AR077468A1 - Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa - Google Patents

Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa

Info

Publication number
AR077468A1
AR077468A1 ARP100102489A ARP100102489A AR077468A1 AR 077468 A1 AR077468 A1 AR 077468A1 AR P100102489 A ARP100102489 A AR P100102489A AR P100102489 A ARP100102489 A AR P100102489A AR 077468 A1 AR077468 A1 AR 077468A1
Authority
AR
Argentina
Prior art keywords
alkyl
ring
optionally substituted
independently selected
halogen
Prior art date
Application number
ARP100102489A
Other languages
English (en)
Inventor
Shelley Allen
Lily Huang
Julia Haas
Timothy Kercher
Yutong Jiang
Jeongbeob Seo
Steven W Andrews
Kevin CONDROSKI
Original Assignee
Array Biopharma 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 Array Biopharma Inc filed Critical Array Biopharma Inc
Publication of AR077468A1 publication Critical patent/AR077468A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
    • C07D453/04—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems having a quinolyl-4, a substituted quinolyl-4 or a alkylenedioxy-quinolyl-4 radical linked through only one carbon atom, attached in position 2, e.g. quinine
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61K31/535—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 oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/22—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 systems contains four or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Inhibidores de las Trk quinasas y son de utilidad en el tratamiento de enfermedades que se pueden tratar con un inhibidor de Trk quinasa tales como dolor, cáncer, inflamacion, enfermedad neurodegenerativas y ciertas enfermedades infecciosas. Reivindicacion 1: Un compuesto que tiene la formula general (1) o una de sus sales, en donde R1 es H o alquilo C1-6; R2 es H, alquilo C1-6, -fluoroalquilo C1-6, -difluoroalquilo C1-6, -trifluoroalquilo C1-6, -cloroalquilo C1-6, -clorofluoroalquilo C2-6,-difluorocloroalquilo C2-6, -clorohidroxialquilo C2-6, -hidroxialquilo C1-6, -dihidroxialquilo C2-6, -(alquil C1-6)CN, -(alquil C1-6)SO2NH2, -(alquil C1-6)NHSO2(alquilo C1-3), -(alquil C1-6)NH2, -(alquil C1-6)NH(alquilo C1-4), -(alquil C1-6)N(alquilo C1-4)2, -(alquil C1-6)NHC(=O)O(alquilo C1-4), -(alquil C1-6)hetCyc1, -(alquil C1-6) hetAr1, hetAr2, hetCyc2, -O(alquilo C1-6) que está opcionalmente sustituido con halogeno, OH o alcoxi C1-4, -O(cicloalquilo C3-6), Cyc1, -(alquil C1-6)(cicloalquilo C3-6), -(alquil C1-6)(alcoxi C1-4), -(hidroxialquil C1-6)(alcoxi C1-4), un anillo cicloalquilo en puente de 7 miembros opcionalmente sustituido con hidroxialquilo C1-6 o un anillo heterocíclico en puente de 7-8 miembros que tiene 1-2 átomos de nitrogeno del anillo; o NR1R2 forma un anillo azacíclico de 4-6 miembros opcionalmente sustituido con uno o varios sustituyentes seleccionados, de modo independiente, de alquilo C1-6, OH, CO2H, (alquil C1-3)CO2H, -O(alquilo C1-6) e hidroxialquilo C1-6; hetCyc1 es un anillo heterocíclico de 5-6 miembros que tiene 1-2 heteroátomos del anillo seleccionados, de modo independiente, de N y O, en donde hetCyc1 está opcionalmente sustituido con oxo, OH, halogeno o alquilo C1-6; hetCyc2 es un anillo heterocíclico ligado a carbono de 6 miembros que tiene 1-2 heteroátomos del anillo seleccionados, de modo independiente, de N y O, en donde hetCyc2 está opcionalmente sustituido con F, SO2NH2, SO2 (alquilo C1-3) o halogeno; hetAr1 es un anillo heteroarilo de 5 miembros que tiene 1-2 heteroátomos del anillo seleccionados, de modo independiente, de N y O y opcionalmente sustituido con alquilo C1-4; hetAr2 es un anillo heteroarilo de 5-6 miembros que tiene 1-2 átomos de nitrogeno del anillo y está opcionalmente sustituido con uno o varios sustituyentes seleccionados, de modo independiente, de alquilo C1-4, cicloalquilo C3-6, halogeno y OH; Cyc1 es un anillo cicloalquilo de 3-6 miembros que está opcionalmente sustituido con uno o varios sustituyentes seleccionados, de modo independiente, de -alquilo C1-4, -OH, -OMe, -CO2H, -(alquil C1-4)OH, halogeno y CF3; Y es (i) fenilo opcionalmente sustituido con uno o varios sustituyentes seleccionados, de modo independiente, de halogeno, alcoxi C1-4, -CF3, -CHF2, -O(alquil C1-4)hetCyc3, -(alquil C1-4) hetCyc3, -O(alquil C1-4)O(alquilo C1-3 ) y -Odihidroxialquilo C3-6 o (ii) un anillo heteroarilo de 5-6 miembros que tiene un heteroátomo del anillo seleccionado de N y S, en donde dicho anillo heteroarilo está opcionalmente sustituido con uno o varios sustituyentes seleccionados, de modo independiente, de halogeno, -O(alquilo C1-4), alquilo C1-4 y NH2 o (iii) un anillo pirid-2-on-3-ilo opcionalmente sustituido con uno o varios sustituyentes seleccionados, de modo independiente, de halogeno y alquilo C1-4; hetCyc3 es un anillo heterocíclico de 5-6 miembros que tiene 1-2 heteroátomos del anillo seleccionados, de modo independiente, de N y O y opcionalmente sustituido con alquilo C1-6; X es -CH2-, -CH2CH2-, -CH2O- o -CH2NRd-; Rd es H o -alquilo C1-4; R3 es H o -alquilo C1-4; cada R4 está seleccionado, de modo independiente, de halogeno, -alquilo C1-4, -OH, -alcoxi C1-4, -NH2, -NH(alquilo C1-4) y -CH2OH; y n es 0, 1, 2, 3, 4, 5 o 6.
ARP100102489A 2009-07-09 2010-07-08 Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa AR077468A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US22419609P 2009-07-09 2009-07-09
US34676710P 2010-05-20 2010-05-20

Publications (1)

Publication Number Publication Date
AR077468A1 true AR077468A1 (es) 2011-08-31

Family

ID=42732102

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP100102489A AR077468A1 (es) 2009-07-09 2010-07-08 Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa

Country Status (22)

Country Link
US (6) US8791123B2 (es)
EP (2) EP3299372B1 (es)
JP (3) JP5716021B2 (es)
KR (3) KR101997055B1 (es)
CN (3) CN106008523B (es)
AR (1) AR077468A1 (es)
AU (1) AU2010271270C1 (es)
CA (2) CA3013618C (es)
CL (1) CL2012000059A1 (es)
CO (1) CO6612183A2 (es)
CR (2) CR20120065A (es)
ES (2) ES2655899T3 (es)
IL (1) IL217414A (es)
MX (2) MX364157B (es)
MY (1) MY162180A (es)
NZ (1) NZ598086A (es)
RU (2) RU2584157C2 (es)
SG (2) SG177553A1 (es)
TW (1) TWI503321B (es)
UY (1) UY32782A (es)
WO (1) WO2011006074A1 (es)
ZA (1) ZA201200982B (es)

Families Citing this family (131)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2738026C (en) 2008-09-22 2017-01-24 Array Biopharma Inc. Substituted imidazo[1,2b]pyridazine compounds as trk kinase inhibitors
PT2725028T (pt) 2008-10-22 2016-08-31 Array Biopharma Inc Compostos de pirazolo[1,5-]pirimidina substituídos como intermediários na síntese de inibidores de cinase trk
PE20131197A1 (es) 2008-10-31 2013-11-06 Genentech Inc Compuestos de pirazolopirimidina como inhibidores de jak y composiciones farmaceuticas que los contienen
RS56995B1 (sr) 2008-12-19 2018-05-31 Vertex Pharma Derivati pirazina korisni kao inhibitori atr kinaze
UA110324C2 (en) 2009-07-02 2015-12-25 Genentech Inc Jak inhibitory compounds based on pyrazolo pyrimidine
AR077468A1 (es) 2009-07-09 2011-08-31 Array Biopharma Inc Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa
PL2918588T3 (pl) * 2010-05-20 2017-10-31 Array Biopharma Inc Związki makrocykliczne jako inhibitory kinazy TRK
WO2012034095A1 (en) * 2010-09-09 2012-03-15 Irm Llc Compounds and compositions as trk inhibitors
US8637516B2 (en) 2010-09-09 2014-01-28 Irm Llc Compounds and compositions as TRK inhibitors
GEP20156285B (en) * 2011-02-25 2015-05-11 Aierem Elelsi Compounds and compositions as trk inhibitors
SI2712358T1 (sl) 2011-05-13 2017-03-31 Array Biopharma, Inc. Spojine pirolidinil sečnine, pirolidinil tiosečnine in pirolidinil gvanidina kot inhibitorji kinaze trka
PT2940017T (pt) 2011-09-30 2019-10-31 Vertex Pharma Processos para a produção de compostos úteis como inibidores de atr quinase
CN108464983A (zh) 2011-09-30 2018-08-31 沃泰克斯药物股份有限公司 用atr抑制剂治疗胰腺癌和非小细胞肺癌
SG11201405561RA (en) * 2012-03-09 2014-10-30 Lexicon Pharmaceuticals Inc PYRAZOLO[1,5-a]PYRIMIDINE-BASED COMPOUNDS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE
NZ700580A (en) 2012-04-05 2016-07-29 Vertex Pharma Compounds useful as inhibitors of atr kinase and combination therapies thereof
SI2841428T1 (sl) 2012-04-24 2018-12-31 Vertex Pharmaceuticals Incorporated Inhibitorji DNA-PK
MA37975B2 (fr) * 2012-09-11 2021-03-31 Genzyme Corp Inhibiteurs de synthase de glucosylcéramide
WO2014078322A1 (en) 2012-11-13 2014-05-22 Array Biopharma Inc. Thiazolyl and oxazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
US9822118B2 (en) 2012-11-13 2017-11-21 Array Biopharma Inc. Bicyclic heteroaryl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors
WO2014078372A1 (en) 2012-11-13 2014-05-22 Array Biopharma Inc. Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
US9828360B2 (en) 2012-11-13 2017-11-28 Array Biopharma Inc. Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors
WO2014078325A1 (en) 2012-11-13 2014-05-22 Array Biopharma Inc. N-(monocyclic aryl),n'-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
SI2920166T1 (sl) * 2012-11-13 2017-01-31 Array Biopharma, Inc. Spojine uree, tiouree, gvanidina in cianogvanidina, primerne za zdravljenje bolečine
CN104781255B (zh) * 2012-11-13 2017-10-24 阵列生物制药公司 作为trka激酶抑制剂的n‑吡咯烷基、n’‑吡唑基‑脲、硫脲、胍和氰基胍化合物
WO2014078417A1 (en) 2012-11-13 2014-05-22 Array Biopharma Inc. Pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
US9969694B2 (en) 2012-11-13 2018-05-15 Array Biopharma Inc. N-(arylalkyl)-N′-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors
WO2014078328A1 (en) 2012-11-13 2014-05-22 Array Biopharma Inc. N-bicyclic aryl,n'-pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
US9340546B2 (en) 2012-12-07 2016-05-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
RU2667907C9 (ru) * 2013-02-19 2019-01-31 Оно Фармасьютикал Ко., Лтд. ИНГИБИРУЮЩЕЕ Trk СОЕДИНЕНИЕ
PT2989106T (pt) 2013-04-25 2017-03-15 Beigene Ltd Compostos heterocíclicos fundidos como inibidores da proteína quinase
EP3628749A1 (en) 2013-07-30 2020-04-01 Blueprint Medicines Corporation Ntrk2 fusions
TW201542550A (zh) * 2013-09-06 2015-11-16 Lexicon Pharmaceuticals Inc 吡唑并［１，５－ａ］嘧啶基化合物、包含彼之組合物以及使用彼之方法
PL3702373T3 (pl) 2013-09-13 2022-12-05 Beigene Switzerland Gmbh Przeciwciała anty-PD1 i ich zastosowanie jako środki terapeutyczne i diagnostyczne
EP3057953B1 (en) 2013-10-17 2018-08-15 Vertex Pharmaceuticals Incorporated Co-crystals of (s)-n-methyl-8-(1-((2'-methyl-[4,5'-bipyrimidin]-6-yl)amino)propan-2-yl)quinoline-4-carboxamide and deuterated derivatives thereof as dna-pk inhibitors
TWI663159B (zh) * 2013-12-10 2019-06-21 美商健臻公司 原肌球蛋白相關之激酶（ｔｒｋ）抑制劑
WO2015104602A2 (en) 2014-01-08 2015-07-16 Wockhardt Limited A process for the preparation of anagliptin and its intermediates thereof
DK3572416T3 (da) 2014-01-24 2022-12-12 Turning Point Therapeutics Inc Diaryl-makrocykler som modulatorer af proteinkinaser
IN2014MU01191A (es) 2014-03-29 2015-10-02 Wockhardt Ltd
CR20160583A (es) 2014-05-15 2017-02-23 Array Biopharma Inc 1-((3s,4r)-4-(3-fluorofenil)-1-(2-metoxietil)pirrolidin-3-il)-3-(4-metil-3-(2-metilpirimidin-5-il)-1-fenil-1h-pirazol-5-il)urea como inhibidor de trka cinasa
EP3145929B1 (en) 2014-05-23 2021-01-13 F. Hoffmann-La Roche AG 5-chloro-2-difluoromethoxyphenyl pyrazolopyrimidine compounds which are jak inhibitors
WO2015181747A1 (en) 2014-05-28 2015-12-03 Novartis Ag Novel pyrazolo pyrimidine derivatives and their use as malt1 inhibitors
AU2015271030B2 (en) 2014-06-05 2019-05-16 Vertex Pharmaceuticals Incorporated Radiolabelled derivatives of a 2-amino-6-fluoro-n-[5-fluoro-pyridin-3-yl]- pyrazolo [1,5-a] pyrimidin-3-carboxamide compound useful as ATR kinase inhibitor, the preparation of said compound and different solid forms thereof
PL3157566T3 (pl) 2014-06-17 2019-10-31 Vertex Pharma Metoda leczenia nowotworu przy użyciu kombinacji inhibitorów chk1 i atr
KR102003754B1 (ko) 2014-07-03 2019-07-25 베이진 엘티디 Pd-l1 항체와 이를 이용한 치료 및 진단
JP5979335B2 (ja) * 2014-08-18 2016-08-24 小野薬品工業株式会社 Ｔｒｋ阻害化合物の酸付加塩
EA032872B1 (ru) * 2014-09-17 2019-07-31 Онкодизайн С.А. Макроциклические ингибиторы rip2-киназы
US10570135B2 (en) 2014-11-06 2020-02-25 Lysosomal Therapeutics Inc. Substituted pyrazolo[1,5-A]pyrimidines and their use in the treatment of medical disorders
KR102649887B1 (ko) 2014-11-16 2024-03-22 어레이 바이오파마 인크. (s)-n-(5-((r)-2-(2,5-디플루오로페닐)-피롤리딘-1-일)-피라졸로[1,5-a]피리미딘-3-일)-3-히드록시피롤리딘-1-카르복스아미드 히드로겐 술페이트의 결정질 형태
US9701681B2 (en) 2014-12-15 2017-07-11 Cmg Pharmaceutical Co., Ltd. Fused ring heteroaryl compounds and their use as Trk inhibitors
CA2988423A1 (en) 2015-06-01 2016-12-08 Loxo Oncology, Inc. Methods of diagnosing and treating cancer
WO2017004342A1 (en) 2015-07-02 2017-01-05 Tp Therapeutics, Inc. Chiral diaryl macrocycles as modulators of protein kinases
EA035049B1 (ru) 2015-07-16 2020-04-22 Аррэй Байофарма Инк. СОЕДИНЕНИЯ ЗАМЕЩЕННОГО ПИРАЗОЛО[1,5-a]ПИРИДИНА В КАЧЕСТВЕ ИНГИБИТОРОВ RET КИНАЗЫ
DK3325488T3 (da) * 2015-07-21 2020-09-14 Turning Point Therapeutics Inc Chiral diaryl-makrocyklus og anvendelse deraf til behandling af cancer
CA2995997A1 (en) 2015-08-26 2017-03-02 Blueprint Medicines Corporation Compounds and compositions useful for treating disorders related to ntrk
JP7187308B2 (ja) 2015-09-30 2022-12-12 バーテックス ファーマシューティカルズ インコーポレイテッド Ｄｎａ損傷剤とａｔｒ阻害剤との組み合わせを使用する、がんを処置するための方法
CN108697708A (zh) 2015-10-26 2018-10-23 洛克索肿瘤学股份有限公司 Trk抑制剂抗性癌症中的点突变以及与此相关的方法
WO2017073706A1 (ja) * 2015-10-30 2017-05-04 中外製薬株式会社 ジヒドロナフト［２，３－ｂ］ベンゾフラン誘導体
SG10201912607SA (en) * 2015-11-19 2020-02-27 Blueprint Medicines Corp Compounds and compositions useful for treating disorders related to ntrk
MA44612A (fr) 2016-04-04 2019-02-13 Loxo Oncology Inc Méthodes de traitement de cancers pédiatriques
TN2018000335A1 (en) 2016-04-04 2020-01-16 Loxo Oncology Inc Liquid formulations of (s)-n-(5-((r)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide
US10045991B2 (en) 2016-04-04 2018-08-14 Loxo Oncology, Inc. Methods of treating pediatric cancers
MX2018012208A (es) 2016-04-06 2019-03-28 Lysosomal Therapeutics Inc Compuestos a base de imidazo [1,5-a] pirimidinil carboxamida y su uso en el tratamiento de trastornos médicos.
KR20230104752A (ko) 2016-04-06 2023-07-10 비알 - 알&디 인베스트먼츠, 에스.에이. 피라졸로[1,5-a]피리미디닐 카르복스아미드 화합물및 의학적 장애의 치료에서의 그의 용도
MX2018012207A (es) 2016-04-06 2019-03-28 Lysosomal Therapeutics Inc Compuestos de pirrol[1,2-a]pirimidinil carboxamida y su uso en el tratamiento de trastornos médicos.
SG11201809693SA (en) 2016-05-05 2018-11-29 Lysosomal Therapeutics Inc SUBSTITUTED IMIDAZO[1,2-b]PYRIDAZINES, SUBSTITUTED IMIDAZO[1,5-b]PYRIDAZINES, RELATED COMPOUNDS, AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
CN110049987B (zh) 2016-05-18 2022-02-18 阵列生物制药公司 制备化合物及其盐的方法
WO2018007885A1 (en) 2016-07-05 2018-01-11 Beigene, Ltd. COMBINATION OF A PD-l ANTAGONIST AND A RAF INHIBITOR FOR TREATING CANCER
KR20230162137A (ko) 2016-08-16 2023-11-28 베이진 스위찰랜드 게엠베하 (s)-7-(1-아크릴로일피페리딘-4-일)-2-(4-페녹시페닐)-4,5,6,7-테트라-하이드로피라졸로 [1,5-a] 피리미딘-3-카르복스아미드의 제조 및 그 용도
TWI739887B (zh) 2016-08-19 2021-09-21 英屬開曼群島商百濟神州有限公司 使用包含btk抑制劑的組合產品治療癌症
TW201815418A (zh) 2016-09-27 2018-05-01 Vertex Pharma 使用dna破壞劑及dna-pk抑制劑之組合治療癌症的方法
KR101881650B1 (ko) * 2016-10-02 2018-07-24 재단법인대구경북과학기술원 뇌유래신경성장인자를 과발현하는 우울증 동물모델 및 이의 제조방법
TWI704148B (zh) 2016-10-10 2020-09-11 美商亞雷生物製藥股份有限公司 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物
JOP20190077A1 (ar) 2016-10-10 2019-04-09 Array Biopharma Inc مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret
JOP20190092A1 (ar) 2016-10-26 2019-04-25 Array Biopharma Inc عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها
CA3041942C (en) 2016-10-28 2023-03-14 Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Amino pyrazolopyrimidine compound used as neurotrophic factor tyrosine kinase receptor inhibitor
CN108003161B (zh) * 2016-10-28 2020-10-09 正大天晴药业集团股份有限公司 神经营养因子酪氨酸激酶受体抑制剂
EP3571203B1 (en) 2017-01-18 2023-06-07 Array BioPharma Inc. Substituted pyrazolo[1,5-a]pyrazine compounds as ret kinase inhibitors
WO2018136663A1 (en) 2017-01-18 2018-07-26 Array Biopharma, Inc. Ret inhibitors
EP3573989A4 (en) 2017-01-25 2020-11-18 Beigene, Ltd. CRYSTALLINE FORMS OF (S) -7- (1- (BUT-2-YNOYL) -PIPERIDINE-4-YL) -2- (4-PHENOXYPHENYL) -4,5,6,7-TETRAHYDROPYRAZOLO [1,5-A ] PYRIMIDINE-3-CARBOXAMIDE, MANUFACTURING AND USES THEREOF
JOP20190213A1 (ar) 2017-03-16 2019-09-16 Array Biopharma Inc مركبات حلقية ضخمة كمثبطات لكيناز ros1
AU2018274577A1 (en) 2017-05-22 2019-10-10 F. Hoffmann-La Roche Ag Therapeutic compounds and compositions, and methods of use thereof
CA3066518A1 (en) 2017-06-26 2019-01-03 Beigene, Ltd. Immunotherapy for hepatocellular carcinoma
CN109824566A (zh) * 2017-07-19 2019-05-31 浙江师范大学 一种(r)-2-(2,5-二氟苯基)吡咯烷的合成方法
CA3070621A1 (en) * 2017-07-28 2019-01-31 Nimbus Lakshmi, Inc. Tyk2 inhibitors and uses thereof
JP6916562B2 (ja) * 2017-08-11 2021-08-11 テリジーン リミテッドＴｅｌｉｇｅｎｅ Ｌｔｄ． 化合物、その薬学的に許容される塩、溶媒和物、立体異性体及び互変異性体、並びに薬物組成物、過剰増殖性障害治療剤、過剰増殖性障害予防剤、薬物、癌治療剤、癌予防剤、及びキナーゼシグナル伝達調節剤
WO2019034009A1 (en) 2017-08-12 2019-02-21 Beigene, Ltd. BTK INHIBITOR WITH ENHANCED DOUBLE SELECTIVITY
TWI791053B (zh) 2017-10-10 2023-02-01 美商亞雷生物製藥股份有限公司 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物
TWI812649B (zh) 2017-10-10 2023-08-21 美商絡速藥業公司 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物
MA50456A (fr) 2017-10-26 2020-09-02 Array Biopharma Inc Formulations d'un inhibiteur de kinase trk macrocyclique
US11786529B2 (en) 2017-11-29 2023-10-17 Beigene Switzerland Gmbh Treatment of indolent or aggressive B-cell lymphomas using a combination comprising BTK inhibitors
TWI802635B (zh) 2018-01-18 2023-05-21 美商亞雷生物製藥股份有限公司 作為ｒｅｔ激酶抑制劑之經取代吡咯并[2,3-d]嘧啶化合物
JP6997876B2 (ja) 2018-01-18 2022-02-04 アレイ バイオファーマ インコーポレイテッド Ｒｅｔキナーゼ阻害剤としての置換ピラゾリル［４，３－ｃ］ピリジン化合物
US11524963B2 (en) 2018-01-18 2022-12-13 Array Biopharma Inc. Substituted pyrazolo[3,4-d]pyrimidines as RET kinase inhibitors
CN110156813B (zh) * 2018-02-13 2023-07-25 北京诺诚健华医药科技有限公司 作为trk抑制剂的杂环化合物
PL3762368T3 (pl) 2018-03-08 2022-06-06 Incyte Corporation ZWIĄZKI AMINOPIRAZYNODIOLOWE JAKO INHIBITORY PI3K-γ
CN111936500B (zh) * 2018-03-14 2023-09-01 重庆复尚源创医药技术有限公司 作为TRK激酶抑制剂的取代的(2-氮杂双环[3.1.0]己-2-基)吡唑[1,5-a]嘧啶和咪唑[1,2-b]哒嗪化合物
EP3773725A1 (en) 2018-03-29 2021-02-17 Loxo Oncology Inc. Treatment of trk-associated cancers
CN110294761B (zh) * 2018-06-08 2020-09-08 南京雷正医药科技有限公司 作为Trk激酶抑制剂的取代的吡唑并[1,5-a]嘧啶化合物
CN110627812B (zh) 2018-06-25 2022-10-11 北京诺诚健华医药科技有限公司 作为trk抑制剂的杂环化合物
US11046658B2 (en) 2018-07-02 2021-06-29 Incyte Corporation Aminopyrazine derivatives as PI3K-γ inhibitors
CA3224949A1 (en) 2018-07-31 2020-02-06 Loxo Oncology, Inc. Spray-dried dispersions, formulations, and polymorphs of (s)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1h-pyrazole-4-carboxamide
WO2020038457A1 (zh) * 2018-08-23 2020-02-27 珠海联邦制药股份有限公司 作为JAK抑制剂的[1，2，4]***并[1，5-a]吡啶类化合物及其应用
CN110857304B (zh) * 2018-08-24 2021-05-18 北京富龙康泰生物技术有限公司 Trk抑制剂、其制备方法和用途
CA3111984A1 (en) 2018-09-10 2020-03-19 Array Biopharma Inc. Fused heterocyclic compounds as ret kinase inhibitors
CN113271940A (zh) * 2018-10-15 2021-08-17 林伯士拉克许米公司 Tyk2抑制剂和其用途
CN111171049B (zh) * 2018-11-09 2021-06-04 山东轩竹医药科技有限公司 酪氨酸激酶抑制剂及其用途
CN111269233A (zh) * 2018-12-05 2020-06-12 上海轶诺药业有限公司 一类咪唑并芳环类化合物的制备和应用
CN113166156B (zh) * 2018-12-07 2024-02-27 贝达药业股份有限公司 酪氨酸激酶抑制剂、组成及其方法
EP3898626A1 (en) 2018-12-19 2021-10-27 Array Biopharma, Inc. Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of fgfr tyrosine kinases
WO2020131674A1 (en) 2018-12-19 2020-06-25 Array Biopharma Inc. 7-((3,5-dimethoxyphenyl)amino)quinoxaline derivatives as fgfr inhibitors for treating cancer
WO2020172505A1 (en) 2019-02-22 2020-08-27 Regeneron Pharmaceuticals, Inc. Rodents having genetically modified sodium channels and methods of use thereof
CN111718351B (zh) * 2019-03-19 2021-10-12 华中师范大学 含氧取代吡唑并嘧啶化合物和药物组合物及其应用
CA3129665A1 (en) 2019-03-21 2020-09-24 Onxeo A dbait molecule in combination with kinase inhibitor for the treatment of cancer
CN111848626B (zh) * 2019-04-30 2021-11-30 江苏柯菲平医药股份有限公司 Trk激酶抑制剂及其用途
JP7420403B2 (ja) * 2019-05-08 2024-01-23 ティーワイケー メディシンズ インコーポレーテッド キナーゼ阻害剤として使用される化合物およびその応用
WO2021027503A1 (zh) * 2019-08-12 2021-02-18 罗欣药业(上海)有限公司 三环类化合物、其制备方法、中间体及应用
EP4054579A1 (en) 2019-11-08 2022-09-14 Institut National de la Santé et de la Recherche Médicale (INSERM) Methods for the treatment of cancers that have acquired resistance to kinase inhibitors
CN111138437B (zh) * 2019-12-04 2021-03-05 杭州华东医药集团新药研究院有限公司 取代的吡唑并[1,5-a]嘧啶氨基酸衍生物及其用途
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
CN115210232B (zh) * 2020-01-22 2024-03-01 上海齐鲁制药研究中心有限公司 吡唑并杂芳环类化合物及其应用
CA3169832A1 (en) * 2020-02-13 2021-08-19 Zhuhai United Laboratories Co., Ltd. Use of jak inhibitors in preparation of drugs for treatment of jak kinase related diseases
CN114437077B (zh) * 2020-11-04 2024-01-30 浙江同源康医药股份有限公司 用作激酶抑制剂的化合物及其应用
WO2021249450A1 (zh) * 2020-06-11 2021-12-16 贝达药业股份有限公司 酪氨酸激酶抑制剂的盐型、晶型、药物组合物及其用途
CN111777549A (zh) * 2020-07-07 2020-10-16 中瀚(齐河县)生物医药科技有限公司 一种2-甲氧基-3-溴-5-氟吡啶的合成工艺
WO2022018695A1 (en) 2020-07-24 2022-01-27 Genzyme Corporation Pharmaceutical compositions comprising venglustat
CN113563343B (zh) * 2020-07-27 2022-05-24 杭州邦顺制药有限公司 取代的吡唑并[1,5-a]嘧啶化合物及其用途
CN112645955B (zh) * 2020-12-24 2022-11-04 四川国康药业有限公司 一种[1,2,4]***并[4,3-b]哒嗪类化合物及其制备方法和用途
US20240092759A1 (en) * 2021-01-08 2024-03-21 Yale University Non-Covalent Inhibitors of the Main Protease of SARS-CoV-2 and Methods of Use
CN112979646B (zh) * 2021-03-08 2022-01-14 北京富龙康泰生物技术有限公司 一种咪唑并吡啶类衍生物
CN114907247A (zh) * 2022-04-21 2022-08-16 上海陶术生物科技有限公司 吡咯烷中间体及吡咯烷盐类化合物的制备方法
US11786531B1 (en) 2022-06-08 2023-10-17 Beigene Switzerland Gmbh Methods of treating B-cell proliferative disorder

Family Cites Families (255)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ234143A (en) 1989-06-28 1991-10-25 Mcneil Ppc Inc Aqueous pharmaceutical suspension formulation for administering substantially insoluble pharmaceutical agents
KR100229343B1 (ko) 1993-11-30 1999-11-01 윌리암스 로저 에이 염증치료용 치환 피라졸일벤젠술폰아미드
US5430021A (en) 1994-03-18 1995-07-04 Pharmavene, Inc. Hydrophobic drug delivery systems
US5844092A (en) 1994-03-18 1998-12-01 Genentech, Inc. Human TRK receptors and neurotrophic factor inhibitors
US5877016A (en) 1994-03-18 1999-03-02 Genentech, Inc. Human trk receptors and neurotrophic factor inhibitors
CA2206201A1 (en) 1996-05-29 1997-11-29 Yoshiaki Isobe Pyrazole derivatives and their pharmaceutical use
JP3898296B2 (ja) 1996-08-28 2007-03-28 ポーラ化成工業株式会社 ピロロピラゾロピリミジン化合物及びこれを有効成分とする医薬
AU7079998A (en) 1997-04-25 1998-11-24 Takeda Chemical Industries Ltd. Condensed pyridazine derivatives, their production and use
UA74546C2 (en) 1999-04-06 2006-01-16 Boehringer Ingelheim Ca Ltd Macrocyclic peptides having activity relative to hepatitis c virus, a pharmaceutical composition and use of the pharmaceutical composition
US6534085B1 (en) 1999-09-23 2003-03-18 Bioresponse L.L.C. Phytochemicals for promoting weight loss
DK1292680T3 (da) 2000-06-22 2010-03-08 Genentech Inc Agonist-anti-TrkC monoklonale antistoffer
TWI312347B (en) 2001-02-08 2009-07-21 Eisai R&D Man Co Ltd Bicyclic nitrogen-containing condensed ring compounds
CA2448956C (en) 2001-05-30 2017-10-03 Genentech, Inc. Anti-ngf antibodies for the treatment of various disorders
US7101572B2 (en) 2001-12-07 2006-09-05 Unilab Pharmatech, Ltd. Taste masked aqueous liquid pharmaceutical composition
US20030199525A1 (en) 2002-03-21 2003-10-23 Hirst Gavin C. Kinase inhibitors
MXPA04010441A (es) 2002-04-23 2005-02-14 Shionogi & Co Derivado de pirazolo[1,5-a]pirimidina e inhibidor de nad(p)h oxidasa que contiene el mismo.
US7449488B2 (en) 2002-06-04 2008-11-11 Schering Corporation Pyrazolopyrimidines as protein kinase inhibitors
ITMI20021620A1 (it) 2002-07-23 2004-01-23 Novuspharma Spa Composto ad ativita' antitumorale
JP4024624B2 (ja) * 2002-08-26 2007-12-19 富士通株式会社 半導体装置の製造方法及び製造装置
CN1880317B (zh) * 2002-09-04 2012-10-10 先灵公司 作为细胞周期蛋白依赖性激酶抑制剂的吡唑并嘧啶
EP1537116B1 (en) 2002-09-04 2010-06-02 Schering Corporation Pyrazolopyrimidines suitable for the treatment of cancer diseases
US7196078B2 (en) 2002-09-04 2007-03-27 Schering Corpoartion Trisubstituted and tetrasubstituted pyrazolopyrimidines as cyclin dependent kinase inhibitors
US7119200B2 (en) * 2002-09-04 2006-10-10 Schering Corporation Pyrazolopyrimidines as cyclin dependent kinase inhibitors
US8580782B2 (en) 2002-09-04 2013-11-12 Merck Sharp & Dohme Corp. Substituted pyrazolo[1,5-a]pyrimidines as cyclin dependent kinase inhibitors
AU2003299651A1 (en) 2002-12-11 2004-06-30 Merck And Co., Inc. Tyrosine kinase inhibitors
US7262199B2 (en) 2002-12-11 2007-08-28 Merck & Co., Inc. Tyrosine kinase inhibitors
GB0303910D0 (en) 2003-02-20 2003-03-26 Merck Sharp & Dohme Therapeutic agents
US7514446B2 (en) 2003-02-20 2009-04-07 Smithkline Beecham Corporation Pyrimidine compounds
US20070037150A1 (en) 2003-02-21 2007-02-15 The Johns Hopkins University Tyrosine kinome
JP2004277337A (ja) * 2003-03-14 2004-10-07 Sumitomo Pharmaceut Co Ltd ピラゾロ［１，５−ａ］ピリミジン誘導体
WO2004087707A1 (en) * 2003-03-31 2004-10-14 Vernalis (Cambridge) Limited Pyrazolopyrimidine compounds and their use in medicine
EP1615667A2 (en) 2003-04-11 2006-01-18 Novo Nordisk A/S Combinations of an 11-beta-hydroxysteroid dehydrogenase type 1 inhibitor and a glucocorticoid receptor agonist
US20060094699A1 (en) 2003-04-11 2006-05-04 Kampen Gita Camilla T Combination therapy using an 11beta-hydroxysteroid dehydrogenase type 1 inhibitor and a glucocorticoid receptor agonist to minimize the side effects associated with glucocorticoid receptor agonist therapy
EP1615697A2 (en) 2003-04-11 2006-01-18 Novo Nordisk A/S New pyrazolo[1,5-a] pyrimidine derivatives and pharmaceutical use thereof
US20070042941A1 (en) 2003-04-28 2007-02-22 Mitsuomi Hirashima Galectin 9-inducing factors
PA8603801A1 (es) 2003-05-27 2004-12-16 Janssen Pharmaceutica Nv Derivados de la quinazolina
JP2005008581A (ja) * 2003-06-20 2005-01-13 Kissei Pharmaceut Co Ltd 新規なピラゾロ［１，５−ａ］ピリミジン誘導体、それを含有する医薬組成物およびそれらの用途
EA009517B1 (ru) 2003-06-27 2008-02-28 Байер Кропсайенс Аг Пиразолопиримидины
TWI382031B (zh) 2003-07-15 2013-01-11 Amgen Inc 作為選擇性神經生長因子（ｎｇｆ）通道抑制劑之人類抗-ｎｇｆ中和抗體
US7491794B2 (en) 2003-10-14 2009-02-17 Intermune, Inc. Macrocyclic compounds as inhibitors of viral replication
US7169918B2 (en) 2003-10-27 2007-01-30 Genelabs Technologies, Inc. Methods for preparing 7-(2′-substituted-β-D-ribofuranosyl)-4-(NR2R3)-5-(substituted ethyn-1-yl)-pyrrolo[2,3-d]pyrimidine derivatives
MY141220A (en) 2003-11-17 2010-03-31 Astrazeneca Ab Pyrazole derivatives as inhibitors of receptor tyrosine kinases
TW200529849A (en) 2003-11-28 2005-09-16 Novartis Ag Diaryl urea derivatives in the treatment of protein kinase dependent diseases
US7799772B2 (en) 2003-12-18 2010-09-21 Janssen Pharmaceutica N.V. Pyrido-and pyrimidopyrimidine derivatives as anti-profilerative agents
PL1696920T3 (pl) 2003-12-19 2015-03-31 Plexxikon Inc Związki i sposoby opracowywania modulatorów Ret
WO2005068424A1 (en) 2004-01-20 2005-07-28 Cell Therapeutics Europe S.R.L. Indolinone derivatives as receptor tyrosine kinase ihibitors
US20050222171A1 (en) 2004-01-22 2005-10-06 Guido Bold Organic compounds
WO2005099363A2 (en) 2004-03-26 2005-10-27 Whitehead Institute For Biomedical Research Methods of diagnosing, preventing and treating cancer metastasis
CN1938311A (zh) 2004-03-30 2007-03-28 因特蒙公司 作为病毒复制抑制剂的大环化合物
GB0512324D0 (en) 2005-06-16 2005-07-27 Novartis Ag Organic compounds
PE20060664A1 (es) 2004-09-15 2006-08-04 Novartis Ag Amidas biciclicas como inhibidores de cinasa
AU2005304784B2 (en) 2004-11-04 2011-03-24 Vertex Pharmaceuticals Incorporated Pyrazolo[1,5-a]pyrimidines useful as inhibitors of protein kinases
JO3088B1 (ar) 2004-12-08 2017-03-15 Janssen Pharmaceutica Nv مشتقات كوينازولين كبيرة الحلقات و استعمالها بصفتها موانع كينيز متعددة الاهداف
DE102005003687A1 (de) 2005-01-26 2006-07-27 Sphingo Tec Gmbh Immunoassay zur Bestimmung der Freisetzung von Neurotensin in die Zirkulation
DK1853602T3 (da) 2005-02-16 2010-09-20 Astrazeneca Ab Kemiske forbindelser
CN101119996A (zh) * 2005-02-16 2008-02-06 阿斯利康(瑞典)有限公司 化学化合物
DK1869049T3 (da) 2005-03-21 2009-05-18 Lilly Co Eli Imidazopyridazinforbindelser
CN101208093A (zh) 2005-04-27 2008-06-25 阿斯利康(瑞典)有限公司 吡唑-嘧啶衍生物在治疗疼痛中的用途
US20080287437A1 (en) 2005-05-16 2008-11-20 Astrazeneca Ab Pyrazolylaminopyrimidine Derivatives Useful as Tyrosine Kinase Inhibitors
CN100406650C (zh) 2005-06-05 2008-07-30 徐斌 一种抗特大变位的模块式梳型桥梁伸缩缝装置
ITRM20050290A1 (it) 2005-06-07 2006-12-08 Lay Line Genomics Spa Uso di molecole in grado di inibire il legame tra ngf e il suo recettore trka come analgesici ad effetto prolungato.
DK1893612T3 (da) 2005-06-22 2011-11-21 Plexxikon Inc Pyrrol [2,3-B]pyridin-derivater som proteinkinasehæmmere
US20070025540A1 (en) 2005-07-07 2007-02-01 Roger Travis Call center routing based on talkativeness
GEP20105124B (en) 2005-07-25 2010-11-25 Array Biopharma Inc Novel macrocyclic inhibitors of hepatitis c virus replication
US20100216798A1 (en) 2005-07-29 2010-08-26 Astellas Pharma Inc Fused heterocycles as lck inhibitors
CN101232871A (zh) 2005-08-03 2008-07-30 伊士曼化工公司 生育酚聚乙二醇琥珀酸酯粉末及其制备方法
AU2006283592A1 (en) 2005-08-22 2007-03-01 Amgen Inc. Pyrazolopyridine and pyrazolopyrimidine compounds useful as kinase enzymes modulators
US20070049591A1 (en) 2005-08-25 2007-03-01 Kalypsys, Inc. Inhibitors of MAPK/Erk Kinase
JP5366548B2 (ja) 2005-08-25 2013-12-11 クレアビリス・セラピューティクス・エスピーエー Ｋ‐２５２ａおよびその誘導体のポリマー結合体
DE102005042742A1 (de) 2005-09-02 2007-03-08 Schering Ag Substituierte Imidazo[1,2b]pyridazine als Kinase-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel
US20070078136A1 (en) 2005-09-22 2007-04-05 Bristol-Myers Squibb Company Fused heterocyclic compounds useful as kinase modulators
US20070082900A1 (en) 2005-10-06 2007-04-12 Schering Corporation Methods for inhibiting protein kinases
AR057979A1 (es) 2005-10-06 2008-01-09 Schering Corp PIRAZOLPIRIMIDINAS COMO INHIBIDORAS DE PROTEíNA QUINASA. COMPOSICIONES FARMACEUTICAS.
CA2624772C (en) * 2005-10-11 2011-11-29 Centre National De La Recherche Scientifique (Cnrs) Compounds and kits for the detection and the quantification of cell apoptosis
KR20080056295A (ko) 2005-10-11 2008-06-20 인터뮨, 인크. Ｃ형 간염 바이러스 복제를 억제하기 위한 화합물 및 방법
AU2006304875B2 (en) 2005-10-21 2013-01-17 Exelixis, Inc. Pyrazolo-pyrimidines as casein kinase II (CK2) modulators
WO2007057399A2 (en) 2005-11-15 2007-05-24 Boehringer Ingelheim International Gmbh Treatment of cancer with indole derivatives
GB0524436D0 (en) 2005-11-30 2006-01-11 Novartis Ag Organic compounds
JP5474354B2 (ja) 2005-12-30 2014-04-16 アステックス、セラピューティックス、リミテッド 医薬化合物
WO2007084815A2 (en) 2006-01-19 2007-07-26 Janssen Pharmaceutica, N.V. Substituted thienopyrimidine kinase inhibitors
EP1978958A4 (en) 2006-01-24 2009-12-02 Merck & Co Inc INHIBITION OF TYROSINE KINASE RET
KR100846988B1 (ko) 2006-03-06 2008-07-16 제일약품주식회사 신규한 티에노피리미딘 유도체 또는 이의 약학적으로허용가능한 염, 이의 제조방법 및 이를 함유하는 약학조성물
MX2008011220A (es) 2006-03-07 2008-09-11 Array Biopharma Inc Compuestos de pirazol heterobiciclicos y metodos de uso.
ZA200808966B (en) 2006-03-27 2010-03-31 Nerviano Medical Sciences Srl Pyridyl- and pyrimidinyl-substituted pyrrole-, thiophene- and furane-derivatives as kinase inhibitors
GB0606805D0 (en) 2006-04-04 2006-05-17 Novartis Ag Organic compounds
WO2007129161A2 (en) 2006-04-26 2007-11-15 F. Hoffmann-La Roche Ag Thieno [3, 2-d] pyrimidine derivative useful as pi3k inhibitor
CN101443009A (zh) 2006-05-18 2009-05-27 卫材R&D管理有限公司 针对甲状腺癌的抗肿瘤剂
US7389632B2 (en) 2006-06-10 2008-06-24 Uhlmann Pac-Systeme Gmbh & Co. Kg Apparatus for distributing small objects in a fill station
EP1873157A1 (en) * 2006-06-21 2008-01-02 Bayer Schering Pharma Aktiengesellschaft Pyrazolopyrimidines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same
TWI419889B (zh) * 2006-07-05 2013-12-21 Mitsubishi Tanabe Pharma Corp 吡唑并〔１，５-ａ〕嘧啶化合物
US20100029619A1 (en) 2006-08-04 2010-02-04 Takeda Pharmaceutical Company Limted Fused heterocyclic compound
US7531539B2 (en) 2006-08-09 2009-05-12 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
CN101594909A (zh) 2006-09-07 2009-12-02 比奥根艾迪克Ma公司 用于治疗炎性病症、细胞增殖性失调、免疫失调的irak调节剂
WO2008031551A2 (en) 2006-09-12 2008-03-20 Novartis Forschungsstiftung, Zweigniederlassung Non-neuroendocrine cancer therapy
CA2664378A1 (en) 2006-09-29 2008-04-03 Novartis Ag Pyrazolopyrimidines as pi3k lipid kinase inhibitors
CN101522682A (zh) 2006-10-30 2009-09-02 诺瓦提斯公司 作为抗炎剂的杂环化合物
EP2086979B1 (en) 2006-11-06 2015-06-03 Tolero Pharmaceuticals, Inc. Imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine derivatives and their use as protein kinase inhibitors
PE20121126A1 (es) 2006-12-21 2012-08-24 Plexxikon Inc Compuestos pirrolo [2,3-b] piridinas como moduladores de quinasa
WO2008079909A1 (en) 2006-12-21 2008-07-03 Plexxikon, Inc. Pyrrolo [2,3-b] pyridines as kinase modulators
EP2094701A2 (en) 2006-12-21 2009-09-02 Plexxikon, Inc. Compounds and methods for kinase modulation, and indications therefor
US20080234267A1 (en) 2007-03-20 2008-09-25 Karen Elizabeth Lackey Compounds and Methods of Treatment
US20080234262A1 (en) 2007-03-21 2008-09-25 Wyeth Pyrazolopyrimidine analogs and their use as mtor kinase and pi3 kinase inhibitors
JP2010522716A (ja) 2007-03-28 2010-07-08 イノバシア・アクチボラゲット ステアロイル−ＣｏＡデサチュラーゼのインヒビターとしてのピラゾロ［１，５−Ａ］ピリミジン
US8138181B2 (en) 2007-04-03 2012-03-20 Array Biopharma Inc. Imidazo[1,2-a]pyridine compounds as receptor tyrosine kinase inhibitors
WO2008137794A1 (en) 2007-05-04 2008-11-13 Irm Llc Compounds and compositions as c-kit and pdgfr kinase inhibitors
CA2687909C (en) 2007-06-21 2015-09-15 Janssen Pharmaceutica Nv Indolin-2-ones and aza-indolin-2-ones
AR067478A1 (es) 2007-07-09 2009-10-14 Astrazeneca Ab Compuestos derivados de morfolina pirimidina
US20100190777A1 (en) 2007-07-17 2010-07-29 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
EP2178861B1 (en) 2007-07-19 2014-08-20 Merck Sharp & Dohme Corp. Heterocyclic amide compounds as protein kinase inhibitors
CN103923072B (zh) 2007-07-20 2017-05-31 内尔维阿诺医学科学有限公司 作为具有激酶抑制剂活性的取代的吲唑衍生物
WO2009017838A2 (en) 2007-08-01 2009-02-05 Exelixis, Inc. Combinations of jak-2 inhibitors and other agents
CN101827609B (zh) 2007-08-10 2014-03-12 里珍纳龙药品有限公司 抗人神经生长因子的高亲和力人抗体
CN101883774A (zh) 2007-10-16 2010-11-10 惠氏有限责任公司 噻吩并嘧啶和吡唑并嘧啶化合物及其用作mtor激酶和pi3激酶抑制剂的用途
EA201000603A1 (ru) 2007-10-23 2010-12-30 Новартис Аг ПРИМЕНЕНИЕ АНТИТЕЛ К TrkB ДЛЯ ЛЕЧЕНИЯ РЕСПИРАТОРНЫХ НАРУШЕНИЙ
WO2009060197A1 (en) 2007-11-08 2009-05-14 Centro Nacional De Investigaciones Oncologicas (Cnio) Imidazopyridazines for use as protein kinase inhibitors
CN101970440A (zh) 2007-11-28 2011-02-09 先灵公司 作为蛋白激酶抑制剂的2-氟吡唑并[1，5-a]嘧啶类
WO2009071480A2 (en) 2007-12-04 2009-06-11 Nerviano Medical Sciences S.R.L. Substituted dihydropteridin-6-one derivatives, process for their preparation and their use as kinase inhibitors
WO2009092049A1 (en) 2008-01-17 2009-07-23 Irm Llc Improved anti-trkb antibodies
US20090227556A1 (en) 2008-01-31 2009-09-10 Eisai R&D Management Co., Ltd. Receptor tyrosine kinase inhibitors comprising pyridine and pyrimidine derivatives
EP2254886B1 (en) 2008-03-28 2016-05-25 Nerviano Medical Sciences S.r.l. 3,4-dihydro-2h-pyrazino[1,2-a]indol-1-one derivatives active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them
CN102056927B (zh) 2008-05-13 2014-06-25 Irm责任有限公司 作为激酶抑制剂的稠合含氮杂环及其组合物
PE20091846A1 (es) 2008-05-19 2009-12-16 Plexxikon Inc DERIVADOS DE PIRROLO[2,3-d]-PIRIMIDINA COMO MODULADORES DE CINASAS
US8158636B2 (en) 2008-05-19 2012-04-17 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
KR101257158B1 (ko) 2008-05-23 2013-04-23 노파르티스 아게 단백질 티로신 키나제 억제제로서의 퀴놀린 및 퀴녹살린의 유도체
JP5767965B2 (ja) 2008-06-10 2015-08-26 プレキシコン インコーポレーテッドＰｌｅｘｘｉｋｏｎ Ｉｎｃ． キナーゼを調節する５ｈ−ピロロ［２，３−ｂ］ピラジン誘導体、およびその適応症
EP2323664B1 (en) 2008-07-29 2015-01-07 Nerviano Medical Sciences S.r.l. Use of a cdk inhibitor for the treatment of glioma
WO2010031816A1 (en) 2008-09-19 2010-03-25 Nerviano Medical Sciences S.R.L. 3,4 DIHYDRO-2H-PYRROLO[1,2-a]PYRAZIN-1-ONE DERIVATIVES
CA2738026C (en) 2008-09-22 2017-01-24 Array Biopharma Inc. Substituted imidazo[1,2b]pyridazine compounds as trk kinase inhibitors
PT2725028T (pt) 2008-10-22 2016-08-31 Array Biopharma Inc Compostos de pirazolo[1,5-]pirimidina substituídos como intermediários na síntese de inibidores de cinase trk
PE20131197A1 (es) 2008-10-31 2013-11-06 Genentech Inc Compuestos de pirazolopirimidina como inhibidores de jak y composiciones farmaceuticas que los contienen
US8912194B2 (en) 2008-11-24 2014-12-16 Nerviano Medical Sciences S.R.L. CDK inhibitor for the treatment of mesothelioma
JO3265B1 (ar) 2008-12-09 2018-09-16 Novartis Ag مثبطات بيريديلوكسى اندولات vegf-r2 واستخدامها لعلاج المرض
ES2637174T3 (es) 2009-02-12 2017-10-11 Cell Signaling Technology, Inc. Expresión de ROS mutante en el cáncer de hígado humano
WO2010111527A1 (en) 2009-03-26 2010-09-30 Plexxikon, Inc. Pyrazolo [ 3, 4 -b] pyridines as kinase inhibitors and their medical use
EP3045457B1 (en) 2009-06-15 2018-05-09 Nerviano Medical Sciences S.r.l. Substituted pyrimidinylpyrrolopyridinone derivatives, process for their preparation and their use as kinase inhibitors
AR077468A1 (es) 2009-07-09 2011-08-31 Array Biopharma Inc Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa
ES2524576T3 (es) 2010-01-29 2014-12-10 Nerviano Medical Sciences S.R.L. Derivados de 6,7-dihidroimidazo[1,5-a]pirazin-8(5H)-ona como moduladores de proteína cinasa
JP2013519706A (ja) 2010-02-18 2013-05-30 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル 癌転移を予防するための方法
WO2011127219A1 (en) 2010-04-06 2011-10-13 Caris Life Sciences Luxembourg Holdings Circulating biomarkers for disease
US8383793B2 (en) 2010-04-15 2013-02-26 St. Jude Children's Research Hospital Methods and compositions for the diagnosis and treatment of cancer resistant to anaplastic lymphoma kinase (ALK) kinase inhibitors
TWI619713B (zh) 2010-04-21 2018-04-01 普雷辛肯公司 用於激酶調節的化合物和方法及其適應症
US8543395B2 (en) 2010-05-18 2013-09-24 Shazam Entertainment Ltd. Methods and systems for performing synchronization of audio with corresponding textual transcriptions and determining confidence values of the synchronization
PL2918588T3 (pl) 2010-05-20 2017-10-31 Array Biopharma Inc Związki makrocykliczne jako inhibitory kinazy TRK
EP2606067B1 (en) 2010-08-19 2018-02-21 Zoetis Belgium S.A. Anti-ngf antibodies and their use
US8637516B2 (en) 2010-09-09 2014-01-28 Irm Llc Compounds and compositions as TRK inhibitors
WO2012034095A1 (en) 2010-09-09 2012-03-15 Irm Llc Compounds and compositions as trk inhibitors
JP2014005206A (ja) 2010-10-22 2014-01-16 Astellas Pharma Inc アリールアミノヘテロ環カルボキサミド化合物
KR20190112175A (ko) 2010-12-01 2019-10-02 앨더바이오 홀딩스 엘엘씨 항―ｎｇｆ 조성물 및 그의 용도
ES2586588T3 (es) 2011-01-26 2016-10-17 Nerviano Medical Sciences S.R.L. Derivados tricíclicos, procedimiento para su preparación y su uso como inhibidores de quinasa
WO2012101032A1 (en) 2011-01-26 2012-08-02 Nerviano Medical Sciences S.R.L. Tricyclic pyrrolo derivatives, process for their preparation and their use as kinase inhibitors
PL2672967T3 (pl) 2011-02-07 2019-04-30 Plexxikon Inc Związki i sposoby modulacji kinaz i wskazania ku temu
US9199979B2 (en) 2011-02-24 2015-12-01 Nerviano Medical Sciences S.R.L. Thiazolylphenyl-benzenesulfonamido derivatives as kinase inhibitors
GEP20156285B (en) 2011-02-25 2015-05-11 Aierem Elelsi Compounds and compositions as trk inhibitors
US9284298B2 (en) 2011-04-11 2016-03-15 Nerviano Medical Sciences S.R.L. Pyrazolyl-pyrimidine derivatives as kinase inhibitors
ES2616458T3 (es) 2011-04-19 2017-06-13 Nerviano Medical Sciences S.R.L. Pirimidil pirroles sustituidos activos como inhibidores de quinasas
KR101953272B1 (ko) 2011-05-12 2019-02-28 네르비아노 메디칼 사이언시스 에스.알.엘. 키나제 억제제로서 활성인 치환된 인다졸 유도체
SI2712358T1 (sl) 2011-05-13 2017-03-31 Array Biopharma, Inc. Spojine pirolidinil sečnine, pirolidinil tiosečnine in pirolidinil gvanidina kot inhibitorji kinaze trka
EP2736514B1 (en) 2011-07-28 2017-10-18 Nerviano Medical Sciences S.r.l. Alkynyl substituted pyrimidinyl-pyrroles active as kinases inhibitors
JP6063945B2 (ja) 2011-10-07 2017-01-18 ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ キナーゼ阻害剤としての４−アルキル置換３，４−ジヒドロピロロ［１，２−ａ］ピラジン−１（２Ｈ）−オン誘導体
ES2639064T3 (es) 2011-10-07 2017-10-25 Nerviano Medical Sciences S.R.L. Derivados de 3,4-dihidropirrolo[1,2-a]pirazin-1(2h)-ona sustituidos como inhibidores de cinasa
WO2013059740A1 (en) 2011-10-21 2013-04-25 Foundation Medicine, Inc. Novel alk and ntrk1 fusion molecules and uses thereof
RU2014119150A (ru) 2011-11-14 2015-12-27 Тесаро, Инк. Модулирование некоторых тирозинкиназ
US9045479B2 (en) 2011-12-12 2015-06-02 Dr. Reddy's Laboratories Ltd. Substituted heterocyclic compounds as tropomyosin receptor kinase a (TrkA) inhibitors
US8377946B1 (en) 2011-12-30 2013-02-19 Pharmacyclics, Inc. Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors
TW201350479A (zh) 2012-04-26 2013-12-16 Ono Pharmaceutical Co Ｔｒｋ阻害化合物
JP2013226108A (ja) 2012-04-27 2013-11-07 Astellas Pharma Inc 新規ｎｔｒｋ２活性化変異の検出法
RU2602071C2 (ru) 2012-05-23 2016-11-10 НЕРВИАНО МЕДИКАЛ САЙЕНСИЗ С.р.л. Способ получения n-[5-(3,5-дифторбензил)-1н-индазол-3-ил]-4-(4-метилпиперазин-1-ил)-2-(тетрагидропиран-4-иламино)бензамида
TWI585088B (zh) 2012-06-04 2017-06-01 第一三共股份有限公司 作爲激酶抑制劑之咪唑并［１，２－ｂ］嗒衍生物
DK2872491T3 (da) 2012-07-11 2021-08-09 Blueprint Medicines Corp Inhibitorer af fibroblastvækstfaktorreceptoren
EP2689778A1 (en) 2012-07-27 2014-01-29 Pierre Fabre Medicament Derivatives of azaindoles or diazaindoles for treating pain
CN104507923B (zh) 2012-08-02 2018-02-09 内尔维阿诺医学科学有限公司 作为激酶抑制剂的取代的吡咯类活性剂
EP2890815B1 (en) 2012-08-31 2019-03-20 The Regents of the University of Colorado Methods for diagnosis and treatment of cancer
CN104703600A (zh) 2012-09-07 2015-06-10 埃克塞里艾克西斯公司 用于治疗肺腺癌的met、vegfr和ret的抑制剂
US20140084039A1 (en) 2012-09-24 2014-03-27 Electro Scientific Industries, Inc. Method and apparatus for separating workpieces
JP2014082984A (ja) 2012-10-23 2014-05-12 Astellas Pharma Inc 新規ｎｔｒｋ２活性化変異の検出法
WO2014071419A2 (en) 2012-11-05 2014-05-08 Foundation Medicine, Inc. Novel fusion molecules and uses thereof
CA2890207A1 (en) 2012-11-05 2014-05-08 Foundation Medicine, Inc. Novel ntrk1 fusion molecules and uses thereof
JP6326057B2 (ja) 2012-11-07 2018-05-16 ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ 置換ピリミジニルおよびピリジニル−ピロロピリジノン、これらの調製のための方法、およびキナーゼ阻害剤としてのこれらの使用
WO2014078322A1 (en) 2012-11-13 2014-05-22 Array Biopharma Inc. Thiazolyl and oxazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
US9969694B2 (en) 2012-11-13 2018-05-15 Array Biopharma Inc. N-(arylalkyl)-N′-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors
SI2920166T1 (sl) 2012-11-13 2017-01-31 Array Biopharma, Inc. Spojine uree, tiouree, gvanidina in cianogvanidina, primerne za zdravljenje bolečine
US9828360B2 (en) 2012-11-13 2017-11-28 Array Biopharma Inc. Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors
WO2014078417A1 (en) 2012-11-13 2014-05-22 Array Biopharma Inc. Pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
WO2014078328A1 (en) 2012-11-13 2014-05-22 Array Biopharma Inc. N-bicyclic aryl,n'-pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
WO2014078325A1 (en) 2012-11-13 2014-05-22 Array Biopharma Inc. N-(monocyclic aryl),n'-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
CN104781255B (zh) 2012-11-13 2017-10-24 阵列生物制药公司 作为trka激酶抑制剂的n‑吡咯烷基、n’‑吡唑基‑脲、硫脲、胍和氰基胍化合物
US9822118B2 (en) 2012-11-13 2017-11-21 Array Biopharma Inc. Bicyclic heteroaryl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors
WO2014078372A1 (en) 2012-11-13 2014-05-22 Array Biopharma Inc. Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
BR112015002626A2 (pt) 2012-11-29 2017-09-26 Yeda Res & Dev métodos para prevenção de metástases tumorais, tratamento e prognostico do câncer e identificação dos agentes que são inibidores da metástase putativa
US9447135B2 (en) 2012-12-14 2016-09-20 University Of Kentucky Research Foundation Semi-synthetic mithramycin derivatives with anti-cancer activity
US9127055B2 (en) 2013-02-08 2015-09-08 Astellas Pharma Inc. Method of treating pain with anti-human NGF antibody
RU2667907C9 (ru) 2013-02-19 2019-01-31 Оно Фармасьютикал Ко., Лтд. ИНГИБИРУЮЩЕЕ Trk СОЕДИНЕНИЕ
US20160010068A1 (en) 2013-02-22 2016-01-14 Boris C. Bastian Fusion polynucleotides and fusion polypeptides associated with cancer and particularly melanoma and their uses as therapeutic and diagnostic targets
WO2014134096A1 (en) 2013-02-27 2014-09-04 Oregon Health & Science University Methods of treating cancers characterized by aberrent ros1 activity
WO2014152777A2 (en) 2013-03-15 2014-09-25 Insight Genetics, Inc. Methods and compositions for the diagnosis and treatment of cancers resistant to ros1 inhibitors
EP2968551B1 (en) 2013-03-15 2021-05-05 The Trustees of Columbia University in the City of New York Fusion proteins and methods thereof
MA38394B1 (fr) 2013-03-15 2018-04-30 Glaxosmithkline Ip Dev Ltd Dérivés pyridine utilisés comme inhibiteurs de la kinase réarrangée au cours de la transfection (ret)
CN113337604A (zh) 2013-03-15 2021-09-03 莱兰斯坦福初级大学评议会 循环核酸肿瘤标志物的鉴别和用途
WO2014150751A2 (en) 2013-03-15 2014-09-25 Novartis Ag Biomarkers associated with brm inhibition
US9499522B2 (en) 2013-03-15 2016-11-22 Blueprint Medicines Corporation Compositions useful for treating disorders related to kit
US20140315199A1 (en) 2013-04-17 2014-10-23 Life Technologies Corporation Gene fusions and gene variants associated with cancer
US10072298B2 (en) 2013-04-17 2018-09-11 Life Technologies Corporation Gene fusions and gene variants associated with cancer
EP2997030B1 (en) 2013-05-14 2017-08-09 Nerviano Medical Sciences S.R.L. Pyrrolo[2,3-d]pyrimidine derivatives, process for their preparation and their use as kinase inhibitors
JP2016520131A (ja) 2013-05-30 2016-07-11 プレキシコン インコーポレーテッドＰｌｅｘｘｉｋｏｎ Ｉｎｃ． キナーゼ調節のための化合物、およびその適応
CA2917735C (en) 2013-07-11 2017-04-18 Betta Pharmaceuticals Co., Ltd Protein tyrosine kinase modulators and methods of use
WO2015012397A1 (ja) 2013-07-26 2015-01-29 公益財団法人がん研究会 Ｎｔｒｋ３融合体の検出法
US10875930B2 (en) 2013-07-30 2020-12-29 Blueprint Medicines Corporation PIK3C2G fusions
EP3628749A1 (en) 2013-07-30 2020-04-01 Blueprint Medicines Corporation Ntrk2 fusions
WO2015039006A1 (en) 2013-09-16 2015-03-19 The General Hospital Corporation Methods of treating cancer
DK3057969T3 (en) 2013-10-17 2018-09-24 Blueprint Medicines Corp COMPOSITIONS USED FOR TREATMENT OF DISEASES RELATED TO ENZYMETE KIT
US9334263B2 (en) 2013-10-17 2016-05-10 Blueprint Medicines Corporation Compositions useful for treating disorders related to kit
WO2015061229A1 (en) 2013-10-24 2015-04-30 Georgetown University Methods and compositions for treating cancer
EP3060560A1 (en) 2013-10-25 2016-08-31 Blueprint Medicines Corporation Inhibitors of the fibroblast growth factor receptor
WO2015064621A1 (ja) 2013-10-29 2015-05-07 公益財団法人がん研究会 新規融合体及びその検出法
WO2015108992A1 (en) 2014-01-15 2015-07-23 Blueprint Medicines Corporation Heterobicyclic compounds and their use as fgfr4 receptor inhibitors
DK3572416T3 (da) 2014-01-24 2022-12-12 Turning Point Therapeutics Inc Diaryl-makrocykler som modulatorer af proteinkinaser
DK3102555T3 (da) 2014-02-05 2021-08-09 VM Oncology LLC Sammensætninger af forbindelser og anvendelser deraf
TWI672141B (zh) 2014-02-20 2019-09-21 美商醫科泰生技 投予ｒｏｓ１突變癌細胞之分子
WO2015161274A1 (en) 2014-04-18 2015-10-22 Blueprint Medicines Corporation Pik3ca fusions
WO2015161277A1 (en) 2014-04-18 2015-10-22 Blueprint Medicines Corporation Met fusions
CR20160583A (es) 2014-05-15 2017-02-23 Array Biopharma Inc 1-((3s,4r)-4-(3-fluorofenil)-1-(2-metoxietil)pirrolidin-3-il)-3-(4-metil-3-(2-metilpirimidin-5-il)-1-fenil-1h-pirazol-5-il)urea como inhibidor de trka cinasa
WO2015183836A1 (en) 2014-05-27 2015-12-03 Brian Haynes Compositions, methods, and uses related to ntrk2-tert fusions
WO2015183837A1 (en) 2014-05-27 2015-12-03 Brian Haynes Compositions, methods, and uses related to ntrk2-tert fusions
US20170114415A1 (en) 2014-05-30 2017-04-27 The Regents Of The University Of Colorado, A Body Corporate Activating ntrk1 gene fusions predictive of kinase inhibitor therapy
EP3155118A1 (en) 2014-06-10 2017-04-19 Blueprint Medicines Corporation Pkn1 fusions
WO2015191666A2 (en) 2014-06-10 2015-12-17 Blueprint Medicines Corporation Raf1 fusions
US10370725B2 (en) 2014-07-17 2019-08-06 Blueprint Medicines Corporation FGR fusions
WO2016011147A1 (en) 2014-07-17 2016-01-21 Blueprint Medicines Corporation Prkc fusions
EP3169808B1 (en) 2014-07-17 2019-05-22 Blueprint Medicines Corporation Trio:tert fusion in cancer
KR20170042614A (ko) 2014-08-01 2017-04-19 파마싸이클릭스 엘엘씨 Btk 저해제를 이용한 치료에 대한 dlbcl의 반응을 예측하기 위한 바이오마커
WO2016022569A1 (en) 2014-08-04 2016-02-11 Blueprint Medicines Corporation Compositions useful for treating disorders related to kit
JP5979335B2 (ja) 2014-08-18 2016-08-24 小野薬品工業株式会社 Ｔｒｋ阻害化合物の酸付加塩
MX2017004810A (es) 2014-10-14 2017-10-16 Novartis Ag Moleculas de anticuerpo que se unen a pd-l1 y usos de las mismas.
WO2016075224A1 (en) 2014-11-14 2016-05-19 Nerviano Medical Sciences S.R.L. 6-amino-7-bicyclo-7-deaza-purine derivatives as protein kinase inhibitors
KR102649887B1 (ko) 2014-11-16 2024-03-22 어레이 바이오파마 인크. (s)-n-(5-((r)-2-(2,5-디플루오로페닐)-피롤리딘-1-일)-피라졸로[1,5-a]피리미딘-3-일)-3-히드록시피롤리딘-1-카르복스아미드 히드로겐 술페이트의 결정질 형태
US20170356052A1 (en) 2014-11-18 2017-12-14 Blueprint Medicines Corporation Prkacb fusions
US9701681B2 (en) 2014-12-15 2017-07-11 Cmg Pharmaceutical Co., Ltd. Fused ring heteroaryl compounds and their use as Trk inhibitors
MY190974A (en) 2015-05-20 2022-05-25 Massachusetts Gen Hospital Shared neoantigens
US20180177792A1 (en) 2015-05-29 2018-06-28 Ignyta, Inc. Compositions and methods for treating patients with rtk mutant cells
CA2988423A1 (en) 2015-06-01 2016-12-08 Loxo Oncology, Inc. Methods of diagnosing and treating cancer
US9782400B2 (en) 2015-06-19 2017-10-10 Macau University Of Science And Technology Oncogenic ROS1 and ALK kinase inhibitor
AU2015101722A4 (en) 2015-06-19 2016-05-19 Macau University Of Science And Technology Oncogenic ros1 and alk kinase inhibitor
GB201511546D0 (en) 2015-07-01 2015-08-12 Immatics Biotechnologies Gmbh Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
WO2017004342A1 (en) 2015-07-02 2017-01-05 Tp Therapeutics, Inc. Chiral diaryl macrocycles as modulators of protein kinases
CN108697708A (zh) 2015-10-26 2018-10-23 洛克索肿瘤学股份有限公司 Trk抑制剂抗性癌症中的点突变以及与此相关的方法
US20170224662A1 (en) 2016-01-22 2017-08-10 The Medicines Company Aqueous Formulations and Methods of Preparation and Use Thereof
WO2017155018A1 (ja) 2016-03-11 2017-09-14 小野薬品工業株式会社 Ｔｒｋ阻害剤抵抗性の癌治療剤
US10045991B2 (en) 2016-04-04 2018-08-14 Loxo Oncology, Inc. Methods of treating pediatric cancers
TN2018000335A1 (en) 2016-04-04 2020-01-16 Loxo Oncology Inc Liquid formulations of (s)-n-(5-((r)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide
EP3445361A1 (en) 2016-04-19 2019-02-27 Exelixis, Inc. Triple negative breast cancer treatment method
WO2017201156A1 (en) 2016-05-18 2017-11-23 Duke University Method of treating kras wild-type metastatic colorectal cell carcinoma using cabozantinib plus panitumumab
CN110049987B (zh) 2016-05-18 2022-02-18 阵列生物制药公司 制备化合物及其盐的方法
JOP20190092A1 (ar) 2016-10-26 2019-04-25 Array Biopharma Inc عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها
JOP20190213A1 (ar) 2017-03-16 2019-09-16 Array Biopharma Inc مركبات حلقية ضخمة كمثبطات لكيناز ros1
MA50456A (fr) 2017-10-26 2020-09-02 Array Biopharma Inc Formulations d'un inhibiteur de kinase trk macrocyclique

Also Published As

Publication number Publication date
US10251889B2 (en) 2019-04-09
KR20170116230A (ko) 2017-10-18
CA2767648C (en) 2018-09-04
RU2584157C2 (ru) 2016-05-20
MX364157B (es) 2019-04-15
MX2012000513A (es) 2012-04-30
MY162180A (en) 2017-05-31
ES2655899T3 (es) 2018-02-22
CA3013618C (en) 2021-03-09
US20190365763A1 (en) 2019-12-05
RU2016114128A3 (es) 2019-10-21
CA3013618A1 (en) 2011-01-13
US9796724B2 (en) 2017-10-24
US9682979B2 (en) 2017-06-20
JP2012532888A (ja) 2012-12-20
IL217414A (en) 2014-01-30
US20170114069A1 (en) 2017-04-27
AU2010271270C1 (en) 2015-08-13
KR101784977B1 (ko) 2017-10-16
US9782415B2 (en) 2017-10-10
KR101997055B1 (ko) 2019-07-05
CN102596957A (zh) 2012-07-18
US20120108568A1 (en) 2012-05-03
JP6114765B2 (ja) 2017-04-12
US8791123B2 (en) 2014-07-29
CO6612183A2 (es) 2013-02-01
JP5716021B2 (ja) 2015-05-13
NZ598086A (en) 2014-02-28
CN110003214B (zh) 2021-12-21
ZA201200982B (en) 2014-07-30
KR20190000384A (ko) 2019-01-02
SG177553A1 (en) 2012-03-29
CN106008523A (zh) 2016-10-12
US20180263984A1 (en) 2018-09-20
RU2012104493A (ru) 2013-08-20
UY32782A (es) 2012-01-31
US20170119770A1 (en) 2017-05-04
EP3299372B1 (en) 2020-01-08
EP2451812A1 (en) 2012-05-16
CL2012000059A1 (es) 2012-07-20
TWI503321B (zh) 2015-10-11
ES2774654T3 (es) 2020-07-22
CN110003214A (zh) 2019-07-12
CR20120065A (es) 2012-03-06
CN106008523B (zh) 2019-01-25
US10758542B2 (en) 2020-09-01
KR101933123B1 (ko) 2018-12-28
US20150031667A1 (en) 2015-01-29
TW201105676A (en) 2011-02-16
JP2017082004A (ja) 2017-05-18
AU2010271270B2 (en) 2015-01-22
JP2015063568A (ja) 2015-04-09
SG10201603095TA (en) 2016-05-30
EP2451812B1 (en) 2017-11-08
RU2016114128A (ru) 2018-11-28
AU2010271270A1 (en) 2012-03-01
EP3299372A1 (en) 2018-03-28
KR20120089634A (ko) 2012-08-13
CA2767648A1 (en) 2011-01-13
IL217414A0 (en) 2012-02-29
CN102596957B (zh) 2016-06-29
WO2011006074A1 (en) 2011-01-13
CR20120641A (es) 2013-03-11

Similar Documents

Publication Publication Date Title
AR077468A1 (es) Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa
AR074052A1 (es) Compuestos pirazolo{1,5-a}pirimidina sustituida como inhibidores de trk cinasa
PE20211411A1 (es) Compuestos de anillo fusionado
AR079541A1 (es) Compuestos sustituidos de n-(1h-indazol-4-il) imidazo (1,2-a) piridin-3-carboxamida como inhibidores de cfms
PE20151249A1 (es) Derivados de pirazolopirimidina como inhibidores de jak quinasas
PE20050691A1 (es) Proceso para preparar carboxamidas 2-aminotiazol-5-aromaticas como inhibidores de la cinasa
PE20070855A1 (es) Derivados de 4-amino-pirrolotriazina sustituida como inhibidores de quinasas
PE20190811A1 (es) Derivados de pirazolopirimidinas como inhibidor de quinasa
AR065556A1 (es) Derivados de 3-(( 1,2,4) triazolo (4,3-a) piridin -7-il) benzamida
AR081919A1 (es) Compuestos macrociclicos como inhibidores de quinasa trk y procesos de preparacion de los mismos
AR056691A1 (es) Derivados pirrolopirimidina como inhibidores de syk
PE20080841A1 (es) Derivados de quinazolinona e isoquinolinona y su uso para el tratamiento o prevencion de trastornos relacionados con el estres o la depresion
AR040477A1 (es) Benzoilureas heterociclicamente sustituidas, procedimiento para su preparacion y su uso como farmacos
MX368066B (es) Derivados de quinazolin-4-ona sustituida.
PE20151413A1 (es) Inhibidores de bmi-1 de pirimidina inversa sustituida
AR086367A1 (es) Compuestos de pirrolidinil urea y pirrolidinil tiourea como inhibidores de cinasa trka
PE20141974A1 (es) Compuestos de heterociclilo
PA8783501A1 (es) Derivados de quinaxolina como inhibidores de la actividad de cinasa de tirosina de las cinasas janus
ECSP10010585A (es) Compuestos de 2- imido- 3- metil pirrolo pirimidinona fenilo- sustituidos como inhibidores bace- 1, composiciones, y su uso
PE20070218A1 (es) COMPUESTOS DE CICLOALQUILO AMINO-HIDANTOINA Y USO DE ESTOS PARA LA MODULACION DE ß-SECRETASA
PE20110411A1 (es) Imidazopiridazinacarbonitrilos como inhibidores de quinasa
AR033678A1 (es) Derivados de quinolina, procedimiento para prepararlos, uso de los mismos para la preparacion de medicamentos y los medicamentos que contienen dichos derivados
AR053778A1 (es) Compuestos de quinazolina para el tratamiento de desordenes mediados por la proteina quinasa
AR053364A1 (es) Compuesto de 1h-imidazo 84,5-c) piridin -2- ilo, composicion farmaceutica que lo comprende, proceso para prepararla y su uso para preparar un medicamento para tratamiento de cancer o artritis
AR076008A1 (es) Derivados de hidroximetil-isoxazol moduladores de receptores gaba a, composiciones farmaceuticas que los contienen, metodo para prepararlos y uso de los mismos para el tratamiento del alzheimer y otros trastornos cognitivos.

Legal Events

Date Code Title Description
FA Abandonment or withdrawal
FB Suspension of granting procedure