The method of obtaining piperazine-adipate
(57) Abstract:The invention relates to the field of chemistry, to a method for the chemical substance that manifests anthelminthic properties, and can be used in agriculture to treat animals. The aim of the invention is to simplify the process technology. The process is suggested by the interaction hexahydropyrazino with adipic acid in the solid phase under stirring at a temperature of 20-25oC at a molar ratio of 1:1 to achieve the reaction mass pH 6-7 and subsequent distillation of the liberated in the reaction of water and drying of the target product. The invention relates to a method for producing piperazine-adipate, which is an anthelmintic drug used to treat animals.Known method (patent Poland 56 135) obtain piperazine-adipate, which consists in the interaction piperazine-uranyl and adipic acid in the aquatic environment:
< / BR>The reaction is carried out as follows.130 kg (0,89 g-mol) of adipic acid are dissolved at 70-80oC 300 kg (16,67 g-mol) of distilled water, then add 1 kg of activated carbon, and conducting filtering piperazine - 0,89 g-mol) in 80 kg of distilled water with a temperature of 70oC to establish pH 6-7,5. The molar ratio of adipic acid piperazine 1 1. The mixture is distilled in a vacuum to 240 kg of water, the residue is cooled to 18oC and filtered. The precipitate is washed with a small amount of distilled water and dried at 60oC. the mother liquor is diluted with water to a total volume of 400 l and used for dissolving the following portions of adipic acid. After several cycles the mother liquor is evaporated to 4/5 and after recrystallization from water (mass ratio of water piperazine-adipate 7 1) allocate an additional amount of piperazine-adipate. The total yield of 95-96% (based on adipic acid.The disadvantage of this method is the complexity of the technological process, based on: 1) the need for pre-cleaning of adipic acid; 2) the use of scarce activated carbon for the purification of acid; 3) the disposal of large quantities of waste water; 4) the presence of various equipment (reactor, filter, refrigerator, collection and others) to build the process flowsheet.The aim of the invention is the simplification of the process of obtaining piperazine-adipate.Supplied with the x mark PLN or drier "Violet". The mixing is carried out at a temperature of 20-25oC for 1.5-2 h, the molar ratio of components 1 1. It releases water of crystallization and is formed piperazine-adipate in paste form. If 70oC, vacuum and continuously operating the agitator is stripped separated from the reaction of water for 2-3 hours Following example illustrates the method of obtaining piperazine-adipate.Example.In mixer brand PLN or drier "Violet" download at 20-25oC g (2.65 g-mol) piperazine-uranyl and 386,9 g (2.65 g-mol) of adipic acid and stirred at this temperature for 1.5-2 h, forming a paste with a pH of aqueous paste 6-6,1. Then to the mixer or dryer hook up the vacuum, heated to 60-90oC and distilled water with the receiving water in the sink for 2-2,5 hours Get 605,9 g dry piperazine-adipate, a yield of 99%
Thus, the proposed method can greatly simplify the process of obtaining piperazine-adipate due to:
1) the reaction product education and drying in a single unit, eliminating a number of equipment;
2) reduction of wastewater, because the mixing of the reagents is carried out in the solid phase in the absence of solvent. the s reagent ratio 1 1, characterized in that the interaction is carried out in the apparatus mixers brand PLN or drier "Violet" in the solid phase at 20 25oC and stirring, followed by distillation of the reaction water at 70 to 80oWith the vacuum.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to amide of δ-amino-γ-hydroxy-ω-arylalcane acid of formula and its pharmaceutically acceptable salts. Also described are pharmaceutical compositions, which include said compounds, and application of said compounds for preparation of medication, intended for treatment of pathological states, associated with renin activity, in particular for treatment of hypertension.
EFFECT: obtaining pharmaceutically acceptable salts, which possess rennin-inhibiting ability.
21 cl, 161 ex
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to a new method for preparing 5-(4-fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxotetrahydropyran-2-yl)ethyl]-2-isopropyl-4-phenyl-1H-pyrrol-3-carboxylic acid phenylamide that involves conversion of methylcyano acetate to the end compound for 8 or less stages. Also, invention relates to value intermediate compounds that are synthesized as result of realization of above indicated stages of the claimed method. 5-(4-Fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxotetrahydropyran-2-yl)ethyl]-2-isopropyl-4-phenyl-1H-pyrrol-3-carboxylic acid phenylamide is a value intermediate compound used in synthesis of the drug atorvastatin calcium that is used as hypolipidemic and/or hypocholesterolemic agent. Proposed method allows avoiding usage of expensive chiral parent substances and to reduce the synthesis process time.
EFFECT: improved preparing method.
12 cl, 3 ex
FIELD: pharmaceutical chemistry, medicine.
SUBSTANCE: invention relates to new compounds of formula I ,
solvates or pharmaceutically acceptable salts having antiarrhythmic activity, including ventrical fibrillation, as well as pharmaceutical compositions containing the same. Compounds of present invention are useful in treatment or prevention of arrhythmia, modulation of ion channel activity, for topic or local anesthesia, etc. In formula I X is direct bond, -C(R6,R14)-Y- and C(R13)=CH-; Y is direct bond, O, S, and C1-C4-alkylene; R13 is hydrogen, C1-C6-alkyl, C3-C8-cycloalkyl, unsubstituted aryl or benzyl; R1 and R2 are independently C3-C8-alkoxyalkyl, C1-C8-hydroxyalkyl and C7-C12-aralkyl; or R1 and R2 together with nitrogen atom directly attached thereto form ring of formula II ,
wherein said ring is formed by nitrogen and 3-9 ring atoms selected independently from carbon, sulfur, nitrogen and oxygen, etc; R3 and R4 are independently attached to cyclohexane ring in 3-, 4-, 5-, or 6-position and represent independently hydrogen, hydroxyl, C1-C6-alkyl and C1-C6-alkoxy; and when R3 and R4 are bound with the same atom of cyclohexane ring they may form together 5- or 6-membered spiroheterocycle ring containing one or two heteroatoms selected from oxygen and sulfur; A is C5-C12-alkyl, C3-C13-carbocyclic ring, or ring structure as defined herein.
EFFECT: new antiarrhythmic drugs.
30 cl, 12 dwg, 34 ex
FIELD: organic chemistry, insecticides.
SUBSTANCE: invention describes dialkylamide derivatives of pyrethroid acids of the general formula (III): wherein R1 and R2 represent organic radicals and each radical represents ethyl, or they both can be bound and in common with nitrogen atom represent piperidide, hexamethyleneimide, morpholide. Represented compounds are used as chemical agents for control of insect-pests in agriculture, veterinary science and cattle breeding.
EFFECT: valuable properties of compounds.
2 dwg, 4 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention proposes compounds of the general formula (1): wherein X is chosen from sulfur atom and methylene group; X1 is chosen from sulfur atom and methylene group; X2 is chosen from oxygen (O), sulfur (S) atoms and methylene group; X3 means -NR5 or carbonyl group; R1 means hydrogen atom or nitrile group; R and R3 are chosen independently from hydrogen atom (H) and (C1-C6)-alkyl; R4 means R4A when X3 means -NR5 and R4B when X3 means carbonyl group; R4A is chosen from -R6R7NC(=O), -R6R7NC(=S), -R8(CH2)qC(=O), -R8(CH2)qC(=S), -R8(CH2)qSO2 and -R8(CH2)qOC(=O); R4B means -R6R7N; R5 means hydrogen atom (H); R6 and R7 are chosen independently from -R8(CH2)q, or they form in common -(CH2)2-Z1-(CH2)2- or -CHR9-X2-CH2-CHR10-; R8 is chosen from hydrogen atom (H), (C1-C4)-alkyl, cycloalkyl group condensed with benzene ring, acyl, dialkylcarbamoyl, dialkylamino-group, N-alkylpiperidyl, optionally substituted aryl, optionally substituted α-alkylbenzyl, optionally substituted aroyl, optionally substituted arylsulfonyl and optionally substituted heteroaryl representing monocyclic 5- and 6-membered ring aromatic group with one or two heteroatoms chosen from nitrogen, oxygen and sulfur atoms, and derivatives of abovementioned rings condensed with benzene; R9 and R10 are chosen independently from hydrogen atom (H), hydroxymethyl and cyanomethyl groups; Z1 is chosen from -(CH2)r-, -O-, and -N((CH2)q)R8)-; Z2 means optionally the substituted ortho-phenylene group; m = 1-3; n = 0-4; p = 2-5; q = 0-3, and r = 1 or 3. Proposed compounds are inhibitors of dipeptidyl-peptidase IV and can be used in preparing pharmaceutical compositions designated for treatment of different diseases, among them, diabetes mellitus of type 2.
EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical composition.
22 cl, 8 tbl, 453 ex
SUBSTANCE: invention relates to dipeptide mimetic selected from glutaminyl thiazolidine or glutaminyl pyrrolodine and salts thereof as well as to using of such compounds in treatment of abnormal glucose tolerance, glucoseuria, diabetes mellitus and other disordered as well as complications associated with diabetes mellitus in mammalians.
EFFECT: new effectors of dipeptidyl peptidase IV.
18 cl, 3 tbl, 2 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel derivatives of carboxylic acid represented by the general formula (I): , their pharmaceutically acceptable salts or esters wherein values Y, L, X, T, Z, M, R1, W and are given in the invention claim. Proposed compounds possess insulin-sensitizing effect and they are double agonists with respect to PPARα and γ, and triple agonists with respect to PPARα, β(δ) and γ. Except for, the invention relates to a medicinal agent and pharmaceutical compositions based on the claimed derivatives of carboxylic acid, to methods for prophylaxis or treatment of diseases, and to using derivatives carboxylic acid for preparing a medicinal agent.
EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.
56 cl, 2 tbl, 609 ex
FIELD: chemistry, pharmaceutical.
SUBSTANCE: invention pertains to compounds with formula I , where: n is an integer equal 1 or 2; p is an integer from 1 to 7; A is chosen from one or more radicals X and/or Y; X represents methylene group, substituted when necessary by one or two C1-6-alkyl groups; Y represents C2-alkenyl, C2-alkenyl; G represents a single bonds, oxygen or C=O. The compound can be used as ferment FAAH inhibitor for pain killing, inflammation or nerve-degenerative diseases. Description is given of the method of obtaining compounds, pharmaceutical compositions based on them and their use.
EFFECT: design of a method of obtaining alkylhomopiperazinecarboxylates and their use for pain killing, treating inflammation or nervous degenerative diseases.
11 cl, 2 tbl, 7 ex
FIELD: chemistry, pharmaceutics.
SUBSTANCE: invention relates to compounds of formula 1 and their pharmaceutically acceptable salts as inhibitors of post-proline aminopepdidases, as well as to pharmaceutical composition based on them and application for manufacturing such composition, and to method of inhibition with their application. Compounds can be applied for treatment of diseases mediated by activity of post-proline aminopeptidases, such as type II diabetes and disturbed tolerance to glucose. In general formula 1 ,
either G1 represents -CH2-X2-(CH2)a-G3, and G2 represents H, or G2 represents -CH2-(CH2)a-G3, and G1 represents H; G3 is selected from group according to general formula 2 ,
group according to general formula 3
and group according to general formula 4 ;
a is 0, 1 or 2; b is 1 or 2; X1 is selected from CH2, S, CF2, CHF and O; X2 is selected from CH2; X3, X4 and X5 are selected from N; X6 is selected from NH; X7 is selected from NH; R1 is selected from H and CN; R2 represents H; R3 is selected from H, Cl, OH, NH2, NH-C1-C10alkyl and N(C1-C10alkyl)2; R4, R5, R6, R7 and R8 are independently selected from H, Br, Cl, F, OH, NO2; R9 represents H; R10, R11, R12, R13 and R14 are independently selected from H, Cl and CF3; R15 and R16 are independently selected from H, C1-C10alkyl, C1-C10alkenyl, C3-C10cycloalkyl, C3-C10cycloalkenyl, quinoline, naphtyl and -CH2-L-R17; R17 is selected from C1-C10alkyl, phenyl, naphtyl, quinolinyl and indolyl; L is selected from covalent bond, CH=CH and -C6H4-; on condition that when R15 and R16 both represent H, and b is 1, then X1 does not represent S or CH2.
EFFECT: obtaining compounds that can be applied for treatment of diseases mediated by activity of post-proline aminopeptidases, such as type II diabetes and disturbed tolerance to glucose.
58 cl, 10 tbl, 1705 ex
SUBSTANCE: present invention pertains to derivatives of 1-(4-benzylpiperazin-1-yl)-3-phenylpropenone, which are antagonists of the chemokine (CCR-1) receptor, with general formula I or its pharmaceutical salts or ester, where substitutes are defined in the description text. The invented compounds can be used for making pharmaceutical compositions, as well as in pharmaceutics for making medicinal agents, with inhibiting effect on chemokine (CCR-1) receptors.
EFFECT: obtaining compounds, used as medicinal agents, with inhibiting effect on chemokine receptors.
10 cl, 113 ex
SUBSTANCE: invention relates to new crystalline modifications of N-α-(2,4,6-triisopropylphenylsulphonyl)-3-hydroxyamidino-(L)-phenylalanine-4-ethoxycarbonyl piperazide and/or its salts. Such crystalline modifications have high stability particularly at low hygroscopicity compared to known amorphous forms of the compound.
EFFECT: invention relates to a method of obtaining such new crystalline modifications, to pharmaceutical compositions containing these new crystalline modifications and their use as an anti-tumour agent.
26 cl, 7 tbl, 13 ex, 20 dwg