NO832376L - Cephalosporin-antibiotika. - Google Patents

Cephalosporin-antibiotika.

Info

Publication number: NO832376L
Authority: NO; Norway
Prior art keywords: compound; acid; formula; group; salt
Prior art date: 1982-06-30

Application number

NO832376A

Other languages

English (en)

Norwegian (no)

Inventor

Brian Edgar Looker

Original Assignee

Glaxo Group Ltd

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.)

1982-06-30

Filing date

1983-06-29

Publication date

1984-01-02

1983-06-29 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

1984-01-02 Publication of NO832376L publication Critical patent/NO832376L/no

Links

229940124587 cephalosporin Drugs 0.000 title description 15
229930186147 Cephalosporin Natural products 0.000 title description 14
239000003242 anti bacterial agent Substances 0.000 title description 11
150000001780 cephalosporins Chemical class 0.000 title description 10
229940088710 antibiotic agent Drugs 0.000 title description 9
150000001875 compounds Chemical class 0.000 claims description 80
-1 methyl- Chemical group 0.000 claims description 45
239000002253 acid Substances 0.000 claims description 43
150000003839 salts Chemical class 0.000 claims description 37
150000002148 esters Chemical class 0.000 claims description 28
231100000252 nontoxic Toxicity 0.000 claims description 22
230000003000 nontoxic effect Effects 0.000 claims description 22
238000000034 method Methods 0.000 claims description 17
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
239000003795 chemical substances by application Substances 0.000 claims description 15
238000006243 chemical reaction Methods 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 10
230000000903 blocking effect Effects 0.000 claims description 8
239000007858 starting material Substances 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
230000009467 reduction Effects 0.000 claims description 4
238000012546 transfer Methods 0.000 claims description 4
125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 3
125000003277 amino group Chemical group 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
NSQKMEKRFGBLLV-LGAWNBMASA-N (6r,7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(cyclopropylmethoxyimino)acetyl]amino]-3-(carbamoyloxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)N)C(O)=O)C(=O)C(\C=1N=C(N)SC=1)=N/OCC1CC1 NSQKMEKRFGBLLV-LGAWNBMASA-N 0.000 claims description 2
230000015572 biosynthetic process Effects 0.000 claims description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
239000000243 solution Substances 0.000 description 51
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
150000007513 acids Chemical class 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
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239000012044 organic layer Substances 0.000 description 12
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
229910052757 nitrogen Inorganic materials 0.000 description 11
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
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239000000047 product Substances 0.000 description 10
238000005917 acylation reaction Methods 0.000 description 9
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229910052943 magnesium sulfate Inorganic materials 0.000 description 9
235000019341 magnesium sulphate Nutrition 0.000 description 9
239000007787 solid Substances 0.000 description 9
238000003756 stirring Methods 0.000 description 9
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
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235000019253 formic acid Nutrition 0.000 description 8
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JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 6
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239000005457 ice water Substances 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
239000000843 powder Substances 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
230000010933 acylation Effects 0.000 description 5
150000008064 anhydrides Chemical class 0.000 description 5
238000006266 etherification reaction Methods 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000006260 foam Substances 0.000 description 5
239000011521 glass Substances 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
229910000147 aluminium phosphate Inorganic materials 0.000 description 4
239000012267 brine Substances 0.000 description 4
150000004820 halides Chemical class 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
239000012346 acetyl chloride Substances 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
125000002252 acyl group Chemical group 0.000 description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
238000010945 base-catalyzed hydrolysis reactiony Methods 0.000 description 3
WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
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239000012065 filter cake Substances 0.000 description 3
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150000008282 halocarbons Chemical class 0.000 description 3
229910052736 halogen Inorganic materials 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
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159000000000 sodium salts Chemical class 0.000 description 3
239000012453 solvate Substances 0.000 description 3
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
ANNZTRJVIPPAMS-GDWJVWIDSA-N (2z)-2-(cyclopropylmethoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid Chemical compound C=1SC(NC(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=NC=1/C(C(=O)O)=N/OCC1CC1 ANNZTRJVIPPAMS-GDWJVWIDSA-N 0.000 description 2
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SXBDXXFTJVHSAF-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-3-en-8-one Chemical compound S1C=CCN2C(=O)C[C@H]21 SXBDXXFTJVHSAF-ZCFIWIBFSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
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ITLHXEGAYQFOHJ-UHFFFAOYSA-N [diazo(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(=[N+]=[N-])C1=CC=CC=C1 ITLHXEGAYQFOHJ-UHFFFAOYSA-N 0.000 description 2
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125000001931 aliphatic group Chemical group 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
125000005205 alkoxycarbonyloxyalkyl group Chemical group 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
150000001649 bromium compounds Chemical class 0.000 description 2
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QHTOIDKCEPKVCM-ZCFIWIBFSA-N cepham Chemical compound S1CCCN2C(=O)C[C@H]21 QHTOIDKCEPKVCM-ZCFIWIBFSA-N 0.000 description 2
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SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
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ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
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GRWKNBPOGBTZMN-UHFFFAOYSA-N 2-benzyl-3-phenylpropane-1,2-diamine Chemical compound C=1C=CC=CC=1CC(N)(CN)CC1=CC=CC=C1 GRWKNBPOGBTZMN-UHFFFAOYSA-N 0.000 description 1
PKYBZMHFUXKMRC-UHFFFAOYSA-M 2-ethyl-5-phenyl-1,2-oxazol-2-ium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.O1[N+](CC)=CC=C1C1=CC=CC=C1 PKYBZMHFUXKMRC-UHFFFAOYSA-M 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
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239000004475 Arginine Substances 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
239000004358 Butane-1, 3-diol Substances 0.000 description 1
NGYSSPXNUSZXHK-SLAYKFERSA-N C(N)(=O)OCC=1CS[C@H]2N(C=1C(=O)OC(C)OC(C)=O)C([C@H]2NC(\C(\C=1N=C(SC=1)NC(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)=N/OCC1CC1)=O)=O Chemical compound C(N)(=O)OCC=1CS[C@H]2N(C=1C(=O)OC(C)OC(C)=O)C([C@H]2NC(\C(\C=1N=C(SC=1)NC(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)=N/OCC1CC1)=O)=O NGYSSPXNUSZXHK-SLAYKFERSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
241000588697 Enterobacter cloacae Species 0.000 description 1
241000588921 Enterobacteriaceae Species 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
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241000192125 Firmicutes Species 0.000 description 1
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108010087702 Penicillinase Proteins 0.000 description 1
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239000004793 Polystyrene Substances 0.000 description 1
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241000588769 Proteus <enterobacteria> Species 0.000 description 1
241000588770 Proteus mirabilis Species 0.000 description 1
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241000191967 Staphylococcus aureus Species 0.000 description 1
241000191963 Staphylococcus epidermidis Species 0.000 description 1
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238000010521 absorption reaction Methods 0.000 description 1
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RRNJROHIFSLGRA-JEDNCBNOSA-N acetic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.NCCCC[C@H](N)C(O)=O RRNJROHIFSLGRA-JEDNCBNOSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
125000005041 acyloxyalkyl group Chemical group 0.000 description 1
125000005042 acyloxymethyl group Chemical group 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
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230000000844 anti-bacterial effect Effects 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
239000013011 aqueous formulation Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000012431 aqueous reaction media Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
244000052616 bacterial pathogen Species 0.000 description 1
230000008901 benefit Effects 0.000 description 1
LWKSTSKGZABZPC-OXQOHEQNSA-N benzhydryl (6r,7r)-7-amino-3-(carbamoyloxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1[C@@H](C(N11)=O)N)CC(COC(N)=O)=C1C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 LWKSTSKGZABZPC-OXQOHEQNSA-N 0.000 description 1
125000006267 biphenyl group Chemical group 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
235000019437 butane-1,3-diol Nutrition 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
SHZIWNPUGXLXDT-UHFFFAOYSA-N caproic acid ethyl ester Natural products CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 description 1
239000002775 capsule Substances 0.000 description 1
230000002252 carbamoylating effect Effects 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
150000001728 carbonyl compounds Chemical class 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
125000005518 carboxamido group Chemical group 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 1
229960001668 cefuroxime Drugs 0.000 description 1
150000001782 cephems Chemical class 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
229940106681 chloroacetic acid Drugs 0.000 description 1
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
229920006026 co-polymeric resin Polymers 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000007799 cork Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
150000004292 cyclic ethers Chemical class 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
239000003405 delayed action preparation Substances 0.000 description 1
238000011161 development Methods 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
KKFBLNMRJSAFAA-FAJYDZGRSA-N ethyl (2z)-2-hydroxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetate Chemical compound CCOC(=O)C(=N/O)\C1=CSC(NC(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 KKFBLNMRJSAFAA-FAJYDZGRSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
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230000022244 formylation Effects 0.000 description 1
238000006170 formylation reaction Methods 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
229940047650 haemophilus influenzae Drugs 0.000 description 1
230000002140 halogenating effect Effects 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
239000012433 hydrogen halide Substances 0.000 description 1
229910000039 hydrogen halide Inorganic materials 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
229940006461 iodide ion Drugs 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical class C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
229960005357 lysine acetate Drugs 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
244000005700 microbiome Species 0.000 description 1
238000002156 mixing Methods 0.000 description 1
HSZCJVZRHXPCIA-UHFFFAOYSA-N n-benzyl-n-ethylaniline Chemical compound C=1C=CC=CC=1N(CC)CC1=CC=CC=C1 HSZCJVZRHXPCIA-UHFFFAOYSA-N 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
150000002924 oxiranes Chemical class 0.000 description 1
244000052769 pathogen Species 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
229950009506 penicillinase Drugs 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
239000004584 polyacrylic acid Substances 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
229920005990 polystyrene resin Polymers 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
229940007042 proteus vulgaris Drugs 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
208000020029 respiratory tract infectious disease Diseases 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
229940001584 sodium metabisulfite Drugs 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1
AAMCVENDCXWDPJ-UHFFFAOYSA-N sulfanyl acetate Chemical class CC(=O)OS AAMCVENDCXWDPJ-UHFFFAOYSA-N 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
125000000542 sulfonic acid group Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 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
150000003512 tertiary amines Chemical class 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
238000005866 tritylation reaction Methods 0.000 description 1
208000019206 urinary tract infection Diseases 0.000 description 1
239000003981 vehicle Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/587—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with aliphatic hydrocarbon radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms, said aliphatic radicals being substituted in the alpha-position to the ring by a hetero atom, e.g. with m >= 0, Z being a singly or a doubly bound hetero atom

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Cephalosporin Compounds (AREA)

NO832376A 1982-06-30 1983-06-29 Cephalosporin-antibiotika. NO832376L (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB8218874		1982-06-30
GB8222236		1982-08-02

Publications (1)

Publication Number	Publication Date
NO832376L true NO832376L (no)	1984-01-02

Family

ID=26283232

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO832376A NO832376L (no)	1982-06-30	1983-06-29	Cephalosporin-antibiotika.

Country Status (16)

Country	Link
US (1)	US4560683A (da)
EP (1)	EP0098161A3 (da)
AU (2)	AU1638183A (da)
DE (1)	DE3323462A1 (da)
DK (1)	DK299083A (da)
ES (1)	ES523682A0 (da)
FI (1)	FI832385L (da)
FR (1)	FR2529555A1 (da)
GB (1)	GB2123414B (da)
GR (1)	GR77529B (da)
IT (1)	IT1212876B (da)
LU (1)	LU84887A1 (da)
NL (1)	NL8302309A (da)
NO (1)	NO832376L (da)
PT (1)	PT76960B (da)
SE (1)	SE8303727L (da)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL68992A (en) *	1982-06-29	1991-06-10	Astra Laekemedel Ab	Alpha-bromo diethyl carbonate and process for the preparation of ethoxycarbonyloxy esters of penicillanic acids
DE3348300C2 (de) *	1982-06-29	1994-04-21	Astra Laekemedel Ab	Verwendung von alpha-Bromdiethylcarbonat
EP0148004A3 (en) *	1983-12-30	1986-04-23	Glaxo Group Limited	Cephalosporin antibiotics
GB8504072D0 (en) *	1985-02-18	1985-03-20	Fujisawa Pharmaceutical Co	Cephem compounds

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3966717A (en) *	1971-05-14	1976-06-29	Glaxo Laboratories Limited	7-β-Acylamido-3-carbamoyloxymethylceph-3-em-4-carboxylic acids and salts thereof
US4033950A (en) *	1971-05-14	1977-07-05	Glaxo Laboratories Limited	3-Hydroxymethyl-7β-(2-alkoxy-or benzyloxyimino-2-arylacetamido)ceph-3-em-4-carboxylic acids and salts thereof
US4162360A (en) *	1973-12-21	1979-07-24	Glaxo Laboratories Limited	3-Carbamoyloxymethyl-7-substituted oximino acetamido cephalosporanic acid derivatives
US3946002A (en) *	1974-07-11	1976-03-23	Lilly Industries Limited	Process for preparing cephalosporins
DK154939C (da) *	1974-12-19	1989-06-12	Takeda Chemical Industries Ltd	Analogifremgangsmaade til fremstilling af thiazolylacetamido-cephemforbindelser eller farmaceutisk acceptable salte eller estere deraf
US4166115A (en) *	1976-04-12	1979-08-28	Fujisawa Pharmaceutical Co., Ltd.	Syn 7-oxoimino substituted derivatives of cephalosporanic acid
GR63088B (en) *	1976-04-14	1979-08-09	Takeda Chemical Industries Ltd	Preparation process of novel cephalosporins
FR2361895A1 (fr) *	1976-08-20	1978-03-17	Roussel Uclaf	Nouvelles oximes derivees de l'acide 3-carbamoyloxymethyl 7-amino thiazolyl acetamido cephalosporanique, leur procede de preparation et leur application comme medicaments
DE2714880A1 (de) *	1977-04-02	1978-10-26	Hoechst Ag	Cephemderivate und verfahren zu ihrer herstellung
DE2716677C2 (de) *	1977-04-15	1985-10-10	Hoechst Ag, 6230 Frankfurt	Cephemderivate und Verfahren zu ihrer Herstellung
GB2029824B (en) *	1978-05-26	1983-02-16	Glaxo Group Ltd	7-oximino-2-amino-4-thiazolyl acetamido cephens
EP0025199B1 (en) *	1979-09-03	1984-10-31	Fujisawa Pharmaceutical Co., Ltd.	Cephem compounds, processes for their preparation and pharmaceutical compositions containing them
EP0037797A3 (de) *	1980-03-11	1981-12-16	Ciba-Geigy Ag	Cephalosporinverbindungen, Verfahren zu ihrer Herstellung, sie enthaltende pharmazeutische Zusammensetzungen und ihre Verwendung

1983
- 1983-06-29 GR GR71809A patent/GR77529B/el unknown
- 1983-06-29 SE SE8303727A patent/SE8303727L/xx not_active Application Discontinuation
- 1983-06-29 GB GB08317617A patent/GB2123414B/en not_active Expired
- 1983-06-29 AU AU16381/83A patent/AU1638183A/en not_active Abandoned
- 1983-06-29 IT IT8348598A patent/IT1212876B/it active
- 1983-06-29 AU AU16379/83A patent/AU1637983A/en not_active Abandoned
- 1983-06-29 FR FR8310796A patent/FR2529555A1/fr active Pending
- 1983-06-29 DE DE19833323462 patent/DE3323462A1/de not_active Withdrawn
- 1983-06-29 EP EP83303758A patent/EP0098161A3/en not_active Withdrawn
- 1983-06-29 ES ES523682A patent/ES523682A0/es active Granted
- 1983-06-29 NL NL8302309A patent/NL8302309A/nl not_active Application Discontinuation
- 1983-06-29 PT PT76960A patent/PT76960B/pt unknown
- 1983-06-29 US US06/509,043 patent/US4560683A/en not_active Expired - Fee Related
- 1983-06-29 NO NO832376A patent/NO832376L/no unknown
- 1983-06-29 LU LU84887A patent/LU84887A1/fr unknown
- 1983-06-29 FI FI832385A patent/FI832385L/fi not_active Application Discontinuation
- 1983-06-29 DK DK299083A patent/DK299083A/da not_active Application Discontinuation

Also Published As

Publication number	Publication date
NL8302309A (nl)	1984-01-16
GB2123414A (en)	1984-02-01
FI832385L (fi)	1983-12-31
FI832385A0 (fi)	1983-06-29
US4560683A (en)	1985-12-24
PT76960A (en)	1983-07-01
GB2123414B (en)	1985-12-04
GR77529B (da)	1984-09-24
DK299083D0 (da)	1983-06-29
AU1638183A (en)	1984-01-05
FR2529555A1 (fr)	1984-01-06
PT76960B (en)	1986-01-24
EP0098161A2 (en)	1984-01-11
ES8500957A1 (es)	1984-11-01
DK299083A (da)	1983-12-31
IT1212876B (it)	1989-11-30
ES523682A0 (es)	1984-11-01
AU1637983A (en)	1984-01-05
LU84887A1 (fr)	1984-03-07
SE8303727L (sv)	1984-02-03
IT8348598A0 (it)	1983-06-29
SE8303727D0 (sv)	1983-06-29
DE3323462A1 (de)	1984-01-12
GB8317617D0 (en)	1983-08-03
EP0098161A3 (en)	1985-04-24

Publication	Publication Date	Title
US3974153A (en)	1976-08-10	7-Hydrocarbonoxy imino-acetamido-3-carbamoyloxy methylceph-3-em-4 carboxylic acids
NO155347B (no)	1966-12-08	Analogifremgangsmaate ved fremstilling av et terapeutisk aktivt (6r,7r)-7-((z)-2-(2-amino-tiazol-4-yl)-2-(2-karboksy-prop-2-oksyimino)-acetamido)-3-(1-pyridiniummetyl)cef-3-em-4-karboksylat.
FI65432C (fi)	1984-05-10	Foerfarande foer framstaellning av antibakteriella 7beta-arylmalonamido-7alfa-metoxi-3-tiadiazolyltiometyl-1-detia-1-oxa-3-cefem-4-karbonsyror eller derivat daerav
DD202720A5 (de)	1983-09-28	Verfahren zur herstellung von cephalosporinderivaten
KR830000606B1 (ko)	1983-03-17	세팔로스포린 항생제의 제조방법
FI65623C (fi)	1984-06-11	Foerfarande foer framstaellning av antibiotiskt aktiv (6r 7r)-3-karbamoyloximetyl-7-(2-(fur-2-yl)-2-metoxiiminoacetamido)-cef-3-em-4-karboxylsyra samt dennas icke-giftiga salter
DE2460537C2 (de)	1987-01-22	7-&beta;-Acylamido-3-em-4-carbonsäure-Antibiotika
US4138555A (en)	1979-02-06	(6R,7R)-7-[2-aryl-2-(etherified oximino)acetamido]-3-carbamoyloxymethylceph-3-em-4-carboxylic acid 1-oxides
NO793688L (no)	1980-05-19	Fremgangsmaate ved fremstilling av cephalosporinderivater
US5607927A (en)	1997-03-04	Cephalosporin derivative
NO832376L (no)	1984-01-02	Cephalosporin-antibiotika.
NO800828L (no)	1980-09-23	Fremgangsmaate ved fremstilling av cefalosporinantibiotika
KR830001130B1 (ko)	1983-06-14	세팔로스포린 항생제의 제조방법
CA1074297A (en)	1980-03-25	Cephalosporins
CA1073901A (en)	1980-03-18	Cephalosporins
US4200746A (en)	1980-04-29	Cephalosporins
US4179502A (en)	1979-12-18	7[2-Hydroxyiminoacetamido]cephalosporins
NO832375L (no)	1984-01-02	Cephalosporin-antibiotika.
NO834304L (no)	1984-05-25	Cephalosporinantibiotika
EP0482657A2 (en)	1992-04-29	Cephem compounds, their production and use
KR910007980B1 (ko)	1991-10-05	신규 세팔로스포린계 항생제 및 이의 제조방법
GB2051066A (en)	1981-01-14	Cephalosporin derivatives suitable for oral administration
CA1067068A (en)	1979-11-27	3-CARBAMOYLOXYMETHYL-7-(.alpha.-(1-CARBOXYCYCLOBUT-1-OXYIMINO)-.alpha.-(FUR-2-YL) ACETAMIDO) CEPH-3-EM-4-CARBOXYLIC ACID
KR950011746B1 (ko)	1995-10-09	3-프로페닐세펨 유도체
EP0095329A2 (en)	1983-11-30	Cephalosporin antibiotics