CN1106790A - Acetylsalicylate deriv. - Google Patents
Acetylsalicylate deriv. Download PDFInfo
- Publication number
- CN1106790A CN1106790A CN 94111849 CN94111849A CN1106790A CN 1106790 A CN1106790 A CN 1106790A CN 94111849 CN94111849 CN 94111849 CN 94111849 A CN94111849 A CN 94111849A CN 1106790 A CN1106790 A CN 1106790A
- Authority
- CN
- China
- Prior art keywords
- ester
- acetyloxy
- phenyl
- chemical name
- acetylsalicylic acid
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
Abstract
This invention discloses new derivatives of acetyl salicylate. They respectively are: acetyl salicylic paeonol ester (chemical name: 2- acetyl-5-methoxy phenyl 2-(acetyloxy)benzoate), acetylsalicylic 7-hydroxy isoflavone ester (chemical name: 7- 2-(acetyloxy) benzoyloxy]-3-phenyl-4H-1-benzopyran-4-one), acetylsalicylic 4-methylol phenyl ester (chemical name: 4-methylol phenyl 2-(acetyloxy) benzoate), and acetylsalicylic vanilin ester (chemical name: 4-methanoyl-2-methoxy phenyl 2-(acetyloxy) benzoate). These four new compounds have similar pharmacological action as acetyl salicylates medicine, but have stronger antithrombotic action.
Description
The present invention is new acetylsalicylic acid ester derivative, is that a class has antipyretic-antalgic, the new acetylsalicylate class medicine of anti-thrombosis function.
In the prior art, acetylsalicylic acid (acetoxy-benzoic acid) ester compound mainly contains following document and patent report at present:
1.a: Xu Mingxia etc.: several catalyzer are to the comparison of synthetic vinegar willow ester yield
West China Journal of Pharmaceutical Sciences 1986 1(3) 188
B: Sun Changan etc.: synthetic " Chinese Journal of Pharmaceuticals " of guacetisal
1990 21（8） 387
C: Chen Jiangang etc.: 147-8 synthetic " Lanzhou medical college journal " 1991 17(3 of guacetisal)
2. intercalation bright pair etc.: 36-40 synthetic " Chinese pharmaceutical chemistry magazine " 1994 4(1 of 7-acetyl bigcatkin willow acyloxy flavone derivative)
3. the high synthesizing technology of " Puyantong " CN of Tang Wei 1067881A 911072306
Structural formula of compound in the above-mentioned document is respectively:
New compound of the present invention and above-mentioned three kinds of compounds promptly all belong to the acetylsalicylic acid ester derivative in that partly similarity is arranged aspect basic chemical structure and the pharmacological action.Compound of the prior art (I) (III) has the antipyretic-antalgic anti-inflammatory action, and the pharmacological action of compound (II) is still among research.And new compound of the present invention has notable difference with prior art (I) (II) (III) on chemical structure, though all have the basic chemical structure of acetylsalicylate
But because the substituent R difference, and generated new acetylsalicylic acid ester derivative.
The objective of the invention is to seek that to have a pharmacologically active strong, toxic side effect is little, can supply the clinical new acetylsalicylate class medicine of selecting for use.The new compound name is called:
(1) ASPA (chemical name: 2-(Acetyloxy) benzoic acid 2-acetyl-5-methoxy phenyl ester, 2-(acetoxyl group) phenylformic acid-2-ethanoyl-5-methoxyl group phenyl ester); (2) acetylsalicylic acid-7-hydroxyisoflavone ester (chemical name: 7-[2-(Acetyloxy) benzoxy]-3-phenyl-4H-1-benzopyrane-4-one, the 7-[2-(acetoxyl group) benzoyloxy]-3-phenyl-4H-1-chromene-4-ketone); (3) acetylsalicylic acid-4-methylol phenyl ester (chemical name: 2-(Acetyloxy) benzoic acid 4-hydroxy methyl phenyl ester, 2-(acetoxyl group) phenylformic acid-4-methylol phenyl ester); (4) acetylsalicylic acid vanilla aldehydo-ester (chemical name: 2-(Acetyloxy) benzoic acid 4-formyl-2-methoxy phenyl ester, 2-(acetoxyl group) phenylformic acid 4-formyl radical-2-methoxyl group phenyl ester).
Such compound chemical structure formula is as follows:
The present invention is a raw material with acetylsalicylic acid, Paeonol, 7-hydroxyisoflavone, 4-methylolphenol, Vanillin etc., adopts following route synthetic:
Synthesizing of I, ASPA (1)
Synthesizing of II, acetylsalicylic acid-7-hydroxyisoflavone ester (2)
Synthesizing of III, acetylsalicylic acid-4-methylol phenyl ester (3)
Synthesizing of IV, acetylsalicylic acid vanilla aldehydo-ester
More than four kinds of acetylsalicylic acid ester derivatives and synthetic method thereof, have not yet to see reported in literature.
The simple synthetic method of four kinds of new compounds of the present invention, raw material is easy to get, cost is lower, and yield is higher.Pharmacological evaluation shows that four kinds of new acetylsalicylic acid ester derivatives are except that effects such as the antipyretic-antalgic with acetylsalicylic acid class medicine, anti-inflammatory, anticoagulant, also have vasodilation or improve effects such as blood circulation, especially anti-thrombosis function is stronger, be applicable to control cardiovascular and cerebrovascular embolism class diseases, as coronary heart disease, cerebral thrombosis.Because new compound has pharmacologically active after the hydrolysis in vivo, so oral administration is little to gastrointestinal irritation than acetylsalicylic acid class medicine, patient is easy to accept.
The preparation of embodiment 1 ASPA (1)
Get acetylsalicylic acid 4.5g, 2 of dimethyl formamides (DMF), sulfur oxychloride 2.2ml removes the excess chlorination sulfoxide and gets acyl chlorides in about 2 hours of 65-70 ℃ of reaction, adds small amount of acetone.Other gets sodium hydroxide 1.48g, and Paeonol 3.53g adds water-toluene and a small amount of bromogeramine, adds acyl chlorides liquid, reaction below 20 ℃.The separation of methylbenzene layer, boil off toluene after, the precipitation use ethyl alcohol recrystallization, yield 60.2%, mp91-92 ℃, IR(cm
-1): 3016,3110(V
-C=CH), 1770(V
CH3COO-), 1750(V
Ar-COO-), 1690(V
-COCH3).NMR（ppm）：2.29（S，3H，-OCOCH
3）。2.49（S，3H，-COCH
3），3.89（S，3H，-OCH
3）。Ultimate analysis: calculated value C 65.83%, H 4.91%, measured value C 65.64%, H 4.51%.
The preparation of embodiment 2 acetylsalicylic acid-7-hydroxyisoflavone ester (2)
Get acetylsalicylic acid 4.54g, sulfur oxychloride 2.07ml, DMF2 drips, 65-70 ° react acyl chlorides.Other gets sodium hydroxide 1.34g, and 7-hydroxyisoflavone 5.71g adds water-toluene, and bromogeramine and acyl chlorides get white precipitate by embodiment 1 method, use acetone recrystallization, yield 72.7%, mp170-172 ℃, IR:1770(V
CH3COO-) 1750(V
ArCOO-), 1640,1580(V
CCOC).NMR:2.29(S, 3H ,-OCOCH
3), 6.48(S, H
3 ') 8.40(S, H
2 '), 7.15-8.37(m, 11H, phenyl ring hydrogen).Ultimate analysis: calculated value C 71.98%; H 4.03%, measured value C 71.68%, and H 4.33%.
The preparation of embodiment 3 acetylsalicylic acid-4-methylol phenyl ester (3)
Get acetylsalicylic acid 7.21g, sulfur oxychloride 5.81ml, DMF3 drips, 65-70 ° react acyl chlorides.Other gets sodium hydroxide 2.56g, to methylolphenol 1.4g, adds water-methylene dichloride, and a small amount of bromogeramine and acyl chlorides must precipitate with reference to embodiment 1 method, use acetone recrystallization, yield 62.8%, mp107-108 ℃.IR：3400（V
OH），1770（V
CH3COO-），1755（V
Ar-COO-）。NMR：2.30（S，3H，-OCOCH
3），4.71（S 2H，-CH
2O-），7.72（q，H
4），8.24（q，H
6）。Ultimate analysis: calculated value C 67.12%, H 4.93%, measured value C 67.35% H 4.62%.
The preparation of embodiment 4 acetylsalicylic acid vanilla aldehydo-esters (4)
Get acetylsalicylic acid 4.32g, sulfur oxychloride 3.2ml, DMF2 drips, 65-70 ℃ react acyl chlorides.Other gets sodium hydroxide 2.4g, and Vanillin 3.12g adds water, and methylene dichloride and a small amount of bromogeramine must precipitate with reference to embodiment 1 method, use acetone recrystallization, yield 73.85%, mp.118-120 ℃.IR：1770（V
CH3COO-），1750（V
ArCOO-），1670（V
-CHO）。NMR：2.29（S，3H，OCOCH
3），3.89（S，3H，-OCH
3），9.96（S，1H，-CHO）。Ultimate analysis: calculated value: C 64.96%, H 4.49%, measured value: C 64.65%, and H 4.28%.
Claims (1)
1, the medicinal new acetylsalicylic acid of a class (acetoxy-benzoic acid) ester derivative, chemical structural formula is as follows:
These four kinds new acetylsalicylic acid ester derivatives are respectively:
(1) ASPA (chemical name: 2-(Acetyloxy) benzoic acid2-acetyl-5-methoxy phenyl ester, 2-(acetoxyl group) phenylformic acid-2-ethanoyl-5-methoxyl group phenyl ester); (2) acetylsalicylic acid-7-hydroxyisoflavone ester (chemical name: 7-[2-(Acetyloxy) benzoxy]-3-phenyl-4H-1-benzopyrane-4-one, 7-[2-(acetoxyl group) benzoyloxy]-3-phenyl-4H-1-chromene-4-ketone); (3) acetylsalicylic acid-4-methylol phenyl ester (chemical name: 2-(Acetyloxy) benzoic acid4-hyroxymethyl phenyl ester, 2-(acetoxyl group) phenylformic acid-4-methylol phenyl ester); (4) acetylsalicylic acid vanilla aldehydo-ester (chemical name: 2-(Acetyloxy) benzoic acid-4-formyl-2-methoxy phenyl ester, 2-(acetoxyl group) phenylformic acid 4-formyl radical-2-methoxyl group phenyl ester).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN94111849A CN1054119C (en) | 1994-07-25 | 1994-07-25 | Acetylsalicylate deriv. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN94111849A CN1054119C (en) | 1994-07-25 | 1994-07-25 | Acetylsalicylate deriv. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1106790A true CN1106790A (en) | 1995-08-16 |
| CN1054119C CN1054119C (en) | 2000-07-05 |
Family
ID=5035678
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN94111849A Expired - Fee Related CN1054119C (en) | 1994-07-25 | 1994-07-25 | Acetylsalicylate deriv. |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1054119C (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101768147B (en) * | 2009-08-21 | 2012-02-29 | 南京大学中国医药城研发中心 | Chrysin and substituted salicylate composites, manufacturing method thereof and use thereof |
| CN102381979A (en) * | 2011-09-06 | 2012-03-21 | 南通惠康国际企业有限公司 | Method for preparing salicylic acid p-octyl phenyl ester as light stabilizer |
| US8158810B2 (en) * | 2006-07-27 | 2012-04-17 | Gilead Sciences, Inc. | ALDH-2 inhibitors in the treatment of addiction |
| CN101585770B (en) * | 2009-07-09 | 2012-07-18 | 南京中医药大学 | Caffeic acid diester compounds and preparation method thereof, and application thereof in preparing medicine for curing thrombus |
| CN103450087A (en) * | 2013-09-13 | 2013-12-18 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Preparation method of paeonol and ozagrel conjugate |
| CN103467383A (en) * | 2013-09-13 | 2013-12-25 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Conjugate of paeonol and ozagrel, pharmaceutical composition and medical application of conjugate |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1039535C (en) * | 1991-06-17 | 1998-08-19 | 华西医科大学药学院 | Synthesizing technology of " Puyantong" |
-
1994
- 1994-07-25 CN CN94111849A patent/CN1054119C/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8158810B2 (en) * | 2006-07-27 | 2012-04-17 | Gilead Sciences, Inc. | ALDH-2 inhibitors in the treatment of addiction |
| CN101585770B (en) * | 2009-07-09 | 2012-07-18 | 南京中医药大学 | Caffeic acid diester compounds and preparation method thereof, and application thereof in preparing medicine for curing thrombus |
| CN101768147B (en) * | 2009-08-21 | 2012-02-29 | 南京大学中国医药城研发中心 | Chrysin and substituted salicylate composites, manufacturing method thereof and use thereof |
| CN102381979A (en) * | 2011-09-06 | 2012-03-21 | 南通惠康国际企业有限公司 | Method for preparing salicylic acid p-octyl phenyl ester as light stabilizer |
| CN103450087A (en) * | 2013-09-13 | 2013-12-18 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Preparation method of paeonol and ozagrel conjugate |
| CN103467383A (en) * | 2013-09-13 | 2013-12-25 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Conjugate of paeonol and ozagrel, pharmaceutical composition and medical application of conjugate |
| CN103450087B (en) * | 2013-09-13 | 2015-07-01 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Preparation method of paeonol and ozagrel conjugate |
| CN103467383B (en) * | 2013-09-13 | 2015-07-15 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Conjugate of paeonol and ozagrel, pharmaceutical composition and medical application of conjugate |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1054119C (en) | 2000-07-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP3174327B2 (en) | 7-Chromanyl esters of phenol and benzoic acid having retinoid-like activity | |
| CA1334424C (en) | Thiochroman esters of phenols and terephthallates having retinoid-like activity | |
| JPH04139178A (en) | Chroman ester with retinoide-like activity | |
| NL8002370A (en) | ESTERS OF ACYL CARNITINES, METHODS FOR PREPARING THE SAME AND PHARMACEUTICAL PREPARATIONS CONTAINING SUCH ESTERS. | |
| CN1054119C (en) | Acetylsalicylate deriv. | |
| NO173938C (en) | Analogous Procedures for the Preparation of Therapeutically Active Pyrido-Pyridazinone Acetic Acids | |
| AU693599B2 (en) | New diosmetin compounds, a process for their preparation and pharmaceutical compositions containing them | |
| JP4144917B2 (en) | Novel diosmethic acid, its ester, and pharmaceutical composition containing them | |
| EP0335164A2 (en) | Ester derivatives of neopentanol, process for their preparation and their use as medicines | |
| US4539326A (en) | 5-Oxo-5H-(1)benzopyrano(2,3-b)pyridine derivatives, their production and use as anti-inflammatory agents | |
| EP0232089B1 (en) | Quinone amides, their production and use | |
| HU208421B (en) | Process for producing starting materials for producing 3-acyl-2-oxindol-carboxamides ofantiphlogistic activity | |
| US3865842A (en) | Beta-{8 benzo(b) thienyl-3{9 -alpha-allyl-propionic acid esters | |
| US4797498A (en) | Flavonoxypropanolamines and esters of flavonoxypropanolamines as antiarrhythmic agents | |
| JPS60104084A (en) | 4h-benzo(4,5)cyclohepta(1,2-b)thiophene derivative | |
| JPS6345678B2 (en) | ||
| EP0180416A2 (en) | Benzoic acid analogues and their production | |
| JP3198395B2 (en) | Amino coumaran derivative | |
| US5292751A (en) | 5,7-dihydroxy-2-methyl-8-(4-(3-hydroxy-1-(1-propyl))piperidinyl)-4H-1-benzopyran-4-one, its preparation and its use | |
| US4820837A (en) | 1-hydroxy-oxo-5H-pyrido(3,2-a)phenoxazine-3-carboxylic acid esters | |
| JPS63216867A (en) | Sugar lactam derivative and anti-inflammatory agent containing same | |
| CH659058A5 (en) | 2- (4-BIPHENYLYL) -4'-HALOGEN) -4-WITCH ACID, SUCH CONTAINING MEDICINES AND USE OF 2- (4-BIPHENYLYL) -4-WITCH ACID DERIVATIVES IN THE PRODUCTION OF MEDICINAL PRODUCTS. | |
| US3849572A (en) | Biphenyleneacetic acid anti-inflammatory agents | |
| KR810001974B1 (en) | Process for preparing esters of 1,4-ethano-10-hydroxy-5-oxo-5h-(1)-benzopyrano(3,4-b)pyridines | |
| JP3094474B2 (en) | Isoquinolinone derivative and method for producing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C53 | Correction of patent for invention or patent application | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: PATENTEE; FROM: PHARMACEUTICAL COLLEGE, HUAXI MEDICAL UNIV. TO: SHANGHAI CHE-HUNG FOR INVESTMENT DEVELOPMENT CO., LTD. |
|
| CP03 | Change of name, title or address |
Address after: 201103 Shanghai City No. 38 Zhang Yang road Huadu building 26 floor Patentee after: Shanghai Hongyi Investment Development Co., Ltd. Address before: No. three, No. 17 South Renmin Road, Chengdu Patentee before: Medicine College, Huaxi Medical Univ. |
|
| ASS | Succession or assignment of patent right |
Owner name: HUNAN YADA PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: SHANGHAI CHE-HUNG FOR INVESTMENT DEVELOPMENT CO., LTD. Effective date: 20030425 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20030425 Address after: 410126 Hunan, Changsha, Asia Road (Zhang Gongling) Patentee after: Hunan Yada Pharmaceutical Co., Ltd. Address before: 201103 Shanghai City No. 838 Zhang Yang road Huadu building 26 floor Patentee before: Shanghai Hongyi Investment Development Co., Ltd. |
|
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Jia Xiuqi Document name: Notice of conformity |
|
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |