WO2017098421A1 - Composés benzothiadiazine - Google Patents

Composés benzothiadiazine Download PDF

Info

Publication number
WO2017098421A1
WO2017098421A1 PCT/IB2016/057415 IB2016057415W WO2017098421A1 WO 2017098421 A1 WO2017098421 A1 WO 2017098421A1 IB 2016057415 W IB2016057415 W IB 2016057415W WO 2017098421 A1 WO2017098421 A1 WO 2017098421A1
Authority
WO
WIPO (PCT)
Prior art keywords
chloro
dioxide
benzo
amino
thiadiazine
Prior art date
Application number
PCT/IB2016/057415
Other languages
English (en)
Inventor
Jerry Leroy Adams
Laura E. ATOR
Kevin J. Duffy
Todd L. Graybill
Terence John Kiesow
Yiqian LIAN
Michael Lee Moore
Jeffrey M. Ralph
Lance Howard Ridgers
Original Assignee
Glaxosmithkline Intellectual Property Development Limited
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 Glaxosmithkline Intellectual Property Development Limited filed Critical Glaxosmithkline Intellectual Property Development Limited
Publication of WO2017098421A1 publication Critical patent/WO2017098421A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/15—Six-membered rings
    • C07D285/16—Thiadiazines; Hydrogenated thiadiazines
    • C07D285/18—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines
    • C07D285/20—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems
    • C07D285/22—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D285/24—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom
    • C07D285/26—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom substituted in position 6 or 7 by sulfamoyl or substituted sulfamoyl radicals
    • C07D285/28—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom substituted in position 6 or 7 by sulfamoyl or substituted sulfamoyl radicals with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached in position 3
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/549—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D471/04—Ortho-condensed systems

Definitions

  • the present invention relates to substituted benzothiadiazine derivatives that are inhibitors of the activity of CD73.
  • the present invention also relates to pharmaceutical compositions comprising such compounds and methods of using such compounds in the treatment of cancer, pre-cancerous syndromes and other diseases associated with CD73 inhibition, such as AIDS, autoimmune diseases, infections, atherosclerosis, and ischemia- reperfusion injury.
  • ATP extracellular adenosine triphosphate
  • adenosine A2A and A2B receptors engage the immunosuppressive actions of adenosine A2A and A2B receptors on the infiltrating lymphocytes, shielding cells from an excessive inflammatory response and thereby providing a self-limiting mechanism to resolve the immune response.
  • hypoxia has been shown to increase adenosine levels by 10-20-fold compared with normal levels.
  • adenosine elevation is sufficient to maintain a chronic suppression of the innate immune response, resulting in immune tolerance and, subsequently, uncontrolled malignant growth.
  • CD73 is a glycophosphatidylinositol-anchored di-Zn 2+ metallo-phosphatase specific for the dephosphorylation of purine and pyrimidine ribo- and deoxyribonucleoside monophosphates to the corresponding nucleoside, with adenosine monophosphate (AMP) being the preferred substrate of CD73.
  • AMP adenosine monophosphate
  • CD73-catalyzed conversion of AMP to adenosine is thought to be the major contributor to extracellular adenosine in the tumor microenvironment. Its expression is directly regulated by HIF1 a, consistent with the observed increase in extracellular adenosine under hypoxic conditions.
  • CD73 is overexpressed in multiple solid tumor types and leukaemias, including aggressive and difficult to treat tumours, such as glioblastoma and ovarian tumours.
  • T Reg T-regulatory cells
  • CD73 and CD39 both CD73 and CD39, thus providing a mechanism for the conversion of ATP to adenosine that only depends on T Reg cells.
  • siRNA small-interfering ribonucleic acids
  • small-molecule inhibitors of CD73 are expected to have the ability to relieve the adenosine-mediated immunosuppression of the tumor microenvironment and alone, or incombination with other agents, provide a treatment for cancer.
  • CD73 inhibitors are also expected to be useful for other diseases mediated by adenosine and its action on adenosine receptors.
  • CD73 inhibitors could be used for enhancing immune responses, enhancing immunization, and increasing inflammatory responses, as well as treating a wide range of conditions including neurological, neurodegenerative and CNS diseases, including depression, Parkinson's disease, cerebral and cardiac ischemic diseases, sleep disorders, and fibrosis. (7-10)
  • the invention is directed to substituted benzothiadiazine derivatives. Specifically, the invention is directed to compounds according to Formula (I):
  • R, R1 , R2, R3, R4 an( R5 are as defined below; or a pharmaceutically acceptable salt thereof.
  • the present invention also relates to the discovery that the compounds of Formula (I) are active as inhibitors of CD73.
  • This invention also relates to a method of treating cancer, which comprises administering to a subject in need thereof an effective amount of a CD73 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof.
  • This invention also relates to a method of treating pre-cancerous syndromes, which comprises administering to a subject in need thereof an effective amount of a CD73 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof.
  • This invention also relates to a method of treating AIDS, which comprises administering to a subject in need thereof an effective amount of a CD73 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof.
  • This invention also relates to a method of treating autoimmune diseases, which comprises administering to a subject in need thereof an effective amount of a CD73 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof.
  • This invention also relates to a method of treating infections, which comprises administering to a subject in need thereof an effective amount of a CD73 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof.
  • This invention also relates to a method of treating atherosclerosis, which comprises administering to a subject in need thereof an effective amount of a CD73 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof.
  • This invention also relates to a method of treating ischemia-reperfusion injury, which comprises administering to a subject in need thereof an effective amount of a CD73 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof.
  • This invention also relates to a method of treating a disease state selected from: myocardial infarction, cardiovascular disease, atherosclerosis, ocular diseases, and arrhythmias, which comprises administering to a subject in need thereof an effective amount of a CD73 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof.
  • the invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in therapy.
  • the invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of cancer.
  • the invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of pre-cancerous syndromes.
  • the invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of AIDS.
  • the invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of autoimmune diseases.
  • the invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of infections.
  • the invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of atherosclerosis.
  • the invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of ischemia-reperfusion injury.
  • the invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of a disease state selected from: myocardial infarction, cardiovascular disease, atherosclerosis, ocular diseases, and arrhythmias.
  • a disease state selected from: myocardial infarction, cardiovascular disease, atherosclerosis, ocular diseases, and arrhythmias.
  • the invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of cancer.
  • the invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of pre-cancerous syndromes.
  • the invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of AIDS.
  • the invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of autoimmune diseases.
  • the invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of infections.
  • the invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of atherosclerosis.
  • the invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of ischemia-reperfusion injury.
  • the invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of a disease state selected from: myocardial infarction, cardiovascular disease, atherosclerosis, ocular diseases, and arrhythmias.
  • a disease state selected from: myocardial infarction, cardiovascular disease, atherosclerosis, ocular diseases, and arrhythmias.
  • pharmaceutical compositions that comprise a pharmaceutical carrier and a compound of Formula (I) or a pharmaceutically acceptable salt thereof.
  • the invention also relates to a pharmaceutical composition as defined above for use in therapy. Also included in the present invention are methods of co-administering the presently invented CD73 inhibiting compounds with a further anti-neoplastic agent or agents.
  • the invention also relates to a combination for use in therapy which comprises a therapeutically effective amount of (i) a compound of Formula (I) or a pharmaceutically acceptable salt thereof; and (ii) at least one anti-neoplastic agent.
  • This invention relates to novel compounds of Formula (I):
  • R is selected from:
  • Ci -4alkoxy substituted with from 1 to 5 substituents independently selected from: fluoro, chloro, bromo, oxo, -OH and -CN,
  • Ci-4alkoxy substituted with from 1 to 5 substituents independently selected from: fluoro, chloro, bromo, oxo, -OH and -CN,
  • Ci-4alkyl substituted with from one to five substituents independently selected from: fluoro, chloro, bromo, iodo, Ci -4alkyl, Ci -4alkyloxy, -OH, -COOH, -CF3, -Cl-4alkylOCl -4alkyl, -NO2, -NH2 and -CN, Cl-4alkyloxy,
  • R 3 is selected from:
  • Ci-4alkyl substituted with from one to five substituents independently selected from: fluoro, chloro, bromo, iodo, Ci -4alkyl, Ci -4alkyloxy, -OH, -COOH, -CF3, -Cl-4alkylOCl -4alkyl, -NO2, -NH2 and -CN,
  • Ci-4alkyloxy substituted with from one to five substituents independently selected from: fluoro, chloro and bromo, and
  • Ci-4alkyl substituted with from one to five substituents independently selected from: fluoro, chloro, bromo, iodo, Ci -4alkyl, Ci -4alkyloxy, -OH, -COOH, -CF3, -Cl-4alkylOCl -4alkyl, -NO2, -NH2 and -CN,
  • Ci-4alkyl substituted with from one to five substituents independently selected from: fluoro, chloro, bromo, iodo, Ci -4alkyl, Ci -4alkyloxy, -OH, -COOH, -CF3, -Cl-4alkylOCl -4alkyl, -NO2, -NH2 and -CN, Cl-4alkyloxy,
  • R is selected from:
  • R is selected from:
  • Ci-4alkyl substituted with from one to five substituents independently selected from: fluoro, chloro, -OH, and -NH2; is selected from:
  • Ci-4alkyl substituted with from one to five substituents independently selected from: fluoro, chloro, bromo, iodo, Ci -4alkyl, Ci -4alkyloxy, -OH, -COOH, -CF3, -Cl-4alkylOCl -4alkyl, -NO2, -NH2 and -CN, Cl-4alkyloxy,
  • Ci-4alkyl substituted with from one to five substituents independently selected from: fluoro, chloro, bromo, iodo, Ci -4alkyl, Ci -4alkyloxy, -OH, -COOH, -CF3, -Cl-4alkylOCl -4alkyl, -NO2, -NH2 and -CN,
  • Ci-4alkyl substituted with from one to five substituents independently selected from: fluoro, chloro, bromo, iodo, Ci -4alkyl, Ci -4alkyloxy, -OH, -COOH, -CF3, -Cl-4alkylOCl -4alkyl, -NO2, -NH2 and -CN,
  • R 5 is selected from:
  • Ci-4alkyl substituted with from one to five substituents independently selected from: fluoro, chloro, bromo, iodo, Cl -4alkyl, Cl -4alkyloxy,
  • R 2 is selected from:
  • R 3 is selected from:
  • R 4 is selected from:
  • R 5 is selected from:
  • R is selected from:
  • R 2 is selected from:
  • R 3 is selected from:
  • R 4 is selected from:
  • R 5 is selected from:
  • Ci-4alkoxy substituted with from 1 to 5 substituents independently selected from: fluoro, chloro, bromo, oxo, -OH and -CN,
  • R is selected from:
  • R 2 is selected from: hydrogen
  • R 3 is selected from:
  • R 4 is selected from:
  • R 5 is selected from:
  • R is selected from:

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)

Abstract

L'invention concerne des dérivés de benzothiadiazine substitués. L'invention concerne en particulier des composés de formule (I), dans lesquels R, R1, R2, R3, R4 et R5 sont tels que définis dans la description. Les composés de l'invention sont des inhibiteurs de CD73 et peuvent être utiles dans le traitement du cancer, de syndromes précancéreux et de maladies associées à l'inhibition de CD73, telles que le SIDA, les maladies auto-immunes, les infections, l'athérosclérose, et une lésion de reperfusion ischémique. Par conséquent, l'invention concerne en outre des compositions pharmaceutiques comprenant un composé de l'invention. L'invention concerne en outre des procédés d'inhibition de l'activité de CD73 et le traitement de troubles associés à celui-ci à l'aide d'un composé de l'invention ou d'une composition pharmaceutique comprenant un composé de l'invention.
PCT/IB2016/057415 2015-12-08 2016-12-07 Composés benzothiadiazine WO2017098421A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562264419P 2015-12-08 2015-12-08
US62/264,419 2015-12-08

Publications (1)

Publication Number Publication Date
WO2017098421A1 true WO2017098421A1 (fr) 2017-06-15

Family

ID=57590742

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2016/057415 WO2017098421A1 (fr) 2015-12-08 2016-12-07 Composés benzothiadiazine

Country Status (1)

Country Link
WO (1) WO2017098421A1 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019002606A1 (fr) 2017-06-30 2019-01-03 Selvita S.A. Modulateurs de 5,6-bicyclo-imidazo[1,2-a]pyrazine du récepteur a2a de l'adénosine
WO2019053617A1 (fr) * 2017-09-12 2019-03-21 Glaxosmithkline Intellectual Property Development Limited Composés chimiques
WO2019068907A1 (fr) 2017-10-06 2019-04-11 Innate Pharma Restauration de l'activité de lymphocytes t par l'axe cd39/cd73
WO2020128036A1 (fr) 2018-12-21 2020-06-25 Ryvu Therapeutics S.A. Modulateurs du récepteur a2a de l'adénosine
WO2020146795A1 (fr) 2019-01-11 2020-07-16 Omeros Corporation Procédés et compositions pour le traitement du cancer
WO2020211668A1 (fr) * 2019-04-15 2020-10-22 Bioardis Llc Inhibiteurs de cd73
US10881681B2 (en) 2018-09-11 2021-01-05 Risen (Suzhou) Pharma Tech Co., Ltd. CD73 inhibitors and pharmaceutical uses thereof
WO2021236818A1 (fr) * 2020-05-19 2021-11-25 Board Of Regents Of The University Of Nebraska Benzothiadiazines halogénées pour le traitement du cancer
EP3843714A4 (fr) * 2018-08-27 2022-04-20 Arcus Biosciences, Inc. Inhibiteurs de cd73
US11332492B2 (en) 2018-08-28 2022-05-17 Jiangsu Hengrui Medicine Co., Ltd. CD73 inhibitors and therapeutic uses thereof
WO2022121914A1 (fr) * 2020-12-10 2022-06-16 上海翰森生物医药科技有限公司 Régulateur de dérivé à cycle oxo-azote, son procédé de préparation et son application
US11377503B2 (en) 2018-06-18 2022-07-05 Innate Pharma Antibodies that bind human CD39 and inhibit ATPase activity of a soluble extracellular domain human CD39 polypeptide
US11492346B2 (en) 2019-06-18 2022-11-08 Pfizer Inc. Benzisoxazole sulfonamide derivatives
US11530234B2 (en) 2018-09-11 2022-12-20 Risen (Suzhou) Pharma Tech Co., Ltd. CD73 inhibitors and pharmaceutical uses thereof
US11578136B2 (en) 2017-03-16 2023-02-14 Innate Pharma Compositions and methods for treating cancer
WO2023201267A1 (fr) 2022-04-13 2023-10-19 Gilead Sciences, Inc. Polythérapie pour le traitement de cancers exprimant trop-2
US11911372B2 (en) 2018-06-28 2024-02-27 Ctxt Pty Ltd Compounds

Citations (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5342947A (en) 1992-10-09 1994-08-30 Glaxo Inc. Preparation of water soluble camptothecin derivatives
US5491237A (en) 1994-05-03 1996-02-13 Glaxo Wellcome Inc. Intermediates in pharmaceutical camptothecin preparation
US5559235A (en) 1991-10-29 1996-09-24 Glaxo Wellcome Inc. Water soluble camptothecin derivatives
US5681835A (en) 1994-04-25 1997-10-28 Glaxo Wellcome Inc. Non-steroidal ligands for the estrogen receptor
WO1997049692A1 (fr) * 1996-06-21 1997-12-31 Novo Nordisk A/S Derives de 1,2,4-benzothiadiazine, leur preparation et leur utilisation
US6113918A (en) 1997-05-08 2000-09-05 Ribi Immunochem Research, Inc. Aminoalkyl glucosamine phosphate compounds and their use as adjuvants and immunoeffectors
US6268391B1 (en) 1997-08-06 2001-07-31 Glaxo Wellcome Inc. Benzylidene-1,3-dihydro-indol-2-one derivatives a receptor tyrosine kinase inhibitors, particularly of Raf kinases
EP1125585A1 (fr) 1999-08-30 2001-08-22 Japan Tobacco Inc. Traitements de maladies immunitaires
WO2001090129A2 (fr) 2000-05-19 2001-11-29 Corixa Corporation Traitement prophylactique et therapeutique de maladies infectieuses et autres avec des composes a base de mono- et disaccharides
WO2002059110A1 (fr) 2000-12-21 2002-08-01 Glaxo Group Limited Composes chimiques
US6525028B1 (en) 2002-02-04 2003-02-25 Corixa Corporation Immunoeffector compounds
EP1374901A1 (fr) 2001-03-01 2004-01-02 Japan Tobacco, Inc. Dispositifs de rejet du greffon
EP1374902A1 (fr) 2001-03-27 2004-01-02 Japan Tobacco Inc. Remedes contre les affections intestinales inflammatoires
WO2004004771A1 (fr) 2002-07-03 2004-01-15 Ono Pharmaceutical Co., Ltd. Compositions immunostimulantes
WO2004056875A1 (fr) 2002-12-23 2004-07-08 Wyeth Anticorps anti pd-1 et utilisations
WO2004072286A1 (fr) 2003-01-23 2004-08-26 Ono Pharmaceutical Co., Ltd. Substance specifique a pd-1 humain
WO2005000231A2 (fr) 2003-06-06 2005-01-06 Smithkline Beecham Corporation Antagonistes du recepteur il-8
US6911434B2 (en) 2002-02-04 2005-06-28 Corixa Corporation Prophylactic and therapeutic treatment of infectious and other diseases with immunoeffector compounds
WO2005121142A1 (fr) 2004-06-11 2005-12-22 Japan Tobacco Inc. Dérivés de 5-amino-2,4,7-trioxo-3,4,7,8-tétrahydro-2h-pyrido’2,3-d! pyrimidine et composés apparentés pour le traitement du cancer
US6984720B1 (en) 1999-08-24 2006-01-10 Medarex, Inc. Human CTLA-4 antibodies
US20060014768A1 (en) 2004-06-11 2006-01-19 Japan Tobacco Inc. Pyrimidine compound and medical use thereof
WO2006016997A2 (fr) 2004-07-08 2006-02-16 Corixa Corporation Composes d'aminoalkylglucosaminide phosphate et leur utilisation
US7129219B2 (en) 2000-08-04 2006-10-31 Corixa Corporation Immunoeffector compounds
WO2008039876A1 (fr) * 2006-09-26 2008-04-03 Case Western Reserve University Signalisation de cytokine
WO2008098104A1 (fr) 2007-02-07 2008-08-14 Smithkline Beecham Corporation Inhibiteurs de l'activité de akt
WO2008137915A2 (fr) 2007-05-07 2008-11-13 Medimmune, Llc Anticorps anti-icos et leur utilisation en traitement oncologique, de transplantation et maladie auto-immune
WO2008156712A1 (fr) 2007-06-18 2008-12-24 N. V. Organon Anticorps dirigés contre le récepteur humain de mort programmée pd-1
US7504101B2 (en) 1998-02-24 2009-03-17 Sisters Of Providence In Oregon Methods for enhancing antigen-specific immune response using antibodies that bind OX-40
US7550140B2 (en) 2002-06-13 2009-06-23 Crucell Holland B.V. Antibody to the human OX40 receptor
US7605238B2 (en) 1999-08-24 2009-10-20 Medarex, Inc. Human CTLA-4 antibodies and their uses
WO2010027827A2 (fr) 2008-08-25 2010-03-11 Amplimmune, Inc. Polypeptides co-stimulateurs ciblés et leurs procédés d'utilisation dans le traitement du cancer
WO2010056804A1 (fr) 2008-11-12 2010-05-20 Medimmune, Llc Formulation d’anticorps
WO2010077634A1 (fr) 2008-12-09 2010-07-08 Genentech, Inc. Anticorps anti-pd-l1 et leur utilisation pour améliorer la fonction des lymphocytes t
US7758852B2 (en) 2002-04-03 2010-07-20 Merck Serono Sa OX40R binding agents
US7943743B2 (en) 2005-07-01 2011-05-17 Medarex, Inc. Human monoclonal antibodies to programmed death ligand 1 (PD-L1)
WO2011066342A2 (fr) 2009-11-24 2011-06-03 Amplimmune, Inc. Inhibition simultanée de pd-l1/pd-l2
US7960515B2 (en) 2007-12-14 2011-06-14 Bristol-Myers Squibb Company Binding molecules to the human OX40 receptor
US8008449B2 (en) 2005-05-09 2011-08-30 Medarex, Inc. Human monoclonal antibodies to programmed death 1 (PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics
US20110271358A1 (en) 2008-09-26 2011-11-03 Dana-Farber Cancer Institute, Inc. Human anti-pd-1, pd-l1, and pd-l2 antibodies and uses therefor
US20110280877A1 (en) 2010-05-11 2011-11-17 Koji Tamada Inhibition of B7-H1/CD80 interaction and uses thereof
WO2012027328A2 (fr) 2010-08-23 2012-03-01 Board Of Regents, The University Of Texas System Anticorps anti-ox40 et leurs procédés d'utilisation
US8168757B2 (en) 2008-03-12 2012-05-01 Merck Sharp & Dohme Corp. PD-1 binding proteins
WO2012131004A2 (fr) 2011-03-31 2012-10-04 INSERM (Institut National de la Santé et de la Recherche Médicale) Anticorps dirigés contre icos et utilisation de ceux-ci
WO2013019906A1 (fr) 2011-08-01 2013-02-07 Genentech, Inc. Procédés de traitement du cancer à l'aide d'antagonistes se liant à l'axe pd-1 et inhibiteurs de mek
US20130034559A1 (en) 2009-11-24 2013-02-07 Medlmmune Limited Targeted Binding Agents Against B7-H1
WO2013028231A1 (fr) 2011-08-23 2013-02-28 Board Of Regents, The University Of Texas System Anticorps anti-ox40 et leurs procédés d'utilisation
WO2013079174A1 (fr) 2011-11-28 2013-06-06 Merck Patent Gmbh Anticorps anti-pd-l1 et utilisations associées
US20130309250A1 (en) 2012-05-15 2013-11-21 Bristol-Myers Squibb Company Cancer immunotherapy by disrupting pd-1/pd-l1 signaling
WO2014055897A2 (fr) 2012-10-04 2014-04-10 Dana-Farber Cancer Institute, Inc. Anticorps monoclonaux humains anti pd-l1 et procédés d'utilisation

Patent Citations (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5559235A (en) 1991-10-29 1996-09-24 Glaxo Wellcome Inc. Water soluble camptothecin derivatives
US5342947A (en) 1992-10-09 1994-08-30 Glaxo Inc. Preparation of water soluble camptothecin derivatives
US6207716B1 (en) 1994-04-25 2001-03-27 Glaxo Wellcome Inc. Non-steroidal ligands for the estrogen receptor
US5877219A (en) 1994-04-25 1999-03-02 Glaxo Wellcomeinc. Non-steroidal ligands for the estrogen receptor
US5681835A (en) 1994-04-25 1997-10-28 Glaxo Wellcome Inc. Non-steroidal ligands for the estrogen receptor
US5491237A (en) 1994-05-03 1996-02-13 Glaxo Wellcome Inc. Intermediates in pharmaceutical camptothecin preparation
US6063923A (en) 1994-05-03 2000-05-16 Glaxo Wellcome Inc. Preparation of a camptothecin derivative by intramolecular cyclisation
WO1997049692A1 (fr) * 1996-06-21 1997-12-31 Novo Nordisk A/S Derives de 1,2,4-benzothiadiazine, leur preparation et leur utilisation
US6113918A (en) 1997-05-08 2000-09-05 Ribi Immunochem Research, Inc. Aminoalkyl glucosamine phosphate compounds and their use as adjuvants and immunoeffectors
US6268391B1 (en) 1997-08-06 2001-07-31 Glaxo Wellcome Inc. Benzylidene-1,3-dihydro-indol-2-one derivatives a receptor tyrosine kinase inhibitors, particularly of Raf kinases
US7504101B2 (en) 1998-02-24 2009-03-17 Sisters Of Providence In Oregon Methods for enhancing antigen-specific immune response using antibodies that bind OX-40
US7605238B2 (en) 1999-08-24 2009-10-20 Medarex, Inc. Human CTLA-4 antibodies and their uses
US6984720B1 (en) 1999-08-24 2006-01-10 Medarex, Inc. Human CTLA-4 antibodies
EP1125585A1 (fr) 1999-08-30 2001-08-22 Japan Tobacco Inc. Traitements de maladies immunitaires
WO2001090129A2 (fr) 2000-05-19 2001-11-29 Corixa Corporation Traitement prophylactique et therapeutique de maladies infectieuses et autres avec des composes a base de mono- et disaccharides
US7129219B2 (en) 2000-08-04 2006-10-31 Corixa Corporation Immunoeffector compounds
WO2002059110A1 (fr) 2000-12-21 2002-08-01 Glaxo Group Limited Composes chimiques
EP1374901A1 (fr) 2001-03-01 2004-01-02 Japan Tobacco, Inc. Dispositifs de rejet du greffon
EP1374902A1 (fr) 2001-03-27 2004-01-02 Japan Tobacco Inc. Remedes contre les affections intestinales inflammatoires
US6911434B2 (en) 2002-02-04 2005-06-28 Corixa Corporation Prophylactic and therapeutic treatment of infectious and other diseases with immunoeffector compounds
US6525028B1 (en) 2002-02-04 2003-02-25 Corixa Corporation Immunoeffector compounds
US7858765B2 (en) 2002-04-03 2010-12-28 Merck Serono Sa OX40R binding agents
US7758852B2 (en) 2002-04-03 2010-07-20 Merck Serono Sa OX40R binding agents
US7550140B2 (en) 2002-06-13 2009-06-23 Crucell Holland B.V. Antibody to the human OX40 receptor
US8168179B2 (en) 2002-07-03 2012-05-01 Ono Pharmaceutical Co., Ltd. Treatment method using anti-PD-L1 antibody
WO2004004771A1 (fr) 2002-07-03 2004-01-15 Ono Pharmaceutical Co., Ltd. Compositions immunostimulantes
US7595048B2 (en) 2002-07-03 2009-09-29 Ono Pharmaceutical Co., Ltd. Method for treatment of cancer by inhibiting the immunosuppressive signal induced by PD-1
US7488802B2 (en) 2002-12-23 2009-02-10 Wyeth Antibodies against PD-1
US7521051B2 (en) 2002-12-23 2009-04-21 Medimmune Limited Methods of upmodulating adaptive immune response using anti-PD-1 antibodies
WO2004056875A1 (fr) 2002-12-23 2004-07-08 Wyeth Anticorps anti pd-1 et utilisations
WO2004072286A1 (fr) 2003-01-23 2004-08-26 Ono Pharmaceutical Co., Ltd. Substance specifique a pd-1 humain
WO2005000231A2 (fr) 2003-06-06 2005-01-06 Smithkline Beecham Corporation Antagonistes du recepteur il-8
US20060014768A1 (en) 2004-06-11 2006-01-19 Japan Tobacco Inc. Pyrimidine compound and medical use thereof
WO2005121142A1 (fr) 2004-06-11 2005-12-22 Japan Tobacco Inc. Dérivés de 5-amino-2,4,7-trioxo-3,4,7,8-tétrahydro-2h-pyrido’2,3-d! pyrimidine et composés apparentés pour le traitement du cancer
WO2006016997A2 (fr) 2004-07-08 2006-02-16 Corixa Corporation Composes d'aminoalkylglucosaminide phosphate et leur utilisation
US8008449B2 (en) 2005-05-09 2011-08-30 Medarex, Inc. Human monoclonal antibodies to programmed death 1 (PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics
US7943743B2 (en) 2005-07-01 2011-05-17 Medarex, Inc. Human monoclonal antibodies to programmed death ligand 1 (PD-L1)
US8383796B2 (en) 2005-07-01 2013-02-26 Medarex, Inc. Nucleic acids encoding monoclonal antibodies to programmed death ligand 1 (PD-L1)
WO2008039876A1 (fr) * 2006-09-26 2008-04-03 Case Western Reserve University Signalisation de cytokine
WO2008098104A1 (fr) 2007-02-07 2008-08-14 Smithkline Beecham Corporation Inhibiteurs de l'activité de akt
WO2008137915A2 (fr) 2007-05-07 2008-11-13 Medimmune, Llc Anticorps anti-icos et leur utilisation en traitement oncologique, de transplantation et maladie auto-immune
US8354509B2 (en) 2007-06-18 2013-01-15 Msd Oss B.V. Antibodies to human programmed death receptor PD-1
WO2008156712A1 (fr) 2007-06-18 2008-12-24 N. V. Organon Anticorps dirigés contre le récepteur humain de mort programmée pd-1
US7960515B2 (en) 2007-12-14 2011-06-14 Bristol-Myers Squibb Company Binding molecules to the human OX40 receptor
US8168757B2 (en) 2008-03-12 2012-05-01 Merck Sharp & Dohme Corp. PD-1 binding proteins
WO2010027827A2 (fr) 2008-08-25 2010-03-11 Amplimmune, Inc. Polypeptides co-stimulateurs ciblés et leurs procédés d'utilisation dans le traitement du cancer
US20110271358A1 (en) 2008-09-26 2011-11-03 Dana-Farber Cancer Institute, Inc. Human anti-pd-1, pd-l1, and pd-l2 antibodies and uses therefor
US8552154B2 (en) 2008-09-26 2013-10-08 Emory University Anti-PD-L1 antibodies and uses therefor
WO2010056804A1 (fr) 2008-11-12 2010-05-20 Medimmune, Llc Formulation d’anticorps
WO2010077634A1 (fr) 2008-12-09 2010-07-08 Genentech, Inc. Anticorps anti-pd-l1 et leur utilisation pour améliorer la fonction des lymphocytes t
US8217149B2 (en) 2008-12-09 2012-07-10 Genentech, Inc. Anti-PD-L1 antibodies, compositions and articles of manufacture
US20130034559A1 (en) 2009-11-24 2013-02-07 Medlmmune Limited Targeted Binding Agents Against B7-H1
WO2011066342A2 (fr) 2009-11-24 2011-06-03 Amplimmune, Inc. Inhibition simultanée de pd-l1/pd-l2
US20110280877A1 (en) 2010-05-11 2011-11-17 Koji Tamada Inhibition of B7-H1/CD80 interaction and uses thereof
WO2012027328A2 (fr) 2010-08-23 2012-03-01 Board Of Regents, The University Of Texas System Anticorps anti-ox40 et leurs procédés d'utilisation
WO2012131004A2 (fr) 2011-03-31 2012-10-04 INSERM (Institut National de la Santé et de la Recherche Médicale) Anticorps dirigés contre icos et utilisation de ceux-ci
WO2013019906A1 (fr) 2011-08-01 2013-02-07 Genentech, Inc. Procédés de traitement du cancer à l'aide d'antagonistes se liant à l'axe pd-1 et inhibiteurs de mek
WO2013028231A1 (fr) 2011-08-23 2013-02-28 Board Of Regents, The University Of Texas System Anticorps anti-ox40 et leurs procédés d'utilisation
WO2013079174A1 (fr) 2011-11-28 2013-06-06 Merck Patent Gmbh Anticorps anti-pd-l1 et utilisations associées
US20130309250A1 (en) 2012-05-15 2013-11-21 Bristol-Myers Squibb Company Cancer immunotherapy by disrupting pd-1/pd-l1 signaling
WO2014055897A2 (fr) 2012-10-04 2014-04-10 Dana-Farber Cancer Institute, Inc. Anticorps monoclonaux humains anti pd-l1 et procédés d'utilisation

Non-Patent Citations (94)

* Cited by examiner, † Cited by third party
Title
"Tyrosine Kinase Signalling in Breast cancer:erbB Family Receptor Tyrosine Kniases", BREAST CANCER RES., vol. 2, no. 3, 2000, pages 176 - 183
ABRAHAM, R.T., CURRENT OPINION IN IMMUNOLOGY, vol. 8, no. 3, 1996, pages 412 - 8
ADAMS J; KAUFFMAN M, CANCER INVEST, vol. 22, no. 2, 2004, pages 304 - 11
ALII ET AL., ONCOGENE, vol. 24, 2005, pages 39 - 46
ALLARD, B. ET AL.: "CD73-Generated Adenosine: Orchestrating the Tumor-Stroma Interplay to Promote Cancer Growth", J. BIOMED. BIOTECH., 2012, pages 8
AL-RASHIDA MARIYA ET AL: "2-Alkoxy-3-(sulfonylarylaminomethylene)-chroman-4-ones as potent and selective inhibitors of ectonucleotidases", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 115, 3 March 2016 (2016-03-03), EDITIONS SCIENTIFIQUE ELSEVIER, PARIS, FR, pages 484 - 494, XP029505150, ISSN: 0223-5234, DOI: 10.1016/J.EJMECH.2016.02.073 *
ANDREW J PEAT ET AL: "Synthesis and Evaluation of 7-Substituted-3-cyclobutylamino- 4H-1,2,4-benzothiadiazine-1,1-dioxide Derivatives as KATP Channel Agonists", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 12, no. 20, 1 January 2002 (2002-01-01), PERGAMON, AMSTERDAM, NL, pages 2977 - 2980, XP009193161, ISSN: 0960-894X *
ANTONIOLI, L. ET AL.: "Immunity, inflammation and cancer: a leading role for adenosine", NATURE REV. CANCER, vol. 13, 2013, pages 842 - 857
ASHBY, M.N., CURRENT OPINION IN LIPIDOLOGY., vol. 9, no. 2, 1998, pages 99 - 102
BALASUBRAMANIAN ET AL., CANCER LETTERS, vol. 280, 2009, pages 211 - 221
BALL ET AL., PROGRESS IN CELL CYCLE RES., vol. 3, 1997, pages 125
BERNARD PIROTTE ET AL: "Chloro-Substituted 3-Alkylamino-4 H -1,2,4-benzothiadiazine 1,1-Dioxides as ATP-Sensitive Potassium Channel Activators: Impact of the Position of the Chlorine Atom on the Aromatic Ring on Activity and Tissue Selectivity", JOURNAL OF MEDICINAL CHEMISTRY, vol. 53, no. 1, 14 January 2010 (2010-01-14), US, pages 147 - 154, XP055337324, ISSN: 0022-2623, DOI: 10.1021/jm9010093 *
BERTRAND, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 45, 2010, pages 2095 - 2116
BIOCHIM. BIOPHYS. ACTA, vol. 1423, no. 3, 1989, pages 19 - 30
BLAY, J.; WHITE, T. D.; HOSKIN, D. W.: "The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine", CANCER RES., vol. 57, 1997, pages 2602 - 2605
BOLEN, J.B.; BRUGGE, J.S., ANNUAL REVIEW OF IMMUNOLOGY, vol. 15, 1997, pages 371 - 404
BOUMA ET AL., J. ANTIMICROB. CHEMOTHER., vol. 42, no. 6, 1998, pages 817 - 20
BOVERIE S ET AL: "Effect on insulin release of compounds structurally related to the potassium-channel opener 7-chloro- 3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide (BPDZ 73): introduction of heteroatoms on the 3-alkylamino side chain of the benzothiadiazine 1,1-dioxide ring", JOURNAL OF PHARMACY AND PHARMACOLOGY, vol. 53, no. 7, 1 January 2001 (2001-01-01), JOHN WILEY & SONS LTD, LONDON; GB, pages 973 - 980, XP009193164, ISSN: 0022-3573 *
BREKKEN, R.A ET AL.: "Selective Inhibition of VEGFR2 Activity by a monoclonal Anti-VEGF antibody blocks tumor growth in mice", CANCER RES., vol. 60, 2000, pages 5117 - 5124
BRODT, P; SAMANI, A.; NAVAB, R., BIOCHEMICAL PHARMACOLOGY, vol. 60, 2000, pages 1101 - 1107
BRUNS CJ ET AL., CANCER RES., vol. 60, 2000, pages 2926 - 2935
CANMAN, C.E.; LIM, D.S., ONCOGENE, vol. 17, no. 25, 1998, pages 3301 - 3308
CHEN, J. F.; ELTZSCHIG, H. K.; FREDHOLM, B. B.: "Adenosine receptors as drug targets - what are the challenges?", NAT. REV. DRUG DISCOV., vol. 12, 2013, pages 265 - 286
CHRISTOPHER BLACKBURN ET AL: "Synthesis of 3-Amino-1,2,4-benzothiadi- azine 1,1-Dioxides via a Tandem Aza-Wittig/Heterocumulene Annulation", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 70, no. 24, 1 November 2005 (2005-11-01), pages 10206 - 10209, XP055337338, ISSN: 0022-3263, DOI: 10.1021/jo051843h *
D. A. TENNANT, NATURE REVIEWS, 2010, pages 267
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 10 March 2011 (2011-03-10), "2H-1,2,4-Benzothiadiazin-3-amine, N-cyclopropyl-7-(1-methylethyl)-, 1,1-dioxide", XP002766246, Database accession no. 1267895-55-5 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 2 September 2011 (2011-09-02), XP002766245, Database accession no. 1327121-78-7 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 22 September 2004 (2004-09-22), "4H-1,2,4-Benzothiadiazin-3-amine, N-(4,6-dimethyl-2-pyrimidinyl)-4-methyl-, 1,1-dioxide", XP002766252, Database accession no. 749197-81-7 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 23 January 2008 (2008-01-23), "4H-1,2,4-Benzothiadiazin-3-amine, N-cycloprpyl-4-methyl-, 1,1-dioxide", XP002766250, Database accession no. 10000576-02-2 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 28 July 2006 (2006-07-28), "4H-1,2,4-Benzothiadiazin-3-amine, N-(3-methylphenyl)-, 1,1-dioxide", XP002766251, Database accession no. 896681-79-1 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 29 January 2001 (2001-01-29), "4H-1,2,4-Benzothiadiazin-3-amine, N-(4,6-dimethyl-2-pyrimidinyl)-4-methyl-,1,1-dioxide, monohydrochloride", XP002766254, Database accession no. 317821-65-1 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 6 June 2008 (2008-06-06), "2H-1,2,4-Benzothiadiazin-3-amine, 7-chloro-N-(6-fluoro-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-, 1,1-dioxide", XP002766249, Database accession no. 1026002-59-4 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 6 September 2011 (2011-09-06), XP002766244, Database accession no. 1328837-27-9 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 7 September 2011 (2011-09-07), XP002766243, Database accession no. 1329561-17-2 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 8 April 2003 (2003-04-08), "Benzoic acid, 2-[(4-methyl-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)amino]-methyl ester", XP002766253, Database accession no. 502137-70- *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 8 March 2011 (2011-03-08), "2H-1,2,4-Benzothiadiazin-3-amine, N-cyclopropyl-7-ethyl-,1,1-dioxide", XP002766248, Database accession no. 1266939-29-0 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 8 September 2011 (2011-09-08), XP002766242, Database accession no. 1330176-09-4 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 9 March 2011 (2011-03-09), XP002766247, Database accession no. 1267452-41-4 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 9 September 2011 (2011-09-09), XP002766241, Database accession no. 1330241-80-9 *
DRUGS OF THE FUTURE, vol. 32, no. 4, 2007, pages 315 - 322
FELING, ANGEW. CHEM. INT. ED. ENGL, vol. 42, no. 3, 2003, pages 355 - 7
GHIRINGHELLI, F ET AL.: "Activation of the NLRP3 inflammasome in dendritic cells induces IL-1 ?-dependent adaptive immunity against tumors", NAT. MED., vol. 15, 2009, pages 1170 - 1178
GOTTLICHER ET AL., EMBO J., vol. 20, no. 24, 2001, pages 6969 - 6978
GREEN, M.C. ET AL.: "Monoclonal Antibody Therapy for Solid Tumors", CANCER TREAT. REV., vol. 26, no. 4, 2000, pages 269 - 286
JACKSON, S.P., INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND CELL BIOLOGY, vol. 29, no. 7, 1997, pages 935 - 8
JIA W ET AL., BLOOD, vol. 102, no. 5, 1 September 2003 (2003-09-01), pages 1824 - 32
KATH, JOHN C., EXP. OPIN. THER. PATENTS, vol. 10, no. 6, 2000, pages 803 - 818
KLAUS G JENSEN ET AL: "Phosphorus Pentoxide in Organic Synthesis", CHEMICA SCRIPTA, vol. 20, no. 5, 1 January 1982 (1982-01-01), KUNGLIGA VETENSKAPSAKADEMIEN, SE, pages 248 - 250, XP009193160, ISSN: 0004-2056 *
KUHN DJ ET AL., BLOOD, vol. 110, 2007, pages 3281 - 3290
LACKEY, K. ET AL., BIOORGANIC AND MEDICINAL CHEMISTRY LETTERS, 2000, pages 223 - 226
LEE ET AL., MOL CELL ENDOCRINOL., vol. 188, 2002, pages 47 - 54
MANDAPATHIL, M. ET AL.: "Adenosine and prostaglandin e2 cooperate in the suppression of immune responses mediated by adaptive regulatory T cells", J. BIOL. CHEM., vol. 285, 2010, pages 27571 - 27580
MARKS ET AL., NATURE BIOTECHNOLOGY, vol. 25, 2007, pages 84 - 90
MARTINEZ-LACACI, L. ET AL., INT. J. CANCER, vol. 88, no. 1, 2000, pages 44 - 52
MASSAGUE, J.; WEIS-GARCIA, F., CANCER SURVEYS., vol. 27, 1996, pages 41 - 64
P. LEDER, CANCER CELL, vol. 9, 2006, pages 425
PASCAL DE TULLIO ET AL: "Three-Dimensional Quantitative Structure-Activity Relationships of ATP-Sensitive Potassium (K ATP ) Channel Openers Belonging to the 3-Alkylamino-4 H -1,2,4-benzo- and 3-Alkylamino-4 H -1,2,4-pyridothiadiazine 1,1-Dioxide Families", JOURNAL OF MEDICINAL CHEMISTRY, vol. 49, no. 23, 1 November 2006 (2006-11-01), US, pages 6779 - 6788, XP055337249, ISSN: 0022-2623, DOI: 10.1021/jm060534w *
PEARCE, L.R ET AL., NATURE REVIEWS MOLECULAR CELL BIOLOGY, vol. 11, 2010, pages 9 - 22
PETERSEN ET AL: "Synthesis of 3-Amino- and 3-Substituted Amino-2H-1,2,4-benzothiadiazine 1,1-Dioxides", ACTA CHEMICA SCANDINAVICA, vol. 27, no. 7, 1 January 1973 (1973-01-01), WILEY-BLACKWELL MUNKSGAARD, DENMARK, pages 2655 - 2660, XP009193159, ISSN: 0001-5393 *
PHILIP, P.A.; HARRIS, A.L., CANCER TREATMENT AND RESEARCH, vol. 78, 1995, pages 3 - 27
POWIS, G.; KOZIKOWSKI A.: "New Molecular Targets for Cancer Chemotherapy", 1994, CRC PRESS
RAFFA L ET AL: "Azione Cardiovascolare Di Derivati Dell'1,2,4-Benzotiadiazin-1,1-Diossido", IL FARMACO, vol. 27, 1 January 1974 (1974-01-01), ELSEVIER FRANCE * EDITIONS SCIENTIFIQUES ET MEDICALES, FR, pages 411 - 423, XP009193158, ISSN: 0014-827X *
RAFFA L ET AL: "Ricerche Nel Campo Della 1,2,4-Benzotiadiazina", IL FARMACO, vol. 27, 1 January 1972 (1972-01-01), ELSEVIER FRANCE * EDITIONS SCIENTIFIQUES ET MEDICALES, FR, pages 509 - 516, XP009193157, ISSN: 0014-827X *
REGATEIRO, F. S. ET AL.: "CD73 and adenosine generation in the creation of regulatory microenvironments", CLIN. EXP. IMMUNOL., vol. 171, 2013, pages 1 - 7
REILLY RT ET AL., CANCER RES., vol. 60, 2000, pages 3569 - 3576
RICHON ET AL., PROC. NAT ACAD. SCI. U.S.A., vol. 97, no. 18, 2000, pages 10014 - 10019
ROSANIA ET AL., EXP. OPIN. THER. PATENTS, vol. 10, no. 2, 2000, pages 215 - 230
SANJAY BHATTARAI ET AL: "[alpha],[beta]-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto -5'-Nucleotidase (CD73) Inhibitors", JOURNAL OF MEDICINAL CHEMISTRY, vol. 58, no. 15, 13 August 2015 (2015-08-13), US, pages 6248 - 6263, XP055337552, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.5b00802 *
SCHAROVSKY, O.G.; ROZADOS, V.R.; GERVASONI, S.I.; MATAR, P., JOURNAL OF BIOMEDICAL SCIENCE, vol. 7, no. 4, 2000, pages 292 - 8
SCHREIBER AB; WINKLER ME; DERYNCK R., SCIENCE, vol. 232, 1986, pages 1250 - 1253
SHAWVER ET AL., DDT, vol. 2, 2 February 1997 (1997-02-02)
SINH, S.; COREY, S.J., JOURNAL OF HEMATOTHERAPY AND STEM CELL RESEARCH, vol. 8, no. 5, 1999, pages 465 - 80
SMITHGALL, T.E, JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, vol. 34, no. 3, 1995, pages 125 - 32
SORRENTINO, R. ET AL.: "The adenosinergic system in cancer", ONCOLMMUNOLOGY, vol. 2, 2013, pages E22448
STAGG, J.; SMYTH, M. J.: "Extracellular adenosine triphosphate and adenosine in cancer", ONCOGENE, vol. 29, 2010, pages 5346 - 5358
STENGER, COMMUNITY ONCOLOGY, vol. 4, 2007, pages 384 - 386
STÉPHANE BOVERIE ET AL: "Effect on K ATP Channel Activation Properties and Tissue Selectivity of the Nature of the Substituent in the 7- and the 3-Position of 4 H -1,2,4-Benzothiadiazine 1,1-Dioxides", JOURNAL OF MEDICINAL CHEMISTRY, vol. 48, no. 10, 1 May 2005 (2005-05-01), US, pages 3492 - 3503, XP055337336, ISSN: 0022-2623, DOI: 10.1021/jm0311339 *
SYNNESTVEDT, K. ET AL., ECTO-5'-NUCLEOTIDASE (CD73) REGULATION BY HYPOXIA-INDUCIBLE FACTOR-1 MEDIATES PERMEABILITY CHANGES IN INTESTINAL EPITHELIA
T. GREENE; P. WUTS: "Protecting Groups in Organic Synthesis(4th ed.)", 2006, JOHN WILEY & SONS
TOPLISS J G ET AL: "3,4-DIHYDRO-3-IMINO-2H-1,2,4-BENZOTHIADIAZINE 1,1-DIOXIDES", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 28, 1 September 1963 (1963-09-01), AMERICAN CHEMICAL SOCIETY ETC., pages 2313 - 2319, XP001013582, ISSN: 0022-3263, DOI: 10.1021/JO01044A038 *
TSUBASA INOKUMA ET AL: "Bifunctional Hydrogen-Bond Donors That Bear a Quinazoline or Benzothiadiazine Skeleton for Asymmetric Organocatalysis", CHEMISTRY - A EUROPEAN JOURNAL, vol. 17, no. 37, 1 January 2011 (2011-01-01), pages 10470 - 10477, XP009193163, ISSN: 0947-6539 *
V.T. DEVITA AND S. HELLMAN: "Cancer Principles and Practice of Oncology, 6th edition", 15 February 2001, LIPPINCOTT WILLIAMS & WILKINS PUBLISHERS
VIGUSHIN ET AL., ANTICANCER DRUGS, vol. 13, no. 1, January 2002 (2002-01-01), pages 1 - 13
VINODHKUMAR ET AL., BIOMEDICINE & PHARMACOTHERAPY, vol. 62, 2008, pages 85 - 93
WANG, Y. ET AL., BIOORG. MED. CHEM. LETT., vol. 17, 2007, pages 3864 - 3867
WATER JS ET AL., J. CLIN. ONCOL., vol. 18, 2000, pages 1812 - 1823
WHO DRUG INFORMATION, vol. 27, no. 1, 2013, pages 68 - 69
WHO DRUG INFORMATION, vol. 27, no. 2, 2013, pages 161 - 162
WILLIAMSON ET AL., THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 118, no. 6, December 2006 (2006-12-01), pages 1369 - 74
WORKMAN, PAUL AND KERR, DAVID,: "New Molecular Targets for Cancer Chemotherapy", 1994, CRC PRESS, article LOFTS, F. J. ET AL.: "Growth factor receptors as targets"
YAMAMOTO, T.; TAYA, S.; KAIBUCHI, K., JOURNAL OF BIOCHEMISTRY, vol. 126, no. 5, 1999, pages 799 - 803
YEN L ET AL., ONCOGENE, vol. 19, 2000, pages 3460 - 3469
YUSUKE KOBAYASHI ET AL: "A Powerful Hydrogen-Bond-Donating Organocatalyst for the Enantioselective Intramolecular Oxa-Michael Reaction of a,b- Unsaturated Amides and Esters", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, vol. 52, no. 42, 1 January 2013 (2013-01-01), WILEY - V C H VERLAG GMBH & CO. KGAA, DE, pages 11114 - 11118, XP009193162, ISSN: 1433-7851 *
ZHONG, H ET AL., CANCER RES, vol. 60, no. 6, 2000, pages 1541 - 1545

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11578136B2 (en) 2017-03-16 2023-02-14 Innate Pharma Compositions and methods for treating cancer
WO2019002606A1 (fr) 2017-06-30 2019-01-03 Selvita S.A. Modulateurs de 5,6-bicyclo-imidazo[1,2-a]pyrazine du récepteur a2a de l'adénosine
WO2019053617A1 (fr) * 2017-09-12 2019-03-21 Glaxosmithkline Intellectual Property Development Limited Composés chimiques
WO2019068907A1 (fr) 2017-10-06 2019-04-11 Innate Pharma Restauration de l'activité de lymphocytes t par l'axe cd39/cd73
US11377503B2 (en) 2018-06-18 2022-07-05 Innate Pharma Antibodies that bind human CD39 and inhibit ATPase activity of a soluble extracellular domain human CD39 polypeptide
US11911372B2 (en) 2018-06-28 2024-02-27 Ctxt Pty Ltd Compounds
US11931343B2 (en) 2018-08-27 2024-03-19 Arcus Biosciences, Inc. CD73 inhibitors
EP3843714A4 (fr) * 2018-08-27 2022-04-20 Arcus Biosciences, Inc. Inhibiteurs de cd73
US11332492B2 (en) 2018-08-28 2022-05-17 Jiangsu Hengrui Medicine Co., Ltd. CD73 inhibitors and therapeutic uses thereof
US10881681B2 (en) 2018-09-11 2021-01-05 Risen (Suzhou) Pharma Tech Co., Ltd. CD73 inhibitors and pharmaceutical uses thereof
US11530234B2 (en) 2018-09-11 2022-12-20 Risen (Suzhou) Pharma Tech Co., Ltd. CD73 inhibitors and pharmaceutical uses thereof
WO2020128036A1 (fr) 2018-12-21 2020-06-25 Ryvu Therapeutics S.A. Modulateurs du récepteur a2a de l'adénosine
WO2020146795A1 (fr) 2019-01-11 2020-07-16 Omeros Corporation Procédés et compositions pour le traitement du cancer
CN114206841A (zh) * 2019-04-15 2022-03-18 博奥阿迪斯生物科技公司 Cd73抑制剂
WO2020211668A1 (fr) * 2019-04-15 2020-10-22 Bioardis Llc Inhibiteurs de cd73
US11492346B2 (en) 2019-06-18 2022-11-08 Pfizer Inc. Benzisoxazole sulfonamide derivatives
WO2021236818A1 (fr) * 2020-05-19 2021-11-25 Board Of Regents Of The University Of Nebraska Benzothiadiazines halogénées pour le traitement du cancer
WO2022121914A1 (fr) * 2020-12-10 2022-06-16 上海翰森生物医药科技有限公司 Régulateur de dérivé à cycle oxo-azote, son procédé de préparation et son application
WO2023201267A1 (fr) 2022-04-13 2023-10-19 Gilead Sciences, Inc. Polythérapie pour le traitement de cancers exprimant trop-2

Similar Documents

Publication Publication Date Title
WO2017098421A1 (fr) Composés benzothiadiazine
WO2017153952A1 (fr) Dérivés de 5-sulfamoyl-2-hydroxybenzamide
EP2549868B1 (fr) Composés chimiques
EP2330909B1 (fr) Composés chimiques
US8598156B2 (en) Chemical compounds
WO2012061557A2 (fr) Composés chimiques
JP2010535804A (ja) Ｐｉ３キナーゼ阻害薬としてのキノキサリン誘導体
EP2167092A2 (fr) Dérivés de quinazoline en tant qu'inhibiteurs de la kinase pi3
WO2013096151A1 (fr) Composés chimiques
JP2010529031A (ja) Ｐｉ３キナーゼ阻害剤としてのナフチリジン誘導体
EP2624696A1 (fr) Dérivés de benzimidazole utilisés comme inhibiteurs de pi3 kinase
WO2013095761A1 (fr) Dérivés d'imidizopyridine comme inhibiteurs de la pi3 kinase
WO2015056180A1 (fr) Dérivés d'indoline utilisés comme inhibiteurs de perk
WO2019049061A1 (fr) Dérivés de 5-(1 h-benzo[d]imidazo-2-yl)-pyridin-2-amine et de 5-(3h-imidazo[4,5-b]pyridin-6-yl)-pyridin-2-amine utilisés en tant qu'inhibiteurs d'histone acétyltransférase de c-myc et p300/cbp pour le traitement du cancer
WO2011103546A1 (fr) Triazolones utilisées comme inhibiteurs d'acides gras synthase
JP5964426B2 (ja) 脂肪酸シンターゼ阻害剤
WO2010120854A1 (fr) Composés chimiques
WO2019053617A1 (fr) Composés chimiques
JP5554833B2 (ja) Ｐｉ３キナーゼ阻害剤としてのチアゾロピリミジノン誘導体
WO2013096153A1 (fr) Composés chimiques
WO2019021208A1 (fr) Dérivés d'indazole utiles en tant qu'inhibiteurs de perk

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16816401

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 16816401

Country of ref document: EP

Kind code of ref document: A1