[go: up one dir, main page]

AR085908A1 - DERIVADOS DE 3-BUTIN-2-OL Y DE CARBONITRILO CON ACTIVIDAD INHIBIDORA DE LA QUINASA INDUCTORA DE NF-kB (NIK) - Google Patents

DERIVADOS DE 3-BUTIN-2-OL Y DE CARBONITRILO CON ACTIVIDAD INHIBIDORA DE LA QUINASA INDUCTORA DE NF-kB (NIK)

Info

Publication number
AR085908A1
AR085908A1 ARP120100848A ARP120100848A AR085908A1 AR 085908 A1 AR085908 A1 AR 085908A1 AR P120100848 A ARP120100848 A AR P120100848A AR P120100848 A ARP120100848 A AR P120100848A AR 085908 A1 AR085908 A1 AR 085908A1
Authority
AR
Argentina
Prior art keywords
link
alkyl
group
alkylene
heterocycloalkyl
Prior art date
Application number
ARP120100848A
Other languages
English (en)
Inventor
Jianwen Feng
Pui Leng Loke
Christian A G N Montalbetti
Steven Staben
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of AR085908A1 publication Critical patent/AR085908A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/0805—Compounds with Si-C or Si-Si linkages comprising only Si, C or H atoms
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • 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
    • 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
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • 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
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three 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
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Pulmonology (AREA)
  • Reproductive Health (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Endocrinology (AREA)
  • Pain & Pain Management (AREA)
  • Dermatology (AREA)
  • Transplantation (AREA)
  • Otolaryngology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Estos compuestos y las composiciones farmacéuticas que los contienen son útiles para el tratamiento de enfermedades y trastornos, en los que se observa una señalización no deseada o sobreactivada de la NF-kB.Reivindicación 1: Compuestos de la fórmula (1) en los que en la fórmula (1): Y es nitrógeno y el subíndice b es el número entero 0, o Y es carbono y el subíndice b es el número entero 1; R1 es alquilo C1-2, haloalquilo C1-2 o -CH2-OH; R2 es alquilo C1-6, haloalquilo C1-6, cicloalquilo de 3 - 7 eslabones, alquileno C1-6-cicloalquilo de 3 - 7 eslabones, fenilo, heteroarilo de 5 - 6 eslabones, C(=O)Rx2a, -C(=O)ORx2a o -C(=O)NRx2aRx2b, en el que Rx2a se elige entre el grupo formado por hidrógeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, heteroalquilo C1-6, cicloalquilo de 3 - 8 eslabones, heteroalquilo de 3 - 8 eslabones, -(alquileno C1-6)-(cicloalquilo de 3 - 8 eslabones), -(alquileno C1-6)-(heterocicloalquilo de 3 - 8 eslabones), -(alquileno C1-6)-(arilo de 6 eslabones) y -(alquileno C1-6)-(heteroarilo de 5 - 6 eslabones), y Rx2b se elige entre el grupo formado por hidrógeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6 y heteroalquilo C1-6; en la que, si Rx2a y Rx2b están unidos al mismo átomo de nitrógeno, entonces podrán combinarse opcionalmente entre sí para formar un heterocicloalquilo de 3 - 7 eslabones que contiene además 0 - 2 heteroátomos adicionales elegidos entre N, O y S; o como alternativa, R1 y R2 se combinan para formar un cicloalquilo de 3 - 8 eslabones o un heterocicloalquilo de 3 - 8 eslabones y opcionalmente está fusionado a ellos un anillo heteroarilo de 5 - 6 eslabones que contiene 1 - 3 heteroátomos elegidos entre N, O y S; y en la que porciones alifática y/o aromática de R1 y R2 ya sea con independencia, ya sea en combinación, están opcionalmente sustituidas por 1 - 5 sustituyentes RR1/2 elegidos entre el grupo formado por F, Cl, Br, I, -OH, -NH2, -SH, -CF3, -OCF3, -SF5, -OCH3, -(Xa)0-1-CN, -(Xa)0-1-NO2, -(Xa)0-1-N3, -(Xa)0-1-OH, -(Xa)0-1-H, -(Xa)0-1-ORa, -(Xa)0-1-N(H)Ra, -(Xa)0-1-N(H)2, -(Xa)0-1-N(Ra)2, -(Xa)0-1-SRa, -(Xa)0-1-SH, -(Xa)0-1C(O)Ra, -(Xa)0-1-S(O)2Ra, -(Xa)0-1-S(O)Ra, -(Xa)0-1-N(H)-S(O)2Ra, -(Xa)0-1-N(Ra)S(O)2Ra, -(Xa)0-1-OC(O)Ra, -(Xa)0-1-N(H)-C(O)ORa, -(Xa)0-1-N(Ra)C(O)ORa, -(Xa)0-1-C(=O)ORa, -(Xa)0-1-C(=O)OH, -(Xa)0-1-C(=O)N(H)Ra, -(Xa)0-1-C(=O)N(Ra)Ra, -(Xa)0-1-N(H)C(=O)Ra, -(Xa)0-1-N(Ra)C(=O)Ra, -(Xa)0-1-N(H)C(=O)ORa y -(Xa)0-1-N(Ra)C(=O)ORa, en los que Xa se elige entre el grupo formado por alquileno C1-6, alquenileno C2-6, alquinileno C2-6, heteroalquileno C1-6,cicloalquileno de 3 - 6 eslabones y heterocicloalquileno de 3 - 6 eslabones, y Ra con independencia de cada aparición se elige entre el grupo formado por alquilo C1-6, haloalquilo C1-6, heteroalquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo de 3 - 7 eslabones y heterocicloalquilo de 3 - 7 eslabones; A se elige entre el grupo de fórmulas (2), en los que X1, X2 y X3 son con independencia N o CR5, en los que por lo menos uno de X1, X2 y X3 es CR5, en el que R5 se elige entre el grupo formado por hidrógeno, alquilo C1-4, haloalquilo C1-4, halógeno, -O(alquilo C1-6), (heterocicloalquilo de 3 - 6 eslabones)-(alquileno C1-3)-oxi-, -CN, -NO2, -NH-(alquilo C1-6), -NH2 y -N(alquilo C1-6)2; R3 es heteroarilo de 5 - 10 eslabones opcionalmente sustituido por NRx3aRx3b, en el que Rx3a y Rx3b con independencia entre sí se eligen entre el grupo formado por hidrógeno, alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, alcoxi C1-6, heteroalquilo C1-6, arilo de 6 - 10 eslabones y heteroarilo de 5 - 10 eslabones; en la fórmula (1), R3 y los grupos Rx3a y Rx3b de R3, si están presentes, están además opcionalmente sustituidos con independencia entre sí por 1 - 5 sustituyentes RR3 elegidos entre el grupo formado por F, Cl, Br, I, -OH, -NH2, -SH, -CF3, -OCF3, -SF5, -OCH3, -(Xb)0-1-CN, -(Xb)0-1-NO2, -(Xb)0-1-N3, -(Xb)-OH, -(Xb)-H, -(Xb)0-1-ORb, -(Xb)0-1-N(H)Rb, -(Xb)-N(H)2, -(Xb)0-1-N(Rb)2, -(Xb)0-1-SRb, -(Xb)0-1-SH, -(Xb)0-1-C(O)Rb, -(Xb)0-1-S(O)2Rb, -(Xb)0-1-S(O)Rb, -(Xb)0-1-N(H)S(O)2Rb, -(Xb)0-1-N(Rb)S(O)2Rb, -(Xb)0-1-OC(O)Rb, -(Xb)0-1-N(H)C(O)ORb, -(Xb)0-1-N(Rb)C(O)ORb, -(Xb)0-1-C(=O)ORb, -(Xb)0-1-C(=O)OH, -(Xb)0-1-C(=O)N(H)Rb, -(Xb)0-1-C(=O)N(Rb)Rb, -(Xb)0-1-N(H)C(=O)Rb, -(Xb)0-1-N(Rb)C(=O)Rb, -(Xb)0-1-N(H)C(=O)ORb y -(Xb)0-1-N(Rb)C(=O)ORb, en los que Xb se elige entre el grupo formado por alquileno C1-6, alquenileno C2-6, alquinileno C2-6, heteroalquileno C1-6, cicloalquileno C3-6 y heterocicloalquileno C3-6, y Rb con independencia de cada aparición se elige entre el grupo formado por alquilo C1-6, haloalquilo C1-6, heteroalquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo de 3 - 7 eslabones y heterocicloalquilo de 3 - 7 eslabones; R4 es -(L)0-1-Rx4a, en el que L se elige entre el grupo formado por -O-, -N(H)-, -C(=O)-, alquileno C1-4, haloalquileno C1-4, alquenileno C2-4, alquinileno C2-4 y heteroalquileno C1-4 y Rx4a se elige entre el grupo formado por hidrógeno, alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6 y heteroalquilo C1-6, cicloalquilo de 3 - 6 eslabones, heterocicloalquilo de 3 - 9 eslabones, arilo de 6 - 10 eslabones y heteroarilo de 5 - 10 eslabones; en la que las porciones alifática o aromática de R4 están sustituidas con independencia por 0 - 5 sustituyentes RR4 elegidos entre el grupo formado por alquilo C2-6, haloalquilo C1-6, heteroalquilo C1-6, alcoxi C1-6, (alquil C1-6)amino, di(alquil C1-6)amino, heterocicloalquilo C3-6, F, Cl, Br, I, -OH, -NH2, -SH, -CF3, -OCF3, -SF5, -(Xc)0-1-CN, -(Xc)0-1-NO2, -(Xc)0-1-N3, -(Xc)-OH, -(Xc)0-1-ORc, -(Xc)-H, -(Xc)0-1-Rc, -(Xc)0-1-N(H)Rc, -(Xc)0-1-N(Rc)2, -(Xc)0-1-SRc, -(Xc)0-1-C(O)Rc, -(Xc)0-1-S(O)2Rc, -(Xc)0-1-S(O)Rc, -(Xc)0-1-N(H)S(O)2Rc, -(Xc)0-1-N(Rc)-S(O)2Rc, -(Xc)0-1-C(=O)ORc, -(Xc)0-1-C(=O)OH, -(Xc)0-1-C(=O)N(H)Rc, -(Xc)0-1-C(=O)N(Rc)Rc, -(Xc)0-1-N(H)C(=O)Rc y -(Xc)0-1-N(Rc)C(=O)Rc, en los que Xc se elige entre el grupo formado por alquileno C1-6, alquenileno C2-6, alquinileno C2-6, heteroalquileno C1-6, cicloalquileno C3-6 y heterocicloalquileno C3-6, y Rc con independencia de cada aparición se elige entre el grupo formado por alquilo C1-6, haloalquilo C1-6, heteroalquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo de 3 - 7 eslabones, heterocicloalquilo de 3 - 7 eslabones, fenilo y heteroarilo de 5 - 6 eslabones; en la que cualesquiera dos grupos Rc unidos al mismo átomo de nitrógeno se combinan opcionalmente para formar un heterocicloalquilo de 3 - 7 eslabones o un heteroarilo de 5 - 10 eslabones que contienen 1 - 3 heteroátomos elegidos entre N, O y S.
ARP120100848A 2011-03-16 2012-03-15 DERIVADOS DE 3-BUTIN-2-OL Y DE CARBONITRILO CON ACTIVIDAD INHIBIDORA DE LA QUINASA INDUCTORA DE NF-kB (NIK) AR085908A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201161453494P 2011-03-16 2011-03-16

Publications (1)

Publication Number Publication Date
AR085908A1 true AR085908A1 (es) 2013-11-06

Family

ID=45894445

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP120100848A AR085908A1 (es) 2011-03-16 2012-03-15 DERIVADOS DE 3-BUTIN-2-OL Y DE CARBONITRILO CON ACTIVIDAD INHIBIDORA DE LA QUINASA INDUCTORA DE NF-kB (NIK)

Country Status (12)

Country Link
US (2) US8901313B2 (es)
EP (1) EP2686314A1 (es)
JP (1) JP2014508183A (es)
KR (1) KR20130133051A (es)
CN (1) CN103476768B (es)
AR (1) AR085908A1 (es)
BR (1) BR112013023681A2 (es)
CA (1) CA2827161A1 (es)
MX (1) MX2013010513A (es)
RU (1) RU2013142648A (es)
TW (1) TW201247650A (es)
WO (1) WO2012123522A1 (es)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9067917B2 (en) 2013-03-15 2015-06-30 Janssen Pharmaceutica Nv 1,2,5-substituted benzimidazoles as FLAP modulators
US8952177B2 (en) 2013-03-15 2015-02-10 Janssen Pharmaceutica Nv 1,2,6-substituted benzimidazoles as FLAP modulators
WO2014170421A1 (en) * 2013-04-19 2014-10-23 F. Hoffmann-La Roche Ag Serine/threonine kinase inhibitors
TWI663166B (zh) * 2013-04-24 2019-06-21 健生藥品公司 新化合物
US20160096850A9 (en) * 2013-08-22 2016-04-07 Genentech, Inc. Alkynyl alcohols and methods of use
WO2015025026A1 (en) * 2013-08-22 2015-02-26 F. Hoffmann-La Roche Ag Alkynyl alcohols and methods of use
TWI627173B (zh) * 2013-09-26 2018-06-21 比利時商健生藥品公司 作為ＮＩＫ抑制劑的新穎３－（１Ｈ－吡唑－４－基）－１Ｈ－吡咯并［２，３－ｃ］吡啶衍生物
TWI704146B (zh) * 2013-09-26 2020-09-11 比利時商健生藥品公司 用作ＮＩＫ抑制劑之新的1-(４-嘧啶基)-１Ｈ-吡唑並[３,２-ｃ]吡啶衍生物
CA2957046C (en) 2014-08-04 2022-11-15 Nuevolution A/S Optionally fused heterocyclyl-substituted derivatives of pyrimidine useful for the treatment of inflammatory, metabolic, oncologic and autoimmune diseases
MX371152B (es) 2014-10-23 2020-01-20 Janssen Pharmaceutica Nv Nuevos derivados de pirazolopirimidina como inhibidores de la cinasa inductora de nf-kb (nk).
AU2015334917B2 (en) 2014-10-23 2019-08-29 Janssen Pharmaceutica Nv New compounds as NIK inhibitors
BR112017008039B1 (pt) * 2014-10-23 2023-04-11 Janssen Pharmaceutica N.V. Derivados de pirazol como inibidores de nik, seu uso no tratamento ou prevenção de câncer e composição farmacêutica que os compreende
AU2015334914B2 (en) * 2014-10-23 2019-09-19 Janssen Pharmaceutica Nv New thienopyrimidine derivatives as NIK inhibitors
CN104529735A (zh) * 2014-12-08 2015-04-22 苏州施亚生物科技有限公司 一种1-(5-溴-4-氯-2-氟苯基)-乙酮的合成方法
CN107406427A (zh) * 2015-02-25 2017-11-28 豪夫迈·罗氏有限公司 炔基醇及其使用方法
EP3433235A4 (en) * 2016-03-21 2019-12-18 Regents of the University of Minnesota INDOL AND INDAZOL COMPOUNDS AND THERAPEUTIC USE THEREOF
SG11201809751XA (en) 2016-05-26 2018-12-28 Zeno Royalties & Milestones Llc Egfr inhibitor compounds
JP7140751B2 (ja) * 2016-08-24 2022-09-21 エフ．ホフマン－ラ ロシュ アーゲー ２－アザビシクロ［３．１．０］ヘキサン－３－オン誘導体及び使用方法
KR20250073542A (ko) 2018-03-09 2025-05-27 리커리엄 아이피 홀딩스, 엘엘씨 치환된 1,2-다이하이드로-3H-피라졸로[3,4-d]피리미딘-3-온
US11149011B2 (en) 2018-03-20 2021-10-19 Plexxikon Inc. Compounds and methods for IDO and TDO modulation, and indications therefor
CN109320503B (zh) * 2018-12-10 2022-07-01 怀化学院 苯并咪唑炔胺类化合物的无金属一锅合成方法
HUE068694T2 (hu) * 2019-05-31 2025-01-28 Janssen Pharmaceutica Nv NF-KB indukáló kináz kismolekulás inhibitorai
CN110183383A (zh) * 2019-06-25 2019-08-30 深圳市格物致欣化学技术有限公司 3-醛基-1h-取代吲唑及其制备方法
WO2021124277A1 (en) 2019-12-20 2021-06-24 Nuevolution A/S Compounds active towards nuclear receptors
US11685727B2 (en) 2019-12-20 2023-06-27 Nuevolution A/S Compounds active towards nuclear receptors
TWI794742B (zh) 2020-02-18 2023-03-01 美商基利科學股份有限公司 抗病毒化合物
JP7429799B2 (ja) 2020-02-18 2024-02-08 ギリアード サイエンシーズ， インコーポレイテッド 抗ウイルス化合物
TWI775313B (zh) 2020-02-18 2022-08-21 美商基利科學股份有限公司 抗病毒化合物
EP4126874A1 (en) 2020-03-31 2023-02-08 Nuevolution A/S Compounds active towards nuclear receptors
AU2021249530A1 (en) 2020-03-31 2022-12-01 Nuevolution A/S Compounds active towards nuclear receptors
CN113831325A (zh) * 2020-06-23 2021-12-24 沈阳药科大学 新型吲哚类衍生物及其制备方法和应用
US11697666B2 (en) 2021-04-16 2023-07-11 Gilead Sciences, Inc. Methods of preparing carbanucleosides using amides
KR20240049311A (ko) 2021-08-18 2024-04-16 길리애드 사이언시즈, 인코포레이티드 인지질 화합물 및 이의 제조 및 사용 방법
CN113816957B (zh) * 2021-10-29 2023-04-07 浙江工业大学 4-(7-氮杂吲哚)-2-氨基嘧啶类化合物及其应用

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US5804374A (en) 1980-12-05 1998-09-08 Massachusetts Insti. Technology Nuclear factors associates with transcriptional regulation
UA71889C2 (uk) 1996-04-02 2005-01-17 Йєда Рісерч Енд Дівелопмент Ко. Лтд. Модулятори зв'язаного з рецептором tnf фактора (traf), їх одержання та застосування
JP3990061B2 (ja) * 1998-01-05 2007-10-10 エーザイ・アール・アンド・ディー・マネジメント株式会社 プリン誘導体および糖尿病の予防・治療剤としてのアデノシンａ２受容体拮抗剤
NZ516260A (en) 1999-07-02 2004-08-27 Eisai Co Ltd Fused imidazole compounds and remedies for diabetes mellitus
US7329679B2 (en) 2000-01-27 2008-02-12 Schering Aktiengesellschaft 1,2 Diarylbenzimidazoles and their pharmaceutical use
CA2517517C (en) 2003-03-03 2012-12-18 Array Biopharma, Inc. P38 inhibitors and methods of use thereof
ES2578254T3 (es) 2003-12-03 2016-07-22 Ym Biosciences Australia Pty Ltd Inhibidores de cinasas basados en azol
TW200736260A (en) 2005-11-10 2007-10-01 Smithkline Beecham Corp Inhibitors of Akt activity
WO2008043019A1 (en) 2006-10-04 2008-04-10 Pharmacopeia, Inc 8-substituted 2-(benzimidazolyl) purine derivatives for immunosuppression
US20080108104A1 (en) 2006-11-02 2008-05-08 Colorado State University Research Foundation Identification of bacterial species and subspecies using lipids
WO2009158011A1 (en) 2008-06-26 2009-12-30 Amgen Inc. Alkynyl alcohols as kinase inhibitors
CN106518856B (zh) 2008-12-19 2020-04-28 沃泰克斯药物股份有限公司 用作atr激酶抑制剂的化合物
US9382226B2 (en) * 2010-07-21 2016-07-05 Merck Sharp & Dohme Corp. Aldosterone synthase inhibitors

Also Published As

Publication number Publication date
MX2013010513A (es) 2013-10-07
TW201247650A (en) 2012-12-01
CN103476768B (zh) 2015-07-08
KR20130133051A (ko) 2013-12-05
CA2827161A1 (en) 2012-09-20
BR112013023681A2 (pt) 2016-12-13
HK1193089A1 (en) 2014-09-12
US20120214762A1 (en) 2012-08-23
JP2014508183A (ja) 2014-04-03
US20150038460A1 (en) 2015-02-05
US8901313B2 (en) 2014-12-02
RU2013142648A (ru) 2015-04-27
EP2686314A1 (en) 2014-01-22
CN103476768A (zh) 2013-12-25
WO2012123522A1 (en) 2012-09-20

Similar Documents

Publication Publication Date Title
AR085908A1 (es) DERIVADOS DE 3-BUTIN-2-OL Y DE CARBONITRILO CON ACTIVIDAD INHIBIDORA DE LA QUINASA INDUCTORA DE NF-kB (NIK)
CR20130333A (es) Compuestos indol o análogos de los mismos útiles en el tratamiento de la degeneración macular relacionada con la edad (dmae)
AR092108A1 (es) Piridazina 1,4 disustituida, analogos de la misma y metodos para tratar las enfermedades relacionadas con deficiencia del smn
AR094557A1 (es) Tiadiazol, análogos del mismo, y métodos para el tratamiento de condiciones relacionadas con deficiencia de smn
CR20140135A (es) Nuevos derivados de aril-quinolina
CR20140089A (es) Nuevos derivados bicíclicos de dihidroquinolina-2-ona
AR070221A1 (es) Derivados de ftalazinona inhibidores de polimerasas, composiciones farmaceuticas que los contienen y usos de los mismos para prevenir y/o tratar tumores cancerigenos,lesiones isquemicas y otras enfermedades asociadas.
PE20150623A1 (es) Moduladores de la ruta del complemento y usos de los mismos
EA201101089A1 (ru) Производные оксадиазола в качестве агонистов рецептора s1p1
CR20140091A (es) Nuevos derivados dihidroquinolina-2-ona
CU20090048A7 (es) Nuevos derivados de diosmetina, su procedimiento de preparación y las composiciones farmacéuticas que los contienen
AR088760A1 (es) Derivados de pirrolopirimidina y purina
AR083367A1 (es) Compuestos de tipo quinazolinona como antagonistas de crth
CR20130338A (es) Compuestos heterocíclicos nitrogenados sustituidos fusionados en posición 6,6 y usos de los mismos
AR067759A1 (es) Compuestos de pirazol utiles como moduladores de la enzima raf asociada al crecimiento celular anormal
MX2012008049A (es) Compuestos heterociclicos triciclicos, composiciones y metodos de uso de los mismos,.
AR052903A1 (es) Compuestos de bis arilo y heteroarilo sustituidos como antagonistas selectivos de 5ht2a, composiciones farmaceuticas que los contienen y su empleo en el tratamiento de trastornos del sueno.
AR085920A1 (es) Derivados benzimidazolicos utiles como agentes antitumorales y composiciones farmaceuticas que los contienen
AR076850A1 (es) Derivados sustituidos de indazol y aza-indazol como moduladores de la gamma secretasa.
AR084412A1 (es) Compuestos de piridina fusionados, utiles como inhibidores de caseina quinasa, y las composiciones farmaceuticas que los contienen
AR092288A1 (es) Ligandos del receptor ep1
CU20160010A7 (es) NUEVOS COMPUESTOS ISOINDOLlNA O ISOQUINOLlNA ÚTILES COMO INHIBIDORES ANTIAPOPTÓTICOS Bcl-2 Y COMPOSICIONES FARMACÉUTICAS QUE LOS CONTIENEN
PE20161323A1 (es) Compuestos de triazolopiridina, composiciones y metodos de uso de los mismos
PE20141940A1 (es) Compuestos triciclicos, composiciones que los comprenden y usos de los mismos
MX372721B (es) Ánalogos halogenados de agentes antifi-broticos.

Legal Events

Date Code Title Description
FA Abandonment or withdrawal