HRP20221217T1 - Spojevi inhibitori beta-laktamaze - Google Patents
Spojevi inhibitori beta-laktamaze Download PDFInfo
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- HRP20221217T1 HRP20221217T1 HRP20221217TT HRP20221217T HRP20221217T1 HR P20221217 T1 HRP20221217 T1 HR P20221217T1 HR P20221217T T HRP20221217T T HR P20221217TT HR P20221217 T HRP20221217 T HR P20221217T HR P20221217 T1 HRP20221217 T1 HR P20221217T1
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- Prior art keywords
- alkyl
- alkoxy
- independently
- cycloalkyl
- phenyl
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- 150000001875 compounds Chemical class 0.000 title claims 23
- 239000003781 beta lactamase inhibitor Substances 0.000 title 1
- 229940126813 beta-lactamase inhibitor Drugs 0.000 title 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 title 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 20
- 150000003839 salts Chemical class 0.000 claims 17
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 15
- 239000001257 hydrogen Substances 0.000 claims 15
- 229910052739 hydrogen Inorganic materials 0.000 claims 15
- 125000000217 alkyl group Chemical group 0.000 claims 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims 12
- 125000005843 halogen group Chemical group 0.000 claims 12
- 150000002431 hydrogen Chemical class 0.000 claims 11
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 9
- 125000001072 heteroaryl group Chemical group 0.000 claims 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 6
- -1 -OH Chemical group 0.000 claims 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims 3
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims 3
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 125000003545 alkoxy group Chemical group 0.000 claims 3
- 125000001188 haloalkyl group Chemical group 0.000 claims 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 3
- 229910052757 nitrogen Inorganic materials 0.000 claims 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 3
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims 2
- 208000035143 Bacterial infection Diseases 0.000 claims 2
- KEJCWVGMRLCZQQ-YJBYXUATSA-N Cefuroxime axetil Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(=O)OC(C)OC(C)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 KEJCWVGMRLCZQQ-YJBYXUATSA-N 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims 2
- 239000003782 beta lactam antibiotic agent Substances 0.000 claims 2
- LTINZAODLRIQIX-FBXRGJNPSA-N cefpodoxime proxetil Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC)C(=O)OC(C)OC(=O)OC(C)C)C(=O)C(=N/OC)\C1=CSC(N)=N1 LTINZAODLRIQIX-FBXRGJNPSA-N 0.000 claims 2
- 229960004797 cefpodoxime proxetil Drugs 0.000 claims 2
- 229960002620 cefuroxime axetil Drugs 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 208000019206 urinary tract infection Diseases 0.000 claims 2
- 239000002132 β-lactam antibiotic Substances 0.000 claims 2
- 229940124586 β-lactam antibiotics Drugs 0.000 claims 2
- 201000001178 Bacterial Pneumonia Diseases 0.000 claims 1
- 206010060803 Diabetic foot infection Diseases 0.000 claims 1
- 208000036209 Intraabdominal Infections Diseases 0.000 claims 1
- 206010023424 Kidney infection Diseases 0.000 claims 1
- 206010024971 Lower respiratory tract infections Diseases 0.000 claims 1
- 206010035664 Pneumonia Diseases 0.000 claims 1
- 206010037596 Pyelonephritis Diseases 0.000 claims 1
- 206010040047 Sepsis Diseases 0.000 claims 1
- 206010062255 Soft tissue infection Diseases 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 125000006242 amine protecting group Chemical group 0.000 claims 1
- 230000001580 bacterial effect Effects 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 239000007800 oxidant agent Substances 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 201000007094 prostatitis Diseases 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B43/00—Formation or introduction of functional groups containing nitrogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
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- C07—ORGANIC CHEMISTRY
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0834—Compounds having one or more O-Si linkage
- C07F7/0892—Compounds with a Si-O-N linkage
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Claims (16)
1. Spoj prema formuli (I):
[image]
ili njegova farmaceutski prihvatljiva sol, u kojoj:
R1 je -C(O)NR7R8, -CN, fenil, 5-6 člani heteroaril, -C(O)NR’NR’C(O)R9, -C(O)NR’OR10, ili C1-C6 alkil grupa, gdje je alkil grupa supstituirana s jednom do tri grupe izabrane između halo, C1-C3 alkoksi, -OH, -CN, -NR7R8, -NR7COR9, 5-6 člani heteroaril i 5-7 člani heterociklil, i gdje su fenil i heteroaril predstavljeni s R1 opcionalno i neovisno supstituirani s 1-3 grupe izabrane između halo, -OH, C1-C3 alkoksi, -CN, -NR7R8, i -CONR7R8;
R2 i R3 su neovisno izabrani između vodika, halo, C1-C3 alkil, i C3-C6 cikloalkil;
R4 i R5 su neovisno izabrani između vodika, halo, -CN, -CO2R9, C1-C3 alkil, i C1-C3 haloalkil;
R6 je vodik, C1-C12 alkil, C1-C4 alkil-C1-C3 alkoksi-(NR’C1-C6 alkil)-C1-C3 alkoksi, C1-C4 alkil-C1-C3 alkoksi-C1-C3 alkoksi, C2-C12 alkenil, C3-C10 cikloalkil, 5-6 člani heteroaril i 5-7 člani heterociklil, gdje alkil, alkenil, cikloalkil, heteroaril i
heterociklil su opcionalno i neovisno supstituirani s 1-6 grupa izabranih između karboksil, halo, C1-C6 alkoksi, C1-C6 alkil i fenil;
svaki R7 i R8 su neovisno vodik, C1-C3 alkil, C1-C3 alkoksi, fenil, C3-C6 cikloalkil, 4-7 člani heterociklil, ili 5-6 člani heteroaril, gdje alkil, alkoksi, fenil, cikloalkil, heterociklil ili heteroaril predstavljeni s R7 ili R8 je opcionalno i
neovisno supstituiran s 1-6 grupa izabranih između 5-6 članog heterociklila opcionalno supstituiranog s jednim ili dva -F atoma, karbonilom ili -CO(OC1-6 alkil), 5-6 članog heteroarila, -CN, -OH, C1-C3 alkila opcionalno supstituiranog s -NH2 ili-OH, C1-C3 haloalkila, C1-C3 haloalkoksi, C1-C3 alkoksi -NHCO(C1-C3alkil), -NHCO(C1-C3alkoksi), -S(O)2NR’R", -NHS(O)2NR’R", -NHS(O)2(C1-C3alkil), -NR’R", i -C(O)NR’R";
svaki R9 je C1-C6 alkil, C1-C6 haloalkil, C1-C6 haloalkoksi ili C1-C6 alkoksi;
svaki R10 je C1-C3 alkil opcionalno supstituiran s 1-6 grupa izabranih između 5-6 članog heterociklila opcionalno supstituiranog s jedan ili dva -F atoma, karbonila ili -CO(OC1-6 alkil), C3-C6 cikloalkila, 5-6 članog heteroarila, -CN, -OH, -NHCO(C1-C3 alkil), -NHCO(C1-C3 alkoksi), -S(O)2NR’R", -NHS(O)2NR’R", -NHS(O)2(C1-C3 alkil), -NR’R", ili -C(O)NR’R"; i
svaki R’ i R" je neovisno vodik, metil, etil ili propil; ili R’ i R" uzeti zajedno s dušikom za koji su vezani tvore 5-6 člani heterociklil; uz uvjet da barem jedan od R2 i R3 je drugačiji od vodika.
2. Spoj prema zahtjevu 1 ili njegova farmaceutski prihvatljiva sol, gdje R6 je C1-C12 alkil, C1-C4 alkilC1-C3 alkoksi-(NR’C1-C6 alkil)-C1-C3 alkoksi, C1-C4 alkil-C1-C3 alkoksi-C1-C3 alkoksi, C2-C12 alkenil, C3-C10 cikloalkil, 5-6 člani heteroaril i 5-7 člani heterociklil, gdje alkil, alkenil, cikloalkil, heteroaril i heterociklil su opcionalno i neovisno supstituirani s 1-6 grupa izabranih između karbonil, halo, C1-C6 alkoksi, C1-C6 alkil i fenil.
3. Spoj prema zahtjevu 1 ili 2, prema formuli (III):
[image]
ili njegova farmaceutski prihvatljiva sol.
4. Spoj prema bilo kojem od zahtjeva 1 do 3 ili njegova farmaceutski prihvatljiva sol, gdje je R3C1-C3 alkil.
5. Spoj prema bilo kojem od zahtjeva 1 do 4 ili njegova farmaceutski prihvatljiva sol, gdje R1 je -C(O)NR7R8.
6. Spoj prema zahtjevu 3, prema formuli (V):
[image]
ili njegova farmaceutski prihvatljiva sol.
7. Spoj prema bilo kojem od zahtjeva 1 do 6 ili njegova farmaceutski prihvatljiva sol, gdje R6 je C1-C12 alkil, kao što je kada je R6etil, izopropil, 2-butil ili izopentil.
8. Spoj prema bilo kojem od zahtjeva 1 do 7 ili njegova farmaceutski prihvatljiva sol, gdje su R4 i R5 neovisno H, metil ili fluoro.
9. Spoj prema zahtjevu 8 ili njegova farmaceutski prihvatljiva sol, gdje je jedan od R4 i R5 vodik, a drugi je fluoro.
10. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, gdje je spoj formule:
[image]
11. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, gdje je spoj formule:
[image]
12. Farmaceutski sastav koji sadrži spoj kako je zahtijevano u bilo kojem od zahtjeva 1 do 11, ili njegova farmaceutski prihvatljiva sol, i barem jedan farmaceutski prihvatljiv nosač, razrjeđivač ili ekscipijens.
13. Farmaceutski sastav prema zahtjevu 12, koja sadrži još betalaktamski antibiotik, kao što je cefpodoksim proksetil ili cefuroksim aksetil.
14. Spoj prema bilo kojem od zahtjeva 1 do 11 ili njegova farmaceutski prihvatljiva sol, za upotrebu u liječenju bakterijske infekcije kod subjekta kome je to potrebno, tako što je bakterijska infekcija izabrana iz grupe koju čine komplicirana infekcija urinarnog trakta, nekomplicirana infekcija urinarnog trakta, infekcija bubrega, infekcija donjeg respiratornog trakta, bolnička bakterijska pneumonija (HAP), pneumonija, akutni bakterijski prostatitis, akutna bakterijska infekcija kože i mekog tkiva, sepsa, intra-abdominalna infekcija i infekcija dijabetičkog stopala, kao kada je spoj davan u kombinaciji s betalaktamskim antibiotikom kao što je cefpodoksim proksetil ili cefuroksim aksetil.
15. Postupak za stvaranje spoja formule VI:
[image]
ili njegove soli, gdje:
R1 je -C(O)NR7R8, -C(O)OR7, -CH2OR7, -CN, fenil, 5-6 člani heteroaril, -C(O)NR’NR’C(O)R9, -C(O)NR’OR10, ili C1-C6 alkil grupa, gdje alkil grupa je supstituirana s jednom do tri grupe izabrane između halo, C1-C3 alkoksi, -OH, -CN, -NR7R8, -NR7COR9, 5-6 člani heteroaril i 5-7 člani heterociklil, i
gdje fenil i heteroaril predstavljeni sa R1 su opcionalno i neovisno supstituirani s 1-3 grupe izabrane između halo, -OH, C1-C3 alkoksi, -CN, -NR7R8, i -CONR7R8;
R2 i R3 su svaki neovisno izabrani između vodika, halo, C1-C3 alkil, i C3-C6 cikloalkil, uz uvjet da barem jedan od R2 i R3 je drugačiji od vodika;
svaki R7 i R8 su neovisno vodik, C1-C3 alkil, C1-C3 alkoksi, fenil, C3-C6 cikloalkil, 4-7 člani heterociklil, ili 5-6 člani heteroaril, gdje alkil, alkoksi, fenil, cikloalkil, heterociklil ili heteroaril predstavljen s R7 ili R8 je opcionalno i neovisno susptituiran s 1-6 grupe izabrane između 5-6 članog heterociklila opcionalno supstituiranog s jedan ili dva -F atoma, karbonila ili -CO(OC1-6 alkil), 5-6 članog heteroarila, -CN, -OH, C1-C3 alkila opcionalno supstituiranog s -NH2 ili-OH, C1-C3 haloalkilom, C1-C3 haloalkoksi, C1-C3 alkoksi -NHCO(C1-C3alkil), -NHCO(C1-C3alkoksi), -S(O)2NR’R", -NHS(O)2NR’R", -NHS(O)2(C1-C3alkil), -NR’R", i -C(O)NR’R";
svaki R9 je C1-C6 alkil, C1-C6 haloalkil, C1-C6 haloalkoksi ili C1-C6 alkoksi;
svaki R’ i R" je neovisno vodik, metil, etil ili propil; ili R’ i R" uzeti zajedno s dušikom za koji su vezani tvore 5-6 člani heterociklil; i
PG i PG’ su svaki neovisno zaštitna grupa za amin; postupak obuhvaća reagiranje spoja formule XI:
[image]
ili njegove soli, sa PG’NHOH u prisustvu oksidansa da se dobije spoj formule VI.
16. Postupak dobivanja spoja formule VI:
[image]
ili njegove soli, gdje:
R1 je -C(O)NR7R8, -C(O)OR7, -CH2OR7, -CN, fenil, 5-6 člani heteroaril, -C(O)NR’NR’C(O)R9, -C(O)NR’OR10, ili C1-C6 alkil grupa, gdje je alkil grupa supstituirana s jednom do tri grupe izabrane između halo, C1-C3 alkoksi, -OH, -CN, -NR7R8, -NR7COR9, 5-6 člani heteroaril i 5-7 člani heterociklil, i gdje fenil i heteroaril predstavljeni s R1 su opcionalno i neovisno supstituirani s 1-3 grupe izabrane između halo, -OH, C1-C3 alkoksi, -CN, -NR7R8, i -CONR7R8;
R2 i R3 su svaki neovisno izabrani između vodika, halo, C1-C3 alkil, i C3-C6 cikloalkil, uz uvjet da barem jedan od R2 i R3 je drugačiji od vodika;
svaki R7 i R8 su neovisno vodik, C1-C3 alkil, C1-C3 alkoksi, fenil, C3-C6 cikloalkil, 4-7 člani heterociklil, ili 5-6 člani heteroaril, gdje alkil, alkoksi, fenil, cikloalkil, heterociklil ili heteroaril predstavljeni s R7 ili R8 je opcionalno ili neovisno supstituiran s 1-6 grupa izabranih između 5-6 članog heterociklil opcionalno supstituiranog s jednim ili dva -F atoma, karbonilom ili -CO(OC1-6 alkil), 5-6 članog heteroarila, -CN, -OH, C1-C3 alkila opcionalno supstituirnog s -NH2 ili-OH, C1-C3 haloalkilom, C1-C3 haloalkoksi, C1-C3 alkoksi -NHCO(C1-C3alkil), -NHCO(C1-C3alkoksi), -S(O)2NR’R", -NHS(O)2NR’R", -NHS(O)2(C1-C3alkil), -NR’R", i -C(O)NR’R";
svaki R9 je C1-C6 alkil, C1-C6 haloalkil, C1-C6 haloalkoksi ili C1-C6 alkoksi;
svaki R’ i R" je neovisno vodik, metil, etil ili propil; ili R’ i R" uzeti zajedno s dušikom na koji su vezani da tvore 5-6 člani heterociklil; i
PG i PG’ su svaki neovisno zaštitna grupa za amino; postupak obuhvaća reagiranje spoja formule XI:
[image]
ili njene soli, sa PG’N=O da bi se dobio spoj formule VI.
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| EP17784063.4A EP3512851B1 (en) | 2016-09-16 | 2017-09-15 | Beta-lactamase inhibitor compounds |
| PCT/US2017/051692 WO2018053215A1 (en) | 2016-09-16 | 2017-09-15 | Beta-lactamase inhibitor compounds |
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| US11905286B2 (en) | 2018-08-09 | 2024-02-20 | Antabio Sas | Diazabicyclooctanones as inhibitors of serine beta-lactamases |
| CN112209928B (zh) * | 2019-07-10 | 2023-02-17 | 华东理工大学 | 共价键标记丝氨酸类beta-内酰胺酶的试剂及制备和应用 |
| CN110898999A (zh) * | 2019-11-26 | 2020-03-24 | 中国矿业大学 | 一种煤焦油基煤泥浮选药剂及其制备方法 |
| CN111790439B (zh) * | 2020-07-29 | 2022-12-27 | 成都能特科技发展有限公司 | 一种手性二级胺二苯基膦芳甲酰胺双功能催化剂及其制备方法与应用 |
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