WO2021195279A3 - Small molecule inhibitors of oncogenic chd1l with preclinical activity against colorectal cancer - Google Patents

Small molecule inhibitors of oncogenic chd1l with preclinical activity against colorectal cancer Download PDF

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Publication number
WO2021195279A3
WO2021195279A3 PCT/US2021/023981 US2021023981W WO2021195279A3 WO 2021195279 A3 WO2021195279 A3 WO 2021195279A3 US 2021023981 W US2021023981 W US 2021023981W WO 2021195279 A3 WO2021195279 A3 WO 2021195279A3
Authority
WO
WIPO (PCT)
Prior art keywords
chd1l
inhibitors
cancers
small molecule
driven
Prior art date
Application number
PCT/US2021/023981
Other languages
French (fr)
Other versions
WO2021195279A2 (en
Inventor
Daniel V. Labarbera
Joshua M. ABBOTT
Qiong ZHOU
Adedoyin D. ABRAHAM
Hector ESQUER
Brett Joseph PRIGARO
Original Assignee
The Regents Of The University Of Colorado, A Body Corporate
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
Application filed by The Regents Of The University Of Colorado, A Body Corporate filed Critical The Regents Of The University Of Colorado, A Body Corporate
Priority to CN202180037594.1A priority Critical patent/CN115667553A/en
Priority to AU2021244209A priority patent/AU2021244209A1/en
Priority to CA3172987A priority patent/CA3172987A1/en
Priority to EP21775064.5A priority patent/EP4127209A2/en
Priority to JP2022557840A priority patent/JP2023520330A/en
Publication of WO2021195279A2 publication Critical patent/WO2021195279A2/en
Publication of WO2021195279A3 publication Critical patent/WO2021195279A3/en
Priority to US17/953,221 priority patent/US20230103444A1/en

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Classifications

    • 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
    • C07D403/12—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 chain containing hetero atoms as chain links
    • 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
    • C07D239/02—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
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • 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

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Treatment of CHD1L-driven cancers, including TCF transcription-driven cancers and EMT-driven cancers using CHD1L inhibitors. Small molecule inhibitors of CHDL1 which inhibit CHD1L ATPase and inhibit CHD1L-dependent TCF-transcription have been identified. CHD1L inhibitors prevent the TCF-complex from binding to Wnt response elements and promoter sites. More specifically, CHD1L inhibitors induce the reversion of EMT. CHD1L inhibitors are useful in the treatment of various cancers and particularly CRC and m-CRC. The CHD1L-driven cancer is among others, CRC, breast cancer, glioma, liver cancer, lung cancer or gastrointestinal (GI) cancers. CHD1L inhibitors of formulas I and XX and salts thereof as defined herein are provided as well as pharmaceutical compositions containing CHD1L inhibitors. Synergistic combinations of CHD1L inhibitors with other antineoplastic agents are also described.
PCT/US2021/023981 2020-03-24 2021-03-24 Small molecule inhibitors of oncogenic chd1l with preclinical activity against colorectal cancer WO2021195279A2 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
CN202180037594.1A CN115667553A (en) 2020-03-24 2021-03-24 Small molecule inhibitors of oncogenic CHD1L with preclinical activity against colorectal cancer
AU2021244209A AU2021244209A1 (en) 2020-03-24 2021-03-24 Small molecule inhibitors of oncogenic CHD1L with preclinical activity against colorectal cancer
CA3172987A CA3172987A1 (en) 2020-03-24 2021-03-24 Small molecule inhibitors of oncogenic chd1l with preclinical activity against colorectal cancer
EP21775064.5A EP4127209A2 (en) 2020-03-24 2021-03-24 Small molecule inhibitors of oncogenic chd1l with preclinical activity against colorectal cancer
JP2022557840A JP2023520330A (en) 2020-03-24 2021-03-24 Small molecule inhibitor of oncogenic CHD1L with preclinical activity against colorectal cancer
US17/953,221 US20230103444A1 (en) 2020-03-24 2022-09-26 Small molecule inhibitors of oncogenic chd1l with preclinical activity against colorectal cancer

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202062994259P 2020-03-24 2020-03-24
US62/994,259 2020-03-24
US202163139394P 2021-01-20 2021-01-20
US63/139,394 2021-01-20

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US17/953,221 Continuation US20230103444A1 (en) 2020-03-24 2022-09-26 Small molecule inhibitors of oncogenic chd1l with preclinical activity against colorectal cancer

Publications (2)

Publication Number Publication Date
WO2021195279A2 WO2021195279A2 (en) 2021-09-30
WO2021195279A3 true WO2021195279A3 (en) 2021-11-11

Family

ID=77892666

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2021/023981 WO2021195279A2 (en) 2020-03-24 2021-03-24 Small molecule inhibitors of oncogenic chd1l with preclinical activity against colorectal cancer

Country Status (6)

Country Link
EP (1) EP4127209A2 (en)
JP (1) JP2023520330A (en)
CN (1) CN115667553A (en)
AU (1) AU2021244209A1 (en)
CA (1) CA3172987A1 (en)
WO (1) WO2021195279A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2022354855A1 (en) * 2021-09-30 2024-04-18 The Regents Of The University Of Colorado, A Body Corporate Small molecule inhibitors of oncogenic chd1l with preclinical activity against colorectral cancer
CN114457007B (en) * 2022-02-28 2024-05-28 合肥燃音生物科技有限公司 Uniform single organoid model based on micro-pore plate and preparation method thereof
WO2023213833A1 (en) * 2022-05-02 2023-11-09 Eisbach Bio Gmbh Use of alc1 inhibitors and synergy with parpi
CN115290774B (en) * 2022-07-21 2023-07-21 重庆医科大学 Application of uridine diphosphate glucuronic acid in preparation of reagent for detecting liver cancer

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140243403A1 (en) * 2011-06-03 2014-08-28 The General Hospital Corporation Treating colorectal, pancreatic, and lung cancer
US20190048424A1 (en) * 2013-06-19 2019-02-14 The Regents Of The University Of California Biomarkers of Response to Inhibition of Poly-ADP Ribose Polymerase (PARP) in Cancer

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140243403A1 (en) * 2011-06-03 2014-08-28 The General Hospital Corporation Treating colorectal, pancreatic, and lung cancer
US20190048424A1 (en) * 2013-06-19 2019-02-14 The Regents Of The University Of California Biomarkers of Response to Inhibition of Poly-ADP Ribose Polymerase (PARP) in Cancer

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ABBOTT ET AL.: "First-in-Class Inhibitors of Oncogenic CHD1L with Preclinical Activity against Colorectal Cancer", MOLECULAR CANCER THERAPEUTICS, vol. 19, 4 June 2020 (2020-06-04), pages 1598 - 1612, XP055970742 *
CHENG W. ET AL.: "CHD1 L: a novel oncogene", MOLECULAR CANCER, vol. 12, no. 1, 21 December 2013 (2013-12-21), pages 170, XP021176926 *
DATABASE Pubchem 18 October 2012 (2012-10-18), Database accession no. 60491642 *
LIU ET AL.: "CHD1L Promotes Lineage Reversionof Hepatocellular Carcinoma Through Opening Chromatin for Key Developmental Transcription Factors", HEPATOLOGY, vol. 63, no. 5, 11 January 2016 (2016-01-11), pages 1544 - 1559, XP071562695 *

Also Published As

Publication number Publication date
CN115667553A (en) 2023-01-31
EP4127209A2 (en) 2023-02-08
AU2021244209A1 (en) 2022-11-03
CA3172987A1 (en) 2021-09-30
JP2023520330A (en) 2023-05-17
WO2021195279A2 (en) 2021-09-30

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