H), 6.48 in (s, 1H), a 4.03 (t, J=6,8 Hz, 2H), 3,86 (s, 2H), of 2.45 (s, 3H), 1,92-of 1.73 (m, 2H), 1,73-of 1.52 (m, 1H), 1,43-1,11 (m, 2H), were 0.94 (d, J=6,8 Hz, 6N).

Example 1(21)

1-(4-(2-(3-Forfinal)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.45 (chloroform:methanol = 10:1).

NMR (CDCl3): δ of 7.69 (d, J=8,8 Hz, 2H), 7,35-7,20 (m, 2H), 7,09-6,85 (m, 7H), 6,47 (s, 1H), 4,25 (t, J=6.6 Hz, 2H), 3,84 (s, 2H), 3,12 (t, J=6.6 Hz, 2H), 2,42 (s, 3H).

Example 1 (22)

1-(4-(2-(3-Methoxyphenyl)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.35 (ethyl acetate).

NMR (CDCl3): δ 7,72-to 7.68 (m, 2H), 7,44 and 7.36 (m, 1H), 7,28-7,22 (m, 2H), 7,06-to 6.88 (m, 6N), 6.48 in (s, 1H), 4,24 (t, J=7,0 Hz, 2H), 3,86 (s, 5H), 3.15 in (t, J=7,0 Hz, 2H), 2,44 (s, 3H).

Example 1(23)

1-(4-(2-(2-Thienyl)ethoxy)Ben is oil)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 10:1).

NMR (CDCl3): δ of 7.69 (d, J=8.6 Hz, 2H), 7,18 (m, 1H), 7,02-of 6.90 (m, 7H), 6,47 (s, 1H), 4.26 deaths (t, J=6,8 Hz, 2H), 3,84 (s, 2H), 3,35 (t, J=6,8 Hz, 2H), 2,43 (s, 3H).

Example 1(24)

1-(4-(2-(2-Were)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 9:1).

NMR (CDCl3): δ of 7.69 (d, J=9.0 Hz, 2H), 7.23 percent-6,91 (m, N), 6.48 in (s, 1H), 4,23 (t, J=7.2 Hz, 2H), 3,86 (s, 2H), and 3.16 (t, J=7.2 Hz, 2H), 2,44 (s, 3H), 2,39 (s, 3H).

Example 1(25)

1-(4-(2-(3-Were)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 9:1).

NMR (CDCl3): δ of 7.69 (d, J=8,8 Hz, 2H), 7,19-6,92 (m, N), 6.48 in (s, 1H), 4,24 (t, J=7.2 Hz, 2H), 3,86 (s, 2H), 3,10 (t, J=7.2 Hz, 2H), 2,44 (s, 3H), of 2.36 (s, 3H).

Example 1(26)

1-(4-(2-(4-Were)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 9:1).

NMR (CDCl3): δ of 7.69 (d, J=8,8 Hz, 2H), 7.18 in-6,92 (m, N), of 6.49 (s, 1H), 4,23 (t, J=6.6 Hz, 2H), a 3.87 (s, 2H), 3,10 (t, J=6.6 Hz, 2H), 2,44 (s, 3H), of 2.34 (s, 3H).

Example 1(27)

1-(4-(2-Cyclohexylmethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 9:1)

NMR (CDCl3): δ of 7.70 (d, J=8,8 Hz, 2H), 7,06-6,91 (m, 5H), 6.48 in (s, 1H), 4,08 (t, J=6,8 Hz, 2H), 3,86 (s, 2H), 2,44 (s, 3H), 1,81-of 0.95 (m, 13H).

Example 1(28)

1-(4-(2-(4-Dimethylaminophenyl)ATOC and)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 9:1).

NMR (CDCl3): δ of 7.69 (d, J=8.6 Hz, 2H), 7,17 (d, J=8.6 Hz, 2H), 7,06-6,92 (m, 5H), 6.73 x (d, J=8.6 Hz, 2H), 6.48 in (s, 1H), 4,20 (t, J=7.4 Hz, 2H), 3,86 (s, 2H), 3.04 from (t, J=7.4 Hz, 2H), 2,93 (C, 6N), 2,44 (s, 3H).

Example 1 (29)

1-(4-(2-(3-Thienyl)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 10:1).

NMR (CDCl3): δ of 7.69 (d, J=9.0 Hz, 2H), 7,30 (DD, J=4,0, 3.0 Hz, 1H), 7,11 (m, 1H), 7,06-7,01 (m, 2H), of 6.96-6,92 (m, 4H), 6.48 in (s, 1H), 4,25 (t, J=6.6 Hz, 2H), 3,85 (s, 2H), 3,17 (t, J=6.6 Hz, 2H), 2,43 (s, 3H)).

Example 1(30)

1-(4-(2-(4-Chlorophenyl)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.45 (chloroform:methanol = 10:1).

NMR (CDCl3): δ of 7.69 (d, J=8,4 Hz, 2H), 7,33-7,20 (m, 5H),? 7.04 baby mortality-PC 6.82 (m, 4H), of 6.49 (s, 1H), 4,23 (t, J=6.6 Hz, 2H), 3,86 (s, 2H), 3,11 (t, J=6.6 Hz, 2H), 2,44 (s, 3H).

Example 1(31)

1-(4-(2-(2-Forfinal)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.45 (chloroform:methanol = 10:1).

NMR (CDCl3): δ to 7.68 (d, J=8,8 Hz, 2H), 7,40-was 7.08 (m, 4H), 7,05-of 6.90 (m, 5H), 6,47 (s, 1H), 4.26 deaths (t, J=6,8 Hz, 2H), 3,84 (s, 2H), 3,18 (t, J=6,8 Hz, 2H), 2,43 (s, 3H).

Example 1(32)

1-(4-(2-(4-Forfinal)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.45 (chloroform:methanol = 10:1).

NMR (CDCl3): δ of 7.70 (d, J=9.0 Hz, 2H), 7,30-7,21 (m, 2H), 7,06-of 6.90 (m, 7H), 6.48 in (s, 1H), 4,23 (t, J=6.6 Hz, 2H),3,85 (s, 2H), 3,11 (t, J=6.6 Hz, 2H), 2,43 (s, 3H).

Example 1(33)

1-(4-(2-(2-Naphthyl)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.47 (chloroform:methanol = 9:1)

NMR (CDCl3): δ 7,86-of 6.90 (m, 14N), of 6.49 (s, 1H), 4,35 (t, J=7.2 Hz, 2H), 3,86 (s, 2H), and 3.31 (t, J=7.2 Hz, 2H), 2,43 (s, 3H).

Example 1(34)

1-(4-(2-(4-Cyanophenyl)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.40 (chloroform:methanol = 9:1).

NMR (CDCl3): δ of 7.70 (d, J=8,8 Hz, 2H), 7,63 (d, J=8,2 Hz, 2H), 7,42 (d, J=8,2 Hz, 2H), 7.03 is-of 6.90 (m, 5H), 6.48 in (s, 1H), 4,28 (t, J=6.4 Hz, 2H), 3,85 (s, 2H), 3,20 (t, J=6.4 Hz, 2H), 2,43 (s, 3H).

Example 1(35)

1-(4-(2-tert-Butoxyethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 9:1).

NMR (CDCl3): δ of 7.69 (d, J=8,8 Hz, 2H),? 7.04 baby mortality-6,94 (m, 5H), 6.48 in (s, 1H), 4,17 (t, J=5,2 Hz, 2H), 3,86 (s, 2H), 3,76 (t, J=5,2 Hz, 2H), 2,44 (s, 3H), 1,25 (s, N).

Example 1(36)

1-(4-(2-(2-Methoxyphenyl)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.45 (chloroform:methanol = 10:1).

NMR (CDCl3): δ of 7.69 (d, J=8,8 Hz, 2H), 7,22 (d, J=7.2 Hz, 2H),? 7.04 baby mortality-6,93 (m, 7H), 6,47 (s, 1H), 4,24 (t, J=7.4 Hz, 2H), 3,85 (s, 2H), 3,85 (s, 3H), 3,14 (t, J=7.4 Hz, 2H), 2,43 (s, 3H).

Example 1(37)

1-(3-Propoxyphenyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.47 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,40-6,99 (m, 7H), 6.48 in (1H), of 3.94 (t, J=6.6 Hz, 2H), 3,85 (s, 2H), 2,41 (s, 3H), of 1.81 (m, 2H), of 1.03 (t, J=7.4 Hz, 3H).

Example 1(38)

1-(4-(2-(3-Pyridyl)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.30 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 8,61 (s, 1H), 8,54 (DD, J=3.0 Hz, 1H), 7,71-to 7.67 (m, 3H), 7,34-7,31 (m, 1H), 7,05-6,89 (m, 5H), of 6.52 (s, 1H), 4,25 (t, J=6.4 Hz, 2H), a 3.87 (s, 2H), 3,14 (t, J=6.4 Hz, 2H), 2,42 (s, 3H).

Example 1(39)

1-(4-(2-(4-Pyridyl)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.30 (chloroform:methanol = 9:1).

NMR (CDCl3): δ to 8.57 (d, J=6.2 Hz, 2H), of 7.70 (d, J=8,8 Hz, 2H), 7,29 (m, 2H),? 7.04 baby mortality-6,89 (m, 5H), of 6.52 (s, 1H), 4,28 (t, J=6.4 Hz, 2H), 3,86 (s, 2H), 3.15 in (t, J=6.4 Hz, 2H), 2,42 (s, 3H).

Example 1(40)

1-(4-(2-(1-Naphthyl)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.47 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 8,13-8,08 (m, 1H), 7,92-7,87 (m, 1H), 7,83 to 7.75 (m, 1H), 7,69 (d, J=8.7 Hz, 2H), to 7.61-7,47 (m, 2H), of 7.48-7,41 (m, 2H), 7,07-of 6.90 (m, 5H), 6.48 in (s, 1H), 4,39 (t, J=7.5 Hz, 2H), a 3.87 (s, 2H), 3,63 (t, J=7.5 Hz, 2H), 2,43 (s, 3H).

Example 1(41)

1-(4-(3-Ethoxypropane)-3-methoxybenzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.55 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,34 (d, J=1.8 Hz, 1H), 7,27 (DD, J=8,4, 1.8 Hz, 1H), 7,10-6,93 (m, 3H), 6.89 in (d, J=8,4 Hz, 1H), 6.48 in (s, 1H), 4,19 (t, J=6.4 Hz, 2H), 3,85 (s, 3H), 3,83 (s, 2H), 3,62 (t, J=5.8 Hz, 2H), 3,50 (square, J=6,8 Hz, 2H), 2,44 (s, 3H), 2.13 in (m, 2H), 1,19 (t, J=6.8 Hz, 3H).

PR is measures 1(42)

1-(4-Hexyloxybenzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.44 (ethyl acetate).

NMR (CDCl3): δ 7,72-of 7.69 (m, 2H), 7,06-6,93 (m, 5H), of 6.49 (s, 1H), Android 4.04 (t, J=6.5 Hz, 2H), a 3.87 (s, 2H), of 2.45 (s, 3H), 1.9 to 1.8 m (m, 2H), a 3.87 (s, 2H), of 2.45 (s, 3H), 1.9 to 1.8 m (m, 2H), 1,6-1,4 (m, 2H), 1,4-1,3 (m, 4H), 1,0-0,9 (m, 3H).

Example 1(43)

1-(4-Butoxybenzoyl)-3-(4-methoxybenzyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.43 (ethyl acetate).

NMR (CDCl3): δ 7,75-7,72 (m, 2H), 7,11-6,92 (m, 7H), 6,82-6,79 (m, 2H), 4,15 (s, 2H), of 4.05 (t, J=6.5 Hz, 2H), 3,76 (s, 3H), and 3.72 (s, 2H), 2,35 (s, 3H), of 1.9 and 1.7 (m, 2H), 1,6-1,4 (m, 2H), and 1.00 (t, J=7,0 Hz, 3H).

Example 1(44)

1-(4-(2-(2-Methoxyethoxy)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.20 (ethyl acetate).

NMR (CDCl3): δ 7,71-to 7.68 (m, 2H), 7,06-6,91 (m, 5H), 6.48 in (s, 1H), 4,24-is 4.21 (m, 2H), 3,92-to 3.89 (m, 2H), 3,85 (s, 2H), 3,76-to 3.73 (m, 2H), 3,61-to 3.58 (m, 2H), 3,40 (s, 3H), of 2.44 (s, 3H).

Example 1(45)

1-(4-(3-Methoxyphenoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf 0,12 (ethyl acetate).

NMR (CDCl3): δ 7,72-of 7.69 (m, 2H), 7,08-6,94 (m, 5H), 6.48 in (s, 1H), 4,15 (t, J=6.5 Hz, 2H), 3,86 (s, 2H), to 3.58 (t, J=6.0 Hz, 2H), 3,37 (s, 3H), of 2.44 (s, 3H), 2,13-2,05 (m, 2H).

Example 1(46)

1-(4-Methoxybenzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.41 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 7,72 (d, J=9.0 Hz, 2H), 7,08-6,92 (m,5H), of 6.50 (s, 1H), 3,90 (s, 3H), 3,88 (s, 2H), of 2.45 (s, 3H).

Example 1(47)

1-(4-(5-Methylfuran-2-yl)methoxybenzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.40 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,72 (d, J=8.6 Hz, 2H), 7,07-to 6.95 (m, 5H), of 6.49 (s, 1H), 6,36 (d, J=3.2 Hz, 1H), of 5.99 (d, J=3.2 Hz, 1H), 5,02 (s, 2H), 3,86 (s, 2H), 2,44 (s, 3H), 2,32 (s, 3H).

Example 1(48)

1-(4-(2-Methoxyethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.44 (chloroform:methanol = 10:1).

NMR (CDCl3): δ of 7.70 (d, J=8,8 Hz, 2H), 7.03 is-6,93 (m, 5H), 6.48 in (s, 1H), 4,21 (t, J=5.0 Hz, 2H), 3,85 (s, 2H), 3,79 (t, J=5.0 Hz, 2H), 3,47 (s, 3H), of 2.44 (s, 3H).

Example 1(49)

1-(4-(2-(3-Nitrophenyl)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.37 (chloroform:methanol = 9:1).

NMR (CDCl3): δ by 8.22-8,16 (m, 1H), 8,16-8,10 (m, 1H), 7,74 to 7.62 (m, 3H), 7,52 (t, J=8,1 Hz, 1H), 7,08-of 6.90 (m, 5H), of 6.49 (s, 1H), or 4.31 (t, J=6.3 Hz, 2H), a 3.87 (s, 2H), 3,26 (t, J=6.3 Hz, 2H), 2,43 (s, 3H).

Example 1(50)

1-(4-(3-Phenylpropoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.41 (chloroform:methanol = 9:1).

NMR (CDCl3): δ of 7.70 (d, J=9,3 Hz, 2H), 7,34-7,16 (m, 5H), 7,08-to 6.88 (m, 5H), of 6.50 (s, 1H), of 4.05 (t, J=6.3 Hz, 2H), 3,88 (s, 2H), 2,84 (t, J=6.3 Hz, 2H), of 2.45 (s, 3H), 2,20-2,10 (m, 2H).

Example 1(51)

(±)-1-(4-(3-Phenyloxy-2-hydroxypropoxy)benzoyl)-2-methylindole-4-acetic acid

<> TLC: Rf of 0.33 (chloroform:methanol = 10:1).

NMR (CDCl3): δ of 7.69 (d, J=8,8 Hz, 2H), 7,33-of 7.23 (m, 2H), 7,06-of 6.90 (m, 8H), 6,47 (s, 1H), 4,43 (m, 1H), 4,24-to 4.15 (m, 4H), 3,83 (s, 2H), 2,42 (s, 3H).

Example 1(52)

1-(4-Cyclohexyloxycarbonyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.25 (ethyl acetate).

NMR (CDCl3): δ 7,71-to 7.68 (m, 2H), 7,08-6,91 (m, 5H), of 6.49 (s, 1H), 4,42-4,32 (m, 1H), 3,86 (s, 2H), of 2.45(s, 3H), 2,08 is 1.96 (m, 2H), 1,88-of 1.78 (m, 2H), 1,64-1,32 (m, 6N).

Example 1(53)

1-(4-Ethoxybenzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.21 (ethyl acetate).

NMR (CDCl3): δ 7,72-of 7.69 (m, 2H), 7,08-6,93 (m, 5H), of 6.49 (s, 1H), 4,10 (sq, J=7,0 Hz, 2H), 3,86 (s, 2H), of 2.45 (s, 3H), of 1.46 (t, J=7.0 Hz, 3H).

Example 1(54)

1-(4-(3-Butenyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf and 0.28 (ethyl acetate).

NMR (CDCl3): δ 7,72-of 7.69 (m, 2H), 7,08-6,94 (m, 5H), of 6.49 (s, 1H), 5,98-to 5.85 (m, 1H), 5,23-5,13 (m, 2H), 4,10 (t, J=6.5 Hz, 2H), 3,86 (s, 2H), 2,64-of 2.56 (m, 2H), of 2.45 (s, 3H).

Example 1(55)

1-(4-(2-(2,6-Acid), ethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf 0.26 (ethyl acetate).

NMR (CDCl3): δ 7,71-to 7.68 (m, 2H), 7,20 (t, J=8.5 Hz, 1H), 7,07-6,98 (m, 5H), to 6.57 (d, J=8.5 Hz, 2H), 6.48 in (s, 1H), 4,17-4,11 (m, 2H), a 3.87 (s, 2H), 3,84 (C, 6N), 3,23-3,18 (m, 2H), of 2.45 (s, 3H).

Example 1(56)

1-(4-Butoxybenzoyl)-2,3-dimethylindole-4-acetic acid

TLC: Rf of 0.44 (chlorine the product:methanol = 10:1).

NMR (CDCl3): δ 7,72-the 7.65 (m, 2H), 7,07-of 6.90 (m, 5H), 4,07 (s, 2H), Android 4.04 (t, J=6.4 Hz, 2H), 2,39 (s, 3H), of 2.30 (s, 3H), 1,87-of 1.74 (m, 2H), 1.60-to of 1.41 (m, 2H), 0,99 (t, J=7.4 Hz, 3H).

Example 1(57)

1-(3-Butoxybenzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.48 (chloroform:methanol = 10:1).

NMR (CDCl3): δ of 7.36 (m, 1H), 7.24 to 6,99 (m, 6N), 6,48 (d, J=1.2 Hz, 1H), 3,98 (t, J=6.4 Hz, 2H), 3,85 (s, 2H), 2,41 (d, J=1.2 Hz, 3H), 1,84 is 1.70 (m, 2H), 1,58-to 1.38 (m, 2H), of 0.96 (t, J=7.2 Hz, 3H).

Example 1(58)

1-(3-Pentyloxybenzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.47 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,35 (m, 1H), 7.24 to 6,99 (m, 6N), 6,48 (d, J=1.0 Hz, 1H), 3,97 (t, J=6.4 Hz, 2H), 3,85 (s, 2H), 2,41 (d, J=1.0 Hz, 3H), 1,84-1,72 (m, 2H), 1,50-of 1.32 (m, 4H), to 0.92 (t, J=7.0 Hz, 3H).

Example 1(59)

1-(3-Hexyloxybenzoyl)-2-methylindole-4-acetic acid

TLC: Rf and 0.46 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,35 (m, 1H), 7.24 to 6,98 (m, 6N), 6,48 (d, J=1.0 Hz, 1H), 3,97 (t, J=6.6 Hz, 2H), 3,85 (s, 2H), 2,41 (d, J=1.0 Hz, 3H), 1.85 to 1.69 in (m, 2H), 1,53 of 1.28 (m, 6N), of 0.90 (m, 3H).

Example 1(60)

1-(3-Benzyloxybenzyl)-2-methylindole-4-acetic acid

TLC: Rf and 0.46 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,44-to 7.18 (m, N), 7,10-of 6.99 (m, 3H), 6.48 in (d, J=1.0 Hz, 1H), to 5.08 (s, 2H), 3,85 (s, 2H), 2,36 (d, J=1.0 Hz, 3H).

Example 1(61)

1-(3-Penetrateinto)-2-methylindole-4-acetic acid

TLC: Rf and 0.46 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,39-6,97 (m, N), 6,48 (d, J=1.2 Hz, 1H), 4,20 (t, J=7,0 Hz, 2H), 3,85 (s, 2H), to 3.09 (t, J=7,0 Hz, 2H), 2.40 a (d, J=1.2 Hz, 3H).

Example 1 (62)

1-(3-(3-Phenylpropoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.47 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,40-6,98 (m, N), 6,48 (d, J=1.0 Hz, 1H), 3,98 (t, J=6.2 Hz, 2H), 3,85 (s, 2H), 2,80 (t, J=7.2 Hz, 2H), 2,41 (d, J=1.0 Hz, 3H), 2,17-2,03 (m, 2H).

Example 1(63)

1-(4-(2-(2-Triptoreline)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf and 0.46 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 7,73-the 7.65 (m, 3H), 7,56 was 7.45 (m, 2H), 7,42-7,33 (m, 1H), 7,08-of 6.90 (m, 5H), of 6.49 (s, 1H), 4,27 (t, J=6.6 Hz, 2H), a 3.87 (s, 2H), 3,34 (t, J=6.6 Hz, 2H), 2,44 (s, 3H).

Example 1(64)

1-(4-(2-(2-Triptoreline)ethoxy)benzoyl)-2-methyl-3-methoxymethyl-4-acetic acid

TCX: Rf of 0.56 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 7,74-the 7.65 (m, 3H), EUR 7.57 was 7.45 (m, 2H), 7,42-7,30 (m, 1H), 7,14-7,10 (m, 1H), 7,05-to 6.80 (m, 1H), 6,98-of 6.90 (m, 3H), 4,71 (s, 2H), 4,27 (t, J=6.6 Hz, 2H), 4.09 to (s, 2H), 3,47 (s, 3H), 3,34 (t, J=6,6 Hz, 2H), 2,46 (s, 3H).

Example 1(65)

1-(4-(2-(3-Nitrophenyl)ethoxy)benzoyl)-2-methyl-3-methoxymethyl-4-acetic acid

TLC: Rf of 0.54 (chloroform:methanol = 9:1).

NMR (CDCl3): δ by 8.22-8,18 (m, 1H), 8,16-8,11 (m, 1H), 7,71 (d, J=8.7 Hz, 2H), 7.68 per-of 7.60 (m, 1H), 7,52 (t, J=7.8 Hz, 1H), 7,1-to 7.09 (m, 1H), 7,00 (t, J=8,1 Hz, 1H), 6,97-of 6.90 (m, 3H), 4,70 (s, 2H), 4,32 (t, J=6.3 Hz, 2H), 4.09 to (s, 2H), 3.46 in (s, 3H), 3,26 (t, J=6.3 Hz, 2H), of 2.45 (s, 3H).

Example 1(66)

1-(4-(2-Phenoxyethyl)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.45 (chloroform:methanol = 10:1).

NMR (CDCl3): δ to 7.64 (d, J=8,4 Hz, 2H), was 7.36 (d, J=8,4 Hz, 2H), 7,24 (d, J=8.0 Hz, 2H), 7.03 is-6,85 (m, 6N), 6,47 (s, 1H), 4,20 (t, J=6.6 Hz, 2H), 3,81 (s, 2H), 3.15 in (t, J=6.6 Hz, 2H), 2,39 (s, 3H).

Example 1(67)

(±)-1-(4-(2-Phenyl-2-hydroxyethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.33 (chloroform:methanol = 10:1).

NMR (CDCl3): δ EUR 7.57 (d, J=8,2 Hz, 2H), 7,32 (s, 5H), of 6.99 (m, 1H), 6,93-6,86 (m, 4H), 6,44 (s, 1H), of 5.34 (DD, J=8,0, 3.6 Hz, 1H), 3,97 (DD, J=12,2, 8.0 Hz, 1H), 3,86 (DD, J=12,2, 3.6 Hz, 1H), 3,81 (s, 2H), 2,37 (, 3H).

Example 1(68)

1-(4-(2-(3-AMINOPHENYL)ethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.47 (chloroform:methanol = 9:1).

NMR (CDCl3): δ of 7.70 (d, J=9.0 Hz, 2H), 7,16-of 6.90 (m, 6N), 6,72 is 6.67 (m, 1H), 6,65-6,56 (m, 2H), of 6.49 (s, 1H), 4,23 (t, J=7.2 Hz, 2H), a 3.87 (s, 2H), 3,05 (t, J=7.2 Hz, 2H), of 2.45 (s, 3H).

Example 1(69)

1-(4-(2-(3-AMINOPHENYL)ethoxy)benzoyl)-2-methyl-3-methoxymethyl-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 9:1).

NMR (CDCl3): δ of 7.70 (d, J=9.0 Hz, 2H), 7,16-was 7.08 (m, 2H), 7,01 (t, J=8,4 Hz, 1H), 6,97-of 6.90 (m, 3H), of 6.71 of 6.66 (m, 1H), 6,64-6,56 (m, 2H), 4,70 (s, 2H), 4,23 (t, J=7.2 Hz, 2H), 4.09 to (s, 2H), 3.46 in (s, 3H), 3,05 (t,J=7.2 Hz, 2H), the 2.46 (s, 3H).

Example 1(70)

1-(4-Butoxybenzoyl)-2-ethylindole-4-acetic acid

TLC: Rf of 0.55 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 7,71 (d, J=8.7 Hz, 2H), 7,07-6,86 (m, 5H), 6,53 (s, 1H), of 4.05 (t, J=6.3 Hz, 2H), with 3.89 (s, 2H), 2,87 (sq, J=7.5 Hz, 2H), 1,90-of 1.35 (m, 4H), 1,24 (t, J=7.5 Hz, 3H), of 0.97 (t, J=7.5 Hz, 3H).

Example 1(71)

1-(4-(2-Phenoxyethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.55 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 7,72 (d, J=9.0 Hz, 2H), 7,32 (t, J=7.8 Hz, 2H), 7,08-6,92 (m, 8H), of 6.49 (s, 1H), 4,46-4,34 (m, 4H), a 3.87 (s, 2H), of 2.45 (s, 3H).

Example 1(72)

(±)-1-(4-(2-Methoxy-2-phenylethane)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf value of 0.52 (chloroform:methanol = 10:1).

NMR (CDCl3): δ to 7.59 (d, J=9.0 Hz, 2H), 7,38-7,30 (m, 5H),? 7.04 baby mortality-to 6.80 (m, 5H), 6,44 (s, 1H), 5,44 (DD, J=8,0, 4.0 Hz, 1H), 3,84 (DD, J=10,8, 8.0 Hz, 1H), 3,83 (USS, 2N), the 3.65 (DD, J=10,8, 4.0 Hz, 1H), 3,47 (s, 3H), 2,39 (s, 3H).

Example 1(73)

1-(4-Phenylbenzyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 7,84 for 7.78 (m, 2H), 7,74-7,66 (m, 4H), 7,52-7,38 (m, 3H), 7,10-6,98 (m, 3H), of 6.52 (s, 1H), a 3.87 (s, 2H), 2,46 (s, 3H).

Example 1(74)

1-(4-Phenyldiazonium)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 10:1).

NMR (CDCl3): δ 8,04-of 7.96 (m, 4H), of 7.90-7,86 (m, 2H), 7,60-7,52(m, 3H), 7,10-7,00 (m, 3H), 6,53 (s, 1H), a 3.87 (s, 2H), 2,46 (s, 3H).

Example 1(75)

1-(4-Butoxybenzoyl)-2,5-dimethylindole-4-acetic acid

TCX: Rf of 0.53 (chloroform:methanol = 10:1).

NMR (CDCl3): δ to 7.68 (d, J=9,3 Hz, 2H), 6,93 (d, J=9,3 Hz, 2H), 6,85 (d, J=9.0 Hz, 1H), PC 6.82 (d, J=9.0 Hz, 1H), 6,44 (s, 1H), Android 4.04 (t, J=6.6 Hz, 2H), 3,86 (s, 2H), 2,43 (s, 3H), is 2.37 (s, 3H), of 1.80 (m, 2H), of 1.53 (m, 2H), 0,99 (t, J=7.5 Hz, 3H).

Reference example 9

Methyl ester 2-methylindol-4-carboxylic acid

To a solution of 2-methyl-4-triftormetilfosfinov (6,32 g, obtained in reference example 1) in methanol (33,43 ml) and N,N-dimethylformamide (200 ml), add triethylamine (6.3 ml) and tetrakis(triphenylphosphine)palladium (2.6 g). The atmosphere in the vessel is replaced by carbon monoxide and the mixture was stirred at 60°With during the night. After completion of the reaction to the mixture are added water and ethyl acetate and the mixture is then extracted. The aqueous layer was extracted with ethyl acetate. The combined organic layers are successively washed with water and saturated aqueous sodium chloride, dried and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (n-hexane-ethyl acetate), obtaining mentioned in the title compound (4,29 g)having the following physical data.

TLC: Rf 0,18 (toluene).

Reference example 10

2-Methylindol-4-carboxylic acid

To a solution of methyl ester 2-methylindol-4-carboxylic acid (4.3 g, obtained in reference example 9) in a mixture of methanol-dioxane (10 ml + 10 ml) is added 5 N aqueous sodium hydroxide solution (10 ml) and the mixture was stirred at 60°With during the night. To the reaction solution was added 2 N hydrochloric acid and then extracted with ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layers are successively washed with water and saturated aqueous sodium chloride, dried and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (chloroform-methanol), getting named the title compound (1.6 g)having the following physical data.

TLC: Rf of 0.48 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 8,14-8,04 (ush., 1H), to 7.93 (DD, 1H), 7,52 (m, 1H), 7,18 (DD, 1H), 6,94 (m, 1H), 3,71 (s, 3H).

Reference example 11

Benzyl ether of 2-methylindol-4-carboxylic acid

To a solution of 2-methylindol-4-carboxylic acid (690 mg, obtained in reference example 10) in N,N-dimethylformamide (10 ml) at room temperature is added anhydrous potassium carbonate (815 mg) and benzylbromide (0.7 ml) and the mixture was stirred at 80°C for 2 hours. To the reaction solution was added water and ethyl acetate, and the mixture is then extracted. The aqueous layer EC is tracerout with ethyl acetate. The combined organic layers are successively washed with water and saturated aqueous sodium chloride, dried and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (hexane-ethyl acetate), obtaining mentioned in the title compound (610 mg)having the following physical data.

TLC: Rf of 0.44 (hexane:ethyl acetate = 8:2).

NMR (CDCl3): δ 8,05 (USS, 1H), to $ 7.91 (d, 1H), 7,54-7,24 (m, 7H), to 6.88 (m, 1H), 5,44 (s, 2H), 2,48 (s, 3H).

Reference example 12

Benzyl ester 1-(4-butoxybenzoyl)-2-methylindol-4-carboxylic acid

To a solution of benzyl ester 2-methylindol-4-carboxylic acid (690 mg, obtained in reference example 11) in N,N-dimethylformamide (8 ml) at 0°add sodium hydride (114 mg, 60%) and the mixture is stirred at the same temperature for 30 minutes. To the reaction mixture 4-butoxybenzoate (0.54 ml) and the mixture is stirred at room temperature overnight. To the reaction mixture are added water and ethyl acetate and then the mixture is separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers are successively washed with water and saturated aqueous sodium chloride, dried and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (hexane-ethyl acetate), obtaining mentioned in connection (1,02 g), having the following physical data.

TLC: Rf and 0.61 (hexane:ethyl acetate = 8:2).

NMR (CDCl3): δ 8,10-of 6.90 (m, 13H), the 5.45 (s, 2H), of 4.05 (t, 2H), 2,44 (s, 3H), 1,86-of 1.74 (m, 2H), 1.60-to a 1.45 (m, 2H), 0,99 (t, 3H).

Example 2

(1) 1-(4-Butoxybenzoyl)-2-methylindol-4-carboxylic acid and (2) 1-(4-butoxybenzoyl)-2-methyl-2,3-dihydroindol-4-carboxylic acid

To a solution of benzyl ester 1-(4-butoxybenzoyl)-2-methylindol-4-carboxylic acid (1,02 g, obtained in reference example 12) in methanol (10 ml) and ethyl acetate (5 ml) is added palladium on charcoal (100 mg). The atmosphere in the vessel is replaced with hydrogen and the mixture is stirred at room temperature overnight. The reaction mixture was filtered through celite (trademark). The chloroform filtrate and after washing Celica are combined and then concentrated under reduced pressure. The residue is purified column chromatography on silica gel (chloroform-methanol), getting named the title compound having the following physical data.

(1) Indole

TLC: Rf is 0.59 (chloroform:methanol = 9:1).

NMR (CDCl3): δ to 7.99 (d, J=8,1 Hz, 1H), of 7.70 (d, J=9.0 Hz, 2H), was 7.36 (d, J=8,1 Hz, 1H), 7,21 (USS, 1H), 7,13 (t, J=8,1 Hz, 1H), 6,97 (d, J=9.0 Hz, 2H), 4,06 (t, J=6.6 Hz, 2H), 2,48 (s, 3H), 1,88 to 1.76 (m, 2H), 1,60-of 1.46 (m, 2H), and 1.00 (t, J=7.5 Hz, 3H).

(2) Indolin

TLC: Rf of 0.53 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 7,74 (DD, 1H), of 7.64-7,46 (ush, 1H), 7,50 (d, 2H), and 7.1 (t, 1H), 6,93 (d, 2H), 4,84-4,70 (m, 1H), was 4.02 (t, 2H), 3,65 (DD, 1H), up 3.22 (DD, 1H), 1,86 to 1.76 (m, 2H), 1.60-to a 1.45 (m, 2H), 1,24 (d, 3H), and 1.00 (t, 3H).

Reference example 13

Methyl ester 2-methylindol-4-biloxicasino acid

To a solution of 2-methyl-4-hydroxyindole (5 g) in N,N-dimethylformamide (50 ml) at room temperature is added anhydrous potassium carbonate (11.7 g) and methylbromide (3,54 ml) and the mixture was stirred at 80°C for 2 hours. To the reaction mixture is added ice water, getting named the title compound (5.4 g)having the following physical data.

TLC: Rf of 0.75 (benzene:ethyl acetate = 4:1).

NMR (CDCl3): δ 8,00-to 7.84 (br, 1H),? 7.04 baby mortality-6,94 (m, 2H), 6,45 and 5.36 (m, 2H), of 4.77 (s, 2H), 3,80 (s, 3H), 2,43 (s, 3H).

Reference example 14

2-Methylindol-4-alexianna acid

To a solution of methyl ester 2-methylindol-4-biloxicasino acid (5.4 g) in methanol (18 ml)-dioxane (36 ml) is added 5 N aqueous sodium hydroxide solution (15 ml) and the mixture is stirred at room temperature for 1 hour. To the reaction solution was added 2 N hydrochloric acid, getting named the title compound (3.5 g)having the following physical data.

TLC: Rf of 0.20 (chloroform:methanol = 9:1).

Reference example 15

Allyl ester 2-methylindol-4-biloxicasino acid

To a solution of methylindol-4-biloxicasino acid (2 g) in N,N-dimethylformamide (20 ml) is added anhydrous potassium carbonate (2,02 g) and allylbromide (1,27 ml) and the mixture was stirred at 80° C for 2 hours. To the reaction mixture are added water and ethyl acetate and then the mixture is separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers are successively washed with water and saturated aqueous sodium chloride, dried and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (n-hexane-ethyl acetate), obtaining mentioned in the title compound (1,88 mg)having the following physical data.

TLC: Rf of 0.50 (n-hexane:ethyl acetate = 7:3).

Reference example 16

Allyl ester 1-(4-butoxybenzoyl)-2-methylindol-4-biloxicasino acid

To a solution of allyl ester 2-methylindol-4-biloxicasino acid (900 mg) in N,N-dimethylformamide (10 ml) at 0°add sodium hydride (147 mg, 60%) and the mixture is stirred at the same temperature for 30 minutes. To the reaction mixture 4-butoxybenzoate (0,70 ml) and the mixture is stirred at room temperature overnight. To the reaction mixture are added water and ethyl acetate and then the mixture is separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers are successively washed with water and saturated aqueous sodium chloride, dried and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (hexane-atilas the tat), getting named the title compound (800 mg)having the following physical data.

TLC: Rf 0,63 (n-hexane:ethyl acetate = 7:3).

NMR (CDCl3): δ of 7.69 (d, 2H), 7,00-6,85 (m, 3H), of 6.68 (d, 1H), to 6.67 (s, 1H), 6,47 (d, 1H), 6,00-by 5.87 (m, 1H), 5.40 to-and 5.30 (m, 1H), 5,30-5,24 (m, 1H), 4,78 (s, 2H), 4.75 V-and 4.68 (m, 2H), of 4.05 (t, 2H), 2,42 (s, 3H), 1,87 is 1.75 (m, 2H), 1.60-to a 1.45 (m, 2H), and 1.00 (t, 3H).

Example 3

1-(4-Butoxybenzoyl)-2-methylindol-4-alexianna acid

The compound of the present invention having the following physical data receive is similar to the method of example 1 using the compound obtained in reference example 16.

TLC: Rf of 0.38 (chloroform:methanol:acetic acid= 90:9:1).

NMR (CDCl3): δ of 7.70 (d, J=9.0 Hz, 2H), 6,98-6,89 (m, 3H), of 6.71 (d, J=8,4 Hz, 1H), 6,60-to 6.57 (m, 1H), 6,51 (d, J=8,4 Hz, 1H), 4,84 (s, 2H), of 4.05 (t, J=6.6 Hz, 2H), 2,43 (s, 3H), 1,87 is 1.75 (m, 2H), 1,59-of 1.44 (m 2N), and 1.00 (t, J=7.5 Hz, 3H).

Examples 3(1)-3 (6)

Each connection having the following physical data, receive by methods analogous series of reactions of reference examples 13, 14, 15 and 16 and example 3.

Example 3(1)

1-(4-(2-Ethoxyethoxy)benzoyl)-2-methylindolin-4-oxiana acid

TLC: Rf 0,19 (methylene chloride:methanol = 9:1).

NMR (CDCl3): δ to 7.68 (d, J=8.5 Hz, 2H), 6,97 (d, J=8.5 Hz, 2H), 6,91 (m, 1H), 6,66 (d, J=8.5 Hz, 1H), return of 6.58 (s, 1H), of 6.49 (d, J=8.0 Hz, 1H), of 4.77 (s, 2H), 4,20 (t, J=5.0 Hz, 2H), 3,83 (t, J=5.0 Hz, 2H), 3,62 (sq, J=7,0 Hz, 2H), 2,41 (who, 3H), of 1.26 (t, J=7.0 Hz, 3H).

Example 3(2)

1-(4-Propylacetate)-2-methylindolin-4-oxiana acid

TLC: Rf to 0.39 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 7,73-to 7.67 (m, 2H), 6,97-of 6.90 (m, 3H), 6,72 (d, J=8,4 Hz, 1H), 6,59 (s, 1H), of 6.52 (d, J=7.5 Hz, 1H), 4,80 (s, 2H), 4,01 (t, J=6.6 Hz, 2H), 2,43 (s, 3H), of 1.86 (dt, J=7,5, and 6.6 Hz, 2H), with 1.07 (t, J=7.5 Hz, 3H).

Example 3(3)

1-(4-Penetrateinto)-2-methylindolin-4-oxiana acid

TLC: Rf of 0.35 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 7,71-to 7.67 (m, 2H), 7,37-7,25 (m, 5H), 6,97-6,89 (m, 3H), 6,70 (d, J=8,4 Hz, 1H), return of 6.58 (s, 1H), of 6.52 (d, J=8,1 Hz, 1H), 4,80 (s, 2H), 4.26 deaths (t, J=6.9 Hz, 2H), 3,14 (t, J=6.9 Hz, 2H), 2,43 (s, 3H)).

Example 3(4)

1-(4-Benzyloxybenzyl)-2-methylindolin-4-oxiana acid

TLC: Rf of 0.48 (chloroform:methanol = 10:1).

NMR (DMSO-d6): δ the 7.65 (d, J=8,8 Hz, 2H), 7,51-7,33 (m, 5H), 7,17 (d, J=8,8 Hz, 2H), 6,93 (t, J=8,2 Hz, 1H), 6,59-of 6.52 (m, 3H), to 5.21 (s, 2H), of 4.77 (s, 2H), 2,32 (s, 3H).

Example 3(5)

1-(4-(3-Methylbutoxy)benzoyl)-2-methylindolin-4-oxiana acid

TCX: Rf and 0.46 (chloroform:methanol = 5:1).

NMR (CDCl3): δ to 7.64 (d, J=8.6 Hz, 2H), 6,92-6,84 (m, 3H), 6,70-of 6.45 (m, 3H), 4.72 in (s, 2H), of 4.05 (t, J=6.6 Hz, 2H), is 2.37 (s, 3H)and 1.83 (m, 1H), 1,72 (m, 2H), 0,97 (d, J=6,4 Hz, 6N).

Example 3(6)

1-(4-Phenoxybenzoyl)-2-methylindolin-4-oxiana acid

TCX: Rf 0.26 (chlorine is of the form:methanol = 9:1).

NMR (CDCl3): δ of 7.70 (d, J=8.7 Hz, 2H), 6,98-of 6.90 (m, 3H), 6,72 (d, J=8.7 Hz, 1H), 6,58 (USS, 1H), of 6.52 (d, J=8,1 Hz, 1H), 4,80 (s, 2H), Android 4.04 (t, J=6.6 Hz, 2H), 2,43 (s, 3H), 2,10-of 1.30 (m, 7H), of 0.95 (t, J=6,9 Hz, 3H).

Reference example 17

Methyl ester 3-(2-methylindol-4-yl)acrylic acid

To a solution of 2-methyl-4-triftormetilfullerenov (3.2 g, obtained in reference example 2) in N,N-dimethylformamide (50 ml) is added methyl ester of acrylic acid (2,24 ml), diisopropylethylamine (5,9 ml) and dichlorobis(triphenylphosphine) palladium(II) (238 mg) and the mixture was stirred at 95°C for 2 days. To the reaction mixture are added water and ethyl acetate and then the mixture is separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers are successively washed with water and saturated aqueous sodium chloride, dried and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (hexane-ethyl acetate), obtaining mentioned in the title compound (950 mg)having the following physical data.

TLC: Rf of 0.50 (hexane:ethyl acetate = 8:2).

Reference example 18

3-(2-Methylindol-4-yl)acrylic acid

Named the title compound (700 mg)having the following physical data, receive by the method similar to reference example 14, using the methyl ester of 3-(methylindol-4-yl)acrylic acid (950 mg, obtained in reference example 17).

TCX: Rf of 0.54 (chloroform:methanol = 9:1).

Reference example 19

Allyl ester 3-(2-methylindol-4-yl)acrylic acid

Named the title compound (240 mg)having the following physical data, receive by the method similar to reference example 15 using 3-(2-methylindol-4-yl)acrylic acid (300 mg) obtained in reference example 18).

TLC: Rf of 0.43 (hexane:ethyl acetate = 8:2).

Reference example 20

Allyl ester 3-(1-(4-butoxybenzoyl)-2-methylindol-4-yl)acrylic acid

Named the title compound (545 mg)having the following physical data, receive by the method similar to reference example 16, using allyl ester 3-(2-methylindol-4-yl)acrylic acid (240 mg) obtained in reference example 19).

TLC: Rf 0,59 (hexane:ethyl acetate = 8:2).

NMR (CDCl3): δ 8,10-of 8.00 (m, 1H), of 7.70 (d, 2H), 7,39 (d, 1H), 7,10-of 6.90 (m, 4H), 6,72 (s, 1H), return of 6.58 (d, 1H), 6,10-5,95 (m, 1H), 5,95-to 5.85 (m, 1H), of 5.82-of 5.75 (m, 1H), 4.80 to 4,70 (m, 2H), 4,10-4,00 (m, 2H), 2,47 (, 3H), 1,90 is 1.70 (m, 2H), 1.70 to of 1.40 (m, 2H), 1,10-of 0.95 (m, 3H).

Example 4

3-(1-(4-Butoxybenzoyl)-2-methylindol-4-yl)acrylic acid

Named the title compound (374 mg)having the following physical data, receive according to the method similar to example 1, with the use of the allyl ester 3-(1-(4-butoxybenzoyl)-2-methylindol-4-yl)acrylic acid (413 mg, obtained in reference example 20).

TLC: Rf of 0.53 (chloroform:methanol = 9:1).

NMR (CDCl3): δ is 8.16 (d, J=16.2 Hz, 1H), of 7.70 (d, J=9.0 Hz, 2H), 7,43 (USD, J=7.2 Hz, 1H), 7,15-7,03 (m, 2H), of 6.96 (d, J=9.0 Hz, 2H), 6,74 (USS, 1H), 6,59 (d, J=16.2 Hz, 1H), 4,06 (t, J=6.3 Hz, 2H), 2,48 (s, 3H), 1,88 to 1.76 (m, 2H), 1.60-to of 1.46 (m, 2H), and 1.00 (t, J=7.2 Hz, 3H).

Examples 4(1)-4(7)

Each connection having the following physical data, receive by methods analogous series of reactions of reference examples 17, 18, 19, 20 and example 4.

Example 4(1)

3-(1-(4-Benzyloxybenzyl)-2-methylindol-4-yl)-2-acrylic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

NMR (DMSO-d6): δ of 7.90 (d, J=16 Hz, 1H), 7,65 (d, J=8.6 Hz, 2H), 7,60-7,30 (m, 6N), 7,17 (d, J=8.6 Hz, 2H), 7,16-7,05 (m, 2H), 6.90 to (s, 1H), 6,60 (d, J=16 Hz, 1H), total of 5.21 (s, 2H), a 2.36 (s, 3H).

Example 4(2)

3-(1-(4-Pentyloxybenzoyl)-2-methylindol-4-yl)-2-acrylic acid

TLC: Rf 0.31 in (chloroform:methanol = 9:1).

NMR (CDCl3): δ 8,15 (d, J=15,9 Hz, 1H), of 7.70 (d, J=9.0 Hz, 2H), 7,43 (d, J=7.2 Hz, 1H), 7,15-7,02 (m, 2H), of 6.96 (d, J=9.0 Hz, 2H), 6,74 (s, 1H), return of 6.58 (d, J=15,9 Hz, 1H), of 4.05 (t, J=6.3 Hz, 2H), 2,48 (s, 3H), 2,00-of 1.30 (m, 7H), of 0.95 (t, J=7.2 Hz, 3H).

Example 4(3)

3-(1-(4-Penetrateinto)-2-methylindol-4-yl)-2-acrylic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1)

NMR (CDCl3): δ is 8.16 (d, J=16 Hz, 1H), 7,68 (d, J=9.0 Hz, 2H), 7,44-7,26 (m, 6N), to 7.09 (m, 2H), of 6.96 (d, J=9.0 Hz, 2H), 6,74 (s, 1H), return of 6.58 (d, J=16 Hz, 1 is), 4,27 (t, J=7,0 Hz, 2H), 3.15 in (t, J=7,0 Hz, 2H), 2,47 (s, 3H).

Example 4(4)

3-(1-(4-(3-Methylbutoxy)benzoyl)-2-methylindol-4-yl)-2-acrylic acid

TLC: Rf of 0.60 (chloroform:methanol = 10:1).

NMR (DMSO-d6): δ 12,4 (USS, 1H), of 7.90 (d, J=16 Hz, 1H), 7,66-of 7.60 (m, 2H), 7,52 (USD, J=6,4 Hz, 2H), 7,11-7,05 (m, 4H), 6.90 to (s, 1H), 6,59 (d, J=16 Hz, 1H), 4.09 to (t, J=6.4 Hz, 2H), a 2.36 (s, 3H), 1,90 of 1.50 (m, 3H), to 0.92 (DD, J=6,4, 2.0 Hz, 6N).

Example 4(5)

3-(1-(4-(2-Ethoxyethoxy)benzoyl)-2-methylindol-4-yl)-2-acrylic acid

TLC: Rf of 0.60 (ethyl acetate).

NMR (CDCl3): δ 8,15 (d, J=15,9 Hz, 1H), of 7.70 (d, J=9.0 Hz, 2H), 7,42 (m, 1H), 7,09-6,98 (m, 4H), 6,74 (s, 1H), return of 6.58 (d, J=15,9 Hz, 1H), 4,22 (t, J=4.6 Hz, 2H), 3,84 (t, J=4.6 Hz, 2H), 3,63 (sq, J=7,0 Hz, 2H), 2,48 (d, J=1.0 Hz, 3H), of 1.27 (t, J=7.0 Hz, 3H).

Example 4(6)

3-(1-(4-Propylacetate)-2-methylindol-4-yl)-2-acrylic acid

TLC: Rf of 0.48 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 8,15 (d, J=15,9 Hz, 1H), 7,71 (d, J=8.7 Hz, 2H), 7,43 (USD, J=7.2 Hz, 1H), 7,15-7,03 (m, 2H), 6,97 (d, J=8.7 Hz, 2H), 6,74 (s, 1H), return of 6.58 (d, J=15,9 Hz, 1H), was 4.02 (t, J=6.6 Hz, 2H), 2,48 (s, 3H), 1,95-of 1.80 (m, 2H), with 1.07 (t, J=7.5 Hz, 3H).

Example 4(7)

3-(1-(4-(2-(Pyridin-2-yl)ethoxy)benzoyl)-2-methylindol-4-yl)-2-acrylic acid

TLC: Rf of 0.40 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 8,61 (d, J=5.0 Hz, 1H), 8,13 (d, J=16.0 Hz, 1H), 7,71-to 6.95 (m, 10H), 6,72 (s, 1H), return of 6.58 (d, J=16.0 Hz, 1H), 4,19 (t, J=6,8 Hz, 2H), 3,34 (t, J=6,8 Hz, 2H), 2,45(s, 3H).

Example 5

3-(1-(4-Butoxybenzoyl)-2-methylindol-4-yl)propionic acid

To a solution of 3-(1-(4-butoxybenzoyl)-2-methylindol-4-yl)acrylic acid (300 mg, obtained in example 4) in a mixture of methanol-ethyl acetate (5 ml + 5 ml) at room temperature is added palladium on charcoal (100 mg). The atmosphere in the vessel is replaced with hydrogen and the mixture is stirred at room temperature for 2 hours. The mixture is filtered through celite (trademark). The chloroform filtrate and after washing Celica are combined and then concentrated under reduced pressure. The residue is purified column chromatography on silica gel (chloroform-methanol), getting named the title compound (25 mg)having the following physical data.

TLC: Rf of 0.58 (chloroform:methanol = 9:1).

NMR (CDCl3): δ of 7.70 (d, J=9,3 Hz, 2H), 7,00-6,86 (m, 5H), 6.48 in (s, 1H), of 4.05 (t, J=6.6 Hz, 2H), 3.75 to the 3.65 (br, 1H), 3,19 (t, J=8,4 Hz, 2H), and 2.79 (t, J=8,4 Hz, 2H), of 2.45 (s, 3H), 1,87-1,72 (m, 2H), 1.60-to 1,40 m 2N), and 1.00 (t, J=7.5 Hz, 3H).

Reference example 21

Benzyl ether of 4-(1-(4-butoxybenzoyl)-2-methylindol-4-yl)butane acid

(1) To a solution of 3-(1-(4-butoxybenzoyl)-2-methylindol-4-yl)propionic acid (1.77 g, obtained in example 5) in toluene (20 ml) at room temperature add oxalicacid (0,64 ml) and N,N-dimethylformamide (few drops) and the mixture AC who're asked at room temperature for 1 hour.

(2) To a solution of the carboxylic acid obtained in (1), in tetrahydrofuran and acetonitrile (4 ml + 4 ml) at 0°add trimethylsilyldiazomethane (4,67 ml, 2 M). The mixture is stirred at the same temperature for 1 hour and then concentrated under reduced pressure. To the residue add benzyl alcohol (4 ml) and 2,4,6-kallidin (4 ml) and the mixture was stirred at 180°C for 30 minutes. After cooling to room temperature the reaction mixture was purified column chromatography on silica gel (hexane-ethyl acetate), obtaining mentioned in the title compound (460 mg)having the following physical data.

TLC: Rf of 0.51 (hexane:ethyl acetate = 8:2).

Example 6

4-(1-(4-Butoxybenzoyl)-2-methylindol-4-yl)butane acid

Named the title compound (170 mg)having the following physical data, receive according to the method similar to example 2, using the benzyl ester of 4-(1-(4-butoxybenzoyl)-2-methylindol-4-yl)butane acid (460 mg, obtained in reference example 21).

TLC: Rf of 0.50 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 7,71 (d, J=9.0 Hz, 2H), 7,00-6,86 (m, 5H), 6.48 in (s, 1H), of 4.05 (t, J=6.6 Hz, 2H), 2,90 (t, J=7.2 Hz, 2H), 2,48-of 2.38 (m, 5H), 2,14-2,00 (m, 2H), 2.00 in of 1.40 (m, 5H), and 1.00 (t, J=7.5 Hz, 3H).

Examples 7 through 7(228)

Compounds of the present invention having the following physical data, get on techniques similar to the series of reactions of reference example 7 → reference example 8 → 1. In examples 7(37) and 7(151) hydroxy - or amino protect protective group, the protective group is removed before the reaction, corresponding to example 1.

Example 7

1-(4-Butoxybenzoyl)-5-methoxy-2-methylindole-4-acetic acid

TLC: Rf of 0.48 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 434 (M+K)+, 418 (M+Na)+, 396 (M+H)+.

NMR (CDCl3): δ 7,70-to 7.67 (m, 2H), 6,98-6,93 (m, 3H), 6,70 (d, J=9,3 Hz, 1H), 6,41 (s, 1H), of 4.05 (t, J=6.5 Hz, 2H), 3,90 (s, 2H), 3,86 (s, 3H), 2,41 (s, 3H), equal to 1.82 (m, 2H), and 1.54 (m, 2H), and 1.00 (t, J=7.5 Hz, 3H).

Example 7(1)

1-(4-(2-Methylbutoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 418 (M+K)+, 402 (M+Na)+.

Example 7(2)

1-(4-Cyclopentylacetyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 376 (M-N)-.

Example 7(3)

1-(4-(1-Ethylpropoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.51 (chloroform:methanol = 10:1)

MS: (APCI, neg.): 378 (M-N)-.

Example 7(4)

1-(4-(Tetrahydrofuran-3-yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 378 (M-N)-.

Example 7(5)

1-(4-(1,2-Dimethyl is aproxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 418 (M+K)+, 402 (M+Na)+.

Example 7(6)

1-(4-Cyclobutylmethyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 402 (M+K)+, 386 (M+Na)+.

Example 7(7)

1-(4-(1-Methylcyclopropyl)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 416 (M+K)+, 400 (M+Na)+.

Example 7(8)

1-(4-Cyclobutylmethyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 416 (M+K)+, 400 (M+Na)+.

Example 7(9)

1-(4-(2-Benzyloxyethyl)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 442 (M-N)-.

Example 7(10)

1-(4-Cyclopropylmethoxy)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 402 (M+K)+, 386 (M+Na)+.

Example 7(11)

1-(4-(3,7-Dimethyl-6-octene-1-yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 486 (M+K)+ , 470 (M+Na)+.

Example 7(12)

1-(4-(3-(3,4-Acid), propyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf value of 0.52 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 526 (M+K)+, 510 (M+Na)+.

Example 7(13)

1-(4-(4-(4-Methoxyphenyl)bucalossi)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf value of 0.52 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 510 (M+K)+, 494 (M+Na)+.

Example 7(14)

1-(4-(2,3,5,6-Tetrahydropyran-4-yloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.33 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 432 (M+K)+, 416 (M+Na)+, 393 (M)+.

Example 7(15)

1-(4-(1-Methylpropyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.33 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 365 (M)+.

Example 7(16)

1-(4-(5-Chloropentane)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf 0.28 in (chloroform:methanol = 10:1).

MS: (MALDI, position.): 436 (M+Na)+, 413 (M)+.

Example 7(17)

1-(4-(2,3,4,5-Tetrahydrofuran-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.27 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 432 (M+K)+, 416 (M+Na)+, 394 (M+H)+, 393 (M)+.

Example 7(18)

1-(4-2-(N,N-Diethylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf 0,08 (chloroform:methanol = 2:1).

MS: (MALDI, position.): 409 (M+N)+.

Example 7(19)

1-(4-(2-(piperidine-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.16 (chloroform:methanol = 2:1).

MS: (MALDI, position.): 443 (M+Na)+, 421 (M+N)+.

Example 7(20)

1-(4-(2-Cyclopentyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.33 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 428 (M+Na)+, 406 (M+H)+.

Example 7(21)

1-(4-(3-Methoxy-3-methylbutoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.34 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 448 (M+Na)+, 432 (M+N)+.

Example 7(22)

1-(4-(2-(3,5-Dimethylpyrazol-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.33 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 430 (M-N)-.

Example 7(23)

1-(4-(2-(N,N-Diallylamine)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf 0.31 in (chloroform:methanol = 10:1).

MS: (APCI, neg.): 431 (M-N)-.

Example 7(24)

1-(4-(6-(N,N-Dimethylamino)hexyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 435 (M-N) .

Example 7(25)

1-(4-(3-buten-1 yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 360 (M-N)-.

Example 7(26)

1-(4-Cyclohexylmethoxy)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 444 (M+K)+, 428 (M+Na)+.

Example 7 (27)

1-(4-(2-(Pyrrol-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 441 (M+K)+, 425 (M+Na)+.

Example 7(28)

1-(4-(2-(3,4-Acid), ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 512 (M+K)+, 496 (M+Na)+.

Example 7(29)

1-(4-(3-Pentyn-1 yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 414 (M+K)+, 398 (M+Na)+.

Example 7(30)

1-(4-Privateplacement)-2-methylindole-4-acetic acid

TCX: Rf of 0.55 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 480 (M+K)+, 464 (M+Na)+.

Example 7(31)

1-(4-(4-Methylthiopurine)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 450 (M+K)+, 434 (M+Na)+.

Example 7(32)

1-(4-(4-Pentyn-1 yloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 414 (M+K)+, 398 (M+Na)+.

Example 7(33)

1-(4-(2-Feniltiometilindol)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 484 (M+K)+, 468 (M+Na)+.

Example 7(34)

1-(4-(4-Penten-1 yloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 416 (M+K)+, 400 (M+Na)+.

Example 7(35)

1-(4-(5-HEXEN-1-yloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 430 (M+K)+, 414 (M+Na)+.

Example 7(36)

1-(4-(2-Benzyldimethylamine)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 498 (M+K)+, 482 (M+Na)+.

Example 7(37)

1-(4-(6-Hydroxyhexyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.47 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 508 (M+K)+, 492 (M+Na)+.

Example 7(38)

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 496 (M+K)+, 480 (M+Na)+.

Example 7(39)

1-(4-(2-Butoxyethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 408 (M-N)-.

Example 7(40)

1-(4-(3-Methyloxiran-3-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 392 (M-N)-.

Example 7(41)

1-(4-(2-(N-ethyl-N-(3-were)amino)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.55 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 471 (M+H)+.

Example 7(42)

1-(4-(2-(N-Methyl-N-phenylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.55 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 481 (M+K)+, 465 (M+Na)+, 443 (M+N)+.

Example 7(43)

1-(4-(3-(4-Methoxyphenyl)propyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 496 (M+K)+, 480 (M+Na)+.

Example 7(44)

1-(4-(3-Nonen-1 yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (MALDI, the floor is W.): 470 (M+K) +, 454 (M+Na)+.

Example 7(45)

1-(4-(2-(4-Chlorophenylthio)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 518 (M+K)+, 502 (M+Na)+.

Example 7(46)

1-(4-(2-Phenyleneoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.55 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 427 (M-N)-.

Example 7(47)

1-(4-(3-(Pyridin-3-yl)propyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.57 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 467 (M+K)+, 451 (M+Na)+.

Example 7(48)

1-(4-(2-(3-Triptoreline)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.60 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 520 (M+K)+, 504 (M+Na)+.

Example 7(49)

1-(4-(2-(2-Chlorophenoxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf and 0.61 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 504 (M+K)+, 488 (M+Na)+.

Example 7(50)

1-(4-(2-(3-Methylphenoxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.65 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 482 (M+K)+, 466 (M+Na)+.

Example 7(51)

1-(4-Butoxybenzoyl)-6-methoxy-2-meth is lindol-4-acetic acid

TLC: Rf of 0.44 (chloroform:methanol = 10:1).

MS: (MALDI, position.): 434 (M+K)+, 418 (M+Na)+, 395 (M)+.

NMR (CDCl3): δ of 7.70 (m, 2H), 6,95 (m, 2H), 6.73 x (d, J=2.1 Hz, 1H), of 6.68 (d, J=2.1 Hz, 1H), 6,38 (s, 1H), Android 4.04 (t, J=6.6 Hz, 2H), 3,81 (s, 2H), the 3.65 (s, 3H), of 2.34 (s, 3H), of 1.81 (m, 2H)and 1.51 (m, 2H), 0,99 (t, J=7.5 Hz, 3H).

Example 7(52)

1-(4-(Thiophene-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 404 (M-N)-.

Example 7(53)

1-(4-(2-(2-Chlorethylene)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 414 (M-N)-.

Example 7(54)

1-(4-(2-(Morpholine-4-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.33 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 421 (M-N)-.

Example 7(55)

1-(4-(5-Hexyne-1-yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf value of 0.52 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 388 (M-N)-.

Example 7(56)

1-(4-(4-Methyl-3-penten-1 yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 390 (M-N)-.

Example 7(57)

1-(4-(2-(5-Methylfuran-2-yl)ethyloxy)benzoyl)-2-methylindol-4-vinegar is Aya acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1)

MS: (APCI, neg.): 416 (M-N)-.

Example 7(58)

1-(4-(2-(Furan-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 402 (M-N)-.

Example 7(59)

1-(4-(2-Cyclobutylmethyl)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 406 (M-N)-.

Example 7(60)

1-(4-(2-(2,4-Differenl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 448 (M-N)-.

Example 7(61)

1-(4-(2-(2,5-Differenl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1)

MS: (APCI, neg.): 448 (M-N)-.

Example 7(62)

1-(4-(2-(2-Ethoxyphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 456 (M-N)-.

Example 7(63)

1-(4-(2-(2-Methylpropyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 408 (M-N)-.

Example 7(64)

1-(4-(4-Methoxybenzyloxy)benzoyl)-2-marked the Dol-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 394 (M-N)-.

Example 7(65)

1-(4-(2-(2,5-Dimetilfenil)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1)

MS: (APCI, neg.): 440 (M-N)-.

Example 7(66)

1-(4-(2-(2-(2-Methoxyethoxy)ethyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.55 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 454 (M-N)-.

Example 7(67)

1-(4-(2-(2,4-Acid), ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf value of 0.52 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 472 (M-N)-.

Example 7(68)

1-(4-(2-(2,3-Differenl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 448 (M-N)-.

Example 7(69)

1-(4-(1-Phenylcyclopropane)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 438 (M-N)-.

Example 7(70)

1-(4-(2-(3-Methoxymethyl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 456 (M-N)-.

Example 7(71)

1-(4-(Fouras is-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1)

MS: (APCI, neg.): 388 (M-N)-.

Example 7(72)

1-(4-(2-(N-Benzyl-N-methylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.35 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 455 (M-N)-.

Example 7(73)

1-(4-(2-(2-Butoxyethoxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.55 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 452 (M-N)-.

Example 7(74)

1-(4-(2-Methoxy-3-phenoxypropionic)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 472 (M-N)-.

Example 7(75)

1-(4-(2-(4-Methylphenoxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.44 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 442 (M-N)-.

Example 7(76)

1-(4-(2-(2-(2-Ethoxyethoxy)ethyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.36 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 468 (M-N)-.

Example 7(77)

1-(4-(2-(Naphthalene-1-ylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.33 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 477 (M-N)-.

Example 7(78)

1-(4(2-(Naphthalene-1-yloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.37 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 478 (M-N)-.

Example 7(79)

1-(4-(2-(Pyrazole-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.32 (chloroform:methanol = 10:1)

MS: (APCI, neg.): 402 (M-N)-.

Example 7(80)

1-(4-(2-(2-Propen-1-yloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.33 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 392 (M-N)-.

Example 7(81)

1-(4-(4,4,4-Triptoreline)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.40 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 418 (M-N)-.

Example 7(82)

1-(4-(Indan-2-yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.36 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 424 (M-N)-.

Example 7(83)

1-(4-(2-(2-Methylphenoxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.38 (chloroform:methanol = 10:1)

MS: (APCI, neg.): 442 (M-N)-.

Example 7(84)

1-(4-(1,4-Benzodioxan-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.34 (chloroform:methanol = 10:1).

MS: (FAB, position.): 458 (M+N)+.

NMR (CDCl3): δ 7,71 (d, J=8,8 Hz, 2H), 7,09-PC 6.82 (m, N), 6.48 in (s, 1H), br4.61 (m, 2H, was 4.42 (DD, J=11.8 in, and 2.6 Hz, 1H), to 4.38-4,18 (m, 3H), of 3.84 (s, 2), 2,43 (s, 3H).

Example 7(85)

1-(4-(2-(2-Chlorophenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf to 0.39 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 446 (M-N)-.

Example 7(86)

1-(4-(2-(2-Ethoxyethoxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.37 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 424 (M-N)-.

Example 7(87)

1-(4-(5-Ethoxyphenoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.35 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 422 (M-N)-.

Example 7(88)

1-(4-(5-Methoxybenzyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.33 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 408 (M-N)-.

Example 7(89)

1-(4-((3E)-4-Phenyl-3-butene-1-yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.29 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 438 (M-N)-.

Example 7(90)

1-(4-(2-(N-Benzoyl-N-methylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.30 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 469 (M-N)-.

Example 7(91)

1-(4-(4-Ethoxymethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.34 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 408 (M-N)-.

Example 7(92)

1-(4-(3-(Pyrrol-1-yl)propyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.43 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 415 (M-N)-.

Example 7(93)

1-(4-(2-(Naphthalene-2-yloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.40 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 478 (M-N)-.

Example 7(94)

1-(4-(2-(2,4,6-Trimetilfenil)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.40 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 454 (M-N)-.

Example 7(95)

1-(4-(3-Benzyloxypropionic)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.41 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 456 (M-N)-.

Example 7(96)

1-(4-(3,3,4,4,5,5,6,6,6-Nonforensic)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf is 0.42 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 554 (M-N)-.

Example 7(97)

1-(4-(3-Phenoxyphenoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.44 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 442 (M-N)-.

Example 7(98)

1-(4-(3-(2-Forations)propyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.35 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 412 (M-N)-.

Example 7(99)

1-(4-(2-Cyclopentylacetyl)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.36 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 420 (M-N)-.

Example 7 (100)

1-(4-(3-(2,2,2-Triptoreline)propyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.41 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 448 (M-N)-.

Example 7(101)

1-(4-(2-Cyclopropylmethoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.47 (chloroform:methanol = 10:1)

MS: (APCI, neg.): 406 (M-N)-.

Example 7(102)

1-(4-(2-(3,3,3-Triplications)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf to 0.39 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 448 (M-N)-.

Example 7(103)

1-(4-(2-(2,2,2-Triptoreline)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf to 0.39 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 434 (M-N)-.

Example 7(104)

1-(4-(2-(2-Forations)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.38 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 398 (M-N)-.

Example 7(105)

1-(4-(2-(2,-Dichlorophenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.44 (chloroform:methanol = 10:1)

MS: (APCI, neg.): 480 (M-N)-.

Example 7(106)

1-(4-(2-(2,3,4,5,6-Pentamethylbenzyl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 482 (M-N)-.

Example 7 (107)

1-(4-(3,3,3-Triplications)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.32 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 404 (M-N)-.

Example 7(108)

1-(4-(2-(4-Methyl-1,3-thiazol-5-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf 0.28 in (chloroform:methanol = 10:1).

MS: (APCI, neg.): 433 (M-N)-.

Example 7(109)

1-(4-(2-(Imidazol-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.45 (chloroform:methanol = 2:1).

MS: (FAB, position.): 404 (M+N)+.

Example 7(110)

1-(4-(2-(2-Mei-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf 0.28 in (chloroform:methanol = 2:1).

MS: (APCI, neg.): 416 (M-N)-.

Example 7(111)

1-(4-(1,3-Dioksiinien-4-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.45 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 442 (M-N)-.

Example 7(112)

1-(4-Naphthalene-1-yl is ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.43 (chloroform:methanol = 9:1)

MS: (APCI, neg.): 448 (M-N)-.

Example 7(113)

1-(4-(3-(2-Pyrrolidino-1 ylpropionic)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.38 (chloroform:methanol = 9:1).

MS: (APCI, neg., 20): 433 (M-N)-.

Example 7(114)

1-(4-(Pyridine-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf is 0.42 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 399 (M-N)-.

Example 7 (115)

1-(4-(1-Ventilations)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.45 (chloroform;methanol = 9:1).

MS: (APCI, neg.): 426 (M-N)-.

Example 7(116)

1-(4-((3Z)-3-Octene-1-yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 418 (M-N)-.

Example 7(117)

1-(4-(2-Phenylpropoxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.48 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 426 (M-N)-.

Example 7(118)

1-(4-(Naphthalene-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.45 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 448 (M-N)-.

Example 7(119)

1-(4-(3-Chloropropoxy)benzoyl)-2-methylindole-4-acetic acid is the

TLC: Rf of 0.43 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 384 (M-H)-.

Example 7(120)

1-(4-(2-(2,3-Dimetilfenil)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.47 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 440 (M-N)-.

NMR (CDCl3): δ of 7.70 (d, J=8.7 Hz, 2H), 7,12-of 6.90 (m, 8H), of 6.49 (s, 1H), 4,21 (t, J=7.5 Hz, 2H), a 3.87 (s, 2H), 3,19 (t, J=7.5 Hz, 2H), of 2.45 (s, 3H), 2,31 (s, 3H), of 2.30 (s, 3H).

Example 7(121)

1-(4-(2-(4-Ethoxymethylene)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.48 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 456 (M-N)-.

NMR (CDCl3): δ of 7.69 (d, J=9.0 Hz, 2H), 7,34-7,24 (m, 3H), 7,10-6,85 (m, 6N), 6.48 in (s, 1H), of 4.45 (s, 2H), 4,24 (t, J=6.9 Hz, 2H), 3,86 (s, 2H), 3,40 (s, 3H), of 3.13 (t, J=6.9 Hz, 2H), 2,44 (s, 3H).

Example 7(122)

1-(4-(2,2,3,3,3-Pentafluoropropane)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.48 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 440 (M-N)-.

NMR (CDCl3): δ 7,72 (d, J=9.0 Hz, 2H), 7,08-6,92 (m, 5H), of 6.49 (s, 1H), 3,90 (s, 2H), 3,86 (s, 2H), of 2.45 (s, 3H).

Example 7(123)

1-(4-(2-(2,6-Differenl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.48 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 448 (M-N)-.

Mr (CDCl3): δ of 7.69 (d, J=9.0 Hz, 2H), 7,08-6,85 (m, 8H), of 6.49 (s, 1H), 4,25 (t, J=6.6 Hz, 2H), a 3.87 (2H), 3,26-and 3.16 (m, 2H), 2,44 (s, 3H).

Example 7(124)

1-(4-(3-Phenoxybenzyl)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.55 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 490 (M-N)-.

NMR (CDCl3): δ 7,71 (d, J=8.7 Hz, 2H), 7,40-6,85 (m, 14N), of 6.49 (s, 1H), 5,12 (s, 2H), a 3.87 (s, 2H), 2,44 (s, 3H).

Example 7 (125)

1-(4-Methoxyethoxymethyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.45 (chloroform:methanol = 10:1)

MC: (APCI, neg.): 352 (M-N)-.

NMR (CDCl3): δ of 7.70 (d, J=9.0 Hz, 2H), to 7.09 (d, J=9.0 Hz, 2H), 7,08-6,97 (m, 3H), 6.48 in (s, 1H), 5,26 (s, 2H), 3,85 (s, 2H), 3,51 (s, 3H), 2,43 (s, 3H).

Example 7 (126)

1-(4-(2-(2,5-Dimethyloxazole-4-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.33 (chloroform:methanol = 9:1).

MC: (APCI, neg.): 431 (M-N)-.

NMR (CDCl3): δ to 7.67 (d, J=8.7 Hz, 2H), 7,08-6,86 (m, 5H), of 6.50 (s, 1H), 4,22 (t, J=6.6 Hz, 2H), 3,86 (s, 2H), 2,90 (t, J=6.6 Hz, 2H), 2,44 (s, 3H), 2,39 (s, 3H), and 2.26 (s, 3H).

Example 7(127)

1-(4-(2-(4-Methoxy-3-were)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.58 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 456 (M-N)-.

NMR (CDCl3): δ of 7.69 (d, J=9,3 Hz, 2H), 7,11-6,87 (m, 7H), 6,79 (d, J=8,1 Hz, 1H), 6.48 in (s, 1H), 4,21 (t, J=7.2 Hz, 2H), 3,86 (s, 2H), 3,82 (s, 3H), 3,05 (t, J=7.2 Hz, 2H), 2,44 (s, 3H), 2,22 (s, 3H).

Example 7 (128)

1-(4-(2-(3-Ethoxyphenyl)ethyloxy)benzoyl-2-methylindole-4-acetic acid

TCX: Rf of 0.56 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 456 (M-N)-.

NMR (CDCl3): δ of 7.70 (d, J=8.7 Hz, 2H), 7,26-7,20 (m, 1H), 7,08-6,76 (m, 8H), of 6.49 (s, 1H), 4,25 (t, J=7.2 Hz, 2H), 4.04 the (sq, J=7.2 Hz, 2H), a 3.87 (s, 2H), 3,11 (t, J=7.2 Hz, 2H), of 2.45 (s, 3H), of 1.42 (t, J=7,2 Hz, 3H).

Example 7(129)

1-(4-(2-(1,3-Dihydrobenzo[C]furan-5-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 454 (M-N)-.

NMR (CDCl3): δ of 7.70 (d, J=8.7 Hz, 2H), 7,22-to 7.15 (m, 2H), 7,07-6,86 (m, 6N), of 6.49 (s, 1H), 5,11 (s, 4H), 4,25 (t, J=6.9 Hz, 2H), a 3.87 (s, 2H), and 3.16 (t, J=6.9 Hz, 2H), 2,44 (s, 3H).

Example 7(130)

1-(4-(2-Butene-1-yloxy)benzoyl)-2-methylindole-4-acetic acid (a mixture of forms EZ)

TLC: Rf of 0.53 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 362 (M-N)-.

NMR (CDCl3): δ of 7.70 (d, J=9.0 Hz, 2H), 7,10-of 6.90 (m, 5H), of 6.49 (s, 1H), 6,00-of 5.83 (m, 1H), 5,80-5,70 (m, 1H), 4,55 (d, J=6.0 Hz, 2H), a 3.87 (s, 2H), of 2.45 (s, 3H), of 1.78(d, J=7.8 Hz, 3H).

Example 7(131)

1-(4-(2-(6-Methylpyridin-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf 0.31 in (chloroform:methanol = 10:1).

MS: (EI, position.): 428 (M)+.

NMR (CDCl3): δ 7.68 per-7,63 (m, 2H), 7,55 (DD, J=6,6, and 6.6 Hz, 1H), 7,11? 7.04 baby mortality (m, 3H), 6,98-6,87 (m, 4H), 6,51 (s, 1H), 4,33 (t, J=6.6 Hz, 2H), 3,86 (s, 2H), 3,26 (t, J=6.6 Hz, 2H), has 2.56 (s, 3H), 2,43 (s, 3H).

Example 7(132)

1-(4-(2-(3-Methylpyridin-2-yl)ethyloxy)be the zoilus)-2-methylindole-4-acetic acid

TCX: Rf of 0.32 (chloroform:methanol = 10:1).

MS: (EI, position.): 428 (M)+.

NMR (CDCl3): δ 8,43 (DD, J=5,1, 1.2 Hz, 1H), 7,66-to 7.61 (m, 2H), 7,51 (DD, J=7,5, 1.2 Hz, 1H), 7,13 (DD, J=7,5, 5,1 Hz, 1H), 7,06 (DD, J=7,2, 1.2 Hz, 1H), 6,95 (DD, J=8,1, 7.2 Hz, 1H), 6,91-6,86 (m, 3H), of 6.52 (s, 1H), and 4.40 (t, J=6.6 Hz, 2H), 3,86 (s, 2H), 3,32 (t, J=6.6 Hz, 2H), 2,42 (s, 3H), 2,41 (s, 3H).

Example 7(133)

1-(4-(2-Chlorethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.53 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 370 (M-N)-.

NMR (CDCl3): δ 7,72 (d, J=9,3 Hz, 2H), 7,08-to 6.88 (m, 5H), of 6.50 (s, 1H), 4,32 (t, J=6.0 Hz, 2H), 3,90-a-3.84 (m, 4H), of 2.45 (s, 3H).

Example 7(134)

1-(4-(2-(Benzo[b]thiophene-3-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 468 (M-N)-.

NMR (CDCl3): δ to $ 7.91-7,80 (m, 2H), of 7.70 (d, J=8.7 Hz, 2H), 7,46-7,30 (m, 2H), 7,30-7,24 (m, 1H), 7,08-to 6.88 (m, 5H), 6.48 in (s, 1H), to 4.38 (t, J=6.9 Hz, 2H), a 3.87 (s, 2H), 3,40 (t, J=6.9 Hz, 2H), 2,44 (s, 3H).

Example 7(135)

1-(4-Ethoxyethylacetate)-2-methylindole-4-acetic acid

TLC: Rf of 0.45 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 366 (M-H)-.

NMR (CDCl3): δ 7,63 (d, J=8,8 Hz, 2H), 7,05-of 6.90 (m, 5H), 6,41 (d, J=0.8 Hz, 1H), 5,24 (s, 2H), 3,79 (s, 2H), 3,67 (sq, J=7.2 Hz, 2H), 2,36 (d, J=0.8 Hz, 3H), of 1.16 (t, J=7.2 Hz, 3H).

Example 7(136)

1-(4-Acetyloxybenzoic)-2-methylindole-4-acetic acid is the

TLC: Rf of 0.53 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 350 (M-N)-.

NMR (CDCl3): δ to 7.77 (d, J=8.7 Hz, 2H), 7,28-7,17 (m, 2H), 7,10-6,94 (m, 3H), 6,51 (s, 1H), a 3.87 (s, 2H), 2,43 (s, 3H), of 2.35 (s, 3H).

Example 7(137)

1-(4-(2-Propyne-1-yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf is 0.59 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 346 (M-N)-.

NMR (CDCl3): δ 7,73 (d, J=9.0 Hz, 2H), 7,09-of 6.90 (m, 5H), of 6.50 (s, 1H), 4,79 (d, J=2.4 Hz, 2H), a 3.87 (s, 2H), 2,58 (t, J=2.4 Hz, 1H), of 2.45 (s, 3H).

Example 7(138)

1-(4-(2-Propen-1-yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.45 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 348 (M-N)-.

NMR (CDCl3): δ 7,71 (d, J=8.7 Hz, 2H), 7,10-of 6.90 (m, 5H), of 6.49 (s, 1H), 6,15-6,00 (m, 1H), 5,50-of 5.40 (m, 1H), 5.40 to-and 5.30 (m, 1H), 4,65-4,60 (m, 2H), a 3.87 (s, 2H), of 2.45 (s, 3H).

Example 7(139)

1-(4-(2-butyn-1 yloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 360 (M-N)-.

NMR (CDCl3): δ 7,72 (d, J=9.0 Hz, 2H), 7,08-6,92 (m, 5H), of 6.49 (s, 1H), 4,78-4,70 (m, 2H), a 3.87 (s, 2H), of 2.45 (s, 3H), of 1.88 (t, J=2,4 Hz, 3H).

Example 7(140)

1-(4-(3-Penten-1 yloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 376 (M-N)-.

NMR (CDCl3): δ of 7.70 (DD, J=6,9, 2,4 Hz, 2 is), 7,05-6,92 (m, 5H), 6.48 in (d, J=0.6 Hz, 1H), 5,70-of 5.40 (m, 2H), of 4.05 (t, J=6.6 Hz, 2H), 3,86 (s, 2H), 2,52 (m, 2H), 2,44 (d, J=0.6 Hz, 3H), 1.69 in (m, 3H).

Example 7(141)

1-(4-(2-(1-Methylindol-Z-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 465 (M-N)-.

NMR (CDCl3): δ 7,70-7,63 (m, 3H), 7,35-7,20 (m, 2H), 7,14 (m, 1H), 7,03 (m, 1H), 7,05-6,93 (m, 5H), 6,47 (d, J=1.2 Hz, 1H), 4,29 (t, J=6.9 Hz, 2H), 3,85 (s, 2H), of 3.77 (s, 3H), of 3.28 (t, J=6.9 Hz, 2H), 2,43 (d, J=1.2 Hz, 3H).

Example 7(142)

1-(4-(2-(1,2,3,4-Tetrahydronaphthalen-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.53 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 452 (M-N)-.

NMR (CDCl3): δ 7,72 (DD, J=6,9, 1.8 Hz, 2H), 7,12-7,10 (m, 4H),? 7.04 baby mortality (m, 1H), 7.03 is-to 6.95 (m, 4H), of 6.49 (s, 1H), was 4.02 (d, J=6.3 Hz, 2H), a 3.87 (s, 2H), 3,01 (DD, J=14 and 4.2 Hz, 1H), 2,92-2,87 (m, 2H), 2,68 (DD, J=14, 10.5 Hz, 1H), of 2.45 (s, 3H), 2,35 (m, 1H), 2,10 (m, 1H), 1,65 (m, 1H).

Example 7(143)

1-(4-(2-(1,2,3,4-Tetrahydroquinolin-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 467 (M-N)-.

NMR (CDCl3): δ of 7.70 (d, J=8.7 Hz, 2H), 7,15-of 6.90 (m, 7H), 6,65-6,55 (m, 2H), 6,47 (s, 1H), 4,22 (t, J=5.7 Hz, 2H), 3,84 (s, 2H), of 3.73 (t, J=5.7 Hz, 2H), 3,44 (t, J=5.7 Hz, 2H), was 2.76 (t, J=5.7 Hz, 2H), 2,43 (s, 3H), 2.00 in 1,90 (m, 2H).

Example 7(144)

1-(4-(2-Hydroxy-(1-hydroxymethyl)ethyloxy)benzoyl)-2-methylindole-4-acetic sour is and

TCX: Rf 0,12 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 382 (M-N)-.

NMR (CDCl3): δ of 7.70 (d, J=8.7 Hz, 2H), 7,10-of 6.90 (m, 5H), of 6.52 (s, 1H), 4,58-4,48 (m, 1H), 3,90 (d, J=6.0 Hz, 4H), 3,83 (s, 2H), 2,44 (s, 3H).

Example 7(145)

1-(4-(2-(2-Ethylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.35 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 440 (M-N)-.

NMR (CDCl3): δ 7,72-to 7.67 (m, 2H), 7,26-to 7.15 (m, 3H), 7,06-of 6.90 (m, 6N), of 6.49 (d, J=0.9 Hz, 1H), 4,23 (t, J=7.5 Hz, 2H), a 3.87 (s, 2H), 3,18 (t, J=7.5 Hz, 2H), 2,74 (sq, J=7.5 Hz, 2H), 2,44 (d, J=0.9 Hz, 3H), of 1.27 (t, J=7.5 Hz, 3H).

Example 7(146)

1-(4-(2-(2-Ethoxymethylene)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.34 (chloroform:methanol = 10:1).

MS: (FAB, position.): 458 (M+H)+.

NMR (CDCl3): δ 7,71-to 7.67 (m, 2H), 7,37-of 7.23 (m, 3H), 7,06-6,93 (m, 6N), 6.48 in (s, 1H), of 4.54 (s, 2H), 4,27 (t, J=7.5 Hz, 2H), 3,86 (s, 2H), 3,41 (s, 3H), 3,21 (t, J=7.5 Hz, 2H), 2,44 (d, J=0.6 Hz, 3H).

Example 7(147)

1-(4-(3,4-Dihydro-2H-benzo[b]Piran-3-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.34 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 454 (M-N)-.

NMR (CDCl3): δ 7,72-the 7.43 (m, 5H), 7,15-PC 6.82 (m, 6N), of 6.49 (s, 1H), 4,36 (m, 1H), 4,17 (m, 1H), 4,08 (d, J=6,9 Hz, 2H), a 3.87 (s, 2H), 3.04 from (DD, J=16.5, and 6.0 Hz, 1H), 2,78 (DD, J=16.5, and a 7.2 Hz, 1H), 2.63 in (m, 1H), 2,44 (d, J=1.2 Hz, 3H).

Example 7(148)

1-(4-(Indan-2-ylmethylene)Ben is oil)-2-methylindole-4-acetic acid

TLC: Rf of 0.35 (chloroform:methanol = 10:1).

MS: (FAB, position.): 440 (M+N)+.

NMR (CDCl3): δ 7,73-to 7.68 (m, 2H), 7,26-6,93 (m, N), of 6.49 (s, 1H), Android 4.04 (d, J=6,9 Hz, 2H), a 3.87 (s, 2H), 3,19 (DD, J=16.5, and 7.5 Hz, 2H), to 3.02 (m, 1H), 2,89 (DD, J=16.5, and of 6.0 Hz, 2H), 2,44 (d, J=1.2 Hz, 3H).

Example 7(149)

1-(4-(2-(1,4-Benzodioxan-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.44 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 470 (M-N)-.

NMR (CDCl3): δ 7,71 (d, J=8.7 Hz, 2H), 7,10-to 6.80 (m, N), of 6.49 (s, 1H), 4,50-and 4.40 (m, 1H), to 4.38-4,17 (m, 3H), 4,01 (DD, J=11,4, 7.2 Hz, 1H), 3,86 (s, 2H), 2,44 (s, 3H), 2,17 (sq, J=6.0 Hz, 2H).

Example 7(150)

1-(4-(3,4-Dihydro-2H-benzo[b]Piran-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf is 0.49 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 454 (M-N)-.

NMR (CDCl3): δ 7,74-to 7.67 (m, 2H), 7,06-6,87 (m, N), of 6.49 (s, 1H), 4,45 (m, 1H), to 4.38-to 4.15 (m, 2H), 3,86 (s, 2H), 3.00 and is 2.80 (m, 2H), 2,44 (s, 3H), 2,30-1,90 (m, 2H).

Example 7 (151)

1-(4-(3,4-Dihydro-2H-1,4-benzoxazin-2-ylmethylene)-benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.25 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 455 (M-N)-.

NMR (CDCl3): δ 7,76-7,40 (m, 3H), 7,10-6,89 (m, 4H), 6.89 in-6,60 (m, 4H), of 6.49 (s, 1H), 4,60 (m, 1H), or 4.31 (DD, J=9,8, 5.0 Hz, 1H), 4,24 (DD, J=9,8, 6.2 Hz, 1H), 3,86 (s, 2H), to 3.58 (DD, J=11.8 in, 3.0 Hz, 1H), 3,42 (DD, J=11.8 in, and 6.6 Hz, 1H), 2,44 (s, 3H).

Example 7(152)

1(4-(4-Methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf 0.26 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 469 (M-N)-.

NMR (CDCl3): δ 7,78-7,40 (m, 3H), 7,10-of 6.78 (m, 6N), was 6.73 (d, J=8.0 Hz, 2H), of 6.49 (s, 1H), and 4.68 (m, 1H), or 4.31 (DD, J=10,0, 5,2 Hz, 1H), 4,20 (DD, J=10,0, 6.4 Hz, 1H), 3,86 (s, 2H), 3,41 (DD, J=11,6, 2.8 Hz, 1H), 3.27 to (DD, J=11,6, and 6.6 Hz, 1H), 2,92 (s, 3H), of 2.44 (s, 3H).

Example 7(153)

1-(4-(1,3-Dioksiinien-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.33 (chloroform:methanol = 10:1).

MS: (FAB, position.): 444 (M+N)+.

NMR (CDCl3): δ 7,74-of 7.69 (m, 2H), 7,06-6,85 (m, N), 6,50-6,47 (m, 2H), 4,35 (d, J=4,2 Hz, 2H), 3,85 (s, 2H), 2,43 (d, J=0.9 Hz, 3H).

Example 7(154)

1-(4-(Benzo[b]furan-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.38 (chloroform:methanol = 10:1).

MS: (FAB, position.): 440 (M+N)+.

NMR (CDCl3): δ 7,76-7,71 (m, 2H), to 7.59 (m, 1H), 7,51 (m, 1H), 7,32 (m, 1H), 7,25 (m, 1H), 7,11-6,92 (m, 5H), at 6.84 (d, J=0.6 Hz, 1H), of 6.49 (m, 1H), 5,26 (s, 2H), a 3.87 (s, 2H), 2,45 (d, J=1.2 Hz, 3H).

Example 7(155)

1-(4-(2,3-Dihydrobenzo[b]furan-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.34 (chloroform:methanol = 10:1).

MS: (EI, position.): 441 (M)+.

NMR (CDCl3): δ 7,73-of 7.69 (m, 2H), 7.23 percent for 7.12 (m, 2H), 7,06-PC 6.82 (m, 7H), of 6.49 (d, J=1.2 Hz, 1H), 5,20 (m, 1H), 4,29 (DD, J=a 9.9, 6.3 Hz, 1H), 4,20 (DD, J=9,9, 4,2 Hz, 1H), 3,86 (s, 2H), 3,42 (DD, J=15,9, 9.6 Hz, 1H), 3,17 (DD, J=15,9, and 8.4 Hz, 1H), 2,44 (d, J=1.2 Hz, 3H).

Example 7(156)

1-(4-(2-(2,5-Acid), ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 10:1).

MS: (FAB, position.): 474 (M+N)+.

NMR (CDCl3): δ of 7.69 (m, 2H), 7,08-6,92 (m, 5H), 6,86-6,72 (m, 3H), 6.48 in (s, 1H), 4,24 (t, J=6,8 Hz, 2H), 3,86 (s, 2H), 3,81 (s, 3H), of 3.77 (s, 3H), of 3.12 (t, J=6,8 Hz, 2H), 2,44 (s, 3H).

Example 7(157)

1-(4-(2,3-Dihydrobenzo[b]furan-3-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.45 (chloroform:methanol = 10:1).

MS: (FAB, position.): 442 (M+N)+.

NMR (CDCl3): δ of 7.70 (m, 2H), 7,31 (d, J=7,4 Hz, 1H), 7,21 (m, 1H), 7,10-PC 6.82 (m, 7H), of 6.49 (s, 1H), 4,73 (t, J=9.6 Hz, 1H), 4,55 (DD, J=9,6, 4.6 Hz, 1H), 4,29-3,88 (m, 3H), 3,86 (s, 2H), 2,44 (s, 3H).

Example 7(158)

1-(4-(2-Cyclopropylmethoxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf is 0.42 (chloroform:methanol = 10:1).

MS: (FAB, position.): 394 (M+N)+.

NMR (CDCl3): δ 7,71 (m, 2H), 7,12-to 6.88 (m, 5H), of 6.49 (s, 1H), 4,19 (t, J=4.6 Hz, 2H), 3,97-3,82 (m, 4H), 3,42 (m, 1H), 2,44 (s, 3H), 0,72 is 0.58 (m, 2H), 0,58-0,46 (m, 2H).

Example 7(159)

1-(4-(2-(2,4-Dimetilfenil)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 440 (M-N)-.

NMR (CDCl3): δ of 7.69 (d, J=9.0 Hz, 2H), 7,12 (d, J=7.5 Hz, 1H), 7,08-of 6.90 (m, 7H), of 6.49 (s, 1H), 4,20 (t, J=7.5 Hz, 2H), a 3.87 (s, 2H), 3,12 (t, J=7.5 Hz, 2H), of 2.45 (s, 3H), of 2.36 (s, 3H), 2,31 (s, 3H).

Example 7(160)

1-(4-(2-(2,6-Dimetilfenil)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf is 0.59 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 440 (M-N)-.

NMR (CDCl3): δ of 7.70 (d, J=9.0 Hz, 2H), 7,09-of 6.90 (m, 8H), of 6.49 (s, 1H), 4,13 (t, J=7.2 Hz, 2H), 3,88 (s, 2H), up 3.22 (t, J=7.2 Hz, 2H), of 2.45 (s, 3H), 2,41 (C, 6N).

Example 7(161)

1-(4-(2-(Benzo[b]thiophene-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf and 0.61 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 468 (M-N)-.

NMR (CDCl3): δ 7,82-7,76 (m, 1H), 7,75-to 7.68 (m, 3H), 7,37-7,24 (m, 2H), 7,16 (s, 1H), 7,08-6,92 (m, 5H), of 6.49 (s, 1H), 4,36 (t, J=6.3 Hz, 2H), a 3.87 (s, 2H), 3.43 points (t, J=6.3 Hz, 2H), 2,44 (s, 3H).

Example 7(162)

1-(4-(2-(2-Methoxyphenoxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf value of 0.52 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 458 (M-N)-.

NMR (CDCl3): δ of 7.70 (d, J=9.0 Hz, 2H), 7.03 is-6,92 (m, N), 6,48 (d, J=0.9 Hz, 1H), 4,42 (s, 4H), 3,85 (s, 3H), of 3.84 (s, 2H), 2,44 (d, J=0.9 Hz, 3H).

Example 7(163)

Acetate 1-(4-(2-(N-ethyl-N-phenylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 10:1).

MC: (APCI, neg.): 455 (M-N)-.

NMR (CDCl3): δ to 7.67 (d, J=9.0 Hz, 2H), 7,26-7,20 (m, 2H),? 7.04 baby mortality-to 6.88 (m, 5H), 6,76 of 6.66 (m, 3H), of 6.45 (d, J=0.9 Hz, 1H), 4,17 (d, J=6,8 Hz, 2H), 3,83 (s, 2H), 3,74 (t, J=6,8 Hz, 2H), 3,47 (sq, J=7.2 Hz, 2H), to 2.42 (d, J=0.9 Hz, 3H),of 2.06 (s, 3H), 1,19 (t, J=7.2 Hz, 3H).

Example 7(164)

1-(4-(2-(Indol-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 10:1).

MC: (APCI, neg.): 451 (M-N)-.

NMR (CDCl3): δ 7.68 per-7,63 (m, 3H), 7,41 (d, J=8.0 Hz, 1H), 7,26-7,21 (m, 2H), 7,14-6,86 (m, 8H), is 6.54 (DD, J=3,0, 0.6 Hz, 1H), 6.48 in (s, 1H), 4,58 (t, J=5.4 Hz, 2H), 4,36 (t, J=5.4 Hz, 2H), 3,86 (s, 2H), 2,42 (, 3H).

Example 7(165)

1-(4-(2-(3-Methylpyridin-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.44 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 427 (M-N)-.

NMR (CDCl3): δ 8,43 (m, 1H), to 7.64 (d, J=6,9 Hz, 2H), 7,49 (m, 1H), 7,21 (d, J=8,1 Hz, 1H), 7,05 (d, J=8,1 Hz, 1H), 7,00-6,85 (m, 4H), 6,53 (d, J=0.9 Hz, 1H), 4,33 (t, J=6.6 Hz, 2H), 3,85 (s, 2H), 3,26 (t, J=6,6 Hz, 2H), 2,41 (d, J=0.9 Hz, 3H), 2,31 (s, 3H).

Example 7(166)

1-(4-(2-(Benzo[b]furan-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform: methanol = 9:1).

MS: (APCI, neg.): 452 (M-N)-.

NMR (CDCl3): δ 7,76-7,42 (m, 4H), 7,30-7,17 (m, 2H), 7,10-of 6.90 (m, 5H), to 6.57 (s, 1H), of 6.49 (s, 1H), 4,42 (t, J=6.6 Hz, 2H), a 3.87 (s, 2H), 3,32 (t, J=6.6 Hz, 2H), 2,44 (s, 3H).

Example 7(167)

1-(4-(4-Methyl-3,4-dihydro-2H-1,4-benzoxazin-3-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.37 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 469 (M-N)-.

NMR (CDCl3): δ 7,72-to 7.67 (m, 2H), 7,06-for 6.81 m, 7H), 6,69-6,62 (m, 2H), of 6.49 (m, 1H), 4,48 (DD, J=11,1, 1.8 Hz, 1H), 4,14 (d, J=7.5 Hz, 2H), 4,13 (DD, J=11,1, 2.4 Hz, 1H), 3,86 (s, 2H), 3,74 (m, 1H), is 3.08 (s, 3H), 2,44 (d, J=1.2 Hz, 3H).

Example 7(168)

1-(4-(2-(2,4-Dimethoxyphenoxy)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf value of 0.52 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 488 (M-N)-.

NMR (CDCl3): δ 7,72 to 7.62 (m, 3H), 7,58 is 7.50 (m, 1H), 7,49-7,41 (m, 1H), 7,06-6,85 (m, 4H), 6,53-6.48 in (m, 2H), to 6.39 (DD, J=8,7, 2.7 Hz, 1H), 4,45-4,30 (m, 4H), 3,85 (s, 2H), 3,83 (s, 3H), of 3.78 (s, 3H), 2,44 (d, J=0.9 Hz, 3H).

Example 7(169)

1-(4-(2-(4-Methylpyridin-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.44 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 427 (M-N)-.

NMR (CDCl3): δ 8,44 (d, J=6,6 Hz, 1H), to 7.64 (d, J=8.7 Hz, 2H), 7,13-6,86 (m, 7H), of 6.52 (d, J=0.8 Hz, 1H), 4,34 (t, J=6.2 Hz, 2H), 3,85 (s, 2H), 3,26 (t, J=6.2 Hz, 2H), 2,41 (d, J=0.8 Hz, 3H), 2,31 (s, 3H).

Example 7 (170)

1-(4-(4-Ethyl-3,4-dihydro-2H-1,4-benzoxazin-3-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf 0.28 in (chloroform:methanol = 10:1).

MS: (APCI, neg.): 483 (M-N)-.

NMR (CDCl3): δ 7,80-EUR 7.57 (m, 2H), 7,10-6,79 (m, 7H), 6,79-6,56 (m, 2H), of 6.49 (s, 1H), 4,68 ñ 4.50 (m, 1H), or 4.31 (DD, J=9,6, and 5.2 Hz, 1H), 4,21 (DD, J=9,6, 6.2 Hz, 1H), 3,86 (s, 2H), 3,57-3,20 (m, 4H), of 2.44 (s, 3H), of 1.17 (t, J=7.4 Hz, 3H).

Example 7(171)

1-(4-(2-(N-Methyl-N-(3-were)amino)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.27 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 455 (M-N)-.

NMR (CDCl3): δ to 7.68 (d, J=8,8 Hz, 2H), 7,21-6,87 (m, 6N), 6,63-of 6.52 (m, 3H), 6.48 in (s, 1H), 4,22 (t, J=6.0 Hz, 2H), 3,85 (s, 2H), 3,79 (t, J=6.0 Hz, 2H), 3,06 (s, 3H), 2,43 (s, 3H), 2,32 (s, 3H).

Example 7(172)

1-(4-(3,4-Dihydro-2H-1,5-benzodioxepin-3-yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.54 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 456 (M-N)-.

NMR (CDCl3): δ 7,78-7,42 (m, 6N), 7,10-of 6.90 (m, 5H), of 6.50 (s, 1H), 5.08 to 4,96 (m, 1H), 4,57 (DD, J=12,6, 4,2 Hz, 2H), 4,47 (DD, J=12,6, 4,2 Hz, 2H), a 3.87 (s, 2H), of 2.45 (s, 3H).

Example 7(173)

1-(4-(3,4-Dihydro-2H-1,5-benzodioxepin-3-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 470 (M-N)-.

NMR (CDCl3): δ 7,78-7,42 (m, 5H), 7,10-of 6.90 (m, 6N), of 6.50 (s, 1H), 4,40-to 4.28 (m, 4H), 4.26 deaths (d, J=6,9 Hz, 2H), a 3.87 (s, 2H), 2,80-2,70 (m, 1H), of 2.45 (s, 3H).

Example 7(174)

1-(4-(1,4-Benzodioxan-6-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.40 (chloroform:methanol = 10:1).

MS: (EI, position.): 457 (M)+.

NM NMR (CDCl3): δ 7,73-to 7.68 (m, 2H), 7,07-of 6.90 (m, 8H), of 6.49 (s, 1H), to 5.03 (s, 2H), 4,27 (s, 4H), a 3.87 (s, 2H), 2,45 (d, J=0.9 Hz, 3H).

Example 7(175)

1-(4-(2-(4-Methoxy-2-were)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.37 (chlorofo the m:methanol = 10:1).

MS: (EI, position.): 457 (M)+.

NMR (CDCl3): δ 7,72-to 7.67 (m, 2H), 7,15 (d, J=8,1 Hz, 1H), 7,06-6,91 (m, 5H), 6,76-of 6.71 (m, 2H), of 6.49 (s, 1H), 4,18 (t, J=7.2 Hz, 2H), 3,86 (s, 2H), 3,79 (s, 3H), to 3.09 (t, J=7.2 Hz, 2H), 2,44 (d, J=0.9 Hz, 3H), is 2.37 (s, 3H).

Example 7(176)

1-(4-(1-Methyl-1,2,3,4-tetrahydroquinolin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf to 0.39 (chloroform:methanol = 10:1).

MS: (EI, position.): 468 (M)+.

NMR (CDCl3): δ 7,72-to 7.67 (m, 2H), 7,12 (m, 1H), 7,06-6,91 (m, 6N), 6,68 return of 6.58 (m, 2H), of 6.49 (m, 1H), 4,13 (DD, J=9,3, 5.7 Hz, 1H), 4,00 (DD, J=9,3, 7.5 Hz, 1H), 3,86 (s, 2H), 3,79 (m, 1H), of 3.07 (s, 3H), 2,89-2,70 (m, 2H), 2,44 (d, J=0.9 Hz, 3H), 2,19 (m, 1H), 2,02 (m, 1H).

Example 7(177)

1-(4-(2-(2,3-Dihydrobenzo[b]furan-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 454 (M-N)-.

NMR (CDCl3): δ 7,72 (d, J=8.7 Hz, 2H), 7,22-6,76 (m, N), of 6.50 (s, 1H), 5,10-5,00 (m, 1H), 4,40-4,20 (m, 2H), 3,88 (s, 2H), 3,41 (DD, J=15,6, and 8.4 Hz, 1H), 2,97 (DD, J=15,6, 7.5 Hz, 1H), 2,46 (s, 3H), 2,35-of 2.15 (m, 2H).

Example 7(178)

1-(4-(4,7-Dimethyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.48 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 483 (M-N)-.

NMR (CDCl3): δ of 7.69 (DD, J=8,8, 2,2 Hz, 2H),? 7.04 baby mortality-of 6.90 (m, 6N), 6,70-6,63 (m, 2H), 6.48 in (s, 1H)and 4.65 (m, 1H), 4,28 (DD, J=7,2, 5,1 Hz, 1H), 4,23 (DD, J=7,2, 2.5 Hz, 1H), 3,85 (s, 2H), 3,32 (DD, J=12,4, 2.6 Hz, 1H), 3,20 DD, J=12,4, 6,6 Hz, 1H), 2,87 (s, 3H), of 2.44 (s, 3H), of 2.23 (s, 3H).

Example 7(179)

1-(4-(4,6-Dimethyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.48 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 483 (M-N)-.

NMR (CDCl3): δ of 7.69 (m, 2H),? 7.04 baby mortality-of 6.90 (m, 6N), was 6.73 (d, J=8.0 Hz, 1H), 6,53 (s, 1H), 6.48 in (s, 1H)and 4.65 (m, 1H), 4,28 (DD, J=7,2, 5,1 Hz, 1H), 4,22 (DD, J=7,2, 2.5 Hz, 1H), 3,85 (s, 2H), 3,35 (DD, J=12,2, 3,0 Hz, 1H), 3,25 (DD, J=12,2, 6.2 Hz, 1H), 2,90 (s, 3H), of 2.44 (s, 3H), and 2.27 (s, 3H).

Example 7(180)

1-(4-(1-Methylindolin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf is 0.49 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 453 (M-N)-.

NMR (CDCl3): δ 7,76-7,66 (m, 2H), 7,20-6,46 (m, 10H), 5,00 is 2.80 (m, 5H), a 3.87 (s, 2H), 2,94 and 2.91 in (each s, total 3H), of 2.45 (s, 3H).

Example 7(181)

1-(4-(4,5-Dimethyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.51 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 483 (M-N)-.

NMR (CDCl3): δ 7,74 (d, J=9.0 Hz, 2H), 7,08-6,84 (m, 6N), 6,82 to 6.75 (m, 2H), 6,50 (s, 1H), 4,55 is 4.45 (m, 1H), 4,36 (DD, J=9,9, 4.5 Hz, 1H), 4,22 (DD, J=9,9, 4.5 Hz, 1H), a 3.87 (s, 2H), 3.27 to (DD, J=13,8, 2.4 Hz, 1H)that is 3.08 (DD, J=13,8, 9.9 Hz, 1H), 2,78 (s, 3H), of 2.45 (s, 3H), of 2.33 (s, 3H).

Example 7(182)

1-(4-(4-Acetyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 497 (M-N)-.

NMR (CDCl3): δ 7,75 to 7.62 (m, 4H), 7,15-of 6.90 (m, 7H), of 6.49 (s, 1H), with 4.64 (USS, 2H), 4,25 (m, 2H), 3,86 (s, 2H), 3,60 (USS, 1H), 2,44 (s, 3H), of 2.35 (s, 3H).

Example 7(183)

1-(4-(3-Acetyl-2,3-dihydro-1,3-benzoxazol-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.34 (chloroform:methanol = 10:1).

MS: (FAB, position.): 485 (M+N)+.

NMR (CDCl3): δ to 7.67 (d, J=9,3 Hz, 2H), 7,10-of 6.90 (m, N), 6,66 (USS, 1H), 6.48 in (s, 1H), 4,40 (USS, 2H), 3,86 (s, 2H), 2,43 (s, 3H), 2,43 (d, J=0.9 Hz, 3H).

Example 7(184)

1-(4-(4,6,8-Trimethyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.36 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 497 (M-N)-.

NMR (CDCl3): δ 7,74-of 7.69 (m, 2H), 7,07-6,93 (m, 5H), of 6.49 (s, 1H), 6,40 (s, 1H), 6,40 (s, 1H)and 4.65 (m, 1H), or 4.31 (DD, J=9,9, 4.8 Hz, 1H), 4,21 (DD, J=a 9.9, 6.3 Hz, 1H), a 3.87 (s, 2H), 3,39 (DD, J=11,7, 2.7 Hz, 1H), 3,24 (DD, J=11,7, 6.0 Hz, 1H), 2,89 (s, 3H), of 2.45 (d, J=0.6 Hz, 3H), 2,24 (s, 3H), and 2.14 (s, 3H).

Example 7(185)

1-(4-((3Z)-3-HEXEN-1-yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf value of 0.52 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 390 (M-N)-.

NMR (CDCl3): δ of 7.70 (DD, J=6,9, and 2.1 Hz, 2H), 7,06-6,92 (m, 5H), 6.48 in (d, J=0.9 Hz, 1H), 5.56mm (m, 1H), 5.40 to (m, 1H), of 4.05 (t, J=6.9 Hz, 2H), 3,86 (s, 2H), 2.57 m (m, 2H), 2,44 (d, J=0.9 Hz, 3H), 2,11 (m, 2H), to 1.00 (t, J=7.2 Hz, 3H).

Example 7(186)

p> 1-(4-(4-Methyl-1,3-dioksiinien-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf value of 0.52 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 456 (M-N)-.

NMR (CDCl3): δ 7,71 (DD, J=6,9, and 2.1 Hz, 2H),? 7.04 baby mortality-to 6.95 (m, 5H), 6,80 is 6.67 (m, 2H), 6.48 in-6,44 (m, 2H), 4,35 (d, J=4,2 Hz, 2H), 3,85 (s, 2H), 2,44 (d, J=0.9 Hz, 3H), of 2.23 (s, 3H).

Example 7(187)

1-(4-(5-Methyl-1,3-dioksiinien-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf value of 0.52 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 456 (M-N)-.

NMR (CDCl3): δ 7,71 (m, 2H), 7,06-6,92 (m, 6N), 6,75-of 6.65 (m, 2H), of 6.49-6,44 (m, 2H), 4,32 (d, J=4,2 Hz, 2H), 3,86 (s, 2H), 2,44 (d, J=0.9 Hz, 3H), to 2.29 (s, 3H).

Example 7(188)

1-(4-((4E)-4-HEXEN-1-yloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.40 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 390 (M-N)-.

NMR (CDCl3): δ 7,72-to 7.67 (m, 2H), 7,05-6,92 (m, 5H), 6.48 in (s, 1H), 5,56-of 5.40 (m, 2H), Android 4.04 (t, J=6.6 Hz, 2H), 3,85 (s, 2H), 2,44 (d, J=0.9 Hz, 3H), 2,22 with 2.14 (m, 2H), 1,92 of-1.83 (m, 2H), 1,67-of 1.65 (m, 3H).

Example 7(189)

1-(4-((3E)-3-HEXEN-1-yloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.38 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 390 (M-N)-.

NMR (CDCl3): δ 7,72-to 7.68 (m, 2H), 7,06-6,93 (m, 5H), 6.48 in (s, 1H), 5,64 (dt, J=15,3, 6.0 Hz, 1H), 5,48 (dt, J=15,3, and 6.6 Hz, 1H), of 4.05 (t, J=6.9 Hz, 2H), 3,86 (s, 2H), 2,52 (dt, J=6,6 and 6.9 Hz, 2H), 2,44 (d, J=0.9 Hz, 3H), 2.05 is (DQC., J=6,0, 7 Hz, 2H), 0,99 (t, J=7.5 Hz, 3H).

Example 7(190)

1-(4-(3-(N-Methyl-N-phenylamino)propylacetate)-5-methylindole-4-acetic acid

TCX: Rf of 0.44 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 455 (M-N)-.

NMR (CDCl3): δ 7,71 (d, J=9.0 Hz, 2H), 7,26-7,16 (m, 2H), 7,08-6,92 (m, 5H), 6,79 of 6.66 (m, 3H), of 6.49 (s, 1H), 4.09 to (t, J=5.7 Hz, 2H), a 3.87 (s, 2H), only 3.57 (t, J=6.9 Hz, 2H), 2,60 (s, 3H), of 2.45 (s, 3H), 2,20-2,00 (m, 2H).

Example 7(191)

1-(4-(4-Methanesulfonyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 533 (M-N)-.

NMR (CDCl3): δ 7,72 (m, 3H), 7,12-6,91 (m, 8H), of 6.50 (s, 1H), 4,56 (USS, 1H), 4,46-4.26 deaths (m, 3H), 3,88 (s, 2H), only 3.57 (DD, J=13,8, and 9.3 Hz, 1H), to 3.02 (s, 3H) at 2.45 (s, 3H).

Example 7(192)

1-(4-(4-Methyl-7-methoxy-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.40 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 499 (M-N)-.

NMR (CDCl3): δ 7,75 to 7.62 (m, 4H),? 7.04 baby mortality-of 6.90 (m, 4H), of 6.66 (d, J=9.0 Hz, 1H), of 6.49 (s, 1H), 6.48 in (d, J=9.0 Hz, 1H), 4,70 (m, 1H), 4,30 (DD, J=12,0, a 5.4 Hz, 1H), 4,24 (m, 1H), a 3.87 (s, 2H), 3,74 (s, 3H), 3.33 and (DD, J=11,4, 2.7 Hz, 1H), 3,18 (DD, J=11,7, 6,6, 1H), 2,86 (s, 3H), of 2.45 (s, 3H).

Example 7(193)

1-(4-(2,2-Dimethyl-1,3-dioxolane-4-ylmethylene)benzoyl)2-methylindole-4-acetic acid

TCX: Rf of 0.38 (chloroform:methanol = 10:1).

MC (FAB, position.): 424 (M+N)+.

NMR (CDCl3): δ 7,73-to 7.68 (m, 2H), 7,06-6,92 (m, 5H), 6.48 in (s, 1H), to 4.52 (m, 1H), 4,20 (DD, J=8,4, and 6.6 Hz, 1H), 4,13 (DD, J=9,6, 5.7 Hz, 1H), Android 4.04 (DD, J=9,6, 5.7 Hz, 1H), 3,94 (DD, J=8,4, 5.7 Hz, 1H), 3,86 (s, 2H)that is 2.44 (s, 3H), of 1.48 (s, 3H), of 1.42 (s, 3H).

Example 7(194)

1-(4-(6-Fluoro-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 10:1).

MS: (APCI, position.): 489 (M+N)+.

NMR (CDCl3): δ 7,72 (d, J=8.7 Hz, 2H), 7,08-of 6.90 (m, 5H), 6,74 (DD, J=8,7, 5.4 Hz, 1H), 6,50 (s, 1H), 6.35mm (m, 2H), 4,60 (m, 1H), 4,30 (DD, J=9,9, 5,1 Hz, 1H), 4,19 (DD, J=a 9.9, 6.3 Hz, 1H), a 3.87 (s, 2H), 3,41 (DD, J=11,7, 3.6 Hz, 1H), 3,30 (DD, J=11,7, and 6.6 Hz, 1H), 2.91 in (s, 3H), of 2.45 (s, 3H).

Example 7(195)

1-(4-(4,5-Dimethyl-1,3-dioxolane-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.35 (chloroform:methanol = 10:1).

MS: (EI, position.): 423 (M)+.

NMR (CDCl3): δ 7,72-to 7.67 (m, 2H), 7,05-of 6.90 (m, 5H), 6.48 in (s, 1H), 5,54 and 5,44 and 5,27 (each t, J=4,2 Hz, total 1H), 4,36-4 : 31 and 4,28-to 4.23 and 3.74 at 3.69 (each m, total 2H), 4,14 and 4.09 to and a 4.03 (each d, J=4,2 Hz, total 2H), 3,85 (s, 2H), 2,44 (d, J=0,6 Hz, 3H), 1,38-1,17 (m, 6N).

Example 7(196)

1-(4-((3Z)-3-Penten-1 yloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 376 (M-N)-.

NMR (CDCl3): δ of 7.69 (m, 2H), 7,08-6,93 (m, 5H), of 6.49 (d, J=1.2 Hz, 1H), 5,64-of 5.40 (m, 2H), 4,06 (t, J=7,0 Hz, 2H), 3,86 (s, 2 is), 2,60 (m, 2H), 2,44 (d, J=1.2 Hz, 3H), of 1.70 (m, 3H).

Example 7(197)

1-(4-(1,3-Benzodithiol-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.51 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 458 (M-N)-.

NMR (CDCl3): δ of 7.70 (m, 2H), 7,25-7,20 (m, 2H), 7,19-7,10 (m, 1H), 7,08-PC 6.82 (m, 6N), 6.48 in (s, 1H), 6,36 (DD, J=6,9, and 4.5 Hz, 1/5H), 6,13 (DD, J=4.2, and 2.1 Hz, 4/5H), of 4.45 (DD, J=10,5, 6,9 Hz, 1/5H), 4,17 (dd, J=10,5, 4.5 Hz, 1/5H), of 3.84 (s, 2H), 3,34 (DD, J=13,2, 2.1 GHz, 4/5H), 3,23 (DD, J=13,2, 4,2 Hz, 4/5H), 2,43 (s, 3H).

Example 7(198)

1-(4-(1,4-Benzodioxan-5-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.50 (chloroform:methanol = 10:1).

MS: (APCI, position.): 471 (M+H)+.

NMR (CDCl3): δ of 7.69 (d, J=8.7 Hz, 2H), 7,10-of 6.90 (m, 5H), to 6.80 (s, J=8,7, 3H), 6.48 in (s, 1H), 4,34-4,18 (m, 6N), 3,86 (s, 2H), 3,12 (t, J=7.2 Hz, 2H), 2,44 (s, 3H).

Example 7 (199)

1-(4-(1,4-Benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.25 (chloroform:methanol = 10:1).

MS: (FAB, position.): 474 (M+N)+.

NMR (CDCl3): δ 7,73 (d, J=8.7 Hz, 2H), 7,12-6,83 (m, N), of 6.49 (s, 1H), and 4.68 (m, 1H), 4,37 (DD, J=of 9.6, 4.8 Hz, 1H), 4.26 deaths (DD, J=a 9.6, 6.3 Hz, 1H), 3,86 (s, 2H), 3,26 is 3.15 (m, 2H), of 2.45 (s, 3H).

Example 7(200)

1-(4-(1,4-Benzoxazin-S,S-dioxide-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.15 (chloroform:methanol = 10:1).

MS: (FAB, position.): 506 (M+N)+.

YAM is (CDCl 3): δ 7,88-of 7.60 (m, 4H), 7,60-7,40 (m, 3H), 7.23 percent-7,10 (m, 1H), 7,10-6,85 (m, 3H), of 6.50 (s, 1H), 5.25 in (m, 1H), 4,48 (DD, J=10,2, 4,2 Hz, 1H), and 4.40 (DD, J=10,2, 4,2 Hz, 1H), 3,86 (s, 2H), 3,76 (DD, J=13,8, 12,0 Hz, 1H), to 3.58 (DD, J=13,8, 1.5 Hz, 1H), of 2.45 (s, 3H).

Example 7(201)

1-(4-(Pyrazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.50 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 400 (M-N)-.

NMR (CDCl3): δ 8,86 (S, 1H), 8,65-8,55 (m, 2H), 7,74 (d, J=8.7 Hz, 2H), 7,13-of 6.90 (m, 5H), of 6.50 (s, 1H), 5,33 (s, 2H), a 3.87 (s, 2H), of 2.45 (s, 3H).

Example 7(202)

1-(4-(2,3-Dihydro-1-ethylindole-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.45 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 467 (M-N)-.

NMR (CDCl3): δ 7,76-to 7.68 (m, 2H), 7,16-6,44 (m, 10H), 5,00 is 2.80 (m, 7H), a 3.87 (s, 2H), of 2.45 (s, 3H), 1,20-1,10 (m, 3H).

Example 7(203)

1-(4-(2,3,4,5-Tetrahydrofuran-Z-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.33 (chloroform:methanol = 9:1).

MS: (MALDI, position.): 393 (M+H)+, 416 (M+Na)+.

NMR (CDCl3): δ 7,71 (d, J=8.7 Hz, 2H), 7,08-6,98 (m, 3H), 6,95 (d, J=8.7 Hz, 2H), of 6.49 (s, 1H), 4,05-3,70 (m, 8H), 2,85-of 2.72 (m, 1H), 2,44 (s, 3H), 2,22-of 2.08 (m, 1H), 1,82 is 1.70 (m, 1H).

Example 7 (204)

1-(4-(2-(2-Phenyl-5-methoxazole-4-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.47 (chloroform:methanol = 9:1).

MS: (FAB, position.): 495 (M+N)+.

Example 7(205)

1-(4-(2-(2,3-Acid), ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf 0.5 (chloroform:methanol = 10:1).

MC: (APCI, position.): 474 (M+N)+.

NMR (CDCl3): δ of 7.69 (d, J=9.0 Hz, 2H), 7,08-6,92 (m, 6N), 6,86 (m, 2H), 6.48 in (s, 1H), 4,25 (t, J=7.5 Hz, 2H), 3,88 (C, 6N), of 3.84 (s, 2H), 3.15 in (t, J=7.5 Hz, 2H), 2,44 (s, 3H).

Example 7 (206)

1-(4-(4-Methyl-6-triftorperasin-2-ylmethylene)-benzoyl)-2-methylindole-4-acetic acid

TCX: Rf 0.5 (chloroform:methanol = 10:1).

MC: (APCI, position.): 539 (M+N)+.

NMR (CDCl3): δ 7,73 (d, J=9.0 Hz, 2H), 7,06-6,86 (m, 8H), of 6.50 (s, 1H), 4,70 (m, 1H), or 4.31 (DD, J=9,9, 4.8 Hz, 1H), 4,21 (DD, J=a 9.9, 6.3 Hz, 1H), a 3.87 (s, 2H), of 3.45 (DD, J=11,7, 2.7 Hz, 1H), 3,33 (DD, J=11,7, 6,6 Hz, 1H), 2,96 (s, 3H), of 2.45 (s, 3H).

Example 7 (207)

1-(4-(2-(1,2,3,4-Tetrahydronaphthalen-5-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.4 (chloroform:methanol = 10:1).

MC: (APCI, position.): 468 (M+N)+.

NMR (CDCl3): δ of 7.69 (d, J=9.0 Hz, 2H), 7,10-6,92 (m, 8H), of 6.49 (s, 1H), 4,22 (t, J=7.5 Hz, 2H), 3,86 (s, 2H), 3,12 (t, J=7.5 Hz, 2H), and 2.79 (m, 4H), of 2.44 (s, 3H), 1,89-to 1.77 (m, 4H).

Example 7(208)

1-(4-Cinoxacin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.38 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 450 (M-N)-.

NMR (CDCl3): δ 9,12 (s, 1H), 8,20-8,08 (m, 2H), 7,88 for 7.78 (m, 2H), of 7.75 (d, J=9.0 Hz, 2H), and 7.3 (d, J=9.0 Hz, 2H), 7,10-of 6.90 (m, 3H), of 6.50 (s, 1H), 5,51 (s, 2H), 3,88 (s, 2H), of 2.45 (s, 3H).

Example 7(209)

1-(4-(6-Chloro-4-methylbenzothiazol-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.38 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 503 (M-N)-.

NMR (CDCl3): δ 7,72 (d, J=9.0 Hz, 2H), 7,08-of 6.90 (m, 5H), 6,74 (DD, J=7,8, and 0.9 Hz, 1H), 6,68-6,60 (m, 2H), of 6.49 (t, J=0.9 Hz, 1H), 4,68-4,56 (m, 1H), 4,29 (DD, J=9,9, 4.8 Hz, 1H), 4,19 (DD, J=9,9, 6.0 Hz, 1H), a 3.87 (s, 2H), 3,41 (DD, J=11,7, 2.7 Hz, 1H), 3,29 (DD, J=11,7, and 6.6 Hz, 1H), 2.91 in (s, 3H), of 2.45 (s, 3H).

Example 7(210)

1-(4-(2-(6,6-Dimethyl[3.1.1]bisiklet-2-enyl)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf value of 0.52 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 456 (M-N)-.

Example 7(211)

1-(4-([2.2.1]Bicycloheptane-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf value of 0.52 (chloroform:methanol = 10:1

MC: (APCI, neg.): 416 (M-N)-.

Example 7(212)

1-(4-(Oxetan-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf value of 0.52 (chloroform:methanol = 10:1).

MC: (APCI, neg.): 378 (M-N)-.

Example 7(213)

1-(4-(4-Methylpyrazine[2,3-b]oxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.34 (chloroform:methanol = 10:1).

MS: (FAB, position.): 473 (M+N)+.

NMR (CDCl3): δ 7,75-7,71 (who, 3H), the 7.43 (d, J=3.3 Hz, 1H), 7,07-6,92 (m, 5H), of 6.50 (s, 1H), 4,80 (m, 1H), and 4.40 (DD, J=9,9, 4.5 Hz, 1H), 4.26 deaths (DD, J=9,9, and 6.6 Hz, 1H), a 3.87 (s, 2H), 3,65 (DD, J=12,3, 3.3 Hz, 1H)and 3.59 (DD, J=12,3, 6,9 Hz, 1H), 3,17 (s, 3H), of 2.45 (d, J=0.9 Hz, 3H).

Example 7(214)

1-(4-(Tetrahydropyran-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.44 (chloroform:methanol = 9:1).

MS: (FAB, position.): 407 (M+N)+.

Example 7(215)

1-(4-(2-(N-(2-Cyanoethyl)-N-phenylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic acid

TCX: Rf of 0.40 (chloroform:methanol = 9:1).

MS: (FAB, glycerol + m-NBA): 482 (M+H)+.

Example 7(216)

1-(4-(1,4-Dimethyl-1,2,3,4-tetrahydroquinoxalin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.48 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 482 (M-N)-.

NMR (CDCl3): δ of 7.70 (d, J=9.0 Hz, 2H), 7,08-6,92 (m, 5H), 6,80 of 6.66 (m, 2H), 6,62-6.48 in (m, 3H), 4,27-4,07 (m, 2H), a 3.87 (s, 2H), 3,83-to 3.73 (m, 1H), 3,36-3,20 (m, 2H), 3,05 (s, 3H), 2,88 (s, 3H), of 2.45 (s, 3H).

Example 7(217)

1-(4-(5-fluoro-4-methyl-3,4-dihydro-2H-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.47 (chloroform:methanol = 9:1).

MS: (b.): 488 (M)+.

NMR (CDCl3): δ 7,72 (d, J=9.0 Hz, 2H), 7,08-of 6.90 (m, 5H), 6,83-of 6.73 (m, 1H), 6,58-of 6.45 (m, 3H), 4,76-of 4.66 (m, 1H), 4,37 (DD, J=9,9, 5,1 Hz, 1H), 4,24 (DD, J=9,9, and 6.6 Hz, 1H), a 3.87 (s, 2H), 3.46 in (DD, J=12,0, 2.7 Hz, 1H), 3,34 (DD, J=12,0, 6.6 G is, 1H), equal to 2.94 (s, 3H), of 2.45 (s, 3H).

Example 7(218)

1-(4-(4,8-Dimethyl-3,4-dihydro-2H-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.48 (chloroform:methanol = 9:1).

MS: (neg.): 483 (M-N)-.

NMR (CDCl3): δ 7,76-7,66 (m, 2H), 7,08-of 6.90 (m, 6N), 6,82-6,74 (m, 1H), return of 6.58 (d, J=7.5 Hz, 1H), of 6.49 (s, 1H), 4,74 with 4.64 (m, 1H), 4,33 (DD, J=9,9, a 5.4 Hz, 1H), 4,23 (DD, J=a 9.9, 6.3 Hz, 1H), a 3.87 (s, 2H), 3,41 (DD, J=11,4, 2.7 Hz, 1H), 3,26 (DD, J=11,4, 6.3 Hz, 1H), 2.91 in (s, 3H), of 2.45 (s, 3H), of 2.18 (s, 3H).

Example 7(219)

1-(4-(4-Methyl-3,4-dihydro-2H-benzothiazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.48 (chloroform:methanol = 10:1).

MS: (APCI, neg.): 485 (M-N)-.

NMR (CDCl3): δ to 7.68 (d, J=8.7 Hz, 2H), 7,22-6,92 (m, 7H), 6,70-of 6.65 (m, 2H), 6,47 (s, 1H), 4,27 (DD, J=9,6, and 9.3 Hz, 1H), 4,16 (DD, J=9,3, 5,1 Hz, 1H), 3,83 (s, 2H), to 3.67 (m, 1H), only 3.57 (m, 2H), 2.91 in (s, 3H), 2,42 (s, 3H).

Example 7(220)

1-(4-(4-Methyl-3,4-dihydro-2H-pyrido[3,2-b]oxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.35 (chloroform:methanol = 9:1).

MS: (FAB, position.): 472 (M+H)+.

NMR (CDCl3): δ 7,81 (DD, J=5,1, 1.8 Hz, 1H), 7,73 (d, J=8.7 Hz, 2H), 7,10-of 6.90 (m, 6N), 6,56 (DD, J=7,8, 5,1 Hz, 1H), 6,50 (s, 1H), 4,67-4,58 (m, 1H), or 4.31 (DD, J=9,9, 5,1 Hz, 1H), 4,20 (DD, J=9,9, 6.0 Hz, 1H), a 3.87 (s, 2H), to 3.58 (DD, J=12,0, 3.0 Hz, 1H), 3,49 (DD, J=12,0, 6,9 Hz, 1H), 3.15 in (s, 3H), of 2.45 (s, 3H).

Example 7(221)

1-(4-(4-Methyl-3,4-dihydro-2H-pyrido[2,3-b]oxazin-2 elmete is hydroxy)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.40 (chloroform:methanol = 10:1).

MS: (FAB, position.): 472 (M+N)+.

NMR (CDCl3): δ 7,74-of 7.69 (m, 2H), to 7.67 (DD, J=5,1, 1.5 Hz, 1H), 7,05-6,85 (m, 7H), 6,51 (s, 1H), 4,82 (m, 1H), 4,37 (DD, J=9,6, 4,2 Hz, 1H), 4,23 (DD, J=a 9.6 and 6.9 Hz, 1H), a 3.87 (s, 2H), of 3.45 (DD, J=12,0, 3.3 Hz, 1H), and 3.31 (DD, J=12,0, 7,0 Hz, 1H), 2,92 (s, 3H), 2,44 (d, J=0.9 Hz, 3H).

Example 7(222)

1-(4-(7-Fluoro-4-methyl-3,4-dihydro-2H-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.33 (chloroform:methanol = 9:1).

MS: (MARDI, position.): 488 (M)+.

NMR (CDCl3): δ to 7.77-to 7.61 (m, 2H), to 7.59-7,41 (m, 2H), 7,08-of 6.90 (m, 4H), 6,60 (d, J=8.1 Hz, 2H), 6,50 (s, 1H), 4.75 in with 4.65 (m, 1H), 4,34-4,18 (m, 2H), 3,86 (s, 2H), 3,40-3,18 (m, 2H), 2,87 (s, 3H), of 2.44 (s, 3H).

Example 7(223)

1-(4-(7-Cyano-4-methyl-3,4-dihydro-2H-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf 0.31 in (chloroform:methanol = 9:1

MC: (APCI, position.): 495 (M)+, 518 (M+Na)+.

NMR (CDCl3): δ 7,72 (d, J=8.7 Hz, 2H), 7,09-PC 6.82 (m, 8H), of 6.50 (s, 1H), 4,78-of 4.67 (m, 1H), 4,35-4,18 (m, 2H), a 3.87 (s, 2H), 3,49-3,30 (m, 2H), 2.95 and (s, 3H), of 2.45 (s, 3H).

Example 7(224)

1-(4-(4-Methyl-6-methoxy-3,4-dihydro-2H-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.40 (chloroform:methanol = 10:1).

MC: (APCI, position.): 501 (M+N)+.

NMR (CDCl3): δ 7,72 (d, J=8.7 Hz, 2H), 7,08-of 6.90 (m, 5H), to 6.75 (d, J=8.7 Hz, 1H), of 6.49(s, 1H), 6,29 (d, J=2.7 Hz, 1H), 6,23 (DD, J=8,7, 2.7 Hz, 1H), br4.61 (m, 1H), 4,30 (DD, J=9,9, 4.8 Hz, 1H), 4,18 (m, 1H), a 3.87 (s, 2H), 3,76 (s, 3H), 3,40 (DD, J=11,4, 9.0 Hz, 1H), or 3.28 (DD, J=11,4, 6,Hz, 1H), only 2.91 (s, 3H), of 2.44 (s, 3H).

Example 7(225)

1-(4-(1-Methylindolin-3-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.47 (chloroform:methanol = 9:1).

MS: (APCI, neg.): 453 (M-N)-.

NMR (CDCl3): δ 7,74-to 7.68 (m, 3H), 7,22-7,10 (m, 2H), 7,08-of 6.90 (m, 4H), 6,72 (t, J=6,6 Hz, 1H), 6,53 (d, J=8,1 Hz, 1H), of 6.49 (s, 1H), 4,24-4,06 (m, 2H), a 3.87 (s, 2H), 3,78-3,70 (m, 1H), 3,49 (t, J=8,1 Hz, 1H), to 3.38 (DD, J=9,0, 5,1 Hz, 1H), and 2.79 (s, 3H), of 2.45 (s, 3H).

Example 7(226)

1-(4-(4-Methyl-3,4-dihydro-2H-benzoxazin-2-yl)carbylamine)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.48 (chloroform:methanol = 10:1).

MC: (APCI, neg.): 482 (M-N)-.

NMR (CDCl3): δ 8,53 (s, 1H), 7,72 (s, 4H), 7,20-of 6.90 (m, 5H), 6,80-6,70 (m, 2H), of 6.49 (s, 1H), 4,89 (DD, J=6,9, and 3.3 Hz, 1H), 3,85 (s, 2H), only 3.57 (DD, J=12,0, 3.3 Hz, 1H), 3,44 (DD, J=12,0, 6,9 Hz, 1H), 2,92 (s, 3H), 2,49 (s, 3H).

Example 7(227)

1-(4-N-Methyl-N-(4-methyl-3,4-dihydro-2H-benzoxazin-2-ylcarbonyl)amino)benzoyl)-2-methylindole-4-acetic acid

TLC: Rf of 0.48 (chloroform:methanol = 10:1).

NMR (CDCl3): δ to 7.77 (d, J=8.7 Hz, 2H), 7,43 (d, J=8.7 Hz, 2H), 7,05 (d, J=6.3 Hz, 1H), 6.90 to to 6.75 (m, 3H), 6,70-6,55 (m, 3H), of 6.49 (s, 1H), 4,77 (USD, J=6.3 Hz, 1H), 3,84 (s, 2H), 3,53 (DD, J=12,0, 7.8 Hz, 1H), 3,40 (s, 3H), 3,30 (DD, J=12,0, 2.4 Hz, 1H), 2,86 (s, 3H), 2,41 (s, 3H).

Example 7(228)

TLC: Rf value of 0.52 (chloroform:methanol = 10:1).

NMR (CDCl3): δ of 7.69 (d, J=9,3 Hz, 2H), 7,07-to 6.88 (m, 5H), 6.48 in (s, 1H), 4,50-4,30 (m, 1H), 4,17-3,95 (m, 2H), 3,85 (s, 2H), 3,42 (DD, J=16.5, and 8,1 Hz, 1H), 2,50-2,20 (m) 2,44 (s) total 5H, 2,09-1,94 (m) and 1.79-1,67 (m) just 1H, 1,50-1,22 (m, 1H), 1,15-of 1.05 (m, 3H).

In addition, the compound obtained in example 7(224), can be obtained following the procedures analogous series of reactions of reference example 22 → reference example 23 → reference example 24 → reference example 25 → reference example 26 → reference example 27 → reference example 28 → example 8.

Reference example 22

2-Etoxycarbonyl-6-methoxy-3,4-dihydro-2H-benzoxazin

To a solution of 2-amino-4-methoxyphenol (5.5 g) in acetone (200 ml) is added potassium carbonate (5 g) and the mixture was stirred at 40°C in argon atmosphere. To the mixture is added dropwise ethyl 1,2-dibromopropionate and potassium carbonate (15 g) and the mixture is refluxed for 15 hours. After cooling to room temperature the mixture is filtered. The filtrate is poured into water and then extracted with ethyl acetate (3 times). The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (n-hexane:atilas is tat = 10:1), getting named the title compound (1.65 g)having the following physical data.

TLC: Rf of 0.44 (n-hexane:ethyl acetate = 2:1).

Reference example 23

2-Hydroxymethyl-6-methoxy-3,4-dihydro-2H-benzoxazin

To a solution of lithium aluminum hydride (560 mg) in tetrahydrofuran (50 ml) in an argon atmosphere is added dropwise a solution of the compound obtained in the above referential example (1.65 g)in tetrahydrofuran (30 ml) and the mixture is stirred for 15 minutes. To the reaction mixture is added saturated aqueous solution of sodium chloride and the mixture extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (n-hexane:ethyl acetate = 4:1), getting named the title compound (1.3 g)having the following physical data.

TLC: Rf to 0.17 (n-hexane:ethyl acetate = 2:1).

Reference example 24

2-Hydroxymethyl-6-methoxy-4-methyl-3,4-dihydro-2H-benzoxazin

To a solution of compound (1.3 g)obtained in the above reference example, in a mixture of acetone (50 ml) - N,N-dimethylformamide (10 ml) is added potassium carbonate (10 g) and methyliodide (3 ml) and the mixture was stirred at 58°C for 2 hours. To the mixture we use the t methyliodide (3 ml), and the mixture is stirred for 12 hours. The reaction mixture was poured into water and then extracted with ethyl acetate (3 times). The organic layer was washed with saturated aqueous sodium chloride and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (n-hexane:ethyl acetate = 2:1), getting named the title compound (140 mg)having the following physical data.

TLC: Rf of 0.25 (n-hexane:ethyl acetate = 2:1).

Reference example 25

Benzyl ether of 2-methylindole-4-acetic acid

To a solution of compound (55,0 g)obtained in reference example 5 in N,N-dimethylformamide (500 ml) with vigorous stirring in an argon atmosphere add potassium carbonate (109 g). To the mixture add benzylbromide (34,6 ml) and the mixture is stirred at room temperature for 2 hours. The reaction solution was poured into water (2000 ml) and extracted with toluene. The organic layer is successively washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure. The residue is purified column chromatography on silica gel (n-hexane:ethyl acetate = 5:1), getting named the title compound (70,3 g)having the following physical data.

The SH: Rf 0,85 (n-hexane:ethyl acetate = 1:1).

Reference example 26

Benzyl ester 1-(4-acetoxybenzoic)-2-methylindole-4-acetic acid

A mixture of 4-acetoxybenzoic acid (516 mg) and oxalicacid (0.5 ml) is stirred for 30 minutes. The mixture is concentrated under reduced pressure, obtaining 4-acetoxybenzoic.

To a solution of the compound (400 mg)obtained in reference example 25, in methylene chloride (7 ml) at room temperature is added sodium hydroxide (286 mg) and tetrabutylammonium (20 mg). The mixture was added to the solution obtained above 4-acetoxybenzoic in methylene chloride (3 ml) and the mixture is stirred at room temperature overnight. The reaction mixture is filtered and the filtrate concentrated under reduced pressure. The residue is purified column chromatography on silica gel (n-hexane:ethyl acetate = 7:3), getting named the title compound (500 mg)having the following physical data.

TLC: Rf 0.34 in (n-hexane:ethyl acetate = 7:3).

NMR (CDCl3): δ 7,76 (d, J=8.7 Hz, 2H), 7,40-7,20 (m, 7H), 7,08-6,92 (m, 3H), 6,47 (s, 1H), further 5.15 (s, 2H), 3,88 (s, 2H), 2.40 a (s, 3H), of 2.35 (s, 3H).

Reference example 27

Benzyl ester 1-(4-hydroxybenzoyl)-2-methylindole-4-acetic acid

The compound (500 mg)obtained in reference example 26, dissolved in a mixture of 5% solution of piperidine-methylene chloride (5 ml) and the mixture paramashiva the t for 1 hour. The reaction mixture was concentrated and the residue purified column chromatography on silica gel (chloroform:methanol = 19:1), getting named the title compound (450 mg)having the following physical data.

TLC: Rf and 0.61 (chloroform:methanol = 9:1).

NMR (CDCl3): δ 7,72 (m, 2H), 7,44-7,26 (m, 5H), 7,08-6,84 (m, 5H), of 6.45 (s, 1H), of 5.83 (USS, 1H), further 5.15 (s, 2H), 3,88 (s, 2H), 2,42 (s, 3H).

Reference example 28

Benzyl ester 1-(4-(6-methoxy-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

To a solution of compound (60 mg)obtained in reference example 24 in methylene chloride (10 ml) was successively added triphenylphosphine (76 mg), compound (95 mg)obtained in reference example 27, and diethylazodicarboxylate (126 mg) and the mixture is stirred for 3 hours. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (n-hexane:ethyl acetate = 4:1)to give the compound of the present invention (85 mg)having the following physical data.

TLC: Rf of 0.57 (n-hexane:ethyl acetate = 1:1).

NMR (CDCl3): δ 7,71 (d, J=9.0 Hz, 2H), 7,32 (m, 5H), 7,08-of 6.90 (m, 5H), to 6.75 (d, J=8,4 Hz, 1H), 6,46 (s, 1H), 6,28 (d, J=2.7 Hz, 1H), 6,23 (DD, J=8,7, 27 Hz, 1H), further 5.15 (s, 2H), 4,60 (m, 1H), 4,27 (DD, J=9,9, and 6.6 Hz, 1H), 4,18 (DD, J=a 9.9, 6.3 Hz, 1H), 3,88 (s, 2H), 3,76 (s, 3H), 3,39 (DD, J=11,7, 2.7 Hz, 1H), 3.27 to (DD, J=11,7, and 6.6 Hz, 1H), 2,90 (s, 3H), 2,42 (s, 3H).

Example 8 (same connection as in example 7(224))

1-(4-(6-Methoxy-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethylene)benzoyl)-2-methylindole-4-acetic acid

Mix the compound (50 mg)obtained in the above-described example, ethyl acetate (5 ml) and palladium hydroxide (100 mg). The mixture is stirred for 2 hours in argon atmosphere. The reaction mixture is filtered and the filtrate concentrated under reduced pressure. The residue is purified column chromatography on silica gel (chloroform:methanol = 10:1)to give the compound of the present invention (85 mg)having the following physical data.

TLC: Rf of 0.40 (chloroform:methanol = 10:1).

MS: (APCI, position.): 501 (M+N)+.

NMR (CDCl3): δ 7,72 (d, J=8.7 Hz, 2H), 7,08-of 6.90 (m, 5H), to 6.75 (d, J=8.7 Hz, 1H), of 6.49 (s, 1H), 6,29 (d, J=2.7 Hz, 1H), 6,23 (DD, J=8,7, 2.7 Hz, 1H), br4.61 (m, 1H), 4,30 (DD, J=9,9, 4.8 Hz, 1H), 4,18 (m, 1H), a 3.87 (s, 2H), 3,76 (s, 3H), 3,40 (DD, J=11,4, 9.0 Hz, 1H), or 3.28 (DD, J=11,4, and 6.6 Hz, 1H), 2.91 in (s, 3H), of 2.44 (s, 3H).

In addition to the compound 7(224), get methods analogous series of reactions of reference example 28 → example 8, can be obtained by using corresponding compounds, the compounds of examples 1-1(75), examples 7-7(223), (225) and (228).

Connection examples 1(8), 1(51), 1(67), 1(68), 1(69), Primero(37) and 7(51) can be obtained protecting the hydroxy - or amino protecting group, followed by removal of the protective group before the interaction in the corresponding example 9.

Example compositions 1

The following listed components are mixed in the usual way and pressed, receiving 100 tablets, each containing 5 mg of active ingredient.

- 1-(4-(2-Propylacetate)benzoyl)-2-
methylindole-4-acetic acid500 mg
- Calcixerollic200 mg
- Stearate100 mg
- Microcrystalline cellulose9.2 grams

1. Derived indole represented by the formula (I)

where R1represents hydroxy;

R2represents a hydrogen atom, (C1-6)-alkyl, (C1-6)-alkoxy, (C2-6)-alkoxyalkyl or 4-methoxybenzyl;

R3represents a hydrogen atom or (C1-6)-alkyl;

R4and R5each independently represents a hydrogen atom, (C1-6)-alkyl or (C1-6)-alkoxy;

D represents a simple bond, (C1-6)-alkylene, (C2-6)-albaniles or (C1-6)-oxyalkylene;

in-G-R6

1) G represents a simple bond, (C1-6)-alkylene, which can be C is substituted by 1-2 oxygen atoms and/or sulfur atoms, (C2-6)-albaniles, which may be substituted by 1 or 2 oxygen atoms, where alkylene and albaniles can be substituted by hydroxy or (C1-4)-alkoxy, -NHC(O)-or diazo;

R6represents a saturated or unsaturated carbocyclic ring, (C3-15) or a 4-15 membered heterocyclic ring containing 1 to 5 nitrogen atoms, sulfur atoms and/or oxygen atoms, where the ring may be substituted by 1-5 substituents selected from (C1-6)alkyl, (C1-10)alkoxy, halogen atom, hydroxy, trihalomethyl, nitro, amino, phenyl, phenoxy, (C2-6)-acyl, (C1-6)-alkanesulfonyl and cyano;

2) G and R6taken together, represent

(i) (C1-15)alkyl which may be substituted by 1 to 4 oxygen atoms and/or sulfur atoms;

(ii) (C2-15)-alkenyl, which may be substituted by 1 or 2 oxygen atoms; or

(iii) (C2-15)-quinil, which may be substituted by 1 or 2 oxygen atoms,

where alkyl may be substituted by 1-12 substituents selected from halogen atom, hydroxy, oxo and NR11R12where R11and R12each independently represents (C1-6)-alkyl, (C2-6)-alkenyl, phenyl, benzoyl, naphthyl or (C1-6)-alkyl substituted by phenyl;

n equals the number of 1-3;

m equals the number of 1-3;

i equals the number of 1-4; and

represents a simple bond or double bond,

or its non-toxic salt.

2. Derived indole according to claim 1, where D represents a simple bond, or its non-toxic salt.

3. Derived indole according to claim 1, where D is (C1-6)-alkylene, or its non-toxic salt.

4. Derived indole according to claim 1, where D represents (C2-6)-albaniles, or its non-toxic salt.

5. Derived indole according to claim 1, where D is (C1-6)-oxyalkylene, or its non-toxic salt.

6. Derived indole according to claim 1, where R6represents a saturated or unsaturated carbocyclic ring, (C3-15), where the ring may be substituted by 1-5 substituents selected from (C1-6)alkyl, (C1-10)alkoxy, halogen atom, hydroxy, trihalomethyl, nitro, amino, phenyl, phenoxy, (C2-6)-acyl, (C1-6)-alkanesulfonyl and cyano, or its non-toxic salt.

7. Derived indole according to claim 1, where R6represents a 4-15 membered heterocyclic ring containing 1 to 5 nitrogen atoms, sulfur atoms and/or oxygen atoms, where the ring may be substituted by 1-5 substituents selected (C1-6)alkyl, (C1-10)alkoxy, halogen atom, hydroxy, trihalomethyl, nitro, amino, phenyl, phenoxy, (C2-6)-acyl, (C1-6)-alkanesulfonyl and cyano, or its non-toxic salt.

8. Derived indole according to claim 1, where G and R6taken together, represent

(i) (C1-15)alkyl which may be substituted by 1 to 4 oxygen atoms and/or sulfur atoms;

(ii) (C2-15)-alkenyl, which can be zames the n 1-2 oxygen atoms; or

(iii) (C2-15)-quinil, which may be substituted by 1 or 2 oxygen atoms,

where alkyl may be substituted by 1-12 substituents selected from halogen atom, hydroxy, oxo and NR11R12where R11and R12each independently represents (C1-6)-alkyl, (C2-6)-alkenyl, phenyl, benzoyl, naphthyl or (C1-6)-alkyl substituted by phenyl, or its non-toxic salt.

9. A method of obtaining a carboxylic acid represented by the formula (Ia)

where all the symbols have the meanings specified below,

comprising the reaction of removing the protective group of the compound represented by formula (IV)

where R20represents allyl or benzyl group, and other symbols have the meanings indicated in claim 1.

10. The DP antagonist-receptor containing as an active ingredient derived indole of the formula (I) or its non-toxic salt.

11. 2-Methylindole-4-acetic acid.

Priority 09.03.2000, 2000-64696, JP, paragraphs 2, 3, 4, 5, 9, 10;

Priority 31.07.2000, 2000-231857, JP, paragraphs 1, 6, 7, 8;

Priority 08.03.2001, PCT/JP01/01817, JP, item 11.



 

Same patents:

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to biologically active compounds, in particular, to substituted 5R1,6R2-thiadiazine-2-amines and pharmaceutical compositions comprising thereof that can be used in medicine as potential pharmacologically active substances eliciting the unique combination of properties: expressed anticoagulant activity in combination with capacity to inhibit aggregation of platelets. Effect of these substances differ from preparations used in medicinal practice and they can be used therefore in treatment of such diseases as myocardium infarction, disturbance in cerebral circulation, rejection of transplanted organs and tissues and so on. Indicated compounds correspond to the formula (I):

wherein values of radicals R1, R2 and R3 are given in the invention claim.

EFFECT: valuable medicinal properties of compounds.

4 cl, 2 tbl, 7 dwg, 33 ex

FIELD: organic chemistry, pesticides, agriculture.

SUBSTANCE: invention relates to compounds that elicit high pesticide activity and can be used in control of pests of domestic and agricultural animals. Indicated compounds show the formula (I):

wherein R1 means halogen atom, (C1-C6)-halogenalkyl; R2 means hydrogen atom (H), (C1-C6)-alkyl, (C1-C6)-alkylene-phenyl; X1 means nitrogen atom (N); X2 means group C(CN); X3 means oxygen atom (O); Q means CH; R3 and R4 mean independently of one another hydrogen atom (H) or in common with carbon atom with which they are bound form (C3-C7)-cycloalkyl ring; R5 means a substitute taken among group including (C1-C6)-halogenalkyl, halogen atom being if m above 1 then substitutes R5 can be similar or different; m = 1, 2 or 3; n = 0 or 1. Also, invention describes a method for their preparing and method for control of pests.

EFFECT: valuable pesticide properties of compounds.

7 cl, 3 tbl, 14 ex

FIELD: organic chemistry, chemical technology, agriculture.

SUBSTANCE: invention describes substituted azadioxocycloalkenes of the general formula (I): wherein A means unsubstituted or methyl-substituted dimethylene; Ar means unsubstituted or fluorine-substituted ortho-phenylene, thiophendiyl or pyridindiyl; E means group of the formula: wherein G means oxygen atom, groups -O-CH2-, -CH2-O- or -C(CH3)=N-O-CH2-; Z means unsubstituted or substituted phenyl, pyrimidinyl or thiadiazolyl, or naphthyl. Invention describes 4 methods for preparing compounds of the formula (I), 5 species of intermediate compounds used for preparing compounds of the formula (I), fungicide agents comprising compound of the formula (I) as an active substance, a method for preparing fungicide agents, method for control of harmful fungi using compound of the formula (I). Compounds of the formula (I) show fungicide properties and therefore they can be used in agriculture.

EFFECT: improved preparing methods, valuable properties of compounds.

13 cl, 5 tbl, 18 ex

FIELD: organic chemistry.

SUBSTANCE: method relates to new method for production of 5-chloro-4-[(2-imidazoline-2-yl)amino]-2,1,3-benzothiadiazole hydrochloride of formula I . Claimed compound is high effective drug and is used in medicine as myorelaxant of central action. Claimed method includes condensation of N,N-dimethyldichloromethyleneammonium chloride with 5-chloro-4-amino-1,1,3-benzothiadiazole in organic solvent followed by treatment of formed alpha-chloroformamidine of formula R-N=C(Cl)N(CH3)2, wherein R is 5-chloro-2,1,3-benzothiazol-4-yl, with ethylenediamine. Formed intermediate of formula R-N=C(NH-CH2-CH2-NH2)N(CH3)2 is treated with hydrochloric acid, heated in organic solvent and 5-chloro-4-[(2-imidazoline-2-yl)amino]-2,1,3-benzothiadiazole hydrochloride of formula I is isolated.

EFFECT: simplified method for preparation of target compound directly in hydrochloride form.

FIELD: pharmaceutical industry, medicine.

SUBSTANCE: invention relates to 5-membered N-heterocyclic compounds and salts thereof having hypoglycemic and hypolipidemic activity of general formula I , wherein R1 is optionally substituted C1-C8-alkyl, optionally substituted C6-C14-aryl or optionally substituted 5-7-membered heterocyclic group, containing in ring 1-4 heteroatoms selected from oxygen, sulfur and nitrogen; or condensed heterocyclic group obtained by condensation of 5-7-membered monoheterocyclic group with 6-membered ring containing 1-2 nitrogen atoms, benzene ring, or 5-membered ring containing one sulfur atom; { is direct bond or -NR6-, wherein R6 is hydrogen atom or C1-C6-alkyl; m = 0-3, integer; Y is oxygen, -SO-, -SO2- or -NHCO-; A ring is benzene ring, condensed C9-C14-aromatic hydrocarbon ring or 5-6-membered aromatic heterocyclic ring containing 1-3 heteroatoms selected from oxygen and nitrogen, each is optionally substituted with 1-3 substituents selected from C7-C10-aralkyloxy; hydroxyl and C1-C4-alkoxy; n = 1-8, integer; B ring is nitrogen-containing 5-membered heterocycle optionally substituted with C1-C4-alkyl; X1 is bond, oxygen or -O-SO2-; R2 is hydrogen atom, C1-C8-alkyl, C7-C13-aralkyl or C6-C14-aryl or 5-6-membered heterocyclic group containing in ring 1-3 heteroatoms selected from oxygen, sulfur and nitrogen, optionally substituted with 1-3 substituents; W is bond, C1-C20-alkylene or C1-C20-alkenylene; R3 is -OR8 (R8 is hydrogen or C1-C4-alkyl) or -NR9R10 (R9 and R10 are independently hydrogen or C1-C4-alkyl). Compounds of present invention are useful in treatment of diabetes mellitus, hyperlipidemia, reduced glucose tolerance, and controlling of retinoid-associated receptor.

EFFECT: new medicines for treatment of diabetes mellitus, hyperlipidemia, etc.

26 cl, 518 ex, 3 tbl

FIELD: organic chemistry, pharmaceutical composition.

SUBSTANCE: new isoindoline-1-on-glucokinase activators of general formula I , as well as pharmaceutically acceptable salts or N-oxide thereof are disclosed. In formula A is phenyl optionally substituted with one or two halogen or one (law alkyl)sulfonyl group, or nitro group; R1 is C3-C9cycloalkyl; R2 is optionally monosubstituted five- or six-membered heterocyclic ring bonded via carbon atom in cycle to amino group, wherein five- or six-membered heteroaromatic ring contains one or two heteroatoms selected form sulfur, oxygen or nitrogen, one of which is nitrogen atom adjacent to carbon atom bonded to said amino group; said cycle is monocyclic or condensed with phenyl via two carbon atoms in cycle; said monosubstituted with halogen or law alkyl heteroaromatic ring has monosubstituted carbon atom in cycle which in not adjacent to carbon atom bonded to amino group; * is asymmetric carbon atom. Claimed compounds have glucokinase inhibitor activity and useful in pharmaceutical composition for treatment of type II diabetes.

EFFECT: new isoindoline-1-on-glucokinase activators useful in treatment of type II diabetes.

23 cl, 3 dwg, 43 ex

FIELD: organic chemistry, heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of heteroarylalkylpiperazine of the general formula (I):

wherein m = 1, 2 or 3; q means NH or oxygen atom (O); R1, R2, R3, R4 and R5 are taken independently among the group including hydrogen atom, (C1-C15)-alkyl, OR20 wherein R20 represents hydrogen atom; R6, R7 and R8 represent hydrogen atom; R9, R10, R11, R12, R13, R14, R15 and R16 are taken independently among the group including hydrogen atom, (C1-C4)-alkyl; or R9 and R10 in common with carbon atom to which they are joined form carbonyl group; R17 means heteroaryl that is taken among the group including indolyl, benzoxazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, pyridyl, benzopyrazinyl substituted optionally with 1-2 substitutes taken among the group including hydrogen atom, CF3 group, (C1-C8)-alkyl, phenyl, CON(R20)2. Compounds elicit property as a partial inhibitor of oxidation of fatty acids and can be used in therapy for protection of skeletal muscles against results of muscular or systemic diseases. Also, invention describes a pharmaceutical composition based on the claimed compounds.

EFFECT: valuable medicinal properties of compounds.

39 cl, 3 tbl, 25 ex

The invention relates to organic chemistry and can find application in medicine

The invention relates to new derivatives of nitrogen-containing heterocyclic compounds of the formula

or their pharmaceutically acceptable salts, where R1represents H, COCOR2, COOR3or SO2R3, R2is1-6alkyl, C1-6alkenyl,5-7cycloalkyl, 2-thienyl, 3-thienyl, phenyl or substituted phenyl, R3is phenylalkyl,represents a saturated five-membered nitrogen-containing heterocyclic ring with one nitrogen atom or benzododecinium saturated six-membered nitrogen-containing heterocyclic ring;is oxazol, oxadiazole or thiazole, And is associated with carbon atom of the five-membered heteroaromatic rings and represents COO(CH2)mAr,where R1has the values listed above or is CONR4(CH2)mAr or (CH2)mO(CH2)nAr and R1cannot be COCOR2or SO2R3, R4represents H or<

The invention relates to sulfhemoglobinemia heterocyclic compound represented by formula (I), its pharmaceutically acceptable salts and their hydrates

where the values of A, B, K, T, W, X, Y, U, V, Z, R1specified in paragraph 1 of the claims

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivative of aroylpiperazine of the formula (I):

wherein Y means lower alkylene; R1 means phenyl with 1 or 2 substitutes taken among group consisting of trihalogen-(lower)-alkyl, halogen atom, lower alkylamino-, di-(lower)-alkylamino- and nitro-group; R2 means phenyl or indolyl and each comprises 1 or 2 substitutes taken among group consisting of lower alkyl, trihalogen-(lower)-alkyl, lower alkylene dioxy-, hydroxy-group, hydroxy-(lower)-alkyl, lower alkoxy- lower alkylamino- and di-(lower)-alkylamino-group; R3 means hydrogen atom; R4 means morpholinyl-(lower)-alkyl comprising 1 or 2 substitutes taken among group consisting of ethyl, hydroxy-(lower)-alkyl, halogen-(lower)-alkyl and lower alkoxy-(lower)-alkyl, or morpholinyl-(lower)-alkynyl that can comprise 1 or 2 substitutes taken among group consisting of ethyl, propyl, isopropyl, isobutyl, spirocyclo-(lower)-alkyl, lower alkoxy-(lower)-alkyl, hydroxy-(lower)-alkyl, carboxy-(lower)-alkyl, di-(lower)-alkyl-carbamoyl, lower alkoxycarbonyl and halogen-(lower)-alkyl. Also, invention relates to a method for preparing, pharmaceutical composition based on these compounds and a method for treatment of tachykinine-mediated diseases, such as respiratory diseases, ophthalmic, cutaneous, inflammatory diseases, and as analgetic agents. Describes compounds are antagonists of tachykinine.

EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical composition.

8 cl, 94 ex

FIELD: organic chemistry, chemical technology, agriculture.

SUBSTANCE: invention describes substituted azadioxocycloalkenes of the general formula (I): wherein A means unsubstituted or methyl-substituted dimethylene; Ar means unsubstituted or fluorine-substituted ortho-phenylene, thiophendiyl or pyridindiyl; E means group of the formula: wherein G means oxygen atom, groups -O-CH2-, -CH2-O- or -C(CH3)=N-O-CH2-; Z means unsubstituted or substituted phenyl, pyrimidinyl or thiadiazolyl, or naphthyl. Invention describes 4 methods for preparing compounds of the formula (I), 5 species of intermediate compounds used for preparing compounds of the formula (I), fungicide agents comprising compound of the formula (I) as an active substance, a method for preparing fungicide agents, method for control of harmful fungi using compound of the formula (I). Compounds of the formula (I) show fungicide properties and therefore they can be used in agriculture.

EFFECT: improved preparing methods, valuable properties of compounds.

13 cl, 5 tbl, 18 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of tetrahydroisoquinoline of the formula [I] wherein R1 represents hydrogen atom or lower alkyl; R2 represents alkyl having optionally a substitute taken among alkoxycarbonyl and carboxy-group, cycloalkyl, cycloalkylalkyl, aryl having optionally a substitute taken among lower alkyl, arylalkyl having optionally a substitute taken among lower alkyl, lower alkoxy-group, halogen atom and acyl, alkenyl, alkynyl, or monocyclic heterocyclylalkyl wherein indicated heterocycle comprises 5- or 6-membered ring comprising nitrogen atom and having optionally a substitute taken among lower alkyl; R3 represents hydrogen atom or lower alkoxy-group; A represents a direct bond or >N-R5 wherein R5 represents lower alkyl; B represents lower alkylene; Y represents aryl or monocyclic or condensed heterocyclyl comprising at least one heteroatom taken among oxygen atom and nitrogen atom and having optionally a substitute taken among lower alkyl, carboxy-group, aryl, alkenyl, cycloalkyl and thienyl, or to its pharmaceutically acceptable salt. Also, invention relates to pharmaceutical composition eliciting hypoglycaemic and hypolipidemic effect based on these derivatives. Invention provides preparing new compounds and pharmaceutical agents based on thereof, namely, hypoglycaemic agent, hypolipidemic agent, an agent enhancing resistance to insulin, therapeutic agent used for treatment of diabetes mellitus, therapeutic agent against diabetic complication, agent enhancing the tolerance to glucose, agent against atherosclerosis, agent against obesity, an anti-inflammatory agent, agent for prophylaxis and treatment of PPAR-mediated diseases and agent used for prophylaxis and treatment of X-syndrome.

EFFECT: valuable medicinal properties of compounds and composition.

13 cl, 7 tbl, 75 ex

FIELD: organic chemistry, heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention relates to new heterocyclic compounds corresponding to general formulas: (I) , (II) , (Ia) and (Ib) wherein substitutes have values given in the description. Such compounds are reversible inhibitors of cathepsins S, K, F, L and B. Also, invention relates to a method for preparing these compounds, pharmaceutical composition eliciting inhibitory activity with respect to cysteine proteases and to a method for modulation of autoimmune diseases, treatment of Alzheimer's disease and osteoporosis.

EFFECT: improved method for preparing, valuable medicinal properties of compounds.

42 cl, 106 ex

FIELD: pharmaceutical industry, medicine.

SUBSTANCE: invention relates to 5-membered N-heterocyclic compounds and salts thereof having hypoglycemic and hypolipidemic activity of general formula I , wherein R1 is optionally substituted C1-C8-alkyl, optionally substituted C6-C14-aryl or optionally substituted 5-7-membered heterocyclic group, containing in ring 1-4 heteroatoms selected from oxygen, sulfur and nitrogen; or condensed heterocyclic group obtained by condensation of 5-7-membered monoheterocyclic group with 6-membered ring containing 1-2 nitrogen atoms, benzene ring, or 5-membered ring containing one sulfur atom; { is direct bond or -NR6-, wherein R6 is hydrogen atom or C1-C6-alkyl; m = 0-3, integer; Y is oxygen, -SO-, -SO2- or -NHCO-; A ring is benzene ring, condensed C9-C14-aromatic hydrocarbon ring or 5-6-membered aromatic heterocyclic ring containing 1-3 heteroatoms selected from oxygen and nitrogen, each is optionally substituted with 1-3 substituents selected from C7-C10-aralkyloxy; hydroxyl and C1-C4-alkoxy; n = 1-8, integer; B ring is nitrogen-containing 5-membered heterocycle optionally substituted with C1-C4-alkyl; X1 is bond, oxygen or -O-SO2-; R2 is hydrogen atom, C1-C8-alkyl, C7-C13-aralkyl or C6-C14-aryl or 5-6-membered heterocyclic group containing in ring 1-3 heteroatoms selected from oxygen, sulfur and nitrogen, optionally substituted with 1-3 substituents; W is bond, C1-C20-alkylene or C1-C20-alkenylene; R3 is -OR8 (R8 is hydrogen or C1-C4-alkyl) or -NR9R10 (R9 and R10 are independently hydrogen or C1-C4-alkyl). Compounds of present invention are useful in treatment of diabetes mellitus, hyperlipidemia, reduced glucose tolerance, and controlling of retinoid-associated receptor.

EFFECT: new medicines for treatment of diabetes mellitus, hyperlipidemia, etc.

26 cl, 518 ex, 3 tbl

FIELD: organic chemistry, pharmacology.

SUBSTANCE: invention relates to new flavone, xanthone and coumarone derivatives of formula I

[R and R1 each are independently lower C1-C6-alkyl or together with nitrogen atom attached thereto form 4-8-membered heterocycle, optionally containing one or more heteroatoms, selected from group comprising N or O, wherein said heterocycle is optionally substituted with benzyl; Z has formula (A) , wherein R3 and R4 each are independently hydrogen, optionally substituted aromatic group containing in cyclic structure from 5 to 10 carbon atoms, wherein substituents are the same or different and represent lower C1-C4-alkyl, OR10 (OR10 is hydrogen, saturated or unsaturated lower C1-C6-alkyl or formula ) or linear or branched C1-C6-hydrocarbon; or R2 and R3 together with carbon atom attached thereto form 5-6-membered carbocycle; and R4 represents hydrogen or attaching site of group –OCH2-C≡CCH2NRR1; or formula (B) , wherein R5 is hydrogen, linear or branched lower C1-C6-hydrocarbon, with the proviso, that when Z represents R and R1 both are not methyl or R and R1 together with nitrogen atom attached thereto cannot form groups , or ]. Also disclosed are drug component with proliferative activity for prophylaxis or treatment of neoplasm and pharmaceutical composition with proliferative activity based on the same. Derivatives of present invention have antyproliferative properties and are useful as modulators of drug resistance in cancer chemotherapy; as well as in pharmaceuticals for prophylaxis or treatment of neoplasm, climacteric disorders or osteoporosis.

EFFECT: new compounds with value bioactive effect.

31 cl, 2 tbl, 32 ex

FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: invention relates to substituted 3-oxo-1,2,3,4-tetrahydroxinoxalines of general formula 1 , wherein R1 represents substituted sulfanyl or substituted sulfonyl group, containing as substituent optionally substituted C1-C4-alkyl, optionally substituted C3-C8-cycloalkyl, aryl-(C1-C4)alkyl optionally substituted in aril or alkyl group, heterocyclyl-(C1-C4)alkyl optionally substituted in heterocycle or alkyl group; R2 and R3 independently represent hydrogen, halogen, CN, NO2, optionally substituted hydroxyl, optionally substituted amino group, optionally substituted carboxylic group, optionally substituted carbamoyl group, optionally substituted arylcarbonyl group or optionally substituted heterocyclylcarbonyl group; R4 and R5 independently represent hydrogen or inert substituent. Claimed compounds are high effective kaspase-3 inhibitors and are useful in production of pharmaceutical compositions for treatment of diseases associated with excess apoptosis activation, as well as for experimental investigations of apoptosis in vivo and in vitro. Also disclosed are pharmaceutical composition in form of tablets, capsules or injections in pharmaceutically acceptable package, as well as method for production thereof and therapy method.

EFFECT: pharmaceutical composition for apoptosis treatment and investigation.

6 cl, 3 dwg, 8 ex, 1 tbl

FIELD: organic chemistry, pharmaceutical composition.

SUBSTANCE: new isoindoline-1-on-glucokinase activators of general formula I , as well as pharmaceutically acceptable salts or N-oxide thereof are disclosed. In formula A is phenyl optionally substituted with one or two halogen or one (law alkyl)sulfonyl group, or nitro group; R1 is C3-C9cycloalkyl; R2 is optionally monosubstituted five- or six-membered heterocyclic ring bonded via carbon atom in cycle to amino group, wherein five- or six-membered heteroaromatic ring contains one or two heteroatoms selected form sulfur, oxygen or nitrogen, one of which is nitrogen atom adjacent to carbon atom bonded to said amino group; said cycle is monocyclic or condensed with phenyl via two carbon atoms in cycle; said monosubstituted with halogen or law alkyl heteroaromatic ring has monosubstituted carbon atom in cycle which in not adjacent to carbon atom bonded to amino group; * is asymmetric carbon atom. Claimed compounds have glucokinase inhibitor activity and useful in pharmaceutical composition for treatment of type II diabetes.

EFFECT: new isoindoline-1-on-glucokinase activators useful in treatment of type II diabetes.

23 cl, 3 dwg, 43 ex

FIELD: organic chemistry, heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention relates to nitrogen-containing heterocyclic derivatives of the formula (I): A-B-D-E (I) wherein A means 5- or 6-membered heteroaryl comprising one or two nitrogen atoms in ring; B means ethenylene; D mean phenylene; E means group -N(COR)-SO2-G wherein G means phenyl; R means 5- or 6-membered heteroaryl or heteroarylmethyl comprising one or two nitrogen atoms in ring, or group -(CH2)n-N(R5)R6 wherein n means a whole number from 1 to 5; R5 and R6 are similar or different and mean: hydrogen atom, (C1-C6)-alkyl, hydroxyalkyl, aminoalkyl; or R5 and R6 in common with nitrogen atom can form 5-7-membered cyclic amino-group -N(R5)R6 that can comprise, except for nitrogen atom, also oxygen, sulfur or nitrogen atom as a component forming the ring, or their N-oxides. Compounds of the formula (I) elicit anticancer activity and can be used in medicine.

EFFECT: valuable medicinal properties of compounds.

10 cl, 1 tbl, 24 ex

FIELD: organic chemistry or heterocyclic compounds, chemical technology.

SUBSTANCE: invention relates to technology for manufacturing heterocyclic compounds, in particular, to technology for manufacturing 3-methyl-1,2,4-triazolyl-5-thioacetate morpholinium that is known as a substance for pharmaceutical designation "thiotriazoline". Invention describes a method for preparing 3-methyl-1,2,4-triazolyl-5-thioacetate morpholinium that involves reaction of 3-methyl-1,2,4-triazolyl-5-thioacetic acid with morpholine in liquid medium wherein methylene chloride is used as a liquid medium. Method provides significant elevating the yield percent of the end product, enhances its quality and significant reducing industrial consumptions.

EFFECT: improved preparing method.

4 cl, 1 tbl, 4 ex

The invention relates to sulfhemoglobinemia heterocyclic compound represented by formula (I), its pharmaceutically acceptable salts and their hydrates

where the values of A, B, K, T, W, X, Y, U, V, Z, R1specified in paragraph 1 of the claims

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