CA1218054A - 3,7-disubstituted-3-cephem-4-carboxylic acid compounds and processes for preparation thereof - Google Patents
3,7-disubstituted-3-cephem-4-carboxylic acid compounds and processes for preparation thereofInfo
- Publication number
- CA1218054A CA1218054A CA000273202A CA273202A CA1218054A CA 1218054 A CA1218054 A CA 1218054A CA 000273202 A CA000273202 A CA 000273202A CA 273202 A CA273202 A CA 273202A CA 1218054 A CA1218054 A CA 1218054A
- Authority
- CA
- Canada
- Prior art keywords
- amino
- methyl
- thiazol
- pharmaceutically acceptable
- cephem
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- -1 3,7-disubstituted-3-cephem-4-carboxylic acid compounds Chemical class 0.000 title claims abstract description 227
- 238000000034 method Methods 0.000 title claims abstract description 166
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 166
- 150000003839 salts Chemical class 0.000 claims abstract description 141
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 78
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 55
- 239000001257 hydrogen Substances 0.000 claims abstract description 49
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 41
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 37
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 22
- 229910052736 halogen Chemical group 0.000 claims abstract description 20
- 150000002367 halogens Chemical group 0.000 claims abstract description 20
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical group C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims abstract description 10
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims description 68
- 125000006239 protecting group Chemical group 0.000 claims description 33
- 238000003379 elimination reaction Methods 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 125000003277 amino group Chemical group 0.000 claims description 23
- 150000002148 esters Chemical class 0.000 claims description 20
- YGBFLZPYDUKSPT-MRVPVSSYSA-N cephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C[C@H]21 YGBFLZPYDUKSPT-MRVPVSSYSA-N 0.000 claims description 14
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 8
- 125000004149 thio group Chemical group *S* 0.000 claims description 7
- SLKAERFZHLLPQD-AZMWARKLSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-oxoacetyl]amino]-3-[(5-methyl-1,3,4-oxadiazol-2-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CC1=NN=C(O1)SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1)N)=O)=O SLKAERFZHLLPQD-AZMWARKLSA-N 0.000 claims description 6
- CIVOJQCLZZYQPW-AZMWARKLSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-oxoacetyl]amino]-3-[(4-methyl-1,2,4-triazol-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1C(=NN=C1)SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1)N)=O)=O CIVOJQCLZZYQPW-AZMWARKLSA-N 0.000 claims description 5
- NGMMJBSHHOGWON-AZMWARKLSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-oxoacetyl]amino]-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CC1=NN=C(S1)SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1)N)=O)=O NGMMJBSHHOGWON-AZMWARKLSA-N 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- ZZXNMKAXAPUGEG-GENIYJEYSA-N (6R)-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-7-[[2-oxo-2-[2-(propylsulfonylamino)-1,3-thiazol-4-yl]acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1N=NN=C1SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1)NS(=O)(=O)CCC)=O)=O ZZXNMKAXAPUGEG-GENIYJEYSA-N 0.000 claims description 3
- VGGCDQVHTXUHNF-IWSPRGBSSA-N (6R)-7-[[2-(2-formamido-1,3-thiazol-4-yl)-2-oxoacetyl]amino]-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CC1=NN=C(S1)SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1NC(SC=1)=NC=O)=O)=O VGGCDQVHTXUHNF-IWSPRGBSSA-N 0.000 claims description 2
- HAIZQFRSZRBLOZ-RKSKCOGQSA-N (6R)-7-[[2-(2-formamido-1,3-thiazol-4-yl)-2-oxoacetyl]amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1NC(SC=1)=NC=O)=O)=O HAIZQFRSZRBLOZ-RKSKCOGQSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 11
- 125000005236 alkanoylamino group Chemical group 0.000 claims 7
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims 5
- PJHXXMQHJUUNJZ-RKSKCOGQSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-oxoacetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1N=NN=C1SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1)N)=O)=O PJHXXMQHJUUNJZ-RKSKCOGQSA-N 0.000 claims 3
- JUHQIWGFUNTLQA-RKSKCOGQSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-oxoacetyl]amino]-8-oxo-3-(1,3,4-thiadiazol-2-ylsulfanylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1C(=NN=C1)SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1)N)=O)=O JUHQIWGFUNTLQA-RKSKCOGQSA-N 0.000 claims 3
- LYOCXTAUEMCFFT-AZMWARKLSA-N (6R)-7-[[2-[2-(methylamino)-1,3-thiazol-4-yl]-2-oxoacetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1N=NN=C1SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1)NC)=O)=O LYOCXTAUEMCFFT-AZMWARKLSA-N 0.000 claims 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 3
- NESUGMKJMQHBDF-MGAKOFKPSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-oxoacetyl]amino]-3-(carbamoyloxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C(N)(=O)OCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1)N)=O)=O NESUGMKJMQHBDF-MGAKOFKPSA-N 0.000 claims 2
- SNOGVZLOCDEBDC-RKSKCOGQSA-N (6r)-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-7-[[2-oxo-2-(2-oxo-3h-1,3-thiazol-4-yl)acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)C(NC(=O)C(=O)C=3NC(=O)SC=3)[C@H]2SC1 SNOGVZLOCDEBDC-RKSKCOGQSA-N 0.000 claims 2
- CZVYEPKVCSJBMT-MGAKOFKPSA-N (6r)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-oxoacetyl]amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)C)C(O)=O)NC(=O)C(=O)C1=CSC(N)=N1 CZVYEPKVCSJBMT-MGAKOFKPSA-N 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- IFXAOAVRCWYUQA-RKSKCOGQSA-N (6R)-3-(carbamoyloxymethyl)-7-[[2-(2-formamido-1,3-thiazol-4-yl)-2-oxoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C(N)(=O)OCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1)NC=O)=O)=O IFXAOAVRCWYUQA-RKSKCOGQSA-N 0.000 claims 1
- GOMDONMCEIHIQG-AZMWARKLSA-N (6R)-7-[[2-(2-formamido-1,3-thiazol-4-yl)-2-oxoacetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1N=NN=C1SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1)NC=O)=O)=O GOMDONMCEIHIQG-AZMWARKLSA-N 0.000 claims 1
- CHQCGSAHLGCBJC-AZMWARKLSA-N (6R)-7-[[2-(2-formamido-1,3-thiazol-4-yl)-2-oxoacetyl]amino]-8-oxo-3-(1,3,4-thiadiazol-2-ylsulfanylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1C(=NN=C1)SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1NC(SC=1)=NC=O)=O)=O CHQCGSAHLGCBJC-AZMWARKLSA-N 0.000 claims 1
- SQHLYGBEOIBDPH-AZMWARKLSA-N (6R)-7-[[2-(2-formamido-1,3-thiazol-5-yl)-2-oxoacetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1N=NN=C1SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C1=CN=C(S1)NC=O)=O)=O SQHLYGBEOIBDPH-AZMWARKLSA-N 0.000 claims 1
- KMOVJBTZADCXQE-URRWNQLISA-N (6R)-7-[[2-(5-chloro-2-formamido-1,3-thiazol-4-yl)-2-oxoacetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1N=NN=C1SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1Cl)NC=O)=O)=O KMOVJBTZADCXQE-URRWNQLISA-N 0.000 claims 1
- ZFRPZRJGEGWTGM-RGUGMKFQSA-N (6R)-7-[[2-[2-(2-methylbutan-2-yloxycarbonylamino)-1,3-thiazol-4-yl]-2-oxoacetyl]amino]-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CC1=NN=C(S1)SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1NC(SC=1)=NC(=O)OC(C)(C)CC)=O)=O ZFRPZRJGEGWTGM-RGUGMKFQSA-N 0.000 claims 1
- OIEVMRYSLOEZPD-WVQRXBFSSA-N (6R)-7-[[2-[2-(2-methylbutan-2-yloxycarbonylamino)-1,3-thiazol-4-yl]-2-oxoacetyl]amino]-8-oxo-3-(1,3,4-thiadiazol-2-ylsulfanylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1C(=NN=C1)SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1)NC(=O)OC(C)(C)CC)=O)=O OIEVMRYSLOEZPD-WVQRXBFSSA-N 0.000 claims 1
- WPLHECOSCKGREN-AZMWARKLSA-N (6R)-7-[[2-[2-(methylcarbamothioylamino)-1,3-thiazol-4-yl]-2-oxoacetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1N=NN=C1SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1)NC(NC)=S)=O)=O WPLHECOSCKGREN-AZMWARKLSA-N 0.000 claims 1
- ISERRHHJOIKCIH-RGUGMKFQSA-N (6R)-7-[[2-[2-[methyl(2-methylbutan-2-yloxycarbonyl)amino]-1,3-thiazol-4-yl]-2-oxoacetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1N=NN=C1SCC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=O)C=1N=C(SC=1)N(C(=O)OC(C)(C)CC)C)=O)=O ISERRHHJOIKCIH-RGUGMKFQSA-N 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 28
- 125000002947 alkylene group Chemical group 0.000 abstract description 14
- 125000001424 substituent group Chemical group 0.000 abstract description 7
- 230000000845 anti-microbial effect Effects 0.000 abstract description 2
- 244000000010 microbial pathogen Species 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 270
- 239000000203 mixture Substances 0.000 description 194
- 241000786363 Rhampholeon spectrum Species 0.000 description 138
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 113
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 110
- 238000006243 chemical reaction Methods 0.000 description 104
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 87
- 239000002253 acid Substances 0.000 description 86
- 239000010410 layer Substances 0.000 description 78
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 73
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 70
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- 239000000243 solution Substances 0.000 description 57
- 239000007864 aqueous solution Substances 0.000 description 55
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
- 238000003756 stirring Methods 0.000 description 44
- 235000011167 hydrochloric acid Nutrition 0.000 description 43
- 229960000443 hydrochloric acid Drugs 0.000 description 43
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- 239000002904 solvent Substances 0.000 description 39
- 238000001816 cooling Methods 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 36
- 239000000843 powder Substances 0.000 description 33
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 31
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 31
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
- 229940022663 acetate Drugs 0.000 description 26
- 238000001914 filtration Methods 0.000 description 26
- 150000002500 ions Chemical class 0.000 description 26
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 24
- 235000011054 acetic acid Nutrition 0.000 description 23
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 22
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
- 235000017557 sodium bicarbonate Nutrition 0.000 description 20
- 239000000284 extract Substances 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 230000009467 reduction Effects 0.000 description 18
- 238000006722 reduction reaction Methods 0.000 description 18
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
- 125000002252 acyl group Chemical group 0.000 description 17
- 230000007062 hydrolysis Effects 0.000 description 17
- 238000006460 hydrolysis reaction Methods 0.000 description 17
- 230000002829 reductive effect Effects 0.000 description 17
- 239000007858 starting material Substances 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 14
- 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 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- 125000003368 amide group Chemical group 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- 229910052708 sodium Inorganic materials 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 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 11
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 235000019253 formic acid Nutrition 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 10
- 229910052783 alkali metal Inorganic materials 0.000 description 10
- 229910052751 metal Inorganic materials 0.000 description 10
- 239000002184 metal Substances 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- 239000003223 protective agent Substances 0.000 description 10
- 229910000033 sodium borohydride Inorganic materials 0.000 description 10
- 239000012279 sodium borohydride Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 description 9
- 230000002411 adverse Effects 0.000 description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 7
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 7
- 230000008030 elimination Effects 0.000 description 7
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- XXBDWLFCJWSEKW-UHFFFAOYSA-N dimethylbenzylamine Chemical compound CN(C)CC1=CC=CC=C1 XXBDWLFCJWSEKW-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- XNVRKLCQBZTGNA-UHFFFAOYSA-N ethyl 2-(2-amino-1,3-thiazol-4-yl)-2-oxoacetate Chemical compound CCOC(=O)C(=O)C1=CSC(N)=N1 XNVRKLCQBZTGNA-UHFFFAOYSA-N 0.000 description 1
- UAGSMUJDTUOTFP-UHFFFAOYSA-N ethyl 2-(2-formamido-1,3-thiazol-4-yl)acetate Chemical compound CCOC(=O)CC1=CSC(NC=O)=N1 UAGSMUJDTUOTFP-UHFFFAOYSA-N 0.000 description 1
- VNTBUKWXDXMDSQ-UHFFFAOYSA-N ethyl 2-(2-oxo-3h-1,3-thiazol-4-yl)acetate Chemical compound CCOC(=O)CC1=CSC(=O)N1 VNTBUKWXDXMDSQ-UHFFFAOYSA-N 0.000 description 1
- VJNVIPBXFCGLJH-UHFFFAOYSA-N ethyl 2-[2-(2-methylbutan-2-yloxycarbonylamino)-1,3-thiazol-4-yl]-2-oxoacetate Chemical compound CCOC(=O)C(=O)C1=CSC(NC(=O)OC(C)(C)CC)=N1 VJNVIPBXFCGLJH-UHFFFAOYSA-N 0.000 description 1
- FNZGLUZYTZFOCC-UHFFFAOYSA-N ethyl 2-[2-(2-methylbutan-2-yloxycarbonylamino)-1,3-thiazol-4-yl]acetate Chemical compound CCOC(=O)CC1=CSC(=NC(=O)OC(C)(C)CC)N1 FNZGLUZYTZFOCC-UHFFFAOYSA-N 0.000 description 1
- UZGRKQXLTXIECD-UHFFFAOYSA-N ethyl 2-[2-(methanesulfonamido)-1,3-thiazol-4-yl]-2-(oxan-2-yloxy)acetate Chemical compound C=1SC(NS(C)(=O)=O)=NC=1C(C(=O)OCC)OC1CCCCO1 UZGRKQXLTXIECD-UHFFFAOYSA-N 0.000 description 1
- LRVKRWBZGGSQIP-UHFFFAOYSA-N ethyl 2-[2-(methanesulfonamido)-1,3-thiazol-4-yl]acetate Chemical compound CCOC(=O)CC1=CSC(NS(C)(=O)=O)=N1 LRVKRWBZGGSQIP-UHFFFAOYSA-N 0.000 description 1
- HTOLAYHMKSOVRH-UHFFFAOYSA-N ethyl 2-[2-[methyl(2-methylbutan-2-yloxycarbonyl)amino]-1,3-thiazol-4-yl]acetate Chemical compound CCOC(=O)CC1=CSC(N(C)C(=O)OC(C)(C)CC)=N1 HTOLAYHMKSOVRH-UHFFFAOYSA-N 0.000 description 1
- MDXRSSZZBWYKOU-UHFFFAOYSA-N ethyl 2-hydroxy-2-[2-(methanesulfonamido)-1,3-thiazol-4-yl]acetate Chemical compound CCOC(=O)C(O)C1=CSC(=NS(C)(=O)=O)N1 MDXRSSZZBWYKOU-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000005935 hexyloxycarbonyl group Chemical group 0.000 description 1
- ATADHKWKHYVBTJ-UHFFFAOYSA-N hydron;4-[1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol;chloride Chemical compound Cl.CNCC(O)C1=CC=C(O)C(O)=C1 ATADHKWKHYVBTJ-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 239000011133 lead Substances 0.000 description 1
- 150000002697 manganese compounds Chemical class 0.000 description 1
- UOGMEBQRZBEZQT-UHFFFAOYSA-L manganese(2+);diacetate Chemical compound [Mn+2].CC([O-])=O.CC([O-])=O UOGMEBQRZBEZQT-UHFFFAOYSA-L 0.000 description 1
- CESXSDZNZGSWSP-UHFFFAOYSA-L manganese(2+);diacetate;tetrahydrate Chemical compound O.O.O.O.[Mn+2].CC([O-])=O.CC([O-])=O CESXSDZNZGSWSP-UHFFFAOYSA-L 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- BJCROPYUAJFHNG-UHFFFAOYSA-N methyl 2-(2-formamido-1,3-thiazol-4-yl)-2-oxoacetate Chemical compound COC(=O)C(=O)C1=CSC(NC=O)=N1 BJCROPYUAJFHNG-UHFFFAOYSA-N 0.000 description 1
- KGXOXBXSSLBMHH-UHFFFAOYSA-N methyl 2-(2-formamido-1,3-thiazol-4-yl)acetate Chemical compound COC(=O)CC1=CSC(=NC=O)N1 KGXOXBXSSLBMHH-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- VMESOKCXSYNAKD-UHFFFAOYSA-N n,n-dimethylhydroxylamine Chemical compound CN(C)O VMESOKCXSYNAKD-UHFFFAOYSA-N 0.000 description 1
- JVHPKYBRJQNPAT-UHFFFAOYSA-N n-cyclohexyl-2,2-diphenylethenimine Chemical compound C1CCCCC1N=C=C(C=1C=CC=CC=1)C1=CC=CC=C1 JVHPKYBRJQNPAT-UHFFFAOYSA-N 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910000480 nickel oxide Inorganic materials 0.000 description 1
- KPADFPAILITQBG-UHFFFAOYSA-N non-4-ene Chemical compound CCCCC=CCCC KPADFPAILITQBG-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 1
- 125000003431 oxalo group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- GNRSAWUEBMWBQH-UHFFFAOYSA-N oxonickel Chemical compound [Ni]=O GNRSAWUEBMWBQH-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910003445 palladium oxide Inorganic materials 0.000 description 1
- JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 235000014786 phosphorus Nutrition 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- KPBSJEBFALFJTO-UHFFFAOYSA-N propane-1-sulfonyl chloride Chemical compound CCCS(Cl)(=O)=O KPBSJEBFALFJTO-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 238000006894 reductive elimination reaction Methods 0.000 description 1
- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- UIIMBOGNXHQVGW-DYCDLGHISA-M sodium deuterio carbonate Chemical compound C([O-])(O[2H])=O.[Na+] UIIMBOGNXHQVGW-DYCDLGHISA-M 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 125000005934 tert-pentyloxycarbonyl group Chemical group 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- QXJQHYBHAIHNGG-UHFFFAOYSA-N trimethylolethane Chemical compound OCC(C)(CO)CO QXJQHYBHAIHNGG-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 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
- 239000001974 tryptic soy broth Substances 0.000 description 1
- 108010050327 trypticase-soy broth Proteins 0.000 description 1
- 239000012000 urushibara nickel Substances 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—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, cefaclor, or cephalexine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- C07D277/32—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 hetero atoms or with 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
- C07D277/34—Oxygen atoms
-
- 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
- C07D277/32—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 hetero atoms or with 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
- C07D277/38—Nitrogen atoms
- C07D277/40—Unsubstituted amino or imino radicals
-
- 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
- C07D277/32—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 hetero atoms or with 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
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
-
- 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
- C07D277/32—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 hetero atoms or with 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
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/48—Acylated amino or imino radicals by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof, e.g. carbonylguanidines
-
- 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
- C07D277/32—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 hetero atoms or with 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
- C07D277/38—Nitrogen atoms
- C07D277/50—Nitrogen atoms bound to hetero atoms
- C07D277/52—Nitrogen atoms bound to hetero atoms to sulfur atoms, e.g. sulfonamides
-
- 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)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000477197A CA1209577A (en) | 1976-03-09 | 1985-03-21 | 3,7-disubstituted-3-cephem-4-carboxylic acid compounds and processes for preparation thereof |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9425/76A GB1575803A (en) | 1976-03-09 | 1976-03-09 | 3,7 disubstituted 3 cephem 4 carboxylic acid compounds andprocesses for the preparation thereof |
| GB9425/76 | 1976-03-09 | ||
| GB41145/76 | 1976-10-04 | ||
| GB4114576 | 1976-10-04 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000477197A Division CA1209577A (en) | 1976-03-09 | 1985-03-21 | 3,7-disubstituted-3-cephem-4-carboxylic acid compounds and processes for preparation thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1218054A true CA1218054A (en) | 1987-02-17 |
Family
ID=26242927
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000273202A Expired CA1218054A (en) | 1976-03-09 | 1977-03-04 | 3,7-disubstituted-3-cephem-4-carboxylic acid compounds and processes for preparation thereof |
Country Status (10)
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL69246A (en) * | 1982-08-07 | 1986-07-31 | Tanabe Seiyaku Co | 7-((2-aminothiazolyl-2-pyrrolidonyl or(piperidonyl)-oxyimino)acetamido)cephem carboxylic acid derivatives,their preparation and pharmaceutical compositions containing them |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4093803A (en) * | 1971-05-14 | 1978-06-06 | Glaxo Laboratories Limited | 7β-[2-Etherified oximino-2-(thienyl-, furyl- or pyridylacetamido)] cephalosporins |
| GB1399086A (en) * | 1971-05-14 | 1975-06-25 | Glaxo Lab Ltd | Cephalosporin compounds |
| SE417968B (sv) * | 1972-10-20 | 1981-04-27 | Fujisawa Pharmaceutical Co | Forfarande for framstellning av penamderivat |
| US4113940A (en) * | 1973-03-15 | 1978-09-12 | Fujisawa Pharmaceutical Co., Ltd. | 7-amino 2-lower alkyl-2 or 3-cephem-4-carboxylic acid derivatives and processes for preparation thereof |
| JPS5119765A (en) * | 1974-08-09 | 1976-02-17 | Takeda Chemical Industries Ltd | Aminochiazoorujudotaino seizoho |
| 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 |
| US4298606A (en) * | 1974-12-19 | 1981-11-03 | Takeda Chemical Industries, Ltd. | Thiazolylacetamido compounds |
| GR63088B (en) * | 1976-04-14 | 1979-08-09 | Takeda Chemical Industries Ltd | Preparation process of novel cephalosporins |
-
1977
- 1977-03-01 IE IE439/77A patent/IE44888B1/en not_active IP Right Cessation
- 1977-03-04 CA CA000273202A patent/CA1218054A/en not_active Expired
- 1977-03-07 SE SE7702547A patent/SE437832B/xx not_active IP Right Cessation
- 1977-03-07 HU HU77FU363A patent/HU176455B/hu unknown
- 1977-03-07 HU HU77FU349A patent/HU179016B/hu not_active IP Right Cessation
- 1977-03-07 AR AR266766A patent/AR218241A1/es active
- 1977-03-07 MX MX775517U patent/MX4658E/es unknown
- 1977-03-08 ES ES456625A patent/ES456625A1/es not_active Expired
- 1977-03-08 DK DK101477A patent/DK168863B1/da not_active IP Right Cessation
- 1977-03-09 DE DE19772760288 patent/DE2760288A1/de active Pending
-
1978
- 1978-03-07 ES ES467635A patent/ES467635A1/es not_active Expired
- 1978-03-27 AR AR271539A patent/AR222010A1/es active
- 1978-12-16 ES ES476075A patent/ES476075A1/es not_active Expired
- 1978-12-16 ES ES476076A patent/ES476076A1/es not_active Expired
- 1978-12-16 ES ES476077A patent/ES476077A1/es not_active Expired
-
1983
- 1983-04-12 SE SE8302027A patent/SE454988B/sv not_active IP Right Cessation
-
1984
- 1984-01-18 US US06/571,700 patent/US4560765A/en not_active Expired - Lifetime
-
1991
- 1991-07-25 DK DK911396A patent/DK139691D0/da not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SE437832B (sv) | 1985-03-18 |
| DK139691A (da) | 1991-07-25 |
| DK168863B1 (da) | 1994-06-27 |
| DE2760288A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1985-05-09 |
| IE44888L (en) | 1977-09-09 |
| SE8302027D0 (sv) | 1983-04-12 |
| DK139691D0 (da) | 1991-07-25 |
| MX4658E (es) | 1982-07-19 |
| AR218241A1 (es) | 1980-05-30 |
| HU179016B (en) | 1982-08-28 |
| US4560765A (en) | 1985-12-24 |
| IE44888B1 (en) | 1982-05-05 |
| HU176455B (en) | 1981-03-28 |
| SE454988B (sv) | 1988-06-13 |
| ES476075A1 (es) | 1979-05-16 |
| ES476076A1 (es) | 1979-05-16 |
| SE8302027L (sv) | 1983-04-12 |
| ES476077A1 (es) | 1979-05-16 |
| ES467635A1 (es) | 1979-09-01 |
| DK101477A (da) | 1977-09-10 |
| ES456625A1 (es) | 1978-07-16 |
| SE7702547L (sv) | 1977-09-10 |
| AR222010A1 (es) | 1981-04-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |