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(e)-2-(4-{ [3-(2,4-dimethoxyphenyl)acrylamido]methyl} -1h-1,2,3-triazole-1-yl)-2-isopropyl-9-(4-methyl piperazine-1-yl)-3,7-dioxo-3,7-dihydro-2h-furo[3,2-g]chromen, having analgesic activity
(e)-2-(4-{ [3-(2,4-dimethoxyphenyl)acrylamido]methyl} -1h-1,2,3-triazole-1-yl)-2-isopropyl-9-(4-methyl piperazine-1-yl)-3,7-dioxo-3,7-dihydro-2h-furo[3,2-g]chromen, having analgesic activity
IPC classes for russian patent (e)-2-(4-{ [3-(2,4-dimethoxyphenyl)acrylamido]methyl} -1h-1,2,3-triazole-1-yl)-2-isopropyl-9-(4-methyl piperazine-1-yl)-3,7-dioxo-3,7-dihydro-2h-furo[3,2-g]chromen, having analgesic activity (RU 2549574):
Another patents in same IPC classes:
Chromone derivatives, method for preparing them and therapeutic uses thereof Chromone derivatives, method for preparing them and therapeutic uses thereof / 2545214
Invention refers to new chromone derivatives of general formula
Quinolone compound and pharmaceutical composition Quinolone compound and pharmaceutical composition / 2544530
Invention refers to organic chemistry, namely to new quinolin-4-one derivatives of formula (1) or to its pharmaceutically acceptable salt, wherein R1 represents: (1) hydrogen, (2) C1-C6 alkyl, (35) carbamoyl-C1-C6 alkyl optionally containing morpholinyl-C1-C6 alkyl, or (36) phosphonoxy-C1-C6 alkyl optionally containing one or two C1-C6 alkyl groups on a phosphonoxy group; R2 represents: (1) hydrogen or (2) C1-C6 alkyl; R3 represents phenyl, thienyl or furyl, wherein a phenyl ring presented by R3, can be substituted by one C1-C6 alkoxy group; R4 and R5 are bound to form a group presented by any of the following formulas: , , , , , , or a group presented by the following formula: a group optionally containing one or more substitutes specified in a group consisting of C1-C6 alkyl groups and oxogroups; R6 represents hydrogen; and R7 represents C1-C6 alkoxy group. The invention also refers to a pharmaceutical composition based on the compound of formula , to a preventive and/or therapeutic agent based on the compound of formula (1), using the compound of formula (1), a method for preparing the compound of formula , as well as to specific compounds.
Method for making and prescribing sphaelactone derivate and its composites Method for making and prescribing sphaelactone derivate and its composites / 2537319
Invention refers to micheliolide derivatives of formula , a based pharmaceutical composition and using them for treating cancer. In formula (I) R1 represents H, -C(O)R4, wherein R4 represents C1-8alkyl; R2=R3 represents a double bond, or R3 represents H, and R2 represents substituted alkyl having from 1 to 8 carbon atoms, wherein a substitute represents -NR7R8; or its pharmaceutically acceptable salts; and wherein R7 and R8 can be identical or different, and represent C1-8alkyl; X represents oxygen; Y represents a single bond.
Usnic acid derivatives as anti-tumour agents Usnic acid derivatives as anti-tumour agents / 2536873
Invention provides benzylidene furanone derivatives of (+)-usnic acid of formula 6-13 as anti-tumour agents. The compounds exhibit cytotoxic activity with respect to tumour cell lines CEM-13, U-937, MT-4.
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Invention concerns Mycobacterium tuberculosis growth inhibitors representing (+) and (-)-enantiomers of derivatives of usnic acid containing a furilidene furanone fragment, namely (10R,4Z)-8,13-dihydroxy-7,10-dimethyl-4-(2-furanylmethylidene)-5,16-dioxatetracyclo[7.7.0.02.6.010.15]hexadeca-1,6,8,12,14-pentaen-3,11-dione 4a and (10S,4Z)-8,13-dihydroxy-7,10-dimethyl-4-(2-furanylmethylidene)-5,16-dioxatetracyclo[7.7.0.02.6.010.15]hexadeca-1,6,8,12,14-pentaen-3,11-dione 4b
Method of obtaining pyripyropene derivatives Method of obtaining pyripyropene derivatives / 2532441
Invention relates to a method of obtaining pyripyropene derivatives, namely a compound of formula C: , where R represents a linear chain, a branched chain or cyclic C2-6alkylcarbonyl, on condition that, when an alkyl fragment in an alkylcarbonyl group represents a branched chain or a cyclic group, R represents C3-6alkylcarbonyl, including: selective acylation of hydroxyl groups in 1-position and 11-position of a compound B1, represented by formula B1: with an acylating agent in one-three stages in the presence or absence of a base. (i) compound C is obtained by acylation of hydroxyl groups in 1-position and 11-position of the compound B1 in one stage; (ii) method, including obtaining the compound C by acylation in two stages, consisting of stages: acylation of the hydroxyl group in 11-position of the compound B1 with the acylating agent with obtaining the compound B2, represented by formula B2: , where R is determined in formula C; and additional acylation of the hydroxyl group in 1-position of the compound B2; or (iii) method, including obtaining the compound C by acylation in three stages, consisting of stages: acylation of the hydroxyl group in 11-position of the compound B1 with obtaining the compound B2, represented by formula B2: , where R is determined in the formula C; transfer of acyl in 11-position of the compound B2 to hydroxyl in 1-position with obtaining the compound B3, represented by formula B3: , where R is such as determined in the formula C; and acylation of hydroxyl group in 11-position of the compound B3.
Novel (poly)aminoalkylaminoalkylamide, alkyl-urea or alkyl-sulfonamide derivatives of epipodophyllotoxin, method of obtaining thereof and method of application thereof in therapy as anti-cancer medications Novel (poly)aminoalkylaminoalkylamide, alkyl-urea or alkyl-sulfonamide derivatives of epipodophyllotoxin, method of obtaining thereof and method of application thereof in therapy as anti-cancer medications / 2529676
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Invention relates to a method of producing a compound C of formula: [1] where R' is a linear, branched or cyclic C2-6 alkyl carbonyl group. In this method, the protective group for the hydroxy group in position 7 used is R1b; where R1b is a formyl group, optionally substituted with a linear C1-4 alkyl carbonyl group, optionally substituted benzyl group, a -SiR3R4R5 group, where R3, R4 and R5 are independently a linear or branched C1-4 alkyl group or a phenyl group, which can be substituted with a halogen atom, a C1-6alkyloxy-C1-6alkyl group, which can be substituted with a halogen atom, C1-6alkylthio-C1-6alkyl group, which can be substituted with a halogen atom, a linear, branched or cyclic C1-6alkyl group, which can be substituted with a halogen atom (in case of branched or cyclic, denotes a C3-4alkyl group), C2-6alkenyl group, which can be substituted with a halogen atom, C2-6alkynyl group, which can be substituted with a halogen atom, or an optionally substituted saturated or unsaturated 5-member or 6-member heterocyclic group. The invention also includes methods of producing intermediate compounds B2a and B2b and the compound of formula 2Bb itself.
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2-(5-ethyl-1,3,4-thiadiazolyl)amide of 2-(4-bromophenyl)-4-oxo-4-phenyl-2-butenoic acid, having analgesic effect 2-(5-ethyl-1,3,4-thiadiazolyl)amide of 2-(4-bromophenyl)-4-oxo-4-phenyl-2-butenoic acid, having analgesic effect / 2549572
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Method for producing methyl 1-[(1,3-dioxo-2,3-dihydro-1h-inden-2-yl)-(4-methylphenyl)methyl]cyclohexane carboxylate showing analgesic activity Method for producing methyl 1-[(1,3-dioxo-2,3-dihydro-1h-inden-2-yl)-(4-methylphenyl)methyl]cyclohexane carboxylate showing analgesic activity / 2549566
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Suppositories for treating hemorrhoid, proctitis and other proctologic inflammations / 2545994
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Pde10 inhibitors and compositions containing them and methods Pde10 inhibitors and compositions containing them and methods / 2545456
Invention refers to compounds of formula (I) and their pharmaceutically acceptable salts, wherein A is thiazolyl, oxazolyl, thienyl, furyl, imidazolyl, pyrazolyl or oxadiazolyl (structures of which are presented in cl.1 of the patent claim), R1 represents C1-6alkyl; R2 represents (i) phenyl substituted by halogen; C1-6alkyl optionally substituted by morpholine or C1-6dialkylamino; C1-6alkoxy optionally substituted by halogen; or heterocyclyl, wherein a heterocyclyl substitute is specified in morpholine; pyrazolyl optionally substituted by C1-6alkyl; piperidinyl; pyrrolidinyl; oxadiazolyl substituted by C1-6alkyl; furyl substituted by C1-6alkyl; dioxydoisothiazolidinyl; triazolyl; tetrazolyl substituted by C1-6alkyl, tridiazolyl substituted by C1-6alkyl; thiazolyl substituted by C1-6alkyl; pyridyl; or pyrazinyl; (ii) substituted or unsubstituted heterocyclyl specified in quinolinyl; pyridyl substituted by C1-6alkoxy or morpholinyl; or benzo [d] [1, 2, 3] triazolyl substituted by C1-6alkyl; R3 represents phenyl substituted by 2 or 3 substitutes specified in halogen; C1-6alkyl; C1-6alkoxy optionally substituted by halogen; hydroxy group; cyano; or -C(=O)ORa, wherein Ra represents phenyl; R4 represents hydrogen, C1-6alkyl or C1-6halogenalkyl. The invention also refers to a pharmaceutical composition containing the compounds of formula (I), a method for PDE10 inhibition, a method of treating neurological disorders, and to intermediate compounds: 2-(4-chlor-3,5-dimethoxyphenyl)furan and 4-(5-methyl-1,3,4-thiadiazol-2-yl)benzaldehyde.

FIELD: biotechnology.

SUBSTANCE: invention relates to a low-toxic (E)-2-(4-{[3-(2,4-dimethoxyphenyl)acrylamido]methyl}-1H-1,2,3-triazole-1-yl)-2-isopropyl-9-(4-methyl piperazine-1-yl)-3,7-dioxo-3,7-dihydro-2H-furo[3,2-g]chromen of formula (I) , having the analgesic activity in the test "acetic acid-induced writhing". The said property enables to use this compound in medicine.

EFFECT: compound of formula I is prepared from furocoumarin peucedanine contained in the plant Peucedanum morisonii.

1 tbl, 5 ex

 

The invention relates to a new chemical compound, specifically to (E)-2-(4-{[3-(2,4-dimethoxyphenyl)acrylamido]methyl}-1H-1,2,3-triazole-1-yl)-2-isopropyl-9-(4-methylpiperazin-1-yl)-3,7-diokso-3,7-dihydro-2H-furo[3,2-g]chromene of formula (I)

with analgesic activity.

These properties suggest the potential use of the compounds in medicine as a pharmaceutical drug.

Despite the presence of a large group of substances having analgesic activity, the discovery of compounds such action has not abated. This is due to a number of side effects that are typical of known analgesics (psychic dependence, disturbance of accommodation, etc.). Analysis of literature data shows that the synthesis and pharmacological testing of new chemical compounds that are different from existing feature and selectivity, the selectivity of binding to a specific type of opioid receptors, prolonged effect and lack of side effects is an urgent task.

Linear furocoumarins (psoralens) are used in PUVA (psoralen + UV radiation) therapy for the treatment of autoimmune or Hyper-proliferative skin diseases, including psoriasis and vitiligo [Santana, L; Urierte, E.; Roleira, F.; Milhazes, N., Borges F. Furocoumarins in Medcinal Chemistry. Synthesis, Natural Occurrence and Biological Activity. Curr. Med. Chem. 2004, 77,3239-3261; Wu, L.; Wang, X.; Xu, W.; Farzaneh, F.; Xu, R. The structure and pharmacological functions ofcoumarins and their derivatives. Curr. Med. Chem. 2009, 16, 4236-4260]. In the past two decades found new potential therapeutic application of furocoumarins. For example, natural furocoumarins bergapten imperatorin and itemperatures [Chen, Y.-F.; Tsai, H.-Y.; Wu, T.-S. Anti-inflammatory and analgesic activities from roots of Angelica pubescens. Planta Med. 1995, 61,2-8], containing extracts [Singh D., Singh, V., Goel R. K. Traditional Uses, Phytochemistry and Pharmacology of Ficus religiosa: A review. J. Ethnopharmacol., 2011, 134 565-583; K. M. M. Koriem, Asaad G. F., Megahed H. A., H. Zahran, M. S. Arbid Evaluation of Antihyperlipedemic, Anti-inflammatory, Analgesic, And Antipyretic Activities of Ethenolic Extract of Ammi Majus Seeds in Albino Rats And Mice, Internat. J. Toxicol., 2012, 31 (3) 294-300] possess analgesic activity in vivo in various models of pain (hot plate, acetic cramps, retraction of the tail). The mechanism of pain reactions of coumarins has not been studied. Investigation of the mechanisms of analgesic activity suggests that the analgesic effect of natural and synthetic coumarins correlates with inhibition of neutrophil migraine, cytokine release and production of prostaglandin PGEz [Keri R. S., K. M. Hosamani, Shingalapur R. V., M. H. Hugar Analgesic, Anti-pyretic and DNA Cleavage Studies of Novel Pyrimidine Derivatives of Coumarin Moiety. Eur. J. Med. Chem., 2010, 45, 2597-2605; Oliveira de Lima F., Nanato F. R., Couto R. D., Barbosa F. J. M., X. P. Nunes, S. R. Ribeiro, Scares M. B. P., Villarreal C. F. Mechanisms Involved in the Antinociceptive Effects of 7-Hydroxycoumarin. J. Nat. Prod., 2011, 74, 4, 596-602; Sadhya V., Giles D., Mathev V., Basavarajaswamy G., Abraham, R. Synthesis, Phaermacological Evaluation and Doking Studies of Coumarin Derivatives. Eur. J. Med. Chem., 2011, 46, 4696-4701]. N-Substituted 3-arylalkanolamine patented as agents for the treatment of rheumatoid arthritis and neurological disorders [Patent WO 2005072731. Busch, V.; Johnson, A. T.; Martin, R.; Mohan, R.; Stevens, W. C.]. Arylacetamides 1,2,3-triazoles also possess neuroprotective activity [Jiaranaikulwanitch J., Govitrapong P., Fokin V. V., Vajragupta O. From BACE1 Inhibitor to Multifunctionality of Tryptoline and Tryptamine Triazole Derivatives for Alzheimer's Disease]. As can be seen, the combination of the molecule a few farmakofore fragments allows to obtain compounds with an expanded range of biological effects (pain and neurotropic activity).

The object of the invention is to develop a new analgesic agent on the basis of available connections: plant furocoumarins peucedanum (II), N-methylpiperazine and (E)-3-(3,5-dimethoxyphenyl)acrylic acid.

The problem is solved a new chemical compound (E)-2-(4-{[3-(2,4-dimethoxyphenyl)acrylamido]methyl}-1H-1,2,3-triazole-1-yl)-2-isopropyl-9-(4-metile-perazine-1-yl)-3,7-diokso-3,7-dihydro-2H-furo[3,2-g]chrominum of formula (I) exhibiting a pronounced analgesic activity

Analogous to the structure of the claimed compounds is furocoumarins peucedanin of formula (II) having antitumor�th activity and inducing apoptosis of tumor cells [Bartnik, M.; Glowniak, K.; Jakubowicz-Gil, J.; Pawlikowska-Pawlega, V.; Gawron, A. Effect of peucedanin and bergapten (5-MOP), furanocoumarins isolated from Peucedanum tauricum Bieb. (Apiaceae) fruits, on apoptosis induction and heat-shock protein expression in HeLa cells. Herba Polomca, 2006, 52(4), 71-78]. This compound was also the starting material for obtaining the analgesic agent (I). The compound (II) were isolated by extraction of the roots of peucedanum Morrison [E. E. Schultz, T. N. Petrova, M. M. Shakirov, E. I. Chernyak, L. M. Pokrovsky, S. A. Nekhoroshev, G. A. Tolstikov. Coumarins of the roots of peucedanum Morrison (Peucedanum morisonii Bess.). Chemistry for sustainable development. 2003. T. 11. S. 683-688]. The said plant is widely represented in the flora of Siberia; the content of the compound (II) in the roots of peucedanum Morrison reaches 4% by weight of air-dry raw material. Peucedanin extracted from plant material by extraction with an organic solvent and subsequent recrystallization. Thus, peucedanin (II) is a highly available connection to obtain on the basis of various pharmacologically valuable derivatives.

Analogous to the properties of the claimed compound is a nonsteroidal anti-inflammatory drug diclofenac sodium (ortofen, voltaren) (III). The main disadvantage of specified pharmacological effect of the drug is an anti-inflammatory effect [M. D. Mashkovsky. Medications of the twentieth century. M.: New wave. 319 p.].

The method of obtaining the compound (I) of peucedanum (II) is implemented as shown in the diagram 1. Bromination peucedanum (II) N-bromosuccinimide or bromine in chloroform leads to 2-bromoisatin (IV) (yield 92%) [S. A. Osadchy, E. E. Schultz, M. M. Shakirov, G. A. Tolstikov. The study of plant coumarins. Message 1. Some transformations peucedanum. Izvestiya an. Chemical series. 2006. No. 2. P. 362-366]. In the interaction of 2-via (IV) with sodium azide is formed 2-asadoorian (V) (yield 81%) [V. A. Lipaev, E. E. Schultz, E. A. Makhnev, M. M. Shakirov, G. A. Tolstikov. The study of plant coumarins. XII. Synthesis of 2-(1,2,3-triazolyl)modified by furocoumarins. Chemistry of heterocyclic compounds. 2013. No. 4. S. 591-601]. The aminomethylpyridine of furocoumarin (V) the action of N-methylpiperazine and formalin in boiling methanol leads to 2-azido-9-(4-methylpiperazin-1-yl)areoplane (VI) (yield 65%). In the interaction of azide (VI) with terminal Alkino (VII) under conditions catalyzed by copper sulphate reactions 1,3-dipolar cycloaddition selectively formed (E)-2-(4-{[3-(2,4-dimethoxyphenyl)acrylamido]methyl}-1H-1,2,3-triazole-1-yl)-2-isopropyl-9-(4-methylpiperazin-1-yl)-3,7-diokso-3,7-dihydro-2H-furo[3,2-g]chromen (I) in the form of a yellow crystalline substance (yield 70%). The total output of the agent (I) on the initial plant metabolite peucedanin is 34%. (E)-3-[2,4-Dimethoxyphenyl-N-prop-2-inyl)]acrylamide (VII) is also a new connection. It was obtained by condensation of (E)-3-(2,4-dimethoxyphenyl)acrylic acid with propargylamine in the presence of N-hydroxybenzotriazole and N,N-diisopropylcarbodiimide (yield 90%).

An advantage of the invention is a method of producing the compound (I) by chemical modification of available plant coumarin peucedanum (II). Physico-chemical constants of new, first obtained compounds (VI, VII, I) are given in examples 1-3.

Biological activity of compound (I) was studied by determining the toxicity and analgesic activity in the test "acetic cramps".

3. Acute toxicity was determined on outbred mice weighing 18-23 g after a single intragastric route of administration. Toxicity parameters were calculated according to the method of Cerberus. It is established that the LD50 of compound (I) exceeds the maximum possible for a single administration of a dose of 3000 mg/kg. Compound belongs to the 3rd class of mild-toxic compounds. LD50product comparison of diclofenac-sodium (III) is 350 mg/kg [A. M. of Dill, Inflammation, Medicine, M., 1979,448 p.].

Analgesic activity of compound (I) was studied on the model of visceral pain "acetic cramps" by a single injection in doses of 50 and 10 mg/kg. "Acetic cramps" was reproduced by intraperitoneal injection of 0.75% acetic acid at 0.1 ml per animal. Assessment activity is p�vslas by the number of writhing for 3 min. The analgesic activity of the compounds was compared with the activity of the parent compound peucedanum (II) and active agent (III) is introduced in a dose of 50 mg/kg. the Results are presented in table 1. The table data shows that the compound (I) on the model of pain response induced by administration of a chemical stimulus that reliably reduces pain reaction and 4-6 times reduces the number of writhing at the doses of 50 and 10 mg/kg. Thus, the compound has a pronounced analgesic activity. His activity in the dose of 10 mg/kg similar activity of diclofenac sodium (III), taken at a dose of 50 mg/kg. Peucedanin (II) does not possess analgesic activity (% reduction in pain response was 3.6%).

Table 1
The effect of compound (I) on the level of pain sensitivity in the test "acetic cramps"
Name of input connections and dose Analgesic activity
The number of writhing for 3 min control
The number of writhing % Oubre
The compound (I), 50 �g/kg 1.1±0.4* 7.6±1.1 85.6
The compound (I), 10 mg/kg 1.9±0.3* 9.1±1.8 79.8
Peucedanin (II), 50 mg/kg 7.4±2.9* 7.6±1.1 3.6
Diclofenac (III), 50 mg/kg 2.0±0.7* 7.6±1.1 73.2
Diclofenac (III), 50 mg/kg 2.5±1.2* 9.1±1.8 73.0
* - P value<0.05, which indicates a significant difference from the control group; UBR - reducing the pain response.

The invention is illustrated by the following examples.

Example 1. Getting 2-azido-9-(4-methylpiperazin-1-yl)derivatives of oreoselone (VI). To a hot solution (55-60°C) 1.0 g (3.5 mmol) of the azide derivatives of oreoselone (V) and 1.4 g (14 mmol) of N-methylpiperazine in 5 ml of methanol was added 0.6 g (14 mmol) of formaldehyde. The reaction mixture was boiled for 10 h (TLC control), cooled and added 3 ml of water, the product was extracted with CH2Cl2(4×4 ml), the combined extracts dried over MgSO4and pack�Riva. After column chromatography on silica gel (eluent - chloroform) was obtained 0.9 g (65%) of oily compound (VI). The IR spectrum, ν, cm-1: 2962, 2935, 2877, 2837, 2792, 2682, 2110, 1753, 1730, 1680, 1614, 1456, 1415, 1365, 1355, 1286, 1168, 1146, 1126, 1095, 1053, 1010, 939, 920, 821, 783. UV spectrum (EtOH), λmaxnm (lgε): 258 (3.99), 308 (3.63), 353 (3.83). The NMR spectrum1H, CDCl3d, M. D. (400 MHz): 0.86 [6H, d, (N3)2CH, J=7 Hz], 1.95 (3H, s, N-CN3), 2.10 (4H, m, H12,13,15,16), 2.37 (4H, m, H12,13,15,16), 3.18 [1H, m, (CH3)2WithN], 3.72 (2H, s, H10), 6.06 (1H, d, H6, J=9.8 Hz), 7.45 (1H, d, H5, J=9.8 Hz), 7.52 (1H, s, H4). The NMR spectrum13With, CDCl3d, M. D. (400 MHz): 15.81, 16.05 ((WithN3)2SN), 29.67 (10), 30.87 [(CH3)2WithN], 45.85 (N-WithN3), 51.11 {With12,16), 52.45 (13,15), 96.62 (2), 110.81 (9), 115.06 (6), 115.23 (C3a), 116.14 (C4a), 124.17 (C4), 143.44 (C5), 158.81 (C9a), 161.02 (C8a), 171.22 (C=O), 193.44 (3). Found, %: C 59.83; H 5.20; N, 17.88. C20H23N5O4. Calculated, %: C 60.44; H 5.83; N, 17.62. Mass spectrum, m/z (IRel, %): 399 (2), 398 (7), 397 (26), 341 (3), 326 (4), 304 (6), 273 (20), 272 (80), 201 (21), 113 (45), 112 (18), 100 (27), 99 (60), 98 (31), 85 (63), 83 (100), 70 (60), 58 (53), 44 (15), 43 (38), 42 (33). Found: [M] 397.1743. C20H23H5O4. Calculated: 397.1745.

Example 2. Preparation of (E)-3-[2,4-dimethoxyphenyl-N-(prop-2-inyl)]acrylamide (VII). To a solution of 0.62 g (3 mmol) of (E)-3-(2,4-dimethoxyphenyl)acre�type acid in 10 ml of DMF was added, with stirring, 0.23 g (1.5 mmol) of N-hydroxybenzotriazole. To the resulting solution at room temperature was added 0.31 g (3.1 mmol) of propargylamine and 0.303 g (3 mmol) of triethylamine. After 5 minutes, to the solution was added 0.47 g (3.75 mmol) of N,N-diisopropylcarbodiimide obtained reaction mixture was stirred for 18 h. after the reaction was added 20 ml of water, the product was extracted with methylene chloride (4×5 ml) and left the solution overnight. The precipitate was filtered, the solution was dried and evaporated. Received 0.66 g (90%) of compound (VII). So a MP 88-89°C (from ether). The IR spectrum, ν, cm-1: 3340, 3066, 2970, 2875, 2115, 1743, 1730, 1620,1571, 1525, 1477, 1390, 1352, 1288,1233, 1170, 1137, 1120, 1097, 914, 827, 742, 509. UV spectrum (EtOH), λmaxnm (lgε): 222 (4.17), 255 (4.58), 294 (4.08), 306 (4.02), 350 (4.11). The NMR spectrum1H (CDCl3), δ, M. D. (400 MHz): 2.34 (1H, H1), 3.78 (3H, OSN3), 3.80 (3H, OSN3), 4.10 (2H, m, H3), 6.71 (1H, d, H6, J=16 Hz), 6.88 (1H, DD, H5', J1=8.1 Hz, J2=1.8 Hz), 6.96 (1H, d, H3', J=1.8 Hz), 7.08 (1H, d, H6', J=8.1 Hz), 7.86 (1H, H7, J 16 Hz), 8.34 (1H, m, NH). The NMR spectrum13With, CDCl3d, M. D. (400 MHz): 34.81 (3), is at 54.86 (AboutWithN3), 55.05 (AboutWithN3), 70.12 (1), 80.56 (C2), 98.96 (C3'), 105.73 (5'), 114.14 (6), 117.83 (1'), 129.27 (6'), 142.52 (2'), 161.07 (7), 161.48 (4'), 164.18 (5). The mass spectrum. Found: [M] 245.1045. C14H15NO3. Calculated: 245.1046.

Example 3. Synthesis of (E)-2-(4-{[3-(2,4-DIMET�xifei)acrylamido]methyl}-1H-1,2,3-triazole-1-yl)-2-isopropyl-9-(4-methylpiperazin-1-yl)-3,7-diokso-3,7-dihydro-2H-furo[3,2-g]chromene (I). To a solution of 0.4 g (1 mmol) 2-azido-9-(4-methylpiperazin-1-yl)derivatives of oreoselone (VI) in 10 ml of CH2Cl2sequentially added a solution of 30 mg (15 mol%, 0.15 mmol) sodium ascorbate, 12 mg (5 mol%, 0.05 mmol) CuSO4×5H2O in 10 ml of water and 0.29 g (1.2 mmol) of the compound (VII). The reaction mixture was stirred at 40°C for 8 h, then cooled, added 3 ml of water and was extracted with CH2Cl2(3×10 ml). The combined organic layers were washed with water and dried over MgSO4. The solvent was evaporated in vacuo, the residue was chromatographically on a column of silica gel (eluent - chloroform, chloroform-ethanol, 50:2). The fractions containing the product were precrystallization out of the ether, was obtained 0.45 g (70%) of compound (I). So a MP of 112-113°C (diethyl ether). The IR spectrum, ν, cm-1: 3434, 3060, 2958, 2871, 1731, 1691, 1670, 1631, 1620, 1545, 1481, 1462, 1431, 1365, 1344, 1250, 1213, 1200, 1139, 1118, 1080, 1047, 1028, 933, 883, 810, 723, 696, 620, 602. The NMR spectrum1H (CDCl3), δ, M. D. (400 MHz): 1.07 [6H, d, (N3)2CH, J=7 Hz], 2.25 (3H, s, N-CN3), 2.35 (4H, m, H12,13,15,16), 2.57 (4H, m, H12,13,15,16), 3.08 (1H, d, H10, J=7.8 Hz), 3.12 [1H, m, (CH3)2WithN], 3.14 (1H, d, H10, J=7.8 Hz), 3.78 (3H, OSN3), 3.82 (3H, OSN3), 4.10 (1H, d, H6', J=8.3 Hz), 4.18 (1H, d, H6', J=8.3 Hz), 6.33 (1H, d, H6, J=9.6 Hz), 6.50 (1H, d, H9', J=15.4 Hz), 6.62 (1H, d, H3", J=1.8 Hz), 6.97 (1H, DD, H5", J1=8.2 Hz, J2=1.8 Hz), 6.97 (1H, m, NH), 7.04 (1H, d, H6�' , J=8.2 Hz), 7.65 (1H, d, H5, J=9.6 Hz), 7.86 (1H, d, H10', J=15.4 Hz), 7.88 (1H, s, H4), 7.96 (1H, s, H5'). The NMR spectrum13With, CDCl3d, M. D. (400 MHz): 15.38, 15.73 [(CH3)2SN], 29.39 [(CH3)2SN], 33.50 (10), is at 34.65 (6'), 45.96 (N-CH3), is at 51.97 (12,16), 54.03 (C13,15), 54.83 (och3), 55.65 (och3), 95.95 (3"), 101.53 (2), 102.66 (C5"), 110.84 (5'), 113.17 (3), 114.84 (C3a), 115.09 (9), 115.14 (C9'), is at 115.64 which is (C4a), 123.97 (4'), 128.71 (6"), 128.84 (4), 135.76 (10'), 141.68 (C1"), 143.37 (5), 152.92 (2"), 158.48 (C8a), 159.79 (C9a), 165.73 (5), 166.08 (4"), 170.85 (8'), 192.00 (3). Found, %: C 63.24; H 5.59; N, 12.95. C34H38N6O8. Calculated, %: C 63.54; H 5.96; N, 13.08.

Example 4. Study of analgesic activity of compound (I) in the test "acetic cramps". The experiment was carried out on outbred mice-males weighing 22-25 g. Experimental groups were formed based on 8 animals in each. "Acetic cramps" was reproduced by intraperitoneal injection of 0.75% acetic acid at 0.1 ml per animal. One group intraperitoneally one hour before play model was introduced investigational agent (I) at a dose of 50 mg/kg, the second group received the drug (III) in the same dose, the third group peucedanin (II). Animals of the control group in� - Odile 0.2 ml of water per 10 g of animal weight. Evaluation activity was carried out according to the number of writhing for 3 min. As can be seen, the number of writhing in control group amounted to 7.6±1.1, with the introduction of the agent (I) the number of writhing was significantly decreased to 1.1±0.4, and with the introduction of diclofenac (III) to 2.0±0.7 (table.1).

Example 5. Study of analgesic activity of compound (I) in the test "acetic cramps" when administered in the dose of 10 mg/kg. Used three groups of experimental animals. One group intraperitoneally one hour before play model was introduced investigational agent (I) in the dose of 10 mg/kg, the second group received the drug (III) in the effective dose of 50 mg/kg, the third group (control) 0.2 ml of water per 10 g of animal weight. Evaluation activity was carried out according to the number of writhing for 3 min. As can be seen, the number of writhing in control group amounted to 9.1±1.8, with the introduction of the agent (I) the number of writhing was significantly reduced to 1.9±0.3, and with the introduction of diclofenac (III) up to 2.5±1.2 (tab.1).

Thus, the study established that the compound (I) has a strong analgesic effect, and the changes are reliable as compared with those in animals in the control group. Agent (I) blocks the development of painful effect caused by the introduction of acetic acid, and exhibits a high analgesic activity. About�ebbelwoi the effect of compound (I), introduced in the dose of 10 mg/kg, comparable analgesic activity comparison drug "Diclofenac", introduced in the effective dose of analgesic action of 50 mg/kg.

Thus, the present invention has the following advantages, namely:

- Analgesic activity in the test "acetic cramps".

- Use to obtain the claimed compounds available plant raw materials - a common landscape plant peucedanum Morrison.

Scheme. Synthesis of (E)-2-(4-{[3-(3,5-dimethoxyphenyl)acrylamido]methyl}-1H-1,2,3-triazolyl)-2-isopropyl-9-(4-methylpiperazin-1-yl)-3,7-diokso-3,7-dihydro-2H-furo[3,2-g]chromene (I)

(E)-2-(4-{[3-(2,4-dimethoxyphenyl)acrylamido]methyl}-1H-1,2,3-triazole-1-yl)-2-isopropyl-9-(4-methylpiperazin-1-yl)-3,7-diokso-3,7-dihydro-2H-furo[3,2-g]chromen of formula (I)

with analgesic activity.

 
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