CN102321088A - Novel anti-schistosomiasis compound - Google Patents
Novel anti-schistosomiasis compound Download PDFInfo
- Publication number
- CN102321088A CN102321088A CN201110226285A CN201110226285A CN102321088A CN 102321088 A CN102321088 A CN 102321088A CN 201110226285 A CN201110226285 A CN 201110226285A CN 201110226285 A CN201110226285 A CN 201110226285A CN 102321088 A CN102321088 A CN 102321088A
- Authority
- CN
- China
- Prior art keywords
- compound
- compsn
- schistosomicide
- fluke
- larva
- 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.)
- Pending
Links
- KTUBLJFPBFDRRE-UHFFFAOYSA-N O=C(C1CCCCC1)N(CC1N2Cc3ccccc13)CC2=O Chemical compound O=C(C1CCCCC1)N(CC1N2Cc3ccccc13)CC2=O KTUBLJFPBFDRRE-UHFFFAOYSA-N 0.000 description 1
- BOESOANWDKJAPO-UHFFFAOYSA-N O=C(CNC1)N(C2)C1c1c2cccc1 Chemical compound O=C(CNC1)N(C2)C1c1c2cccc1 BOESOANWDKJAPO-UHFFFAOYSA-N 0.000 description 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-N OC(C1CCCCC1)=O Chemical compound OC(C1CCCCC1)=O NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a compound of general formula I, and various medicinal salts, various isomers, and oxynitrides thereof which are suitable for human and animals. The compound has the effect of killing schistosome adult worms and larvae in human body or animal body. In the structure general formula I, n1 is 1, 2, 3, and n2 is 1, 2, 3, 4, 5.
Description
Technical field the present invention relates to the infecting both domestic animals and human property disease that a kind of compounds for treating imago of blood fluke and larva cause.
The background technology schistosomicide is the prevailing disease that causes owing to infect three kinds of main schistosomicide (Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum).Over 40 years, PRAZIQUANTEL BP 98 remains and is widely used in unique active drug that the various imago of blood fluke of control humans and animals infect.Because its a large amount of and life-time service has produced drug resistance at present; Do not treat and still have active drug so far to the schistosomicide that the schistosomicide larva infects, that is, the bilharzial patient of early infection has only the larva of wait to grow up in vivo and grows for treating behind the adult.Disclosing the whole world according to the World Health Organization has 200,000,000 people to infect schistosomicide, the infected threat of 600,000,000 people of having an appointment, and the high number of the infected of schistosomicide has 2,000 ten thousand, has every year at least 280000 people to die from schistosomicide.And " national comprehensive regulation schistosomicide ' 15 ' plan " data that the Ministry of Health and National Development and Reform Committee issue show; China does not control the concentrated lakes and marhshes area and the big mountain area of being distributed in, 108 counties of schistosomiasis propagation at present as yet, and the animal host is numerous, and snail distribution is extensive; Receive such environmental effects very big; Preventing and controlling are difficulty especially, and superinfection is still very serious, and epidemic situation is in very unsteady state.In the face of so numerous schistosomiasis infection crowds only a kind of chemicals of PRAZIQUANTEL BP 98 be very disproportionate, therefore need the new antischistosomal drug of development badly.
Summary of the invention:
1, a kind of compound of general formula I is applicable to the various salt of humans and animals on it is medicinal, and various isomer, oxynitrides.
General structure I,
Wherein,
n
1Be 1,2,3;
n
2Be 1,2,3,4,5;
Wherein preferred but compound that be not limited to is::
2, compound of the present invention is used to kill the effect of human body or interior imago of blood fluke of animal body and larva.
3, compound of the present invention is used for treating the drug effect of schistosomicide disease
4, compound of the present invention is as a kind of compsn, and said compsn comprises pharmaceutically acceptable carrier, and this compound is as the treatment significant quantity of activeconstituents.
Pharmacology
The compounds of this invention shows unexpectedly and is suitable for treating schistosomicide, comprises the infecting both domestic animals and human property disease that adult and larva cause. the present invention also relates to compound with the general formula I of preceding text definition; With its acid of pharmaceutically accepting or base addition salt; Comprise quaternary salt; Stereochemistry heterogeneous forms, N-oxygen compound form is used as medicine, and following any pharmaceutical composition is used for treating schistosomicide in preparation, comprises the purposes of the medicine of the infecting both domestic animals and human property disease that adult and larva cause.
Therefore, the method that the present invention provides a kind of treatment to suffer from the schistosomicide disease on the other hand, this method comprise the The compounds of this invention of treating significant quantity or pharmaceutical composition gives the patient or trouble is held.
The compounds of this invention shows the schistosomicide adult; Activity with larva; The mechanism of action of this compounds is not studied clear as yet, maybe be relevant with the bilharzial calcium channel of such compound effects, promptly cause the extensively impaired of the movable excitement of polypide, polypide muscle contracture and cortex rapidly; Thereby cause the liver of worm to move; Influence body surface dietetic alimentation, excretion and the defense function of worm and the metabolism disorder of secondary, and the infringement of cortex and peeling off then destroyed the concomitant immunity mechanism that worm is able in host, survive, the immune attack that appears for host's schistosomicide specific antibody of its body surface antigenic determinant provides target site.
The present invention also relates to compsn, it comprises pharmaceutically acceptable carrier and as the The compounds of this invention of controlling 3 significant quantities of activeconstituents.The compounds of this invention can be deployed into the different pharmaceutical form that is used for the administration purpose.As the illustration of appropriate combination thing is common all compsns that adopt of whole body administration medicine.Be preparation pharmaceutical composition of the present invention, the specific compound of significant quantity (optional with the additive salt form) closely combines as activeconstituents and drug acceptable carrier, depends on the dosage form that administration is required, and said carrier can be taked various ways.These pharmaceutical compositions are preferably the single dose form that particularly is fit to the injection of oral administration or parenteral.For example, when the compsn of preparation oral dosage form, at oral liquid such as suspensoid, syrup under the situation of emulsion and solution, can adopt any usual drug media, like water, and terepthaloyl moietie, oil, alcohol etc.; Perhaps at powder agent, pill under the situation of capsule and tablet, adopts for example starch of solid carrier, sugar, kaolin, thinner, tackiness agent etc.
The mode that depends on administration; Said drug regimen preferably includes 0.05-99% weight, the more preferably activeconstituents of 0.1-70% weight, and preferred 1-99.95% weight; The more preferably pharmaceutically acceptable carrier of 30-99.9% weight, all per-cents all calculate based on total compsn.
The preparation of embodiment one typical compound 1-3:
In the round-bottomed flask that magnetic agitation is housed, add 1-1 (188mg, 1mmol), heptanaphthenic acid (128mg, 1mmol), EDCI (211mg, 1.1mmol) and DMAP (139mg, 1.1mmol).Stirred overnight under the room temperature is with 1% salt sour water and alternately washing of saturated sodium carbonate solution, at last with washing.Concentrate behind the anhydrous magnesium sulfate drying white solid .Mp 132-135 (277mg, yield 93%).
In the round-bottomed flask that magnetic agitation is housed, add 1-1 (188mg, 1mmol), cyclopentanecarboxylic acid (114mg, 1mmol), EDCI (211mg, 1.1mmol) and DMAP (139mg, 1.1mmol).Stirred overnight under the room temperature is with 1% salt sour water and alternately washing of saturated sodium carbonate solution, at last with washing.Concentrate behind the anhydrous magnesium sulfate drying white solid Mp 128-130 (256mg, yield 90.14%).
Biological effect:
Measure the in vitro method of compound anti schistosoma:
1, the adult vitro culture: 42 days male insects of gather living place DMEM nutrient solution (10/3ml/ ware), grouping dosing.Every ware adds each 3ul of compound respectively, and final concentration is that 50 (mol/ml, control group add DMS03 (1 (with reference to other experimental group dosing maximum dose levels).Fully shake up after the dosing, put into 37 ℃, 5%CO: incubator.Polypide is washed 3 times with saline water in overnight cultures (16h) back, adds fresh medium, the schistosomicide vigor state under stereoscopic microscope behind observation cultivation .24h～72h, and photologging.The result sees table 1,2, and the larva vitro culture: 16 days larvas that gather to live place DMEM nutrient solution (10/3ml/ ware), grouping dosing.Every ware adds each 3ul of compound respectively, and final concentration is that 50 (mol/ml, control group add DMS03 (1 (with reference to other experimental group dosing maximum dose levels).Fully shake up after the dosing, put into 37 ℃, 5%CO: incubator.Polypide is washed 3 times with saline water in overnight cultures (16h) back, adds fresh medium, the schistosomicide vigor state under stereoscopic microscope behind observation cultivation .24h～72h, and photologging.The result sees table 1,
Table 1, the test of 42 days adults of compound schistosomicide and 16 days larvas
Mortality ratio grade: A is 100%-80% in the table; B is 80%-60%; C is 60%-40%; D is 40%-0%.
Claims (7)
1. the compound of a general formula I is applicable to the various salt of humans and animals on it is medicinal, and various isomer, oxynitrides.
General structure I,
Wherein,
n
1Be 1,2,3;
n
2Be 1,2,3,4,5;
2. compound as claimed in claim 1 is characterized in that said compound is preferably certainly:
3. like the described compound of claim 1-2, it is characterized in that this compounds is used to kill imago of blood fluke and larva in human body or the animal body, and the effect of tapeworm, cysticercus, clonorchis sinensis, lung fluke, fasciloopsis.
4. like each compound among the claim 1-2, it is characterized in that as medicine.
5. compsn, said compsn comprise pharmaceutically acceptable carrier and like the treatment significant quantity of the described compound of claim 1-2 as activeconstituents.
6. like the described compound of claim 1-2, or the described compsn of claim 5, it is characterized in that being used to treat schistosomicide, and the drug effect in the tapeworm, cysticercus, clonorchis sinensis, lung fluke, fasciloopsis disease
7. method of treating imago of blood fluke and larva and tapeworm, cysticercus, clonorchis sinensis, lung fluke, fasciloopsis disease; Said method comprises described each compound of claim 1-2 of the significant quantity of treatment, or the described compsn of claim 5 gives said patient or trouble is held.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110226285A CN102321088A (en) | 2011-08-03 | 2011-08-03 | Novel anti-schistosomiasis compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110226285A CN102321088A (en) | 2011-08-03 | 2011-08-03 | Novel anti-schistosomiasis compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102321088A true CN102321088A (en) | 2012-01-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110226285A Pending CN102321088A (en) | 2011-08-03 | 2011-08-03 | Novel anti-schistosomiasis compound |
Country Status (1)
| Country | Link |
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| CN (1) | CN102321088A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103910725A (en) * | 2013-01-09 | 2014-07-09 | 江南大学 | Praziquantel analogue, preparation method and application thereof |
| CN105028403A (en) * | 2015-06-19 | 2015-11-11 | 赣南师范学院 | Preparation method for biomass charcoal anti-schistosoma cercaria slow-release pharmaceutical preparation |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4661489A (en) * | 1983-07-16 | 1987-04-28 | Beecham Group P.L.C. | Benzazepines, and their use as anthelminthics |
| DE3619030A1 (en) * | 1986-06-06 | 1987-12-10 | Bayer Ag | Compositions for topical use |
| CN102267998A (en) * | 2011-05-31 | 2011-12-07 | 孙德群 | Novel anti-parasitic pyrazine isoquinoline derivative |
-
2011
- 2011-08-03 CN CN201110226285A patent/CN102321088A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4661489A (en) * | 1983-07-16 | 1987-04-28 | Beecham Group P.L.C. | Benzazepines, and their use as anthelminthics |
| DE3619030A1 (en) * | 1986-06-06 | 1987-12-10 | Bayer Ag | Compositions for topical use |
| CN102267998A (en) * | 2011-05-31 | 2011-12-07 | 孙德群 | Novel anti-parasitic pyrazine isoquinoline derivative |
Non-Patent Citations (1)
| Title |
|---|
| O.V.SHEKHTER，等，: "Synthesis of Tricylic Systems Incorporating the Azepine Ring", 《CHEMISTRY OF HETEROCYCLIC COMPOUNDS》, vol. 26, no. 12, 31 December 1990 (1990-12-31), XP009017932, DOI: doi:10.1007/BF00473968 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103910725A (en) * | 2013-01-09 | 2014-07-09 | 江南大学 | Praziquantel analogue, preparation method and application thereof |
| CN103910725B (en) * | 2013-01-09 | 2015-12-02 | 江南大学 | One class Praziquantel Analogues, Preparation Method And The Use |
| CN105028403A (en) * | 2015-06-19 | 2015-11-11 | 赣南师范学院 | Preparation method for biomass charcoal anti-schistosoma cercaria slow-release pharmaceutical preparation |
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| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
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| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
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Application publication date: 20120118 |