Method of producing 5,6-dihydropyrrolo[2,1-a]isoquinoline derivatives

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 5,6-dihydropyrrolo[2,1-a]isoquinoline derivatives 1-4 having the general structural formula: , where 1 - R=CH3, 2 - R=CH2CH3, 3 - R=CH2CF3, 4 - R=CH(CH3)2, characterised by that 6,7-diethoxy-3,4-dihydro-1-(3,4-diethoxybenzoyl)isoquinoline is mixed with methyl propiolate and methane, or ethanol, or 2,2,2-trifluoroethanol, or isopropanol and stirred at temperature of +50°C, the precipitate obtained at the end of the reaction and after removing reagents, is crystallised in ether.

EFFECT: method of producing derivatives which can be used as intermediate compounds when producing biologically active compounds.

4 ex

 

The invention relates to a new method of obtaining compounds of General structural formula 1-4:

The synthesis of the family structure of the compounds described in the following publications: N. N. Poligalova, A. G. Mikhailovskii, E. V. Vikhareva, M. I. Vakhrin. Enamines of the 1,2,3,4-tetrahydroisoquinolines series in the Chichibabin synthesis of pyrrolo[2,1-a]isoquinolines and in reaction with oxalil chloride. Chemistry of Heterocyclic Compounds, 2007, Vol. 43, №7, 900-905:

and also in work: (Shun Su, John A. Porco, etc. Synthesis of Pyrroloisoquinolines Related to the Lamellaris Using Silver-Catalyzed Cycloisomerisation/Dipolar Cycloaddition. Journal of American Chemical Societe, 2007, Vol. 129, №25, 7744-7745:

A fragment of 5.6-dihydropyrrolo[2,1-a]isoquinoline is part of such alkaloids as cryptaustoline (i) and cryptovoline (ii), which exhibit various biological activity, in particular antileukemic, antitumor, and are inhibitors of tubulin polymerization. Synthetic analogue - diacetoxytoluene 5,6-dihydropyrrolo[2,1-a]isoquinoline (iii) has an affinity for estrogen receptors:

The technical result for the solution of which the invention is directed, is to develop a new method of synthesis of derivatives of 5,6-dihydropyrrolo[2,1-a]isoquinolines via three-component reaction. The technical result is achieved by the fact that h�about the method of obtaining derivatives of 5,6-dihydropyrrolo[2,1-a]isoquinolines with the General structural formula:

is that 6,7-diethoxy-3,4-dihydro-1-(3,4-diethoxybenzoic)isoquinoline was mixed with methylpropionate and methanol or ethanol, or 2,2,2-triptoreline, or isopropanol and stirred at +50°C, the residue obtained after the reaction and removal of reagents, crystallized in ether.

Thus, the proposed method allows using three-component reaction of an excess of methylpropionate and methanol or ethanol, or 2,2,2-triptoreline, or isopropanol 6,7-diethoxy-3,4-dihydro-1-(3,4-diethoxybenzoic)isoquinoline to find the derivatives of 5,6-dihydropyrrolo[2,1-a]isoquinolines 1-4.

The method is carried out as follows. Mixed 6,7-diethoxy-3,4-dihydro-1-(3,4-diethoxybenzoic)isoquinoline (1 mol), methylpropionate (3 mol) and methanol or ethanol, or 2,2,2-triptoreline, or isopropanol (11 mol), then stirred at +50°C. progress of the reaction monitored by thin-layer chromatography on sorbfil. The reaction time is 2 to 9 days depending on the nature of alcohol. After the reaction, the solvent was evaporated to dryness, the residue obtained is triturated in ether until crystallization of compounds 1-4. Thus, derivatives of 5,6-dihydropyrrolo[2,1-a]isoquinolines 1-4 prepared from 6,7-diethoxy-3,4-dihydro-1-(3,4-diethoxybenzoic)of isoquinoline in cooperation�AI with methylpropionate and various alcohols at a temperature of +50°C:

The outputs of compounds 1-4 ranged from 22 to 92% and depend on the nature of alcohol.

The structure of obtained compounds was confirmed by mass spectrometry, IR spectroscopy and PMR spectroscopy. The structure of compound 1 was confirmed also by XRD.

Example 1

Mix of 0.41 g (0.001 mole) of 6,7-diethoxy-3,4-dihydro-1-(3,4-diethoxybenzoic)isoquinoline, 0.25 g (0,003 mol) methylpropionate and 5 ml (0.11 mole) of methanol. The reaction is conducted under stirring at +50°C. progress of the reaction monitored by TLC (sorbfil, ethyl acetate-hexane, 1:2). The reaction takes place in 9 days. The solvent was evaporated, the obtained reaction mixture is crystallized in ether. Get 0.11 g of compound 1 in the form of white crystals.

Methyl 1-(3,4-dioxyphenyl)-3-methoxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-2-carboxylate (1): yield 22%, white crystals with a MP 137-139°C, Rf0,65 (sorbfil, ethyl acetate-hexane, 1:1). IR spectrum (in KBr), υ/cm-1: 1700 (CO2CH3). Spectrum of1H NMR (CDCl3, 400 MHz): δ=1.15 (t, 3H, J=6.9 Hz, O-CH2CH3), 1.40 (t, 6H, J=6.9 Hz, O-CH2CH3), 1.45 (t, 3H, J=6.9 Hz, O-CH2CH3), 2.93 (t, 2H, J=6.2 Hz, 6-CH2), 3.54 (q, 2H, J=6.9 Hz, O-CH2CH3), 3.60 (s, 3H, 3-OCH3), 3.97 (t, 2H,.J=6.2 Hz, 5-CH2), 4.05 (s, 3H, CO2CH3), 4.00-4.08 (m, 4H, O-CH2CH3), 4.12 (q, 2H, J=6.9 Hz, O-CH2CH3), 6.45 (s, 1H, 7-H), 6.64 (s, 1H, 10-), 6.84-6.92 (m, 3H, CH-Ar). Found: C 68.35%, H 6.92%, N 2.75%. Mass spectrum, m/z: 509 (M+). C29H35NO7. M 509. Calculated: C 68.32%, H 6.93%, N 2.76%. M 509.

Example 2

Mix of 0.41 g (0.001 mole) of 6,7-diethoxy-3,4-dihydro-1-(3,4-diethoxybenzoic)isoquinoline, 0.25 g (0,003 mol) methylpropionate and 4 ml (0.11 mole) of ethanol. The reaction is conducted under stirring at +50°C. progress of the reaction monitored by TLC, (sorbfil, ethyl acetate-hexane, 1:2). The reaction takes place in 6 days. The solvent was evaporated, the obtained reaction mixture is crystallized in ether. Get 0.25 g of compound 2 as white crystals.

Methyl 1-(3,4-dioxyphenyl)-3-ethoxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-2-carboxylate (2): yield 63%, white crystals with a MP 121-123°C, Rf0,53 (sorbfil, ethyl acetate-hexane, 1:1). The IR spectrum, υ/cm-1: 1702 (CO2CH3). Spectrum of1H NMR (CDCl3, 400 MHz): δ=1.15 (t, 3H, J=6.9 Hz, O-CH2-CH3), 1.37-1.43 (m, 6H, O-CH2-CH3), 1.42-1.47 (m, 6H, O-CH2-CH3), 2.92 (t, 2H, J=6.2 Hz, 6-CH2), 3.54 (q, 2H, J=6.9 Hz, O-CH2-CH3), 3.59 (s, 3H, CO2CH3), 3.97 (t, 2H, J=6.2 Hz, 5-CH2), 4.03 (q, 4H, J=6.9 Hz,-CH2-CH3), 4.11 (q, 2H, J=6.9 Hz, O-CH2-CH3), 4.30 (q, 2H, J=6.9 Hz, 3-O-CH2-CH3), 6.45 (s, 1H, 7-H), 6.63 (s, 1H, 10-H), 6.81-6.91 (m, 3H, CH-Ar). Found: C 68.78%, H 7.35%, N 2.96%. Mass spectrum, m/z: 523 (M+). C30H37NO7. M 523. Calculated: C, 68.83%, H 7.07%, N 2.68%.

P�emer 3

Mix of 0.41 g (0.001 mole) of 6,7-diethoxy-3,4-dihydro-1-(3,4-diethoxybenzoic)isoquinoline, 0.25 g (0,003 mol) methylpropionate and 15 ml (0.11 mole) of 2,2,2-triptoreline. The reaction is conducted under stirring at +50°C. progress of the reaction monitored by TLC (sorbfil, ethyl acetate-hexane, 1:2). The reaction takes place for 2 days. The solvent was evaporated, the obtained reaction mixture is crystallized in ether. Get 0,38 g of compound 3 as white crystals.

Methyl 1-(3,4-dioxyphenyl)-3-(2,2,2-triptoreline)-5,6-dihydropyrrolo[2,1-a]isoquinoline-2-carboxylate (3): yield 92%, white crystals with a MP 157-159°C, Rf0,58 (sorbfil, ethyl acetate-hexane, 1:1). The IR spectrum, υ/cm-1: 1685 (CO2CH3). Spectrum of1H NMR (CDCl3, 400 MHz): δ=1.15 (t, 3H, J=6.9 Hz, O-CH2-CH3), 1.36-1.43 (m, 6H, O-CH2-CH3), 1.46 (t, 3H, J=6.9 Hz, O-CH2-CH3), 2.93 (t, 2H, J=6.2 Hz, 6-CH2), 3.53 (q, 2H, J=6.9 Hz,-CH2-CH3), 3.57 (s, 3H, CO2CH3), 3.96-4.08 (m, 6H, O-CH2-CH3, 5-CH2), 4.12 (q, 2H, J=6.9 Hz,-CH2-CH3), 4.70 (q, 2H, J=8.2 Hz, 3-O-CH2CF3), 6.44 (s, 1H, 7-H), 6.64 (s, 1H, 10-H), 6.81-6.87 (m, 2H, CH-Ar), 6.89 (d, 1H, J=8.3 Hz, CH-Ar). Found: C 62.28%, H 5.90 N 2.38%. Mass spectrum, m/z: 577 (M+). C30H34F3NO7. M 577. Calculated: C, 62.38%, H 5.93 N 2.43%.

Example 4

Mix of 0.41 g (0.001 mole) of 6,7-diethoxy-3,4-dihydro-1-(3,4-diethoxybenzoic)isoquinoline, 0.25 g (0,003 mol) of methyl�propiolate and 5 ml (0.11 mole) of isopropanol. The reaction is conducted with stirring at 50°C. progress of the reaction monitored by TLC (sorbfil, ethyl acetate-hexane, 1:2). The reaction takes place in 5 days. The solvent was evaporated, the obtained reaction mixture is crystallized in ether. Gain of 0.14 g of compound 4 in the form of white crystals.

Methyl 1-(3,4)-dioxyphenyl-3-isopropoxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-2-carboxylate (4): yield 27%, white crystals with a MP 138-140°C, Rf0,56 (sorbfil, ethyl acetate-hexane, 1:1). The IR spectrum, υ/cm-1: 1700 (CO2CH3). Spectrum of1H NMR (CDCl3, 400 MHz): δ=1.15 (t, 3H,.J=6.9 Hz, CH(CH3)2), 1.34-1.43 (m, 12H, O-CH2-CH3), 1.45 (d, 3H,J=6.9 Hz, CH(CH3)2), 2.90 (t, 2H, J=6.2 Hz, 6-CH2), 3.54 (q, 2H, J=6.9 Hz, O-CH2-CH3), 3.57 (s, 3H, CO2CH3), 3.96 (t, 2H, J=6.2 Hz, 5-CH2), 3.99-4.08 (m, 4H, O-CH2-CH3), 4.76 (Sept, 2H, J=6.9 Hz, 3-CH(CH3)2), 6.46 (s, 1H, 7-H), 6.63 (s, 1H, 10-H), 6.83-6.91 (m, 3H, CH-Ar). Found: C, 69.05%, H 7.21 N 2.34%. Mass spectrum, m/z: 537 (M+). C31H39NO7. M 537. Calculated: C 69.25%, H 7.31 N 2.61%.

The method of obtaining derivatives of 5,6-dihydropyrrolo[2,1-a]isoquinolines with 1-4 of the General structural formula:

1 - R=CH3
2 - R=CH2CH3
3 - R=CH2CF3
4 - R=CH(CH3)2
characterized in that 6,7-diethoxy-3,4-dihydro-1-(3,4-diethoxybenzoic)isoquinoline was mixed with methylprop�Olathe and methanol, or ethanol, or 2,2,2-triptoreline, or isopropanol and stirred at +50°C, the residue obtained after the reaction and removal of reagents, crystallized in ether.



 

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18 cl, 1 tbl, 257 ex

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6 cl, 53 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of organic chemistry, namely to heterocyclic compound of general formula (I) or to its pharmaceutically acceptable salt, acid salt or stereoisomer, where Y: NRa and N+R1R2X-; Z: bond, -(CH2)p, -CHOH, -CH=CH-, -C≡C-, -CONH- and -CO-; Rb: C1-C8 alkyl, C2-C8 alkenyl, C6-C10 aryl, -NR5R6,: , and ; with each alkyl, alkenyl and aryl, representing Rb, possibly, contains 1-3 substituents, selected from C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl, C1-C4 alkoxy, C6-C10 aryl, 5-, 6- and 7-membered heterocyclyl, containing 1-3 heteroatoms, selected from nitrogen, oxygen and sulphur, halogen, -OH, -NH2, -CN and -NO2; Rc: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkinyl, C3-C10 cycloalkyl, C3-C8 cycloalkenyl, C1-C4 alkoxy, C6-C10 aryl, 5-, 6-, 7- and 8-membered monocyclic heterocyclyl, containing 1-3 heteroatoms, selected from nitrogen, oxygen and sulphur, 9- and 10-membered bicyclic heterocyclyl, containing 1-3 heteroatoms, selected from nitrogen, oxygen and sulphur; with C1-C6 alkyl, C2-C6 alkenyl C2-C6 alkinyl, C3-C10 cycloalkyl, C3-C8 cycloalkenyl, C6-C10aryl, 5-, 6-, 7-, 8-membered monocyclic heterocyclyl and 9- and 10-membered bicyclic heterocyclyl, representing Rc, possibly contain 1-5 substituents, selected from the group, consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C3-C6 cycloalkyl, C4-C8 cycloalkenyla, halogen, -OH, -NH2, C6-C10 (A)(A')(A")(A'")aryl, (A)(A')(A")(A'")heterocyclyl, containing 1-3 heteroatom, selected from nitrogen, oxygen and sulphur, NR14R15, (CH2)pNR14R15, -CN, -NO2, oxo, -COOR14, SOR14, SO2R14, SO2NR14R15, NR15SO2R16, COR14, CONR14R15 and NR15COR16; with each (A), (A'), (A") and (A'")independently absent or representing C1-C4 alkyl, and each heterocyclyl (A)(A')(A")(A'")heterocyclyl is independently selected from the group, consisting of 5-, 6-, 7- and 8-membered monocyclic heterocyclyl, containing 1-3 heteroatoms, selected from nitrogen, oxygen and sulphur, and 9- and 10-membered bicyclico heterocyclyl, containing 1-3 heteroatoms, selected from nitrogen, oxygen and sulphur; the remaining radicals have values given in i.1;and on condition that, if Rc represents heterocyclyl, said heterocyclyl is bound directly through carbon atom of heterocyclyl ring. Invention also relates to particular compounds and to pharmaceutical composition based on formula (I) compound.

EFFECT: obtained are novel imidazopyrazine and imidazodiazepine derivatives, useful for prevention or treatment of disease or condition, severity of which is reduced by receptors to cannabinoids.

21 cl, 5 dwg, 4 tbl, 71 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new cyclic indolysincarboxamides and azaindolysincarboxamides of formulas Ia and Ib:

presented below, wherein the values of R, Ra, R10, R20, R30, R40, Y, n, p and q are specified in cl. 1 of formula. What is described is a method for preparing them.

EFFECT: compounds exhibit rennin-inhibitory activity that enables using them in the pharmaceutical composition and for treating hypertension.

11 cl, 4 tbl, 17 ex

FIELD: organic chemistry, antibacterial agents.

SUBSTANCE: invention describes 8-cyano-1-cyclopropyl-7-(1S,6S)-2,8-diazabicyclo-[4.3.0]-nonane-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid of the formula (I): with the crystalline modification A and a drug eliciting effect against pathogenic microorganisms. The prepared crystalline modification shows stability and doesn't transform to another crystalline modification or amorphous form being even at prolonged storage.

EFFECT: improved and valuable properties of compound.

4 cl, 4 dwg, 6 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes 8-cyano-1-cyclopropyl-7-(1S,6S-2,8-diazabicyclo-[4.3.0]-nonane-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid of the formula (I):

in the crystalline modification B and a medicinal agent based on thereof that elicits effect against pathogenic microorganisms. Indicated modification of compound of the formula (I) shows stability and insignificant absorption of air moisture ant doesn't convert to another crystalline modification or amorphous form being even in the prolonged storage.

EFFECT: valuable properties of agent.

4 cl, 4 dwg, 6 ex

FIELD: organic chemistry, medicine pharmacy.

SUBSTANCE: invention describes 8-cyano-1-cyclopropyl-7-(1S,6S-2,8-diazabicyclo-[4.3.0]-nonane8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid in the crystalline modification C of the formula (I):

and a medicinal agent eliciting effect against pathogenic microorganisms. This crystalline modification of compound of the formula (I) elicits low hygroscopicity, satisfied friability and can be processed easily to galenic preparations.

EFFECT: valuable properties of agent.

4 cl, 7 dwg, 1 tbl, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes 8-cyclo-1-cyclopropyl-7-(1S,6S-2,8-diazabicyclo-[4.3.0]-nonane-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid of the formula (I):

in crystalline modification D and a medicinal agent based on thereof eliciting effect against pathogenic microorganisms. The prepared crystalline form of compound of the formula (I) shows low hygroscopicity and can be processed to galenic preparations easily and it has the highest filled density and satisfied fluidity.

EFFECT: valuable properties of agent.

4 cl, 7 dwg, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new imidazoquinolines of the formula (1): wherein R, R1, R2 and n have values given in the description. Compounds elicit effect of immunomodulating agents inducing biosynthesis of cytokines in animals in treatment of different pathologies, among them viral and neoplastic diseases. Also, invention relates to a pharmaceutical preparation used for inducing interferon-α or tumor necrosis α-factor, to a method for inducing biosynthesis of cytokines in animals and to methods for treatment of viral diseases and neoplasm pathologies in animals. Invention provides preparing new biologically active compounds.

EFFECT: improved inducing method, valuable properties of compounds and pharmaceutical preparation.

23 cl, 10 tbl, 231 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention proposes compound of the formula (I): wherein cycle A represents imidazo[1,2-a]pyrid-3-yl or pyrazole[2,3-a]pyrid-3-yl; R2 is joined to cyclic carbon atom and taken among halogen atom, cyano-group, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, (C1-C6)-alkyl-S(O)a wherein a = 0, phenyl, phenylthio- or (heterocyclic group)-thio-group wherein any (C1-C6)-alkyl, phenyl or heterocyclic group can be substituted optionally by carbon atom with one or some G wherein heterocyclic group represents saturated, partially saturate or unsaturated, mono- or bicyclic structure comprising 4-12 atoms among them at least atom is taken among nitrogen, sulfur or oxygen atom that can be bound if another variants are not specified with unsaturated, mono- or bicyclic structure comprising 4-12 atoms among them at least one atom is taken among nitrogen, sulfur or oxygen atoms that can be bound if another variants are not specified with carbon or nitrogen atom wherein group -CH2- can be substituted optionally with -C(O)- and cyclic atom can carry optionally (C1-C6)-alkyl group and to form quaternary compound, or cyclic atom of nitrogen and/or sulfur can be oxidized to form N-oxide and/or S-oxides; m = 0-2 and R2 values can be similar or different; R1 means halogen atom, (C1-C3)-alkyl-S(O)a wherein a = 0 wherein any (C1-C3)-alkyl can be substituted optionally by carbon atom with one or some J; n = 0-1; cycle B represents phenyl or phenyl condensed with (C5-C7)-cycloalkyl cycle; R3 means halogen atom or sulfamoyl; p = 0-2 and R3 values can be similar or different; R4 means group A-E- wherein A is taken among (C1-C6)-alkyl, phenyl, heterocyclic group, (C3-C8)-cycloalkyl, phenyl-(C1-C6)-alkyl, (heterocyclic group)-(C1-C6)-alkyl or (C3-C8)-cycloalkyl-(C1-C6)-alkyl wherein (C1-C6)-alkyl, phenyl, heterocyclic group, (C3-C8)-cycloalkyl, phenyl-(C1-C6)-alkyl, (heteroccyclic group)-(C1-C6)-alkyl or (C3-C8)-cycloalkyl-(C1-C6)-alkyl can be substituted optionally by carbon atom with one or some D and wherein above mentioned heterocyclic group comprises fragment -NH- then nitrogen atom can be substituted optionally with group taken among R; E means a simple bond or -O-, -C(O)-, -N(Ra)C(O)- or -N(Ra)SO2-, -S(O)r wherein Ra means hydrogen atom or (C1-C6)-alkyl and r = 0-2; D is taken independently among hydroxy-, amino- (C1-C6)-alkoxy-, N-(C1-C6-alkyl)-amino-, N,N-(C1-C6-alkyl)-amino-, (C1-C6)-alkoxycarbonylamino- and benzyloxycarbonylamino-group wherein any (C1-C6)-alkyl or phenyl can be substituted optionally by carbon atom with one or some K; q = 0-1; G, J and K are taken independently among hydroxy-, dimethylamino-, diethylamino-group; R is taken among (C1-C4)-alkyl; or its pharmaceutically acceptable salt. Invention proposes applying pyrimidine compounds for inhibition of activity of kinases CDK2, CDK4 and CDK6 in cellular cycle eliciting anti-proliferative properties. Indicated properties have value in treatment of cancer diseases (solid tumors and leukemia), fibroproliferative and differential disorders, psoriasis, rheumatoid arthritis, Kaposi's sarcoma, hemangioma, acute and chronic nephropathy, atheroma, atherosclerosis, arterial repeated stenosis, osseous and ophthalmic diseases with proliferation of cellular tissue in vessels.

EFFECT: valuable medicinal properties of compounds.

22 cl, 99 ex

FIELD: organic chemistry, madicine.

SUBSTANCE: tricyclic benzodiazepines of formula I as well as their pharmaceutical acceptable salts, pharmaceutical composition containing the same and methods for hypertension treatment are disclosed. In formula A is -C(O)-; Y is CH2 or CH as olefinic site; X is CH2 or CH as olefinic site S, O or NR3 (R3 is C1-C8-alkyl) with the proviso that when Y is CH, X also is CH; Z is N or CH; R1 is hydrogen, C1-C8-alkyl, C1-C8-alkoxy or halogen; R2 is NR4COAr (R4 is hydrogen; Ar is phenyl optionally substituted with 1-3 substitutes independently selected from C1-C8-alkyl, halogen, hydroxyl, fluorinated C1-C8-alkylthio and another phenyl optionally substituted with substitute selected from C1-C4-alkyl, halogen, and hydroxyl); R5 is hydrogen, C1-C4-alkyl, C1-C4-alkoxy, fluorine, chlorine, hydroxyl or di-(C1-C4)-alkylamino.

EFFECT: improved pharmaceutical composition for hypertension treatment.

12 cl, 5 tbl, 52 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to a new improved method for preparing 6-methyl-2-(4-methylphenyl)-imidazolo[1,2-a]pyridine-3-(N,N-dimethylacetamide) of the formula (I) or its pharmaceutically acceptable acid additive salts. Method involves interaction of ester of the general formula (II) (wherein R is a lower alkyl or phenyl-lower alkyl) with dimethylamine in polar aproton solvent and if necessary conversion of synthesized compound of the formula (I) to pharmaceutically acceptable acid additive salt. Compound of the formula (I) is the known effective sedative agent used in therapy. Also, invention relates to intermediate compounds of the general formula (II) wherein R is a lower alkyl or phenyl-lower alkyl using in this method. Method provides preparing highly pure product for a single stage being without applying harmful and toxic reagents.

EFFECT: improved method for preparing.

16 cl, 15 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of cyclic amide of the formula (I)

or its salt, or hydrate, or solvate wherein X represents (C1-C6)-alkyl, (C1-C6)-alkyl substituted with phenyl, (C2-C6)-alkenyl substituted with phenyl or halogenphenyl, (C2-C6)-alkynyl substituted with phenyl, phenyl that can be substituted with (C1-C6)-alkyl; one or more halogen atom, nitro-group, phenyl, (C1-C6)-alkoxy-group, halogen-(C1-C6)-alkyl, halogen-(C1-C6)-alkoxy-group, phenyl-(C1-C6)-alkyl, (C1-C6)-alkoxyphenyl-(C1-C6)-alkyl, amino-group, optionally substituted with (C1-C6)-alkyl, acetyl, (C1-C6)-alkoxy-group, substituted with phenyl, phenylcarbonyl, furanyl; 1- or 2-naphthyl, monocyclic (C3-C8)-cycloalkyl, amino-group substituted with one or more substitutes taken among phenyl, halogenphenyl, (C1-C6)-alkoxyphenyl, (C1-C6)-alkyl, halogen-(C1-C6)-alkyl, phenyl-(C1-C6)-alkyl; 5- or 6-membered monocyclic heterocyclic group comprising 1 or 2 heteroatoms, such as nitrogen (N), oxygen (O), sulfur (S) atom optionally substituted with halogenphenyl, halogen atom, benzyl, (C1-C6)-alkyl, phenyl; 8-10-membered bicyclic heteroaryl group comprising 1 or 2 heteroatoms taken among N, O and optionally substituted with halogen atom; 8-10-membered polycyclic cycloalkyl group; Q means -CH2-, -CO-, -O-, -S-, -CH(OR7)- or -C(=NR8)- wherein R7 means hydrogen atom (H), (C1-C6)-alkyl; R8 means OH, (C1-C)-alkoxy-group, acylamino-group, (C1-C6)-alkoxycarbonylamino-group, phenyl-(C1-C6)-alkoxy-group; n = 0-5; B represents group or wherein each among R3, R4, R5 and R6 represents independently substitute taken among group consisting of hydrogen atom (H), halogen atom, NO2 (nitro-group), (C1-C6)-alkoxy-group, CN (cyano-group); m = 1 or 2; ring represents 5- or 6-membered aromatic heterocyclic ring comprising one or two heteroatoms taken among O, S, N. Compound of the formula (I) elicit activity inhibiting binding sigma-receptors that allows their using as component of medicinal agent.

EFFECT: valuable medicinal properties of compounds.

21 cl, 2 sch, 4 tbl, 183 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new substituted 1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines of the general formula (1)

that are effective inhibitors if caspase-3 that can be used for preparing medicinal agents and for experimental (in vitro, in vivo) investigation of apoptosis processes as "pharmacological tools". Also, invention proposes pharmaceutical composition and a method for their preparing and applying. In the general formula (1) radicals R1, R2, R3 and R8 represent independently of one another hydrogen atom, halogen atom, CF3, CN, inert substitute, optionally substituted hydroxyl group, optionally substituted carboxy-(C1-C6)-alkyl group, optionally substituted carbamoyl group; R4 represents hydrogen atom, halogen atom, inert substitute, optionally substituted amino-group, substituted hydroxyl group; R5 represents hydrogen atom, inert substitute, optionally substituted hydroxy-(C1-C5)-alkyl, optionally substituted amino-(C1-C7)-alkyl, optionally substituted amino-group, optionally substituted hydroxyl group; R6 and R7 represent independently of one another hydrogen atom, inert substitute, optionally substituted amino-(C1-C7)-alkyl, optionally substituted amino-group, optionally substituted hydroxyl group; or R6 and R7 in common with nitrogen atom to which they are bound represent optionally substituted and optionally additionally including heteroatom taken among group: oxygen, nitrogen or sulfur, 3-10-membered cycle; or R6 and R7 in common with nitrogen atom to which they are bound represent condensed heterocycle being optionally substituted and optionally additionally including heteroatom taken among group: oxygen, nitrogen or sulfur.

EFFECT: improved preparing method and treatment.

9 cl, 19 sch, 7 tbl, 25 ex

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