JP4486363B2 - 置換３−フェニル−５−アルコキシ−１，３，４−オキサジアゾール−２−オン、これの製造方法および薬剤での使用 - Google Patents
置換３−フェニル−５−アルコキシ−１，３，４−オキサジアゾール−２−オン、これの製造方法および薬剤での使用 Download PDFInfo
- Publication number
- JP4486363B2 JP4486363B2 JP2003571261A JP2003571261A JP4486363B2 JP 4486363 B2 JP4486363 B2 JP 4486363B2 JP 2003571261 A JP2003571261 A JP 2003571261A JP 2003571261 A JP2003571261 A JP 2003571261A JP 4486363 B2 JP4486363 B2 JP 4486363B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- alkyl
- compound
- phenyl
- hydrogen
- 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 description 10
- 239000003814 drug Substances 0.000 title claims 4
- 238000002360 preparation method Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- -1 aryl halogen Chemical class 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical class ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 2
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 102000019280 Pancreatic lipases Human genes 0.000 description 11
- 108050006759 Pancreatic lipases Proteins 0.000 description 11
- 229940116369 pancreatic lipase Drugs 0.000 description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 102000004882 Lipase Human genes 0.000 description 6
- 108090001060 Lipase Proteins 0.000 description 6
- 239000004367 Lipase Substances 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 229940040461 lipase Drugs 0.000 description 6
- 235000019421 lipase Nutrition 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 0 Cc1cc(NN)c(*)c(C)c1* Chemical compound Cc1cc(NN)c(*)c(C)c1* 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229910052731 fluorine Chemical group 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000011737 fluorine Chemical group 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000000465 moulding Methods 0.000 description 3
- 229940049964 oleate Drugs 0.000 description 3
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-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
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- DAQCUXYFZBBWOG-UHFFFAOYSA-N 5-dodecoxy-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCC)=NN1C1=CC=C(OC(F)(F)F)C=C1 DAQCUXYFZBBWOG-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- PVNIQBQSYATKKL-UHFFFAOYSA-N tripalmitin Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC PVNIQBQSYATKKL-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- WWQYTEPUEUNBOM-SANMLTNESA-N (2,5-dioxopyrrolidin-1-yl) (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-(1h-indol-3-yl)propanoate Chemical compound O=C([C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)ON1C(=O)CCC1=O WWQYTEPUEUNBOM-SANMLTNESA-N 0.000 description 1
- 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
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- BFCFYVKQTRLZHA-UHFFFAOYSA-N 1-chloro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1Cl BFCFYVKQTRLZHA-UHFFFAOYSA-N 0.000 description 1
- PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 1
- JSMHDBKKRKIODL-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)-5-dodecoxy-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCC)=NN1C1=CC=C(Cl)C(Cl)=C1 JSMHDBKKRKIODL-UHFFFAOYSA-N 0.000 description 1
- XFXATWRVESLWOD-UHFFFAOYSA-N 3-(3,5-dichlorophenyl)-5-dodecoxy-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCC)=NN1C1=CC(Cl)=CC(Cl)=C1 XFXATWRVESLWOD-UHFFFAOYSA-N 0.000 description 1
- MSJAIQHIBPBEEV-UHFFFAOYSA-N 3-(3-fluorophenyl)-5-hexadecoxy-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCCCCCC)=NN1C1=CC=CC(F)=C1 MSJAIQHIBPBEEV-UHFFFAOYSA-N 0.000 description 1
- QLCWFCMKOBSFOZ-UHFFFAOYSA-N 3-(3-fluorophenyl)-5-octoxy-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCC)=NN1C1=CC=CC(F)=C1 QLCWFCMKOBSFOZ-UHFFFAOYSA-N 0.000 description 1
- DXNJIIBCBHPGSQ-UHFFFAOYSA-N 3-[3,5-bis(trifluoromethyl)phenyl]-5-dodecoxy-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCC)=NN1C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 DXNJIIBCBHPGSQ-UHFFFAOYSA-N 0.000 description 1
- USVHPVMUQWBGMQ-UHFFFAOYSA-N 3-[4-(4-chlorophenoxy)phenyl]-5-hexadecoxy-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCCCCCC)=NN1C(C=C1)=CC=C1OC1=CC=C(Cl)C=C1 USVHPVMUQWBGMQ-UHFFFAOYSA-N 0.000 description 1
- ZWGZPZUDKAILJM-UHFFFAOYSA-N 3-[4-(trifluoromethoxy)phenyl]-5-undecoxy-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCC)=NN1C1=CC=C(OC(F)(F)F)C=C1 ZWGZPZUDKAILJM-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- KTEODHASAFPODP-UHFFFAOYSA-N 5-(2-butoxyethoxy)-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCOCCCC)=NN1C1=CC=C(OC(F)(F)F)C=C1 KTEODHASAFPODP-UHFFFAOYSA-N 0.000 description 1
- KAWBGZHWHSUWLS-UHFFFAOYSA-N 5-(2-docosoxyethoxy)-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCOCCCCCCCCCCCCCCCCCCCCCC)=NN1C1=CC=C(OC(F)(F)F)C=C1 KAWBGZHWHSUWLS-UHFFFAOYSA-N 0.000 description 1
- FCHJQWWCWWMWIO-UHFFFAOYSA-N 5-(2-dodecoxyethoxy)-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCOCCCCCCCCCCCC)=NN1C1=CC=C(OC(F)(F)F)C=C1 FCHJQWWCWWMWIO-UHFFFAOYSA-N 0.000 description 1
- ANEHBGWFDKFACL-UHFFFAOYSA-N 5-(2-naphthalen-1-yloxyethoxy)-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1N1C(=O)OC(OCCOC=2C3=CC=CC=C3C=CC=2)=N1 ANEHBGWFDKFACL-UHFFFAOYSA-N 0.000 description 1
- CXWCAERLHPSWPE-UHFFFAOYSA-N 5-(3-phenoxyphenoxy)-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1N1C(=O)OC(OC=2C=C(OC=3C=CC=CC=3)C=CC=2)=N1 CXWCAERLHPSWPE-UHFFFAOYSA-N 0.000 description 1
- USJCNWJSEUOJHB-UHFFFAOYSA-N 5-(4-octylphenoxy)-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound C1=CC(CCCCCCCC)=CC=C1OC(OC1=O)=NN1C1=CC=C(OC(F)(F)F)C=C1 USJCNWJSEUOJHB-UHFFFAOYSA-N 0.000 description 1
- CFRTWRNZFNJJQX-UHFFFAOYSA-N 5-(7-phenylheptoxy)-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1N1C(=O)OC(OCCCCCCCC=2C=CC=CC=2)=N1 CFRTWRNZFNJJQX-UHFFFAOYSA-N 0.000 description 1
- VJPXSIAXZGJFFS-KTKRTIGZSA-N 5-[(z)-octadec-9-enoxy]-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCC\C=C/CCCCCCCC)=NN1C1=CC=C(OC(F)(F)F)C=C1 VJPXSIAXZGJFFS-KTKRTIGZSA-N 0.000 description 1
- RCSTXABZZTZXMV-UHFFFAOYSA-N 5-[2-(2-hexoxyethoxy)ethoxy]-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCOCCOCCCCCC)=NN1C1=CC=C(OC(F)(F)F)C=C1 RCSTXABZZTZXMV-UHFFFAOYSA-N 0.000 description 1
- JGMJGAQTZUBYFP-UHFFFAOYSA-N 5-[2-(4-fluorophenyl)ethoxy]-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound C1=CC(F)=CC=C1CCOC(OC1=O)=NN1C1=CC=C(OC(F)(F)F)C=C1 JGMJGAQTZUBYFP-UHFFFAOYSA-N 0.000 description 1
- VORQVZRCSGBZKE-UHFFFAOYSA-N 5-decoxy-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCC)=NN1C1=CC=C(OC(F)(F)F)C=C1 VORQVZRCSGBZKE-UHFFFAOYSA-N 0.000 description 1
- DOGSHHAIGJHIDD-UHFFFAOYSA-N 5-dodecoxy-3-(2-methyl-4-nitrophenyl)-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCC)=NN1C1=CC=C([N+]([O-])=O)C=C1C DOGSHHAIGJHIDD-UHFFFAOYSA-N 0.000 description 1
- AVCWQAFZYHEIDX-UHFFFAOYSA-N 5-dodecoxy-3-(3-fluorophenyl)-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCC)=NN1C1=CC=CC(F)=C1 AVCWQAFZYHEIDX-UHFFFAOYSA-N 0.000 description 1
- YOZKBGNPARHOOJ-UHFFFAOYSA-N 5-dodecoxy-3-(3-methoxyphenyl)-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCC)=NN1C1=CC=CC(OC)=C1 YOZKBGNPARHOOJ-UHFFFAOYSA-N 0.000 description 1
- JYEIXTIYFRUDMV-UHFFFAOYSA-N 5-dodecoxy-3-(3-methyl-4-nitrophenyl)-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCC)=NN1C1=CC=C([N+]([O-])=O)C(C)=C1 JYEIXTIYFRUDMV-UHFFFAOYSA-N 0.000 description 1
- VRIHMKLCOJEQDE-UHFFFAOYSA-N 5-dodecoxy-3-(3-nitrophenyl)-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCC)=NN1C1=CC=CC([N+]([O-])=O)=C1 VRIHMKLCOJEQDE-UHFFFAOYSA-N 0.000 description 1
- DFJDTKQNVOIBSM-UHFFFAOYSA-N 5-dodecoxy-3-(4-methoxyphenyl)-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCC)=NN1C1=CC=C(OC)C=C1 DFJDTKQNVOIBSM-UHFFFAOYSA-N 0.000 description 1
- KZSGDHSOIULPGW-UHFFFAOYSA-N 5-dodecoxy-3-(4-phenylmethoxyphenyl)-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCC)=NN1C(C=C1)=CC=C1OCC1=CC=CC=C1 KZSGDHSOIULPGW-UHFFFAOYSA-N 0.000 description 1
- UBBJMUOIUVQVTH-UHFFFAOYSA-N 5-dodecoxy-3-[3-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCC)=NN1C1=CC=CC(C(F)(F)F)=C1 UBBJMUOIUVQVTH-UHFFFAOYSA-N 0.000 description 1
- YJAYMTUHVNAYAQ-UHFFFAOYSA-N 5-dodecoxy-3-[3-[(4-fluorophenyl)methoxy]-4-nitrophenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCC)=NN1C1=CC=C([N+]([O-])=O)C(OCC=2C=CC(F)=CC=2)=C1 YJAYMTUHVNAYAQ-UHFFFAOYSA-N 0.000 description 1
- ZXBXMCCGRVLPFN-UHFFFAOYSA-N 5-hexadecoxy-3-(3-phenylmethoxyphenyl)-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCCCCCC)=NN1C1=CC=CC(OCC=2C=CC=CC=2)=C1 ZXBXMCCGRVLPFN-UHFFFAOYSA-N 0.000 description 1
- HKIIVKOWULQILO-UHFFFAOYSA-N 5-hexadecoxy-3-(4-methoxyphenyl)-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCCCCCC)=NN1C1=CC=C(OC)C=C1 HKIIVKOWULQILO-UHFFFAOYSA-N 0.000 description 1
- AZTCGCZGIUAACA-UHFFFAOYSA-N 5-hexadecoxy-3-(4-nitrophenyl)-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCCCCCC)=NN1C1=CC=C([N+]([O-])=O)C=C1 AZTCGCZGIUAACA-UHFFFAOYSA-N 0.000 description 1
- WAWMFDDWYFKRLW-UHFFFAOYSA-N 5-hexadecoxy-3-(4-phenylmethoxyphenyl)-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCCCCCC)=NN1C(C=C1)=CC=C1OCC1=CC=CC=C1 WAWMFDDWYFKRLW-UHFFFAOYSA-N 0.000 description 1
- NQWZPEJRZHFWTB-UHFFFAOYSA-N 5-hexadecoxy-3-[3-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCCCCCC)=NN1C1=CC=CC(OC(F)(F)F)=C1 NQWZPEJRZHFWTB-UHFFFAOYSA-N 0.000 description 1
- YFKQDPGJRYBXTH-UHFFFAOYSA-N 5-hexadecoxy-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCCCCCC)=NN1C1=CC=C(OC(F)(F)F)C=C1 YFKQDPGJRYBXTH-UHFFFAOYSA-N 0.000 description 1
- LSMDTJGWMAMALY-UHFFFAOYSA-N 5-hexadecoxy-3-phenyl-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCCCCCC)=NN1C1=CC=CC=C1 LSMDTJGWMAMALY-UHFFFAOYSA-N 0.000 description 1
- QXYASWOKQJIWSV-UHFFFAOYSA-N 5-octoxy-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCC)=NN1C1=CC=C(OC(F)(F)F)C=C1 QXYASWOKQJIWSV-UHFFFAOYSA-N 0.000 description 1
- WOEUAJWNBJVHPZ-UHFFFAOYSA-N 5-octoxy-3-phenyl-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCC)=NN1C1=CC=CC=C1 WOEUAJWNBJVHPZ-UHFFFAOYSA-N 0.000 description 1
- UUTYLSKGIIEBRI-UHFFFAOYSA-N 5-phenoxy-3h-1,3,4-oxadiazol-2-one Chemical class O1C(=O)NN=C1OC1=CC=CC=C1 UUTYLSKGIIEBRI-UHFFFAOYSA-N 0.000 description 1
- PSPURMODQIRUPG-UHFFFAOYSA-N 5-tetradecoxy-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCCCC)=NN1C1=CC=C(OC(F)(F)F)C=C1 PSPURMODQIRUPG-UHFFFAOYSA-N 0.000 description 1
- CWIPYBTXUPMXSY-UHFFFAOYSA-N 5-tridecoxy-3-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-one Chemical compound O=C1OC(OCCCCCCCCCCCCC)=NN1C1=CC=C(OC(F)(F)F)C=C1 CWIPYBTXUPMXSY-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- WRDABNWSWOHGMS-UHFFFAOYSA-N AEBSF hydrochloride Chemical compound Cl.NCCC1=CC=C(S(F)(=O)=O)C=C1 WRDABNWSWOHGMS-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 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
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- UENOCNZZJOCVKE-JMPHAEBRSA-N O([C@@H]1CC2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)C(OC1=O)=NN1C1=CC=C(OC(F)(F)F)C=C1 Chemical compound O([C@@H]1CC2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)C(OC1=O)=NN1C1=CC=C(OC(F)(F)F)C=C1 UENOCNZZJOCVKE-JMPHAEBRSA-N 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 102000000019 Sterol Esterase Human genes 0.000 description 1
- 108010055297 Sterol Esterase Proteins 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- BAECOWNUKCLBPZ-HIUWNOOHSA-N Triolein Natural products O([C@H](OCC(=O)CCCCCCC/C=C\CCCCCCCC)COC(=O)CCCCCCC/C=C\CCCCCCCC)C(=O)CCCCCCC/C=C\CCCCCCCC BAECOWNUKCLBPZ-HIUWNOOHSA-N 0.000 description 1
- PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- GWFWCTYACJWQKP-UHFFFAOYSA-N [4-(trifluoromethoxy)phenyl]hydrazine Chemical compound NNC1=CC=C(OC(F)(F)F)C=C1 GWFWCTYACJWQKP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229920006318 anionic polymer Polymers 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 239000013011 aqueous formulation Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003705 background correction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000001530 fumaric acid 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
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 150000005171 halobenzenes Chemical class 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 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
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
- 229960001947 tripalmitin Drugs 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C07D271/113—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10208987A DE10208987A1 (de) | 2002-02-28 | 2002-02-28 | Substituierte 3-Phenyl-5-alkoxi-1,3,4-oxidiazol-2-one, ihre Herstellung und Verwendung in Arzneistoffen |
| PCT/EP2003/001484 WO2003072555A1 (de) | 2002-02-28 | 2003-02-14 | Substituierte 3-phenyl-5-alkoxy-1,3,4-oxadiazol-2-one sowie ihre herstellung und verwendung in arzneistoffen |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005519085A JP2005519085A (ja) | 2005-06-30 |
| JP2005519085A5 JP2005519085A5 (enExample) | 2006-03-30 |
| JP4486363B2 true JP4486363B2 (ja) | 2010-06-23 |
Family
ID=27740558
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003571261A Expired - Fee Related JP4486363B2 (ja) | 2002-02-28 | 2003-02-14 | 置換３−フェニル−５−アルコキシ−１，３，４−オキサジアゾール−２−オン、これの製造方法および薬剤での使用 |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP1480960B1 (enExample) |
| JP (1) | JP4486363B2 (enExample) |
| KR (1) | KR20040095240A (enExample) |
| CN (1) | CN1639137A (enExample) |
| AR (1) | AR038701A1 (enExample) |
| AT (1) | ATE557012T1 (enExample) |
| AU (1) | AU2003226977A1 (enExample) |
| BR (1) | BR0307921A (enExample) |
| CA (1) | CA2477031A1 (enExample) |
| CO (1) | CO5611146A2 (enExample) |
| DE (1) | DE10208987A1 (enExample) |
| HR (1) | HRP20040782A2 (enExample) |
| HU (1) | HUP0402671A3 (enExample) |
| IL (1) | IL163683A0 (enExample) |
| MA (1) | MA27172A1 (enExample) |
| MX (1) | MXPA04007960A (enExample) |
| NO (1) | NO20044090L (enExample) |
| PE (1) | PE20030928A1 (enExample) |
| PL (1) | PL370423A1 (enExample) |
| RU (1) | RU2004128933A (enExample) |
| TW (1) | TW200400951A (enExample) |
| WO (1) | WO2003072555A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7074822B2 (en) | 2004-02-23 | 2006-07-11 | Solvay Pharmaceuticals Gmbh | Alkyl carbamate-substituted β-lactones, process for their preparation, and pharmaceutical compositions containing them |
| CA2585175A1 (en) | 2004-10-25 | 2006-05-04 | Solvay Pharmaceuticals Gmbh | Pharmaceutical compositions comprising cb1 cannabinoid receptor antagonists and potassium channel openers for the treatment of diabetes mellitus type i, obesity and related conditions |
| CA2710743A1 (en) * | 2007-12-27 | 2009-07-09 | Bial-Portela & Ca., S.A. | 5-o-substituted 3-n-phenyl-1,3,4-oxadiazolones for medical use |
| TW201028406A (en) | 2008-12-23 | 2010-08-01 | Bial Portela & Ca Sa | 5-O-substituted 3-N-aryl-1,3,4-oxadiazolones for medical use |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19942354A1 (de) * | 1999-09-04 | 2001-03-08 | Aventis Pharma Gmbh | Substituierte 3-Phenyl-5-alkoxi-1,3,4-oxdiazol-2-one, ihre Herstellung und Verwendung in Arzneimitteln |
| WO2001066531A1 (de) * | 2000-03-07 | 2001-09-13 | Aventis Pharma Deutschland Gmbh | Substituierte 3-phenyl-5-alkoxi-1,3,4-oxdiazol-2-one (und) ihre verwendung zur hemmung der hormonsensitiven lipase |
-
2002
- 2002-02-28 DE DE10208987A patent/DE10208987A1/de not_active Withdrawn
-
2003
- 2003-02-05 PE PE2003000134A patent/PE20030928A1/es not_active Application Discontinuation
- 2003-02-14 AT AT03742936T patent/ATE557012T1/de active
- 2003-02-14 CN CNA038047837A patent/CN1639137A/zh active Pending
- 2003-02-14 AU AU2003226977A patent/AU2003226977A1/en not_active Abandoned
- 2003-02-14 HU HU0402671A patent/HUP0402671A3/hu unknown
- 2003-02-14 JP JP2003571261A patent/JP4486363B2/ja not_active Expired - Fee Related
- 2003-02-14 MX MXPA04007960A patent/MXPA04007960A/es unknown
- 2003-02-14 KR KR10-2004-7013485A patent/KR20040095240A/ko not_active Withdrawn
- 2003-02-14 EP EP03742936A patent/EP1480960B1/de not_active Expired - Lifetime
- 2003-02-14 PL PL03370423A patent/PL370423A1/xx not_active Application Discontinuation
- 2003-02-14 WO PCT/EP2003/001484 patent/WO2003072555A1/de not_active Ceased
- 2003-02-14 HR HR20040782A patent/HRP20040782A2/hr not_active Application Discontinuation
- 2003-02-14 IL IL16368303A patent/IL163683A0/xx unknown
- 2003-02-14 CA CA002477031A patent/CA2477031A1/en not_active Abandoned
- 2003-02-14 BR BR0307921-0A patent/BR0307921A/pt not_active Application Discontinuation
- 2003-02-14 RU RU2004128933/04A patent/RU2004128933A/ru not_active Application Discontinuation
- 2003-02-26 TW TW092103969A patent/TW200400951A/zh unknown
- 2003-02-26 AR ARP030100624A patent/AR038701A1/es unknown
-
2004
- 2004-07-27 MA MA27803A patent/MA27172A1/fr unknown
- 2004-08-26 CO CO04083779A patent/CO5611146A2/es not_active Application Discontinuation
- 2004-09-27 NO NO20044090A patent/NO20044090L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| HRP20040782A2 (en) | 2005-02-28 |
| NO20044090L (no) | 2004-11-04 |
| PE20030928A1 (es) | 2003-12-17 |
| EP1480960B1 (de) | 2012-05-09 |
| EP1480960A1 (de) | 2004-12-01 |
| AU2003226977A1 (en) | 2003-09-09 |
| AR038701A1 (es) | 2005-01-26 |
| CO5611146A2 (es) | 2006-02-28 |
| KR20040095240A (ko) | 2004-11-12 |
| MA27172A1 (fr) | 2005-01-03 |
| CN1639137A (zh) | 2005-07-13 |
| RU2004128933A (ru) | 2005-04-20 |
| BR0307921A (pt) | 2004-12-21 |
| MXPA04007960A (es) | 2004-11-26 |
| ATE557012T1 (de) | 2012-05-15 |
| TW200400951A (en) | 2004-01-16 |
| IL163683A0 (en) | 2005-12-18 |
| HUP0402671A2 (hu) | 2005-04-28 |
| WO2003072555A1 (de) | 2003-09-04 |
| CA2477031A1 (en) | 2003-09-04 |
| DE10208987A1 (de) | 2003-09-11 |
| JP2005519085A (ja) | 2005-06-30 |
| HUP0402671A3 (en) | 2006-07-28 |
| PL370423A1 (en) | 2005-05-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2780433C (en) | Sphingosine 1 phosphate receptor modulators and methods of chiral synthesis | |
| EP1988091B1 (en) | Tricyclic compounds | |
| US6506778B2 (en) | Acylphenylurea derivatives, a process for their preparation and their use as pharmaceuticals | |
| RS61829B1 (sr) | Selektivni modulatori receptora sfingozin 1 fosfata i metode hiralne sinteze | |
| AU2004311909A1 (en) | Triazole, oxadiazole and thiadiazole derivative as PPAR modulators for the treatment of diabetes | |
| HUE034647T2 (hu) | Oxálsavamidok mint neprilizin inhibitorok, gyógyszerkészítményeik és elõállításuk | |
| KR20080072688A (ko) | 옥사디아졸 유도체 | |
| US6596742B1 (en) | Substituted 3-phenyl-5-alkoxy-1,3,4-oxadiazol-2-ones, their preparation and their use in medicaments | |
| JPH11513376A (ja) | 選択的β▲下３▼−アドレナリン作動剤 | |
| JP4486363B2 (ja) | 置換３−フェニル−５−アルコキシ−１，３，４−オキサジアゾール−２−オン、これの製造方法および薬剤での使用 | |
| JP2005519079A (ja) | 膵臓リパーゼを阻害する薬剤を製造するための、置換された３−フェニル−５−アルコキシ−１，３，４−オキサジアゾール−２−オンの使用 | |
| EP2463279B1 (en) | 4-(1,2,4-dioxazol-3-yl)benzamides for the treatment of diabetes and obesity | |
| US6900233B2 (en) | Substituted 3-phenyl-5-alkoxy-3H-(1,3,4)-oxadiazol-2-ones, pharmaceutical composition and method for treating obesity thereof | |
| TW202239756A (zh) | 作為組蛋白去乙醯酶6抑制劑之1,3,4-㗁二唑硫羰基化合物及包含該等化合物之醫藥組合物 | |
| US20030236288A1 (en) | Use of substituted 3-phenyl-5-alkoxy-3H-(1,3,4)-oxadizol-2-ones for inhibiting pancreatic lipase | |
| EP1940815B1 (en) | Salts of modulators of ppar and methods of treating metabolic disorders | |
| CA2770405A1 (en) | Sulfone derivative | |
| JP4560259B2 (ja) | ベンズイミダゾール化合物及びそれを含む医薬 | |
| MX2011005094A (es) | Derivados de azepinona. | |
| RU2271350C2 (ru) | Производные ацилфенилмочевины, фармацевтическая композиция и способ ее получения | |
| JP4220827B2 (ja) | 安息香酸誘導体及びこれを含有する医薬 | |
| HK1171011B (en) | Sulfone derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060209 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060209 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090901 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091130 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20100302 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20100326 |
|
| 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: 20130402 Year of fee payment: 3 |
|
| LAPS | Cancellation because of no payment of annual fees |