IE911529A1 - 9-Substituted compounds of¹3Ó,11Ó-Epoxy-3,4,5,5aÓ,6,7,8,8a,9,11,11a-undecahydro-3ß,6Ó,9¹-trimethylfurano[3,4-j][1,2]-benzodioxepin, processes for¹their preparation and their use as antiprotozoal and¹antiviral agents - Google Patents

9-Substituted compounds of¹3Ó,11Ó-Epoxy-3,4,5,5aÓ,6,7,8,8a,9,11,11a-undecahydro-3ß,6Ó,9¹-trimethylfurano[3,4-j][1,2]-benzodioxepin, processes for¹their preparation and their use as antiprotozoal and¹antiviral agents

Info

Publication number: IE911529A1
Authority: IE; Ireland
Prior art keywords: formula; compounds; epoxy; stands; benzodioxepin
Prior art date: 1990-05-07

Application number

IE152991A

Other languages

English (en)

Original Assignee

Hoechst Ag

Priority date (The priority date 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 date listed.)

1990-05-07

Filing date

1991-05-06

Publication date

1991-11-20

1991-05-06 Application filed by Hoechst Ag filed Critical Hoechst Ag

1991-11-20 Publication of IE911529A1 publication Critical patent/IE911529A1/en

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 106
238000002360 preparation method Methods 0.000 title claims description 23
238000000034 method Methods 0.000 title claims description 14
239000003795 chemical substances by application Substances 0.000 title claims description 3
230000000842 anti-protozoal effect Effects 0.000 title description 2
239000003904 antiprotozoal agent Substances 0.000 title description 2
WITJHZRCLVXYCA-UHFFFAOYSA-N 3h-1,2-benzodioxepine Chemical compound C1=CCOOC2=CC=CC=C21 WITJHZRCLVXYCA-UHFFFAOYSA-N 0.000 claims description 37
125000000217 alkyl group Chemical group 0.000 claims description 20
238000011282 treatment Methods 0.000 claims description 19
125000003118 aryl group Chemical group 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 15
-1 trimethylfurano[3,4-j ] [1,2]benzodioxepin Chemical compound 0.000 claims description 13
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 12
125000000547 substituted alkyl group Chemical group 0.000 claims description 11
125000000623 heterocyclic group Chemical group 0.000 claims description 9
125000000304 alkynyl group Chemical group 0.000 claims description 8
125000001424 substituent group Chemical group 0.000 claims description 8
125000003342 alkenyl group Chemical group 0.000 claims description 7
201000004792 malaria Diseases 0.000 claims description 6
150000003839 salts Chemical class 0.000 claims description 6
125000005017 substituted alkenyl group Chemical group 0.000 claims description 5
125000004426 substituted alkynyl group Chemical group 0.000 claims description 5
239000002253 acid Substances 0.000 claims description 4
229960002521 artenimol Drugs 0.000 claims description 4
125000003710 aryl alkyl group Chemical group 0.000 claims description 4
125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
241000700605 Viruses Species 0.000 claims description 3
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
229910052757 nitrogen Inorganic materials 0.000 claims description 3
229910052717 sulfur Inorganic materials 0.000 claims description 3
101100295738 Gallus gallus COR3 gene Proteins 0.000 claims description 2
239000003638 chemical reducing agent Substances 0.000 claims description 2
150000001805 chlorine compounds Chemical class 0.000 claims description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
239000007800 oxidant agent Substances 0.000 claims description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 7
238000004519 manufacturing process Methods 0.000 claims 3
201000010099 disease Diseases 0.000 claims 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
229910052760 oxygen Inorganic materials 0.000 claims 2
238000011321 prophylaxis Methods 0.000 claims 2
BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
230000000078 anti-malarial effect Effects 0.000 abstract description 3
239000003430 antimalarial agent Substances 0.000 abstract description 3
230000000840 anti-viral effect Effects 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
239000003921 oil Substances 0.000 description 36
235000019198 oils Nutrition 0.000 description 36
239000011541 reaction mixture Substances 0.000 description 36
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
239000000047 product Substances 0.000 description 25
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
239000000741 silica gel Substances 0.000 description 20
229910002027 silica gel Inorganic materials 0.000 description 20
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
238000007920 subcutaneous administration Methods 0.000 description 18
229940093499 ethyl acetate Drugs 0.000 description 17
235000019439 ethyl acetate Nutrition 0.000 description 17
239000000243 solution Substances 0.000 description 17
238000003818 flash chromatography Methods 0.000 description 14
239000003960 organic solvent Substances 0.000 description 14
239000003208 petroleum Substances 0.000 description 13
239000002904 solvent Substances 0.000 description 12
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
239000000284 extract Substances 0.000 description 11
239000000203 mixture Substances 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
241000699670 Mus sp. Species 0.000 description 8
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 7
230000000694 effects Effects 0.000 description 7
208000015181 infectious disease Diseases 0.000 description 7
BPHQBZSCFFLZKD-UHFFFAOYSA-N 3,13,14-trioxatricyclo[7.5.0.01,5]tetradeca-4,6,8,10-tetraene Chemical class C1=CCOOC23COC=C3C=CC=C21 BPHQBZSCFFLZKD-UHFFFAOYSA-N 0.000 description 6
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
150000002431 hydrogen Chemical class 0.000 description 6
229940073584 methylene chloride Drugs 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
JIZALCXEGHXRGJ-UHFFFAOYSA-N 3H-1,2-benzodioxepine-9-carboxylic acid Chemical compound O1OCC=CC2=C1C(=CC=C2)C(=O)O JIZALCXEGHXRGJ-UHFFFAOYSA-N 0.000 description 5
239000000725 suspension Substances 0.000 description 5
WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
229950005499 carbon tetrachloride Drugs 0.000 description 4
229960003677 chloroquine Drugs 0.000 description 4
WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 4
238000001816 cooling Methods 0.000 description 4
239000002274 desiccant Substances 0.000 description 4
229910052736 halogen Inorganic materials 0.000 description 4
150000002367 halogens Chemical class 0.000 description 4
SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 4
WADSJYLPJPTMLN-UHFFFAOYSA-N 3-(cycloundecen-1-yl)-1,2-diazacycloundec-2-ene Chemical compound C1CCCCCCCCC=C1C1=NNCCCCCCCC1 WADSJYLPJPTMLN-UHFFFAOYSA-N 0.000 description 3
IGRKCXLMEOBIEZ-UHFFFAOYSA-N 3H-1,2-benzodioxepine-9-carbaldehyde Chemical compound O1OCC=CC2=C1C(=CC=C2)C=O IGRKCXLMEOBIEZ-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000013543 active substance Substances 0.000 description 3
BJDCWCLMFKKGEE-ISOSDAIHSA-N artenimol Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-ISOSDAIHSA-N 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
150000001722 carbon compounds Chemical class 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
238000002512 chemotherapy Methods 0.000 description 3
229930016266 dihydroartemisinin Natural products 0.000 description 3
239000003814 drug Substances 0.000 description 3
229940079593 drug Drugs 0.000 description 3
238000001035 drying Methods 0.000 description 3
238000010828 elution Methods 0.000 description 3
238000000605 extraction Methods 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
150000008282 halocarbons Chemical class 0.000 description 3
239000010410 layer Substances 0.000 description 3
230000003287 optical effect Effects 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
230000009385 viral infection Effects 0.000 description 3
238000005406 washing Methods 0.000 description 3
MZZVFXMTZTVUFO-UHFFFAOYSA-N 1-chloro-4-isothiocyanatobenzene Chemical compound ClC1=CC=C(N=C=S)C=C1 MZZVFXMTZTVUFO-UHFFFAOYSA-N 0.000 description 2
SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
241000725303 Human immunodeficiency virus Species 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
239000007832 Na2SO4 Substances 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
208000036142 Viral infection Diseases 0.000 description 2
PRDBLLIPPDOICK-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]methanamine Chemical compound NCC1=CC=C(C(F)(F)F)C=C1 PRDBLLIPPDOICK-UHFFFAOYSA-N 0.000 description 2
239000003463 adsorbent Substances 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
239000008112 carboxymethyl-cellulose Substances 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
239000002026 chloroform extract Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
239000008298 dragée Substances 0.000 description 2
239000012259 ether extract Substances 0.000 description 2
239000002024 ethyl acetate extract Substances 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
238000001914 filtration Methods 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
238000007912 intraperitoneal administration Methods 0.000 description 2
208000032839 leukemia Diseases 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 2
238000012552 review Methods 0.000 description 2
229910001961 silver nitrate Inorganic materials 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
LKZOLNNUWQQMDP-UHFFFAOYSA-M triphenyl-[[4-(trifluoromethyl)phenyl]methyl]phosphanium;bromide Chemical compound [Br-].C1=CC(C(F)(F)F)=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 LKZOLNNUWQQMDP-UHFFFAOYSA-M 0.000 description 2
125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
125000005999 2-bromoethyl group Chemical group 0.000 description 1
125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
241000224453 Mycoplasma coccoides Species 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
241000224017 Plasmodium berghei Species 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
206010037075 Protozoal infections Diseases 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
239000012670 alkaline solution Substances 0.000 description 1
125000003302 alkenyloxy group Chemical group 0.000 description 1
125000005599 alkyl carboxylate group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
125000005133 alkynyloxy group Chemical group 0.000 description 1
239000003443 antiviral agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
238000011888 autopsy Methods 0.000 description 1
238000012925 biological evaluation Methods 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
238000009395 breeding Methods 0.000 description 1
230000001488 breeding effect Effects 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
239000000872 buffer Substances 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000004359 castor oil Substances 0.000 description 1
235000019438 castor oil Nutrition 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
229960001701 chloroform Drugs 0.000 description 1
125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
229940125890 compound Ia Drugs 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
239000002027 dichloromethane extract Substances 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
210000003743 erythrocyte Anatomy 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
235000013305 food Nutrition 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
239000005457 ice water Substances 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
238000007918 intramuscular administration Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000002540 isothiocyanates Chemical class 0.000 description 1
231100000518 lethal Toxicity 0.000 description 1
230000001665 lethal effect Effects 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
244000045947 parasite Species 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
239000000843 powder Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000007787 solid Substances 0.000 description 1
210000000952 spleen Anatomy 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012360 testing method Methods 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
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 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1

Classifications

- 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
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- 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
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/20—Spiro-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Virology (AREA)
Tropical Medicine & Parasitology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

IE152991A 1990-05-07 1991-05-06 9-Substituted compounds of¹3Ó,11Ó-Epoxy-3,4,5,5aÓ,6,7,8,8a,9,11,11a-undecahydro-3ß,6Ó,9¹-trimethylfurano[3,4-j][1,2]-benzodioxepin, processes for¹their preparation and their use as antiprotozoal and¹antiviral agents IE911529A1 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP90108580		1990-05-07

Publications (1)

Publication Number	Publication Date
IE911529A1 true IE911529A1 (en)	1991-11-20

Family

ID=8203955

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IE152991A IE911529A1 (en)	1990-05-07	1991-05-06	9-Substituted compounds of¹3Ó,11Ó-Epoxy-3,4,5,5aÓ,6,7,8,8a,9,11,11a-undecahydro-3ß,6Ó,9¹-trimethylfurano[3,4-j][1,2]-benzodioxepin, processes for¹their preparation and their use as antiprotozoal and¹antiviral agents

Country Status (11)

Country	Link
US (1)	US5246930A (2)
EP (1)	EP0456149A1 (2)
JP (1)	JPH04225983A (2)
KR (1)	KR920005722A (2)
AU (1)	AU639095B2 (2)
BR (1)	BR9101822A (2)
IE (1)	IE911529A1 (2)
IL (1)	IL98071A0 (2)
PT (1)	PT97577A (2)
TW (1)	TW198722B (2)
ZA (1)	ZA913393B (2)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH07500325A (ja) *	1991-10-14	1995-01-12	ザユニバーシティオブシドニー	環状パーオキシアセタール化合物
HK1040709B (zh) *	1998-07-14	2004-06-25	香港科技大学	抗寄生虫青蒿素衍生物，制备方法及组合物和用途
IN191696B (2) *	1999-02-12	2003-12-20	Council Scient Ind Res
US7842719B2 (en) *	2002-10-31	2010-11-30	Kemin Foods, L.C.	Use of endoperoxides for the treatment of infections caused by flaviviridae, including hepatitis C, bovine viral diarrhea and classical swine fever virus
US20110206636A1 (en) *	2003-09-16	2011-08-25	Kemin Foods, LLC	Use of Endoperoxides for the Treatment of Infections Caused by Flaviviridae, Including Hepatitis C, Bovine Viral Diarrhea and Classical Swine Fever Virus
CN1311832C (zh) *	2005-01-12	2007-04-25	四川科伦药业股份有限公司	溴代二氢青蒿素的医药用途
CN103159777A (zh) *	2013-03-05	2013-06-19	华东师范大学	一种卤代青蒿素衍生物的合成方法
CN104086560A (zh) *	2014-07-03	2014-10-08	唐心建	卤代青蒿素母核、卤代青蒿素衍生物、卤代双氢青蒿素、卤代脱羰青蒿素以及医药用途
CN107011356A (zh) *	2017-06-08	2017-08-04	温州医科大学附属第二医院、温州医科大学附属育英儿童医院	一种脱水双氢青蒿素的合成方法
CN110981887B (zh) *	2019-09-12	2022-05-17	延边大学	一类二氢青蒿素类化合物及其制备方法和医用用途
KR102266875B1 (ko) *	2019-12-12	2021-06-18	대한민국	감자 바이러스 y 방제용 화합물

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4963683A (en) *	1986-12-18	1990-10-16	Sri International	Process for preparing polyoxa tetracyclic compounds
CH679486A5 (2) *	1986-12-18	1992-02-28	Stanford Res Inst Int
GB8804372D0 (en) *	1988-02-25	1988-03-23	World Health Org	Synthesis of dihydroqinghaosu derivatives
EP0362730A1 (en) *	1988-10-04	1990-04-11	Hoechst Aktiengesellschaft	Artemisinin derivatives, processes for their preparation and their use as antiprotozoal agents

1990
- 1990-12-11 TW TW079110403A patent/TW198722B/zh active
1991
- 1991-04-29 AU AU76185/91A patent/AU639095B2/en not_active Ceased
- 1991-05-02 JP JP3128261A patent/JPH04225983A/ja active Pending
- 1991-05-03 US US07/694,203 patent/US5246930A/en not_active Expired - Fee Related
- 1991-05-06 PT PT97577A patent/PT97577A/pt not_active Application Discontinuation
- 1991-05-06 KR KR1019910007284A patent/KR920005722A/ko not_active Withdrawn
- 1991-05-06 IE IE152991A patent/IE911529A1/en unknown
- 1991-05-06 ZA ZA913393A patent/ZA913393B/xx unknown
- 1991-05-06 IL IL98071A patent/IL98071A0/xx unknown
- 1991-05-06 BR BR919101822A patent/BR9101822A/pt not_active Application Discontinuation
- 1991-05-06 EP EP91107304A patent/EP0456149A1/en not_active Withdrawn

Also Published As

Publication number	Publication date
ZA913393B (en)	1992-02-26
AU7618591A (en)	1991-11-07
PT97577A (pt)	1992-01-31
JPH04225983A (ja)	1992-08-14
EP0456149A1 (en)	1991-11-13
AU639095B2 (en)	1993-07-15
KR920005722A (ko)	1992-04-03
US5246930A (en)	1993-09-21
BR9101822A (pt)	1991-12-17
TW198722B (2)	1993-01-21
IL98071A0 (en)	1992-06-21

Publication	Publication Date	Title
EP0362730A1 (en)	1990-04-11	Artemisinin derivatives, processes for their preparation and their use as antiprotozoal agents
US5246930A (en)	1993-09-21	9-substituted compounds of 3α, 11α-epoxy-3,4,5,5aα,6,7,8,8a,9,11,11a-undecahydro-3β,6.alpha.,9-trimethylfurano[3,4-j][1,2]benzodioxepin, processes for their preparation and their use as antiprotozoal and antiviral agents
US4786635A (en)	1988-11-22	Novel benzothiazine derivatives
US4788216A (en)	1988-11-29	Medicinal uses for podophyllotoxins
US5225427A (en)	1993-07-06	10-substituted ether derivatives of dihydroartemisinin, process for their preparation and their use as antiprotozoal agents
FI93116C (fi)	1995-02-27	Stereospesifinen menetelmä furo/3,4-c/pyridiini-enantiomeerien valmistamiseksi
US3267107A (en)	1966-08-16	3-(4'-5'-methylenedioxy-phenyl)-7, 8-dimethoxy-1, 2, 3, 4,-tetrahydroisoquinolines
US4818753A (en)	1989-04-04	Synthesis and method of use for 2, 4 diaminoquinazoline
CA2368815A1 (en)	2000-10-26	Novel synthesis and crystallization of piperazine ring-containing compounds
US5116837A (en)	1992-05-26	2,9-dihydro-(6 or 7)-(3-oxo-2,3,4,5-tetrahydropyridazinyl)-pyrazolo [4,3-B]-1,4-benzoxazines
CA2127374C (fr)	2004-12-07	Nouveau derive de l'isoindolinone, sa preparation et les compositions pharmaceutiques qui le contiennent
US3455929A (en)	1969-07-15	Esters of 1,4-dihydroquinoline-n-carboxylic acids and thione acids
EP0270692A1 (en)	1988-06-15	Antiarrhythmic agent
US20030088094A1 (en)	2003-05-08	Novel synthesis and crystallization of piperazine ring-containing compounds
FR2768431A1 (fr)	1999-03-19	Nouveaux analogues optiquement purs de la camptothecine, nouvel intermediaire de synthese optiquement pur et son procede de preparation
US3595861A (en)	1971-07-27	Novel synthesis of 2-quinazolinepropionic acids and derivatives
US5578596A (en)	1996-11-26	2-alkoxy-5,6,7,8-tetrahydroquinoxaline derivatives, and production method and use thereof
FR2795071A1 (fr)	2000-12-22	Nouveaux derives de carboxylate de 7-oxo-2,3,7,14- tetrahydro-1h-benzo[b]pyrano[3,2,h] acridine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
NL7809726A (nl)	1980-03-28	Nieuwe tetracyclische verbindingen.
CA2493090C (fr)	2012-04-24	Nouveaux derives de benzo[b]chromeno-naphthyridin-7-one et de pyrano[2'3':7,8]quino[2,3-b]quinoxalin-7-one, leur procede de preparation et les compositions pharmaceutiques qui lescontiennent
SE446181B (sv)	1986-08-18	Substituerad kinazolin samt forfarande for dess framstellning
EP0027679A2 (en)	1981-04-29	Substituted-5-((7-chloro-4-quinolinyl)amino)-3-(amino-methyl)-(1,1'-biphenyl)-2-ol compounds; processes for their production; and pharmaceutical compositions containing the compounds
US4548947A (en)	1985-10-22	1-(Substituted-aryl)-dihydro-1H-pyrrolizine-3,5-[2H,6H-]diones and use for reversing amnesia
US3649634A (en)	1972-03-14	4-alkoxy-2 3-dihydro-1h-pyrrolo(2.3-b)quinoline compounds
FR2826005A1 (fr)	2002-12-20	Synthese totale de la galanthamine, de ses analogues et de ses derives