CO2017011183A2 - Inhibidores de indolamina-2,3-dioxigenasa composiciones que los contienen y métodos de preparación - Google Patents

Inhibidores de indolamina-2,3-dioxigenasa composiciones que los contienen y métodos de preparación

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Publication number
CO2017011183A2
CO2017011183A2 CONC2017/0011183A CO2017011183A CO2017011183A2 CO 2017011183 A2 CO2017011183 A2 CO 2017011183A2 CO 2017011183 A CO2017011183 A CO 2017011183A CO 2017011183 A2 CO2017011183 A2 CO 2017011183A2
Authority
CO
Colombia
Prior art keywords
indolamine
compositions containing
preparation methods
inhibitor compositions
dioxygenase inhibitor
Prior art date
Application number
CONC2017/0011183A
Other languages
English (en)
Inventor
Natesan Murugesan
Weiwei Guo
James Aaron Balog
Emily Charlotte Cherney
Audris Huang
Jay A Markwalder
Steven P Seitz
Weifang Shan
David K Williams
Susheel Jethanand Nara
Saumya Roy
Soodamani Thangavel
Ramesh Kumar Sistla
Srinivas Cheruku
Srinivasan Thangathirupathy
Yadagiri Kanyaboina
Nagalakshmi Pulicharla
Original Assignee
Bristol Myers Squibb Co
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=55702190&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CO2017011183(A2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of CO2017011183A2 publication Critical patent/CO2017011183A2/es

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    • C07—ORGANIC CHEMISTRY
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    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/40—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/42—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
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    • C07C275/40—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by nitrogen atoms not being part of nitro or nitroso groups
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    • A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
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Abstract

Se describen compuestos que modulan o inhiben la actividad enzimática de la indolamina 2,3-dioxigenasa (IDO), composiciones farmacéuticas que contienen els compuestos y métodos para tratar trastornos proliferativos, tales como cáncer, infecciones virales y/o trastornos inflamatorios que utilizan los compuestos de la invención.
CONC2017/0011183A 2015-04-03 2017-10-31 Inhibidores de indolamina-2,3-dioxigenasa composiciones que los contienen y métodos de preparación CO2017011183A2 (es)

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US201562142589P 2015-04-03 2015-04-03
PCT/US2016/025531 WO2016161269A1 (en) 2015-04-03 2016-04-01 Inhibitors of indoleamine 2,3-dioxygenase for the treatment of cancer

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Families Citing this family (40)

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Publication number Priority date Publication date Assignee Title
CR20200362A (es) 2014-02-13 2020-10-26 Incyte Corp CICLOPROPILAMINA COMO INHIBIDORES DE LA LSD1 (Divisional 2016-0395)
US9527835B2 (en) 2014-02-13 2016-12-27 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
HUE046273T2 (hu) 2014-02-13 2020-02-28 Incyte Corp Ciklopropilaminok mint LSD1 inhibitorok
TW201613925A (en) 2014-07-10 2016-04-16 Incyte Corp Imidazopyrazines as LSD1 inhibitors
US9695167B2 (en) 2014-07-10 2017-07-04 Incyte Corporation Substituted triazolo[1,5-a]pyridines and triazolo[1,5-a]pyrazines as LSD1 inhibitors
US9695168B2 (en) 2014-07-10 2017-07-04 Incyte Corporation Substituted imidazo[1,5-α]pyridines and imidazo[1,5-α]pyrazines as LSD1 inhibitors
US9944647B2 (en) 2015-04-03 2018-04-17 Incyte Corporation Heterocyclic compounds as LSD1 inhibitors
US10399932B2 (en) * 2015-04-03 2019-09-03 Bristol-Myers Squibb Company Inhibitors of indoleamine-2,3-dioxygenase for the treatment of cancer
JP7427363B2 (ja) 2015-08-12 2024-02-05 インサイト・ホールディングス・コーポレイション Ｌｓｄ１阻害剤の塩
RU2018112830A (ru) * 2015-09-24 2019-10-24 ГлаксоСмитКлайн Интеллекчуал Проперти (N2) Лимитед Модуляторы индоламин-2,3-диоксигеназы
WO2018116107A1 (en) * 2016-12-20 2018-06-28 Glaxosmithkline Intellectual Property Development Limited Modulators of indoleamine 2,3-dioxygenase
US10787442B2 (en) 2016-12-20 2020-09-29 Glaxosmithkline Intellectual Property Development Limited Modulators of indoleamine 2,3-dioxygenase
EP3559009B1 (en) 2016-12-22 2021-04-07 Calithera Biosciences, Inc. Compositions and methods for inhibiting arginase activity
US11173145B2 (en) 2017-01-17 2021-11-16 Board Of Regents, The University Of Texas System Compounds useful as inhibitors of indoleamine 2,3-dioxygenase and/or tryptophan dioxygenase
US20200188482A1 (en) * 2017-04-28 2020-06-18 The Brigham And Women`S Hospital, Inc. Targeting gamma-delta t cells in obesity and cachexia
JP2020518669A (ja) 2017-05-03 2020-06-25 ビバーチェ セラピューティクス，インク． 非縮合三環式化合物
WO2018219309A1 (zh) * 2017-06-02 2018-12-06 沈阳化工研究院有限公司 一种芳乙烯衍生物及其应用
BR112019027363A2 (pt) * 2017-06-28 2020-07-07 Glaxosmithkline Intellectual Property Development Limited composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, método para tratar uma doença ou condição, e, uso de um composto ou sal
CN107325019B (zh) * 2017-08-11 2019-11-22 石河子大学 芳胺基苯甲酰胺类化合物及n-芳基-芳胺基苯甲酰胺类化合物的制备方法
CN111542315B (zh) 2017-08-21 2023-05-12 维瓦斯治疗公司 苯并磺酰基化合物
US11180497B2 (en) * 2017-10-18 2021-11-23 Angex Pharmaceutical, Inc. Cyclic compounds as immunomodulating agents
CN109836356B (zh) * 2017-11-24 2022-03-08 沈阳化工研究院有限公司 一种芳甲醚衍生物及其应用
US11524943B1 (en) 2017-12-06 2022-12-13 Vivace Therapeutics, Inc. Benzocarbonyl compounds
WO2019136157A2 (en) 2018-01-05 2019-07-11 Dicerna Pharmaceuticals, Inc. Reducing beta-catenin and ido expression to potentiate immunotherapy
WO2019136112A1 (en) * 2018-01-05 2019-07-11 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
EP3793551A4 (en) 2018-05-16 2022-01-26 Vivace Therapeutics, Inc. OXADIAZOLE COMPOUNDS
WO2020010223A1 (en) * 2018-07-06 2020-01-09 Gilead Sciences, Inc. Therapeutic heterocyclic compounds
WO2020018670A1 (en) 2018-07-17 2020-01-23 Board Of Regents, The University Of Texas System Compounds useful as inhibitors of indoleamine 2,3-dioxygenase and/or tryptophan dioxygenase
WO2020023355A1 (en) * 2018-07-23 2020-01-30 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
WO2020047198A1 (en) 2018-08-31 2020-03-05 Incyte Corporation Salts of an lsd1 inhibitor and processes for preparing the same
CN109608334B (zh) * 2019-01-11 2021-07-13 盐城通海生物科技有限公司 一种合成4-甲氧基巴豆酸甲酯的方法
MX2021009189A (es) * 2019-02-01 2021-11-12 Glaxosmithkline Ip Dev Ltd Belantamab mafodotin en combinación con pembrolizumab para el tratamiento del cáncer.
KR102386849B1 (ko) * 2019-10-14 2022-04-13 포항공과대학교 산학협력단 면역치료를 위한 환경 반응형 접착성 항체전달체 및 이의 제조방법
WO2021102618A1 (en) * 2019-11-25 2021-06-03 InventisBio Co., Ltd. Novel salts of indoleamine 2,3-dioxygenase inhibitors
CN113214138A (zh) * 2020-02-04 2021-08-06 中国医学科学院药物研究所 苯丙酸类衍生物、及其制法和药物组合物与用途
US11839659B2 (en) 2020-07-02 2023-12-12 Northwestern University Proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of indoleamine 2,3-dioxygenase (IDO) protein
CN112174891B (zh) * 2020-11-02 2022-02-01 浙江省农业科学院 一种氟唑菌苯胺代谢物的制备方法
JP2024016314A (ja) * 2020-12-24 2024-02-07 小野薬品工業株式会社 一般式（ｉ－ａ）で示される化合物、その薬学的に許容される塩、またはそれらの水和物と免疫チェックポイント阻害薬および／またはｅｐ４受容体拮抗薬との組み合わせ
EP4301358A2 (en) 2021-03-05 2024-01-10 Universität Basel Vizerektorat Forschung Compositions for the treatment of ebv associated diseases or conditions
EP4052705A1 (en) 2021-03-05 2022-09-07 Universität Basel Vizerektorat Forschung Compositions for the treatment of ebv associated diseases or conditions

Family Cites Families (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3622337A (en) * 1968-08-02 1971-11-23 Gaf Corp Cyan color formers for color photography
US4252894A (en) * 1975-10-22 1981-02-24 Gaf Corporation Hydrophilic color coupler composition containing diepoxide
EP1505966A4 (en) 2002-05-10 2006-08-30 Bristol Myers Squibb Co 1,1-DISUBSTITUTED CYCLOALKYL DERIVATIVES AS FACTOR XA HEMMER
US7868205B2 (en) 2003-09-24 2011-01-11 Methylgene Inc. Inhibitors of histone deacetylase
CN101445469B (zh) * 2003-09-24 2013-02-13 梅特希尔基因公司 组蛋白脱乙酰基酶抑制剂
TWI309240B (en) 2004-09-17 2009-05-01 Hoffmann La Roche Anti-ox40l antibodies
PT2343320T (pt) 2005-03-25 2018-01-23 Gitr Inc Anticorpos anti-gitr e as suas utilizações
BRPI0608604B8 (pt) 2005-05-10 2021-05-25 Incyte Corp moduladores de 2,3-dioxigenase de indolamina e composição farmacêutica
KR101607288B1 (ko) 2005-07-01 2016-04-05 이. 알. 스퀴부 앤드 선즈, 엘.엘.씨. 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날 항체
CA2634198C (en) 2005-12-20 2014-06-03 Incyte Corporation N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase
EP2009005A4 (en) 2006-04-19 2010-06-02 Astellas Pharma Inc AZOLECARBOXAMIDE DERIVATIVE
US20080125470A1 (en) 2006-09-19 2008-05-29 Incyte Corporation N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase
CL2007002650A1 (es) 2006-09-19 2008-02-08 Incyte Corp Compuestos derivados de heterociclo n-hidroxiamino; composicion farmaceutica, util para tratar cancer, infecciones virales y desordenes neurodegenerativos entre otras.
EP1987839A1 (en) 2007-04-30 2008-11-05 I.N.S.E.R.M. Institut National de la Sante et de la Recherche Medicale Cytotoxic anti-LAG-3 monoclonal antibody and its use in the treatment or prevention of organ transplant rejection and autoimmune disease
AU2008275589B2 (en) 2007-07-12 2013-11-21 Gitr, Inc. Combination therapies employing GITR binding molecules
EP2044949A1 (en) 2007-10-05 2009-04-08 Immutep Use of recombinant lag-3 or the derivatives thereof for eliciting monocyte immune response
CA2707308C (en) 2007-11-30 2016-08-02 Newlink Genetics Corporation Ido inhibitors
AR072999A1 (es) 2008-08-11 2010-10-06 Medarex Inc Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos
EP3929216A1 (en) 2008-12-09 2021-12-29 F. Hoffmann-La Roche AG Anti-pd-l1 antibodies and their use to enhance t-cell function
BR112012004823B1 (pt) 2009-09-03 2021-11-30 Merck Sharp & Dohme Corp Anticorpo ou fragmento de ligação de antígeno do mesmo, uso de um anticorpo ou um fragmento de ligação de antígeno do mesmo, e composição farmacêutica
WO2011056652A1 (en) 2009-10-28 2011-05-12 Newlink Genetics Imidazole derivatives as ido inhibitors
RS54596B1 (en) 2009-12-10 2016-08-31 F. Hoffmann-La Roche Ag Antibodies Binding to Extracellular Domain 4 of Human CSF1R and Their Use
BR112012022210B1 (pt) 2010-03-04 2021-08-17 Macrogenics, Inc Anticorpo isolado ou seu fragmento imunorreativo, molécula de ácido nucleico, composição farmacêutica, e, uso do anticorpo isolado
MX2012010014A (es) 2010-03-05 2012-09-21 Hoffmann La Roche Anticuerpos contra csf-1r humano y sus usos.
KR101647871B1 (ko) 2010-03-05 2016-08-11 에프. 호프만-라 로슈 아게 인간 ｃｓｆ-1ｒ에 대한 항체 및 이의 용도
TR201900368T4 (tr) 2010-05-04 2019-02-21 Five Prime Therapeutics Inc Csf1r'ye bağlanan antikorlar.
MY177065A (en) 2010-09-09 2020-09-03 Pfizer 4-1bb binding molecules
NO2694640T3 (es) 2011-04-15 2018-03-17
JP6072771B2 (ja) 2011-04-20 2017-02-01 メディミューン，エルエルシー Ｂ７−ｈ１およびｐｄ−１に結合する抗体およびその他の分子
PT2785375T (pt) 2011-11-28 2020-10-29 Merck Patent Gmbh Anticorpos anti-pd-l1 e usos destes
MX356337B (es) 2011-12-15 2018-05-23 Hoffmann La Roche Anticuerpos contra csf-1r humano y sus usos.
KR20140127855A (ko) 2012-02-06 2014-11-04 제넨테크, 인크. Csf1r 억제제를 사용하는 조성물 및 방법
AR090263A1 (es) 2012-03-08 2014-10-29 Hoffmann La Roche Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma
BR112014028013A2 (pt) 2012-05-11 2018-02-27 Five Prime Therapeutics Inc métodos para tratar uma condição associada com artrite reumatoide, artrite reumatoide, lesões de pele, nefrite lúpica, lúpus, uma condição inflamatória, distúrbio de cd16+, método para reduzir o número de monócitos cd16+, métodos para desacelerar a progressão de uma condição renal,de formação de panos e de perda óssea
UY34887A (es) 2012-07-02 2013-12-31 Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos
SG11201501413YA (en) 2012-08-31 2015-03-30 Five Prime Therapeutics Inc Methods of treating conditions with antibodies that bind colony stimulating factor 1 receptor (csf1r)
MA38483A1 (fr) * 2013-03-15 2018-02-28 Bristol Myers Squibb Co Inhibiteurs de l'ido
PT2970155T (pt) * 2013-03-15 2018-07-02 Bristol Myers Squibb Co Inibidores de indoleamina 2,3-dioxigenase (ido)
EA029981B1 (ru) * 2013-08-27 2018-06-29 Бристол-Майерс Сквибб Компани Ингибиторы ido
US10399932B2 (en) * 2015-04-03 2019-09-03 Bristol-Myers Squibb Company Inhibitors of indoleamine-2,3-dioxygenase for the treatment of cancer

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