CN104844606A - Novel anti-parasite pyrazine isoquinoline derivative - Google Patents
Novel anti-parasite pyrazine isoquinoline derivative Download PDFInfo
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- CN104844606A CN104844606A CN201510117197.1A CN201510117197A CN104844606A CN 104844606 A CN104844606 A CN 104844606A CN 201510117197 A CN201510117197 A CN 201510117197A CN 104844606 A CN104844606 A CN 104844606A
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- membered
- nitrogen heterocycles
- membered saturated
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- GPBRIMOJKVDGLP-UHFFFAOYSA-N isoquinoline;pyrazine Chemical class C1=CN=CC=N1.C1=NC=CC2=CC=CC=C21 GPBRIMOJKVDGLP-UHFFFAOYSA-N 0.000 title abstract description 5
- 230000002141 anti-parasite Effects 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 29
- 239000003814 drug Substances 0.000 claims abstract description 16
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 12
- 239000000203 mixture Substances 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 241000242677 Schistosoma japonicum Species 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 208000030852 Parasitic disease Diseases 0.000 claims description 5
- 241001327965 Clonorchis sinensis Species 0.000 claims description 4
- 241000242678 Schistosoma Species 0.000 claims description 3
- 241000242541 Trematoda Species 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 230000002147 killing effect Effects 0.000 claims 4
- 241000935974 Paralichthys dentatus Species 0.000 claims 1
- 244000045947 parasite Species 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 201000004409 schistosomiasis Diseases 0.000 description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 6
- 238000003760 magnetic stirring Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 206010033794 paragonimiasis Diseases 0.000 description 3
- FSVJFNAIGNNGKK-UHFFFAOYSA-N 2-[cyclohexyl(oxo)methyl]-3,6,7,11b-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4-one Chemical compound C1C(C2=CC=CC=C2CC2)N2C(=O)CN1C(=O)C1CCCCC1 FSVJFNAIGNNGKK-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- -1 ketone compound Chemical class 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229960002957 praziquantel Drugs 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 241000242722 Cestoda Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical class ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- QCJNDVFLHORPLZ-UHFFFAOYSA-N O=C(C1CCCCC1)N(CC1)CC(c2ccccc2CC2)N2C1=O Chemical compound O=C(C1CCCCC1)N(CC1)CC(c2ccccc2CC2)N2C1=O QCJNDVFLHORPLZ-UHFFFAOYSA-N 0.000 description 1
- NTHWGLTXWCGVOW-UHFFFAOYSA-N O=C(CCNC1)N(CC2)C1c1c2cccc1 Chemical compound O=C(CCNC1)N(CC2)C1c1c2cccc1 NTHWGLTXWCGVOW-UHFFFAOYSA-N 0.000 description 1
- 241000565675 Oncomelania Species 0.000 description 1
- 241000242680 Schistosoma mansoni Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 206010048282 zoonosis Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a novel anti-parasite pyrazine isoquinoline derivative. The invention relates to a compound which is shown in a structural general formula I, wherein A is selected from the following formula, B is selected from saturated nitrogen heterocycles comprising five-membered saturated nitrogen heterocycles, six-membered saturated nitrogen heterocycles and seven-membered saturated nitrogen heterocycles, C is selected from saturated nitrogen heterocycles comprising five-membered saturated nitrogen heterocycles, six-membered saturated nitrogen heterocycles and seven-membered saturated nitrogen heterocycles, D is selected form saturated rings comprising three-membered saturated rings, four-membered saturated rings, five-membered saturated rings, six-membered saturated rings and seven-membered saturated rings. The invention relates to the application of the compound, a medical composition and a medicine. The compound is shown in the specification.
Description
Technical Field
The invention relates to a novel pyrazine isoquinoline derivative for treating parasitic diseases, in particular to a medicine composition and a medicine comprising a pyrazine isoquinoline derivative component for treating zoonosis diseases caused by schistosomiasis, tapeworm, cysticercus, clonorchis sinensis, paragonimiasis pulmonalis and fasciola zingiberis.
Background
Schistosomiasis is an epidemic caused by infection with three major species of schistosomiasis (Schistosoma mansoni, Schistosoma japonicum and Schistosoma japonicum). For 40 years, praziquantel is still the only effective drug widely used for preventing and treating various adult schistosomiasis infections of human and animals. Drug resistance has been developed at present due to its large and long-term use; however, there is no effective drug therapy for schistosomiasis infected by schistosome. According to the disclosure of the world health organization, there are 2 hundred million people infected with schistosomiasis worldwide, about 6 hundred million people are threatened to be infected, and 2 million people with high schistosomiasis are present, and at least 280000 people die of schistosomiasis every year. The data of ' fifteen ' plan for comprehensive treatment of schistosomiasis nationwide ' issued by Ministry of public health and the State development and improvement Commission show that 108 counties which do not control the propagation of schistosomiasis currently are intensively distributed in the lake and marsh regions and the mountain regions, the number of animal hosts is large, the distribution of oncomelania is wide, the influence of environmental factors is great, the prevention and treatment work is particularly difficult, the repeated infection is still very serious, and the epidemic situation is in a very unstable state. In the face of such a large number of people infected with schistosomiasis, only one chemical drug of praziquantel is not suitable, so that the development of a new anti-schistosomiasis drug is urgently needed.
Disclosure of Invention
A compound of formula I, its pharmaceutically acceptable salts, its isomers and oxynitrides suitable for use in humans and animals. The structural general formula is shown as formula I,
wherein,
a is an unsaturated ring including a benzene ring, a pyridine ring and a nitroxide dipolar pyridine ring;
b is saturated nitrogen heterocycle, including five-membered, six-membered and seven-membered saturated nitrogen heterocycle, which can be substituted by C1-C4 alkyl or form 3-5-membered saturated fused ring;
c is a saturated nitrogen heterocycle including five-, six-, and seven-membered saturated nitrogen heterocycles, which may be a ketone or non-ketone compound;
d is a saturated ring, including ternary, quaternary, quinary, senary, and heptatomic saturated rings;
a is selected from the following groups:
b + C is selected from the following groups:
d is selected from the following groups:
among the preferred but not limiting compounds are:
the compounds of the present invention have unexpectedly been shown to be suitable for the treatment of parasitic diseases, especially human and animal comorbidity diseases caused by schistosomiasis, cestode, cysticercus, clonorchis sinensis, paragonimiasis zingiberis the present invention also relates to the use of a compound of formula I as defined above, pharmaceutically acceptable acid or base addition salts thereof, including quaternary salts, stereochemically isomeric forms, N-oxide compounds, as a medicament, and the use of any of the following pharmaceutical compositions for the manufacture of a medicament for the treatment of parasitic diseases, including human and animal comorbidity diseases caused by schistosomiasis, cestode, cysticercus, clonorchis sinensis, paragonimiasis zingiberis.
Thus, in another aspect, the invention provides a method of treating a subject suffering from a parasitic disease, including schistosomiasis, which comprises administering to the subject or subject a therapeutically effective amount of a compound or pharmaceutical composition of the invention.
The invention also relates to compositions comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound of the invention. The compounds of the present invention may be formulated in different pharmaceutical forms for administration purposes. Illustrative of suitable compositions are all compositions commonly employed for systemic administration of drugs. To prepare the pharmaceutical compositions of this invention, an effective amount of the particular compound, optionally in addition salt form, as the active ingredient is combined in intimate association with a pharmaceutically acceptable carrier, which carrier may take a wide variety of forms depending on the form of preparation desired for administration. These pharmaceutical compositions are preferably in single dosage form, especially suitable for oral administration or parenteral injection. For example, in the preparation of compositions in oral dosage form, in the case of oral liquid preparations such as suspensions, syrups, emulsions and solutions, any usual pharmaceutical media may be employed, such as water, glycols, oils, alcohols and the like; or in the case of powders, pills, capsules and tablets, solid carriers such as starches, sugars, kaolin, diluents, binders and the like.
Depending on the mode of administration, the pharmaceutical combination preferably comprises 0.05 to 99% by weight, more preferably 0.1 to 70% by weight of the active ingredient, and preferably 1 to 99.95% by weight, more preferably 30 to 99.9% by weight of a pharmaceutically acceptable carrier, all percentages being calculated on the total composition.
Detailed Description
Examples preparation of typical compounds 1-3:
to a round bottom flask equipped with magnetic stirring was added 1-1(188mg, 1mmol), cyclohexanecarboxylic acid (128mg, 1mmol), EDCI (211mg, 1.1mmol) and DMAP (139mg, 1.1 mmol). Stirred at room temperature overnight, washed alternately with 1% hydrochloric acid water and saturated sodium carbonate solution and finally with water. The residue was dried over anhydrous magnesium sulfate and concentrated to give MP132-135(277mg, yield 93%) as a white solid.
To a round bottom flask equipped with magnetic stirring was added 1-1(188mg, 1mmol), cyclopentanecarboxylic acid (114mg, 1mmol), EDCI (211mg, 1.1mmol) and DMAP (139mg, 1.1 mmol). Stirred at room temperature overnight, washed alternately with 1% hydrochloric acid water and saturated sodium carbonate solution and finally with water. After drying over anhydrous magnesium sulfate, concentration gave Mp128-130 as a white solid (256mg, yield 90.14%).
To a round bottom flask equipped with magnetic stirring was added 1-1(188mg, 1mmol), cycloheptanecarboxylic acid (142mg, 1mmol), EDCI (211mg, 1.1mmol) and DMAP (139mg, 1.1 mmol). Stirred at room temperature overnight, washed alternately with 1% hydrochloric acid water and saturated sodium carbonate solution and finally with water. The anhydrous magnesium sulfate was dried and concentrated to give a white solid, Mp137-139(287mg, 92% yield).
Example two preparation of representative Compounds 10-12:
a round-bottomed flask equipped with magnetic stirring was charged with 10-1(232mg, 1mmol), cyclohexanecarboxylic acid (128mg, 1mmol), EDCI (211mg, 1.1mmol) and DMAP (139mg, 1.1 mmol). Stirred at room temperature overnight, washed alternately with 1% hydrochloric acid water and saturated sodium carbonate solution and finally with water. The mixture was dried over anhydrous magnesium sulfate and concentrated to give Mp143-146(324mg, yield 95%) as a white solid.
To a round bottom flask equipped with magnetic stirring was added 10-1(232mg, 1mmol), cycloheptanecarboxylic acid (142mg, 1mmol), EDCI (211mg, 1.1mmol) and DMAP (139mg, 1.1 mmol). Stirred at room temperature overnight, washed alternately with 1% hydrochloric acid water and saturated sodium carbonate solution and finally with water. The anhydrous magnesium sulfate was dried and concentrated to give MP 138-141 (295mg, yield 90%) as a white solid.
To a round bottom flask equipped with magnetic stirring was added 10-1(232mg, 1mmol), cycloheptanecarboxylic acid (142mg, 1mmol), EDCI (211mg, 1.1mmol) and DMAP (139mg, 1.1 mmol). Stirred at room temperature overnight, washed alternately with 1% hydrochloric acid water and saturated sodium carbonate solution and finally with water. Dry over anhydrous magnesium sulfate and concentrate to give a white solid Mp149-153(316mg, 89% yield).
Examples three biological effects
The in vitro method for measuring the schistosoma japonicum resistance of the compound comprises the following steps: adult in-vitro culture: live male adults were collected and placed in DMEM medium (10 strips/3 ml/dish) and dosed in groups. Adding 3ul of compound into each dish respectively, adding DMS03(1 (referring to other experimental groups for adding the highest dose) into a control group with the final concentration of 50 mol/ml, adding the DMS03, fully shaking up after adding the DMS, placing the DMS into an incubator with the temperature of 37 ℃ and the CO content of 5 percent, washing the worm body for 3 times by using physiological saline after culturing overnight (16h), adding a fresh culture solution, observing the vitality state of the schistosome after culturing for 24h to 72h under a stereoscopic microscope, and recording images, wherein the results are shown in a table 1.
TABLE 1
| Compound (I) | Number of insects | Mortality grade | Compound (I) | Number of insects | Mortality grade |
| 1 | 20 | A | 35 | 20 | A |
| 4 | 20 | A | 37 | 20 | A |
| 7 | 20 | A | 40 | 20 | A |
| 13 | 20 | A | 43 | 20 | A |
| 18 | 20 | A | 46 | 20 | A |
| 19 | 20 | A | 50 | 20 | A |
| 21 | 20 | A | 54 | 20 | A |
| 22 | 20 | A | 57 | 20 | A |
| 24 | 20 | A | 62 | 20 | A |
| 28 | 20 | A | 64 | 20 | A |
| 29 | 20 | A | 66 | 20 | A |
| 30 | 20 | A | 67 | 20 | A |
| 34 | 20 | A | 69 | 20 | A |
Mortality rating in table: a is 100-80%.
Claims (10)
1. A compound is shown as a structural general formula I,
wherein,
a is selected from
B is selected from saturated nitrogen heterocycles, including five-membered, six-membered and seven-membered saturated nitrogen heterocycles;
c is selected from saturated nitrogen heterocycles, including five-membered, six-membered and seven-membered saturated nitrogen heterocycles;
d is selected from saturated rings, including ternary, quaternary, quinary, hexahydric and heptatomic saturated rings.
2. The compound of claim 1, further comprising a C1-C4 alkyl substituent on the B ring, or a 3-5 membered saturated fused ring substituent.
3. A compound according to claim 1 or 2, wherein B + C is selected from one of the groups of formulae II, III, IV, V, VI, VII, VIII, IX, X, XI, XII and XIII,
4. a compound according to claim 3, wherein the compound is selected from at least one of the compounds of formula 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68 and 69,
5. use of a compound according to any one of claims 1 to 4 for the manufacture of a medicament for the prevention or treatment of a parasitic disease, wherein the parasite is selected from at least one of schistosoma, cestode, cysticercus, clonorchis sinensis, fluke scuba and fasciola.
6. A pharmaceutically acceptable salt of a compound according to any one of claims 1 to 4.
7. A pharmaceutical composition having killing effect on Schistosoma japonicum, wherein the active ingredient of the pharmaceutical composition comprises the compound according to any one of claims 1-4, and preferably the composition further comprises a pharmaceutically acceptable carrier.
8. A pharmaceutical composition having killing effect on schistosoma japonicum, wherein the active ingredient of the pharmaceutical composition comprises a pharmaceutically acceptable salt of the compound of claim 6, preferably the composition further comprises a pharmaceutically acceptable carrier.
9. A medicament having a killing effect on schistosoma japonicum, wherein the active ingredient of the medicament comprises the compound according to any one of claims 1-4, and preferably the medicament further comprises a pharmaceutically acceptable carrier.
10. A drug having a killing effect on Schistosoma japonicum, which is characterized in that an active ingredient of the drug comprises a pharmaceutically acceptable salt of the compound according to claim 6, and preferably the drug further comprises a pharmaceutically acceptable carrier.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510117197.1A CN104844606B (en) | 2011-05-31 | 2011-05-31 | Parasiticide pyrazine isoquinoline derivative |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110154047.XA CN102267998B (en) | 2011-05-31 | 2011-05-31 | Novel anti-parasitic pyrazine isoquinoline derivative |
| CN201510117197.1A CN104844606B (en) | 2011-05-31 | 2011-05-31 | Parasiticide pyrazine isoquinoline derivative |
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| CN201110154047.XA Division CN102267998B (en) | 2011-05-31 | 2011-05-31 | Novel anti-parasitic pyrazine isoquinoline derivative |
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| Publication Number | Publication Date |
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| CN104844606A true CN104844606A (en) | 2015-08-19 |
| CN104844606B CN104844606B (en) | 2017-03-01 |
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| CN201110154047.XA Expired - Fee Related CN102267998B (en) | 2011-05-31 | 2011-05-31 | Novel anti-parasitic pyrazine isoquinoline derivative |
| CN201510117838.3A Expired - Fee Related CN104788457B (en) | 2011-05-31 | 2011-05-31 | Novel anti-parasitic pyrazine isoquinoline derivative |
| CN201510117197.1A Expired - Fee Related CN104844606B (en) | 2011-05-31 | 2011-05-31 | Parasiticide pyrazine isoquinoline derivative |
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| CN201510117838.3A Expired - Fee Related CN104788457B (en) | 2011-05-31 | 2011-05-31 | Novel anti-parasitic pyrazine isoquinoline derivative |
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| CN102321088A (en) * | 2011-08-03 | 2012-01-18 | 威海秀水药物研发有限公司 | Novel anti-schistosomiasis compound |
| CN113754666A (en) * | 2021-09-07 | 2021-12-07 | 凯美克(上海)医药科技有限公司 | Benzopyrazine compound and synthesis method thereof |
Citations (2)
| 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 |
| CN1683346A (en) * | 2005-03-01 | 2005-10-19 | 江苏工业学院 | Praziquantel synthetic process |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3619030A1 (en) * | 1986-06-06 | 1987-12-10 | Bayer Ag | Compositions for topical use |
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2011
- 2011-05-31 CN CN201110154047.XA patent/CN102267998B/en not_active Expired - Fee Related
- 2011-05-31 CN CN201510117838.3A patent/CN104788457B/en not_active Expired - Fee Related
- 2011-05-31 CN CN201510117197.1A patent/CN104844606B/en not_active Expired - Fee Related
Patent Citations (2)
| 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 |
| CN1683346A (en) * | 2005-03-01 | 2005-10-19 | 江苏工业学院 | Praziquantel synthetic process |
Non-Patent Citations (1)
| Title |
|---|
| 胡玉琴，等: "血吸虫病化学预防药物4H-吡嗪并〔2,1-a〕异喹啉衍生物的合成", 《中国药物化学杂志》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102267998B (en) | 2015-05-13 |
| CN102267998A (en) | 2011-12-07 |
| CN104844606B (en) | 2017-03-01 |
| CN104788457A (en) | 2015-07-22 |
| CN104788457B (en) | 2017-08-25 |
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