JP2015500880A5 - - Google Patents
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- JP2015500880A5 JP2015500880A5 JP2014548825A JP2014548825A JP2015500880A5 JP 2015500880 A5 JP2015500880 A5 JP 2015500880A5 JP 2014548825 A JP2014548825 A JP 2014548825A JP 2014548825 A JP2014548825 A JP 2014548825A JP 2015500880 A5 JP2015500880 A5 JP 2015500880A5
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- 238000000034 method Methods 0.000 claims description 29
- 150000001875 compounds Chemical class 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 108090000467 Interferon-beta Proteins 0.000 claims description 12
- ASLUCFFROXVMFL-UHFFFAOYSA-N andrographolide Natural products CC1(CO)C(O)CCC2(C)C(CC=C3/C(O)OCC3=O)C(=C)CCC12 ASLUCFFROXVMFL-UHFFFAOYSA-N 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 201000006417 multiple sclerosis Diseases 0.000 claims description 9
- -1 3- (3-furanyl) -propyl Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
- BOJKULTULYSRAS-OTESTREVSA-N Andrographolide Chemical compound C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CCC1=C)(CO)C)\C=C1/[C@H](O)COC1=O BOJKULTULYSRAS-OTESTREVSA-N 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- WKKBRRFSRMDTJB-JYBIWHBTSA-N 4-[2-[(1R,4aS,5R,8aS)-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]ethyl]-2H-furan-5-one Chemical compound C([C@H]1[C@]2(C)CCC[C@]([C@H]2CCC1=C)(CO)C)CC1=CCOC1=O WKKBRRFSRMDTJB-JYBIWHBTSA-N 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 239000000651 prodrug Substances 0.000 claims description 6
- 229940002612 prodrug Drugs 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000000837 carbohydrate group Chemical group 0.000 claims description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 230000037396 body weight Effects 0.000 claims description 4
- YIIRVUDGRKEWBV-UHFFFAOYSA-N (E)-3-(2-((1R,4aS,5R,6R,8aS)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylenedecahydronaphthalen-1-yl)ethylidene)furan-2(3H)-one Natural products C=C1CCC2C(C)(CO)C(O)CCC2(C)C1CC=C1C=COC1=O YIIRVUDGRKEWBV-UHFFFAOYSA-N 0.000 claims description 3
- XMJAJFVLHDIEHF-CRBRZBHVSA-N 14-Deoxy-11,12-didehydroandrographolide Chemical compound C(/[C@@H]1C(=C)CC[C@H]2[C@@]1(C)CC[C@@H](O)[C@]2(CO)C)=C\C1=CCOC1=O XMJAJFVLHDIEHF-CRBRZBHVSA-N 0.000 claims description 3
- XMJAJFVLHDIEHF-UHFFFAOYSA-N 14-deoxy-11, 12-didehydroandrographolide Natural products OCC1(C)C(O)CCC2(C)C1CCC(=C)C2C=CC1=CCOC1=O XMJAJFVLHDIEHF-UHFFFAOYSA-N 0.000 claims description 3
- YIIRVUDGRKEWBV-YSDSKTICSA-N 14-deoxy-11,12-didehydroandrographolide Natural products C[C@@]1(CO)[C@H](O)CC[C@@]2(C)[C@H](CC=C/3C=COC3=O)C(=C)CC[C@H]12 YIIRVUDGRKEWBV-YSDSKTICSA-N 0.000 claims description 3
- BNLCOXWUZAOLDT-UHFFFAOYSA-N 14-deoxy-11-hydroxyandrographolide Natural products OCC1(C)C(O)CCC2(C)C1CCC(=C)C2C(O)CC1=CCOC1=O BNLCOXWUZAOLDT-UHFFFAOYSA-N 0.000 claims description 3
- XBINLYXLOLWNSB-UHFFFAOYSA-N 14-deoxy-11-oxoandrographolide Natural products CC1(CO)C(O)CCC2(C)C1CCC(=C)C2C(=O)CC3=CC(=O)OC3 XBINLYXLOLWNSB-UHFFFAOYSA-N 0.000 claims description 3
- SJKRRZPXYGTAGA-UHFFFAOYSA-N 14-deoxy-12-methoxyandrographolide Natural products C=C1CCC2C(C)(CO)C(O)CCC2(C)C1CC(OC)C1=CCOC1=O SJKRRZPXYGTAGA-UHFFFAOYSA-N 0.000 claims description 3
- KHQNSSJNIXVKMK-UHFFFAOYSA-N 14-deoxy-12R-hydroxyandrographolide Natural products C=C1CCC2C(C)(CO)C(O)CCC2(C)C1CC(O)C1=CCOC1=O KHQNSSJNIXVKMK-UHFFFAOYSA-N 0.000 claims description 3
- LMOGEODVJJLYGW-UHFFFAOYSA-N 14-deoxy-17beta-hydroxyandrographolide Natural products OCC1CCC2C(C)(CO)C(O)CCC2(C)C1CCC1=CCOC1=O LMOGEODVJJLYGW-UHFFFAOYSA-N 0.000 claims description 3
- GVRNTWSGBWPJGS-DSJDWBEOSA-N 14-deoxyandrographolide Natural products O=C1C(CC[C@@H]2C(=C)CC[C@@H]3[C@@](CO)(C)[C@H](O)CC[C@]23C)=CCO1 GVRNTWSGBWPJGS-DSJDWBEOSA-N 0.000 claims description 3
- WKKBRRFSRMDTJB-UHFFFAOYSA-N 19-hydroxy-labda 8(17),13-diene-15,16-olide Natural products C=C1CCC2C(C)(CO)CCCC2(C)C1CCC1=CCOC1=O WKKBRRFSRMDTJB-UHFFFAOYSA-N 0.000 claims description 3
- KHQNSSJNIXVKMK-UQZPWQSVSA-N 4-[(1r)-2-[(1r,4as,5r,6r,8as)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1h-naphthalen-1-yl]-1-hydroxyethyl]-2h-furan-5-one Chemical compound C1([C@H](O)C[C@H]2[C@]3(C)CC[C@@H](O)[C@]([C@H]3CCC2=C)(CO)C)=CCOC1=O KHQNSSJNIXVKMK-UQZPWQSVSA-N 0.000 claims description 3
- WQHWOZANSOUSAY-LZBAHHAZSA-N 4-[(e)-2-[(1r,4as,5r,6r,8ar)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1h-naphthalen-1-yl]ethenyl]-2-[2-[(1r,4as,5r,6r,8ar)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1h-naphthalen-1 Chemical compound C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CCC1=C)(CO)C)C(C1C=C(\C=C\[C@H]2[C@@]3(CC[C@@H](O)[C@@](C)(CO)[C@H]3CCC2=C)C)C(=O)O1)C1=CCOC1=O WQHWOZANSOUSAY-LZBAHHAZSA-N 0.000 claims description 3
- LMOGEODVJJLYGW-UQZPWQSVSA-N 4-[2-[(1r,2s,4as,5r,6r,8as)-6-hydroxy-2,5-bis(hydroxymethyl)-5,8a-dimethyl-1,2,3,4,4a,6,7,8-octahydronaphthalen-1-yl]ethyl]-2h-furan-5-one Chemical compound C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CC[C@@H]1CO)(CO)C)CC1=CCOC1=O LMOGEODVJJLYGW-UQZPWQSVSA-N 0.000 claims description 3
- WZHWNAKOQGIEEB-NDLGOLERSA-N 4-[2-[(1r,4as,5r,6r,8ar)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1h-naphthalen-1-yl]-2-oxoethyl]-2h-furan-5-one Chemical compound O=C([C@@H]1C(=C)CC[C@H]2[C@@]1(C)CC[C@@H](O)[C@]2(CO)C)CC1=CCOC1=O WZHWNAKOQGIEEB-NDLGOLERSA-N 0.000 claims description 3
- GVRNTWSGBWPJGS-YSDSKTICSA-N 4-[2-[(1r,4as,5r,6r,8as)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1h-naphthalen-1-yl]ethyl]-2h-furan-5-one Chemical compound C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CCC1=C)(CO)C)CC1=CCOC1=O GVRNTWSGBWPJGS-YSDSKTICSA-N 0.000 claims description 3
- YGCYRQKJYWQXHG-RDNQFMDVSA-N 4-[2-[(1r,4as,5r,8as)-5,8a-dimethyl-2-methylidene-5-[[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]-3,4,4a,6,7,8-hexahydro-1h-naphthalen-1-yl]ethyl]-2h-furan-5-one Chemical compound C([C@@]1(C)[C@H]2CCC(=C)[C@@H](CCC=3C(OCC=3)=O)[C@]2(C)CCC1)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O YGCYRQKJYWQXHG-RDNQFMDVSA-N 0.000 claims description 3
- YQZCSRAURNLCEK-WZLKLWACSA-N 4-[2-[(1s,2r,4as,5r,6r,8ar)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethylspiro[3,4,4a,6,7,8-hexahydro-1h-naphthalene-2,2'-oxirane]-1-yl]ethyl]-2h-furan-5-one Chemical compound C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CC[C@@]11OC1)(CO)C)CC1=CCOC1=O YQZCSRAURNLCEK-WZLKLWACSA-N 0.000 claims description 3
- YQZCSRAURNLCEK-UHFFFAOYSA-N 8,17-epoxy-14-deoxyandrographolide Natural products C1OC21CCC1C(C)(CO)C(O)CCC1(C)C2CCC1=CCOC1=O YQZCSRAURNLCEK-UHFFFAOYSA-N 0.000 claims description 3
- WQHWOZANSOUSAY-UHFFFAOYSA-N Bisandrographolide A Natural products C=C1CCC2C(C)(CO)C(O)CCC2(C)C1CC(C1C=C(C=CC2C3(CCC(O)C(C)(CO)C3CCC2=C)C)C(=O)O1)C1=CCOC1=O WQHWOZANSOUSAY-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- XMJAJFVLHDIEHF-YSDSKTICSA-N dehydroandrographolide Natural products C([C@@H]1C(=C)CC[C@H]2[C@@]1(C)CC[C@@H](O)[C@]2(CO)C)=CC1=CCOC1=O XMJAJFVLHDIEHF-YSDSKTICSA-N 0.000 claims description 3
- MEEPUSVTMHGIPC-UHFFFAOYSA-N deoxyandrographiside Natural products OC1CCC2(C)C(CCC=3C(OCC=3)=O)C(=C)CCC2C1(C)COC1OC(CO)C(O)C(O)C1O MEEPUSVTMHGIPC-UHFFFAOYSA-N 0.000 claims description 3
- GVRNTWSGBWPJGS-UHFFFAOYSA-N deoxyandrographolide Natural products C=C1CCC2C(C)(CO)C(O)CCC2(C)C1CCC1=CCOC1=O GVRNTWSGBWPJGS-UHFFFAOYSA-N 0.000 claims description 3
- BBGWVUQBIGGVLS-UHFFFAOYSA-N neoandrographolide Natural products CC1(COC2OC(CO)C(O)C(O)C2O)C(O)CCC3(C)C(CCC4=C(O)COC4=O)C(=C)CCC13 BBGWVUQBIGGVLS-UHFFFAOYSA-N 0.000 claims description 3
- YGCYRQKJYWQXHG-UHFFFAOYSA-N neoandrographoside Natural products C1CCC2(C)C(CCC=3C(OCC=3)=O)C(=C)CCC2C1(C)COC1OC(CO)C(O)C(O)C1O YGCYRQKJYWQXHG-UHFFFAOYSA-N 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 102100026720 Interferon beta Human genes 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000000539 dimer Substances 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 2
- 229930182470 glycoside Natural products 0.000 claims description 2
- 150000002338 glycosides Chemical class 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000000178 monomer Substances 0.000 claims description 2
- 102000003996 Interferon-beta Human genes 0.000 claims 10
- 241000023320 Luma <angiosperm> Species 0.000 claims 2
- 241000746375 Andrographis Species 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 230000023105 myelination Effects 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- 208000016192 Demyelinating disease Diseases 0.000 description 8
- 102000014150 Interferons Human genes 0.000 description 8
- 108010050904 Interferons Proteins 0.000 description 8
- 229940079322 interferon Drugs 0.000 description 8
- BOJKULTULYSRAS-QPSYGYIJSA-N (3z,4s)-3-[2-[(1r,4as,5r,6r,8as)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1h-naphthalen-1-yl]ethylidene]-4-hydroxyoxolan-2-one Chemical compound C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CCC1=C)(CO)C)\C=C1\[C@H](O)COC1=O BOJKULTULYSRAS-QPSYGYIJSA-N 0.000 description 1
- BOJKULTULYSRAS-BEUDANMRSA-N Andropanolide Natural products O=C1/C(=C/C[C@@H]2C(=C)CC[C@@H]3[C@@](CO)(C)[C@H](O)CC[C@]23C)/[C@H](O)CO1 BOJKULTULYSRAS-BEUDANMRSA-N 0.000 description 1
- UCCHTKQRBNYFTP-UHFFFAOYSA-N C(CCCCCCCCC)[ClH]CCCCCCCCCC Chemical compound C(CCCCCCCCC)[ClH]CCCCCCCCCC UCCHTKQRBNYFTP-UHFFFAOYSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161578650P | 2011-12-21 | 2011-12-21 | |
| US61/578,650 | 2011-12-21 | ||
| PCT/US2012/070568 WO2013096423A1 (en) | 2011-12-21 | 2012-12-19 | Combination therapy with interferon and andrographolides for multiple sclerosis |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015500880A JP2015500880A (ja) | 2015-01-08 |
| JP2015500880A5 true JP2015500880A5 (https=) | 2016-02-18 |
| JP5936707B2 JP5936707B2 (ja) | 2016-06-22 |
Family
ID=48669439
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014548825A Active JP5936707B2 (ja) | 2011-12-21 | 2012-12-19 | インターフェロンおよびアンドログラホリドを用いた多発性硬化症のための併用療法 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US9060994B2 (https=) |
| EP (1) | EP2670406B1 (https=) |
| JP (1) | JP5936707B2 (https=) |
| AU (1) | AU2012359081B2 (https=) |
| BR (1) | BR112014015178A2 (https=) |
| CA (1) | CA2853779C (https=) |
| CL (1) | CL2014001663A1 (https=) |
| ES (1) | ES2554459T3 (https=) |
| RU (1) | RU2014113967A (https=) |
| WO (1) | WO2013096423A1 (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017214346A1 (en) * | 2016-06-08 | 2017-12-14 | Innobiosciences, Llc | Andrographolide treats progressive forms of multiple sclerosis |
| US11318153B2 (en) | 2018-06-25 | 2022-05-03 | Bialpha International Sdn. Bhd. | Method of using Neoandrographolide for lowering blood sugar, lowering blood lipid, improving liver function and improving renal function |
| CN109824655B (zh) * | 2019-04-08 | 2021-09-24 | 沈阳药科大学 | 穿心莲内酯化合物及其制备方法和用途 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1043027A1 (en) * | 1999-04-08 | 2000-10-11 | Applied Research Systems ARS Holding N.V. | Treatment of multiple sclerosis with a combination of Interferon and Growth hormone |
| US6410590B1 (en) | 2000-02-03 | 2002-06-25 | Dr. Reddy's Research Foundation | Compounds having antitumor activity: process for their preparation and pharmaceutical compositions containing them |
| US20050181033A1 (en) * | 2000-06-29 | 2005-08-18 | Dekker John P.Iii | Method for delivering interferons to the intradermal compartment |
| WO2003025541A2 (en) * | 2001-09-18 | 2003-03-27 | Chiron Corporation | Methods for treating multiple sclerosis |
| CN1921872A (zh) * | 2004-02-03 | 2007-02-28 | 智利南方大学 | 用于激活PPR－γ受体而治疗自身免疫性疾病和阿尔茨海默病的提取自穿心莲的半日花烷型二萜类组合物 |
| US20050220764A1 (en) | 2004-04-01 | 2005-10-06 | Schering Aktiengesellschaft | Higher-doses of interferon-beta for treatment of multiple sclerosis |
| US20080108641A1 (en) | 2006-02-08 | 2008-05-08 | Ajami Alfred M | Compounds for treating inflammatory disorders, demyelinating disdorders and cancers |
| KR20120098578A (ko) | 2009-06-22 | 2012-09-05 | 에스케이바이오팜 주식회사 | 피로의 치료 또는 예방 방법 |
-
2012
- 2012-12-19 US US13/984,124 patent/US9060994B2/en active Active
- 2012-12-19 CA CA2853779A patent/CA2853779C/en active Active
- 2012-12-19 WO PCT/US2012/070568 patent/WO2013096423A1/en not_active Ceased
- 2012-12-19 RU RU2014113967A patent/RU2014113967A/ru not_active Application Discontinuation
- 2012-12-19 ES ES12859754.9T patent/ES2554459T3/es active Active
- 2012-12-19 EP EP12859754.9A patent/EP2670406B1/en active Active
- 2012-12-19 AU AU2012359081A patent/AU2012359081B2/en active Active
- 2012-12-19 JP JP2014548825A patent/JP5936707B2/ja active Active
- 2012-12-19 BR BR112014015178A patent/BR112014015178A2/pt not_active Application Discontinuation
-
2014
- 2014-06-20 CL CL2014001663A patent/CL2014001663A1/es unknown
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