RU2067584C1 - 20(54)20(29)-lupen-[(2,3:3,4)-5,5-dimethylhexene-2-one]-28-oic acid showing coagulating activity - Google Patents
20(54)20(29)-lupen-[(2,3:3,4)-5,5-dimethylhexene-2-one]-28-oic acid showing coagulating activity Download PDFInfo
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- RU2067584C1 RU2067584C1 RU94001704A RU94001704A RU2067584C1 RU 2067584 C1 RU2067584 C1 RU 2067584C1 RU 94001704 A RU94001704 A RU 94001704A RU 94001704 A RU94001704 A RU 94001704A RU 2067584 C1 RU2067584 C1 RU 2067584C1
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- Prior art keywords
- lupen
- dimethylhexene
- oic acid
- coagulating activity
- acid showing
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- 239000002253 acid Substances 0.000 title claims abstract description 5
- 230000001112 coagulating effect Effects 0.000 title abstract 2
- 230000000694 effects Effects 0.000 claims abstract description 7
- 230000015271 coagulation Effects 0.000 claims description 4
- 238000005345 coagulation Methods 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 239000000126 substance Substances 0.000 abstract description 5
- SLJTWDNVZKIDAU-SVAFSPIFSA-N Betulonic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C SLJTWDNVZKIDAU-SVAFSPIFSA-N 0.000 abstract description 4
- SLJTWDNVZKIDAU-CKURCAGRSA-N Betulonic acid Natural products CC(=C)[C@@H]1CC[C@@]2(CC[C@]3(C)[C@@H](CC[C@@H]4[C@@]5(C)CCC(=O)C(C)(C)[C@@H]5CC[C@@]34C)[C@@H]12)C(=O)O SLJTWDNVZKIDAU-CKURCAGRSA-N 0.000 abstract description 4
- OZXIZRZFGJZWBF-UHFFFAOYSA-N 1,3,5-trimethyl-2-(2,4,6-trimethylphenoxy)benzene Chemical compound CC1=CC(C)=CC(C)=C1OC1=C(C)C=C(C)C=C1C OZXIZRZFGJZWBF-UHFFFAOYSA-N 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- SHOJXDKTYKFBRD-UHFFFAOYSA-N mesityl oxide Natural products CC(C)=CC(C)=O SHOJXDKTYKFBRD-UHFFFAOYSA-N 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 2
- 238000007363 ring formation reaction Methods 0.000 abstract description 2
- 231100000053 low toxicity Toxicity 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- XDPFHGWVCTXHDX-UHFFFAOYSA-M menadione sodium sulfonate Chemical compound [Na+].C1=CC=C2C(=O)C(C)(S([O-])(=O)=O)CC(=O)C2=C1 XDPFHGWVCTXHDX-UHFFFAOYSA-M 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
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Abstract
Description
Изобретение относится к химико-фармацевтической промышленности, а именно к новым биологически активным веществам, на основе которых могут быть созданы препараты, обладающие коагуляционной активностью. The invention relates to the pharmaceutical industry, in particular to new biologically active substances, on the basis of which preparations with coagulation activity can be created.
Заявляемые соединения относятся к новым производным лупена, а именно к 20(29)-лупен(2,3:3,4)-5,5-диметилгексен-2-он)-28-овым кислотам формулы:
Приводимое в заявке производные лупена, его свойства и биологическая активность в литературе не описаны.The inventive compounds belong to new derivatives of lupene, namely to 20 (29) -lupene (2,3: 3,4) -5,5-dimethylhexen-2-one) -28-ovoy acids of the formula:
Derived in the application derivatives of lupene, its properties and biological activity are not described in the literature.
Ближайшим аналогом по структуре является бетулоновая кислота, не обладающая биологической активностью /5/:
Аналогом по действию к заявляемому соединению является викасол /1/.The closest analogue in structure is betulonic acid, which does not have biological activity / 5 /:
An analogue in action to the claimed compound is vicasol / 1 /.
Целью изобретения является получение нового производного лупена, обладающего более выраженной коагуляционной активностью.
The aim of the invention is to obtain a new derivative of lupene with more pronounced coagulation activity.
Поставленная цель достигнута синтезом соединения формулы
которое получают реакцией циклизации по Робинсону из бетулоновой кислоты и окиси мезитила.The goal is achieved by the synthesis of compounds of the formula
which is obtained by the Robinson cyclization reaction from betulonic acid and mesityl oxide.
Пример. 20(29)-лупен-(2,3:3,4)-5,5-диметилгексен-2-он-28-овая кислота: к 0,5 М бетулоновой кислоты растворенной в 250 мл этанола, содержащего 0,25 г едкого кали, на холоду прибавляют по каплям 0,75 М свежеперегнанной окиси мезитила и кипятят 3 ч, выделенный обычным способом продукт присоединения по Михаэлю без очистки растворяют в минимальном количестве бензола и после добавления 0,5 мл пиперидина кипятят 1 ч. Растворитель отгоняют, остаток кристаллизуют из бутанола. Example. 20 (29) -lupene- (2,3: 3,4) -5,5-dimethylhexen-2-one-28-oic acid: to 0.5 M betulonic acid dissolved in 250 ml of ethanol containing 0.25 g potassium hydroxide, in the cold 0.75 M of freshly distilled mesityl oxide is added dropwise and boiled for 3 hours, the Michael addition product isolated in the usual way is dissolved in a minimal amount of benzene without purification and after adding 0.5 ml of piperidine, it is boiled for 1 hour. The solvent is distilled off, the residue crystallize from butanol.
Тпл. более 300o C
Вычислено, С 80,90 Н 8,99
Найдено, С 8,67 Н 9,151 ИК-спектр, вазелиновое масло: 3460, 1720, 1680, 1100, 870 (с -1)
Исследования биологической активности проводились в лаборатории фармакологического скрининга при кафедре органической химии ПФИ. Влияние соединения на свертывание крови проводилось на бодрствующих белых крысах-самцах весом 200 230 г. Кровь для исследования брали из вены языка и записывали коагулограмму с помощью стандартного коагулографа Н 338 1. По записям на бумажной ленте рассчитывали время свертывания крови. Одновременно проводились серии опытов (в каждой серии по 6 животных) с введением внутрибрюшинной 1 мл физиологического раствора (контроль) и этанола викасола в дозе 10 мг/кг.Mp more than 300 o C
Calculated, C 80.90 N 8.99
Found, C, 8.67; H, 9.151; IR spectrum, liquid paraffin: 3460, 1720, 1680, 1100, 870 (s -1)
Studies of biological activity were carried out in the laboratory of pharmacological screening at the Department of Organic Chemistry, PFI. The effect of the compound on blood coagulation was carried out on awake white male rats weighing 200,230 g. Blood for examination was taken from the vein of the tongue and a coagulogram was recorded using a standard coagulograph H 338 1. The time of blood coagulation was calculated on paper tape. At the same time, a series of experiments (in each series of 6 animals) was carried out with the introduction of intraperitoneal 1 ml of physiological saline (control) and Vikasol ethanol at a dose of 10 mg / kg.
Новое соединение в дозе 10 мг/кг, а также физраствор и эталон вводили в два приема за 24 и за 1 ч до начала опыта. Эталонный препарат предложен /2/ как препарат сравнения при исследовании коагуляционной активности. The new compound at a dose of 10 mg / kg, as well as saline and standard was administered in two doses for 24 and 1 hour before the start of the experiment. A reference preparation is proposed / 2 / as a comparison preparation in the study of coagulation activity.
Результаты опытов статистически обработаны /4/ и приведены в таблице. The results of the experiments are statistically processed / 4 / and are shown in the table.
2. Определение острой токсичности и расчеты осуществляли по методу Кербера /3/. Белым мышам массой 18 20 г внутрибрюшинно вводили по 0,5 мл суспензии исследуемого вещества, приготовленной с добавлением 1 2 капель твина-80. На каждую дозу в опыте брали по 6 мышей, установлено, что исследуемого вещества составляет более 870 мг/кг, следовательно данное вещество относится к классу практически нетоксичных веществ. 2. The determination of acute toxicity and the calculations were carried out according to the method of Kerber / 3 /. White mice weighing 18 to 20 g were intraperitoneally injected with 0.5 ml of a suspension of the test substance prepared with the addition of 1 2 drops of Tween-80. For each dose in the experiment, 6 mice were taken, it was found that the test substance was more than 870 mg / kg, therefore this substance belongs to the class of practically non-toxic substances.
3. Результаты проведенных исследований показывают, что заявляемое соединение обладает выраженным гемостатическим действием, превышающим активность лекарственного препарата викасол, являясь при этом практически нетоксичным. 3. The results of the studies show that the claimed compound has a pronounced hemostatic effect that exceeds the activity of the drug Vikasol, while being practically non-toxic.
Это свидетельствует о целесообразности дальнейших исследований данного вещества с целью создания эффективного лекарственного препарата. This indicates the feasibility of further studies of this substance in order to create an effective drug.
Claims (1)
обладающая коагуляционной активностью.20 (29) -Lupen - [(2,3: 3,4) -5,5-dimethylhexen-2-one] -28-oic acid of the formula
possessing coagulation activity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU94001704A RU2067584C1 (en) | 1994-01-18 | 1994-01-18 | 20(54)20(29)-lupen-[(2,3:3,4)-5,5-dimethylhexene-2-one]-28-oic acid showing coagulating activity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU94001704A RU2067584C1 (en) | 1994-01-18 | 1994-01-18 | 20(54)20(29)-lupen-[(2,3:3,4)-5,5-dimethylhexene-2-one]-28-oic acid showing coagulating activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU94001704A RU94001704A (en) | 1995-12-27 |
| RU2067584C1 true RU2067584C1 (en) | 1996-10-10 |
Family
ID=20151603
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU94001704A RU2067584C1 (en) | 1994-01-18 | 1994-01-18 | 20(54)20(29)-lupen-[(2,3:3,4)-5,5-dimethylhexene-2-one]-28-oic acid showing coagulating activity |
Country Status (1)
| Country | Link |
|---|---|
| RU (1) | RU2067584C1 (en) |
-
1994
- 1994-01-18 RU RU94001704A patent/RU2067584C1/en active
Non-Patent Citations (1)
| Title |
|---|
| Машковский М.Д. Лекарственные средства. М.: 1985, Т.1, с.512. Очерин А.А. Методические рекомендации по составлению заявки на изобретение - биологически активные соединения. Пермь, 1980. Першин Г.Н. Методы экспериментальной химиотерапии М., 1971, с. 526-531. Урбах В.Ю. Математическая статистика для биологов и медиков, М., 1963. * |
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