CZ295705B6 - Cyklodepsipeptidové deriváty sloučeniny PF1022 a farmaceutický prostředek s jejich obsahem - Google Patents
Cyklodepsipeptidové deriváty sloučeniny PF1022 a farmaceutický prostředek s jejich obsahem Download PDFInfo
- Publication number
- CZ295705B6 CZ295705B6 CZ1998855A CZ85598A CZ295705B6 CZ 295705 B6 CZ295705 B6 CZ 295705B6 CZ 1998855 A CZ1998855 A CZ 1998855A CZ 85598 A CZ85598 A CZ 85598A CZ 295705 B6 CZ295705 B6 CZ 295705B6
- Authority
- CZ
- Czechia
- Prior art keywords
- meleu
- group
- phlac
- lac
- alkoxy
- Prior art date
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- 108010002156 Depsipeptides Proteins 0.000 title claims abstract description 36
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 4
- 239000000126 substance Substances 0.000 title abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 283
- -1 morpholino, pyrrolidino Chemical group 0.000 claims description 200
- XJODGRWDFZVTKW-LURJTMIESA-N (2s)-4-methyl-2-(methylamino)pentanoic acid Chemical compound CN[C@H](C(O)=O)CC(C)C XJODGRWDFZVTKW-LURJTMIESA-N 0.000 claims description 143
- YJNUXGPXJFAUQJ-LYWANRAQSA-N PF1022A Chemical compound C([C@@H]1C(=O)N(C)[C@H](C(O[C@H](C)C(=O)N(C)[C@@H](CC(C)C)C(=O)O[C@H](CC=2C=CC=CC=2)C(=O)N(C)[C@@H](CC(C)C)C(=O)O[C@H](C)C(=O)N(C)[C@@H](CC(C)C)C(=O)O1)=O)CC(C)C)C1=CC=CC=C1 YJNUXGPXJFAUQJ-LYWANRAQSA-N 0.000 claims description 136
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 92
- 229910052757 nitrogen Inorganic materials 0.000 claims description 75
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 70
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 57
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 42
- 125000003277 amino group Chemical group 0.000 claims description 40
- 125000005843 halogen group Chemical group 0.000 claims description 38
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 36
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 35
- 125000004122 cyclic group Chemical group 0.000 claims description 35
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 125000001424 substituent group Chemical group 0.000 claims description 29
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 23
- 230000000507 anthelmentic effect Effects 0.000 claims description 22
- 125000006239 protecting group Chemical group 0.000 claims description 20
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 19
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 19
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 14
- 229920006395 saturated elastomer Polymers 0.000 claims description 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- VOXXWSYKYCBWHO-QMMMGPOBSA-N (S)-3-phenyllactic acid Chemical group OC(=O)[C@@H](O)CC1=CC=CC=C1 VOXXWSYKYCBWHO-QMMMGPOBSA-N 0.000 claims description 9
- 125000003282 alkyl amino group Chemical group 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 8
- 150000005326 tetrahydropyrimidines Chemical class 0.000 claims description 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 7
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 7
- VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 claims description 7
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 7
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 6
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
- 150000003222 pyridines Chemical class 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical group C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- JJBDWBUEPCGFMN-UHFFFAOYSA-N 3-phenyl-1,2,4-oxadiazole Chemical compound O1C=NC(C=2C=CC=CC=2)=N1 JJBDWBUEPCGFMN-UHFFFAOYSA-N 0.000 claims description 3
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 208000030852 Parasitic disease Diseases 0.000 abstract description 4
- 230000002265 prevention Effects 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 344
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 237
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 189
- 238000006243 chemical reaction Methods 0.000 description 173
- 239000000203 mixture Substances 0.000 description 163
- 239000002904 solvent Substances 0.000 description 106
- 125000003118 aryl group Chemical group 0.000 description 90
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 81
- 238000000034 method Methods 0.000 description 74
- 238000010898 silica gel chromatography Methods 0.000 description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
- 238000005481 NMR spectroscopy Methods 0.000 description 66
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 61
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 60
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 56
- 238000003786 synthesis reaction Methods 0.000 description 54
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 52
- 230000015572 biosynthetic process Effects 0.000 description 50
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 46
- 239000000843 powder Substances 0.000 description 44
- 239000012044 organic layer Substances 0.000 description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- 238000001704 evaporation Methods 0.000 description 41
- 230000008020 evaporation Effects 0.000 description 40
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 38
- 238000001816 cooling Methods 0.000 description 38
- 230000008569 process Effects 0.000 description 35
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 34
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 32
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 27
- 239000011780 sodium chloride Substances 0.000 description 27
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 26
- 238000012360 testing method Methods 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- 229910000027 potassium carbonate Inorganic materials 0.000 description 23
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 21
- 235000009518 sodium iodide Nutrition 0.000 description 20
- 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 20
- 239000003054 catalyst Substances 0.000 description 19
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 239000007858 starting material Substances 0.000 description 18
- 238000001914 filtration Methods 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- 229910052763 palladium Inorganic materials 0.000 description 16
- 244000045947 parasite Species 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 15
- 238000006722 reduction reaction Methods 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 14
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 14
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 14
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- 230000009467 reduction Effects 0.000 description 13
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 12
- 239000012954 diazonium Substances 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 12
- 239000012043 crude product Substances 0.000 description 11
- 150000001989 diazonium salts Chemical class 0.000 description 11
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 10
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 10
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 10
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 241000244206 Nematoda Species 0.000 description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 238000010531 catalytic reduction reaction Methods 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 125000004093 cyano group Chemical group *C#N 0.000 description 8
- 238000000855 fermentation Methods 0.000 description 8
- 230000004151 fermentation Effects 0.000 description 8
- 238000005755 formation reaction Methods 0.000 description 8
- 239000012442 inert solvent Substances 0.000 description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Chemical compound OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- WOCIAKWEIIZHES-UHFFFAOYSA-N ruthenium(iv) oxide Chemical compound O=[Ru]=O WOCIAKWEIIZHES-UHFFFAOYSA-N 0.000 description 6
- 235000010288 sodium nitrite Nutrition 0.000 description 6
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
- GXVUZYLYWKWJIM-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanamine Chemical class NCCOCCN GXVUZYLYWKWJIM-UHFFFAOYSA-N 0.000 description 5
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- 241001494479 Pecora Species 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 239000002198 insoluble material Substances 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 150000002828 nitro derivatives Chemical class 0.000 description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 125000004434 sulfur atom Chemical group 0.000 description 5
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
- REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 4
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 239000003377 acid catalyst Substances 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 229940124339 anthelmintic agent Drugs 0.000 description 4
- 239000000921 anthelmintic agent Substances 0.000 description 4
- 238000010533 azeotropic distillation Methods 0.000 description 4
- 239000002026 chloroform extract Substances 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 4
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 4
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- 239000003826 tablet Substances 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
- BFFLLBPMZCIGRM-QMMMGPOBSA-N tert-butyl (2s)-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1CO BFFLLBPMZCIGRM-QMMMGPOBSA-N 0.000 description 1
- QQWYQAQQADNEIC-RVDMUPIBSA-N tert-butyl [(z)-[cyano(phenyl)methylidene]amino] carbonate Chemical compound CC(C)(C)OC(=O)O\N=C(/C#N)C1=CC=CC=C1 QQWYQAQQADNEIC-RVDMUPIBSA-N 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Tropical Medicine & Parasitology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24405195 | 1995-09-22 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CZ85598A3 CZ85598A3 (cs) | 1998-08-12 |
| CZ295705B6 true CZ295705B6 (cs) | 2005-10-12 |
Family
ID=17113003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ1998855A CZ295705B6 (cs) | 1995-09-22 | 1996-09-20 | Cyklodepsipeptidové deriváty sloučeniny PF1022 a farmaceutický prostředek s jejich obsahem |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6329338B1 (en:Method) |
| EP (1) | EP0903347B1 (en:Method) |
| KR (1) | KR19990063676A (en:Method) |
| CN (1) | CN1082051C (en:Method) |
| AT (1) | ATE299871T1 (en:Method) |
| AU (1) | AU727532B2 (en:Method) |
| BR (1) | BR9610527A (en:Method) |
| CA (1) | CA2232668C (en:Method) |
| CZ (1) | CZ295705B6 (en:Method) |
| DE (1) | DE69634961T2 (en:Method) |
| DK (1) | DK0903347T3 (en:Method) |
| ES (1) | ES2246496T3 (en:Method) |
| HU (1) | HU228004B1 (en:Method) |
| IL (1) | IL123776A (en:Method) |
| NO (1) | NO310622B1 (en:Method) |
| NZ (1) | NZ318515A (en:Method) |
| PL (1) | PL186168B1 (en:Method) |
| WO (1) | WO1997011064A1 (en:Method) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2262679A1 (en) * | 1996-08-07 | 1998-02-12 | Meiji Seika Kaisha, Ltd. | Process for producing cyclodepsipeptide compounds and novel cyclodepsipeptide |
| WO1998037088A1 (en) * | 1997-02-19 | 1998-08-27 | Meiji Seika Kaisha Ltd. | Derivatives of cyclodepsipeptide, pf1022 substance |
| DE19811559A1 (de) * | 1998-03-17 | 1999-09-23 | Bayer Ag | Cyclooctadepsipeptide |
| US7109018B1 (en) | 1999-09-29 | 2006-09-19 | Meiji Seika Kaisha, Ltd. | Transformant producing secondary metabolite modified with functional group and novel biosynthesis genes |
| DE10031044A1 (de) * | 2000-06-26 | 2002-01-03 | Bayer Ag | Endoparasitizide Mittel zur freiwilligen oralen Aufnahme durch Tiere |
| DE10104362A1 (de) * | 2001-02-01 | 2002-08-08 | Bayer Ag | Kristallmodifikation eines cyclischen Depsipeptids mit besserer Wirksamkeit |
| DE102004055316A1 (de) * | 2004-11-16 | 2006-05-18 | Bayer Healthcare Ag | Verhinderung vertikaler Endoparasiten-Infektionen |
| DE102008022520A1 (de) | 2008-05-07 | 2009-11-12 | Bayer Animal Health Gmbh | Feste Arzneimittelformulierung mit verzögerter Freisetzung |
| DE102008030764A1 (de) | 2008-06-28 | 2009-12-31 | Bayer Animal Health Gmbh | Kombination von Amidin-Derivaten mit cyclischen Depsipeptiden |
| DE102008031284A1 (de) | 2008-07-02 | 2010-01-07 | Bayer Schering Pharma Aktiengesellschaft | Neue Bekämpfungsmöglichkeit der Giardiose |
| DE102008031283A1 (de) * | 2008-07-02 | 2010-01-07 | Bayer Schering Pharma Aktiengesellschaft | Neue Bekämpfungsmöglichkeit von durch Trichomonadida hervorgerufenen Krankheiten |
| DE102009012423A1 (de) | 2009-03-10 | 2010-09-16 | Bayer Animal Health Gmbh | Zubereitung auf Ölbasis |
| WO2012028556A1 (en) | 2010-08-31 | 2012-03-08 | Bayer Animal Health Gmbh | Macrocyclic lactones and their use and their combinations with other active substances |
| DE102010064245A1 (de) | 2010-12-28 | 2012-06-28 | Bayer Animal Health Gmbh | Makrocylischen Lactone und deren Verwendung und deren Kombinationen mit anderen Wirkstoffen |
| BR112017024773A2 (pt) | 2015-05-20 | 2018-11-06 | Merial, Inc. | compostos depsipeptídeos anti-helmínticos |
| WO2017116702A1 (en) | 2015-12-28 | 2017-07-06 | Merial, Inc. | Anthelmintic depsipeptide compounds |
| BR112019009977A2 (pt) | 2016-11-16 | 2019-08-27 | Boehringer Ingelheim Animal Health Usa Inc | compostos depsipeptídicos anti-helmínticos |
| US12122759B2 (en) * | 2017-11-07 | 2024-10-22 | Elanco Animal Health Gmbh | Method for the synthesis of cyclic depsipeptides |
| JP7164608B2 (ja) | 2017-11-29 | 2022-11-01 | ゾエティス・サービシーズ・エルエルシー | 内部寄生性デプシペプチド |
| SG11202010187RA (en) | 2018-05-10 | 2020-11-27 | Zoetis Services Llc | Endoparasitic depsipeptides |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH477172A (de) * | 1965-05-18 | 1969-08-31 | Agripat Sa | Beifuttermittel |
| EP0103895A3 (en) * | 1982-09-22 | 1985-07-03 | Meiji Seika Kabushiki Kaisha | Novel hydroxylamine derivatives, production and use thereof |
| NO176766C (no) * | 1989-02-07 | 1995-05-24 | Meiji Seika Kaisha | Fremgangsmåte for fremstilling av en forbindelse med anthelmintaktivitet |
| AU669883B2 (en) * | 1992-03-17 | 1996-06-27 | Astellas Pharma Inc. | Depsipeptide derivative, production thereof and use thereof |
| JP2873894B2 (ja) * | 1992-10-19 | 1999-03-24 | 明治製菓株式会社 | 環状デプシペプチドおよびその製造法 |
| CN1073560C (zh) * | 1993-02-19 | 2001-10-24 | 明治制果株式会社 | 环缩酚酸肽pf1022衍生物 |
| DE4317432A1 (de) * | 1993-05-26 | 1994-12-01 | Bayer Ag | Octacyclodepsipeptide mit endoparasitizider Wirkung |
| DE4317457A1 (de) * | 1993-05-26 | 1994-12-01 | Bayer Ag | Octacyclodepsipeptide mit endoparasitizider Wirkung |
| JPH07233068A (ja) * | 1993-12-27 | 1995-09-05 | Meiji Seika Kaisha Ltd | 高コレステロール血症、高脂血症又は動脈硬化症の治療薬 |
-
1996
- 1996-09-20 NZ NZ318515A patent/NZ318515A/xx not_active IP Right Cessation
- 1996-09-20 PL PL96326024A patent/PL186168B1/pl unknown
- 1996-09-20 DE DE69634961T patent/DE69634961T2/de not_active Expired - Lifetime
- 1996-09-20 CA CA2232668A patent/CA2232668C/en not_active Expired - Lifetime
- 1996-09-20 WO PCT/JP1996/002730 patent/WO1997011064A1/ja not_active Ceased
- 1996-09-20 ES ES96931283T patent/ES2246496T3/es not_active Expired - Lifetime
- 1996-09-20 EP EP96931283A patent/EP0903347B1/en not_active Expired - Lifetime
- 1996-09-20 IL IL12377696A patent/IL123776A/en not_active IP Right Cessation
- 1996-09-20 CN CN96198101A patent/CN1082051C/zh not_active Expired - Lifetime
- 1996-09-20 US US09/043,558 patent/US6329338B1/en not_active Expired - Lifetime
- 1996-09-20 BR BR9610527-5A patent/BR9610527A/pt not_active Application Discontinuation
- 1996-09-20 KR KR1019980702138A patent/KR19990063676A/ko not_active Ceased
- 1996-09-20 AT AT96931283T patent/ATE299871T1/de active
- 1996-09-20 AU AU70019/96A patent/AU727532B2/en not_active Expired
- 1996-09-20 DK DK96931283T patent/DK0903347T3/da active
- 1996-09-20 HU HU0001164A patent/HU228004B1/hu unknown
- 1996-09-20 CZ CZ1998855A patent/CZ295705B6/cs not_active IP Right Cessation
-
1998
- 1998-03-19 NO NO19981250A patent/NO310622B1/no not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| IL123776A0 (en) | 1998-10-30 |
| PL326024A1 (en) | 1998-08-17 |
| HU228004B1 (en) | 2012-08-28 |
| ATE299871T1 (de) | 2005-08-15 |
| EP0903347A4 (en:Method) | 1999-03-24 |
| MX9802268A (es) | 1998-08-30 |
| AU7001996A (en) | 1997-04-09 |
| WO1997011064A1 (en) | 1997-03-27 |
| DK0903347T3 (da) | 2005-11-21 |
| KR19990063676A (ko) | 1999-07-26 |
| ES2246496T3 (es) | 2006-02-16 |
| EP0903347B1 (en) | 2005-07-20 |
| CN1082051C (zh) | 2002-04-03 |
| CZ85598A3 (cs) | 1998-08-12 |
| US6329338B1 (en) | 2001-12-11 |
| DE69634961D1 (de) | 2005-08-25 |
| DE69634961T2 (de) | 2006-04-20 |
| CA2232668A1 (en) | 1997-03-27 |
| NO310622B1 (no) | 2001-07-30 |
| CA2232668C (en) | 2011-10-18 |
| HUP0001164A2 (hu) | 2000-11-28 |
| NO981250L (no) | 1998-05-22 |
| BR9610527A (pt) | 1999-12-21 |
| HUP0001164A3 (en) | 2001-04-28 |
| JP4001381B1 (en:Method) | 2007-10-31 |
| CN1201456A (zh) | 1998-12-09 |
| PL186168B1 (pl) | 2003-11-28 |
| NZ318515A (en) | 2000-05-26 |
| AU727532B2 (en) | 2000-12-14 |
| EP0903347A1 (en) | 1999-03-24 |
| IL123776A (en) | 2002-09-12 |
| NO981250D0 (no) | 1998-03-19 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PD00 | Pending as of 2000-06-30 in czech republic | ||
| MK4A | Patent expired |
Effective date: 20160920 |