MA37383A1 - Compose heterobicycliques comme inhibiteurs de la beta lactamase - Google Patents
Compose heterobicycliques comme inhibiteurs de la beta lactamaseInfo
- Publication number
- MA37383A1 MA37383A1 MA37383A MA37383A MA37383A1 MA 37383 A1 MA37383 A1 MA 37383A1 MA 37383 A MA37383 A MA 37383A MA 37383 A MA37383 A MA 37383A MA 37383 A1 MA37383 A1 MA 37383A1
- Authority
- MA
- Morocco
- Prior art keywords
- inhibitors
- beta
- compounds
- beta lactamase
- pharmaceutically acceptable
- Prior art date
Links
- 108090000204 Dipeptidase 1 Proteins 0.000 title 1
- -1 Heterobicyclic compound Chemical class 0.000 title 1
- 102000006635 beta-lactamase Human genes 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 3
- 150000003839 salts Chemical class 0.000 abstract 2
- 208000035143 Bacterial infection Diseases 0.000 abstract 1
- 208000022362 bacterial infectious disease Diseases 0.000 abstract 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 abstract 1
- 239000003781 beta lactamase inhibitor Substances 0.000 abstract 1
- 229940126813 beta-lactamase inhibitor Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 208000015181 infectious disease Diseases 0.000 abstract 1
- 239000002132 β-lactam antibiotic Substances 0.000 abstract 1
- 229940124586 β-lactam antibiotics Drugs 0.000 abstract 1
Classifications
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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
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—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
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
-
- 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
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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
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
La présente invention concerne des composés qui sont des inhibiteurs de la bêta-lactamase. Ces composés et leurs sels acceptables sur le plan pharmaceutique sont utiles en combinaison avec des antibiotiques de type bêta-lactame, ou seuls, pour le traitement d'infections bactériennes, y compris d'infections provoquées par des organismes résistant aux médicaments, y compris des organismes multi-résistants. La présente invention comprend des composés de formule (ia), ou un sel acceptable sur le plan pharmaceutique desdits composés, les valeurs de r1, r2, r3 et r4 étant telles que définies dans la description.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261618993P | 2012-04-02 | 2012-04-02 | |
| PCT/GB2013/050869 WO2013150296A1 (fr) | 2012-04-02 | 2013-04-02 | Composés hétérobicycliques comme inhibiteurs de la bêta-lactamase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MA37383A1 true MA37383A1 (fr) | 2016-06-30 |
Family
ID=48083562
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MA37383A MA37383A1 (fr) | 2012-04-02 | 2013-04-02 | Compose heterobicycliques comme inhibiteurs de la beta lactamase |
Country Status (41)
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR090539A1 (es) | 2012-04-02 | 2014-11-19 | Astrazeneca Ab | COMPUESTOS INHIBIDORES DE b LACTAMASA |
| TWI690317B (zh) | 2014-11-17 | 2020-04-11 | 英商安特西醫療有限公司 | 用於治療抗藥性細菌感染之組合療法 |
| HK1244791A1 (zh) | 2015-03-31 | 2018-08-17 | 拜欧蒂姆公司 | 杂环化合物及它们在预防或治疗细菌感染中的应用 |
| EP3075733A1 (fr) * | 2015-03-31 | 2016-10-05 | Mutabilis | Nouveaux composés hétérocycliques et leur utilisation dans la prévention ou le traitement d'infections bactériennes |
| CA2980085A1 (fr) | 2015-03-31 | 2016-10-06 | Mutabilis | Nouveaux composes heterocycliques et utilisation de ceux-ci pour prevenir ou traiter des infections bacteriennes |
| EP3075381A1 (fr) * | 2015-04-03 | 2016-10-05 | Mutabilis | Nouveaux composés hétérocycliques et leur utilisation dans la prévention ou le traitement d'infections bactériennes |
| EP3277277B1 (fr) * | 2015-04-03 | 2021-01-06 | Mutabilis | Nouveaux composés hétérocycliques et leur utilisation dans la prévention ou le traitement d'infections bactériennes |
| CN107580595B (zh) * | 2015-05-07 | 2020-09-18 | 拜欧蒂姆公司 | 杂环化合物及它们在预防或治疗细菌感染中的应用 |
| EP3091018A1 (fr) * | 2015-05-07 | 2016-11-09 | Mutabilis | Nouveaux composés hétérocycliques et leur utilisation dans la prévention ou le traitement d'infections bactériennes |
| CN108137567A (zh) | 2015-10-02 | 2018-06-08 | 乐高化学生物科学股份有限公司 | 用于抑制β-内酰胺酶的组合物和方法 |
| EP3184529A1 (fr) | 2015-12-23 | 2017-06-28 | Mutabilis | Nouveaux composés hétérocycliques et leur utilisation dans la prévention ou le traitement d'infections bactériennes |
| WO2017203266A1 (fr) | 2016-05-25 | 2017-11-30 | Entasis Therapeutics Limited | Polythérapie pour le traitement d'infections bactériennes résistantes |
| SG11201901658PA (en) | 2016-09-16 | 2019-04-29 | Entasis Therapeutics Ltd | Beta-lactamase inhibitor compounds |
| JOP20190061A1 (ar) | 2016-09-28 | 2019-03-26 | Novartis Ag | مثبطات بيتا-لاكتاماز |
| EP3301094A1 (fr) * | 2016-09-30 | 2018-04-04 | Mutabilis | Nouveaux composés hétérocycliques et leur utilisation dans la prévention ou le traitement d'infections bactériennes |
| EP3300736B1 (fr) | 2016-09-30 | 2021-05-05 | Mutabilis | Composition comprenant un composé antibiotique et un composé hétérocyclique et leur utilisation pour prévenir ou traiter des infections bactériennes |
| EA037916B1 (ru) * | 2017-02-08 | 2021-06-07 | Энтасис Терапеутикс Лимитед | Соединения-ингибиторы бета-лактамаз |
| PT3630111T (pt) * | 2017-05-08 | 2022-03-01 | Entasis Therapeutics Inc | Compostos e métodos de tratamento de infeções bacterianas |
| US10085999B1 (en) * | 2017-05-10 | 2018-10-02 | Arixa Pharmaceuticals, Inc. | Beta-lactamase inhibitors and uses thereof |
| WO2019221122A1 (fr) | 2018-05-14 | 2019-11-21 | 国立大学法人名古屋大学 | INHIBITEUR DE β-LACTAMASE |
| US11905286B2 (en) | 2018-08-09 | 2024-02-20 | Antabio Sas | Diazabicyclooctanones as inhibitors of serine beta-lactamases |
| EP3608318A1 (fr) * | 2018-08-09 | 2020-02-12 | Antabio SAS | Derives de diaazabicyclooctanone comme antibiotiques |
| EP4272831A3 (fr) * | 2018-08-09 | 2024-02-21 | Antabio SAS | Diazabicyclooctanones comme inhibiteurs de sérine beta-lactamases |
| RU2739761C2 (ru) * | 2018-09-27 | 2020-12-28 | Федеральное государственное бюджетное научное учреждение Уфимский федеральный исследовательский центр Российской академии наук | Способ получения n-алкил-n-{ [3-алкил-3,8-диазабицикло[3.2.1]окта-1(7),5-диен-8-ил]метил} аминов и их применение в качестве средств с антимикробной активностью |
| CN111196808B (zh) * | 2018-11-16 | 2022-10-18 | 南京圣和药业股份有限公司 | 二氮杂双环类化合物及其应用 |
| CN110615790A (zh) * | 2019-10-24 | 2019-12-27 | 北京融英医药科技有限公司 | 一种利格列汀制备工艺的改进方法 |
| US20220194791A1 (en) * | 2020-12-22 | 2022-06-23 | Tokyo Ohka Kogyo Co., Ltd. | Method for producing aqueous solution of purified orthoperiodic acid, method for producing semiconductor device, and aqueous solution of orthoperiodic acid |
| US20250352521A1 (en) * | 2021-01-20 | 2025-11-20 | Entasis Therapeutics Limited | Fixed dosage antibiotic compositions |
| CN113979981B (zh) * | 2021-10-22 | 2023-04-07 | 天津医科大学 | 一种巯基响应型脱碱基位点捕获试剂及应用 |
| WO2023206580A1 (fr) | 2022-04-29 | 2023-11-02 | Entasis Therapeutics Limited | Formes cristallines de durlobactam |
| CN118271319B (zh) * | 2022-12-30 | 2025-02-28 | 成都四面体药物研究有限公司 | 一种β-内酰胺酶抑制剂含脲双环化合物、其制备方法及其用途 |
| WO2024227071A1 (fr) | 2023-04-26 | 2024-10-31 | Entasis Therapeutics Limited | Synthèse de durlobactam |
| CN116693531A (zh) * | 2023-06-09 | 2023-09-05 | 河南师范大学 | 一种桥联多环内酰胺类化合物的合成方法 |
| CN119998293A (zh) | 2023-08-08 | 2025-05-13 | 成都四面体药物研究有限公司 | 一种含脲三环的β-内酰胺酶抑制剂、其制备方法及其用途 |
| WO2025106662A1 (fr) | 2023-11-15 | 2025-05-22 | Entasis Therapeutics, Inc. | Préparation d'intermédiaires d'acide boronique utiles dans la préparation de composés pour le traitement d'infections bactériennes |
| WO2025239896A1 (fr) | 2024-05-16 | 2025-11-20 | Entasis Therapeutics, Inc. | Traitement de pneumonie bactérienne nosocomiale et pneumonie bactérienne acquise sous ventilation mécanique provoquée par des isolats sensibles de complexe acinetobacter baumannii-calcoaceticus |
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| ATE177099T1 (de) * | 1993-12-29 | 1999-03-15 | Pfizer | Diazabicyclische neurokinin antagonisten |
| FR2812635B1 (fr) * | 2000-08-01 | 2002-10-11 | Aventis Pharma Sa | Nouveaux composes heterocycliques, preparation et utilisation comme medicaments notamment comme anti- bacteriens |
| FR2835186B1 (fr) * | 2002-01-28 | 2006-10-20 | Aventis Pharma Sa | Nouveaux composes heterocycliques, actifs comme inhibiteurs de beta-lactamases |
| US7439253B2 (en) | 2002-12-06 | 2008-10-21 | Novexel | Heterocyclic compounds, their preparation and their use as medicaments, in particular as antibacterials and beta-lactamase inhibitors |
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| FR2936798B1 (fr) * | 2008-10-03 | 2012-09-28 | Novexel | Nouveaux composes heterocycliques azotes, leur preparation et leur utilisation comme medicaments antibacteriens. |
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| FR2937034B1 (fr) | 2008-10-10 | 2012-11-23 | Novexel | Nouveaux composes heterocycliques azotes, leur preparation et leur utilisation comme medicaments antibacteriens |
| FR2951171A1 (fr) | 2009-10-09 | 2011-04-15 | Novexel | Nouveau sel de sodium d'un compose azabicyclique sous forme enantiomere cristallisee et nouvelles formes polymorphes et pseudopolymorphes ainsi que leur preparation |
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| JP2015512419A (ja) | 2012-03-30 | 2015-04-27 | キュービスト ファーマシューティカルズ, インコーポレイテッド | イソオキザゾールβ−ラクタマーゼ阻害剤 |
| AR090539A1 (es) | 2012-04-02 | 2014-11-19 | Astrazeneca Ab | COMPUESTOS INHIBIDORES DE b LACTAMASA |
| HUE046893T2 (hu) | 2012-05-30 | 2020-04-28 | Meiji Seika Pharma Co Ltd | Új ß-laktamáz inhibitor és eljárás elõállítására |
| ES2672100T3 (es) | 2012-08-25 | 2018-06-12 | Wockhardt Limited | Derivados de 1,6-diazabiciclo[3,2,1]octano-7-ona y su uso en el tratamiento de infecciones bacterianas |
| WO2014141132A1 (fr) | 2013-03-14 | 2014-09-18 | Naeja Pharmaceutical Inc. | Nouveaux composés hétérocycliques et leur utilisation en tant qu'agents antibactériens et inhibiteurs de β-lactamase |
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