NO874699L - Fremgangsmaate for frenstilling av nye substituerte cefalosporin-sulfoner. - Google Patents
Fremgangsmaate for frenstilling av nye substituerte cefalosporin-sulfoner.Info
- Publication number
- NO874699L NO874699L NO874699A NO874699A NO874699L NO 874699 L NO874699 L NO 874699L NO 874699 A NO874699 A NO 874699A NO 874699 A NO874699 A NO 874699A NO 874699 L NO874699 L NO 874699L
- Authority
- NO
- Norway
- Prior art keywords
- substituted
- alkyl
- thia
- azabicyclo
- oxo
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 63
- 238000000034 method Methods 0.000 title claims description 35
- 229930186147 Cephalosporin Natural products 0.000 title abstract description 14
- 229940124587 cephalosporin Drugs 0.000 title abstract description 14
- 150000001780 cephalosporins Chemical class 0.000 title description 7
- -1 cephalosporin sulfones Chemical class 0.000 claims abstract description 120
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 50
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 30
- 125000004432 carbon atom Chemical group C* 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- 239000000047 product Substances 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 10
- 125000004423 acyloxy group Chemical group 0.000 claims description 10
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 125000005518 carboxamido group Chemical group 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 7
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 150000002431 hydrogen Chemical group 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 4
- 125000005035 acylthio group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 3
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims description 3
- 125000005024 alkenyl aryl group Chemical group 0.000 claims description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 3
- 125000005025 alkynylaryl group Chemical group 0.000 claims description 3
- 125000003368 amide group Chemical group 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 3
- 150000003457 sulfones Chemical class 0.000 claims description 3
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 3
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 2
- 125000004946 alkenylalkyl group Chemical group 0.000 claims description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims description 2
- 239000007800 oxidant agent Substances 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical class [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims 2
- 239000013067 intermediate product Substances 0.000 claims 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 1
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 239000003602 elastase inhibitor Substances 0.000 abstract description 4
- 230000001796 anti-degenerative effect Effects 0.000 abstract description 3
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 3
- 230000003389 potentiating effect Effects 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 189
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 123
- 239000000243 solution Substances 0.000 description 98
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 72
- 235000019439 ethyl acetate Nutrition 0.000 description 67
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- 238000005481 NMR spectroscopy Methods 0.000 description 56
- 239000011541 reaction mixture Substances 0.000 description 55
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- 239000010410 layer Substances 0.000 description 49
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 39
- 239000012044 organic layer Substances 0.000 description 38
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
- 239000000203 mixture Substances 0.000 description 34
- 239000003921 oil Substances 0.000 description 32
- 235000019198 oils Nutrition 0.000 description 32
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- 229910052938 sodium sulfate Inorganic materials 0.000 description 28
- 235000011152 sodium sulphate Nutrition 0.000 description 28
- 238000003756 stirring Methods 0.000 description 28
- 239000000741 silica gel Substances 0.000 description 26
- 229910002027 silica gel Inorganic materials 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
- 239000012267 brine Substances 0.000 description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 239000002904 solvent Substances 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
- 235000017557 sodium bicarbonate Nutrition 0.000 description 19
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 102000035195 Peptidases Human genes 0.000 description 15
- 108091005804 Peptidases Proteins 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 239000004365 Protease Substances 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 238000001816 cooling Methods 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 12
- HSHGZXNAXBPPDL-HZGVNTEJSA-N 7beta-aminocephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 10
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- 102000016387 Pancreatic elastase Human genes 0.000 description 10
- 108010067372 Pancreatic elastase Proteins 0.000 description 10
- 230000004054 inflammatory process Effects 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 229910004373 HOAc Inorganic materials 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000005457 ice water Substances 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- 125000002252 acyl group Chemical group 0.000 description 8
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- 238000004587 chromatography analysis Methods 0.000 description 7
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- 238000003818 flash chromatography Methods 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- SCNWTQPZTZMXBG-UHFFFAOYSA-N 2-methyloct-2-enoic acid Chemical compound CCCCCC=C(C)C(O)=O SCNWTQPZTZMXBG-UHFFFAOYSA-N 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
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- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 6
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
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- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- LUPQVSUBJUDFPD-UHFFFAOYSA-N 3-(acetyloxymethyl)-7-diazonio-2-[(2-methylpropan-2-yl)oxycarbonyl]-5-thia-1-azabicyclo[4.2.0]octa-2,7-dien-8-olate Chemical compound S1CC(COC(=O)C)=C(C(=O)OC(C)(C)C)N2C(=O)C(=[N+]=[N-])C12 LUPQVSUBJUDFPD-UHFFFAOYSA-N 0.000 description 5
- 206010014561 Emphysema Diseases 0.000 description 5
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- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 5
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- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 229940126062 Compound A Drugs 0.000 description 4
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
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- KZHFTGRLEUMEHG-UHFFFAOYSA-N methyl 3-[[propan-2-yloxy(propan-2-yloxycarbamoyl)amino]methyl]benzoate Chemical compound C(C)(C)ON(C(O)=NOC(C)C)CC1=CC(=CC=C1)C(=O)OC KZHFTGRLEUMEHG-UHFFFAOYSA-N 0.000 description 3
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- 239000011734 sodium Substances 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US93019386A | 1986-11-12 | 1986-11-12 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO874699D0 NO874699D0 (no) | 1987-11-11 |
| NO874699L true NO874699L (no) | 1988-05-13 |
Family
ID=25459038
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO874699A NO874699L (no) | 1986-11-12 | 1987-11-11 | Fremgangsmaate for frenstilling av nye substituerte cefalosporin-sulfoner. |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP0267723B1 (ja) |
| JP (1) | JPS63198688A (ja) |
| KR (1) | KR880006249A (ja) |
| CN (1) | CN87107753A (ja) |
| AT (1) | ATE133954T1 (ja) |
| AU (1) | AU611104B2 (ja) |
| CA (1) | CA1339275C (ja) |
| DE (1) | DE3751700D1 (ja) |
| DK (1) | DK590787A (ja) |
| FI (1) | FI874839A (ja) |
| HU (1) | HUT52511A (ja) |
| IL (1) | IL84359A0 (ja) |
| NO (1) | NO874699L (ja) |
| NZ (1) | NZ222399A (ja) |
| PT (1) | PT86074B (ja) |
| ZA (1) | ZA878467B (ja) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8808701D0 (en) * | 1988-04-13 | 1988-05-18 | Erba Carlo Spa | Beta-lactam derivatives |
| GB8811388D0 (en) * | 1988-05-13 | 1988-06-15 | Erba Carlo Spa | 1,1-dioxo-cephem-4-carbothiolic acid derivatives |
| US4992541A (en) * | 1989-08-01 | 1991-02-12 | Merck & Co., Inc. | Process for the preparation of 1,1-dioxo-7-substituted cephems |
| AU661453B2 (en) * | 1989-10-06 | 1995-07-27 | Synphar Laboratories, Inc. | Novel 2-spirocyclopropyl cephalosporin sulfone derivatives and processes for the preparation thereof |
| US5264429A (en) * | 1989-10-06 | 1993-11-23 | Synphar Laboratories, Inc. | 2-spirocyclopropyl cephalosporin sulfone derivatives |
| US5258377A (en) * | 1991-04-08 | 1993-11-02 | Taiho Pharmaceutical Co., Ltd. | 2-spirocyclopropyl 4-acylcephems |
| US5348953A (en) * | 1991-06-25 | 1994-09-20 | Merck & Co., Inc. | Substituted azetidinones as anti-inflammatory and antidegenerative agents |
| DE69331089T2 (de) * | 1992-02-18 | 2002-07-18 | Otsuka Kagaku K.K., Osaka | Beta-Laktam und Cepham Verbindungen und Ihre Herstellung |
| GB2266526A (en) * | 1992-03-17 | 1993-11-03 | Merck & Co Inc | Substituted cephalosporin sulfones useful in the treatment of leukemia |
| GB2266525A (en) * | 1992-03-17 | 1993-11-03 | Merck & Co Inc | Substituted cephalosporin sulfone compositions useful in the treatment of leukemia |
| WO1993024493A1 (fr) * | 1992-05-27 | 1993-12-09 | Teijin Limited | Derive de cephalosporine |
| CA2147129A1 (en) * | 1992-10-27 | 1994-05-11 | James B. Doherty | New substituted azetidinones as anti-inflammatory and antidegenerative agents |
| US5591737A (en) * | 1992-12-17 | 1997-01-07 | Merck & Co., Inc. | Substituted azetidinones as anti-inflammatory and antidegenerative agents |
| US5439904A (en) * | 1993-12-07 | 1995-08-08 | Synphar Laboratories, Inc. | 2-spiro(2'-spirocycloalkyl)cyclopropyl cephalosporin sulfones as antiinflammatory and antigenerative agents |
| US5747485A (en) * | 1995-04-13 | 1998-05-05 | Merck & Co., Inc. | Substituted azetidiones as anti-inflammatory and antidegenerative agents |
| WO1997007805A1 (en) * | 1995-08-31 | 1997-03-06 | Smithkline Beecham Corporation | Interleukin converting enzyme and apoptosis |
| WO1997008174A1 (en) * | 1995-08-31 | 1997-03-06 | Smithkline Beecham Corporation | Interleukin converting enzyme and apoptosis |
| GB9525697D0 (en) * | 1995-12-15 | 1996-02-14 | Pharmacia Spa | Cephem derivatives |
| CN106543206B (zh) * | 2016-09-22 | 2018-08-31 | 济南康和医药科技有限公司 | 一种头孢类二聚体化合物的制备方法 |
| CN113372368B (zh) * | 2020-03-09 | 2022-04-12 | 苏州爱科百发生物医药技术有限公司 | 一种弹性蛋白酶抑制剂前药及其用途 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4623645A (en) * | 1983-04-18 | 1986-11-18 | Merck & Co., Inc. | Substituted cephalosporin sulfoxides as anti-inflammatory and antidegenerative agents |
| EP0124081A3 (en) * | 1983-05-02 | 1986-11-26 | Merck & Co. Inc. | New substituted cephalosporin sulfones as antiinflammatory and antidegenerative agents, pharmaceutical compositions containing the same and processes for making them |
| US4699904A (en) * | 1985-07-01 | 1987-10-13 | Merck & Co., Inc. | Tetrazolyl derivatives of β-lactams useful as elastase inhibitors |
-
1987
- 1987-11-02 EP EP87309688A patent/EP0267723B1/en not_active Expired - Lifetime
- 1987-11-02 NZ NZ222399A patent/NZ222399A/xx unknown
- 1987-11-02 AT AT87309688T patent/ATE133954T1/de not_active IP Right Cessation
- 1987-11-02 DE DE3751700T patent/DE3751700D1/de not_active Expired - Lifetime
- 1987-11-03 AU AU80624/87A patent/AU611104B2/en not_active Expired - Fee Related
- 1987-11-03 IL IL84359A patent/IL84359A0/xx unknown
- 1987-11-03 FI FI874839A patent/FI874839A/fi not_active IP Right Cessation
- 1987-11-04 PT PT86074A patent/PT86074B/pt not_active IP Right Cessation
- 1987-11-10 CA CA000551525A patent/CA1339275C/en not_active Expired - Fee Related
- 1987-11-11 DK DK590787A patent/DK590787A/da not_active Application Discontinuation
- 1987-11-11 CN CN198787107753A patent/CN87107753A/zh active Pending
- 1987-11-11 KR KR870012677A patent/KR880006249A/ko not_active Application Discontinuation
- 1987-11-11 NO NO874699A patent/NO874699L/no unknown
- 1987-11-11 ZA ZA878467A patent/ZA878467B/xx unknown
- 1987-11-11 HU HU875022A patent/HUT52511A/hu unknown
- 1987-11-12 JP JP62284386A patent/JPS63198688A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| NO874699D0 (no) | 1987-11-11 |
| DE3751700D1 (de) | 1996-03-21 |
| CA1339275C (en) | 1997-08-12 |
| DK590787A (da) | 1988-05-13 |
| KR880006249A (ko) | 1988-07-22 |
| IL84359A0 (en) | 1988-04-29 |
| FI874839A (fi) | 1988-05-13 |
| EP0267723A2 (en) | 1988-05-18 |
| AU611104B2 (en) | 1991-06-06 |
| HUT52511A (en) | 1990-07-28 |
| NZ222399A (en) | 1991-07-26 |
| PT86074A (en) | 1987-12-01 |
| ZA878467B (en) | 1988-09-28 |
| CN87107753A (zh) | 1988-06-29 |
| DK590787D0 (da) | 1987-11-11 |
| ATE133954T1 (de) | 1996-02-15 |
| EP0267723A3 (en) | 1989-12-06 |
| PT86074B (pt) | 1990-11-07 |
| EP0267723B1 (en) | 1996-02-07 |
| FI874839A0 (fi) | 1987-11-03 |
| AU8062487A (en) | 1988-05-19 |
| JPS63198688A (ja) | 1988-08-17 |
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