CN1709891A - Medicinal compound, its composition and use in pharmaceutical process - Google Patents
Medicinal compound, its composition and use in pharmaceutical process Download PDFInfo
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- CN1709891A CN1709891A CN 200510021090 CN200510021090A CN1709891A CN 1709891 A CN1709891 A CN 1709891A CN 200510021090 CN200510021090 CN 200510021090 CN 200510021090 A CN200510021090 A CN 200510021090A CN 1709891 A CN1709891 A CN 1709891A
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- cyclopentyl
- phenyl
- quinuclidine
- ethyl
- oxethyl
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Abstract
This invention has disclosed a manufacturing method to bromine-1-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxy-ethoxy)-quinuclidine compounds and its application. This invention has selectivity broken M1 and M3 acceptor, but almost has no breaking effect to M2 acceptor, and this compound does not cumulate in brain, has treated and offered the most basic condition to COPD using long-term and part medicines.
Description
Technical field
The present invention relates to a kind of quaternary amines medical compounds and composition thereof, especially relate to bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine medical compounds and composition thereof.The invention still further relates to simultaneously this medical compounds and composition thereof preparation treatment chronic obstructive pulmonary disease and bronchitis and with chronic obstructive pulmonary disease and bronchitis diseases associated medicine in application.
Background technology
Chronic obstructive pulmonary disease and bronchitis are a kind of common diseases, along with the progress of disease will have a strong impact on patient's work and life, even death take place, thereby are subject to the people's attention day by day.Be listed as the 6th because of this disease causes dead number in the world at present, and had influence on the 4%-6% of population more than 45 years old.The chronic obstructive pulmonary disease of the U.S. in 1985 and bronochitic estimate to reach 5,400,000 people, wherein, and in the patient of over-65s, because of chronic obstructive pulmonary disease and bronchitis cause that dead number increases sharply.China is investigated in the recent period, and chronic obstructive pulmonary disease and bronchitis account for about 3% of population more than 15 years old, and the elderly's incidence is higher.
Anticholinergic agent is one of the most effective medicine of treatment COPD patient.The vagal tone that its blocking-up exists in all air flues makes the air flue of constriction obtain expansion, and makes mucus produce minimizing.
In parasympathetic ganglion, postganglionic [nerve and the unstriated muscle of human airway, there are three kinds of M-ChR hypotypes respectively, be M1, M2, M3, they have different physiological functions, wherein the M1 acceptor mainly is to make the cholinergic nerve signal pass through parasympathetic ganglion, after the M2 acceptor is positioned at sympathetic ganglion, release to vagusstoff plays the reverse feedback regulating effect, and the M3 acceptor is positioned on unstriated muscle and the body of gland, and the airway smooth muscle that the mediation acetylcholine causes shrinks and mucus secretion.
Bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine medical compounds is a kind of novel quaternary ammonium anticholinergic agent, and it has optionally act on M1 in human body, and the M3 acceptor is to the almost not effect of M2 acceptor; Simultaneously it is difficult for seeing through hemato encephalic barrier in human body, does not accumulate in brain, for long-term prescription and the topical treatment of COPD provides the most basic condition.
Summary of the invention
The object of the present invention is to provide bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine medical compounds and composition thereof and this medical compounds and composition preparation treatment chronic obstructive pulmonary disease and bronchitis and with chronic obstructive pulmonary disease and bronchitis diseases associated medicine in application.
Concrete technical scheme of the present invention is as follows:
A kind of medical compounds is characterized in that having following chemical structural formula:
Its chemical name is: bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine
Molecular formula is: C
22H
34NO
2Br
Molecular weight is: 424.42
Described medical compounds contains 2 chiral carbon atoms, and exists with the form of four kinds of steric isomers, and medical compounds of the present invention comprises isomer or the blended isomeric forms that these are independent.
The composition of medical compounds of the present invention is characterized in that containing bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine of the pharmaceutically acceptable form of any dosage and the pharmaceutically acceptable carrier of choosing wantonly.
The composition of described medical compounds is characterized in that bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine that it contains 1-100mg and pharmaceutically can accept form.
The composition of described medical compounds is characterized in that containing following pharmaceutically acceptable dosage: 1mg, 2mg, 3mg, 4mg, 5mg, 6mg, 7mg, 8mg, 9mg, 10mg, 20mg, 30mg, 40mg, 50mg, 100mg.
Described bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) the pharmaceutically acceptable solvate of quinuclidine comprises various organic solvents, hydrate.
Bromination-1-ethyl-the 3-of the pharmaceutically acceptable form of described any dosage (2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine comprises human and two kinds of purposes of beasts.
The preparation of compositions method of medical compounds of the present invention is: quinuclidine mixes with pharmaceutically acceptable carrier, and the optional combination thing is configured to supply with the form of medicine with the bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) of the pharmaceutically acceptable form of any dosage.
The form that described composition can be supplied with medicine is: make various formulations by the universal method on the technology of pharmaceutics, comprise oral dosage forms such as tablet, dispersible tablet, chewable tablet, capsule, granule, oral liquid, dry suspensoid, and the eye drops of per os or gi tract external administration form, be coated with an agent, nasal drop, sprays, aerosol, the sprays of per os spray delivery especially.
Described preparation comprises auxiliary material necessary on the technology of pharmaceutics, comprises thinner, tackiness agent, disintegrating agent, lubricant, correctives, the perfume compound of tablet; The solvent of oral liquid, stablizer, acid-base modifier; The solubility promoter of injection, oxidation inhibitor, acid-base modifier.
Described and chronic obstructive pulmonary disease and bronchitis diseases associated comprise bronchial asthma.
The invention has the advantages that:
1, medical compounds of the present invention can optionally be blocked M1, M3 acceptor, and the M2 acceptor is not almost had blocking effect, is a kind of novel quaternary ammonium anticholinergic agent.
2, medical compounds of the present invention and composition thereof are difficult for seeing through the hemato encephalic barrier of human body, do not accumulate in brain.
When 3, this compound compositions of the pharmaceutically acceptable form of any dosage of the present invention sucks in patient's body by spray delivery, easier of pulmonary deposition, thus play therapeutic action preferably.
Embodiment
The invention will be further described below by specific embodiment, but do not limit the present invention in any way.
Embodiment 1
The preparation of bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine
In 3 mouthfuls of reaction flasks, take by weighing 3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine 20g, and adding anhydrous diethyl ether 100ml, temperature rising reflux, slowly the diethyl ether solution of dripping bromine ethane is to excessive, dropwise the back and continued back flow reaction 2 hours, cooling was left standstill 12 hours, filtration obtains the crystal of white, gets product 16.7g.Molecular formula is C
22H
34NO
2Br, the ultimate analysis theoretical value is C:62.30%; H:8.01%; N:3.30%; Br:18.87%, the actual measured value of ultimate analysis is: C:61.57%; H:7.88%; N:3.46%; Br:19.26%.
Embodiment 2
The preparation of the aerosol of bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine
Bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine bromine is dissolved in the pure solution of formation in the dehydrated alcohol, should installs in the aerosol jar by pure solution branch, seal, and then in the aerosol jar, pour into propellent (fluorine Lyons or 134A).
Embodiment 3
The preparation of bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine injection
With bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine formation aqueous solution that is dissolved in the water, install to this aqueous solution branch in the ampoule or in the cillin bottle, seal.
Embodiment 4
The test of pesticide effectiveness
We utilize [
3H] QNB as research m receptor tagged ligand, [
3H] characteristics such as QNB has good stability, and specificity is high and dissociate slowly, replace by bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine is competitive [
3H] QNB is to different tissues m receptor bonded inhibition experiment, and obtain it and suppress mark aglucon in conjunction with 50% dosage (IC
50), IC
50More little, show that to be subjected to the avidity of reagent and corresponding M acceptor big more, experimental result shows: bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine all has difference to the m receptor avidity of rat layer, heart and submaxillary gland, and it is in proper order: M
1＞M
3＞M
2, pharmacological experiment finds that in the general treatment scope, this product does not have the effect of obvious quickening heart rate, infers that thus it is to M yet
2Acceptor does not have tangible blocking effect, and it has certain selectivity to m receptor.
Claims (8)
1, a kind of medical compounds is characterized in that having following chemical structural formula:
Its chemical name is: bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine
Molecular formula is: C
22H
34NO
2Br
Molecular weight is: 424.42
2, the composition of medical compounds as claimed in claim 1, it is characterized in that it be by bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine of the pharmaceutically acceptable form of any dosage mixes with optional pharmaceutically acceptable carrier and must, and be configured to supply with the form of medicine with the optional combination thing.
3, the composition of medical compounds as claimed in claim 2 is characterized in that bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine that it contains 1-100mg and pharmaceutically can accept form.
4,, it is characterized in that bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine that it contains 1-10mg and pharmaceutically can accept form as claim 2 or 3 described medical compounds compositions.
5,, it is characterized in that bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine that it contains 1mg and pharmaceutically can accept form as claim 2 or 3 described medical compounds compositions.
6,, it is characterized in that bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine that it contains 5mg and pharmaceutically can accept form as claim 2 or 3 described medical compounds compositions.
7,, it is characterized in that bromination-1-ethyl-3-(2-phenyl-2-cyclopentyl-2-hydroxyl-oxethyl) quinuclidine that it contains 10mg and pharmaceutically can accept form as claim 2 or 3 described medical compounds compositions.
8, medical compounds of the present invention and composition thereof preparation treatment chronic obstructive pulmonary disease and bronchitis and with chronic obstructive pulmonary disease and bronchitis diseases associated medicine in application.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510021090 CN1709891A (en) | 2005-06-16 | 2005-06-16 | Medicinal compound, its composition and use in pharmaceutical process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510021090 CN1709891A (en) | 2005-06-16 | 2005-06-16 | Medicinal compound, its composition and use in pharmaceutical process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1709891A true CN1709891A (en) | 2005-12-21 |
Family
ID=35706186
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510021090 Pending CN1709891A (en) | 2005-06-16 | 2005-06-16 | Medicinal compound, its composition and use in pharmaceutical process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1709891A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007045151A1 (en) * | 2005-10-20 | 2007-04-26 | Cachet Pharmaceutical Co., Ltd. | Compounds and their pharmaceutical compositions for the treatment of nasal cavum hypersecretion and chronic obstructive pulmonary disease |
| CN111377920A (en) * | 2018-12-27 | 2020-07-07 | 银谷制药有限责任公司 | Method for refining quinine compound containing quaternary ammonium group |
-
2005
- 2005-06-16 CN CN 200510021090 patent/CN1709891A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007045151A1 (en) * | 2005-10-20 | 2007-04-26 | Cachet Pharmaceutical Co., Ltd. | Compounds and their pharmaceutical compositions for the treatment of nasal cavum hypersecretion and chronic obstructive pulmonary disease |
| CN1769286B (en) * | 2005-10-20 | 2010-10-06 | 嘉事堂药业股份有限公司 | Compound and pharmaceutical composition for treating nasal oversecreation and chronic obstructive pulmonary disease |
| CN111377920A (en) * | 2018-12-27 | 2020-07-07 | 银谷制药有限责任公司 | Method for refining quinine compound containing quaternary ammonium group |
| CN111377920B (en) * | 2018-12-27 | 2021-10-26 | 银谷制药有限责任公司 | Method for refining quinine compound containing quaternary ammonium group |
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