CN109071511B - 可用于治疗细菌感染的两性离子性炔丙基连接的抗叶酸剂 - Google Patents

可用于治疗细菌感染的两性离子性炔丙基连接的抗叶酸剂 Download PDF

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CN109071511B
CN109071511B CN201780006105.XA CN201780006105A CN109071511B CN 109071511 B CN109071511 B CN 109071511B CN 201780006105 A CN201780006105 A CN 201780006105A CN 109071511 B CN109071511 B CN 109071511B
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compound
dhfr
compounds
acid
infection
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CN109071511A (zh
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丹尼斯·赖特
埃米·C·安德森
埃里克·斯科凯拉
纳伦德兰·古姆迪蓬尼达亚南
桑托什·凯希佩迪
斯特凡妮·雷韦
迈克尔·N·隆巴多
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University of Connecticut
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University of Connecticut
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members 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
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C07D239/49—Two nitrogen atoms with an aralkyl radical, or substituted aralkyl radical, attached in position 5, e.g. trimethoprim
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A61P31/06—Antibacterial agents for tuberculosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members 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
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN201780006105.XA 2016-01-08 2017-01-09 可用于治疗细菌感染的两性离子性炔丙基连接的抗叶酸剂 Expired - Fee Related CN109071511B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662276494P 2016-01-08 2016-01-08
US62/276,494 2016-01-08
PCT/US2017/012702 WO2017120575A1 (en) 2016-01-08 2017-01-09 Zwitterionic propargyl-linked antifolates useful for treating bacterial infections

Publications (2)

Publication Number Publication Date
CN109071511A CN109071511A (zh) 2018-12-21
CN109071511B true CN109071511B (zh) 2022-06-07

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US (1) US10870625B2 (enExample)
EP (1) EP3400222B1 (enExample)
JP (1) JP6925344B2 (enExample)
CN (1) CN109071511B (enExample)
WO (1) WO2017120575A1 (enExample)

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Publication number Priority date Publication date Assignee Title
CN110590767B (zh) * 2019-08-29 2021-10-08 南方科技大学 一种合成amg837的方法
CN111848430B (zh) * 2020-07-22 2022-12-09 马鞍山诺恩特医药科技有限公司 2-([1,1’-联苯]-4-基)-2-甘氨酸类化合物的合成方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009025919A2 (en) * 2007-06-04 2009-02-26 University Of Connecticut 5-propargyl-pyrimidine derivatives as inhibitors of dihydrofolate reductase with antibacterial antiprotozoal, antifungal and anticancer properties
US20150225353A1 (en) * 2014-02-12 2015-08-13 Dennis L. Wright Heterocyclic and Cyclic Analogs of Propargyl-Linked Inhibitors of Dihydrofolate Reductase

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8853228B2 (en) * 2007-06-04 2014-10-07 University Of Connecticut Heterocyclic analogs of propargyl-linked inhibitors of dihydrofolate reductase
US8767716B2 (en) * 2011-09-19 2014-07-01 Vonage Network, Llc Systems and methods of routing IP telephony data packet communications

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009025919A2 (en) * 2007-06-04 2009-02-26 University Of Connecticut 5-propargyl-pyrimidine derivatives as inhibitors of dihydrofolate reductase with antibacterial antiprotozoal, antifungal and anticancer properties
US20150225353A1 (en) * 2014-02-12 2015-08-13 Dennis L. Wright Heterocyclic and Cyclic Analogs of Propargyl-Linked Inhibitors of Dihydrofolate Reductase

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
2,4-Diamino-5-(2-arylpropargyl)pyrimidine derivatives as new nonclassical antifolates for human dihydrofolate reductase inhibition;Oztekin Algul,等;《J Mol Graph Model.》;20110228;第608-613页 *
Acetylenic Linkers in Lead Compounds: A Study of the Stability of the Propargyl-Linked Antifolates;Wangda Zhou,等;《DRUG METABOLISM AND DISPOSITION》;20120718;第2002-2008页 *
In vitro biological activity and structural analysis of 2,4-diamino-5-(2-arylpropargyl)pyrimidine inhibitors of Candida albicans;Janet L. Paulsen，等;《Bioorganic & Medicinal Chemistry》;20090617;第4866-4872页 *
MRSA Isolates from United States Hospitals Carry dfrG and dfrK Resistance Genes and Succumb to Propargyl-Linked Antifolates;Stephanie M. Reeve,等;《Cell Chemical Biology》;20161222;第1458-1467页 *
Propargyl-Linked Antifolates are Dual Inhibitors of Candida albicans and Candida glabrata;Narendran G-Dayanandan,等;《J. Med. Chem.》;20140225;第2643-2656页 *
Prospective Screening of Novel Antibacterial Inhibitors of Dihydrofolate Reductase for Mutational Resistance;Kathleen M. Frey,等;《Antimicrobial Agents and Chemotherapy》;20120731;第3556-3562页 *
Structural analysis of the active sites of dihydrofolate reductase from two species of Candida uncovers ligand-induced conformational changes shared among species;Janet L. Paulsen,等;《Bioorg Med Chem Lett.》;20130331;第1279-1284页 *
Structure-Based Approach to the Development of Potent and Selective Inhibitors of Dihydrofolate Reductase from Cryptosporidium;David B. Bolstad,等;《J. Med. Chem.》;20081231;第6839-6852页 *
Toward New Therapeutics for Skin and Soft Tissue Infections: Propargyl-Linked Antifolates Are Potent Inhibitors of MRSA and Streptococcus pyogenes;Kishore Viswanathan，等;《PLoS ONE》;20120228;第1-9页 *
Towards New Antifolates Targeting Eukaryotic Opportunistic Infections;Jieying Liu,等;《EUKARYOTIC CELL》;20090430;第483-486页 *
Towards the understanding of resistance mechanisms in clinically isolated trimethoprim-resistant, methicillin-resistant Staphylococcus aureus dihydrofolate reductase;Kathleen M. Frey,等;《Journal of Structural Biology》;20091221;第93-97页 *

Also Published As

Publication number Publication date
EP3400222B1 (en) 2021-07-14
US10870625B2 (en) 2020-12-22
EP3400222A1 (en) 2018-11-14
US20190002413A1 (en) 2019-01-03
WO2017120575A1 (en) 2017-07-13
JP6925344B2 (ja) 2021-08-25
CN109071511A (zh) 2018-12-21
JP2019504834A (ja) 2019-02-21

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