CA2871650C - Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (par4) inhibitors for treating platelet aggregation - Google Patents

Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (par4) inhibitors for treating platelet aggregation Download PDF

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Publication number
CA2871650C
CA2871650C CA2871650A CA2871650A CA2871650C CA 2871650 C CA2871650 C CA 2871650C CA 2871650 A CA2871650 A CA 2871650A CA 2871650 A CA2871650 A CA 2871650A CA 2871650 C CA2871650 C CA 2871650C
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alkyl
halo
alkoxy
substituted
groups
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French (fr)
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CA2871650A1 (en
Inventor
Jacques Banville
Roger Remillard
Edward H. Ruediger
Daniel H. Deon
Marc Gagnon
Laurence Dube
Julia GUY
Eldon Scott Priestley
Shoshana L. POSY
Brad D. MAXWELL
Pancras C. Wong
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Universite de Montreal
Bristol Myers Squibb Co
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Universite de Montreal
Bristol Myers Squibb Co
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    • 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
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/433—Thidiazoles
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    • 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
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    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4355—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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    • 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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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    • A61K31/4965—Non-condensed pyrazines
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    • A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
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    • 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
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    • 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
    • A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/54—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 sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • A—HUMAN NECESSITIES
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    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
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    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/041—Heterocyclic compounds
    • A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K51/0453—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
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    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
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    • C07D513/04—Ortho-condensed systems
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    • 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
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    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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  • Health & Medical Sciences (AREA)
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  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
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  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
CA2871650A 2012-04-26 2013-04-24 Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (par4) inhibitors for treating platelet aggregation Active CA2871650C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201261638577P 2012-04-26 2012-04-26
US61/638,577 2012-04-26
US201361787680P 2013-03-15 2013-03-15
US61/787,680 2013-03-15
PCT/US2013/037956 WO2013163279A1 (en) 2012-04-26 2013-04-24 Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (par4) inhibitors for treating platelet aggregation

Publications (2)

Publication Number Publication Date
CA2871650A1 CA2871650A1 (en) 2013-10-31
CA2871650C true CA2871650C (en) 2017-09-19

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CA2871650A Active CA2871650C (en) 2012-04-26 2013-04-24 Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (par4) inhibitors for treating platelet aggregation

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US (6) US9688695B2 (enExample)
EP (3) EP3632919B1 (enExample)
JP (1) JP6073464B2 (enExample)
KR (3) KR20200127273A (enExample)
CN (2) CN108383858B (enExample)
AR (1) AR090834A1 (enExample)
AU (1) AU2013251632B2 (enExample)
BR (1) BR112014026643B1 (enExample)
CA (1) CA2871650C (enExample)
CL (1) CL2014002915A1 (enExample)
CO (1) CO7160040A2 (enExample)
CY (2) CY1119466T1 (enExample)
DK (3) DK2841437T3 (enExample)
EA (1) EA026724B1 (enExample)
ES (3) ES2640916T3 (enExample)
FI (1) FI3632919T3 (enExample)
HR (3) HRP20221495T1 (enExample)
HU (3) HUE048654T2 (enExample)
IL (1) IL235246B (enExample)
LT (2) LT2841437T (enExample)
MX (1) MX354175B (enExample)
MY (1) MY175061A (enExample)
NZ (1) NZ631027A (enExample)
PE (1) PE20142285A1 (enExample)
PH (1) PH12014502173B1 (enExample)
PL (3) PL3632919T3 (enExample)
PT (3) PT2841437T (enExample)
RS (3) RS63975B1 (enExample)
SG (1) SG11201406757SA (enExample)
SI (3) SI3243826T1 (enExample)
SM (3) SMT202000049T1 (enExample)
TN (1) TN2014000436A1 (enExample)
TW (1) TWI572605B (enExample)
UY (1) UY34763A (enExample)
WO (1) WO2013163279A1 (enExample)
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JP6073464B2 (ja) * 2012-04-26 2017-02-01 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ 血小板凝集を治療するためのプロテアーゼ活性化受容体４（ｐａｒ４）阻害剤としてのイミダゾチアジアゾールおよびイミダゾピラジン誘導体
EP2847200B1 (en) * 2012-04-26 2017-03-29 Bristol-Myers Squibb Company Imidazothiadiazole derivatives as protease activated receptor 4 (par4) inhibitors for treating platelet aggregation
EP2855489B1 (en) 2012-04-26 2017-01-04 Bristol-Myers Squibb Company Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (par4) inhibitors for treating platelet aggregation
TWI568722B (zh) 2012-06-15 2017-02-01 葛蘭馬克製藥公司 作爲ｍＰＧＥＳ－１抑制劑之三唑酮化合物
EP2943485B1 (en) 2013-01-14 2017-09-20 Incyte Holdings Corporation Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors
HUE050215T2 (hu) 2013-01-15 2020-11-30 Incyte Holdings Corp Pim kináz inhibitorokként hasznos tiazolkarboxamid és piridinkarboxamid vegyületek
TW201605866A (zh) 2013-08-23 2016-02-16 英塞特公司 可用作ｐｉｍ激酶抑制劑之呋喃并－及噻吩并－吡啶甲醯胺化合物
US9617279B1 (en) 2014-06-24 2017-04-11 Bristol-Myers Squibb Company Imidazooxadiazole compounds
US9598419B1 (en) 2014-06-24 2017-03-21 Universite De Montreal Imidazotriazine and imidazodiazine compounds
US9580418B2 (en) 2014-07-14 2017-02-28 Incyte Corporation Bicyclic aromatic carboxamide compounds useful as Pim kinase inhibitors
WO2016010897A1 (en) 2014-07-14 2016-01-21 Incyte Corporation Bicyclic heteroaromatic carboxamide compounds useful as pim kinase inhibitors
ES2929208T3 (es) 2015-02-26 2022-11-25 Univ Montreal Compuestos de imidazotiadiazol como inhibidores de PAR4
EP3262052A1 (en) 2015-02-26 2018-01-03 Bristol-Myers Squibb Company Benzothiazole and benzothiophne compounds
US9540347B2 (en) 2015-05-29 2017-01-10 Incyte Corporation Pyridineamine compounds useful as Pim kinase inhibitors
US9789087B2 (en) 2015-08-03 2017-10-17 Thomas Jefferson University PAR4 inhibitor therapy for patients with PAR4 polymorphism
TWI734699B (zh) 2015-09-09 2021-08-01 美商英塞特公司 Ｐｉｍ激酶抑制劑之鹽
WO2017059251A1 (en) 2015-10-02 2017-04-06 Incyte Corporation Heterocyclic compounds useful as pim kinase inhibitors
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