KR100759144B1 - 1,2,4-트리옥솔란 항말라리아제 - Google Patents
1,2,4-트리옥솔란 항말라리아제 Download PDFInfo
- Publication number
- KR100759144B1 KR100759144B1 KR1020037016719A KR20037016719A KR100759144B1 KR 100759144 B1 KR100759144 B1 KR 100759144B1 KR 1020037016719 A KR1020037016719 A KR 1020037016719A KR 20037016719 A KR20037016719 A KR 20037016719A KR 100759144 B1 KR100759144 B1 KR 100759144B1
- Authority
- KR
- South Korea
- Prior art keywords
- spiro
- adamantane
- decane
- trioxaspiro
- cis
- 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.)
- Expired - Lifetime
Links
- RZYIPLSVRHWROD-UHFFFAOYSA-N 1,2,4-trioxolane Chemical compound C1OCOO1 RZYIPLSVRHWROD-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 239000003430 antimalarial agent Substances 0.000 title description 15
- 230000000078 anti-malarial effect Effects 0.000 title description 10
- MAAKQSASDHJHIR-UHFFFAOYSA-N trioxolane Chemical group C1COOO1 MAAKQSASDHJHIR-UHFFFAOYSA-N 0.000 claims abstract description 325
- 238000000034 method Methods 0.000 claims abstract description 141
- 201000004792 malaria Diseases 0.000 claims abstract description 54
- 150000001875 compounds Chemical class 0.000 claims abstract description 46
- 125000003003 spiro group Chemical group 0.000 claims abstract description 34
- 201000004409 schistosomiasis Diseases 0.000 claims abstract description 10
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 9
- 201000011510 cancer Diseases 0.000 claims abstract description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 615
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 586
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims description 492
- 239000000203 mixture Substances 0.000 claims description 236
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 73
- -1 Oxaspiro [4.5] decane mesylate Chemical compound 0.000 claims description 67
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 54
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 49
- OYKIERKRPUDEIV-UHFFFAOYSA-N decane;hydrochloride Chemical compound Cl.CCCCCCCCCC OYKIERKRPUDEIV-UHFFFAOYSA-N 0.000 claims description 32
- 150000002576 ketones Chemical class 0.000 claims description 29
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 239000001301 oxygen Substances 0.000 claims description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 21
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 20
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 239000011593 sulfur Substances 0.000 claims description 19
- YCOZIPAWZNQLMR-UHFFFAOYSA-N pentadecane Chemical compound CCCCCCCCCCCCCCC YCOZIPAWZNQLMR-UHFFFAOYSA-N 0.000 claims description 16
- 230000002265 prevention Effects 0.000 claims description 16
- 125000002723 alicyclic group Chemical group 0.000 claims description 15
- RNXNMGPFJLESKN-UHFFFAOYSA-N 1-oxaspiro[4.5]decane Chemical compound C1CCOC21CCCCC2 RNXNMGPFJLESKN-UHFFFAOYSA-N 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- NAUWDMTWMDTGJV-UHFFFAOYSA-N CS(O)(=O)=O.CCCCCCCCCC Chemical compound CS(O)(=O)=O.CCCCCCCCCC NAUWDMTWMDTGJV-UHFFFAOYSA-N 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 9
- CTDQAGUNKPRERK-UHFFFAOYSA-N spirodecane Chemical compound C1CCCC21CCCCC2 CTDQAGUNKPRERK-UHFFFAOYSA-N 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 150000001299 aldehydes Chemical class 0.000 claims description 7
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 7
- 150000001408 amides Chemical class 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- CPEWRRZKGWVYIZ-UHFFFAOYSA-N decane;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCC.OC(=O)CC(O)(C(O)=O)CC(O)=O CPEWRRZKGWVYIZ-UHFFFAOYSA-N 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 6
- 125000000524 functional group Chemical group 0.000 claims description 6
- 150000002596 lactones Chemical class 0.000 claims description 6
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 6
- 150000002923 oximes Chemical class 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 5
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims description 5
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 5
- 229910052744 lithium Inorganic materials 0.000 claims description 4
- 229940124530 sulfonamide Drugs 0.000 claims description 4
- 150000003456 sulfonamides Chemical class 0.000 claims description 4
- 150000003457 sulfones Chemical class 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 150000007857 hydrazones Chemical class 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 150000007659 semicarbazones Chemical class 0.000 claims description 3
- VZOUNANDPPKHBS-UHFFFAOYSA-N chembl462188 Chemical group C1CCCCC21OC1(C3CC4CC(C3)CC1C4)OO2 VZOUNANDPPKHBS-UHFFFAOYSA-N 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 125000005543 phthalimide group Chemical group 0.000 claims description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims 6
- 238000010511 deprotection reaction Methods 0.000 claims 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims 4
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 3
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 3
- 239000004202 carbamide Substances 0.000 claims 3
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims 3
- 230000003301 hydrolyzing effect Effects 0.000 claims 3
- 150000001241 acetals Chemical class 0.000 claims 2
- 230000000069 prophylactic effect Effects 0.000 claims 2
- WFJFGMLKAISFOZ-UHFFFAOYSA-N 1-amino-3-iminourea Chemical group NN=C(O)N=N WFJFGMLKAISFOZ-UHFFFAOYSA-N 0.000 claims 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 1
- 150000002009 diols Chemical class 0.000 claims 1
- 230000035876 healing Effects 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 239000007800 oxidant agent Substances 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 150000003509 tertiary alcohols Chemical class 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 244000045947 parasite Species 0.000 abstract description 19
- BLUAFEHZUWYNDE-NNWCWBAJSA-N artemisinin Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-NNWCWBAJSA-N 0.000 abstract description 12
- 229930101531 artemisinin Natural products 0.000 abstract description 11
- 229960004191 artemisinin Drugs 0.000 abstract description 10
- 231100000252 nontoxic Toxicity 0.000 abstract description 2
- 230000003000 nontoxic effect Effects 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- 239000007787 solid Substances 0.000 description 307
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 298
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 294
- 239000000243 solution Substances 0.000 description 288
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 200
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 187
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 157
- 239000012043 crude product Substances 0.000 description 156
- 238000003818 flash chromatography Methods 0.000 description 145
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 144
- 239000000741 silica gel Substances 0.000 description 141
- 229910002027 silica gel Inorganic materials 0.000 description 141
- 238000004458 analytical method Methods 0.000 description 140
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 105
- COPCAFIJNXYIDM-UHFFFAOYSA-N n-methoxyadamantan-2-imine Chemical compound C1C(C2)CC3CC1C(=NOC)C2C3 COPCAFIJNXYIDM-UHFFFAOYSA-N 0.000 description 88
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 83
- 239000012267 brine Substances 0.000 description 72
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 72
- 239000003208 petroleum Substances 0.000 description 57
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 53
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 52
- 239000011541 reaction mixture Substances 0.000 description 51
- 239000012044 organic layer Substances 0.000 description 49
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 40
- 238000006243 chemical reaction Methods 0.000 description 37
- 238000001914 filtration Methods 0.000 description 29
- 239000002904 solvent Substances 0.000 description 29
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 25
- 239000000284 extract Substances 0.000 description 25
- 239000002244 precipitate Substances 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 24
- 235000019439 ethyl acetate Nutrition 0.000 description 20
- 239000000706 filtrate Substances 0.000 description 20
- 239000010410 layer Substances 0.000 description 19
- 238000001953 recrystallisation Methods 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- 239000012230 colorless oil Substances 0.000 description 18
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 15
- 238000002425 crystallisation Methods 0.000 description 13
- 230000008025 crystallization Effects 0.000 description 13
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 13
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 10
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 10
- 239000006227 byproduct Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000007429 general method Methods 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 208000015181 infectious disease Diseases 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000000354 decomposition reaction Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- FNGZJMXDYHQKOC-UHFFFAOYSA-N C1C(O)(CC2C3)CC3CC1C2(O1)OOC1(CC1)CCC21OCCO2 Chemical compound C1C(O)(CC2C3)CC3CC1C2(O1)OOC1(CC1)CCC21OCCO2 FNGZJMXDYHQKOC-UHFFFAOYSA-N 0.000 description 6
- 241000157855 Cinchona Species 0.000 description 6
- 241000223960 Plasmodium falciparum Species 0.000 description 6
- IYKFYARMMIESOX-UHFFFAOYSA-N adamantanone Chemical compound C1C(C2)CC3CC1C(=O)C2C3 IYKFYARMMIESOX-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- DCZFGQYXRKMVFG-UHFFFAOYSA-N cyclohexane-1,4-dione Chemical compound O=C1CCC(=O)CC1 DCZFGQYXRKMVFG-UHFFFAOYSA-N 0.000 description 6
- 210000003743 erythrocyte Anatomy 0.000 description 6
- 229940098779 methanesulfonic acid Drugs 0.000 description 6
- LCXYEPLVWLASCI-UHFFFAOYSA-N n-methoxycyclohexanimine Chemical compound CON=C1CCCCC1 LCXYEPLVWLASCI-UHFFFAOYSA-N 0.000 description 6
- 235000001258 Cinchona calisaya Nutrition 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 5
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- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 4
- JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical compound COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 description 4
- KCKZIWSINLBROE-UHFFFAOYSA-N 3,4-dihydro-1h-naphthalen-2-one Chemical compound C1=CC=C2CC(=O)CCC2=C1 KCKZIWSINLBROE-UHFFFAOYSA-N 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
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- 235000011852 gelatine desserts Nutrition 0.000 description 4
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 4
- SXWRTZOXMUOJER-UHFFFAOYSA-N hydron;piperidin-4-one;chloride;hydrate Chemical compound O.Cl.O=C1CCNCC1 SXWRTZOXMUOJER-UHFFFAOYSA-N 0.000 description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
- 229910052742 iron Inorganic materials 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 4
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- WWKVFWLVVSEMCQ-UHFFFAOYSA-N spiro[1h-2-benzofuran-3,1'-cyclohexane] Chemical compound C12=CC=CC=C2COC21CCCCC2 WWKVFWLVVSEMCQ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
- A61P33/12—Schistosomicides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D323/00—Heterocyclic compounds containing more than two oxygen atoms as the only ring hetero atoms
- C07D323/02—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/10—Spiro-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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Dental Preparations (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/886,666 US6486199B1 (en) | 2001-06-21 | 2001-06-21 | Spiro and dispiro 1,2,4-trioxolane antimalarials |
| US09/886,666 | 2001-06-21 | ||
| PCT/US2002/019767 WO2003000676A1 (en) | 2001-06-21 | 2002-06-21 | 1,2,4-trioxolane antimalarials |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20040030697A KR20040030697A (ko) | 2004-04-09 |
| KR100759144B1 true KR100759144B1 (ko) | 2007-09-14 |
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| KR1020037016719A Expired - Lifetime KR100759144B1 (ko) | 2001-06-21 | 2002-06-21 | 1,2,4-트리옥솔란 항말라리아제 |
Country Status (24)
| Country | Link |
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| US (1) | US6486199B1 (https=) |
| EP (1) | EP1414813B1 (https=) |
| JP (1) | JP4303585B2 (https=) |
| KR (1) | KR100759144B1 (https=) |
| CN (1) | CN1545508B (https=) |
| AT (1) | ATE339411T1 (https=) |
| AU (1) | AU2002327183B2 (https=) |
| BR (1) | BRPI0210549B8 (https=) |
| CA (1) | CA2451006C (https=) |
| CY (1) | CY1106214T1 (https=) |
| DE (1) | DE60214733T8 (https=) |
| DK (1) | DK1414813T3 (https=) |
| ES (1) | ES2271323T3 (https=) |
| HU (1) | HUP0400246A3 (https=) |
| IL (1) | IL159474A0 (https=) |
| MX (1) | MXPA03011915A (https=) |
| NO (1) | NO20035721L (https=) |
| PL (1) | PL226418B1 (https=) |
| PT (1) | PT1414813E (https=) |
| RU (1) | RU2271357C2 (https=) |
| SI (1) | SI1414813T1 (https=) |
| UA (1) | UA78709C2 (https=) |
| WO (1) | WO2003000676A1 (https=) |
| YU (1) | YU100703A (https=) |
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| WO2003103592A2 (en) * | 2002-06-06 | 2003-12-18 | University Of Washington | Covalent conjugates between artemisinin-related endoperoxides and iron-carrying proteins and methods of use |
| US6825230B2 (en) * | 2002-06-21 | 2004-11-30 | Medicines For Malaria Venture Mmv | Spiro and dispiro 1,2,4-trixolane antimalarials |
| US20080125441A1 (en) * | 2002-06-21 | 2008-05-29 | Medicines For Malaria Venture Mmv | Spiro and dispiro 1,2,4-trioxolane antimalarials |
| US6906205B2 (en) * | 2002-06-21 | 2005-06-14 | Medicines For Malaria Venture Mmv | Spiro and dispiro 1,2,4-trioxolane antimalarials |
| US7371778B2 (en) * | 2002-06-21 | 2008-05-13 | Medicines For Malaria Venture Mmv | Spiro and dispiro 1,2,4-trioxolane antimalarials |
| FR2862304A1 (fr) * | 2003-11-14 | 2005-05-20 | Centre Nat Rech Scient | Molecules duales racemiques ou achirales contenant un derive peroxydique, leur synthese et leurs applications therapeutiques |
| EP1789380A1 (de) * | 2004-07-23 | 2007-05-30 | Justus-Liebig-Universität Giessen | Aminoadamantan-derivate, verfahren zu ihrer herstellung und ihre verwendung |
| US20060040761A1 (en) * | 2004-08-23 | 2006-02-23 | Sam-Kyu Shin | Scale mark mat for putting practice |
| US8067620B2 (en) | 2005-05-04 | 2011-11-29 | Medicines For Malaria Venture Mmv | Dispiro 1,2,4-trioxolane antimalarials |
| US20090042821A1 (en) * | 2005-05-18 | 2009-02-12 | Arno Appavoo Enose | Stable dosage forms of spiro and dispiro 1,2,4-trioxolane antimalarials |
| WO2007036947A1 (en) * | 2005-09-30 | 2007-04-05 | Ipca Laboratories Limited | Delayed release anti-malarial composition |
| DE602006013668D1 (de) | 2005-10-04 | 2010-05-27 | Director General Defence Res & | Aus gomphostemma niveum isolierte verbindung gegen malaria |
| US20070231300A1 (en) * | 2006-03-28 | 2007-10-04 | Washington, University Of | Covalent conjugates between endoperoxides and transferrin and lactoferrin receptor-binding agents |
| AR060404A1 (es) | 2006-04-11 | 2008-06-11 | Novartis Ag | Compuestos organicos utiles como inhibidores de dipeptidil-peptidasa iv |
| US20090306091A1 (en) * | 2006-05-17 | 2009-12-10 | Vyas Madhavrao Shingatgeri | Antimalarial therapy using a combination of synthetic artemisinin derivative and bisquinoline derivative |
| US8569519B2 (en) * | 2006-05-24 | 2013-10-29 | Ranbaxy Laboratories Limited | Process for the preparation of dispiro 1,2,4-trioxolane antimalarials (OZ277) |
| FR2902100A1 (fr) * | 2006-06-13 | 2007-12-14 | Sanofi Aventis Sa | Molecules duales contenant un derive peroxydique, leur synthese et leurs applications en therapeutique |
| GB0619333D0 (en) * | 2006-09-30 | 2006-11-08 | Univ Liverpool | Dispiro tetraoxane compounds |
| WO2008046109A2 (en) * | 2006-10-13 | 2008-04-17 | University Of Washington | Conjugates of artemisinin-related endoperoxides and hydrazone derivatives for the treatment of cancer |
| FR2924343A1 (fr) * | 2007-12-04 | 2009-06-05 | Palumed Sa | Nouvelles utilisations therapeutiques de molecules duales contenant un derive peroxydique. |
| WO2010001824A1 (ja) | 2008-07-01 | 2010-01-07 | 国立大学法人 岡山大学 | 新規抗住血吸虫剤 |
| WO2010011684A2 (en) | 2008-07-21 | 2010-01-28 | The Regents Of The University Of California | Prodrug and fluoregenic compositions and methods for using the same |
| AP2014007413A0 (en) | 2011-07-14 | 2014-02-28 | Ranbaxy Lab Ltd | Stable dosage forms of arterolane and piperaquine |
| WO2015123595A1 (en) | 2014-02-14 | 2015-08-20 | The Regents Of The University Of California | Cyclic peroxides as prodrugs for selective delivery of agents |
| CA2971763A1 (en) * | 2014-12-23 | 2016-06-30 | Bergenbio Asa | Inhibitors of akt kinase |
| RU2601315C1 (ru) * | 2015-06-10 | 2016-11-10 | Федеральное государственное бюджетное учреждение науки Институт нефтехимии и катализа Российской академии наук | Способ получения пентаоксаспироалканов |
| WO2019005977A1 (en) * | 2017-06-27 | 2019-01-03 | The Regents Of The University Of California | Trioxolane agents |
| CN108424371B (zh) * | 2018-01-19 | 2021-07-16 | 北京理工大学 | 2-(4-氨基环己基)-乙酸乙酯的制备方法 |
| US20210386814A1 (en) * | 2020-05-20 | 2021-12-16 | Amanuel Tesfazion | Methods and compound for the treatment of malaria |
| US20240101584A1 (en) * | 2021-02-01 | 2024-03-28 | Westlake University | Targeted delivery of 1,2,4,5 tetraoxane compounds and their uses |
| CN117085004A (zh) * | 2023-09-27 | 2023-11-21 | 赣南师范大学 | 一种2,6-二苯亚甲基环己酮类似物在制备抗血吸虫药物中的应用 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3621062A (en) | 1966-10-25 | 1971-11-16 | Sterling Drug Inc | 2-(8-cyclohexyloctanoyl or 7-cyclohexylheptanoyl)-1-naphthol |
| US3673222A (en) | 1969-11-26 | 1972-06-27 | Sydney Archer | 2-(8-cyclohexyloctyl or 7-cyclohexylheptyl)-1,4-naphthoquinone and process for preparation and use thereof |
| US3682991A (en) | 1970-10-19 | 1972-08-08 | Sterling Drug Inc | 3,3,5-trimethylcyclohexyl-alkyl-carboxylic acids |
| SU1421743A1 (ru) * | 1987-02-18 | 1988-09-07 | Физико-химический институт им.А.В.Богатского | Способ получени 11-нитро-12- @ (2-метокси)-этокси @ -бензо-9-краун-3 |
| US4916204A (en) | 1987-07-31 | 1990-04-10 | Massachusetts Institute Of Technology | Pure polyanhydride from dicarboxylic acid and coupling agent |
| US4816478A (en) | 1987-08-24 | 1989-03-28 | Thornfeldt Carl R | Treatment of acquired immunodeficiency syndrome |
| US5053342A (en) | 1987-12-24 | 1991-10-01 | Litmus Concepts, Inc. | Fecal occult blood test reagents |
| US5559145A (en) | 1988-06-01 | 1996-09-24 | Oxaco S.A. | 1,2,4-trioxane derivatives |
| US5270344A (en) | 1988-06-24 | 1993-12-14 | Stephen Herman | Method of treating a systemic disorder using trioxolane and diperoxide compounds |
| JP2867529B2 (ja) | 1990-01-22 | 1999-03-08 | 三菱電機株式会社 | 投写型表示装置 |
| US5216175A (en) | 1990-03-23 | 1993-06-01 | Sri International | Antimalarial analogs of artemisinin |
| US5219880A (en) | 1991-03-29 | 1993-06-15 | Dermatologic Research Corporation | Treatment of viral tumors and hemorrhoids with artemisinin and derivatives |
| DE4125201C1 (https=) * | 1991-07-30 | 1992-10-01 | Fraunhofer-Gesellschaft Zur Foerderung Der Angewandten Forschung Ev, 8000 Muenchen, De | |
| US5510356A (en) | 1991-10-03 | 1996-04-23 | University Of Nebraska Board Of Regents | Bisquinolines and processes for their production and use to treat malaria |
| US5171676A (en) | 1991-10-31 | 1992-12-15 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of introducing hydroxyl groups into artemisinin and its derivatives |
| US5430148A (en) | 1992-03-31 | 1995-07-04 | Agouron Pharmaceuticals, Inc. | Antiproliferative quinazolines |
| JP3567990B2 (ja) | 1992-07-28 | 2004-09-22 | ザ、プロクター、エンド、ギャンブル、カンパニー | 架橋陽イオン重合体とアルコキシ化エーテルとを含有する局所用途用医薬組成物 |
| US5721209A (en) | 1995-02-03 | 1998-02-24 | The Regents Of The University Of California | Iron chelator and inhibitor of iron-mediated oxidant injury |
| US5780675A (en) | 1995-04-28 | 1998-07-14 | The University Of New Mexico | Deoxygossylic compounds |
| US5578637A (en) | 1995-05-03 | 1996-11-26 | University Of Washington | Methods of inhibition or killing cancer cells using an endoperoxide |
| US5817692A (en) | 1995-11-22 | 1998-10-06 | The Johns Hopkins University | Endoperoxides useful as antiparasitic agents |
| US5672624A (en) | 1995-11-22 | 1997-09-30 | The Johns Hopkins University | Endoperoxides useful as antiparasitic agents |
| US5932591A (en) | 1996-12-02 | 1999-08-03 | Johns Hopkins University | C3 substituted trioxanes useful as antiparasitic drugs |
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Non-Patent Citations (1)
| Title |
|---|
| J. Org. Chem, Vol. 56, 1991, pp6591-6595 |
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