CN106727581A - 一类氨基醇类化合物的抗寄生虫用途 - Google Patents
一类氨基醇类化合物的抗寄生虫用途 Download PDFInfo
- Publication number
- CN106727581A CN106727581A CN201510829261.9A CN201510829261A CN106727581A CN 106727581 A CN106727581 A CN 106727581A CN 201510829261 A CN201510829261 A CN 201510829261A CN 106727581 A CN106727581 A CN 106727581A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- branched
- straight
- formula
- base
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 33
- 230000002141 anti-parasite Effects 0.000 title claims abstract description 8
- 239000003096 antiparasitic agent Substances 0.000 title abstract description 5
- 208000009366 Echinococcosis Diseases 0.000 claims abstract description 13
- 206010014096 Echinococciasis Diseases 0.000 claims abstract description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 5
- -1 C5-C6 rings Chemical group 0.000 claims description 51
- 239000003814 drug Substances 0.000 claims description 27
- 125000000623 heterocyclic group Chemical group 0.000 claims description 27
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 25
- 238000006467 substitution reaction Methods 0.000 claims description 22
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 17
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 16
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 125000004193 piperazinyl group Chemical group 0.000 claims description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- 125000002757 morpholinyl group Chemical group 0.000 claims description 12
- 125000005936 piperidyl group Chemical group 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- JEYWNNAZDLFBFF-UHFFFAOYSA-N Nafoxidine Chemical compound C1CC2=CC(OC)=CC=C2C(C=2C=CC(OCCN3CCCC3)=CC=2)=C1C1=CC=CC=C1 JEYWNNAZDLFBFF-UHFFFAOYSA-N 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 229950002366 nafoxidine Drugs 0.000 claims description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 5
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000003053 piperidines Chemical class 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 239000005864 Sulphur Substances 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000005110 aryl thio group Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 150000001555 benzenes Chemical class 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 claims description 2
- 241000242678 Schistosoma Species 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 3
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 claims 3
- 238000005984 hydrogenation reaction Methods 0.000 claims 2
- 125000005493 quinolyl group Chemical group 0.000 claims 2
- 238000007347 radical substitution reaction Methods 0.000 claims 2
- 125000003107 substituted aryl group Chemical group 0.000 claims 2
- LAOOXBLMIJHMFO-UHFFFAOYSA-N 1-[2-(diethylamino)ethylamino]-4-methylthioxanthen-9-one;hydron;chloride Chemical group Cl.S1C2=CC=CC=C2C(=O)C2=C1C(C)=CC=C2NCCN(CC)CC LAOOXBLMIJHMFO-UHFFFAOYSA-N 0.000 claims 1
- 241000754688 Cercaria Species 0.000 claims 1
- 241000242722 Cestoda Species 0.000 claims 1
- 150000002118 epoxides Chemical class 0.000 claims 1
- XWINCPYLXQTPQV-UHFFFAOYSA-N piperazine Chemical compound C1CNCCN1.C1CNCCN1 XWINCPYLXQTPQV-UHFFFAOYSA-N 0.000 claims 1
- 230000001843 schistosomicidal effect Effects 0.000 claims 1
- 241000244160 Echinococcus Species 0.000 abstract description 12
- 230000002147 killing effect Effects 0.000 abstract description 8
- 208000030852 Parasitic disease Diseases 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 241001442514 Schistosomatidae Species 0.000 abstract description 4
- 201000004409 schistosomiasis Diseases 0.000 abstract description 4
- 238000009510 drug design Methods 0.000 abstract 1
- 150000002611 lead compounds Chemical class 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 238000005457 optimization Methods 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- 230000000694 effects Effects 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 7
- 150000003248 quinolines Chemical class 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 244000045947 parasite Species 0.000 description 4
- 201000003808 Cystic echinococcosis Diseases 0.000 description 3
- 241000242677 Schistosoma japonicum Species 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 0 *CC(CN(*)*)O Chemical compound *CC(CN(*)*)O 0.000 description 2
- 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
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000002726 cyst fluid Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229960002957 praziquantel Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- 229930183010 Amphotericin Natural products 0.000 description 1
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 description 1
- 241001465677 Ancylostomatoidea Species 0.000 description 1
- 241000244203 Caenorhabditis elegans Species 0.000 description 1
- 201000000077 Cysticercosis Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 206010019668 Hepatic fibrosis Diseases 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 208000031816 Pathologic Dilatation Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 241000224016 Plasmodium Species 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000019532 Schistosoma japonicum infectious disease Diseases 0.000 description 1
- 208000009434 Schistosomiasis japonica Diseases 0.000 description 1
- 208000003837 Second Primary Neoplasms Diseases 0.000 description 1
- 206010044608 Trichiniasis Diseases 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- YKKPYMXANSSQCA-UHFFFAOYSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-(3-pyrazol-1-ylazetidin-1-yl)methanone Chemical compound N1(N=CC=C1)C1CN(C1)C(=O)C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F YKKPYMXANSSQCA-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229960002669 albendazole Drugs 0.000 description 1
- HXHWSAZORRCQMX-UHFFFAOYSA-N albendazole Chemical compound CCCSC1=CC=C2NC(NC(=O)OC)=NC2=C1 HXHWSAZORRCQMX-UHFFFAOYSA-N 0.000 description 1
- 229940009444 amphotericin Drugs 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- FCPVYOBCFFNJFS-LQDWTQKMSA-M benzylpenicillin sodium Chemical class [Na+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)CC1=CC=CC=C1 FCPVYOBCFFNJFS-LQDWTQKMSA-M 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 150000001716 carbazoles Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 201000006675 intestinal schistosomiasis Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- OPXLLQIJSORQAM-UHFFFAOYSA-N mebendazole Chemical compound C=1C=C2NC(NC(=O)OC)=NC2=CC=1C(=O)C1=CC=CC=C1 OPXLLQIJSORQAM-UHFFFAOYSA-N 0.000 description 1
- 230000004630 mental health Effects 0.000 description 1
- 210000001758 mesenteric vein Anatomy 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 208000004441 taeniasis Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- 208000003982 trichinellosis Diseases 0.000 description 1
- 201000007588 trichinosis Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 206010048282 zoonosis Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一类含氮杂环氨基醇类化合物的抗寄生虫用途。研究结果表明，此类化合物对于血吸虫和包虫等具有明显的杀灭和抑制作用。本发明为治疗血吸虫病和包虫病先导化合物的发现提供了依据，在此基础上进行的药物设计和优化将会丰富寄生虫病治疗方法。
Description
技术领域
本发明涉及一类含氮杂环氨基醇(醇胺)类化合物在医药方面的新用途，更具体地涉及含氮杂环氨基醇(醇胺)类化合物在制备抗寄生虫药物中的应用。
背景技术
我国的寄生虫种类繁多，可感染人的寄生虫约有229种。1988-1992年全国人体寄生虫分布调查报告显示，我国寄生虫感染率为62.63％，感染人数达7.08亿。近年来，随着寄生虫病防控力度的加强以及人民生活水平和卫生条件的改善，寄生虫病的防治在我国取得了巨大的成绩，但是目前仍面临严峻的挑战：如国际交流日益频繁和疟原虫抗药株的存在为疟疾防治添加了新的难度；肠道寄生虫的感染仍十分严重，钩虫、蛔虫、鞭虫的感染人数分别为1.94、5.31和1.12亿；组织内寄生虫病如旋毛虫病、囊虫病、包虫病等在西南、西北地区是常见和多发病种；随着人民生活水平的提高和一些不良饮食习惯的存在，食源性寄生虫病的种类和发病人数也在不断增加。
棘球蚴病俗称包虫病，是全球分布的重要人畜共患疾病之一，严重危害人民健康并且给畜牧业带来巨大的经济损失。据不完全统计，我国包虫病患者高达60～70万，受威胁人群约为达6600万以上。包虫病在患者体内发展缓慢，主要产生占位性病变，使患者丧失劳动能力，对患者的身心健康造成严重的损害。尤其是泡球蚴病，死亡率高，有“寄生虫肿瘤”和“第二癌症”之称。但是，目前治疗包虫病仅有甲苯达唑和阿苯达唑两个药物，且这些药物的治愈率仅为30％左右。亟待找到新的有效替代药物，最终达到提高药物治疗效果，减轻患者疾病痛苦的目标。
血吸虫病仍是目前一些发展中国家，特别是撒哈拉以南非洲地区的一个重要的公共卫生问题。据估计全球有2亿以上的人感染血吸虫，其中1.2亿人有临床症状。血吸虫的主要病理损伤是虫卵肉芽肿所导致的肝脏纤维化。吡喹酮是血吸虫治疗的唯一药物且疗效较好，但是在一些地区已经出现了吡喹酮的抗药性。为了丰富血吸虫的治疗手段，亟需寻到新的治疗药物。
发明内容
发明人在前期实验研究基础上发现具有如下结构特征的化合物对寄生虫具有一定的药理作用：同时具有取代或未取代的氨基和取代或未取代的羟基；N原子和O原子之间间隔1-3个碳原子；以及至少一个N原子以杂环或稠杂环存在。因此，对具有上述结构特征的一系列化合物进行了研究，结果发现该类化合物具有显著的体外抗血吸虫和棘球蚴的活性，从而完成本发明。
本发明提供了以下式(I)或式(II)所示杂环氨基醇(醇胺)类化合物在抗寄生虫方面的用途。
其中，n＝0-2；R选自下组：氢、直链或支链的C1-C8烷基、卤素取代的直连或支链C1-C8烷基、烷氧基或烷硫基、C5-C6环、芳环、芳香杂环和稠杂环、芳氧基和芳硫基；R1和R2和与它们相连的N原子组成取自下组的杂环、取代杂环或取代稠杂环基：吡咯基、四氢吡咯基、咪唑基、哌嗪基、哌啶基、吗啉基、氢化喹啉基、咔唑基、嘌呤基和吲哚基；R3和R4选自：氢、直链或支链的C1-C5 烷基、卤代的直链或支链的C 1-C5烷基；或R3和R4和与它们相连的N原子组成取自下组的杂环、取代杂环或取代稠杂环基：吡咯基、四氢吡咯基、咪唑基、哌嗪基、哌啶基、吗啉基、氢化喹啉基、咔唑基、嘌呤基和吲哚基。
例如，式(I)或式(II)所示杂环氨基醇类化合物可以是如下式I-A、式I-B、式I-C或式II-A化合物：
更具体地，举例如下：
一、I-A结构举例
1.当式I-A中R1、R2与氮原子组成取代哌嗪基时，式I化合物为哌嗪氨基醇类化合物，结构式如下：
式中，X为亚甲基或选自氧、硫的杂原子；R5选自：直链或支链的C1-C5烷基，卤代直链或支链的C1-C5烷基，取代杂环、取代稠杂环、取代苯、取代稠环芳基、取代苯甲基等；R6选自、直链或支链的C1-C5烷基、卤代的直链或支链C1-C5烷基取代苯基、取代苯并吡咯基、取代哌啶基、取代哌嗪基、取代嘧啶基或取代吡啶基。
2.当式I-A中R1、R2与氮原子组成取代哌啶基时，式I化合 物为哌啶氨基醇类化合物，结构式如下：
式中，X为亚甲基或选自氧、硫的杂原子；R5选自取代杂环、取代稠杂环、取代苯、取代苯烷基、取代巯基、取代烷氧基、取代芳氧基、芳环或杂环取代的氨基；R6选自直链或支链的C1-C5烷基、卤代的直链或支链C1-C5烷基、取代苯基、取代苯并吡咯基、取代哌啶基、取代哌嗪基、取代嘧啶基或者取代吡啶基。
二、II-A结构举例
1.当式II-A中R1、R2与氮原子组成取代咔唑基时，式II化合物为咔唑氨基醇类化合物：
式中，
R3和R4选自：氢、直链或支链的C1-C5烷基、卤代的直链或支链的C1-C5烷基；或R3和R4和与它们相连的N原子组成取自下组的杂环、取代杂环或取代稠杂环基：吡咯基、四氢吡咯基、咪唑基、哌嗪基、哌啶基、吗啉基、氢化喹啉基、咔唑基、嘌呤基和吲哚基。
2.当式II-A中，R1、R2与氮原子组成取代吲哚基时，式II化合物为吲哚氨基醇类化合物，结构式如下：
R3和R4选自：氢、直链或支链的C1-C5烷基、卤代的直链或支链的C1-C5烷基；或R3和R4和与它们相连的N原子组成取自下组的杂环、取代杂环或取代稠杂环基：吡咯基、四氢吡咯基、咪唑基、哌嗪基、哌啶基、吗啉基、氢化喹啉基、咔唑基、嘌呤基和吲哚基。；R5、R6选自：氢、卤素、羟基、硝基、氨基、直链或支链的C1-C5烷基、卤代的直链或支链的C1-C5烷基。
3.当式II-A中，R1、R2与氮原子组成取代嘌呤环时，式II化合物为嘌呤氨基醇类化合物，结构式如下：
R3和R4选自：氢、直链或支链的C1-C5烷基、卤代的直链或支链的C1-C5烷基；或R3和R4和与它们相连的N原子组成取自下组的杂环、取代杂环或取代稠杂环基：吡咯基、四氢吡咯基、咪唑基、哌嗪基、哌啶基、吗啉基、氢化喹啉基、咔唑基、嘌呤基和吲哚基。R8、R9选自：氢、直链或支链的C1-C5烷基、卤代的直链或支链的C1-C5烷基、芳基、苄基或杂环基取代的亚甲基；或R8和R9与相连的氮原子组成选自下组的含氮杂环基：吡咯基、四氢吡咯基、咪唑基、哌啶基、吗啉基和哌嗪基。
上述化合物至今未见其具有抗血吸虫和包虫活性的报道。
本发明利用上述化合物作为活性成分，单独或组合使用或与其他药物配合制备成在临床上可以使用的各种不同剂型的用于寄生虫 病治疗的药物。
在治疗寄生虫病中，用本发明的化合物，以常规的制剂工艺，单独使用或与其他药物配合制备成在临床上可以使用的各种不同剂型的药物。如：注射剂、散剂、丸剂、胶囊剂、片剂、微囊剂、软胶囊剂、膜剂、栓剂、膏剂、酊剂、冲剂、气雾剂等各种制剂。
药理实验结果表明，本发明的化合物具有显著地杀灭血吸虫和棘球蚴的作用，提示可以用于抗寄生虫治疗。
具体实施方式
实施例1体外杀灭血吸虫作用效果
实验材料及实验方法
血吸虫的收集：日本血吸虫尾蚴感染昆明小鼠(SPF级)35d后,用冰冷的亨氏盐平衡液将寄生于小鼠肠系膜静脉的日本血吸虫成虫冲出体外并置于亨氏盐平衡液中备用。
血吸虫的体外培养：用RPMI1640培养基加10％的小牛血清(热灭活)、青霉素100u/mL、链霉素100u/mL和二性霉素2.5μg/mL等为培养液。12孔板培养血吸虫，每孔容量为4mL，培养合抱雌、雄虫4对。
给药方式：药物以二甲基亚砜配置成一定浓度的药液，吸取一定体积的药液加入培养皿中，使培养皿中的药物浓度为20μg/ml、10μg/ml和5μg/ml。
观察指标：死亡率100％
实验结果
化合物1-12在20μg/ml浓度下，体外对日本血吸虫均有100％的杀灭活性。其中化合物11和化合物12在10μg/ml和5μg/ml的浓度下均有100％的杀灭活性。
表1氨基醇类化合物体外杀灭日本血吸虫活性
实施例2体外杀灭棘球蚴原头节作用效果
实验材料及实验方法
棘球蚴原头节的采集：在流行区采集棘球蚴囊，吸取含有原头节的囊液，将此囊液倾至容量为50ml的圆底离心管中，自然沉淀10min后，去上清液，随后用生理盐水将含原头节的沉淀物洗涤5-8次，每次10min。将一定量的含青霉素钠盐50万u/L的生理盐水加至洗涤完毕的原头节中，混悬均匀后吸取10-20μl，在倒置显微镜下计数，并观察原头节存活状况。
棘球蚴原头节的体外培养：培养器皿可用24孔板，每孔加培养基1.6ml及待试药物溶液0.2ml。每孔加入定量原头节，然后置于5％CO2、相对湿度为95％的37℃温箱培养。
给药方式：药物以二甲基亚砜配置成一定浓度的药液，吸取一定体积的药液加入培养皿中，使培养皿中的药物浓度为待测定浓度。
观察指标：给药后72小时用台盼蓝染液对原头节进行染色，死亡的原头节会被染成深蓝色，计数进行原头节活性计算。
原头节活性＝活的原头节数目/原头节总数×100％。
实验结果：化合物8及化合物13-23均对棘球蚴原头节具有一定程度的杀灭作用，在20μg/ml浓度下，原头节死亡率结果如表2所示。
实施例3体外对棘球蚴生发层细胞的抑制效果
实验材料及实验方法
继发棘球蚴小鼠模型的建立：在流行区采集棘球蚴囊，取出并用HBSS清洗其中的原头节。接种时将原头节稀释至4000只/ml备用。用1ml注射器吸取原头节悬液0.5ml(2000只原头节)，用75％酒精擦涂小鼠皮肤，将原头节注入小鼠腹腔内。该模型建立8-10月后可用于后续实验。
生发层细胞的分离：剖检上述小鼠，取出其体内的棘球蚴囊，用生理盐水清洗囊3-5次后将其剪碎后加入0.25％胰酶，37℃消化 10-30分钟，取上清液500rpm离心5分钟后弃去上清，用1640培养基制备细胞悬液。
给药方式：药物以二甲基亚砜配置成一定浓度的药液，吸取一定体积的药液加入培养皿中，使培养皿中的药物浓度为20μg/ml、10μg/ml和5μg/ml。
细胞活性检测：分别于给药后72小时后弃去培养基，加入5mg/ml的MTT溶液50μl，置于37℃，2h后加入100μl DMSO，待甲臜全部溶解后用紫外分光光度计测量570nm波长下的吸光度。计算该待测药物对生发层细胞活性的抑制率：细胞活性抑制率＝[(对照度吸光度值-调零孔吸光度值)-(药物组吸光度值-调零孔吸光度值)]/(对照度吸光度值-调零孔吸光度值)×100％。
实验结果
化合物8及化合物13-23均对棘球蚴生发层细胞的生长具有一定的抑制作用，在20μg/ml浓度下的抑制率及半数抑制浓度IC50如表2所示。
表2氨基醇类化合物对包虫的体外活性试验
*N/A未测及。
Claims (6)
1.式(I)或式(II)所示氨基醇类化合物在制备抗寄生虫药物中的用途
其中，n＝0-2；R选自下组：氢、直链或支链的C1-C8烷基、卤素取代的直连或支链C1-C8烷基、烷氧基或烷硫基、C5-C6环、芳环、芳香杂环和稠杂环、芳氧基和芳硫基；R1、R2和相连的N原子组成取自下组的杂环、取代杂环或取代稠杂环基：吡咯基、四氢吡咯基、咪唑基、哌嗪基、哌啶基、吗啉基、氢化喹啉基、咔唑基、嘌呤基和吲哚基；R3和R4选自：氢、直链或支链的C1-C5烷基、卤代的直链或支链的C1-C5烷基、或R3和R4与相连的N原子组成取自下组的杂环、取代杂环或取代稠杂环基：吡咯基、四氢吡咯基、咪唑基、哌嗪基、哌啶基、吗啉基、氢化喹啉基、咔唑基、嘌呤基和吲哚基。
2.如权利要求1所述的应用，其中所述式(I)或式(II)所示氨基醇类化合物选自如下式I-A、式I-B、式I-C或式II-A化合物：
其中，R选自下组：氢、直链或支链的C1-C8烷基、卤素取 代的直连或支链C1-C8烷基、烷氧基或烷硫基、C5-C6环、芳环、芳香杂环和稠杂环、芳氧基和芳硫基；R1、R2和相连的N原子组成取自下组的杂环、取代杂环或取代稠杂环基：吡咯基、四氢吡咯基、咪唑基、哌嗪基、哌啶基、吗啉基、氢化喹啉基、咔唑基、嘌呤基和吲哚基；R3和R4选自：氢、直链或支链的C1-C5烷基、卤代的直链或支链的C1-C5烷基、或R3和R4和与它们相连的N原子组成取自下组的杂环、取代杂环或取代稠杂环基：吡咯基、四氢吡咯基、咪唑基、哌嗪基、哌啶基、吗啉基、氢化喹啉基、咔唑基、嘌呤基和吲哚基。
3.如权利要求2所述的应用，其中所述式I-A化合物选自式I-A1所示哌嗪氨基醇类化合物和式I-A2所示哌啶氨基醇类化合物
式中，X为亚甲基或选自氧、硫的杂原子；式中，R6选自下组：氢、直链或支链的C1-C5烷基、卤代的直链或支链的C1-C5烷基、取代芳基或苄基、杂环基取代的亚甲基、取代杂环或稠杂环基。式I-A1中，R5选自下组：氢、直链或支链的C1-C5烷基、卤代的直链或支链的C1-C5烷基、取代芳基或苄基、杂环基取代的亚甲基、取代杂环或稠杂环基。式I-A2中，R5选自下组：取代杂环、取代稠杂环、取代苯、取代苯烷基、取代巯基、取代烷氧基、取代芳氧基、芳环或杂环取代的氨基。
4.如权利要求2所述的应用，其中所述式II-A化合物选自式II-A1所示咔唑氨基醇类化合物、式II-A2所示吲哚氨基醇类化合物和式II-A3所示嘌呤氨基醇类化合物
式中，R3和R4选自：氢、直链或支链的C1-C5烷基、卤代的直链或支链的C1-C5烷基、或R3和R4和与它们相连的N原子组成取自下组的杂环、取代杂环或取代稠杂环基：吡咯基、四氢吡咯基、咪唑基、哌嗪基、哌啶基、吗啉基、氢化喹啉基、咔唑基、嘌呤基和吲哚基。R8、R9选自：氢、直链或支链的C1-C5烷基、卤代的直链或支链的C1-C5烷基、芳基、苄基或杂环基取代的亚甲基；或R8和R9与相连的氮原子组成选自下组的含氮杂环基：吡咯基、四氢吡咯基、咪唑基、哌啶基、吗啉基和哌嗪基。
5.如权利要求1所述的应用，其中所述抗寄生虫药物为抗血吸虫药或抗包虫药。
6.如权利要求5所述的应用，其中所述抗包虫药包括抗棘球蚴原头节的药物和抗棘球蚴生发层细胞的药物。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510829261.9A CN106727581A (zh) | 2015-11-25 | 2015-11-25 | 一类氨基醇类化合物的抗寄生虫用途 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510829261.9A CN106727581A (zh) | 2015-11-25 | 2015-11-25 | 一类氨基醇类化合物的抗寄生虫用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106727581A true CN106727581A (zh) | 2017-05-31 |
Family
ID=58963415
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510829261.9A Pending CN106727581A (zh) | 2015-11-25 | 2015-11-25 | 一类氨基醇类化合物的抗寄生虫用途 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106727581A (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115737648A (zh) * | 2021-09-03 | 2023-03-07 | 中国疾病预防控制中心寄生虫病预防控制所(国家热带病研究中心) | 二苯甲基哌嗪类化合物在治疗包虫病中的应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106518750A (zh) * | 2015-09-15 | 2017-03-22 | 中国疾病预防控制中心寄生虫病预防控制所 | 咔唑氨基醇类化合物及其制备方法和抗寄生虫病的用途 |
-
2015
- 2015-11-25 CN CN201510829261.9A patent/CN106727581A/zh active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106518750A (zh) * | 2015-09-15 | 2017-03-22 | 中国疾病预防控制中心寄生虫病预防控制所 | 咔唑氨基醇类化合物及其制备方法和抗寄生虫病的用途 |
Non-Patent Citations (1)
| Title |
|---|
| JEROME MOLETTE，ET AL.: "Identification and Optimization of an Aminoalcohol-Carbazole Series with Antimalarial Properties", 《ACS MEDICAL CHEMITRY LETTERS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115737648A (zh) * | 2021-09-03 | 2023-03-07 | 中国疾病预防控制中心寄生虫病预防控制所(国家热带病研究中心) | 二苯甲基哌嗪类化合物在治疗包虫病中的应用 |
| CN115737648B (zh) * | 2021-09-03 | 2024-06-25 | 中国疾病预防控制中心寄生虫病预防控制所(国家热带病研究中心) | 二苯甲基哌嗪类化合物在治疗包虫病中的应用 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102497873A (zh) | 用于增加生存年限和健康年限的组合物和方法 | |
| RU2554497C2 (ru) | Композиция для инъекций, содержащая гидроксихлорохин, для местного применения при лечении рака | |
| CN104510747B (zh) | 一种环烯醚萜苷的药物新用途 | |
| Muhedier et al. | Tacrolimus, a rapamycin target protein inhibitor, exerts anti-cystic echinococcosis effects both in vitro and in vivo | |
| Shu-Hua et al. | Schistosoma japonicum: effect of artemether on glutathione S-transferase and superoxide dismutase | |
| CN101965185A (zh) | 茶多酚在制备预防或治疗肿瘤药物中的应用 | |
| CN106727581A (zh) | 一类氨基醇类化合物的抗寄生虫用途 | |
| CN103142683B (zh) | 用于治疗奶牛乳腺炎和子宫内膜炎的含有苦豆子总碱的中药灌注液及其制备方法 | |
| CN102048727A (zh) | 芒柄花黄素在制备抑制血管生成药物中的应用 | |
| CN102166205A (zh) | 丹皮酚及其衍生物的医药新用途 | |
| CN104257656B (zh) | 一种协同增强抑制肿瘤生长的药物组合物 | |
| CN101031295B (zh) | 原生动物感染病的预防或治疗用药物组合物 | |
| CN102813914B (zh) | 一种用于治疗或预防脑血管及相关疾病的药物组合物 | |
| CN102335171B (zh) | 一类n-(2-噻唑)苯甲酰胺衍生物的应用 | |
| CN114903908A (zh) | 甘露糖抑制细胞焦亡减轻化疗药物毒副作用的应用 | |
| CN102349907B (zh) | 包含西洛他唑的治疗精神分裂症药物 | |
| CN106074564B (zh) | 熊果酸在制备抗包虫药物中的应用 | |
| CN106176747B (zh) | 他克林在制备治疗包虫病药物中的应用 | |
| CN102836152B (zh) | 酸浆苦素b在制备治疗和/或预防血吸虫病药物中的应用 | |
| CN106344609A (zh) | 臭氧化油在神经系统疾病中的防治应用 | |
| CN102058579B (zh) | 去氢木香内酯在制备抑制血管生成药物中的应用 | |
| CN110051734A (zh) | 一种抗结肠炎相关性结肠癌的药物组合物及其应用 | |
| Mitsui et al. | In vitro effect of current antimalarial drugs on the survival of paired Schistosoma mansoni adult worms and their egg production. | |
| CN103768222B (zh) | 一种治疗阿尔茨海默病的药物组合物及其制备方法和应用 | |
| Jong et al. | Travel medicine problems encountered in emergency departments |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhang Haobing Inventor after: Wei Yufen Inventor after: Jiang Bin Inventor after: Xu Lili Inventor after: Zheng Qi Inventor after: Huo Lele Inventor after: Chen Ying Inventor after: Liu Ni Inventor after: Tu Zhen Inventor after: Zhao Yuning Inventor after: Liu Congshan Inventor after: Hu Wei Inventor after: Xue Jian Inventor after: Ju Chuan Inventor after: Duan Liping Inventor after: Tao Yi Inventor after: Yao Junmin Inventor after: Wang Weisi Inventor before: Zhang Haobing Inventor before: Zheng Qi Inventor before: Huo Lele Inventor before: Tu Zhen Inventor before: Zhao Yuning Inventor before: Chen Ying Inventor before: Liu Ni Inventor before: Liu Congshan Inventor before: Xue Jian Inventor before: Duan Liping Inventor before: Tao Yi Inventor before: Yao Junmin Inventor before: Wang Weisi Inventor before: Wei Yufen Inventor before: Xu Lili |
|
| CB03 | Change of inventor or designer information | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170531 |
|
| RJ01 | Rejection of invention patent application after publication |