CN109180600A - A kind of thymol analog and its application - Google Patents
A kind of thymol analog and its application Download PDFInfo
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- CN109180600A CN109180600A CN201811108568.XA CN201811108568A CN109180600A CN 109180600 A CN109180600 A CN 109180600A CN 201811108568 A CN201811108568 A CN 201811108568A CN 109180600 A CN109180600 A CN 109180600A
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- thymol
- analog
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- present
- inflammatory
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- 125000003639 thymyl group Chemical class C1(=CC(C)=CC=C1C(C)C)* 0.000 title claims abstract description 22
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- 239000003814 drug Substances 0.000 claims description 3
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 abstract description 22
- 239000005844 Thymol Substances 0.000 abstract description 11
- 229960000790 thymol Drugs 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 4
- 229940124599 anti-inflammatory drug Drugs 0.000 abstract description 3
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 abstract 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 abstract 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 abstract 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 abstract 1
- 229960002739 oxaprozin Drugs 0.000 abstract 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- QGVLYPPODPLXMB-UBTYZVCOSA-N (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5H-cyclopropa[3,4]benzo[1,2-e]azulen-5-one Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 description 4
- -1 1- ethyl-(3- dimethylaminopropyl) Chemical group 0.000 description 3
- DXRFZHILMCWCNG-UHFFFAOYSA-N N,N-dimethyl-1,8-naphthyridin-2-amine Chemical compound C1=CC=NC2=NC(N(C)C)=CC=C21 DXRFZHILMCWCNG-UHFFFAOYSA-N 0.000 description 2
- 206010034464 Periarthritis Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000001741 anti-phlogistic effect Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- UILPJVPSNHJFIK-UHFFFAOYSA-N Paeonol Chemical class COC1=CC=C(C(C)=O)C(O)=C1 UILPJVPSNHJFIK-UHFFFAOYSA-N 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 206010044302 Tracheitis Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000005977 kidney dysfunction Effects 0.000 description 1
- 206010024378 leukocytosis Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 206010044008 tonsillitis Diseases 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种麝香草酚类似物及其应用，所述麝香草酚类似物结构如式(Ⅰ)所示：本发明所述麝香草酚类似物由奥沙普秦和麝香草酚在1‑乙基‑(3‑二甲基氨基丙基)碳酰二亚胺盐酸盐和二甲氨基吡啶作用下缩合而成，制备方法简单、高效。本发明的麝香草酚类似物可用于制备抗炎药物，具有抗炎效果好，毒副作用小的优点。The invention discloses a thymol analog and an application thereof. The structure of the thymol analog is shown in formula (I): The thymol analog of the present invention is condensed by oxaprozin and thymol under the action of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and dimethylaminopyridine The preparation method is simple and efficient. The thymol analog of the invention can be used for preparing anti-inflammatory drugs, and has the advantages of good anti-inflammatory effect and small toxic and side effects.
Description
Technical field
The present invention relates to field of medicaments, and in particular to a kind of thymol analog and its application.
Technical background
Inflammation is a clinical common pathologic process, can be born in the tissue and each organ at each position of body, such as hair
Capsulitis, tonsillitis, pneumonia, hepatitis, ephritis etc..Usually there is acute inflammation red, swollen, hot, pain, function the variation such as to hide, together
It is often accompanied by the general reactions such as fever, leukocytosis at any time.Clinically, the treatment of inflammation is with oral non-steroidal anti-inflammatory drugs
It is main.Olsapozine is one of clinically used non-steroidal anti-inflammatory drugs, to rheumatic arthritis, rheumatoid arthritis, Bones and joints
Inflammation, ankylosing spondylitis, neck shoulder wrist syndrome, scapulohumeral periarthritis, gout and wound and postoperative anti-inflammatory analgesic etc. have preferable effect
Fruit.But research is it has also been found that take for a long time, the adverse reactions such as patient Yi Fasheng digestive tract ulcer, serious liver and kidney dysfunction.Therefore,
Its structure is transformed, reducing or avoid its toxic side effect is the hot spot currently paid close attention to.
Thymol is also referred to as thymol, Thymol etc., can promote tra cheo-oesophageal voice, be conducive to tracheal mucus
Secretion, easily play phlegm-dispelling functions, then added with bactericidal effect, therefore can be used for treating tracheitis, pertussis etc..There is biology by two
Active group is effectively stitched together, and is the current important method for finding new medicine.Therefore, we are for the first time by olsapozine
Organically combine with thymol, to have the function that reduce toxic side effect, enhance its antiphlogistic effects.
Summary of the invention
The purpose of the present invention is to provide a kind of thymol analog and its applications in preparing anti-inflammatory drugs.
The structural formula of the thymol analog is as follows:
To achieve the goals above, The technical solution adopted by the invention is as follows:
The preparation of thymol analog provided by the invention: by 2.0mmol thymol, 2.0mmol under nitrogen protection
Olsapozine and 2.4mmol 1- ethyl-(3- dimethylaminopropyl) phosphinylidyne diimmonium salt hydrochlorate are added in 5mL methylene chloride
Dissolution, addition 0.2mmol dimethylamino naphthyridine are catalyst, react at room temperature 4h, with silica gel column purification up to the present invention after concentration
The thymol analog.
Pellet thymol analog application in preparing anti-inflammatory drugs.
The antiphlogistic effects of the thymol analog are 54.6%.
Specific embodiment
Purposes, technical schemes and advantages in order to better illustrate the present invention, below in conjunction with specific embodiment to this hair
It is bright to be illustrated.
Embodiment 1
The preparation of thymol analog of the present invention: under nitrogen protection that 2.0mmol thymol, 2.0mmol is difficult to understand
Sha Puqin and 2.4mmol 1- ethyl-(3- dimethylaminopropyl) phosphinylidyne diimmonium salt hydrochlorate is added molten in 5mL methylene chloride
Solution, addition 0.2mmol dimethylamino naphthyridine are catalyst, react at room temperature 4h, with silica gel column purification up to institute of the present invention after concentration
State thymol analog.
Embodiment 2
The present embodiment studies the anti-inflammatory effect of thymol analog by the mice auricle swelling model that phorbol exters induce.
Phorbol exters, olsapozine, thymol, the dissolution of thymol analog are stand-by in acetone.The female of 6 week old
ICR mouse 20 is only randomly divided into 5 groups, every group 4.Mouse right ear uses acetone, olsapozine, thymol and thymol respectively
Class Local treatment is stimulated with phorbol exters after 30min, and the mouse of unused phorbol exters stimulation is as blank control.To all after 6 hours
Mouse implements euthanasia, takes the auricle of mouse right ear 9mm diameter and weighing.And calculate inhibiting effect=[(only TPA)-(compound
+ TPA)]/[(only TPA)-(only acetone)] × 100%.
As the result is shown: inflammation, inhibiting rate 54.6%, hence it is evident that higher than olsapozine can be effectively suppressed in paeonol derivative
30.4% and thymol 10.8%.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811108568.XA CN109180600A (en) | 2018-09-21 | 2018-09-21 | A kind of thymol analog and its application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811108568.XA CN109180600A (en) | 2018-09-21 | 2018-09-21 | A kind of thymol analog and its application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109180600A true CN109180600A (en) | 2019-01-11 |
Family
ID=64909519
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811108568.XA Pending CN109180600A (en) | 2018-09-21 | 2018-09-21 | A kind of thymol analog and its application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109180600A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2179032C1 (en) * | 2000-12-25 | 2002-02-10 | Закрытое акционерное общество "ИНТЕЛФАРМ" | Agent for chronic prostatitis healing |
| CN1352551A (en) * | 1999-05-27 | 2002-06-05 | 尤罗塞尔蒂克股份有限公司 | Preparations for the application of anti-inflammatory agents |
| CN102731301A (en) * | 2012-07-02 | 2012-10-17 | 栗进才 | Thymol ester derivatives, its preparation method and application thereof |
| US20170056347A1 (en) * | 2015-09-01 | 2017-03-02 | First Wave Biopharma | Methods and compositions for treating conditions associated with an abnormal inflammatory responses |
-
2018
- 2018-09-21 CN CN201811108568.XA patent/CN109180600A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1352551A (en) * | 1999-05-27 | 2002-06-05 | 尤罗塞尔蒂克股份有限公司 | Preparations for the application of anti-inflammatory agents |
| RU2179032C1 (en) * | 2000-12-25 | 2002-02-10 | Закрытое акционерное общество "ИНТЕЛФАРМ" | Agent for chronic prostatitis healing |
| CN102731301A (en) * | 2012-07-02 | 2012-10-17 | 栗进才 | Thymol ester derivatives, its preparation method and application thereof |
| US20170056347A1 (en) * | 2015-09-01 | 2017-03-02 | First Wave Biopharma | Methods and compositions for treating conditions associated with an abnormal inflammatory responses |
Non-Patent Citations (1)
| Title |
|---|
| 项光亚等: ""奥丙嗪衍生物的合成及其生物活性研究"", 《中国药物化学杂志》 * |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190111 |