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WO2009133560A1 - Dérivés de bis-(nucléotide monophosphate) cycliques non hydrolysables et perméables et leurs utilisations - Google Patents

Dérivés de bis-(nucléotide monophosphate) cycliques non hydrolysables et perméables et leurs utilisations Download PDF

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Publication number
WO2009133560A1
WO2009133560A1 PCT/IL2009/000456 IL2009000456W WO2009133560A1 WO 2009133560 A1 WO2009133560 A1 WO 2009133560A1 IL 2009000456 W IL2009000456 W IL 2009000456W WO 2009133560 A1 WO2009133560 A1 WO 2009133560A1
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WO
WIPO (PCT)
Prior art keywords
hydrocarbyl
compound
derivative
nucleotide monophosphate
identified
Prior art date
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PCT/IL2009/000456
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English (en)
Inventor
Raphael Mayer
Original Assignee
Smart Assays
Priority date (The priority date 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 date listed.)
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Publication of WO2009133560A1 publication Critical patent/WO2009133560A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
    • 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

Definitions

  • S. aureus is an important pathogen of humans, and biofilm formation is essential for its virulence and pathogenesis, as well as for its ability to resist antibiotic treatment. Moreover, its biofilm formation is strongly associated with BAP, an EAL protein likely to be a c- di-GMP phosphodiesterase (Lasa, 2006). Karaolis et at. demonstrated that extra- cellular addition of c-di-GMP showed activity against isolates of S. aureus, including methicillin resistant S. aureus (MRSA).
  • MRSA methicillin resistant S. aureus
  • R 2 is H, Ci-C 5 alkyl or absent
  • R 7 and R 8 each independently is H, halogen, O-hydrocarbyl, S-hydrocarbyl,
  • NR 1 ]R 12 heteroaryl, unsubstituted hydrocarbyl or hydrocarbyl substituted by halogen, CN, SCN, NO 2 , OR 11 , SR 11 , NR 11 R 12 or heteroaryl, wherein R 11 and R 12 each independently is H or hydrocarbyl or R 11 and R 12 together with the nitrogen atom to which they are attached form a 5- or 6-membered saturated heterocyclic ring optionally containing 1-2 further heteroatoms selected from oxygen, nitrogen or sulfur, the additional nitrogen being unsubstituted or substituted by alkyl substituted by halogen, hydroxyl or phenyl;
  • step a compound 8 (900 mg, 1.2 mmol) and phosphoramidite 9 (1.15 mg 1.2 mmol) were dissolved in acetonitrile (8 ml), powdered molsieves (3A, 400 mg) were added and the mixture was then stirred for 30 min. IMP (400 mg, 2.4 mmol) was added and the mixture was stirred for 1 h. 31 P-NMR analysis revealed complete conversion ( 31 P-NMR: ⁇ 139.8, 139.5 and 119.0 (broad) ppm). The mixture was diluted with EtOAc (50 ml) and filtered over glass filter.
  • step a a heterogeneous solution of phosphoramidite 30 (10.0 g, 10.3 mmol), powdery molsieves (3A 5 2.00 g) and allylalcohol (0.88 ml, 12.9 mmol) in acetonitrile (40 ml) was stirred for 30 min at room temperature under N 2 atmosphere. IMP (3.5 g, 20.75 mmol) was then added to the reaction mixture and stirring was continued for additional 30 min.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Communicable Diseases (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne de nouveaux dérivés de bis-(nucléotide monophosphate) cycliques non hydrolysables et perméables et des compositions pharmaceutiques les renfermant. Les dérivés de bis-(nucléotide monophosphate) cycliques de la présente invention sont utiles pour le traitement d’infections bactériennes, en particulier, pour la perturbation de la régulation bactérienne et/ou de la transduction bactérienne des signaux, la perturbation ou la réduction de la pathogénicité bactérienne et/ou la perturbation ou la réduction d’une activité associée à la pathogénicité bactérienne telle que la formation de biofilm.
PCT/IL2009/000456 2008-04-29 2009-04-30 Dérivés de bis-(nucléotide monophosphate) cycliques non hydrolysables et perméables et leurs utilisations WO2009133560A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US4871208P 2008-04-29 2008-04-29
US61/048,712 2008-04-29

Publications (1)

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WO2009133560A1 true WO2009133560A1 (fr) 2009-11-05

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Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103936805A (zh) * 2013-01-18 2014-07-23 昆山市工业技术研究院小核酸生物技术研究所有限责任公司 一种核苷酸和/或寡核苷酸及其制备方法
WO2014179335A1 (fr) 2013-04-29 2014-11-06 Memorial Sloan Kettering Cancer Center Compositions et procédés pour altérer la signalisation par un second messager
US9718848B2 (en) 2015-12-03 2017-08-01 Glaxosmithkline Intellectual Property Development Limited Compounds
US9724408B2 (en) 2013-05-18 2017-08-08 Aduro Biotech, Inc. Compositions and methods for activating stimulator of interferon gene-dependent signalling
US9770467B2 (en) 2012-06-08 2017-09-26 Aduro Biotech, Inc. Compositions and methods for cancer immunotherapy
US10047115B2 (en) 2015-01-29 2018-08-14 Glaxosmithkline Intellectual Property Development Limited Cyclic dinucleotides useful for the treatment of inter alia cancer
WO2018152450A1 (fr) 2017-02-17 2018-08-23 Eisai R&D Management Co., Ltd. Composés dinucléotidiques cycliques pour le traitement du cancer
US10176292B2 (en) 2013-07-31 2019-01-08 Memorial Sloan-Kettering Cancer Center STING crystals and modulators
WO2019043634A2 (fr) 2017-08-30 2019-03-07 Beijing Xuanyi Pharmasciences Co., Ltd. Di-nucléotides cycliques en tant que stimulateurs de modulateurs de gènes d'interféron
US10450341B2 (en) 2014-06-04 2019-10-22 Glaxosmithkline Intellectual Property Development Limited Cyclic di-nucleotides as modulators of STING
WO2019232392A1 (fr) 2018-06-01 2019-12-05 Eisai R&D Management Co., Ltd. Méthodes de traitement du cancer de la vessie
US10980825B2 (en) 2016-12-01 2021-04-20 Takeda Pharmaceutical Company Limited Cyclic dinucleotide
CN112867727A (zh) * 2018-10-12 2021-05-28 上海济煜医药科技有限公司 环二核苷酸类化合物及其应用
US11542293B2 (en) 2017-11-10 2023-01-03 Takeda Pharmaceutical Company Limited Sting modulator compounds, and methods of making and using
US11691990B2 (en) 2018-08-16 2023-07-04 Eisai R&D Management Co., Ltd Salts of compounds and crystals thereof
US11725024B2 (en) 2020-11-09 2023-08-15 Takeda Pharmaceutical Company Limited Antibody drug conjugates
US11787833B2 (en) 2019-05-09 2023-10-17 Aligos Therapeutics, Inc. Modified cyclic dinucleoside compounds as sting modulators
US11873319B2 (en) 2013-05-03 2024-01-16 The Regents Of The University Of California Cyclic di-nucleotide induction of type I interferon

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2257704A (en) * 1991-07-18 1993-01-20 Erba Carlo Spa Cyclic oligonucleotides phosphorothioates
WO2005030186A2 (fr) * 2003-07-28 2005-04-07 Univ Maryland Procede permettant d'attenuer la virulence d'agents pathogenes microbiens et d'inhiber la formation d'un biofilm microbien
WO2006045041A2 (fr) * 2004-10-18 2006-04-27 The Board Of Trustees Of The Leland Stanford Junior University Procede permettant de detruire un biofilm microbien et interference en physiologie cellulaire microbienne

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2257704A (en) * 1991-07-18 1993-01-20 Erba Carlo Spa Cyclic oligonucleotides phosphorothioates
WO2005030186A2 (fr) * 2003-07-28 2005-04-07 Univ Maryland Procede permettant d'attenuer la virulence d'agents pathogenes microbiens et d'inhiber la formation d'un biofilm microbien
WO2006045041A2 (fr) * 2004-10-18 2006-04-27 The Board Of Trustees Of The Leland Stanford Junior University Procede permettant de detruire un biofilm microbien et interference en physiologie cellulaire microbienne

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GUGA P ET AL: "Cyclization versus oligomerization of SP- and RP-5'-OH-N<4>-benzoyl-2'-deoxycytidine-3'-O-(2-thio-4,4-pentamethylen e-1,3,2-oxathiaphospholane)s", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 62, no. 11, 13 March 2006 (2006-03-13), pages 2698 - 2704, XP025001677, ISSN: 0040-4020, [retrieved on 20060313] *
HYODO M ET AL: "Synthesis of cyclic bis(3'-5')diguanylic acid (c-di-GMP) analogs", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 62, no. 13, 27 March 2006 (2006-03-27), pages 3089 - 3094, XP025001725, ISSN: 0040-4020, [retrieved on 20060327] *

Cited By (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9770467B2 (en) 2012-06-08 2017-09-26 Aduro Biotech, Inc. Compositions and methods for cancer immunotherapy
CN103936805B (zh) * 2013-01-18 2016-12-28 昆山市工业技术研究院小核酸生物技术研究所有限责任公司 一种核苷酸和/或寡核苷酸及其制备方法
CN103936805A (zh) * 2013-01-18 2014-07-23 昆山市工业技术研究院小核酸生物技术研究所有限责任公司 一种核苷酸和/或寡核苷酸及其制备方法
US10385091B2 (en) 2013-04-29 2019-08-20 Memorial Sloan Kettering Cancer Center Compositions and methods for altering second messenger signaling
EP2991655A4 (fr) * 2013-04-29 2017-01-04 Memorial Sloan Kettering Cancer Center Compositions et procédés pour altérer la signalisation par un second messager
JP2016524593A (ja) * 2013-04-29 2016-08-18 メモリアル スローン−ケタリング キャンサー センター セカンドメッセンジャーのシグナル伝達を変えるための組成物及び方法
US9840533B2 (en) 2013-04-29 2017-12-12 Memorial Sloan Kettering Cancer Center Compositions and methods for altering second messenger signaling
WO2014179335A1 (fr) 2013-04-29 2014-11-06 Memorial Sloan Kettering Cancer Center Compositions et procédés pour altérer la signalisation par un second messager
US11014956B2 (en) 2013-04-29 2021-05-25 Memorial Sloan Kettering Cancer Center; The Rockefeller Compositions and methods for altering second messenger signaling
AU2014260015B2 (en) * 2013-04-29 2019-11-14 Memorial Sloan Kettering Cancer Center Compositions and methods for altering second messenger signaling
EP4398254A3 (fr) * 2013-04-29 2024-10-23 Memorial Sloan Kettering Cancer Center Compositions et procédés pour modifier la signalisation d'un second messager
US10131686B2 (en) 2013-04-29 2018-11-20 Memorial Sloan Kettering Cancer Center Compositions and methods for altering second messenger signaling
US11873319B2 (en) 2013-05-03 2024-01-16 The Regents Of The University Of California Cyclic di-nucleotide induction of type I interferon
US10653774B2 (en) 2013-05-18 2020-05-19 Aduro Biotech, Inc. Compositions and methods for activating “stimulator of interferon gene”-dependent signalling
US9724408B2 (en) 2013-05-18 2017-08-08 Aduro Biotech, Inc. Compositions and methods for activating stimulator of interferon gene-dependent signalling
US10176292B2 (en) 2013-07-31 2019-01-08 Memorial Sloan-Kettering Cancer Center STING crystals and modulators
US10450341B2 (en) 2014-06-04 2019-10-22 Glaxosmithkline Intellectual Property Development Limited Cyclic di-nucleotides as modulators of STING
US10047115B2 (en) 2015-01-29 2018-08-14 Glaxosmithkline Intellectual Property Development Limited Cyclic dinucleotides useful for the treatment of inter alia cancer
US10364266B2 (en) 2015-12-03 2019-07-30 Glaxosmithkline Intellectual Property Development Limited Compounds
US9994607B2 (en) 2015-12-03 2018-06-12 Glaxosmithkline Intellectual Property Development Limited Compounds
US9718848B2 (en) 2015-12-03 2017-08-01 Glaxosmithkline Intellectual Property Development Limited Compounds
US10730907B2 (en) 2015-12-03 2020-08-04 Glaxosmithkline Intellectual Property Development Limited Compounds
US10980825B2 (en) 2016-12-01 2021-04-20 Takeda Pharmaceutical Company Limited Cyclic dinucleotide
US11666594B2 (en) 2016-12-01 2023-06-06 Takeda Pharmaceutical Company Limited Antibody-drug conjugates comprising a cyclic dinucleotide
US12171777B2 (en) 2016-12-01 2024-12-24 Takeda Pharmaceutical Company Limited Methods of making a cyclic dinucleotide
US10618930B2 (en) 2017-02-17 2020-04-14 Eisai R&D Management Co., Ltd. Compounds for the treatment of cancer
EP4008403A1 (fr) 2017-02-17 2022-06-08 Eisai R&D Management Co., Ltd. Composés pour le traitement du cancer
WO2018152450A1 (fr) 2017-02-17 2018-08-23 Eisai R&D Management Co., Ltd. Composés dinucléotidiques cycliques pour le traitement du cancer
WO2018152453A1 (fr) 2017-02-17 2018-08-23 Eisai R&D Management Co., Ltd. Dérivé de di-nucléotides cycliques pour le traitement du cancer
US10246480B2 (en) 2017-02-17 2019-04-02 Eisai R&D Management Co., Ltd. Compounds for the treatment of cancer
US11339188B2 (en) 2017-02-17 2022-05-24 Eisai R&D Management Co., Ltd. Compounds for the treatment of cancer
JP7311514B2 (ja) 2017-08-30 2023-07-19 ベイジン シュエンイー ファーマサイエンシズ カンパニー， リミテッド インターフェロン遺伝子刺激因子調節薬としての環状ジヌクレオチド
US11773132B2 (en) 2017-08-30 2023-10-03 Beijing Xuanyi Pharmasciences Co., Ltd. Cyclic di-nucleotides as stimulator of interferon genes modulators
JP2020532585A (ja) * 2017-08-30 2020-11-12 ベイジン シュエンイー ファーマサイエンシズ カンパニー， リミテッド インターフェロン遺伝子刺激因子調節薬としての環状ジヌクレオチド
WO2019043634A2 (fr) 2017-08-30 2019-03-07 Beijing Xuanyi Pharmasciences Co., Ltd. Di-nucléotides cycliques en tant que stimulateurs de modulateurs de gènes d'interféron
US11542293B2 (en) 2017-11-10 2023-01-03 Takeda Pharmaceutical Company Limited Sting modulator compounds, and methods of making and using
US12054512B2 (en) 2017-11-10 2024-08-06 Takeda Pharmaceutical Company Limited Sting modulator compounds, and methods of making and using
WO2019232392A1 (fr) 2018-06-01 2019-12-05 Eisai R&D Management Co., Ltd. Méthodes de traitement du cancer de la vessie
US11691990B2 (en) 2018-08-16 2023-07-04 Eisai R&D Management Co., Ltd Salts of compounds and crystals thereof
CN112867727B (zh) * 2018-10-12 2024-05-17 上海济煜医药科技有限公司 环二核苷酸类化合物及其应用
JP7492523B2 (ja) 2018-10-12 2024-05-29 シャンハイ ジェミンケア ファーマシューティカル カンパニー，リミティド 環状ジヌクレオチド化合物及びその使用
EP3868773A4 (fr) * 2018-10-12 2022-07-13 Shanghai Jemincare Pharmaceuticals Co., Ltd. Composé dinucléotide cyclique et ses applications
CN112867727A (zh) * 2018-10-12 2021-05-28 上海济煜医药科技有限公司 环二核苷酸类化合物及其应用
JP2022508786A (ja) * 2018-10-12 2022-01-19 シャンハイ ジェミンケア ファーマシューティカルズ カンパニー、リミテッド 環状ジヌクレオチド化合物及びその使用
US11787833B2 (en) 2019-05-09 2023-10-17 Aligos Therapeutics, Inc. Modified cyclic dinucleoside compounds as sting modulators
US11725024B2 (en) 2020-11-09 2023-08-15 Takeda Pharmaceutical Company Limited Antibody drug conjugates
US12221460B2 (en) 2020-11-09 2025-02-11 Takeda Pharmaceutical Company Limited Antibody drug conjugates

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