SK5982003A3 - 1-Methylcarbapenem derivatives - Google Patents

1-Methylcarbapenem derivatives Download PDF

Info

Publication number: SK5982003A3
Authority: SK; Slovakia
Prior art keywords: group; azetidin; thio; hydroxyethyl; carboxylic acid
Prior art date: 2000-11-16

Application number

SK598-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Yoshiyuki Kobayashi

Tsuyoshi Shinozuka

Osamu Kanno

Original Assignee

Sankyo Co

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.)

2000-11-16

Filing date

2001-11-14

Publication date

2004-05-04

2001-11-14 Application filed by Sankyo Co filed Critical Sankyo Co

2004-05-04 Publication of SK5982003A3 publication Critical patent/SK5982003A3/sk

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
235000017550 sodium carbonate Nutrition 0.000 description 6
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
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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)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Communicable Diseases (AREA)
Pharmacology & Pharmacy (AREA)
Oncology (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)

SK598-2003A 2000-11-16 2001-11-14 1-Methylcarbapenem derivatives SK5982003A3 (en)

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 (zh)
EP (1)	EP1340757B1 (zh)
KR (1)	KR100832287B1 (zh)
CN (1)	CN1289498C (zh)
AT (1)	ATE342266T1 (zh)
AU (2)	AU2002215212B2 (zh)
BR (1)	BR0115454A (zh)
CA (1)	CA2429346A1 (zh)
CZ (1)	CZ300137B6 (zh)
DE (1)	DE60123827T2 (zh)
DK (1)	DK1340757T3 (zh)
ES (1)	ES2273902T3 (zh)
HU (1)	HUP0303204A3 (zh)
IL (1)	IL155931A0 (zh)
MX (1)	MXPA03004372A (zh)
NO (1)	NO20032198L (zh)
NZ (1)	NZ525934A (zh)
PL (1)	PL362132A1 (zh)
PT (1)	PT1340757E (zh)
RU (1)	RU2247725C2 (zh)
SK (1)	SK5982003A3 (zh)
TW (1)	TWI242013B (zh)
WO (1)	WO2002040483A1 (zh)
ZA (1)	ZA200303796B (zh)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1408027A4 (en) *	2001-07-18	2006-08-30	Mitsui Chemicals Inc	DIAMINE DERIVATIVE, PROCESS FOR PRODUCING DIAMINE DERIVATIVE, AND FUNGICIDE CONTAINING THE DIAMINE DERIVATIVE AS THE ACTIVE INGREDIENT
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 (en) *	2004-09-20	2006-03-22	4Sc Ag	Novel piperidin-4-yl-thiazole-carboxamide analogues as inhibitors of T-cell proliferation and uses thereof
US7601745B2 (en) *	2004-09-27	2009-10-13	4Sc Ag	Heterocyclic NF-kB inhibitors
KR20090004976A (ko)	2006-04-19	2009-01-12	아스테라스 세이야쿠 가부시키가이샤	아졸카르복사미드 유도체
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
MX2010004499A (es)	2007-10-24	2010-05-20	Astellas Pharma Inc	Compuesto de azolcarboxamida o sal de el.
PL2666774T3 (pl)	2008-01-18	2015-06-30	Merck Sharp & Dohme	Inhibitory beta-laktamazy
KR20150095888A (ko)	2012-12-19	2015-08-21	노파르티스 아게	오토탁신 억제제
US9409895B2 (en)	2012-12-19	2016-08-09	Novartis Ag	Autotaxin inhibitors
AR126215A1 (es) *	2021-06-23	2023-09-27	Hoffmann La Roche	Proceso novedoso

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0272455B1 (en) *	1986-11-24	1993-02-10	Fujisawa Pharmaceutical Co., Ltd.	3-Pyrrolidinylthio-1-azabicyclo [3.2.0] hept-2-ene-2-carboxylic acid compounds
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 CN CNB018220703A patent/CN1289498C/zh not_active Expired - Fee Related
- 2001-11-14 CA CA002429346A patent/CA2429346A1/en not_active Abandoned
- 2001-11-14 RU RU2003114408/04A patent/RU2247725C2/ru not_active IP Right Cessation
- 2001-11-14 BR BR0115454-0A patent/BR0115454A/pt not_active IP Right Cessation
- 2001-11-14 IL IL15593101A patent/IL155931A0/xx unknown
- 2001-11-14 MX MXPA03004372A patent/MXPA03004372A/es active IP Right Grant
- 2001-11-14 DE DE60123827T patent/DE60123827T2/de not_active Expired - Fee Related
- 2001-11-14 SK SK598-2003A patent/SK5982003A3/sk unknown
- 2001-11-14 WO PCT/JP2001/009960 patent/WO2002040483A1/ja active IP Right Grant
- 2001-11-14 HU HU0303204A patent/HUP0303204A3/hu unknown
- 2001-11-14 PT PT01983800T patent/PT1340757E/pt unknown
- 2001-11-14 EP EP01983800A patent/EP1340757B1/en not_active Expired - Lifetime
- 2001-11-14 KR KR1020037006664A patent/KR100832287B1/ko not_active IP Right Cessation
- 2001-11-14 DK DK01983800T patent/DK1340757T3/da active
- 2001-11-14 ES ES01983800T patent/ES2273902T3/es not_active Expired - Lifetime
- 2001-11-14 AU AU2002215212A patent/AU2002215212B2/en not_active Ceased
- 2001-11-14 AU AU1521202A patent/AU1521202A/xx active Pending
- 2001-11-14 CZ CZ20031325A patent/CZ300137B6/cs not_active IP Right Cessation
- 2001-11-14 NZ NZ525934A patent/NZ525934A/en unknown
- 2001-11-14 PL PL01362132A patent/PL362132A1/xx not_active Application Discontinuation
- 2001-11-14 AT AT01983800T patent/ATE342266T1/de not_active IP Right Cessation
- 2001-11-15 TW TW090128317A patent/TWI242013B/zh not_active IP Right Cessation
2003
- 2003-05-15 US US10/439,198 patent/US7001897B2/en not_active Expired - Fee Related
- 2003-05-15 NO NO20032198A patent/NO20032198L/no not_active Application Discontinuation
- 2003-05-15 ZA ZA200303796A patent/ZA200303796B/en unknown

Also Published As

Publication number	Publication date
DK1340757T3 (da)	2007-02-12
HUP0303204A2 (hu)	2003-12-29
AU1521202A (en)	2002-05-27
CA2429346A1 (en)	2002-05-23
EP1340757A1 (en)	2003-09-03
DE60123827T2 (de)	2007-05-31
BR0115454A (pt)	2003-09-23
US20040014962A1 (en)	2004-01-22
KR20030048151A (ko)	2003-06-18
CN1289498C (zh)	2006-12-13
MXPA03004372A (es)	2003-08-19
RU2247725C2 (ru)	2005-03-10
CN1486317A (zh)	2004-03-31
EP1340757B1 (en)	2006-10-11
HUP0303204A3 (en)	2010-04-28
PT1340757E (pt)	2006-12-29
NO20032198L (no)	2003-07-16
EP1340757A4 (en)	2005-01-26
IL155931A0 (en)	2003-12-23
KR100832287B1 (ko)	2008-05-26
NO20032198D0 (no)	2003-05-15
ATE342266T1 (de)	2006-11-15
AU2002215212B2 (en)	2004-10-14
NZ525934A (en)	2004-09-24
CZ20031325A3 (cs)	2003-10-15
US7001897B2 (en)	2006-02-21
TWI242013B (en)	2005-10-21
WO2002040483A1 (fr)	2002-05-23
ES2273902T3 (es)	2007-05-16
CZ300137B6 (cs)	2009-02-18
ZA200303796B (en)	2004-08-16
PL362132A1 (en)	2004-10-18
DE60123827D1 (en)	2006-11-23

Publication	Publication Date	Title
HU196800B (en)	1989-01-30	Process for producing carbepeneme derivatives and pharmaceutical compositions containing them as active component
JPH0853453A (ja)	1996-02-27	２−［１−（１，３−チアゾリン−２−イル）アゼチジン−３−イル］チオ−カルバペネム化合物
SK5982003A3 (en)	2004-05-04	1-Methylcarbapenem derivatives
JPH05339269A (ja)	1993-12-21	１−メチルカルバペネム誘導体
RU2097383C1 (ru)	1997-11-27	Производные карбапенема и способ их получения
CZ298246B6 (cs)	2007-08-01	Deriváty 1-methylkarbapenu, zpusob jejich prípravy a farmaceutické prostredky, které je obsahují
EP3430013B1 (en)	2023-11-15	Carbapenem compounds
HU191066B (en)	1987-01-28	Process for preparing carbapenem derivatives
RU2162088C2 (ru)	2001-01-20	1-метилкарбапенем или его фармакологически приемлемые соли, композиция, способ предупреждения или лечения бактериальных инфекций
JP3199300B2 (ja)	2001-08-13	１−メチルカルバペネム誘導体
JP2002212182A (ja)	2002-07-31	１−メチルカルバペネム誘導体
JP2004043438A (ja)	2004-02-12	１−メチルカルバペネム誘導体を含有する医薬
JPH1171277A (ja)	1999-03-16	１−メチルカルバペネム誘導体を含有する抗菌剤
WO2004067532A1 (ja)	2004-08-12	新規カルバペネム誘導体
HU213265B (en)	1997-04-28	Process for producing 4-(substituted alkyl)-carbapenem derivatives and pharmaceutical compositions containing the same
JPH10204086A (ja)	1998-08-04	１−メチルカルバペネム誘導体
JP2007291048A (ja)	2007-11-08	１β−メチルカルバペネム誘導体を含有する医薬
JPH09249668A (ja)	1997-09-22	カルバペネム化合物、その製造法および剤
JP2006151815A (ja)	2006-06-15	新規カルバペネム誘導体
JPH04321688A (ja)	1992-11-11	２−（置換ピロリジニルチオ）カルバペネム誘導体
WO1994005667A1 (en)	1994-03-17	Carbapenem derivatives and processes for preparing the same
WO2006049148A1 (ja)	2006-05-11	１β－メチルカルバペネム誘導体
JPH1081686A (ja)	1998-03-31	カルバペネム化合物、その製造法および剤
JP2006151970A (ja)	2006-06-15	１β−メチルカルバペネム誘導体
JPH04234886A (ja)	1992-08-24	１−アザビシクロ［３．２．０］ヘプト−２−エン−２−カルボン酸化合物

Legal Events

Date	Code	Title	Description
2011-07-06	FB9A	Suspension of patent application procedure