AR073818A1 - Imidazopiridazinacarbonitrilos utiles como inhibidores de quinasa - Google Patents

Imidazopiridazinacarbonitrilos utiles como inhibidores de quinasa

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Publication number
AR073818A1
AR073818A1 ARP090103910A ARP090103910A AR073818A1 AR 073818 A1 AR073818 A1 AR 073818A1 AR P090103910 A ARP090103910 A AR P090103910A AR P090103910 A ARP090103910 A AR P090103910A AR 073818 A1 AR073818 A1 AR 073818A1
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Brian Fink
Libing Chen
Yufen Zhao
Liqi He
Ashvinikumar V Gavai
Soong-Hoon Kim
Andrew Nation
Litai Zhang
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Bristol Myers Squibb Co
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Publication of AR073818A1 publication Critical patent/AR073818A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/50Pyridazines; Hydrogenated pyridazines
    • A61K31/5025Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/08Drugs for disorders of the urinary system of the prostate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/14Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02Heterocyclic 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 two hetero rings
    • C07D498/04Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
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  • Rheumatology (AREA)
  • Oncology (AREA)
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  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Diabetes (AREA)
  • Biomedical Technology (AREA)
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  • Dermatology (AREA)
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  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Mobile Radio Communication Systems (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Las imidazopiridazinas de formula (1) inhiben la actividad de proteína quinasas haciéndolas utiles como agentes contra el cáncer. Reivindicacion 1: Un compuesto caracterizado porque tiene la formula (1) o una sal farmacéuticamente aceptable del mismo, en el que R1 se selecciona de H, F, Cl, Br, CN, y alquilo C1-6; R2 se selecciona de arilo sustituido con 0-5 R2a y heteroarilo sustituido con 0-5 R2a; R2a, en cada caso, se selecciona independientemente entre H, F, CI, Br, =O, CN, NO2, -ORb, -S(O)pRc, -C(=O)Rd, -NRaRa, -(CR2bR2c)r-C(=O)NRaRa, -NRaC(=O)Rd, -NRaC(=O)ORb, -OC(=O)NRaRa, NRaC(=O)NRaRa, -(CR2bR2c)rC(=O)ORb, -S(O)2NRaRa, -NRaS(O)2NRaRa, -NRaS(O)2Rc, alquilo C1-6 sustituido con 0-5 Re, -(CR2bR2c)r-carbociclilo C3-6 sustituido con 0-5 Re y -(CR2bR2c)r-heterociclilo sustituido con 0-5 Re; R2b, en cada caso, se selecciona independientemente entre H y alquilo C1-6 sustituido con 0-5 Re; R2c, en cada caso, se selecciona independientemente entre H y alquilo C1-6 sustituido con 0-5 Re; R3 se selecciona de H, F, CI, Br, CN, -ORb, -NRaRa, -C(=O)NRaRa, -NRaS(O)2Rc, -NRaC(=O)Rd, -NRaC(=O)ORb, y alquilo C1-6 sustituido con 0-5 Re; R4 se selecciona de H, alquilo C1-6 sustituido con 0-5 Re; -(CR4bR4c)rORb, -(CR4bR4c)rS(O)pRc, -(CR4bR4c)rC(=O)Rd, -(CR4bR4c)rNRaRa, -(CR4bR4c)rC(=O)NRaRa, -(CR4bR4c)rNRaC(=O)Rd, -(CR4bR4c)rNRaC(=O)ORb, -(CR4bR4c)rOC(=O)NRaRa, -(CR4bR4c)rNRaC(=O)NRaRa, -(CR4bR4c)rC(=O)ORb, -(CR4bR4c)rS(O)2NRaRa, -(CR4bR4c)rNRaS(O)2NRaRa, -(CR4bR4c)rNRaS(O)2Rc, -(CR4bR4c)r-carbociclilo C3-6 sustituido con 0-5 R4a, -(CR4bR4c)r-heterociclilo sustituido con 0-5 R4a; R4a, en cada caso, se selecciona independientemente entre F, Cl, Br, alquilo C1-6 sustituido con 0-5 Re, alquenilo C2-6, alquinilo C2-6, NO2, =O, CN, -SO3H, -S(O)pRc, -S(O)2NRaRa, -NRaS(O)2Rc, -ORb, -NRaRa, -NRaC(=O)Rd, -NRaC(=O)NRaRa, -C(=O)ORb, -C(=O)Rd, -OC(=O)Rd, -C(=O)NRaRa, cicloalquilo C3-6, heterociclilo y arilo; R4b en cada caso, se selecciona independientemente entre H y alquilo C1-6 sustituido con 0-5 Re; R4c, en cada caso, se selecciona independientemente entre H y alquilo C1-6 sustituido con 0-5 Re; R5 se selecciona de H y alquilo C1-6 sustituido con 0-5 Re; R6 se selecciona de H y alquilo C1-6 sustituido con 0-5 Re; Ra, en cada caso se selecciona independientemente entre H, CN, alquilo C1-6 sustituido con 0-5 Re, alquenilo C2-6 sustituido con 0-5 Re, alquinilo C2-6 sustituido con 0-5 Re, -(CH2)r-carbociclilo C3-10 sustituido con 0-5 Re y -(CH2)r-heterociclilo sustituido con 0-5 Re; o Ra y Ra junto con el átomo de nitrogeno al que están unidos forman un anillo heterocíclico sustituido con 0-5 Re; Rb, en cada caso, se selecciona independientemente entre H, alquilo C1-6 sustituido con 0-5 Re, alquenilo C2-6 sustituido con 0-5 Re, alquinilo C2-6 sustituido con 0-5 Re, -(CH2)r-carbociclilo C3-10 sustituido con 0-5 Re y -(CH2)r-heterociclilo sustituido con 0-5 Re; Rc, en cada caso, se selecciona independientemente entre alquilo C1-6 sustituido con 0-5 Re, alquenilo C2-6 sustituido con 0-5 Re, alquinilo C2-6 sustituido con 0-5 Re, carbociclilo C3-6 y heterociclilo; Rd, en cada caso, se selecciona independientemente entre H, alquilo C1-6 sustituido con 0-5 Re, alquenilo C2-6 sustituido con 0-5 Re, alquinilo C2-6 sustituido con 0-5 Re, -(CH2)r-carbociclilo C3-10 sustituido con 0-5 Re y -(CH2)r-heterociclilo sustituido con 0-5 Re; Re, en cada caso, se selecciona independientemente entre alquilo C1-6 sustituido con 0-5 Rf, alquenilo C2-6, alquinilo C2-6, -(CH2)r-cicloalquilo C3-6, F, Cl, Br, CN, NO2, =O, CO2H, -(CH2)rO-alquilo C1-5, -(CH2)rOH, SH y -(CH2)rNRfRf; Rf, en cada caso, se selecciona independientemente entre H, alquilo C1-5, cicloalquilo C3-6 y fenilo, o Rf y Rf junto con el átomo de nitrogeno al que están unidos forman un anillo heterocíclico; p, en cada caso, se selecciona independientemente entre 0, 1 y 2; y r, en cada caso, se selecciona independientemente entre 0, 1, 2, 3 y 4.
ARP090103910A 2008-10-09 2009-10-09 Imidazopiridazinacarbonitrilos utiles como inhibidores de quinasa AR073818A1 (es)

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EP (1) EP2350081B1 (es)
JP (1) JP5560278B2 (es)
KR (1) KR20110075010A (es)
CN (1) CN102245609B (es)
AR (1) AR073818A1 (es)
AU (1) AU2009302360B2 (es)
BR (1) BRPI0920135A2 (es)
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