DD216932A5 - Verfahren zur herstellung von neuen 7-oxabicycloheptan-substituierten prostaglandin-analogen - Google Patents
Verfahren zur herstellung von neuen 7-oxabicycloheptan-substituierten prostaglandin-analogen Download PDFInfo
- Publication number
- DD216932A5 DD216932A5 DD84260892A DD26089284A DD216932A5 DD 216932 A5 DD216932 A5 DD 216932A5 DD 84260892 A DD84260892 A DD 84260892A DD 26089284 A DD26089284 A DD 26089284A DD 216932 A5 DD216932 A5 DD 216932A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- oxabicyclo
- i7hept
- heptenoic acid
- item
- procedure
- Prior art date
Links
- 150000003180 prostaglandins Chemical class 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 186
- 150000001875 compounds Chemical class 0.000 claims abstract description 91
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 23
- 230000008569 process Effects 0.000 claims abstract description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 11
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 6
- 150000001340 alkali metals Chemical group 0.000 claims abstract description 5
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 5
- 229940006138 antiglaucoma drug and miotics prostaglandin analogues Drugs 0.000 claims abstract description 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 3
- 125000005356 cycloalkylalkenyl group Chemical group 0.000 claims abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 229
- -1 (hydroxymethyl) amino Chemical group 0.000 claims description 85
- 239000002253 acid Substances 0.000 claims description 43
- 150000004702 methyl esters Chemical class 0.000 claims description 35
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 150000003568 thioethers Chemical class 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- KPSZWAJWFMFMFF-UHFFFAOYSA-N delta-Hexylen-alpha-carbonsaeure Natural products CC=CCCCC(O)=O KPSZWAJWFMFMFF-UHFFFAOYSA-N 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000007983 Tris buffer Chemical group 0.000 claims description 3
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- 239000003146 anticoagulant agent Substances 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 4
- 230000002537 thrombolytic effect Effects 0.000 abstract description 4
- 229940125692 cardiovascular agent Drugs 0.000 abstract 1
- 239000002327 cardiovascular agent Substances 0.000 abstract 1
- FYFFGSSZFBZTAH-UHFFFAOYSA-N methylaminomethanetriol Chemical group CNC(O)(O)O FYFFGSSZFBZTAH-UHFFFAOYSA-N 0.000 abstract 1
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 abstract 1
- PMBXCGGQNSVESQ-UHFFFAOYSA-N 1-Hexanethiol Chemical compound CCCCCCS PMBXCGGQNSVESQ-UHFFFAOYSA-N 0.000 description 136
- 239000000243 solution Substances 0.000 description 132
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 94
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 71
- 239000000203 mixture Substances 0.000 description 68
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 65
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 65
- ZRKMQKLGEQPLNS-UHFFFAOYSA-N 1-Pentanethiol Chemical compound CCCCCS ZRKMQKLGEQPLNS-UHFFFAOYSA-N 0.000 description 54
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 54
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 49
- 239000011541 reaction mixture Substances 0.000 description 48
- 229910052786 argon Inorganic materials 0.000 description 47
- 239000000741 silica gel Substances 0.000 description 46
- 229910002027 silica gel Inorganic materials 0.000 description 46
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
- 239000003921 oil Substances 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 37
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 36
- 239000000460 chlorine Substances 0.000 description 32
- 239000003480 eluent Substances 0.000 description 30
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 30
- 235000019341 magnesium sulphate Nutrition 0.000 description 30
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 26
- 238000004458 analytical method Methods 0.000 description 24
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 22
- 229910052740 iodine Inorganic materials 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- 150000003254 radicals Chemical class 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 19
- 239000011630 iodine Substances 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- 229920006395 saturated elastomer Polymers 0.000 description 19
- 239000008096 xylene Substances 0.000 description 19
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 239000007789 gas Substances 0.000 description 17
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 17
- 239000011780 sodium chloride Substances 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 15
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 14
- 230000001681 protective effect Effects 0.000 description 14
- 239000012267 brine Substances 0.000 description 13
- 239000000284 extract Substances 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 12
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- FWBXAOOHHILPSR-UHFFFAOYSA-N cyclohexylmethanethiol Chemical compound SCC1CCCCC1 FWBXAOOHHILPSR-UHFFFAOYSA-N 0.000 description 11
- 239000011261 inert gas Substances 0.000 description 11
- 239000012259 ether extract Substances 0.000 description 10
- 150000001299 aldehydes Chemical class 0.000 description 9
- CMKBCTPCXZNQKX-UHFFFAOYSA-N cyclohexanethiol Chemical compound SC1CCCCC1 CMKBCTPCXZNQKX-UHFFFAOYSA-N 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- 230000008020 evaporation Effects 0.000 description 9
- SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical compound CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 description 9
- 229940126062 Compound A Drugs 0.000 description 8
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- URIRDRHUUFRHAS-UHFFFAOYSA-N hexyl methanesulfonate Chemical compound CCCCCCOS(C)(=O)=O URIRDRHUUFRHAS-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 7
- 238000001816 cooling Methods 0.000 description 7
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
- 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 6
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 150000003462 sulfoxides Chemical class 0.000 description 6
- 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 6
- YURNCBVQZBJDAJ-UHFFFAOYSA-N 2-heptenoic acid Chemical compound CCCCC=CC(O)=O YURNCBVQZBJDAJ-UHFFFAOYSA-N 0.000 description 5
- IUSDGVJFDZRIBR-UHFFFAOYSA-N 3-phenylpropane-1-thiol Chemical compound SCCCC1=CC=CC=C1 IUSDGVJFDZRIBR-UHFFFAOYSA-N 0.000 description 5
- WVDYBOADDMMFIY-UHFFFAOYSA-N Cyclopentanethiol Chemical compound SC1CCCC1 WVDYBOADDMMFIY-UHFFFAOYSA-N 0.000 description 5
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- AKRQHOWXVSDJEF-UHFFFAOYSA-N heptane-1-sulfonic acid Chemical compound CCCCCCCS(O)(=O)=O AKRQHOWXVSDJEF-UHFFFAOYSA-N 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical group OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
- ZMRFRBHYXOQLDK-UHFFFAOYSA-N 2-phenylethanethiol Chemical compound SCCC1=CC=CC=C1 ZMRFRBHYXOQLDK-UHFFFAOYSA-N 0.000 description 4
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- WQAQPCDUOCURKW-UHFFFAOYSA-N butanethiol Chemical compound CCCCS WQAQPCDUOCURKW-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 4
- 238000006266 etherification reaction Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 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 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- MNDIARAMWBIKFW-UHFFFAOYSA-N 1-bromohexane Chemical compound CCCCCCBr MNDIARAMWBIKFW-UHFFFAOYSA-N 0.000 description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
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- VPIAKHNXCOTPAY-UHFFFAOYSA-N Heptane-1-thiol Chemical compound CCCCCCCS VPIAKHNXCOTPAY-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
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- KOGOBKOHQTZGIS-UHFFFAOYSA-N cyclohexyl methanesulfonate Chemical compound CS(=O)(=O)OC1CCCCC1 KOGOBKOHQTZGIS-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- IQQDLHGWGKEQDS-UHFFFAOYSA-N methyl hept-2-enoate Chemical compound CCCCC=CC(=O)OC IQQDLHGWGKEQDS-UHFFFAOYSA-N 0.000 description 3
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
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- 239000007858 starting material Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 3
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- SEVPGNFKEDEULZ-UHFFFAOYSA-M 1-pyridin-1-ium-1-ylethanone;chloride Chemical compound [Cl-].CC(=O)[N+]1=CC=CC=C1 SEVPGNFKEDEULZ-UHFFFAOYSA-M 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- MLOSJPZSZWUDSK-UHFFFAOYSA-N 4-carboxybutyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC(=O)O)C1=CC=CC=C1 MLOSJPZSZWUDSK-UHFFFAOYSA-N 0.000 description 2
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- SSUFDOMYCBCHML-UHFFFAOYSA-N CCCCC[S](=O)=O Chemical group CCCCC[S](=O)=O SSUFDOMYCBCHML-UHFFFAOYSA-N 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 150000004703 alkoxides Chemical class 0.000 description 2
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- 125000002950 monocyclic group Chemical group 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- AYOOGWWGECJQPI-NSHDSACASA-N n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-3-(3-propan-2-yloxy-1h-pyrazol-5-yl)imidazo[4,5-b]pyridin-5-amine Chemical compound N1C(OC(C)C)=CC(N2C3=NC(N[C@@H](C)C=4N=CC(F)=CN=4)=CC=C3N=C2)=N1 AYOOGWWGECJQPI-NSHDSACASA-N 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- GRJPLADOIKKOGS-UHFFFAOYSA-N octyl methanesulfonate Chemical compound CCCCCCCCOS(C)(=O)=O GRJPLADOIKKOGS-UHFFFAOYSA-N 0.000 description 1
- YIYBQIKDCADOSF-UHFFFAOYSA-N pent-2-enoic acid Chemical compound CCC=CC(O)=O YIYBQIKDCADOSF-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- GZQUFIUZBLOTMM-UHFFFAOYSA-N pentyl methanesulfonate Chemical compound CCCCCOS(C)(=O)=O GZQUFIUZBLOTMM-UHFFFAOYSA-N 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- JLYXXMFPNIAWKQ-UHFFFAOYSA-N γ Benzene hexachloride Chemical compound ClC1C(Cl)C(Cl)C(Cl)C(Cl)C1Cl JLYXXMFPNIAWKQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
- C07C405/0008—Analogues having the carboxyl group in the side-chains replaced by other functional groups
- C07C405/0025—Analogues having the carboxyl group in the side-chains replaced by other functional groups containing keto groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/474,913 US4474803A (en) | 1983-03-14 | 1983-03-14 | 7-Oxabicycloheptane substituted thio prostaglandin analogs useful in treating platelet aggregation and bronchoconstriction |
| US52332083A | 1983-08-15 | 1983-08-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD216932A5 true DD216932A5 (de) | 1985-01-02 |
Family
ID=27044617
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD84260892A DD216932A5 (de) | 1983-03-14 | 1984-03-14 | Verfahren zur herstellung von neuen 7-oxabicycloheptan-substituierten prostaglandin-analogen |
Country Status (24)
| Country | Link |
|---|---|
| KR (1) | KR840009085A (da) |
| AT (1) | AT383600B (da) |
| AU (1) | AU567919B2 (da) |
| CA (1) | CA1256887A (da) |
| CH (1) | CH658247A5 (da) |
| DD (1) | DD216932A5 (da) |
| DE (1) | DE3409124A1 (da) |
| DK (1) | DK155584A (da) |
| ES (1) | ES8506270A1 (da) |
| FI (1) | FI841008A (da) |
| FR (1) | FR2542743B1 (da) |
| GB (1) | GB2136428B (da) |
| GR (1) | GR79881B (da) |
| HU (1) | HU190530B (da) |
| IE (1) | IE57027B1 (da) |
| IL (1) | IL71184A0 (da) |
| IT (1) | IT1173442B (da) |
| LU (1) | LU85249A1 (da) |
| NL (1) | NL8400797A (da) |
| NO (1) | NO840960L (da) |
| NZ (1) | NZ207361A (da) |
| PL (1) | PL246663A1 (da) |
| PT (1) | PT78242B (da) |
| SE (1) | SE8401398L (da) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4513103A (en) * | 1983-10-21 | 1985-04-23 | E. R. Squibb & Sons, Inc. | 7-Oxabicycloheptane ethers useful in the treatment of thrombolytic disease |
| US4526900A (en) * | 1984-01-26 | 1985-07-02 | E. R. Squibb & Sons, Inc. | 7-Oxabicycloheptane substituted oxa prostaglandin analogs and their use in the treatment of thrombolytic disease |
| US4542157A (en) * | 1984-04-27 | 1985-09-17 | E. R. Squibb & Sons, Inc. | 7-Oxabicycloheptane substituted oxa prostaglandin analogs and their use in the treatment of thrombolytic disease |
| US4560698A (en) * | 1984-06-04 | 1985-12-24 | E. R. Squibb & Sons, Inc. | 7-Oxabicycloheptane substituted thio prostaglandin analogs and their use in the treatment in thrombolytic disease |
| US4661506A (en) * | 1984-11-30 | 1987-04-28 | E. R. Squibb & Sons, Inc. | 7-oxabicycloheptane substituted ox prostaglandin analogs |
| US4588743A (en) * | 1985-01-22 | 1986-05-13 | E. R. Squibb & Sons, Inc. | 7-oxabicycloheptane-substituted oxa prostaglandin analogs and their use in the treatment of thrombolytic disease |
| US4607049A (en) * | 1985-04-22 | 1986-08-19 | E. R. Squibb & Sons, Inc. | 7-oxabicycloheptane substituted thio prostaglandin analogs useful in the treatment of thrombolytic disease |
| US4608386A (en) * | 1985-04-26 | 1986-08-26 | E. R. Squibb & Sons, Inc. | 7-oxabicycloheptane ethers useful in the treatment of thrombotic diseases |
| US4611006A (en) * | 1985-06-28 | 1986-09-09 | E. R. Squibb & Sons, Inc. | 5,6-epoxy-7-oxabicycloheptane substituted ethers useful in the treatment of thrombotic disease |
| US4654356A (en) * | 1985-08-01 | 1987-03-31 | E. R. Squibb & Sons, Inc. | 7-oxabicycloheptane substituted diacid diamide prostaglandin analogs |
| US4673685A (en) * | 1986-07-23 | 1987-06-16 | E. R. Squibb & Sons, Inc. | Hydroximic acids of 7-oxabicycloheptane substituted ethers and thioethers useful in the treatment of thrombotic disease |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4143054A (en) * | 1977-11-04 | 1979-03-06 | E. R. Squibb & Sons, Inc. | 7-oxabicycloheptane- and 7-oxabicycloheptene compounds |
| ZA829068B (en) * | 1980-07-01 | 1983-02-23 | Nat Res Dev | Prostaglandins |
| AU561739B2 (en) * | 1981-12-23 | 1987-05-14 | British Technology Group Limited | Prostaglandins |
| US4549030A (en) * | 1982-12-13 | 1985-10-22 | The Upjohn Company | Organic compounds and process |
| US4526900A (en) * | 1984-01-26 | 1985-07-02 | E. R. Squibb & Sons, Inc. | 7-Oxabicycloheptane substituted oxa prostaglandin analogs and their use in the treatment of thrombolytic disease |
| US4542157A (en) * | 1984-04-27 | 1985-09-17 | E. R. Squibb & Sons, Inc. | 7-Oxabicycloheptane substituted oxa prostaglandin analogs and their use in the treatment of thrombolytic disease |
-
1984
- 1984-03-01 CA CA000448662A patent/CA1256887A/en not_active Expired
- 1984-03-02 AU AU25235/84A patent/AU567919B2/en not_active Ceased
- 1984-03-02 NZ NZ207361A patent/NZ207361A/en unknown
- 1984-03-05 IE IE525/84A patent/IE57027B1/xx unknown
- 1984-03-06 GR GR73998A patent/GR79881B/el unknown
- 1984-03-08 IL IL71184A patent/IL71184A0/xx unknown
- 1984-03-08 GB GB08406100A patent/GB2136428B/en not_active Expired
- 1984-03-13 SE SE8401398A patent/SE8401398L/xx not_active Application Discontinuation
- 1984-03-13 KR KR1019840001248A patent/KR840009085A/ko not_active Application Discontinuation
- 1984-03-13 NL NL8400797A patent/NL8400797A/nl not_active Application Discontinuation
- 1984-03-13 PT PT78242A patent/PT78242B/pt unknown
- 1984-03-13 NO NO840960A patent/NO840960L/no unknown
- 1984-03-13 DE DE19843409124 patent/DE3409124A1/de not_active Withdrawn
- 1984-03-13 FI FI841008A patent/FI841008A/fi not_active Application Discontinuation
- 1984-03-13 HU HU841001A patent/HU190530B/hu unknown
- 1984-03-13 AT AT0083484A patent/AT383600B/de not_active IP Right Cessation
- 1984-03-13 ES ES530548A patent/ES8506270A1/es not_active Expired
- 1984-03-13 FR FR8403835A patent/FR2542743B1/fr not_active Expired
- 1984-03-13 DK DK155584A patent/DK155584A/da not_active IP Right Cessation
- 1984-03-13 CH CH1244/84A patent/CH658247A5/fr not_active IP Right Cessation
- 1984-03-14 IT IT20049/84A patent/IT1173442B/it active
- 1984-03-14 DD DD84260892A patent/DD216932A5/de unknown
- 1984-03-14 PL PL24666384A patent/PL246663A1/xx unknown
- 1984-03-14 LU LU85249A patent/LU85249A1/fr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GB2136428A (en) | 1984-09-19 |
| AU2523584A (en) | 1984-09-20 |
| ATA83484A (de) | 1986-12-15 |
| CH658247A5 (fr) | 1986-10-31 |
| AT383600B (de) | 1987-07-27 |
| IT1173442B (it) | 1987-06-24 |
| FR2542743B1 (fr) | 1987-10-30 |
| HU190530B (en) | 1986-09-29 |
| SE8401398D0 (sv) | 1984-03-13 |
| PL246663A1 (en) | 1985-03-26 |
| FI841008A (fi) | 1984-09-15 |
| PT78242A (en) | 1984-04-01 |
| ES530548A0 (es) | 1985-07-01 |
| NL8400797A (nl) | 1984-10-01 |
| SE8401398L (sv) | 1984-09-15 |
| DE3409124A1 (de) | 1984-09-27 |
| KR840009085A (ko) | 1984-12-24 |
| NO840960L (no) | 1984-09-17 |
| PT78242B (en) | 1986-05-27 |
| LU85249A1 (fr) | 1984-11-14 |
| NZ207361A (en) | 1986-12-05 |
| CA1256887A (en) | 1989-07-04 |
| FR2542743A1 (fr) | 1984-09-21 |
| DK155584D0 (da) | 1984-03-13 |
| IE57027B1 (en) | 1992-03-25 |
| DK155584A (da) | 1984-09-15 |
| GB8406100D0 (en) | 1984-04-11 |
| GB2136428B (en) | 1986-09-10 |
| IE840525L (en) | 1984-09-14 |
| GR79881B (da) | 1984-10-31 |
| ES8506270A1 (es) | 1985-07-01 |
| IT8420049A0 (it) | 1984-03-14 |
| HUT34179A (en) | 1985-02-28 |
| IL71184A0 (en) | 1984-06-29 |
| FI841008A0 (fi) | 1984-03-13 |
| AU567919B2 (en) | 1987-12-10 |
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