CA1056815A - Derives alkyl ou heterothro alkyloxy ou alkylthia de carbonylthioacetylcephalosporines - Google Patents

Derives alkyl ou heterothro alkyloxy ou alkylthia de carbonylthioacetylcephalosporines

Info

Publication number: CA1056815A
Authority: CA; Canada
Prior art keywords: methyl; thio; oxo; amino; ene
Prior art date: 1974-05-10
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA223,673A

Other languages

English (en)

Other versions

CA223673S (en

Inventor

Uwe D. Treuner

Hermann Breuer

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

ER Squibb and Sons LLC

Original Assignee

ER Squibb and Sons LLC

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.)

1974-05-10

Filing date

1975-04-02

Publication date

1979-06-19

1974-05-10 Priority claimed from US468727A external-priority patent/US3929776A/en

1974-08-30 Priority claimed from US05/501,902 external-priority patent/US3931170A/en

1975-04-02 Application filed by ER Squibb and Sons LLC filed Critical ER Squibb and Sons LLC

1979-06-19 Application granted granted Critical

1979-06-19 Publication of CA1056815A publication Critical patent/CA1056815A/fr

Status Expired legal-status Critical Current

Links

125000000217 alkyl group Chemical group 0.000 title claims abstract description 55
-1 carbonyl thioacetyl cephalosporins Chemical class 0.000 title claims description 107
229930186147 Cephalosporin Natural products 0.000 title description 3
229940124587 cephalosporin Drugs 0.000 title description 3
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
239000001257 hydrogen Substances 0.000 claims abstract description 18
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 15
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 12
150000003839 salts Chemical class 0.000 claims abstract description 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 4
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 34
238000000034 method Methods 0.000 claims description 24
150000001875 compounds Chemical class 0.000 claims description 15
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 11
125000003831 tetrazolyl group Chemical group 0.000 claims description 8
KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 18
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 8
125000000623 heterocyclic group Chemical group 0.000 abstract description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 5
229910052757 nitrogen Inorganic materials 0.000 abstract description 4
125000004076 pyridyl group Chemical group 0.000 abstract description 4
125000001544 thienyl group Chemical group 0.000 abstract description 4
229910052799 carbon Inorganic materials 0.000 abstract description 3
125000002541 furyl group Chemical group 0.000 abstract description 3
125000001181 organosilyl group Chemical group [SiH3]* 0.000 abstract description 3
125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 abstract description 3
125000005037 alkyl phenyl group Chemical group 0.000 abstract description 2
239000003242 anti bacterial agent Substances 0.000 abstract description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 2
229910052717 sulfur Inorganic materials 0.000 abstract 2
239000011593 sulfur Substances 0.000 abstract 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
125000004122 cyclic group Chemical group 0.000 abstract 1
229910052760 oxygen Inorganic materials 0.000 abstract 1
239000001301 oxygen Substances 0.000 abstract 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 182
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 107
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 61
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 60
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
239000002253 acid Substances 0.000 description 38
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
SCNWTQPZTZMXBG-UHFFFAOYSA-N 2-methyloct-2-enoic acid Chemical compound CCCCCC=C(C)C(O)=O SCNWTQPZTZMXBG-UHFFFAOYSA-N 0.000 description 18
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 18
239000000047 product Substances 0.000 description 18
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 17
239000000243 solution Substances 0.000 description 17
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
239000000203 mixture Substances 0.000 description 14
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 12
150000002431 hydrogen Chemical group 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
239000003208 petroleum Substances 0.000 description 9
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 9
238000003756 stirring Methods 0.000 description 9
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 7
239000000843 powder Substances 0.000 description 7
239000002904 solvent Substances 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 6
238000001816 cooling Methods 0.000 description 6
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 6
150000003536 tetrazoles Chemical class 0.000 description 6
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
235000011167 hydrochloric acid Nutrition 0.000 description 5
229960000443 hydrochloric acid Drugs 0.000 description 5
229960003424 phenylacetic acid Drugs 0.000 description 5
239000003279 phenylacetic acid Substances 0.000 description 5
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 5
125000001113 thiadiazolyl group Chemical group 0.000 description 5
125000004515 1,2,4-thiadiazol-3-yl group Chemical group S1N=C(N=C1)* 0.000 description 4
125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
FPVUWZFFEGYCGB-UHFFFAOYSA-N 5-methyl-3h-1,3,4-thiadiazole-2-thione Chemical compound CC1=NN=C(S)S1 FPVUWZFFEGYCGB-UHFFFAOYSA-N 0.000 description 4
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
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 4
239000007864 aqueous solution Substances 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
150000002500 ions Chemical class 0.000 description 4
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
239000012071 phase Substances 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000011734 sodium Substances 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
125000004516 1,2,4-thiadiazol-5-yl group Chemical group S1N=CN=C1* 0.000 description 3
125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
239000013078 crystal Substances 0.000 description 3
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 3
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 3
229910052700 potassium Inorganic materials 0.000 description 3
239000011591 potassium Substances 0.000 description 3
229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
235000015497 potassium bicarbonate Nutrition 0.000 description 3
239000011736 potassium bicarbonate Substances 0.000 description 3
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 3
159000000000 sodium salts Chemical class 0.000 description 3
239000007787 solid Substances 0.000 description 3
125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 description 2
MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 description 2
KPZGRMZPZLOPBS-UHFFFAOYSA-N 1,3-dichloro-2,2-bis(chloromethyl)propane Chemical compound ClCC(CCl)(CCl)CCl KPZGRMZPZLOPBS-UHFFFAOYSA-N 0.000 description 2
VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 2
QPHZWABVAIGWHI-UHFFFAOYSA-N 3-methyl-2h-1,2,4-thiadiazole-5-thione Chemical group CC1=NSC(S)=N1 QPHZWABVAIGWHI-UHFFFAOYSA-N 0.000 description 2
GBEPMLYZCPHOBB-UHFFFAOYSA-N 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CCSC2CCN12 GBEPMLYZCPHOBB-UHFFFAOYSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
239000002585 base Substances 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
150000001780 cephalosporins Chemical class 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
238000001035 drying Methods 0.000 description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000000605 extraction Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000004108 freeze drying Methods 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
208000015181 infectious disease Diseases 0.000 description 2
239000012948 isocyanate Substances 0.000 description 2
150000002513 isocyanates Chemical class 0.000 description 2
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
229910021645 metal ion Inorganic materials 0.000 description 2
HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
125000004708 n-butylthio group Chemical group C(CCC)S* 0.000 description 2
239000003921 oil Substances 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 2
CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
125000001425 triazolyl group Chemical group 0.000 description 2
238000001665 trituration Methods 0.000 description 2
WYUSVOMTXWRGEK-NOZJJQNGSA-N (6r,7r)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(methoxymethyl)-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)C(O)=O)C(=O)C(=NOC)C1=CSC(N)=N1 WYUSVOMTXWRGEK-NOZJJQNGSA-N 0.000 description 1
125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 description 1
125000001506 1,2,3-triazol-5-yl group Chemical group [H]N1N=NC([H])=C1[*] 0.000 description 1
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
HZMCMMVCBAJHET-UHFFFAOYSA-N 2,2-dimethylpropanoyloxymethyl 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound CC(C)(C)C(=O)OCOC(=O)C1=CCSC2CCN12 HZMCMMVCBAJHET-UHFFFAOYSA-N 0.000 description 1
DGSFZGQIUBBSDK-UHFFFAOYSA-N 2,3-dihydrothiadiazole-5-thiol Chemical compound C1(=CNNS1)S DGSFZGQIUBBSDK-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
QYIGFZOHYGYBLX-UHFFFAOYSA-N 2-phenyl-2-sulfanylacetic acid Chemical compound OC(=O)C(S)C1=CC=CC=C1 QYIGFZOHYGYBLX-UHFFFAOYSA-N 0.000 description 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
GOLXRNDWAUTYKT-UHFFFAOYSA-N 3-(1H-indol-3-yl)propanoic acid Chemical compound C1=CC=C2C(CCC(=O)O)=CNC2=C1 GOLXRNDWAUTYKT-UHFFFAOYSA-N 0.000 description 1
QGDVHQNSOVXYMW-UHFFFAOYSA-N 3-amino-3-oxopropanethioic s-acid Chemical compound NC(=O)CC(O)=S QGDVHQNSOVXYMW-UHFFFAOYSA-N 0.000 description 1
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
YCXCBCPBERCFOT-UHFFFAOYSA-N 4-methyl-1,3,4-thiadiazolidine-2-thione Chemical compound CN1CSC(S)=N1 YCXCBCPBERCFOT-UHFFFAOYSA-N 0.000 description 1
OBRJBKJCXLWCTB-UHFFFAOYSA-N 4-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CC(=O)SC2CCN12 OBRJBKJCXLWCTB-UHFFFAOYSA-N 0.000 description 1
FZEVMBJWXHDLDB-UHFFFAOYSA-N 5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical compound S1CC=CN2C(=O)CC21 FZEVMBJWXHDLDB-UHFFFAOYSA-N 0.000 description 1
125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
IKWLIQXIPRUIDU-UHFFFAOYSA-N 8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CCSC2CC(=O)N12 IKWLIQXIPRUIDU-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
229910014033 C-OH Inorganic materials 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
229910014570 C—OH Inorganic materials 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 description 1
VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
241001024304 Mino Species 0.000 description 1
BTMKEDDEMKKSEF-QGZVFWFLSA-N N-[5-[[4-[5-chloro-4-fluoro-2-(2-hydroxypropan-2-yl)anilino]pyrimidin-2-yl]amino]-2-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-4-methoxyphenyl]prop-2-enamide Chemical compound C(C=C)(=O)NC1=C(C=C(C(=C1)NC1=NC=CC(=N1)NC1=C(C=C(C(=C1)Cl)F)C(C)(C)O)OC)N1C[C@@H](CC1)N(C)C BTMKEDDEMKKSEF-QGZVFWFLSA-N 0.000 description 1
241000588767 Proteus vulgaris Species 0.000 description 1
241000589517 Pseudomonas aeruginosa Species 0.000 description 1
241000607142 Salmonella Species 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
241000191967 Staphylococcus aureus Species 0.000 description 1
241000193996 Streptococcus pyogenes Species 0.000 description 1
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
MCRWZBYTLVCCJJ-DKALBXGISA-N [(1s,3r)-3-[[(3s,4s)-3-methoxyoxan-4-yl]amino]-1-propan-2-ylcyclopentyl]-[(1s,4s)-5-[6-(trifluoromethyl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone Chemical compound C([C@]1(N(C[C@]2([H])C1)C(=O)[C@@]1(C[C@@H](CC1)N[C@@H]1[C@@H](COCC1)OC)C(C)C)[H])N2C1=CC(C(F)(F)F)=NC=N1 MCRWZBYTLVCCJJ-DKALBXGISA-N 0.000 description 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
239000003637 basic solution Substances 0.000 description 1
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 description 1
230000015572 biosynthetic process Effects 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
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
229960002588 cefradine Drugs 0.000 description 1
RDLPVSKMFDYCOR-UEKVPHQBSA-N cephradine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CCC=CC1 RDLPVSKMFDYCOR-UEKVPHQBSA-N 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 1
230000000694 effects Effects 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical group CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000006260 foam Substances 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
CGJMROBVSBIBKP-UHFFFAOYSA-N malonamic acid Chemical compound NC(=O)CC(O)=O CGJMROBVSBIBKP-UHFFFAOYSA-N 0.000 description 1
WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical class [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
BLIJXOOIHRSQRB-PXYINDEMSA-N n-[(2s)-1-[3-(3-chloro-4-cyanophenyl)pyrazol-1-yl]propan-2-yl]-5-(1-hydroxyethyl)-1h-pyrazole-3-carboxamide Chemical compound C([C@H](C)NC(=O)C=1NN=C(C=1)C(C)O)N(N=1)C=CC=1C1=CC=C(C#N)C(Cl)=C1 BLIJXOOIHRSQRB-PXYINDEMSA-N 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
229940007042 proteus vulgaris Drugs 0.000 description 1
150000003254 radicals Chemical group 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000001226 reprecipitation Methods 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1

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
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/36—Methylene radicals, substituted by sulfur atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Cephalosporin Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA223,673A 1974-05-10 1975-04-02 Derives alkyl ou heterothro alkyloxy ou alkylthia de carbonylthioacetylcephalosporines Expired CA1056815A (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US468727A US3929776A (en)	1974-05-10	1974-05-10	3-Heterothio derivatives of {8 (thioalkoxycarbonyl)thioacetyl{9 cephalosporins
US05/501,902 US3931170A (en)	1974-08-30	1974-08-30	3-Heterothio derivatives of (carbamoylthioacetyl)cephalosporins

Publications (1)

Publication Number	Publication Date
CA1056815A true CA1056815A (fr)	1979-06-19

Family

ID=27042510

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA223,673A Expired CA1056815A (fr)	1974-05-10	1975-04-02	Derives alkyl ou heterothro alkyloxy ou alkylthia de carbonylthioacetylcephalosporines

Country Status (5)

Country	Link
JP (1)	JPS50154285A (fr)
CA (1)	CA1056815A (fr)
DE (1)	DE2520829A1 (fr)
FR (1)	FR2269955B1 (fr)
GB (1)	GB1500582A (fr)

1975
- 1975-04-02 CA CA223,673A patent/CA1056815A/fr not_active Expired
- 1975-04-08 GB GB1439875A patent/GB1500582A/en not_active Expired
- 1975-05-06 FR FR7514147A patent/FR2269955B1/fr not_active Expired
- 1975-05-09 DE DE19752520829 patent/DE2520829A1/de not_active Withdrawn
- 1975-05-10 JP JP5589875A patent/JPS50154285A/ja active Pending

Also Published As

Publication number	Publication date
DE2520829A1 (de)	1975-11-20
JPS50154285A (fr)	1975-12-12
GB1500582A (en)	1978-02-08
FR2269955B1 (fr)	1978-07-28
FR2269955A1 (fr)	1975-12-05

Publication	Publication Date	Title
CA1272713A (fr)	1990-08-14	Carboxyalkenamidocephalosporines
CA1104125B (fr)	1981-06-30	Derives de la cephalosporine
US3516997A (en)	1970-06-23	3,7-disubstituted cephalosporin compounds and preparation thereof
US3828037A (en)	1974-08-06	Trifluoromethylmercaptoacetamidocephalosporins
CA1065854A (fr)	1979-11-06	Derives du 7-acetoacetamidocephem
CA1056815A (fr)	1979-06-19	Derives alkyl ou heterothro alkyloxy ou alkylthia de carbonylthioacetylcephalosporines
US3931170A (en)	1976-01-06	3-Heterothio derivatives of (carbamoylthioacetyl)cephalosporins
JP2529093B2 (ja)	1996-08-28	セファロスポリン中間体の製造方法
CA1057738A (fr)	1979-07-03	(((alkylthiocarbonyl)oxy) acetyl) cephalosporines
US3996216A (en)	1976-12-07	3-Heterothio derivatives of (formylamino)acetylamino-7-alpha-methoxy cephalosporins
CA1057740A (fr)	1979-07-03	Derives de la 3-heterothio (alkoxycarbonyl et alkoxythiocarbonyl)-thioacetyl) cephalosporine
US4005081A (en)	1977-01-25	3-Heterothiomethyl-7α-methoxy-7β-tetrazolylmethylthioacetamido-3-cephem derivatives
US3950330A (en)	1976-04-13	3-Alkylthio and 3-heterothio derivatives of [[(thioalkoxy)thiocarbonyl]oxy]acetyl cephalosporins
US3994889A (en)	1976-11-30	3-Heterothio derivatives of (α-thiocarbonylaminol)-7α-methoxy-cephalosporins
CA1075679A (fr)	1980-04-15	3-heterothio-7-thioureidocephalosporines
US3960850A (en)	1976-06-01	3-Heterothio derivatives of [(alkoxycarbonyl)oxyacetyl]cephalosporins
US3929782A (en)	1975-12-30	1,2,4-Oxadiazolonylacetyl cephalosporins
US3978050A (en)	1976-08-31	3-Tetrazolyl and other derivatives of [[(alkoxy)thiocarbonyl]oxy]acetyl cephalosporins
US3929776A (en)	1975-12-30	3-Heterothio derivatives of {8 (thioalkoxycarbonyl)thioacetyl{9 cephalosporins
US3996219A (en)	1976-12-07	3-Heterothio derivatives of (α-thiocarbonylamino) cephalosporins
US3989696A (en)	1976-11-02	3-Heterothio[(oxyalkyl)thioacetyl]cephalosporin derivatives
US4144241A (en)	1979-03-13	5-Sulfomethyl-1,3,4-thiadiazole-2-thiol
US5585485A (en)	1996-12-17	Cephalosporin intermediate products
US4003893A (en)	1977-01-18	3-Heterothio[(thioalkyl)thioacetyl]cephalosporanic derivatives
US3926983A (en)	1975-12-16	3-Heterothio{8 (alkoxycarbonyl)thioacetyl{9 cephalosporanic derivatives