PE20190348A1 - Moduladores de la via de estres integrada - Google Patents

Moduladores de la via de estres integrada

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Publication number
PE20190348A1
PE20190348A1 PE2018002316A PE2018002316A PE20190348A1 PE 20190348 A1 PE20190348 A1 PE 20190348A1 PE 2018002316 A PE2018002316 A PE 2018002316A PE 2018002316 A PE2018002316 A PE 2018002316A PE 20190348 A1 PE20190348 A1 PE 20190348A1
Authority
PE
Peru
Prior art keywords
modulators
independently
compounds
integrated stress
isr
Prior art date
Application number
PE2018002316A
Other languages
English (en)
Inventor
Carmela Sidrauski
Marina Pliushchev
Jennifer M Frost
Lawrence A Black
Xiangdong Xu
Ramzi Farath Sweis
Lei Shi
Qinwei I Zhang
Yunsong Tong
Charles W Hutchins
Seungwon Chung
Michael J Dart
Original Assignee
Calico Life Sciences Llc
Abbvie 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
Application filed by Calico Life Sciences Llc, Abbvie Inc filed Critical Calico Life Sciences Llc
Publication of PE20190348A1 publication Critical patent/PE20190348A1/es

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    • 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
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    • 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
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    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/48—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring being part of a condensed ring system of the same carbon skeleton
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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    • C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
    • C07C311/12—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
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    • C07C311/23—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atoms of the sulfonamide groups bound to acyclic carbon atoms
    • C07C311/24—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atoms of the sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D213/66—One oxygen atom attached in position 3 or 5 having in position 3 an oxygen atom and in each of the positions 4 and 5 a carbon atom bound to an oxygen, sulphur, or nitrogen atom, e.g. pyridoxal
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    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07C2602/38—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing five carbon atoms
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    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
    • C07C2602/40—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing six carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
    • C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
    • C07C2602/44—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing eight carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/56—Ring systems containing bridged rings
    • C07C2603/90—Ring systems containing bridged rings containing more than four rings

Abstract

Referido a compuestos de Formula I o sus sales, solvatos, hidratos, tautomeros o estereoisomeros farmaceuticamente aceptables, los cuales son moduladores de la via de estres integrada (ISR). Estos compuestos de formula (I) se caracterizan porque: D es un cicloalquilo, monociclico en puente, heterociclo monociclico en puente o cubanilo, entre otros; L1 y L2 son independientemente, alquileno C1-C6, alquenileno C2-C6, entre otros; R1 y R2 son independientemente, H, alquilo C1-C6, alcoxi C1-C6, entre otros; A y W son independientemente fenilo, o heteroarilo de 5-6 miembros; t es 0 o 1. Entre los compuestos preferidos tenemos: 2-(4-cloro-3-fluorofenoxi)-N-{(2S)-4-[2-(4-clorofenoxi)acetamido]-2-hidroxibiciclo[2.2.2]octan-1-il}acetamida; 2-(3,4-dicloro-3-fluorofenoxi)-N-{3-[2-(piridin-2-il)acetamido]biciclo[1.1.1]pentan-1-il}acetamida; entre otros. Tambien se refiere a composiciones, metodos de produccion y su uso para modular la ISR y para tratar enfermedades, trastornos y afecciones relacionados como enfermedad neurodegenerativa, leucodistrofia, cancer, entre otros.
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Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112019025883A2 (pt) * 2017-06-07 2020-06-30 Glaxosmithkline Intellectual Property Development Limited compostos químicos como inibidores da via de atf4
BR112020000122A2 (pt) * 2017-07-03 2020-07-07 Glaxosmithkline Intellectual Property Development Limited derivados da n-(3-(2-(4-clorofenóxi)acetamido)biciclo[1.1.1] pentan-1-il)-2-ciclobutano-1-carboxamida e compostos relacionados como inibidores do atf4 para tratamento contra o câncer e outras doenças
MX2020001352A (es) * 2017-08-09 2020-03-20 Denali Therapeutics Inc Compuestos, composiciones y metodos.
UY37958A (es) * 2017-11-02 2019-05-31 Abbvie Inc Moduladores de la vía de estrés integrada
MX2020004557A (es) 2017-11-02 2020-10-05 Calico Life Sciences Llc Moduladores de la vía de estrés integrada.
UY37956A (es) * 2017-11-02 2019-05-31 Abbvie Inc Moduladores de la vía de estrés integrada
BR112020011914A2 (pt) 2017-12-13 2020-11-24 Praxis Biotech LLC inibidores de via de resposta de tensão integrada
EP3768660A1 (en) * 2018-03-23 2021-01-27 Denali Therapeutics Inc. Modulators of eukaryotic initiation factor 2
BR112020023115A2 (pt) 2018-06-05 2021-02-02 Praxis Biotech LLC inibidores da via integrada de resposta a tensão
TWI832295B (zh) * 2018-10-11 2024-02-11 美商嘉來克生命科學有限責任公司 整合應激路徑之前藥調節劑
CR20210426A (es) 2019-02-13 2021-09-30 Denali Therapeutics Inc Compuestos, composiciones y métodos
JP2022521605A (ja) * 2019-02-25 2022-04-11 プラクシス バイオテック エルエルシー 統合的ストレス応答経路の阻害剤
BR112021020402A2 (pt) 2019-04-23 2021-12-07 Evotec Int Gmbh Moduladores da via de resposta ao estresse integrada
EP3959210A1 (en) 2019-04-23 2022-03-02 Evotec International GmbH Modulators of the integrated stress response pathway
JP2022536663A (ja) 2019-06-12 2022-08-18 プラクシス バイオテック エルエルシー 統合的ストレス応答経路のモジュレーター
TW202128675A (zh) * 2019-12-06 2021-08-01 美商維泰克斯製藥公司 作為鈉通道調節劑之經取代四氫呋喃
US20230125481A1 (en) 2020-01-28 2023-04-27 Evotec International Gmbh Modulators of the integrated stress response pathway
IL296220A (en) 2020-03-11 2022-11-01 Evotec Int Gmbh Modulators for an integrated stress response pathway
US11351149B2 (en) 2020-09-03 2022-06-07 Pfizer Inc. Nitrile-containing antiviral compounds
JP2023546224A (ja) 2020-10-22 2023-11-01 エヴォテック・インターナショナル・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング 統合ストレス応答経路のモジュレーター
WO2022084448A1 (en) 2020-10-22 2022-04-28 Evotec International Gmbh Modulators of the integrated stress response pathway
KR20230110510A (ko) 2020-10-22 2023-07-24 에보텍 인터내셔널 게엠베하 통합 스트레스 반응 경로의 조절제
US20220184034A1 (en) * 2020-12-10 2022-06-16 Adgero Biopharmaceuticals Holdings, Inc. Methods for treating cutaneous metastatic cancers

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US162A (en) 1837-04-17 Island
US5212A (en) 1847-07-31 Richard m
US4911920A (en) 1986-07-30 1990-03-27 Alcon Laboratories, Inc. Sustained release, comfort formulation for glaucoma therapy
FR2588189B1 (fr) 1985-10-03 1988-12-02 Merck Sharp & Dohme Composition pharmaceutique de type a transition de phase liquide-gel
ATE141502T1 (de) 1991-01-15 1996-09-15 Alcon Lab Inc Verwendung von karrageenan in topischen ophthalmologischen zusammensetzungen
EP1706384A1 (en) * 2004-01-07 2006-10-04 AstraZeneca AB Therapeutic agents i
GB0400196D0 (en) * 2004-01-07 2004-02-11 Astrazeneca Ab Therapeutic agents
ATE553077T1 (de) 2004-07-23 2012-04-15 Nuada Llc Peptidaseinhibitoren
NZ566068A (en) 2005-08-08 2011-03-31 Argenta Discovery Ltd Bicyclo[2.2.1]hept-7-ylamine derivatives and their uses
GB0516314D0 (en) * 2005-08-08 2005-09-14 Argenta Discovery Ltd Compound
CN101917995A (zh) * 2007-09-25 2010-12-15 武田药品工业株式会社 Polo样激酶抑制剂
JP5765342B2 (ja) 2010-08-10 2015-08-19 アステラス製薬株式会社 へテロ環化合物
TWI538905B (zh) * 2010-12-22 2016-06-21 Ｈ 朗德貝克公司 雙環［３．２．１］辛基醯胺衍生物及其用途
JP6806562B2 (ja) * 2013-03-15 2021-01-06 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア ｅＩＦ２α経路の調節因子
US20160318856A1 (en) * 2013-09-11 2016-11-03 The Brigham And Women's Hospital, Inc. Substituted Urea eIF2alpha Kinase Activators

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