JP6564062B2 - ５−リポキシゲナーゼ活性化タンパク質（ｆｌａｐ）阻害剤として有用なピラゾール誘導体 - Google Patents

５−リポキシゲナーゼ活性化タンパク質（ｆｌａｐ）阻害剤として有用なピラゾール誘導体 Download PDF

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JP6564062B2
JP6564062B2 JP2017555792A JP2017555792A JP6564062B2 JP 6564062 B2 JP6564062 B2 JP 6564062B2 JP 2017555792 A JP2017555792 A JP 2017555792A JP 2017555792 A JP2017555792 A JP 2017555792A JP 6564062 B2 JP6564062 B2 JP 6564062B2
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mmol
methyl
reaction mixture
pyrazol
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JP2018514535A (ja
JP2018514535A5 (enExample
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ヨハン・オロフ・ブロッデファルク
ハンス・フレデリク・エムテネス
ケネト・ラーシュ・グランバリ
マーリン・アニタ・レムレル
ダニエル・トール・ペッテルセン
アレン・トーマス・プロウライト
ラーシュ・ヨハン・アンドレアス・ウランデル
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AstraZeneca AB
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/38—Nitrogen atoms
    • C07D231/40—Acylated on said nitrogen atom
    • 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
    • A61K31/41—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
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring 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
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • 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
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
    • C07D231/46—Oxygen atom in position 3 or 5 and nitrogen atom in position 4
    • C07D231/50—Acylated on said nitrogen atom
    • 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
    • C07D417/00—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
    • C07D417/02—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
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Epidemiology (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Vascular Medicine (AREA)
  • Pulmonology (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
JP2017555792A 2015-05-04 2016-05-03 ５−リポキシゲナーゼ活性化タンパク質（ｆｌａｐ）阻害剤として有用なピラゾール誘導体 Active JP6564062B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562156424P 2015-05-04 2015-05-04
US62/156,424 2015-05-04
PCT/EP2016/059848 WO2016177703A1 (en) 2015-05-04 2016-05-03 Pyrazole derivatives useful as 5-lipoxygenase activating protein (flap) inhibitors

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JP2018514535A JP2018514535A (ja) 2018-06-07
JP2018514535A5 JP2018514535A5 (enExample) 2019-05-16
JP6564062B2 true JP6564062B2 (ja) 2019-08-21

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Cited By (1)

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JP2019537586A (ja) * 2016-10-28 2019-12-26 アストラゼネカ・アクチエボラーグＡｓｔｒａｚｅｎｅｃａ Ａｋｔｉｅｂｏｌａｇ （１Ｒ，２Ｒ）−２−［４−（３−メチル−１Ｈ−ピラゾール−５−イル）ベンゾイル］−Ｎ−（４−オキソ−４，５，６，７−テトラヒドロピラゾロ［１，５−ａ］ピラジン−３−イル）シクロヘキサンカルボキサミド

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EA032221B1 (ru) 2015-05-04 2019-04-30 Астразенека Аб Производные пиразола, пригодные в качестве ингибиторов белка, активирующего 5-липоксигеназу (flap)
GB201905721D0 (en) 2019-04-24 2019-06-05 Univ Dundee Compounds
CN110169969B (zh) * 2019-06-28 2022-05-27 南京医科大学 Mk571在制备预防和治疗心脏病药物中应用
CN111084775A (zh) * 2020-02-17 2020-05-01 牡丹江医学院 一种用于治疗癫痫的药物组合物
CN111419800B (zh) * 2020-04-23 2021-03-19 温州医科大学附属第二医院、温州医科大学附属育英儿童医院 用于治疗红斑狼疮的药物制剂及其制备方法
CN111643498B (zh) * 2020-07-20 2021-05-07 黑龙江中医药大学 一种治疗肾结石的药物组合物及其用途
CN111714499B (zh) * 2020-07-27 2021-05-11 黑龙江中医药大学 一种用于治疗多囊卵巢综合征的药物组合物

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EP1670804A2 (en) * 2003-09-10 2006-06-21 GPC Biotech AG Heterobicyclic compounds as pharmaceutically active agents
GB2431927B (en) * 2005-11-04 2010-03-17 Amira Pharmaceuticals Inc 5-Lipoxygenase-activating protein (FLAP) inhibitors
TW200815351A (en) * 2006-05-02 2008-04-01 Astrazeneca Ab Novel compounds
WO2008097930A1 (en) * 2007-02-05 2008-08-14 Amira Pharmaceuticals, Inc. Reverse indoles as 5-lipoxygenase-activating protein (flap) inhibitors
GB0702456D0 (en) * 2007-02-08 2007-03-21 Astrazeneca Ab New combination
JP2010524944A (ja) * 2007-04-20 2010-07-22 シェーリング コーポレイション テトラヒドロピリド［４，３−ｄ］ピリミジノン誘導体およびそれらの使用方法
BRPI0811204A8 (pt) * 2007-05-10 2015-09-22 Bristol Myers Squibb Co Tetra-hidroibenzo-1,4-diazepinas substituídas por arila e heteroarila e uso das mesmas para bloquear a recaptação de norepinefrina, dopamina e serotonina
EP2207547A4 (en) * 2007-10-05 2010-11-17 Amira Pharmaceuticals Inc PROTEIN INHIBITORS THAT ACTIVATE 5-LIPOXYGENASE
EA032221B1 (ru) * 2015-05-04 2019-04-30 Астразенека Аб Производные пиразола, пригодные в качестве ингибиторов белка, активирующего 5-липоксигеназу (flap)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019537586A (ja) * 2016-10-28 2019-12-26 アストラゼネカ・アクチエボラーグＡｓｔｒａｚｅｎｅｃａ Ａｋｔｉｅｂｏｌａｇ （１Ｒ，２Ｒ）−２−［４−（３−メチル−１Ｈ−ピラゾール−５−イル）ベンゾイル］−Ｎ−（４−オキソ−４，５，６，７−テトラヒドロピラゾロ［１，５−ａ］ピラジン−３−イル）シクロヘキサンカルボキサミド
JP7041146B2 (ja) 2016-10-28 2022-03-23 アストラゼネカ・アクチエボラーグ （１Ｒ，２Ｒ）－２－［４－（３－メチル－１Ｈ－ピラゾール－５－イル）ベンゾイル］－Ｎ－（４－オキソ－４，５，６，７－テトラヒドロピラゾロ［１，５－ａ］ピラジン－３－イル）シクロヘキサンカルボキサミド

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US20240317767A1 (en) 2024-09-26
CY1125179T1 (el) 2023-03-24
PT3292105T (pt) 2019-12-13
MY186647A (en) 2021-08-03
PH12017502112B1 (en) 2021-07-02
EA201792341A1 (ru) 2018-05-31
SI3292105T1 (sl) 2020-01-31
LT3670499T (lt) 2021-12-27
PL3670499T3 (pl) 2022-02-14
CN107646036A (zh) 2018-01-30
IL255069B (en) 2019-12-31
EP3292105B1 (en) 2019-10-02
US20230219967A1 (en) 2023-07-13
PT3670499T (pt) 2021-12-24
AU2016258874A1 (en) 2017-12-14
DK3670499T3 (da) 2022-01-03
HUE056875T2 (hu) 2022-03-28
EP3670499B1 (en) 2021-09-29
US12024523B2 (en) 2024-07-02
CA2983668A1 (en) 2016-11-10
JP2018514535A (ja) 2018-06-07
KR20180002784A (ko) 2018-01-08
TW201713625A (zh) 2017-04-16
NZ737672A (en) 2020-11-27
CO2017011506A2 (es) 2018-01-31
DOP2017000244A (es) 2017-11-15
HK1245255A1 (en) 2018-08-24
HRP20192172T1 (hr) 2020-02-21
PL3292105T3 (pl) 2020-04-30
EP3670499A1 (en) 2020-06-24
TN2017000458A1 (en) 2019-04-12
HRP20211993T1 (hr) 2022-04-01
KR102623474B1 (ko) 2024-01-09
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MX2017013571A (es) 2018-02-26
ES2760466T3 (es) 2020-05-14
US20210355127A1 (en) 2021-11-18
BR112017022757A2 (pt) 2018-07-17
US10508119B2 (en) 2019-12-17
RS59671B1 (sr) 2020-01-31
ME03663B (me) 2020-07-20
US11001589B2 (en) 2021-05-11
US20180237439A1 (en) 2018-08-23
SG11201708558RA (en) 2017-11-29
BR112017022757B1 (pt) 2023-02-23
PH12017502112A1 (en) 2018-05-07
SI3670499T1 (sl) 2022-02-28
US11691978B2 (en) 2023-07-04
GT201700220A (es) 2018-12-19
SV2017005549A (es) 2018-03-12
ZA201708189B (en) 2018-11-28
SMT201900691T1 (it) 2020-01-14
IL255069A0 (en) 2017-12-31
RS62729B1 (sr) 2022-01-31
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AU2016258874B2 (en) 2020-04-30
DK3292105T3 (da) 2019-12-09
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US20190084991A1 (en) 2019-03-21
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EA032221B1 (ru) 2019-04-30
CL2017002660A1 (es) 2018-04-13
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WO2016177703A1 (en) 2016-11-10
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