WO2015006754A3 - Pyrimidine derivatives as kinase inhibitors - Google Patents

Pyrimidine derivatives as kinase inhibitors Download PDF

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Publication number
WO2015006754A3
WO2015006754A3 PCT/US2014/046442 US2014046442W WO2015006754A3 WO 2015006754 A3 WO2015006754 A3 WO 2015006754A3 US 2014046442 W US2014046442 W US 2014046442W WO 2015006754 A3 WO2015006754 A3 WO 2015006754A3
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WO
WIPO (PCT)
Prior art keywords
kinase inhibitors
pyrimidine derivatives
compositions
methods
disease
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US2014/046442
Other languages
French (fr)
Other versions
WO2015006754A2 (en
Inventor
Xiao Xu
Xiaobo Wang
Long Mao
Li Zhao
Biao Xi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Acea Biosciences Inc
Original Assignee
Acea Biosciences Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to CN202011022304.XA priority Critical patent/CN112592334B/en
Priority to MX2016000261A priority patent/MX368491B/en
Priority to CN201480049793.4A priority patent/CN105916851A/en
Priority to JP2016525833A priority patent/JP6564771B2/en
Priority to NZ715687A priority patent/NZ715687A/en
Priority to CN202310865044.XA priority patent/CN117486865A/en
Priority to KR1020167002970A priority patent/KR102173433B1/en
Priority to RU2016104388A priority patent/RU2677653C2/en
Priority to EP14748351.5A priority patent/EP3019496B1/en
Priority to BR112016000195A priority patent/BR112016000195A8/en
Priority to SG11201600062RA priority patent/SG11201600062RA/en
Application filed by Acea Biosciences Inc filed Critical Acea Biosciences Inc
Priority to AU2014287016A priority patent/AU2014287016B2/en
Priority to ES14748351T priority patent/ES2761572T3/en
Priority to CA2917364A priority patent/CA2917364C/en
Priority to HK16111490.4A priority patent/HK1223351B/en
Priority to DK14748351T priority patent/DK3019496T3/en
Publication of WO2015006754A2 publication Critical patent/WO2015006754A2/en
Publication of WO2015006754A3 publication Critical patent/WO2015006754A3/en
Priority to IL243420A priority patent/IL243420A0/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61P17/06—Antipsoriatics
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
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    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
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    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C07D239/49—Two nitrogen atoms with an aralkyl radical, or substituted aralkyl radical, attached in position 5, e.g. trimethoprim
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    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
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    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/553—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with halogen atoms or nitro radicals directly attached to ring carbon atoms, e.g. fluorouracil
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    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
    • C—CHEMISTRY; METALLURGY
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    • 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

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  • Chemical & Material Sciences (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Immunology (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

The present invention relates to pharmaceutical compounds, compositions and methods, especially as they are related to compositions and methods for the treatment and/or prevention of a proliferation disorder, a cancer, a tumor, an inflammatory disease, an autoimmune disease, psoriasis, dry eye or an immunologically related disease, and in some embodiments diseases or disorders related to the dysregulation of kinase such as, but not limited to, EGFR (including HER), Alk, PDGFR, BLK, BMX/ETK, FLT3(D835Y), ITK, TEC, TXK, BTK, or JAK, and the respective pathways.
PCT/US2014/046442 2013-07-11 2014-07-11 Heterocyclic compounds and uses thereof Ceased WO2015006754A2 (en)

Priority Applications (17)

Application Number Priority Date Filing Date Title
SG11201600062RA SG11201600062RA (en) 2013-07-11 2014-07-11 Pyrimidine derivatives as kinase inhibitors
CN201480049793.4A CN105916851A (en) 2013-07-11 2014-07-11 Pyrimidine derivatives as kinase inhibitors
JP2016525833A JP6564771B2 (en) 2013-07-11 2014-07-11 Pyrimidine derivatives as kinase inhibitors
NZ715687A NZ715687A (en) 2013-07-11 2014-07-11 Pyrimidine derivatives as kinase inhibitors
CN202310865044.XA CN117486865A (en) 2013-07-11 2014-07-11 Pyrimidine derivatives as kinase inhibitors
KR1020167002970A KR102173433B1 (en) 2013-07-11 2014-07-11 Pyrimidine derivatives as kinase inhibitors
RU2016104388A RU2677653C2 (en) 2013-07-11 2014-07-11 Pyrimidine derivatives as kinase inhibitors
EP14748351.5A EP3019496B1 (en) 2013-07-11 2014-07-11 Pyrimidine derivatives as kinase inhibitors
AU2014287016A AU2014287016B2 (en) 2013-07-11 2014-07-11 Pyrimidine derivatives as kinase inhibitors
CN202011022304.XA CN112592334B (en) 2013-07-11 2014-07-11 Pyrimidine derivatives as kinase inhibitors
MX2016000261A MX368491B (en) 2013-07-11 2014-07-11 Pyrimidine derivatives as kinase inhibitors.
BR112016000195A BR112016000195A8 (en) 2013-07-11 2014-07-11 heterocyclic compounds, pharmaceutical composition, combination, their use, and method for inhibiting a btk or jak tyrosine kinase activity, egfr, alk, pdgfr, blk, bmx / etk, flt3 (d835y), itk, tec, txk, and their respective ways
ES14748351T ES2761572T3 (en) 2013-07-11 2014-07-11 Pyrimidine derivatives as kinase inhibitors
CA2917364A CA2917364C (en) 2013-07-11 2014-07-11 Heterocyclic compounds and uses thereof
HK16111490.4A HK1223351B (en) 2013-07-11 2014-07-11 Pyrimidine derivatives as kinase inhibitors
DK14748351T DK3019496T3 (en) 2013-07-11 2014-07-11 PYRIMIDINE DERIVATIVES AS KINASE INHIBITORS
IL243420A IL243420A0 (en) 2013-07-11 2015-12-30 Heterocyclic compounds and uses thereof

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201361845342P 2013-07-11 2013-07-11
US61/845,342 2013-07-11
US201461923179P 2014-01-02 2014-01-02
US61/923,179 2014-01-02

Publications (2)

Publication Number Publication Date
WO2015006754A2 WO2015006754A2 (en) 2015-01-15
WO2015006754A3 true WO2015006754A3 (en) 2015-03-12

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2014/046442 Ceased WO2015006754A2 (en) 2013-07-11 2014-07-11 Heterocyclic compounds and uses thereof

Country Status (16)

Country Link
US (1) US10562918B2 (en)
EP (1) EP3019496B1 (en)
JP (1) JP6564771B2 (en)
KR (1) KR102173433B1 (en)
CN (3) CN112592334B (en)
AU (1) AU2014287016B2 (en)
BR (1) BR112016000195A8 (en)
CA (1) CA2917364C (en)
DK (1) DK3019496T3 (en)
ES (1) ES2761572T3 (en)
IL (1) IL243420A0 (en)
MX (1) MX368491B (en)
NZ (1) NZ715687A (en)
RU (1) RU2677653C2 (en)
SG (1) SG11201600062RA (en)
WO (1) WO2015006754A2 (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9388185B2 (en) 2012-08-10 2016-07-12 Incyte Holdings Corporation Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors
US9580423B2 (en) 2015-02-20 2017-02-28 Incyte Corporation Bicyclic heterocycles as FGFR4 inhibitors
US10449196B2 (en) 2012-08-06 2019-10-22 ACEA Therapeutics, Inc. EGFR modulators and uses thereof
US10533011B2 (en) 2015-10-09 2020-01-14 ACEA Therapeutics, Inc. Pharmaceutical salts, physical forms, and compositions of pyrrolopyrimidine kinase inhibitors, and methods of making same
US11566028B2 (en) 2019-10-16 2023-01-31 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
US11591329B2 (en) 2019-07-09 2023-02-28 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors

Families Citing this family (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8754114B2 (en) 2010-12-22 2014-06-17 Incyte Corporation Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3
WO2013106792A1 (en) 2012-01-13 2013-07-18 Acea Biosciences Inc. Heterocyclic compounds and uses as anticancer agents.
US9464089B2 (en) 2012-01-13 2016-10-11 Acea Biosciences Inc. Heterocyclic compounds and uses thereof
RS58514B1 (en) 2012-06-13 2019-04-30 Incyte Holdings Corp Substituted tricyclic compounds as fgfr inhibitors
US9266892B2 (en) 2012-12-19 2016-02-23 Incyte Holdings Corporation Fused pyrazoles as FGFR inhibitors
PH12015502383B1 (en) 2013-04-19 2023-02-03 Incyte Holdings Corp Bicyclic heterocycles as fgfr inhibitors
KR102173433B1 (en) 2013-07-11 2020-11-04 에이시아 바이오사이언시스 인코포레이티드. Pyrimidine derivatives as kinase inhibitors
BR112016005199B1 (en) 2013-08-23 2022-02-22 Neupharma, Inc CERTAIN CHEMICAL COMPOUNDS, COMPOSITIONS, AND METHODS
WO2016054987A1 (en) * 2014-10-11 2016-04-14 上海翰森生物医药科技有限公司 Egfr inhibitor, and preparation and application thereof
US10851105B2 (en) 2014-10-22 2020-12-01 Incyte Corporation Bicyclic heterocycles as FGFR4 inhibitors
JP6854762B2 (en) 2014-12-23 2021-04-07 ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド Inhibitor of cyclin-dependent kinase 7 (CDK7)
CN105884695B (en) * 2015-02-13 2019-02-26 山东轩竹医药科技有限公司 Heterocyclic Derivative Tyrosine Kinase Inhibitors
TWI712601B (en) 2015-02-20 2020-12-11 美商英塞特公司 Bicyclic heterocycles as fgfr inhibitors
MA41551A (en) 2015-02-20 2017-12-26 Incyte Corp BICYCLIC HETEROCYCLES USED AS FGFR4 INHIBITORS
USRE50776E1 (en) 2015-03-27 2026-02-03 Dana-Farber Cancer Institute, Inc. Inhibitors of cyclin-dependent kinases
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