KR950005830A - β-락타마제 억제제로서의 2-β-알케닐 페남 유도체 - Google Patents
β-락타마제 억제제로서의 2-β-알케닐 페남 유도체 Download PDFInfo
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- KR950005830A KR950005830A KR1019940020869A KR19940020869A KR950005830A KR 950005830 A KR950005830 A KR 950005830A KR 1019940020869 A KR1019940020869 A KR 1019940020869A KR 19940020869 A KR19940020869 A KR 19940020869A KR 950005830 A KR950005830 A KR 950005830A
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- South Korea
- Prior art keywords
- methyl
- thia
- carboxylate
- aza
- bicyclo
- Prior art date
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- 239000003781 beta lactamase inhibitor Substances 0.000 title claims abstract 3
- 229940126813 beta-lactamase inhibitor Drugs 0.000 title claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims abstract 25
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 12
- 239000001257 hydrogen Substances 0.000 claims abstract 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract 11
- -1 benzyloxy, amino Chemical group 0.000 claims abstract 7
- 150000002431 hydrogen Chemical class 0.000 claims abstract 7
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract 5
- 150000003839 salts Chemical class 0.000 claims abstract 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 4
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract 4
- 239000003782 beta lactam antibiotic agent Substances 0.000 claims abstract 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract 4
- 150000002367 halogens Chemical class 0.000 claims abstract 4
- 229910052717 sulfur Inorganic materials 0.000 claims abstract 4
- 239000002132 β-lactam antibiotic Substances 0.000 claims abstract 4
- 229940124586 β-lactam antibiotics Drugs 0.000 claims abstract 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract 3
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract 3
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 3
- 238000001727 in vivo Methods 0.000 claims abstract 3
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 3
- 208000035143 Bacterial infection Diseases 0.000 claims abstract 2
- 125000000033 alkoxyamino group Chemical group 0.000 claims abstract 2
- 125000003118 aryl group Chemical group 0.000 claims abstract 2
- 125000001965 gamma-lactamyl group Chemical group 0.000 claims abstract 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract 2
- 239000003814 drug Substances 0.000 claims 6
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims 5
- 238000000034 method Methods 0.000 claims 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 230000002401 inhibitory effect Effects 0.000 claims 3
- 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 claims 2
- 239000013543 active substance Substances 0.000 claims 2
- VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 claims 2
- 229960004755 ceftriaxone Drugs 0.000 claims 2
- 229910052708 sodium Inorganic materials 0.000 claims 2
- 239000011734 sodium Substances 0.000 claims 2
- DRNHQKOSAXWVCX-LSTOSFGNSA-M sodium;(2s,3s,5r)-3-[(e)-2-cyanoethenyl]-3-methyl-4,4,7-trioxo-4$l^{6}-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [Na+].O=S1(=O)[C@@](C)(\C=C\C#N)[C@H](C([O-])=O)N2C(=O)C[C@H]21 DRNHQKOSAXWVCX-LSTOSFGNSA-M 0.000 claims 2
- JJCKSYDIUDHYKV-PPMOUGFISA-N (2S,3S,5R)-3-methyl-4,4,7-trioxo-3-[(E)-3-oxo-3-phenylmethoxyprop-1-enyl]-4lambda6-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound C(/[C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C(O)=O)(=O)=O)=C\C(=O)OCC1=CC=CC=C1 JJCKSYDIUDHYKV-PPMOUGFISA-N 0.000 claims 1
- NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 claims 1
- FASWFFAQTUBTSL-UHFFFAOYSA-N 3-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound S1C(=O)C(C(=O)O)N2CCC21 FASWFFAQTUBTSL-UHFFFAOYSA-N 0.000 claims 1
- 229930186147 Cephalosporin Natural products 0.000 claims 1
- 108090000204 Dipeptidase 1 Proteins 0.000 claims 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 claims 1
- 229930182555 Penicillin Natural products 0.000 claims 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims 1
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 claims 1
- 235000001484 Trigonella foenum graecum Nutrition 0.000 claims 1
- 244000250129 Trigonella foenum graecum Species 0.000 claims 1
- ZOCILGRDKSQJQM-RPMOKKKFSA-M [Na+].C(/[C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C([O-])=O)(=O)=O)=C\C(=O)OCC1=CC=CC=C1 Chemical compound [Na+].C(/[C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C([O-])=O)(=O)=O)=C\C(=O)OCC1=CC=CC=C1 ZOCILGRDKSQJQM-RPMOKKKFSA-M 0.000 claims 1
- HDSDLICLANUNBY-PNMNSLMXSA-M [Na+].O=S1(=O)[C@@](C)(\C=C/C(N)=O)[C@H](C([O-])=O)N2C(=O)C[C@H]21 Chemical compound [Na+].O=S1(=O)[C@@](C)(\C=C/C(N)=O)[C@H](C([O-])=O)N2C(=O)C[C@H]21 HDSDLICLANUNBY-PNMNSLMXSA-M 0.000 claims 1
- GSQXUHOIXPEZOL-RQLHMRLNSA-M [Na+].O=S1(=O)[C@](/C=C/C(=O)OCC)(C)[C@H](C([O-])=O)N2C(=O)C[C@H]21 Chemical compound [Na+].O=S1(=O)[C@](/C=C/C(=O)OCC)(C)[C@H](C([O-])=O)N2C(=O)C[C@H]21 GSQXUHOIXPEZOL-RQLHMRLNSA-M 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 229960003022 amoxicillin Drugs 0.000 claims 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims 1
- 229960000723 ampicillin Drugs 0.000 claims 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims 1
- 230000000845 anti-microbial effect Effects 0.000 claims 1
- XMQVYNAURODYCQ-SLFBBCNNSA-N apalcillin Chemical compound C1([C@@H](NC(=O)C=2C(=C3N=CC=CC3=NC=2)O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 XMQVYNAURODYCQ-SLFBBCNNSA-N 0.000 claims 1
- 229950001979 apalcillin Drugs 0.000 claims 1
- UZQCLWUMBJAMRY-SLYNCCJLSA-N benzhydryl (2S,3S,5R)-3-formyl-3-methyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound C(=O)[C@@]1([C@@H](N2C(C[C@H]2S1)=O)C(=O)OC(C1=CC=CC=C1)C1=CC=CC=C1)C UZQCLWUMBJAMRY-SLYNCCJLSA-N 0.000 claims 1
- FBMGFBJIQUKPAK-YYIOOZDNSA-N benzhydryl (2s,3s,5r)-3-[(e)-2-cyanoethenyl]-3-methyl-4,4,7-trioxo-4$l^{6}-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound O=C([C@H]1[C@@](S([C@H]2N1C(C2)=O)(=O)=O)(\C=C\C#N)C)OC(C=1C=CC=CC=1)C1=CC=CC=C1 FBMGFBJIQUKPAK-YYIOOZDNSA-N 0.000 claims 1
- OQJDOGSVJMFFFU-XTSCALQBSA-N benzhydryl (2s,3s,5r)-3-[(e)-3-amino-3-oxoprop-1-enyl]-3-methyl-4,4,7-trioxo-4$l^{6}-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound O=C([C@H]1[C@@](S([C@H]2N1C(C2)=O)(=O)=O)(\C=C\C(N)=O)C)OC(C=1C=CC=CC=1)C1=CC=CC=C1 OQJDOGSVJMFFFU-XTSCALQBSA-N 0.000 claims 1
- FBMGFBJIQUKPAK-FRBBGPADSA-N benzhydryl (2s,3s,5r)-3-[(z)-2-cyanoethenyl]-3-methyl-4,4,7-trioxo-4$l^{6}-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound O=C([C@H]1[C@@](S([C@H]2N1C(C2)=O)(=O)=O)(\C=C/C#N)C)OC(C=1C=CC=CC=1)C1=CC=CC=C1 FBMGFBJIQUKPAK-FRBBGPADSA-N 0.000 claims 1
- OQJDOGSVJMFFFU-FCDMQVLUSA-N benzhydryl (2s,3s,5r)-3-[(z)-3-amino-3-oxoprop-1-enyl]-3-methyl-4,4,7-trioxo-4$l^{6}-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound O=C([C@H]1[C@@](S([C@H]2N1C(C2)=O)(=O)=O)(\C=C/C(N)=O)C)OC(C=1C=CC=CC=1)C1=CC=CC=C1 OQJDOGSVJMFFFU-FCDMQVLUSA-N 0.000 claims 1
- LVSBBLBALRFSIS-ZCSKGCSWSA-N benzhydryl (2s,3s,5r)-3-methyl-7-oxo-3-[(e)-3-oxo-3-phenylmethoxyprop-1-enyl]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound O=C([C@@H]1N2C(=O)C[C@H]2S[C@@]1(C)\C=C\C(=O)OCC=1C=CC=CC=1)OC(C=1C=CC=CC=1)C1=CC=CC=C1 LVSBBLBALRFSIS-ZCSKGCSWSA-N 0.000 claims 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
- 102000006635 beta-lactamase Human genes 0.000 claims 1
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 claims 1
- 229960003669 carbenicillin Drugs 0.000 claims 1
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 claims 1
- 229960000603 cefalotin Drugs 0.000 claims 1
- 229960001139 cefazolin Drugs 0.000 claims 1
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 claims 1
- HVFLCNVBZFFHBT-ZKDACBOMSA-N cefepime Chemical compound S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1C[N+]1(C)CCCC1 HVFLCNVBZFFHBT-ZKDACBOMSA-N 0.000 claims 1
- 229960002100 cefepime Drugs 0.000 claims 1
- HJJDBAOLQAWBMH-YCRCPZNHSA-N cefmenoxime Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NN=NN1C HJJDBAOLQAWBMH-YCRCPZNHSA-N 0.000 claims 1
- 229960003791 cefmenoxime Drugs 0.000 claims 1
- 229940106164 cephalexin Drugs 0.000 claims 1
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 claims 1
- 229940124587 cephalosporin Drugs 0.000 claims 1
- 150000001780 cephalosporins Chemical class 0.000 claims 1
- VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical compound [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CC1=CC=CS1 VUFGUVLLDPOSBC-XRZFDKQNSA-M 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 claims 1
- 229960002182 imipenem Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 claims 1
- 229960002260 meropenem Drugs 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 229960003085 meticillin Drugs 0.000 claims 1
- 229960000198 mezlocillin Drugs 0.000 claims 1
- YPBATNHYBCGSSN-VWPFQQQWSA-N mezlocillin Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC=CC=1)C(=O)N1CCN(S(C)(=O)=O)C1=O YPBATNHYBCGSSN-VWPFQQQWSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 claims 1
- HHXMXAQDOUCLDN-RXMQYKEDSA-N penem Chemical compound S1C=CN2C(=O)C[C@H]21 HHXMXAQDOUCLDN-RXMQYKEDSA-N 0.000 claims 1
- 229940049954 penicillin Drugs 0.000 claims 1
- 229960002292 piperacillin Drugs 0.000 claims 1
- WCMIIGXFCMNQDS-IDYPWDAWSA-M piperacillin sodium Chemical compound [Na+].O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C([O-])=O)C(C)(C)S[C@@H]21 WCMIIGXFCMNQDS-IDYPWDAWSA-M 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 229960003672 propicillin Drugs 0.000 claims 1
- HOCWPKXKMNXINF-XQERAMJGSA-N propicillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C(CC)OC1=CC=CC=C1 HOCWPKXKMNXINF-XQERAMJGSA-N 0.000 claims 1
- DRNHQKOSAXWVCX-PNMNSLMXSA-M sodium;(2s,3s,5r)-3-[(z)-2-cyanoethenyl]-3-methyl-4,4,7-trioxo-4$l^{6}-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [Na+].O=S1(=O)[C@@](C)(\C=C/C#N)[C@H](C([O-])=O)N2C(=O)C[C@H]21 DRNHQKOSAXWVCX-PNMNSLMXSA-M 0.000 claims 1
- 229920002554 vinyl polymer Polymers 0.000 claims 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 claims 1
- 150000002959 penams Chemical class 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/86—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with only atoms other than nitrogen atoms directly attached in position 6 and 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Cephalosporin Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
본 발명은 페남 유도체, 특히 일반식(Ⅰ)의 2β-알케닐-페남 유도체 및 이들 화합물의 약제학적으로 허용되는 염에 관한 것이다.
상기식에서, R1및 R2중의 하나는 -COR4, -CN, -CH2R5, 할로겐, -CH=CHR6또는 Q를 나타내고, 나머지 하나는 수소 또는 저급 알킬을 나타내거나 R1과R2가 함께 γ-락탐 환을 나타내며, R3은 수소, 저급 알킬, 아릴-알킬, 알릴 또는 생체내에서 분해될 수 있는 잔기이고, R4는 수소, 저급 알킬, 저급 알콕시, 벤질옥시, 아미노, 저급 알킬아미노 또는 저급 알킬-저급 알콕아미노이며, R5는 하이드록시, -OCONHR7, -OCONH2또는 N,S 및/또는 O를 함유하고 질소원자를 통해 결합된 5- 또는 6-원 헤테로-방향족 환이고, R6은 -CN 또는 CHO이며; R7은 -OCONH2Cl이고, Q는 N,S 및/또는 O를 함유하는 5- 또는 6-원 헤테로-방향족 환이며, n은 0,1 또는 2이다.
이들 화합물은 우수한 β-락타마제 억제제이다. 당해 화합물은 임의로, β-락탐 항생물질과 함께 세균 감염의 예방 또는 치료에 사용될 수 있다.
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Claims (31)
- 일반식(Ⅰ)의 2β-알케닐-페남 유도체 및 이들 화합물의 약제학적으로 허용되는 염.상기식에서, R1및 R2중의 하나는 -COR4, -CN, -CH2R5, 할로겐, -CH=CHR6또는 Q를 나타내고, 나머지 하나는 수소 또는 저급 알킬을 나타내거나 R1과 R2가 함께 γ-락탐 환을 나타내며, R3은 수소, 저급 알킬, 아릴-알킬, 알릴 또는 생체내에서 분해될 수 있는 잔기이고, R4는 수소, 저급 알킬, 저급 알콕시, 벤질옥시, 아미노, 저급 알킬아미노 또는 저급 알킬-저급 알콕시아미노이며, R5는 하이드록시, -OCONHR7, -OCONH2N,S 및/또는 O를 함유하고 질소원자를 통해 결합된 5- 또는 6-원 헤테로-방향족 환이고, R6는 -CN 또는 CHO이며; R7은 -OCONH2Cl이고, Q는 N,S 및/또는 O를 함유하는 5- 또는 6-원 헤테로-방향족 환이며, n은 0,1 또는 2이다.
- 제 1항에 있어서, R1및 R2중의 하나는 -COR4, -CN 또는 -CH2R5이고 나머지 수소 또는 저급 알킬이며, R3은 수소, 저급 알킬, 아릴-알킬, 알릴 또는 생체내에서 분해될 수 있는 잔기이고, R4는 수소, 저급 알킬, 저급 알콕시, 벤질옥시, 아미노 또는 저급 알킬아미노이며, R5는 하이드록시 또는 -OCONH2이고, R6은 저급 알킬이며, n은 0,1 또는 2인 화합물.
- 제1항 또는 제2항에 있어서, R1이 -CN, 할로겐 또는 COR4이고, R2가 수소이며, R4가 메틸, 저급 알콕시, 벤질옥시 또는 아미노인 화합물.
- 제1항 내지 제3항 중의 어느 한 항에 있어서, n이 0또는 2인 화합물.
- 제1항 내지 제4항 중의 어느 한 항에 있어서, R3이 수소 또는 벤즈하이드릴인 화합물.
- 벤즈하이드릴 (E/Z)-(2S,3S,5R)-3-(2-시아노에테닐)-3-메틸-3-메틸-7-옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트.
- 벤즈하이드릴 (E)-(2S,3S,5R)-3-(2-시아노에테닐)-3-메틸-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트.
- 벤즈하이드릴 (Z)-(2S,3S,5R)-3-(2-시아노에테닐)-3-메틸-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트.
- 나트륨 (E)-(2S,3S,5R)-3-(2-시아노에테닐)-3-메틸-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트.
- 나트륨 (Z)-(2S,3S,5R)-3-(2-시아노에테닐)-3-메틸-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트.
- 나트륨 (E)-(2S,3S,5R)-3-(2-시아노에테닐)-3-메틸-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트.
- [나트륨 (E)-(2S,3S,5R)-3-(메틸-3-(3-옥소-부트-1-에닐)-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트.
- 벤즈하이드릴 (E/Z)-(2S,3S,5R)-3-(2-카바모일-비닐)-3-메틸-7-옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트, 벤즈하이드릴(E)-(2S,3S,5R)-3-(2-카바모일-비닐)-3-메틸-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트, 벤즈하이드릴 (Z)-(2S,3S,5R)-3-(2-카바모일-비닐)-3-메틸-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트, 나트륨 (E)-(2S,3S,5R)-3-(2-카바모닐-비닐)-3-메틸-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트, 나트륨 (Z)-(2S,3S,5R)-3-(2-카바모일-비닐)-3-메틸-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트, 벤즈하이드릴(E)-(2S,3S,5R)-3-(2-에톡시카보닐-비닐닐)-3-메틸-7-옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트, 벤즈하이드릴 (E)-(2S,3S,5R)-3-(2-에톡시카보닐-비닐)-3-메틸-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트, 나트륨 (E)-(2S,3S,5R)-3-(2-에톡시카보닐-비닐)-3-메틸-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트, 벤즈하이드릴(E)-(2S,3S,5R)-3-(2-벤질옥시카보닐-비닐)-3-메틸-7-옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트, 벤즈하이드릴 (E)-(2S,3S,5R)-3-(2-벤질옥시카보닐-비닐)-3-메틸-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트 또는 나트륨 (E)-(2S,3S,5R)-3-(2-벤질옥시카보닐-비닐)-3-메틸-4,4,7-트리옥소-4-티아-1-아자-비사이클로[3,2,0]헵탄-2-카복실레이트.
- 일반식(Ⅱ)의 화합물.상기식에서, R3은 제1항에서 정의한 바와 같다.
- 벤즈하이드릴(2S,3S,5R)-3-포르밀-3-메틸-7-옥소-4-티아-1-아자비사이클로[3,2,0]헵탄-2-카복실레이트.
- 치료적 활성 물질로서 사용하기 위한 제1항 내지 제13항 중의 어느 한 항에 따른 화합물.
- β-락타마제 억제제로서 사용하기 위한 제1항 내지 제13항 중의 어느 한 항에 따른 화합물.
- a)일반식(Ⅱ)의 화합물을 확설화제의 존재하에 일반식의 화합물[여기서, R1및R2는 제 1항에서 정의한 바와 같고, R8은 P(아릴)3, PO(O알킬)2Si(알킬)3또는 할로겐이다]과 반응시키거나, b)n이 O인 일반식(Ⅰ)의 화합물을 산화시키거나, 또는 c)R3이 수소가 아닌 일반식(Ⅰ)의 화합물을 상응하는 유리 산으로 전환시킨 다음, d)필요한 경우, 일반식(Ⅰ)의 산성 화합물을 약제학적으로 허용되는 염으로 전환시킴을 포함하여, 제 1항 내지 제13항중의 어느 한 항에 따른 화합물을 제조하는 방법.상기식에서, R3은 제1항에서 정의한 바와 같다.
- 제1항 내지 제13항중의 어느 한 항에 따른 화합물을 함유하는 약제.
- 제1항 내지 제13항중의 어느 한 항에 따른 화합물을 함유하는 β-락타마제 억제용 약제.
- 제19항 내지 제20항에 있어서, β-락탐 항생물질을 추가로 함유하는 약제.
- 제21항에 있어서, β-락탐 항생물질로서 페니실린, 세팔로스포린, 페넴 또는 카바페넴을 함유하는 약제.
- 제22항에 있어서, 피페라실린, 메즐로실린, 아즐로실린, 아팔실린, 벤질페니실린, 펜옥시메틸페니실린, 카베니실린, 메티실린, 프로피실린, 트리카르실란, 암피실린, 암옥시실린, 메실리남, 세프트리악손, 세프타지딤, 세페타메트, 세페타메트 피복실, 세포탁심, 세프멘옥심, 세프티즈옥심, 세푸르옥심, 세팔로리딘, 세팔로틴, 세파졸린, 세팔렉신, 세폭시틴, 세파세트릴, 세파만돌, 세파피린, 세프라딘, 세팔로글리신, 세프피론, 세페핌, 이미페넴, 메로페넴 또는 이들 화합물중 하나의 약제학적으로 허용되는 염을 함유하는 약제.
- 제22항에 있어서, 세프트리악손 또는 약제학적으로 허용되는 이의 염중의 하나를 함유하는 약제.
- 항균 치료에 동시에, 개별적으로 또는 순차적 단계로 사용하기 위한 배합 제제로서의 제21항 내지 제24항 중의 어느 한 항에 따른 약제.
- 질병을 억제 또는 예방하는데 있어서의 제1항 내지 제13항 중의 어느 한 항에 따른 화합물의 용도.
- 세균 감염을 억제 또는 예방하는데 있어서의 제1항 내지 제13항 중의 어느 한 항에 따른 화합물의 용도.
- 항균-활성 약제를 제조하기 위한, 제 1항 내지 제13항 중의 어느 한 항에 따른 화합물의 용도.
- 제18항에서 특허청구된 방법 또는 명백하게 화학적으로 대등한 방법에 의해 제조된, 제1항 내지 제15항 중의 어느 한 항에 따른 화합물.
- 상기 기술한 바와 같은 본 발명.
- 세균 감염성 질환에 대한 치료를 원하는 환자에게 β-락탐 항생물질과 배합된 제1항 내지 제15항 중의 어느 한 항에 따른 화합물의 유효량을 투여함을 포함하여, 세균 감염성 질환을 치료 또는 예방하는 방법.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
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| AU2012233003B2 (en) * | 2005-12-07 | 2014-12-18 | Basilea Pharmaceutica Ag | Useful combinations of monobactam antibiotics with beta-lactamase inhibitors |
| ES2373461T3 (es) | 2005-12-07 | 2012-02-03 | Basilea Pharmaceutica Ag | Antibióticos útiles de monobactama. |
| US11160787B2 (en) | 2016-07-21 | 2021-11-02 | Conopco, Inc. | 4-(4-chlorophenyl)-5-methylene-pyrrol-2-one and 5-methylene-4-(p-tolyl)pyrrol-2-one for use in the treatment of gram negative bacterial infections |
| WO2018015278A1 (en) | 2016-07-21 | 2018-01-25 | Unilever Plc | Lactams for use in the treatment of skin lesions |
| US10875830B2 (en) | 2016-07-21 | 2020-12-29 | Conopeo, Inc. | Method of treatment |
| US20200230114A1 (en) * | 2019-01-22 | 2020-07-23 | Board Of Regents Of The Nevada System Of Higher Education On Behalf Of Nevada | The use of lipophilic beta-lactam antibiotics and carboxylate esters for the treatment of bacterial infections within citrus and other plant species |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4331677A (en) * | 1978-11-24 | 1982-05-25 | Farmitalia Carlo Erba S.P.A. | 7-Oxo-4-1-aza-bicyclo-[3,2,0]-heptane derivatives |
| US4282236A (en) * | 1979-11-07 | 1981-08-04 | Beecham Group Limited | β-Lactam antibacterial agents, their use in pharmaceutical compositions, and intermediates |
| US4365174A (en) * | 1980-07-31 | 1982-12-21 | Rca Corporation | Pulse counter type circuit for power-up indication |
| ZA826687B (en) * | 1981-09-14 | 1983-07-27 | Pfizer | Beta-lactamase inhibiting 2-beta-substituted-2-alpha-methyl 5(r)penam-3-alpha-carboxylic acid 1,1-dioxides and intermediates therefor |
| GB8509180D0 (en) * | 1985-04-10 | 1985-05-15 | Erba Farmitalia | Penem derivatives |
| US4861768A (en) * | 1986-02-27 | 1989-08-29 | Taiho Pharmaceutical Company, Limited | 2 β-substituted thiomethylpenicillin derivatives and their preparation and use |
| US4891369A (en) * | 1986-12-03 | 1990-01-02 | Taiho Pharmaceutical Company, Limited | 2β-Substituted-methylpenicillanic acid derivatives, and salts and esters thereof |
| US5132300A (en) * | 1989-06-01 | 1992-07-21 | Pfizer Inc. | Beta-lactam elastase inhibitors |
-
1994
- 1994-07-28 TW TW083106901A patent/TW383308B/zh not_active IP Right Cessation
- 1994-08-05 CA CA002129564A patent/CA2129564C/en not_active Expired - Fee Related
- 1994-08-12 DK DK94112622.9T patent/DK0640607T3/da active
- 1994-08-12 DE DE59401750T patent/DE59401750D1/de not_active Expired - Lifetime
- 1994-08-12 AT AT94112622T patent/ATE148705T1/de not_active IP Right Cessation
- 1994-08-12 SG SG1996006785A patent/SG48064A1/en unknown
- 1994-08-12 ES ES94112622T patent/ES2097589T3/es not_active Expired - Lifetime
- 1994-08-12 EP EP94112622A patent/EP0640607B1/de not_active Expired - Lifetime
- 1994-08-18 IL IL11071194A patent/IL110711A/xx not_active IP Right Cessation
- 1994-08-18 HU HU9402391A patent/HUT67880A/hu unknown
- 1994-08-18 JP JP6194133A patent/JP2642314B2/ja not_active Expired - Fee Related
- 1994-08-18 AU AU70356/94A patent/AU674768B2/en not_active Ceased
- 1994-08-19 NZ NZ264272A patent/NZ264272A/en unknown
- 1994-08-22 US US08/293,865 patent/US5637579A/en not_active Expired - Lifetime
- 1994-08-23 CZ CZ942039A patent/CZ203994A3/cs unknown
- 1994-08-23 CN CN94115783A patent/CN1067078C/zh not_active Expired - Fee Related
- 1994-08-23 NO NO943104A patent/NO307054B1/no not_active IP Right Cessation
- 1994-08-23 RU RU94030236A patent/RU2139290C1/ru active
- 1994-08-23 UA UA94085740A patent/UA29435C2/uk unknown
- 1994-08-24 FI FI943885A patent/FI113775B/fi not_active IP Right Cessation
- 1994-08-24 KR KR1019940020869A patent/KR100362294B1/ko not_active Expired - Fee Related
-
1995
- 1995-11-16 US US08/559,104 patent/US5644053A/en not_active Expired - Lifetime
-
1997
- 1997-04-22 GR GR970400890T patent/GR3023228T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2642314B2 (ja) | 1997-08-20 |
| FI113775B (fi) | 2004-06-15 |
| IL110711A (en) | 1999-08-17 |
| SG48064A1 (en) | 1998-04-17 |
| KR100362294B1 (ko) | 2005-08-25 |
| ES2097589T3 (es) | 1997-04-01 |
| CA2129564C (en) | 2006-07-25 |
| FI943885A0 (fi) | 1994-08-24 |
| DE59401750D1 (de) | 1997-03-20 |
| GR3023228T3 (en) | 1997-07-30 |
| CN1067078C (zh) | 2001-06-13 |
| CN1106408A (zh) | 1995-08-09 |
| RU94030236A (ru) | 1996-06-20 |
| EP0640607B1 (de) | 1997-02-05 |
| AU7035694A (en) | 1995-03-09 |
| US5644053A (en) | 1997-07-01 |
| HU9402391D0 (en) | 1994-10-28 |
| NO307054B1 (no) | 2000-01-31 |
| RU2139290C1 (ru) | 1999-10-10 |
| CZ203994A3 (en) | 1995-03-15 |
| EP0640607A1 (de) | 1995-03-01 |
| TW383308B (en) | 2000-03-01 |
| US5637579A (en) | 1997-06-10 |
| NZ264272A (en) | 1996-10-28 |
| HUT67880A (en) | 1995-05-29 |
| UA29435C2 (uk) | 2000-11-15 |
| NO943104L (no) | 1995-02-27 |
| IL110711A0 (en) | 1994-11-11 |
| AU674768B2 (en) | 1997-01-09 |
| DK0640607T3 (da) | 1997-06-16 |
| NO943104D0 (no) | 1994-08-23 |
| ATE148705T1 (de) | 1997-02-15 |
| JPH0782273A (ja) | 1995-03-28 |
| FI943885L (fi) | 1995-02-25 |
| CA2129564A1 (en) | 1995-02-25 |
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