2,6-dimethylanilide of n-cyclohexylpyrrolidine-2-carboxylic acid hydrochloride, having surface, infiltration and conduction anaesthesia activity
SUBSTANCE: invention relates to a novel biologically active 2,6-dimethylanilide of N-cyclohexylpyrrolidine-2-carboxylic acid, having surface, infiltration and conduction anaesthesia activity, considerably better than bupivacaine and ropivacaine with the same or less toxicity.
EFFECT: improved compounds.
The claimed connection relates to the field of organic chemistry class arylamido azacyclopentadecan acids, namely new biologically active 2,6-dimethylaniline N-cyclohexylpiperidine-2-carboxylic acid hydrochloride (I) of the formula:
which can find application as a medicinal poverkhnostnoaktivnykh tools.
As the standards of local anesthetic action used a well-known and widely used local anesthetics bupivacaine and ropivacaine [Mashkovsky PPM Medicines. - 15-ed., Rev., Corr. and supplementary): RIA "New wave": the Publisher Merenkov, 2008. - 1206 S.: ill.].
The aim of the invention is to obtain a new previously undescribed 2,6-dimethylaniline N-cyclohexylpiperidine-2-carboxylic acid hydrochloride, has anesthetic effects. This goal is achieved by the synthesized δ is haralanova acid, followed by its translation into the acid chloride with chloride tiomila. Then the acid chloride mineralsa 2,6-dimethylaniline and cyclized using cyclohexylamine 2.6-dimethylaniline N-cyclohexylpiperidine-2-carboxylic acid, which use gaseous hydrogen chloride is converted into hydrochloride. The scheme for synthesis of:
Synthesis of 2,6-dimethyl what nelida N-cyclohexylpiperidine-2-carboxylic acid hydrochloride carried out by well-known methods, with some modifications. [Lihosherstov A.M., Pryanishnikova N.T., A.S. Lebedev and other Azacycloheptane XIX. Synthesis and an anaesthetic activity of some Mezhidov pyrrolidinecarbonyl-2 acid. // Chem-Pharm. J., 1976, Vol.7, p.36-40.]:
α-bromo-δ-haralanova to-one (II). A mixture of 52.2 g of δ-haralanova acid (I), with 76.8 g of dry bromine and 4 ml of phosphorus trichloride was placed in a round bottom flask of 250 ml with a reflux condenser and was heated on a water bath for 20 h at 80°C and then 2 h at 100°C. the Reaction mass was washed with water in a conical flask (Erlenmeyer), 500 ml, the oily layer was separated using a separating funnel, 500 ml, and the aqueous was extracted several times with benzene. The benzene extracts were combined with the oil and the solution was dried with magnesium sulfate. After distillation of the benzene residue was awarded to 75.1 g II, the output of 90.7 percent.
The acid chloride, α-bromo-δ-haralanova acid (III). It is 103.6 g of chloride tiomila in a round bottom flask of 250 ml with a reflux condenser were added to 75.1 g II, and the mixture was boiled for 1.5 h in a water bath. Excess chloride tiomila drove, the output 73,9 g, 90.7 percent.
2,6-dimethylaniline α-bromo-δ-haralanova acid (IV). In a three-neck round bottom flask of 250 ml, equipped with a dropping funnel and electronically, was placed a solution of 12,94 g of 2,6-dimethylaniline and 10.8 g of triethylamine in 50 ml of chloroform. Next was added for 45 min dropwise a solution of 25.0 g of chlorine is hydride α-bromo-δ-haralanova acid in 40 ml of chloroform at a temperature of 0-10°C (temperature was achieved by placing the flask in cold water with ice), with constant stirring electronically. The resulting solution was heated in a round bottom flask 250 ml) under reflux on water bath for 1 h Precipitated precipitate was filtered. The filtrate was washed with 3% hydrochloric acid solution and then with water until neutral environment. After removal of the solvent amorphous powder of 2,6-dimethylaniline α-bromo-δ-haralanova acid, which is recrystallized from hexane, the yield was 20.4 g, 60%.
2,6-dimethylaniline N-cyclohexylpiperidine-2-carboxylic acid (V). To a solution 7,37 g IV in 100 ml of toluene in a three-neck round bottom flask equipped with addition funnel and electronically, was added dropwise a solution of 3,44 g cyclohexylamine and 4.6 g of triethylamine (to save cyclohexylamine) in 100 ml of toluene. Then the reaction mass was made 0.2 g of potassium iodide and the mixture was heated on a sand bath in a round bottom flask with reflux for 28 hours. Next, the precipitation was filtered. The filtrate was shaken with a saturated solution of potash. Toluene layer was separated and evaporated to dryness. Output V amounted to 3.67 g, 53%.
The hydrochloride of 2,6-dimethylaniline N-cyclohexylpiperidine-2-carboxylic acid (VI). The remainder of the V was dissolved in 200 ml of ether, and let dry hydrogen chloride. The precipitation of the hydrochloride VI was filtered, repeatedly washed with acetone, dried, and p is recrystallization of ethyl alcohol, output 3,70 g, 90%.
The inventive compound is a white crystalline substance with a melting point 278-280°C (decomposition)slowly soluble in ethanol, water, soluble in DMSO, insoluble in acetone, hexane, diethyl ether. The NMR spectrum1H (Mercury - 300 MHz) in DMSO, internal standard TMS) of compound (I) includes: three multiplet six protons of methylene groups tsiklogeksilnogo radical at the nitrogen heteroatom pyrolidine cycle in the area of 1.06-1,63 ppm, multiplet two protons of methylene group pyrolidine cycle when 1,79 is 2.01 ppm, multiplet four protons of methylene groups tsiklogeksilnogo radical at the nitrogen heteroatom pyrolidine cycle when 2,01-2,12 ppm, singlet six protons of the two metal groups of the aromatic ring at 2,17 ppm, multiplet two protons of methylene group pyrolidine cycle when 2,54-2,62 ppm, multiplet two protons methylene group pyrolidine cycle at 3.25 to 3.40 in ppm, multiplet CH-group tsiklogeksilnogo radical at the nitrogen heteroatom pyrolidine cycle in the field 3,55 at 3.69 ppm, a triplet of one proton CH-group pyrolidine cycle when 4,690-4,780 ppm, multiplet three protons of the aromatic ring in the area 7,07-7,16 ppm, a singlet proton-NH - group at 9,34 ppm, a singlet proton chloroethanol acid at 10,65 ppm
The study of biological the activity
Research activity at the surface anesthesia was performed according to the method of Rainier [Manual on experimental (preclinical) study of new pharmacological substances / Under the General editorship of Corr-cor. The RAMS, Professor RU Khabriev. - 2 ed., revised and enlarged extra - M., 2005. - 832 C.]. Generalizirovanny rabbits were placed in a special box with a hole, the locking head. We determined the sensitivity threshold of the cornea of the rabbit to tactile impact. With this purpose we applied a thin metal wire in the form of a loop, without injuring the cornea. Connection and transfer standards (bupivacaine and ropivacaine) was administered in the conjunctival SAC of the eye of the rabbit in the form of a 0.5% solution (in 0.9% sodium chloride). Determined the start time of anesthesia. The first definition of surface anesthesia was performed on 8 minute experience and repeated at 10, 12, 15, 20, etc. up to 60 minutes, a total of 13 measurements. The activity of the substances was evaluated by 2 parameters: index Rainier, a measure of the depth of anaesthesia and the duration of anesthesia. Each substance was investigated in 6 rabbits (12 eyes). The experimental results were processed statistically using student's criterion with p≤0,05.
The active substances in block anesthesia was determined in experiments, the application of a 0.5% solution (in 0.9% sodium chloride) compounds and benchmarks comparison to Segal snye nerves of rats [Manual on experimental (preclinical) study of new pharmacological substances / Under the General editorship of Corr.-cor. RAMP, Professor RU Khabriev. - 2 ed., revised and enlarged extra - M., 2005. - 832 C.]. Electrical irritation of the nerves produced using pacemaker ECL-2 above the site of blockage. Determined the irritation threshold, i.e. the minimum voltage that causes muscle contraction. Then the nerve is wrapped with a cotton clutch and inflicted 0.2 ml of the analyte or standard. Determined the duration of anesthesia in minutes and the depth of anesthesia to increase the threshold of irritation, expressing it in percentage to the original threshold value (the excess of the initial threshold of irritation more than 2 times counted for 100% of the depth of anesthesia). Each substance was evaluated in 4 rats (8 experiments). The experimental results were processed statistically using student's criterion with p≤0,05.
Studying the activity of the substances in infiltration anesthesia was evaluated in experiments on rats according to the method of Bulbring and Waida (Bulbring E., J. Wajda Biological comparison of local anaesthetica. J. Pharmacol. and Exp. Therap., 1945, vol.85, No.1, p.7-84). White rats intradermally (0.05 ml) and subcutaneously (0.45 ml) was injected 0.5% solution (in 0.9% sodium chloride) of the investigated substances. Analgesic effect they have studied at a metered electrical stimulation of the skin of the animal. Determined the irritation threshold, i.e. the minimum voltage that causes muscle contraction. Was determined by the duration of anesthesia in minutes and the depth of anesthesia to increase the threshold of irritation, expressing it in percentage to the original threshold value (the excess of the initial threshold of irritation more than 2 times counted for 100% of the depth of anesthesia). Each substance was evaluated in 4 rats (8 experiments). The experimental results were processed statistically using student's criterion with p≤0,05.
Acute toxicity subcutaneous (s/C) was determined by nonlinear white mice of both sexes weighing 19-25, the test substance and the Comparators were introduced in the form of a 0.5% solution (based on 0.9% sodium chloride solution) in increasing doses. The results were processed by Prozorovsky calculation of the median lethal dose (LD50) when P≤0,05 [Prozorovsky CENTURIES, Prozorovsky BTW, Demchenko V.M. Pharmacol. toxicol., v.41, №4, s-502, 1978].
The results of the study poornathrayeesa activity and acute toxicity of compounds I, bupivacaine and ropivacaine presented in table 1.
|Poornathrayeesa activity and acute toxicity of compounds I, bupivacaine and ropivacaine.|
|Connection||Surface anesthesia||LD50p/K, mg/kg|
|Index Rainier||The duration of anesthesia, min|
|I||1215,1±25,8||of 80.6±4,3||112,0 (64,8-185,9)|
|P1*in comparison with bupivacaine||P1≤0,05||P1≤0,05|
|P2*in comparison with ropivacaine||P1≤0,05||P1≤0,05|
|* for the 12 experiments|
The results of the research activity at infiltration and block anesthesia of compound I, bupivacaine and ropivacaine presented in table 2.
|Infiltration and conduction an anaesthetic activity is connected to the I I, of bupivacaine and ropivacaine.|
|Connection||Infiltration anesthesia||Conduction anesthesia|
|The depth of anesthesia %||The duration of anesthesia, min||The depth of anesthesia %||The duration of anesthesia, min|
|P1*in comparison with bupivacaine||P1≥0,05||P1≤0,05|
|P2*in comparison with ropivacaine||P2≤0,05||/td>||P1≤0,05|
As can be seen from table 1, the inventive compound of formula (I) is 1.3 times that of bupivacaine and 2.0 times ropivacaine depth poverkhnostnoaktivnykh actions. The substance of formula (I) in 1.6 times in comparison with bupivacaine and 2.5 times in comparison with ropivacaine manifests longer poverhnostnoaguoe activity. In addition, the compound of formula (I) exhibits a toxicity equal to the toxicity of ropivacaine and is less toxic than bupivacaine in 1.6.
As can be seen from table 2, the inventive compound of formula (I) in 1.6 times in comparison with ropivacaine manifests longer infiltration.otherwise activity, not yielding to the same indicator of the bupivacaine. The substance of formula (I) is 1.4 times that of bupivacaine and 1.6 times ropivacaine duration prednisonesinusah effect.
Thus, 2,6-dimethylaniline N-cyclohexylpiperidine-2-carboxylic acid hydrochloride exhibits a more pronounced and longer poverhnostnoaguoe action at equal or lesser toxicity than bupivacaine and ropivacaine. The substance of formula (I) greatly exceeds the duration of the activity of ropivacaine and bupivacaine at block anesthesia, surpassing, in addition, the duration of effect of ropivacaine in detail ltrations anesthesia. Therefore, the claimed compound (I) can be used in medicine as a local anesthetic drugs for surface infiltration and block anesthesia.
2,6-Dimethylaniline N-cyclohexylpiperidine-2-carboxylic acid hydrochloride,
active at the surface, infiltration and block anesthesia.
SUBSTANCE: invention relates to pyrrolidine derivatives of formula: where: each of R1, R2, R3, R4, R5 and R6 independently denotes H, C1-10alkyl; R7 denotes C1-10alkyl, a 5-6-member monocyclic aromatic heteroaryl, having one or two heteroatoms selected from N, S, optionally substituted with C1-10alkyl; R denotes H, C1-10alkyl; or R7 and R8, together with a N with which they are attached, form a 5-8-member monocyclic, saturated or unsaturated ring, optionally including a second hateroatom selected from N, S, O, optionally substituted with a halogen, CN, -OR', C1-10alkyl, hydroxyC1-10alkyl, C1-10alkoxyC1-10alkyl, -S(O)2R', -C(O)OR', or form a 8-12-member bicyclic, saturated or unsaturated ring; R' denotes H, C1-10alkyl; m and n are independently equal to 0, 1, 2 or 3; X denotes NRa, Ra denotes H. The compounds are used in a method of inhibiting dipeptidyl peptidase IV.
EFFECT: obtaining pyrrolidine derivatives.
13 cl, 2 dwg, 1 tbl, 26 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to compounds of formula (I) or to its pharmaceutically acceptable salts: wherein: R1 means H, OH, halogen, C1-C6alkyl, C1-C6alkoxy, halogenC1-C6alkyl, halogenC1-C6alkoxy, phenyl; R2a and R2b are identical or different, and mean H, halogen, C1-C6alkyl, C1-C6alkoxy, halogenC1-C6alkyl, halogenC1-C6alkoxy; R3 means C1-C6alkyl; A means a single bond, a vinylene group; B means a single bond; Ar means phenyl optionally substituted by halogen, CN, C1-C6alkyl, C1-C6alkoxy, halogenC1-C6alkyl, halogenC1-C6alkoxy; Z means -COOH, tetrazolyl; m is equal to 0, 1,2, 3, 4, 5, 6; n is equal to 0 or 1.
EFFECT: compounds exhibit calcium-sensing receptor (CaSR) antagonist activity that enables them to be used in treating or preventing a disorder related to disturbed bone or mineral homeostasis, such as osteoporosis.
18 cl, 151 tbl, 190 ex
SUBSTANCE: invention relates to compounds of formula (I) or (II) including enantiomer or diastereomer thereof, where values of R1, R2, R3, R100, R200, R300, A, A1, BG, Q and Q1 are given in claim 1.
EFFECT: compounds can be used to treat proliferative disorders, for example, cancer.
42 cl, 36 dwg, 7 tbl
SUBSTANCE: invention relates to a novel compound 4-methylanilide-N-n-propylpyrrolidine-2-carboxylic acid borate of formula:
, having anthelminthic activity. The compound is obtained through bromination of 5-chlorovaleric acid with subsequent conversion thereof into an acid chloride using thionyl chloride, further amination with 4-methylaniline and then ring closure with n-propylamine in 4-methylanilide-N-n-propylpyrrolidine-2-carboxylic acid and reaction of the latter with boric acid.
EFFECT: high activity of the compound.
SUBSTANCE: invention relates to novel compounds of formula or to its pharmaceutically acceptable salts, where n is 0 or 1; R1 represents H or F; R2 represents C1-4alkyl; R7 represents H or C1-4alkyl; and Z represents hydroxyl C1-6alkyl or C1-6alkoxycarbonyl, or 5- or 6-member heteroaromatic ring, which belongs to aromatic rings which have given number of atoms, of which at least one is N, O or S, the remaining being carbon atoms, and which also optionally has methyl substituting group. Invention also relates to pharmaceutical composition, to application of compounds, as well as to method of obtaining formula I compounds.
EFFECT: obtaining novel biologically active compounds, possessing activity of receptor 5-HT2A antagonists.
9 cl, 25 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to derivatives of nitrogen-containing heterocyclic compounds of the general formula (I'):
wherein R represents the group:
m = 0-3; R1 represents halogen atom, cyano-group and others; X represents oxygen or sulfur atom, or the group -CH2 and others; Z1 and Z2 represents the group -CH2 and others; Q represents oxygen or sulfur atom, or the group -CH2 or -NH; R2 represents substituted phenyl; n = 0-2; R3 represents (C1-C6)-alkyl, (C1-C6)-alkoxycarbonyl group and others; R4, R5, R6 and R7 represent hydrogen atom or (C1-C6)-alkyl and others; R8 represents hydrogen atom, (C1-C6)-alkyl. Compounds of the formula (I') possess of activity modulating activity of chemokine MIP-1α receptors and can be used in medicine in treatment of inflammatory diseases and respiratory ways diseases.
EFFECT: improved preparing method, improved methods for treatment, valuable medicinal properties of compounds and composition.
20 cl, 283 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: what is presented is a pharmaceutical composition in the form of a spray for treating a damage by non-lethal irritants (e.g. pelargonic acid morpholide), containing pediphene in the following proportions, wt/volume %: pediphene hydrochloride 0.01-10.0; sodium chloride 0.1-10.0; water for injections up to 100 ml. What is shown is the efficacy of pediphene in compliance with the declared application ensured by the local anaesthetic effect of the drugs.
EFFECT: drug preparation has no allergenic and immunotoxic properties.
3 dwg, 40 tbl
SUBSTANCE: invention refers to medicine, namely anesthesiology, intensive therapy and endosurgery, and may be used in patients in need of endoscopic transpapillary intervention. That is ensured by an intravenous infusion therapy with crystalloid solutions in the amount of 800-1200 ml. An epidural space is punctured and catheterised at the level of Th VIII - Th IX with the catheter moved by 4-5 cm in the cranial direction. A local anaesthetic solution and Clopheline 100 mcg are introduced through the epidural catheter at the level of Th V - Th X 20 minutes before the endoscopic transpapillary intervention. It is followed by pre-medication enabled by introducing 0.1% atropine 0.5-1 ml and 0.5% relanium 1-2 ml, and the patient is wheeled into a catheterisation laboratory. After the endoscopic transpapillary intervention completed, the patient is transferred into an intensive therapy unit wherein prolonged epidural analgesia is enabled by introducing 0.5-1% lidocaine 10 ml into the epidural space every 4 hours. If observing no clinical manifestations of postoperative pancreatitis, the epidural catheter is removed, and the patient is transferred into a department of surgery for symptomatic treatment.
EFFECT: method enables preventing acute postoperative pancreatitis following such interventions due to action of a general mechanism of pathogenesis of the given pathology.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a pharmaceutical vaginal composition for reducing or relieving uterine dysrhythmia. The composition contains an antidysrhythmia drug in the concentration of 1 wt % to 12.5 wt % and a pharmaceutically acceptable carrier providing prolonged release. The carrier contains a bioadhesive, water-swellable, water-insoluble, cross-linked polycarboxylic acid polymer such as polycarbophil. The drug is specified in prilocaine, mepivacaine, bupivacaine, ropivacaine, ethidocaine, mexiletine, procainamide, moracizin, propaphenone and flecainide.
EFFECT: invention provides reducing or relieving uterine dysrhythmia with prolonged release of said drugs with creating adequate local concentrations and low blood concentrations.
9 cl, 33 ex
SUBSTANCE: after performing main stage of surgery, under visual control needle puncture is performed into retroperitoneum space of right iliac fossa perpendicularly to skin, 1 cm inward from anterior superior iliac spine. Needle is passed inward, downward and frontward to the depth 6-8 cm, sliding on internal surface of iliac bone. Conductor is introduced through needle lumen and polyethylene catheter, through which after the end of operation, after 4-6 and 10-12 hours introduced is naropin in dose 2.5 mg/ml in 0.9% sodium chloride solution, is installed.
EFFECT: method makes it possible to ensure adequate and safe anesthetics in post-operative period due to accuracy of introduction of anesthetic directly in the zone of surgery.
SUBSTANCE: puncture point is anaesthetised by 0.5% bupivacaine. It is followed by puncture of a subdural space with the use of a spinal needle at the level of L3-4, L4-5 from a medial approach. A local anaesthetic is presented by hyperbaric 0.5% bupivacaine 0.8-1.2 ml. The patient is kept seating for 10 minutes.
EFFECT: method enables adequate anaesthesia with ensured maximum perineal myorelaxation combined with decreased drug-induced load on mother's and foetus's bodies.
SUBSTANCE: spray composition contains, wt/vol %: lidocaine hydrochloride 1.0-10.0; benzethonium chloride 5.0·10-4 - 5.0·10-3; sodium chloride 0.1-10.0; water for injections to 100 ml.
EFFECT: use of the declared composition is effective for treating damages by non-lethal irritants.
SUBSTANCE: invention refers to medicine, namely anaesthiology in ophthalmosurgery, and may be used in vitreoretinal surgeries, including those terminated by the stage of introducing silicone oil. For this purpose, 40-45 minutes before the operation, the retrobulbar introduction of a mixture of 2% lidocaine and 0.75% ropivacaine in proportions 1:1 in the amount of 4-5 ml is prescribed. It is followed by the intraoperative intravenous titration introduction of 0.01% nitroglycerine starting with 1 ml 1-2 minute before the introduction of silicone oil in response to a surgeon's signal. The nitroglycerine introduction is terminated when patient's systolic blood pressure becomes lower than the initial values by 10-20%.
EFFECT: method provides adequate anaesthesia combined with a reduced risk of developing complications due to blood pressure correction at the specific stage of surgery.
SUBSTANCE: method involves the intramuscular introduction of the preparations Galavite 200 mcg/mouse and Lidocaine 8 mcg/kg of body weight once a day for three days running every 24 hours to experimental animals CBA line mice suffering a burning injury with underlying mycotic and bacterial infections accompanied by anti-infectious protection suppression.
EFFECT: invention enables creating a model of hospital strain formation which is applicable for studying the variations of the properties of opportunistic microorganisms to increasing virulence and antibiotic resistance.
SUBSTANCE: invention refers to medicine, namely neurology, orthopaedics, reflexotherapy, physiotherapy exercises, recreation therapy and is applicable in integrated treatment of myofascial pain accompanying spine osteochondrosis. Pain management procedures are followed by a complex of exercises with using the HUBER apparatus consisting of seven staticodynamic exercises aimed at strengthening and activation of muscles of upper limb girdle, greater pectoral muscle, pelvic floor muscles and gluteal muscles. It is combined with loading and coordination improvement of left broadest muscle of back, left obliques, left lumbar quadrate muscle. Upper shoulder anchors, broadest muscle of back and rhomboid muscle are relaxed, and postural muscles are coordinated. Lumbar spine muscles are relaxed. Tone in upper extremity and back muscles is strengthened. It is followed by making exercises for activation of muscles of upper limb girdle, pectoral muscles, pelvic floor muscles, gluteal muscles. Then, the exercises for strengthening of lumbar muscles for the purpose of improving the body position coordination, relaxation of back ground of femoral and hip muscles, strengthening of abdominal wall muscles.
EFFECT: method improves support ability of feet, normalises position of the centre of gravity, forms an optimum motor conditions.
3 ex, 7 dwg
SUBSTANCE: invention relates to medicine, namely to anesthesiology and thoracic surgery, and can be used as anesthetic aids in surgery on lung resection. For this purpose carried out is general anesthesia with microrelaxants and artificial lung ventilation in combination with blockades. Before anesthesis induction subpleural blockade is performed. After intubation of patient vagosympathetic blockade is carried out. As local anesthetic, in carrying out said blockades 0.2% ropivacaine solution is used.
EFFECT: method makes it possible to ensure adequate blockade of pain impulse at stages of transduction and transmission in carrying out operation on patients with reduced reserve heart possibilities.
SUBSTANCE: new alicyclic derivatives are described from N,N'-substitute 3,7-diazabicyclo[3.3.1]nonanes of general formula 1
where E is carbonyl group; R1 is H, C1-C6 alkyl, C1-C10alkoxy; R2 is fragments of structural formulas (1.1a), (1.3a) or (1.4a), representing biheterocyclic relevant 5-member nuclei, containing N and/or S as heteroatoms, connected to each other by -CH2-(possibly substituted with alkyl), -C(=O)-, -NH-,-NH-CH2-(possibly substituted with alkyl); other R3 - R4 independently mean H, C1-C6 alkyl, C1-C10alkoxy.
EFFECT: compounds have pharmacological activity and may be used for treatment of Alzheimer's disease, Parkinson's disease and other neurodegenerative pathologies.
8 cl, 7 ex, 1 tbl
SUBSTANCE: invention relates to analogues of benzoquinone-containing ansamycins of formulae
in which radicals and symbols assume values given in the claim, and use thereof to treat and modulate proliferation-associated disorders such as cancer. The present invention describes a method of producing analogues of benzoquinone-containing ansamycins according to which benzoquinone is reduced to hydroquinone and bonded through reaction with a suitable acid.
EFFECT: high solubility and air stability of the obtained ammonium hydroquinone ansamycin analogue.
181 cl, 70 dwg, 38 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a composition of a rapamycin analogue for immunomodulation and antiproliferation that involves a crystalline form of the rapamycin analogue having at least one of the following structures: and a pharmaceutically acceptable carrier. What is also described a method for preparing the crystalline form of the rapamycin analogue.
EFFECT: what is described is a new form of rapamycin, which can be used in the therapeutic treatment.
38 cl, 30 ex, 11 tbl, 21 dwg