JP4768941B2 - 胆汁酸置換フェニルアルケノイルグアニジン、それらの製造方法、医薬または診断薬としてのそれらの使用、およびそれらを含む医薬 - Google Patents
胆汁酸置換フェニルアルケノイルグアニジン、それらの製造方法、医薬または診断薬としてのそれらの使用、およびそれらを含む医薬 Download PDFInfo
- Publication number
- JP4768941B2 JP4768941B2 JP2001521701A JP2001521701A JP4768941B2 JP 4768941 B2 JP4768941 B2 JP 4768941B2 JP 2001521701 A JP2001521701 A JP 2001521701A JP 2001521701 A JP2001521701 A JP 2001521701A JP 4768941 B2 JP4768941 B2 JP 4768941B2
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- hydrogen
- substituted
- phenyl
- methyl
- 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 - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 14
- 239000003814 drug Substances 0.000 title claims abstract 6
- 238000002360 preparation method Methods 0.000 title abstract description 3
- 210000000941 bile Anatomy 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 50
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 36
- 229910052731 fluorine Inorganic materials 0.000 claims description 30
- 229910052801 chlorine Inorganic materials 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 208000001130 gallstones Diseases 0.000 abstract description 8
- 201000001883 cholelithiasis Diseases 0.000 abstract description 4
- 238000011282 treatment Methods 0.000 abstract description 3
- 238000011321 prophylaxis Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 31
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 19
- -1 quaternary ammonium ions Chemical class 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 102100022897 Sodium/hydrogen exchanger 10 Human genes 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000000284 extract Substances 0.000 description 14
- 239000002904 solvent Substances 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 9
- 238000011084 recovery Methods 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000007787 solid Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- 235000012000 cholesterol Nutrition 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229910001413 alkali metal ion Inorganic materials 0.000 description 4
- 150000001340 alkali metals Chemical class 0.000 description 4
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 4
- 239000006286 aqueous extract Substances 0.000 description 4
- 239000003613 bile acid Substances 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 150000001768 cations Chemical group 0.000 description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 210000000232 gallbladder Anatomy 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- UXDVMRALHSFYEG-UHFFFAOYSA-N methyl 4-[3-(2-aminoethoxy)-7,12-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoate Chemical compound OC1CC2CC(OCCN)CCC2(C)C2C1C1CCC(C(C)CCC(=O)OC)C1(C)C(O)C2 UXDVMRALHSFYEG-UHFFFAOYSA-N 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 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 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- 108091006647 SLC9A1 Proteins 0.000 description 3
- 102100030980 Sodium/hydrogen exchanger 1 Human genes 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N Valeric acid Natural products CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000007937 lozenge Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 125000001453 quaternary ammonium group Chemical group 0.000 description 3
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
- MDLVOLVFZJLKNE-UHFFFAOYSA-N 4-[3-[2-[(3-bromobenzoyl)amino]ethoxy]-7,12-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoic acid Chemical compound C1CC2(C)C3CC(O)C4(C)C(C(CCC(O)=O)C)CCC4C3C(O)CC2CC1OCCNC(=O)C1=CC=CC(Br)=C1 MDLVOLVFZJLKNE-UHFFFAOYSA-N 0.000 description 2
- PZDVGXUBCYZLGV-UHFFFAOYSA-N 4-[7,12-dihydroxy-3-[2-[[2-(4-hydroxyphenyl)acetyl]amino]ethoxy]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoic acid Chemical compound C1CC2(C)C3CC(O)C4(C)C(C(CCC(O)=O)C)CCC4C3C(O)CC2CC1OCCNC(=O)CC1=CC=C(O)C=C1 PZDVGXUBCYZLGV-UHFFFAOYSA-N 0.000 description 2
- XQXPVVBIMDBYFF-UHFFFAOYSA-N 4-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C=C1 XQXPVVBIMDBYFF-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical group COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 108091006650 SLC9A2 Proteins 0.000 description 2
- 241000978776 Senegalia senegal Species 0.000 description 2
- 102100030382 Sodium/hydrogen exchanger 2 Human genes 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 125000005037 alkyl phenyl group Chemical group 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000010265 fast atom bombardment Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000002245 gallstone dissolution Methods 0.000 description 2
- 229960000789 guanidine hydrochloride Drugs 0.000 description 2
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- FPICZJRQFDQQBA-UHFFFAOYSA-N methyl 4-[3-[2-[(3-bromobenzoyl)amino]ethoxy]-7,12-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoate Chemical compound C1CC2(C)C3CC(O)C4(C)C(C(C)CCC(=O)OC)CCC4C3C(O)CC2CC1OCCNC(=O)C1=CC=CC(Br)=C1 FPICZJRQFDQQBA-UHFFFAOYSA-N 0.000 description 2
- ZKQIOSQOAJJHJF-UHFFFAOYSA-N methyl 4-[7,12-dihydroxy-3-(2-hydroxyethoxy)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoate Chemical compound OC1CC2CC(OCCO)CCC2(C)C2C1C1CCC(C(C)CCC(=O)OC)C1(C)C(O)C2 ZKQIOSQOAJJHJF-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical group C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- NLAVHUUABUFSIG-UHFFFAOYSA-N 3,4,5-trifluorobenzaldehyde Chemical compound FC1=CC(C=O)=CC(F)=C1F NLAVHUUABUFSIG-UHFFFAOYSA-N 0.000 description 1
- VOIZNVUXCQLQHS-UHFFFAOYSA-N 3-bromobenzoic acid Chemical compound OC(=O)C1=CC=CC(Br)=C1 VOIZNVUXCQLQHS-UHFFFAOYSA-N 0.000 description 1
- QDNUHJGGXXPBNT-UHFFFAOYSA-N 4-(7,12-dihydroxy-10,13-dimethyl-3-methylsulfonyloxy-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl)pentanoic acid Chemical compound OC1CC2CC(OS(C)(=O)=O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 QDNUHJGGXXPBNT-UHFFFAOYSA-N 0.000 description 1
- DRYJLNHOWFTKKA-UHFFFAOYSA-N 4-[3-[2-[[3-[4-(diaminomethylidenecarbamoyl)phenyl]benzoyl]amino]ethoxy]-7,12-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoic acid Chemical compound C1CC2(C)C3CC(O)C4(C)C(C(CCC(O)=O)C)CCC4C3C(O)CC2CC1OCCNC(=O)C(C=1)=CC=CC=1C1=CC=C(C(=O)NC(N)=N)C=C1 DRYJLNHOWFTKKA-UHFFFAOYSA-N 0.000 description 1
- AXCUVZOHDRIOEH-UHFFFAOYSA-N 4-[3-[[2-[4-[4-[4-(diaminomethylideneamino)-4-oxobut-2-en-2-yl]-2,6-difluorophenoxy]phenyl]acetyl]amino]-7,12-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoic acid Chemical compound C1CC2(C)C3CC(O)C4(C)C(C(CCC(O)=O)C)CCC4C3C(O)CC2CC1NC(=O)CC(C=C1)=CC=C1OC1=C(F)C=C(C(C)=CC(=O)NC(N)=N)C=C1F AXCUVZOHDRIOEH-UHFFFAOYSA-N 0.000 description 1
- SIAVMDKGVRXFAX-UHFFFAOYSA-N 4-carboxyphenylboronic acid Chemical compound OB(O)C1=CC=C(C(O)=O)C=C1 SIAVMDKGVRXFAX-UHFFFAOYSA-N 0.000 description 1
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- BGXRCMCVLMXBID-UHFFFAOYSA-N C(C)C(C(=O)O)CC(C)C1CCC2C3C(CC4CC(CCC4(C3CC(C12C)O)C)OCCNC(CC1=CC=C(C=C1)O)=O)O Chemical compound C(C)C(C(=O)O)CC(C)C1CCC2C3C(CC4CC(CCC4(C3CC(C12C)O)C)OCCNC(CC1=CC=C(C=C1)O)=O)O BGXRCMCVLMXBID-UHFFFAOYSA-N 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 101000702450 Homo sapiens Sodium/hydrogen exchanger 3 Proteins 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 101710097665 Leucine aminopeptidase 1 Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- HKVQUJIYCKSBED-UHFFFAOYSA-N NC1CCC2(C3CC(C4(C(CCC4C3C(CC2C1)O)C(C(=O)O)CCC)C)O)C Chemical compound NC1CCC2(C3CC(C4(C(CCC4C3C(CC2C1)O)C(C(=O)O)CCC)C)O)C HKVQUJIYCKSBED-UHFFFAOYSA-N 0.000 description 1
- 241001045988 Neogene Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101710082688 Probable leucine aminopeptidase 1 Proteins 0.000 description 1
- 101100421625 Rattus norvegicus Slc9a3 gene Proteins 0.000 description 1
- 108091006649 SLC9A3 Proteins 0.000 description 1
- 102100030375 Sodium/hydrogen exchanger 3 Human genes 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 102100022147 Torsin-1A-interacting protein 1 Human genes 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- NTECHUXHORNEGZ-UHFFFAOYSA-N acetyloxymethyl 3',6'-bis(acetyloxymethoxy)-2',7'-bis[3-(acetyloxymethoxy)-3-oxopropyl]-3-oxospiro[2-benzofuran-1,9'-xanthene]-5-carboxylate Chemical compound O1C(=O)C2=CC(C(=O)OCOC(C)=O)=CC=C2C21C1=CC(CCC(=O)OCOC(C)=O)=C(OCOC(C)=O)C=C1OC1=C2C=C(CCC(=O)OCOC(=O)C)C(OCOC(C)=O)=C1 NTECHUXHORNEGZ-UHFFFAOYSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- BVSRWCMAJISCTD-UHFFFAOYSA-N ethyl 2-diethoxyphosphorylpropanoate Chemical compound CCOC(=O)C(C)P(=O)(OCC)OCC BVSRWCMAJISCTD-UHFFFAOYSA-N 0.000 description 1
- IJDRABLXWHHVKE-UHFFFAOYSA-N ethyl 2-methyl-3-(3,4,5-trifluorophenyl)prop-2-enoate Chemical compound CCOC(=O)C(C)=CC1=CC(F)=C(F)C(F)=C1 IJDRABLXWHHVKE-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000006260 foam Substances 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
- 239000001963 growth medium Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 102000054754 human SLC9A3 Human genes 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000012105 intracellular pH reduction Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229920000831 ionic polymer Polymers 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- ARNWQMJQALNBBV-UHFFFAOYSA-N lithium carbide Chemical compound [Li+].[Li+].[C-]#[C-] ARNWQMJQALNBBV-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- KHXVOVQKPRFPKK-UHFFFAOYSA-N methyl 4-[3-[2-(1,3-dioxoisoindol-2-yl)ethoxy]-7,12-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoate Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCOC1CC2CC(O)C3C4CCC(C(C)CCC(=O)OC)C4(C)C(O)CC3C2(C)CC1 KHXVOVQKPRFPKK-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 101150091879 neo gene Proteins 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 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 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
- C07J41/0061—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives one of the carbon atoms being part of an amide group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19941764.4 | 1999-09-02 | ||
| DE19941764A DE19941764A1 (de) | 1999-09-02 | 1999-09-02 | Substituierte Acylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikamente oder Diagnostika sowie sie enthaltende Medikamente |
| PCT/EP2000/008025 WO2001017954A1 (de) | 1999-09-02 | 2000-08-17 | Gallensäure-substituierte phenyl-alkenoylguanidine, verfahren zu ihrer herstellung, ihre verwendung als medikamente oder diagnostika sowie sie enthaltende medikamente |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2003508513A JP2003508513A (ja) | 2003-03-04 |
| JP2003508513A5 JP2003508513A5 (enExample) | 2007-10-11 |
| JP4768941B2 true JP4768941B2 (ja) | 2011-09-07 |
Family
ID=7920512
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001521701A Expired - Fee Related JP4768941B2 (ja) | 1999-09-02 | 2000-08-17 | 胆汁酸置換フェニルアルケノイルグアニジン、それらの製造方法、医薬または診断薬としてのそれらの使用、およびそれらを含む医薬 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US6451781B1 (enExample) |
| EP (1) | EP1248768B1 (enExample) |
| JP (1) | JP4768941B2 (enExample) |
| AT (1) | ATE309981T1 (enExample) |
| AU (1) | AU774083B2 (enExample) |
| CA (1) | CA2383729A1 (enExample) |
| DE (2) | DE19941764A1 (enExample) |
| DK (1) | DK1248768T3 (enExample) |
| ES (1) | ES2251403T3 (enExample) |
| IL (1) | IL148250A0 (enExample) |
| WO (1) | WO2001017954A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003048108A2 (en) * | 2001-11-29 | 2003-06-12 | Theracos, Inc | Compounds for treatment of inflammation, diabetes and related disorders |
| US10543207B2 (en) | 2008-12-31 | 2020-01-28 | Ardelyx, Inc. | Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| JP5502106B2 (ja) | 2008-12-31 | 2014-05-28 | アーデリクス，インコーポレーテッド | 体液貯留または塩分過負荷と関連する障害および消化管障害の治療におけるｎｈｅ媒介性アンチポートを阻害するための組成物および方法 |
| WO2018129556A1 (en) * | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| WO2014029984A1 (en) * | 2012-08-21 | 2014-02-27 | Ardelyx, Inc. | Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| KR102287207B1 (ko) | 2013-04-12 | 2021-08-09 | 알데릭스, 인코포레이티드 | Nhe3-결합 화합물 및 포스페이트 수송을 저해하는 방법 |
| UA126283C2 (uk) | 2017-01-09 | 2022-09-14 | Арделікс, Інк. | Сполуки, придатні для лікування розладів шлунково-кишкового тракту |
| CA3049679A1 (en) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Inhibitors of nhe-mediated antiport |
| US12186329B2 (en) | 2018-08-23 | 2025-01-07 | President And Fellows Of Harvard College | Compositions and methods related to cholic acid 7-sulfate as a treatment for diabetes |
| EP3890745B1 (en) | 2018-12-04 | 2025-11-19 | President and Fellows of Harvard College | Synthetic derivatives of cholic acid 7-sulfate and uses thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02286619A (ja) * | 1989-04-28 | 1990-11-26 | Hajime Takigawa | 利胆剤 |
| JPH072891A (ja) * | 1993-05-08 | 1995-01-06 | Hoechst Ag | 単量体胆汁酸誘導体、その調製方法および医薬としてのこれらの化合物の使用 |
| EP0676410A2 (en) * | 1994-04-06 | 1995-10-11 | ALFA WASSERMANN S.p.A. | Bile acids derivatives useful in the therapy of the biliary calculosis from cholesterol and of the pathologies caused by cholestasis |
| JPH09315979A (ja) * | 1996-05-24 | 1997-12-09 | Tokyo Tanabe Co Ltd | 利胆剤 |
| JP2002528460A (ja) * | 1998-10-28 | 2002-09-03 | アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 胆汁酸で置換されたフェニルアルケノイルグアニジン類、その製造方法、その薬剤または診断薬としての使用、およびそれらを含有する薬剤 |
-
1999
- 1999-09-02 DE DE19941764A patent/DE19941764A1/de not_active Withdrawn
-
2000
- 2000-08-17 WO PCT/EP2000/008025 patent/WO2001017954A1/de not_active Ceased
- 2000-08-17 AT AT00958461T patent/ATE309981T1/de not_active IP Right Cessation
- 2000-08-17 EP EP00958461A patent/EP1248768B1/de not_active Expired - Lifetime
- 2000-08-17 IL IL14825000A patent/IL148250A0/xx unknown
- 2000-08-17 AU AU69965/00A patent/AU774083B2/en not_active Ceased
- 2000-08-17 DE DE50011660T patent/DE50011660D1/de not_active Expired - Lifetime
- 2000-08-17 DK DK00958461T patent/DK1248768T3/da active
- 2000-08-17 JP JP2001521701A patent/JP4768941B2/ja not_active Expired - Fee Related
- 2000-08-17 CA CA002383729A patent/CA2383729A1/en not_active Abandoned
- 2000-08-17 ES ES00958461T patent/ES2251403T3/es not_active Expired - Lifetime
- 2000-09-05 US US09/655,725 patent/US6451781B1/en not_active Expired - Lifetime
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02286619A (ja) * | 1989-04-28 | 1990-11-26 | Hajime Takigawa | 利胆剤 |
| JPH072891A (ja) * | 1993-05-08 | 1995-01-06 | Hoechst Ag | 単量体胆汁酸誘導体、その調製方法および医薬としてのこれらの化合物の使用 |
| EP0676410A2 (en) * | 1994-04-06 | 1995-10-11 | ALFA WASSERMANN S.p.A. | Bile acids derivatives useful in the therapy of the biliary calculosis from cholesterol and of the pathologies caused by cholestasis |
| JPH09315979A (ja) * | 1996-05-24 | 1997-12-09 | Tokyo Tanabe Co Ltd | 利胆剤 |
| JP2002528460A (ja) * | 1998-10-28 | 2002-09-03 | アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 胆汁酸で置換されたフェニルアルケノイルグアニジン類、その製造方法、その薬剤または診断薬としての使用、およびそれらを含有する薬剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| ATE309981T1 (de) | 2005-12-15 |
| EP1248768B1 (de) | 2005-11-16 |
| WO2001017954A1 (de) | 2001-03-15 |
| IL148250A0 (en) | 2002-09-12 |
| DE19941764A1 (de) | 2001-03-15 |
| EP1248768A1 (de) | 2002-10-16 |
| DE50011660D1 (de) | 2005-12-22 |
| AU774083B2 (en) | 2004-06-17 |
| AU6996500A (en) | 2001-04-10 |
| CA2383729A1 (en) | 2001-03-15 |
| ES2251403T3 (es) | 2006-05-01 |
| DK1248768T3 (da) | 2006-03-27 |
| JP2003508513A (ja) | 2003-03-04 |
| US6451781B1 (en) | 2002-09-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4616479B2 (ja) | 胆汁酸で置換されたフェニルアルケノイルグアニジン類、その製造方法、その薬剤または診断薬としての使用、およびそれらを含有する薬剤 | |
| JP4768941B2 (ja) | 胆汁酸置換フェニルアルケノイルグアニジン、それらの製造方法、医薬または診断薬としてのそれらの使用、およびそれらを含む医薬 | |
| EP1608671B1 (en) | Oestrogen derivatives as inhibitors of steroid sulphatase | |
| RU2434635C2 (ru) | Применение производных 3,5-втор-4-норхолестана для получения лекарственного средства - цитопротектора | |
| JP2014051525A (ja) | 細胞保護剤を得るためのコレスト−４−エン−３−オン誘導体の使用 | |
| US6339077B1 (en) | Substituted 4-benzylaminoquinolines and their hetero analogs, process for their preparation, pharmaceuticals containing these compounds and use thereof | |
| JP5845274B2 (ja) | 生物学的特性を賦与されたジテルペノイド誘導体 | |
| MXPA02002181A (es) | Fenil-alquenoilguanidinas substituidas del acido biliar, proceso para su preparacion, su uso como medicamentos o agentes de diagnostico, y medicamentos que contienen las mismas. | |
| MXPA01004147A (en) | Bile-acid substituted phenyl alkenoyl guanidines, method for the production thereof, use thereof as medicaments or diagnostic agents and medicaments that contain them | |
| DE10028193A1 (de) | Substituierte 4-Benzylamminochinoline und ihre Heteroanalogen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikamente oder Diagnostika, sowie sie enthaltende Medikamente | |
| DE19945385A1 (de) | Substituierte 4-Benzylaminochinoline und ihre Heteroanlagen, Verfahren zu ihrer Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung | |
| HK1082258B (en) | Oestrogen derivatives as inhibitors of steroid sulphatase |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070815 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070815 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20090929 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20101116 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110214 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20110214 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20110524 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20110617 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140624 Year of fee payment: 3 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |