1-aryl-7-methyl-2-[-(5'-nitro-2'-furyl)vinyl]-pyrido[2,3-d] pyrimidine-4-ones exhibiting antimicrobial activity
(57) Abstract:1-Aryl-7-methyl-2-[-(5'-nitro-2'-furyl)vinyl] -pyrido[2,3-d] -pyrimidine-4-ones of General formula I
< / BR>where R is CH3THE CO3, VG, possess bacteriostatic activity. table 2. The claimed compounds are organic chemistry, to the class of pyrido[2,3-d] pyrimidines, namely to new biologically active 1-aryl-7-methyl-2- [- (5'-nitro-2'-furyl)vinyl]-pyrido[2,3-d]pyrimidine-4-Onam formula (I-b),
< / BR>where Ia R=CH3, IB, R=OCH3, IB, R=Br,
which can find use as a drug of antimicrobials.The closest structural analogue of the claimed compounds is 1-metalorganic-2,7-dimethyl-1,4-dihydropyrido[2,3-d]pyrimidine-4-one formula
< / BR>possessing analgesic activity  . (Author's certificate. USSR N 1783801).Known and used in medical practice antimicrobial drugs furatsilin  and perfloxacin . (Mokrushina, A., Charushin R. N., Chupakhin, O. N. Chem. Pharm. zhurn., N 9, s 5-19 (1995)), which is taken by us as standards for comparison of antimicrobial action.The aim of the invention is to obtain new derivatives of 1-aryl-7-methyl-2- [- (5'-nitro-2'-furyl)W reaction-type aldol condensation between the methyl group in the second position of the 1-aryl-2,7-dimethylpyridin[2,3-d] pyrimidine-4-ones, exhibiting acid properties , and 5-nitrofurfural when heated in glacial acetic acid.< / BR>An example of obtaining the claimed compounds. 1-Aryl-7-methyl-2- [- (5'-nitro-2'-furyl)vinyl] -pyrido[2,3-d] pyrimidine-4-ones (Ia-in). The solution equimolecular quantities (0.01 mol) of 1-aryl-2,7-dimethylpyridin[2,3-d]pyrimidine-4-it 5-nitrofurfural in glacial acetic acid is heated for 10 minutes the precipitation is filtered off and crystallized from acetic acid (table. 1).The claimed compounds are yellow crystalline substance, soluble in DMF, acetic acid, soluble in alcohols. In IR-spectra (UR-20) there are peaks at 1635 - 1645 (CO) cm-1(suspension in vaseline oil). In the PMR spectra (BS-587 A, 80,023 MHz, Tesla DMSO d6connections are In the singlet methyl group with 2.39 memorial plaques, two doublet of the vinyl protons at 6,45 and 7,97 M. D., multiplet, aromatic protons and two protons furan fragment when 7,21 - 7,82 memorial plaques, two doublet protons of the pyridine cycle when of 8.37 - of 8.47 M. D. PMR Spectra of the other compounds also comply with the existing structure.Study of antimicrobial activity of the claimed compounds Ia-in was conducted in the Microbiology Department, you in the presence of antimicrobial activity [4, 5]. To define took out a portion of 0.05 g and was dissolved in 5 ml of the corresponding solvent. A dilution of 1:100. Source drug dilution were prepared on mesopatamia broth (BCH) in a dilution of 1: 500 by mixing (1 ml dilution of 1:100 and 4 ml BCH). For experience took a series of test tubes containing 2 ml of the BCH. The method used twofold serial dilutions by transferring 2 ml of liquid from one tube to another. As control was used tubes with the medium without drug. Research conducted in relation to two types of testmicrowave: gram positive - Staphylococcus Staphylococcus and gram - E. coli. For infection used daily agar culture that had washed in isotonic solution of sodium chloride and brought on the optical standard to a concentration of 500 million microbial cells in 1 ml of Standard breeding bred before 5 million microbial cells in 1 ml After exposure tubes were incubated at 37oC. analysis was performed at 18 to 20 h in the presence of bacterial growth (turbidity environment) or in his absence due to the antibacterial action of the drug. Indicator antibacterial activity of chemical compounds is m is Rob in the standard experiment.Was determined acute toxicity (LD50compounds Ia-in on white mice weighing 22 to 26 g after a single intraperitoneal injection of 2% starch mucus. Eight animals were divided into four groups. Each pair was administered one dose in ascending order. The death of animals were recorded within 1 day. LD50the size of the fluctuations calculated by the Express-method at p = 0.05 .The results are shown in table 2.Compared the antimicrobial activity against Staphylococcus aureus, Escherichia coli, toxicity LD50the investigated compounds in comparison with perfloxacin  and furatsilinom .According to the classification of the toxicity of drugs  compounds Ia, practically non-toxic, and IB allatoxin.As can be seen from table 2 compounds Ia-6.4 times, IB, - 3.2 times more active than perfloxacin and compound Ia - 333 times, IB, - 166 times more active than furatsilin against Staphylococcus aureus. Antimicrobial activity of compounds In more activity perfloxacin 6.4 times that of the compounds I and more active than furatsilin 20, 40 and 640, respectively, in respect of Escherichia coli.Thus 1-aryl-7-methyl-2- [- (low-toxic.Therefore, the claimed compounds Ia-in can be used in medicine as an antimicrobial drugs.Sources of information
1. Author's certificate N 1783801 (USSR) from 22.08.92.2. Mashkovsky M Doctor of medicine (textbook of pharmacotherapy for doctors), M, "Medicine", So 2, S. 358 1993).3. Mokrushina, A., Charushin C. R., Chupakhin, O. N. Chem. Pharm. Journe. N 9, s 5 - 19 (1995).4. Pershin, N. Methods of experimental chemotherapy, M, S. 109 - 111, 546 - 460 (1959).5. The order of the USSR Ministry of health N 250 from 13.03.75. About the unification of the methods of determining the sensitivity of microorganisms to chemotherapeutic drugs, M. (1975).6. Izmerov N. P. and other Parameters toxicometric industrial poisons in a single, M, "Medicine", S. 197 (1977). 1-Aryl-7-methyl-2-[-(5'-nitro-2'-furyl)vinyl] -pyrido[2,3-d] pyrimidine-4-ones of General formula I
< / BR>where I (R = CH3, IB, R = OCH3, IB, R = Br,
with bacteriostatic activity.
-ethyl - 1-(hydroxymethyl)-1,2,3,4, 6,7,12, 12b 1-octahedron(2,3-a)hemolysin (options), 1-ethyl-1 - (hydroxymethyl)-1,2,3,4,6,7-hexahydro-n-indole(2, 3-a)hemolysin and its optically active salt" target="_blank">
(I) where Z is oxygen, sulfur, group NCN иNOR9where R9lower alkyl;
R1hydrogen, hydroxyl, lower alkyl, lower alkenyl, lower alkenylacyl, lower alkoxyl, lower alkanoyl, lower dialkylaminoalkyl, lower alkoxyalkyl, lower alkylthiomethyl, benzyl;
R2hydrogen, lower alkyl, lower foralkyl, lower cycloalkyl, lower cycloalkenyl, lower alkenyl, lower quinil, lower alkoxyalkyl, lower alkylthiomethyl, lower alkanoyl, cyano, phenyl, benzyl, lower alkoxybenzyl, methylsulphonyl;
R3hydrogen, hydroxyl, halogen, nitro, lower alkyl, lower alkoxy, amino, lower mono - or dialkylamino, lower alkynylamino, pyrrolidin-1-yl, pyrrolin-1 - yl, tetrahydropyridine-1-yl, morpholine-1-yl, piperidine-1-yl, methoxyphenylethylamine, methoxybenzylamine;
R4hydrogen, halogen, lower alkyl, nitro, amino;
R5hydrogen, hydroxyl, halogen, lower alkyl, lower alkoxy, trihalomethyl, lower oxyalkyl, cyano;
R8hydrogen, lower alkyl; and when Z is oxygen or sulfur, R2hydrogen, lower alkyl, lower alkenyl, lower quinil, lower alkoxyalkyl, lower alkylthiomethyl, lower alkanoyl, phenyl, benzyl, lower alkoxybenzyl; R3, R4, R5, R6, R7and R8a hydrogen atom or one of the substituents R3, R4, R5, R6, R7and R8the lower alkyl and the other substituents are hydrogen, or one of the substituents R3, R4, R5and R7the halogen and the other substituents R6and R8hydrogen, or one of the substituents R3, R4and R7nitro, and the remaining substituents R5, R6and R8hydrogen, or one of zamestitelei R3, R5and R6is hydroxyl, and the other substituents R4, R7and R8hydrogen, or one of the substituents R3, R4and R7amino and the other substituents R5, R6and R8hydrogen, or one of the substituents R3and R5alkoxy, and the other substituents R4, R6, R7and R8hydrogen, or R5lowest oxyalkyl or cyano, and R3, R4, R6, R7and R8hydrogen, or R7azido, and R3, R4, R5, R6and R83, R4and R5means butyl, and the other substituents R6, R7and R8mean hydrogen, and R6, R7and R8independently of one another denote hydrogen or lower alkyl, provided that at least one of them means hydrogen, or one of the substituents R6, R7and R8means butyl, and the other substituents R3, R4and R5mean hydrogen, R1does not mean hydrogen, lower alkyl, lower alkenyl, benzyl, lower alkanoyl, lower alkoxyalkyl and lower alkylthiomethyl, and their hydrates and pharmacologically tolerable salts have valuable biological properties, particularly an inhibitory effect on reverse transcriptase of the virus HIV-1, so that they can be used for prevention or treatment of AIDS
< / BR>where n = 4-30, highly antiseptic and antidote properties, exceeding the efficiency properties are widely known foreign antiseptic - of chlorhexidine digluconate
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to a new substance eliciting an antiviral and antibacterial activity that is based on derivatives of 2,8-dithioxo-1H-pyrano[2,3-d;6,5-d']dipyrimidine and their 10-aza-analogues. This substance comprises derivative of indicated group of the general formula: A1*M: wherein X is taken among the group: oxygen atom (O), NH, N-alkyl; R1 is taken among the group: hydrogen atom (H), OH, chlorine atom (Cl), O-alkyl, NH2, NH-alkyl, NH-Ar, N-(alkyl)2, SH, S-alkyl; R2 is taken among the group: unsubstituted or substituted phenyl, naphthyl, thienyl; R3 is taken among the group: hydrogen atom (H), chlorine atom (Cl), O-alkyl, NH2, NH-alkyl, S-dihydroxypyrimidinyl; M is absent or taken among the group: cation Na, K, Li, ammonium or any other pharmacologically acceptable cation; or complex of pharmacologically acceptable cation (see above) with anion of one of derivatives of A1 (variants R1-R3 are given above). Invention provides preparing new compounds eliciting an antiviral and antibacterial activity.
EFFECT: valuable medicinal properties of substance.
17 cl, 7 tbl, 16 ex
FIELD: organic chemistry, pharmacy.
SUBSTANCE: invention relates to a new derivative of bicyclic heteroaromatic compound of the general formula (I) or its pharmaceutically acceptable salt eliciting agonistic activity with respect to luteinizing hormone (LH). Compounds can be used for preparing medicinal agents for control ability for conception. In compounds of the general formula (I) R1 represents R7 wherein R7 represents (C6-C10)-aryl optionally substituted with halogen atom at ortho- and/or meta-position; NHR8, OR8 wherein R8 means (C1-C8)-alkyl that can be substituted with halogen atom, (C1-C8)-alkylcarbonyl, (C1-C8)-alkylcarbonyloxy-group, phenyl, (C6-C10)-arylcarbonylamino-group, 5-methyl-2-phenylimidazol-4-yl, (C6)-heterocycloalkyl wherein 1-2 heteroatoms are taken among nitrogen and oxygen atoms, ethyloxycarbonylmethylthio-(C1-C4)-alkoxy-group, amino-group, (C6-C7)-heteroaryl; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R2 represents (C1-C8)-alkyl or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R3 represents (C1-C8)-alkyl possibly substituted with (C6-C14)-aryl possibly substituted with halogen atom, (C1-C4)-alkoxy-group, (C1-C4)-alkoxycarbonyl, mono- or tri-(C6-C10)-cycloalkyl, (C6-C10)-aryl, (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; (C5-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; (C3-C8)-cycloalkyl, (C2-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; X represents sulfur atom (S) or N(R4); Y represents nitrogen atom (N); R4 represents (C1-C8)-alkyl, phenyl-(C1-C8)-alkyl; or X represents sulfur atom (S), and Y represents CH; Z represents NH2 or OH; A represents sulfur (S), oxygen atom (O) or a bond. Also, invention relates to a pharmaceutical composition.
EFFECT: valuable properties of compounds and composition.
14 cl, 1 tbl, 119 ex
FIELD: organic chemistry, pharmaceutical composition.
SUBSTANCE: compounds satisfying the formula I 1 are disclosed, wherein each R1 and R2 independently to one another are H, OH, OA or Hal; or R1 and R2 together are -O-CH2-O- or -O-CH2-CH2-O-; R3 and R4 are A-group; X - group monosubstituted with R8, R5 or R7; R5 is linear or branched C1-C10-alkylene, wherein one or two CH2-groups may be substituted with oxygen atom; R7 is phenyl or phenylmethyl; R8 is COOH, COOA, CONH2, CONHA, CON(A)2 or CN; F is C1-C6-alkyl; and Hal is F, Cl, Br, or I, as well as physiologically acceptable salts or solvates thereof. Methods for production of claimed compounds (I) and pharmaceutical composition containing the same also are disclosed. Said compounds and pharmaceutical composition have activity as phosphodiesterase V inhibitors and are useful in treatment of cardiovascular diseases and potency disorders.
EFFECT: pharmaceutically applicable compounds and compositions.
7 cl, 16 ex
FIELD: organic chemistry and medicine.
SUBSTANCE: invention relates to new imidazole derivatives of general formula I useful as adenosine A3-receptor modulators, as well as to method for cancer treatment and detection of tumor cells using claimed derivatives.
EFFECT: compounds for treatment and diagnosis of improved activity.
13 cl, 4 dwg, 19 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new azaheterocycles comprising fragment of piperidin-2-yl- of the general formula (1):
as separate enantiomers or mixture of enantiomers, or their pharmaceutically acceptable salts, oxides or hydrates. In compounds of the formula (1) R1 represents hydrogen atom, inert substitute or NH-protecting substitute; W represents optionally substituted azaheterocycle, such as: pyridin-3-yl, pyrazolo[1,5-a]pyridin-6-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-7-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-9-yl, imidazo[1,2-a]pyrimidin-6-yl, imidazo[1,2-a]pyrimidin-8-yl or [1,8]naphthyridin-3-yl. Compounds elicit activity with respect to nicotine receptors and can be used in pharmaceutical industry. Also, invention relates to the focused library for search of physiologically active compound-leaders, and to pharmaceutical compositions based on new compounds of the formula (1).
EFFECT: valuable medicinal and pharmacological properties of compounds.
9 cl, 1 tbl, 15 sch, 22 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to applying compounds of the general formula (1):
as inhibitors of caspase-3 that allows their applying as "molecular tools" and as active medicinal substances inhibiting selectively the scheduling cellular death (apoptosis). Also, invention relates to pharmaceutical compositions based on compounds of the formula (1), to a method for their preparing and a method for treatment or prophylaxis of diseases associated with enhanced activation of apoptosis. Also, invention relates to new groups of compounds of the formula 91), in particular, to compounds of the formulae (1.1):
. In indicated structural formulae R1 represents inert substitute; R2, R3 and R4 represent independently of one another hydrogen atom, fluorine atom (F), chlorine atom (Cl), bromine atom (Br), iodine atom (J). CF3, inert substitute, nitro-group (NO2), CN, COOH, optionally substituted sulfamoyl group, optionally substituted carbamide group, optionally substituted carboxy-(C1-C6)-alkyl group; R5 represents oxygen atom or carbon atom included in optionally condensed, optionally substituted and optionally comprising one or some heteroatoms; R6 represents hydrogen atom or inert substitute; X represents sulfur atom or oxygen atom.
EFFECT: improved preparing and applying methods, valuable medicinal and biochemical properties of compounds.
3 cl, 1 dwg, 2 tbl, 1 sch, 8 ex
FIELD: organic chemistry, medicine, biochemistry, pharmacy.
SUBSTANCE: invention relates to 2-aminomethylthieno[2,3-d]pyrimidines of the general formula (I): wherein R1 and R2 in common with C-atoms with which they are bound form 5-7-membered monounsubstituted cycloalkenyl ring; R3 and R4 are similar or different and represent independently of one another (C1-C8)-alkoxy-group or halogen atom; R5 and R6 can be similar or different and represent independently of one another hydrogen atom, linear or branched (C1-C8)-alkyl group that can be substituted with one or more hydroxyl, (C1-C8)-alkoxy-group, amine, mono-(C1-C8-alkyl)-amine or di-(C1-C8-alkyl)-amine groups, or in common with nitrogen atom to which they are bound form a heterocyclic ring that comprises optionally one or more additional nitrogen atoms and substituted with one or more hydroxyl, (C1-C8)-alkoxy- or (C1-C8)-alkylol groups. Compounds elicit the inhibitory effect with respect to activity of phosphodiesterase V and can be used in treatment of cardiovascular system states and in disturbance in the potency injury. Also, invention describes a medicinal preparation based on compounds said, a method for its preparing and a method for preparing compounds.
EFFECT: improved preparing method, valuable medicinal and biochemical properties of compounds.
6 cl, 1 tbl, 16 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new nitrogen-containing aromatic derivatives of the general formula:
wherein Ag represents (1) group of the formula:
; (2) group represented by the formula:
or ; (3) group represented by the formula:
; Xg represents -O-, -S-, C1-6-alkylene group or -N(Rg3)- (wherein Rg3 represents hydrogen atom); Yg represents optionally substituted C6-14-aryl group, optionally substituted 5-14-membered heterocyclic group including at least one heteroatom, such as nitrogen atom or sulfur atom, optionally substituted C1-8-alkyl group; Tg1 means (1) group represented by the following general formula:
; (2) group represented by the following general formula: . Other radical values are given in cl. 1 of the invention claim. Also, invention relates to a medicinal agent, pharmaceutical composition, angiogenesis inhibitor, method for treatment based on these compounds and to using these compounds. Invention provides preparing new compounds and medicinal agents based on thereof in aims for prophylaxis or treatment of diseases wherein inhibition of angiogenesis is effective.
EFFECT: improved treatment method, valuable medicinal properties of compounds and agents.
40 cl, 51 tbl, 741 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel substituted 2-aryl-3-(heteroaryl)imidazo[1,2-a]-pyrimidines of the formula (I):
or to their pharmaceutically acceptable salts wherein: (a) R1 is taken among the group consisting of -NH2, C1-5-alkylamino-, di-C1-5-alkylamino-, phenylmethylamino-group; (b) Y is taken among the group consisting of hydrogen atom (H), halogen atom, piperidine, OR4, SR4, -SO2CH3, NHR4 and NR4R5 wherein R4 and R5 are taken independently among hydrogen atom (H), α-alkylphenyl-C1-5-alkyl, linear or branched alkyl substituted optionally with C3-5-carbocycle, phenyl or substituted phenyl wherein indicated phenyl can be substituted with one or some substituted taken among C1-5-alkoxy-group; (c) R2 represents from one to five members taken independently among the group including hydrogen atom (H), halogen atom, trifluoromethyl; (d) R3 represents hydrogen atom (H), or radicals R3 taken in common form aromatic ring; (e) X represents nitrogen atom (N) or -CH. Also, invention relates to methods for preparing indicated compounds and to a method for treatment based on these compounds. Invention provides preparing novel compounds that can be used in relief states by reducing the level of inflammatory cytokines, for example, the indicated state represents proliferative (rheumatic) arthritis.
EFFECT: valuable medicinal properties of compounds and compositions.
40 cl, 1 tbl, 4 ex