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MX2023002134A - Cereblon ligands and bifunctional compounds comprising the same. - Google Patents

Cereblon ligands and bifunctional compounds comprising the same.

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Publication number
MX2023002134A
MX2023002134A MX2023002134A MX2023002134A MX2023002134A MX 2023002134 A MX2023002134 A MX 2023002134A MX 2023002134 A MX2023002134 A MX 2023002134A MX 2023002134 A MX2023002134 A MX 2023002134A MX 2023002134 A MX2023002134 A MX 2023002134A
Authority
MX
Mexico
Prior art keywords
compounds
cereblon
bifunctional compounds
ligase
same
Prior art date
Application number
MX2023002134A
Other languages
Spanish (es)
Inventor
Craig M Crews
Kurt Zimmermann
Andrew P Crew
Hanqing Dong
Keith R Hornberger
Michael Berlin
Jing Wang
Yimin Qian
Lawrence B Snyder
Original Assignee
Arvinas Operations Inc
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 claimed from US15/953,108 external-priority patent/US20180228907A1/en
Application filed by Arvinas Operations Inc filed Critical Arvinas Operations Inc
Publication of MX2023002134A publication Critical patent/MX2023002134A/en

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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
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    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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    • 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
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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Abstract

La descripción se refiere a compuestos de unión a la ligasa E3 cereblon, que incluyen compuestos bifuncionales que los comprenden, que son útiles como moduladores de ubiquitinación dirigida, especialmente, inhibidores de una variedad de polipéptidos y otras proteínas, que se degradan y/o inhiben de otro modo mediante compuestos bifuncionales, de acuerdo con la presente descripción. En particular, la descripción proporciona compuestos que contienen en un extremo un ligando que se une a la ubiquitina ligasa E3 cereblon, y en el otro extremo un resto que se une a una proteína diana de modo que la proteína diana se ubique cerca de la ubiquitina ligasa para efectuar la degradación (e inhibición) de esa proteína. Pueden sintetizarse compuestos que presentan una amplia gama de actividades farmacológicas coherentes con la degradación/inhibición de los polipéptidos diana de casi cualquier tipo.The disclosure relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising them, which are useful as modulators of targeted ubiquitination, especially, inhibitors of a variety of polypeptides and other proteins, which are degraded and/or inhibited. otherwise by bifunctional compounds, according to the present description. In particular, the disclosure provides compounds containing at one end a ligand that binds to the E3 ubiquitin ligase cereblon, and at the other end a moiety that binds to a target protein so that the target protein is located near the ubiquitin. ligase to effect the degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a wide range of pharmacological activities consistent with the degradation/inhibition of target polypeptides of almost any type.

MX2023002134A 2018-04-13 2020-10-07 Cereblon ligands and bifunctional compounds comprising the same. MX2023002134A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US15/953,108 US20180228907A1 (en) 2014-04-14 2018-04-13 Cereblon ligands and bifunctional compounds comprising the same

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JP (2) JP2021521192A (en)
KR (1) KR20210003804A (en)
CN (2) CN112262134B (en)
AU (2) AU2019251223A1 (en)
CA (1) CA3095912A1 (en)
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JP2021519337A (en) 2018-03-26 2021-08-10 シー４ セラピューティクス， インコーポレイテッド Cereblon binder for the degradation of Ikaras
EP3781156A4 (en) 2018-04-16 2022-05-18 C4 Therapeutics, Inc. SPIROCYCLIC COMPOUNDS
CN112566666A (en) 2018-05-14 2021-03-26 努瓦申生物公司 Compounds targeting anti-cancer nuclear hormone receptors
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CN120698985A (en) 2018-12-20 2025-09-26 C4医药公司 Targeted protein degradation
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