WO2022006432A1 - Compounds having antibacterial activity - Google Patents

Compounds having antibacterial activity Download PDF

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Publication number
WO2022006432A1
WO2022006432A1 PCT/US2021/040143 US2021040143W WO2022006432A1 WO 2022006432 A1 WO2022006432 A1 WO 2022006432A1 US 2021040143 W US2021040143 W US 2021040143W WO 2022006432 A1 WO2022006432 A1 WO 2022006432A1
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WO
WIPO (PCT)
Prior art keywords
group
heteroaryl
aryl
alkyl
alkenyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2021/040143
Other languages
English (en)
French (fr)
Inventor
Zemer Gitai
Hahn Kim
James K. Martin
Joseph P. SHEEHAN
Connor CHAIN
Yong Huang
Shuo Li
Xueming Chen
Chenran JIANG
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shenzhen Bay Laboratory
Princeton University
Original Assignee
Shenzhen Bay Laboratory
Princeton University
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Filing date
Publication date
Application filed by Shenzhen Bay Laboratory, Princeton University filed Critical Shenzhen Bay Laboratory
Priority to JP2023524493A priority Critical patent/JP2023535527A/ja
Priority to CA3183776A priority patent/CA3183776A1/en
Priority to US18/014,032 priority patent/US20230295164A1/en
Priority to CN202180047426.0A priority patent/CN116234808B/zh
Priority to AU2021301264A priority patent/AU2021301264A1/en
Priority to EP21832744.3A priority patent/EP4175953A4/en
Publication of WO2022006432A1 publication Critical patent/WO2022006432A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • 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
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • 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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • 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
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te

Definitions

  • R 1 , R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, imine, cyanoimine, alkylene-aryl, alkylene-heteroaryl, amide, sulfonamide, acid, halo, and urea, wherein the alkyl, alkenyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylene-aryl, alkylene- heteroaryl, amide and sulfonamide are optionally substituted with one or more substituents selected from the group consisting of (C 1 –C 10 )-alkyl, (C 1 –C 10 )-alkenyl, cycloalkyl, heterocycloal
  • R 1 – R 6 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amide, sulfonamide, halo, urea, and –C(O)OR 7 , wherein R7 is selected from the group consisting of hydrogen and alkyl, and wherein each X is independently selected from the group consisting of C, N, O, S, SO 2 , and NR 8 R 9 , wherein R 8 and R 9 are independently selected from the group consisting of hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkenyl, aryl, heteroaryl, amide, sulfonamide, urea and C(O)R 10 wherein R 10 is selected from the group consisting of hydrogen, alkyl, alkenyl, heteroalkyl, cycloal
  • R 1 – R 6 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amide, sulfonamide, halo, urea, and –C(O)OR 7 , wherein R 7 is selected from the group consisting of hydrogen and alkyl, and wherein each X is independently selected from the group consisting of C, N, O, S, SO 2 , and NR 8 R 9 , wherein R 8 and R 9 are independently selected from the group consisting of hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkenyl, aryl, heteroaryl, amide, sulfonamide, urea and C(O)R 10 wherein R 10 is selected from the group consisting of hydrogen, alkyl, alkenyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl and wherein R 10 is
  • alkenyl refers to a straight or branched chain hydrocarbon group having at least one carbon-carbon double bond and optionally substituted with one or more substituents
  • alkynyl refers to a straight or branched chain hydrocarbon group having at least one carbon-carbon triple bond and optionally substituted with one or more substituents including, but not limited to, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amine, and/or alkylsilane.
  • aryl refers to an aromatic monocyclic or multicyclic ring system optionally substituted with one or more ring substituents.
  • heteroaryl refers to an aromatic monocyclic or multicyclic ring system in which one or more of the ring atoms is an element other than carbon, such as nitrogen, oxygen and/or sulfur.
  • cycloalkyl refers to a non-aromatic, mono- or multicyclic ring system optionally substituted with one or more ring substituents.
  • a method comprises administering to a patient having a bacterial infection a therapeutically effective amount of one or more compounds of Formula(s) I-VII.
  • a compound of any of Formulas I-VII is administered in an amount selected from Table I or Table III herein.
  • a combination of two or more compounds of any of Formulas I-VII can be employed in treating a bacterial infection.
  • bacterial infections treated with compounds described herein are selected from Table II.
  • EXAMPLES – Compounds Exhibiting Antibacterial Activity Compounds falling under one or more of Formulas I-VII were prepared according to the following general reaction scheme. Common solvents were purified before use. All reagents were reagent grade and purified where necessary. Reactions were monitored by thin-layer chromatography (TLC) using Whatman precoated silica gel plates. Flash column chromatography was performed over ultrapure silica gel (200 ⁇ 400 mesh) from Merck. 1 H NMR spectra were recorded on a Bruker AVANCE 300 (300 MHz), 400MHz or 500MHz spectrometer.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/US2021/040143 2020-07-02 2021-07-01 Compounds having antibacterial activity Ceased WO2022006432A1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
JP2023524493A JP2023535527A (ja) 2020-07-02 2021-07-01 抗菌活性を有する化合物
CA3183776A CA3183776A1 (en) 2020-07-02 2021-07-01 Compounds having antibacterial activity
US18/014,032 US20230295164A1 (en) 2020-07-02 2021-07-01 Compounds having antibacterial activity
CN202180047426.0A CN116234808B (zh) 2020-07-02 2021-07-01 具有抗菌活性的化合物
AU2021301264A AU2021301264A1 (en) 2020-07-02 2021-07-01 Compounds having antibacterial activity
EP21832744.3A EP4175953A4 (en) 2020-07-02 2021-07-01 COMPOUNDS HAVING ANTIBACTERIAL ACTIVITY

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202063047612P 2020-07-02 2020-07-02
US63/047,612 2020-07-02

Publications (1)

Publication Number Publication Date
WO2022006432A1 true WO2022006432A1 (en) 2022-01-06

Family

ID=79314944

Family Applications (2)

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PCT/US2021/040143 Ceased WO2022006432A1 (en) 2020-07-02 2021-07-01 Compounds having antibacterial activity
PCT/US2021/040171 Ceased WO2022006447A1 (en) 2020-07-02 2021-07-01 Compounds having anticancer activity

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/US2021/040171 Ceased WO2022006447A1 (en) 2020-07-02 2021-07-01 Compounds having anticancer activity

Country Status (7)

Country Link
US (2) US20230295164A1 (https=)
EP (2) EP4175953A4 (https=)
JP (2) JP2023535527A (https=)
CN (2) CN115867354B (https=)
AU (2) AU2021299504A1 (https=)
CA (2) CA3183770A1 (https=)
WO (2) WO2022006432A1 (https=)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118047780A (zh) * 2022-11-09 2024-05-17 中国医学科学院药物研究所 一类喹唑啉杂环化合物及其抗感染和抗肿瘤的应用
WO2024077235A3 (en) * 2022-10-07 2024-07-25 The Trustees Of Princeton University Dihydrofolate reductase inhibitors for anti-biotic resistant infections
EP4387733A4 (en) * 2021-08-17 2025-06-04 Southwest Research Institute CORONAVIRUS INHIBITORS

Families Citing this family (3)

* Cited by examiner, † Cited by third party
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CN119661535B (zh) * 2023-09-21 2026-03-20 中国医学科学院药物研究所 7H-吡咯并[3,2-f]喹唑啉衍生物及其抗感染应用
WO2025194625A1 (zh) * 2024-03-22 2025-09-25 深圳湾实验室坪山生物医药研发转化中心 结核病的预防与治疗
WO2025195460A1 (zh) * 2024-03-22 2025-09-25 深圳湾实验室坪山生物医药研发转化中心 稠环衍生物

Citations (4)

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US20020160963A1 (en) * 2001-02-23 2002-10-31 Maryanoff Bruce E. Aminomethyl-pyrroloquinazoline compounds as thrombin receptor antagonists
US20060094736A1 (en) * 2004-10-22 2006-05-04 Lin Ai J Synthesis and antimalarial activity of pyrrolo[3,2-f]quinazoline-1,3-diamine derivatives
US20140378486A1 (en) * 2013-06-20 2014-12-25 Oregon Health & Science University Pyrroloquinazoline compounds
US20170072014A1 (en) * 2014-05-11 2017-03-16 Tel Hashomer Medical Research Infrastructure And Services Ltd. Par-1 based therapeutic conjugates and uses thereof

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IE45427B1 (en) * 1976-07-09 1982-08-25 American Home Prod Pyrrold 3,2if quinazoline-1,3-diamine and related compounds
US4118561A (en) * 1977-04-06 1978-10-03 American Home Products Corporation 7-(Substituted)-7H-pyrrolo[3,2-f]quinazoline-1,3-diamines
US9920058B2 (en) * 2013-05-06 2018-03-20 Georgia Tech Research Corporation Molecules with potent DHFR binding affinity and antibacterial activity
US11077109B2 (en) * 2017-08-01 2021-08-03 The Trustees Of Princeton University Compounds having antibacterial activity and methods of use
US20210161900A1 (en) * 2018-04-30 2021-06-03 Duke University Compositions and methods for the treatment of senescent tumor cells
CN114514230A (zh) * 2019-08-20 2022-05-17 希望之城 Mettl16抑制剂及其用途

Patent Citations (4)

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US20020160963A1 (en) * 2001-02-23 2002-10-31 Maryanoff Bruce E. Aminomethyl-pyrroloquinazoline compounds as thrombin receptor antagonists
US20060094736A1 (en) * 2004-10-22 2006-05-04 Lin Ai J Synthesis and antimalarial activity of pyrrolo[3,2-f]quinazoline-1,3-diamine derivatives
US20140378486A1 (en) * 2013-06-20 2014-12-25 Oregon Health & Science University Pyrroloquinazoline compounds
US20170072014A1 (en) * 2014-05-11 2017-03-16 Tel Hashomer Medical Research Infrastructure And Services Ltd. Par-1 based therapeutic conjugates and uses thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE PUBCHEM COMPOUND 23 February 2016 (2016-02-23), ANONYMOUS : "7,8-Bis(prop-2-enyl)pyrrolo[3,2-f]quinazoline- 1,3-diamine", XP055897393, retrieved from PUBCHEM Database accession no. 118294432 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4387733A4 (en) * 2021-08-17 2025-06-04 Southwest Research Institute CORONAVIRUS INHIBITORS
WO2024077235A3 (en) * 2022-10-07 2024-07-25 The Trustees Of Princeton University Dihydrofolate reductase inhibitors for anti-biotic resistant infections
CN118047780A (zh) * 2022-11-09 2024-05-17 中国医学科学院药物研究所 一类喹唑啉杂环化合物及其抗感染和抗肿瘤的应用

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Publication number Publication date
EP4175958A1 (en) 2023-05-10
CA3183776A1 (en) 2022-01-06
JP2023532128A (ja) 2023-07-26
EP4175953A4 (en) 2024-08-14
CN115867354B (zh) 2025-08-26
CN116234808A (zh) 2023-06-06
AU2021301264A1 (en) 2023-02-02
EP4175953A1 (en) 2023-05-10
JP2023535527A (ja) 2023-08-17
US20230295164A1 (en) 2023-09-21
CN116234808B (zh) 2025-11-14
EP4175958A4 (en) 2024-07-17
WO2022006447A1 (en) 2022-01-06
US20230242540A1 (en) 2023-08-03
CN115867354A (zh) 2023-03-28
CA3183770A1 (en) 2022-01-06
AU2021299504A1 (en) 2023-02-02

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