NO874699L - Fremgangsmaate for frenstilling av nye substituerte cefalosporin-sulfoner. - Google Patents

Fremgangsmaate for frenstilling av nye substituerte cefalosporin-sulfoner.

Info

Publication number: NO874699L
Authority: NO; Norway
Prior art keywords: substituted; alkyl; thia; azabicyclo; oxo
Prior art date: 1986-11-12

Application number

NO874699A

Other languages

English (en)

Norwegian (no)

Other versions

NO874699D0 (no

Inventor

James B Doherty

Paul E Finke

Raymond A Firestone

William K Hagmann

Shrenik K Shah

Kevan R Thompson

Original Assignee

Merck & Co Inc

Priority date (The priority date 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 date listed.)

1986-11-12

Filing date

1987-11-11

Publication date

1988-05-13

1987-11-11 Application filed by Merck & Co Inc filed Critical Merck & Co Inc

1987-11-11 Publication of NO874699D0 publication Critical patent/NO874699D0/no

1988-05-13 Publication of NO874699L publication Critical patent/NO874699L/no

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
108090000790 Enzymes Proteins 0.000 description 10
206010061218 Inflammation Diseases 0.000 description 10
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
239000003480 eluent Substances 0.000 description 8
210000000224 granular leucocyte Anatomy 0.000 description 8
210000003714 granulocyte Anatomy 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 7
239000000284 extract Substances 0.000 description 7
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
239000000796 flavoring agent Substances 0.000 description 6
235000013355 food flavoring agent Nutrition 0.000 description 6
235000003599 food sweetener Nutrition 0.000 description 6
239000003112 inhibitor Substances 0.000 description 6
239000000463 material Substances 0.000 description 6
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 6
239000000546 pharmaceutical excipient Substances 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
206010039073 rheumatoid arthritis Diseases 0.000 description 6
239000003765 sweetening agent Substances 0.000 description 6
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
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
210000000845 cartilage Anatomy 0.000 description 5
239000007859 condensation product Substances 0.000 description 5
235000014113 dietary fatty acids Nutrition 0.000 description 5
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000000194 fatty acid Substances 0.000 description 5
229930195729 fatty acid Natural products 0.000 description 5
150000004665 fatty acids Chemical class 0.000 description 5
239000000137 peptide hydrolase inhibitor Substances 0.000 description 5
239000000825 pharmaceutical preparation Substances 0.000 description 5
238000002953 preparative HPLC Methods 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 5
239000000375 suspending agent Substances 0.000 description 5
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
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
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 4
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
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
239000007900 aqueous suspension Substances 0.000 description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
239000003086 colorant Substances 0.000 description 4
239000002270 dispersing agent Substances 0.000 description 4
239000000839 emulsion Substances 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000001914 filtration Methods 0.000 description 4
238000009472 formulation Methods 0.000 description 4
230000004968 inflammatory condition Effects 0.000 description 4
210000002540 macrophage Anatomy 0.000 description 4
LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 4
239000001301 oxygen Substances 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
229940094443 oxytocics prostaglandins Drugs 0.000 description 4
230000036961 partial effect Effects 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
239000003755 preservative agent Substances 0.000 description 4
150000003180 prostaglandins Chemical class 0.000 description 4
238000010992 reflux Methods 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
239000003826 tablet Substances 0.000 description 4
239000000080 wetting agent Substances 0.000 description 4
FQUGROPNTBVTAQ-UHFFFAOYSA-N 3-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(N)=C(C(O)=O)N2C(=O)CC21 FQUGROPNTBVTAQ-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
108010028275 Leukocyte Elastase Proteins 0.000 description 3
102000016799 Leukocyte elastase Human genes 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
125000004414 alkyl thio group Chemical group 0.000 description 3
230000037396 body weight Effects 0.000 description 3
210000002808 connective tissue Anatomy 0.000 description 3
238000003795 desorption Methods 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000003814 drug Substances 0.000 description 3
230000032050 esterification Effects 0.000 description 3
238000005886 esterification reaction Methods 0.000 description 3
239000006260 foam Substances 0.000 description 3
239000011521 glass Substances 0.000 description 3
229940057995 liquid paraffin Drugs 0.000 description 3
210000004072 lung Anatomy 0.000 description 3
238000001819 mass spectrum Methods 0.000 description 3
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
238000002156 mixing Methods 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
239000004006 olive oil Substances 0.000 description 3
235000008390 olive oil Nutrition 0.000 description 3
239000000843 powder Substances 0.000 description 3
230000000750 progressive effect Effects 0.000 description 3
235000018102 proteins Nutrition 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
150000003254 radicals Chemical group 0.000 description 3
239000011347 resin Substances 0.000 description 3
229920005989 resin Polymers 0.000 description 3
238000002390 rotary evaporation Methods 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000011343 solid material Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
229910052717 sulfur Inorganic materials 0.000 description 3
239000011593 sulfur Substances 0.000 description 3
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Classifications

- 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)

NO874699A 1986-11-12 1987-11-11 Fremgangsmaate for frenstilling av nye substituerte cefalosporin-sulfoner. NO874699L (no)

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 (de)
JP (1)	JPS63198688A (de)
KR (1)	KR880006249A (de)
CN (1)	CN87107753A (de)
AT (1)	ATE133954T1 (de)
AU (1)	AU611104B2 (de)
CA (1)	CA1339275C (de)
DE (1)	DE3751700D1 (de)
DK (1)	DK590787A (de)
FI (1)	FI874839A7 (de)
HU (1)	HUT52511A (de)
IL (1)	IL84359A0 (de)
NO (1)	NO874699L (de)
NZ (1)	NZ222399A (de)
PT (1)	PT86074B (de)
ZA (1)	ZA878467B (de)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
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
US5264429A (en) *	1989-10-06	1993-11-23	Synphar Laboratories, Inc.	2-spirocyclopropyl cephalosporin sulfone derivatives
EP0494914B1 (de) *	1989-10-06	1998-12-23	Synphar Laboratories Inc.	2-spirocyclopropylcephalosporinderivate und verfahren zu ihrer herstellung
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
WO1993016043A1 (en) *	1992-02-18	1993-08-19	Otsuka Kagaku Kabushiki Kaisha	β-LACTAM COMPOUND AND CEPHEM COMPOUND, AND PRODUCTION THEREOF
GB2266525A (en) *	1992-03-17	1993-11-03	Merck & Co Inc	Substituted cephalosporin sulfone compositions useful in the treatment of leukemia
GB2266526A (en) *	1992-03-17	1993-11-03	Merck & Co Inc	Substituted cephalosporin sulfones useful in the treatment of leukemia
WO1993024493A1 (en) *	1992-05-27	1993-12-09	Teijin Limited	Cephalosporin derivative
JPH08502752A (ja) *	1992-10-27	1996-03-26	メルクエンドカンパニーインコーポレーテッド	抗炎症剤及び抗変性剤としての新規の置換アゼチジノン
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
JPH11514345A (ja) *	1995-08-31	1999-12-07	スミスクライン・ビーチャム・コーポレイション	インターロイキン変換酵素およびアポプトーシス
JPH11511463A (ja) *	1995-08-31	1999-10-05	スミスクライン・ビーチャム・コーポレイション	インターロイキン変換酵素およびアポプトーシス
GB9525697D0 (en) *	1995-12-15	1996-02-14	Pharmacia Spa	Cephem derivatives
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)

* Cited by examiner, † Cited by third party
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 (de) *	1983-05-02	1986-11-26	Merck & Co. Inc.	Substituierte Cephalosporinsulfone mit Antientzündungs- und Antidegenerativwirkung, sie enthaltende Zusammensetzungen und Verfahren zur Herstellung
US4699904A (en) *	1985-07-01	1987-10-13	Merck & Co., Inc.	Tetrazolyl derivatives of β-lactams useful as elastase inhibitors

1987
- 1987-11-02 AT AT87309688T patent/ATE133954T1/de not_active IP Right Cessation
- 1987-11-02 EP EP87309688A patent/EP0267723B1/de not_active Expired - Lifetime
- 1987-11-02 NZ NZ222399A patent/NZ222399A/xx unknown
- 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/FI874839A7/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 CN CN198787107753A patent/CN87107753A/zh active Pending
- 1987-11-11 ZA ZA878467A patent/ZA878467B/xx unknown
- 1987-11-11 NO NO874699A patent/NO874699L/no unknown
- 1987-11-11 HU HU875022A patent/HUT52511A/hu unknown
- 1987-11-11 KR KR870012677A patent/KR880006249A/ko not_active Withdrawn
- 1987-11-11 DK DK590787A patent/DK590787A/da not_active Application Discontinuation
- 1987-11-12 JP JP62284386A patent/JPS63198688A/ja active Pending

Also Published As

Publication number	Publication date
CA1339275C (en)	1997-08-12
PT86074B (pt)	1990-11-07
NZ222399A (en)	1991-07-26
FI874839A0 (fi)	1987-11-03
PT86074A (en)	1987-12-01
EP0267723A3 (en)	1989-12-06
EP0267723B1 (de)	1996-02-07
EP0267723A2 (de)	1988-05-18
KR880006249A (ko)	1988-07-22
JPS63198688A (ja)	1988-08-17
CN87107753A (zh)	1988-06-29
FI874839A7 (fi)	1988-05-13
DK590787A (da)	1988-05-13
ATE133954T1 (de)	1996-02-15
AU8062487A (en)	1988-05-19
AU611104B2 (en)	1991-06-06
DK590787D0 (da)	1987-11-11
IL84359A0 (en)	1988-04-29
NO874699D0 (no)	1987-11-11
HUT52511A (en)	1990-07-28
DE3751700D1 (de)	1996-03-21
ZA878467B (en)	1988-09-28

Publication	Publication Date	Title
US4547371A (en)	1985-10-15	Substituted cephalosporin sulfones as anti-inflammatory and anti-degenerative agents
US4342772A (en)	1982-08-03	β-Lactam compounds, antibacterial compositions thereof and method of use
CA1339275C (en)	1997-08-12	New substituted cephalosporin sulfones as anti-inflammatory and antidegenerative agents
EP0124081A2 (de)	1984-11-07	Substituierte Cephalosporinsulfone mit Antientzündungs- und Antidegenerativwirkung, sie enthaltende Zusammensetzungen und Verfahren zur Herstellung
EP0199630A1 (de)	1986-10-29	Substituierte Azetidinone, diese enthaltende pharmazeutische Zusammensetzungen und ihre Verwendung zur Herstellung von entzündungshemmenden und antidegenerativen Medikamenten
US4623645A (en)	1986-11-18	Substituted cephalosporin sulfoxides as anti-inflammatory and antidegenerative agents
US4699904A (en)	1987-10-13	Tetrazolyl derivatives of β-lactams useful as elastase inhibitors
JP2509689B2 (ja)	1996-06-26	セファロスポリン誘導体およびそれらの製法
US5132301A (en)	1992-07-21	Substituted cephalosporin sulfones as anti-inflammatory and anti-degenerative agents
US4637999A (en)	1987-01-20	Substituted cephalosporins as anti-inflammatory and antidegenerative agents
SU1556541A3 (ru)	1990-04-07	Способ получени фармацевтически приемлемых эфиров 7- @ -[2-(2-амино-4-тиазолил)-алкеноиламино]-3-цефем-4-карбоновой кислоты
EP0378604B1 (de)	1994-03-02	1,1-dioxo-cephem-4-carbothiolsäure-derivate
EP0049855B1 (de)	1986-01-29	Neue Cephalosporinderivate, Verfahren zu ihrer Herstellung und Zwischenprodukte dafür sowie entsprechende pharmazeutische Präparate
GB2266525A (en)	1993-11-03	Substituted cephalosporin sulfone compositions useful in the treatment of leukemia
EP0170192A1 (de)	1986-02-05	Penicillin-Derivate als entzündungshemmende und degenerierungskämpfende Arzneimittel
US5580865A (en)	1996-12-03	2,2-disubstituted cephem sulphones
DE69032857T2 (de)	1999-08-05	2-spirocyclopropylcephalosporinderivate und verfahren zu ihrer herstellung
US4845088A (en)	1989-07-04	Tetrazolyl derivatives of beta-lactams useful as elastase inhibitors
AU647067B2 (en)	1994-03-17	Beta-lactam derivatives
GB2266526A (en)	1993-11-03	Substituted cephalosporin sulfones useful in the treatment of leukemia
US20010011085A1 (en)	2001-08-02	4-substituted cephem derivatives as elastase inhibitors
GB2198640A (en)	1988-06-22	Penicillin derivatives as anti-inflammatory and antidegenerative agents
JP3914276B2 (ja)	2007-05-16	新規なセファロスポリン誘導体またはその塩
CS199669B2 (en)	1980-07-31	Method of producing derivatives of 7 beta-aryl-malonamido-3-substituted thiomethyl-1-oxadethia-3-cephem-4-carboxylic acids
EP0171812A2 (de)	1986-02-19	Cephemderivate