CN103788004A - Benzoxazole hydrochloride - Google Patents
Benzoxazole hydrochloride Download PDFInfo
- Publication number
- CN103788004A CN103788004A CN201210432254.1A CN201210432254A CN103788004A CN 103788004 A CN103788004 A CN 103788004A CN 201210432254 A CN201210432254 A CN 201210432254A CN 103788004 A CN103788004 A CN 103788004A
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- CN
- China
- Prior art keywords
- compound
- benzoxazole
- hydrochloride
- present
- amino
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention discloses a benzoxazole hydrochloride and a preparation method thereof. The compound prepared by the method has activity for inhibiting cyclooxygenase function and lipoxygenase function. The activity is shown in a cell cultivation experiment, wherein a mouse peritoneal cavity cell capable of detecting the effect of the compound on arachidonic acid metabolism is adopted.
Description
Technical field
The present invention relates to a kind of medicine material, be specifically related to a kind of benzoxazole hydrochloride.
Background technology
Heterogeneous ring compound is the organic compound that contains heterocycle structure in molecule.Form the atom of ring except carbon atom, also at least contain a heteroatoms.Heteroatoms comprises oxygen, sulphur, nitrogen etc.Theoretically, heterogeneous ring compound can be regarded as to the derivative of benzene, one or several CH in phenyl ring is replaced by heteroatoms and the compound that generates.Heterogeneous ring compound can and be unified into fused ring heterocycle compound with phenyl ring.
Heterogeneous ring compound has an alkylamino side chain that is linked to phenyl ring, this alkylamino can a saturating step replaces by aromatic base or with the aromatic base of the heterocycle of group, these new compounds are cyclooxygenase and lipoxidase inhibitor, and can be used for the treatment of or alleviate transformation reactions or inflammatory symptom that the Mammals including the mankind occurs.
Known arachidonic acid is the precursor of a few class endogenous metabolism things, and these metabolites are prostaglandin(PG), thromboxane and the leukotriene including prostacyclin.The first step of arachidonic acid metabolism is by Phospholipid hydrolase effect, discharges esterified arachidonic acid and relevant unsaturated lipid acid from membrane phospholipid.Free fatty acids then or by cyclooxygenase metabolism, produces prostaglandin(PG) and thromboxane, or produces hydrogen peroxide fat by lipoxygenase. and acid, such lipid acid can further be transformed into leukotriene.According to the difference of structure, prostaglandin(PG) shows various physiological effects.For example, FGE and PGA suppress gastric secretion and reduce arteriotony.Thromboxane, particularly thromboxane A a are strong vasoconstrictor and platelet aggregation things.Leukotriene is the biological origin of long response time allergin, and this material is a kind of chemical mediator that causes allergy bronchial asthma.
CN 1583752A discloses a kind of synthetic method of benzoxazole, and it includes the synthesis technique of organic compounds, p-penylene-2, and 2 '-bis-(amino benzoxazoles of 5-) are preparations like this: a. is by phosphoric acid and P
2o
5be made into poly phosphoric acid solution; B. in solution, add 2,4-diaminophenol hydrochloride and terephthalic acid; C. add again SnCl
2reductive agent; D. after being dried, neutralization, suction filtration obtain head product; E. head product extracted, be dried, finally obtain glassy yellow powder.2,6-bis-(p-amino-benzene) benzo [1,2-d; 5,4-d '] bis-oxazole is preparation like this; A. by phosphoric acid and P
2o
5be made into poly phosphoric acid solution; B. in solution, add 4,6-diaminoresorcinol hydrochloride and para-amino benzoic acid; C. add SnCl
2reductive agent; D. product is dried to obtain head product through neutralization, suction filtration; E. carry out recrystallization, dry, obtain yellow powder.
Summary of the invention
The object of the present invention is to provide a kind of benzoxazole hydrochloride and preparation method thereof.
One of object of the present invention is to provide a kind of benzoxazole hydrochloride, and described benzoxazole hydrochloride is 6-(N-methyl-N '-3-phenyl propyl amino)-2-benzoxazole keto hydrochloride.
One of object of the present invention is also to provide a kind of preparation method of benzoxazole hydrochloride, and described method comprises the steps:
3-phenylpropionaldehyde is added in the suspension of dry benzene of 6-amino-2-benzoxazolone and 4A type molecular sieve, then at room temperature stir the mixture and within 1-4 hour, add methyl alcohol, at room temperature add sodium borohydride in batches, filtering mixt, concentrated filtrate also adds sodium hydrogen carbonate solution, use dichloromethane extraction organic phase, isolate methylene dichloride phase, with nearly saturated brine washing, dry, decompression is lower obtains thick product except desolventizing, and then from hot ethanol, crystallization obtains 6-(3-phenyl propyl) amino-2-benzoxazole ketone compound;
At-20 ℃～-15 ℃ by sodium borohydride, and the hanging drop of 6-(3-phenyl propyl) amino-2-benzoxazolone is added in the mixing solutions of 3M sulfuric acid and 40% formalin, after interpolation, add methylene dichloride, and add sodium hydrogen carbonate solution to make water alkalization, separate organic layer also with nearly saturated brine washing, the solution that vapourisation under reduced pressure is dry, the residue obtaining is dissolved in ethanol, add the ethereal solution that hydrogen chloride gas is saturated, methylene dichloride-diethyl ether solution recrystallization for throw out of gained, obtain 6-(N-methyl-N '-3-phenyl propyl amino)-2-benzoxazole keto hydrochloride.
The compound that the present invention prepares has the activity that suppresses cyclooxygenase effect and lipoxygenase effect.This activity has been that a kind of cell culture test is shown, uses rat peritoneum chamber inner cell, and this cell can be measured the effect of above-claimed cpd to arachidonic acid metabolism.
The compound that the present invention prepares makes them can be used for controlling the symptom being induced by endogenous metabolism thing to suppressing the ability of two kinds of enzymes, the arachidonic acid that these endogenous metabolism things result from mammalian body.Therefore, compound is valuable preventing and treating in these diseases, the accumulation of above-mentioned arachidonic acid metabolite is the factor that causes these illnesss, as diseases such as allergy bronchial asthma tetter, rheumatic arthritis, osteoarthritis and thrombosis.Like this, in treatment with alleviate aspect the transformation reactions and inflammatory condition of human body, these compounds will have special purposes.
When acceptable salt on compound that the present invention prepares or its pharmacology is during as anti-allergic medicament or antiphlogistic medicament, can use separately this compound to people's prescription, or best and pharmaceutically acceptable carrier or thinner are combined with, according to the pharmacy procedure of standard, make pharmaceutical preparation.A kind of compound can use with multiple conventional route of administration, comprise oral, injection and sucking.In the time of oral administration, every per daily dose of this compound is from about 0.1 to 20 mg/kg of body weight, preferably approximately 0.1 to 1.0 mgs/kg of every days, once takes or part vic.If wish it is drug administration by injection, effective dose will be 0.1 to 1.0 mg/kg of body weight every day.In some cases, it may be necessary that the dosage of use exceeds these scopes, because power is according to each patient's age, body weight with to the different and severity of symptom of medicine reaction, and the drug effect of compound used therefor, dosage will be done necessary change.
Embodiment
For ease of understanding the present invention, it is as follows that the present invention enumerates embodiment.Those skilled in the art should understand, described embodiment only, for helping to understand the present invention, should not be considered as concrete restriction of the present invention.
Embodiment 1
3-phenylpropionaldehyde 10ml is added in the suspension of dry benzene 200ml of 6-amino-2-benzoxazolone 11.5g and 4A type molecular sieve 18g, then at room temperature stir the mixture and within 1 hour, add methyl alcohol 200ml, at room temperature add sodium borohydride 2.5g in batches, filtering mixt, concentrated filtrate also adds 5% sodium bicarbonate, organic with dichloromethane extraction, isolate methylene dichloride phase, with nearly saturated brine washing, dry, decompression is lower to desolventizing, obtain thick product, then from hot ethanol, crystallization obtains 6-(3-phenyl propyl) amino-2-benzoxazole ketone compound of 14g,
Described 6-(3-phenyl propyl) amino-2-benzoxazolone melting point compound is 129-130 ℃.
At-17 ℃, by sodium borohydride 272mg, and the hanging drop of 6-(3-phenyl propyl) amino-2-benzoxazolone 536mg is added in the mixing solutions of 3M sulfuric acid (0.81ml) and 40% formalin (0.46 milliliter).After interpolation, add methylene dichloride (30ml), and add 5% sodium hydrogen carbonate solution to make water alkalization, separate organic layer also with nearly saturated brine washing, the solution that vapourisation under reduced pressure is dry, the residue 479mg obtaining is dissolved in 10ml ethanol, adds 30 milliliters of the ethereal solutions that hydrogen chloride gas is saturated, methylene dichloride-diethyl ether solution recrystallization for throw out of gained, obtains 6-(N-methyl-N '-3-phenyl propyl amino)-2-benzoxazole keto hydrochloride of 337mg.
Applicant's statement, the present invention illustrates detailed process composition and engineering flow process of the present invention by above-described embodiment, but the present invention is not limited to above-mentioned detailed process composition and engineering flow process, do not mean that the present invention must rely on above-mentioned detailed process composition and engineering flow process and could implement.Person of ordinary skill in the field should understand, any improvement in the present invention, and the selections of the equivalence replacement to the each raw material of product of the present invention and the interpolation of ancillary component, concrete mode etc., within all dropping on protection scope of the present invention and open scope.
Claims (1)
1. a benzoxazole hydrochloride, is characterized in that, described benzoxazole hydrochloride chemical formula is 6-(N-methyl-N '-3-phenyl propyl amino)-2-benzoxazole keto hydrochloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210432254.1A CN103788004A (en) | 2012-11-02 | 2012-11-02 | Benzoxazole hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210432254.1A CN103788004A (en) | 2012-11-02 | 2012-11-02 | Benzoxazole hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103788004A true CN103788004A (en) | 2014-05-14 |
Family
ID=50664112
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210432254.1A Pending CN103788004A (en) | 2012-11-02 | 2012-11-02 | Benzoxazole hydrochloride |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103788004A (en) |
-
2012
- 2012-11-02 CN CN201210432254.1A patent/CN103788004A/en active Pending
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20140514 |