SK5982003A3 - 1-Methylcarbapenem derivatives - Google Patents
1-Methylcarbapenem derivatives Download PDFInfo
- Publication number
- SK5982003A3 SK5982003A3 SK598-2003A SK5982003A SK5982003A3 SK 5982003 A3 SK5982003 A3 SK 5982003A3 SK 5982003 A SK5982003 A SK 5982003A SK 5982003 A3 SK5982003 A3 SK 5982003A3
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- azetidin
- thio
- hydroxyethyl
- carboxylic acid
- Prior art date
Links
- YKMONJZIUAOVEM-GDVGLLTNSA-N (5S)-4-methyl-1-azabicyclo[3.2.0]hept-2-en-7-one Chemical class CC1C=CN2[C@H]1CC2=O YKMONJZIUAOVEM-GDVGLLTNSA-N 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 345
- 150000003839 salts Chemical class 0.000 claims abstract description 67
- 150000002148 esters Chemical class 0.000 claims abstract description 61
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 26
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 22
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 12
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 11
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 6
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 4
- 239000004480 active ingredient Substances 0.000 claims abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 5
- -1 1-methylcarbapenem compound Chemical class 0.000 claims description 355
- 239000000203 mixture Substances 0.000 claims description 223
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 165
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 139
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 86
- 229910052739 hydrogen Inorganic materials 0.000 claims description 77
- 125000001424 substituent group Chemical group 0.000 claims description 69
- 239000001257 hydrogen Substances 0.000 claims description 44
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 38
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 125000003277 amino group Chemical group 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
- 229910052760 oxygen Chemical group 0.000 claims description 19
- 239000001301 oxygen Chemical group 0.000 claims description 19
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 239000000460 chlorine Substances 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 239000011593 sulfur Substances 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 8
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 8
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- 125000002393 azetidinyl group Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- QQVUUJNSDZWJLM-KAILVDNBSA-N (4r,5s,6s)-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-3-[1-[4-[[(3r)-pyrrolidin-3-yl]carbamoyl]-1,3-thiazol-2-yl]azetidin-3-yl]sulfanyl-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)SC(C1)CN1C(SC=1)=NC=1C(=O)N[C@@H]1CCNC1 QQVUUJNSDZWJLM-KAILVDNBSA-N 0.000 claims description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical group O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 3
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims 2
- KJTDZYVBJUOGJB-GAJNKVMBSA-N (4r,5s,6s)-3-[1-[4-(aminomethyl)-1,3-thiazol-2-yl]azetidin-3-yl]sulfanyl-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)SC(C1)CN1C1=NC(CN)=CS1 KJTDZYVBJUOGJB-GAJNKVMBSA-N 0.000 claims 1
- QBWNOZDSADJMFC-CZPYZCIJSA-N (4r,5s,6s)-3-[1-[4-[2-aminoethyl(propan-2-yl)carbamoyl]-1,3-thiazol-2-yl]azetidin-3-yl]sulfanyl-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound NCCN(C(C)C)C(=O)C1=CSC(N2CC(C2)SC=2[C@@H]([C@H]3N(C([C@@H]3[C@@H](C)O)=O)C=2C(O)=O)C)=N1 QBWNOZDSADJMFC-CZPYZCIJSA-N 0.000 claims 1
- MLTKNTMEXMZFQB-HOJOPBEUSA-N (4r,5s,6s)-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-3-[1-[4-(piperidin-4-ylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl]sulfanyl-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)SC(C1)CN1C(SC=1)=NC=1C(=O)NC1CCNCC1 MLTKNTMEXMZFQB-HOJOPBEUSA-N 0.000 claims 1
- QQVUUJNSDZWJLM-IUPFNGILSA-N (4r,5s,6s)-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-3-[1-[4-[[(3s)-pyrrolidin-3-yl]carbamoyl]-1,3-thiazol-2-yl]azetidin-3-yl]sulfanyl-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)SC(C1)CN1C(SC=1)=NC=1C(=O)N[C@H]1CCNC1 QQVUUJNSDZWJLM-IUPFNGILSA-N 0.000 claims 1
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 114
- 125000002252 acyl group Chemical group 0.000 abstract description 9
- 239000003242 anti bacterial agent Substances 0.000 abstract description 6
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 5
- 241001465754 Metazoa Species 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 456
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 444
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 280
- 238000006243 chemical reaction Methods 0.000 description 200
- 239000012153 distilled water Substances 0.000 description 184
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 178
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 177
- 239000000243 solution Substances 0.000 description 172
- 239000002904 solvent Substances 0.000 description 161
- 239000011541 reaction mixture Substances 0.000 description 158
- 235000019439 ethyl acetate Nutrition 0.000 description 152
- 229940093499 ethyl acetate Drugs 0.000 description 152
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 139
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 106
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- 229920006395 saturated elastomer Polymers 0.000 description 97
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 93
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 89
- 235000017557 sodium bicarbonate Nutrition 0.000 description 89
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 82
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 81
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 80
- 238000001819 mass spectrum Methods 0.000 description 68
- 230000002829 reductive effect Effects 0.000 description 68
- 238000005160 1H NMR spectroscopy Methods 0.000 description 61
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 61
- 239000010410 layer Substances 0.000 description 61
- 239000012299 nitrogen atmosphere Substances 0.000 description 58
- 239000003480 eluent Substances 0.000 description 57
- 239000007787 solid Substances 0.000 description 57
- 238000004587 chromatography analysis Methods 0.000 description 53
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 52
- 125000006239 protecting group Chemical group 0.000 description 49
- 159000000000 sodium salts Chemical class 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 39
- 239000011780 sodium chloride Substances 0.000 description 39
- 239000003795 chemical substances by application Substances 0.000 description 38
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 36
- 239000011734 sodium Substances 0.000 description 36
- 239000007858 starting material Substances 0.000 description 35
- 239000003960 organic solvent Substances 0.000 description 33
- 230000035484 reaction time Effects 0.000 description 33
- 238000001953 recrystallisation Methods 0.000 description 33
- 238000007792 addition Methods 0.000 description 32
- 239000000706 filtrate Substances 0.000 description 31
- 238000001556 precipitation Methods 0.000 description 31
- YFHNDHXQDJQEEE-UHFFFAOYSA-N acetic acid;hydrazine Chemical compound NN.CC(O)=O YFHNDHXQDJQEEE-UHFFFAOYSA-N 0.000 description 30
- 239000002585 base Substances 0.000 description 28
- 150000002170 ethers Chemical class 0.000 description 28
- 238000005406 washing Methods 0.000 description 28
- 230000002411 adverse Effects 0.000 description 27
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 27
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 26
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 25
- DMKZERWLEGTECU-UEUXDIAVSA-N (4-nitrophenyl)methyl (4R,5S,6S)-3-diphenylphosphoryloxy-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C1(=CC=CC=C1)P(=O)(C1=CC=CC=C1)OC=1[C@@H]([C@@H]2N(C=1C(=O)OCC1=CC=C(C=C1)[N+](=O)[O-])C([C@@H]2[C@@H](C)O)=O)C DMKZERWLEGTECU-UEUXDIAVSA-N 0.000 description 24
- 150000008282 halocarbons Chemical class 0.000 description 24
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 24
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 24
- 238000010898 silica gel chromatography Methods 0.000 description 23
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
- 150000001408 amides Chemical class 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 18
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 17
- 239000002253 acid Substances 0.000 description 17
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 235000011054 acetic acid Nutrition 0.000 description 15
- 230000003472 neutralizing effect Effects 0.000 description 15
- 229910052708 sodium Inorganic materials 0.000 description 15
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- 150000001298 alcohols Chemical class 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 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
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 13
- 150000007530 organic bases Chemical class 0.000 description 13
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
- 229910052783 alkali metal Inorganic materials 0.000 description 10
- 230000003197 catalytic effect Effects 0.000 description 10
- 239000003638 chemical reducing agent Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 150000002825 nitriles Chemical class 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 7
- QLSYIEGOUWSMMQ-UHFFFAOYSA-N acetonitrile;ethyl acetate Chemical compound CC#N.CC#N.CCOC(C)=O QLSYIEGOUWSMMQ-UHFFFAOYSA-N 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 150000007529 inorganic bases Chemical class 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 235000011181 potassium carbonates Nutrition 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 230000008030 elimination Effects 0.000 description 6
- 238000003379 elimination reaction Methods 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
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- 239000012177 spermaceti Substances 0.000 description 1
- 229940084106 spermaceti Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 150000003566 thiocarboxylic acids Chemical class 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
- C07D477/10—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D477/12—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6
- C07D477/16—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6 with hetero atoms or carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 3
- C07D477/20—Sulfur atoms
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000350063 | 2000-11-16 | ||
PCT/JP2001/009960 WO2002040483A1 (fr) | 2000-11-16 | 2001-11-14 | Dérivés 1-méthylcarbapenem |
Publications (1)
Publication Number | Publication Date |
---|---|
SK5982003A3 true SK5982003A3 (en) | 2004-05-04 |
Family
ID=18823361
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK598-2003A SK5982003A3 (en) | 2000-11-16 | 2001-11-14 | 1-Methylcarbapenem derivatives |
Country Status (24)
Country | Link |
---|---|
US (1) | US7001897B2 (de) |
EP (1) | EP1340757B1 (de) |
KR (1) | KR100832287B1 (de) |
CN (1) | CN1289498C (de) |
AT (1) | ATE342266T1 (de) |
AU (2) | AU1521202A (de) |
BR (1) | BR0115454A (de) |
CA (1) | CA2429346A1 (de) |
CZ (1) | CZ300137B6 (de) |
DE (1) | DE60123827T2 (de) |
DK (1) | DK1340757T3 (de) |
ES (1) | ES2273902T3 (de) |
HU (1) | HUP0303204A3 (de) |
IL (1) | IL155931A0 (de) |
MX (1) | MXPA03004372A (de) |
NO (1) | NO20032198L (de) |
NZ (1) | NZ525934A (de) |
PL (1) | PL362132A1 (de) |
PT (1) | PT1340757E (de) |
RU (1) | RU2247725C2 (de) |
SK (1) | SK5982003A3 (de) |
TW (1) | TWI242013B (de) |
WO (1) | WO2002040483A1 (de) |
ZA (1) | ZA200303796B (de) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BR0211291A (pt) * | 2001-07-18 | 2004-08-03 | Mitsui Chemicals Inc | Derivados de diamina, processo para produção dos derivados de diamina e fungicidas contendo os derivados de diamina como ingrediente ativo |
KR100451670B1 (ko) * | 2001-09-14 | 2004-10-08 | 한국화학연구원 | 내성균에 대해 항생작용을 갖는 카바페넴 유도체 및 이의제조방법 |
KR100599876B1 (ko) * | 2004-08-31 | 2006-07-13 | 한국화학연구원 | 2-아릴메틸아제티딘 카바페넴 유도체 및 그의 제조방법 |
EP1637529A1 (de) * | 2004-09-20 | 2006-03-22 | 4Sc Ag | Neue Piperidin-4-yl-Thiazol-Carboxamid-Analog als Inhibitoren für die Vermehrung von T-Zellen und ihre Verwendung |
US7601745B2 (en) * | 2004-09-27 | 2009-10-13 | 4Sc Ag | Heterocyclic NF-kB inhibitors |
EP2009005A4 (de) | 2006-04-19 | 2010-06-02 | Astellas Pharma Inc | Azolcarbonsäureamidderivat |
CN101328179B (zh) * | 2007-06-15 | 2011-01-12 | 山东轩竹医药科技有限公司 | 含有氧代氮杂环的巯基吡咯烷培南衍生物 |
SI2206707T1 (sl) | 2007-10-24 | 2014-11-28 | Astellas Pharma Inc. | Azolkarboksamidna spojina ali njena sol |
ES2533826T3 (es) | 2008-01-18 | 2015-04-15 | Merck Sharp & Dohme Corp. | Inhibidores de beta-lactamasa |
US9409895B2 (en) | 2012-12-19 | 2016-08-09 | Novartis Ag | Autotaxin inhibitors |
WO2014097151A2 (en) | 2012-12-19 | 2014-06-26 | Novartis Ag | Autotaxin inhibitors |
AU2022300325A1 (en) * | 2021-06-23 | 2023-11-02 | F. Hoffmann-La Roche Ag | Process for the preparation of nlrp3 inhibitors |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3784147T2 (de) * | 1986-11-24 | 1993-06-03 | Fujisawa Pharmaceutical Co | 3-pyrrolidinylthio-1-azabicyclo(3.2.0)hept-2-en-2-carbonsaeure-derivate. |
GB9210096D0 (en) * | 1992-05-11 | 1992-06-24 | Fujisawa Pharmaceutical Co | 1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid derivatives and their preparation |
AU682510B2 (en) * | 1993-07-01 | 1997-10-09 | Pfizer Japan Inc. | 2-(1-(1,3-thiazolin-2-yl)azetidin-3-yl)thio-carbapenem derivatives |
DE4423612A1 (de) | 1994-07-06 | 1996-01-11 | Basf Ag | 2-[(Dihydro)pyrazolyl-3'-oxymethylen]-anilide, Verfahren zu ihrer Herstelung und ihre Verwendung |
TW445265B (en) * | 1996-11-25 | 2001-07-11 | Meiji Seika Kaisha | Carbapenem derivatives and antimicrobial agents |
TW200403244A (en) * | 2002-05-14 | 2004-03-01 | Sankyo Co | 1β-Methylcarbapenem derivatives for oral use |
JP2004043438A (ja) * | 2002-05-15 | 2004-02-12 | Sankyo Co Ltd | 1−メチルカルバペネム誘導体を含有する医薬 |
-
2001
- 2001-11-14 MX MXPA03004372A patent/MXPA03004372A/es active IP Right Grant
- 2001-11-14 SK SK598-2003A patent/SK5982003A3/sk unknown
- 2001-11-14 ES ES01983800T patent/ES2273902T3/es not_active Expired - Lifetime
- 2001-11-14 IL IL15593101A patent/IL155931A0/xx unknown
- 2001-11-14 AU AU1521202A patent/AU1521202A/xx active Pending
- 2001-11-14 CN CNB018220703A patent/CN1289498C/zh not_active Expired - Fee Related
- 2001-11-14 NZ NZ525934A patent/NZ525934A/en unknown
- 2001-11-14 AT AT01983800T patent/ATE342266T1/de not_active IP Right Cessation
- 2001-11-14 PL PL01362132A patent/PL362132A1/xx not_active Application Discontinuation
- 2001-11-14 EP EP01983800A patent/EP1340757B1/de not_active Expired - Lifetime
- 2001-11-14 CZ CZ20031325A patent/CZ300137B6/cs not_active IP Right Cessation
- 2001-11-14 KR KR1020037006664A patent/KR100832287B1/ko not_active IP Right Cessation
- 2001-11-14 PT PT01983800T patent/PT1340757E/pt unknown
- 2001-11-14 DE DE60123827T patent/DE60123827T2/de not_active Expired - Fee Related
- 2001-11-14 AU AU2002215212A patent/AU2002215212B2/en not_active Ceased
- 2001-11-14 CA CA002429346A patent/CA2429346A1/en not_active Abandoned
- 2001-11-14 BR BR0115454-0A patent/BR0115454A/pt not_active IP Right Cessation
- 2001-11-14 HU HU0303204A patent/HUP0303204A3/hu unknown
- 2001-11-14 WO PCT/JP2001/009960 patent/WO2002040483A1/ja active IP Right Grant
- 2001-11-14 RU RU2003114408/04A patent/RU2247725C2/ru not_active IP Right Cessation
- 2001-11-14 DK DK01983800T patent/DK1340757T3/da active
- 2001-11-15 TW TW090128317A patent/TWI242013B/zh not_active IP Right Cessation
-
2003
- 2003-05-15 NO NO20032198A patent/NO20032198L/no not_active Application Discontinuation
- 2003-05-15 ZA ZA200303796A patent/ZA200303796B/en unknown
- 2003-05-15 US US10/439,198 patent/US7001897B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
EP1340757A4 (de) | 2005-01-26 |
CZ20031325A3 (cs) | 2003-10-15 |
NO20032198D0 (no) | 2003-05-15 |
NO20032198L (no) | 2003-07-16 |
TWI242013B (en) | 2005-10-21 |
NZ525934A (en) | 2004-09-24 |
US7001897B2 (en) | 2006-02-21 |
DE60123827T2 (de) | 2007-05-31 |
CN1289498C (zh) | 2006-12-13 |
CZ300137B6 (cs) | 2009-02-18 |
WO2002040483A1 (fr) | 2002-05-23 |
US20040014962A1 (en) | 2004-01-22 |
RU2247725C2 (ru) | 2005-03-10 |
ATE342266T1 (de) | 2006-11-15 |
HUP0303204A3 (en) | 2010-04-28 |
CA2429346A1 (en) | 2002-05-23 |
ES2273902T3 (es) | 2007-05-16 |
ZA200303796B (en) | 2004-08-16 |
KR20030048151A (ko) | 2003-06-18 |
KR100832287B1 (ko) | 2008-05-26 |
PT1340757E (pt) | 2006-12-29 |
EP1340757A1 (de) | 2003-09-03 |
DK1340757T3 (da) | 2007-02-12 |
HUP0303204A2 (hu) | 2003-12-29 |
IL155931A0 (en) | 2003-12-23 |
DE60123827D1 (en) | 2006-11-23 |
BR0115454A (pt) | 2003-09-23 |
MXPA03004372A (es) | 2003-08-19 |
CN1486317A (zh) | 2004-03-31 |
AU1521202A (en) | 2002-05-27 |
EP1340757B1 (de) | 2006-10-11 |
AU2002215212B2 (en) | 2004-10-14 |
PL362132A1 (en) | 2004-10-18 |
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FB9A | Suspension of patent application procedure |