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 apoptosisInfo
- 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
Links
- 150000001875 compounds Chemical class 0.000 title abstract 10
- 230000000694 effects Effects 0.000 title abstract 3
- 229940088872 Apoptosis inhibitor Drugs 0.000 title 1
- 239000000158 apoptosis inhibitor Substances 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 7
- 239000001257 hydrogen Substances 0.000 abstract 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 6
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 6
- 125000002947 alkylene group Chemical group 0.000 abstract 5
- 125000003118 aryl group Chemical group 0.000 abstract 4
- 125000001072 heteroaryl group Chemical group 0.000 abstract 4
- 125000000623 heterocyclic group Chemical group 0.000 abstract 4
- 230000006907 apoptotic process Effects 0.000 abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 2
- 208000035475 disorder Diseases 0.000 abstract 2
- -1 phenyloxy Chemical group 0.000 abstract 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 abstract 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- 230000002074 deregulated effect Effects 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 abstract 1
- 125000005842 heteroatom Chemical group 0.000 abstract 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 1
- 230000002062 proliferating effect Effects 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- 229910052717 sulfur Inorganic materials 0.000 abstract 1
Classifications
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- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (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
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.
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) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140309265A1 (en) * | 2011-11-09 | 2014-10-16 | Ensemble Therapeutics | Macrocyclic compounds for inhibition of inhibitors of apoptosis |
| EP2917228A1 (en) * | 2012-11-09 | 2015-09-16 | Ensemble Therapeutics Corporation | Macrocyclic compounds for inhibition of inhibitors of apoptosis |
| TR201911139T4 (tr) | 2013-03-15 | 2019-08-21 | Zymeworks Inc | Sitotoksik ve anti-mitotik bileşikler ve bunları kullanmanın yöntemleri. |
| 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 |
| CN106255513B (zh) | 2013-12-27 | 2022-01-14 | 酵活有限公司 | 用于药物偶联物的含磺酰胺连接系统 |
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| 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 |
| WO2016118666A1 (en) | 2015-01-20 | 2016-07-28 | Arvinas, Inc. | Compounds and methods for the targeted degradation of the androgen receptor |
| US12312316B2 (en) | 2015-01-20 | 2025-05-27 | Arvinas Operations, 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 |
| ES2858151T3 (es) | 2016-05-20 | 2021-09-29 | Hoffmann La Roche | Conjugados de PROTAC-anticuerpo y procedimientos de uso |
| 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 |
| KR102570992B1 (ko) | 2016-11-01 | 2023-08-28 | 아비나스 오퍼레이션스, 인코포레이티드 | 타우(Tau)-단백질 표적화 프로탁(PROTAC) 및 관련 사용 방법 |
| CN110291087B (zh) | 2016-12-01 | 2024-07-09 | 阿尔维纳斯运营股份有限公司 | 作为雌激素受体降解剂的四氢萘和四氢异喹啉衍生物 |
| EP3559006A4 (en) | 2016-12-23 | 2021-03-03 | Arvinas Operations, Inc. | COMPOUNDS AND METHODS FOR TARGETED DEGRADATION OF F TAL LIVER KINASE POLYPEPTIDES |
| WO2018119441A1 (en) | 2016-12-23 | 2018-06-28 | Arvinas, Inc. | Egfr proteolysis targeting chimeric molecules and associated methods of use |
| US10723717B2 (en) | 2016-12-23 | 2020-07-28 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides |
| US11173211B2 (en) | 2016-12-23 | 2021-11-16 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides |
| 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 |
| US10604506B2 (en) | 2017-01-26 | 2020-03-31 | Arvinas Operations, Inc. | Modulators of estrogen receptor proteolysis and associated methods 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 |
| US11028088B2 (en) | 2018-03-10 | 2021-06-08 | Yale University | Modulators of BTK proteolysis and methods of use |
| CN112218859B (zh) | 2018-04-04 | 2024-10-29 | 阿尔维纳斯运营股份有限公司 | 蛋白水解调节剂及相关使用方法 |
| JP7515175B2 (ja) | 2018-07-31 | 2024-07-12 | ファイメクス株式会社 | 複素環化合物 |
| CN112912376A (zh) | 2018-08-20 | 2021-06-04 | 阿尔维纳斯运营股份有限公司 | 用于治疗神经变性疾病的具有E3泛素连接酶结合活性并靶向α-突触核蛋白的蛋白水解靶向嵌合(PROTAC)化合物 |
| CN119954801A (zh) | 2019-07-17 | 2025-05-09 | 阿尔维纳斯运营股份有限公司 | Tau蛋白靶向化合物及相关使用方法 |
| US20220402935A1 (en) | 2019-07-31 | 2022-12-22 | Fimecs, Inc. | Heterocyclic compound |
| WO2021026349A1 (en) | 2019-08-08 | 2021-02-11 | Institute For Cancer Research D/B/A The Research Institute Of Fox Chase Cancer Center | Combination therapy for treatment of cancer |
| KR20220054347A (ko) | 2019-08-26 | 2022-05-02 | 아비나스 오퍼레이션스, 인코포레이티드 | 에스트로겐 수용체 분해제로서의 테트라히드로나프탈렌 유도체로 유방암을 치료하는 방법 |
| WO2022047145A1 (en) | 2020-08-28 | 2022-03-03 | Arvinas Operations, Inc. | Rapidly accelerating fibrosarcoma protein degrading compounds and associated methods of use |
| AR123492A1 (es) | 2020-09-14 | 2022-12-07 | Arvinas Operations Inc | Formas cristalinas y amorfas de un compuesto para la degradación dirigida del receptor de estrógeno |
| WO2023056069A1 (en) | 2021-09-30 | 2023-04-06 | Angiex, Inc. | Degrader-antibody conjugates and methods of using same |
| WO2024054591A1 (en) | 2022-09-07 | 2024-03-14 | Arvinas Operations, Inc. | Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use |
| IL322247A (en) | 2023-01-26 | 2025-09-01 | Arvinas Operations Inc | Cerebellon-based KRAS-disrupting proteins and related uses |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5230865B2 (ja) * | 2004-07-15 | 2013-07-10 | テトラロジック ファーマシューティカルズ コーポレーション | Ｉａｐ結合性化合物 |
| US7517906B2 (en) * | 2005-02-25 | 2009-04-14 | Tetralogic Pharmaceuticals Corporation | Dimeric IAP inhibitors |
| US8338565B2 (en) * | 2008-08-20 | 2012-12-25 | Ensemble Therapeutics Corporation | Macrocyclic compounds for inhibition of tumor necrosis factor alpha |
| MX2011006244A (es) * | 2008-12-10 | 2011-06-27 | Achillion Pharmaceuticals Inc | Nuevos peptidos de 4-amino-4-oxobutanoilo como inhibidores de replica viral. |
| UY33236A (es) * | 2010-02-25 | 2011-09-30 | Novartis Ag | Inhibidores dimericos de las iap |
| US20140309265A1 (en) * | 2011-11-09 | 2014-10-16 | Ensemble Therapeutics | Macrocyclic compounds for inhibition of inhibitors of apoptosis |
-
2013
- 2013-11-07 WO PCT/US2013/068834 patent/WO2014074658A1/en not_active Ceased
- 2013-11-07 AR ARP130104096A patent/AR093404A1/es unknown
- 2013-11-07 EP EP13792833.9A patent/EP2917218B1/en not_active Not-in-force
- 2013-11-07 US US14/074,062 patent/US20140135270A1/en not_active Abandoned
- 2013-11-07 TW TW102140573A patent/TW201428002A/zh unknown
- 2013-11-07 CA CA2930030A patent/CA2930030A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20140135270A1 (en) | 2014-05-15 |
| CA2930030A1 (en) | 2014-05-15 |
| EP2917218B1 (en) | 2017-01-04 |
| TW201428002A (zh) | 2014-07-16 |
| WO2014074658A1 (en) | 2014-05-15 |
| EP2917218A1 (en) | 2015-09-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FB | Suspension of granting procedure |