JPS6160816B2 - - Google Patents
Info
- Publication number
- JPS6160816B2 JPS6160816B2 JP9334979A JP9334979A JPS6160816B2 JP S6160816 B2 JPS6160816 B2 JP S6160816B2 JP 9334979 A JP9334979 A JP 9334979A JP 9334979 A JP9334979 A JP 9334979A JP S6160816 B2 JPS6160816 B2 JP S6160816B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- thienamycin
- dimethylcyclopropanecarboxamide
- carbon atoms
- compound
- 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
Links
- 150000001875 compounds Chemical class 0.000 claims description 59
- 239000002253 acid Substances 0.000 claims description 51
- 239000000203 mixture Substances 0.000 claims description 43
- WKDDRNSBRWANNC-ATRFCDNQSA-N Thienamycin Chemical class C1C(SCCN)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 WKDDRNSBRWANNC-ATRFCDNQSA-N 0.000 claims description 31
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 claims description 30
- -1 thienamycin compound Chemical class 0.000 claims description 27
- 239000003112 inhibitor Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 claims description 10
- 150000001408 amides Chemical class 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 102000004860 Dipeptidases Human genes 0.000 claims description 6
- 108090001081 Dipeptidases Proteins 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 6
- 229940090955 Dipeptidase inhibitor Drugs 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 230000000844 anti-bacterial effect Effects 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 125000000783 acetimidoyl group Chemical group C(C)(=N)* 0.000 claims description 2
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000000539 amino acid group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- 150000001768 cations Chemical class 0.000 claims 1
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 125000004355 nitrogen functional group Chemical group 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 62
- 239000000243 solution Substances 0.000 description 59
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
- 229910001868 water Inorganic materials 0.000 description 49
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 239000000047 product Substances 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- 238000002844 melting Methods 0.000 description 23
- 230000008018 melting Effects 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 23
- 238000004458 analytical method Methods 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- 238000004809 thin layer chromatography Methods 0.000 description 22
- 238000000034 method Methods 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 239000012141 concentrate Substances 0.000 description 17
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 239000013078 crystal Substances 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 239000011734 sodium Substances 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- YBZQRYWKYBZZNT-UHFFFAOYSA-N 2,2-dimethylcyclopropane-1-carboxamide Chemical compound CC1(C)CC1C(N)=O YBZQRYWKYBZZNT-UHFFFAOYSA-N 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- 210000003734 kidney Anatomy 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- TYEYBOSBBBHJIV-UHFFFAOYSA-N 2-oxobutanoic acid Chemical compound CCC(=O)C(O)=O TYEYBOSBBBHJIV-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- GNSHARBPCKRVFP-UHFFFAOYSA-N CCCCCC=CC(O)=O.O Chemical compound CCCCCC=CC(O)=O.O GNSHARBPCKRVFP-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 238000004811 liquid chromatography Methods 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- POUMCBWMYUEVKF-UHFFFAOYSA-N 2,2-dichlorocyclopropane-1-carboxamide Chemical compound NC(=O)C1CC1(Cl)Cl POUMCBWMYUEVKF-UHFFFAOYSA-N 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
- 229910004373 HOAc Inorganic materials 0.000 description 4
- OQAGVSWESNCJJT-UHFFFAOYSA-N Methyl 3-methylbutanoate Chemical compound COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 4
- XMGZWGBXVLJOKE-UHFFFAOYSA-N acetic acid;toluene Chemical compound CC(O)=O.CC1=CC=CC=C1 XMGZWGBXVLJOKE-UHFFFAOYSA-N 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000000855 fermentation Methods 0.000 description 4
- 230000004151 fermentation Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000002808 molecular sieve Substances 0.000 description 4
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- CWMPPVPFLSZGCY-UHFFFAOYSA-N 2-Octenoic Acid Natural products CCCCCC=CC(O)=O CWMPPVPFLSZGCY-UHFFFAOYSA-N 0.000 description 3
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 108090000204 Dipeptidase 1 Proteins 0.000 description 3
- 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 3
- 238000010521 absorption reaction Methods 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 150000003952 β-lactams Chemical class 0.000 description 3
- VUAOXPKYIYYINY-WCIBSUBMSA-N (z)-2-(nonanoylamino)but-2-enoic acid Chemical compound CCCCCCCCC(=O)N\C(=C/C)C(O)=O VUAOXPKYIYYINY-WCIBSUBMSA-N 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- SGRHVVLXEBNBDV-UHFFFAOYSA-N 1,6-dibromohexane Chemical compound BrCCCCCCBr SGRHVVLXEBNBDV-UHFFFAOYSA-N 0.000 description 2
- HXVNBWAKAOHACI-UHFFFAOYSA-N 2,4-dimethyl-3-pentanone Chemical compound CC(C)C(=O)C(C)C HXVNBWAKAOHACI-UHFFFAOYSA-N 0.000 description 2
- ZIQJERGSQODYKF-UHFFFAOYSA-N 2-(3-methylbutanoylamino)but-2-enoic acid Chemical compound CC=C(C(O)=O)NC(=O)CC(C)C ZIQJERGSQODYKF-UHFFFAOYSA-N 0.000 description 2
- 125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 102000003850 Dipeptidase 1 Human genes 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 2
- 239000007993 MOPS buffer Substances 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-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
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000003862 amino acid derivatives Chemical group 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- LSNKBVFMXFAUOF-UHFFFAOYSA-N benzyl methanimidate;hydrochloride Chemical compound Cl.N=COCC1=CC=CC=C1 LSNKBVFMXFAUOF-UHFFFAOYSA-N 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 2
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 2
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 150000003951 lactams Chemical class 0.000 description 2
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Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US92721378A | 1978-07-24 | 1978-07-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5551023A JPS5551023A (en) | 1980-04-14 |
| JPS6160816B2 true JPS6160816B2 (de) | 1986-12-23 |
Family
ID=25454404
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9334979A Granted JPS5551023A (en) | 1978-07-24 | 1979-07-24 | Use of thienamycin antibiotic together with dipeptidase inhibitor |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPS5551023A (de) |
| ZA (1) | ZA793745B (de) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0384410A1 (de) | 1989-02-21 | 1990-08-29 | Banyu Pharmaceutical Co., Ltd. | Zusammensetzung gegen Mikroben |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA825747B (en) * | 1981-08-10 | 1984-03-28 | Merck & Co Inc | Combination of 2-substituted penems with dipeptidase inhibitors |
| EP0161546B1 (de) * | 1984-04-30 | 1989-12-13 | Merck & Co. Inc. | Mischung von 2-substituierten Carbapenemen mit Dipeptidase-Inhibitoren |
| JPS63290860A (ja) * | 1987-05-22 | 1988-11-28 | Sanraku Inc | アミノエチルシステイン誘導体 |
-
1979
- 1979-07-23 ZA ZA00793745A patent/ZA793745B/xx unknown
- 1979-07-24 JP JP9334979A patent/JPS5551023A/ja active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0384410A1 (de) | 1989-02-21 | 1990-08-29 | Banyu Pharmaceutical Co., Ltd. | Zusammensetzung gegen Mikroben |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5551023A (en) | 1980-04-14 |
| ZA793745B (en) | 1981-02-25 |
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