JP2020505460A - ポリヒドロキシフタラジノン化合物、その製造方法および利用 - Google Patents
ポリヒドロキシフタラジノン化合物、その製造方法および利用 Download PDFInfo
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- JP2020505460A JP2020505460A JP2019560453A JP2019560453A JP2020505460A JP 2020505460 A JP2020505460 A JP 2020505460A JP 2019560453 A JP2019560453 A JP 2019560453A JP 2019560453 A JP2019560453 A JP 2019560453A JP 2020505460 A JP2020505460 A JP 2020505460A
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- polyhydroxyphthalazinone
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- 230000036581 peripheral resistance Effects 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000003075 phytoestrogen Substances 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
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- 238000012545 processing Methods 0.000 description 1
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- 230000001737 promoting effect Effects 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
-
- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
-
- 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
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (10)
- 化学構造一般式が式(I)で示されることを特徴とするポリヒドロキシフタラジノン化合物。 (式中、R1、R2、R3、R4は、それぞれ独立して水素、ヒドロキシ基、C1〜3アルコキシ基またはハロゲンであり、R5は、水素、C1〜4アルキル基、C1〜4ハロゲン化アルキル基、フェニル基またはシアノ基であり、R6は、水素またはハロゲンである。)
- 前記R1、R2、R3はヒドロキシ基であり、R4およびR6は水素であり、R5は水素、C1〜4アルキル基、C1〜4ハロゲン化アルキル基、フェニル基またはシアノ基であることを特徴とする請求項1に記載のポリヒドロキシフタラジノン化合物。
- 前記R1、R2、R3はヒドロキシ基であり、R4およびR6は水素であり、R5は塩素または臭素であることを特徴とする請求項1に記載のポリヒドロキシフタラジノン化合物。
- 前記R1、R2、R3はヒドロキシ基であり、R4は水素またはハロゲンであり、R5は水素であり、R6は塩素または臭素であることを特徴とする請求項1に記載のポリヒドロキシフタラジノン化合物。
- 化合物(1)を出発原料としてアルキルまたはフェニルグリニャール試薬と反応させ、対応する第二級アルコール化合物(2)を得て、さらに化合物(3)に臭化し、化合物(3)は、カルボキシル化反応を経て化合物(4)を得て、化合物(4)は、酸化させ(5)を生成し、化合物(5)および対応するヒドラジンは、縮合反応を経て化合物(6)を生成し、化合物(6)は、脱メチル反応を経て、目的化合物(7)を得るステップを含み、化学反応式は以下のとおりであることを特徴とする請求項2に記載のポリヒドロキシフタラジノン化合物の製造方法。
- 化合物(8)とヒドラジンと縮合させ化合物(9)を生成し、化合物(9)は、さらにハロゲン化反応を経て中間体(10)を得て、化合物(10)は脱メチル反応を経て、目的化合物(11)を得るステップを含み、化学反応式は以下のとおりであることを特徴とする請求項3に記載のポリヒドロキシフタラジノン化合物の製造方法。
- 化合物(12)とブロモスクシンイミドまたはクロロスクシンイミドとを反応させ化合物(13)を生成し、化合物(13)は、さらに脱メチル化反応を経て、目的化合物(14)を得るステップを含み、化学反応式は以下のとおりであることを特徴とする請求項4に記載のポリヒドロキシフタラジノン化合物の製造方法。
- エストロゲンに関連する疾患を治療および/または予防する医薬品の製造における請求項1〜4のいずれかに記載のポリヒドロキシフタラジノン化合物の利用。
- 前記エストロゲンに関連する疾患は、前立腺疾患、腫瘍、尿道生殖器疾患、胃腸疾患、炎症、骨粗鬆症、末梢血管疾患、アルツハイマー病、パーキンソン病、脳卒中、眼疾患、関節炎、更年期ホットフラッシュ、心血管疾患、肥満および脂肪肝を含むことを特徴とする請求項8に記載の利用。
- 請求項1〜4のいずれかに記載のポリヒドロキシフタラジノン化合物またはその塩と、薬理学的に許容される添加剤とを含むことを特徴とする医薬組成物。
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CN201710369422.XA CN107082764B (zh) | 2017-05-23 | 2017-05-23 | 一类多羟基酞嗪酮化合物、其制备方法及应用 |
PCT/CN2018/086244 WO2018214736A1 (zh) | 2017-05-23 | 2018-05-10 | 一类多羟基酞嗪酮化合物、其制备方法及应用 |
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WO2007058392A1 (ja) * | 2005-11-21 | 2007-05-24 | Japan Tobacco Inc. | ヘテロ環化合物およびその医薬用途 |
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CN107082764B (zh) * | 2017-05-23 | 2018-11-02 | 上海锐聚恩新药研发有限公司 | 一类多羟基酞嗪酮化合物、其制备方法及应用 |
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US20190389809A1 (en) | 2019-12-26 |
US10640469B2 (en) | 2020-05-05 |
JP6823853B2 (ja) | 2021-02-03 |
WO2018214736A1 (zh) | 2018-11-29 |
EP3564215A4 (en) | 2019-12-18 |
EP3564215A1 (en) | 2019-11-06 |
CN107082764B (zh) | 2018-11-02 |
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