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WO2000034259A1 - Derives de 2-r-5-amino-1,3,4-thiadiazole bioactifs - Google Patents

Derives de 2-r-5-amino-1,3,4-thiadiazole bioactifs Download PDF

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Publication number
WO2000034259A1
WO2000034259A1 PCT/RU1998/000406 RU9800406W WO0034259A1 WO 2000034259 A1 WO2000034259 A1 WO 2000034259A1 RU 9800406 W RU9800406 W RU 9800406W WO 0034259 A1 WO0034259 A1 WO 0034259A1
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different
substances
acyl
things
items
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PCT/RU1998/000406
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English (en)
Russian (ru)
Inventor
Rimma Iliinichna Ashkinazi
Viktor Iosifovich Krutikov
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Priority to PCT/RU1998/000406 priority Critical patent/WO2000034259A1/fr
Priority to AU36320/99A priority patent/AU3632099A/en
Publication of WO2000034259A1 publication Critical patent/WO2000034259A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C07D285/135—Nitrogen atoms

Definitions

  • the substances are mainly intended for use in medical practice, for the treatment of viral diseases caused by chlamydia, as well as diseases that are related to malignant
  • Chas ⁇ zab ⁇ levaniya vi ⁇ usn ⁇ y and ba ⁇ e ⁇ ialn ⁇ y ⁇ i ⁇ dy ⁇ e ⁇ ayu ⁇ on ⁇ ne reduce a ⁇ ivn ⁇ s ⁇ i immunn ⁇ y sis ⁇ emy ⁇ ganizma, ⁇ e ⁇ mu ⁇ blema s ⁇ zdaniya e ⁇ e ⁇ ivny ⁇ ⁇ e ⁇ a ⁇ a ⁇ v to treat immun ⁇ de ⁇ itsi ⁇ ny ⁇ s ⁇ s ⁇ yany ⁇ azlichn ⁇ g ⁇ ⁇ is ⁇ zhdeniya ⁇ a ⁇ zhe yavlyae ⁇ sya ⁇ dn ⁇ y of a ⁇ ualneyshi ⁇ .
  • Etazol - 2- (4-Mineral-8-benzene sulfamide) -5-ethyl-1,3,4-thiadiazole It has antibacterial activity in relation to illnesses, pneumonia, meningitis, atherosclerosis, and atherosclerosis. Described, for example, diacarb - acetylamine-1,3,4-thiadiazole-5-sulfamide. It is used in the form of a medicinal product, and also for the treatment of glaucoma. It is written, in particular, in operation [1].
  • Butazolamide - 2-Butyrilamine-1,3,4-thiadiazole-5-sulfamide has the following structural formula
  • Butazolamide is a very good antibiotic, but, unfortunately, it is not very active in the treatment of viruses, chlamydia, and it does not always affect the body.
  • the task of the invention is reduced to the chemical synthesis of biologically active substances. Possessing beneficial, immunocompromising, immunostimulating, antiaggregati ⁇
  • the present invention is a.
  • Experiment 1 determination of the action on the virus of the group (with Table 3); Experiment 2 - determination of the activity-inducing activity (with Table 4);
  • Experiment 3 division of the action on S.Gasnoglag-5 (with Tables 5 and 6); EXPERIMENT 4 - Determination of anti-aggregation activity (with Table 7); EXPERIMENT 5 —Definition of psychoactive activity (with Table 8); EXPERIMENT b - Determination of the analgesic activity (With Table 9).
  • Experiment 7 determination of the division of toxicity (With Table 10);
  • the method of synthesis is based on the interaction of the corresponding nitrile, sodium hydroxide, and thermosemic acid base at a temperature of 70 ° C.
  • the range of the reaction is 3-5 hours.
  • the target products are separated from the reactive mass by neutralizing its by-product from industrial waste by-products of 9-10, by-product from the by-product If compounds with a substituted amine group are synthesized, then the substances obtained by the process indicated above are handled by the following method. Suspension of amine and hydrochloride hydrochloric acid in a dry tank is heated by heating the battery for 3 hours, and it is free of charge. The waste is processed by ethanol, the resulting sediment after filtering is installed.
  • P ⁇ i sin ⁇ eze gid ⁇ azida amin ⁇ -2-1,3,4- ⁇ iadiaz ⁇ l-2-yl-u ⁇ susn ⁇ y ⁇ isl ⁇ y XIII is ⁇ lz ⁇ van e ⁇ il ⁇ vy e ⁇ i ⁇ e ⁇ y ⁇ isl ⁇ y, ⁇ y ⁇ as ⁇ v ⁇ yali in e ⁇ il ⁇ v ⁇ m s ⁇ i ⁇ e in ⁇ ea ⁇ tsi ⁇ nnuyu weight d ⁇ bavlyali 5 ⁇ i ⁇ a ⁇ ny izby ⁇ gid ⁇ azingid ⁇ a ⁇ a, za ⁇ em mixture nag ⁇ evali ⁇ i 80 ° C within 1 h. The resulting products were washed, washed and dried.
  • Example 1 Synthesis II III, IV, V, VI, XI and XII.
  • Substance VI A flask equipped with a mechanical stirrer and a thermocouple accommodates 67.3 g (0.55 mol) of cyanogenic acid and 200 g of sulfuric acid. The mixture is heated to 70 ° C and, while stirring, the mixture add 59 g (0.65 mol) of tisemisicobaside. The treated mass is heated for 3 hours in a boiling water bath, poured into 300 g of ice and neutralized with a 25% ammonia solution before 9-10. The resulting solution is left for 2 hours at 0 ° C.
  • a single flask contains 1 89 g of hydride of 2-amine-1,3,4-thiadiazol-2-yl-acetic acid, 1 5 g of solution and 50 ml of acid within 3 h.
  • the mixture is cooled, filtered, washed with ethanol, removed from the mixture and ethanol-dimethylamide
  • cherries were cultivated on a re-cultivated cultivar of the cell, obtained from the bank of the cell culture Institute of Cytology ⁇
  • EXCEPTION 2 The separation of the interactivity of the detected substances The induction of the synthesis of the claimed preparations was carried out on the basis of the treatment of the patients. (the nameplate data in the human body are the main producers of the internet). To receive the culture of lymphomas, they used a fresh (12 hours after the fence) health unit (not the second group). In order to isolate the lymph nodes, the patient’s acquired area, received from a healthy patient, was subjected to the center of the patient’s cardiac indefensibility. The indicated fraction was removed and diluted with healthy ⁇ -1640, which contains 5% of the fetal serum content, 0.3 mg / ml, 50 mg / ml, 50 ml / ml.
  • the concentration of the limbs was taken into account after scraping with methyl blue and the number of cells in the camera Goryaeva.
  • the inventories of the claimed substances diluted the healthy medium ⁇ -1640, so that the final concentrations of the substances amounted to 100 mg / l, 10 mg / l, 1 mg / l.
  • the final concentration of lymphocytes in the industrial mixture was 3x10 cells / ml.
  • the following components were delivered: 1) the control panel of the integrated products of the Internet (IF) lymphomas; 2) the outlet of the industrial process and the impact of the standard industry of ⁇ -methyl- ⁇ - (a,,-glucose-amyl-amide) -methyl-amide
  • the method used a solid immunodeficiency method with the use of the conversion of oxidase in the form of an indicator of the disease.
  • the efficiency of the bound transoxidase was measured using an automatic device for microplates with a microprocessor at a wavelength of 450 nm.
  • the activity of the physical components of the physical components of the physical equipment, which contain the known quantity of the components, was shared.
  • a calibrated, free-wheeling device is used (using the automatic process data)
  • the results of the analysis are expressed in ⁇ activity of ⁇ per ml in the given industrial system, containing 3x106 lymphocytes / ml. Each experimental and contact point was studied in 4 parallel parameters. Interaction with an immune reaction.
  • the cells were introduced into the environment at an end concentration of 1x10 c / ml. After the arrival of the minority in the Republic, they introduced standard infectious doses of chlamydia, which are stored in a frozen state at -70 ° ⁇ . For instant cells, the test compound in the end concentration of 100 mg / l was added. The process was centered at 2400 ⁇ for 60 minutes at a room temperature and incubated at 37 ° C for 2 hours. After this, the food was changed to a new one, containing 5% of fetal calf serum and cycloheximide (2 mcg / ml) with the addition of the claimed compounds to the same.
  • the group of human subjects was studied in a fortified plasma of healthy donations of 50 ⁇ 3 years with the unit ⁇ -1.
  • the studied substance was added to samples of plasma plasma (100 ⁇ g / ml) by inducing aggregation with an adenosine powder (2.5 ⁇ mol / L).
  • the maximum irreversible aggregation of drugs in the market (consumer) was taken as 100%, and in the case of calculating it was taken into account. Aggregation inhibition was more than 50% higher and the given concentration was rated as significant.
  • aspirates were used and aspirin (9 ⁇ g / ml), which inhibited the aggregation of alcohol and this concentration by 100%.
  • the first available material randomly selected from 42 of the claimed ones, was an indication of the presence of activity, which is more likely to be injurious
  • the first available material randomly selected from 42 of the claimed ones, was an indication of the presence of activity, which is more likely to be harmful
  • the first conditional matter that was randomly selected from the 42 claimed is the presence of activity, which is likely to be greater than the previous one. that others are available and more effective. ⁇ 00/3 9 ⁇ / ⁇ 8 / 00406

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention se rapporte au domaine de la médecine, plus précisément à celui de la pharmacologie, et concerne des diazoles synthétiques et bioactifs consistant en des dérivés de 2-R-5-amino-1,3,4-thiadiazole. Ces substances sont notamment destinées à la pratique médicale, et permettent de traiter des maladies virales déclenchées par des chlamydiae ainsi que des maladies s'accompagnant d'un déficit immunitaire, notamment des tumeurs malignes. Cette invention a pour but de créer de nouveaux composés chimiques qui possèdent une activité antivirale importante ainsi qu'une activité antimicrobienne (anti-chlamydia), qui stimulent la production d'interférons endogènes dans l'organisme et qui possèdent également des actions antiagrégantes, analgésiques et psycho-dépressives. Cette invention consiste à synthétiser un nouveau groupe de substances consistant en des dérivés de 2-R-5-amino-1,3,4-thiadiazole qui correspondent à la formule générale (1) où R1 est choisi dans le groupe comprenant alkyle, aryle et -CH2-CH2C(0)NH-N=CH-Z, étant entendu que Z représente aryle ou pipéronyle, tandis que R2 est choisi dans le groupe comprenant H et (a), étant entendu que Y représente aryle ou hétéroaryle. Cette invention concerne également des procédés généraux de production de ces substances, 4 exemples de synthèse de ces substances, les résultats d'identification de chacune des 42 substances synthétisées, ainsi que des données sur la vérification expérimentale de l'activité biologique de ces substances par rapport aux préparations connues et utilisées aux mêmes fins.
PCT/RU1998/000406 1998-12-04 1998-12-04 Derives de 2-r-5-amino-1,3,4-thiadiazole bioactifs Ceased WO2000034259A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/RU1998/000406 WO2000034259A1 (fr) 1998-12-04 1998-12-04 Derives de 2-r-5-amino-1,3,4-thiadiazole bioactifs
AU36320/99A AU3632099A (en) 1998-12-04 1998-12-04 Biologically active 2-r-5-amino-1,3,4-thiadiazole derivatives

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/RU1998/000406 WO2000034259A1 (fr) 1998-12-04 1998-12-04 Derives de 2-r-5-amino-1,3,4-thiadiazole bioactifs

Publications (1)

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WO2000034259A1 true WO2000034259A1 (fr) 2000-06-15

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AU (1) AU3632099A (fr)
WO (1) WO2000034259A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102276555A (zh) * 2011-08-09 2011-12-14 陕西科技大学 噻二唑类Mannich碱及其制备方法和用途

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1430386A (en) * 1972-06-08 1976-03-31 Ici Ltd Anti-bacterial process
US3992396A (en) * 1974-07-05 1976-11-16 Sandoz, Inc. 2-Amino-5-(substituted or unsubstituted phenylalkyl)-thiadiazoles
GB1482691A (en) * 1973-09-21 1977-08-10 Lilly Co Eli Preparation of 2-amino-5-alkyl-1,3,4-thiadiazoles
SU845783A3 (ru) * 1977-08-15 1981-07-07 Эли Лилли Энд Компани (Фирма) Способ получени тиадиазолилбензамидов

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1430386A (en) * 1972-06-08 1976-03-31 Ici Ltd Anti-bacterial process
GB1482691A (en) * 1973-09-21 1977-08-10 Lilly Co Eli Preparation of 2-amino-5-alkyl-1,3,4-thiadiazoles
US3992396A (en) * 1974-07-05 1976-11-16 Sandoz, Inc. 2-Amino-5-(substituted or unsubstituted phenylalkyl)-thiadiazoles
SU845783A3 (ru) * 1977-08-15 1981-07-07 Эли Лилли Энд Компани (Фирма) Способ получени тиадиазолилбензамидов

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 47, Columbus, Ohio, US; abstract no. 3856C, "alzats <<i>>" column 9323; *
CHEMICAL ABSTRACTS, vol. 48, Columbus, Ohio, US; abstract no. 3551F, "alzats f" column 4540; *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102276555A (zh) * 2011-08-09 2011-12-14 陕西科技大学 噻二唑类Mannich碱及其制备方法和用途

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