Substituted 1-pyridyl-2-azolyl-1-(2-phenylethenyl)ethan-1-ols and application thereof as fungicides
FIELD: organic synthesis.
SUBSTANCE: invention provides substituted 1-pyridyl-2-azolyl-1-(2-phenylethenyl)ethan-1-ols having general formula I:
where Py denotes 2-, 3-, or 4-pyridyl, Z nitrogen atom or CH group, and R1 and R2, independently from each other, are hydrogen or halogen atom, or trifluoromethyl group. Claimed compounds are applied as agricultural, industrial, medical, or veterinarian fungicides for controlling harmful fungi.
EFFECT: enhanced fungi control efficiency.
2 cl, 3 tbl
The invention relates to the chemistry of heterocyclic compounds, namely, the substituted 1-pyridinyl-2-azolyl-1-(2-phenylethenyl)atenolol-1 of General formula I,
where PY represents 2-pyridinyl, 3-pyridinyl or 4-pyridinyl, Z denotes a nitrogen atom or a group CH, R1and R2independently from each other mean a hydrogen atom, halogen, triptorelin group that exhibit fungicidal activity and can be used as agricultural, industrial, medical or veterinary fungicides.
Known 3,3-dimethyl-1-(1H-1,2,4-triazolyl-1)-1-(4-chlorphenoxy)-butanone-2, or triadimefon, which is used as a systemic fungicide for control of diseases of wheat powdery mildew, rust), Apple (powdery mildew, scab), cucumbers and melons (powdery mildew), vine (oidium, grey rot), tomato greenhouse (powdery mildew), black currant (American powdery mildew) and other crops [Handbook of pesticides /LNB, Kvinnoforum, Sreen, Tneaa. - M.: Chemistry, 1985. - 352 S.].
Known pyridinemethanol General formula II,
where R1means phenyl, 4-chlorophenyl or cyclohexyl, R2means4-C8cycloalkenyl or3-C8cycloalkyl, as well as their salts, which have funghi is IGNOU activity and can be used to suppress fungi, damaging crops and ornamental plants [U.S. Pat. U.S. No. 3794656, class C 07 D 31/24 (CDD 260-290 R), 1974].
The toxicity of drugs is not critical for their application. Among agricultural fungicides known low toxicity of dichloran (LD50for rat 4000 mg/kg orally) and highly toxic edifenphos (LD50for rats 150 mg/kg orally) [LNK, Kvinnoforum, Sreen. Pesticides and plant growth regulators. - M.: Chemistry, 1995. - 576 S.].
The technical problem solved by the present invention is to expand the range of fungicides for effective action against harmful fungi.
To solve this problem, synthesize substituted 2-azolyl-1-(2-arylidene)pyridinemethanol General formula I, having fungicidal activity.
According to the invention 1-pyridinyl-2-azolyl-1-(2-phenylethenyl)-ethanola-1 of General formula I obtained by heating 1-pyridinyl-1-(2-oxiranyl)-4-arylpropionic-2 with imidazole or triazole in the presence of solid alkali metal hydroxide in the environment of high-boiling polar aprotic solvent, for example N-methylpyrrolidone, dimethylformamide or dimethyl sulfoxide, at 100-150°in the presence of water or without it
where Py, Z, R1, R2have the same meanings as in formula I.
Similar processes Pris the unity of triazole and imidazole to other substituted oxiranes described in the literature [J.M.Bentley, R.V.Jones, P.J.Wareham. A general anionic mechanism for thermodinamic control of regioselectivity in the N-alkylation of heterocycles // Tetrahedron Letters. 1989. Vol. 30.No.30.P.4013-4016].
Substituted 1-pyridinyl-1-(2-oxiranyl)-4-arylpropionic-2 receive the reaction of the Corey-Chaykovsky of substituted 1-pyridinyl-3-allpaper-2-ones-1 when interacting with their salts trimethylsilane in dimethyl sulfoxide or dimethyl sulfide in the presence of a strong base, for example, of potassium tert-butylate, tert-Aminata sodium or sodium hydride, or in the interfacial conditions at a temperature of from -10 to +5°With:
where Ru and R1, R2have the same meanings as in formula I, And - denotes the anion of the acid. In - means basis.
For other substrates such reaction is known [E.J.Corey, M.Chaykovsky. Dimethyloxosulfonium methylide ((CH3)2SO2and dimethylsulfonium methylide (CH3)2SCH2. Formation and application to organic syntheses // Journal of the American Chemical Society. 1965. Vol. 87. No. 6. P. 1353-1364].
Substituted 1-pyridinyl-3-allpaper-2-ones-1 are known and are obtained by condensation of allerigies with aromatic aldehydes [C.S.Marvel et al. Pyridine analogs of chalcone and their polymerization reactions // Journal of Organic Chemistry. 1955. Vol. 20. P. 1785-1792; U.S. Pat. UK No. 1216617, class C 07 D 31/32,1969] in the presence of bases
Example 1. To a solution of 1,045 g (5 mmol) of 1-(3-pyridinyl)-3-phenylpropan-2-it-1 and 1.43 g (7 mmol) of iodide trimethylsulfonium 3.5 ml dimethyls is lfixed added dropwise over 30 min a solution of 0.7 g (6,27 mmol) of potassium tert-butylate in 3 ml of dimethyl sulfoxide in an inert atmosphere while cooling the reaction mass in the bath with a mixture of ice and salt. Then the reaction mass is stirred for 15 min and added dropwise 30 ml of water. The product is extracted with four 50 ml of diethyl ether, the extract washed with saturated sodium chloride solution and dried over magnesium sulfate. The solvent is distilled off and obtain 0.95 g (85%). 1-(3-pyridinyl)-1-(2-oxiranyl)-3-phenylpropan-2. An NMR spectrum1H (DMSO-d6that δ, ppm, J, Hz): 3,19 and 3,28 (AB-system, 2H, CH2, J=9,3), 6.50 and 6,69 (AB-system, 2H, CH=CH, J=19,0), 7,25-7,52 (m, 6N, 5 CH arene., 1 CH of pyrid.), 7,86, 8,58, 8,68 (all d, 1H, CH of pyrid.).
Example 2. To a solution of 0,245 g (3.5 mmol) of imidazole in 2 ml of dimethylformamide was added 1 drop of water, 0.04 g (1 mmol) of sodium hydroxide and 0.95 g (of 4.25 mmol) of 1-(3-pyridinyl)-1-(2-oxiranyl)-3-phenylpropan-2 and stirred for 4 h at 120°C. Then the reaction mass is then cooled, poured into 25 ml of water and leave for a few hours. The precipitated crystals are filtered and recrystallized from ethanol. Get 0,83 g (57%) of 1-(3-pyridyl)-2-(1-imidazolyl)-1-(2-phenylethenyl)ethanol-1.
The yields and melting point 1-pyridinyl-2-azolyl-1-(2-phenylethenyl)atenolol-1 are shown in table 1, the data of NMR1N spectra in table 2. NMR1H spectra were recorded on the instrument Varian XL-400 (400 MHz).
Example 3. Testing the biological activity of the compounds was performed in vitro experiments. In the molten sacharose-potato agar was added IP is itheme substance in the form of a composition, containing 3 mg/ml of the active substance, the rest - acetone, 1 ml per 100 ml of agar. To receive agar medium containing 30 mg/l of the test compound. To the medium control was added with pure acetone in the same amount. So prepared medium was poured into Petri dishes, cooled and the surface of the hardened agar were sown pieces of fungal mycelium, after which the cups were incubated for 3 days at 25±0,5°C. Inhibition of mycelium growth was calculated in percentage of the untreated control. As a reference used commercial fungicide triadimefon in the same concentration. The test results presented in table 3.
| Table 1 The outputs and the melting temperature of substituted 1-pyridinyl-2-azolyl-1-(2-phenylethenyl)atenolol-1 of General formula I. | ||||||
| Connection | The position of substitution of the pyridine nucleus | Z | R1 | R2 | Output % | So pl., ° |
| 1 | 2 | SN | N | N | 16 | 145-147 |
| 2 | 2 | SN | N | 4-CL | 14 | 178-180 |
| 3 | 2 | SN | N | 4-VG | 37 | 180-182 |
| 4 | 2 | SN | N | 3-CF3 | 2,6 | oil |
| 5 | 2 | N | N | N | 16 | 128-130 |
| 6 | 2 | N | N | 4-VG | 1,1 | oil |
| 7 | 3 | SN | N | N | 57 | 115-117 |
| 8 | 3 | SN | N | 4-CL | 41 | 118-120 |
| 9 | 3 | SN | N | 4-VG | 49 | 120-122 |
| 10 | 3 | SN | N | 4-F | 47 | 110-112 |
| 11 | 3 | SN | 2-CL | 4-CL | 27 | 105-107 |
| 12 | 3 | SN | N | 3-CF3 | 37 | 108-110 |
| 13 | 3 | N | N | N | 19 | 88-90 |
| 14 | 3 | N | N | 4-CL | 38 | 98-100 |
| 15 | 3 | N | N | 4-VG | 43 | 95-97 |
| 16 | 3 | N | N | 4-F | 24 | 89-91 |
| 17 | 3 | N | N | 3-CF3 | 4 | oil |
| 18 | 4 | SN | N | N | 26 | 100-102 |
| 19 | 4 | SN | N | 4-CL | 3,1 | oil |
| 20 | 4 | SN | N | 4-VG | 12 | 133-135 |
| 21 | 4 | N | N | N | 4,8 | 191-193 |
| 22 | 4 | N | N | 4-CL | 42 | 215-217 |
| 23 | 4 | N | N | 4-VG | 22 | 216-218 |
| Table 3. Rez is ltati tests of substituted 1-pyridinyl-2-azolyl-1-(2-phenylethenyl)atenolol-1 on the fungicidal activity at a concentration of 30 mg/L. Legend: V.i. - Venturia inaequalis, R.s. -Rhizoctonia solani, F.o. - Fusarium oxysporum, F.m. - Fusarium moniliforme, H.s. - Helminthosporium sativum, S.s. - Sclerotinia sclerotiorum. | ||||||
| Connection | Inhibition of radial growth of the mycelium of fungi in% of control | |||||
| V.i. | R.s. | F.o. | F.m. | H.s. | S.s. | |
| 1 | 70 | 50 | 63 | 79 | 100 | 25 |
| 2 | 100 | 67 | 97 | 98 | 100 | 100 |
| 3 | 100 | 67 | 100 | 100 | 100 | 100 |
| 5 | 50 | 61 | 37 | 71 | 100 | 19 |
| 8 | 57 | 6 | 30 | 41 | 37 | 0 |
| 9 | 87 | 47 | 44 | 61 | 90 | 15 |
| 10 | 0 | 28 | 13 | 32 | 7 | 0 |
| 11 | 52 | 21 | 35 | 37 | 30 | 0 |
| 13 | 22 | 53 | 18 | 40 | 21 | 17 |
| 20 | 40 | 42 | 38 | 63 | 81 | 22 |
| 23 | 43 | 34 | 33 | 65 | 67 | 11 |
| Standard | 64 | 56 | 72 | 95 | 66 | 69 |
1. Substituted 1-pyridinyl-2-azolyl-1-(2-phenylethenyl)ethanola-1 of General formula I
where PY represents 2-pyridinyl, 3-pyridinyl or 4-pyridinyl, Z denotes a nitrogen atom or a group CH, R1and R2independently from each other mean a hydrogen atom, halogen, triptorelin group.
2. The use of substituted 1-pyridinyl-2-azolyl-1-(2-phenylethenyl)atenolol-1 according to claim 1 as fungicides.
FIELD: organic chemistry, medicine.
SUBSTANCE: invention describes N-substituted azaheterocyclic carboxylic acids and their esters of the formula (I):
wherein R1 and R2 represent independently hydrogen, halogen atom, NR6R7 or (C1-C6)-alkyl; Y represents >N-CH2 or >C=CH2- wherein only underlined atom is a component of the ring system; X represents -O-, -S-, -CH2CH2- wherein R6 and R7 represent independently (C1-C6)-alkyl; r = 1, 2 or 3; Z represents heterocycle taken among formulas (a), (b), (c), (d), (f), (k), (g) and (j) given in the invention claim. Also, invention relates to a method for their preparing and pharmaceutical composition based on compounds of the formula (I). Invention describes a method for inhibition of neurogenous pain, inflammation and blood glucose level increase to patient by administration to patient the effective dose of compound of the formula (I). Compounds of the formula (I) elicit ability to inhibit the neurogenous pain and blood glucose enhanced level.
EFFECT: improved preparing method, valuable medicinal properties of compounds.
13 cl, 1 tbl, 30 ex
< / BR>where Z denotes a group of General formula II
< / BR>where A, B, X, Z, R1-R10have the meanings indicated in the claims, as well as the way they are received and drug based on these compounds
< / BR>and their pharmaceutically acceptable salts, esters, where Y is O; Q is CH; X, Z and Z' each independently represent CH or N; m=0-1; n=0-4; R1and R2independently selected from H, F, Cl, Br, OCH3OC2H5, OCH2CF3CH3WITH2H5, CF3isopropylate; R3represents H; R4and R5represent H or phenyl, except that R1represents H, R2represents H, Cl or CF3, R3, R4and R5=N, Y=0, and Q=CH, if m=0 and n=1; and also except that R1represents H, R2is OCH3, R3, R4and R5=H, Y=0, Q=CH, if m=0 and n=2
< / BR>where a denotes (R1SO2NR2-), (R3R60NSO2NR2-); X represents-NH-, -CH2- or-OCH2-; Y represents 2-imidazoline, 2-oxazoline or 4-imidazole; R1means (NISS
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to compounds of the formula (I):
wherein X means group of the formula (X-1) wherein R15 means halogen atom, (lower)-alkyl and perfluoro-(lower)-alkyl; R16 means hydrogen, halogen atom and (lower)-alkyl; or X means group of the formula (X-2) wherein Het means 5- or 6-membered heteroaromatic ring comprising 1 or 2 heteroatoms as nitrogen (N) atom; R15 and R16 have values indicated above for (X-1); R30 means hydrogen atom or (lower)-alkyl; p means a whole number from 0 to 1; or X means group of the formula (X-3) wherein R18 means aryl; R19 means unsubstituted arylalkyl or heteroarylalkyl representing 6-membered heteroaromatic ring comprising nitrogen (N) atom as a heteroatom; R20 means unsubstituted (lower)-alkanoyl; Y means group of the formula (Y-1) wherein R22 and R23 mean independently from one another hydrogen atom, (lower)-alkyl, halogen atom or perfluoro-(lower)-alkyl and at least one of radicals R22 and R23 doesn't mean hydrogen atom; R24 means hydrogen atom; or Y means group of the (Y-3) wherein R25 means group of the formula: R26-(CH2)e- wherein R26 means (lower)-alkoxy-group, (lower)-alkylthio-group, (lower)-alkylsulfonyl; or R26 means group of the formula: -NR28R29 wherein R28 means hydrogen atom; R29 means (lower)-alkanoyl or (lower)-alkylaminocarbonyl; Q means -(CH2)f- wherein e means a whole number from 0 to 4; f means a whole number from 1 to 3; a bond denoted as a dotted line can be hydrogenated optionally; and to its pharmaceutically acceptable salts and esters. Also, invention proposes a pharmaceutical composition designated for treatment or prophylaxis of rheumatic arthritis, cerebrospinal sclerosis, intestine inflammatory disease and asthma and containing compound of the formula (I) or its pharmaceutically acceptable salt or ester in combination with a compatible pharmaceutical carrier. Invention proposes derivatives of thioamide inhibiting interaction between α4-comprising integrins and VCAM-1.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.
20 cl, 1 tbl, 86 ex
FIELD: organic chemistry, medicine.
SUBSTANCE: invention describes N-substituted azaheterocyclic carboxylic acids and their esters of the formula (I):
wherein R1 and R2 represent independently hydrogen, halogen atom, NR6R7 or (C1-C6)-alkyl; Y represents >N-CH2 or >C=CH2- wherein only underlined atom is a component of the ring system; X represents -O-, -S-, -CH2CH2- wherein R6 and R7 represent independently (C1-C6)-alkyl; r = 1, 2 or 3; Z represents heterocycle taken among formulas (a), (b), (c), (d), (f), (k), (g) and (j) given in the invention claim. Also, invention relates to a method for their preparing and pharmaceutical composition based on compounds of the formula (I). Invention describes a method for inhibition of neurogenous pain, inflammation and blood glucose level increase to patient by administration to patient the effective dose of compound of the formula (I). Compounds of the formula (I) elicit ability to inhibit the neurogenous pain and blood glucose enhanced level.
EFFECT: improved preparing method, valuable medicinal properties of compounds.
13 cl, 1 tbl, 30 ex
FIELD: organic chemistry, pharmacy.
SUBSTANCE: invention relates to new derivatives of benzimidazole represented by the following formula (I) or its salt:
wherein R1 represents (lower)-alkyl group; R2 represents aromatic (lower)-alkyl group that can be substituted with one or more groups taken among halogen atom, alkyl group, halogen-(lower)-alkyl group, nitro-group, aromatic group, aromatic (lower)-alkoxy-group, (lower)-cycloalkyloxy-(lower)-alkyl group, aromatic (lower)-alkyl group, aromatic (lower)-alkenyl group, aromatic (lower)-alkynyl group, aromatic oxy-(lower)-alkyl group, (lower)-cycloalkyl-(lower)-alkoxy-group, alkenyl group, (lower)-alkoxy-group, (lower)-alkylthio-group and (lower)-alkanesulfonylcarbamoyl group; R3 represents alkyl group, hydroxy-(lower)-alkyl group, alkenyl group, aromatic group, halogenated aromatic group, (lower)-alkyl aromatic group, (lower)-alkenyl aromatic group or aromatic (lower)-alkenyl group; -X- represents cross-linking group represented by one of the following formulas: (II)
, (III)
, (IV)
, (V)
. Also, invention relates to pharmaceutical compositions eliciting activity that reduces blood glucose level based on this compound. Invention provides preparing new compounds and pharmaceutical compositions based on thereof used for prophylaxis and treatment of damaged tolerance to glucose, diabetes mellitus, insulin-resistance syndrome, vascular failures syndrome, hyperlipidemia and cardiovascular disorders.
EFFECT: valuable medicinal properties of compounds and compositions.
16 cl, 1 tbl, 86 ex
where R1represents phenyl or pyridinyl, substituted by substituents selected from the group comprising (1) phenyl, (2) furyl, thienyl, (3) halogen, (4) halogen(lower)alkyl, (5) lower alkylthio, (6) nitro, (7) lower alkenyl, optionally substituted phenyl, (8) lower quinil, optionally substituted phenyl, (9) lower alkoxy, optionally substituted cyclo(lower)alkyl or phenyl, (10) lower alkyl, optionally substituted, phenyloxy or (11) amino, optionally substituted protected carboxyla; R2represents lower alkyl; R3represents halogen or lower alkyl; R4represents (1) lower alkenyl, optionally substituted phenyl, (2) phenyl, optionally substituted lower alkyl or lower alkenyl, (3) lower alkyl or (4) thienyl, optionally substituted with halogen; a represents a lower alkylene and L represents a simple bond, a lower albaniles or lower alkylene, optionally substituted phenyl or pyridinyl, or-X-CH2- where X represents O or NR5where R5represents hydrogen or n is
where R1represents hydrogen, halogen, methoxy; R2represents hydrogen, halogen, methyl, ethyl, methoxy; R3represents carboxy, tetrazolyl or CONHSO2R4in which R4represents methyl, ethyl, phenyl, 2,5-dimethylisoxazole, trifluoromethyl; T represents-CH2- or-SO2-; and ring a is 3-chlorophenyl, 4-chlorophenyl, 3-triptoreline, 3,4-dichlorophenyl, 3,4-differenl, 3-fluoro-4-chlorophenyl, 3-chloro-4-forfinal, 2,3-dichloride-5-yl; or their pharmaceutically acceptable salts or esters, as well as pharmaceutical compositions containing them
in which R denotes an element of the formula
R1denotes a methyl radical or ethyl, R2denotes a naphthyl radical, hinely, phenyl, possibly substituted by one or more halogen atoms, alkyl radicals, alkoxyl, hydroxyl, etc.,, R3and R4identical or different, represent a phenyl radical, possibly substituted by one or more halogen atoms, alkyl, alkoxyl, formyl, trifluoromethyl, etc.,, R5denotes an alkyl radical or phenyl, substituted by one or more halogen atoms, R6and R7identical or different, denote a hydrogen atom or an alkyl radical, or R6and R7together with the nitrogen atom to which they are connected, form piperidinyl or pieperazinove cycle, substituted alkyl, R’6and R’7identical or different, denote a hydrogen atom or an alkyl radical, or R’6and R’7together with the nitrogen atom to which they are connected, form a pyrolidine or pieperazinove cycle, possibly substituted by one alkyl radical, cycloalkyl, -ALK-O-ALK, hydroxyalkyl, or R6and R7together with the nitrogen atom to which they are connected, form a loop imidazole, piperazinone, thiomorpholine, etc., R8denotes alkyl, R9denotes a hydrogen atom, an alkyl radical or an alkyl, substituted dialkylamino, phenyl, etc.,, R10and R11identical or different, denote a hydrogen atom or alkyl, R12and R13together with the nitrogen atom to which they are connected, form a loop of the research, a R16and R17together with the nitrogen atom to which they are connected, form a loop of piperidine, R’ denotes a hydrogen atom or the radical-CO-ALK, ALK denotes an alkyl or alkylene, and alkyl or alkylene radicals or their parts and CNS radicals or their parts are straight or branched chain, containing from 1 to 6 carbon atoms, and their optical isomers and their salts with mineral or organic acid
FIELD: organic chemistry, herbicides, agriculture.
SUBSTANCE: invention relates to new substituted benzoylketones of the general formula (I): , all possible tautomeric forms and possible salts that can represent active substance as a component of herbicide agent. In the formula (I) A means (C1-C4)-alkyl; R1 means cyclo-(C3-C6)-alkyl; R2 means hydrogen atom (H), cyano-group (CN); R3 means hydrogen atom (H), halogen atom, CF3, (C1-C4)-alkylsulfonyl; R4 means halogen atom; X means groups:
or
wherein R5 means (C1-C4)-alkyl, (C1-C4)-alkoxy-group, (C1-C4)-alkylthio-group, di-(C1-C6-alkyl)-amino-group; R6 means (C1-C4)-alkyl, (C1-C4)-alkoxy-group, cyclo-(C3-C6)-alkyl; n = 0 or 1 including all possible tautomeric forms and possible salts. Compounds of the formula (I) elicit herbicide activity and can be used in herbicide composition.
EFFECT: valuable properties of compounds.
3 cl, 1 sch, 3 tbl, 13 ex
