[go: up one dir, main page]

WO2014093230A3 - Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity - Google Patents

Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity Download PDF

Info

Publication number
WO2014093230A3
WO2014093230A3 PCT/US2013/073895 US2013073895W WO2014093230A3 WO 2014093230 A3 WO2014093230 A3 WO 2014093230A3 US 2013073895 W US2013073895 W US 2013073895W WO 2014093230 A3 WO2014093230 A3 WO 2014093230A3
Authority
WO
WIPO (PCT)
Prior art keywords
pyrimidine
pyridine compounds
compositions
production
methods
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/US2013/073895
Other languages
French (fr)
Other versions
WO2014093230A2 (en
Inventor
Lesley Liu-Bujalski
Theresa L. Johnson
Andreas Goutopoulos
Hui QIU
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.)
Merck Patent GmbH
Original Assignee
Merck Patent GmbH
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 Merck Patent GmbH filed Critical Merck Patent GmbH
Publication of WO2014093230A2 publication Critical patent/WO2014093230A2/en
Publication of WO2014093230A3 publication Critical patent/WO2014093230A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—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
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • 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
    • 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
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/68—One oxygen atom attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/73—Unsubstituted amino or imino radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/34—One oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D239/48—Two nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/10—Spiro-condensed systems
    • 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
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention provides novel pyrimidine and pyridine compounds which are attached to a warhead, and the manufacture and use for the treatment of hyperproliferative diseases including, but not limited to, cancer, lupus, allergic disorders, Sjogren's disease and rheumatoid arthritis. The invention also describes kinase inhibitors including, but not limited to, inhibitors of Bruton's tyrosine kinase.
PCT/US2013/073895 2012-12-10 2013-12-09 Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity Ceased WO2014093230A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261735186P 2012-12-10 2012-12-10
US61/735,186 2012-12-10

Publications (2)

Publication Number Publication Date
WO2014093230A2 WO2014093230A2 (en) 2014-06-19
WO2014093230A3 true WO2014093230A3 (en) 2014-08-28

Family

ID=49885412

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2013/073895 Ceased WO2014093230A2 (en) 2012-12-10 2013-12-09 Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity

Country Status (1)

Country Link
WO (1) WO2014093230A2 (en)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10857140B2 (en) 2015-05-06 2020-12-08 The Regents Of The University Of California K-Ras modulators
TWI858413B (en) * 2015-11-04 2024-10-11 德商默克專利有限公司 Use of pyrimidine and pyridine compounds with btk inhibitory activity
US10716788B2 (en) 2015-11-17 2020-07-21 Merck Patent Gmbh Methods for treating MS using pyrimidine and pyridine compounds with BTK inhibitory activity
CN113444047B (en) * 2016-07-20 2023-06-16 纳莹(上海)生物科技有限公司 Fluorescent probe and preparation method and application thereof
EP3612526A2 (en) 2017-04-20 2020-02-26 The Regents of the University of California K-ras modulators
TWI694995B (en) * 2017-11-06 2020-06-01 美商美國禮來大藥廠 BTK inhibitor compounds
CN109824603B (en) * 2017-11-23 2021-03-12 浙江省化工研究院有限公司 Pyrimidinamine compound, preparation method and application thereof
CN108069911A (en) * 2017-12-14 2018-05-25 中国药科大学 6- amino -2- phenyl pyrimidine classes compound, preparation method and medical usage
US11325896B2 (en) 2017-12-20 2022-05-10 Vanderbilt University Antagonists of the muscarinic acetylcholine receptor M4
WO2019204442A1 (en) * 2018-04-18 2019-10-24 Theras, Inc. K-ras modulators with a cyanoacrylamide moiety
CN112250666B (en) * 2020-10-09 2022-01-14 广东东阳光药业有限公司 Substituted pyrimidines and their use
US11866421B2 (en) 2021-05-31 2024-01-09 Epigen Biosciences, Inc. Pyrimidine and pyridine amine compounds and usage thereof in disease treatment

Citations (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0658548A1 (en) * 1993-12-17 1995-06-21 Tanabe Seiyaku Co., Ltd. Benzenesulfonamide derivative and process for preparing thereof
WO1996029301A1 (en) * 1995-03-21 1996-09-26 Agrevo Uk Limited Fungicidal compounds
JPH0959160A (en) * 1995-06-16 1997-03-04 Tanabe Seiyaku Co Ltd Pharmaceutical composition
WO1997044325A1 (en) * 1996-05-22 1997-11-27 Basf Aktiengesellschaft 2-(o-[pyrimidin-4-yl]methylene oxy)phenyl acetic acid derivatives and their use in combatting noxious fungi and animal pests
WO2005070934A1 (en) * 2004-01-14 2005-08-04 Amgen Inc. Substituted diazabicycloheptanes and their use as protein kinase inhibitors
US20060217417A1 (en) * 2005-03-28 2006-09-28 Boehringer Ingelheim International Gmbh Pyridine derivatives useful as inhibitors of pkc-theta
WO2007084786A1 (en) * 2006-01-20 2007-07-26 Novartis Ag Pyrimidine derivatives used as pi-3 kinase inhibitors
WO2010022725A1 (en) * 2008-08-27 2010-03-04 Leo Pharma A/S Pyridine derivatives as vegfr-2 receptor and protein tyrosine kinase inhibitors
JP2010209277A (en) * 2009-03-12 2010-09-24 Konica Minolta Medical & Graphic Inc Organic piezoelectric material, ultrasonic vibrator element and ultrasonic probe
WO2011060440A2 (en) * 2009-11-16 2011-05-19 The Regents Of The University Of California Kinase inhibitors
WO2011099764A2 (en) * 2010-02-09 2011-08-18 Hanmi Holdings Co., Ltd. Novel pyrimidine derivative for inhibiting the growth of cancer cells
US20120208815A1 (en) * 2007-03-01 2012-08-16 Matthew Burger Pim kinase inhibitors and methods of their use
WO2012158843A2 (en) * 2011-05-17 2012-11-22 The Regents Of The University Of California Kinase inhibitors
WO2012170976A2 (en) * 2011-06-10 2012-12-13 Merck Patent Gmbh Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity

Patent Citations (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0658548A1 (en) * 1993-12-17 1995-06-21 Tanabe Seiyaku Co., Ltd. Benzenesulfonamide derivative and process for preparing thereof
WO1996029301A1 (en) * 1995-03-21 1996-09-26 Agrevo Uk Limited Fungicidal compounds
JPH0959160A (en) * 1995-06-16 1997-03-04 Tanabe Seiyaku Co Ltd Pharmaceutical composition
WO1997044325A1 (en) * 1996-05-22 1997-11-27 Basf Aktiengesellschaft 2-(o-[pyrimidin-4-yl]methylene oxy)phenyl acetic acid derivatives and their use in combatting noxious fungi and animal pests
WO2005070934A1 (en) * 2004-01-14 2005-08-04 Amgen Inc. Substituted diazabicycloheptanes and their use as protein kinase inhibitors
US20060217417A1 (en) * 2005-03-28 2006-09-28 Boehringer Ingelheim International Gmbh Pyridine derivatives useful as inhibitors of pkc-theta
WO2007084786A1 (en) * 2006-01-20 2007-07-26 Novartis Ag Pyrimidine derivatives used as pi-3 kinase inhibitors
US20120208815A1 (en) * 2007-03-01 2012-08-16 Matthew Burger Pim kinase inhibitors and methods of their use
WO2010022725A1 (en) * 2008-08-27 2010-03-04 Leo Pharma A/S Pyridine derivatives as vegfr-2 receptor and protein tyrosine kinase inhibitors
JP2010209277A (en) * 2009-03-12 2010-09-24 Konica Minolta Medical & Graphic Inc Organic piezoelectric material, ultrasonic vibrator element and ultrasonic probe
WO2011060440A2 (en) * 2009-11-16 2011-05-19 The Regents Of The University Of California Kinase inhibitors
WO2011099764A2 (en) * 2010-02-09 2011-08-18 Hanmi Holdings Co., Ltd. Novel pyrimidine derivative for inhibiting the growth of cancer cells
WO2012158843A2 (en) * 2011-05-17 2012-11-22 The Regents Of The University Of California Kinase inhibitors
WO2012170976A2 (en) * 2011-06-10 2012-12-13 Merck Patent Gmbh Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; CORNELL, CLIVE LEONARD ET AL: "Preparation of 2-naphthyl-3-methoxyacrylates as agrochemical fungicides and pesticides", XP002725287, retrieved from STN Database accession no. 1996:716436 *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; DENNY, WILLIAM A. ET AL: "Potential antitumor agents. 29. Quantitative structure-activity relationships for the antileukemic bisquaternary ammonium heterocycles", XP002725283, retrieved from STN Database accession no. 1979:66509 *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; NISHIKUBO, YUICHI: "Organic piezoelectric materials, ultrasonic vibrators therewith, and ultrasound probes therewith", XP002720931, retrieved from STN Database accession no. 2010:1193753 *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; PEGIADOU, S. ET AL: "The synthesis and characterization of new polymerizable pyrimidines: immobilization of the monomers onto hydrophilic graft copolymeric supports through radiation-induced copolymerization-grafting", XP002725282, retrieved from STN Database accession no. 1998:592481 *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; RACK, MICHAEL ET AL: "Preparation of .alpha.-[2-(pyrimidinyloxymethyl)phenyl]acrylates as agrochemical fungicides and pesticides", XP002725285, retrieved from STN Database accession no. 1997:776155 *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; SHULTZ, MICHAEL D. ET AL: "Optimization of the in vitro cardiac safety of hydroxamate-based Histone deacetylase inhibitors", XP002720930, retrieved from STN Database accession no. 2011:776102 *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; YAMADA, KOICHIRO ET AL: "Preparation of (N-pyrimidinyl)benzenesulfonamide endothelin antagonists", XP002725288, retrieved from STN Database accession no. 1995:890091 *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; YAMADA, KOICHIRO ET AL: "Preparation of pyrimidine derivatives as endothelin antagonists", XP002725286, retrieved from STN Database accession no. 1997:257401 *
DENNY, WILLIAM A. ET AL: "Potential antitumor agents. 29. Quantitative structure-activity relationships for the antileukemic bisquaternary ammonium heterocycles", JOURNAL OF MEDICINAL CHEMISTRY , 22(2), 134-50 CODEN: JMCMAR; ISSN: 0022-2623, 1979, DOI: 10.1021/JM00188A005 *
MI YOUNG CHA ET AL: "Synthesis and Biological Evaluation of Pyrimidine-Based Dual Inhibitors of Human Epidermal Growth Factor Receptor 1 (HER-1) and HER-2 Tyrosine Kinases", JOURNAL OF MEDICINAL CHEMISTRY, vol. 55, no. 6, 22 March 2012 (2012-03-22), pages 2846 - 2857, XP055104213, ISSN: 0022-2623, DOI: 10.1021/jm201758g *
PEGIADOU, S. ET AL: "The synthesis and characterization of new polymerizable pyrimidines: immobilization of the monomers onto hydrophilic graft copolymeric supports through radiation-induced copolymerization-grafting", JOURNAL OF APPLIED POLYMER SCIENCE , 70(2), 211-218 CODEN: JAPNAB; ISSN: 0021-8995, 1998, DOI: 10.1002/(SICI)1097-4628(19981010)70:2<211::AID-APP1>3.0.CO;2-X *
SHULTZ, MICHAEL D. ET AL: "Optimization of the in vitro cardiac safety of hydroxamate-based Histone deacetylase inhibitors", JOURNAL OF MEDICINAL CHEMISTRY , 54(13), 4752-4772 CODEN: JMCMAR; ISSN: 0022-2623, 2011, DOI: 10.1021/JM200388E *

Also Published As

Publication number Publication date
WO2014093230A2 (en) 2014-06-19

Similar Documents

Publication Publication Date Title
WO2014093230A3 (en) Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity
WO2012170976A3 (en) Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity
MX2015007101A (en) Compounds useful as inhibitors of atr kinase.
NZ700580A (en) Compounds useful as inhibitors of atr kinase and combination therapies thereof
SA515360007B1 (en) Heteroaromatic compounds as bruton&#39;s tyrosine kinase (BTK) inhibitors
WO2015039612A8 (en) Compound inhibiting activities of btk and/or jak3 kinases
WO2014145028A3 (en) N-acyl-n&#39;-(pyridin-2-yl) ureas and analogs exhibiting anti-cancer and anti-proliferative activities
HK1214823A1 (en) Tricyclic fused thiophene derivatives as jak inhibitors
HK1246286A1 (en) Lrrk2 inhibitors and methods of making and using the same
MY199511A (en) Novel condensed pyrimidine compound or salt thereof
WO2011143425A3 (en) Compounds useful as inhibitors of atr kinase
WO2014143242A8 (en) Compounds useful as inhibitors of atr kinase
MX2015011818A (en) Quinazoline inhibitors of activating mutant forms of epidermal growth factor receptor.
WO2011143423A3 (en) Compounds useful as inhibitors of atr kinase
HK1199643A1 (en) Oxazolidin- 2 -one compounds and uses thereof as pi3ks inhibitors
WO2014145029A3 (en) N-acyl-n&#39;-(pyridin-2-yl) ureas and analogs exhibiting anti-cancer and anti-proliferative activities
MX380147B (en) SUSTAINED-RELEASE RUXOLITINIB DOSAGE FORMS.
WO2012162254A8 (en) Inhibitors of lrrk2 kinase activity
WO2013151665A3 (en) Modified polynucleotides for the production of proteins associated with human disease
HK1216425A1 (en) 2,3-dihydroimidazol[1,2-c]pyrimidin-5(1h)-one based lipoprotein-associated phospholipase a2 (lp-pla2) inhibitors
TN2017000144A1 (en) 2-amino-6-(difluoromethyl)- 5,5-difluoro-6-phenyl-3,4,5,6-tetrahydropyridines as bace1 inhibitors
TN2017000415A1 (en) Heterocyclylmethyl-thienouracile as antagonists of the adenosine-a2b-receptor
TW201613896A (en) Novel 2,5-substituted pyrimidines
NZ702254A (en) 5-amino[1,4]thiazines as bace 1 inhibitors
HK1201523A1 (en) Heterocyclic carboxamides useful as inhibitors of phosphodiesterase type 10a

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13814709

Country of ref document: EP

Kind code of ref document: A2

122 Ep: pct application non-entry in european phase

Ref document number: 13814709

Country of ref document: EP

Kind code of ref document: A2