SU1114676A1 - 1,5-diphenyl-3-oxyl-4-methylsulfonyl-2,5-dihydropyrrol-2-one as intermediate product for synthesis of 1,5-diphenyl-3-hydroxyethylamino-4-methylsulfonyl-2,5-dihydropyrrol-2-one having antiaggregate effect against thrombocytes - Google Patents

1,5-diphenyl-3-oxyl-4-methylsulfonyl-2,5-dihydropyrrol-2-one as intermediate product for synthesis of 1,5-diphenyl-3-hydroxyethylamino-4-methylsulfonyl-2,5-dihydropyrrol-2-one having antiaggregate effect against thrombocytes Download PDF

Info

Publication number
SU1114676A1
SU1114676A1 SU833606631A SU3606631A SU1114676A1 SU 1114676 A1 SU1114676 A1 SU 1114676A1 SU 833606631 A SU833606631 A SU 833606631A SU 3606631 A SU3606631 A SU 3606631A SU 1114676 A1 SU1114676 A1 SU 1114676A1
Authority
SU
USSR - Soviet Union
Prior art keywords
diphenyl
dihydropyrrol
methylsulfonyl
hydroxyethylamino
synthesis
Prior art date
Application number
SU833606631A
Other languages
Russian (ru)
Inventor
Юрий Сергеевич Андрейчиков
Владимир Леонидович Гейн
Ирина Николаевна Аникина
Борис Яковлевич Сыропятов
Original Assignee
Пермский государственный фармацевтический институт
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Пермский государственный фармацевтический институт filed Critical Пермский государственный фармацевтический институт
Priority to SU833606631A priority Critical patent/SU1114676A1/en
Application granted granted Critical
Publication of SU1114676A1 publication Critical patent/SU1114676A1/en

Links

Landscapes

  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

1.5-Дифенил-3-окси-4-метштсульфонш1-2 ,5-дигидро1шррол-2-он формулы dHj Ogон СбН5-С о СбНу в качестве промежуточного продукта дл  синтеза 1,5-дифенил-З-оксиэтиламино-4-метилсульфоннл-2 ,5-дигидрошфрол 2-она , обладающего антиагре- . г гантной активгностью против тромбоцитов . (Л С1.5-Diphenyl-3-hydroxy-4-metstsulfonsh-1-2, 5-dihydro-1-shrol-2-one of the formula dHj Ogon SbH5-C o SbHu as an intermediate product for the synthesis of 1,5-diphenyl-3-hydroxyethylamino-4-methylsulfonnl-2 , 5-dihydroshfrol 2-she with antiaggre-. A gantny active against platelets. (Ls

Description

«"

9) «vj9) “vj

а I Изобретение относитс  к новому производному пирролона, конкретно к 1,5-дифенил-3-окси-4-метнпсульфонил-2 ,5-дигкдропиррол-2-ону формулы ЙН,02 у который может использоватьс  в качестве промежуточного продукта дл  синтеза 1,5-дифенил-З-оксиэтиламино .4-метилсульфонил-2,5-дигидропиррол-2-она , обладающего антиагрегантной активностью против тромбоцитов. Наиболее близким по структуре к соединению (Г)  вл етс  1.3-дифени -3-ацетокси-4-этилоксикарбонил-2,5-дигидропиррол-2-он ij формулы odoCHj с,н,осо Однако сведени  о его использовании в качестве промежуточного в;оединени  дл  вещества, обладающего антиагрегантной активностью против тромбоцитов, в литературе отсутствую Цель изобретени  - изыскание в р  ду производных пирролона соединени  которое может быть использовано в качестве промежуточного дл  синтеза вещества, обладающего антиагрегантно активностью против тромбоцитов. Указанна  цель достигаетс  П1 именением 1 ,5-дифенил-3-окси-4-метилсульфонил-2 ,5-дигидропиррол-2-она формулы (I) в качестве промежуточного продукта дл  синтеза 1,5-дифенил-З-оксиэтиламино-4-метилсульфонил-2 ,5-дигидропиррол-2-она, обладаю щего антиагрегантной активностью против тромбоцитов. Соединение формулы (1) получают конденсацией бензальдегида, анилина и этилового эфира метилсульфонилпиро виноградной кислоты при комнатной температуре с послед тощей обработкой полученного продукта 2 и. сол ной кислотой. Соединение (I) представл ет собой б1;сцнетное кристаллическое 76 вещество.растворимое в диоксане, диметилсульфоксиде. Пример 1. 1,5-Дифeнил-3-oкcи-4-мeтилcyльфoнил-2 ,5-дигидропиррол-2-он . К 3,88 г (0,02 моль) этилового эфира метилсульфонилпировиноградной кислоты в 18 мл диоксана добавл ют 2,12 г (0,02 моль) бензальдегида и 1,86 г (0,02 моль) анилина. Реакционную смесь вьщерживают при комнатной температуре в течение 48 ч, выпавщиё кристаллы отфильтровывают и обрабатывают 2 и. сол ной кислотой. Получают 6,1 (74,2%) целевого продукта , т.пл. 217-8с с разложением (из спирта). Найдено, %: С 62,12; Н 4,49, N 4,14; S 9,87. С Н, Вычислено, %: С 62,01J Н 4,55; N 4,25; S 9,73. В ИК-спектре соединени  (I) присутствуют полосы поглощени  сульфонильной группы при 1150 и 1315 см , полоса поглощени  при 1650 см обусловленна  наличием в цикле двойной св зи, поглощение лактонного карбонила при 1730, 1630 , полосы поглощени  при 3100 и 3335 счет.гидроксильной группы. В ПМР-спектре вещества, сн том в растворе дейтерированного диметилсульфоксида , кроме мультиплета ароматических протонов с центром при 7,28 М.Д., присутствует синглет метинового протона в положении 5 при 6,15, а также синглет метильной группы при 2,68 м.д. I Соединение(I) может использоватьс  в качестве промежуточного .дл  получени  1,5-дифенил-З-оксиэтиламино-4-метилсульфонил-2 ,5-дигидропиррол-2-она , про вл ющего антиагрегантную активность против тромбоцитов. 1,5-Дифенил-3-оксиэтиламино-4-метилсульфонил-2 ,5-дигидропиррол-2-он получают взаимодействием 1,5-дифенил-3-окси-4-метилсульфонил-2 ,5-дигидропиррол-2-она с этаноламином при комнатной температуре в диоксане. П р и м е р .2. 1,5-Дифeнил-3-oкcиэтилaминo-4-фeнилcyльфoнил-2 ,5-дигидpoпиppoл-2-oн . К 3,29 г (0,01 моль) 1,5-фенил-З-окси-4-метилсульфонил-2 ,5-дигидропиррол-2-она в 30 мл диоксана добавл ют 0,61 г (0,01 моль) этаноламина. а-11146 Реакционную смесь вьщерживают при комнатной температуре в течение 20 ч. Затем вьтавшие кристаллы отфильтровывают . Ползтают 3,3 г (89%) целевого продукта, Т.Ш1. 179-180°С с разло- j жением (из спирта). , Найдено, %: С 61,20; Н 5,79; N7,33; S 8,53. . CjgH , . Вычислецо, %: С 61,13i Н 5,62; ю N 7,50i S 8,58. 1,5-Дифенил-3-оксизтиламино-4-фенилсульфонил-2 ,5-дигищ опиррол-2-он про вл ет высокую антиагрегант76 4 ную активность против тромбоцитов, под его вли нием агрегаци  тромброцитов снижаетс  на 29,2%, а под вли нием известного препарата папаверина, обладающего вьюокЫ антиагрегантной активностью против тромбоцитов на 18,8%. При исследовании острой токсичиости установлено, что средн   токсическа  доза LD соединени  (I) равна 880 (792,8-976,8) мг/кг, а папаверина 27 ,(25,1-30,3), т.е. соадинекие (J) менее токсично, чем эталон сравнени  (в 32,6 раз).a I The invention relates to a new derivative of pyrrolone, specifically to 1,5-diphenyl-3-hydroxy-4-metnpsulfonyl-2, 5-digkdropyrrol-2-one of the formula YH 02, which can be used as an intermediate product for the synthesis of 1, 5-diphenyl-3-hydroxyethylamino .4-methylsulfonyl-2,5-dihydropyrrol-2-one, which has antiplatelet activity against platelets. The closest in structure to the compound (D) is the 1.3-dipheny-3-acetoxy-4-ethyloxycarbonyl-2,5-dihydropyrrol-2-one ij of the formula odoCHj s, n, oso However, information about its use as an intermediate in; Compounds for a substance with antiplatelet activity against platelets are absent in the literature. The purpose of the invention is to find a compound in a series of pyrrolone derivatives that can be used as an intermediate for the synthesis of a substance possessing antiplatelet activity against platelets. This goal is achieved by P1 by the name of 1, 5-diphenyl-3-hydroxy-4-methylsulfonyl-2, 5-dihydropyrrol-2-one of formula (I) as an intermediate product for the synthesis of 1,5-diphenyl-3-hydroxyethylamino-4- methylsulfonyl-2, 5-dihydropyrrol-2-one, which has antiplatelet activity against platelets. The compound of formula (1) is obtained by condensation of benzaldehyde, aniline, and methylsulfonylpyro grape acid ethyl ester at room temperature, followed by treatment of the resulting product 2 and. hydrochloric acid. Compound (I) is b1; 76% crystalline substance soluble in dioxane, dimethyl sulfoxide. Example 1. 1,5-Diphenyl-3-oxy-4-methylsulfonyl-2, 5-dihydropyrrol-2-one. To 2.88 g (0.02 mol) of methyl sulphonyl pyruvic acid ethyl ester in 18 ml of dioxane were added 2.12 g (0.02 mol) of benzaldehyde and 1.86 g (0.02 mol) of aniline. The reaction mixture is held at room temperature for 48 hours, the precipitated crystals are filtered and treated with 2 and. hydrochloric acid. Get 6,1 (74,2%) of the desired product, so pl. 217-8c with decomposition (from alcohol). Found,%: C 62,12; H 4.49, N 4.14; S 9.87. C H, Calculated,%: C 62.01J, H 4.55; N 4.25; S 9.73. The absorption spectrum of the sulfonyl group at 1150 and 1315 cm, the absorption band at 1650 cm due to the presence of a double bond in the cycle, the absorption of lactone carbonyl at 1730, 1630, the absorption band at 3100 and 3335 counts of the hydroxyl group are present in the IR spectrum of compound (I) . In the PMR spectrum of a substance, removed in a solution of deuterated dimethyl sulfoxide, in addition to the multiplet of aromatic protons centered at 7.28 MD, the singlet of the methine proton is present at position 5 at 6.15, and the singlet of the methyl group at 2.68 m .d I Compound (I) can be used as an intermediate to obtain 1,5-diphenyl-3-hydroxyethylamino-4-methylsulfonyl-2, 5-dihydropyrrol-2-one, which exhibits antiplatelet activity against platelets. 1,5-Diphenyl-3-hydroxyethylamino-4-methylsulfonyl-2, 5-dihydropyrrol-2-one is obtained by reacting 1,5-diphenyl-3-hydroxy-4-methylsulfonyl-2, 5-dihydropyrrol-2-one with ethanolamine at room temperature in dioxane. PRI me R. 2. 1,5-Diphenyl-3-oxyethylamino-4-phenylsulfonyl-2, 5-dihydropopyrol-2-one. To 3.29 g (0.01 mol) of 1,5-phenyl-3-hydroxy-4-methylsulfonyl-2, 5-dihydropyrrol-2-one in 30 ml of dioxane was added 0.61 g (0.01 mol) ethanolamine. a-11146 The reaction mixture is held at room temperature for 20 hours. Then, the crystals which have entered are filtered off. Crawl 3.3 g (89%) of the desired product, T.Sh1. 179-180 ° C with decomposition (from alcohol). Found:% C 61.20; H 5.79; N7.33; S 8.53. . CjgH,. Calcd.,%: C, 61.13; H, 5.62; No 7,50i S 8,58. 1,5-Diphenyl-3-oxystilamino-4-phenylsulfonyl-2, 5-digyshirprol-2-one exhibits a high antiaggregant76 4th activity against platelets, under its influence, the aggregation of thrombrocytes decreases by 29.2%, and under by the influence of the well-known drug papaverine, which possesses antiplatelet activity against platelets by 18.8%. In the study of acute toxicity, it was found that the average toxic dose of LD of compound (I) is 880 (792.8-976.8) mg / kg, and papaverine 27, (25.1-30.3), i.e. soadine (J) is less toxic than the reference standard (32.6 times).

Claims (1)

1.5-Дифенил-3-окси-4-метилсульфонил-2,5-дигидропиррол-2-он формулы1.5-Diphenyl-3-hydroxy-4-methylsulfonyl-2,5-dihydropyrrol-2-one of the formula Mi-Ljf J= 0 с6н5 в качестве промежуточного продукта для синтеза 1,5-дифенил-З-оксиэтиламино-4-метилсульфонил-2,5-дигидропиррол-2-она, обладающего антиагре- , гантной активностью против тромбоцитов .Mi-Ljf J = 0 with 6 n 5 as an intermediate for the synthesis of 1,5-diphenyl-3-hydroxyethylamino-4-methylsulfonyl-2,5-dihydropyrrol-2-one, which has antiaggregant activity against platelets.
SU833606631A 1983-03-31 1983-03-31 1,5-diphenyl-3-oxyl-4-methylsulfonyl-2,5-dihydropyrrol-2-one as intermediate product for synthesis of 1,5-diphenyl-3-hydroxyethylamino-4-methylsulfonyl-2,5-dihydropyrrol-2-one having antiaggregate effect against thrombocytes SU1114676A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
SU833606631A SU1114676A1 (en) 1983-03-31 1983-03-31 1,5-diphenyl-3-oxyl-4-methylsulfonyl-2,5-dihydropyrrol-2-one as intermediate product for synthesis of 1,5-diphenyl-3-hydroxyethylamino-4-methylsulfonyl-2,5-dihydropyrrol-2-one having antiaggregate effect against thrombocytes

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
SU833606631A SU1114676A1 (en) 1983-03-31 1983-03-31 1,5-diphenyl-3-oxyl-4-methylsulfonyl-2,5-dihydropyrrol-2-one as intermediate product for synthesis of 1,5-diphenyl-3-hydroxyethylamino-4-methylsulfonyl-2,5-dihydropyrrol-2-one having antiaggregate effect against thrombocytes

Publications (1)

Publication Number Publication Date
SU1114676A1 true SU1114676A1 (en) 1984-09-23

Family

ID=21068899

Family Applications (1)

Application Number Title Priority Date Filing Date
SU833606631A SU1114676A1 (en) 1983-03-31 1983-03-31 1,5-diphenyl-3-oxyl-4-methylsulfonyl-2,5-dihydropyrrol-2-one as intermediate product for synthesis of 1,5-diphenyl-3-hydroxyethylamino-4-methylsulfonyl-2,5-dihydropyrrol-2-one having antiaggregate effect against thrombocytes

Country Status (1)

Country Link
SU (1) SU1114676A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5098927A (en) * 1989-05-15 1992-03-24 Fujisawa Pharmaceutical Co., Ltd. Antiretroviral agent, method of use thereas, and method of preparation
RU2195449C2 (en) * 1995-06-28 2002-12-27 Байер Акциенгезельшафт 2,4,5-trisubstituted phenylketoenoles, intermediate compounds for their synthesis, method and agent for control of insects and spiders based on thereof
WO2003030897A1 (en) * 2001-10-03 2003-04-17 Ucb, S.A. Pyrrolidinone derivatives

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
1. Joannic М., Humbert D., Peason М. Acids diaryl-.1,5-oxo-2-pyrrolidyl-4-carboxyligues. G.r.Acad. sci., 1972, p. 275, 1, 45-48. *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5098927A (en) * 1989-05-15 1992-03-24 Fujisawa Pharmaceutical Co., Ltd. Antiretroviral agent, method of use thereas, and method of preparation
RU2195449C2 (en) * 1995-06-28 2002-12-27 Байер Акциенгезельшафт 2,4,5-trisubstituted phenylketoenoles, intermediate compounds for their synthesis, method and agent for control of insects and spiders based on thereof
WO2003030897A1 (en) * 2001-10-03 2003-04-17 Ucb, S.A. Pyrrolidinone derivatives

Similar Documents

Publication Publication Date Title
US4251520A (en) Glucofuranose derivatives
US2936308A (en) Novel reductones and methods of making them
CS224629B2 (en) Method for producing new derivates of benzoyl-a alfa-hydroxybenzylphenylglykoside
RU1796625C (en) 3-amino-7-nitro-4-(2,3,4-trimethoxyphenyl)-2-phenyl-1(2h) isoquinolone having analeptic effect
SU1114676A1 (en) 1,5-diphenyl-3-oxyl-4-methylsulfonyl-2,5-dihydropyrrol-2-one as intermediate product for synthesis of 1,5-diphenyl-3-hydroxyethylamino-4-methylsulfonyl-2,5-dihydropyrrol-2-one having antiaggregate effect against thrombocytes
GB1581443A (en) Aminosalicylic acid esters
IE40052B1 (en) Indole derivatives
US3755605A (en) Diphenylamine derivatives
Rondestvedt Jr et al. Arylation of unsaturated systems by free radicals. VII. The Meerwein reaction. V. 1 Further arylations of maleimides. Ultraviolet spectra of arylmaleimides, arylmaleic anhydrides and arylmaleo-and fumaronitriles
US4378359A (en) Theophyllinylmethyldioxolane derivatives, methods for their preparation and pharmaceutical compositions containing them
US3772319A (en) 5-amino-4-carboxamido-2-arylimidazoles
US4372976A (en) Novel aryl-aliphatic ketone and its use as an antiviral agent
US4293700A (en) 2,6-Dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid esters and method for preparing same
Wolfrom et al. l-Mannoheptulose (l-Manno-l-tagato-heptose)
Hatchard The Synthesis of Isothiazoles. II. 3, 5-Dimercapto-4-isothiazolecarbonitrile and Its Derivatives
US2409001A (en) Esters of dimethylaminoethanol useful as local anesthetics
Gagnon et al. Syntheses and absorption spectra of 2-substituted-3-hydroxy-5-pyrazolones: 4-n-hexyl-5-pyrazolones-4-C14
Kelly et al. 2-Cyanomethyl-1, 1, 3, 3-tetracyanopropene, a Self-Condensation Product of Malononitrile
Elslager et al. Synthetic Schistosomicides. VI. 4-Substituted 1-(Dialkylaminoalkylamino) naphthalenes1
CH628622A5 (en) METHOD FOR PRODUCING NEW 3-SULFAMOYLBENZOESAIDS SUBSTITUTED IN 4-POSITION.
Thurston et al. Asymmetric syntheses. IV. The action of optically active nitrates on 2-bromo-fluorene
SU677301A1 (en) N-(2-methyl-4-substituted benzenesulfonyl)-n'-butylurea (thiourea) possessing mutagenic activity
Noyce et al. Studies of Configuration. V. The Preparation and Configuration of cis-3-Methoxycyclopentanecarboxylic Acid
US3549657A (en) N-aryl-4,6-dibromo-3-hydroxyphthalimide derivatives
SU1726478A1 (en) 2-hexamethyleneimino-5-(4-bromophenyl)-6h-1, 3, 4-thiadiazine hydroiodide, showing contraceptive activity