DK1497019T3 - Pyrrolo-triazinanilinsammensætninger nyttig som kinasehæmmere - Google Patents

Pyrrolo-triazinanilinsammensætninger nyttig som kinasehæmmere Download PDF

Info

Publication number
DK1497019T3
DK1497019T3 DK03724157.7T DK03724157T DK1497019T3 DK 1497019 T3 DK1497019 T3 DK 1497019T3 DK 03724157 T DK03724157 T DK 03724157T DK 1497019 T3 DK1497019 T3 DK 1497019T3
Authority
DK
Denmark
Prior art keywords
alkyl
substituted
optionally substituted
phenyl
halogen
Prior art date
Application number
DK03724157.7T
Other languages
English (en)
Inventor
Stephen T Wrobleski
Alaric Dyckman
John Hynes
Katerina Leftheris
Chunjian Liu
Original Assignee
Bristol Myers Squibb Co
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 Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Application granted granted Critical
Publication of DK1497019T3 publication Critical patent/DK1497019T3/da

Links

Classifications

    • 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
    • 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
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • A61P17/04—Antipruritics
    • 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
    • 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
    • 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • 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
    • 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
    • A61P31/04—Antibacterial agents
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • 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
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • 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
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • 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
    • 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
    • C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
    • C07D253/08—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 condensed with carbocyclic rings or ring systems
    • C07D253/10—Condensed 1,2,4-triazines; Hydrogenated condensed 1,2,4-triazines

Landscapes

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

Claims (23)

  1. PYRROLO-TRIAZINANILINSAMMENSÆTNINGER NYTTIG SOM KINASEHÆMMERE PATENTKRAV
    1. Forbindelse med formlen (1 *):
    $*) eller enantiomerer, diastereomerer, salte og solvater deraf, hvor X er udvalgt fra -O-, -0C(=0)-, -S-, -S(=0)-, -S02-, -C(=0)-, -C02-, -NR*-, -NRsC(=0)-, -NR8C(=0)NR9-, -NRsC02-, -NR8S02-, -NRsS02NR9-, -S02NR8-, -C=(0)NR8-, halogen, nitro og cyano, eller X ikke er til stede; Y er -C(=0)NH-; B er eventuelt substitueret cycloalkyl, heterocyclo eller heteroaryl; eller aryl substitueret med én Ru og nul til to Ri2; eller er udvalgt fra -C(=0)Ri3, -C02R13 og -C(=0)NR13R13a; Ri og R5 er uafhængigt udvalgt fra hydrogen, alkyl, substitueret alkyl, -OR14, -SR14, 0C(=0)Ri4, -C02Ri4, -C(=0)NRi4Ri4a, -NRi4Ri4a, -S(=0)Ri4, -S02Ri4, -S02NR|4R|4a, -NRi4S02NRi4aRi4i„ NRi4aS02Ri4, -NRi4C(=0)Ri4a, -NRi4C02Ri4a, -NRi4C(=0)NR14aR14b, halogen, nitro og cyano; R2 er hydrogen eller Ci_4alkyl; R3 er hydrogen, methyl, perfluormethyl, methoxy, halogen, cyano, NH2 eller NH(CH3); R4 er udvalgt fra: (a) hydrogen, forudsat at R4 ikke er hydrogen, hvis X er -S(=0)-, -S02-, -NR8C02-, eller -NR8S02- (b) alkyl, alkenyl, og alkynyl eventuelt substitueret med keto og/eller én til fire R17; (c) aryl og heteroaryl eventuelt substitueret med én til tre R[6 og (d) heterocyclo og cycloalkyl eventuelt substitueret med keto og/eller én til tre R^; eller (e) R4 ikke er til stede, hvis X er halogen, nitro eller cyano; R6 er bundet til et hvilket som helst tilgængeligt carbonatom af phenylring A og er ved hver forekomst uafhængigt udvalgt fra alkyl, halogen, trifluormethoxy, trifluormethyl, hydroxy, alkoxy, alkanoyl, alkanoyloxy, thiol, alkylthio, ureido, nitro, cyano, carboxy, carboxyalkyl, carbamyl, alkoxycarbonyl, alkylthiono, arylthiono, arylsulfonylamin, alkylsulfonylamin, sulfonsyre, allcysulfonyl, sulfonamido, phenyl, benzyl, aryloxy, og benzyloxy, hvor hver R6 gruppe til gengæld kan være yderligere substitueret af én til to R18; Rs og R9 er uafhængigt udvalgt fra hydrogen, alkyl, substitueret alkyl, aryl, cycloalkyl, heterocyclo og heteroaryl; Ru er udvalgt fra eventuelt substitueret cycloalkyl, heterocyclo og heteroaryl; R12 er udvalgt fra alkyl, R17, og C1.4alkyl substitueret med keto (=0) og/eller én til tre R17; Rb og Ri3a er udvalgt fra hydrogen, alkyl og substitueret alkyl; R14, R14a og R14b er uafhængigt udvalgt fra hydrogen, alkyl, substitueret alkyl, aryl, cycloalkyl, heterocyclo og heteroaryl, undtagen når Ri4 er bundet til en sulfonylgruppe som i -S(=0)R14, -S02Ri4 og -NRi4a-S02Ri4, så er Ri4 ikke hydrogen; R16 er udvalgt fra alkyl, Ri7, og Ci_4alkyl substitueret med keto (=0) og/eller én til tre R17; Rn er udvalgt fra halogen, haloalkyl, haloalkoxy, nitro, cyano, -SR23, -OR23, -NR23R24, -NR23S02R25, -S02R25, -S02NR23R24, -C02R23, -C(=0)R23, -C(=0)NR23R24, -0C(=0)R23-0C(=0)NR23R24, -NR23C(=0)R24, -NR23C02R24; aryl eller heteroaryl eventuelt substitueret med én til tre R26; eller cycloalkyl eller heterocyclo eventuelt substitueret med keto (=0) og/eller én til tre R26; Ris og R26 er uafhængigt udvalgt fra C^alkyl, C2_6alkenyl, halogen, haloalkyl, haloalkoxy, cyano, nitro, amino, Ci_4alkylamino, aminoCi_4alkyl, hydroxy, hydroxyCi_4alkyl, alkoxy, Ci-4alkylthio, phenyl, benzyl, phenyloxy og benzyloxy; R23 og R24 er hver uafhængigt udvalgt fra hydrogen, alkyl, alkenyl, substitueret alkyl, substitueret alkenyl, aryl, cycloalkyl, heteroaryl, og heterocyclo; R25 er udvalgt fra alkyl, substitueret alkyl, aryl, heteroaryl, cycloalkyl og heterocyclo; og m er 0, 1, 2 eller 3; hvor begrebet "substitueret alkyl" betyder en alkylgruppe substitueret af én til fire substituenter udvalgt fra halogen, hydroxy, alkoxy, keto (=0), alkanoyl, aryloxy, alkanoyloxy, NRaRb, alkanoylamino, aroylamino, aralkanoylamino, alkanoylamino, arylamino, aralkanoylamino, thiol, alkylthio, arylthio, aralkylthio, alkylthiono, arylthiono, aralkylthiono, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, -S02NRaRb, nitro, cyano, -C02H, -CONRaRb, alkoxycarbonyl, aryl, guanidino og heteroaryler eller heterocyklusser, hvor Ra og Rb er udvalgt fra hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyklus og heterocyklusalkyl, og hvor substituenten på alkylen eventuelt til gengæld kan være yderligere substitueret, i hvilket tilfælde den vil være substitueret med én eller flere af C|_4alkyl, C2_4alkcnyl, halogen, haloalkyl, haloalkoxy, cyano, nitro, amino, C[.4alkylamino, aminoC[.4alkyl, hydroxy, hydroxyC|_4alkyl, alkoxy, alkylthio, phenyl, benzyl, phenyloxy og/eller benzyloxy; hvor begrebet "substitueret alkenyl" betyder en alkenylgruppe substitueret af én eller to substituenter udvalgt fra de, der er nævnt ovenfor til substituerede alkylgrupper; og hvor begrebet "eventuelt substitueret cycloalkyl" betyder cycloalkyl, der kan have 0 til 3 substituenter udvalgt fra Rc-grupper, og/eller fra keto (hvor det er passende), der til gengæld kan være substitueret med én til tre R(1-grupper, hvor Rc ved hver forekomst er udvalgt fra alkyl, substitueret alkyl, halogen, trifluormethoxy, trifluormethyl, -SR, -OR, -NRR', -NRS02R', -S02R, -S02NRR', -C02R', -C(=0)R', -C(=0)NRR', -0C(=0)R', -0C(=0)NRR', -NRC(=0)R', -NRC02R', phenyl, C3-7cycloalkyl, og fem- til seks-leddet heterocyclo eller heteroaryl, hvor hver R og R' er udvalgt fra hydrogen, alkyl, substitueret alkyl, alkenyl, substitueret alkenyl, phenyl, C3_7cycloalkyl, og fem- til seks-leddet heterocyclo eller heteroaryl, bortset fra i tilfælde af en sulfonylgruppe, så vil R ikke være hydrogen, og hvor Rd er udvalgt fra C^alkyl, C2_6alkenyl, halogen, haloalkyl, haloalkoxy, cyano, nitro, amino, C|_4alkylamino, aminoC|_4alkyl, hydroxy, hydroxyC|_4alkyl, alkoxy, alkylthio, phenyl, benzyl, phenylethyl, phenyloxy og benzyloxy.
  2. 2. Forbindelse ifølge krav 1, eller et farmaceutisk acceptabelt salt, eller et hydrat deraf, hvor: B er en C3.7cycloalkyl eventuelt substitueret med én til to R7, en fem-leddet heteroaryl eventuelt substitueret med én til to R7, en fem- eller seks-leddet heterocyclo eventuelt substitueret med én til to R7, aryl substitueret med én Ru og nul til to R12; eller er udvalgt fra -C(=0)Ri3, -C02Rb og -C(=0)NRi3Ri3a; R7 er bundet til et hvilket som helst tilgængeligt carbon- eller nitrogenatom af ring B og ved hver forekomst er uafhængigt udvalgt fra keto (=0), alkyl, substitueret alkyl, halogen, haloalkoxy, ureido, cyano, -SR20,-OR20, -NR2OR2i, -NR2oS02R2i, -S02Ri9, S02NR2oR2i, -C02R2o, -C(=0)R2o, -C(=0)NR2oR2i; -OC(=O)R20, OC(=O)NR20R2i; -NR20C(=O)R2i, -NR20CO2R2i, aryl, cycloalkyl, heterocyklus og heteroaryl; og/eller når B er cycloalkyl, kan to R7 grupper samles for at danne en eventuelt substitueret carbon-carbon-bro af tre til fire carbonatomer, eller to R7 grupper kan samles for at danne en kondenseret carbocyklisk, heterocyklisk eller heteroarylring, hvilken kondenseret ring til gengæld eventuelt er substitueret med én til tre R22; R20 og R2i er udvalgt fra hydrogen, alkyl, alkenyl, substitueret alkyl, substitueret alkenyl, phenyl, C3.7cycloalkyl, og fem- til seks-leddet heterocyclo eller heteroaryl; og Ri2 og R22 er uafhængigt udvalgt fra Ci.6alkyl, C2_6alkenyl, halogen, haloalkyl, haloalkoxy, cyano, nitro, amino, Q^alkylamino, aminoC^akyl, hydroxy, hydroxyC^alkyl, alkoxy, alkylthio, phenyl, benzyl, phenyloxy og benzyloxy.
  3. 3. Forbindelse ifølge krav 1, med formlen (la),
    da) eller et farmaceutisk acceptabelt salt eller solvat deraf, hvor: R3 er methyl eller -CF3 X er -C(=())-, -NRgC^O)-, eller -C(=())NRS-, hvor R8 er hydrogen eller Q^alkyl; Yer-C(=0)NH-; R4 er hydrogen, C2-6alkyl, C4_4alkyl eventuelt substitueret med én til tre Ri7, cycloalkyl eller heterocyklus eventuelt substitueret med keto (=0) og/eller én til tre R16; eller aryl eller heteroaryl eventuelt substitueret med én til tre R^; R6a og R6h er uafhængigt udvalgt fra hydrogen, C1.6alkyl, substitueret C^alkyl, halogen, trifluormethoxy, trifluormethyl, -OR27, -C(=0)alkyl, -0C(=0)alkyl, -NR27R28, -SR27, -N02, -CN, -C02R27, -CONH2, -S03H, -S(=0)alkyl, -S(=0)aryl, -NHS02-aryl-R27, -S02NHR27, -CONHR27 og -NHC(=0)NHR27; Ri6 er udvalgt fra Ci^alkyl, Ri7, og C4_4alkyl substitueret med keto (=0) og/eller én til to R17; R17 er udvalgt fra halogen, hydroxy, C4_4alkoxy, trifluormethyl, trifluormethoxy, cyano, nitro, phenyl, benzyl, phenyloxy, benzyloxy, NH2, NH(Ci_4alkyl), N(C4_4alkyl)2, C3.7cycloalkyl, eller fem- eller seks-leddet heteroaryl eller heterocyklus; og R27 og R28 er udvalgt fra hydrogen, Ci.4alkyl, phenyl, C3.7cycloalkyl, og fem- til seks-leddet heterocyclo eller heteroaryl.
  4. 4. Forbindelse ifølge krav 1, eller et farmaceutisk acceptabelt salt eller solvat deraf, hvor: ring B er phenyl substitueret med heterocyklus og nul til én Ri2, eller er en cycloalkyl, heteroaryl eller heterocvclorin? udval vt fra:
    hvor E, G, J og K er udvalgt fra O, S, NH og CH2, forudsat at, når q er 0, så er J og K ikke samtidigt udvalgt fra O og S; og M er N eller CH; hvor hvert hydrogenatom af E, G, J, K og M eventuelt kan udskiftes med en R7-gruppe; R7 og Ri2 er uafhængigt udvalgt fra Ci_6alkyl, substitueret C^alkyl, halogen, trifluormethoxy, trifluormethyl, hydroxy, -Cr4alkoxy, -C(=0)alkyl, -0C(=0)alkyl, NH2, NH/C^alkyl), N(Ci-4alkyl)2, -CN, -C02alkyl, -CONH2, -CONH(CH3), -CON(CH3)2, phenyl, benzyl, C3_7cycloalkyl og fem- til seks-leddet heterocyclo eller heteroaryl; n er 0, 1 eller 2; °gP °S ? er udvalgt fra 0, 1, 2, 3 og 4, forudsat at/? og q taget sammen ikke er større end 4.
  5. 5. Forbindelse ifølge krav 4, eller et farmaceutisk acceptabelt salt eller solvat deraf, hvori: X er -C(=0)-, -C(=0)NH- eller -C(=0)N(Cr4alkyl)-; Y er -C(=0)NH-; R4 er hydrogen, C2.6alkyl, C4_4alkyl eventuelt substitueret med én til tre R|7, aryl eller heteroaryl eventuelt substitueret med én til tre R16, eller cycloalkyl eller heterocyklus eventuelt substitueret med keto (=0), og/eller én til tre R16; R16 er udvalgt fra (4_4alkyl, R17 og (4_4alkyl substitueret med keto og/eller én til to R17; og R[7 er udvalgt fra halogen, hydroxy, C4_4alkoxy, trifluormethyl, trifluormethoxy, cyano, nitro, phenyl, benzyl, phenyloxy, benzyloxy, NH2, NI I(C|^alkyl), og N(C1.4alkyl)2.
  6. 6. Forbindelse ifølge krav 1 eller et farmaceutisk acceptabelt salt eller solvat deraf, hvori R| og R5 uafhængigt er hydrogen eller CH3.
  7. 7. Forbindelse ifølge krav 1, eller et farmaceutisk acceptabelt salt eller solvat deraf, hvori R2 er hydrogen.
  8. 8. Forbindelse ifølge krav 1, eller et farmaceutisk acceptabelt salt eller solvat deraf, hvori R3 er methyl eller -CF3.
  9. 9. Forbindelse ifølge krav 1, eller et farmaceutisk acceptabelt salt eller solvat deraf, hvori X er -C(=0)-eller-C(=0)NH-.
  10. 10. Forbindelse ifølge krav 1, eller et farmaceutisk acceptabelt salt eller solvat deraf, hvori X er -C(=0)NH- og R4 er C2-6alkyl, eventuelt substitueret benzyl, eller en heterocyklisk eller heteroarylring udvalgt fra diazepinyl, morpholinyl, piperidinyl og pyrrolidinyl, hvilken heterocyklus eventuelt er substitueret med én til to af C1.4alkyl, hydroxy, C^alkoxy, phenyl og/eller benzyl.
  11. 11. Forbindelse ifølge krav 1, eller et farmaceutisk acceptabelt salt eller solvat deraf, hvori X er -C(=0)- og R4 er phenyl, pyridyl, pyrimidinyl, eller pyrazinyl eventuelt substitueret med én til to Ci.4alkyl, halogen, hydroxy, Ci_4alkoxy, trifluormethyl, trifluormethoxy, cyano, nitro, phenyl, benzyl, phenyloxy, benzyloxy, NH2, NH(Ci_4alkyl), N(Ci.4alkyl)2 og/eller en Ci_4alkyl substitueret med én til to af halogen, hydroxy, Ci_4alkoxy, trifluormethyl, trifluormethoxy, cyano, nitro, phenyl, benzyl, phenyloxy, benzyloxy, NH2, NH(Ci_4 alkyl) og/eller N(C1.4alkyl)2.
  12. 12. Forbindelse ifølge krav 1, eller et farmaceutisk acceptabelt salt eller sol vat deraf, hvori B er cyclopropyl eller cyclobutyl eventuelt substitueret med én til to R7, phenyl substitueret med en fem- eller seks-leddet heterocyklus og nul til to Ri2, eller B er udvalgt fra én af: °g
    R7 og R12 er uafhængigt udvalgt fra C[.4alkyl, trifluormethyl, trifluormethoxy, halogen, cyano, amino, Ci_4alkylalmino, hydroxy, C'|.4alkoxy, phenyl, benzyl, phenyloxy, og benzyloxy; og n er 0, 1 eller 2.
  13. 13. Forbindelse ifølge krav 1 med formlen (3a),
    (3 a) enantiomerer, diastereomerer, salte og solvater deraf, hvor R3 er methyl eller CF3; X er -C(=0)- eller -C(=0)NH-; R4 er lige eller forgrenet C2-6alkyl; cycloalkyl eventuelt substitueret med keto og/eller op til to R16; heterocyklus eller heteroaryl eventuelt substitueret med keto og/eller op til to Ri6; Ci^alkyl substitueret med op til tre of halogen, trifluormethyl, cyano, hydroxy, alkoxy, haloalkyl, haloalkoxy, nitro, phenyl, phenyloxy eller benzyloxy, hvor phenylgruppen eventuelt er substitueret med én til to R26; eller phenyl eventuelt substitueret med nul til to R16; Rga og R6b er udvalgt fra hydrogen C|_4alkyl, halogen, trifluormethoxy, trifluormethyl, hydroxy, C4. 4alkoxy, nitro og cyano; B er en C3.7cycloalkyl eventuelt substitueret med én til to R7, en fem-leddet heteroaryl eventuelt substitueret med én til to R7, en fem- eller seks-leddet heterocyclo eventuelt substitueret med én til to R7, phenyl substitueret med Ru og nul til to Ri2, -C(=0)Ri3,-C02Ri3 og -C(=0)NR13Ri3a; R7 er bundet til et hvilket som helst tilgængeligt carbon- eller nitrogenatom af ring B og ved hver forekomst er uafhængigt udvalgt fra alkyl, substitueret alkyl, halogen, haloalkoxy, ureido, cyano, trifluormethoxy, trifluormethyl, hydroxy, -Q^alkoxy, -C(=0)alkyl, -0C(=0)alkyl, NH2, NI I(Q.4alkyl), N(C|_4aIkyI)2, -CN, -C02alkyl, -CONH2, -CONH(CH3), -CON(CH3)2, phenyl, benzyl, C3-7cycloalkyl, og fem- til seks-leddet heterocyclo eller heteroaryl; og/eller når B er cycloalkyl, kan to R7-grupper samles for at danne en eventuelt substitueret carbon-carbon-bro af tre til fire carbonatomer, eller to R7-grupper kan samles for at danne en kondenseret carbocyklisk, heterocyklisk eller heteroarylring, hvilken kondenseret ring til gengæld eventuelt er substitueret med én til tre R22; Ru er cycloalkyl, heterocyclo, eller heteroaryl eventuelt substitueret med én til to R15; Ri3 og R13aer udvalgt fra hydrogen og Ci_4alkyl; R12, Ris °g Ri6 ved hver forekomst er uafhængigt udvalgt fra hydrogen, alkyl, trifluormethyl, trifluormethoxy, halogen, cyano, nitro, amino, Ci_4alkylamino, aminoQ^alkyl, haloQ^alkyl, hydroxy, hydroxyCi_4alkyl, alkoxy, phenyl, benzyl, phenyloxy og benzyloxy; R20 og R2i er udvalgt fra hydrogen, alkyl, alkenyl, substitueret alkyl, substitueret alkenyl, aryl, cycloalkyl, heteroaryl, og heterocyclo; og R22 og R26 er udvalgt fra Ci_6alkyl, C2.6alkenyl, halogen, haloalkyl, haloalkoxy, cyano, nitro, amino, Ci_4alkylamino, aminoC^alkyl, hydroxy, hydroxyC|_4aIkyI, alkoxy, alkylthio, phenyl, benzyl, phenyloxy og benzyloxy.
  14. 14. Forbindelse ifølge krav 13, eller et farmaceutisk acceptabelt salt eller solvat deraf, hvori B er phenyl substitueret med heterocyclo og én til to R12; cyclopropyl eller cyclobutyl eventuelt substitueret med én til to R7; eller B er udvalgt fra én af:
    Og Ry er C^alkyl, trifluormethyl, trifluormethoxy, halogen, cyano, amino, Ci.4alkylalmino, hydroxy, Ci.4alkoxy, phenyl, benzyl, phenyloxy, eller benzyloxy; og n er 0, 1 eller 2.
  15. 15. Forbindelse ifølge krav 1 med formlen (2a) eller (2b), (2a)
    i (2b) enantiomerer, diastereomerer, salte og solvater deraf, hvor: R3 er methyl eller CF3; R4a er phenyl eller fem- eller seks-leddet heteroaryl eventuelt substitueret med op til to R16; Ru, er lige eller forgrenet C2_6alkyl; cycloalkyl eventuelt substitueret med keto og/eller op til to R16; heterocyklus eventuelt substitueret med keto og/eller op til to Ri6; eller Q.+alkyl substitueret med op til tre of halogen, trifluormethyl, cyano, hydroxy, alkoxy, haloalkyl, haloalkoxy, nitro, phenyl, phenyloxy eller benzyloxy, hvor phenyl- eller benzylgruppen til gengæld er eventuelt substitueret med én til to R26; R6a er Ci^alkyl, halogen, trifluormethoxy, trifluormethyl, hydroxy, C^alkoxy, eller cyano; B er udvalgt fra phenyl substitueret med heterocyclo eller heteroaryl og op til to R12, cyclopropyl eller cyclobutyl, der hver eventuelt kan være substitueret med én til to R7, eller B er udvalgt fra én af: og
    R7 er Q.zjalkyl, trifluormethyl, trifluormethoxy, halogen, cyano, nitro, amino, Ci_4alkylalmino, hydroxy, C^alkoxy, phenyl, benzyl, phenyloxy eller benzyloxy; R12, Ri6 og Rn ved hver forekomst er uafhængigt udvalgt fra hydrogen, alkyl, trilluormethyl, trifluormethoxy, halogen, cyano, nitro, amino, C1.4alkylalmino, hydroxy, alkoxy, phenyl, benzyl, phenyloxy og benzyloxy; R26 er udvalgt fra C1.4alkyl, trifluormethyl, trifluormethoxy, halogen, cyano, amino, Q. 4alkylalmino, hydroxy, alkoxy, phenyl, benzyl, phenyloxy og benzyloxy; n er 0 eller 1.
  16. 16. Forbindelse ifølge krav 15 eller et farmaceutisk acceptabelt salt eller solvat deraf, hvori B er cyclopropyl eventuelt substitueret med én til to R7, eller B er udvalgt fra: °g
  17. 17. Forbindelse ifølge krav 1 udvalgt fra
    eller salte og solvater deraf.
  18. 18. Forbindelse ifølge krav 1 udvalgt fra
    eller enantiomerer, diastereomerer, salte og solvater deraf.
  19. 19. Forbindelse ifølge krav 1, der er
    eller enantiomerer, diastereomerer, salte og solvater deraf.
  20. 20. Forbindelse ifølge krav 1 med formlen
    eller en enantiomer, diastereomer eller et farmaceutisk acceptabelt salt deraf.
  21. 21. Farmaceutisk sammensætning, der mindst omfatter én forbindelse ifølge et hvilket som helst af kravene 1 til 20 og et farmaceutisk acceptabelt bærestof eller fortyndingsmiddel.
  22. 22. Anvendelse af en farmaceutisk sammensætning ifølge krav 21 til fremstilling af et medikament til behandling af en inflammatorisk forstyrrelse hos en patient.
  23. 23. Anvendelse ifølge krav 22, hvor den inflammatoriske forstyrrelse er udvalgt fra astma, adult respiratorisk stresssyndrom, kronisk obstruktiv lungesygdom, kronisk inflammatorisk lungesygdom, diabetes, inflammatorisk tarmsygdom, osteoporose, psoriasis, transplantatafstødning, atherosklerose og arthritis herunder rheumatoid arthritis, psoriatisk arthritis, traumatisk arthritis, rubella arthritis, arthritis urica og osteoarthritis.
DK03724157.7T 2002-04-23 2003-04-15 Pyrrolo-triazinanilinsammensætninger nyttig som kinasehæmmere DK1497019T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US37493802P 2002-04-23 2002-04-23
PCT/US2003/012426 WO2003090912A1 (en) 2002-04-23 2003-04-15 Pyrrolo-triazine aniline compounds useful as kinase inhibitors

Publications (1)

Publication Number Publication Date
DK1497019T3 true DK1497019T3 (da) 2015-08-03

Family

ID=29270573

Family Applications (1)

Application Number Title Priority Date Filing Date
DK03724157.7T DK1497019T3 (da) 2002-04-23 2003-04-15 Pyrrolo-triazinanilinsammensætninger nyttig som kinasehæmmere

Country Status (30)

Country Link
US (5) US7160883B2 (da)
EP (2) EP2289894A3 (da)
JP (2) JP4669225B2 (da)
KR (1) KR101025675B1 (da)
CN (2) CN1662509A (da)
AR (1) AR039649A1 (da)
AU (1) AU2003231034B2 (da)
BR (1) BR0309669A (da)
CA (1) CA2483164C (da)
DK (1) DK1497019T3 (da)
ES (1) ES2543711T3 (da)
GE (1) GEP20074148B (da)
HR (1) HRP20040988A2 (da)
HU (1) HUE025353T2 (da)
IL (2) IL164573A (da)
IS (1) IS7505A (da)
MX (1) MXPA04010379A (da)
MY (1) MY132094A (da)
NO (1) NO329503B1 (da)
NZ (1) NZ536014A (da)
PE (1) PE20040590A1 (da)
PL (1) PL219736B1 (da)
PT (1) PT1497019E (da)
RS (1) RS92004A (da)
RU (1) RU2375363C2 (da)
SI (1) SI1497019T1 (da)
TW (1) TWI312782B (da)
UA (1) UA78562C2 (da)
WO (1) WO2003090912A1 (da)
ZA (1) ZA200408541B (da)

Families Citing this family (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6867300B2 (en) 2000-11-17 2005-03-15 Bristol-Myers Squibb Company Methods for the preparation of pyrrolotriazine compounds useful as kinase inhibitors
US6670357B2 (en) * 2000-11-17 2003-12-30 Bristol-Myers Squibb Company Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors
PT1497019E (pt) * 2002-04-23 2015-09-10 Bristol Myers Squibb Co Compostos de pirrolotriazina anilina úteis como inibidores de quinase
TW200400034A (en) 2002-05-20 2004-01-01 Bristol Myers Squibb Co Pyrazolo-pyrimidine aniline compounds useful as kinase inhibitors
TW200401638A (en) * 2002-06-20 2004-02-01 Bristol Myers Squibb Co Heterocyclic inhibitors of kinases
TWI329112B (en) * 2002-07-19 2010-08-21 Bristol Myers Squibb Co Novel inhibitors of kinases
AU2003265349A1 (en) * 2002-08-02 2004-02-23 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
TW200420565A (en) * 2002-12-13 2004-10-16 Bristol Myers Squibb Co C-6 modified indazolylpyrrolotriazines
JP2006516653A (ja) 2003-02-05 2006-07-06 ブリストル−マイヤーズ　スクイブ　カンパニー キナーゼ阻害剤ピロロトリアジンの製造方法
EP1667983A4 (en) * 2003-09-23 2010-07-21 Merck Sharp & Dohme PYRAZOL MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
US7419978B2 (en) * 2003-10-22 2008-09-02 Bristol-Myers Squibb Company Phenyl-aniline substituted bicyclic compounds useful as kinase inhibitors
US7309708B2 (en) * 2003-11-20 2007-12-18 Birstol-Myers Squibb Company Hepatitis C virus inhibitors
AU2004299174A1 (en) * 2003-12-10 2005-06-30 Merck Patent Gmbh Diacylhydrazine derivatives
US7102001B2 (en) 2003-12-12 2006-09-05 Bristol-Myers Squibb Company Process for preparing pyrrolotriazine
AU2004309420B2 (en) * 2003-12-23 2008-10-30 Novartis Ag Bicyclic heterocyclic p-38 kinase inhibitors
MY145634A (en) 2003-12-29 2012-03-15 Bristol Myers Squibb Co Pyrrolotriazine compounds as kinase inhibitors
US7064203B2 (en) 2003-12-29 2006-06-20 Bristol Myers Squibb Company Di-substituted pyrrolotriazine compounds
US7459562B2 (en) * 2004-04-23 2008-12-02 Bristol-Myers Squibb Company Monocyclic heterocycles as kinase inhibitors
TW200538453A (en) * 2004-04-26 2005-12-01 Bristol Myers Squibb Co Bicyclic heterocycles as kinase inhibitors
US7102002B2 (en) 2004-06-16 2006-09-05 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
US7173031B2 (en) * 2004-06-28 2007-02-06 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
US7439246B2 (en) * 2004-06-28 2008-10-21 Bristol-Myers Squibb Company Fused heterocyclic kinase inhibitors
US7432373B2 (en) * 2004-06-28 2008-10-07 Bristol-Meyers Squibb Company Processes and intermediates useful for preparing fused heterocyclic kinase inhibitors
US7253167B2 (en) 2004-06-30 2007-08-07 Bristol-Myers Squibb Company Tricyclic-heteroaryl compounds useful as kinase inhibitors
TW200600513A (en) 2004-06-30 2006-01-01 Bristol Myers Squibb Co A method for preparing pyrrolotriazine compounds
US7102003B2 (en) 2004-07-01 2006-09-05 Bristol-Myers Squibb Company Pyrrolotriazine compounds
US7504521B2 (en) 2004-08-05 2009-03-17 Bristol-Myers Squibb Co. Methods for the preparation of pyrrolotriazine compounds
TW200618803A (en) * 2004-08-12 2006-06-16 Bristol Myers Squibb Co Process for preparing pyrrolotriazine aniline compounds useful as kinase inhibitors
US7151176B2 (en) * 2004-10-21 2006-12-19 Bristol-Myers Squibb Company Pyrrolotriazine compounds
ES2350771T3 (es) * 2004-10-26 2011-01-26 Novartis Ag Pirrolo [1,2-d][1,2-4]triazina como inhibidores de quinasas c-jun n-terminal (jnk) y quinasas p-38.
US7534882B2 (en) 2005-04-06 2009-05-19 Bristol-Myers Squibb Company Method for preparing pyrrolotriazine compounds via in situ amination of pyrroles
US20060235020A1 (en) * 2005-04-18 2006-10-19 Soojin Kim Process for preparing salts of 4-[[5-[(cyclopropylamino)carbonyl]-2-methylphenyl]amino]-5-methyl-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide and novel stable forms produced therein
US7405213B2 (en) * 2005-07-01 2008-07-29 Bristol-Myers Squibb Company Pyrrolotriazine compounds useful as kinase inhibitors and methods of treating kinase-associated conditions therewith
US7442700B2 (en) * 2005-07-01 2008-10-28 Bristol-Myers Squibb Company Pyrrolotriazine compounds useful as kinase inhibitors and methods of treating kinase-associated conditions therewith
US7402582B2 (en) * 2005-07-01 2008-07-22 Bristol-Myers Squibb Company Pyrrolotriazine compounds useful as kinase inhibitors and methods of treating kinase-associated conditions therewith
US7348325B2 (en) * 2005-11-30 2008-03-25 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
US8063208B2 (en) 2006-02-16 2011-11-22 Bristol-Myers Squibb Company Crystalline forms of (3R,4R)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol
KR20080107408A (ko) 2006-03-07 2008-12-10 브리스톨-마이어스 스큅 컴퍼니 키나제 억제제로서 유용한 피롤로트리아진 아닐린 전구약물화합물
US7531539B2 (en) 2006-08-09 2009-05-12 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
US8268998B2 (en) 2006-11-03 2012-09-18 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
US7982033B2 (en) 2006-11-03 2011-07-19 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
ES2539620T3 (es) 2008-12-19 2015-07-02 Cephalon, Inc. Pirrolotriazina como inhibidor de ALK y de JAK2
US8399451B2 (en) * 2009-08-07 2013-03-19 Bristol-Myers Squibb Company Heterocyclic compounds
ES2548683T3 (es) 2010-04-23 2015-10-20 Bristol-Myers Squibb Company Amidas del ácido 4-(5-isoxazolil o 5-pirrazolil-1,2,4-oxadiazol-3-il)-mandélico como agonistas de receptor de esfingosina-1-fosfato 1
WO2012031057A1 (en) 2010-09-01 2012-03-08 Bristol-Myers Squibb Company Bms- 582949 for the treatment of resistant rheumatic disease
EP2619190B1 (en) 2010-09-24 2015-08-12 Bristol-Myers Squibb Company Substituted oxadiazole compounds and their use as s1p1 agonists
WO2014082230A1 (zh) * 2012-11-28 2014-06-05 上海希迈医药科技有限公司 吡咯并三嗪类衍生物、其制备方法及其在医药上的应用
CN103848833B (zh) * 2012-11-28 2016-08-31 上海希迈医药科技有限公司 吡咯并三嗪类衍生物、其制备方法及其在医药上的应用
US9447105B2 (en) 2013-01-24 2016-09-20 Council Of Scientific & Industrial Research Triazine compounds and a process for preparation thereof
CN103601722B (zh) * 2013-09-13 2016-03-02 南京华威医药科技开发有限公司 新型抗肿瘤化合物
EP3054955B1 (en) * 2013-10-11 2018-05-30 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
SI3057969T1 (sl) 2013-10-17 2018-10-30 Blueprint Medicines Corporation Sestavki, uporabni za zdravljenje motenj, povezanih s KIT
WO2015091156A1 (en) 2013-12-17 2015-06-25 Boehringer Ingelheim International Gmbh Sulfoximine substituted pyrrolotriazines for pharmaceutical compositions
WO2018129301A1 (en) * 2017-01-05 2018-07-12 Biodesix, Inc. Method for identification of cancer patients with durable benefit from immunotherapy in overall poor prognosis subgroups
US11040979B2 (en) 2017-03-31 2021-06-22 Blueprint Medicines Corporation Substituted pyrrolo[1,2-b]pyridazines for treating disorders related to KIT and PDGFR
BR112020006677A2 (pt) 2017-10-05 2020-10-06 Fulcrum Therapeutics, Inc. uso de inibidores p38 para reduzir a expressão de dux4
US10342786B2 (en) 2017-10-05 2019-07-09 Fulcrum Therapeutics, Inc. P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD
WO2019168874A1 (en) 2018-02-27 2019-09-06 The Research Foundation For The State University Of New York Difluoromethoxylation and trifluoromethoxylation compositions and methods for synthesizing same
EP3762379A1 (en) 2018-03-07 2021-01-13 Bayer Aktiengesellschaft Identification and use of erk5 inhibitors
ES2966512T3 (es) 2019-04-12 2024-04-22 Blueprint Medicines Corp Formas cristalinas de (S)-1-(4-fluorofenil)-1-(2-(4-(6-(1-metil-1H-pirazol-4-il)pirrolo[2,1-f][1,2,4]triazin-4-il)piperazinil)-pirimidin-5-il)etan-1-amina y métodos de elaboración
BR112021020441A2 (pt) 2019-04-12 2021-12-14 Blueprint Medicines Corp Derivados de pirrolotriazina para tratar doenças mediadas por kit e pdgfra
TW202112368A (zh) 2019-06-13 2021-04-01 荷蘭商法西歐知識產權股份有限公司 用於治療有關dux4表現之疾病的抑制劑組合
CN110483439B (zh) * 2019-08-28 2022-12-30 郑州手性药物研究院有限公司 6-氨基甲基-1,1-二氧-1,2-苯并噻唑-3-酮的合成方法
CN110483497B (zh) * 2019-08-28 2022-12-30 郑州手性药物研究院有限公司 6-氨基甲基-1,1-二氧-1,2-苯并噻唑-3-酮中间体及其合成方法
CN110627706B (zh) * 2019-08-28 2023-02-10 郑州手性药物研究院有限公司 2-(4-甲基苄基)-1h-异吲哚-1,3-二酮衍生物及其合成方法
CN121159543A (zh) * 2025-09-19 2025-12-19 合肥综合性国家科学中心大健康研究院 吡咯并[2,1-f][1,2,4]三嗪类化合物及其制备方法和应用、中间体、药物组合物和cGAS激动剂

Family Cites Families (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3629301A (en) 1969-10-24 1971-12-21 Du Pont 3 3-difluoro-2-substituted steroids and their preparation
US4200750A (en) 1977-01-07 1980-04-29 Westwood Pharmaceuticals Inc. 4-Substituted imidazo [1,2-a]quinoxalines
IL107041A (en) * 1992-09-25 2000-02-17 Lilly Co Eli Process for preparing omega(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo-6-¬2,3-d¾pyrimidin-5-YL)alkarylcarboxylic acids and N-(omega-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo¬2,3-d¾pyrimidin-5-YL)alk-aroyl-4-glutamic acids
IL118544A (en) 1995-06-07 2001-08-08 Smithkline Beecham Corp History of imidazole, the process for their preparation and the pharmaceutical preparations containing them
PL187516B1 (pl) 1996-01-11 2004-07-30 Smithkline Beecham Corp Nowe podstawione pochodne imidazolu, sposób ich wytwarzania oraz kompozycja farmaceutyczna zawierająca te związki
US6191131B1 (en) * 1997-07-23 2001-02-20 Dupont Pharmaceuticals Company Azolo triazines and pyrimidines
US5945418A (en) 1996-12-18 1999-08-31 Vertex Pharmaceuticals Incorporated Inhibitors of p38
US6147080A (en) 1996-12-18 2000-11-14 Vertex Pharmaceuticals Incorporated Inhibitors of p38
IL132736A0 (en) 1997-05-22 2001-03-19 Searle & Co 3(5)-Heteroaryl substituted pyrazoles as p38 kinase inhibitors
US6087496A (en) 1998-05-22 2000-07-11 G. D. Searle & Co. Substituted pyrazoles suitable as p38 kinase inhibitors
US6251914B1 (en) 1997-07-02 2001-06-26 Smithkline Beecham Corporation Cycloalkyl substituted imidazoles
WO1999024033A1 (en) * 1997-11-12 1999-05-20 Shionogi & Co., Ltd. Method for the treatment of disorders associated with apoptosis using n-heterocyclic glyoxylamide compounds
US6130235A (en) 1998-05-22 2000-10-10 Scios Inc. Compounds and methods to treat cardiac failure and other disorders
US6184226B1 (en) 1998-08-28 2001-02-06 Scios Inc. Quinazoline derivatives as inhibitors of P-38 α
MXPA01002173A (es) 1998-08-28 2003-07-14 Scios Inc Inhibidores de p38-alfa cinasa.
JP2002526482A (ja) * 1998-09-18 2002-08-20 バーテックス ファーマシューティカルズ インコーポレイテッド ｐ３８のインヒビター
ATE232205T1 (de) 1998-10-01 2003-02-15 Astrazeneca Ab Chinolin- und chinazolin derivate und ihre verwendung als inhibitoren von krankheiten, bei denen cytokine beteiligt wird
CA2346334A1 (en) * 1998-10-14 2000-04-20 Shionogi & Co., Ltd. Composition for treating or preventing ischemia reperfusion injury
GB9906566D0 (en) 1999-03-23 1999-05-19 Zeneca Ltd Chemical compounds
US6982265B1 (en) 1999-05-21 2006-01-03 Bristol Myers Squibb Company Pyrrolotriazine inhibitors of kinases
JP4649046B2 (ja) * 1999-05-21 2011-03-09 ブリストル−マイヤーズ スクイブ カンパニー キナーゼのピロロトリアジン阻害剤
US6787545B1 (en) * 1999-08-23 2004-09-07 Shiongi & Co., Ltd. Pyrrolotriazine derivatives having spla2-inhibitory activities
GB9924092D0 (en) 1999-10-13 1999-12-15 Zeneca Ltd Pyrimidine derivatives
ES2237470T3 (es) 1999-11-10 2005-08-01 Ortho-Mcneil Pharmaceutical, Inc. 2-aril-3-(heteroaril)-imidazo(1,2-alfa)pirimidinas sustituidas; y composiciones farmaceuticas y procedimientos asociados.
US20020065270A1 (en) * 1999-12-28 2002-05-30 Moriarty Kevin Joseph N-heterocyclic inhibitors of TNF-alpha expression
US6906067B2 (en) * 1999-12-28 2005-06-14 Bristol-Myers Squibb Company N-heterocyclic inhibitors of TNF-α expression
US6867300B2 (en) * 2000-11-17 2005-03-15 Bristol-Myers Squibb Company Methods for the preparation of pyrrolotriazine compounds useful as kinase inhibitors
GEP20063915B (en) * 2000-11-17 2006-09-11 Bristol Myers Squibb Co PYRROLOTRIAZINE COMPOUNDS USEFUL AS KINASE INHIBITORS AND USE THEREOF FOR TREATING p38 KINASE-ASSOCIATED CONDITIONS
US6670357B2 (en) * 2000-11-17 2003-12-30 Bristol-Myers Squibb Company Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors
AU2002316421B2 (en) * 2001-06-26 2008-05-15 Bristol-Myers Squibb Company N-heterocyclic inhibitors of TNF-ALPHA expression
TW200300350A (en) * 2001-11-14 2003-06-01 Bristol Myers Squibb Co C-5 modified indazolylpyrrolotriazines
TW200306841A (en) * 2002-04-23 2003-12-01 Bristol Myers Squibb Co Aryl ketone pyrrolo-triazine compounds useful as kinase inhibitors
PT1497019E (pt) * 2002-04-23 2015-09-10 Bristol Myers Squibb Co Compostos de pirrolotriazina anilina úteis como inibidores de quinase
TW200400034A (en) * 2002-05-20 2004-01-01 Bristol Myers Squibb Co Pyrazolo-pyrimidine aniline compounds useful as kinase inhibitors
TWI329112B (en) * 2002-07-19 2010-08-21 Bristol Myers Squibb Co Novel inhibitors of kinases
TWI272271B (en) * 2002-07-19 2007-02-01 Bristol Myers Squibb Co Process for preparing certain pyrrolotriazine compounds
AU2003265349A1 (en) * 2002-08-02 2004-02-23 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
TW200420565A (en) * 2002-12-13 2004-10-16 Bristol Myers Squibb Co C-6 modified indazolylpyrrolotriazines
JP2006516653A (ja) * 2003-02-05 2006-07-06 ブリストル−マイヤーズ　スクイブ　カンパニー キナーゼ阻害剤ピロロトリアジンの製造方法
MY145634A (en) * 2003-12-29 2012-03-15 Bristol Myers Squibb Co Pyrrolotriazine compounds as kinase inhibitors
TW200600513A (en) * 2004-06-30 2006-01-01 Bristol Myers Squibb Co A method for preparing pyrrolotriazine compounds
US7504521B2 (en) * 2004-08-05 2009-03-17 Bristol-Myers Squibb Co. Methods for the preparation of pyrrolotriazine compounds
US7534882B2 (en) * 2005-04-06 2009-05-19 Bristol-Myers Squibb Company Method for preparing pyrrolotriazine compounds via in situ amination of pyrroles
US20060235020A1 (en) * 2005-04-18 2006-10-19 Soojin Kim Process for preparing salts of 4-[[5-[(cyclopropylamino)carbonyl]-2-methylphenyl]amino]-5-methyl-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide and novel stable forms produced therein
KR20080107408A (ko) * 2006-03-07 2008-12-10 브리스톨-마이어스 스큅 컴퍼니 키나제 억제제로서 유용한 피롤로트리아진 아닐린 전구약물화합물

Also Published As

Publication number Publication date
TWI312782B (en) 2009-08-01
US20040082582A1 (en) 2004-04-29
US7462616B2 (en) 2008-12-09
US20110098467A1 (en) 2011-04-28
SI1497019T1 (sl) 2015-08-31
US20090105243A1 (en) 2009-04-23
JP2005523338A (ja) 2005-08-04
KR20040102157A (ko) 2004-12-03
PL219736B1 (pl) 2015-07-31
PT1497019E (pt) 2015-09-10
WO2003090912A9 (en) 2004-01-08
MXPA04010379A (es) 2005-02-17
PE20040590A1 (es) 2004-08-28
EP1497019B1 (en) 2015-05-20
ES2543711T3 (es) 2015-08-21
NO329503B1 (no) 2010-11-01
PL373338A1 (en) 2005-08-22
CN1662509A (zh) 2005-08-31
IS7505A (is) 2004-10-14
IL164573A (en) 2010-12-30
CA2483164C (en) 2011-06-07
US20070043053A1 (en) 2007-02-22
AU2003231034B2 (en) 2009-03-05
JP2010132673A (ja) 2010-06-17
CN102093363B (zh) 2016-12-07
US20100240646A1 (en) 2010-09-23
RS92004A (sr) 2006-12-15
NO20044560L (no) 2004-11-10
AU2003231034A1 (en) 2003-11-10
EP2289894A2 (en) 2011-03-02
WO2003090912A1 (en) 2003-11-06
HUE025353T2 (en) 2016-02-29
JP5226018B2 (ja) 2013-07-03
UA78562C2 (en) 2007-04-10
JP4669225B2 (ja) 2011-04-13
IL164573A0 (en) 2005-12-18
NZ536014A (en) 2006-12-22
TW200402422A (en) 2004-02-16
US7160883B2 (en) 2007-01-09
CA2483164A1 (en) 2003-11-06
AR039649A1 (es) 2005-03-02
EP1497019A1 (en) 2005-01-19
CN102093363A (zh) 2011-06-15
MY132094A (en) 2007-09-28
US7759343B2 (en) 2010-07-20
EP1497019A4 (en) 2006-06-14
GEP20074148B (en) 2007-07-10
IL185604A0 (en) 2008-01-06
EP2289894A3 (en) 2011-07-20
RU2004134337A (ru) 2005-06-27
RU2375363C2 (ru) 2009-12-10
BR0309669A (pt) 2005-03-01
KR101025675B1 (ko) 2011-03-30
HRP20040988A2 (en) 2005-06-30
ZA200408541B (en) 2006-01-25

Similar Documents

Publication Publication Date Title
DK1497019T3 (da) Pyrrolo-triazinanilinsammensætninger nyttig som kinasehæmmere
EP1503996B1 (en) Aryl ketone pyrrolo-triazine compounds useful as kinase inhibitors
US6670357B2 (en) Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors
EP1363910B1 (en) Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors
AU2002232760A1 (en) Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors
JP2009535295A (ja) キナーゼ阻害剤として有用なピロロトリアジンアニリンプロドラッグ化合物
US7388009B2 (en) Heteroaryl-substituted pyrrolo-triazine compounds useful as kinase inhibitors