JPS6310783A - 新規フオルスコリン誘導体 - Google Patents
新規フオルスコリン誘導体Info
- Publication number
- JPS6310783A JPS6310783A JP25594186A JP25594186A JPS6310783A JP S6310783 A JPS6310783 A JP S6310783A JP 25594186 A JP25594186 A JP 25594186A JP 25594186 A JP25594186 A JP 25594186A JP S6310783 A JPS6310783 A JP S6310783A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- group
- forskolin
- reaction
- formula
- 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.)
- Granted
Links
- 150000004160 forskolin derivatives Chemical class 0.000 title description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 6
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 107
- OHCQJHSOBUTRHG-KGGHGJDLSA-N forskolin group Chemical group C(C)(=O)O[C@H]1[C@H]([C@@H]2[C@@]([C@]3(C(C[C@](O[C@]13C)(C)C=C)=O)O)([C@H](CCC2(C)C)O)C)O OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 abstract description 86
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 abstract description 45
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 abstract description 45
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 abstract description 21
- -1 triethylamine Chemical class 0.000 abstract description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 abstract description 19
- 239000002904 solvent Substances 0.000 abstract description 17
- 238000002360 preparation method Methods 0.000 abstract description 4
- 125000001424 substituent group Chemical group 0.000 abstract description 4
- 150000007530 organic bases Chemical class 0.000 abstract description 3
- 206010061598 Immunodeficiency Diseases 0.000 abstract description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 abstract description 2
- 230000007813 immunodeficiency Effects 0.000 abstract description 2
- 229940124549 vasodilator Drugs 0.000 abstract description 2
- 239000003071 vasodilator agent Substances 0.000 abstract description 2
- 206010019280 Heart failures Diseases 0.000 abstract 1
- 210000004556 brain Anatomy 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 229920002554 vinyl polymer Polymers 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
- 238000006243 chemical reaction Methods 0.000 description 74
- 239000000243 solution Substances 0.000 description 47
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 33
- 239000000203 mixture Substances 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 30
- 238000001816 cooling Methods 0.000 description 26
- 239000002274 desiccant Substances 0.000 description 26
- 239000012044 organic layer Substances 0.000 description 26
- 238000010898 silica gel chromatography Methods 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- 239000003921 oil Substances 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- 235000019341 magnesium sulphate Nutrition 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000000034 method Methods 0.000 description 15
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 239000012141 concentrate Substances 0.000 description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 239000012230 colorless oil Substances 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 238000010828 elution Methods 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 102000030621 adenylate cyclase Human genes 0.000 description 8
- 108060000200 adenylate cyclase Proteins 0.000 description 8
- 238000009835 boiling Methods 0.000 description 8
- 239000010410 layer Substances 0.000 description 7
- 239000012046 mixed solvent Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 101150041968 CDC13 gene Proteins 0.000 description 5
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
- 239000012346 acetyl chloride Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 229940125904 compound 1 Drugs 0.000 description 5
- 238000009833 condensation Methods 0.000 description 5
- 230000005494 condensation Effects 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
- 230000009090 positive inotropic effect Effects 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 150000008065 acid anhydrides Chemical class 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 4
- 230000002349 favourable effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 3
- RDTALXUBMCLWBB-UHFFFAOYSA-N 4-(dimethylamino)butanoic acid;hydron;chloride Chemical compound Cl.CN(C)CCCC(O)=O RDTALXUBMCLWBB-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical group [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 3
- VANNPISTIUFMLH-UHFFFAOYSA-N glutaric anhydride Chemical compound O=C1CCCC(=O)O1 VANNPISTIUFMLH-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 238000006462 rearrangement reaction Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 229940014800 succinic anhydride Drugs 0.000 description 3
- 238000009423 ventilation Methods 0.000 description 3
- RBNPOMFGQQGHHO-UHFFFAOYSA-N -2,3-Dihydroxypropanoic acid Natural products OCC(O)C(O)=O RBNPOMFGQQGHHO-UHFFFAOYSA-N 0.000 description 2
- IPXNXMNCBXHYLQ-UHFFFAOYSA-N 2-pyrrolidin-1-ylacetic acid Chemical compound OC(=O)CN1CCCC1 IPXNXMNCBXHYLQ-UHFFFAOYSA-N 0.000 description 2
- HIDJWBGOQFTDLU-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)NCCCC(O)=O HIDJWBGOQFTDLU-UHFFFAOYSA-N 0.000 description 2
- CDIIZULDSLKBKV-UHFFFAOYSA-N 4-chlorobutanoyl chloride Chemical compound ClCCCC(Cl)=O CDIIZULDSLKBKV-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- RBNPOMFGQQGHHO-UWTATZPHSA-N D-glyceric acid Chemical compound OC[C@@H](O)C(O)=O RBNPOMFGQQGHHO-UWTATZPHSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical group COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- VXDSLUMUNWTSDB-UHFFFAOYSA-N acetic acid;chloroform;methanol Chemical compound OC.CC(O)=O.ClC(Cl)Cl VXDSLUMUNWTSDB-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229940127573 compound 38 Drugs 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- WPDITXOBNLYZHH-UHFFFAOYSA-N desacetylforskolin Natural products O1C(C)(C=C)CC(=O)C2(O)C3(C)C(O)CCC(C)(C)C3C(O)C(O)C21C WPDITXOBNLYZHH-UHFFFAOYSA-N 0.000 description 2
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 2
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000001033 ether group Chemical group 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000001077 hypotensive effect Effects 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 2
- LWHYKTAISUZRAD-UHFFFAOYSA-L palladium(2+);carbonate Chemical compound [Pd+2].[O-]C([O-])=O LWHYKTAISUZRAD-UHFFFAOYSA-L 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical group CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 2
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 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
- 230000002861 ventricular Effects 0.000 description 2
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60-254693 | 1985-11-15 | ||
| JP25469385 | 1985-11-15 | ||
| JP61-13771 | 1986-01-27 | ||
| JP61-53709 | 1986-03-13 | ||
| JP61-65947 | 1986-03-26 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3146607A Division JPH0739409B2 (ja) | 1985-11-15 | 1991-05-23 | 新規フォルスコリン誘導体 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6310783A true JPS6310783A (ja) | 1988-01-18 |
| JPH0440350B2 JPH0440350B2 (enrdf_load_stackoverflow) | 1992-07-02 |
Family
ID=17268547
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP25594186A Granted JPS6310783A (ja) | 1985-11-15 | 1986-10-29 | 新規フオルスコリン誘導体 |
| JP3146607A Expired - Fee Related JPH0739409B2 (ja) | 1985-11-15 | 1991-05-23 | 新規フォルスコリン誘導体 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3146607A Expired - Fee Related JPH0739409B2 (ja) | 1985-11-15 | 1991-05-23 | 新規フォルスコリン誘導体 |
Country Status (2)
| Country | Link |
|---|---|
| JP (2) | JPS6310783A (enrdf_load_stackoverflow) |
| CS (1) | CS272221B2 (enrdf_load_stackoverflow) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999056743A1 (en) * | 1996-09-20 | 1999-11-11 | Nippon Kayaku Kabushiki Kaisha | Oral preparations containing forskolin derivatives and process for producing medicinal preparations |
| CN1092650C (zh) * | 1995-05-10 | 2002-10-16 | 花王株式会社 | 异苯并二氢吡喃化合物的制造方法 |
| US6475525B1 (en) | 1996-09-20 | 2002-11-05 | Nippon Kayaku Kabushiki Kaisha | Oral preparations containing forskolin derivatives and process for producing pharmaceutical preparations |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59152380A (ja) * | 1982-12-27 | 1984-08-31 | シエリング・コ−ポレ−シヨン | ラブダン誘導体を含む医薬組成物 |
| JPS61145178A (ja) * | 1984-12-14 | 1986-07-02 | ヘキスト‐ルセル・フアーマシユウテイカルズ・インコーポレイテツド | アミノアシルラブダン、その製造のための方法および中間体 |
| JPS61210081A (ja) * | 1985-03-01 | 1986-09-18 | ヘキスト‐ルセル・フアーマシユウテイカルズ・インコーポレイテツド | ラブダン誘導体およびそれらの製造方法 |
| JPS6289677A (ja) * | 1985-10-02 | 1987-04-24 | ヘキスト・アクチエンゲゼルシヤフト | 新規ポリ酸素化されたラブダン誘導体およびその製法 |
| JPS6323878A (ja) * | 1986-07-11 | 1988-02-01 | ヘキスト・アクチエンゲゼルシヤフト | ７−アシルオキシ−６−アミノアシルオキシポリオキシラブダンおよびその製法 |
-
1986
- 1986-10-29 JP JP25594186A patent/JPS6310783A/ja active Granted
- 1986-11-14 CS CS868287A patent/CS272221B2/cs not_active IP Right Cessation
-
1991
- 1991-05-23 JP JP3146607A patent/JPH0739409B2/ja not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59152380A (ja) * | 1982-12-27 | 1984-08-31 | シエリング・コ−ポレ−シヨン | ラブダン誘導体を含む医薬組成物 |
| JPS61145178A (ja) * | 1984-12-14 | 1986-07-02 | ヘキスト‐ルセル・フアーマシユウテイカルズ・インコーポレイテツド | アミノアシルラブダン、その製造のための方法および中間体 |
| JPS61210081A (ja) * | 1985-03-01 | 1986-09-18 | ヘキスト‐ルセル・フアーマシユウテイカルズ・インコーポレイテツド | ラブダン誘導体およびそれらの製造方法 |
| JPS6289677A (ja) * | 1985-10-02 | 1987-04-24 | ヘキスト・アクチエンゲゼルシヤフト | 新規ポリ酸素化されたラブダン誘導体およびその製法 |
| JPS6323878A (ja) * | 1986-07-11 | 1988-02-01 | ヘキスト・アクチエンゲゼルシヤフト | ７−アシルオキシ−６−アミノアシルオキシポリオキシラブダンおよびその製法 |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1092650C (zh) * | 1995-05-10 | 2002-10-16 | 花王株式会社 | 异苯并二氢吡喃化合物的制造方法 |
| WO1999056743A1 (en) * | 1996-09-20 | 1999-11-11 | Nippon Kayaku Kabushiki Kaisha | Oral preparations containing forskolin derivatives and process for producing medicinal preparations |
| US6475525B1 (en) | 1996-09-20 | 2002-11-05 | Nippon Kayaku Kabushiki Kaisha | Oral preparations containing forskolin derivatives and process for producing pharmaceutical preparations |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0440350B2 (enrdf_load_stackoverflow) | 1992-07-02 |
| CS272221B2 (en) | 1991-01-15 |
| JPH0739409B2 (ja) | 1995-05-01 |
| CS828786A2 (en) | 1990-03-14 |
| JPH05294955A (ja) | 1993-11-09 |
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