ES2686501T3 - Pirazolo[1,5-a]piridinas sustituidas como inhibidores de la quinasa del receptor de tropomiosina (Trk) - Google Patents

Pirazolo[1,5-a]piridinas sustituidas como inhibidores de la quinasa del receptor de tropomiosina (Trk) Download PDF

Info

Publication number
ES2686501T3
ES2686501T3 ES12832784T ES12832784T ES2686501T3 ES 2686501 T3 ES2686501 T3 ES 2686501T3 ES 12832784 T ES12832784 T ES 12832784T ES 12832784 T ES12832784 T ES 12832784T ES 2686501 T3 ES2686501 T3 ES 2686501T3
Authority
ES
Spain
Prior art keywords
alkyl
halogen
optionally substituted
optional substituent
hydrogen
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.)
Active
Application number
ES12832784T
Other languages
English (en)
Inventor
Pradip Kumar Sasmal
Shahadat Ahmed
Ashok Tehim
Vidyadhar Paradkar
Prasanna M. Dattatreya
Nanjegowda Jagadeesh MAVINAHALLI
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.)
Dr Reddys Laboratories Ltd
Original Assignee
Dr Reddys Laboratories Ltd
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 Dr Reddys Laboratories Ltd filed Critical Dr Reddys Laboratories Ltd
Application granted granted Critical
Publication of ES2686501T3 publication Critical patent/ES2686501T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further 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
    • A61K31/495—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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/4995—Pyrazines or piperazines forming part of bridged ring systems
    • 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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further 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
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • 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
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • 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
    • A61P25/06—Antimigraine agents
    • 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
    • A61P35/00—Antineoplastic agents
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Vascular Medicine (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Urology & Nephrology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Diabetes (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Un compuesto de fórmula (I),**Fórmula** sus sales farmacéuticamente aceptables, solvatos farmacéuticamente aceptables o estereoisómeros de los mismos, en donde A es**Fórmula** X1 es CH o N; R1 representa hidrógeno o -alquilo C1-C6; R2 se selecciona independientemente entre hidrógeno, halógeno, ciano, -alquilo C1-C6, haloalquilo C1-C6, haloalcoxi C1-C6, fenilo opcionalmente sustituido con 1 a 3 halógenos o un -O-heterociclilo opcionalmente sustituido en donde el sustituyente opcional se selecciona entre alquilo, -ORi o -C(O)N(Ri)2; cuando X1 es CH, opcionalmente dos R2 presentes en dos átomos de carbono adyacentes se combinan para formar un anillo heterocíclico de 5 a 7 miembros; R3 se selecciona independientemente entre halógeno, ciano, -ORi, -C(O)N(Ri)2 o dos R3 junto con el átomo de carbono al que están anclados forman un grupo espirocicloalquilo C3-C7 anclado a pirrolidina; o dos R3 cuando están unidos a átomos de carbono adyacentes forman un anillo de cicloalquilo C3-C7 fusionado a la pirrolidina; Ra se selecciona entre (i) un grupo seleccionado entre -alquilo C1-C6, hidroxialquilo C1-C6 o -alquil(C1-C6)alcoxi C1-C6 opcionalmente sustituidos en donde el sustituyente opcional se selecciona entre ciano, halógeno o -arilo C6-C12, (ii) un -cicloalquilo C3-C10 opcionalmente sustituido en donde el sustituyente opcional se selecciona entre ciano, -alquilo C1-C6, hidroxilo, halógeno o -Rs, (iii) un -arilo C6-C12 opcionalmente sustituido en donde el sustituyente opcional se selecciona entre ciano, hidroxilo, halógeno, -alquilo C1-C6 o -Rr (iv) un heterociclilo de 5 a 10 miembros opcionalmente sustituido en donde el sustituyente opcional se selecciona entre ciano, hidroxilo, halógeno o-alquilo C1-C6, (v) un heteroarilo de 5 a 10 miembros opcionalmente sustituido en donde el sustituyente opcional se selecciona entre ciano, oxo (>=O), hidroxilo, halógeno, -alquilo C1-C6, -alcoxi C1-C6, -NRcRd o -Rr, (vi)-NR4R5, (vii)-alquil(C1-C6)-arilo C6-C12; Rb representa hidrógeno o halógeno; R4 se selecciona entre hidrógeno, -alquilo C1-C6, -cicloalquilo C3-C10, -hidroxialquilo C1-C6, alcoxialquilo C1-C6, halogenoalquilo C1-C6 o -alquil(C1-C6)-cicloalquilo C3-C10; R5 se selecciona a partir de hidrógeno o -alquilo C1-C6 o -alquil(C1-C6)-cicloalquilo C3-C10; Alternativamente R4 y R5 junto con el átomo de nitrógeno al que están anclados pueden formar un anillo heterocíclico de 5 a 10 miembros opcionalmente sustituido que contiene opcionalmente 1-2 heteroátomos o grupos seleccionados entre -O-, -S-, -N-, -C(>=O)-, -S(>=O)- o -S(>=O)2- adicionales, en donde el sustituyente opcional se selecciona entre hidroxilo, -alquilo C1-C6, -C(>=O)-alquilo C1-C6, mesilo o COORe; Rc y Rd se seleccionan independientemente entre hidrógeno o -alquilo C1-C6; Re se selecciona entre hidrógeno o alquilo; Ri es hidrógeno, -alquilo C1-C6, -haloalquilo C1-C6, -alquil(C1-C6)alcoxi C1-C6, -cicloalquilo C3-C10, -alquil(C1- C6)-cicloalquilo C3-C10 opcionalmente sustituido en donde el sustituyente opcional es halógeno o -alquilo C1-C6 sustituido con 1 a 3 grupos hidroxi; Rr se selecciona independientemente entre un heterociclilo de 5 a 10 miembros o un heteroarilo de 5 a 10 miembros, en donde el sustituyente opcional se selecciona entre hidroxilo, halógeno, -alquilo C1-C6 o -alcoxi C1-C6; Rs es un -alquil(C1-C6)-arilo C6-C10 opcionalmente sustituido, en donde el sustituyente opcional es halógeno; m representa independientemente 0, 1, 2, 3 o 4; y n representa independientemente 0, 1, 2 o 3.
ES12832784T 2011-12-12 2012-12-12 Pirazolo[1,5-a]piridinas sustituidas como inhibidores de la quinasa del receptor de tropomiosina (Trk) Active ES2686501T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN4329CH2011 2011-12-12
PCT/IB2012/003012 WO2013088256A1 (en) 2011-12-12 2012-12-12 Substituted pyrazolo[1,5-a] pyridine as tropomyosin receptor kinase (trk) inhibitors

Publications (1)

Publication Number Publication Date
ES2686501T3 true ES2686501T3 (es) 2018-10-18

Family

ID=47902312

Family Applications (1)

Application Number Title Priority Date Filing Date
ES12832784T Active ES2686501T3 (es) 2011-12-12 2012-12-12 Pirazolo[1,5-a]piridinas sustituidas como inhibidores de la quinasa del receptor de tropomiosina (Trk)

Country Status (16)

Country Link
US (7) US9045478B2 (es)
EP (2) EP2791139B1 (es)
JP (1) JP5990595B2 (es)
KR (2) KR20140105508A (es)
CN (1) CN104114553B (es)
AU (1) AU2012351748B2 (es)
BR (1) BR112014014276A2 (es)
CA (1) CA2858958C (es)
CL (1) CL2014001529A1 (es)
CO (1) CO7071124A2 (es)
DK (1) DK2791138T3 (es)
EA (1) EA025352B1 (es)
ES (1) ES2686501T3 (es)
IL (1) IL233067B (es)
MX (1) MX356401B (es)
WO (2) WO2013088257A1 (es)

Families Citing this family (70)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2952692C (en) 2008-09-22 2020-04-28 Array Biopharma Inc. Substituted imidazo[1,2b]pyridazine compounds
SG10201900514RA (en) 2008-10-22 2019-02-27 Array Biopharma Inc Substituted pyrazolo[1,5-a]pyrimidine compounds as trk 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
BR112012029405B1 (pt) 2010-05-20 2021-01-05 Array Biopharma Inc. compostos macrocíclicos como inibidores de trk quinase, composição farmacêutica, uso de um composto de fórmula i ou um sal farmaceuticamente aceitável do mesmo, processo para a preparação de um composto
CA2858958C (en) * 2011-12-12 2016-10-04 Dr. Reddy's Laboratories Ltd. Substituted pyrazolo[1,5-a]pyridine as tropomyosin receptor kinase (trk) inhibitors
TWI731317B (zh) 2013-12-10 2021-06-21 美商健臻公司 原肌球蛋白相關之激酶（ｔｒｋ）抑制劑
WO2015092610A1 (en) 2013-12-20 2015-06-25 Pfizer Limited N-acylpiperidine ether tropomyosin-related kinase inhibitors
CN103819343B (zh) * 2014-02-17 2016-03-23 青岛农业大学 化合物2-烯丙基-4-氟-6-硝基苯酚的制备方法和农用生物活性
WO2015143652A1 (en) * 2014-03-26 2015-10-01 Merck Sharp & Dohme Corp. TrkA KINASE INHIBITORS,COMPOSITIONS AND METHODS THEREOF
US20170197939A1 (en) 2014-04-15 2017-07-13 Pfizer Inc. Tropomyosin-Related Kinase Inhibitors Containing Both A 1H-Pyrazole And A Pyrimidine Moiety
EP3140298A1 (en) 2014-05-07 2017-03-15 Pfizer Inc. Tropomyosin-related kinase inhibitors
US10059706B2 (en) * 2014-05-08 2018-08-28 Bayer Cropscience Aktiengesellschaft Pyrazolopyridine sulfonamides as nematicides
US9394305B2 (en) 2014-06-23 2016-07-19 Dr. Reddy's Laboratories Ltd. Substituted imidazo[1,2-a]pyridine compounds as tropomyosin receptor kinase a (TrkA) inhibitors
WO2016009296A1 (en) 2014-07-16 2016-01-21 Pfizer Inc. N-acylpiperidine ether tropomyosin-related kinase inhibitors
WO2016020784A1 (en) 2014-08-05 2016-02-11 Pfizer Inc. N-acylpyrrolidine ether tropomyosin-related kinase inhibitors
IL290905B2 (en) 2014-11-16 2023-09-01 Array Biopharma Inc Crystal form of (s)–n-(5–)–2–(r))5,2-difluorophenyl)-pyrrolidine-1-yl)-pyrazolo[5,1-a]pyrimidine-3-yl)-3 -Hydroxypyrrolidine-1-carboxamide hydrogen sulfate
TWI780438B (zh) 2014-12-18 2022-10-11 美商健臻公司 原肌球蛋白相關激酶（ｔｒｋ）抑制劑之醫藥調配物
CN104672121B (zh) * 2015-02-16 2017-10-24 上海华默西医药科技有限公司 2r‑(2,5‑二氟苯基)吡咯烷盐酸盐的制备方法
PL3305788T3 (pl) * 2015-05-29 2021-03-08 Wuxi Fortune Pharmaceutical Co., Ltd Inhibitor kinazy janusowej
WO2017075107A1 (en) 2015-10-26 2017-05-04 Nanda Nisha Point mutations in trk inhibitor-resistant cancer and methods relating to the same
EP3439662B1 (en) 2016-04-04 2024-07-24 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
LT3800189T (lt) 2016-05-18 2023-10-10 Loxo Oncology, Inc. (s)-n-(5-((r)-2-(2,5-difluorfenil)pirolidin-1-il)pirazolo[1,5-a]pirimidin-3- il)-3-hidroksipirolidin-1-karboksamido gavimas
JOP20190092A1 (ar) 2016-10-26 2019-04-25 Array Biopharma Inc عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها
WO2018077246A1 (zh) 2016-10-28 2018-05-03 正大天晴药业集团股份有限公司 用作神经营养因子酪氨酸激酶受体抑制剂的氨基吡唑并嘧啶化合物
JOP20190213A1 (ar) 2017-03-16 2019-09-16 Array Biopharma Inc مركبات حلقية ضخمة كمثبطات لكيناز ros1
KR102629267B1 (ko) * 2017-05-12 2024-01-25 이난타 파마슈티칼스, 인코포레이티드 아폽토시스 신호 조절 키나아제 １ 억제제 및 이의 사용 방법
WO2018218051A1 (en) 2017-05-25 2018-11-29 Enanta Pharmaceuticals, Inc. Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
US10253018B2 (en) 2017-05-25 2019-04-09 Enanta Pharmaceuticals, Inc. Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
WO2018218044A2 (en) 2017-05-25 2018-11-29 Enanta Pharmaceuticals Inc Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
US10738033B2 (en) 2017-05-31 2020-08-11 Nantbio, Inc. Trk inhibition
US10800760B2 (en) 2017-05-31 2020-10-13 Nantbio, Inc. Trk inhibition
CN107286070B (zh) * 2017-07-19 2019-07-16 浙江师范大学 (r)-2-(2,5-二氟苯基)吡咯烷的合成方法及中间体
US10597382B2 (en) 2017-08-28 2020-03-24 Enanta Pharmaceuticals, Inc. Tetrazole containing apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
MA50456A (fr) 2017-10-26 2020-09-02 Array Biopharma Inc Formulations d'un inhibiteur de kinase trk macrocyclique
CN109867671B (zh) * 2017-12-02 2020-07-07 广东东阳光药业有限公司 一种吡唑[1,5-a]吡啶化合物的晶型及其药物组合物和用途
CN109867672B (zh) * 2017-12-02 2020-07-07 广东东阳光药业有限公司 吡唑[1,5-a]吡啶衍生物的盐及其用途
CN109867668B (zh) * 2017-12-02 2021-03-26 广东东阳光药业有限公司 一种吡唑[1,5-a]吡啶化合物的晶型及其药物组合物和用途
EP3727379B1 (en) * 2017-12-20 2025-01-22 Sunshine Lake Pharma Co., Ltd. Crystalline mono-sodium salt of n-(5-(3-cyanopyrazolo[1,5-a]pyridin-5-yl)2-methoxypyridin-3-yl)-2,4-difluoro-benzenesulfonamide
CN108218754B (zh) * 2018-01-23 2021-05-07 广东赛烽医药科技有限公司 一种2-(2,5-二氟苯基)吡咯烷的制备方法
CA3090376A1 (en) 2018-02-06 2019-08-15 University Of Miami Inhibitors of the notch transcriptional activation complex kinase ("nack") and methods for use of the same
CA3095366A1 (en) 2018-03-29 2019-10-03 Loxo Oncology, Inc. Treatment of trk-associated cancers
WO2019213239A1 (en) 2018-05-02 2019-11-07 Enanta Pharmaceuticals Inc. Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
IL278368B2 (en) 2018-05-02 2024-06-01 Enanta Pharm Inc Tetrazole containing apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
GB201811825D0 (en) 2018-07-19 2018-09-05 Benevolentai Bio Ltd Organic compounds
CN108794370A (zh) * 2018-07-31 2018-11-13 上海弈柯莱生物医药科技有限公司 一种拉罗替尼中间体的制备方法
US10968199B2 (en) 2018-08-22 2021-04-06 Enanta Pharmaceuticals, Inc. Cycloalkyl-containing apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
GB201813791D0 (en) 2018-08-23 2018-10-10 Benevolental Bio Ltd Organic compounds
CN111171019A (zh) * 2018-11-13 2020-05-19 上海轶诺药业有限公司 一类五元并六元杂环化合物及其作为蛋白受体激酶抑制剂的用途
WO2020106707A1 (en) 2018-11-19 2020-05-28 Enanta Pharmaceuticals, Inc. Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
CN109593802B (zh) * 2018-12-24 2021-10-01 上海健康医学院 一种(r)-2-(2,5-二氟苯基)吡咯烷或其盐的制备方法
MX2021009863A (es) 2019-03-21 2021-11-12 Onxeo Una molecula dbait en combinacion con inhibidor de quinasa para el tratamiento del cancer.
US11466033B2 (en) 2019-03-25 2022-10-11 Enanta Pharmaceuticals, Inc. Substituted pyridines as apoptosis signal-regulating kinase 1 inhibitors
CN110015980A (zh) * 2019-05-14 2019-07-16 大连联化化学有限公司 一种合成叔丁基亚磺酰胺的方法
CN113939514B (zh) * 2019-06-05 2022-12-27 广州嘉越医药科技有限公司 吡咯并嘧啶类化合物及其应用
CN110751853B (zh) * 2019-10-25 2021-05-18 百度在线网络技术（北京）有限公司 停车位数据的有效性识别方法和装置
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
EP4082614A4 (en) * 2019-12-27 2024-01-24 Japan Tobacco Inc. ACYLSULFAMIDE COMPOUND AND PHARMACEUTICAL USE THEREOF
EP4093404A1 (en) 2020-01-22 2022-11-30 BenevolentAI Bio Limited Topical pharmaceutical compositions comprising imidazo[1,2-b]pyridazine compounds
CA3163585A1 (en) 2020-01-22 2021-07-29 Benevolentai Bio Limited Pharmaceutical compositions and their uses
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
AU2021270672B2 (en) * 2020-05-15 2024-07-25 Cspc Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. Fused aza-heterocyclic amide compound and use thereof
WO2022026565A1 (en) * 2020-07-29 2022-02-03 Ideaya Biosciences, Inc. Cyclized acetamido derivatives as dna polymerase theta inhibitors
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
WO2022234287A1 (en) 2021-05-06 2022-11-10 Benevolentai Bio Limited Imidazopyridazine derivatives useful as trk inhibitors
CN116115618B (zh) * 2021-11-15 2025-07-08 石药集团中奇制药技术（石家庄）有限公司 一种治疗肿瘤的药物
CN116120323B (zh) * 2021-11-15 2025-11-04 石药集团中奇制药技术（石家庄）有限公司 固体形式的氮杂稠环酰胺类化合物及其用途
CN115772170B (zh) * 2021-12-03 2025-05-16 徐诺药业(南京)有限公司 一种吡唑并[1,5-a]吡啶衍生物及其制备方法和应用
WO2024118887A1 (en) * 2022-11-30 2024-06-06 Blueprint Medicines Corporation N-phenyl-pyrazolo[1,5-a]pyridine-3-carboxamide derivatives as wild type c-kit kinase inhibitors for the treatment of urticaria
EP4630423A1 (en) * 2022-12-07 2025-10-15 Third Harmonic Bio, Inc. Compounds and compositions as c-kit kinase inhibitors

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002501506A (ja) * 1997-05-03 2002-01-15 スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー ドーパミンｄ▲下３▼受容体のモジュレーターとしてのテトラヒドロイソキノリン誘導体
JP2003231687A (ja) 2002-02-04 2003-08-19 Japan Tobacco Inc ピラゾリル縮合環化合物及びその医薬用途
AU2003240488A1 (en) * 2002-06-04 2003-12-19 Neogenesis Pharmaceuticals, Inc. Pyrazolo` 1,5a! pyrimidine compounds as antiviral agents
AU2003281664A1 (en) 2002-07-25 2004-02-16 Pfizer Products Inc. Isothiazole derivatives useful as anticancer agents
US7141568B2 (en) 2003-07-09 2006-11-28 Pfizer Italia S.R.L. Pyrrolo[3,4-c]pyrazole derivatives active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them
JP2009518340A (ja) * 2005-12-08 2009-05-07 ノバルティス アクチエンゲゼルシャフト ＥｐｈＢおよびＶＥＧＦＲ２キナーゼ阻害剤としてのピラゾロ［１，５−ａ］ピリジン−３−カルボン酸
AU2008273050A1 (en) 2007-07-11 2009-01-15 Auckland Uniservices Limited Pyrazolo[1,5-a]pyridines and their use in cancer therapy
MX2010012457A (es) 2008-05-13 2010-12-07 Irm Llc Heterociclos que contienen nitrogeno fusionado y composiciones de los mismos como inhibidores de cinasa.
SG10201900514RA (en) 2008-10-22 2019-02-27 Array Biopharma Inc Substituted pyrazolo[1,5-a]pyrimidine compounds as trk kinase inhibitors
JP5959541B2 (ja) 2011-02-25 2016-08-02 ノバルティス アーゲー Ｔｒｋ阻害剤としてのピラゾロ［１，５−ａ］ピリジン
CA2858958C (en) * 2011-12-12 2016-10-04 Dr. Reddy's Laboratories Ltd. Substituted pyrazolo[1,5-a]pyridine as tropomyosin receptor kinase (trk) inhibitors

Also Published As

Publication number Publication date
US20170267677A1 (en) 2017-09-21
US9402833B2 (en) 2016-08-02
CL2014001529A1 (es) 2015-06-26
US9045479B2 (en) 2015-06-02
CN104114553B (zh) 2017-03-01
CA2858958A1 (en) 2013-06-20
AU2012351748B2 (en) 2016-04-14
US10047087B2 (en) 2018-08-14
BR112014014276A2 (pt) 2017-06-13
US20150164869A1 (en) 2015-06-18
JP2015500275A (ja) 2015-01-05
CO7071124A2 (es) 2014-09-30
US20180354951A1 (en) 2018-12-13
EP2791138B1 (en) 2018-06-06
IL233067A0 (en) 2014-07-31
US20150258076A1 (en) 2015-09-17
WO2013088257A1 (en) 2013-06-20
CN104114553A (zh) 2014-10-22
CA2858958C (en) 2016-10-04
EP2791138A1 (en) 2014-10-22
EA201400701A1 (ru) 2014-11-28
US20140371217A1 (en) 2014-12-18
AU2012351748A1 (en) 2014-07-17
MX356401B (es) 2018-05-21
US9289419B2 (en) 2016-03-22
EP2791139A1 (en) 2014-10-22
MX2014006980A (es) 2015-04-08
US10344031B2 (en) 2019-07-09
US20160264572A1 (en) 2016-09-15
EA025352B1 (ru) 2016-12-30
US9045478B2 (en) 2015-06-02
NZ626306A (en) 2015-05-29
IL233067B (en) 2018-03-29
KR20170005894A (ko) 2017-01-16
KR20140105508A (ko) 2014-09-01
WO2013088256A1 (en) 2013-06-20
JP5990595B2 (ja) 2016-09-14
US9670207B2 (en) 2017-06-06
EP2791139B1 (en) 2017-11-08
DK2791138T3 (en) 2018-09-17
KR101849143B1 (ko) 2018-04-16
US20150005280A1 (en) 2015-01-01

Similar Documents

Publication Publication Date Title
ES2686501T3 (es) Pirazolo[1,5-a]piridinas sustituidas como inhibidores de la quinasa del receptor de tropomiosina (Trk)
ES2666870T3 (es) Derivado de dispiropirrolidina
ES2600636T3 (es) Spiro-[1,3]-oxazinas y spiro-[1,4]-oxazepinas como inhibidores de BACE1 y/o BACE2
AR076002A1 (es) Derivados imidazolicos heterociclicos utiles como agentes antivirales para hepatitis c y composiciones farmaceuticas que los comprenden.
AR075383A1 (es) Derivados de triazolo[4,3-b]piridazina
CO6251260A2 (es) Derivados de bifenilo conformacionalmente restringido para uso como inhibidores del virus de la hepatitis c.
AR086554A1 (es) Derivados de la piperidina 3-espirociclica como agonistas de receptores de la ghrelina
AR080314A1 (es) Derivado de 1,3,4,8-tetrahidro-2h-pirido (1,2-a) pirazina y su uso como inhibidor de la hiv integrasa
AR083813A1 (es) Derivados de pirazol aminopirimidina como moduladores de lrrk2
AR060903A1 (es) Derivados de 1,2,3,4-tetrahidro-quinolina como inhibidores de cetp
AR085960A1 (es) 1,3-oxazinas como inhibidores de la bace1 y/o de la bace2
AR061867A1 (es) Derivados de (4,5') bipirimidil 6,4' - diamina como inhibidores de proteinquinasa
AR073314A1 (es) Derivados de indazol o de 4,5,6,7-tetrahidro-indazol
AR085615A1 (es) Derivados de fluoropiridinona utiles como agentes antibacterianos y composiciones farmaceuticas que los contienen
AR081932A1 (es) Derivados de heteroaril imidazolona, composiciones farmaceuticas que los contienen y uso de los mismos en el tratamiento de enfermedades neoplasicas y autoinmunes
AR067413A1 (es) Compuestos heterociclicos que contienen ciclopenta[d]pirimidina inhibidores de proteinquinasas akt, composiciones farmaceuticas que los contienen, metodo de preparacion y uso de las mismas para el tratamiento de enfermedades hiperproliferativas, tales como cancer
AR089568A1 (es) Compuestos heterociclicos y sus metodos de usos
AR087328A1 (es) Derivados de imidazo[1,2-b]piridazina e imidazo[4,5-b]piridina como inhibidores de jak
ECSP099324A (es) Nuevos derivados de aminopirimidina como inhibidores de plk1
AR076900A1 (es) Derivados heterociclicos nitrogenados utiles como agentes antivirales, composiciones farmaceuticas que los contienen y uso de los mismos como inhibidores del vhc
AR062937A1 (es) Compuestos que modulan el receptor cb2
ECSP034475A (es) Derivados de 4-fenil-piridin como antagonistas del receptor de neuroquinina-1
CO6321244A2 (es) Pirrolopiridinas como inhibidores de cinasa
AR066562A1 (es) Derivados de pirrol condensados; una formulacion farmaceutica en base al compuesto y su uso para preparar medicamentos
AR069435A1 (es) Derivados de aminotiazol, proceso para la obtencion de los mismos, composiciones farmaceuticas y su uso como inhibidores de la fbpasa