AR093404A1 - Compuestos macrociclicos que modulan la actividad de los inhibidores de la apoptosis - Google Patents

Compuestos macrociclicos que modulan la actividad de los inhibidores de la apoptosis

Info

Publication number
AR093404A1
AR093404A1 ARP130104096A ARP130104096A AR093404A1 AR 093404 A1 AR093404 A1 AR 093404A1 AR P130104096 A ARP130104096 A AR P130104096A AR P130104096 A ARP130104096 A AR P130104096A AR 093404 A1 AR093404 A1 AR 093404A1
Authority
AR
Argentina
Prior art keywords
independently
hydrogen
cycloalkyl
alkyl
compound
Prior art date
Application number
ARP130104096A
Other languages
English (en)
Inventor
M Borzilleri Robert
Zhang Yong
M Miller Michael
A Seigal Benjamin
Original Assignee
Bristol Myers Squibb Co
Ensemble Therapeutics Corp
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 Bristol Myers Squibb Co, Ensemble Therapeutics Corp filed Critical Bristol Myers Squibb Co
Publication of AR093404A1 publication Critical patent/AR093404A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • 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
    • 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
    • C07D471/08—Bridged systems
    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/18—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/18—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/50—Cyclic peptides containing at least one abnormal peptide link
    • C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
    • C07K7/56—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation not occurring through 2,4-diamino-butanoic acid

Abstract

Compuestos que modulan la actividad de los inhibidores de la actividad de la apoptosis (IAP), composiciones farmacéuticas que contienen esos compuestos y métodos para tratar trastornos proliferativos y trastornos de apoptosis desregulada, tal como cáncer, mediante el uso de los compuestos de la presente. Reivindicación 1: Un compuesto caracterizado por la fórmula (1) o una sal de aquel aceptable desde el punto de vista farmacéutico, en donde cada n es independientemente 1 ó 2; cada R¹ es independientemente hidrógeno, alquilo C₁₋₄ opcionalmente sustituido, cicloalquilo, hidroxialquilo, heterociclilo o -(alquileno C₁₋₄)-R⁴, en donde cada R⁴ es independientemente hidrógeno, -COOH, arilo, heteroarilo o cicloalquilo, y en donde al menos un R¹ no es hidrógeno; y cada R² es hidrógeno; o R¹ y R² se toman en forma conjunta con el átomo de carbono al que se unen habitualmente para formar un cicloalquilo; cada R⁶ es independientemente -(alquileno C₁₋₄)-R⁹, en donde cada R⁹ se selecciona independientemente de hidrógeno, arilo, heteroarilo y cicloalquilo; en donde cualquier porción arilo, heteroarilo o cicloalquilo de R⁶ se sustituye opcionalmente con hasta dos sustituyentes seleccionados independientemente de halo, CF₃, OH, alcoxi C₁₋₄, alquenil C₁₋₄oxi, fenilo, feniloxi y fenilmetiloxi; y en donde un -CH₂- en la porción -(alquileno C₁₋₄)- de R⁶ se reemplaza opcionalmente por -O-; cada R⁷ es independientemente alquilo C₁₋₄; cada R⁸ es independientemente alquilo C₁₋₄; cada X es independientemente un resto del grupo de fórmulas (2); cada uno de Z y Z es independientemente un resto seleccionado del grupo de fórmulas (3); en donde cada línea ondulada representa un punto de unión al compuesto; sin embargo, Z y Z no pueden ser ambos el resto de fórmula (4) en ningún compuesto determinado; cada Y es independientemente un compuesto del grupo de fórmulas (5) en donde: la línea ondulada 1 representa un punto de unión a una porción -C=O del compuesto; la línea ondulada 2 representa un punto de unión a una porción -NH del compuesto; la línea ondulada 3 representa un primer punto de unión a Z; la línea ondulada 4 representa un segundo punto de unión a Z; m = 0 - 3; n = 1 - 3, p = 0 - 4; y A es -C(O)R³ o un resto del grupo de fórmulas (6) (inclusive las diversas formas tautoméricas); R³ es OH, NHCN, NHSO₂R¹⁰, NHOR¹¹ o N(R¹²)(R¹³); R¹⁰ y R¹¹ son hidrógeno opcionalmente sustituido: -alquilo C₁₋₄, cicloalquilo, arilo, heteroarilo, heterociclilo o heterocicloalquilo; cada uno de R¹² y R¹³ se selecciona independientemente de hidrógeno, -alquilo C₁₋₄, -(alquilen C₁₋₄)-NH-(alquilo C₁₋₄) y -(alquilen C₁₋₄)-O-(hidroxialquilo C₁₋₄), o R¹² y R¹³ se toman en forma conjunta con el átomo de nitrógeno al que se unen habitualmente para formar un heterociclilo saturado que comprende, opcionalmente, otro heteroátomo seleccionado de N, O y S, y en donde el heterociclo saturado se sustituye opcionalmente con metilo.
ARP130104096A 2012-11-09 2013-11-07 Compuestos macrociclicos que modulan la actividad de los inhibidores de la apoptosis AR093404A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201261724579P 2012-11-09 2012-11-09

Publications (1)

Publication Number Publication Date
AR093404A1 true AR093404A1 (es) 2015-06-03

Family

ID=49620313

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP130104096A AR093404A1 (es) 2012-11-09 2013-11-07 Compuestos macrociclicos que modulan la actividad de los inhibidores de la apoptosis

Country Status (6)

Country Link
US (1) US20140135270A1 (es)
EP (1) EP2917218B1 (es)
AR (1) AR093404A1 (es)
CA (1) CA2930030A1 (es)
TW (1) TW201428002A (es)
WO (1) WO2014074658A1 (es)

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EP2776409B1 (en) * 2011-11-09 2016-02-03 Ensemble Therapeutics Corporation Macrocyclic compounds for inhibition of inhibitors of apoptosis
WO2014074665A1 (en) * 2012-11-09 2014-05-15 Bristol-Myers Squibb Company Macrocyclic compounds for inhibition of inhibitors of apoptosis
PT2968440T (pt) * 2013-03-15 2019-07-31 Zymeworks Inc Compostos citotóxicos e antimitóticos e métodos de utilização dos mesmos
GB201311891D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel compound
GB201311888D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel compounds
ES2916722T3 (es) 2013-12-27 2022-07-05 Zymeworks Inc Sistemas de enlace que contienen sulfonamida para conjugados de fármacos
WO2016079527A1 (en) 2014-11-19 2016-05-26 Tetralogic Birinapant Uk Ltd Combination therapy
WO2016097773A1 (en) 2014-12-19 2016-06-23 Children's Cancer Institute Therapeutic iap antagonists for treating proliferative disorders
KR20230119040A (ko) 2015-01-20 2023-08-14 아비나스 오퍼레이션스, 인코포레이티드 안드로겐 수용체의 표적화된 분해를 위한 화합물 및방법
US20170327469A1 (en) 2015-01-20 2017-11-16 Arvinas, Inc. Compounds and methods for the targeted degradation of androgen receptor
WO2016197114A1 (en) 2015-06-05 2016-12-08 Arvinas, Inc. Tank-binding kinase-1 protacs and associated methods of use
WO2017030814A1 (en) 2015-08-19 2017-02-23 Arvinas, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
PL3458101T3 (pl) 2016-05-20 2021-05-31 F. Hoffmann-La Roche Ag Koniugaty PROTAC-przeciwciało i sposoby ich stosowania
WO2018053302A1 (en) * 2016-09-19 2018-03-22 Ensemble Therapeutics Corporation Macrocyclic compounds for the inhibition of indoleamine-2,3-dioxygenase activity and use thereof
MX2019005007A (es) 2016-11-01 2019-07-18 Arvinas Inc Protac dirigidos a la proteína tau y métodos asociados de uso.
KR102173464B1 (ko) 2016-12-01 2020-11-04 아비나스 오퍼레이션스, 인코포레이티드 에스트로겐 수용체 분해제로서의 테트라히드로나프탈렌 및 테트라히드로이소퀴놀린 유도체
EP3559002A4 (en) 2016-12-23 2021-02-17 Arvinas Operations, Inc. CHEMERICAL MOLECULES TARGETING EGFR PROTEOLYSIS AND RELATED METHODS OF USE
EP3559006A4 (en) 2016-12-23 2021-03-03 Arvinas Operations, Inc. COMPOUNDS AND METHODS FOR TARGETED DEGRADATION OF FETAL LIVER KINASE POLYPEPTIDES
US11173211B2 (en) 2016-12-23 2021-11-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides
KR102564201B1 (ko) 2016-12-23 2023-08-07 아비나스 오퍼레이션스, 인코포레이티드 급속 진행성 섬유육종 폴리펩티드의 표적화 분해를 위한 화합물 및 방법
US11191741B2 (en) 2016-12-24 2021-12-07 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide
EP3573977A4 (en) 2017-01-26 2020-12-23 Arvinas Operations, Inc. EESTROGEN RECEPTOR PROTEOLYSIS MODULATORS AND RELATED METHOD OF USE
EP3710443A1 (en) 2017-11-17 2020-09-23 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of interleukin-1 receptor-associated kinase 4 polypeptides
EP3765026A4 (en) 2018-03-10 2021-12-22 Yale University BTK PROTEOLYSIS MODULATORS AND METHODS FOR USE
CA3095494C (en) 2018-04-04 2023-11-07 Arvinas Operations, Inc. Modulators of proteolysis and associated methods of use
US11639354B2 (en) 2018-07-31 2023-05-02 Fimecs, Inc. Heterocyclic compound
WO2020041331A1 (en) 2018-08-20 2020-02-27 Arvinas Operations, Inc. Proteolysis targeting chimeric (protac) compound with e3 ubiquitin ligase binding activity and targeting alpha-synuclein protein for treating neurodegenerative diseases
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EP2776409B1 (en) * 2011-11-09 2016-02-03 Ensemble Therapeutics Corporation Macrocyclic compounds for inhibition of inhibitors of apoptosis

Also Published As

Publication number Publication date
EP2917218A1 (en) 2015-09-16
EP2917218B1 (en) 2017-01-04
TW201428002A (zh) 2014-07-16
US20140135270A1 (en) 2014-05-15
CA2930030A1 (en) 2014-05-15
WO2014074658A1 (en) 2014-05-15

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