WO2010083465A1 - Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer - Google Patents

Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer Download PDF

Info

Publication number
WO2010083465A1
WO2010083465A1 PCT/US2010/021275 US2010021275W WO2010083465A1 WO 2010083465 A1 WO2010083465 A1 WO 2010083465A1 US 2010021275 W US2010021275 W US 2010021275W WO 2010083465 A1 WO2010083465 A1 WO 2010083465A1
Authority
WO
WIPO (PCT)
Prior art keywords
optionally substituted
benzo
dihydro
cyclohepta
pyridazin
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US2010/021275
Other languages
English (en)
French (fr)
Inventor
Yasumichi Hitoshi
Sacha Holland
Donald G. Payan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Rigel Pharmaceuticals Inc
Original Assignee
Rigel Pharmaceuticals 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 Rigel Pharmaceuticals Inc filed Critical Rigel Pharmaceuticals Inc
Priority to CA2749843A priority Critical patent/CA2749843C/en
Priority to HK12104971.1A priority patent/HK1164146B/en
Priority to JP2011546409A priority patent/JP5858789B2/ja
Priority to AU2010204578A priority patent/AU2010204578B2/en
Priority to EP10700686.8A priority patent/EP2387395B1/en
Priority to BRPI1007046-0A priority patent/BRPI1007046B1/pt
Priority to PL10700686T priority patent/PL2387395T3/pl
Priority to SG2011051174A priority patent/SG172997A1/en
Priority to RU2011132118/15A priority patent/RU2555326C2/ru
Priority to CN201080004818.0A priority patent/CN102281875B/zh
Priority to ES10700686.8T priority patent/ES2528032T3/es
Publication of WO2010083465A1 publication Critical patent/WO2010083465A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/243—Platinum; Compounds thereof
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings

Definitions

  • this invention is directed to combination therapies designed to prevent, treat or manage cancer, preferably metastatic cancer, in a patient, wherein the combination therapies comprise administering an AxI inhibitor to the patient in need thereof in combination with one or more chemotherapeutic agents.
  • this invention provides methods of preventing, treating or managing cancer, preferably metastatic cancer, in a patient comprising administering to the patient in need thereof a therapeutically or prophylactically effective amount of an AxI inhibitor in combination with the administration of a therapeutically or prophylactically effective amount of one or more chemotherapeutic agents.
  • Optionally substituted alkenyl refers to an alkenyl radical, as defined above, which is optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, oxo, thioxo, trimethylsilanyl, -OR 20 , -OC(O)-R 20 , -N(R 20 ) 2 , -C(O)R 20 , -C(O)OR 20 , -C(O)N(R 20 ) 2 , -N(R 20 )C(O)OR 20 , -N(R 20 )C(O)R 20 , -N(R 20 )S(O) 2 R 20 , -S(O) 1 OR 20 (where t is 1 or 2), -S(O) P R 20 (where p is O, 1 or 2), and -S(O) 2 N(R 20 ) 2 where each R 20 is independently selected from the group consisting of hydrogen, al
  • Optionally substituted cycloalkylalkenyl refers to a cycloalkylalkenyl radical, as defined above, wherein the alkenylene chain of the cycloalkylalkenyl radical is an optionally substituted alkenylene chain, as defined above, and the cycloalkyl radical of the cycloalkylalkenyl radical is an optionally substituted cycloalkyl radical as defined above.
  • Optionally substituted heteroarylalkynyl refers to a heteroarylalkynyl radical, as defined above, wherein the alkynylene chain of the heteroarylalkynyl radical is an optionally substituted alkynylene chain, as defined above, and the heteroaryl radical of the heteroarylalkynyl radical is an optionally substituted heteroaryl radical, as defined above.
  • alkyl alkyl, halo, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; and
  • R 3 is selected from the group consisting of 6,7-dihydro-5H-benzo[2,3]azepino[4,5- ⁇ yridazin-3-yl, (Z)-dibenzo[£j][l,4]thiazepin-l 1-yl, 6,7-dihydro-5H- benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, and 6,7-dihydro-5H- benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted a
  • one embodiment of the methods of preventing, treating or managing cancer, preferably metastatic cancer, in a patient comprising administering to the patient in need thereof a therapeutically or prophylactically effective amount of an AxI inhibitor in combination with the administration of a therapeutically or prophylactically effective amount of one or more chemotherapeutic agents, is the method wherein the AxI inhibitor is a compound of formula (I) selected from the group consisting of: 1 -(6,7-dihydro-5H-benzo [6,7] cyclohepta[ 1 ,2-c]pyridazin-3 -yl)-N '3 -(7-(pyrrolidin- 1 -yl)-
  • another embodiment of the methods of preventing, treating or managing cancer, preferably metastatic cancer, in a patient comprising administering to the patient in need thereof a therapeutically or prophylactically effective amount of an AxI inhibitor in combination with the administration of a therapeutically or prophylactically effective amount of one or more chemotherapeutic agents, is the method wherein the AxI inhibitor is l-(6,7-dihydro-5H-pyrido[2',3':6,7]cyclohepta[l,2-c]pyridazin-3-yl)-N 3 -(3-fluoro-4-(4- (pyrrolidin- 1 -yl)piperidin- 1 -yl)phenyl)- 1 H- 1 ,2,4-triazole-3 ,5-diamine.
  • the AxI inhibitor is l-(6,7-dihydro-5H-pyrido[2',3':6,7]cyclohepta[l,2-c]pyrida
  • Exemplary antitumor antibiotics include, by way of example and not limitation, actinomycin D, daunorubicin, and bleomycin.
  • An exemplary enzyme effective as an anti-neoplastic agent is L-asparaginase.
  • Exemplary platinum complexes and coordination compounds include, by way of example and not limitation, cisplatin (cw-diamminedichloridoplatinum(II) (CDDP)), carboplatin and oxaliplatin.
  • an AxI inhibitor is administered simultaneously with, prior to, or after administration of one or more other chemotherapeutic agents, as described herein, by the same route of administration or by different routes.
  • Such combination therapy includes administration of a single pharmaceutical dosage formulation which contains an AxI inhibitor and one or more additional chemotherapeutic agents, as well as administration of the AxI inhibitor and each chemotherapeutic agent in its own separate pharmaceutical dosage formulation.
  • the AxI inhibitor and the other one or more chemotherapeutic agents can be administered to the patient together in a single oral dosage composition such as a tablet or capsule, or each agent can be administered in separate oral dosage formulations.
  • a mixture of the compound of formula (De) and phosphoryl chloride is refluxed for a period of time of between about 1 hour and 3 hours, preferably for about 2 hours to aromatize and chlorinate the ring containing the N-N linkage.
  • the compound of formula (Df) is isolated from the reaction mixture by standard isolation techniques known to one skilled in the art.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
PCT/US2010/021275 2009-01-16 2010-01-15 Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer Ceased WO2010083465A1 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
CA2749843A CA2749843C (en) 2009-01-16 2010-01-15 Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer
HK12104971.1A HK1164146B (en) 2009-01-16 2010-01-15 Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer
JP2011546409A JP5858789B2 (ja) 2009-01-16 2010-01-15 転移性癌の予防、治療、または管理のための併用療法に用いるためのａｘｌ阻害薬
AU2010204578A AU2010204578B2 (en) 2009-01-16 2010-01-15 AXL inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer
EP10700686.8A EP2387395B1 (en) 2009-01-16 2010-01-15 Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer
BRPI1007046-0A BRPI1007046B1 (pt) 2009-01-16 2010-01-15 Inibidores axl para uso em terapia de combinação para evitar, tratar ou controlar o câncer metastático.
PL10700686T PL2387395T3 (pl) 2009-01-16 2010-01-15 Inhibitory Axl do zastosowania w terapii skojarzonej do zapobiegania, leczenia lub postępowania z nowotworem przerzutowym
SG2011051174A SG172997A1 (en) 2009-01-16 2010-01-15 Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer
RU2011132118/15A RU2555326C2 (ru) 2009-01-16 2010-01-15 ИНГИБИТОРЫ Axl ДЛЯ ПРИМЕНЕНИЯ В КОМБИНИРОВАННОЙ ТЕРАПИИ ДЛЯ ПРЕДОТВРАЩЕНИЯ, УСТРАНЕНИЯ ИЛИ ЛЕЧЕНИЯ МЕТАСТAЗИРУЮЩЕГО РАКА
CN201080004818.0A CN102281875B (zh) 2009-01-16 2010-01-15 预防、治疗或应对转移癌的使用axl抑制剂的组合疗法
ES10700686.8T ES2528032T3 (es) 2009-01-16 2010-01-15 Inhibidores de Axl para su uso en terapia de combinación para prevenir, tratar o manejar cáncer metastásico

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14544809P 2009-01-16 2009-01-16
US61/145,448 2009-01-16

Publications (1)

Publication Number Publication Date
WO2010083465A1 true WO2010083465A1 (en) 2010-07-22

Family

ID=41683427

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2010/021275 Ceased WO2010083465A1 (en) 2009-01-16 2010-01-15 Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer

Country Status (13)

Country Link
US (5) US8546433B2 (enExample)
EP (1) EP2387395B1 (enExample)
JP (2) JP5858789B2 (enExample)
CN (1) CN102281875B (enExample)
AU (1) AU2010204578B2 (enExample)
BR (1) BRPI1007046B1 (enExample)
CA (1) CA2749843C (enExample)
ES (1) ES2528032T3 (enExample)
PL (1) PL2387395T3 (enExample)
PT (1) PT2387395E (enExample)
RU (1) RU2555326C2 (enExample)
SG (1) SG172997A1 (enExample)
WO (1) WO2010083465A1 (enExample)

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8546433B2 (en) 2009-01-16 2013-10-01 Rigel Pharmaceuticals, Inc. Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer
WO2015077375A1 (en) 2013-11-20 2015-05-28 Signalchem Lifesciences Corp. Quinazoline derivatives as tam family kinase inhibitors
WO2015081257A2 (en) 2013-11-27 2015-06-04 Signalchem Lifesciences Corporation Aminopyridine derivatives as tam family kinase inhibitors
WO2015082887A3 (en) * 2013-12-02 2015-07-30 Bergenbio As Use of kinase inhibitors
WO2015156674A3 (en) * 2014-04-10 2015-12-17 Stichting Het Nederlands Kanker Instituut Method for treating cancer
WO2016193680A1 (en) * 2015-05-29 2016-12-08 Bergenbio As Combination therapy with axl inhibitor and immune checkpoint modulator or oncolytic virus
EP3184121A2 (en) 2012-07-25 2017-06-28 Salk Institute For Biological Studies Lipid membranes with exposed phosphatidylserine as tam ligands, use for treating autoimmune diseases
US9994553B2 (en) 2014-11-14 2018-06-12 Bergenbio As Process for the purification of the Axl tyrosine receptor kinase inhibitor “R428”
CN109384774A (zh) * 2017-08-11 2019-02-26 中国科学院上海药物研究所 一类多取代的吡嗪/三嗪酰胺类化合物及其制备方法和应用
US10317405B2 (en) 2012-05-02 2019-06-11 Bergenbio Asa Methods of detecting Akt3 and administering Ax1 inhibitor
WO2020188015A1 (en) 2019-03-21 2020-09-24 Onxeo A dbait molecule in combination with kinase inhibitor for the treatment of cancer
WO2021032883A1 (en) 2019-08-22 2021-02-25 Bergenbio Asa Combination therapy of a patient subgroup
CN112739349A (zh) * 2018-09-18 2021-04-30 圣诺康生命科学公司 用于治疗血癌的组合疗法
WO2021089791A1 (en) 2019-11-08 2021-05-14 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the treatment of cancers that have acquired resistance to kinase inhibitors
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
WO2021191197A1 (en) 2020-03-23 2021-09-30 Bergenbio Asa Combination therapy comprising an axl inhibitor
WO2021214492A1 (en) 2020-04-24 2021-10-28 Bergenbio Asa Method of selecting patients for treatment with a combination of an axl inhibitor and an immune checkpoint modulator
WO2022200463A1 (en) 2021-03-23 2022-09-29 Bergenbio Asa Combination of axl antibodies and ace inhibitors in the treatment of fibrosis
WO2022220227A1 (ja) * 2021-04-14 2022-10-20 エーザイ・アール・アンド・ディー・マネジメント株式会社 テトラヒドロピリドピリミジン化合物
WO2023247769A1 (en) 2022-06-24 2023-12-28 Bergenbio Asa Dosage regimen for axl inhibitor
WO2024206858A1 (en) 2023-03-30 2024-10-03 Revolution Medicines, Inc. Compositions for inducing ras gtp hydrolysis and uses thereof
WO2024229406A1 (en) 2023-05-04 2024-11-07 Revolution Medicines, Inc. Combination therapy for a ras related disease or disorder
US12195482B1 (en) 2022-06-28 2025-01-14 Arcus Biosciences, Inc. Compounds as inhibitors of AXL
WO2025034702A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Rmc-6291 for use in the treatment of ras protein-related disease or disorder
WO2025080946A2 (en) 2023-10-12 2025-04-17 Revolution Medicines, Inc. Ras inhibitors
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
US12441707B2 (en) 2019-12-30 2025-10-14 Tyra Biosciences, Inc. Indazole compounds
WO2025240847A1 (en) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Ras inhibitors

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007030680A2 (en) * 2005-09-07 2007-03-15 Rigel Pharmaceuticals, Inc. Triazole derivatives useful as axl inhibitors
ES2607065T3 (es) * 2006-12-29 2017-03-29 Rigel Pharmaceuticals, Inc. Triazoles N3-heteroaril sustituidos y triazoles N5-heteroaril sustituidos útiles como inhibidores de axl
CA2710043C (en) 2006-12-29 2016-02-09 Rigel Pharmaceuticals, Inc. Bicyclic aryl and bicyclic heteroaryl substituted triazoles useful as axl inhibitors
PL2114955T3 (pl) 2006-12-29 2013-06-28 Rigel Pharmaceuticals Inc Triazole podstawione mostkowanym bicyklicznym arylem oraz mostkowanym bicyklicznym heteroarylem użyteczne jako inhibitory Axl
ME01832B (me) 2006-12-29 2014-12-20 Rigel Pharmaceuticals Inc Policiklični heteroaril supstituisani triazoli koji su korisni kao axl inhibitori
CN101622252B (zh) 2006-12-29 2015-04-22 里格尔制药公司 用作axl抑制剂的取代三唑
JP5635909B2 (ja) * 2007-10-26 2014-12-03 ライジェル ファーマシューティカルズ， インコーポレイテッド Ａｘｌ阻害剤として有用な多環アリール置換トリアゾール及び多環ヘテロアリール置換トリアゾール
HRP20170317T1 (hr) 2008-02-15 2017-04-21 Rigel Pharmaceuticals, Inc. Spojevi pirimidin-2-amina i njihova uporaba kao inhibitora jak kinaza
CA2730251C (en) 2008-07-09 2016-08-09 Rigel Pharmaceuticals, Inc. Bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors
CA2730231C (en) 2008-07-09 2016-10-18 Rigel Pharmaceuticals, Inc. Polycyclic heteroaryl substituted triazoles useful as axl inhibitors
JP4644273B2 (ja) * 2008-07-15 2011-03-02 本田技研工業株式会社 車両周辺監視装置
US8916574B2 (en) 2009-09-28 2014-12-23 Qilu Pharmaceutical Co., Ltd. 4-(substituted anilino)-quinazoline derivatives useful as tyrosine kinase inhibitors
WO2015161230A1 (en) * 2014-04-19 2015-10-22 Massachusetts Institute Of Technology Methods of reducing kinase inhibitor resistance
CN106083764B (zh) * 2016-07-11 2018-09-18 上海皓元生物医药科技有限公司 一种用于制备axl抑制剂的高纯度中间体的手性拆分方法
KR20200085307A (ko) * 2017-11-04 2020-07-14 아라바이브 바이올로직스, 인크. Axl 유인 수용체를 이용한 전이성 암의 치료 방법

Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6258360B1 (en) 1989-05-04 2001-07-10 Igen International, Inc. Prodrugs activated by targeted catalytic proteins
US20050118604A1 (en) 2002-10-29 2005-06-02 Rigel Pharmaceuticals, Incorporated Modulators of angiogenesis and tumorigenesis
WO2007030680A2 (en) 2005-09-07 2007-03-15 Rigel Pharmaceuticals, Inc. Triazole derivatives useful as axl inhibitors
US7351729B2 (en) 2002-03-08 2008-04-01 Signal Pharmaceuticals, Llc JNK inhibitors for use in combination therapy for treating or managing proliferative disorders and cancers
WO2008045978A1 (en) 2006-10-10 2008-04-17 Rigel Pharmaceuticals, Inc. Pinane-substituted pyrimidinediamine derivatives useful as axl inhibitors
US20080117789A1 (en) 2006-11-17 2008-05-22 Sharp Kabushiki Kaisha Optical pickup device
WO2008080134A2 (en) 2006-12-22 2008-07-03 Rigel Pharmaceuticals, Inc. 4-amin0-2- (hetero) arylamino-5- (hetero) arylthiazoles useful as axl inhibitors
WO2008083367A2 (en) 2006-12-29 2008-07-10 Rigel Pharmaceuticals, Inc. Polycyclic heteroaryl substituted triazoles useful as axl inhibitors
WO2008083353A1 (en) 2006-12-29 2008-07-10 Rigel Pharmaceuticals, Inc. Bicyclic aryl and bicyclic heteroaryl substituted triazoles useful as axl inhibitors
WO2008083354A1 (en) 2006-12-29 2008-07-10 Rigel Pharmaceuticals, Inc. N3-heteroaryl substituted triazoles and n5-heteroaryl substituted triazoles useful as axl inhibitors
WO2008083356A1 (en) 2006-12-29 2008-07-10 Rigel Pharmaceuticals, Inc. Substituted triazoles useful as axl inhibitors
WO2008083357A1 (en) 2006-12-29 2008-07-10 Rigel Pharmaceuticals, Inc. Bridged bicyclic aryl and bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors
WO2009054864A1 (en) 2007-10-26 2009-04-30 Rigel Pharmaceuticals, Inc. Polycyclic aryl substituted triazoles and polycyclic heteroaryl substituted triazoles useful as axl inhibitors

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1403866A (en) * 1971-12-06 1975-08-28 Wyeth John & Brother Ltd Derivatives of 3-amino-1,2,4-triazoles
US4512992A (en) * 1980-06-13 1985-04-23 Burroughs Wellcome Co. Treatment with dialkoxy pyridopyrimidine compounds
WO1990007926A1 (en) 1989-01-20 1990-07-26 Pfizer Inc. 3-(1,2,5,6-tetrahydropyridyl)-pyrrolopyridines
US5750545A (en) 1993-07-23 1998-05-12 The Green Cross Corporation Triazole derivative and pharmaceutical use thereof
UA71971C2 (en) 1999-06-04 2005-01-17 Agoron Pharmaceuticals Inc Diaminothiazoles, composition based thereon, a method for modulation of protein kinases activity, a method for the treatment of diseases mediated by protein kinases
GB9918180D0 (en) 1999-08-02 1999-10-06 Smithkline Beecham Plc Novel compositions
BR0116792A (pt) 2000-12-22 2004-02-17 Ortho Mcneil Pharm Inc Derivados de diamina de triazol substituìdos como inibidores de quinase
DE10123586A1 (de) 2001-05-08 2002-11-28 Schering Ag 3,5-Diamino-1,2,4-triazole als Kinase Inhibitoren
TWI335221B (en) 2001-09-27 2011-01-01 Alcon Inc Inhibtors of glycogen synthase kinase-3 (gsk-3) for treating glaucoma
MXPA04010778A (es) 2002-05-03 2005-03-07 Janssen Pharmaceutica Nv Microemulsiones polimericas.
CN100345593C (zh) 2002-08-06 2007-10-31 东丽株式会社 用于制备肾脏疾病的治疗或预防药物中的用途
AR042052A1 (es) * 2002-11-15 2005-06-08 Vertex Pharma Diaminotriazoles utiles como inhibidores de proteinquinasas
AU2004220176A1 (en) 2003-03-14 2004-09-23 Astrazeneca Ab Novel fused triazolones and the uses thereof
CA2526387A1 (en) 2003-06-12 2004-12-23 Astellas Pharma Inc. Benzamide derivative or salt thereof
AR045731A1 (es) 2003-08-06 2005-11-09 Vertex Pharma Compuestos de aminotriazol utiles como inhibidores de quinasas de proteinas
CN1934107A (zh) 2004-01-30 2007-03-21 Ab科学公司 作为酪氨酸激酶抑制剂的2－(3－取代芳基)氨基－4－芳基－噻唑
KR20070036025A (ko) 2004-02-11 2007-04-02 얀센 파마슈티카 엔.브이. 치환된 트리아졸 화합물의 제조방법
JP4812763B2 (ja) 2004-05-18 2011-11-09 ライジェル ファーマシューティカルズ， インコーポレイテッド シクロアルキル置換ピリミジンジアミン化合物およびそれらの用途
AU2005272815A1 (en) 2004-08-13 2006-02-23 Genentech, Inc. Thiazole based inhibitors of ATP-utilizing enzymes
ATE493401T1 (de) 2004-09-17 2011-01-15 Vertex Pharma Als proteinkinaseinhibitoren geeignete diaminotriazolverbindungen
HRP20100715T1 (hr) 2004-10-21 2011-02-28 Vertex Pharmaceuticals Incorporated Triazoli korisni kao inhibitori protein kinaza
US20060166936A1 (en) 2004-10-29 2006-07-27 Hayley Binch Diaminotriazole compounds useful as inhibitors of protein kinases
KR20070085433A (ko) 2004-11-24 2007-08-27 노파르티스 아게 Ｊａｋ 저해제들과 ｂｃｒ-ａｂｌ, ｆｌｔ-3, ｆａｋ 또는ｒａｆ 키나제 저해제들 중 하나 이상의 조합물
US20070166388A1 (en) * 2005-02-18 2007-07-19 Desai Neil P Combinations and modes of administration of therapeutic agents and combination therapy
WO2007070872A1 (en) 2005-12-15 2007-06-21 Rigel Pharmaceuticals, Inc. Kinase inhibitors and their uses
US8217037B2 (en) 2006-04-07 2012-07-10 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Thiazole and thiophene analogues, and their use in treating autoimmune diseases and cancers
FR2908131B1 (fr) 2006-11-03 2009-01-09 Univ Haute Alsace Etablissemen Derives d'aminobenzocycloheptene,leurs procedes de preparation et leur utilisation en therapeutique
WO2008157131A1 (en) 2007-06-15 2008-12-24 Irm Llc Protein kinase inhibitors and methods for using thereof
HRP20170317T1 (hr) 2008-02-15 2017-04-21 Rigel Pharmaceuticals, Inc. Spojevi pirimidin-2-amina i njihova uporaba kao inhibitora jak kinaza
CA2730231C (en) 2008-07-09 2016-10-18 Rigel Pharmaceuticals, Inc. Polycyclic heteroaryl substituted triazoles useful as axl inhibitors
CA2730251C (en) 2008-07-09 2016-08-09 Rigel Pharmaceuticals, Inc. Bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors
BRPI1007046B1 (pt) * 2009-01-16 2019-07-16 Rigel Pharmaceuticals, Inc. Inibidores axl para uso em terapia de combinação para evitar, tratar ou controlar o câncer metastático.

Patent Citations (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6258360B1 (en) 1989-05-04 2001-07-10 Igen International, Inc. Prodrugs activated by targeted catalytic proteins
US7351729B2 (en) 2002-03-08 2008-04-01 Signal Pharmaceuticals, Llc JNK inhibitors for use in combination therapy for treating or managing proliferative disorders and cancers
US20050118604A1 (en) 2002-10-29 2005-06-02 Rigel Pharmaceuticals, Incorporated Modulators of angiogenesis and tumorigenesis
EP1563094A2 (en) 2002-10-29 2005-08-17 Rigel Pharmaceuticals, Inc. Modulators of angiogenesis and tumorigenesis
WO2007030680A2 (en) 2005-09-07 2007-03-15 Rigel Pharmaceuticals, Inc. Triazole derivatives useful as axl inhibitors
US20070213375A1 (en) 2005-09-07 2007-09-13 Rigel Pharmaceuticals, Inc. Triazole derivatives useful as Axl inhibitors
WO2008045978A1 (en) 2006-10-10 2008-04-17 Rigel Pharmaceuticals, Inc. Pinane-substituted pyrimidinediamine derivatives useful as axl inhibitors
US20080153815A1 (en) 2006-10-10 2008-06-26 Rigel Pharmaceuticals, Inc. Pinane-substituted pyrimidinediamine derivatives useful as axl inhibitors
US20080117789A1 (en) 2006-11-17 2008-05-22 Sharp Kabushiki Kaisha Optical pickup device
WO2008080134A2 (en) 2006-12-22 2008-07-03 Rigel Pharmaceuticals, Inc. 4-amin0-2- (hetero) arylamino-5- (hetero) arylthiazoles useful as axl inhibitors
WO2008083367A2 (en) 2006-12-29 2008-07-10 Rigel Pharmaceuticals, Inc. Polycyclic heteroaryl substituted triazoles useful as axl inhibitors
WO2008083353A1 (en) 2006-12-29 2008-07-10 Rigel Pharmaceuticals, Inc. Bicyclic aryl and bicyclic heteroaryl substituted triazoles useful as axl inhibitors
WO2008083354A1 (en) 2006-12-29 2008-07-10 Rigel Pharmaceuticals, Inc. N3-heteroaryl substituted triazoles and n5-heteroaryl substituted triazoles useful as axl inhibitors
WO2008083356A1 (en) 2006-12-29 2008-07-10 Rigel Pharmaceuticals, Inc. Substituted triazoles useful as axl inhibitors
WO2008083357A1 (en) 2006-12-29 2008-07-10 Rigel Pharmaceuticals, Inc. Bridged bicyclic aryl and bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors
US20080176847A1 (en) 2006-12-29 2008-07-24 Rigel Pharmaceuticals, Inc. Bridged bicyclic aryl and bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors
US20080182862A1 (en) 2006-12-29 2008-07-31 Rigel Pharmaceuticals, Inc. N3-heteroaryl substituted triazoles and n5-heteroaryl substituted triazoles useful as axl inhibitors
US20080188454A1 (en) 2006-12-29 2008-08-07 Rigel Pharmaceuticals, Inc. Bicyclic aryl and bicyclic heteroaryl substituted triazoles useful as axl inhibitors
US20080188474A1 (en) 2006-12-29 2008-08-07 Rigel Pharmaceuticals, Inc. Substituted triazoles useful as axl inhibitors
US20080188455A1 (en) 2006-12-29 2008-08-07 Rigel Pharmaceuticals, Inc. Polycyclic heteroaryl substituted triazoles useful as axl inhibitors
WO2009054864A1 (en) 2007-10-26 2009-04-30 Rigel Pharmaceuticals, Inc. Polycyclic aryl substituted triazoles and polycyclic heteroaryl substituted triazoles useful as axl inhibitors
US20090111816A1 (en) 2007-10-26 2009-04-30 Rigel Pharmaceuticals, Inc. Polycyclic aryl substituted triazoles and polycyclic heteroaryl substituted triazoles useful as axl inhibitors

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
"Advanced Organic Chemistry: Reactions, Mechanisms, and Structure", December 2000, WILEY
"The Merck Manuals Online Medical Library For HealthCare Professionals at www.mercksource.com and Goodman and Gilmans The Pharmacological Basis of Therapeutics", 1996, MCGRAW HILL, article "Commonly Used Antineoplastic Drugs", pages: 1381 - 1287
ARDITTI ET AL., MOL. CANCER THERAP., vol. 4, no. 2, 2005, pages 325 - 331
CURRENT PROTOCOLS IN IMMUNOLOGY, 2000, pages 20.2.1 - 20.2.16
ELICL, E. L.; WILCN, S. H.: "Stereochemistry of Organic Compounds", 1994, WILEY & SONS
GREENE, T.W.; P.G.M. WUTS: "Greene's Protective Groups in Organic Synthesis", 1999, WILEY
HOLLAND ET AL.: "Multiple roles for the receptor tyrosine kinase axl in tumor formation", CANCER RES., vol. 65, 2005, pages 9294 - 303, XP009111560, DOI: doi:10.1158/0008-5472.CAN-05-0993
J. DAVID ROZZELL; ANDREAS S. BOMMARIUS: "Transminations. Enzyme Catalysis in Organic Synthesis", 2002, pages: 873 - 893
PULASKI, B.A. ET AL., CURRENT PROTOCOLS IN IMMUNOLOGY, 2000, pages 20.2.1 - 20.2.16
TRAFALIS ET AL., BR. J HOEMATOL., vol. 128, no. 3, 2005, pages 343 - 50
V. PEESAPATI; S.C. VENKATA, INDIAN J CHEM., vol. 41B, 2002, pages 839

Cited By (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8546433B2 (en) 2009-01-16 2013-10-01 Rigel Pharmaceuticals, Inc. Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer
US10317405B2 (en) 2012-05-02 2019-06-11 Bergenbio Asa Methods of detecting Akt3 and administering Ax1 inhibitor
EP3184121A2 (en) 2012-07-25 2017-06-28 Salk Institute For Biological Studies Lipid membranes with exposed phosphatidylserine as tam ligands, use for treating autoimmune diseases
WO2015077375A1 (en) 2013-11-20 2015-05-28 Signalchem Lifesciences Corp. Quinazoline derivatives as tam family kinase inhibitors
WO2015081257A2 (en) 2013-11-27 2015-06-04 Signalchem Lifesciences Corporation Aminopyridine derivatives as tam family kinase inhibitors
WO2015082887A3 (en) * 2013-12-02 2015-07-30 Bergenbio As Use of kinase inhibitors
US9801880B2 (en) 2013-12-02 2017-10-31 Bergenbio As Use of kinase inhibitors
WO2015156674A3 (en) * 2014-04-10 2015-12-17 Stichting Het Nederlands Kanker Instituut Method for treating cancer
US9994553B2 (en) 2014-11-14 2018-06-12 Bergenbio As Process for the purification of the Axl tyrosine receptor kinase inhibitor “R428”
WO2016193680A1 (en) * 2015-05-29 2016-12-08 Bergenbio As Combination therapy with axl inhibitor and immune checkpoint modulator or oncolytic virus
EP3804723A1 (en) 2015-05-29 2021-04-14 BerGenBio ASA Combination therapy
US11534440B2 (en) 2015-05-29 2022-12-27 Bergenbio Asa Combination therapy with Axl inhibitor and immune checkpoint modulator or oncolytic virus
CN109384774A (zh) * 2017-08-11 2019-02-26 中国科学院上海药物研究所 一类多取代的吡嗪/三嗪酰胺类化合物及其制备方法和应用
CN109384774B (zh) * 2017-08-11 2023-02-17 中国科学院上海药物研究所 一类多取代的吡嗪/三嗪酰胺类化合物及其制备方法和应用
CN112739349A (zh) * 2018-09-18 2021-04-30 圣诺康生命科学公司 用于治疗血癌的组合疗法
US12097194B2 (en) 2018-09-18 2024-09-24 Signalchem Lifesciences Corporation Combination therapy for treating blood cancer
CN112739349B (zh) * 2018-09-18 2024-03-01 圣诺康生命科学公司 用于治疗血癌的组合疗法
WO2020188015A1 (en) 2019-03-21 2020-09-24 Onxeo A dbait molecule in combination with kinase inhibitor for the treatment of cancer
WO2021032883A1 (en) 2019-08-22 2021-02-25 Bergenbio Asa Combination therapy of a patient subgroup
WO2021089791A1 (en) 2019-11-08 2021-05-14 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the treatment of cancers that have acquired resistance to kinase inhibitors
US12441707B2 (en) 2019-12-30 2025-10-14 Tyra Biosciences, Inc. Indazole compounds
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
WO2021191197A1 (en) 2020-03-23 2021-09-30 Bergenbio Asa Combination therapy comprising an axl inhibitor
WO2021214492A1 (en) 2020-04-24 2021-10-28 Bergenbio Asa Method of selecting patients for treatment with a combination of an axl inhibitor and an immune checkpoint modulator
WO2022200463A1 (en) 2021-03-23 2022-09-29 Bergenbio Asa Combination of axl antibodies and ace inhibitors in the treatment of fibrosis
WO2022220227A1 (ja) * 2021-04-14 2022-10-20 エーザイ・アール・アンド・ディー・マネジメント株式会社 テトラヒドロピリドピリミジン化合物
JPWO2022220227A1 (enExample) * 2021-04-14 2022-10-20
WO2023247769A1 (en) 2022-06-24 2023-12-28 Bergenbio Asa Dosage regimen for axl inhibitor
US12195482B1 (en) 2022-06-28 2025-01-14 Arcus Biosciences, Inc. Compounds as inhibitors of AXL
WO2024206858A1 (en) 2023-03-30 2024-10-03 Revolution Medicines, Inc. Compositions for inducing ras gtp hydrolysis and uses thereof
WO2024229406A1 (en) 2023-05-04 2024-11-07 Revolution Medicines, Inc. Combination therapy for a ras related disease or disorder
WO2025034702A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Rmc-6291 for use in the treatment of ras protein-related disease or disorder
WO2025080946A2 (en) 2023-10-12 2025-04-17 Revolution Medicines, Inc. Ras inhibitors
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
WO2025240847A1 (en) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Ras inhibitors

Also Published As

Publication number Publication date
PL2387395T3 (pl) 2015-03-31
RU2555326C2 (ru) 2015-07-10
EP2387395B1 (en) 2014-10-15
JP2015007135A (ja) 2015-01-15
RU2011132118A (ru) 2013-02-27
EP2387395A1 (en) 2011-11-23
AU2010204578A1 (en) 2011-07-28
HK1164146A1 (en) 2012-09-21
JP2012515225A (ja) 2012-07-05
US20100196511A1 (en) 2010-08-05
JP5858789B2 (ja) 2016-02-10
CN102281875B (zh) 2017-09-22
US20170042891A1 (en) 2017-02-16
ES2528032T3 (es) 2015-02-03
US20190336500A1 (en) 2019-11-07
CA2749843C (en) 2017-09-05
CA2749843A1 (en) 2011-07-22
US8546433B2 (en) 2013-10-01
US20130338161A1 (en) 2013-12-19
CN102281875A (zh) 2011-12-14
AU2010204578B2 (en) 2016-05-12
SG172997A1 (en) 2011-08-29
PT2387395E (pt) 2015-02-04
BRPI1007046B1 (pt) 2019-07-16
US20210379064A1 (en) 2021-12-09
BRPI1007046A2 (pt) 2015-07-21

Similar Documents

Publication Publication Date Title
US20210379064A1 (en) Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer
JP7549627B2 (ja) Ａｘｌインヒビタおよび免疫チェックポイントモジュレータまたは腫瘍溶解性ウィルスによる併用療法
EP2114954B1 (en) Bicyclic aryl and bicyclic heteroaryl substituted triazoles useful as axl inhibitors
EP2326641B1 (en) Polycyclic heteroaryl substituted triazoles useful as axl inhibitors
EP2074115B1 (en) N3-heteroaryl substituted triazoles and n5-heteroaryl substituted triazoles useful as axl inhibitors
EP2476679B1 (en) Substituted triazoles useful as AXL inhibitors
HK1164146B (en) Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer
HK40049850A (en) Combination therapy
PREVENTING Hitoshi et al.
HK1174631B (en) N3-heteroaryl substituted triazoles and n5-heteroaryl substitued triazoles useful as axl inhibitors
HK1158625B (en) Polycyclic heteroaryl substituted triazoles useful as axl inhibitors

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 201080004818.0

Country of ref document: CN

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

Ref document number: 10700686

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2010204578

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 5381/DELNP/2011

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 2749843

Country of ref document: CA

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2011546409

Country of ref document: JP

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2010204578

Country of ref document: AU

Date of ref document: 20100115

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2010700686

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2011132118

Country of ref document: RU

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: PI1007046

Country of ref document: BR

ENP Entry into the national phase

Ref document number: PI1007046

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20110715