WO2000017203A1 - Pyrrolopyrimidines utilisees comme inhibiteurs de proteines kinases - Google Patents

Pyrrolopyrimidines utilisees comme inhibiteurs de proteines kinases Download PDF

Info

Publication number
WO2000017203A1
WO2000017203A1 PCT/US1999/021560 US9921560W WO0017203A1 WO 2000017203 A1 WO2000017203 A1 WO 2000017203A1 US 9921560 W US9921560 W US 9921560W WO 0017203 A1 WO0017203 A1 WO 0017203A1
Authority
WO
WIPO (PCT)
Prior art keywords
substituted
unsubstituted
pyrimidin
amino
pyrrolo
Prior art date
Application number
PCT/US1999/021560
Other languages
English (en)
Inventor
Gavin C. Hirst
David Calderwood
Rainer Munschauer
Paul Rafferty
Lee D. Arnold
David N. Johnston
Original Assignee
Basf Aktiengesellschaft
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
Priority to KR1020017003532A priority Critical patent/KR20010085824A/ko
Priority to EP99969415A priority patent/EP1114053A1/fr
Priority to SK384-2001A priority patent/SK3842001A3/sk
Priority to JP2000574112A priority patent/JP2002526500A/ja
Priority to NZ510588A priority patent/NZ510588A/en
Priority to AU60484/99A priority patent/AU753555C/en
Priority to CA002344249A priority patent/CA2344249A1/fr
Priority to IL14186699A priority patent/IL141866A0/xx
Application filed by Basf Aktiengesellschaft filed Critical Basf Aktiengesellschaft
Priority to BR9913887-5A priority patent/BR9913887A/pt
Priority to US09/537,167 priority patent/US6713474B2/en
Publication of WO2000017203A1 publication Critical patent/WO2000017203A1/fr
Priority to BG105346A priority patent/BG105346A/xx
Priority to NO20011356A priority patent/NO20011356L/no
Priority to HK02100227.3A priority patent/HK1039326A1/zh

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
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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
    • A61P31/04—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
    • A61P31/18—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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring

Definitions

  • endothelial-cell specific receptor PTKs such as KDR and Tie-2 mediate the angiogenic process, and are thus involved in supporting the progression of cancers and other diseases involving inappropriate vascularization (e.g., diabetic retinopathy, choroidal neovascularization due to age-related macular degeneration, psoriasis, arthritis, retinopathy of prematurity, infantile hemangiomas).
  • inappropriate vascularization e.g., diabetic retinopathy, choroidal neovascularization due to age-related macular degeneration, psoriasis, arthritis, retinopathy of prematurity, infantile hemangiomas.
  • E/CDK2 are thought to mediate the onset of S-phase (Matsushima et al., Molecular
  • Ring A is more preferably substituted with F, CI, and nitro.
  • the present invention provides a method of treating a protein kinase-mediated condition in a patient, comprising adiminstering to the patient a therapeutically or prophylactically effective amount of one or more compounds of Formula I.
  • a "protein kinase-mediated condition" is a medical condition, such as a disease or other undesirable physical condition, the genesis or progression of which depends, at least in part, on the activity of at least one protein kinase.
  • the protein kinase can be, for example, a protein tyrosine kinase or a protein serine/threonine kinase.
  • the patient to be treated can be any animal, and is preferably a mammal, such as a domesticated animal or a livestock animal. More preferably, the patient is a human.
  • compositions for use in accordance with the present invention thus may be formulated in conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen.
  • the agents of the invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer.
  • physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer.
  • penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.
  • the compounds can be formulated readily by combining the active compounds with pharmaceutically acceptable carriers well known in the art.
  • Such carriers enable the compounds of the invention to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated.
  • Pharmaceutical preparations for oral use can be obtained by combining the active compound with a solid excipient, optionally grinding a resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores.
  • compositions comprising a compound of the invention formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition.
  • a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition.
  • mice were randomized and divided into groups of 5- 10. Test compounds were administered by i.p., i.v. or p.o. routes depending on solubility and vehicle at doses ranging from 1-100 mg/kg. Vehicle control group received vehicle only and two groups were left untreated.
  • R 2 and R 3 are as previously defined with a compound of formula RjX' in which Rj represents an alkyl group or an aralkyl group and X' represents a leaving group, for example halo, mesyloxy or tosyloxy.
  • Rstrich R 3 L and ring A are as previously defined with a halogenating agent for example an iodinating agent, e.g. N-iodosuccinimide, or a brominating agent, e.g. N- bromosuccinimide, or a chlorinating agent, e.g. N-chlorosuccinimide.
  • a halogenating agent for example an iodinating agent, e.g. N-iodosuccinimide, or a brominating agent, e.g. N- bromosuccinimide, or a chlorinating agent, e.g. N-chlorosuccinimide.
  • Example 70 4-Amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl-N- [2-(N,N-dimethy lamino)propyl] acetamide
  • Example 103 l-[4-Amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]- N-( 1 -hydroxyprop-2-yl)propanamide
  • Example 469 In a similar manner to Example 469, the product from the previous example was treated with hydrazine hydrate to give 7-(2-aminoethyl)-5-(4-phenoxyphenyl)- 7H-pyrrolo[2,3-d]pyrimidin-4-ylamine hydrochloride, m.p. 284-285°C.
  • Example 188 cis-7-(3-mo ⁇ holinocyclopent-l-yl)-5-(4-phenoxyphenyl)-7H- pyrrolo[2,3-d]pyrimidin-4-ylamine and trans-7-(3-mo ⁇ holinocyclopent- 1 -yl)-5-(4- phenoxyphenyl)-7H-pyrrolo[2,3-d]-pyrimidin-4-ylamine
  • the hydrobromide salt was converted into the free base by warming with dilute sodium hydroxide solution (100 ml of 5% w/v solution) and ethanol (60 ml) with stirring and removing the ethanol by distillation. The mixture was cooled and the solid was collected by filtration and washed well with water to give 5-(4- phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine.

Abstract

L'invention concerne des composés chimiques, représentés par la formule développée (I), ainsi que des sels et des métabolites physiologiquement acceptables de ces composés. Ces composés inhibent l'activité des sérine/thréonine kinases et des tyrosine kinases. Plusieurs de ces kinases, dont l'activité est inhibée par ces composés, jouent un rôle dans des processus immunologiques, hyperprolifératifs, ou angiogéniques. Les composés de l'invention peuvent, de ce fait, améliorer des états pathologiques, pour lesquels l'angiogenèse ou l'hyperprolifération des cellules endothéliales constituent un facteur. Ces composés peuvent être utilisés pour le traitement du cancer, des troubles hyperprolifératifs, de la polyarthrite rhumatoïde, des dysfonctionnement du système immunitaire, des rejets du greffon, et des troubles inflammatoires.
PCT/US1999/021560 1998-09-18 1999-09-17 Pyrrolopyrimidines utilisees comme inhibiteurs de proteines kinases WO2000017203A1 (fr)

Priority Applications (13)

Application Number Priority Date Filing Date Title
CA002344249A CA2344249A1 (fr) 1998-09-18 1999-09-17 Pyrrolopyrimidines utilisees comme inhibiteurs de proteines kinases
SK384-2001A SK3842001A3 (en) 1998-09-18 1999-09-17 Pyrrolopyrimidines as protein kinase inhibitors (revised)
JP2000574112A JP2002526500A (ja) 1998-09-18 1999-09-17 プロテインキナーゼ阻害剤としてのピロロピリミジン
NZ510588A NZ510588A (en) 1998-09-18 1999-09-17 Pyrrolopyrimidines as protein kinase inhibitors
AU60484/99A AU753555C (en) 1998-09-18 1999-09-17 Pyrrolopyrimidines as protein kinase inhibitors
KR1020017003532A KR20010085824A (ko) 1998-09-18 1999-09-17 단백질 키나아제 억제제로서의 피롤로피리미딘
IL14186699A IL141866A0 (en) 1998-09-18 1999-09-17 Pyrrolopyrimidines as protein kinase inhibitors
EP99969415A EP1114053A1 (fr) 1998-09-18 1999-09-17 Pyrrolopyrimidines utilisees comme inhibiteurs de proteines kinases
BR9913887-5A BR9913887A (pt) 1998-09-18 1999-09-17 Composto, e, métodos de inibir a atividade de proteìna quinase, de tratar um paciente que tenha uma condição que seja mediada pela atividade da proteìna quinase e de diminuir a fertilidade em um paciente
US09/537,167 US6713474B2 (en) 1998-09-18 2000-03-29 Pyrrolopyrimidines as therapeutic agents
BG105346A BG105346A (en) 1998-09-18 2001-03-15 Pyrolopyrimidines as protein kinase inhibitors
NO20011356A NO20011356L (no) 1998-09-18 2001-03-16 Pyrrolopyrimidiner som proteinkinase-inhibitorer
HK02100227.3A HK1039326A1 (zh) 1998-09-18 2002-01-11 4氨基吡咯並嘧啶作為激酶抑制劑

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US10094698P 1998-09-18 1998-09-18
US10083498P 1998-09-18 1998-09-18
US10083298P 1998-09-18 1998-09-18
US10083398P 1998-09-18 1998-09-18
US60/100,832 1998-09-18
US60/100,833 1998-09-18
US60/100,946 1998-09-18
US60/100,834 1998-12-03

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US09/537,167 Continuation-In-Part US6713474B2 (en) 1998-09-18 2000-03-29 Pyrrolopyrimidines as therapeutic agents

Publications (1)

Publication Number Publication Date
WO2000017203A1 true WO2000017203A1 (fr) 2000-03-30

Family

ID=27493158

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/021560 WO2000017203A1 (fr) 1998-09-18 1999-09-17 Pyrrolopyrimidines utilisees comme inhibiteurs de proteines kinases

Country Status (19)

Country Link
EP (1) EP1114053A1 (fr)
JP (1) JP2002526500A (fr)
KR (1) KR20010085824A (fr)
CN (1) CN1335849A (fr)
AU (1) AU753555C (fr)
BG (1) BG105346A (fr)
BR (1) BR9913887A (fr)
CA (1) CA2344249A1 (fr)
CZ (1) CZ2001960A3 (fr)
HK (1) HK1039326A1 (fr)
HU (1) HUP0200403A3 (fr)
ID (1) ID29028A (fr)
IL (1) IL141866A0 (fr)
NO (1) NO20011356L (fr)
NZ (1) NZ510588A (fr)
PL (1) PL346700A1 (fr)
SK (1) SK3842001A3 (fr)
TR (1) TR200101186T2 (fr)
WO (1) WO2000017203A1 (fr)

Cited By (81)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001072751A1 (fr) * 2000-03-29 2001-10-04 Knoll Gesellschaft Mit Beschraenkter Haftung Pyrrolopyrimidines utilisees comme inhibiteurs de tyrosine kinases
WO2002000661A1 (fr) * 2000-06-26 2002-01-03 Pfizer Products Inc. Composes pyrrolo[2,3-d]pyrimidine en tant qu'agents immunosuppresseurs
US6593326B1 (en) 1998-12-24 2003-07-15 Astrazeneca Ab 2,4-diamino pyrimidine compounds having anti-cell proliferative activity
US6627754B2 (en) 1999-12-10 2003-09-30 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
US6632820B1 (en) 1998-08-29 2003-10-14 Astrazeneca Ab Pyrimidine compounds
US6635762B1 (en) 1998-06-19 2003-10-21 Pfizer Inc. Monocyclic-7H-pyrrolo[2,3-d]pyrimidine compounds, compositions, and methods of use
US6649608B2 (en) 2000-03-01 2003-11-18 Astrazeneca Ab 2,4-di(hetero-)arylamino (oxy)-5-substituted pyrimidines as antineoplastic agents
US6670368B1 (en) 1999-04-06 2003-12-30 Astrazeneca Ab Pyrimidine compounds with pharmaceutical activity
US6710052B2 (en) 2000-03-01 2004-03-23 Astrazeneca Pyrimidine compounds
US6713474B2 (en) 1998-09-18 2004-03-30 Abbott Gmbh & Co. Kg Pyrrolopyrimidines as therapeutic agents
US6716831B1 (en) 1999-03-06 2004-04-06 Astrazeneca Ab 2,4-diamino-pyrimidine deprivatives having anti-cell proliferative activity
WO2004043962A1 (fr) * 2002-11-12 2004-05-27 Novartis Ag Derives de 4-amino-5-phenyl-7-cyclohexyl-pyrrolo[2,3-d]pyrimidine
US6838464B2 (en) 2000-03-01 2005-01-04 Astrazeneca Ab 2,4-Di(hetero-)arylamino(-oxy)-5-substituted pyrimidines as antineaoplastic agents
US6844341B2 (en) 2001-02-17 2005-01-18 Astrazeneca Ab Pyrimidine derivatives for inhibition of cell proliferation
US6855719B1 (en) 1999-08-21 2005-02-15 Astrazeneca Ab Imidazo[1,2-A]pyridine and pyrazolo[2,3-A]pyridine derivatives
US6906065B2 (en) 2000-03-28 2005-06-14 Astrazeneca Ab 4-Amino-5-cyano-2-anilino-pyrimidine derivatives and their use as inhibitors of cell-cycle kinases
US6908920B2 (en) 2000-07-11 2005-06-21 Astrazeneca Ab Pyrimidine derivatives
US6939872B2 (en) 2001-05-30 2005-09-06 Astrazeneca Ab 2-anilino-pyrimidine derivatives as cyclin dependent kinase inhibitors
WO2005097800A1 (fr) * 2004-04-02 2005-10-20 Osi Pharmaceuticals, Inc. Inhibiteurs de la proteine kinase heterobicycliques a substitution de noyau bicyclique 6,6
WO2006012422A1 (fr) 2004-07-20 2006-02-02 Osi Pharmaceuticals, Inc. Imidazotriazines comme inhibiteurs de la tyrosine kinase
US20060025383A1 (en) * 2004-02-03 2006-02-02 Neil Wishart Aminobenzoxazoles as therapeutic agents
US7081454B2 (en) 2001-03-28 2006-07-25 Bristol-Myers Squibb Co. Tyrosine kinase inhibitors
WO2006102079A1 (fr) * 2005-03-17 2006-09-28 Novartis Ag N- [3- (1-amin0-5, 6, 7, 8-tetrahydro-2, 4, 4b-triazafluoren-9-yle)-phenyl] benzamides utilises en tant qu'inhibiteurs de tyrosine/threonine kinase, en particulier la b-raf kinase
US7153964B2 (en) 2000-03-01 2006-12-26 Astrazeneca Ab Pyrimidine compounds
US7176212B2 (en) 1998-08-29 2007-02-13 Astrazeneca Ab 2,4-diamino pyrimidine compounds having anti-cell proliferative activity
WO2007035744A1 (fr) 2005-09-20 2007-03-29 Osi Pharmaceuticals, Inc. Marqueurs biologiques predictifs d'une reaction anticancereuse aux inhibiteurs kinase du recepteur du facteur de croissance 1 analogue a l'insuline
JP2007511596A (ja) * 2003-11-17 2007-05-10 ファイザー・プロダクツ・インク 癌の治療において有用なピロロピリミジン化合物
WO2007064993A2 (fr) 2005-12-02 2007-06-07 Osi Pharmaceuticals, Inc. Inhibiteurs bicycliques de la proteine kinase
US7250420B2 (en) 2002-11-26 2007-07-31 Pfizer Inc. Method of treatment of transplant rejection
US7271262B2 (en) 2002-12-19 2007-09-18 Pfizer Inc Pyrrolopyrimidine derivatives
US7312215B2 (en) 2003-07-29 2007-12-25 Bristol-Myers Squibb Company Benzimidazole C-2 heterocycles as kinase inhibitors
WO2007056170A3 (fr) * 2005-11-02 2008-01-03 Bayer Healthcare Ag Derives pyrrolo-[2,1-f]-[1,2,4]-triazin-4-ylamines inhibiteurs de la igf-1r kinase pour le traitement des cancers et autres maladies hyperproliferatives
US7326699B2 (en) 2001-05-14 2008-02-05 Novartis Ag 4-Amino-5-phenyl-7-cyclobutyl-pyrrolo(2,3-d)pyrimidine derivatives
CN100372849C (zh) * 2001-08-30 2008-03-05 诺瓦提斯公司 作为半胱氨酸蛋白酶抑制剂的吡咯并嘧啶化合物
US7345038B2 (en) 2003-03-12 2008-03-18 Pfizer, Inc Pyridyloxymethyl and benzisoxazole azabicyclic derivatives
US7369946B2 (en) 2000-03-29 2008-05-06 Abbott Gmbh & Co. Kg Method of identifying inhibitors of Tie-2
US7427616B2 (en) 2002-08-06 2008-09-23 Astrazeneca Ab Condensed pyridines and pyrimidines with tie2 (TEK) activity
US7427626B2 (en) 2003-05-16 2008-09-23 Astrazeneca Ab 2-Anilino-4-(imidazol-5-yl)-pyrimidine derivatives and their use as cdk (cdk2) inhibitors
US7442697B2 (en) 2002-03-09 2008-10-28 Astrazeneca Ab 4-imidazolyl substituted pyrimidine derivatives with CDK inhibitory activity
US7446105B2 (en) 2002-03-09 2008-11-04 Astrazeneca Ab Pyrimidine compounds
US7465728B2 (en) 2002-03-09 2008-12-16 Astrazeneca Ab Derivatives of 4-(imidazol-5-yl)-2-(4-sulfoanilino)pyrimidine with CDK inhibitory activity
US7485638B2 (en) 2002-03-09 2009-02-03 Astrazeneca Ab Pyrimidine compounds
US7579344B2 (en) 2003-05-16 2009-08-25 Astrazeneca Ab Pyrimidine derivatives possessing cell-cycle inhibitors activity
US7595325B2 (en) 2004-05-27 2009-09-29 Pfizer Inc. Substituted pyrrolo[2,3-d]pyrimidine derivatives useful in cancer treatment
US7655652B2 (en) 2004-02-03 2010-02-02 Astrazeneca Ab Imidazolo-5-yl-2-anilinopyrimidines as agents for the inhibition of cell proliferation
US7745428B2 (en) 2005-09-30 2010-06-29 Astrazeneca Ab Imidazo[1,2-A]pyridine having anti-cell-proliferation activity
WO2010099137A2 (fr) 2009-02-26 2010-09-02 Osi Pharmaceuticals, Inc. Procédés in situ pour surveiller l'état emt de cellules tumorales in vivo
WO2010099139A2 (fr) 2009-02-25 2010-09-02 Osi Pharmaceuticals, Inc. Thérapie anti-cancer combinée
WO2010099364A2 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Méthodes d'identification d'agents qui inhibent les cellules cancéreuses mésenchymateuses ou leur formation
WO2010099363A1 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Méthodes d'identification d'agents qui inhibent les cellules cancéreuses mésenchymateuses ou leur formation
WO2010099138A2 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Procédés pour l'identification d'agents qui inhibent les cellules tumorales de type mésenchymateuses ou leur formation
WO2010126960A1 (fr) * 2009-04-29 2010-11-04 Locus Pharmaceuticals, Inc. Composés de pyrrolotriazine
EP2251340A1 (fr) 2003-07-10 2010-11-17 Aventis Pharma S.A. Tetrahydro-1h-pyrazolo[3,4-c] pyridines substituees, compositions les contenant et utilisation
EP2258700A1 (fr) 2006-05-09 2010-12-08 Pfizer Products Inc. Dérivés d'acides aminés cycloalkyles et compositions pharmaceutiques les contenant
WO2011109584A2 (fr) 2010-03-03 2011-09-09 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de kinase du récepteur du facteur de croissance insulinique 1
WO2011109572A2 (fr) 2010-03-03 2011-09-09 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de kinase du récepteur du facteur de croissance insulinique 1
WO2011112666A1 (fr) 2010-03-09 2011-09-15 OSI Pharmaceuticals, LLC Thérapie anticancéreuse combinatoire
US8133899B2 (en) 2008-08-20 2012-03-13 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
WO2012116040A1 (fr) 2011-02-22 2012-08-30 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de la kinase du récepteur du facteur de croissance 1 analogue à l'insuline dans le carcinome hépatocellulaire
WO2012120469A1 (fr) * 2011-03-08 2012-09-13 Novartis Ag Composés hétéroaryliques bicycliques de type fluorophényle
WO2012149014A1 (fr) 2011-04-25 2012-11-01 OSI Pharmaceuticals, LLC Utilisation de signatures de gènes de tem dans la découverte de médicaments contre le cancer, diagnostics et traitement du cancer
US8377946B1 (en) 2011-12-30 2013-02-19 Pharmacyclics, Inc. Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors
WO2013152252A1 (fr) 2012-04-06 2013-10-10 OSI Pharmaceuticals, LLC Polythérapie antinéoplasique
WO2014017659A1 (fr) 2012-07-27 2014-01-30 独立行政法人理化学研究所 Agent destiné à traiter ou à supprimer une récidive de leucémie myélogène aiguë
US8710104B2 (en) 2008-11-07 2014-04-29 Triact Therapeutics, Inc. Catecholic butanes and use thereof for cancer therapy
WO2015068767A1 (fr) 2013-11-08 2015-05-14 小野薬品工業株式会社 Dérivé de pyrrolopyrimidine
WO2015077866A1 (fr) * 2013-11-26 2015-06-04 Pharmascience Inc. Inhibiteurs de protéines kinases
WO2015132799A3 (fr) * 2014-02-03 2015-11-12 Cadila Healthcare Limited Nouveaux composés hétérocycliques
US9321772B2 (en) 2011-09-02 2016-04-26 The Regents Of The University Of California Substituted pyrazolo[3,4-D]pyrimidines and uses thereof
US9381246B2 (en) 2013-09-09 2016-07-05 Triact Therapeutics, Inc. Cancer therapy
US9624224B2 (en) 2013-09-30 2017-04-18 Pharmacyclics Llc Inhibitors of Bruton's tyrosine kinase
US9758524B2 (en) 2011-07-19 2017-09-12 Merck Sharp & Dohme B.V. 4-imidazopyridazin-1-yl-benzamides as Btk inhibitors
US9834575B2 (en) 2013-02-26 2017-12-05 Triact Therapeutics, Inc. Cancer therapy
US9862722B2 (en) 2011-07-13 2018-01-09 Pharmacyclics Llc Inhibitors of Bruton's tyrosine kinase
US10131668B2 (en) 2012-09-26 2018-11-20 The Regents Of The University Of California Substituted imidazo[1,5-a]pYRAZINES for modulation of IRE1
JP2018536716A (ja) * 2015-12-02 2018-12-13 アストライア セラピューティクス， エルエルシーＡｓｔｒａｅａ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｌｌｃ ピペリジニルノシセプチン受容体化合物
US10426760B2 (en) 2007-07-17 2019-10-01 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
WO2021038540A1 (fr) 2019-08-31 2021-03-04 Sun Pharma Advanced Research Company Limited Acides cycloalkylidènecarboxyliques et dérivés en tant qu'inhibiteurs de la btk
US11166951B2 (en) 2014-08-11 2021-11-09 Acerta Pharma B.V. Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor, a JAK-2 inhibitor, and/or a BCL-2 inhibitor
CN115298177A (zh) * 2019-10-11 2022-11-04 因赛特公司 作为cdk2抑制剂的双环胺
US11827617B2 (en) 2015-12-02 2023-11-28 Astraea Therapeutics, Llc Piperidinyl nociceptin receptor compounds

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2397575A1 (fr) * 2000-01-13 2001-07-19 Tularik Inc. Agents antibacteriens
US7338957B2 (en) * 2003-08-28 2008-03-04 Irm Llc Compounds and compositions as protein kinase inhibitors
TW200626142A (en) * 2004-09-21 2006-08-01 Glaxo Group Ltd Chemical compounds
CA2605738C (fr) * 2005-04-25 2013-10-01 Merck Patent Gesellschaft Mit Beschraenkter Haftung Nouveaux aza-heterocycles constituant des inhibiteurs de kinases
EP2004645A2 (fr) * 2006-02-14 2008-12-24 Vertex Pharmaceuticals, Inc. Pyrrolo(3,2-c) pyridines utiles en tant qu' inhibiteurs de proteines-kinases
US8217177B2 (en) * 2006-07-14 2012-07-10 Amgen Inc. Fused heterocyclic derivatives and methods of use
ES2570429T3 (es) * 2008-10-16 2016-05-18 Univ California Inhibidores de heteroaril quinasa de anillo condensado
JPWO2010084944A1 (ja) * 2009-01-22 2012-07-19 田辺三菱製薬株式会社 新規ピロロ［２，３−ｄ］ピリミジン化合物
US7718662B1 (en) * 2009-10-12 2010-05-18 Pharmacyclics, Inc. Pyrazolo-pyrimidine inhibitors of bruton's tyrosine kinase
EP2809673B1 (fr) 2012-01-31 2016-11-02 Nanjing Allgen Pharma Co. Ltd. Molécules spirocycliques en tant qu'inhibiteurs de tyrosine kinase de bruton
CA2833701A1 (fr) * 2013-11-19 2015-05-19 Pharmascience Inc. Inhibiteurs de proteine kinase
KR20210057014A (ko) * 2018-09-13 2021-05-20 깃세이 야쿠힌 고교 가부시키가이샤 이미다조피리디논 화합물
CN112961159B (zh) * 2020-03-05 2022-07-01 四川大学华西医院 氨基嘧啶并吡唑/吡咯类衍生物及其制备方法和用途
CN112961158B (zh) * 2020-03-05 2022-07-01 四川大学华西医院 氨基嘧啶并吡唑/吡咯类衍生物及其制备方法和用途
CN117402161A (zh) * 2022-07-06 2024-01-16 上海科恩泰生物医药科技有限公司 一种具有fgfr抑制作用的亚砜亚胺类化合物、包含其的药物组合物及其用途

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3036390A1 (de) * 1980-09-26 1982-05-13 Troponwerke GmbH & Co KG, 5000 Köln Neue pyrrolo-pyrimidine, verfahren zu ihrer herstellung und ihre verwendung bei der herstellung von biologischen wirkstoffen
EP0496617A1 (fr) * 1991-01-23 1992-07-29 Gensia, Inc. Inhibiteurs de kinase d'adénosine
WO1994017803A1 (fr) * 1993-02-03 1994-08-18 Gensia, Inc. Inhibiteurs de l'adenosine kinase
WO1996010028A1 (fr) * 1994-09-29 1996-04-04 Novartis Ag PYRROLO[2,3-d]PYRIMIDINES ET LEUR UTILISATION
WO1996040686A1 (fr) * 1995-06-07 1996-12-19 Abbott Laboratories Composes de cyclopentane substitue heterocycliques
WO1997028161A1 (fr) * 1996-02-01 1997-08-07 Novartis Ag Nouvelles pyrrolo(2,3-d)pyrimidines et leur utilisation en tant qu'inhibiteurs de tyrosine kinase
US5665721A (en) * 1995-06-07 1997-09-09 Abbott Laboratories Heterocyclic substituted cyclopentane compounds
WO1997032879A1 (fr) * 1996-03-06 1997-09-12 Novartis Ag 7-ALKYLE-PYRROLO[2,3-d]PYRIMIDINES
WO1997034895A1 (fr) * 1996-03-15 1997-09-25 Novartis Ag NOUVELLES N-7-HETEROCYCLYL-PYRROLO[2,3-d]PYRIMIDINES ET LEUR UTILISATION
WO1998041525A1 (fr) * 1997-03-19 1998-09-24 Basf Aktiengesellschaft Pyrrolo [2,3] pyrimidines et leur utilisation comme inhibiteurs de la tyrosine kinase

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3036390A1 (de) * 1980-09-26 1982-05-13 Troponwerke GmbH & Co KG, 5000 Köln Neue pyrrolo-pyrimidine, verfahren zu ihrer herstellung und ihre verwendung bei der herstellung von biologischen wirkstoffen
EP0496617A1 (fr) * 1991-01-23 1992-07-29 Gensia, Inc. Inhibiteurs de kinase d'adénosine
WO1994017803A1 (fr) * 1993-02-03 1994-08-18 Gensia, Inc. Inhibiteurs de l'adenosine kinase
WO1996010028A1 (fr) * 1994-09-29 1996-04-04 Novartis Ag PYRROLO[2,3-d]PYRIMIDINES ET LEUR UTILISATION
WO1996040686A1 (fr) * 1995-06-07 1996-12-19 Abbott Laboratories Composes de cyclopentane substitue heterocycliques
US5665721A (en) * 1995-06-07 1997-09-09 Abbott Laboratories Heterocyclic substituted cyclopentane compounds
WO1997028161A1 (fr) * 1996-02-01 1997-08-07 Novartis Ag Nouvelles pyrrolo(2,3-d)pyrimidines et leur utilisation en tant qu'inhibiteurs de tyrosine kinase
WO1997032879A1 (fr) * 1996-03-06 1997-09-12 Novartis Ag 7-ALKYLE-PYRROLO[2,3-d]PYRIMIDINES
WO1997034895A1 (fr) * 1996-03-15 1997-09-25 Novartis Ag NOUVELLES N-7-HETEROCYCLYL-PYRROLO[2,3-d]PYRIMIDINES ET LEUR UTILISATION
WO1998041525A1 (fr) * 1997-03-19 1998-09-24 Basf Aktiengesellschaft Pyrrolo [2,3] pyrimidines et leur utilisation comme inhibiteurs de la tyrosine kinase
NO994509L (no) * 1997-03-19 1999-09-17 Basf Ag Pyrrolo[2,3]pyrimidiner og deres anvendelse som tyrosinaseinhibitorer

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
C. G. DAVE ET AL.: "Synthesis & Biologic Activity of Pyrrolo[2,3-d]pyrimidines", INDIAN J. CHEM. SECT. B, vol. 27, no. 1-12, 1988, pages 778 - 780, XP002125874 *

Cited By (127)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7569569B2 (en) 1998-06-19 2009-08-04 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
US6635762B1 (en) 1998-06-19 2003-10-21 Pfizer Inc. Monocyclic-7H-pyrrolo[2,3-d]pyrimidine compounds, compositions, and methods of use
US6632820B1 (en) 1998-08-29 2003-10-14 Astrazeneca Ab Pyrimidine compounds
US7176212B2 (en) 1998-08-29 2007-02-13 Astrazeneca Ab 2,4-diamino pyrimidine compounds having anti-cell proliferative activity
US6713474B2 (en) 1998-09-18 2004-03-30 Abbott Gmbh & Co. Kg Pyrrolopyrimidines as therapeutic agents
US6593326B1 (en) 1998-12-24 2003-07-15 Astrazeneca Ab 2,4-diamino pyrimidine compounds having anti-cell proliferative activity
US6716831B1 (en) 1999-03-06 2004-04-06 Astrazeneca Ab 2,4-diamino-pyrimidine deprivatives having anti-cell proliferative activity
US6670368B1 (en) 1999-04-06 2003-12-30 Astrazeneca Ab Pyrimidine compounds with pharmaceutical activity
US6855719B1 (en) 1999-08-21 2005-02-15 Astrazeneca Ab Imidazo[1,2-A]pyridine and pyrazolo[2,3-A]pyridine derivatives
US7265221B2 (en) 1999-12-10 2007-09-04 Pfizer, Inc. Pyrrolo[2,3-d]pyrimidine compounds
US7601727B2 (en) 1999-12-10 2009-10-13 Pfizer, Inc. Pyrrolo[2,3-d]pyrimidine compounds
US7091208B2 (en) 1999-12-10 2006-08-15 Pfizer Inc. Pyrrolo[2,3-D]pyrimidine compounds
US7842699B2 (en) 1999-12-10 2010-11-30 Pfizer Inc. Pyrrolo[2,3-D]pyrimidine compounds
US6627754B2 (en) 1999-12-10 2003-09-30 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
USRE41783E1 (en) 1999-12-10 2010-09-28 Pfizer Inc. Pyrrolo[2,3-D]pyrimidine compounds
US6838464B2 (en) 2000-03-01 2005-01-04 Astrazeneca Ab 2,4-Di(hetero-)arylamino(-oxy)-5-substituted pyrimidines as antineaoplastic agents
US7153964B2 (en) 2000-03-01 2006-12-26 Astrazeneca Ab Pyrimidine compounds
US6710052B2 (en) 2000-03-01 2004-03-23 Astrazeneca Pyrimidine compounds
US6649608B2 (en) 2000-03-01 2003-11-18 Astrazeneca Ab 2,4-di(hetero-)arylamino (oxy)-5-substituted pyrimidines as antineoplastic agents
US7067522B2 (en) 2000-03-01 2006-06-27 Astrazeneca Ab 2,4,DI (hetero-) arylamino (-oxy)-5-substituted pyrimidines as antineoplastic agents
US6906065B2 (en) 2000-03-28 2005-06-14 Astrazeneca Ab 4-Amino-5-cyano-2-anilino-pyrimidine derivatives and their use as inhibitors of cell-cycle kinases
US7369946B2 (en) 2000-03-29 2008-05-06 Abbott Gmbh & Co. Kg Method of identifying inhibitors of Tie-2
WO2001072751A1 (fr) * 2000-03-29 2001-10-04 Knoll Gesellschaft Mit Beschraenkter Haftung Pyrrolopyrimidines utilisees comme inhibiteurs de tyrosine kinases
US6696567B2 (en) 2000-06-26 2004-02-24 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
EP1686130A1 (fr) * 2000-06-26 2006-08-02 Pfizer Products Incorporated Pyrrolo[2,3-d]pyrimidines comme agents immunosuppressifs.
WO2002000661A1 (fr) * 2000-06-26 2002-01-03 Pfizer Products Inc. Composes pyrrolo[2,3-d]pyrimidine en tant qu'agents immunosuppresseurs
US7192963B2 (en) 2000-06-26 2007-03-20 Pfizer Inc Pyrrolo[2,3-d]pyrimidine compounds
CN100351253C (zh) * 2000-06-26 2007-11-28 辉瑞产品公司 作为免疫抑制剂的吡咯并[2,3－d]嘧啶化合物
US6908920B2 (en) 2000-07-11 2005-06-21 Astrazeneca Ab Pyrimidine derivatives
US6844341B2 (en) 2001-02-17 2005-01-18 Astrazeneca Ab Pyrimidine derivatives for inhibition of cell proliferation
US7081454B2 (en) 2001-03-28 2006-07-25 Bristol-Myers Squibb Co. Tyrosine kinase inhibitors
US7223757B2 (en) 2001-03-28 2007-05-29 Bristol-Myers Squibb Company Tyrosine kinase inhibitors
US7326699B2 (en) 2001-05-14 2008-02-05 Novartis Ag 4-Amino-5-phenyl-7-cyclobutyl-pyrrolo(2,3-d)pyrimidine derivatives
US6939872B2 (en) 2001-05-30 2005-09-06 Astrazeneca Ab 2-anilino-pyrimidine derivatives as cyclin dependent kinase inhibitors
CN100372849C (zh) * 2001-08-30 2008-03-05 诺瓦提斯公司 作为半胱氨酸蛋白酶抑制剂的吡咯并嘧啶化合物
US7465728B2 (en) 2002-03-09 2008-12-16 Astrazeneca Ab Derivatives of 4-(imidazol-5-yl)-2-(4-sulfoanilino)pyrimidine with CDK inhibitory activity
US7446105B2 (en) 2002-03-09 2008-11-04 Astrazeneca Ab Pyrimidine compounds
US7485638B2 (en) 2002-03-09 2009-02-03 Astrazeneca Ab Pyrimidine compounds
US7442697B2 (en) 2002-03-09 2008-10-28 Astrazeneca Ab 4-imidazolyl substituted pyrimidine derivatives with CDK inhibitory activity
US7427616B2 (en) 2002-08-06 2008-09-23 Astrazeneca Ab Condensed pyridines and pyrimidines with tie2 (TEK) activity
WO2004043962A1 (fr) * 2002-11-12 2004-05-27 Novartis Ag Derives de 4-amino-5-phenyl-7-cyclohexyl-pyrrolo[2,3-d]pyrimidine
US7250420B2 (en) 2002-11-26 2007-07-31 Pfizer Inc. Method of treatment of transplant rejection
US7271262B2 (en) 2002-12-19 2007-09-18 Pfizer Inc Pyrrolopyrimidine derivatives
US7345038B2 (en) 2003-03-12 2008-03-18 Pfizer, Inc Pyridyloxymethyl and benzisoxazole azabicyclic derivatives
US7427626B2 (en) 2003-05-16 2008-09-23 Astrazeneca Ab 2-Anilino-4-(imidazol-5-yl)-pyrimidine derivatives and their use as cdk (cdk2) inhibitors
US7579344B2 (en) 2003-05-16 2009-08-25 Astrazeneca Ab Pyrimidine derivatives possessing cell-cycle inhibitors activity
EP2251340A1 (fr) 2003-07-10 2010-11-17 Aventis Pharma S.A. Tetrahydro-1h-pyrazolo[3,4-c] pyridines substituees, compositions les contenant et utilisation
US7312215B2 (en) 2003-07-29 2007-12-25 Bristol-Myers Squibb Company Benzimidazole C-2 heterocycles as kinase inhibitors
JP2007511596A (ja) * 2003-11-17 2007-05-10 ファイザー・プロダクツ・インク 癌の治療において有用なピロロピリミジン化合物
US7655652B2 (en) 2004-02-03 2010-02-02 Astrazeneca Ab Imidazolo-5-yl-2-anilinopyrimidines as agents for the inhibition of cell proliferation
US20060025383A1 (en) * 2004-02-03 2006-02-02 Neil Wishart Aminobenzoxazoles as therapeutic agents
US8735405B2 (en) 2004-04-02 2014-05-27 OSI Pharmaceuticals, LLC 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitors
EP2168968A1 (fr) * 2004-04-02 2010-03-31 OSI Pharmaceuticals, Inc. Inhibiteurs hétérobicycliques de la protéine kinase à anneau bicyclique substitué en 6,6
EP2305682A1 (fr) 2004-04-02 2011-04-06 OSI Pharmaceuticals, Inc. Inhibiteurs hétérobicycliques de la protéine kinase à anneau bicyclique substitué en 6,6
EA012873B1 (ru) * 2004-04-02 2009-12-30 Оси Фармасьютикалз, Инк. 6,6-бициклические кольцевые замещенные гетеробициклические ингибиторы протеинкиназ
US8101613B2 (en) 2004-04-02 2012-01-24 OSI Pharmaceuticals, LLC 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitors
EP2308879A1 (fr) 2004-04-02 2011-04-13 OSI Pharmaceuticals, Inc. Inhibiteurs hétérobicycliques de la protéine kinase à anneau bicyclique substitué en 6,6
US8367826B2 (en) 2004-04-02 2013-02-05 OSI Pharmaceuticals, LLC 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitors
CN102924458A (zh) * 2004-04-02 2013-02-13 Osi制药有限责任公司 6,6-双环取代的杂双环蛋白激酶抑制剂
WO2005097800A1 (fr) * 2004-04-02 2005-10-20 Osi Pharmaceuticals, Inc. Inhibiteurs de la proteine kinase heterobicycliques a substitution de noyau bicyclique 6,6
CN102924458B (zh) * 2004-04-02 2014-11-05 Osi制药有限责任公司 6,6-双环取代的杂双环蛋白激酶抑制剂
US7820662B2 (en) 2004-04-02 2010-10-26 Osi Pharmaceuticals, Inc. 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitors
US7595325B2 (en) 2004-05-27 2009-09-29 Pfizer Inc. Substituted pyrrolo[2,3-d]pyrimidine derivatives useful in cancer treatment
WO2006012422A1 (fr) 2004-07-20 2006-02-02 Osi Pharmaceuticals, Inc. Imidazotriazines comme inhibiteurs de la tyrosine kinase
WO2006102079A1 (fr) * 2005-03-17 2006-09-28 Novartis Ag N- [3- (1-amin0-5, 6, 7, 8-tetrahydro-2, 4, 4b-triazafluoren-9-yle)-phenyl] benzamides utilises en tant qu'inhibiteurs de tyrosine/threonine kinase, en particulier la b-raf kinase
EP2372363A1 (fr) 2005-09-20 2011-10-05 OSI Pharmaceuticals, Inc. Marqueurs biologiques prédictifs d'une réaction anticancéreuse aux inhibiteurs kinase du récepteur du facteur de croissance 1 analogue à l'insuline
WO2007035744A1 (fr) 2005-09-20 2007-03-29 Osi Pharmaceuticals, Inc. Marqueurs biologiques predictifs d'une reaction anticancereuse aux inhibiteurs kinase du recepteur du facteur de croissance 1 analogue a l'insuline
US7745428B2 (en) 2005-09-30 2010-06-29 Astrazeneca Ab Imidazo[1,2-A]pyridine having anti-cell-proliferation activity
US8431695B2 (en) 2005-11-02 2013-04-30 Bayer Intellectual Property Gmbh Pyrrolo[2,1-f][1,2,4]triazin-4-ylamines IGF-1R kinase inhibitors for the treatment of cancer and other hyperproliferative diseases
WO2007056170A3 (fr) * 2005-11-02 2008-01-03 Bayer Healthcare Ag Derives pyrrolo-[2,1-f]-[1,2,4]-triazin-4-ylamines inhibiteurs de la igf-1r kinase pour le traitement des cancers et autres maladies hyperproliferatives
WO2007064993A2 (fr) 2005-12-02 2007-06-07 Osi Pharmaceuticals, Inc. Inhibiteurs bicycliques de la proteine kinase
EP2258700A1 (fr) 2006-05-09 2010-12-08 Pfizer Products Inc. Dérivés d'acides aminés cycloalkyles et compositions pharmaceutiques les contenant
US10426760B2 (en) 2007-07-17 2019-10-01 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US8987283B2 (en) 2008-08-20 2015-03-24 Zoetis Llc Pyrrolo[2,3-D]pyrimidine compounds
US9271981B2 (en) 2008-08-20 2016-03-01 Zoetis Services Llc Pyrrolo[2,3-D]pyrimidine compounds
US8133899B2 (en) 2008-08-20 2012-03-13 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
US9161939B2 (en) 2008-08-20 2015-10-20 Zoetis Services Llc Pyrrolo[2,3-d]pyrimidine compounds
US8710104B2 (en) 2008-11-07 2014-04-29 Triact Therapeutics, Inc. Catecholic butanes and use thereof for cancer therapy
WO2010099139A2 (fr) 2009-02-25 2010-09-02 Osi Pharmaceuticals, Inc. Thérapie anti-cancer combinée
WO2010099137A2 (fr) 2009-02-26 2010-09-02 Osi Pharmaceuticals, Inc. Procédés in situ pour surveiller l'état emt de cellules tumorales in vivo
WO2010099364A2 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Méthodes d'identification d'agents qui inhibent les cellules cancéreuses mésenchymateuses ou leur formation
WO2010099363A1 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Méthodes d'identification d'agents qui inhibent les cellules cancéreuses mésenchymateuses ou leur formation
WO2010099138A2 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Procédés pour l'identification d'agents qui inhibent les cellules tumorales de type mésenchymateuses ou leur formation
EP2424368A4 (fr) * 2009-04-29 2012-10-17 Locus Pharmaceuticals Inc Composés de pyrrolotriazine
WO2010126960A1 (fr) * 2009-04-29 2010-11-04 Locus Pharmaceuticals, Inc. Composés de pyrrolotriazine
US8765754B2 (en) 2009-04-29 2014-07-01 Locus Pharmaceuticals, Inc. Pyrrolotriazine compounds
EP2424368A1 (fr) * 2009-04-29 2012-03-07 Locus Pharmaceuticals, Inc. Composés de pyrrolotriazine
WO2011109584A2 (fr) 2010-03-03 2011-09-09 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de kinase du récepteur du facteur de croissance insulinique 1
WO2011109572A2 (fr) 2010-03-03 2011-09-09 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de kinase du récepteur du facteur de croissance insulinique 1
WO2011112666A1 (fr) 2010-03-09 2011-09-15 OSI Pharmaceuticals, LLC Thérapie anticancéreuse combinatoire
WO2012116040A1 (fr) 2011-02-22 2012-08-30 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de la kinase du récepteur du facteur de croissance 1 analogue à l'insuline dans le carcinome hépatocellulaire
WO2012120469A1 (fr) * 2011-03-08 2012-09-13 Novartis Ag Composés hétéroaryliques bicycliques de type fluorophényle
CN103492390A (zh) * 2011-03-08 2014-01-01 诺瓦提斯公司 氟苯基双环杂芳基化合物
WO2012149014A1 (fr) 2011-04-25 2012-11-01 OSI Pharmaceuticals, LLC Utilisation de signatures de gènes de tem dans la découverte de médicaments contre le cancer, diagnostics et traitement du cancer
US9862722B2 (en) 2011-07-13 2018-01-09 Pharmacyclics Llc Inhibitors of Bruton's tyrosine kinase
US10934296B2 (en) 2011-07-19 2021-03-02 Merck Sharp & Dohme B.V. 4-imidazopyridazin-1-yl-benzamides as Btk inhibitors
US10239883B2 (en) 2011-07-19 2019-03-26 Merck Sharp & Dohme B.V. 4-imidazopyridazin-1-yl-benzamides as BTK inhibitors
US9758524B2 (en) 2011-07-19 2017-09-12 Merck Sharp & Dohme B.V. 4-imidazopyridazin-1-yl-benzamides as Btk inhibitors
US9790226B2 (en) 2011-07-19 2017-10-17 Merck Sharp & Dohme B.V. 4-imidazopyridazin-1-yl-benzamides and 4-imidazotriazin-1-yl-benzamides as BtK inhibitors
US9895373B2 (en) 2011-09-02 2018-02-20 The Regents Of The University Of California Substituted pyrazolo[3,4-D]pyrimidines and uses thereof
US9321772B2 (en) 2011-09-02 2016-04-26 The Regents Of The University Of California Substituted pyrazolo[3,4-D]pyrimidines and uses thereof
US9273051B2 (en) 2011-12-30 2016-03-01 Pharmacyclics Llc Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors
US8377946B1 (en) 2011-12-30 2013-02-19 Pharmacyclics, Inc. Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors
US9546172B2 (en) 2011-12-30 2017-01-17 Pharmacyclics Llc Pyrazolo[3,4-d]pyrimidine and pyrazolo[2,3-d]pyrimidine compounds as kinase inhibitors
WO2013152252A1 (fr) 2012-04-06 2013-10-10 OSI Pharmaceuticals, LLC Polythérapie antinéoplasique
US9604988B2 (en) 2012-07-27 2017-03-28 Riken Agent for treating or inhibiting recurrence of acute myeloid leukemia
WO2014017659A1 (fr) 2012-07-27 2014-01-30 独立行政法人理化学研究所 Agent destiné à traiter ou à supprimer une récidive de leucémie myélogène aiguë
US10822340B2 (en) 2012-09-26 2020-11-03 The Regents Of The University Of California Substituted imidazolopyrazine compounds and methods of using same
US11613544B2 (en) 2012-09-26 2023-03-28 The Regents Of The University Of California Substituted imidazo[1,5-a]pyrazines for modulation of IRE1
US10131668B2 (en) 2012-09-26 2018-11-20 The Regents Of The University Of California Substituted imidazo[1,5-a]pYRAZINES for modulation of IRE1
US9834575B2 (en) 2013-02-26 2017-12-05 Triact Therapeutics, Inc. Cancer therapy
US9381246B2 (en) 2013-09-09 2016-07-05 Triact Therapeutics, Inc. Cancer therapy
US9624224B2 (en) 2013-09-30 2017-04-18 Pharmacyclics Llc Inhibitors of Bruton's tyrosine kinase
EP3067356A4 (fr) * 2013-11-08 2017-03-22 ONO Pharmaceutical Co., Ltd. Dérivé de pyrrolopyrimidine
US9586967B2 (en) 2013-11-08 2017-03-07 Ono Pharmaceutical Co., Ltd. Pyrrolo pyrimidine derivative
WO2015068767A1 (fr) 2013-11-08 2015-05-14 小野薬品工業株式会社 Dérivé de pyrrolopyrimidine
WO2015077866A1 (fr) * 2013-11-26 2015-06-04 Pharmascience Inc. Inhibiteurs de protéines kinases
US9840509B2 (en) 2014-02-03 2017-12-12 Cadila Healthcare Limited Heterocyclic compounds
WO2015132799A3 (fr) * 2014-02-03 2015-11-12 Cadila Healthcare Limited Nouveaux composés hétérocycliques
US11166951B2 (en) 2014-08-11 2021-11-09 Acerta Pharma B.V. Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor, a JAK-2 inhibitor, and/or a BCL-2 inhibitor
US11654143B2 (en) 2014-08-11 2023-05-23 Acerta Pharma B.V. Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor, a JAK-2 inhibitor, and/or a BCL-2 inhibitor
JP2018536716A (ja) * 2015-12-02 2018-12-13 アストライア セラピューティクス， エルエルシーＡｓｔｒａｅａ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｌｌｃ ピペリジニルノシセプチン受容体化合物
JP7011596B2 (ja) 2015-12-02 2022-02-10 アストライア セラピューティクス， エルエルシー ピペリジニルノシセプチン受容体化合物
US11827617B2 (en) 2015-12-02 2023-11-28 Astraea Therapeutics, Llc Piperidinyl nociceptin receptor compounds
USRE49825E1 (en) 2015-12-02 2024-02-06 Astraea Therapeutics, Llc Piperidinyl nociceptin receptor compounds
WO2021038540A1 (fr) 2019-08-31 2021-03-04 Sun Pharma Advanced Research Company Limited Acides cycloalkylidènecarboxyliques et dérivés en tant qu'inhibiteurs de la btk
CN115298177A (zh) * 2019-10-11 2022-11-04 因赛特公司 作为cdk2抑制剂的双环胺

Also Published As

Publication number Publication date
NO20011356D0 (no) 2001-03-16
HUP0200403A2 (en) 2002-06-29
PL346700A1 (en) 2002-02-25
AU753555C (en) 2003-07-03
AU753555B2 (en) 2002-10-24
JP2002526500A (ja) 2002-08-20
CN1335849A (zh) 2002-02-13
CZ2001960A3 (cs) 2001-10-17
KR20010085824A (ko) 2001-09-07
ID29028A (id) 2001-07-26
TR200101186T2 (tr) 2001-10-22
SK3842001A3 (en) 2002-04-04
BG105346A (en) 2001-12-29
HUP0200403A3 (en) 2004-07-28
CA2344249A1 (fr) 2000-03-30
NO20011356L (no) 2001-05-16
EP1114053A1 (fr) 2001-07-11
HK1039326A1 (zh) 2002-04-19
IL141866A0 (en) 2002-03-10
BR9913887A (pt) 2001-10-23
AU6048499A (en) 2000-04-10
NZ510588A (en) 2003-08-29

Similar Documents

Publication Publication Date Title
AU753555C (en) Pyrrolopyrimidines as protein kinase inhibitors
US6713474B2 (en) Pyrrolopyrimidines as therapeutic agents
EP1114052B1 (fr) 4-aminopyrrolopyrimidines utilisees comme inhibiteurs de kinases
WO2001072751A1 (fr) Pyrrolopyrimidines utilisees comme inhibiteurs de tyrosine kinases
US7829570B2 (en) Substituted 4-amino isoxazolo[5,4-d]pyrimidines as kinase inhibitors
CA2440714C (fr) Pyrazolopyrimidines utiles comme agents therapeutiques
EP1212327B1 (fr) Pyrazolopyrimidines en tant qu'agents therapeutiques
US7863444B2 (en) 4-aminopyrrolopyrimidines as kinase inhibitors
US20030199525A1 (en) Kinase inhibitors
EP1268481A2 (fr) Inhibiteurs de kinase utilises comme agents therapeutiques
US20020156081A1 (en) Pyrazolopyrimidines as therapeutic agents
MXPA01002785A (en) Pyrrolopyrimidines as protein kinase inhibitors
AU2002316030A1 (en) Pyrazolopyrimidines as therapeutic agents

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 99813217.9

Country of ref document: CN

WWE Wipo information: entry into national phase

Ref document number: 09537167

Country of ref document: US

AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 141866

Country of ref document: IL

ENP Entry into the national phase

Ref document number: 2344249

Country of ref document: CA

Ref document number: 2344249

Country of ref document: CA

Kind code of ref document: A

Ref document number: 1999 105346

Country of ref document: BG

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: PV2001-960

Country of ref document: CZ

WWE Wipo information: entry into national phase

Ref document number: 1999969415

Country of ref document: EP

Ref document number: 2001/02204

Country of ref document: ZA

Ref document number: 510588

Country of ref document: NZ

Ref document number: PA/a/2001/002785

Country of ref document: MX

Ref document number: 3842001

Country of ref document: SK

Ref document number: 60484/99

Country of ref document: AU

Ref document number: 200102204

Country of ref document: ZA

Ref document number: IN/PCT/2001/376/CHE

Country of ref document: IN

ENP Entry into the national phase

Ref document number: 2000 574112

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 1020017003532

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: P20010283A

Country of ref document: HR

WWE Wipo information: entry into national phase

Ref document number: 2001/01186

Country of ref document: TR

WWP Wipo information: published in national office

Ref document number: 1999969415

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWP Wipo information: published in national office

Ref document number: 1020017003532

Country of ref document: KR

WWP Wipo information: published in national office

Ref document number: PV2001-960

Country of ref document: CZ

WWG Wipo information: grant in national office

Ref document number: 60484/99

Country of ref document: AU

WWW Wipo information: withdrawn in national office

Ref document number: 1999969415

Country of ref document: EP

WWR Wipo information: refused in national office

Ref document number: 1020017003532

Country of ref document: KR