JP2015500880A5 - - Google Patents

Info

Publication number

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

Authority

JP

Japan

Prior art keywords

group

combination

formula

compound

amount

Prior art date

2012-12-19

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.)

Granted

Links

• Espacenet
• Global Dossier
• Discuss

• 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