Method for synthesis of 4-(1h-indol-3-yl)-but-3-en-2-one derivatives

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of novel 4-(1H-indol-3-yl)-but-3-en-2-one derivatives of general formula 3: , : which can be used in synthesis of novel preparations for pharmaceutical and agricultural purposes. The method involves mixing 2-alkyl-5-(2-amino-4-alkylphenyl)-furans 1 with aromatic and heteroaromatic aldehydes 2 in acetic acid in equimola ratio at temperature 35°C for 40 minutes in the presence of 0.01 ml hydrochloric acid.

EFFECT: improved method.

2 tbl, 5 ex

 

The invention relates to the field of organic chemistry - synthesis of heterocyclic compounds - derivatives of 4-(1H-indol-3-yl)-but-3-EN-2-it, which can be used in the synthesis of new pharmaceutical drugs and agricultural purposes.

The invention relates to a developing method of obtaining derivatives of 4-(1H-indol-3-yl)-but-3-EN-2-it General formula 3, which can be used in the synthesis of anti-cancer drugs - analogues of the alkaloid surapaneni [Guo, X.; Hu, W.; Cheng, S.; Wang, L.; Chang, J. Synth. Comm., 2006, 36, 781; Wu, T., Liou, M., Lee, S. Tetrahedron Lett. 1989, 30, 6649].

3A-

IndexRR1R2
3ANCH3
3bHC2H5
3bClCH3
3GCl CH3
3DClCH3
3rdCH3CH3
3KOch3CH3

The literature describes various approaches to the synthesis of derivatives of 4-(1H-indol-3-yl)-but-3-EN-2-it. Typically, the initial compounds already contain ready indole fragment, to which further being completed chain but-3-EN-2-it. So, by aldol condensation of 3-formylindole and acetone in the presence of aqueous NaOH receive the appropriate 4-(1H-indol-3-yl)-but-3-EN-2-ones [Paul, S., Gupta, M. Synth. Comm., 2005, 35, 213; Guo, X., Hu, W., Cheng, S., Wang, L., Chang, J. Synth. Comm., 2006, 36, 781; Caballero, E., Longieras, N., Zausa, E., del Rey, B., Medarde, M., Tome, F. Tetrahedron Lett., 2001, 42, 7233]. Condensation 3H-indoles with 4-methoxybutyl-3-EN-2-one in aqueous acetic acid also leads to the formation of 4-(1H-indol-3-yl)-but-3-EN-2-ones of the frame [Teuber, N., Schmitt, G. Tetrahedron Lett., 1971, 52, 4911].

There are also methods based on the construction of the indole skeleton is. One such example is the reaction of cyclization of derivatives of 2-alkynylamino with alkenes in the presence of a palladium catalyst, leading to a derivative of 4-(1H-indol-3-yl)-but-3-EN-2-[Yasuhara, A., Kaneko, M., Sakamoto, T. Heterocycles, 1998, 48, 1783; Yasuhara, A., Sakamoto, T., Takeda, Y., Suzuki, N. Chem. Pharm. Bull., 2002, 50, 235].

The disadvantages of these methods are the need using the original compounds containing ready indole fragment, which often can be difficult to access, or use of expensive catalysts based on palladium.

In the basis of the proposed method is the reaction of electrophilic opening the furan cycle similar to the one described in [Kusuhara N., Sugano Y., Takagi H., Miyake M., Yamamura K. Chem. Commun., 1997, 1951; M. Sasabe, Mouda V., Takagi H., Sugane T., H., Yamamura K. J. Chem., Perkin Trans. 1, 2000, 3786; Butin A.V., Tsiunchik F.A., Abaev V.T., Zavodnik V.E. Synlett, 2008, 8, 1145], which shows the reaction of intramolecular interaction of furan with electrophilic carbon atom, leading to the opening of furan cycle and, as a consequence, the formation of condensed Carbo - and heterocyclic systems.

The technical result is the synthesis of derivatives of 4-(1H-indol-3-yl)-but-3-EN-2-it 3 based on the electrophilic recyclization furan cycle, allowing to expand the range of potentially biologically active substances that represent a convenient starting compounds for the synthesis of the taxes of the natural alkaloid surapaneni.

The technical result is achieved by the fact that stirred in acetic acid in equimolar ratio available 2-alkyl-5-(2-amino-4-alkylphenyl)-furan 1 with aromatic and heteroaromatic aldehydes 2 at 35°C for 40 min in the presence of 0.01 ml of hydrochloric acid. Alkyl-5-(2-amino-4-alkylphenyl)-furan 1 obtained by the known method [Butin, A.V. Tetrahedron Lett. 2006, 47, 4113]. Most likely the formation of unsaturated derivatives of indole is the result of electrophilic disclosure and subsequent recyclization furan ring intermediate formed yliniemi connections A.

The melting temperature, the data of elemental analysis and spectral characteristics of 4-(1H-indol-3-yl)-but-3-EN-2-ones 3A-K are listed in table 1.

The technical result allows to expand the number of derivatives of 4-(1H-indol-3-yl)-but-3-EN-2-ones 3A-K, and thus the range of potentially biologically active compounds.

Thus, the set of essential features set forth in the claims, allows to achieve the desired technical result.

Table 1
Outputs and physico-chemical characterization of 4-(1H-indol-3-yl)-but-3-EN-2-ones 3
No.DeputyYou move %tPL, °CFound, %Range1H NMR (DMSO-D6), (δ, ppm and KCCB, J, Hz)Range13With NMR (DMSO-D6), (δ, ppm)
Calculated, %
RR1R2NN
1234567891011
3ANCH379257-258Ar), 7.30-7.35 (m, 1H, HAr), 7.53-7.55 (m, 1H, HAr), 7.73 (d, J=15.9 Hz, 1H, =CH), 7.91 (d, J=9.0 Hz, 2H, HAr), 8.04-8.06 (m, 1H, HAr), 8.45 (d, J=9.0 Hz, 2H, HAr), 12.40 (c, 1H, NH)27.9, 110.0, 112.5, 120.9, 121.7, 123.9, 124.0, 124.1 (2C), 125.7, 130.5 (2C), 135.8, 137.3, 137.4, 140.4, 147.2, has 197.5
3bNWith2H570208-2091.02 (t, J=7.4 Hz, 3H, Me), 2.60 (q, J=7.4 Hz, 2H, CH2), 6.84 (d, J=15.9 Hz, 1H, =CH), 7.08 (d, J=8.7 Hz, 1H, HAr), 7.18-7.28 (m, 2H, HAr), 7.33 (d, J=2.4 Hz, 1H, HAr), 7.41 (DD, J=2.4, 8.7 Hz, 1H, HAr), 7.45-7.48 (m,1H, HAr), 7.58 (d, J=15.9 Hz, 1H, =CH), 7.98-8.01 (m, 1H, HAr), 10.33 (s, 1H, HE), 11.98 (s, 1H, NH)8.5, 33.8, 109.5, 112.1, 117.8, 119.9, 120.2, 120.5, 121.1, 122.4, 122.7, 125.3, 130.2, 131.2, 136.1, 136.8, 140.1, 154.5, 199.7
3bC1CH376237-238 2.27 (s, 3H, Me), 3.86 (s, 6N, OMe), 6.84 (d, J=16.2 Hz, 1H, =CH), 7.13-7.23 (m, 4H, HAr), 7.47 (d, J=1.8 Hz, 1H, HAr), 7.77 (d, J=16.2 Hz, 1H, =CH), 7.98 (d, J=8.4 Hz, 1H, HAr), 12.18(c, 1H, NH)27.8, 55.7 (2C), 107.8, 111.5, 111.9, 112.5, 121.4, 121.8, 122.4, 122.6, 122.9, 124.7, 127.3, 136.5, 137.2, 144.8, 148.9, 149.8, 197.2
3GC1CH380267-2682.34 (s, 3H, Me), 2.43 (s, 3H, Me), 6.39 (d, J=3.3 Hz, 1H, HFur), 6.80 (d, J=16.2 Hz, 1H, =CH), 6.98 (d, J=3.3 Hz, 1H, HFur), 7.17 (DD, J=2.1, 8.7 Hz, 1H, HAr), 7.43 (d, J=2.1 Hz, 1H, HAr), 7.93 (d, J=8.7 Hz, 1H, HAr), 8.17 (d, J=16.2 Hz, 1H, =CH), 12.17 (s, 1H, NH)13.5, 27.4, 107.4, 108.8, 111.4, 112.5, 121.5,121.9, 123.5, 124.4, 127.7, 133.3, 135.9, 137.7, 144.2, 154.1, 197.4

Continuation of table 1
3DCl CH375237-2382.32 (s, 3H, Me), 6.87 (d, J=16.2 Hz, 1H, =CH), 7.21 (DD, J=1.8, 8.4 Hz, 1H, HAr), 7.33 (d, J=5.1 Hz, 1H, HTh), 7.47 (d, J=1.8 Hz, 1H, HAr), 7.56 (DD, J=1.2, 3.0 Hz, 1H, HTh), 7.87 (DD, J=1.2 and 5.4 Hz, 1H, HTh), 7.96 (d, J=16.2 Hz, 1H, =CH), 7.98 (d, J=8.7 Hz, 1H, HAr), 12.29 (c, 1H, NH)27.9, 108.7, 111.6, 121.6, 121.9, 123.7, 124.5, 127.9, 128.5, 128.7, 129.4, 131.4, 135.3, 137.3, 137.5, 197.3
3rdCH3CH374266-2672.26 (s, 3H, Me), 2.44 (s, 3H, Me), 6.85 (d, J=16.2 Hz, 1H, =CH), 7.06 (DD, J=1.5, 8.1 Hz, 1H, HAr), 7.28 (d, J=1.5 Hz, 1H, HAr), 7.55 (d, J=8.4 Hz, 2H, HAr), 7.67 (d, J=16.2 Hz, 1H, =CH), 7.79 (d, J=8.4 Hz, 2H, HAr), 7.87 (d, J=8.1 Hz, 1H, HAr), 12.06 (c, 1H, NH)21.3, 27.9, 108.6, 112.0, 120.4, 122.5, 122.6, 123.1, 123.6, 130.3, 131.3 (2C), 131.9 (2C), 132.7, 136.5, 137.4, 141.9, 197.2
3KOch3CH379116-1171.16 (t, J=6.9 Hz, 3H, Me), 2.07 (s, 3H, Me), 3.83 (s, 3H, Me), 4.19 (q, J=6.9 Hz, 2H, CH2), 6.67 (d, J=16.2 Hz, 1H, =CH), 6.88 (DD, J=2.1, 8.6 Hz, 1H, HAr), 6.92 (d, J=2.1 Hz, 1H, HAr),7.19 (d, J=16.2 Hz, 1H, =CH), 7.23-7.28 (m, 1H, HAr), 7.38-7.45 (m, 2H, HAr), 7.63 (d, J=9.0 Hz, 1H, HAr), 7.92 (d, J=8.6 Hz, 1H, HAr), 7.95-8.01 (m, 1H, HAr), 8.15 (d, J=9.0 Hz, 1H, HAr), 11.89 (s, 1H, NH)14.8, 27.9, 55.3, 64.5, 95.1, 110.6, 110.7, 115.1, 119.6, 120.4, 121.0, 123.9, 124.2, 127.4, 128.2, 128.3, 128.4, 131.4, 133.8, 136.7, 138.2, 138.6, 154.9, 156.2, 196,8

Examples of the proposed method of obtaining 4-(2-[4-nitrophenyl]-1H-indol-3-yl)-but-3-EN-2-she 3A.

Example 1.

A mixture of 0.5 g (3 mmol) of 2-methyl-5-(2-AMINOPHENYL)-furan 1A, 0.45 g (3 mmol) of 4-nitrobenzaldehyde, 10 ml of acetic acid and 0.01 ml of hydrochloric acid was stirred at 35°C for 40 minutes and Then the reaction mixture is poured into 100 ml of water, neutralize NaHCO3, extracted with ethyl acetate (3×15 ml), the combined organic fractions are dried with sodium sulfate, tfilter is to see with activated charcoal and evaporated under reduced pressure. The residue is separated on silica gel brand KSK (production LLC Sorbolene) fraction of 5-40 μm, eluent CH2Cl2/hexane (1:4)to exit from the top of impurities, and the target product remains in the upper layer of silica gel, then eluent acetone. Recrystallized from a mixture of acetone/ethanol. Yield 79% (0.72 g).

Tpl.=257-258°C.

Found for C18H14N2About3, %: C, 70.47; H 4.51; N, 9.31.

Calculated: C, 70.58; H 4.61; N, 9.15.

Range1H NMR (DMSO-D6), (δ, ppm and coupling constants, J, Hz): 2.30 (s, 3H, CH3), 6.94 (d, 1H, J=16.2 Hz, =CH), 7.23-7.28 (m, 1H, HAr), 7.30-7.36 (m, 1H, HAr), 7.53-7.55 (m, 1H, HAr), 7.73 (d, J=16.2 Hz, 1H, =CH), 7.91 (d, J=8.9 Hz, 2H, HAr), 8.04-8.06 (m, 1H, HAr), 8.45 (d, J=8.9 Hz, 2H, HAr).

Range13With NMR (DMSO-D6), (δ, m D.): 27.9, 110.0, 112.5, 120.9, 121.7, 123.9, 124.0, 124.1 (2C), 125.7, 130.5 (2C), 135.8, 137.3, 137.4, 140.4, 147.2, has 197.5.

Example 2.

A mixture of 0.5 g (3 mmol) of 2-methyl-5-(2-AMINOPHENYL)-furan 1a, 0.45 g (3 mmol) of 4-nitrobenzaldehyde, 10 ml of acetic acid and 0.01 ml of acid was stirred at 35°C for 8 hours. Then the reaction mixture is poured into 100 ml of water, neutralize NaHCO3, extracted with ethyl acetate (3×15 ml), the combined organic fractions are dried with sodium sulfate, filtered with activated charcoal and evaporated under reduced pressure. The residue is separated on silica gel brand KSK (production LLC Sorbolene) fraction of 5-40 μm, eluent CH2Cl2/hexane (:4), to exit from the top of impurities, and the target product remains in the upper layer of silica gel, then eluent acetone. Recrystallized from a mixture of acetone/ethanol. Yield 60% (0.55 g).

Example 3.

A mixture of 0.5 g (3 mmol) of 2-methyl-5-(2-AMINOPHENYL)-furan 1A, 0.45 g (3 mmol) of 4-nitrobenzaldehyde, 10 ml of acetic acid and 0.01 ml of hydrochloric acid was stirred at 60°C for 40 minutes and Then the reaction mixture is poured into 100 ml of water, neutralize NaHCO3, extracted with ethyl acetate (3×15 ml), the combined organic fractions are dried with sodium sulfate, filtered with activated charcoal and evaporated under reduced pressure. The residue is separated on silica gel brand KSK (production LLC Sorbolene) fraction of 5-40 μm, eluent CH2Cl2/hexane (1:4)to exit from the top of impurities, and the target product remains in the upper layer of silica gel, then eluent acetone. Recrystallized from a mixture of acetone/ethanol. Exit 67% (0.62 g).

Example 4.

A mixture of 0.5 g (3 mmol) of 2-methyl-5-(2-AMINOPHENYL)-furan 1A, 0.45 g (3 mmol) of 4-nitrobenzaldehyde, 10 ml of acetic acid and 0.01 ml of hydrochloric acid is boiled for 10 minutes and Then the reaction mixture is poured into 100 ml of water, neutralize Panso3, extracted with ethyl acetate (3×15 ml), the combined organic fractions are dried with sodium sulfate, filtered with activated charcoal and evaporated under reduced pressure. the STATCOM share on silica gel brand KSK (production LLC Sorbolene) fraction of 5-40 μm, eluent CH2Cl2/hexane (1:4)to exit from the top of impurities, and the target product remains in the upper layer of silica gel, then eluent acetone. Recrystallized from a mixture of acetone/ethanol. Exit 40% (0.37 g).

Example 5.

A mixture of 0.5 g (3 mmol) of 2-methyl-5-(2-AMINOPHENYL)-furan 1A, 0.45 g (3 mmol) of 4-nitrobenzaldehyde, 10 ml of acetic acid and 0.01 ml of hydrochloric acid is stirred at 15°C for 40 minutes and Then the reaction mixture is poured into 100 ml of water, neutralize Panso3, extracted with ethyl acetate (3×15 ml), the combined organic fractions are dried with sodium sulfate, filtered with activated charcoal and evaporated under reduced pressure. The residue is separated on silica gel brand KSK (production LLC Sorbolene) fraction of 5-40 μm, eluent CH2Cl2/hexane (1:4)to exit from the top of impurities, and the target product remains in the upper layer of silica gel, then eluent acetone. Recrystallized from a mixture of acetone/ethanol. Output 15% (0.14 g).

Table 2 shows data on the effect of reaction time and temperature of the reaction mixture to yield 4-(2-[4-nitrophenyl]-1H-indol-3-yl)-but-3-EN-2-she 3A (examples 1-5).

Table 2
The influence of reaction conditions on the yield of 4-(2-[4-nitrophenyl]-1H-indol-3-yl)-but-3-EN-2-she 3A
ExampleTemperature, °CThe reaction timeOutput %
13540 min84
2358 hours60
36040 min67
4boiling10 min40
51540 min15

As can be seen from table 2, the optimal condition for the synthesis of the desired product 4-(1H-indol-3-yl)-but-3-EN-2-it 3 is stirring in acetic acid 2-alkyl-5-(2-amino-4-alkylphenyl)-furan 1 with aldehydes 2 at 35°C for 40 min, in the presence of 0.01 ml of hydrochloric acid.

A longer reaction time, as well as the increase in the temperature of the reaction mixture, accompanied by a strong resinification and, as a consequence, the reduction of the yield of the target product.

Conducting the reaction at temperatures below 35°C is not provides the complete conversion of the starting compounds, and gate 4-(1H-indol-3-yl)-but-3-EN-2-it 3 does not exceed 15%.

The claimed method received a number of derivatives of 4-(1H-indol-3-yl)-but-3-EN-2-she 3A-K.

The method of obtaining derivatives of 4-(1H-indol-3-yl)-but-3-EN-2-ones of General formula 3

3A to

IndexRR1R2
3AHCH3
3bHWith2H5
3bClCH3
3GClCH3
3DClCH3
3rdCH3 CH3
3KOch3CH3

characterized by the fact that stirred in acetic acid in equimolar ratio available 2-alkyl-5-(2-amino-4-alkylphenyl)-furan 1, aromatic and heteroaromatic aldehydes 2 at 35°C for 40 min in the presence of 0.01 ml of hydrochloric acid.



 

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2 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

where the carbon atom denoted * is in R- or S-configuration; X is a concentrated bicyclic carbocycle or heterocycle selected from a group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, indazolyl, indolyl, benzooxazolyl, benzothiazolyl, indenyl, indanyl, dihydrobenzocycloheptenyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, quinoxalinyl, 2H-chromenyl, imidazo[1.2-a]pyridinyl, pyrazolo[1.5-a]pyridinyl, and condensed bicyclic carbocycle or condensed bicyclic heterocycle, optionally substituted with substitutes (1 to 4) which are defined below for R14; R1 is H, C1-C6-alkyl, C3-C6-cyclalkyl, C1-C3-alkyl, substituted OR11, -NR9R10 or -CN; R2 is H, C1-C6-alkyl, or gem-dimethyl; R3 is H, -OR11, C1-C6-alkyl or halogen; R4 is H, halogen, -OR11, -CN, C1-C6-alkyl, C1-C6-alkyl, substituted -NR9R10, C3-C6-cycloalkyl, substituted -NR9R10, C(O)R12; or R4 is morpholinyl, piperidinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, isoxazolyl, pyrrolidinyl, piperazinyl, 2-oxo-2H-pyridinyl, [1.2.4]triazolo[4.3-a]pyridinyl, 3-oxo-[1.2.4]triazolo[4.3-a]pyridinyl, quinoxalinyl, which are optionally substituted with substitutes (1 to 4) which are defined below for R14; R5 is H or C1-C6-alkyl; R6 is H, C1-C6-alkyl, or -OR11; R7 is H; R8 is H, -OR9, C1-C6-alkyl, -CN; R9 is H or C1-C4-alkyl; R10 is H or C1-C4-alkyl; or R9 and R10 taken together with the nitrogen atom to which they are bonded form morpholine; R11 is H, C1-C4-alkyl; R12 is C1-C6-alkyl; R14 in each case is independently selected from a substitute selected from a group consisting of halogen, -OR11, -NR11R12, C1-C6-alkyl, which is optionally substituted with 1-3 substitutes, in each case independently selected from a group consisting of C1-C3-alkyl, aryl; or to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition, to a method of obtaining formula (I) compounds, as well as to a method of treating disorders.

EFFECT: obtaining new biological active compounds having norepinephrine, dopamine and serotonin reuptake selective inhibitory activity.

90 cl, 162 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel 1-thio-D-glucitol compounds of formula I or to pharmaceutically acceptable salts thereof or hydrates of the compound or salts: , [where R1, R2, R3 and R4 are identical or different, and each is a hydrogen atom, C1-C6-alkyl group), A is -(CH2)n-, -CONH(CH2)n-, -O- or -(CH2)nCH=CH- (where n is an integer from 0 to 3, Ar1 is an arylene group, heteroarylene group, which is an unsaturated 5-9-member mono- or bicyclic group, containing 1-2 heteroatoms, selected from S and N, Ar2 is an aryl group or heteroaryl group which is an unsaturated 5-9-member mono- or bicyclic group containing 1-2 heteroatoms selected from O, S and N, and R5, R6, R7, R8, R9 and R10 are identical or different, and each is (i) a hydrogen atom, (ii) a halogen atom, (iii) a hydroxyl group, (iv) C1-8-alkyl group, optionally substituted with hydroxyl group(s), (v) -(CH2)m-Q {where m is an integer from 0 to 4, and Q is -CO2H, -ORc1, -CO2Ra3, -SRe1, -NHRa6 or -NRa7Ra7 (where each of Ra3, Ra6 and Ra7 is a C1-6-alkyl group, Rc1 is a C1-6-alkyl group, and Rc1 is a C1-6-alkyl group)}, (vi) -O-(CH2)m'-Q' {where m' is an integer from 1 to 4, and Q' is a hydroxyl group,-CO2H, -CO2Ra8, -CONRa10Ra10, -NRa12Ra12 (where each of Ra8, Ra10 and Ra12 is a C1-6-alkyl group)}, (vii) -ORf {where Rf is C3-7-cycloalkyl group or tetrahydropyranyl group)}, (viii) morpholine group, (ix) phenyl group, (x) pyridyl group]. The invention also relates to 1-thio-D-glucitol compounds of formulae IA, II, III, IV, to a pharmaceutical agent, to methods of obtaining 1-thio-D-glucitol compounds, as well as to compounds of formulae XIII, XIV.

EFFECT: obtaining novel biologically active compounds which are inhibitors of sodium-dependent co-transporter-2-glucose.

25 cl, 140 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I) and to its pharmaceutically acceptable additive salts, optionally in the form of stereochemical isomer and exhibiting anti-HIV antiviral activity, particularly having HIV inhibitor properties and applied as a drug. In formula , -a1=a2-a3=a4- represents a bivalent radical of formula -CH=CH-CH=CH-(a-1); -b1=b2-b3-b4 - represents a bivalent radical of formula -CH=CH-CH=CH- (b-1); n is equal to 0, 1, 2, 3, 4; m is equal to 0, 1, 2; each R1 independently represents hydrogen; each R2 represents hydrogen; R2a represents cyano; X1 represents -NR1-; R3 represents C1-6alkyl, substituted cyano; C2-6alkrnyl, substituted cyano; R4 represents halogen; C1-6alkyl; R5 represents 5 or 6-member completely unsaturated cyclic system where one, two or three members of the cycle represent heteroatoms, each independently specified from the group consisting of nitrogen, oxygen and sulphur and where the rest members of the cycle represent carbon atoms; and where 6-member cyclic system can be optionally annelated with a benzene cycle; and where any carbon atom in the cycle can be independently optionally substituted with a substitute specified from C1-6alkyl, amino, mono- and diC1-4alkylamino, aminocarbonyl, mono-and diC1-4alkylcarbonylamino, phenyl and Het; where Het represents pyridyl, thienyl, furanyl; Q represents hydrogen The invention also concerns a pharmaceutical composition.

EFFECT: preparation of the new anti-HIV antiviral compounds.

4 cl, 2 tbl, 22 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula where: R1 denotes -OR1', -SR1", 6-member heterocycloalkyl with one O atom and possibly one N atom, phenyl or 5-member heteroaryl with two N atoms, 6-member heteraryl with one N atom; R1'/R1" denote C1-6-alkyl, C1-6-alkyl substituted with a halogen, -(CH2)x-C3-6cycloalkyl or -(CH2)x-phenyl; R2 denotes S(O)2-C1-6-alkyl, -S(O)2NH-C1-6-alkyl, CN; denotes the group: , and where one extra N atom of the nucleus of an aromatic or partially aromatic bicyclic amine may be present in form of its oxide ; R3 - R10 denotes H, halogen, C1-6-alkyl, C3-6cycloalkyl, 4-6-member heterocycloalkyl with one N or O atom, 6-member heterocycloalkyl with two O atoms or two N atoms, 6-8-member heterocycloalkyl containing on N atom or one O or S atom, 5-member heteroaryl with two or three N atoms, 5-member heteroaryl with one S atom, in which one carbon atom may be also substituted with N or O, 6-member heteroaryl with one or two N atoms, C1-6-alkoxy, CN, NO2, NH2, phenyl, -C(O)-5-member cyclic amide, S-C1-6-alkyl, -S(O)2-C1-6-alkyl, C1-6-alkyl substituted with halogen;C1-6-alkoxy substituted with halogen, C1-6-alkyl substituted with OH, -O-(CH2)y-C1-6-alkoxy, -O(CH2)yC(O)N(C1-6-alkyl)2, -C(O)-C1-6-alkyl, -O-(CH2)x-phenyl, -O-(CH2)x-C3-6cycloalkyl, -O-(CH2)x-6-member heterocycloalkyl with one O atom, -C(O)O-C1-6-alkyl, -C(O)-NH-C1-6-alkyl, -C(O)-N(C1-6-alkyl)2, 2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl or 3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl; R' and R'" in group (e) together with -(CH2)2- with which it is bonded can form a 6-member ring; R, R', R" and R"' independently denote H, C1-6-alkyl; and where all groups - phenyl, cycloalkyl, cyclic amine, heterocycloalkyl or 5- or 6-member heteroaryl, as defined for R1, R1', R1" and R3 - R10, can be unsubstituted or substituted with one or more substitutes selected from OH, =O, halogen, C1-6-alkyl, phenyl, C1-6-alkyl substituted with halogen, or C1-6-alkoxy; n, m o, p, q, r, s and t = 1 , 2; x =0, 1 or 2; y = 1 , 2; and their pharmaceutically acceptable acid addition salts.

EFFECT: compounds have glycine transporter 1 inhibiting activity, which enables their use in a pharmaceutical composition.

20 cl, 2 tbl, 12 dwg, 382 ex

FIELD: medicine.

SUBSTANCE: invention refers to a polymer derivative of cytidine antimetabolite of formula (1) which can be used as an antineoplastic drug: (1), where R is hydrogen or alkyl; A is hydrogen, acyl or alkoxycarbonyl; m is within 3 to 200; n is within 5 to 2000; X is a residue of cytidine antimetabolite, hydroxyl or a hydrophobic substitute, and X means a residue of cytidine antimetabolite in amount 3-100 % m, hydroxyl in amount 0-95 % m and the hydrophobic substitute in amount 0-80 % m.

EFFECT: preparation of new antineoplastic compounds.

8 cl, 5 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of 4(5)-(2-hetaryl) and 4(5)-(2-hetaryl)-2-(2'-hetaryl)-imidazoles of general formula R=2-furyl, 2-thienyl; R'H; and R=2-furyl, 2-thienyl; R'=2-furyl is obtained using 2-bromoacetylfuran (thiophene) of general formula 2-thienyl and aldehydes in the presence of copper acetate, synthesis of a 2-bromoacetylfuran (thiophene) precursor is carried out by reacting 2-acetylfuran (thiophene) with copper (II) bromide.

EFFECT: increased safety of the process.

2 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds, specifically to 4-substituted-3-(1-alkyl-2-chloro-1H-indol-3-yl)furan-2,5-diones of general formula I , where R1=H, C1-C6 alkyl; R2=H, C1-C6 alkyl, C1-C6 alkoxy; R3=phenyl, naphthyl, 2-phenyl-1-ethenyl, thienyl, furyl, pyrrolyl, benzothiophenyl, benzofuranyl, indolyl, synthesis method thereof and use as compounds capable of photochemical generation of stable fluorophores of formula II, which can be used, for instance in information storage systems, particularly as photosensitive components of material for three-dimensional recording and storage of information. The invention also relates to novel 4,5-substituted-6-alkyl-1H-furo[3,4-c]carbazole-1,3(6H)diones of general formula II , where R1=H, C1-C6 alkyl; R2=H, C1-C6 alkyl, C1-C6 alkoxy; R4=H, R5=phenyl, R4, R5=benzo, naphtho, thieno, furo, pyrrolo, benzothieno, benzofuro, indolo, method for synthesis of said compounds and use as fluorophores.

EFFECT: obtaining novel compounds and possibility of using said compounds as fluorophores.

14 cl, 2 tbl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new chroman derivatives of formula I: , or to their pharmaceutically acceptable salts where m has a value of 0; p has a value of 2; q has a value of 2; Ar represents phenyl optionally substituted with halogen atom; R2 represents ; X represents -NR9-; n has a value of 2 or 3; each R3, R4, R5 and R6 independently represents hydrogen or C1-12alkyl; each R7 and R8 independently represents either hydrogen, or C1-12-alkyl, or R7 and R8 together with nitrogen whereto attached, can form 4-6-members ring, or one of R7 and R8 and one of R5 and R6 together with atoms whereto attached can form 4-6-members ring; and R9 represents hydrogen or C1-12-alkyl, or when R7 represents hydrogen or methyl, R9 together with R8 and atoms whereto attached can form 6-members ring.

EFFECT: preparation of chroman new derivatives and the pharmaceutical composition containing compounds of formula (I).

22 cl, 1 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of existing and novel N-sulfamoyl- N'-arylpiperazines and their physiologically compatible acid-addition salts of formula I , where Ar denotes a monocyclic or bicyclic C6-C10aryl in which ring carbon atoms are optionally substituted with 1-3 nitrogen or oxygen atoms, and/or where the C6-C10aryl ring system optionally contains 3-5 double bonds, and/or where the C6-C10aryl ring system is optionally substituted with 1 or 2 substitutes which can be identical or different and which can be selected from a group containing halogen, trifluoromethyl, cyano group, nitro group, C1-C4alkyl, C1-C4alkoxy group, C1-C4alkylsulfonyl; and two oxygen atoms which are bonded to two neighbouring carbon atoms of the C6-C10aryl ring system and are bonded by a C1-C2alkylene bridge; or where the C6-C10aryl ring system is substituted with phenyl which can optionally be substituted in the phenyl ring by one substitute which can be selected from a group containing halogen; for preventing or treating obesity and related diseases.

EFFECT: design of a method of obtaining the said compounds and a pharmaceutical composition based on the said compounds.

25 cl, 9 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: in novel compounds of the formula (I) R is radical selected out of i) , ii) , iii) , iv) , where R7 is halogen, cyano, C1-4alkyl, C1-4alkoxy; p is integer within 0 to 3; R1 is hydrogen, C2-4alkenyl or C1-4alkyl; R2 is hydrogen or C1-4alkyl; R3 and R4 are independently hydrogen or C1-4alkyl; R5 is: phenyl substituted with 1-3 groups selected independently out of trifluoromethyl, C1-4alkyl, cyano or halogen; naphthyl substituted with 1-3 groups selected independently out of trifluoromethyl, C1-4alkyl, cyano or halogen; benzofurane substituted with 1-3 groups selected independently out of C1-4alkyl or halogen; R6 is hydrogen or (CH2)qR8; R8 is hydrogen; m is zero or 1; n is 1; q is an integer within 1 to 4; r is 1 or 2; provided that if R5 is phenyl substituted with 1-3 groups selected independently out of trifluoromethyl, C1-4alkyl, cyano or halogen, then R is not radical i) ; and pharmaceutically acceptable salts or solvates thereof. The invention also refers to method (A) of compound obtainment, to compound application, to pharmaceutical composition, as well as to mammal treatment method.

EFFECT: obtainment of novel bioactive compounds with tachykinin receptor antagonist activity.

16 cl, 116 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds - 5-[3-(4-benzyloxyphenylthio)-fur-2-yl]-imidazolidine-2,4-diones and their formula (IV) or pharmaceutically acceptable salts thereof , where R is selected from a group consisting of phenyl, 4-benzyloxyphenyl, 4-diphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 2-methoxyphenyl, 3,5-dimethoxyphenyl, 4-chlorophenyl, 3-chlorophenyl, 2-chlorophenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl and 3-trifluoromethylphenyl, useful as human microphage elastase (MMP-12) inhibitors, as well as pharmaceutical compositions based on the said compounds and inhibition method.

EFFECT: obtaining compounds useful as human microphage elastase (MMP-12) inhibitors, as well as design of pharmaceutical compositions based on the said compounds and inhibition method.

6 cl, 1 dwg,1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: described is a compound selected from a group consisting of formula II formula III and formula IV , or its salt or ester, where G1 is selected from a group which includes - (CR1R2)n-, n equals 0 or 1; R1 and R2 are independently selected from a group which includes hydrogen; X1, X2 and X3 are independently selected from a group consisting of hydrogen, optionally substituted lower alkyl, halogen, optionally substituted lower alkoxy, G2 is a heterocycloalkyl linker optionally substituted with X4 and X5, where the heterocycloalkyl linker is selected from a group consisting of piperazinyl, 3,6-dihydro-2N-pyridinyl, [1,4]diazepanyl, 3,9-diazabicyclo[3,3,1]nonyl; X4 and X5 are independently selected from a group consisting of hydrogen and optionally substituted lower alkyl; CO2R; R is selected from a group consisting of optionally substituted lower alkyl and hydrogen; G3 is a bond; G4 is selected from a group consisting of hydrogen, aryl, selected from phenyl which is optionally substituted with a lower alkyl, halogen, lower haloalkyl or lower haloalkoxy; heteroaryl selected from pyridinyl which is optionally substituted with a halogen or lower haloalkyl; and optionally substituted cycloheteroalkyl selected from 1,3-benzodioxolyl. Described also are specific compounds and a pharmaceutical composition.

EFFECT: disclosed compounds are used as modulators of receptors activated by a peroxisomal proliferator.

5 cl, 2 tbl, 117 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel indole derivatives, specifically to hydrogen halides of N-[2-(1-alkyl-1H-indol-3-yl)-1-(4-alkylpiperazine-1-carbonyl)-vinyl]-2-fluorobenzamide of formula I: , where R1 and R2=alkyl C1-C6, X=Cl, Br, having local anaesthetic and antiarhythmic activity.

EFFECT: obtaining new indole derivatives having useful biological properties.

11 tbl, 1 ex

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