CA2952111C - Small molecule efflux pump inhibitors - Google Patents

Small molecule efflux pump inhibitors Download PDF

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Publication number
CA2952111C
CA2952111C CA2952111A CA2952111A CA2952111C CA 2952111 C CA2952111 C CA 2952111C CA 2952111 A CA2952111 A CA 2952111A CA 2952111 A CA2952111 A CA 2952111A CA 2952111 C CA2952111 C CA 2952111C
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substituted
unsubstituted
bacterial infection
infection
efflux pump
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CA2952111A
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French (fr)
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CA2952111A1 (en
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Paul M. DUNMAN
Catlyn E. Blanchard
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University of Rochester
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University of Rochester
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
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    • A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
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    • A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
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    • A61K31/403—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 carbocyclic rings, e.g. carbazole
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    • 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
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    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
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US9834514B2 (en) * 2015-04-20 2017-12-05 New Mexico Tech Research Foundation Antibiotic sensitivity-restoring and photosensitive agents
US11110080B2 (en) 2017-03-27 2021-09-07 The Regents Of The University Of Colorado, A Body Corporate Small molecule inhibitors of bacterial efflux pumps and methods of using same
BR102018007822A2 (pt) 2017-04-20 2018-11-06 Gilead Sciences, Inc. composto, métodos para inibir pd-1, pd-l1 e/ou interação de pd-1/pd-l1 e para tratamento de câncer, composição farmacêutica, e, kit para tratamento de ou prevenção de câncer ou uma doença ou condição
CN107216305B (zh) * 2017-05-03 2020-05-08 中国人民解放军第四军医大学 一类苯并吡喃类化合物及其应用
CN111971271B (zh) * 2018-01-09 2023-10-10 香港理工大学 一种具有抗菌活性的化合物
KR102708681B1 (ko) 2018-02-13 2024-09-26 길리애드 사이언시즈, 인코포레이티드 Pd-1/pd-l1 억제제
EP4600247A3 (en) 2018-04-19 2025-11-19 Gilead Sciences, Inc. Pd-1/pd-l1 inhibitors
UA126421C2 (uk) 2018-07-13 2022-09-28 Гіліад Сайєнсіз, Інк. Інгібітори pd-1/pd-l1
JP7309725B2 (ja) 2018-08-21 2023-07-18 杏林製薬株式会社 ２環性ヘテロ芳香環誘導体
CN108822089A (zh) * 2018-08-22 2018-11-16 大连理工大学 2-芳基咪唑烷类化合物、制备方法及其作为Hsp90抑制剂在抗肿瘤上的应用
US11236085B2 (en) 2018-10-24 2022-02-01 Gilead Sciences, Inc. PD-1/PD-L1 inhibitors
WO2023044364A1 (en) 2021-09-15 2023-03-23 Enko Chem, Inc. Protoporphyrinogen oxidase inhibitors

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5989832A (en) 1995-04-21 1999-11-23 Microcide Pharmaceuticals, Inc. Method for screening for non-tetracycline efflux pump inhibitors
CN1188512A (zh) 1995-04-21 1998-07-22 迈克罗赛药品公司 外流泵抑制剂
US20030220338A1 (en) * 2001-07-16 2003-11-27 Watkins Will J. Fungal efflux pump inhibitors
BRPI0512865A (pt) 2004-06-30 2008-04-08 Novartis Ag método para aumentar a suscetibilidade de inibidores da deformilase de peptìdio usando inibidores de bomba de efluxo
FR2873692B1 (fr) * 2004-07-29 2006-12-01 Univ Claude Bernard Lyon COMPOSITIONS CONTENANT, EN ASSOCIATION AVEC UN AGENT ANTIMICROBIEN, UN COMPOSE THIOPHENIQUE OU BENZOTHIOPHENIQUE DE FORMULE(I)PRESENTANT UNE ACTIVITE INHIBITRICE DE POMPE NorA
US8268865B2 (en) * 2007-05-11 2012-09-18 Rempex Pharmaceuticals, Inc. Quaternary alkyl ammonium bacterial efflux pump inhibitors and therapeutic uses thereof
CN101301289B (zh) 2008-05-22 2010-09-22 中国科学院微生物研究所 小檗碱及其结构类似物在逆转多药耐药泵中的应用
WO2011006158A2 (en) * 2009-07-10 2011-01-13 University Of Maryland, Baltimore Targeting nad biosynthesis in bacterial pathogens
US8933018B2 (en) * 2011-02-07 2015-01-13 Rempex Pharmaceuticals, Inc. Boron containing polybasic bacterial efflux pump inhibitors and therapeutic uses thereof
CN103156844B (zh) 2011-12-15 2016-11-16 天津市国际生物医药联合研究院 西弗碱类化合物在制备抑制ndm-1活性的药物中的应用
US20150237857A1 (en) 2012-08-10 2015-08-27 Mcmaster University Antibacterial inhibitors

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EP3154534A1 (en) 2017-04-19

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