WO2020051564A1 - Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides - Google Patents

Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides Download PDF

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Publication number
WO2020051564A1
WO2020051564A1 PCT/US2019/050114 US2019050114W WO2020051564A1 WO 2020051564 A1 WO2020051564 A1 WO 2020051564A1 US 2019050114 W US2019050114 W US 2019050114W WO 2020051564 A1 WO2020051564 A1 WO 2020051564A1
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WIPO (PCT)
Prior art keywords
optionally substituted
alkyl
group
ulm
substituted
Prior art date
Application number
PCT/US2019/050114
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English (en)
French (fr)
Inventor
Andrew P. Crew
Keith R. Hornberger
Jing Wang
Craig M. Crews
Saul Jaime-Figueroa
Hanqing Dong
Yimin Qian
Kurt Zimmerman
Original Assignee
Arvinas Operations, Inc.
Yale University
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.)
Filing date
Publication date
Priority to KR1020217009937A priority Critical patent/KR102642203B1/ko
Priority to CA3109981A priority patent/CA3109981A1/en
Priority to MX2021002559A priority patent/MX2021002559A/es
Priority to EP19773614.3A priority patent/EP3846907A1/en
Priority to JP2021512854A priority patent/JP2022500368A/ja
Priority to AU2019335516A priority patent/AU2019335516B2/en
Application filed by Arvinas Operations, Inc., Yale University filed Critical Arvinas Operations, Inc.
Priority to KR1020247005115A priority patent/KR20240028539A/ko
Priority to CN201980073600.1A priority patent/CN113164775A/zh
Publication of WO2020051564A1 publication Critical patent/WO2020051564A1/en
Priority to IL281188A priority patent/IL281188A/en
Priority to AU2022228150A priority patent/AU2022228150A1/en
Priority to JP2023127233A priority patent/JP2023159166A/ja

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero 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
    • A61K31/435—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
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • 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
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • 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
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
PCT/US2019/050114 2018-09-07 2019-09-07 Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides WO2020051564A1 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
CA3109981A CA3109981A1 (en) 2018-09-07 2019-09-07 Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides
MX2021002559A MX2021002559A (es) 2018-09-07 2019-09-07 Compuestos policiclicos y metodos para la degradacion dirigida de polipeptidos de fibrosarcoma rapidamente acelerado.
EP19773614.3A EP3846907A1 (en) 2018-09-07 2019-09-07 Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides
JP2021512854A JP2022500368A (ja) 2018-09-07 2019-09-07 急速進行性線維肉腫ポリペプチドの標的分解のための多環式化合物および方法
AU2019335516A AU2019335516B2 (en) 2018-09-07 2019-09-07 Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides
KR1020217009937A KR102642203B1 (ko) 2018-09-07 2019-09-07 급속 진행형 섬유육종 폴리펩티드의 표적화 분해를 위한 다중 고리 화합물 및 방법
KR1020247005115A KR20240028539A (ko) 2018-09-07 2019-09-07 급속 진행형 섬유육종 폴리펩티드의 표적화 분해를 위한 다중 고리 화합물 및 방법
CN201980073600.1A CN113164775A (zh) 2018-09-07 2019-09-07 用于迅速加速性纤维肉瘤多肽的靶向降解的多环化合物和方法
IL281188A IL281188A (en) 2018-09-07 2021-03-02 Polycyclic compounds and methods for targeted reduction of rapidly accelerating fibrosarcoma polypeptides
AU2022228150A AU2022228150A1 (en) 2018-09-07 2022-09-08 Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides
JP2023127233A JP2023159166A (ja) 2018-09-07 2023-08-03 急速進行性線維肉腫ポリペプチドの標的分解のための多環式化合物および方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862728581P 2018-09-07 2018-09-07
US62/728,581 2018-09-07

Publications (1)

Publication Number Publication Date
WO2020051564A1 true WO2020051564A1 (en) 2020-03-12

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2019/050114 WO2020051564A1 (en) 2018-09-07 2019-09-07 Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides

Country Status (9)

Country Link
EP (1) EP3846907A1 (ko)
JP (2) JP2022500368A (ko)
KR (2) KR20240028539A (ko)
CN (1) CN113164775A (ko)
AU (2) AU2019335516B2 (ko)
CA (1) CA3109981A1 (ko)
IL (1) IL281188A (ko)
MX (1) MX2021002559A (ko)
WO (1) WO2020051564A1 (ko)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021126974A1 (en) * 2019-12-17 2021-06-24 Orionis Biosciences, Inc. Bifunctional agents for protein recruitment and/or degradation
WO2021201036A1 (ja) * 2020-03-31 2021-10-07 田辺三菱製薬株式会社 ヒドロキシピロリジン誘導体およびその医薬用途
WO2021255212A1 (en) 2020-06-19 2021-12-23 F. Hoffmann-La Roche Ag Braf degraders
WO2021255213A1 (en) * 2020-06-19 2021-12-23 F. Hoffmann-La Roche Ag Heterobifunctional compounds as degraders of braf
WO2022047145A1 (en) * 2020-08-28 2022-03-03 Arvinas Operations, Inc. Rapidly accelerating fibrosarcoma protein degrading compounds and associated methods of use
US11524949B2 (en) 2017-11-16 2022-12-13 C4 Therapeutics, Inc. Degraders and Degrons for targeted protein degradation
WO2022266206A1 (en) * 2021-06-16 2022-12-22 Erasca, Inc. Kras inhibitor conjugates
WO2022270994A1 (ko) 2021-06-25 2022-12-29 한국화학연구원 유비퀴틴 프로테오좀 경로를 통해 비티케이 분해작용을 가지는 신규한 이작용성 헤테로사이클릭 화합물과 이의 용도
US11584748B2 (en) 2018-04-16 2023-02-21 C4 Therapeutics, Inc. Spirocyclic compounds
WO2023023941A1 (en) * 2021-08-24 2023-03-02 Biofront Ltd (Cayman) Hpk1 degraders, compositions comprising the hpki degrader, and methods of using the same
US11753397B2 (en) 2018-03-26 2023-09-12 C4 Therapeutics, Inc. Cereblon binders for the degradation of ikaros
US11912682B2 (en) 2021-01-13 2024-02-27 Monte Rosa Therapeutics, Inc. Isoindolinone compounds
US11957759B1 (en) 2022-09-07 2024-04-16 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (RAF) degrading compounds and associated methods of use
WO2024089272A1 (en) * 2022-10-28 2024-05-02 Institut National De La Sante Et De La Recherche Medicale New inhibitors of phosphatidylinositol 3-kinase

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* Cited by examiner, † Cited by third party
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CA3235512A1 (en) * 2021-10-22 2023-04-27 Xiaobao Yang Crbn e3 ligase ligand compound, protein degrader developed based thereon and their applications
CN115894450B (zh) * 2021-11-30 2023-09-12 山东如至生物医药科技有限公司 一种新型多环类化合物及其组合物和用途
WO2023098656A1 (en) * 2021-11-30 2023-06-08 Beigene, Ltd. Compounds for the degradation of egfr kinase
CN115806503A (zh) * 2022-12-02 2023-03-17 中国海洋大学 一种选择性组蛋白去乙酰化酶抑制剂及其制备方法和应用

Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006069063A1 (en) 2004-12-20 2006-06-29 Genentech, Inc. Pyrrolidine inhibitors of iap
US7244851B2 (en) 2004-07-02 2007-07-17 Genentech, Inc. Inhibitors of IAP
WO2007101347A1 (en) 2006-03-07 2007-09-13 Aegera Therapeutics Inc. Bir domain binding compounds
WO2008014236A1 (en) 2006-07-24 2008-01-31 Tetralogic Pharmaceuticals Corporation Dimeric iap inhibitors
US7345081B2 (en) 2004-03-23 2008-03-18 Genentech, Inc. Azabicyclo-octane inhibitors of IAP
US7419975B2 (en) 2004-04-07 2008-09-02 Novartis Ag Organic compounds
WO2008128171A2 (en) 2007-04-13 2008-10-23 The Regents Of The University Of Michigan Diazo bicyclic smac mimetics and the uses thereof
US20080269140A1 (en) 2004-01-16 2008-10-30 The Regents Of The University Of Michigan Conformationally Constrained Smac Mimetics and the Uses Thereof
WO2013071039A1 (en) 2011-11-09 2013-05-16 Ensemble Therapeutics Macrocyclic compounds for inhibition of inhibitors of apoptosis
WO2014055461A1 (en) 2012-10-02 2014-04-10 Bristol-Myers Squibb Company Iap antagonists
US20140302523A1 (en) 2010-12-07 2014-10-09 Yale University Small-Molecule Hydrophobic Tagging of Fusion Proteins and Induced Degradation of Same
US20140356322A1 (en) 2012-01-12 2014-12-04 Yale University Compounds & Methods for the Enhanced Degradation of Targeted Proteins & Other Polypeptides by an E3 Ubiquitin Ligase
WO2015006524A1 (en) 2013-07-12 2015-01-15 Bristol-Myers Squibb Company Iap antagonists
US20150291562A1 (en) 2014-04-14 2015-10-15 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
US20160058872A1 (en) 2014-04-14 2016-03-03 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
US20160272639A1 (en) 2015-03-18 2016-09-22 Arvinas, Inc. Compounds and methods for the enhanced degradation of targeted proteins
US20180179183A1 (en) * 2016-12-23 2018-06-28 Arvinas, Inc. Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201504314D0 (en) * 2015-03-13 2015-04-29 Univ Dundee Small molecules
EP3544957A4 (en) * 2016-11-22 2020-09-02 Dana-Farber Cancer Institute, Inc. KINASE PROTEIN DEGRADATION BY CONJUGATION OF KINASE PROTEIN INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE

Patent Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080269140A1 (en) 2004-01-16 2008-10-30 The Regents Of The University Of Michigan Conformationally Constrained Smac Mimetics and the Uses Thereof
US7345081B2 (en) 2004-03-23 2008-03-18 Genentech, Inc. Azabicyclo-octane inhibitors of IAP
US7419975B2 (en) 2004-04-07 2008-09-02 Novartis Ag Organic compounds
US7244851B2 (en) 2004-07-02 2007-07-17 Genentech, Inc. Inhibitors of IAP
WO2006069063A1 (en) 2004-12-20 2006-06-29 Genentech, Inc. Pyrrolidine inhibitors of iap
WO2007101347A1 (en) 2006-03-07 2007-09-13 Aegera Therapeutics Inc. Bir domain binding compounds
WO2008014236A1 (en) 2006-07-24 2008-01-31 Tetralogic Pharmaceuticals Corporation Dimeric iap inhibitors
WO2008128171A2 (en) 2007-04-13 2008-10-23 The Regents Of The University Of Michigan Diazo bicyclic smac mimetics and the uses thereof
US20140302523A1 (en) 2010-12-07 2014-10-09 Yale University Small-Molecule Hydrophobic Tagging of Fusion Proteins and Induced Degradation of Same
WO2013071039A1 (en) 2011-11-09 2013-05-16 Ensemble Therapeutics Macrocyclic compounds for inhibition of inhibitors of apoptosis
US20140356322A1 (en) 2012-01-12 2014-12-04 Yale University Compounds & Methods for the Enhanced Degradation of Targeted Proteins & Other Polypeptides by an E3 Ubiquitin Ligase
WO2014055461A1 (en) 2012-10-02 2014-04-10 Bristol-Myers Squibb Company Iap antagonists
WO2015006524A1 (en) 2013-07-12 2015-01-15 Bristol-Myers Squibb Company Iap antagonists
US20150291562A1 (en) 2014-04-14 2015-10-15 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
US20160058872A1 (en) 2014-04-14 2016-03-03 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
US20160272639A1 (en) 2015-03-18 2016-09-22 Arvinas, Inc. Compounds and methods for the enhanced degradation of targeted proteins
US20180179183A1 (en) * 2016-12-23 2018-06-28 Arvinas, Inc. Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides

Non-Patent Citations (26)

* Cited by examiner, † Cited by third party
Title
A. J. LEVINE ET AL., GENES DEV., vol. 7, 1993, pages 1126 - 1132
A. J. LEVINE ET AL., NATURE, vol. 408, 2000, pages 307 - 310
A. VAZQUEZ ET AL., NAT. REV. DRUG. DIS., vol. 7, 2008, pages 979 - 982
ARDECKY, RJ ET AL.: "Design, sysnthesis and evaluation of inhibitor of apoptosis (IAP) antagonists that are highly selective for the BIR2 domain of XIAP", BIOORG. MED. CHEM., vol. 23, no. 14, 2013, pages 4253 - 7, XP028573314, doi:10.1016/j.bmcl.2013.04.096
ASANO, M ET AL.: "Design, sterioselective synthesis, and biological evaluation of novel tri-cyclic compounds as inhibitor of apoptosis proteins (IAP) antagonists", BIOORG. MED. CHEM., vol. 21, no. 18, 2013, pages 5725 - 37, XP028693346, doi:10.1016/j.bmc.2013.07.020
COHEN, F ET AL.: "Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold", J. MED. CHEM., vol. 52, no. 6, 2009, pages 1723 - 30
COHEN, F. ET AL.: "Antogonists of inhibitors of apoptosis proteins based on thiazole amide isosteres", BIOORG. MED. CHEM. LETT., vol. 20, no. 7, 2010, pages 2229 - 33
COHEN, F. ET AL.: "Antogonists of inhibitors of apoptosis proteins based on thiazole amide isosteres", BIOORG. MED. CHEM., vol. 20, no. 7, 2010, pages 2229 - 33
FLYGARE, J.A. ET AL.: "Small-molecule pan-IAP antagonists: a patent review", EXPERT OPIN. THER. PAT., vol. 20, no. 2, 2010, pages 251 - 67, XP009140763
FLYGARE, J.A. ET AL.: "Small-molecule pan-IAP antagonists: a patent review", EXPERT OPIN. THER. PAT.,, vol. 20, no. 2, 2010, pages 251 - 67, XP009140763
HENNESSY, EJ ET AL.: "Discovery of aminopiperidine-based Smac mimetics as IAP antagonists", BIOORG. MED. CHEM. LETT., vol. 22, no. 4, 2012, pages 1960 - 4, XP055160024, doi:10.1016/j.bmcl.2011.12.109
HIRD, AW ET AL.: "Structure-based design and synthesis of tricyclic IAP (Inhibitors of Apoptosis Proteins) inhibitors", BIOORG. MED. CHEM. LETT., vol. 24, no. 7, 2014, pages 1820 - 4, XP028835153, doi:10.1016/j.bmcl.2014.02.016
J. DI ET AL., CURRENT CANCER DRUG TARGETS, vol. 11, no. 8, 2011, pages 987 - 994
J. MOMAND ET AL., CELL, vol. 69, 1992, pages 1237 - 1245
J. ROTH ET AL., EMBO J., vol. 17, 1998, pages 554 - 564
KIM, KS: "Discovery of tetrahydroisoquinolinebased bivalent heterodimeric IAP antagonists", BIOORG. MED. CHEM. LETT., vol. 24, no. 21, 2014, pages 5022 - 9, XP029077480, doi:10.1016/j.bmcl.2014.09.022
M. HOLLSTEIN ET AL., SCIENCE, vol. 233, 1991, pages 49 - 53
MANNHOLD, R. ET AL.: "IAP antagonists: promising candidates for cancer therapy", DRUG DISCOV. TODAY, vol. 15, no. 5-6, 2010, pages 210 - 9, XP026946351, doi:10.1016/j.drudis.2010.01.003
NDUBAKU, C. ET AL.: "Antagonism of c-IAP and XIAP proteins is required for efficient induction of cell death by small-molecule IAP antagonists", ACS CHEM. BIOL., vol. 4, no. 7, 2009, pages 557 - 566, XP002658259, doi:10.1021/cb900083m
P. CHENE ET AL., NAT. REV. CANCER, vol. 3, 2003, pages 102 - 109
PEREZ HL: "Discovery of potent heterodimeric antagonists of inhibitor of apoptosis proteins (IAPs) with sustained antitumor activity", J. MED. CHEM., vol. 58, no. 3, 2015, pages 1556 - 62
SCHNEEKLOTH ET AL.: "Targeted intracellular protein degradation induced by a small molecule: En route to chemical proteomics", BIOORG. MED. CHEM. LETT., vol. 18, 2008, pages 5904 - 5908, XP025627166, doi:10.1016/j.bmcl.2008.07.114
VAMOS, M. ET AL.: "Expedient synthesis of highly potent antagonists of inhibitor of apoptosis proteins (IAPs) with unique selectivity for ML-IAP", ACS CHEM. BIOL., vol. 8, no. 4, 2013, pages 725 - 32, XP055282328, doi:10.1021/cb3005512
VASSILEV ET AL.: "In vivo activation of the p53 pathway by small-molecule antagonists of MDM2", SCIENCE, vol. 303, 2004, pages 844 - 848, XP002338500, doi:10.1126/science.1092472
WANG, J ET AL.: "Discovery of novel second mitochondrial-derived activator of caspase mimetics as selective inhibitor or apoptosis protein inhibitors", J. PHARMACOL. EXP. THER., vol. 349, no. 2, 2014, pages 319 - 29
Y. HAUPT ET AL., NATURE, vol. 387, 1997, pages 296 - 299

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WO2024089272A1 (en) * 2022-10-28 2024-05-02 Institut National De La Sante Et De La Recherche Medicale New inhibitors of phosphatidylinositol 3-kinase

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