5-formyl-substituted indoline spirobenzopyrans and method of producing them

FIELD: chemistry.

SUBSTANCE: present invention relates to new compounds, and more specifically to 5-formyl-substituted indoline spirobenzopyrans with general formula 1 where R1, R2 - Alk or c-Alk; R3 -CHO or NO2 group (electron-acceptor substitute), with photochromic properties. The invention also relates to the method of producing 5-formyl substituted derivatives of indoline spirobenzopyrans with formula 1. Spirobenzopyrans, which have electron-acceptor substitutes in the pyran part of the molecule, are subjected to direct selective formylation in position 5 in a trifluoroacetic acid medium with urotropine (hexamethylenetetramine) at boiling point of the mixture in an inert atmosphere for 1-1.5 hours. The obtained 5-formyl-substituted spirobenzopyrans are photochromic compounds are photochromic and can be used for making new photochromic materials (recording devices or information storage; photo-switching activity of biological objects and polymer matrices, complex formation; information security media, maps, special document protection equipment) or as advanced initial compounds for further synthesis of a large number of new photochromic objects.

EFFECT: wider field of application of the compounds.

2 cl, 1 tbl, 3 ex

 

The present invention relates to a convenient method of functional modifications of the classical photochromic indolinone of spiropyran (SP) indolinone fragment molecules with obtaining new 5-formyl-substituted of spiropentane General formula SP-5-CHO

The reaction formirovaniya indolinone of spiropentane

where R1, R2- Alk-or c-Alk,

R3- SNO or NO2group (electron-acceptors Deputy).

To photochromic compounds are substances that are capable of reversible transformation from one state to another, occurring in at least one direction under the action of light and accompanied by the change of the absorption in the visible region of the spectrum. Today the main directions of the use of photochromic compounds and materials are: device information storage and recording devices; photoperiodicity activity of biological objects and polymer matrices, complex formation; information protection, ID card, special. protection documents; cosmetics, fotograiya clothing and art.

Indolinone spirometery well - known class of photochromic compounds. The most pronounced photochromic properties have molecules spiropyrans with acceptor substituents in paranavai part, took Ivanushki lifetime colored merocyanine form [Sachsen E.R., Martynov VP, Efros PS Synthesis and properties of spiropyrans capable of reversible disclosure Pyrenophora rings. / CHC. 1979. No. 2. S-459]. Substitution for indolinone part of the molecule does not lead to significant changes of maximum absorption of a colored form, conditions and parameters of the photochromic reaction is often predictable, making it a very promising modification indolinone fragment for insertion into the required system environment or accession to the substrate [Pancerny VI, Halberstam M.A., don N.A. ABOUT the influence of the substituents at positions 5 and 8' on the reaction rate dark discoloration photograhing solutions 1,3 .3m-trimethylspiro-[indoline-2,2'-[2H-1]benzopyrano]. CHC. 1973. No. 5. S-658. Pancerny VI, Halberstam M.A. ABOUT the influence of the substituents at positions 5 and 8' on the absorption spectra merocyanine forms of spiropyrans. CHC. 1973. No. 5. S-662].

The presence of a formyl group in indolinone part allows a large number of reactions with her participation while maintaining the rest of the molecule of spiropyran, for example for the attachment of linkers/spacers of different nature.

The classic way obtain spiropyranes is condensation derivatives indolenine (1,3 .3m-trimethyl-2-methyleneindoline, the basis of Fisher's) or their Quaternary salts with substituted salicylic aldehydes. The process is carried out, the heating is by boiling in an inert atmosphere of solutions of initial reagents in different solvents (alcohols, toluene, dimethylformamide) [Ono H., Osada, S. Photochromic compound. / Patent 3692800 (US). 1972]. The product distinguish crystallization or by chromatography on a small layer of sorbent. However, such direct synthesis is often too expensive, difficult or impossible for a number of substituted spiropyrans because of problems with the availability and/or cost of the starting materials. Derivatives of salicylic aldehyde, generally available, sufficiently stable during storage, easy to be cleaned, getting them is a modification of the salicylic aldehyde or formirovanie phenol derivatives. Therefore, the best approach of obtaining the desired Deputy Pyrenophora fragment is the synthesis of spiropyrans derived from salicylic aldehyde containing this Deputy or group-predecessor, it is easy to convert the target. Unlike salicylic aldehydes getting some proizvodnyh indolenine is of great difficulties, the simplest and most accessible derivative is 1,3 .3m-trimethyl-2-methyleneindoline.

In the literature there are a number of reactions of electrophilic substitution derivatives of spiropyranes held on the 5th position indolinone fragment [Sachsen E.R., Zvenigorod L.A., Lesenok N.G., Martynova VP Bromination of spiropyranes and restore their nitro-derivatives. /CHC. 1977. No. 10. S-1326; Samoilov the LOCALITY, Halberstam M.A. ON some substitution reactions in a series of photochromic indolinospiropyrans./ CHC. 1977. No. 8. S-1068; Halberstam M.A., Bondarenko, E.M., Frolova O.R. and other Synthesis and photochromic properties of 5-acetylnueraminic of indolinospiropyrans].

However, it was also shown that when formirovanii on Vilsmeier or acylation systems: acetic anhydride in the presence of epirate boron TRIFLUORIDE in chloroform; benzoyl chloride with aluminum trichloride in carbon disulfide or benzoyl chloride in the environment of dimethylaniline, formyl or acyl group is introduced at position 3' [Halberstam M.A., Artamonova N.N., Samoilov I.E. Synthesis of 3'-allsamsung indolinone of spiropyrans. / CHC. 1975. No. 2. S-203].

The technical result of the invention to provide 5-formyl-substituted indolinone of spiropentane that can be used as the most promising source of compounds for the further synthesis of large numbers of new photochromic objects.

The technical result of the invention is a method for the regioselective introduction of a formyl group at the 5th position indolinone core molecules spiropyranes. We found that under the reaction conditions Duff direct formulation of the photochromic spiropyrans having electron-acceptor substituents in paranavai part of the molecule, the advantage is only held on the 5th position indolinone core molecule. The optimal conditions of the process are heated in triperoxonane acid at boiling mixture source spiropyran and excess 2-4 EQ. urotropine (hexamethylenetetramine, NMT) in an inert atmosphere. Heating the reaction mass at temperatures below the boiling point increases the time of carrying out the reaction, it is necessary to increase the excess of urotropine and generally does not affect the overall yield of the reaction. Triperoxonane acid is commercially available reagent is easily removed by distillation in vacuum, perfectly mixed with water, thereby making the reaction product is simple and the process is relatively cheap. To raise the temperature of holding such reactions as the environment also apply polyphosphoric and methansulfonate acid, however, for this class of compounds necessary, the use of these reagents is not. The presence of traces of oxygen significantly reduces the yield of the reaction, increases the amount of by-products that cause resinification and oxidation of the reaction mass, it is therefore necessary to carry out the reaction formirovaniya in an inert atmosphere. The amount of the excess of urotropine depends on structural features of the original spiropyran, lack formuliruiutsia agent can lead to a low degree of conversion source spiropyran, large houses the TCA his to increase the proportion of by-products, secondary substitution at positions 3' and 7 have a place to be in large excess of hexamine.

These spirometer SP-5-CHO are photochromic compounds and can be used for further new photochromic materials.

For illustration of this present invention are described below in the following examples of experimental procedures formirovaniya derivatives of spiropyrans.

Example 1. The technique of synthesis of 6'-nitro-1,3 .3m-trimethyl-5-formylindole-2-Spiro-2'-2H-chromene (I). To a solution of 5.0 g (15.5 mmol) of 1,3 .3m-trimethyl-6'-nitrospira(indoline-2,2'-[2H]chromene) in 30 ml triperoxonane acid was added 8.7 g (62.0 mmol) of hexamethylenetetramine and heated at boiling for 1 hour in argon atmosphere. Then the reaction mass was poured into 200 ml of ice. The precipitation was filtered. For separation of the target product used flash chromatography on silica gel, eluent - petroleum ether (BP. 40-70°C) - methylene chloride (1:3, by volume). Additionally, the product was purified by crystallization from alcohol. Received 4.6 g (13.1 mmol) of the product (I) (85%), with TPL 168-170°C. Rf0.35 ("Silufol UV-254, Kavalier, Czech Republic, detection of spots - the impact on the developed plate natural light). Mass spectrum, m/z: 351, [M]+. An NMR spectrum1H (DMSO-d6, δ, ppm, J/Hz): 1.15 (3H, si-CH3), 1.27 (3H, s, 3b With the 3), 2.82 (3H, s, 1-CH3), 6.04 (1H, d, J 10.4, 3'-H), 6.81 (1H, d, J 8.3, 7-H), 6.93 (1H, d, J 9.0. 8'-H), 7.28 (1H, d, J 10.3, 4'-H), 7.65 (1H, d, J 1.5, 4-H), 7.76 (1H, DC, J 8.1/1.5, 6-H), 8.02 (1H, DD, J 9.0/2.9, 7'-H), 8.25 (1H, d, J 2.9, 5'-H), 9.77 (1H, s, 5-SNO).

Found (percent): C, 67.98; H, 5.33; N, 8.02; O, 18.67. C20H18N2O4. Calculated (%): C, 68.56; H, 5.18; N, 8.0; Oh, 18.27. Spectral-kinetic characteristics (I), see table 1.

Example 2. 8'-Nitro-1,3 .3m-trimethyl-5-formylindole-2-Spiro-2'-2H-chromen (II). The compound (II) received, were isolated and purified as in (I) (example 1) from 5 g (15.5 mmol) and 1,2,3-trimethyl-8'-nitrospira(indoline-2,2'-[2H]chromene) and 8.7 g (62.0 mmol) of hexamethylenetetramine. Got 4.3 g (12.3 mmol) of the product (II) (79%), with TPL 197-199°C. Rf0.25 (detection spots - the impact on the developed plate natural light). Mass spectrum, m/z: 351, [M]+. An NMR spectrum1H (DMSO-d6, δ, ppm, J/Hz): 1.16 (3H, s, 3A-CH3), 1.31 (3H, s, 3-CH3), 2.81 (3H, s, 1-CH3), 6.03 (1H, d, J 10.4, 3'-H), 6.80 (1H, d, J 8.3, 7-H), 7.05 (1H, m, J 8.0, 6'-H), 7.22 (1H, d, J 10.3, 4'-N), 7.58 (1H, DD, J 7.6/1.5. 6-H), 7.64 (1H, d, 1.5, 4-H), 7.74 (1H, DD, J 8.0/1.7, 5'-H), 7.76 (1H, DD, J 8.0/1.7, 7'-H), 9.77 (1H. with a 5 - SNO). Found (percent): C, 68.38; H, 5.23; N, 8.07; O, 18.32. With20H18N2O4. Calculated (%): C, 68.56; H, 5.18; N, 8.0; Oh, 18.27. Spectral-kinetic characteristics (II), see table 1.

Example 3. 5,6'-Diformyl-1,3 .3m-trimethylindolenine-2-Spiro-2'-2H-chromen (III).

The compound (III) was obtained similarly to (I) (example 1) from 5 g (15.5 mmol) of 1,2,3-Tr is methyl-6'-formiller(indoline-2,2'-[2H]chromene) and 4.6 g (32.8 mmol) of hexamethylenetetramine in the course of 1.5 hours. The precipitation was filtered. The mother solution was slowly podslushivaet 1 M potassium hydroxide solution to pH 7, then carried out the extraction of the product in methylene chloride 2 times. The organic phase was dried over sodium sulfate, then the solvent was removed in vacuum. Next, the combined extracts and the filtrate was chromatographically on a small layer of silica gel, eluent - petroleum ether (BP. 40-70°C) - methylene chloride (1:3, by volume). Obtained 4.2 g (12.6 mmol) of the product (III) (77%), with TPL 164-166°C. Rf0.20 (detection spots - the impact on the developed plate natural light). Mass spectrum, m/z: 334, [M]+. An NMR spectrum1H (DMSO-d6, δ, ppm, J/Hz): 1.15 (3H, s, 3A-CH3), 1.27 (3H, s, 3-CH3), 2.81 (3H, s, 1-CH3), 5.95 (1H, d, J 10.3, 3'-H), 6.79 (1H, d, J 8.3, 7-H), 6.91 (1H, m, J 8.3, 8'-H), 7.22 (1H, d, J 10.3, 4'-H), 7.64 (1H, d, J 1.7, 4-H), 7.71 (1H, DD, J 8.6/2.1, 7'-H), 7.76 (1H, DD, J 8.1/1.7, 6-H), 7.82 (1H, d, 2.0, 5'-H), 9.77 (1H, s, 5-SNO), 9.83 (1H, s, 6'-SNO). Found (percent): C, 75.35; H, 5.83; N, 4.07; O, 14.75. C21H19NO3. Calculated (%): C, 75.66; H, 5.74; N, 4.2; Oh, 14.40. Spectral-kinetic characteristics (III), see table 1.

Table 1.
Spectral-kinetic characteristics of derivatives of spiropyrans (I-III) in solution.
ConnectionSolvent is λAnmλBnm∆ DfotkBAwith-1t1/2c
IEthanol3285700.850.1240
Toluene318585 square, 6250.900.2413
IIEthanol3255800.70.4850
Toluene317600 square, 6400.450.845
IIIEthanol325570.90.3960
Toluene 317580 square, 6200.231.642

1. 5-Formyl-substituted formula indolinone spirometery General formula

where R1, R2- Alk-or c-Alk;
R3- SNO or NO2group (electron-acceptor Deputy), possessing photochromic properties.

2. The method of obtaining 5-formyl-substituted indolinone of spiropentane, characterized in that spiropyran General formula

where R1, R2and R3have the above meanings, is subjected to direct selective formirovanie in position 5 in trifluoroacetic acid with urotropine (hexamethylenetetramine) at the boiling temperature of the mixture in an inert atmosphere for 1-1,5 hours



 

Same patents:

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for preparing 3,4-diaryl(hetaryl)maleimides of the formula (I): wherein R means (C1-C4)-alkyl or benzyl, or phenyl; R1 means bromine atom (Br) or aryl, such as phenyl or naphthyl substituted with alkyl, alkoxy-group or halogen atom; unsubstituted hetaryl or substituted, such as thienyl-, benzothienyl-, furyl-, benzofuryl-, pyrrolyl or indolyl- wherein substitutes represent alkyl, alkoxy-, alkylthio-group, halogen atom or trifluoromethyl group; Ar means aryl, such as phenyl or naphthyl substituted with alkyl, alkoxy-group or halogen atom; unsubstituted hetaryl or substituted, such as thienyl-, benzothienyl-, furyl-, benzofuryl-, pyrrolyl or indolyl- wherein substitutes represent alkyl, alkoxy-, alkylthio-group, halogen atom or trifluoromethyl group with exception for 3,4-di-(2,5-dimethyl-3-thienyl)-1-butylmaleimide. Method involves interaction of aryl(hetaryl)boronic acid of the formula: ArB(OH)2 wherein Ar has abovementioned values with N-substituted 3,4-dibromomaleimide of the formula (III): or N-substituted 3-bromo-4-aryl(hetaryl)maleimide of the formula (IV) wherein R and Ar have abovementioned values and with using palladium catalyst in the presence of base in organic solvent medium. Also, invention to some new derivatives of 3,4-diaryl(hetaryl)maleimides that show photochrome properties.

EFFECT: improved preparing method.

7 cl, 2 dwg, 14 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to new compounds with formula I, their pharmaceutical salts and to complex esters. The invented compounds have inhibiting propertied towards catepsin K and can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved, for example, inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumorous diseases. In general formula I R represents H, R13 represents (inferior)alkyl, C3-C10cylcloalkyl or C3-C10cycloalkyl(inferior)alkyl, each of which is independently optionally substituted with a halogen atom, hydroxyl, CN, NO2 or optionally mono- or di(inferior)alkyl substituted amino group; and R14 represents H or optionally substituted phenyl, phenyl-W-, phenyl(inferior)alkyl-W-, C3-C10cycloalkyl, C3-C10cycloalkyl-W-, N-heterocyclyl, N-heterocyclyl -W-. Substitutes of the indicated values of radicals are shown in the formula of invention. The invention also relates to methods of obtaining the compounds.

EFFECT: obtaining pyrrolopyrimidines with inhibiting properties towards catepsin K, which can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved.

4 cl, 59 tbl, 10 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of derivatives of indolinospiropyrane of the formula (1): wherein R1 means (C1-C18)-alkyl; each among R2 and R3 mean independently (C1-C4)-alkyl; R4 means hydrogen atom, hydroxy-group, trichloromethyl, trifluoromethyl formyl, (C1-C)-alkyl, halogen atom, (C1-C4)-alkoxy-, nitro-group; x = 1 or 2. Method comprises the following steps: (i) synthesis of indoline on polymeric carrier of the formula (III): wherein R1 means (C1-C18)-alkyl; each among R2 and R means independently (C1-C4)-alkyl; (ii) treatment of indoline-carrying polymeric carrier wherein this carrier represents hydroxy-resin at temperature from 50°C to 120°C in inert atmosphere for time from 14 h to 11 days with a derivative of salicylic aldehyde of the formula (VI): wherein R4 means hydrogen atom, hydroxy-group, trichloromethyl, trifluoromethyl, formyl, (C1-C4)-alkyl, halogen atom, (C1-C4)-alkoxy-, nitro-group; x = 1 or 2 to yield indolinospiropyrane compound of the formula (I), and (iii) release of indolinospiropyrane compound of the formula (I). Invention proves synthesis of novel derivatives of indolinospiropyrane possessing photochromic properties.

EFFECT: improved method of synthesis.

8 cl, 28 ex

FIELD: organic chemistry.

SUBSTANCE: invention describes C2-phenyl-substituted cyclic ketoenols of the general formula: wherein W means hydrogen atom, alkyl with 1-6 carbon atoms; X means alkyl with 1-6 carbon atoms, alkenyl with 2-6 carbon atoms; Y means hydrogen atom, methyl, ethyl, isopropyl, alkenyl with 2-6 carbon atoms, ethynyl; Z means hydrogen atom, alkyl with 1-6 carbon atoms under condition that at least one of residues W, X, Y or Z means a chain with at least 2 carbon atoms but only one of residues X and Y can mean alkenyl with 2-6 carbon atoms; CKE means one of the following groups: , , and wherein A means hydrogen atom, alkyl with 1-6 carbon atoms; B means hydrogen atom, alkyl with 1-6 carbon atoms; A and B in common with carbon atom to which they are bound mean cycloalkyl with 5-6 carbon atoms wherein the ring carbon atom can be substituted with oxygen atom and can be substituted with alkyl with 1-6 carbon atoms or alkoxyl with 1-6 carbon atoms; A and B in common mean group of the formula: D means hydrogen atom or phenyl substituted with fluorine atom if CKE means group of the formula (4); G means hydrogen atom (a) or one of groups of the formula: or wherein R1 means alkyl with 1-6 carbon atoms, alkoxymethyl with 1-2 carbon atoms; R2 means alkyl with 1-4 carbon atoms; A and Q1 in common mean alkanediyl with 3-4 carbon atoms; Q2 means hydrogen atom. Invention provides preparing compound of the formula (I) possessing with insecticide, acaricide and herbicide activity.

EFFECT: valuable properties of compounds.

2 cl, 8 tbl, 32 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention proposes derivative of 3,4-dihydroisoquinoline of the formula (I) or its nontoxic salt and a pharmaceutical agent comprising its as an active component (wherein all symbols have the same values as given in description). Compound of the formula (I) possesses agonistic effect on CB2-receptors and, therefore, it can be used for prophylaxis and/or treatment of different diseases, for example, asthma, nasal allergy, atopic dermatitis, autoimmune diseases, rheumatic arthritis, immune dysfunction, postoperative pain and carcinomatous pain.

EFFECT: valuable medicinal properties of derivatives.

14 cl, 33 tbl, 561 ex

FIELD: pharmaceutical chemistry, in particular pharmaceutical compositions.

SUBSTANCE: new spyro(2H-1-benzopyrane-2,4'-piperidine) derivatives of general formula I

and pharmaceutically acceptable salts thereof are disclosed. In formula dotted line is optional bond; Y is 1-4 substituents independently selected from hydrogen, halogen, C1-C4-alkyl, optionally substituted with one or more halogen, C1-C6-alkyloxy, optionally substituted with halogen or C3-C6-cycloalkyl, C2-C6-alkenyloxy, C2-C6-alkinyloxy, C3-C6-cycloalkyloxy, C6-C12-aryloxy, arylalkyloxy, pyridilmethoxy, SR3, NR3R4, OSO2R5, and NR3SO2R4; or two Y together may form O-(CH2)n-O or O-(CF2)n-O, wherein n is 1 or 2: or Y is condensed C5-C6-aryl group; X is 1-3 substituents independently selected from hydrogen, halogen, hydroxyl, C1-C6-alkoxy, and C1-C4-alkyl; R1 is hydrogen, C1-C4-alkyl, or C6-C12-aryl; R2, R3, and R4 are independently hydrogen or C1-C4-alkyl; R5 is C6-C12-aryl. Also disclosed are pharmaceutical compositions including said derivatives and having activity in relation to CNS.

EFFECT: new compounds with valuable pharmacological action.

9 cl, 1 tbl, 83 ex

The invention relates to new derivatives of galantamine General formula I:

where R1-R5, G1-G3and W have the meanings indicated in the claims, and the invention relates to a method for producing these compounds, medicinal product and the method of its production

The invention relates to a derivative phthalazine General formula (I) or their pharmaceutically acceptable salts, or hydrates, where R1and R2are the same or different from each other and each represents a halogen atom, a C1-C4alkyl group which may be substituted by a halogen atom, a hydroxyl group or a C1-C4alkoxygroup, which may be substituted by a halogen atom, or cyano; X represents a cyano, a halogen atom, hydroxyimino, optional O-substituted C1-C4alkyl group, or a heteroaryl group selected from thiazoline, thienyl, pyrazolidine, triazolinones and tetrazolyl groups that may be substituted WITH1-C4alkyl group; Y represents a cyclic amino group (i) - (v) described in paragraph 1 of the claims; (vi) etinilnoy or ethyl group substituted WITH1-C4alkyl group, which, in turn, replaced by a number of deputies referred to in paragraph 1 of the claims; (vii) optionally substituted phenyl group; (viii) pyridyloxy or thiazolidine group

The invention relates to new derivatives of pyrrolidinone possessing biological activity, in particular derivatives of 1H-3-aryl-pyrrolidin-2,4-dione

FIELD: pharmaceutical chemistry, in particular pharmaceutical compositions.

SUBSTANCE: new spyro(2H-1-benzopyrane-2,4'-piperidine) derivatives of general formula I

and pharmaceutically acceptable salts thereof are disclosed. In formula dotted line is optional bond; Y is 1-4 substituents independently selected from hydrogen, halogen, C1-C4-alkyl, optionally substituted with one or more halogen, C1-C6-alkyloxy, optionally substituted with halogen or C3-C6-cycloalkyl, C2-C6-alkenyloxy, C2-C6-alkinyloxy, C3-C6-cycloalkyloxy, C6-C12-aryloxy, arylalkyloxy, pyridilmethoxy, SR3, NR3R4, OSO2R5, and NR3SO2R4; or two Y together may form O-(CH2)n-O or O-(CF2)n-O, wherein n is 1 or 2: or Y is condensed C5-C6-aryl group; X is 1-3 substituents independently selected from hydrogen, halogen, hydroxyl, C1-C6-alkoxy, and C1-C4-alkyl; R1 is hydrogen, C1-C4-alkyl, or C6-C12-aryl; R2, R3, and R4 are independently hydrogen or C1-C4-alkyl; R5 is C6-C12-aryl. Also disclosed are pharmaceutical compositions including said derivatives and having activity in relation to CNS.

EFFECT: new compounds with valuable pharmacological action.

9 cl, 1 tbl, 83 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention proposes derivative of 3,4-dihydroisoquinoline of the formula (I) or its nontoxic salt and a pharmaceutical agent comprising its as an active component (wherein all symbols have the same values as given in description). Compound of the formula (I) possesses agonistic effect on CB2-receptors and, therefore, it can be used for prophylaxis and/or treatment of different diseases, for example, asthma, nasal allergy, atopic dermatitis, autoimmune diseases, rheumatic arthritis, immune dysfunction, postoperative pain and carcinomatous pain.

EFFECT: valuable medicinal properties of derivatives.

14 cl, 33 tbl, 561 ex

FIELD: organic chemistry.

SUBSTANCE: invention describes C2-phenyl-substituted cyclic ketoenols of the general formula: wherein W means hydrogen atom, alkyl with 1-6 carbon atoms; X means alkyl with 1-6 carbon atoms, alkenyl with 2-6 carbon atoms; Y means hydrogen atom, methyl, ethyl, isopropyl, alkenyl with 2-6 carbon atoms, ethynyl; Z means hydrogen atom, alkyl with 1-6 carbon atoms under condition that at least one of residues W, X, Y or Z means a chain with at least 2 carbon atoms but only one of residues X and Y can mean alkenyl with 2-6 carbon atoms; CKE means one of the following groups: , , and wherein A means hydrogen atom, alkyl with 1-6 carbon atoms; B means hydrogen atom, alkyl with 1-6 carbon atoms; A and B in common with carbon atom to which they are bound mean cycloalkyl with 5-6 carbon atoms wherein the ring carbon atom can be substituted with oxygen atom and can be substituted with alkyl with 1-6 carbon atoms or alkoxyl with 1-6 carbon atoms; A and B in common mean group of the formula: D means hydrogen atom or phenyl substituted with fluorine atom if CKE means group of the formula (4); G means hydrogen atom (a) or one of groups of the formula: or wherein R1 means alkyl with 1-6 carbon atoms, alkoxymethyl with 1-2 carbon atoms; R2 means alkyl with 1-4 carbon atoms; A and Q1 in common mean alkanediyl with 3-4 carbon atoms; Q2 means hydrogen atom. Invention provides preparing compound of the formula (I) possessing with insecticide, acaricide and herbicide activity.

EFFECT: valuable properties of compounds.

2 cl, 8 tbl, 32 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of derivatives of indolinospiropyrane of the formula (1): wherein R1 means (C1-C18)-alkyl; each among R2 and R3 mean independently (C1-C4)-alkyl; R4 means hydrogen atom, hydroxy-group, trichloromethyl, trifluoromethyl formyl, (C1-C)-alkyl, halogen atom, (C1-C4)-alkoxy-, nitro-group; x = 1 or 2. Method comprises the following steps: (i) synthesis of indoline on polymeric carrier of the formula (III): wherein R1 means (C1-C18)-alkyl; each among R2 and R means independently (C1-C4)-alkyl; (ii) treatment of indoline-carrying polymeric carrier wherein this carrier represents hydroxy-resin at temperature from 50°C to 120°C in inert atmosphere for time from 14 h to 11 days with a derivative of salicylic aldehyde of the formula (VI): wherein R4 means hydrogen atom, hydroxy-group, trichloromethyl, trifluoromethyl, formyl, (C1-C4)-alkyl, halogen atom, (C1-C4)-alkoxy-, nitro-group; x = 1 or 2 to yield indolinospiropyrane compound of the formula (I), and (iii) release of indolinospiropyrane compound of the formula (I). Invention proves synthesis of novel derivatives of indolinospiropyrane possessing photochromic properties.

EFFECT: improved method of synthesis.

8 cl, 28 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to new compounds with formula I, their pharmaceutical salts and to complex esters. The invented compounds have inhibiting propertied towards catepsin K and can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved, for example, inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumorous diseases. In general formula I R represents H, R13 represents (inferior)alkyl, C3-C10cylcloalkyl or C3-C10cycloalkyl(inferior)alkyl, each of which is independently optionally substituted with a halogen atom, hydroxyl, CN, NO2 or optionally mono- or di(inferior)alkyl substituted amino group; and R14 represents H or optionally substituted phenyl, phenyl-W-, phenyl(inferior)alkyl-W-, C3-C10cycloalkyl, C3-C10cycloalkyl-W-, N-heterocyclyl, N-heterocyclyl -W-. Substitutes of the indicated values of radicals are shown in the formula of invention. The invention also relates to methods of obtaining the compounds.

EFFECT: obtaining pyrrolopyrimidines with inhibiting properties towards catepsin K, which can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved.

4 cl, 59 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new compounds, and more specifically to 5-formyl-substituted indoline spirobenzopyrans with general formula 1 where R1, R2 - Alk or c-Alk; R3 -CHO or NO2 group (electron-acceptor substitute), with photochromic properties. The invention also relates to the method of producing 5-formyl substituted derivatives of indoline spirobenzopyrans with formula 1. Spirobenzopyrans, which have electron-acceptor substitutes in the pyran part of the molecule, are subjected to direct selective formylation in position 5 in a trifluoroacetic acid medium with urotropine (hexamethylenetetramine) at boiling point of the mixture in an inert atmosphere for 1-1.5 hours. The obtained 5-formyl-substituted spirobenzopyrans are photochromic compounds are photochromic and can be used for making new photochromic materials (recording devices or information storage; photo-switching activity of biological objects and polymer matrices, complex formation; information security media, maps, special document protection equipment) or as advanced initial compounds for further synthesis of a large number of new photochromic objects.

EFFECT: wider field of application of the compounds.

2 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds -(Z)-1'-R-6',6'-dimethyl-3-(phenyl(arylamino)methylene)-6',7'-dihydro-3H-spiro[furane-2,3'-indol]-2',4,4',5(1'H,5'H)-tetraons of formula: , where Ar=phenyl, n-methoxyphenyl, n-tollyl; R=allyl, benzyl, phenyl, n-tollyl, n-methoxyphenyl, α-naphtyl, as well as to method of their obtaining, which consists in the following: isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates are subjected to interaction with N-substituted 3-amino-5,5-dimethylcyclohex-2-enons in medium of inert aprotonic solvent with further separation of target products. Process is carried out at temperature 20-22°C. As solvent, absolute chloroform is used.

EFFECT: obtaining compounds possessing analgesic activity.

4 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) or pharmaceutically acceptable salts thereof where R1 and R2 together denote a group selected form groups of formula (III-1): , where R9 denotes 1) a lower alkyl group, optionally substituted with a halogen atom or lower alkoxy group, 2) an aryl group, 3) an aralkyl group, 4) a heteroarylalkyl group, 5) a heteroaryl group, where the aryl, aralkyl, heteroarylalkyl and heteroaryl groups can be substituted with a halogen atom, lower alkyl group, optionally substituted with a lower alkoxy group or 1-3 halogen atoms, lower alkoxy group, optionally substituted with 1-3 halogen atoms, cyano group, hydroxy group, alkylsulphonyl group, cycloalkylsulphonyl group, aryl group, heteroaryl group, alkylaminocarbonyl group, alkanoyl amino group, alkyl amino group or dialkylamino group; R10 denotes a lower alkyl group, optionally substituted with 1-3 halogen atoms, or a lower alkylsulphonyl group; X9-X12 denotes a carbon atom or a nitrogen atom, where the carbon atom can be independently substituted with a lower alkyl group, optionally substituted with a halogen atom or a lower alkoxy group, lower alkoxy group, optionally substituted with a halogen atom, or a cyano group or a halogen atom; R3 denotes a) a group of formula (II-1): (ii-U where R4 and R5, taken together with a nitrogen atom, form a 5- or 6-member monocyclic ring, where the monocyclic ring may contain a substitute in form of a lower alkyl group, m1 equals 3; or b) a group of formula (II-2): , where R6 denotes a lower alkyl group or cycloalkyl group; m2 equals 1 or 2; X1-X4 all denote carbon atoms, or one of X1-X4 denotes a nitrogen atom and the rest denote carbon atoms; and where "heteroaryl" in each case relates to a 5- or 6-member aromatic ring containing 1-3 heteroatoms selected from a nitrogen atom, oxygen atom and a sulphur atom. The invention also relates to a histamine H3 receptor antagonist or inverse agonist, as well as a preventive or medicinal agent.

EFFECT: obtaining novel biologically active compounds, having histamine H3 receptor antagonist or inverse agonist activity.

11 cl, 8 ex, 1 tbl

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