[go: up one dir, main page]

AR038955A1 - PIRIMIDINONE AND PIRIDONA SUBSTITUTED COMPOUNDS AND METHODS FOR USE - Google Patents

PIRIMIDINONE AND PIRIDONA SUBSTITUTED COMPOUNDS AND METHODS FOR USE

Info

Publication number
AR038955A1
AR038955A1 ARP970105716A ARP970105716A AR038955A1 AR 038955 A1 AR038955 A1 AR 038955A1 AR P970105716 A ARP970105716 A AR P970105716A AR P970105716 A ARP970105716 A AR P970105716A AR 038955 A1 AR038955 A1 AR 038955A1
Authority
AR
Argentina
Prior art keywords
radicals
alkyl
optionally substituted
alkylthio
cyano
Prior art date
Application number
ARP970105716A
Other languages
Spanish (es)
Inventor
Michael J Malone
Nathan B Mantlo
Jeffery A Zablocki
Ulrike D Spohr
Original Assignee
Amgen 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 Amgen Inc filed Critical Amgen Inc
Publication of AR038955A1 publication Critical patent/AR038955A1/en

Links

Classifications

    • 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
    • C07D401/02—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 two hetero rings
    • C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • 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
    • A61P11/16—Central respiratory analeptics
    • 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
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P31/12—Antivirals
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A61P37/08—Antiallergic agents
    • 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
    • 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
    • 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
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Diabetes (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Hematology (AREA)
  • Pulmonology (AREA)
  • Oncology (AREA)
  • Dermatology (AREA)
  • Endocrinology (AREA)
  • Hospice & Palliative Care (AREA)
  • Virology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Emergency Medicine (AREA)
  • Communicable Diseases (AREA)
  • Psychiatry (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Transplantation (AREA)

Abstract

Los compuestos de pirimidinona y piridona sustituidos seleccionados son efectivos para la profilaxis y tratamiento de enfermedades, tales como enfermedades mediadas por TNF-alfa, IL-1beta, IL-6 y/o IL-8, y otras afecciones, tales como dolor y diabetes. Nuevos compuestos, análogos, prodrogas y sales farmacéuticamente aceptables de las mismas, composiciones farmacéuticas y métodos para la profilaxis y el tratamiento de enfermedades y otras afecciones y condiciones que involucran inflamación, dolor, diabetes y lo similar. Procesos para preparar estos compuestos así como productos intermedios útiles en estos procesos. Reivindicación 1: Un compuesto de la fórmula (1) o una sal farmacéuticamente aceptable del mismo, donde X es O, S ó NR5; el grupo molecular (2) es elegido del grupo de fórmulas (3) siempre que el número total combinado de radicales arilo, heteroarilo, cicloalquilo y heterociclilo en -VC(R)W- sea 0-3; U es NR21 ó CHR21; n es un entero de 1-3; R1 y R2 son independientemente -Y ó -Z-Y, y R3 y R4 son cada uno independientemente -Z-Y; siempre que R4 no sea un radical arilo sustituido, (aril sustituido)metilo ó (aril sustituido)etilo, y el número total de radicales arilo, heteroarilo, cicloalquilo y heterociclilo en cada -Y y -Z-Y sea 0-3; donde cada Z es independientemente: (1) un radical alquilo, alquenilo ó alquinilo sustituido optativamente por (a) 1-3 radicales de amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, ciano ó halo, y (b) 1-2 radicales de heterociclilo, arilo o heteroarilo sustituidos optativamente por 1-3 radicales de amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, halo, alquilo ó haloalquilo; (2) un radical heterociclilo sustituido optativamente por 1-3 radicales de amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, alquilo ó haloalquilo; o (3) un radical arilo ó heteroarilo sustituido optativamente por 1-3 radicales de amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, ciano, halo, alquilo ó haloalquilo; cada Y es independientemente: (1) un radical hidrógeno; (2) un radical halo, ciano ó nitro; (3) un radical -C(O)-R20, -C(O)-OR21, -C(O)-NR5R21 ó -C(NR5)-NR5R21; (4) un radical -OR21, -O-C(O)-R21, -O-C(O)-NR5R21 u -O-C(O)-NR22-S(O)2-R20; (5) un radical -SR21, -S(O)-R20, -S(O)2-R20, -S(O)2-NR5R21, -S(O)2NR22-C(O)-R21, -S(O)2-NR22-C(O)-OR20 ó -S(O)2-NR22-C(O)NR5R21; ó (6) un radical -NR5R21, -NR22-C(O)-R21, -NR22-C(O)-OR20, -NR22-C(O)NR5R21, -NR22-C(NR5)-NR5R21, -NR22-S(O)2-R20 ó -NR22S(O)2-NR5R21; donde cada R5 es independientemente (1) radicales hidrógeno; (2) radicales alquilo, alquenilo ó alquinilo sustituidos optativamente por 1-3 radicales de amino, alquilamino, dialquilamino, hidroxi, alcoxi, alquiltio, ciano ó halo; ó (3) radicales arilo, heteroarilo, aralquilo, heteroaralquilo, heterociclilo, heterociclilalquilo, cicloalquilo ó cicloalquilalquilo sustituidos optativamente por 1-3 radicales de amino, alquilamino, dialquilamino, hidroxi, alcoxi, alquiltio, ciano, alquilo ó haloalquilo; donde cada R20 es independientemente (1) un radical alquilo, alquenilo ó alquinilo optativamente sustituidos por 1-3 radicales de -CO2R23 amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, N-(alcoxicarbonil)-N-(alquil)amino, aminocarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, alquilsulfinilo, alquilsulfonilo, ciano, halo ó aralcoxi, aralquiltio, aralquilsulfonilo, cicloalquilo, heterociclilo, arilo ó heteroarilo optativamente sustituidos por 1-3 radicales de amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, alcanoilo, alcoxicarbonilo, hidroxi, alcoxi, alquiltio, alquilsulfinilo, alquilsulfonilo, ciano, halo, alquilo ó haloalquilo; (2) un radical heterociclilo sustituido optativamente por 1-3 radicales de amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, alcoxicarbonilo, hidroxi, alcoxi, alquiltio, ciano, alquilo ó haloalquilo; o (3) radicales arilo ó heteroarilo sustituidos optativamente por 1-3 radicales de amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, alcoxicarbonilo, hidroxi, alcoxi, alquiltio, ciano, halo, azido, alquilo ó haloalquilo; cada R22 es independientemente un radical hidrógeno ó R20; cada R22 es independientemente (1) un radical hidrógeno; (2) un radical alquilo sustituido optativamente por un radical de heterociclilo, arilo ó heteroarilo sustituido optativamente por 1-3 radicales de amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, alquilsulfinilo, alquilsulfonilo, ciano, halo, alquilo ó haloalquilo; ó (3) radicales heterociclilo, arilo ó heteroarilo sustituidos optativamente por 1-3 radicales de amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, alquilsulfinilo, alquilsulfonilo, ciano, halo, alquilo ó haloalquilo; y cada R23 es independientemente hidrógeno ó alquilo, ó arilo, heteroarilo, aralquilo ó heteroaralquilo sustituido optativamente por 1-3 radicales de amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, alquilsulfinilo, alquilsulfonilo, ciano, halo, alquilo ó haloalquilo; y R11 y R12 son independientemente un radical arilo ó heteroarilo sustituido optativamente por 1-3 radicales de (1) R30; (2) radicales halo ó ciano; (3) radicales -C(O)-R30, -C(O)-OR29, -C(O)-NR31R32 ó -C(NR31)NR31R32; (4) radicales -OR29, -O-C(O)-R29, -O-C(O)-NR31R32 ó -O-C(O)-NR33S(O)2-R30; (5) radicales -SR29, -S(O)-R30, -S(O)2-R30, -S(O)2-NR31R32, -S(O)2-NR33-C(O)-R30, -S(O)2-NR33-C(O)-OR30 ó -S(O)2-NR33-C(O)-NR31R32; ó (6) -NR31R32, -NR33-C(O)-R29, -NR33-C(O)-OR30, -NR33-C(O)-NR31R32, -NR33-C(NR31)-NR31R32, -NR33-S(O)2-R30 ó -NR33S(O)2-NR31R32; siempre que (1) R11 no sea un radical 4-piridilo, 4-pirimidinilo, 4-quinolilo ó 6-isoquinolinilo sustituido optativamente por 1-2 sustituyentes; y (2) el número total de radicales arilo, heteroarilo, cicloalquilo y heterociclilo sustituidos en cada uno de R11 y R12 sea 0-1; donde cada R30 es independientemente (1) un radical alquilo, alquenilo ó alquinilo optativamente sustituido por 1-3 radicales de -NR31R31, -CO2R23, hidroxi, alcoxi, alquiltio, alquilsulfinilo, alquilsulfonilo, ciano, halo ó aralcoxi, aralquiltio, aralquilsulfonilo, heterociclilo, arilo ó heteroarilo optativamente sustituidos por 1-3 radicales de los radicales amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, alquilsulfinilo, alquilsulfonilo, ciano, halo, alquilo ó haloalquilo; (2) un radical heterociclilo sustituido optativamente por 1-3 radicales de amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, ciano, halo, alquilo ó haloalquilo; o (3) radicales arilo ó heteroarilo optativamente sustituidos por 1-3 radicales de amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, ciano, alquilo ó haloalquilo; cada R29 es independientemente un radical hidrógeno ó R30; cada R31 y R32 es independientemente (1) radicales hidrógeno; (2) un radical alquilo sustituido optativamente por un radical cicloalquilo, arilo, heterociclilo ó heteroarilo sustituido optativamente por 1-3 radicales de los radicales amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, ciano, alquilo ó haloalquilo; ó (3) un radical arilo, heteroarilo, heterociclilo ó cicloalquilo sustituido optativamente por 1-3 radicales de los radicales amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, ciano, alquilo ó haloalquilo; y donde cada R33 es independientemente (1) un radical hidrógeno; ó (2) un radical alquilo sustituido optativamente por un radical de los radicales heterociclilo, arilo ó heteroarilo optativamente sustituido por 1-3 radicales de amino, alquilamino, dialquilamino, alcanoilamino, alcoxicarbonilamino, alquilsulfonilamino, hidroxi, alcoxi, alquiltio, ciano, alquilo ó haloalquilo.Selected substituted pyrimidinone and pyridone compounds are effective for the prophylaxis and treatment of diseases, such as diseases mediated by TNF-alpha, IL-1 beta, IL-6 and / or IL-8, and other conditions, such as pain and diabetes. . New compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for the prophylaxis and treatment of diseases and other conditions and conditions involving inflammation, pain, diabetes and the like. Processes to prepare these compounds as well as intermediate products useful in these processes. Claim 1: A compound of the formula (1) or a pharmaceutically acceptable salt thereof, wherein X is O, S or NR5; the molecular group (2) is chosen from the group of formulas (3) provided that the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in -VC (R) W- is 0-3; U is NR21 or CHR21; n is an integer of 1-3; R1 and R2 are independently -Y or -Z-Y, and R3 and R4 are each independently -Z-Y; provided that R4 is not a substituted aryl radical, (substituted aryl) methyl or (substituted aryl) ethyl, and the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Y and -Z-Y is 0-3; where each Z is independently: (1) an alkyl, alkenyl or alkynyl radical optionally substituted by (a) 1-3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano or halo radicals, and (b) 1-2 heterocyclyl, aryl or heteroaryl radicals optionally substituted by 1-3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, halo, alkyl or haloalkyl radicals; (2) a heterocyclyl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkyl or haloalkyl; or (3) an aryl or heteroaryl radical optionally substituted by 1-3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, halo, alkyl or haloalkyl radicals; each Y is independently: (1) a hydrogen radical; (2) a halo, cyano or nitro radical; (3) a radical -C (O) -R20, -C (O) -OR21, -C (O) -NR5R21 or -C (NR5) -NR5R21; (4) a radical -OR21, -O-C (O) -R21, -O-C (O) -NR5R21 or -O-C (O) -NR22-S (O) 2-R20; (5) a radical -SR21, -S (O) -R20, -S (O) 2-R20, -S (O) 2-NR5R21, -S (O) 2NR22-C (O) -R21, -S (O) 2-NR22-C (O) -OR20 or -S (O) 2-NR22-C (O) NR5R21; or (6) a radical -NR5R21, -NR22-C (O) -R21, -NR22-C (O) -OR20, -NR22-C (O) NR5R21, -NR22-C (NR5) -NR5R21, -NR22 -S (O) 2-R20 or -NR22S (O) 2-NR5R21; where each R5 is independently (1) hydrogen radicals; (2) alkyl, alkenyl or alkynyl radicals optionally substituted by 1-3 amino, alkylamino, dialkylamino, hydroxy, alkoxy, alkylthio, cyano or halo radicals; or (3) aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl or cycloalkylalkyl radicals optionally substituted by 1-3 amino, alkylamino, dialkylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; where each R20 is independently (1) an alkyl, alkenyl or alkynyl radical optionally substituted by 1-3 radicals of -CO2R23 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, N- (alkoxycarbonyl) -N- (alkyl) amino, aminocarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo or aralkoxy, aralkylthio, aralkylsulfonyl, cycloalkyl, heterocyclyl, aryl or heteroaryl optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkylaminolamino, alkylaminolamino, alkylaminolamino, alkylaminolamino, alkylaminolamino, alkylaminolamino, alkylaminolamino, alkylaminolamino, alkylaminolamino, alkylaminolamino, alkylaminolamino, alkylaminolamino, alkylaminolamino , alkoxycarbonyl, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; (2) a heterocyclyl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, alkoxycarbonyl, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl; or (3) aryl or heteroaryl radicals optionally substituted by 1-3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, alkoxycarbonyl, hydroxy, alkoxy, alkylthio, cyano, halo, azido, alkyl or haloalkyl radicals; each R22 is independently a hydrogen radical or R20; each R22 is independently (1) a hydrogen radical; (2) an alkyl radical optionally substituted by a heterocyclyl, aryl or heteroaryl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo , alkyl or haloalkyl; or (3) heterocyclyl, aryl or heteroaryl radicals optionally substituted by 1-3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl radicals; and each R23 is independently hydrogen or alkyl, or aryl, heteroaryl, aralkyl or heteroaralkyl optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo , alkyl or haloalkyl; and R11 and R12 are independently an aryl or heteroaryl radical optionally substituted by 1-3 radicals of (1) R30; (2) halo or cyano radicals; (3) radicals -C (O) -R30, -C (O) -OR29, -C (O) -NR31R32 or -C (NR31) NR31R32; (4) radicals -OR29, -O-C (O) -R29, -O-C (O) -NR31R32 or -O-C (O) -NR33S (O) 2-R30; (5) radicals -SR29, -S (O) -R30, -S (O) 2-R30, -S (O) 2-NR31R32, -S (O) 2-NR33-C (O) -R30, - S (O) 2-NR33-C (O) -OR30 or -S (O) 2-NR33-C (O) -NR31R32; or (6) -NR31R32, -NR33-C (O) -R29, -NR33-C (O) -OR30, -NR33-C (O) -NR31R32, -NR33-C (NR31) -NR31R32, -NR33- S (O) 2-R30 or -NR33S (O) 2-NR31R32; provided that (1) R11 is not a 4-pyridyl, 4-pyrimidinyl, 4-quinolyl or 6-isoquinolinyl radical optionally substituted by 1-2 substituents; and (2) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals substituted in each of R11 and R12 is 0-1; where each R30 is independently (1) an alkyl, alkenyl or alkynyl radical optionally substituted by 1-3 radicals of -NR31R31, -CO2R23, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo or aralkoxy, aralkylthio, aralkylsulfonyl, heterocyclyl , aryl or heteroaryl optionally substituted by 1-3 radicals of the amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl radicals; (2) a heterocyclyl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, halo, alkyl or haloalkyl; or (3) aryl or heteroaryl radicals optionally substituted by 1-3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; each R29 is independently a hydrogen radical or R30; each R31 and R32 is independently (1) hydrogen radicals; (2) an alkyl radical optionally substituted by a cycloalkyl, aryl, heterocyclyl or heteroaryl radical optionally substituted by 1-3 radicals of the amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl; or (3) an aryl, heteroaryl, heterocyclyl or cycloalkyl radical optionally substituted by 1-3 radicals of the amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; and where each R33 is independently (1) a hydrogen radical; or (2) an alkyl radical optionally substituted by a radical of the heterocyclyl, aryl or heteroaryl radicals optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl

ARP970105716A 1996-12-05 1997-12-04 PIRIMIDINONE AND PIRIDONA SUBSTITUTED COMPOUNDS AND METHODS FOR USE AR038955A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US3212896P 1996-12-05 1996-12-05
US5095097P 1997-06-13 1997-06-13

Publications (1)

Publication Number Publication Date
AR038955A1 true AR038955A1 (en) 2005-02-02

Family

ID=26708010

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP970105716A AR038955A1 (en) 1996-12-05 1997-12-04 PIRIMIDINONE AND PIRIDONA SUBSTITUTED COMPOUNDS AND METHODS FOR USE

Country Status (4)

Country Link
JP (1) JP2002514195A (en)
AR (1) AR038955A1 (en)
TW (1) TW520362B (en)
WO (1) WO1998024782A2 (en)

Families Citing this family (89)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6613942B1 (en) 1997-07-01 2003-09-02 Novo Nordisk A/S Glucagon antagonists/inverse agonists
KR100581199B1 (en) * 1998-06-19 2006-05-17 카이론 코포레이션 Inhibitors of Glycogen Synthase Kinase 3
US7045519B2 (en) 1998-06-19 2006-05-16 Chiron Corporation Inhibitors of glycogen synthase kinase 3
TWI241298B (en) * 1998-09-25 2005-10-11 Mitsubishi Chem Corp Pyrimidone derivatives
JP2002528506A (en) 1998-11-04 2002-09-03 スミスクライン・ビーチャム・コーポレイション Pyridin-4-yl or pyrimidin-4-yl substituted pyrazine
US6350744B1 (en) 1998-11-20 2002-02-26 Merck & Co., Inc. Compounds having cytokine inhibitory activity
JP2002534385A (en) 1999-01-08 2002-10-15 スミスクライン・ビーチャム・コーポレイション New compound
US6503949B1 (en) 1999-05-17 2003-01-07 Noro Nordisk A/S Glucagon antagonists/inverse agonists
US7122666B2 (en) 1999-07-21 2006-10-17 Sankyo Company, Limited Heteroaryl-substituted pyrrole derivatives, their preparation and their therapeutic uses
GB9927844D0 (en) 1999-11-26 2000-01-26 Glaxo Group Ltd Chemical compounds
EP1246823A1 (en) * 1999-12-28 2002-10-09 Pharmacopeia, Inc. Pyrimidine and triazine kinase inhibitors
US6906067B2 (en) 1999-12-28 2005-06-14 Bristol-Myers Squibb Company N-heterocyclic inhibitors of TNF-α expression
GB0003224D0 (en) * 2000-02-11 2000-04-05 Glaxo Group Ltd Chemical compounds
WO2001070727A1 (en) * 2000-03-23 2001-09-27 Sanofi-Synthelabo 2-(arylalkylamino)pyrimidone derivatives and 2-(heteroarylalkylamino)pyrimidone derivatives
EP1136493A1 (en) * 2000-03-23 2001-09-26 Sanofi-Synthelabo 2-(Thienopyridinyl)pyrimidone, 2-(furopyridinyl)pyrimidone 2-(isoquinolinyl)pyrimidone, 2-(pyridoindolyl)pyrimidone and 2-(benzofuropyridinyl)pyrimidone derivatives
EP1136489A1 (en) * 2000-03-23 2001-09-26 Sanofi-Synthelabo 2-[Piperidin-1-yl]pyrimidone derivatives
EP1136483A1 (en) * 2000-03-23 2001-09-26 Sanofi-Synthelabo 2-[Piperazinyl]pyrimidone derivatives
EP1136099A1 (en) * 2000-03-23 2001-09-26 Sanofi-Synthelabo 2-(Indolylalkylamino)pyrimidone derivatives as GSK3beta inhibitors
EP1136482A1 (en) * 2000-03-23 2001-09-26 Sanofi-Synthelabo 2-Amino-3-(alkyl)-pyrimidone derivatives as GSK3beta inhibitors
EP1136486A1 (en) * 2000-03-23 2001-09-26 Sanofi-Synthelabo 2-[Indanylamino]pyrimidone and 2-[tetrahydronaphthalenylamino]pyrimidone derivatives
EP1136491A1 (en) * 2000-03-23 2001-09-26 Sanofi-Synthelabo 2-[(Heteroaryl)alkylamino]pyrimidone derivatives
EP1136484A1 (en) * 2000-03-23 2001-09-26 Sanofi-Synthelabo 2-(Arylalkylamino)pyrimidone derivatives
EP1136485A1 (en) * 2000-03-23 2001-09-26 Sanofi-Synthelabo Aminophenyl pyrimidone derivatives
AU2001262150A1 (en) * 2000-03-23 2001-10-03 Mitsubishi Pharma Corporation 2-(nitrogen-heterocyclic)pyrimidone derivatives
NZ521633A (en) 2000-04-26 2005-01-28 Eisai Co Ltd Use of an adenosine A2 or A2b recpetor antagonist for promoting bowel movement
BR0111158A (en) * 2000-05-12 2004-04-06 Genzyme Corp Compound and physiological salts thereof, method for treating a median condition by tnf-a in a patient
US6562807B2 (en) 2000-06-23 2003-05-13 Novo Nordisk A/S Glucagon antagonists/inverse agonists
GB0021494D0 (en) * 2000-09-01 2000-10-18 Glaxo Group Ltd Chemical comkpounds
WO2002020495A2 (en) * 2000-09-06 2002-03-14 Chiron Corporation Inhibitors of glycogen synthase kinase 3
US6670362B2 (en) 2000-09-20 2003-12-30 Pfizer Inc. Pyridazine endothelin antagonists
US6706744B2 (en) 2000-11-17 2004-03-16 Novo Nordisk A/S Glucagon antagonists/inverse agonists
JP2004513935A (en) 2000-11-17 2004-05-13 ノボ　ノルディスク　アクティーゼルスカブ Glucagon antagonist / inverse agonist
US6821960B2 (en) 2000-11-17 2004-11-23 Noyo Nordisk Pharmaceuticals, Inc. Glucagon antagonists/inverse agonists
GB0112802D0 (en) 2001-05-25 2001-07-18 Glaxo Group Ltd Pyrimidine derivatives
GB0112810D0 (en) * 2001-05-25 2001-07-18 Glaxo Group Ltd Pyrimidine derivatives
GB0119477D0 (en) * 2001-08-09 2001-10-03 Glaxo Group Ltd Pyrimidine derivatives
CN1810802B (en) * 2001-09-21 2011-04-27 三菱制药株式会社 3-substituted-4-pyrimidone derivatives
MXPA04002661A (en) 2001-09-21 2004-11-22 Sanofi Aventis 3-substituted-4-pyrimidone derivatives.
CA2460121C (en) * 2001-09-21 2010-11-02 Mitsubishi Pharma Corporation 3-substituted-4-pyrimidone derivatives
TWI330183B (en) * 2001-10-22 2010-09-11 Eisai R&D Man Co Ltd
TWI301834B (en) * 2001-10-22 2008-10-11 Eisai R&D Man Co Ltd Pyrimidone compound and pharmaceutical composition including the same
US6921762B2 (en) 2001-11-16 2005-07-26 Amgen Inc. Substituted indolizine-like compounds and methods of use
US6762318B2 (en) 2001-12-03 2004-07-13 Novo Nordisk A/S Glucagon antagonists
US6881746B2 (en) 2001-12-03 2005-04-19 Novo Nordick A/S Glucagon antagonists/inverse agonists
AR038368A1 (en) 2002-02-01 2005-01-12 Novartis Ag N-PYRIMIDIN-2-IL-AMINAS SUBSTITUTED COMPOUNDS AS IGE INHIBITORS, A PHARMACEUTICAL COMPOSITION AND THE USE OF SUCH COMPOUNDS FOR THE PREPARATION OF A MEDICINAL PRODUCT
WO2003072548A1 (en) 2002-02-22 2003-09-04 Pharmacia & Upjohn Company Pyridyl sulfone derivatives as 5-ht receptor antagonists
EA007737B1 (en) * 2002-02-28 2006-12-29 Санофи-Авентис HETEROARYL SUBSTITUTED 2-PYRIMIDINYL-6,7,8,9-TETRAHYDROPYRIMIDO[1,2a] PYRIMIDIN-4-ONE DERIVATIVES
WO2003084937A2 (en) * 2002-04-10 2003-10-16 Orchid Chemicals & Pharmaceuticals Limited Pyrimidinedione derivatives useful for the treatment of inflammation and immunological diseases
JP4606161B2 (en) * 2002-05-21 2011-01-05 アムジエン・インコーポレーテツド Substituted heterocyclic compounds and methods of use
ES2278170T3 (en) 2002-07-09 2007-08-01 BOEHRINGER INGELHEIM PHARMA GMBH & CO.KG PHARMACEUTICAL COMPOSITIONS OF ANTICOLINERGIC AND INHIBITORS OF QUINASE P38 IN THE TREATMENT OF RESPIRATORY DISEASES.
ES2263058T3 (en) 2002-08-19 2006-12-01 Glaxo Group Limited PIRIMIDINE DERIVATIVES AS SELECTIVE COX-2 INHIBITORS.
GB0221443D0 (en) 2002-09-16 2002-10-23 Glaxo Group Ltd Pyridine derivates
CA2510170C (en) 2002-12-16 2011-05-24 Mitsubishi Pharma Corporation 3-substituted-4-pyrimidone derivatives
US20060058326A1 (en) * 2003-02-06 2006-03-16 Basf Aktiengesllschaft Pyrimidines, methods for the production thereof, and use thereof
TWI357408B (en) 2003-03-26 2012-02-01 Mitsubishi Tanabe Pharma Corp 3-substituted-4-pyrimidone derivatives
CA2531619A1 (en) * 2003-07-16 2005-01-27 Neurogen Corporation Biaryl piperazinyl-pyridine analogues
EP1653970A4 (en) * 2003-08-13 2008-10-15 Novartis Vaccines & Diagnostic GSK-3 INHIBITORS AND USES
WO2005019202A1 (en) * 2003-08-20 2005-03-03 Amgen Inc. Substituted pyrimdinone derivatives and methods of use
GB0323137D0 (en) 2003-10-03 2003-11-05 Chang Lisa C W 2,4,6- Trisubstituted pyrimidines and their different uses
CA2562244A1 (en) 2004-04-07 2005-10-27 Takeda Pharmaceutical Company Limited Cyclic compounds
US20060035893A1 (en) 2004-08-07 2006-02-16 Boehringer Ingelheim International Gmbh Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders
MY145822A (en) 2004-08-13 2012-04-30 Neurogen Corp Substituted biaryl piperazinyl-pyridine analogues
PE20060777A1 (en) 2004-12-24 2006-10-06 Boehringer Ingelheim Int INDOLINONE DERIVATIVES FOR THE TREATMENT OR PREVENTION OF FIBROTIC DISEASES
US8193206B2 (en) 2005-06-14 2012-06-05 Taigen Biotechnology Co., Ltd. Pyrimidine compounds
NZ564222A (en) * 2005-06-14 2011-10-28 Taigen Biotechnology Co Ltd Pyrimidine compounds
ES2270715B1 (en) 2005-07-29 2008-04-01 Laboratorios Almirall S.A. NEW DERIVATIVES OF PIRAZINA.
WO2007022964A2 (en) 2005-08-24 2007-03-01 Abbott Gmbh & Co. Kg Hetaryl-substituted guanidine compounds and use thereof as binding partners for 5-ht5-receptors
ES2274712B1 (en) 2005-10-06 2008-03-01 Laboratorios Almirall S.A. NEW IMIDAZOPIRIDINE DERIVATIVES.
JP2010505957A (en) 2006-10-10 2010-02-25 アムゲン インコーポレイティッド N-arylpyrazole compounds used for diabetes
EP1992344A1 (en) 2007-05-18 2008-11-19 Institut Curie P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation
BRPI0813629A2 (en) * 2007-07-26 2018-07-10 Novartis Ag pyrimidine derivatives useful in treating inflammatory or allergic conditions
ES2545731T3 (en) 2008-04-21 2015-09-15 Taigen Biotechnology Co., Ltd. Heterocyclic compounds
US9023834B2 (en) 2008-11-13 2015-05-05 Taigen Biotechnology Co., Ltd. Lyophilization formulation
LT2629776T (en) 2010-10-18 2017-11-10 Cerenis Therapeutics Holding Sa Compounds, compositions and methods useful for cholesterol mobilisation
GB201106829D0 (en) 2011-04-21 2011-06-01 Proximagen Ltd Heterocyclic compounds
SG191040A1 (en) 2010-12-23 2013-08-30 Pfizer Glucagon receptor modulators
ES2597972T3 (en) 2011-02-08 2017-01-24 Pfizer Inc Glucagon receptor modulator
BR112014000288A2 (en) 2011-07-22 2017-01-10 Pfizer quinolinyl glucagon receptor modulators
CN103917529B (en) 2011-11-11 2016-08-17 辉瑞大药厂 2-thiopyrimidinones
CA2929394C (en) 2013-12-19 2021-11-16 Sunshine Lake Pharma Co., Ltd. Nitrogenous heterocyclic derivatives and their application in drugs
TWI651310B (en) * 2014-02-20 2019-02-21 日商日本煙草產業股份有限公司 Triterpenoids and their medical use
MA42035A (en) 2015-05-05 2018-03-14 Pfizer 2-THIOPYRIMIDINONES
AR105711A1 (en) 2015-08-17 2017-11-01 Japan Tobacco Inc HYDROXITRIAZINE COMPOUNDS AND THEIR PHARMACEUTICAL USES
JP6817952B2 (en) * 2015-10-29 2021-01-20 あすか製薬株式会社 Pyrimidine derivative
TW202510883A (en) * 2015-11-04 2025-03-16 德商默克專利有限公司 Methods for treating cancer using pyrimidine and pyridine compounds with btk inhibitory activity
EP4295910A3 (en) 2015-11-17 2024-03-20 Merck Patent GmbH Methods for treating multiple sclerosis using pyrimidine and pyridine compounds with btk inhibitory activity
TW201811766A (en) 2016-08-29 2018-04-01 瑞士商諾華公司 N-(pyridin-2-yl)pyridine-sulfonamide derivatives and their use in the treatment of disease
AU2020382827A1 (en) * 2019-11-12 2022-05-26 Genzyme Corporation 6-membered heteroarylaminosulfonamides for treating diseases and conditions mediated by deficient CFTR activity
CN120379982A (en) 2022-12-02 2025-07-25 纽摩拉治疗公司 Methods of treating neurological disorders

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1271116B (en) * 1965-05-04 1968-06-27 Bayer Ag Process for the preparation of 4-hydroxypyrimidines
BE759176A (en) * 1969-11-20 1971-05-19 Sandoz Sa PYRIMIDINE DERIVATIVES, THEIR PREPARATION AND MEDICINAL PRODUCTS CONTAINING THESE DERIVES
US4438117A (en) * 1980-09-03 1984-03-20 E. I. Du Pont De Nemours And Company 2-Substituted thio-4,5-diarylpyrimidines
DE3319843A1 (en) * 1983-06-01 1984-12-06 Ali-Akbar Dipl.-Chem. Dr. 4300 Mülheim Pourzal Process for the preparation of pyrimidines from nitrile and alkynes
US4500533A (en) * 1983-06-22 1985-02-19 Eli Lilly And Company 2,4,5-Triaryl pyrimidines and a method of treating pain, fever, thrombosis, inflammation and arthritis
US5077142A (en) * 1989-04-20 1991-12-31 Ricoh Company, Ltd. Electroluminescent devices
US5620999A (en) * 1994-07-28 1997-04-15 Weier; Richard M. Benzenesulfonamide subtituted imidazolyl compounds for the treatment of inflammation
ATE433446T1 (en) * 1995-10-06 2009-06-15 Merck & Co Inc SUBSTITUTED IMIDAZOLES WITH ANTI-CANCER AND CYTOKIN-INHIBITING EFFECTS
WO1997016442A1 (en) * 1995-10-31 1997-05-09 Merck & Co., Inc. Substituted pyridyl pyrroles, compositions containing such compounds and methods of use
EP0888335A4 (en) * 1996-03-13 2002-01-02 Smithkline Beecham Corp Novel pyrimidine compounds useful in treating cytokine mediated diseases

Also Published As

Publication number Publication date
WO1998024782A3 (en) 1998-08-27
JP2002514195A (en) 2002-05-14
WO1998024782A2 (en) 1998-06-11
TW520362B (en) 2003-02-11

Similar Documents

Publication Publication Date Title
AR038955A1 (en) PIRIMIDINONE AND PIRIDONA SUBSTITUTED COMPOUNDS AND METHODS FOR USE
RU2395500C2 (en) 2,4-pyrimidine diamines used in treating neoplastic diseases, inflammatory and immune disorders
AR037329A1 (en) PIRAZOLO PIRIMIDINONA COMPOUNDS, PROCEDURES FOR THE PREPARATION OF THE SAME, PHARMACEUTICAL COMPOSITIONS OF THE SAME AND USES OF THE SAME IN THE PREPARATION OF MEDICINES
RU2342367C2 (en) Non-nucleozide inhibitors i of reverse transcriptase, intended for treatment of hiv-mediated diseases
CA2307552A1 (en) Substituted pyridine compounds as anti-inflammatory agents
CA2472372A1 (en) Hydroxynaphthyridinone carboxamides useful as hiv integrase inhibitors
MX9206258A (en) DERIVATIVES OF 1,3-DIHYDRO-2H-IMIDAZO (4,5-B) QUINOLIN-2-ONA.
MXPA01006474A (en) Colchinol derivatives as vascular damaging agents.
BG93979A (en) N-(4-PIPERIDINYL)(DIHYDROBENZOFURAN OR DIHYDRO-2H-BENZOPYRAN)CARBOXAMIDE DERIVATIVES, PHARMACEUTICAL COMPOSITION CONTAINING THEM, METHOD OF PREPARING THE DERIVATIVES AND THEIR APPLICATION
AR029383A1 (en) SMALL MOLECULES, THE INTERMEDIARIES FOR THEIR SYNTHESIS, THE PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM AND THEIR USE TO PREPARE A MEDICINAL PRODUCT INTENDED FOR TREATMENT OR PROPHYLAXIS OF INFLAMMATORY DISEASES OR MEDIATIONED BY IMMUNE CELLS
AR008864A1 (en) SUBSTITUTE DIAMINO-1,3,5-TRIAZINE DERIVATIVES, PROCEDURES FOR ITS PREPARATION, PHARMACEUTICAL COMPOSITIONS, PROCEDURE FOR THE PREPARATION OF SUCH COMPOSITIONS, THE USE OF SUCH COMPOUNDS FOR THE PREPARATION OF A USEFUL MEDICINAL PRODUCT FOR HIV INFECTIONS, AND INTERMEDIARY PREPA
HN1998000074A (en) DERIVATIVES FROM MACROLIDES C-4 SUBSTITUTED
EA200501098A1 (en) ANTIBACTERIAL AGENTS
CY1111693T1 (en) ANTIQUE FACTORS
FI20115753L (en) Pharmaceutical compositions for the treatment of diseases caused by IL-6 production
AR046297A1 (en) DPP INHIBITORS - IV METHODS TO PREPARE THEM AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM AS ACTIVE AGENTS
ATE197672T1 (en) MEDICINAL PRODUCTS FOR NERVOUS DISEASES
EA200000990A1 (en) HIV INHIBITIVE PYRIMIDINE DERIVATIVES
AR033525A1 (en) REPLACED ARILMETILAMINS, PHARMACEUTICAL COMPOSITIONS, USE OF THE SAME FOR THE MANUFACTURE OF A MEDICINAL PRODUCT
ES2013067A6 (en) Piperazine derivative or its salt, process for producing the same and pharmaceutical composition comprising the same as active ingredient
AR019496A1 (en) AZALIDAS OF 13 MEMBERS, PHARMACEUTICAL COMPOSITIONS, USE IN THE PREPARATION OF MEDICINES AND PREPARATION OF THE SAME
DK0587088T3 (en) Substituted cyclohexane derivatives, process for their preparation and use of the compounds for the treatment of diseases
ES478605A1 (en) Flavans, process for their preparation and pharmaceutical compositions containing them.
BG101896A (en) Pyrrolidinylhydroxamic acid compounds and method for their preparation
NO930143L (en) PIPERIDE COMPOUNDS, THEIR PREPARATION AND USE

Legal Events

Date Code Title Description
FA Abandonment or withdrawal